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diff --git a/42709.txt b/42709.txt deleted file mode 100644 index b0d788c..0000000 --- a/42709.txt +++ /dev/null @@ -1,44653 +0,0 @@ -The Project Gutenberg EBook of Poisons: Their Effects and Detection, by -Alexander Wynter Blyth - -This eBook is for the use of anyone anywhere at no cost and with -almost no restrictions whatsoever. You may copy it, give it away or -re-use it under the terms of the Project Gutenberg License included -with this eBook or online at www.gutenberg.org - - -Title: Poisons: Their Effects and Detection - A Manual for the Use of Analytical Chemists and Experts - -Author: Alexander Wynter Blyth - -Release Date: May 13, 2013 [EBook #42709] - -Language: English - -Character set encoding: ASCII - -*** START OF THIS PROJECT GUTENBERG EBOOK POISONS: EFFECTS AND DETECTION *** - - - - -Produced by Chris Curnow, Harry Lame and the Online -Distributed Proofreading Team at http://www.pgdp.net (This -file was produced from images generously made available -by The Internet Archive) - - - - - - - - Transcriber's Notes - - Text printed in italics in the original work are transcribed between - underscores, as in _text_. Bold faced and underlined text are - transcribed as =text= and ~text~ respectively. Small capitals have - been transcribed as ALL CAPITALS. Subscripts have been transcribed - as _{...}, as in H_{2}O. Superscripts have been transcribed as - ^{...}, as for example a^{2} for a squared. - - Greek letters are transcribed as [alpha], [beta], etc. [)u] and [=u] - represent u-breve and u-macron respectively. [U] represents a - U-shaped symbol. Other symbols have been transcribed as [Rx] - (prescription take), [dr] (drachm), [oz] (ounce) and [***] - (asterism). - - Chemical structural formulas as given here are approximations of the - structures given in the original work only. Double bonds are - represented by ||, =, // or \\, quadruple bonds by [=]. - - More Transcriber's Notes may be found at the end of this document. - - - - - POISONS: - THEIR EFFECTS AND DETECTION. - - - - -BY THE SAME AUTHOR. - -_Fourth Edition. At Press._ - - FOODS: - THEIR COMPOSITION AND ANALYSIS. - -_With numerous Tables and Illustrations._ - - -=General Contents.= - - History of Adulteration--Legislation, Past and Present--Apparatus - useful to the Food Analyst--"Ash"--Sugar--Confectionery--Honey-- - Treacle--Jams and Preserved Fruits--Starches--Wheaten-Flour--Bread-- - Oats--Barley--Rye--Rice--Maize--Millet--Potato--Peas--Chinese Peas-- - Lentils--Beans--MILK--Cream--Butter--Cheese--Tea--Coffee--Cocoa and - Chocolate--Alcohol--Brandy--Rum--Whisky--Gin--Arrack--Liqueurs--Beer-- - Wine--Vinegar--Lemon and Lime Juice--Mustard--Pepper--Sweet and Bitter - Almond--Annatto--Olive Oil--Water. _Appendix_: Text of English and - American Adulteration Acts. - - "Will be used by every Analyst."--_Lancet._ - - "STANDS UNRIVALLED for completeness of information. . . . A really - 'practical' work for the guidance of practical men."--_Sanitary - Record._ - - "An ADMIRABLE DIGEST of the most recent state of knowledge. . . . - Interesting even to lay-readers."--_Chemical News._ - - -_In Large 8vo, Handsome Cloth._ 21_s._ - - FORENSIC MEDICINE - AND - TOXICOLOGY. - -BY J. DIXON MANN, M.D., F.R.C.P., - -Professor of Medical Jurisprudence and Toxicology in Owens College, -Manchester; Examiner in Forensic Medicine in the University of London, -and in the Victoria University; Physician to the Salford Royal Hospital. - -PART I.--Forensic Medicine. PART II.--Insanity in its Medico-legal -Bearings. PART III.--Toxicology. - - "By far the MOST RELIABLE, MOST SCIENTIFIC, and MOST MODERN book on - Medical Jurisprudence with which we are acquainted."--_Dublin - Medical Journal_. - - "A MOST USEFUL work of reference. . . . Of value to all those who, - as medical men or lawyers, are engaged in cases where the testimony - of medical experts forms a part of the evidence."--_The Law - Journal._ - - -LONDON: CHARLES GRIFFIN & CO., LTD., EXETER ST., STRAND. - - - - - POISONS: - THEIR EFFECTS AND DETECTION. - - A MANUAL FOR THE USE OF ANALYTICAL - CHEMISTS AND EXPERTS. - - _WITH AN INTRODUCTORY ESSAY ON THE GROWTH OF - MODERN TOXICOLOGY._ - - - BY - ALEXANDER WYNTER BLYTH, - M.R.C.S., F.I.C., F.C.S., &c., - BARRISTER-AT-LAW; PUBLIC ANALYST FOR THE COUNTY OF DEVON; AND MEDICAL - OFFICER OF HEALTH AND PUBLIC ANALYST FOR ST. MARYLEBONE. - - - THIRD EDITION, REVISED AND ENLARGED. - - With Tables and Illustrations. - - - LONDON: - CHARLES GRIFFIN AND COMPANY, LIMITED, - EXETER STREET, STRAND. - 1895. - - (_All Rights Reserved._) - - D. VAN NOSTRAND COMPANY, - NEW YORK. - - - - -PREFACE TO THE THIRD EDITION. - - -The present edition, which appears on the same general plan as before, -will yet be found to have been in great part re-written, enlarged, and -corrected. - -Analytical methods which experience has shown to be faulty have been -omitted, and replaced by newer and more accurate processes. - -The intimate connection which recent research has shown to exist between -the arrangement of the constituent parts of an organic molecule and -physiological action, has been considered at some length in a separate -chapter. - -The cadaveric alkaloids or ptomaines, bodies playing so great a part in -food-poisoning and in the manifestations of disease, are in this edition -treated of as fully as the limits of the book will allow. - -The author, therefore, trusts that these various improvements, -modifications, and corrections will enable "POISONS" to maintain the -position which it has for so many years held in the esteem of -toxicologists and of the medical profession generally. - - THE COURT HOUSE, ST. MARYLEBONE, W. - _June, 1895_. - - - - -CONTENTS. - - - PART I.--INTRODUCTORY. - - - I. THE OLD POISON-LORE. - - Section Page - - 1. The History of the _Poison-lehre_--The Origin of Arrow-Poison-- - Greek Myths, 1 - 2. Knowledge of the Egyptians relative to Poisons--Distillation of - Peach-Water, 2 - 3. Roman and Greek Knowledge of Poison--Sanction of Suicide among - the Ancients--The Classification of Poisons adopted by - Dioscorides, 2-4 - 4. Poisoning among Eastern Nations--Slow Poisons, 4, 5 - 5. Hebrew Knowledge of Poisons, 5 - 6. The part which Poison has played in History--Statira--Locusta-- - Britannicus--The Rise of Anatomy--The Death of Alexander the - Great--of Pope Alexander VI.--The Commission of Murder given by - Charles le Mauvais--Royal Poisoners--Charles IX.--King John--A - Female Poisoner boiled alive, 5-9 - 7. The Seventeenth Century Italian Schools of Criminal Poisoning-- - The Council of Ten--John of Ragubo--The Professional Poisoner-- - J. B. Porta's Treatise on _Natural Magic_--Toffana and the - "_Acquetta di Napoli_"--Organic Arsenical Compounds--St. Croix - and Madame de Brinvilliers--Extraordinary Precautions for the - Preservation from Poison of the Infant Son of Henry VIII., 9-13 - - - II. GROWTH AND DEVELOPMENT OF THE MODERN METHODS OF CHEMICALLY - DETECTING POISONS. - - 8. Phases through which the Art of Detecting Poisons has passed, 13 - 9. Treatise of Barthelemy d'Anglais--Hon. Robert Boyle--Nicolas - l'Emery's _Cours de Chimie_--Mead's _Mechanical Theory of - Poisons_--Rise of Modern Chemistry--Scheele's Discoveries, 13, 14 - 10. History of Marsh's Test, 14, 15 - 11. Orfila and his _Traite de Toxicologie_--Orfila's Method of - Experiment, 15 - 12. The Discovery of the Alkaloids--Separation of Narcotine, - Morphine, Strychnine, Delphinine, Coniine, Codeine, Atropine, - Aconitine, and Hyoscyamine, 15, 16 - 13. Bibliography of the Chief Works on Toxicology of the Nineteenth - Century, 16-19 - - - PART II. - - - I. DEFINITION OF POISON. - - 14. The Legal Definition of Poison--English Law as to Poison, 20, 21 - 15. German Law as to Poisoning--French Law as to Poisoning, 21, 22 - 16. Scientific Definition of a Poison--The Author's - Definition, 22, 23 - - - II. CLASSIFICATION OF POISONS. - - 17. Fodere's, Orfila's, Casper's, Taylor's, and Guy's Definition of - Poisons--Poisons arranged according to their Prominent - Effects, 23, 24 - 18. Kobert's Classification, 24, 25 - 19. The Author's Arrangement, 25-28 - - - III. STATISTICS. - - 20. Statistics of Poisoning in England and Wales during the Ten - Years 1883-92--Various Tables, 28-31 - 21. German Statistics of Poisoning, 31-33 - 22. Criminal Poisoning in France, 33, 34 - - - IV. THE CONNECTION BETWEEN TOXIC ACTION AND CHEMICAL COMPOSITION. - - 23. The Influence of Hydroxyl--The Replacement of Hydrogen by a - Halogen--Bamberger's Acylic and Aromatic Bases, 35, 36 - 24. The Replacement of Hydrogen by Alkyls in Aromatic Bodies, 36-38 - 25. The Influence of Carbonyl Groups, 39 - 26. Oscar Loew's Theory as to the Action of Poisons, 39-41 - 27. Michet's Experiments on the relative Toxicity of Metals, 41, 42 - - - V. LIFE TESTS: OR THE IDENTIFICATION OF POISON BY EXPERIMENTS - ON ANIMALS. - - 28. The Action of Poisons on Infusoria, Cephalopoda, Insects, 42-44 - 29. Effect of Poisons on the Heart of Cold-blooded Animals, 44, 45 - 30. The Effect of Poisons on the Iris, 45, 46 - - - VI. GENERAL METHOD OF PROCEDURE IN SEARCHING FOR POISON. - - 31. Concentration in a Vacuum--Drying the Substance--Solvents-- - Destruction of Organic Matter, 46-50 - 32. Autenrieth's General Process--Distillation--Shaking up with - Solvents--Isolation of Metals--Investigation of Sulphides - Soluble in Ammonium Sulphide--of Sulphides Insoluble in Ammonium - Sulphide--Search for Zinc and Chromium--Search for Lead, Silver, - and Barium, 50-53 - - - VII. THE SPECTROSCOPE AS AN AID TO THE IDENTIFICATION OF - CERTAIN POISONS. - - 33. The Micro-Spectroscope--Oscar Brasch's Researches of the Spectra - of Colour Reactions--Wave Lengths, 54-56 - - - _Examination of Blood or of Blood-Stains._ - - 34. Naked-eye Appearance of Blood-Stains--Dragendorff's Process for - Dissolving Blood, 56, 57 - 35. Spectroscopic Appearances of Blood--Spectrum of Hydric Sulphide - Blood--of Carbon Oxide Haemoglobin--Methaemoglobin--of Acid - Haematin--Tests for CO Blood--Piotrowski's Experiments on CO - Blood--Preparation of Haematin Crystals--The Guaiacum Test for - Blood, 57-62 - 36. Distinction between the Blood of Animals and Men--The Alkalies - in various Species of Blood, 62, 63 - - - PART III.--POISONOUS GASES: CARBON MONOXIDE--CHLORINE--HYDRIC - SULPHIDE. - - - I. CARBON MONOXIDE. - - 37. Properties of Carbon Monoxide, 64 - 38. Symptoms--Acute Form--Chronic Form, 64-66 - 39. Poisonous Action on the Blood--Action on the Nervous - System, 66, 67 - 40. _Post-mortem_ Appearances, 67 - 41. Mass Poisonings by Carbon Monoxide--The Leeds Case--The - Darlaston Cases, 67-70 - 42. Detection of Carbon Monoxide--The Cuprous Chloride Method-- - Wanklyn's Method--Hempel's Method, 70, 71 - - - II. CHLORINE. - - 43. Chlorine; its Properties--The Weldon Process of manufacturing - "Bleaching Powder," 71, 72 - 44. Effects of Chlorine, 72 - 45. _Post-mortem_ Appearances, 72 - 46. Detection of Free Chlorine, 72 - - - III. HYDRIC SULPHIDE (SULPHURETTED HYDROGEN). - - 47. Properties of Hydric Sulphide, 72, 73 - 48. Effects of breathing Hydric Sulphide--Action on the Blood--The - Cleator Moor Case, 73, 74 - 49. _Post-mortem_ Appearances, 74 - 50. Detection, 74 - - - PART IV.--ACIDS AND ALKALIES. - - SULPHURIC ACID--HYDROCHLORIC ACID--NITRIC ACID--ACETIC ACID--AMMONIA - --POTASH--SODA--NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM SALTS. - - - I. SULPHURIC ACID. - - 51. Varieties and Strength of the Sulphuric Acids of Commerce-- - Properties of the Acid--Nordhausen Sulphuric Acid, 75, 76 - 52. Properties of Sulphuric Anhydride, 76 - 53. Occurrence of Free Sulphuric Acid in Nature, 76 - 54. Statistics--Comparative Statistics of different Countries, 76, 77 - 55. Accidental, Suicidal, and Criminal Poisoning--Sulphuric Acid in - Clysters and Injections, 77, 78 - 56. Fatal Dose, 78, 79 - 57. Local Action of Sulphuric Acid--Effects on Mucous Membrane, on - the Skin, on Blood, 79, 80 - 58. Action of Sulphuric Acid on Earth, Grass, Wood, Paper, Carpet, - Clothing, Iron--Caution necessary in judging of Spots-- - Illustrative Case, 80, 81 - 59. Symptoms--(1) External Effects--(2) Internal Effects in the - Gullet and Stomach--Intercostal Neuralgia, 81-83 - 60. Treatment of Acute Poisoning by the Mineral Acids, 83 - 61. _Post-mortem_ Appearances--Rapid and Slow Poisoning-- - Illustrative Cases, 83-85 - 62. Pathological Preparations in the different London Hospital - Museums, 85, 86 - 63. Chronic Poisoning, 86 - - - _Detection and Estimation of Free Sulphuric Acid._ - - 64. General Method of Separating the Free Mineral Acids--The Quinine - Process--The Old Process of Extraction by Alcohol--Hilger's Test - for Mineral Acid, 87, 88 - 65. The Urine--Excretion of Sulphates in Health and Disease--The - Characters of the Urine after taking Sulphuric Acid, 88-90 - 66. The Blood in Sulphuric Acid Poisoning, 90 - 67. The Question of the Introduction of Sulphates by the Food-- - Largest possible Amount of Sulphates introduced by this Means-- - Sulphur of the Bile--Medicinal Sulphates, 90, 91 - - - II. HYDROCHLORIC ACID. - - 68. General Properties of Hydrochloric Acid--Discovery--Uses-- - Tests, 91, 92 - 69. Statistics, 92, 93 - 70. Fatal Dose, 93 - 71. Amount of Free Acid in the Gastric Juice, 93, 94 - 72. Influence of Hydrochloric Acid on Vegetation--Present Law on the - Subject of Acid Emanations from Works--The Resistant Powers of - various Plants, 94 - 73. Action on Cloth and Manufactured Articles, 95 - 74. Poisonous Effects of Hydrochloric Acid Gas--Eulenberg's - Experiments on Rabbits and Pigeons, 95, 96 - 75. Effects of the Liquid Acid--Absence of Corrosion of the Skin-- - Pathological Appearances--Illustrative Cases, 96, 97 - 76. _Post-mortem_ Appearances--Preparations in the different London - Museums, 97, 98 - 77. (1) Detection of Free Hydrochloric Acid--Guenzburg's Test--A. - Villiers's and M. Favolle's Test--(2) Quantitative Estimation, - Sjokvist's Method--Braun's Method, 98-101 - 78. Method of Investigating Hydrochloric Acid Stains on Cloth, - &c., 101, 102 - - - III. NITRIC ACID. - - 79. Properties of Nitric Acid, 102, 103 - 80. Use in the Arts, 103 - 81. Statistics, 103 - 82. Fatal Dose, 104 - 83. Action on Vegetation, 104 - 84. Effects of Nitric Acid Vapour--Experiments of Eulenberg and O. - Lassar--Fatal Effect on Man, 104, 105 - 85. Effects of Liquid Nitric Acid--Suicidal, Homicidal, and - Accidental Deaths from the Acid, 105, 106 - 86. Local Action, 106 - 87. Symptoms--The Constant Development of Gas--Illustrative - Cases, 106, 107 - 88. _Post-mortem_ Appearances--Preparations in various Anatomical - Museums, 107-109 - 89. Detection and Estimation of Nitric Acid, 109, 110 - - - IV. ACETIC ACID. - - 90. Symptoms and Detection, 110 - - - V. AMMONIA. - - 91. Properties of Ammonia, 111 - 92. Uses--Officinal and other Preparations, 111, 112 - 93. Statistics of Poisoning by Ammonia, 112 - 94. Poisoning by Ammonia Vapour, 112 - 95. Symptoms--Illustrative Case, 112, 113 - 96. Chronic Effects of the Gas, 113 - 97. Ammonia in Solution--Action on Plants, 113 - 98. Action on Human Beings and Animal Life--Local Action on Skin-- - Action on the Blood--Time of Death, 113-115 - 99. _Post-mortem_ Appearances, 115 - 100. Separation of Ammonia--Tests, 115, 116 - 101. Estimation of Ammonia, 116 - - - VI. CAUSTIC POTASH AND SODA. - - 102. Properties of Potassium Hydrate, 116, 117 - 103. Pharmaceutical Preparations, 117 - 104. Carbonate of Potash, 117 - 105. Bicarbonate of Potash, 117 - 106. Caustic Soda--Sodium Hydrate, 117, 118 - 107. Carbonate of Soda, 118 - 108. Bicarbonate of Soda, 118 - 109. Statistics, 118 - 110. Effects on Animal and Vegetable Life, 118, 119 - 111. Local Effects, 119 - 112. Symptoms, 119 - 113. _Post-mortem_ Appearances, 119-121 - 114. Chemical Analysis, 121 - 115. Estimation of the Fixed Alkalies, 121, 122 - - - VII. NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM SALTS. - - 116. Relative Toxicity of Sodium, Potassium, and Ammonium Salts, 122 - 117. Sodium Salts, 122 - 118. Potassium Salts--Potassic Sulphate--Hydropotassic Tartrate-- - Statistics, 122 - 119. Action on the Frog's Heart, 122 - 120. Action on Warm-Blooded Animals, 122, 123 - 121. Elimination, 123 - 122. Nitrate of Potash, 123 - 123. Statistics, 123 - 124. Uses in the Arts, 123 - 125. Action of Nitrates of Sodium and Potassium--Sodic - Nitrite, 123, 124 - 126. _Post-mortem_ Appearances from Poisoning by Potassic Nitrate, 124 - 127. Potassic Chlorate, 124 - 128. Uses, 124 - 129. Poisonous Properties, 124 - 130. Experiments on Animals, 124, 125 - 131. Effects on Man--Illustrative Cases of the Poisoning of Children - by Potassic Chlorate, 125 - 132. Effects on Adults--Least Fatal Dose, 126 - 133. Elimination, 126 - 134. Essential Action of Potassic Chlorate on the Blood and - Tissues, 126 - 135. Detection and Estimation of Potassic Chlorate, 126, 127 - - - _Toxicological Detection of Alkali Salts._ - - 136. Natural occurrence of Potassium and Sodium Salts in the Blood - and Tissues--Tests for Potassic and Sodic Salts--Tests for - Potassic Nitrate--Tests for Chlorates--Ammonium Salts, 127, 128 - - - PART V.--MORE OR LESS VOLATILE POISONOUS SUBSTANCES CAPABLE OF BEING - SEPARATED BY DISTILLATION FROM NEUTRAL OR ACID LIQUIDS. - - HYDROCARBONS--CAMPHOR--ALCOHOL--AMYL NITRITE--ETHER--CHLOROFORM - AND OTHER ANAESTHETICS--CHLORAL--CARBON BISULPHIDE--CARBOLIC - ACID--NITRO-BENZENE--PRUSSIC ACID--PHOSPHORUS. - - - I. HYDROCARBONS. - - - 1. _Petroleum._ - - 137. Petroleum, 129 - 138. Cymogene, 129 - 139. Rhigolene, 129 - 140. Gasolene, 129 - 141. Benzoline--Distinction between Petroleum-Naphtha, Shale-Naphtha, - and Coal-Tar Naphtha, 129, 130 - 142. Paraffin Oil, 130 - 143. Effects of Petroleum--Experiments on Rabbits, &c., 130, 131 - 144. Poisoning by Petroleum--Illustrative Cases, 131 - 145. Separation and Tests for Petroleum, 131 - - - 2. _Coal-Tar Naphtha--Benzene._ - - 146. Composition of Commercial Coal-Tar Naphtha, 131 - 147. Symptoms observed after Swallowing Coal-Tar Naphtha, 132 - 148. Effects of the Vapour of Benzene, 132 - - - _Detection and Separation of Benzene._ - - 149. Separation of Benzene--(1) Purification; (2) Conversion into - Nitro-Benzene; (3) Conversion into Aniline, 132, 133 - - - 3. _Terpenes--Essential Oils--Oil of Turpentine._ - - 150. Properties of the Terpenes, Cedrenes, and Colophenes, 133 - - - 4. _Oil of Turpentine--Spirits of Turpentine._ - - 151. Terebenthene--Distinction between French and English - Turpentine, 133, 134 - 152. Effects of the Administration of Turpentine, 134 - - - II. CAMPHOR. - - 153. Properties of Camphor, 135 - 154. Pharmaceutical Preparations, 135 - 155. Symptoms of Poisoning by Camphor, 135 - 156. _Post-mortem_ Appearances, 136 - 157. Separation from the Contents of the Stomach, 136 - - - III. ALCOHOLS. - - - 1. _Ethylic Alcohol._ - - 158. Chemical Properties of Alcohol--Statistics of Poisoning by - Alcohol, 136 - 159. Criminal or Accidental Alcoholic Poisoning, 137 - 160. Fatal Dose, 137 - 161. Symptoms of Acute Poisoning by Alcohol, 137, 138 - 162. _Post-mortem_ Appearances, 138, 139 - 163. Excretion of Alcohol, 139, 140 - 164. Toxicological Detection, 140 - - - 2. _Amylic Alcohol._ - - 165. Properties of Amylic Alcohol, 140 - 166. Experiments as to the Effect on Animals of Amylic - Alcohol, 140, 141 - 167. Detection and Estimation of Amylic Alcohol, 141 - 168. Amyl Nitrite--Properties--Symptoms--_Post-mortem_ - Appearances, 141 - - - IV. ETHER. - - 169. Properties of Ethylic Ether, 141, 142 - 170. Ether as a Poison, 142 - 171. Fatal Dose, 142 - 172. Ether as an Anaesthetic, 142, 143 - 173. Separation of Ether from Organic Fluids, &c., 143 - - - V. CHLOROFORM. - - 174. Discovery of Chloroform--Properties, Adulterations, and Methods - for Detecting them, 143-145 - 175. Methods of Manufacturing Chloroform, 145, 146 - - - _Poisonous Effects of Chloroform._ - - - 1. _As a Liquid._ - - 176. Statistics, 146 - 177. Local Action, 146 - 178. Action on Blood, Muscle, and Nerve-Tissue, 146 - 179. General Effects of Liquid Chloroform--Illustrative - Cases, 146, 147 - 180. Fatal Dose, 147 - 181. Symptoms, 148 - 182. _Post-mortem_ Appearances, 148 - - - 2. _The Vapour of Chloroform._ - - 183. Statistics of Deaths through Chloroform--Anaesthesia, 148, 149 - 184. Suicidal and Criminal Poisoning--Illustrative Cases, 149, 150 - 185. Physiological Effects, 150 - 186. Symptoms witnessed in Death from Chloroform Vapour, 150, 151 - 187. Chronic Chloroform Poisoning--Mental Effects from Use of - Chloroform, 151, 152 - 188. _Post-mortem_ Appearances, 152 - 189. The Detection and Estimation of Chloroform--Various - Tests, 152, 153 - 190. Quantitative Estimation, 153 - - - VI. OTHER ANAESTHETICS. - - 191. Methyl Chloride--Methene Dichloride, &c., 154 - 192. Pentane, 154 - 193. Aldehyde, 154 - 194. Paraldehyde, 154 - - - VII. CHLORAL. - - 195. Chloral Hydrate; its Composition and Properties, 154, 155 - 196. Detection, 155 - 197. Quantitative Estimation of Chloral Hydrate, 155, 156 - 198. Effects of Chloral Hydrate on Animals--Depression of Temperature - --Influence on the Secretion of Milk, &c., 156, 157 - 199. Action upon the Blood, 157 - 200. Effects on Man, 157, 158 - 201. Fatal Dose, 158, 159 - 202. Symptoms, 159 - 203. Action of Chloral upon the Brain, 159 - 204. Treatment of Acute Chloral Poisoning, 160 - 205. Chronic Poisoning by Chloral Hydrate, 160, 161 - 206. Manner in which Chloral is Decomposed in, and Excreted from, the - Body, 161, 162 - 207. Separation from Organic Matters--Tests for Chloral, 162, 163 - - - VIII. BISULPHIDE OF CARBON. - - 208. Properties of Bisulphide of Carbon, 163 - 209. Poisoning by Bisulphide of Carbon, 163 - 210. Action on Animals, 163, 164 - 211. Chronic Poisoning by Bisulphide of Carbon--Effects on the Brain, - &c., 164, 165 - 212. _Post-mortem_ Appearances, 165 - 213. Separation and Detection of Carbon Bisulphide--Tests, 165 - 214. Xanthogenic Acid, 165 - 215. Potassic Xanthogenate, 165 - - - IX. THE TAR ACIDS--PHENOL--CRESOL. - - 216. Properties and Sources of Carbolic Acid, 165, 166 - 217. Different Forms of Carbolic Acid--Calvert's Carbolic Acid Powder - --Carbolic Acid Soaps, 166, 167 - 218. Uses of Carbolic Acid, 167 - 219. Statistics Relative to Poisoning by Carbolic Acid, 167-169 - 220. Fatal Dose, 169 - 221. Effects on Animals--Infusoria--Fish--Frogs, 169, 170 - 222. Effects on Warm-Blooded Animals, 170 - 223. Symptoms Produced in Man--External Application--Action on the - Skin--Effects of the Vapour--Use of Carbolic Acid Lotions-- - Injections, &c.--Illustrative Cases, 170-172 - 224. Internal Administration--Illustrative Cases, 173 - 225. General Review of the Symptoms induced by Carbolic Acid, 173, 174 - 226. Changes Produced in the Urine by Carbolic Acid, 174, 175 - 227. The Action of Carbolic Acid considered Physiologically, 175, 176 - 228. Forms under which Carbolic Acid is Excreted, 176 - 229. _Post-mortem_ Appearances, 176, 177 - - - _Tests for Carbolic Acid._ - - 230. (1) The Pine-Wood Test--(2) Ammonia and Hypochlorite Test--(3) - Ferric Chloride--(4) Bromine, 177, 178 - 231. Quantitative Estimation of Carbolic Acid, 178, 179 - 232. Properties of Cresol, and Tests for Distinguishing Cresol and - Carbolic Acid, 179 - 233. Properties of Creasote--Tests, 179, 180 - 234. Separation of Carbolic Acid from Organic Fluids or - Tissues, 180, 181 - 235. Examination of the Urine for Phenol or Cresol, 181 - 236. Assay of Disinfectants, Carbolic Acid Powders--E. Waller's - Process--Koppeschaar's Volumetric Method--Colorimetric Method of - Estimation, 181-183 - 237. Carbolic Acid Powders, 183 - 238. Carbolic Acid Soaps, 183 - - - X. NITRO-BENZENE. - - 239. Properties and Varieties, 183, 184 - 240. Effects of Poisoning by Nitro-Benzene, 184 - 241. Illustrative Cases of Poisoning by Nitro-Benzene Vapour, 184, 185 - 242. Effects Produced by taking Liquid Nitro-Benzene, 185, 186 - 243. Fatal Dose, 186, 187 - 244. Pathological Appearances, 187 - 245. The Essential Action of Nitro-Benzene, 187, 188 - 246. Detection and Separation from the Animal Tissues, 188 - - - XI. DINITRO-BENZOL. - - 247. Properties of Ortho-, Meta-, and Para-Dinitro-Benzol, 189 - 248. Effects of Dinitro-Benzol, 189, 190 - 249. The Blood in Nitro-Benzol Poisoning, 191 - 250. Detection of Dinitro-Benzol, 192 - - - XII. HYDROCYANIC ACID. - - 251. Properties of Hydrocyanic Acid, 192 - 252. Medicinal Preparations of Prussic Acid--Various Strengths of the - Commercial Acid, 192, 193 - 253. Poisoning by Prussic Acid--Uses in the Arts--Distribution in the - Vegetable Kingdom, 193-195 - 254. Composition and Varieties of Amygdalin, 195 - 255. Statistics of Poisoning by Prussic Acid, 195-197 - 256. Accidental and Criminal Poisoning, 197, 198 - 257. Fatal Dose, 198 - 258. Action of Hydric and Potassic Cyanides on Living - Organisms, 198, 199 - 259. Symptoms observed in Animals, 199, 200 - 260. Length of Interval between taking the Poison and Death in - Animals, 200, 201 - 261. Symptoms in Man, 201, 202 - 262. Possible Acts after taking the Poison--Nunneley's - Experiments, 202, 203 - 263. Chronic Poisoning by Hydric Cyanide, 203 - 264. _Post-mortem_ Appearances, 203, 204 - 265. Tests for Hydrocyanic Acid and Cyanide of Potassium--Schoenbein's - Test--Kobert's Test, 204-206 - 266. Separation of Hydric Cyanide or Potassic Cyanide from Organic - Matters--N. Sokoloff's Experiments, 206-208 - 267. How long after Death can Hydric or Potassic Cyanide be - Detected? 208, 209 - 268. Estimation of Hydrocyanic Acid or Potassic Cyanide, 209 - 269. Case of Poisoning by Bitter Almonds, 209, 210 - - - _Poisonous Cyanides other than Hydric and Potassic Cyanides._ - - 270. General Action of the Alkaline Cyanides--Experiments with - Ammonic Cyanide Vapour, 210 - 271. The Poisonous Action of several Metallic and Double Cyanides-- - The Effects of Mercuric and Silver Cyanides; of Potassic and - Hydric Sulphocyanides; of Cyanogen Chloride; of Methyl Cyanide, - and of Cyanuric Acid, 210, 211 - - - XIII. PHOSPHORUS. - - 272. Properties of Phosphorus--Solubility--Effects of Heat on - Phosphorus, 212, 213 - 273. Phosphuretted Hydrogen--Phosphine, 213 - 274. The Medicinal Preparations of Phosphorus, 213 - 275. Matches and Vermin Paste, 213-215 - 276. Statistics of Phosphorus Poisoning, 215, 216 - 277. Fatal Dose, 216 - 278. Effects of Phosphorus, 217 - 279. Different Forms of Phosphorus Poisoning, 217, 218 - 280. Common Form, 218, 219 - 281. Haemorrhagic Form, 219 - 282. Nervous Form, 219 - 283. Sequelae, 219, 220 - 284. Period at which the First Symptoms commence, 220 - 285. Period of Death, 220 - 286. Effects of Phosphorus Vapour--Experiments on Rabbits, 220, 221 - 287. Effects of Chronic Phosphorus Poisoning, 221, 222 - 288. Changes in the Urinary Secretion, 222 - 289. Changes in the Blood, 222, 223 - 290. Antidote--Treatment by Turpentine, 223 - 291. Poisonous Effects of Phosphine, 223, 224 - 292. Coefficient of Solubility of Phosphine in Blood compared with - Pure Water, 224 - 293. _Post-mortem_ Appearances--Effects on the Liver, 224-228 - 294. Pathological Changes in the Kidneys, Lungs, and Nervous - System, 228 - 295. Diagnostic Differences between Acute Yellow Atrophy of the Liver - and Fatty Liver produced by Phosphorus, 228, 229 - 296. Detection of Phosphorus--Mitscherlich's Process--The Production - of Phosphine--Tests Dependent on the Combustion of Phosphine, - 229-232 - 297. The Spectrum of Phosphine--Lipowitz's Sulphur Test--Scherer's - Test, 232, 233 - 298. Chemical Examination of the Urine, 233, 234 - 299. Quantitative Estimation of Phosphorus, 234 - 300. How long can Phosphorus be recognised after Death? 234, 235 - - - PART VI.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES - SEPARATED FOR THE MOST PART BY ALCOHOLIC SOLVENTS. - - - DIVISION I.--VEGETABLE ALKALOIDS. - - - I. GENERAL METHOD OF TESTING AND EXTRACTING ALKALOIDS. - - 301. General Tests for Alkaloids, 236 - 302. Group-Reagents, 236, 237 - 303. Phosphomolybdic, Silico-Tungstic, and Phospho-Tungstic Acids as - Alkaloidal Reagents, 237-239 - 304. Schulze's Reagent, 239 - 305. Dragendorff's Reagent, 239 - 306. Colour Tests, 239 - 307. Stas's Process, 239 - - - _Methods of Separation._ - - 308. Selmi's Process for Separating Alkaloids, 240, 241 - 309. Dragendorff's Process, 241-254 - 310. Shorter Process for Separating some of the Alkaloids, 254, 255 - 311. Scheibler's Process for Alkaloids, 255 - 312. Grandval and Lajoux's Method, 255, 256 - 313. Identification of the Alkaloids, 256 - 314. Sublimation of the Alkaloids, 256-261 - 315. Melting-point, 261 - 316. Identification by Organic Analysis, 261, 262 - 317. Quantitative Estimation of the Alkaloids--Mayer's Reagent-- - Compound of the Alkaloids with Chlorides of Gold and Platinum, - 262-264 - - - II. LIQUID VOLATILE ALKALOIDS. - - - 1. _The Alkaloids of Hemlock_ (_Conium_). - - 318. Botanical Description of Hemlock, 264 - 319. Properties of Coniine--Tests, 264-266 - 320. Other Coniine Bases, 266 - 321. Pharmaceutical Preparations of Hemlock, 266, 267 - 322. Statistics of Coniine Poisoning, 267 - 323. Effects of Coniine on Animals, 267, 268 - 324. Effects of Coniine on Man, 268 - 325. Physiological Action of Coniine, 268 - 326. _Post-mortem_ Appearances--Fatal Dose, 268, 269 - 327. Separation of Coniine from Organic Matters or Tissues, 269 - - - 2. _Tobacco--Nicotine._ - - 328. General Composition of Tobacco, 269, 270 - 329. Quantitative Estimation of Nicotine in Tobacco, 270, 271 - 330. Nicotine; its Properties and Tests, 271-273 - 331. Effects of Nicotine on Animals, 273, 274 - 332. Effects of Nicotine on Man, 274, 275 - 333. Some Instances of Poisoning by Tobacco and Tobacco Juice, 275-277 - 334. Physiological Action of Nicotine, 277, 278 - 335. Fatal Dose, 278 - 336. _Post-mortem_ Appearances, 278 - 337. Separation of Nicotine from Organic Matters, &c., 278, 279 - - - 3. _Piturie._ - - 338. Properties of Piturie, 279 - - - 4. _Sparteine._ - - 339. Properties of Sparteine, 279, 280 - - - 5. _Aniline._ - - 340. Properties of Aniline, 280 - 341. Symptoms and Effects, 280, 281 - 342. Fatal Dose, 281 - 343. Detection of Aniline, 281 - - - III. THE OPIUM GROUP OF ALKALOIDS. - - 344. General Composition of Opium, 281, 282 - 345. Action of Solvents on Opium, 282, 283 - 346. The Methods of Teschemacher and Smith, of Dott and others for - the Assay of Opium, 283, 284 - 347. Medicinal and other Preparations of Opium, 284-288 - 348. Statistics of Opiate Poisoning, 288, 289 - 349. Poisoning of Children by Opium, 289 - 350. Doses of Opium and Morphine--Fatal Dose, 289, 290 - 351. General Method for the Detection of Opium, 290, 291 - 352. Morphine; its Properties, 291, 292 - 353. Morphine Salts; their Solubility, 292, 293 - 354. Constitution of Morphine, 293, 294 - 355. Tests for Morphine and its Compounds--Production of Morphine - Hydriodide--Iodic Acid Test and other Reactions--Transformation - of Morphine into Codeine, 294-296 - 356. Symptoms of Opium and Morphine Poisoning--Action on Animals, - 296-298 - 357. Physiological Action, 298, 299 - 358. Physiological Action of Morphine Derivatives, 299 - 359. Action on Man--(_a_) The Sudden Form; (_b_) the Convulsive Form; - (_c_) a Remittent Form of Opium Poisoning--Illustrative Cases, - 299-303 - 360. Diagnosis of Opium Poisoning, 303, 304 - 361. Opium-Eating, 304-306 - 362. Treatment of Opium or Morphine Poisoning, 306 - 363. _Post-mortem_ Appearances, 306, 307 - 364. Separation of Morphine from Animal Tissues and Fluids, 307 - 365. Extraction of Morphine, 308, 309 - 366. Narcotine; its Properties and Tests, 309, 310 - 367. Effects of Narcotine, 310 - 368. Codeine--Properties of Codeine, 310, 311 - 369. Effects of Codeine on Animals--Claude Bernard's Experiments, 311 - 370. Narceine--Properties of Narceine--Tests, 312, 313 - 371. Effects of Narceine, 313, 314 - 372. Papaverine--Properties of Papaverine--Tests, 314 - 373. Effects of Papaverine, 314 - 374. Thebaine; its Properties, 314, 315 - 375. Thebaine; its Effects, 315 - 376. Cryptopine, 315, 316 - 377. Rh[oe]adine, 316 - 378. Pseudomorphine, 316 - 379. Opianine, 316 - 380. Apomorphine, 316, 317 - 381. Reactions of some of the Rarer Opium Alkaloids, 317 - 382. Tritopine, 317 - 383. Meconin (Opianyl), 317 - 384. Meconic Acid--Effects of Meconic Acid--Tests, 318, 319 - - - IV. THE STRYCHNINE OR TETANUS-PRODUCING GROUP OF ALKALOIDS. - - - 1. _Nux Vomica Group--Strychnine--Brucine--Igasurine._ - - 385. Nux Vomica--Characteristics of the Entire and of the Powdered - Seed, 319 - 386. Chemical Composition of Nux Vomica, 319 - 387. Strychnine--Microscopical Appearances--Properties--Medicinal - Preparations--Strychnine Salts, 319-322 - 388. Pharmaceutical and other Preparations of Nux Vomica, with - Suggestions for their Valuation--Vermin-Killers, 322-324 - 389. Statistics, 324-325 - 390. Fatal Dose--Falck's Experiments on Animals as to the Least Fatal - Dose--Least Fatal Dose for Man, 325-328 - 391. Action on Animals--Frogs, 328, 329 - 392. Effects on Man--Symptoms--Distinction between "Disease Tetanus" - and "Strychnos Tetanus," 329-331 - 393. Diagnosis of Strychnine Poisoning, 331, 332 - 394. Physiological Action--Richet's Experiments--The Rise of - Temperature--Effect on the Blood-Pressure, 332, 333 - 395. _Post-mortem_ Appearances, 333 - 396. Treatment, 333 - 397. Separation of Strychnine from Organic Matters--Separation from - the Urine, Blood, and Tissues, 334-337 - 398. Identification of the Alkaloid--Colour Tests--Physiological - Tests, 337-339 - 399. Hypaphorine, 339 - 400. Quantitative Estimation of Strychnine, 339, 340 - 401. Brucine; its Properties, 340, 341 - 402. Physiological Action of Brucine--Experiments of Falck, 341, 342 - 403. Tests for Brucine, 342, 343 - 404. Igasurine, 344 - 405. Strychnic Acid, 344 - - - 2. _The Quebracho Group of Alkaloids._ - - 406. The Alkaloids of Quebracho--Aspidospermine--Quebrachine, 344 - - - 3. _Pereirine._ - - 407. Pereirine, 344, 345 - - - 4. _Gelsemine._ - - 408. Properties of Gelsemine, 345 - 409. Fatal Dose of Gelsemine, 345 - 410. Effects on Animals--Physiological Action, 345 - 411. Effects of Gelsemine on Man, 346 - 412. Extraction from Organic Matters, or the Tissues of the Body, 347 - - - 5. _Cocaine._ - - 413. Cocaine; its Properties, 47, 348 - 414. Cocaine Hydrochlorate, 348 - 415. Pharmaceutical Preparations, 348 - 416. Separation of Cocaine and Tests, 348, 349 - 417. Symptoms, 349 - 418. _Post-mortem_ Appearances, 349, 350 - 419. Fatal Dose, 350 - - - 6. _Corydaline._ - - 420. Properties of Corydaline, 350 - - - V. THE ACONITE GROUP OF ALKALOIDS. - - 421. Varieties of Aconite--Description of the Flower, and of the - Seeds, 350, 351 - 422. Pharmaceutical Preparations of Aconite, 351 - 423. The Aconite Alkaloids, 351 - 424. Aconitine, 351, 352 - 425. Tests for Aconitine, 352 - 426. Benzoyl-Aconine Properties--Recognition of Benzoic Acid, - 353, 354 - 427. Pyraconitine, 354 - 428. Pyraconine, 354 - 429. Aconine, 355 - 430. Commercial Aconitine--English and German Samples of Aconitine-- - Lethal Dose of the Alkaloid and of the Pharmaceutical - Preparations, 355-358 - 431. Effects of Aconitine on Animal Life--Insects, Fish, Reptiles, - Birds, Mammals, 358-360 - 432. Statistics, 361 - 433. Effects on Man, 361 - 434. Poisoning by the Root (_Reg. v. M'Conkey_), 361, 362 - 435. Poisoning by the Alkaloid Aconitine--Three Cases of - Poisoning, 363, 364 - 436. Lamson's Case, 364, 365 - 437. Symptoms of Poisoning by the Tincture, &c., 365, 366 - 438. Physiological Action, 366 - 439. _Post-mortem_ Appearances, 366, 367 - 440. Separation of Aconitine from the Contents of the Stomach or the - Organs, 367, 368 - - - VI. THE MYDRIATIC GROUP OF ALKALOIDS--ATROPINE--HYOSCYAMINE--SOLANINE - --CYTISINE. - - - 1. _Atropine._ - - 441. The _Atropa belladonna_; its Alkaloidal Content, 368, 369 - 442. The _Datura stramonium_--Distinction between Datura and - Capsicum Seeds, 369, 370 - 443. Pharmaceutical Preparations--(a) Belladonna; (b) - Stramonium, 370, 371 - 444. Properties of Atropine, 371, 372 - 445. Tests for Atropine, Chemical and Physiological, 372-374 - 446. Statistics of Atropine Poisoning, 375 - 447. Accidental and Criminal Poisoning by Atropine--Use of - _Dhatoora_ by the Hindoos, 375, 376 - 448. Fatal Dose of Atropine, 376, 377 - 449. Action on Animals, 377 - 450. Action on Man, 377-380 - 451. Physiological Action of Atropine, 380 - 452. Diagnosis of Atropine Poisoning, 380 - 453. _Post-mortem_ Appearances, 380 - 454. Treatment of Cases of Poisoning by Atropine, 380, 381 - 455. Separation of Atropine from Organic Matters, &c., 381 - - - 2. _Hyoscyamine._ - - 456. Distribution of Hyoscyamine--Properties, 381-383 - 457. Pharmaceutical and other Preparations of Henbane, 383, 384 - 458. Dose and Effects, 384 - 459. Separation of Hyoscyamine from Organic Matters, 385 - - - 3. _Hyoscine._ - - 460. Hyoscine, 385 - - - 4. _Solanine._ - - 461. Distribution of Solanine, 385, 386 - 462. Properties of Solanine, 386 - 463. Solanidine, 386, 387 - 464. Poisoning from Solanine, 387 - 465. Separation from Animal Tissues, 387 - - - 5. _Cytisine._ - - 466. The _Cytisus laburnum_, 387 - 467. Reactions of Cytisine, 388 - 468. Effects on Animals, 389 - 469. Effects on Man--Illustrative Cases, 389, 390 - - - VII. THE ALKALOIDS OF THE VERATRUMS. - - 470. The Alkaloids found in the _Veratrum Viride_ and _Veratrum - Album_--Yield per Kilogram, 390-392 - 471. Veratrine--Cevadine, 392 - 472. Jervine, 393 - 473. Pseudo-jervine, 393 - 474. Protoveratridine, 393 - 475. Rubi-jervine, 394 - 476. Veratralbine, 394 - 477. Veratroidine, 394 - 478. Commercial Veratrine, 394, 395 - 479. Pharmaceutical Preparations, 395 - 480. Fatal Dose, 395 - 481. Effects on Animals--Physiological Action, 395, 396 - 482. Effects on Man--Illustrative Cases, 396 - 483. Symptoms of Acute and Chronic Poisoning, 396, 397 - 484. _Post-mortem_ Signs, 397 - 485. Separation of the Veratrum Alkaloids from Organic Matters, 397 - - - VIII. PHYSOSTIGMINE. - - 486. The Active Principle of the Calabar Bean, 397, 398 - 487. Physostigmine or Eserine--Properties, 398, 399 - 488. Tests, 399 - 489. Pharmaceutical Preparations, 399, 400 - 490. Effects on Animals--On Man--The Liverpool Cases of Poisoning, - 400 - 491. Physiological Action, 401 - 492. _Post-mortem_ Appearances, 401 - 493. Separation of Physostigmine, 401, 402 - 494. Fatal Dose of Physostigmine, 402 - - - IX. PILOCARPINE. - - 495. Alkaloids from the Jaborandi, 402 - 496. Pilocarpine, 402, 403 - 497. Tests, 403 - 498. Effects of Pilocarpine, 403, 404 - - - X. TAXINE. - - 499. Properties of Taxine, 404 - 500. Poisoning by the Common Yew, 404 - 501. Effects on Animals--Physiological Action, 404 - 502. Effects on Man, 404, 405 - 503. _Post-mortem_ Appearances, 405 - - - XI. CURARINE. - - 504. Commercial Curarine--Properties, 405-407 - 505. Physiological Effects, 407 - 506. Separation of Curarine, 407, 408 - - - XII. COLCHICINE. - - 507. Contents of Colchicine in Colchicum Seeds, 408, 409 - 508. Colchicine--Method of Extraction--Properties, 409 - 509. Tests, 409, 410 - 510. Pharmaceutical Preparations, 410 - 511. Fatal Dose, 410, 411 - 512. Effects of Colchicine on Animals, 411 - 513. Effects of Colchicum on Man--Illustrative Cases, 411, 412 - 514. Symptoms Produced by Colchicum--_Post-mortem_ Appearances, - 412, 413 - 515. Separation of Colchicine from Organic Matters, 413 - - - XIII. MUSCARINE AND THE ACTIVE PRINCIPLES OF CERTAIN FUNGI. - - 516. Description of the _Amanita Muscaria_--Use of it by the Natives - of Kamschatka, 413, 414 - 517. Cases of Poisoning by the Fungus itself, 414, 415 - 518. Muscarine--Its Properties and Effects, 415, 416 - 519. Antagonistic Action of Atropine and Muscarine, 416 - 520. Detection of Muscarine, 416, 417 - 521. The _Agaricus Phalloides_--_Phallin_, 417 - 522. _Post-mortem_ Appearances, 417, 418 - 523. The _Agaricus Pantherinus_--The _Agaricus Ruber_--Ruberine - --Agarythrine, 418 - 524. The _Boletus Satanus_, or _Luridus_, 418 - 525. Occasional Effects of the Common Morelle, 418 - - - Division II.--GLUCOSIDES - - - I. DIGITALIS GROUP. - - 526. Description of the _Digitalis Purpurea_, or Foxglove, 419 - 527. Active Principles of the Foxglove--The Digitalins, 419 - 528. Digitalein, 420 - 529. Digitonin--Digitogenin, 420 - 530. Digitalin, 420 - 531. Digitaletin, 420 - 532. Digitoxin--Toxiresin, 420, 421 - 533. Digitaleretin--Paradigitaletin, 421 - 534. Other Active Principles in Digitalis; such as Digitin, - Digitalacrin, Digitalein, &c., 421, 422 - 535. Reactions of the Digitalins, 422 - 536. Pharmaceutical Preparations of Digitalin, 422 - 537. Fatal Dose, 422-424 - 538. Statistics of Poisoning by Digitalis, 424 - 539. Effects on Man--Illustrative Cases, 424-427 - 540. Physiological Action of the Digitalins, 427 - 541. Local Action of the Digitalins, 427, 428 - 542. Action on the Heart and Circulation, 428, 429 - 543. Action of the Digitalins on the Muco-Intestinal Tract and other - Organs, 429 - 544. Action of Digitalin on the Common Blow-Fly, 429 - 545. Action of the Digitalins on the Frog's Heart, 429, 430 - 546. _Post-mortem_ Appearances, 430 - 547. Separation of the Digitalins from Animal Tissues, &c.--Tests, - Chemical and Physiological, 431 - - - II. OTHER POISONOUS GLUCOSIDES ACTING ON THE HEART. - - - 1. _Crystallisable Glucosides._ - - 548. Antiarin--Chemical Properties, 432 - 549. Effects of Antiarin, 432 - 550. Separation of Antiarin, 432 - 551. The Active Principles of the Hellebores--Helleborin-- - Helleborein--Helleboretin, 433 - 552. Symptoms of Poisoning by Hellebore, 433 - 553. Euonymin, 433 - 554. Thevetin, 434 - - - 2. _Substances partly Crystallisable, but which are not Glucosides._ - - 555. Strophantin, 434 - 556. Apocynin, 434 - - - 3. _Non-Crystallisable Glucosides almost Insoluble in Water._ - - 557. Scillain, or Scillitin--Adonidin, 434 - 558. Oleandrin, 435 - 559. Neriin, or Oleander Digitalin, 435 - 560. Symptoms of Poisoning by Oleander, 435, 436 - 561. The Madagascar Ordeal Poison, 436 - - - 4. _Substances which, with other Toxic Effects, behave like the - Digitalins._ - - 562. Erythrophlein, 436 - - - III. SAPONIN--SAPONIN SUBSTANCES. - - 563. The Varieties of Saponins, 436, 437 - 564. Properties of Saponin, 437 - 565. Effects of Saponin, 437, 438 - 566. Action on Man, 438 - 567. Separation of Saponin, 438, 439 - 568. Identification of Saponin, 439 - - - DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS. - - - I. SANTONIN. - - 569. Properties of Santonin, 439, 440 - 570. Poisoning by Santonin, 440 - 571. Fatal Dose, 440 - 572. Effects on Animals, 440 - 573. Effects on Man--Yellow Vision, 440, 441 - 574. _Post-mortem_ Appearances, 441 - 575. Separation from the Contents of the Stomach, 441, 442 - - - II. MEZEREON. - - 576. Cases of Poisoning by the Mezereon, 442 - - - DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES--NOT ADMITTING OF - CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS. - - - I. ERGOT OF RYE. - - 577. Description of the Ergot Fungus, 442, 443 - 578. Chemical Constituents of Ergot--Ergotinine--_Ecboline_-- - _Scleromucin_--Sclerotic Acid--Sclererythrin--Scleroidin-- - Sclerocrystallin--Sphacelic Acid--Cornutin, 443-445 - 579. Detection of Ergot in Flour, 445 - 580. Pharmaceutical Preparations, 445 - 581. Dose, 446 - 582. Ergotism--Historical Notice of Various Outbreaks, 446, 447 - 583. Convulsive Form of Ergotism, 447 - 584. Gangrenous Form of Ergotism--The Wattisham Cases, 447, 448 - 585. Symptoms of Acute Poisoning by Ergot, 448 - 586. Physiological Action, as shown by Experiments on Animals, 448-450 - 587. Separation of the Active Principles of Ergot, 450 - - - II. PICROTOXIN, THE ACTIVE PRINCIPLE OF THE _COCCULUS INDICUS_. - - 588. Enumeration of the Active Principles contained in the - _Menispermum Cocculus_, 451 - 589. Picrotoxin; its Chemical Reactions and Properties, 451, 452 - 590. Fatal Dose, 452 - 591. Effects on Animals, 452, 453 - 592. Effects on Man, 453 - 593. Physiological Action, 453 - 594. Separation from Organic Matters, 453, 454 - - - III. THE POISON OF _ILLICIUM RELIGIOSUM_. - - 595. Dr. Langaard's Researches, 454 - - - IV. PICRIC ACID AND PICRATES. - - 596. Properties of Picric Acid, 454 - 597. Effects of Picric Acid, 454, 455 - 598. Tests, 455 - - - V. CICUTOXIN. - - 599. Description of the _Cicuta Virosa_, 456 - 600. Effects on Animals, 456 - 601. Effects on Man, 456, 457 - 602. Separation of Cicutoxin from the Body, 457 - - - VI. _AETHUSA CYNAPIUM_ (FOOL'S PARSLEY). - - 603. Dr. Harley's Experiments, 457 - - - VII. _[OE]NANTHE CROCATA._ - - 604. The Water Hemlock--Description of the Plant--Cases of - Poisoning, 457, 458 - 605. Effects of the Water Hemlock, as shown by the Plymouth Cases, 458 - 606. _Post-mortem_ Appearances, 459 - - - VIII. OIL OF SAVIN. - - 607. Effects and Properties of Savin Oil, 459 - 608. _Post-mortem_ Appearances, 460 - 609. Separation and Identification, 460 - - - IX. CROTON OIL. - - 610. Chemical Properties of Croton Oil, 461 - 611. Dose--Effects--Illustrative Cases, 461 - 612. _Post-mortem_ Appearances, 461 - 613. Chemical Analysis, 462 - - - X. THE TOXALBUMINS OF CASTOR OIL SEEDS AND ABRUS. - - 614. The Toxalbumin of Castor Oil Seeds, 462 - 615. Toxalbumin of Abrus, 462, 463 - - - XI. ICTROGEN. - - 616. Ictrogen, 463 - - - XII. COTTON SEEDS. - - 617. Cotton Seeds as a Poison, 464 - - - XIII. _LATHYRUS SATIVUS._ - - 618. Poisonous Qualities of Vetchlings, 464, 465 - - - XIV. ARUM--LOCUST-TREE--BRYONY--MALE FERN. - - 619. Arum Maculatum, 465 - 620. The Black Bryony, 465 - 621. The Locust Tree, 465 - 622. Male Fern 465, 466 - - - PART VII.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL - SUBSTANCES. - - - DIVISION I.--POISONS SECRETED BY LIVING ANIMALS. - - - I. POISONOUS AMPHIBIA. - - 623. Poisonous Properties of the Skin of the _Salamandra Maculosa_ - --Salamandrine, &c., 467 - 624. Poison from the Toad, 468 - - - II. THE POISON OF THE SCORPION. - - 625. Various Species of Scorpions--Effects of the Scorpion Poison, 468 - - - III. POISONOUS FISH. - - 626. Poisonous Fish--Illustrative Cases, 468-470 - - - IV. POISONOUS SPIDERS AND INSECTS. - - 627. The Bite of the Tarantula--The Bite of the _Latrodectus - Malmignatus_, 470 - 628. Effects of the Bite of the Katipo, 471 - 629. Ants, &c., 471 - 630. The Poison of Wasps, Bees, and Hornets, 471 - 631. Cantharides, 471 - 632. Cantharidin, 471, 472 - 633. Pharmaceutical Preparations of Cantharides, 472 - 634. Fatal Dose, 472 - 635. Effects on Animals--Radecki's Experiments--Effects on Man-- - Heinrich's Auto-Experiments, 472, 473 - 636. General Symptoms Produced by Cantharides, 473, 474 - 637. _Post-mortem_ Appearances, 474 - 638. Tests for Cantharidin--Distribution in the Body--Dragendorff's - Process, 475-477 - - - V. SNAKE POISON. - - 639. Classes of Poisonous Snakes, 477 - 640. The Poison of the Cobra, 478 - 641. Fatal Dose of Cobra Poison, 479 - 642. Effects on Animals, 479 - 643. Effects on Man, 479, 480 - 644. Antidotes and Treatment--Halford's Treatment by Ammonia-- - Permanganate of Potash, 480, 481 - 645. Detection of the Cobra Venom, 482 - 646. Effects of the Bite of the _Duboia Russellii_, or Russell's - Viper, 483 - 647. The Poison of the Common Viper--The Venom of Naja Haje - (Cleopatra's Asp), 483, 484 - - - DIVISION II.--PTOMAINES--TOXINES. - - 648. Definition of a Ptomaine, 485 - - - _Isolation of Ptomaines._ - - 649. Gautier's Process, 485 - 650. Brieger's Process, 485-487 - 651. Benzoyl Chloride Method, 487, 488 - 652. The Amines, 488-490 - 653. Methylamine, 491 - 654. Dimethylamine, 491 - 655. Trimethylamine, 491 - 656. Ethylamine, 491 - 657. Diethylamine, 491 - 658. Triethylamine, 491 - 659. Propylamine, 491 - 660. Isoamylamine, 492 - - - _Diamines._ - - 661. Rate of Formation of Diamines, 492 - 662. Ethylidenediamine, 492 - 663. Neuridine, 493, 494 - 664. Cadaverine, 494-496 - 665. Putrescine, 496 - 666. Metaphenylenediamine, 497 - 667. Paraphenylenediamine, 497 - 668. Hexamethylenediamine, 497 - 669. Diethylenediamine, 497, 498 - 670. Mydaleine, 498 - 671. Guanidine, 498, 499 - 672. Methylguanidine, 499, 500 - 673. Saprine, 500 - 674. The Choline Group, 500, 501 - 675. Neurine, 501 - 676. Betaine, 501, 502 - 677. Peptotoxine, 502 - 678. Pyridine-like Alkaloid from the Cuttle-fish, 502, 503 - 679. Poisons connected with Tetanus--Tetanine, 503 - 680. Tetanotoxine, 503, 504 - 681. Mydatoxine, 504 - 682. Mytilotoxine, 505 - 683. Tyrotoxicon, 504, 505 - 684. Toxines connected with Hog Cholera, 505, 506 - 685. Other Ptomaines, 506 - - - DIVISION III.--FOOD POISONING. - - 686. The Welbeck--The Oldham--The Bishop Stortford--The - Wolverhampton--The Carlisle, and other Mass Poisonings by - changed Food--Statistics of Deaths from Unwholesome Food, 506-508 - 687. German Sausage Poisoning, 509 - - - PART VIII.--THE OXALIC ACID GROUP OF POISONS. - - 688. Distribution of Oxalic Acid in the Animal and Vegetable - Kingdoms, 510 - 689. Properties and Reactions of Oxalic Acid, 510, 511 - 690. Oxalate of Lime; its Properties, 511, 512 - 691. Use of Oxalic Acid in the Arts, 512 - 692. Properties of Hydropotassic Oxalate (Binoxalate of Potash), 512 - 693. Statistics of Oxalic Acid Poisoning, 512 - 694. Fatal Dose of Oxalic Acid, 513 - 695. Effects of Oxalic Acid and Oxalates on Animals, 513 - 696. Researches of Kobert and Kuessner on the Effects of Sodic - Oxalate, 513, 514 - 697. Effects of Vaporised Oxalic Acid, 514, 515 - 698. Effects of Oxalic Acid and Hydropotassic Oxalate on Man-- - Illustrative Cases, 515, 516 - 699. Physiological Action, 516, 517 - 700. Pathological Changes produced by Oxalic Acid and the Oxalates, - 517, 518 - 701. Preparations in Museums Illustrative of the Effects of Oxalic - Acid, 518 - 702. Pathological Changes produced by the Acid Oxalate of Potash, - 518, 519 - 703. Separation of Oxalic Acid from Organic Substances, the Tissues - of the Body, &c., 519-521 - 704. Oxalate of Lime in the Urine, 521 - 705. Estimation of Oxalic Acid, 521, 522 - - - _Certain Oxalic Bases--Oxalmethyline--Oxalpropyline._ - - 706. The Experiments of Schulz and Mayer on Oxalmethyline, - Chloroxalmethyline, and Oxalpropyline, 522, 523 - - - PART IX.--INORGANIC POISONS. - - - I. PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC SULPHIDE-- - PRECIPITATE YELLOW OR ORANGE. - - - ARSENIC--ANTIMONY--CADMIUM. - - - 1. _Arsenic._ - - 707. Metallic Arsenic; its Chemical and Physical Properties, 524 - 708. Arsenious Anhydride--Arsenious Acid; its Properties and - Solubility, 524, 525 - 709. Arseniuretted Hydrogen (Arsine), 525-527 - 710. Arseniuretted Hydrogen in the Arts, &c, 527 - 711. The Effects of Arseniuretted Hydrogen on Man--Illustrative - Cases, 527, 528 - 712. The Sulphides of Arsenic, 528, 529 - 713. Orpiment, or Arsenic Trisulphide, 529 - 714. Haloid Arsenical Compounds--Chloride of Arsenic--Iodide of - Arsenic, 529 - 715. Arsenic in the Arts, 529, 530 - 716. Pharmaceutical Preparations of Arsenic--Veterinary Arsenical - Medicines--Rat and Fly Poisons--Quack Nostrums--Pigments-- - External Application of Arsenic for Sheep--Arsenical Soaps-- - Arsenical Compounds used in Pyrotechny, 530-534 - 717. Statistics of Poisoning by Arsenic, 534 - 718. Law Relative to the Sale of Arsenic, 535 - 719. Dose of Arsenic, 535 - 720. Effects of Arsenious Acid on Plants, 535, 536 - 721. Effects of Arsenic upon Life--Animalcules--Annelids--Birds-- - Mammals, 536-538 - 722. Effects of Arsenious Acid on Man--Arsenic Eaters, 538, 539 - 723. Manner of Introduction of Arsenic, 539 - 724. Cases of Poisoning by the External Application of Arsenic, - 539-541 - 725. Arsenic in Wall-Papers, 541, 542 - 726. Forms of Arsenical Poisoning--Acute Form, 542 - 727. Subacute Form--Case of the Duc de Praslin, 543 - 728. Nervous Form--Brodie's Experiments on Rabbits--A "Mass" - Poisoning reported by Dr. Coqueret, 544, 545 - 729. Absence of Symptoms, 545, 546 - 730. Slow Poisoning, 546 - 731. The Maybrick Case, 546-548 - 732. Post-mortem Appearances met with in Animals after Arsenical - Poisoning--The Researches of Hugo, 548, 549 - 733. Post-mortem Appearances in Man--Illustrative Pathological - Preparations in Various Museums, 549-551 - 734. Pathological Changes induced in the Gullet and Stomach--Fatty - Degeneration of the Liver and Kidneys--Glossitis--Retardation of - Putrefaction, 551, 552 - 735. Physiological Action of Arsenic, 552, 553 - 736. Elimination of Arsenic--Question of Accumulation of Arsenic, 553 - 737. Antidotes and Treatment, 553, 554 - 738. Detection of Arsenic--Identification of Arsenious Acid in - Substance--Test of Berzelius--Identification of Arsenites and - Arseniates--Detection of Arsenious Acid in Solution-- - Distinguishing Marks between the Sulphides of Tin, Cadmium, - Antimony, and Arsenic--Marsh's Original Test for Arsenic-- - Blondlot's Modification of Marsh's Test--Distinguishing Marks - between Arsenical and Antimonial Mirrors--Reinsch's Tests, - 554-560 - 739. Arsenic in Glycerin, 560 - 740. Arsenic in Organic Matters--Orfila's Method of Destroying - Organic Matter--Extraction with Hydrochloric Acid--Modifications - in the Treatment of Oils--Resinous Matters--Experiments on the - Distribution of Arsenic by Scolosuboff, Ludwig, and Chittenden-- - The Question of Contamination of a Corpse by Arsenical Earth, - 560-562 - 741. Imbibition of Arsenic after Death--Mason's Case, 563-565 - 742. Analysis of Wall-Paper for Arsenic, 565, 566 - 743. Estimation of Arsenic--Galvanic Process of Bloxam--Colorimetric - Methods, 566-568 - 744. Destruction of the Organic Matter by Nitric Acid, and Subsequent - Reduction of the Arsenic Acid to Arseniuretted Hydrogen, and - Final Estimation as Metallic Arsenic, 568-571 - 745. Arsine developed from an Alkaline Solution, 571 - 746. Precipitation as Tersulphide--Methods of Dealing with the - Sulphides obtained--(_a_) Solution in Ammonia and Estimation by - Iodine--(_b_) Drying the Purified Precipitate at a High - Temperature, and then directly weighing--(_c_) Oxidation of the - Sulphide and Precipitation as Ammonia Magnesian Arseniate, or - Magnesia Pyro Arseniate--(_d_) Conversion of the Trisulphide of - Arsenic into the Arseno-Molybdate of Ammonia--Conversion of the - Sulphide into Metallic Arsenic, 571-575 - 747. Conversion of Arsenic into Arsenious Chloride, 575, 576 - - - 2. _Antimony._ - - 748. Properties of Metallic Antimony, 577 - 749. Antimonious Sulphides, 577, 578 - 750. Tartarated Antimony--Tartar Emetic, 578, 579 - 751. Metantimonic Acid, 579 - 752. Pharmaceutical, Veterinary, and Quack Preparations of Antimony-- - (1)Pharmaceutical Preparations--(2) Patent and Quack Pills--(3) - Antimonial Medicines, chiefly Veterinary, 579-582 - 753. Alloys, 582 - 754. Pigments, 582 - 755. Dose, 582 - 756. Effects of Tartar Emetic on Animals--Influence on Temperature-- - Dr. Nevin's Researches on Rabbits, 582, 583 - 757. Effects of Tartar Emetic on Man--Illustrative Cases, 583, 584 - 758. Chronic Antimonial Poisoning, 585 - 759. _Post-mortem_ Appearances--Preparations in Museums--Pathological - Appearances in Rabbits, according to Nevin, 585, 586 - 760. Elimination of Antimony, 586 - 761. Antidotes for Tartar Emetic, 586 - 762. Effects of Chloride or Butter of Antimony, 587 - 763. Detection of Antimony in Organic Matters, 587-589 - 764. Quantitative Estimation of Antimony, 589, 590 - - - 3. _Cadmium._ - - 765. Properties of the Metal Cadmium, 590 - 766. Cadmium Oxide, 590 - 767. Cadmium Sulphide, 590 - 768. Medicinal Preparations of Cadmium--Cadmium Iodide--Cadmium - Sulphate, 590 - 769. Cadmium in the Arts, 590 - 770. Fatal Dose of Cadmium, 590 - 771. Separation and Detection of Cadmium, 590, 591 - - - II. PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID SOLUTION-- - BLACK. - - LEAD--COPPER--BISMUTH--SILVER--MERCURY. - - - 1. _Lead._ - - 772. Lead and its Oxides--Litharge--Minium, or Red Lead, 591, 592 - 773. Sulphide of Lead, 592 - 774. Sulphate of Lead, 592 - 775. Acetate of Lead, 592 - 776. Chloride of Lead--Carbonate of Lead, 592, 593 - 777. Preparations of Lead used in Medicine, the Arts, &c.--(1) - Pharmaceutical--(2) Quack Nostrums--(3) Preparations used in the - Arts--Pigments--Hair Dyes--Alloys, 593, 594 - 778. Statistics of Lead-Poisoning, 594 - 779. Lead as a Poison--Means by which Lead may be taken into the - System, 595, 596 - 780. Effects of Lead Compounds on Animals, 596, 597 - 781. Effects of Lead Compounds on Man--Acute Poisoning--Mass - Poisoning by Lead--Case of Acute Poisoning by the Carbonate of - Lead, 597-599 - 782. Chronic Poisoning by Lead, 599, 600 - 783. Effects of Lead on the Nervous System--Lead as a Factor of - Insanity 600, 601 - 784. Amaurosis Caused by Lead-Poisoning--Influence on the Sexual - Functions--Caries--Epilepsy, 601-603 - 785. Uric Acid in the Blood after Lead-Poisoning, 603 - 786. Influence of Lead on Pregnant Women and on F[oe]tal Life--The - Keighley Case of Poisoning by Water Contaminated by Lead--Case - of _Reg._ v. _L. J. Taylor_, 603-605 - 787. _Post-mortem_ Appearances, 605 - 788. Physiological Action of Lead, 605, 606 - 789. Elimination of Lead, 606 - 790. Fatal Dose, 606, 607 - 791. Antidotes and Treatment, 607 - 792. Localisation of Lead, 607, 608 - 793. Detection and Estimation of Lead, 608, 609 - 794. Detection of Lead in Tartaric Acid, in Lemonade and Aerated - Waters, 609, 610 - - - 2. _Copper._ - - 795. Properties of Copper, 610 - 796. Cupric Oxide, 610 - 797. Cupric Sulphide, 610 - 798. Solubility of Copper in Water and Various Fluids--Experiments of - Carnelley, W. Thompson, and Lehmann, 610-612 - 799. Copper as a Normal Constituent of Animal, Vegetable, and other - Matters--Dupre's Experiments--Bergeron and L. L'Hote's - Researches, 612-614 - 800. The "Coppering" of Vegetables--Copper in Green Peas-- - Phyllocyanic Acid, 614, 615 - 801. Preparations of Copper used in Medicine and the Arts--(1) - Medicinal Preparations--(2) Copper in the Arts, 615, 616 - 802. Dose--Medicinal Dose of Copper, 616, 617 - 803. Effects of Soluble Copper Salts on Animals, 617-619 - 804. Toxic Dose of Copper Salts, 619 - 805. Cases of Acute Poisoning, 619, 620 - 806. Effects of Subacetate, Subchloride, and Carbonate of Copper, 620 - 807. _Post-mortem_ Appearances seen in Acute Poisoning by Copper, - 620, 621 - 808. Chronic Poisoning by Copper, 621, 622 - 809. Detection and Estimation of Copper--General Method--Special - Method for Copper in Solution in Water and other Liquids-- - Detection of Copper in Animal Matters, 622-624 - 810. Volumetric Processes for the Estimation of Copper, 624 - - - 3. _Bismuth._ - - 811. Bismuth as a Metal, 624 - 812. Teroxide of Bismuth, 624 - 813. The Sulphide of Bismuth, 624 - 814. Preparations of Bismuth used in Medicine and the Arts--(1) - Pharmaceutical Preparations--(2) Bismuth in the Arts, 624, 625 - 815. Medicinal Doses of Bismuth, 625 - 816. Toxic Effects of Sub-nitrate of Bismuth, 625, 626 - 817. Extraction and Detection of Bismuth in Animal Matter, 626, 627 - 818. Estimation of Bismuth--Volumetric Processes, 627, 628 - - - 4. _Silver._ - - 819. Properties of Metallic Silver, 628, 629 - 820. Chloride of Silver, 629 - 821. Sulphide of Silver, 629 - 822. Preparations of Silver used in Medicine and the Arts--(1) - Medicinal Preparations--(2) Silver in the Arts, 629, 630 - 823. Medicinal Dose of Silver Compounds, 630 - 824. Effects of Nitrate of Silver on Animals--Chronic Poisoning, - 630, 631 - 825. Toxic Effects of Silver Nitrate on Man--(1) Acute--(2) Chronic - Poisoning, 631, 632 - 826. _Post-mortem_ Appearances, 632 - 827. Detection and Estimation of Silver, 632, 633 - - - 5. _Mercury._ - - 828. The Metal Mercury--Mercurous Chloride, or Calomel, 633, 634 - 829. Sulphide of Mercury, 634 - 830. Medicinal Preparations of Mercury, 634-638 - 831. Mercury in the Arts--The Sulphocyanide of Mercury--Acid Solution - of Nitrate of Mercury, 639 - 832. The more common Patent and Quack Medicines containing Mercury, - 639, 640 - 833. Mercury in Veterinary Medicine, 640 - 834. Medicinal and Fatal Dose, 640, 641 - 835. Poisoning by Mercury--Statistics, 641 - 836. Effects of Mercurial Vapour and of the Non-Corrosive Compounds - of Mercury--(_a_) On Vegetable Life--(_b_) On Animal Life, - 641, 642 - 837. Effects on Man, 642, 643 - 838. Absorption of Mercury by the Skin, 643 - 839. Symptoms of Poisoning by Mercury Vapour, 643, 644 - 840. Mercurial Tremor, 644, 645 - 841. Mercuric Methide--Effects of, as Illustrated by two Cases, - 645, 646 - 842. Effects of the Corrosive Salts of Mercury, 646, 647 - 843. Death from the External Use of Corrosive Sublimate, 647 - 844. Effects of the Nitrates of Mercury, 647 - 845. Case of _Reg._ v. _E. Smith_, 648 - 846. Mercuric Cyanide, 648 - 847. White Precipitate, 648 - 848. Treatment of Acute and Chronic Poisoning, 648 - 849. _Post-mortem_ Appearances--Pathological Preparations in Various - Anatomical Museums, 648-650 - 850. Pathological Appearances from the Effects of Nitrate of Mercury, - 650 - 851. Elimination of Mercury, 650, 651 - 852. Tests for Mercury, 651, 652 - 853. The Detection of Mercury in Organic Substances and Fluids, - 652-654 - 854. Estimation of Mercury--The Dry Method, 654 - 855. Volumetric Processes for the Estimation of Mercury, 654, 655 - - - III. PRECIPITATED BY HYDRIC SULPHIDE FROM A NEUTRAL SOLUTION. - - ZINC--NICKEL--COBALT. - - - 1. _Zinc._ - - 856. Properties of Metallic Zinc, 655, 656 - 857. Carbonate of Zinc, 656 - 858. Oxide of Zinc, 656 - 859. Sulphide of Zinc--Sulphate of Zinc, 656 - 860. Preparation and Uses of Chloride of Zinc, 656, 657 - 861. Zinc in the Arts--Zinc Chromate--Zinc Pigments--Action of Fluids - on Zinc Vessels, 657, 658 - 862. Effects of Zinc, as shown by Experiments on Animals, 658 - 863. Effects of Zinc Compounds on Man--Zinc Oxide, 658, 659 - 864. Sulphate of Zinc, 659 - 865. Zinc Chloride, 659, 660 - 866. _Post-mortem_ Appearances--Illustrated by Specimens in - Pathological Museums, 660, 661 - 867. Detection of Zinc in Organic Liquids or Solids, 661, 662 - 868. Identification of Zinc Sulphide, 662 - - - 2. _Nickel--Cobalt._ - - 869. Experiments of Anderson Stuart on the Toxic Action of Nickel and - Cobalt, 662, 663 - 870. Symptoms witnessed in various Classes of Animals after taking - Doses of Nickel or Cobalt, 663, 664 - 871. Effects on the Circulation and Nervous System, 664 - 872. Action on Striped Muscle, 664 - 873. Separation of Nickel or Cobalt from the Organic Matters or - Tissues, 664, 665 - 874. Estimation of Cobalt or Nickel, 665 - - - IV. PRECIPITATED BY AMMONIUM SULPHIDE. - - IRON--CHROMIUM--THALLIUM--ALUMINIUM--URANIUM. - - - 1. _Iron._ - - 875. Poisonous and Non-Poisonous Salts of Iron, 665 - 876. Ferric Chloride--Pharmaceutical Preparations of Ferric Chloride, - 666 - 877. Effects of Ferric Chloride on Animals, 666 - 878. Effects on Man--Criminal Case at Martinique, 666, 667 - 879. Elimination of Ferric Chloride, 667, 668 - 880. _Post-mortem_ Appearances, 668 - 881. Ferrous Sulphate, 668, 669 - 882. Search for Iron Salts in the Contents of the Stomach, 669, 670 - - - 2. _Chromium._ - - 883. Neutral Chromate of Potash, 670 - 884. Potassic Bichromate, 670 - 885. Neutral Lead Chromate, 670, 671 - 886. Use in the Arts, 671 - 887. Effects of some of the Chromium Compounds on Animal Life, 671 - 888. Effects of some of the Chromium Compounds on Man--Bichromate - Disease, 671, 672 - 889. Acute Poisoning by the Chromates--Illustrative Cases, 672, 673 - 890. Lethal Effects of Chromate of Lead, 673 - 891. _Post-mortem_ Appearances, 674 - 892. Detection of the Chromates and Separation of the Salts of - Chromium from the Contents of the Stomach, 674, 675 - - - 3. _Thallium._ - - 893. Discovery of Thallium--Its Properties, 675, 676 - 894. Effects of Thallium Salts, 676 - 895. Separation of Thallium from Organic Fluids or Tissues, 676 - - - 4. _Aluminium._ - - 896. Aluminium and its Salts, 676, 677 - 897. Action of Alum Salts--Siem's Researches--Alum Baking-Powders, - 677, 678 - 898. _Post-mortem_ Appearances, 678 - 899. Detection of Alumina, 678, 679 - - - 5. _Uranium._ - - 900. Poisonous Properties of Uranium Salts, 679 - 901. Detection and Estimation of Uranium, 679 - - - V. ALKALINE EARTHS. - - - BARIUM. - - 902. Salts of Barium in Use in the Arts, 679, 680 - 903. Chloride of Barium, 680 - 904. Baric Carbonate, 680 - 905. Sulphate of Barium, 680 - 906. Effects of the Soluble Salts of Barium on Animals, 681 - 907. Effects of the Salts of Barium on Man--Fatal Dose, 681, 682 - 908. Symptoms, 682, 683 - 909. Distribution of Barium in the Body, 683 - 910. _Post-mortem_ Appearances, 683, 684 - 911. Separation of Barium Salts from Organic Solids or Fluids, and - their Identification, 684 - - - APPENDIX. - - - TREATMENT, BY ANTIDOTES OR OTHERWISE, OF CASES OF POISONING. - - 912. Instruments, Emetics, and Antidotes Proper for Furnishing an - Antidote Bag, 685, 686 - 913. Poisons Arranged Alphabetically--Details of Treatment, 687-700 - - - DOMESTIC READY REMEDIES FOR POISONING. - - 914. The "Antidote Cupboard," and How to Furnish it, 701 - - - LIST OF ILLUSTRATIONS. - - Williams' Apparatus for Investigating Action of Poisons on the Frog's - Heart, 44 - Ether Recovery Apparatus, 47 - Micro-spectroscope, 48 - Diagram showing Absorption Bands Produced from Colour Reactions, 55 - Haematin Crystals, 61 - Tube for Treatment of Liquids by Ethereal Solvents, 156 - Diagram of Visual Field in Dinitro-benzol Poisoning, 190 - Blondlot's Apparatus for Production of Phosphine, 231 - Apparatus for Sublimation, 258 - Brucine Hydriodide, 342 - Bocklisch's Flask for Distillation in a Vacuum, 486 - Berzelius' Tube for Reduction of Arsenic, 554 - Bent Tube for Assay of Mercury, 654 - - Folding-Chart (Deaths from Intemperance and Liver Disease), to face - p. 136 - - - - - POISONS: - THEIR EFFECTS AND DETECTION. - - - - -PART I.--INTRODUCTORY. - - -I.--The Old Poison-Lore. - -Sec. 1. It is significant that the root "_tox_" of the modern word -_toxicology_ can be traced back to a very ancient word meaning "bow" or -"arrow," or, in its broadest sense, some "tool" used for slaying: hence -it is no far-fetched supposition that the first poison-knowledge was -that of the septic poisons. Perchance the savage found that weapons -soiled with the blood of former victims made wounds fatal; from this -observation the next step naturally would be that of experiment--the -arrow or spear would be steeped in all manner of offensive pastes, and -smeared with the vegetable juices of those plants which were deemed -noxious; and as the effects were mysterious, they would be ascribed to -the supernatural powers, and covered with a veil of superstition. - -The history of the _poison-lehre_, like all history, begins in the -region of the myths: there was a dark saga prevailing in Greece, that in -the far north existed a land ruled by sorcerers--all children of the -sun--and named Aeetes, Perses, Hecate, Medea, and Circe. Later on, the -enchanted land was localised at Colchis, and Aeetes and Perses were said -to be brothers. Hecate was the daughter of Perses; she was married to -Aeetes, and their daughters were Medea and Circe. Hecate was the -discoverer of poisonous herbs, and learned in remedies both evil and -good. Her knowledge passed to Medea, who narcotised the dragon, the -guardian of the golden fleece, and incited Jason to great undertakings. - -In the expedition of the Argonauts, the poets loved to describe Hecate's -garden, with its lofty walls. Thrice-folding doors of ebony barred the -entrance, which was guarded by terrible forms: only the initiated few, -only they who bore the leavened rod of expiation, and the concealed -conciliatory offering of the Medea, could enter into the sanctuary. -Towering above all was the temple of the dread Hecate, whose priestesses -offered to the gods ghastly sacrifices. - -Sec. 2. The oldest Egyptian king, Menes, and Attalus Phylometer, the last -king of Pergamus, were both famous for their knowledge of plants. -Attalus Phylometer was acquainted with hyoscyamus, aconite, conium, -veratrum, and others; he experimented on the preparation of poisons, and -occupied himself in compounding medicines. Mithradetes Eupator stood yet -higher: the receipt for the famous _theriaca_, prepared in later years -at an enormous price, and composed of fifty-four different ingredients, -is ascribed to him. The wonderful skill shown by the Egyptians in -embalming and technical works is sufficient to render it fairly certain -that their chemical knowledge was considerable; and the frequent -operations of one caste upon the dead must have laid the foundations of -a pathological and anatomical culture, of which only traces remain. - -The Egyptians knew prussic acid as extracted in a dilute state from -certain plants, among the chief of which was certainly the peach; on a -papyrus preserved at the Louvre, M. Duteil read, "Pronounce not the name -of I. A. O. under the penalty of the peach!" in which dark threat, -without doubt, lurks the meaning that those who revealed the religious -mysteries of the priests were put to death by waters distilled from the -peach. That the priests actually distilled the peach-leaves has been -doubted by those who consider the art of distillation a modern -invention; but this process was well known to adepts of the third and -fourth centuries, and there is no inherent improbability in the -supposition that the Egyptians practised it. - -Sec. 3. From the Egyptians the knowledge of the deadly drink appears to -have passed to the Romans. At the trial of Antipater,[1] Verus brought a -potion derived from Egypt, which had been intended to destroy Herod; -this was essayed on a criminal, he died at once. In the reign of -Tiberius, a Roman knight, accused of high treason, swallowed a poison, -and fell dead at the feet of the senators: in both cases the rapidity of -action appears to point to prussic acid. - -[1] Jos. Ant., B. xvii. c. 5. - -The use of poison by the Greeks, as a means of capital punishment, -without doubt favoured suicide by the same means; the easy, painless -death of the state prisoner would be often preferred to the sword by one -tired of life. The ancients looked indeed upon suicide, in certain -instances, as something noble, and it was occasionally formally -sanctioned. Thus, Valerius Maximus tells us that he saw a woman of -quality, in the island of Ceos, who, having lived happily for ninety -years, obtained leave to take a poisonous draught, lest, by living -longer, she should happen to have a change in her good fortune; and, -curiously enough, this sanctioning of self-destruction seems to have -been copied in Europe. Mead relates that the people of Marseilles of old -had a poison, kept by the public authorities, in which cicuta was an -ingredient: a dose was allowed to any one who could show why he should -desire death. Whatever use or abuse might be made of a few violent -poisons, Greek and Roman knowledge of poisons, their effects and methods -of detection, was stationary, primitive, and incomplete. - -_Nicander of Colophon_ (204-138 B.C.) wrote two treatises, the most -ancient works on this subject extant, the one describing the effects of -snake venom; the other, the properties of opium, henbane, certain fungi, -colchicum, aconite, and conium. He divided poisons into those which kill -quickly, and those which act slowly. As antidotes, those medicines are -recommended which excite vomiting--_e.g._, lukewarm oil, warm water, -mallow, linseed tea, &c. - -_Apollodorus_ lived at the commencement of the third century B.C.: he -wrote a work on poisonous animals, and one on deleterious medicines; -these works of Apollodorus were the sources from which Pliny, -Heraclitus, and several of the later writers derived most of their -knowledge of poisons. - -_Dioscorides_ (40-90 A.D.) well detailed the effects of cantharides, -sulphate of copper, mercury, lead, and arsenic. By arsenic he would -appear sometimes to mean the sulphides, sometimes the white oxide. -Dioscorides divided poisons, according to their origin, into three -classes, viz.:-- - -1. =Animal Poisons.=--Under this head were classed cantharides and -allied beetles, toads, salamanders, poisonous snakes, a particular -variety of honey, and the blood of the ox, probably the latter in a -putrid state. He also speaks of the "_sea-hare_." The sea-hare was -considered by the ancients very poisonous, and Domitian is said to have -murdered Titus with it. It is supposed by naturalists to have been one -of the genus _Aplysia_, among the _gasteropods_. Both Pliny and -Dioscorides depict the animal as something very formidable: it was not -to be looked at, far less touched. The aplysiae exhale a very nauseous -and f[oe]tid odour when they are approached: the best known of the -species resembles, when in a state of repose, a mass of unformed flesh; -when in motion, it is like a common slug; its colour is reddish-brown; -it has four horns on its head; and the eyes, which are very small, are -situated between the two hinder ones. This aplysia has an ink reservoir, -like the sepia, and ejects it in order to escape from its enemies; it -inhabits the muddy bottom of the water, and lives on small crabs, -mollusca, &c. - -2. =Poisons from Plants.=--Dioscorides enumerates opium, black and white -hyoscyamus (especially recognising the activity of the seeds), -mandragora, which was probably a mixture of various solanaceae, conium -(used to poison the condemned by the people of Athens and the dwellers -of ancient Massilia), elaterin, and the juices of a species of euphorbia -and apocyneae. He also makes a special mention of aconite, the name of -which is derived from _Akon_, a small city in Heraclea. The Greeks were -well aware of the deadly nature of aconite, and gave to it a mythical -origin, from the foam of the dog Cerberus. Colchicum was also known to -Dioscorides: its first use was ascribed to Medea. Veratrum album and -nigrum were famous medicines of the Romans, and a constituent of their -"_rat and mice powders_;" they were also used as insecticides. According -to Pliny, the Gauls dipped their arrows in a preparation of veratrum.[2] -Daphne mezereon, called by the Romans also smilax and taxus, appears to -have been used by Cativolcus, the king of the Eburones, for the purpose -of suicide, or possibly by "taxus" the yew-tree is meant.[3] - -[2] Pliny, xxv. 5. - -[3] _De Bello Gallico_, vi. 31. - -The poisonous properties of certain fungi were also known. Nicander -calls the venomous mushrooms the "evil fermentation of the earth," and -prescribes the identical antidotes which we would perhaps give at the -present time--viz., vinegar and alkaline carbonates. - -3. =Mineral Poisons.=--Arsenic has been already alluded to. The ancients -used it as a caustic and depilatory. Copper was known as sulphate and -oxide; mercury only as cinnabar: lead oxides were used, and milk and -olive-oil prescribed as an antidote for their poisonous properties. The -_poison-lehre_ for many ages was considered as something forbidden. -Galen, in his treatise "On Antidotes," remarks that the only authors who -dared to treat of poisons were Orpheus, Theologus, Morus, Mendesius the -younger, Heliodorus of Athens, Aratus, and a few others; but none of -these treatises have come down to us. From the close similarity of the -amount of information in the treatises of Nicander, Dioscorides, Pliny, -Galen, and Paulus AEgineta, it is probable that all were derived from a -common source. - -Sec. 4. If we turn our attention to early Asiatic history, a very cursory -glance at the sacred writings of the East will prove how soon the art of -poisoning, especially in India, was used for the purpose of suicide, -revenge, or robbery. - -The ancient practice of the Hindoo widow--self-immolation on the burning -pile of her husband--is ascribed to the necessity which the Brahmins -were under of putting a stop to the crime of domestic poisoning. Every -little conjugal quarrel was liable to be settled by this form of secret -assassination, but such a law, as might be expected, checked the -practice. - -Poison was not used to remove human beings alone, for there has been -from time immemorial in India much cattle-poisoning. In the Institutes -of Menu, it is ordained that when cattle die the herdsman shall carry to -his master their ears, their hides, their tails, the skin below their -navels, their tendons, and the liquor oozing from their foreheads. -Without doubt these regulations were directed against cattle-poisoners. - -The poisons known to the Asiatics were arsenic, aconite, opium, and -various solanaceous plants. There has been a myth floating through the -ages that a poison exists which will slay a long time after its -introduction. All modern authors have treated the matter as an -exaggerated legend, but, for my own part, I see no reason why it should -not, in reality, be founded on fact. There is little doubt that the -Asiatic poisoners were well acquainted with the infectious qualities of -certain fevers and malignant diseases. Now, these very malignant -diseases answer precisely to the description of a poison which has no -immediate effects. Plant small-pox in the body of a man, and for a whole -fortnight he walks about, well and hearty. Clothe a person with a -garment soaked in typhus, and the same thing occurs--for many days there -will be no sign of failure. Again, the gipsies, speaking a tongue which -is essentially a deformed _prakrit_, and therefore Indian in origin, -have long possessed a knowledge of the properties of the curious "_mucor -phycomyces_." This was considered an alga by Agaron, but Berkeley -referred it to the fungi. The gipsies are said to have administered the -spores of this fungi in warm water. In this way they rapidly attach -themselves to the mucous membrane of the throat, all the symptoms of a -phthisis follow, and death takes place in from two to three weeks. Mr -Berkeley informed me that he has seen specimens growing on broth which -had been rejected from the stomach, and that it develops in enormous -quantities on oil-casks and walls impregnated with grease. The filaments -are long, from 12 to 18 inches, and it is capable of very rapid -development. - -There is also a modern poison, which, in certain doses, dooms the -unfortunate individual to a terrible malady, simulating, to a -considerable extent, natural disease,--that is phosphorus. This poison -was, however, unknown until some time in the eleventh century, when -Alchid Becher, blindly experimenting on the distillation of urine and -carbon, obtained his "_escarboucle_," and passed away without knowing -the importance of his discovery, which, like so many others, had to be -rediscovered at a later period. - -Sec. 5. The Hebrews were acquainted with certain poisons, the exact nature -of which is not quite clear. The words "_rosch_" and "_chema_" seem to -be used occasionally as a generic term for poison, and sometimes to mean -a specific thing; "_rosch_," especially, is used to signify some -poisonous parasitic plant. They knew yellow arsenic under the name of -"_sam_," aconite under the name of "_boschka_," and possibly "_son_" -means _ergot_.[4] In the later period of their history, when they were -dispersed through various nations, they would naturally acquire the -knowledge of those nations, without losing their own. - -[4] R. J. Wunderbar, _Biblisch-talmudische Medicin_. Leipzig, 1850-60. - -Sec. 6. The part that poison has played in history is considerable. The -pharmaceutical knowledge of the ancients is more graphically and -terribly shown in the deaths of Socrates, Demosthenes, Hannibal, and -Cleopatra, than in the pages of the older writers on poisons. - -In the reign of Artaxerxes II. (Memnon), (B.C. 405-359), Phrysa poisoned -the queen Statira by cutting food with a knife poisoned on one side -only. Although this has been treated as an idle tale, yet two poisons, -aconite and arsenic, were at least well known; either of these could -have been in the way mentioned introduced in sufficient quantity into -food to destroy life. - -In the early part of the Christian era professional poisoners arose, and -for a long time exercised their trade with impunity. Poisoning was so -much in use as a political engine that Agrippina (A.D. 26) refused to -eat of some apples offered to her at table by her father-in-law, -Tiberius. - -It was at this time that the infamous Locusta flourished. She is said to -have supplied, with suitable directions, the poison by which Agrippina -got rid of Claudius; and the same woman was the principal agent in the -preparation of the poison that was administered to Britannicus, by order -of his brother Nero. The details of this interesting case have been -recorded with some minuteness. - -It was the custom of the Romans to drink hot water, a draught nauseous -enough to us, but, from fashion or habit, considered by them a luxury; -and, as no two men's tastes are alike, great skill was shown by the -slaves in bringing the water to exactly that degree of heat which their -respective masters found agreeable.[5] - -[5] Tacitus, lib. xii., xiii. Mentioned also by Juvenal and Suetonius. - -The children of the Imperial house, with others of the great Roman -families, sat at the banquets at a smaller side table, while their -parents reclined at the larger. A slave brings hot water to Britannicus; -it is too hot; Britannicus refuses it. The slave adds cold water; and it -is this cold water that is supposed to have been poisoned; in any case, -Britannicus had no sooner drunk of it than he lost voice and -respiration. Agrippina, his mother, was struck with terror, as well as -Octavia, his sister. Nero, the author of the crime, looks coldly on, -saying that such fits often happened to him in infancy without evil -result; and after a few moments' silence the banquet goes on as before. -If this were not sudden death from heart or brain disease, the poison -must have been either a cyanide or prussic acid. - -In those times no autopsy was possible: although the Alexandrian school, -some 300 years before Christ, had dissected both the living and the -dead, the work of Herophilus and Erasistratus had not been pursued, and -the great Roman and Greek writers knew only the rudiments of human -anatomy, while, as to pathological changes and their true -interpretation, their knowledge may be said to have been absolutely -_nil_. It was not, indeed, until the fifteenth century that the Popes, -silencing ancient scruples, authorised dissections; and it was not until -the sixteenth century that Vesalius, the first worthy of being -considered a great anatomist, arose. In default of pathological -knowledge, the ancients attached great importance to mere outward marks -and discolorations. They noted with special attention spots and -lividity, and supposed that poisons singled out the heart for some quite -peculiar action, altering its substance in such a manner that it -resisted the action of the funeral pyre, and remained unconsumed. It -may, then, fairly be presumed that many people must have died from -poison without suspicion, and still more from the sudden effects of -latent disease, ascribed wrongfully to poison. For example, the death of -Alexander was generally at that time ascribed to poison; but Littre has -fairly proved that the great emperor, debilitated by his drinking -habits, caught a malarious fever in the marshes around Babylon, and died -after eleven days' illness. If, added to sudden death, the body, from -any cause, entered into rapid putrefaction, such signs were considered -by the people absolutely conclusive of poisoning: this belief, indeed, -prevailed up to the middle of the seventeenth century, and lingers still -among the uneducated at the present day. Thus, when Britannicus died, an -extraordinary lividity spread over the face of the corpse, which they -attempted to conceal by painting the face. When Pope Alexander VI. died, -probably enough from poison, his body (according to Guicciardini) became -a frightful spectacle--it was livid, bloated, and deformed; the gorged -tongue entirely filled the mouth; from the nose flowed putrid pus, and -the stench was horrible in the extreme. - -All these effects of decomposition, we know, are apt to arise in coarse, -obese bodies, and accompany both natural and unnatural deaths; indeed, -if we look strictly at the matter, putting on one side the preservative -effects of certain metallic poisons, it may be laid down that generally -the corpses of those dying from poison are _less_ apt to decompose -rapidly than those dying from disease--this for the simple reason that a -majority of diseases cause changes in the fluids and tissues, which -render putrefactive changes more active, while, as a rule, those who -take poison are suddenly killed, with their fluids and tissues fairly -healthy. - -When the Duke of Burgundy desired to raise a report that John, Dauphin -of France, was poisoned (1457), he described the imaginary event as -follows:-- - -"One evening our most redoubtable lord and nephew fell so grievously -sick that he died forthwith. His lips, tongue, and face were swollen; -his eyes started out of his head. It was a horrible sight to see--for so -look people that are poisoned." - -The favourite powder of the professional poisoner, arsenic, was known to -crowned heads in the fourteenth century; and there has come down to us a -curious document, drawn out by Charles le Mauvais, King of Navarre. It -is a commission of murder, given to a certain Woudreton, to poison -Charles VI., the Duke of Valois, brother of the king, and his uncles, -the Dukes of Berry, Burgundy, and Bourbon:-- - -"Go thou to Paris; thou canst do great service if thou wilt: do what I -tell thee; I will reward thee well. Thou shalt do thus: There is a thing -which is called sublimed arsenic; if a man eat a bit the size of a pea -he will never survive. Thou wilt find it in Pampeluna, Bordeaux, -Bayonne, and in all the good towns through which thou wilt pass, at the -apothecaries' shops. Take it and powder it; and when thou shalt be in -the house of the king, of the Count de Valois, his brother, the Dukes of -Berry, Burgundy, and Bourbon, draw near, and betake thyself to the -kitchen, to the larder, to the cellar, or any other place where thy -point can be best gained, and put the powder in the soups, meats, or -wines, provided that thou canst do it secretly. Otherwise, do it not." -Woudreton was detected, and executed in 1384.[6] - -[6] _Tresor de Chartes._ Charles de Navarre. P. Mortonval, vol. ii. p. -384. - -A chapter might be written entitled "royal poisoners." King Charles IX. -even figures as an experimentalist.[7] An unfortunate cook has stolen -two silver spoons, and, since there was a question whether "_Bezoar_" -was an antidote or not, the king administers to the cook a lethal dose -of corrosive sublimate, and follows it up with the antidote; but the man -dies in seven hours, although Pare also gives him oil. Truly a grim -business! - -[7] _[OE]uvres de Pare_, 2nd ed., liv. xx. _Des Vennes_, chap. xliv. p. -507. - -The subtle method of removing troublesome subjects has been more often -practised on the Continent than in England, yet the English throne in -olden time is not quite free from this stain.[8] The use of poison is -wholly opposed to the Anglo-Saxon method of thought. To what anger the -people were wrought on detecting poisoners, is seen in the fact that, in -1542, a young woman was boiled alive in Smithfield for poisoning three -households.[9] - -[8] For example, King John is believed to have poisoned Maud Fitzwalter -by "a poisoned egg." - -"In the reign of King John, the White Tower received one of the first -and fairest of a long line of female victims in that Maud Fitzwalter who -was known to the singers of her time as Maud the Fair. The father of -this beautiful girl was Robert, Lord Fitzwalter, of Castle Baynard, on -the Thames, one of John's greatest barons. Yet the king, during a fit of -violence with the queen, fell madly in love with this young girl. As -neither the lady herself nor her powerful sire would listen to his -disgraceful suit, the king is said to have seized her by force at -Dunmow, and brought her to the Tower. Fitzwalter raised an outcry, on -which the king sent troops into Castle Baynard and his other houses; and -when the baron protested against these wrongs, his master banished him -from the realm. Fitzwalter fled to France with his wife and his other -children, leaving his daughter Maud in the Tower, where she suffered a -daily insult in the king's unlawful suit. On her proud and scornful -answer to his passion being heard, John carried her up to the roof, and -locked her in the round turret, standing on the north-east angle of the -keep. Maud's cage was the highest, chilliest den in the Tower; but -neither cold, nor solitude, nor hunger could break her strength. In the -rage of his disappointed love, the king sent one of his minions to her -room with a poisoned egg, of which the brave girl ate and died."--_Her -Majesty's Tower_, by Hepworth Dixon. Lond., 1869; i. p. 46. - -[9] "This yeare, the 17th of March, was boyled in Smithfield one -Margaret Davie, a mayden, which had pouysoned 3 householdes that she -dwelled in. One being her mistress, which dyed of the same, and one -Darington and his wyfe, which she also dwelled with in Coleman Street, -which dyed of the same, and also one Tinleys, which dyed also of the -same."--Wriotherley's _Chronicle_, A.D. 1542. - -Sec. 7. Two great criminal schools arose from the fifteenth to the -seventeenth centuries in Venice and Italy. The Venetian poisoners are of -earlier date than the Italian, and flourished chiefly in the fifteenth -century. Here we have the strange spectacle, not of the depravity of -individuals, but of the government of the State formally recognising -secret assassination by poison, and proposals to remove this or that -prince, duke, or emperor, as a routine part of their deliberations. -Still more curious and unique, the dark communings of "_the council of -ten_" were recorded in writing, and the number of those who voted for -and who voted against the proposed crime, the reason for the -assassination, and the sum to be paid, still exist in shameless black -and white. Those who desire to study this branch of secret history may -be referred to a small work by Carl Hoff, which gives a brief account of -what is known of the proceedings of the council. One example will here -suffice. On the 15th of December 1513 a Franciscan brother, John of -Ragubo, offered a selection of poisons, and declared himself ready to -remove any objectionable person out of the way. For the first successful -case he required a pension of 1500 ducats yearly, which was to be -increased on the execution of future services. The presidents, Girolando -Duoda and Pietro Guiarina, placed the matter before the "ten" on the 4th -of January 1514, and on a division (10 against 5) it was resolved to -accept so patriotic an offer, and to experiment first on the Emperor -Maximilian. The bond laid before the "ten" contained a regular -tariff--for the great Sultan 500 ducats, for the King of Spain 150 -ducats, but the journey and other expenses were in each case to be -defrayed; the Duke of Milan was rated at 60, the Marquis of Mantua at -50, the Pope could be removed at 100 ducats. The curious offer thus -concludes:--"The farther the journey, the more eminent the man, the more -it is necessary to reward the toil and hardships undertaken, and the -heavier must be the payment." The council appear to have quietly -arranged thus to take away the lives of many public men, but their -efforts were only in a few cases successful. When the deed was done, it -was registered by a single marginal note, "_factum_." - -What drugs the Venetian poisoners used is uncertain. The Italians -became notorious in the sixteenth and seventeenth centuries for their -knowledge of poisons, partly from the deeds of Toffana and others, and -partly from the works of J. Baptista Porta, who wrote a very -comprehensive treatise, under the title of _Natural Magic_,[10] and -managed to slide into the text, in the sections on cooking (_De Re -Coquinaria_, lib. xiv.), a mass of knowledge as to the preparation of -poisons. There are prescriptions that little accord with the title, -unless indeed the trades of cook and poisoner were the same. He gives a -method of drugging wine with belladonna root, for the purpose of making -the loaded guest loathe drink; he also gives a list of solanaceous -plants, and makes special mention of nux vomica, aconite, veratrum, and -mezereon. Again, in the section (_De Ancupio_, lib. xv.) he gives a -recipe for a very strong poison which he calls "_venenum lupinum_;" it -is to be made of the powdered leaves of _Aconitum lycoctonum_, _Taxus -baccata_, powdered glass, caustic lime, sulphide of arsenic, and bitter -almonds, the whole to be mixed with honey, and made into pills the size -of a hazel-nut. - -[10] J. Bapt. Porta, born 1537, died 1615. _Neapolitani Magiae -Naturalis._ Neapoli, 1589. - -In the section _De Medicis Experimentis_ he gives a process to poison a -sleeping person: the recipe is curious, and would certainly not have the -intended effect. A mixture of hemlock juice, bruised datura, stramonium, -belladonna, and opium is placed in a leaden box with a perfectly fitting -cover, and fermented for several days; it is then opened under the nose -of the sleeper. Possibly Porta had experimented on small animals, and -had found that such matters, when fermented, exhaled enough carbonic -acid gas to kill them, and imagined, therefore, that the same thing -would happen if applied to the human subject. However this may be, the -account which Porta gives of the effects of the solanaceous plants, and -the general tone of the work, amply prove that he was no theorist, but -had studied practically the actions of poisons. - -The iniquitous Toffana (or Tophana) made solutions of arsenious acid of -varying strength, and sold these solutions in phials under the name of -"_Acquetta di Napoli_" for many years. She is supposed to have poisoned -more than 600 persons, among whom were two Popes--viz., Pius III. and -Clement XIV. The composition of the Naples water was long a profound -secret, but is said to have been known by the reigning Pope and by the -Emperor Charles VI. The latter told the secret to Dr Garelli, his -physician, who, again, imparted the knowledge to the famous Friedrich -Hoffman in a letter still extant. Toffana was brought to justice in -1709, but, availing herself of the immunity afforded by convents, -escaped punishment, and continued to sell her wares for twenty years -afterwards. When Kepfer[11] was in Italy he found her in a prison at -Naples, and many people visited her, as a sort of lion (1730). With the -_Acqua Toffana_, the "_Acquetta di Perugia_" played at the same time its -part. It is said to have been prepared by killing a hog, disjointing the -same, strewing the pieces with white arsenic, which was well rubbed in, -and then collecting the juice which dropped from the meat; this juice -was considered far more poisonous than an ordinary solution of arsenic. -The researches of Selmi on compounds containing arsenic, produced when -animal bodies decompose in arsenical fluids, lend reason and support to -this view; and probably the juice would not only be very poisonous, but -act in a different manner, and exhibit symptoms different from those of -ordinary arsenical poisoning. Toffana had disciples; she taught the art -to Hieronyma Spara, who formed an association of young married women -during the popedom of Alexander VII.; these were detected on their own -confession.[12] - -[11] Kepfer's _Travels_. Lond., 1758. - -[12] Le Bret's _Magazin zu Gebrauche der Staat u. Kirchen-Geschichte_, -Theil 4. Frankfort and Leipzig, 1774. - -Contemporaneously with Toffana, another Italian, Keli, devoted himself -to similar crimes. This man had expended much as an adept searching for -the philosopher's stone, and sought to indemnify himself by entering -upon what must have been a profitable business. He it was who instructed -M. de St. Croix in the properties of arsenic; and St. Croix, in his -turn, imparted the secret to his paramour, Madame de Brinvilliers. This -woman appears to have been as cold-blooded as Toffana; she is said to -have experimented on the patients at the Hotel Dieu, in order to -ascertain the strength of her powders, and to have invented "les poudres -de succession." She poisoned her father, brothers, sister, and others of -her family; but a terrible fate overtook both her and St. Croix. The -latter was suffocated by some poisonous matters he was preparing, and -Madame de Brinvilliers' practices having become known, she was obliged -to take refuge in a convent. Here she was courted by a police officer -disguised as an abbe, lured out of the convent, and, in this way brought -to justice, was beheaded[13] and burnt near Notre Dame, in the middle -of the reign of Louis XIV.[14] - -[13] The Marchioness was imprisoned in the Conciergerie and tortured. -Victor Hugo, describing the rack in that prison, says, "The Marchioness -de Brinvilliers was stretched upon it stark naked, fastened down, so to -speak, quartered by four chains attached to the four limbs, and there -suffered the frightful extraordinary torture by water," which caused her -to ask "How are you going to contrive to put that great barrel of water -in this little body?"--_Things seen by Victor Hugo_, vol. i. - -The water torture was this:--a huge funnel-like vessel was fitted on to -the neck, the edge of the funnel coming up to the eyes; on now pouring -water into the funnel so that the fluid rises above the nose and mouth, -the poor wretch is bound to swallow the fluid or die of suffocation; if -indeed the sufferer resolve to be choked, in the first few moments of -unconsciousness the fluid is swallowed automatically, and air again -admitted to the lungs; it is therefore obvious that in this way -prodigious quantities of fluid might be taken. - -[14] For the court of poisoners (_chambre ardente_) and the histories of -St. Croix, De Brinvilliers, the priest Le Sage, the women La Voisin, and -La Vigoureux, the reader may be referred to Voltaire's _Siecle de Louis -XIV._, Madame de Sevigne's _Lettres_, Martiniere's _Hist. de la Regne de -Louis XIV._, Strutzel, _De Venenis_, &c. - -The numerous attempts of the Italian and Venetian poisoners on the lives -of monarchs and eminent persons cast for a long time a cloud over regal -domestic peace. Bullets and daggers were not feared, but in their place -the dish of meat, the savoury pasty, and the red wine were regarded as -possible carriers of death. No better example of this dread can be found -than, at so late a period as the reign of Henry VII.,[15] the -extraordinary precautions thought necessary for preserving the infant -Prince of Wales. - -[15] Henry VIII., at one time of his life, was (or pretended to be) -apprehensive of being poisoned; it was, indeed, a common belief of his -court that Anne Boleyn attempted to dose him. "The king, in an interview -with young Prince Henry, burst into tears, saying that he and his sister -(meaning the Princess Mary) might thank God for having escaped from the -hands of that accursed and venomous harlot, who had intended to poison -them."--_A Chronicle of England during the Reign of the Tudors_, by W. -J. Hamilton. Introduction, p. xxi. - -"No person, of whatsoever rank, except the regular attendants in the -nursery, should approach the cradle, except with an order from the -king's hand. The food supplied to the child was to be largely -'_assayed_,' and his clothes were to be washed by his own servants, and -no other hand might touch them. The material was to be submitted to all -tests. The chamberlain and vice-chamberlain must be present, morning and -evening, when the prince was washed and dressed, and nothing of any kind -bought for the use of the nursery might be introduced until it was -washed and perfumed. No person, not even the domestics of the palace, -might have access to the prince's rooms except those who were specially -appointed to them, nor might any member of the household approach -London, for fear of their catching and conveying infection."[16] - -[16] Froude's _History of England_, vol. iii. p. 262. - -However brief and imperfect the foregoing historical sketch of the part -that poison has played may be, it is useful in showing the absolute -necessity of a toxicological science--a science embracing many branches -of knowledge. If it is impossible now for Toffanas, Locustas, and other -specimens of a depraved humanity to carry on their crimes without -detection; if poison is the very last form of death feared by eminent -political persons; it is not so much owing to a different state of -society, as to the more exact scientific knowledge which is applied -during life to the discrimination of symptoms, distinguishing between -those resulting from disease and those due to injurious substances, and -after death to a highly developed pathology, which has learned, by -multiplied observations, all the normal and abnormal signs in tissues -and organs; and, finally, to an ever-advancing chemistry, which is able -in many instances to separate and detect the hurtful and noxious thing, -although hid for months deep in the ground. - - -II.--Growth and Development of the Modern Methods of Chemically -Detecting Poisons. - -Sec. 8. The history of the detection of poisons has gone through several -phases. The first phase has already been incidentally touched -upon--_i.e._, detection by antecedent and surrounding circumstances, -aided sometimes by experiments on animals. If the death was sudden, if -the post-mortem decomposition was rapid, poison was indicated: sometimes -a portion of the food last eaten, or the suspected thing, would be given -to an animal; if the animal also died, such accumulation of proof would -render the matter beyond doubt. The modern toxicologists are more -sceptical, for even the last test is not of itself satisfactory. It is -now known that meat may become filled with bacilli and produce rapid -death, and yet no poison, as such, has been added. - -In the next phase, the doctors were permitted to dissect, and to -familiarise themselves with pathological appearances. This was a great -step gained: the apoplexies, heart diseases, perforations of the -stomach, and fatal internal haemorrhages could no longer be ascribed to -poison. If popular clamour made a false accusation, there was more -chance of a correct judgment. It was not until the end of the eighteenth -and the beginning of the present century, however, that chemistry was -far enough advanced to test for the more common mineral poisons; the -modern phase was then entered on, and toxicology took a new departure. - -Sec. 9. From the treatise of Barthelemy d'Anglais[17] in the thirteenth -century (in which he noticed the poisonous properties of quicksilver -vapour), up to the end of the fifteenth century, there are numerous -treatises upon poison, most of which are mere learned compilations, and -scarcely repay perusal. In the sixteenth century, there are a few works, -such, for example, as Porta, which partook of the general advancement of -science, and left behind the stereotyped doctrine of the old classical -schools.[18] - -[17] _De Rerum Proprietaribus._ - -[18] In the sixteenth century it was not considered proper to write upon -poisons. Jerome Cardan declared a poisoner worse than a brigand, "and -that is why I have refused not only to teach or experiment on such -things, but even to know them."--_J. Cardan: De Subtilitate_. Basel, -1558. - -In the seventeenth century the Honourable Robert Boyle made some shrewd -observations, bearing on toxicology, in his work on "The usefulness of -Natural Philosophy," &c.: Oxford, 1664. Nicolas L'Emery also wrote a -_Cours de Chimie_,--quite an epitome of the chemical science of the -time.[19] - -[19] _Cours de Chimie, contenant la maniere de faire les operations qui -sont en usage dans la Medecine._ Paris, 1675. - -In the eighteenth century still further advances were made. Richard Mead -published his ingenious _Mechanical Theory of Poisons_. Great chemists -arose--Stahl, Marggraf, Brandt, Bergmann, Scheele, Berthollet, -Priestley, and lastly, Lavoisier--and chemistry, as a science, was born. -Of the chemists quoted, Scheele, in relation to toxicology, stands -chief. It was Scheele who discovered prussic acid,[20] without, however, -noting its poisonous properties; the same chemist separated oxalic acid -from sorrel,[21] and made the important discovery that arsenic united -with hydrogen, forming a f[oe]tid gas, and, moreover, that this gas -could be decomposed by heat.[22] From this observation, a delicate test -for arsenic was afterwards elaborated, which for the first time rendered -the most tasteless and easily administered poison in the whole world at -once the easiest of detection. The further history of what is now called -"Marsh's Test" is as follows:-- - -[20] _Opuscula Chemica_, vol. ii. pp. 148-174. - -[21] _De Terra Rhubarbi et Acido Acetosellae._ _Nova Acta Acad. Veg. -Sued. Anni_, 1784. _Opuscula Chemica_, vol. ii. pp. 187-195. - -Bergmann first described oxalic acid as obtained by the oxidation of -saccharine bodies; but Scheele recognised its identity with the acid -contained in sorrel. - -[22] _Memoires de Scheele_, t. i., 1775. - -Sec. 10. Proust[23] observed that a very f[oe]tid hydrogen gas was -disengaged when arsenical tin was dissolved in hydrochloric acid, and -that arsenic was deposited from the inflamed gas on cold surfaces which -the flame touched. Trommsdorff next announced, in 1803, that when -arsenical zinc was introduced into an ordinary flask with water and -sulphuric acid, an arsenical hydrogen was disengaged; and if the tube -was sufficiently long, arsenic was deposited on its walls.[24] -Stromeyer, Gay-Lussac, Thenard, Gehlen, and Davy later studied this gas, -and Serullas in 1821 proposed this reaction as a toxicological test. -Lastly, in 1836, Marsh published his Memoir.[25] He elaborated a special -apparatus of great simplicity, developed hydrogen by means of zinc and -sulphuric acid, inflamed the issuing gas, and obtained any arsenic -present as a metal, which could be afterwards converted into arsenious -acid, &c. - -[23] Proust, _Annales de Chimie_, t. xxviii., 1798. - -[24] _Nicholson's Journal_, vol. vi. - -[25] "Description of a New Process of Separating Small Quantities of -Arsenic from Substances with which it is mixed." _Ed. New. Phil. -Journal_, 1836. - -This brief history of the so-called "Marsh's Test" amply shows that -Marsh was not the discoverer of the test. Like many other useful -processes, it seems to have been evolved by a combination of many minds. -It may, however, be truly said that Marsh was the first who perfected -the test and brought it prominently forward. - -Sec. 11. Matthieu Joseph Bonaventura Orfila must be considered the father -of modern toxicology. His great work, _Traite de Toxicologie_, was first -published in 1814, and went through many editions. Orfila's chief merit -was the discovery that poisons were absorbed and accumulated in certain -tissues--a discovery which bore immediate fruit, and greatly extended -the means of seeking poisons. Before the time of Orfila, a chemist not -finding anything in the stomach would not have troubled to examine the -liver, the kidney, the brain, or the blood. The immense number of -experiments which Orfila undertook is simply marvellous. Some are of -little value, and teach nothing accurately as to the action of -poisons--as, for example, many of those in which he tied the gullet in -order to prevent vomiting, for such are experiments under entirely -unnatural conditions; but there are still a large number which form the -very basis of our pathological knowledge. - -Orfila's method of experiment was usually to take weighed or measured -quantities of poison, to administer them to animals, and then after -death--first carefully noting the changes in the tissues and organs--to -attempt to recover by chemical means the poison administered. In this -way he detected and recovered nearly all the organic and inorganic -poisons then known; and most of his processes are, with modifications -and improvements, in use at the present time.[26] - -[26] Orfila's chief works are as follows:-- - -_Traite de Toxicologie._ 2 vols. 8vo. Paris, 1814. - -_Lecons de Chimie, appliquees a la Med. Pratique._ 16mo. Brussels, 1836. - -_Memoire sur la Nicotine et la Conicine._ Paris, 1851. - -_Lecons de la Med. Legale._ 8vo. Paris, 1821. - -_Traite des Exhumations Juridiques, et Considerations sur les Changemens -Physiques que les Cadavres eprouvent en se pourrissant._ 2 tom. Paris, -1831. - -Sec. 12. The discovery of the alkaloids at the commencement of this century -certainly gave the poisoner new weapons; yet the same processes -(slightly modified) which separated the alkaloids from plants also -served to separate them from the human body. In 1803 Derosne discovered -narcotine and morphine, but he neither recognised the difference between -these two substances, nor their basic properties. Sertuerner from 1805 -devoted himself to the study of opium, and made a series of discoveries. -Robiquet, in 1807, recognised the basic characters of narcotine. In 1818 -Pelletier and Caventou separated strychnine; in 1819 brucine; and in the -same year delphinine was discovered simultaneously by Brande, Lassaigne, -and Feneuille. Coniine was recognised by Giesecke in 1827, and in the -following year, 1828, nicotine was separated by Reimann and Posselt. In -1832 Robiquet discovered codeine; and in 1833 atropine, aconitine, and -hyoscyamine were distinguished by Geiger and Hesse. Since then, every -year has been marked by the separation of some new alkaloid, from either -animal or vegetable substances. So many workers in different countries -now began to study and improve toxicology, that it would exceed the -limits and be foreign to the scope of this treatise to give even a brief -_resume_ of their labours. It may, notwithstanding, be useful to append -a short bibliography of the chief works on toxicology of the present -century. - -Sec. 13.--BIBLIOGRAPHY OF THE CHIEF WORKS ON TOXICOLOGY (NINETEENTH -CENTURY). - - ANGLADA, JOS.--"Traite de Toxicologie Generale, &c." Montpellier et - Paris, 1835. - - AUTENRIETH.--"Kurze Anleitung zur Auffindung der Gifte." Freiburg, - 1892. - - BANDLIN, O.--"Die Gifte." Basel, 1869-1873. - - BAUMERT, G.--"Lehrbuch der gerichtl. Chemie." Braunschweig, 1889-92. - - BAYARD, HENRI.--"Manuel Pratique de Medecine Legale." Paris, 1843. - - BELLINI, RANIERI.--"Manuel de Tossicologia." Pisa, 1878. - - BERLIN, N. J.--"Nachricht, die gewoehnlichen Gifte chemisch zu - entdecken." Stockholm, 1845. - - BERNARD, C.--"Lecons sur les Effets des Substances Toxiques et - Medicamenteuses." Paris, 1857. - - BERTRAND, C. A. R. A.--"Manuel Medico-Legale des Poisons introduits - dans l'Estomac, et les Moyens Therapeutiques qui leur conviennent: - suivi d'un Plan d'Organisation Medico-Judiciaire, et d'un Tableau de - la Classification Generale des Empoisonnemens." Paris, 1818. - - BINZ, C.--"Intoxicationen" in Gerhardt's "Handbuch der - Kinderkrankheiten." iii. Heft. Tuebingen, 1878. - - BLYTH, A. WYNTER.--"A Manual of Practical Chemistry: The Analysis of - Foods and the Detection of Poisons." London, 1879. - - BOCKER, FRIEDER. WILHELM.--"Die Vergiftungen in forensischer u. - klinischer Beziehung." Iserlohn, 1857. - - BOeHM, R., NAUNYN, B., und VON BOECK, H.--"Handbuch der - Intoxicationen." (Bd. 15 of the German edition of Ziemssen's - Cyclopaedia.) - - BRANDT, PHOeBUS, und RATZEBURG.--"Deutschlands Giftgewaechse." Berlin, - 1834-38 (2 vols. with 56 coloured plates). - - BRIAND, J., et CHAUDE, ERN.--"Manuel Complet de Medecine Legale." - (The latest edition, 1879.) The chemical portion is by J. Bouis. - - BUCHNER, E.--"Lehrbuch der gerichtlichen Medicin fuer Aerzte u. - Juristen." 3rd ed. Muenchen, 1872. - - CASPER, J. L.--"Handbuch der gerichtlichen Medicin." 7th ed. Berlin, - 1881. - - CHEVALLIER, A.--"Traite de Toxicologie et de Chimie Judiciaire." - Paris, 1868. - - CHIAJE, STEF.--"Enchiridis di Tossicologia teorico-pratica." 3rd ed. - Napoli, 1858. - - CHRISTISON, ROBERT.--"A Treatise on Poisons." Edinburgh, 1830. (A - third edition appeared in 1836.) - - CORNEVIN, C.--"Des Plantes Veneneuses." Paris, 1887. - - DEVERGIE, ALPHONSE.--"Medecine Legale, Theorique, et Pratique." 3rd - ed. Paris, 1852. - - DRAGENDORFF, JEAN GEORGES.--"Die gerichtlich-chemische Ermittelung - von Giften in Nahrungsmitteln, Luftgemischen, Speiseresten, - Koerpertheilen." &c. St. Petersburg, 1868. 3rd ed. Goettingen, 1888. - - ---- "Untersuchungen aus dem Pharmaceutischen Institute in Dorpat. - Beitraege zur gerichtlichen Chemie einzelner organischer Gifte." - Erstes Heft. St. Petersburg, 1871. - - ---- "Jahresbericht ueber die Fortschritte der Pharmacognosie, - Pharmacie, und Toxicologie." Herausgegeben von Dr. Dragendorff. - 1876. - - DUFLOS, A.--"Handbuch der angewandten gerichtlich-chemischen Analyse - der chemischen Gifte, ihre Erkennung in reinem Zustande u. in - Gemengen betreffend." Breslau u. Leipzig, 1873. - - EULENBERG, DR. HERMANN.--"Handbuch der Gewerbe-Hygiene." Berlin, - 1876. - - FALCK, C. PH.--"Die Klinischwichtigen Intoxicationen." (Handbuch der - spec. Pathologie u. Therapie red. von R. Virchow, Bd. 2.) Erlangen, - 1854. - - FALCK, FERD. AUG.--"Lehrbuch der praktischen Toxicologie." - Stuttgart, 1880. - - FLANDIN, C.--"Traite des Poisons, ou Toxicologie appliquee a la - Medecine Legale, a la Physiologie, et a la Therapeutique." Paris, - 1847, 1853. - - FROeHNER, EUG.--"Lehrbuch der Toxicologie fuer Thieraerzte." Stuttgart, - 1890. - - GALTIER, C. P.--"Traite de Toxicologie Medico-Legale et de la - Falsification des Aliments," &c. Paris, 1845. - - ---- "Traite de Toxicologie Medicale, Chimique et Legale," &c. - Paris, 1855. A later edition of the same work. - - GREENE, WILL. H.--"A Practical Handbook of Medical Chemistry, - applied to Clinical Research and the Detection of Poisons." - Philadelphia, 1880. - - GUERIN, G.--"Traite Pratique d'Analyse Chimique et de Recherches - Toxicologiques." Paris, 1893. - - GUY, W. A., and FERRIER, DAVID.--"Principles of Forensic Medicine." - London, 1874. - - HARNACK, ERICH.--"Lehrbuch der Arzneimittellehre," &c. Hamburg, - 1883. - - HASSELT, VAN, A. W. M.--"Handbuch der Giftlehre fuer Chemiker, - Aerzte, Apotheker, u. Richtspersonen." (A German translation of the - original Dutch edition, edited by J. B. Henkel. Braunschweig, 1862. - Supplemental vol. by N. Husemann, Berlin, 1867.) - - HELWIG, A.--"Das Mikroskop in der Toxicologie." 64 photographs, roy. - 8vo, Mainz, 1865. - - HEMMING, W. D.--"Aids to Forensic Medicine and Toxicology." London, - 1877. - - HERMANN, L.--"Lehrbuch der experimentellen Toxicologie." 8vo. - Berlin, 1874. - - HOFFMANN, E. R.--"Lehrbuch der gerichtlichen Medicin." 5th ed. Wien, - 1890-91. - - HUSEMANN and A. HILGER.--"Die Pflanzenstoffe in chemischer, - pharmakologischer, u. toxicologischer Hinsicht." 2nd ed. Berlin, - 1882. - - HUSEMANN, TH., and HUSEMANN, A.--"Handbuch der Toxicologie." Berlin, - 1862. (Suppl. Berlin, 1867.) - - KOBERT, RUD.--"Lehrbuch der Intoxicationen." Stuttgart, 1893. - - KOEHLER, R.--"Handbuch der speciellen Therapie, einschliesslich der - Behandlung der Vergiftungen." 3rd ed. 2 vols. roy. 8vo. Tuebingen, - 1869. - - LESSER, ADOLF.--"Atlas der gerichtlichen Medicin." Berlin, 1883. - - LOEW, OSCAR.--"Ein natuerliches System der Gift-Wirkungen." Muenchen, - 1893. - - LUDWIG, E.--"Medicinische Chemie in Anwendung auf gerichtliche - Untersuchungen." - - MAHON, A.--"Medecine Legale et Police Medicale." Paris, 1807. - - MARX, K. F. H.--"Die Lehre von den Giften." Goettingen, 1827-29. - - MASCHKA, J.--"Handbuch der gerichtlichen Medicin." Tuebingen, - 1881-82. This work is under the editorship of Dr. Maschka, and - contains separate articles on medico-legal and toxicological - questions by various eminent toxicologists, somewhat after the - manner of Ziemssen's Cyclopaedia. - - MENDE, LUD. JUL. CASP.--"Ausfuehrliches Handbuch der gerichtlichen - Medicin." 1819-32. - - MOHR, FRIED.--"Chemische Toxicologie." Braunschweig, 1874. - - MONTGARNY, H. DE.--"Essai de Toxicologie, et specialement avec la - Jurisprudence Medicale." Paris, 1878. - - MONTMAHON, E. S. DE.--"Manuel Medico-Legale des Poisons," &c. Paris, - 1824. - - MUTEL, D. PH.--"Des Poisons, consideres sous le rapport de la - Medecine Pratique," &c. Montpellier et Paris, 1835. - - NACQUET, A.--"Legal Chemistry: A guide to the detection of Poisons, - Examination of Stains, &c., as applied to Chemical Jurisprudence." - New York, 1876. - - A translation from the French; see "Foods, their Composition and - Analysis," page 43. - - NICOLAI, JOH. ANT. HEINR.--"Handbuch der gerichtlichen Medicin." - Berlin, 1841. - - The chemical portion is by F. R. Simon. - - OGSTON, F.--"Lectures on Medical Jurisprudence." London, 1878. - - ORFILA, MATTHIEU JOS. BONAVENTURA.--"Traite des Poisons, ou - Toxicologie Generale." Paris, 1st ed., 1814; 5th ed., 1852. - - ORFILA et LESUEUR.--"Traite de Medecine legale." Paris, 1821; 4th - ed., Paris, 1848. - - OTTO, F. G.--"Anleitung zur Ausmittelung der Gifte." Braunschweig, - 1856; 5th ed., 1875. 6th ed. by Robert Otto, Braunschweig, 1884. - - PRAAG VAN, LEONIDES, u. OPWYRDA, R. J.--"Leerboek voor practische - giftleer." In Zwei Theilen. Utrecht, 1871. - - RABUTEAU, A.--"Elemens de Toxicologie et de Medecine Legale, - appliquees a l'Empoisonnement." Paris, 1873. 2nd ed. by Ed. - Bourgoing. Paris, 1888. - - REESE, JOHN J.--"Manual of Toxicology, including the consideration - of the Nature, Properties, Effects, and Means of Detection of - Poisons, more especially in their Medico-legal relations." - Philadelphia, 1874. - - REMER, W. H. G.--"Lehrbuch der polizeilich-gerichtlichen Chemie." - Bd. 1 u. 2. 3. Auflage, Helmstadt, 1824. - - SCHNEIDER, F. C.--"Die gerichtliche Chemie fuer Gerichtsaerzte u. - Juristen." Wien, 1852. - - SCHNEIDER, P. J.--"Ueber die Gifte in medicinisch-gerichtlicher u. - gerichtlich-polizeilicher Ruecksicht." 2nd ed., 1821. - - SELMI, F.--"Studi di Tossicologia Chimica." Bologna, 1871. - - SOBERNHEIM, JOS. FR. u. SIMON, J. F.--"Handbuch der praktischen - Toxicologie," &c. Berlin, 1838. - - SONNENSCHEIN, L.--"Handbuch der gerichtlichen Medicin." Berlin, - 1860. A new edition by Dr. A. Classen. Berlin, 1881. - - TARDIEU, A.--"Etude Medico-Legale et Clinique sur l'Empoisonnement, - avec la Collaboration de M. T. Roussin pour la partie de l'expertise - relative a la Recherche Chimique des Poisons." Paris, 1867. - - TAYLOR, ALFRED SWAINE.--"On Poisons in relation to Medical - Jurisprudence and Medicine." 3rd ed. 1875. Manual, 1879. - - ---- "Principles and Practice of Medical Jurisprudence." 3 vols. - London, 1873. - - WERBER, ANT.--"Lehrbuch der praktischen Toxicologie." Erlangen, - 1869. - - WOOD, HORATIO C.--"Therapeutics, Materia Medica, and Toxicology." - Philadelphia, 1874. - - WOODMANN, W. BATHURST, and TIDY, CH.--"A Handy-Book of Forensic - Medicine and Toxicology." London, 1877. - - WORMLEY, THEODORE G.--"Micro-Chemistry of Poisons, including their - Physiological, Pathological, and Legal Relations." New York, 1857. - - WURTZ, A.--"Traite Elementaire de Chimie Medicale, comprenant - quelques notions de Toxicologie," &c. 2nd ed. Paris, 1875. - - - - -PART II. - - -I.--Definition of Poison. - -Sec. 14. The term "_Poison_" may be considered first in its legal, as -distinct from its scientific, aspect. - -_The legal definition_ of "poison" is to be gathered from the various -statute-books of civilised nations. - -The English law enacts that: "Whoever shall administer, or cause to be -administered to, or taken by any person, any poison or other destructive -thing, with intent to commit murder, shall be guilty of felony." - -Further, by the Criminal Consolidation Act, 1861: "Whosoever shall, by -any other means other than those specified in any of the preceding -sections of this Act, attempt to commit murder, shall be guilty of -felony." - -It is therefore evident that, by implication, the English law defines a -poison to be a destructive thing administered to, or taken by, a person, -and it must necessarily include, not only poisons which act on account -of their inherent chemical and other properties after absorption into -the blood, but mechanical irritants, and also specifically-tainted -fluids. Should, for example, a person give to another milk, or other -fluid, knowing, at the same time, that such fluid is contaminated by the -specific poison of scarlet fever, typhoid, or any serious malady capable -of being thus conveyed, I believe that such an offence could be brought -under the first of the sections quoted. In fine, the words "_destructive -thing_" are widely applicable, and may be extended to any substance, -gaseous, liquid, or solid, living or dead, which, if capable at all of -being taken within the body, may injure or destroy life. According to -this view, the legal idea of "poison" would include such matters as -boiling water, molten lead, specifically-infected fluids, the flesh of -animals dying of diseases which may be communicable to man, powdered -glass, diamond dust, &c. Evidence must, however, be given of guilty -intent. - -The words, "administered to or taken by," imply obviously that the -framers of the older statute considered the mouth as the only portal of -entrance for criminal poisoning, but the present law effectually guards -against any attempt to commit murder, no matter by what means. There is -thus ample provision for all the strange ways by which poison has been -introduced into the system, whether it be by the ear, nose, brain, -rectum, vagina, or any other conceivable way, so that, to borrow the -words of Mr. Greaves (_Notes on Criminal Law Consolidation_), "the -malicious may rest satisfied that every attempt to murder which their -perverted ingenuity may devise, or their fiendish malignity suggest, -will fall within some clause of this Act, and may be visited with penal -servitude for life." - -Since poison is often exhibited, not for the purpose of taking life, but -from various motives, and to accomplish various ends--as, for example, -to narcotise the robber's victim (this especially in the East), to quiet -children, to create love in the opposite sex (love philters), to detect -the secret sipper by suitably preparing the wine, to expel the -inconvenient fruit of illicit affection, to cure inebriety by polluting -the drunkard's drink with antimony, and, finally, to satisfy an aimless -spirit of mere wantonness and wickedness, the English law enacts "that -whosoever shall unlawfully or maliciously administer to, or cause to be -taken by, any other person, any poison or other destructive or noxious -thing, so as thereby to endanger the life of such person, or so as -thereby to inflict upon such person any grievous bodily harm, shall be -guilty of felony." - -There is also a special provision, framed, evidently, with reference to -volatile and stupefying poisons, such as chloroform, tetrachloride of -carbon, &c.:-- - -"Whoever shall unlawfully apply, or administer to, or cause to be taken -by any person, any chloroform, laudanum, or other stupefying or -overpowering drug, matter, or thing, with intent, in any such case, -thereby to enable himself or any other person to commit, or with intent, -&c., to assist any other person in committing, any indictable offence, -shall be guilty of felony." - -Sec. 15. The German statute, as with successive amendments it now stands, -enacts as follows:[27]-- - -[27] "Wer vorsaetzlich einem Andern, um dessen Gesundheit zu beschaedigen, -Gift oder andere Stoffe beibringt, welche die Gesundheit zu zerstoeren -geeignet sind, wird mit Zuchthaus von zwei bis zu zehn Jahren bestraft. - -"Ist durch die Handlung eine schwere Koerperverletzung verursacht worden, -so ist auf Zuchthaus nicht unter fuenf Jahren, und wenn durch die -Handlung der Tod verursacht worden, auf Zuchthaus nicht unter zehn -Jahren oder auf lebenslaengliches Zuchthaus zu erkennen. - -"Ist die vorsaetzliche rechtswidrige Handlung des Gift--&c.,--Beibringens -auf das 'Toedten' gerichtet, soll also durch dieselbe gewollter Weise der -Tod eines Anderen herbeigefuehrt werden, so kommt in betracht: Wer -vorsaetzlich einen Menschen toedtet, wird, wenn er die Toedtung mit -Ueberlegung ausgefuehrt hat, wegen Mordes mit dem Tode bestraft." - -"Whoever wilfully administers (_beibringt_) to a person, for the purpose -of injuring health, poison, or any other substance having the property -of injuring health, will be punished by from two to ten years' -imprisonment. - -"If by such act a serious bodily injury is caused, the imprisonment is -not to be less than five years; if death is the result, the imprisonment -is to be not under ten years or for life. - -"If the death is wilfully caused by poison, it comes under the general -law: 'Whoever wilfully kills a man, and if the killing is premeditated, -is on account of murder punishable with death.'" - -The French law runs thus (Art. 301, _Penal Code_):--"Every attempt on -the life of a person, by the effect of substances which may cause death, -more or less suddenly, in whatever manner these substances may have been -employed or administered, and whatever may have been the results, is -called poisoning."[28] - -[28] "Est qualifie _empoisonnement_--tout attentat a la vie d'une -personne par l'effet de substances qui peuvent donner la mort plus ou -moins promptement, de quelque maniere que ces substances aient ete -employees ou administrees, et quelles qu'en aient ete les suites."--Art. -301, _Penal Code_. - -There is also a penalty provided against any one who "shall have -occasioned the illness or incapacity for personal work of another, by -the voluntary administration, in any manner whatever, of substances -which, without being of a nature to cause death, are injurious to -health."[29] - -[29] "Celui qui aura occasionne a autrui une maladie ou incapacite de -travail personnel en lui administrant volontairement, de quelque maniere -que ce soit, des substances qui, sans etre de nature a donner la mort, -sont nuisibles a la sante."--Art. 317, _Penal Code_. - -Sec. 16. =Scientific Definition of a Poison.=--A true scientific definition -of a poison must exclude all those substances which act -mechanically,--the physical influences of heat, light, and electricity; -and parasitic diseases, whether caused by the growth of fungus, or the -invasion of an organism by animal parasites, as, for example, -"trichinosis," which are not, so far as we know, associated with any -poisonous product excreted by the parasite;--on the other hand, it is -now recognised that pathogenic micro-organisms develop poisons, and the -symptoms of all true infections are but the effects of "toxines." The -definition of poison, in a scientific sense, should be broad enough to -comprehend not only the human race, but the dual world of life, both -animal and vegetable. - -Husemann and Kobert are almost the only writers on poisons who have -attempted, with more or less success, to define poison by a -generalisation, keeping in view the exclusion of the matters enumerated. -Husemann says--"We define poisons as such inorganic, or organic -substances as are in part capable of artificial preparation, in part -existing, ready-formed, in the animal or vegetable kingdom, which, -without being able to reproduce themselves, through the chemical nature -of their molecules under certain conditions, change in the healthy -organism the form and general relationship of the organic parts, and, -through annihilation of organs, or destruction of their functions, -injure health, or, under certain conditions, destroy life." Kobert -says:--"Poisons are organic or inorganic unorganised substances -originating in the organism itself, or introduced into the organism, -either artificially prepared, or ready formed in nature, which through -their chemical properties, under certain conditions, so influence the -organs of living beings, that the health of these beings is seriously -influenced temporarily or permanently." - -In the first edition of this work I made an attempt to define a poison -thus:--_A substance of definite chemical composition, whether mineral or -organic, may be called a poison, if it is capable of being taken into -any living organism, and causes, by its own inherent chemical nature, -impairment or destruction of function_. I prefer this definition to -Kobert's, and believe that it fairly agrees with what we know of -poisons. - - -II.--Classification of Poisons. - -Sec. 17. At some future time, with a more intimate knowledge of the way in -which each poison acts upon the various forms of animal and vegetable -life, it may be possible to give a truly scientific and philosophical -classification of poisons--one based neither upon symptoms, upon local -effects, nor upon chemical structure, but upon a collation and -comparison of all the properties of a poison, whether chemical, -physical, or physiological. No perfect systematic arrangement is at -present attainable: we are either compelled to omit all classification, -or else to arrange poisons with a view to practical utility merely. - -From the latter point of view, an arrangement simply according to the -most prominent symptoms is a good one, and, without doubt, an assistance -to the medical man summoned in haste to a case of real or suspected -poisoning. Indeed, under such circumstances, a scheme somewhat similar -to the following, probably occurs to every one versed in toxicology:-- - - -A. POISONS CAUSING DEATH IMMEDIATELY, OR IN A FEW MINUTES. - -There are but few poisons which destroy life in a few minutes. Omitting -the strong mineral acids, carbon monoxide, carbon dioxide, with the -irrespirable gases,--_Prussic acid_, _the cyanides_, _oxalic acid_, and -occasionally _strychnine_, are the chief poisons coming under this head. - - -B. IRRITANT POISONS (symptoms mainly pain, vomiting, and purging). - -_Arsenic_, _antimony_, _phosphorus_, _cantharides_, _savin_, _ergot_, -_digitalis_, _colchicum_, _zinc_, _mercury_, _lead_, _copper_, _silver_, -_iron_, _baryta_, _chrome_, _yew_, _laburnum_, _and putrid animal -substances._ - - -C. IRRITANT AND NARCOTIC POISONS (symptoms those of an irritant nature, -with the addition of more or less pronounced cerebral indications). - -To this class more especially belong _oxalic acid_ and _the oxalates_, -with several poisons belonging to the purely narcotic class, but which -produce occasionally irritant effects. - - -D. POISONS MORE ESPECIALLY AFFECTING THE NERVOUS SYSTEM. - -1. NARCOTICS (chief symptom insensibility, which may be preceded by more -or less cerebral excitement): _Opium_, _Chloral_, _Chloroform_. - -2. DELIRIANTS (delirium for the most part a prominent symptom): -_Belladonna_, _hyoscyamus_, _stramonium_, _with others of the -Solanaceae_, to which may be added--_poisonous fungi_, _Indian hemp_, -_lolium temulentum_, _[oe]nanthe crocata_, and _camphor_. - -3. CONVULSIVES.--Almost every poison has been known to produce -convulsive effects, but the only true convulsive poisons are the -_alkaloids of the strychnos class_. - -4. COMPLEX NERVOUS PHENOMENA: _Aconite_, _digitalis_, _hemlock_, -_calabar bean_, _tobacco_, _lobelia inflata_, and _curara_. - - * * * * * - -Sec. 18. KOBERT'S CLASSIFICATION.--The latest authority on -poisons--Kobert--has classified poisons according to the following -scheme:-- - - -I. POISONS WHICH CAUSE COARSE ANATOMICAL CHANGES OF THE ORGANS. - - A. Those which specially irritate the part to which they are - applied. - - 1. _Acids._ - - 2. _Caustic alkalies._ - - 3. _Caustic salts_, especially those of the heavy metals. - - 4. Locally irritating organic substances which neither can be - classified as corrosive acids nor alkalies, nor as corrosive salts; - such are:--_cantharidine_, _phrynine_, and others in the animal - kingdom, _croton oil_ and _savin_ in the vegetable kingdom. Locally - irritating colours, such as the _aniline dyes_. - - 5. Gases and vapours which cause local irritation when breathed, - such as _ammonia_, _chlorine_, _iodine_, _bromine_, and _sulphur - dioxide_. - - B. Those which have but little effect locally, but change - anatomically other parts of the body; such as _lead_, _phosphorus_, - and others. - - -II. BLOOD POISONS. - - 1. Blood poisons interfering with the circulation in a purely - physical manner, such as _peroxide of hydrogen_, _ricine_, _abrine_. - - 2. Poisons which have the property of dissolving the red blood - corpuscle, such as the _saponins_. - - 3. Poisons which, with or without primary solution of the red blood - corpuscles, produce in the blood methaemoglobin; such as _potassic - chlorate_, _hydrazine_, _nitrobenzene_, _aniline_, _picric acid_, - _carbon disulphide_. - - 4. Poisons having a peculiar action on the colouring matter of the - blood, or on its decomposition products, such as _hydric sulphide_, - _hydric cyanide_, and the _cyanides_ and _carbon monoxide_. - - -III. POISONS WHICH KILL WITHOUT THE PRODUCTION OF COARSE ANATOMICAL -CHANGE. - - 1. Poisons affecting the cerebro-spinal system; such as - _chloroform_, _ether_, _nitrous oxide_, _alcohol_, _chloral_, - _cocaine_, _atropine_, _morphine_, _nicotine_, _coniine_, - _aconitine_, _strychnine_, _curarine_, and others. - - 2. Heart Poisons; such as, _digitalis_, _helleborin_, _muscarine_. - - -IV. POISONOUS PRODUCTS OF TISSUE CHANGE. - - 1. Poisonous albumin. - - 2. Poisons developed in food. - - 3. Auto-poisoning, _e.g._ uraemia, glycosuria, oxaluria. - - 4. The more important products of tissue change; such as, _fatty - acids_, _oxyacids_, _amido-fatty acids_, _amines_, _diamines_, and - _ptomaines_. - - * * * * * - -Sec. 19. I have preferred an arrangement which, as far as possible, follows -the order in which a chemical expert would search for an unknown -poison--hence an arrangement partly chemical and partly symptomatic. -First the chief gases which figure in the mortality statistics are -treated, and then follow in order other poisons. - -A chemist, given a liquid to examine, would naturally test first its -reaction, and, if strongly alkaline or strongly acid, would at once -direct his attention to the mineral acids or to the alkalies. In other -cases, he would proceed to separate volatile matters from those that -were fixed, lest substances such as prussic acid, chloroform, alcohol, -and phosphorus be dissipated or destroyed by his subsequent operations. - -Distillation over, the alkaloids, glucosides, and their allies would -next be naturally sought, since they can be extracted by alcoholic and -ethereal solvents in such a manner as in no way to interfere with an -_after_-search for metals. - -The metals are last in the list, because by suitable treatment, after -all organic substances are destroyed, either by actual fire or powerful -chemical agencies, even the volatile metals may be recovered. The metals -are arranged very nearly in the same order as that in which they would -be separated from a solution--viz., according to their behaviour to -hydric and ammoniac sulphides. - -There are a few poisons, of course, such as the oxalates of the -alkalies, which might be overlooked, unless sought for specially; but it -is hoped that this is no valid objection to the arrangement suggested, -which, in greater detail, is as follows:-- - - -A.--POISONOUS GASES. - - 1. Carbon monoxide. - 2. Chlorine. - 3. Hydric sulphide. - - -B.--ACIDS AND ALKALIES. - - 1. Sulphuric acid. - 2. Hydrochloric acid. - 3. Nitric acid. - 4. Potash. - 5. Soda. - 6. Ammonia. - 7. Neutral sodium, potassium, and ammonium salts. - -In nearly all cases of death from any of the above, the analyst, from -the symptoms observed during life, from the surrounding circumstances, -and from the pathological appearances and evident chemical reactions of -the fluids submitted, is put at once on the right track, and has no -difficulty in obtaining decided results. - - -C.--POISONOUS SUBSTANCES CAPABLE OF BEING SEPARATED BY DISTILLATION FROM -EITHER NEUTRAL OR ACID LIQUIDS. - - 1. Hydrocarbons. - 2. Camphor. - 3. Alcohols. - 4. Amyl-nitrite. - 5. Chloroform and other anaesthetics. - 6. Carbon disulphide. - 7. Carbolic acid. - 8. Nitro-benzene. - 9. Prussic acid. - 10. Phosphorus. - -The volatile alkaloids, which may also be readily distilled by strongly -alkalising the fluid, because they admit of a rather different mode of -treatment, are not included in this class. - - -D.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE MOST -PART BY ALCOHOLIC SOLVENTS. - - -DIVISION I.--VEGETABLE ALKALOIDS. - - 1. Liquid volatile alkaloids, alkaloids of hemlock, nicotine, - piturie, sparteine, aniline. - 2. The opium group of alkaloids. - 3. The strychnine or tetanic group of alkaloids--strychnine, brucine, - igasurine. - 4. The aconite group of alkaloids. - 5. The mydriatic group of alkaloids--atropine, hyoscyamine, solanin, - cytisine. - 6. The alkaloids of the veratrines. - 7. Physostigmine. - 8. Pilocarpine. - 9. Taxine. - 10. Curarine. - 11. Colchicin. - 12. Muscarine and the active principles of certain fungi. - -There would, perhaps, have been an advantage in arranging several of the -individual members somewhat differently--_e.g._, a group might be made -of poisons which, like pilocarpine and muscarine, are antagonistic to -atropine; and another group suggests itself, the physiological action of -which is the opposite of the strychnos class; solanin (although classed -as a mydriatic, and put near to atropine) has much of the nature of a -glucoside, and the same may be said of colchicin; so that, if the -classification were made solely on chemical grounds, solanin would have -followed colchicin, and thus have marked the transition from the -alkaloids to the glucosides. - - -DIVISION II.--GLUCOSIDES. - - 1. The digitalis group. - 2. Other poisonous glucosides acting on the heart. - 3. Saponin. - -The glucosides, when fairly pure, are easily recognised; they are -destitute of nitrogen, neutral in reaction, and split up into sugar and -other compounds when submitted to the action of saponifying agents, such -as boiling with dilute mineral acids. - - -DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF THE ORGANIC ACIDS. - - 1. Santonin. - 2. Mezereon. - -It is probable that this class will in a few years be extended, for -several other organic anitrogenous poisons exist, which, when better -known, will most likely prove to be anhydrides. - - -DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES NOT ADMITTING OF -CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS. - -Ergot, picrotoxin, the poison of _Illicium religiosum_, cicutoxin, -_AEthusa cynapium_, _[OE]nanthe crocata_, croton oil, savin oil, the -toxalbumins of castor oil and _Abrus_. - -The above division groups together various miscellaneous toxic -principles, none of which can at present be satisfactorily classified. - - -E.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL SUBSTANCES. - - -DIVISION I.--POISONS SECRETED BY THE LIVING. - - 1. Poisonous amphibia. - 2. Poison of the scorpion. - 3. Poisonous fish. - 4. Poisonous insects--spiders, wasps, bees, beetles, &c. - 5. Snake poison. - - -DIVISION II.--POISONS FORMED IN DEAD ANIMAL MATTERS. - - 1. Ptomaines. - 2. Poisoning by putrid or changed foods--sausage poisoning. - - -F.--THE OXALIC ACID GROUP. - - -G.--INORGANIC POISONS. - - -DIVISION I.--PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC -SULPHIDE--PRECIPITATE, YELLOW OR ORANGE. - - Arsenic, antimony, cadmium. - - -DIVISION II.--PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID -SOLUTION--BLACK. - - Lead, copper, bismuth, silver, mercury. - - -DIVISION III.--PRECIPITATED FROM A NEUTRAL SOLUTION BY HYDRIC SULPHIDE. - - Zinc, nickel, cobalt. - - -DIVISION IV.--PRECIPITATED BY AMMONIA SULPHIDE. - - Iron, chromium, thallium, aluminium. - - -DIVISION V.--ALKALINE EARTHS. - - Barium. - - -III.--Statistics. - -Sec. 20. The number of deaths from poison (whether accidental, suicidal, or -homicidal), as compared with other forms of violent, as well as natural -deaths, possesses no small interest; and this is more especially true -when the statistics are studied in a comparative manner, and town be -compared with town, country with country. - -The greater the development of commercial industries (especially those -necessitating the use or manufacture of powerful chemical agencies), the -more likely are accidents from poisons to occur. It may also be stated, -further, that the higher the mental development of a nation, the more -likely are its homicides to be caused by subtle poison--its suicides by -the euthanasia of chloral, morphine, or hemlock. - -Other influences causing local diversity in the kind and frequency of -poisoning, are those of race, of religion, of age and sex, and the -mental stress concomitant with sudden political and social changes. - -In the ten years from 1883-1892, there appear to have died from poison, -in England and Wales, 6616 persons, as shown in the following tables:-- - -DEATHS FROM POISON IN ENGLAND AND WALES DURING THE TEN YEARS 1883-92. - - +----------------------------+---------+---------+---------+---------+ - | |Accident | | | | - | | or | | | | - | | Negli- |Suicide. | Murder. | Total. | - | | gence. | | | | | | | - +----------------------------+----+----+----+----+----+----+----+----+ - | | M. | F. | M. | F. | M. | F. | M. | F. | - | | | | | | | | | | - | METALS. | | | | | | | | | - | | | | | | | | | | - |Arsenic, | 37| 14| 37| 20| 1| 1| 75| 35| - |Antimony, | 3| ...| 1| 2| ...| ...| 4| 2| - |Copper, | 4| 1| 2| 1| ...| ...| 6| 2| - |Lead, | 831| 209| 1| 2| ...| ...| 832| 211| - |Silver Nitrate, | 1| ...| ...| ...| ...| ...| 1| ...| - |Zinc Chloride (or Sulphate),| 7| ...| 4| ...| ...| ...| 11| ...| - |Mercury, | 22| 11| 16| 8| 2| 1| 40| 20| - |Chromic Acid, | 1| ...| ...| ...| ...| ...| 1| ...| - |Iron Perchloride, | ...| ...| ...| 1| ...| ...| ...| 1| - | | | | | | | | | | - | ALKALINE EARTHS. | | | | | | | | | - | | | | | | | | | | - |Lime, | 2| ...| ...| 1| ...| ...| 2| 1| - |Barium Chloride, | 1| ...| ...| ...| ...| ...| 1| ...| - | | | | | | | | | | - | THE ALKALIES AND THEIR | | | | | | | | | - | SALTS. | | | | | | | | | - | | | | | | | | | | - |Ammonia, | 39| 25| 18| 16| ...| ...| 57| 41| - |Caustic Soda, | 3| 4| ...| 1| ...| ...| 3| 5| - | " Potash, | 8| 10| 1| ...| ...| ...| 9| 10| - |Potassic Chlorate, | 1| ...| ...| ...| ...| ...| 1| ...| - | " Bichromate, | 2| 2| 7| 3| ...| ...| 9| 5| - | " Bromide, | 1| ...| ...| ...| ...| ...| 1| ...| - | " Binoxalate | | | | | | | | | - | (Sorrel), | 1| 3| 1| 4| ...| ...| 2| 7| - | | | | | | | | | | - | ACIDS. | | | | | | | | | - | | | | | | | | | | - |Sulphuric Acid, | 30| 9| 29| 24| 1| ...| 60| 33| - |Nitric " | 18| 7| 18| 9| ...| ...| 36| 16| - |Hydrochloric Acid, | 48| 18| 83| 55| ...| ...| 131| 73| - |Oxalic " | 17| 6| 114| 86| ...| ...| 131| 92| - |Tartaric " | ...| 1| ...| ...| ...| ...| ...| 1| - |Acetic " | 4| 3| ...| 2| ...| ...| 4| 5| - |Carbolic " | 169| 101| 219| 271| ...| 1| 388| 373| - |Hydrofluoric " | ...| ...| ...| 1| ...| ...| ...| 1| - |Phosphorus (including | | | | | | | | | - |Lucifer matches), | 24| 47| 28| 56| ...| ...| 52| 103| - |Iodine, | 6| 7| 1| 1| ...| ...| 7| 8| - | | | | | | | | | | - | VOLATILE LIQUIDS. | | | | | | | | | - | | | | | | | | | | - |Paraffin (Petroleum), | 9| 2| 1| ...| ...| ...| 10| 2| - |Benzoline, | 3| 2| ...| 1| ...| ...| 3| 3| - |Naphtha, | 1| ...| ...| ...| ...| ...| 1| ...| - |Carbon Bisulphide, | ...| ...| 1| ...| ...| ...| 1| ...| - |Turpentine, | 5| 1| ...| 3| ...| ...| 5| 4| - |Methylated Spirit, | ...| 2| 1| 2| ...| ...| 1| 4| - |Alcohol, | 81| 24| 1| 2| ...| ...| 82| 26| - |Chloroform, | 57| 41| 9| 5| 1| ...| 67| 46| - |Ether, | 5| 2| ...| ...| ...| ...| 5| 2| - |Spt. Etheris Nitrosi, | 1| ...| ...| ...| ...| ...| 1| ...| - |Anaesthetic (kind not | | | | | | | | | - |stated), | 4| 3| ...| ...| ...| ...| 4| 3| - |Oil of Juniper, | 1| ...| ...| ...| ...| ...| 1| ...| - | | | | | | | | | | - | OPIATES AND NARCOTICS. | | | | | | | | | - | | | | | | | | | | - |Opium, Laudanum--Morphia, | 503| 373| 330| 167| 4 | 2 | 837| 542| - |Soothing Syrup, Paregoric, | | | | | | | | | - |&c. | 18| 22| 2| 3| ...| ...| 20| 25| - |Chlorodyne, | 56| 30| 8| 8| ...| ...| 64| 38| - |Chloral, | 89| 22| 14| 1| 1 | ...| 104| 23| - | | | | | | | | | | - | CYANIDES. | | | | | | | | | - | | | | | | | | | | - |Prussic Acid, and Oil of | | | | | | | | | - | Almonds, | 17| 11| 203| 19| 2 | 8 | 222| 38| - |Potassium Cyanide, | 19| 21| 100| 22| 3 | 1 | 122| 44| - | | | | | | | | | | - | ALKALOIDS. | | | | | | | | | - | | | | | | | | | | - |Strychnine and Nux Vomica, | 22| 21| 65| 85| 4 | 4 | 91| 110| - |Vermin-Killer, | 2| 6| 49| 69| 1 | ...| 52| 75| - |Atropine, | 2| ...| 1| ...| ...| ...| 3| ...| - |Belladonna, | 36| 20| 11| 9| ...| ...| 47| 29| - |Aconite, | 19| 21| 9| 10| ...| ...| 28| 31| - |Ipecacuanha, | 1| 1| ...| ...| ...| ...| 1| 1| - |Cocaine, | 3| ...| ...| ...| ...| ...| 3| ...| - | | | | | | | | | | - | MISCELLANEOUS. | | | | | | | | | - | | | | | | | | | | - |Antipyrine, | 1| ...| ...| ...| ...| ...| 1| ...| - |Cantharides, | 1| ...| ...| 1| ...| ...| 1| 1| - |Camphorated Oil, | 1| ...| ...| ...| ...| ...| 1| ...| - |Croton Oil, | 1| ...| ...| ...| ...| ...| 1| ...| - |Cayenne Pepper, | 1| ...| ...| ...| ...| ...| 1| ...| - |Syrup of Rhubarb, | 1| ...| ...| ...| ...| ...| 1| ...| - |Colchicum, | 2| ...| ...| ...| ...| ...| 2| ...| - |Hemlock, | 3| 1| ...| ...| ...| ...| 3| 1| - |Water Hemlock, | 5| 6| ...| ...| ...| ...| 5| 6| - |Colocynth, | ...| 2| ...| ...| ...| ...| ...| 2| - |Castor Oil Seeds, | 1| 1| ...| ...| ...| ...| 1| 1| - |Laburnum Seeds, | 2| 1| ...| ...| ...| ...| 2| 1| - |Thorn Apple, | 1| ...| ...| ...| ...| ...| 1| ...| - |Yew Leaves or Berries, | 3| 2| ...| ...| ...| ...| 3| 2| - |Crow-foot, | ...| 1| ...| ...| ...| ...| ...| 1| - |Whin-flower, | 1| ...| ...| ...| ...| ...| 1| ...| - |Pennyroyal, | ...| 1| ...| ...| ...| ...| ...| 1| - |Meadow Crow-foot, | ...| 1| ...| ...| ...| ...| ...| 1| - |Arum Seeds, | ...| 1| ...| ...| ...| ...| ...| 1| - |Bitter Aloes, | ...| 1| ...| 1| ...| ...| ...| 2| - |Cocculus Indicus, | ...| ...| 1| ...| ...| ...| 1| ...| - |Horse Chestnut, | ...| 1| ...| ...| ...| ...| ...| 1| - |Creosote, | 1| ...| ...| ...| ...| ...| 1| ...| - |Spirits of Tar (Oil of Tar),| 2| 1| ...| ...| ...| ...| 2| 1| - |Nitro-Glycerine, | 1| ...| ...| ...| ...| ...| 1| ...| - |Camphor, | ...| 1| ...| ...| ...| ...| ...| 1| - |Tobacco, | 4| ...| 1| ...| ...| ...| 5| ...| - |Lobelia, | 1| ...| ...| ...| ...| ...| 1| ...| - |Fungi, | 13| 10| ...| ...| ...| ...| 13| 10| - |Poisonous Weeds, | 2| ...| ...| ...| ...| ...| 2| ...| - |Hellebores, | ...| ...| 1| 1| ...| ...| 1| 1| - |Kind not stated, | 216| 158| 256| 167| 3 | 1 | 475| 326| - | +----+----+----+----+----+----+----+----+ - | |2498|1292|1644|1140| 23| 19|4165|2551| - | | \ / | \ / | \ / | \ / | - | | 3790 | 2784 | 42 | 6616 | - +----------------------------+---------+---------+---------+---------+ - -Although so large a number of substances destroy life by accident or -design, yet there are in the list only about 21 which kill about 2 -persons or above each year: the 21 substances arranged in the order of -their fatality are as follows:-- - - Actual deaths in - ten years ending 1892. - Caustic potash 19 - Poisonous fungi 23 - Aconite 59 - Mercury 60 - Belladonna 76 - Sulphuric acid 93 - Ammonia 98 - Chlorodyne 102 - Alcohol 108 - Arsenic 110 - Chloroform 113 - Vermin-killer 127 - Chloral 127 - Phosphorus 155 - Cyanide of potassium 166 - Strychnine 201 - Nitric acid 204 - Prussic acid 260 - Carbolic acid 762 - Lead 1043 - Opiates 1324 - -In each decade there are changes in the position on the list. The most -significant difference between the statistics now given and the -statistics for the ten years ending 1880, published in the last edition -of this work, is that in the former decade carbolic acid occupied a -comparatively insignificant place; whereas in the ten years ending 1892, -deaths from carbolic acid poisoning are the most frequent form of fatal -poisoning save lead and opiates. - -The following table gives some German statistics of poisoning:-- - -TABLE SHOWING THE ADMISSIONS INTO VARIOUS MEDICAL INSTITUTIONS[30] IN -BERLIN OF PERSONS SUFFERING FROM THE EFFECTS OF POISON DURING THE THREE -YEARS 1876, 1877, 1878. - -[30] Viz., the Koenigl. Charite, Allg. Staedtisches Krankenhaus, -Staedtisches Baracken-Lazareth, Bethanien, St. Helwoeg's-Lazarus, -Elisabethen-Krankenhaus, Augusta Hospital, and the Institut fuer -Staatsarzneikunde. - - +--------------------------------------+--------+--------+--------+ - | | Males. |Females.| Total. | - +--------------------------------------+--------+--------+--------+ - | Charcoal Vapour, | 77 | 78 | 155 | - | Sulphuric Acid, | 24 | 54 }| | - | Hydrochloric Acid, | 4 | 4 }| 93 | - | Nitric Acid, and Aqua Regia, | 7 | ... }| | - | Phosphorus, | 13 | 28 | 41 | - | Cyanide of Potassium, | 29 | 3 }| | - | Prussic Acid, | 5 | 1 }| 38 | - | Oxalic Acid, and Oxalate of Potash, | 11 | 8 | 19 | - | Alcohol, | 12 | 2 | 14 | - | Arsenic, | 7 | 5 | 12 | - | Morphine, | 8 | 1 }| | - | Opium, | 2 | 1 }| 12 | - | Potash or Soda Lye, | 2 | 6 | 8 | - | Chloral, | 3 | 4 | 7 | - | Chloroform, | 4 | 2 | 6 | - | Sewer Gas, | 5 | ... | 5 | - | Strychnine, | ... | 4 | 4 | - | Atropine, | 1 | 2 | 3 | - | Copper Sulphate, | 1 | 2 | 3 | - | Nitrobenzol, | 2 | ... | 2 | - | Carbolic Acid, | ... | 2 | 2 | - | Chromic Acid, | 1 | 1 | 2 | - | Burnt Alum, | ... | 1 | 1 | - | Ammonium Sulphide, | 1 | ... | 1 | - | Datura Stramonium, | ... | 1 | 1 | - | Petroleum, | ... | 1 | 1 | - | Benzine, | 1 | ... | 1 | - | Ether, | 1 | ... | 1 | - | Prussic Acid and Morphine, | 1 | ... | 1 | - | Prussic Acid and Chloral, | 1 | ... | 1 | - | Turpentine and Sal Ammoniac, | ... | 1 | 1 | - | +--------+--------+--------+ - | | 223 | 212 | 435 | - +--------------------------------------+--------+--------+--------+ - -=Suicidal Poisoning.=--Poisons which kill more than one person -suicidally each year are only 19 in number, as follows:-- - - Deaths from suicide - during the ten years - ending 1892. - - Potassic bichromate 10 - Chloroform 14 - Chloral 15 - Chlorodyne 16 - Aconite 19 - Belladonna 20 - Mercury 24 - Nitric acid 27 - Ammonia 34 - Sulphuric acid 53 - Arsenic 77 - Phosphorus 84 - Vermin-killer 118 - Prussic acid 122 - Hydrochloric acid 138 - Strychnine 150 - Oxalic acid 200 - Prussic acid 222 - Opiates 281 - Phenol 290 - -In the ten years ending 1880, suicidal deaths from vermin-killers, from -prussic acid, from cyanide of potassium, and from opiates were all more -numerous than deaths from phenol, whereas at present phenol appears to -be the poison most likely to be chosen by a suicidal person. - - -Criminal Poisoning. - -Sec. 22. Some useful statistics of criminal poisoning have been given by -Tardieu[31] for the 21 years 1851-1871, which may be summarised as -follows:-- - -[31] _Etude Medico-Legale sur l'Empoisonnement_, Paris, 1875. - - Total accusations of Poisoning in the 21 years, 793 - - RESULTS OF THE POISONING:-- - Death, 280 } - Illness, 346 } 872 - Negative, 246 } - - ACCUSED:-- - Men, 304 } 703 - Women, 399 } - - NATURE OF POISON EMPLOYED:-- - Arsenic, 287 - Phosphorus, 267 - - { Sulphate, 120 } - Copper { Acetate (Verdigris), 39 } 159 - - { Sulphuric Acid, 36 } - Acids { Hydrochloric Acid, 8 } 47 - { Nitric Acid, 3 } - - Cantharides, 30 - - Nux Vomica, 5 } 12 - Strychnine, 7 } - - { Opium, 6 } - Opiates { Laudanum, 3 } 10 - { Sedative Water, 1 } - - Salts of Mercury, 8 - - Sulphate of Iron, 6 - - Preparations of Antimony, 5 - - Ammonia, 4 - - Cyanides {Prussic Acid, 2 } - {Cyanide of Potassium, 2 } 4 - - Hellebore, 3 - - Datura Stramonium, 3 - - Powdered Glass, 3 - - Digitalin, 2 - - Potash, 2 - - Sulphate of Zinc, 2 - - Eau de Javelle (a solution of Hypochlorite of Potash), 1 - - Tincture of Iodine, 1 - - Croton Oil, 1 - - Nicotine, 1 - - Belladonna, 1 - - "Baume Fiovarenti," 1 - - Euphorbia, 1 - - Acetate of Lead, 1 - - Carbonic Acid Gas, 1 - - Laburnum Seeds, 1 - - Colchicum, 1 - - Mushrooms, 1 - - Sulphuric Ether, 1 - --- - Total, 867 - === - -It hence may be concluded, according to these statistics of criminal -poisoning, that of 1000 attempts in France, either to injure or to -destroy human life by poison, the following is the most probable -selective order:-- - - Arsenic, 331 - Phosphorus, 301 - Preparations of Copper, 183 - The Mineral Acids, 54 - Cantharides, 35 - Strychnine, 14 - Opiates, 12 - Mercurial preparations, 9 - Antimonial preparations, 6 - Cyanides (that is, Prussic Acid and Potassic Cyanide), 5 - Preparations of Iron, 5 - -This list accounts for 955 poisonings, and the remaining 45 will be -distributed among the less used drugs and chemicals. - - -IV.--The Connection between Toxic Action and Chemical Composition. - -Sec. 23. Considerable advance has been made of late years in the study of -the connection which exists between the chemical structure of the -molecule of organic substances and physiological effect. The results -obtained, though important, are as yet too fragmentary to justify any -great generalisation; the problem is a complicated one, and as Lauder -Brunton justly observes:-- - -"The physiological action of a drug does not depend entirely on its -chemical composition nor yet on its chemical structure, so far as that -can be indicated even by graphic formula, but upon conditions of -solubility, instability, and molecular relations, which we may hope to -discover in the future, but with which we are as yet imperfectly -acquainted."[32] - -[32] _Introduction to Modern Therapeutics_, Lond., 1892. 136. - -The occurrence of hydroxyl, whether the substance belong to the simpler -chain carbon series or to the aromatic carbon compounds, appears to -usually endow the substance with more or less active and frequently -poisonous properties, as, for example, in the alcohols, and as in -hydroxylamine. It is also found that among the aromatic bodies the toxic -action is likely to increase with the number of hydroxyls: thus phenol -has one hydroxyl, resorcin two, and phloroglucin three; and the toxic -power is strictly in the same order, for, of the three, phenol is least -and phloroglucin most poisonous. - -Replacing hydrogen by a halogen, especially by chlorine, in the fatty -acids mostly produces substances of narcotic properties, as, for -instance, monochloracetic acid. In the sulphur compounds, the entrance -of chlorine modifies the physiological action and intensifies toxicity: -thus ethyl sulphide (C_{2}H_{5})_{2}S is a weak poison, monochlorethyl -sulphide C_{2}H_{5}C_{2}H_{4}ClS a strong poison, and dichlorethyl -sulphide C_{4}H_{8}Cl_{2}S a very strong poison: the vapour kills -rabbits within a short time, and a trace of the oil applied to the ear -produces intense inflammation of both the eyes and the ear.[33] - -[33] V. Meyer, _Ber. d. Chem. Ges._, XX., 1725. - -The weight of the molecule has an influence in the alcohols and acids of -the fatty series; for instance, ethyl, propyl, butyl, and amyl alcohols -show as they increase in carbon a regular increase in toxic power; the -narcotic actions of sodium propionate, butyrate, and valerianate also -increase with the rising carbon. Nitrogen in the triad condition in the -amines is far less poisonous than in the pentad condition. - -Bamberger[34] distinguishes two classes of hydrogenised bases derived -from [alpha] and [beta] naphthylamine, by the terms "acylic" and -"aromatic." The acylic contains the four added hydrogens in the amidogen -nucleus, the aromatic in the other nucleus, thus - -[34] _Ber._, xxii. 777-778. - - CH CNH_{2} - /\ /\ - / \C/ \ - CH | | | CH - | | | - CH | | | CH - \ /C\ / - \/ \/ - CH CH - - [alpha] Naphthylamine. - - CH CH - /\ /\ - / \C/ \ - CH | | | CNH_{2} - | | | - CH | | | CH - \ /C\ / - \/ \/ - CH CH - - [beta] Naphthylamine. - - CH CH_{2} - /\ /\ - / \C/ \ - CH | | | CNH_{3} - | | | - CH | | | CH_{2} - \ /C\ / - \/ \/ - CH CH_{2} - - Acylic tetrahydro-[alpha] Naphthylamine. - - CH_{2} CH - /\ /\ - / \C/ \ - CH_{2}| | | CNH_{2} - | | | - CH_{2}| | | CH - \ /C\ / - \/ \/ - CH_{2} CH - - Aromatic tetrahydro-[beta] Naphthylamine. - -The acylic [beta] tetrahydro-naphthylamine, the [beta] -tetrahydroethylnaphthylamine, and the [beta] -tetrahydromethylnaphthylamine all cause dilatation of the pupil and -produce symptoms of excitation of the cervical sympathetic nerve; the -other members of the group are inactive. - -Sec. 24. The result of replacing hydrogen by alkyls in aromatic bodies has -been studied by Schmiedeberg and others; replacing the hydrogen of the -amidogen by ethyl or methyl, usually results in a body having a more or -less pronounced narcotic action. The rule is that methyl is stronger -than ethyl, but it does not always hold good; ortho-amido-phenol is not -in itself poisonous, but when two hydrogens of the amidogen group are -replaced by two methyls thus-- - - HO - /\ - / \ - | |NH_{2} - | | - | | - \ / - \/ - - HO - /\ - / \ - | |N(CH_{3})_{2} - | | - | | - \ / - \/ - -the resulting body has a weak narcotic action. - -It would naturally be inferred that the replacement of the H in the -hydroxyl by a third methyl would increase this narcotic action, but this -is not so: on the other hand, if there are three ethyl groups in the -same situation a decidedly narcotic body is produced. - -The influence of position of an alkyl in the aromatic bodies is well -shown in ortho-, para- and meta-derivatives. Thus the author proved some -years ago that with regard to disinfecting properties, ortho-cresol was -more powerful than meta-; meta-cresol more powerful than para-; so again -ortho-aceto-toluid is poisonous, causing acute nephritis; -meta-aceto-toluid has but feeble toxic actions but is useful as an -antipyretic; and para-aceto-toluid is inactive. - -In the trioxybenzenes, in which there are three hydroxyls, the toxic -action is greater when the hydroxyls are consecutive, as in pyrogallol, -than when they are symmetrical, as in phloroglucin. - - OH - /\ - / \ - | |OH - | | - | |OH - \ / - \/ - - Pyrogallol. - - OH - /\ - / \ - | | - | | - HO| |OH - \ / - \/ - - Phloroglucin. - -The introduction of methyl into the complicated molecule of an alkaloid -often gives curious results: thus methyl strychnine and methyl brucine -instead of producing tetanus have an action on voluntary muscle like -curare. - -Benzoyl-ecgonine has no local anaesthetic action, but the introduction of -methyl into the molecule endows it with a power of deadening the -sensation of the skin locally; on the other hand, cocethyl produces no -effect of this kind. - -Drs. Crum Brown and Fraser[35] have suggested that there is some -relation between toxicity and the saturated or non-saturated condition -of the molecule. - -[35] _Journ. Anat. and Phys._, vol. ii. 224. - -Hinsberg and Treupel have studied the physiological effect of -substituting various alkyls for the hydrogen of the hydroxyl group in -para-acetamido-phenol. - -Para-aceto-amido-phenol when given to dogs in doses of 0.5 grm. for -every kilogr. of body weight causes slight narcotic symptoms, with -slight paralysis; there is cyanosis and in the blood much methaemoglobin. - -In men doses of half a gramme (7.7 grains) act as an antipyretic, -relieve neuralgia and have weak narcotic effects. - -The following is the result of substituting certain alkyls for H in the -HO group. - -(1) =Methyl.=--The narcotic action is strengthened and the antipyretic -action unaffected. The methaemoglobin in the blood is somewhat less. - -(2) =Ethyl.=--Action very similar, but much less methaemoglobin is -produced. - -(3) =Propyl.=--Antipyretic action a little weaker. Methaemoglobin in the -blood smaller than in para-acetamido-phenol, but more than when the -methyl or ethyl compound is administered. - -(4) =Amyl.=--Antipyretic action decreased. - -The smallest amount of toxicity is in the ethyl substitution; while the -maximum antipyretic and antineuralgic action belongs to the methyl -substitution. - -Next substitution was tried in the Imid group. It was found that -substituting ethyl for H in the imid group annihilated the narcotic and -antipyretic properties. No methaemoglobin could be recognised in the -blood. - -Lastly, simultaneous substitution of the H of the HO group by ethyl and -the substitution of an alkyl for the H in the NH group gave the -following results:-- - -=Methyl.=--In dogs the narcotic action was strengthened, the -methaemoglobin in the blood diminished. In men the narcotic action was -also more marked as well as the anti-neural action. The stomach and -kidneys were also stimulated. - -=Ethyl.=--In dogs the narcotic action was much strengthened, while the -methaemoglobin was diminished. In men the antipyretic and anti-neural -actions were unaffected. - -=Propyl.=--In dogs the narcotic action was feebler than with methyl or -ethyl, and in men there was diminished antipyretic action. - -=Amyl.=--In dogs the narcotic action was much smaller. - -From this latter series the conclusion is drawn that the maximum of -narcotic action is obtained by the introduction of methyl and the -maximum antipyretic action by the introduction of methyl or ethyl. The -ethyl substitution is, as before, the less toxic.[36] - -[36] _Ueber die physiologische Wirkung des p-amido-phenol u. einiger -Derivate desselben._ O. Hinsberg u. G. Treupel, _Archiv f. Exp. Pathol. -u. Pharm._, B. 33, S. 216. - -The effect of the entrance of an alkyl into the molecule of a substance -is not constant; sometimes the action of the poison is weakened, -sometimes strengthened. Thus, according to Stolnikow, dimethyl resorcin, -C_{6}H_{4}(OCH_{3})_{2}, is more poisonous than resorcin -C_{6}H_{4}(OH)_{2}. Anisol C_{6}H_{5}OCH_{3}, according to Loew, is more -poisonous to algae, bacteria, and infusoria than phenol C_{6}H_{5}OH. On -the other hand, the replacement by methyl of an atom of hydrogen in the -aromatic oxyacids weakens their action; methyl salicylic acid - - O.CH_{3} - / - C_{6}H_{4} - \ - COOH - -is weaker than salicylic acid - - OH - / - C_{6}H_{4} . - \ - COOH - -Arsen-methyl chloride, As(CH_{3})Cl_{2}, is strongly poisonous, but the -introduction of a second methyl As(CH_{3})_{2}Cl makes a comparatively -weak poison. - -Sec. 25. In some cases the increase of CO groups weakens the action of a -poison; thus, in allantoin there are three carbonyl (CO) groups; this -substance does not produce excitation of the spinal cord, but it -heightens muscular irritability and causes, like xanthin, muscular -rigidity; alloxantin, with a similar structure but containing six -carbonyl groups, does not possess this action. - - NH--CH--NH - | | | - CO | CO - | | | - NH--CO NH_{2} - - Allantoin. - - NH--CO CO--HN - | | | | - | | O | | - | |/ \| | - CO--C---C CO - | | | | - NH--CO CO--HN - - Alloxantin. - -Sec. 26. A theory of general application has been put forward and supported -with great ability by Oscar Loew[37] which explains the action of -poisons by presuming that living has a different composition to dead -albumin; the albumin of the chemist is a dead body of a definite -composition and has a stable character; living albumin, such as -circulates in the blood or forms the protoplasm of the tissues, is not -"stable" but "labile"; Loew says:--"If the old idea is accepted that -living albumin is chemically the same substance as that which is dead, -numerous toxic phenomena are inexplicable. It is impossible, for -instance, to explain how it is that diamide N_{2}H_{4} and hydroxylamine -NH_{2}OH are toxic, even with great dilution, on all living animals; -whilst neither of those substances have the smallest action on dead -plasma or the ordinary dissolved passive albumin, there must therefore -be present in the albumin of the living plasma a grouping of atoms in a -"_labile_" condition (_Atomgruppirungen labiler Art_) which are capable -of entering into reactions; such, according to our present knowledge, -can only be the aldehyde and the ketone groups. The first mentioned -groups are more labile and react in far greater dilution than the latter -groups." - -[37] _Ein natuerliches System der Gift-Wirkungen_, Muenchen, 1893. - -Loew considers that all substances which enter into combination with -aldehyde or ketone groups must be poisonous to life generally. For -instance, hydroxylamine, diamide and its derivatives, phenylhydrazine, -free ammonia, phenol, prussic acid, hydric sulphide, sulphur dioxide and -the acid sulphites all enter into combination with aldehyde. - -So again the formation of imide groups in the aromatic ring increases -any poisonous properties the original substance possesses, because the -imide group easily enters into combination with aldehyde; thus -piperidine (CH_{2})_{5}NH is more poisonous than pyridine (CH)_{5}N; -coniine NH(CH_{2})_{4}CH-CH_{2}-CH_{2}CH_{3}, is more poisonous than -collidine N(CH)_{4}C-CH-(CH_{3})_{2}; pyrrol (CH)_{4}NH than pyridine -(CH)_{5}N; and amarin,[38] - - C_{6}H_{5}-CH-NH - | \ - | CH-C_{6}H_{5}, - | / - C_{6}H_{5}-C=N - -than hydrobenzamide - - C_{6}H_{5}-CH=N - \ - CH-C_{6}H_{5}. - / - C_{6}H_{5}-CH=N - -[38] Th. Weyl (_Lehrbuch der organischen Chemie_) states (p. 385) that -amarin is not poisonous, but Baccheti (_Jahr. d. Chemie_, 1855) has -shown that 250 mgrms. of the acetate will kill a dog, 80 mgrms. a -guinea-pig; and that it is poisonous to fishes, birds, and frogs: -hydrobenzamide in the same doses has no effect. - -If the theory is true, then substances with "labile" amido groups, on -the one hand, must increase in toxic activity if a second amido group is -introduced; and, on the other, their toxic qualities must be diminished -if the amido group is changed into an imido group by the substitution of -an atom of hydrogen for an alkyl. - -Observation has shown that both of these requirements are satisfied; -phenylenediamine is more poisonous than aniline; toluylenediamine more -poisonous than toluidine. Again, if an atom of hydrogen in the amido -(NH_{2}) group in aniline be replaced by an alkyl, _e.g._ methyl or -ethyl, the resulting substance does not produce muscular spasm; but if -the same alkyl is substituted for an atom of hydrogen in the benzene -nucleus the convulsive action remains unaffected. - -If an acidyl, as for example the radical of acetic acid, enter into the -amido group, then the toxic action is notably weakened; thus, -acetanilide is weaker than aniline, and acetylphenylhydrazine is weaker -than phenylhydrazine. If the hydrogen of the imido group be replaced by -an alkyl or an acid radical, and therefore tertiary bound nitrogen -restored, the poisonous action is also weakened. - -In xanthin there are three imido groups; the hydrogen of two of these -groups is replaced by methyl in theobromin; and in caffein the three -hydrogens of the three imido groups are replaced by three methyls, -thus:-- - - NH--CH - | || - CO C--NH - | | \ - | | CO - | | / - NH--C==N - - Xanthin. - - N.CH_{3}--CH - | || - CO C--N.CH_{3} - | | \ - | | CO - | | / - NH-----C==N - - Theobromin. - - N.CH_{3}--CH - | || - CO C--N.CH_{3} - | | \ - | | CO - | | / - N.CH_{3}--C==N - - Caffein. - -and experiment has shown that theobromin is weaker than xanthin, and -caffein still weaker than theobromin. - -Loew[39] makes the following generalisations:-- - -[39] _Ein natuerliches System der Gift-Wirkungen_, Muenchen, 1893. - -1. Entrance of the carboxyl or sulpho groups weakens toxic action. - -2. Entrance of a chlorine atom exalts the toxic character of the -catalytic poisons (Loew's catalytic poisons are alcohols, ether, -chloroform, chloral, carbon tetrachloride, methylal, carbon disulphide -and volatile hydrocarbons). - -3. Entrance of hydroxyl groups in the catalytic poisons of the fatty -series weakens toxic character; on the other hand, it exalts the -toxicity of the substituting poisons. (Examples of Loew's class of -"substituting" poisons are hydroxylamine, phenylhydrazine, hydric -cyanide, hydric sulphide, aldehyde, and the phenols.) - -4. A substance increases in poisonous character through every influence -which increases its power of reaction with aldehyde or amido groups. If, -for example, an amido or imido group in the poison molecule be made more -"labile," or if thrice linked nitrogen is converted into nitrogen -connected by two bands, whether through addition of water or -transposition (_umlagerung_) or if a second amido group enters, the -poisonous quality is increased. Presence of a negative group may modify -the action. - -5. Entrance of a nitro group strengthens the poisonous character. If a -carboxyl or a sulpho group is present in the molecule, or if, in passing -through the animal body, negative groups combine with the poison -molecule, or carboxyl groups are formed in the said molecule; in such -cases the poisonous character of the nitro group may not be apparent. - -6. Substances with double carbon linkings are more poisonous than the -corresponding saturated substances. Thus neurine with the double linking -of the carbon of CH_{2} is more poisonous than choline; vinylamine than -ethylamine. - - CH==CH_{2} - / - (CH_{3})_{3}N - \ - OH - - Neurine. - - CH_{2}--CH_{2}OH - / - (CH_{3})_{3}N - \ - OH - - Choline. - - CH_{2} - || - CH.NH_{2} - - Vinylamine. - - CH_{3} - | - CH_{2}.NH_{2} - - Ethylamine. - -Sec. 27. M. Ch. Michet[40] has investigated the comparative toxicity of the -metals by experiments on fish, using species of _Serranus_, -_Crenolabrus_, and _Julius_. The chloride of the metal was dissolved in -water and diluted until just that strength was attained in which the -fish would live 48 hours; this, when expressed in grammes per litre, he -called "_the limit of toxicity_." - -[40] "_De la Toxicite comparee des differents Metaux._" _Note de M. Ch. -Michet. Compt. Rend._, t. xciii., 1881, p. 649. - -The following is the main result of the inquiry, by which it will be -seen that there was found no relation between "the limit of toxicity" -and the atomic weight. - -TABLE SHOWING THE RESULTS OF EXPERIMENTS ON FISH. - - No. of Limit of - Experiments. Metal. Toxicity. - - 20. Mercury, .00029 - 7. Copper, .0033 - 20. Zinc, .0084 - 10. Iron, .014 - 7. Cadmium, .017 - 6. Ammonium, .064 - 7. Potassium, .10 - 10. Nickel, .126 - 9. Cobalt, .126 - 11. Lithium, .3 - 20. Manganese .30 - 6. Barium, .78 - 4. Magnesium, 1.5 - 20. Strontium, 2.2 - 5. Calcium, 2.4 - 6. Sodium, 24.17 - - -V.--Life-Tests; or the Identification of Poison by Experiments on -Animals. - -Sec. 28. A philosophical investigation of poisons demands a complete -methodical examination into their action on every life form, from the -lowest to the highest. Our knowledge is more definite with regard to the -action of poisons on man, dogs, cats, rabbits, and frogs than on any -other species. It may be convenient here to make a few general remarks -as to the action of poisons on infusoria, the cephalopoda, and insects. - -=Infusoria.=--The infusoria are extremely sensitive to the poisonous -alkaloids and other chemical agents. Strong doses of the alkaloids cause -a contraction of the cell contents, and somewhat rapid disintegration of -the whole body; moderate doses at first quicken the movements, then the -body gets perceptibly larger, and finally, as in the first case, there -is disintegration of the animal substance. - -Rossbach[41] gives the following intimations of the proportion of the -toxic principle necessary to cause death:--Strychnine 1 part dissolved -in 1500 of water; veratrine 1 in 8000; quinine 1 in 5000; atropine 1 in -1000; the mineral acids 1 in 400-600; salts 1 in 200-300. - -[41] N. J. Rossbach, _Pharm. Zeitschr. fuer Russland_, xix. 628. - -The extraordinary sensitiveness of the infusoria, and the small amount -of material used in such experiments, would be practically useful if -there were any decided difference in the symptoms produced by different -poisons. But no one could be at all certain of even the class to which -the poison belongs were he to watch, without a previous knowledge of -what had been added to the water, the motions of poisoned infusoria. -Hence the fact is more curious than useful. - -=Cephalopoda.=--The action of a few poisons on the cephalopoda has been -investigated by M. E. Yung.[42] Curara placed on the skin had no effect, -but on the branchiae led to general paralysis. If given in even fifteen -times a greater dose than necessary to kill a rabbit, it was not always -fatal. Strychnine, dissolved in sea-water, in the proportion of 1 to -30,000, causes most marked symptoms. The first sign is relaxation of the -chromataphore muscle and the closing of the chromataphores; the animal -pales, the respiratory movements become more powerful, and at the end of -a notable augmentation in their number, they fall rapidly from the -normal number of 25 to 5 a minute. Then tetanus commences after a time, -varying with the dose of the poison; the arm stiffens and extends in -fan-like form, the entire body is convulsed, the respiration is in -jerks, the animal empties his pouch, and at the end of a few minutes is -dead, in a state of great muscular rigidity. If at this moment it is -opened, the venous heart is found still beating. Nicotine and other -poisons were experimented with, and the cephalopoda were found to be -generally sensitive to the active alkaloids, and to exhibit more or less -marked symptoms. - -[42] _Compt. Rend._, t. xci. p. 306. - -=Insects.=--The author devoted considerable time, in the autumn of 1882, -to observations on the effect of certain alkaloids on the common -blow-fly, thinking it possible that the insect would exhibit a -sufficient series of symptoms of physiological phenomena to enable it to -be used by the toxicologist as a living reagent. If so, the cheapness -and ubiquity of the tiny life during a considerable portion of the year -would recommend it for the purpose. Provided two blow-flies are caught -and placed beneath glass shades--the one poisoned, the other not--it is -surprising what a variety of symptoms can, with a little practice, be -distinguished. Nevertheless, the absence of pupils, and the want of -respiratory and cardiac movements, are, in an experimental point of -view, defects for which no amount or variety of merely muscular symptoms -can compensate. - -From the nature of the case, we can only distinguish in the poisoned fly -dulness or vivacity of movement, loss of power in walking on smooth -surfaces, irritation of the integument, disorderly movements of the -limbs, protrusion of the fleshy proboscis, and paralysis, whether of -legs or wings. My experiments were chiefly made by smearing the extracts -or neutral solutions of poisons on the head of the fly. In this way some -of it is invariably taken into the system, partly by direct absorption, -and partly by the insect's efforts to free itself from the foreign -substance, in which it uses its legs and proboscis. For the symptoms -witnessed after the application of saponin, digitalin, and aconitine, -the reader is referred to the articles on those substances. - -In poisoning by sausages, bad meat, curarine, and in obscure cases -generally, in the present state of science, experiments on living -animals are absolutely necessary. In this, and in this way only, in very -many instances, can the expert prove the presence of zymotic, or show -the absence of chemical poison. - -The Vivisection Act, however, effectually precludes the use of -life-tests in England save in licensed institutions. Hence the "methods" -of applying life-tests described in former editions will be omitted. - - Sec. 29. =Effect of poisons on the heart of Cold-blooded Animals.=--The - Vivisection Act does not, however, interfere with the use of certain - living tests, such, for instance, as the testing of the action of - poisons upon the recently extirpated hearts of cold-blooded animals. - -[Illustration: Williams' Apparatus.] - - The heart of the frog, of the turtle, of the tortoise, and of the - shark will beat regularly for a long time after removal from the - body, if supplied with a regular stream of nutrient fluid. The - fluids used for this purpose are the blood of the herbivora diluted - with common salt solution, or a serum albumin solution, or a 2 per - cent. solution of gum arabic in which red blood corpuscles are - suspended. The simplest apparatus to use is that known as - "Williams'." Williams' apparatus consists of two glass bulbs (see - diagram), the one, P, containing nutrient fluid to which a known - quantity of the poison has been added; the other, N, containing the - same fluid but to which no poison has been added; these bulbs are - connected by caoutchouc tubing to a three-way tube, T, and each - piece of caoutchouc tubing has a pressure screw clip, V^{1} and V; - the three-way tube is connected with a wider tube containing a valve - float, F, which gives free passage of fluid in one direction only, - that is, in the direction of the arrow; this last wide tube is - connected with a Y piece of tubing, which again is connected with - the aorta of the heart under examination, the other leg of the Y - tube is connected with another wide tube, X, having a float valve, - F^{2}: the float containing a drop of mercury and permitting (like - the float valve F) passage in one direction only of fluid, it is - obvious that if the clip communicating with N is opened and the clip - communicating with P is closed, the normal fluid will circulate - alone through the heart; if, on the other hand, the P clip is open - and the N clip closed, the poisoned blood will alone feed the heart. - It is also clear that by raising or depressing the bulbs, the - circulating fluid can be delivered at any pressure, high or low. - Should a bubble of air get into the tubes, it can be got rid of by - removing the cork at S and bringing the fluid up to the level of the - top of the aperture. The observation is made by first ascertaining - the number and character of the beats when the normal fluid is - circulating, and then afterwards when the normal is replaced by the - poisoned fluid. A simpler but less accurate process is to pith two - frogs, excise their respective hearts, and place the hearts in - watch-glasses containing either serum or a solution of common salt - (strength 0.75 per cent.); to the one heart is now added a solution - of the poison under examination, and the difference in the behaviour - and character of the beats noted. - - The phenomena to be specially looked for are the following:-- - - 1. The heart at the height of the poisoning is arrested in diastole. - 2. The heart at the height of the poisoning is arrested in systole. - - =Arrest in diastole.=--The arrest may be preceded by the - contractions becoming weaker and weaker, or after the so-called - heart peristalsis; or it may be preceded by a condition in which the - auricle shows a different frequency to the ventricle. - - The final diastole may be the diastole of paralysis or the diastole - of irritation. - - The diastole of irritation is produced by a stimulus of the - inhibitory ganglia, and only occurs after poisoning by the muscarine - group of poisons. This condition may be recognised by the fact that - contraction may be excited by mechanical and electrical stimuli or - by the application of atropine solution; the latter paralyses the - inhibitory nervous centres, and therefore sets the mechanism going - again. The diastole of paralysis is the most frequent form of death. - It may readily be distinguished from the muscarine diastole; for, in - muscarine diastole, the heart is full of blood and larger than - normal; but in the paralytic form the heart is not fully extended, - besides which, although, if normal blood replace that which is - poisoned, the beats may be restored for a short time, the response - is incomplete, and the end is the same; besides which, atropine does - not restore the beats. The diastole of paralysis may depend on - paralysis of the so-called excito-motor ganglia (as with iodal), or - from paralysis of the muscular structure (as with copper). - - Sec. 30. =The effect of poisons on the iris.=--Several poisons affect - the pupil, causing either contraction or dilatation. The most - suitable animal is the cat; the pupil of the cat readily showing - either state. - - =Toxic myosis, or toxic contraction of the pupil.=--There are two - forms of toxic myosis, one of which is central in its origin. In - this form, should the poison be applied to the eye itself, no marked - contraction follows; the poison must be swallowed or injected - subcutaneously to produce an effect. The contraction remains until - death. - - The contraction in such a case is considered to be due to a - paralysis of the dilatation centre; it is a "_myosis paralytica - centralis_;" the best example of this is the contraction of the - pupil caused by morphine. - - In the second case the poison, whether applied direct to the eye or - entering the circulation by subcutaneous injection, contracts the - pupil; the contraction persists if the eye is extirpated, but in all - cases the contraction may be changed into dilatation by the use of - atropine. An example of this kind of myosis is the action of - muscarine. It is dependent on the stimulation of the ends of the - nerves which contract the pupil, especially the ends of the _nervus - oculomotorius_ supplying the sphincter iridis; this form of myosis - is called _myosis spastica periphera_. A variety of this form is the - _myosis spastica muscularis_, depending on stimulation of the musc. - sphincter iridis, seen in poisoning by physostigmine. This causes - strong contraction of the pupil when locally applied; the - contraction is not influenced by small local applications of - atropine, but it may be changed to dilatation by high doses. - Subcutaneous injection of small doses of physostigmine does not - alter the pupil, but large poisonous doses contracts the pupil in a - marked manner. - - =Toxic mydriasis, or toxic dilatation of the pupil.=--The following - varieties are to be noticed:-- - - 1. Toxic doses taken by the mouth or given by subcutaneous injection - give rise to strong dilatation; this vanishes before death, giving - place to moderate contraction. This form is due to stimulation of - the dilatation centre, later passing into paralysis. An example is - found in the action of aconite. - - 2. After subcutaneous or local application, a dilatation neutralised - by physostigmine in moderate doses. This is characteristic of - [beta]-tetrahydronaphthylamine. - - 3. After subcutaneous injection, or if applied locally in very small - doses, dilatation occurs persisting to death. Large doses of - physostigmine neutralise the dilatation, but it is not influenced by - muscarine or pilocarpine: this form is characteristic of atropine, - and it has been called _mydriasis paralytica periphera_. - - The heart at the height of the poisoning stops in systole. - - =2. Arrest in systole.=--The systole preceding the arrest is far - stronger than normal, the ventricle often contracting up into a - little lump. Contraction of this kind is specially to be seen in - poisoning by digitalis. In poisoning by digitalis the ventricle is - arrested before the auricle; in muscarine poisoning the auricle - stops before the ventricle. If the reservoir of Williams' apparatus - is raised so as to increase the pressure within the ventricle the - beat may be restored for a time, to again cease. - - A frog's heart under the influence of any poison may be finally - divided into pieces so as to ascertain if any parts still contract; - the significance of this is, that the particular ganglion supplying - that portion of the heart has not been affected: the chief ganglia - to be looked for are Remak's, on the boundary of the sinus and - auricle; Ludwig's, on the auricle and the septum of the auricle; - Bidder's, on the atrioventricular border, especially in the valves; - and Dogiel's ganglion, between the muscular fibres. According to - Dogiel, poisons acting like muscarine affect every portion of the - heart, and atropine restores the contractile power of every portion. - - -VI.--General Method of Procedure in Searching for Poison. - -Sec. 31. Mineral substances, or liquids containing only inorganic matters, -can cause no possible difficulty to any one who is practised in -analytical investigation; but the substances which exercise the skill of -the expert are organic fluids or solids. - -The first thing to be done is to note accurately the manner in which the -samples have been packed, whether the seals have been tampered with, -whether the vessels or wrappers themselves are likely to have -contaminated the articles sent; and then to make a very careful -observation of the appearance, smell, colour, and reaction of the -matters, not forgetting to take the weight, if solid--the volume, if -liquid. All these are obvious precautions, requiring no particular -directions. - -If the object of research is the stomach and its contents, the contents -should be carefully transferred to a tall conical glass; the organ cut -open, spread out on a sheet of glass, and examined minutely by a lens, -picking out any suspicious-looking substance for closer observation. -The mucous membrane should now be well cleansed by the aid of a -wash-bottle, and if there is any necessity for destroying the stomach, -it may be essential in important cases to have it photographed. The -washings having been added to the contents of the stomach, the sediment -is separated and submitted to inspection, for it must be remembered -that, irrespective of the discovery of poison, a knowledge of the nature -of the food last eaten by the deceased may be of extreme value. - -If the death has really taken place from disease, and not from poison, -or if it has been caused by poison, and yet no definite hint of the -particular poison can be obtained either by the symptoms or by the -attendant circumstances, the analyst has the difficult task of -endeavouring to initiate a process of analysis which will be likely to -discover any poison in the animal, vegetable, or mineral kingdom. For -this purpose I have devised the following process, which differs from -those that have hitherto been published mainly in the prominence given -to operations in a high vacuum, and the utilisation of biological -experiment as a matter of routine. Taking one of the most difficult -cases that can occur--viz., one in which a small quantity only of an -organic solid or fluid is available--the best method of procedure is the -following:-- - -[Illustration] - -A small portion is reserved and examined microscopically, and, if -thought desirable, submitted to various "cultivation" experiments. The -greater portion is at once examined for volatile matters, and having -been placed in a strong flask, and, if neutral or alkaline, feebly -acidulated with tartaric acid, connected with a second or receiving -flask by glass tubing and caoutchouc corks. The caoutchouc cork of the -receiving flask has a double perforation, so as to be able, by a second -bit of angle tubing, to be connected with the mercury-pump described in -the author's work on "Foods," the figure of which is here repeated (see -the accompanying figure). With a good water-pump having a sufficient -length of fall-tube, a vacuum may be also obtained that for practical -purposes is as efficient as one caused by mercury; if the fall-tube -delivers outside the laboratory over a drain, no offensive odour is -experienced when dealing with putrid, stinking liquids. A vacuum having -been obtained, and the receiving-flask surrounded with ice, a distillate -for preliminary testing may be generally got without the action of any -external heat; but if this is too slow, the flask containing the -substances or liquid under examination may be gently heated by a -water-bath--water, volatile oils, a variety of volatile substances, such -as prussic acid, hydrochloric acid, phosphorus, &c., if present, will -distil over. It will be well to free in this way the substance, as much -as possible, from volatile matters and water. When no more will come -over, the distillate may be carefully examined by redistillation and the -various appropriate tests. - -[Illustration: This figure is from "Foods." B is a bell-jar, which can -be adapted by a cork to a condenser; R is made of iron; the rim of the -bell-jar is immersed in mercury, which the deep groove receives.] - -The next step is to dry the sample thoroughly. This is best effected -also in a vacuum by the use of the same apparatus, only this time the -receiving-flask is to be half filled with strong sulphuric acid. By now -applying very gentle heat to the first flask, and cooling the sulphuric -acid receiver, even such substances as the liver in twenty-four hours -may be obtained dry enough to powder. - -Having by these means obtained a nearly dry friable mass, it is reduced -to a coarse powder, and extracted with petroleum ether; the extraction -may be effected either in a special apparatus (as, for example, in a -large "Soxhlet"), or in a beaker placed in the "Ether recovery -apparatus" (see fig.), which is adapted to an upright condenser. The -petroleum extract is evaporated and leaves the fatty matter, possibly -contaminated by traces of any alkaloid which the substance may have -contained; for, although most alkaloids are insoluble in petroleum -ether, yet they are taken up in small quantities by oils and fats, and -are extracted with the fat by petroleum ether. It is hence necessary -always to examine the petroleum extract by shaking it up with water, -slightly acidulated with sulphuric acid, which will extract from the fat -any trace of alkaloid, and will permit the discovery of such alkaloids -by the ordinary "group reagents." - -The substance now being freed for the most part from water and from fat, -is digested in the cold with absolute alcohol for some hours; the -alcohol is filtered off, and allowed to evaporate spontaneously, or, if -speed is an object, it may be distilled _in vacuo_. The treatment is -next with hot alcohol of 90 per cent., and, after filtering, the dry -residue is exhausted with ether. The ether and alcohol, having been -driven off, leave extracts which may be dissolved in water and tested, -both chemically and biologically, for alkaloids, glucosides, and organic -acids. It must also be remembered that there are a few metallic -compounds (as, for example, corrosive sublimate) which are soluble in -alcohol and ethereal solvents, and must not be overlooked. - -The residue, after being thus acted upon successively by petroleum, by -alcohol, and by ether, is both water-free and fat-free, and also devoid -of all organic poisonous bases and principles, and it only remains to -treat it for metals. For this purpose, it is placed in a retort, and -distilled once or twice to dryness with a known quantity of strong, pure -hydrochloric acid. - -If arsenic, in the form of arsenious acid, were present, it would distil -over as a trichloride, and be detected in the distillate; by raising the -heat, the organic matter is carbonised, and most of it destroyed. The -distillate is saturated with hydric sulphide, and any precipitate -separated and examined. The residue in the retort will contain the fixed -metals, such as zinc, copper, lead, &c. It is treated with dilute -hydrochloric acid, filtered, the filtrate saturated with SH_{2} and any -precipitate collected. The filtrate is now treated with sufficient sodic -acetate to replace the hydric chloride, again saturated with SH_{2} and -any precipitate collected and tested for _zinc_, _nickel_, and _cobalt_. -By this treatment, viz.:-- - - 1. Distillation in a vacuum at a low temperature, - 2. Collecting the volatile products, - 3. Dehydrating the organic substances, - 4. Dissolving out from the dry mass fatty matters and alkaloids, - glucosides, &c., by ethereal and alcoholic solvents, - 5. Destroying organic matter and searching for metals, - ---a very fair and complete analysis may be made from a small amount of -material. The process is, however, somewhat faulty in reference to -phosphorus, and also to oxalic acid and the oxalates; these poisons, if -suspected, should be specially searched for in the manner to be more -particularly described in the sections treating of them. In most cases, -there is sufficient material to allow of division into three parts--one -for organic poisons generally, one for inorganic, and a third for -reserve in case of accident. When such is the case, although, for -organic principles, the process of vacuum distillation just described -still holds good, it will be very much the most convenient way not to -use that portion for metals, but to operate on the portion reserved for -the inorganic poisons as follows by destruction of the organic matter. - -The destruction of organic matter through simple distillation by means -of pure hydrochloric acid is at least equal to that by sulphuric acid, -chlorate of potash, and the carbonisation methods. The object of the -chemist not being to dissolve every fragment of cellular tissue, muscle, -and tendon, but simply all mineral ingredients, the less organic matter -which goes into solution the better. That hydrochloric acid would fail -to dissolve sulphate of baryta and sulphate of lead, and that sulphide -of arsenic is also almost insoluble in the acid, is no objection to the -process recommended, for it is always open to the analyst to treat the -residue specially for these substances. The sulphides precipitated by -hydric sulphide from an acid solution are--arsenic, antimony, tin, -cadmium, lead, bismuth, mercury, copper, and silver. Those not -precipitated are--iron, manganese, zinc, nickel, and cobalt. - -As a rule, one poison alone is present; so that if there should be a -sulphide, it will belong only exceptionally to more than one metal. - -The colour of the precipitate from hydric sulphide is either yellowish -or black. The yellow and orange precipitates are sulphur, sulphides of -arsenic, antimony, tin, and cadmium. In pure solutions they may be -almost distinguished by their different hues, but in solutions -contaminated by a little organic matter the colours may not be -distinctive. The sulphide of arsenic is of a pale yellow colour; and if -the very improbable circumstance should happen that arsenic, antimony, -and cadmium occur in the same solution, the sulphide of arsenic may be -first separated by ammonia, and the sulphide of antimony by sulphide of -sodium, leaving cadmic sulphide insoluble in both processes. - -The black precipitates are--lead, bismuth, mercury, copper, and silver. -The black sulphide is freed from arsenic, if present, by ammonia, and -digested with dilute nitric acid, which will dissolve all the sulphides, -save those of mercury and tin, so that if a complete solution is -obtained (sulphur flocks excepted), it is evident that both these -substances are absent. The presence of copper is betrayed by the blue -colour of the nitric acid solution, and through its special reactions; -lead, by the deep yellow precipitate which falls by the addition of -chromate of potash and acetate of soda to the solution; bismuth, through -a white precipitate on dilution with water. If the nitric acid leaves a -black insoluble residue, this is probably sulphide of mercury, and -should be treated with concentrated hydrochloric acid to separate flocks -of sulphur, evaporated to dryness, again dissolved, and tested for -mercury by iodide of potassium, copper foil, &c., as described in the -article on _Mercury_. Zinc, nickel, and cobalt are likewise tested for -in the filtrate as described in the respective articles on these metals. - - -AUTENRIETH'S GENERAL PROCESS. - - Sec. 32. A general method of procedure has been published by W. - Autenrieth.[43] - -[43] _Kurze Anleitung zur Auffindung der Gifte_, Freiburg, 1892. - - He divides poisonous substances, for the purposes of separation and - detection, into three classes:-- - - I. Poisons capable of distillation from an acid aqueous solution. - II. Organic substances which are not capable of distillation from - acid solutions. - III. Metallic poisons. - - Where possible, the fluid or solids submitted to the research are - divided into four equal parts, one of the parts to be kept in - reserve in case of accident or as a control; one of the remaining - three parts to be distilled; a second to be investigated for organic - substances; and a third for metals. After the extraction of organic - substances from part No. II. the residue may be added to No. III. - for the purpose of search after metals; and, if the total quantity - is small, the whole of the process may be conducted without - division. - - -I. SUBSTANCES SEPARATED BY DISTILLATION. - - The substances are placed in a capacious flask, diluted if necessary - with water to the consistence of a thin soup, and tartaric acid - added to distinct acid reaction, and distilled. - - In this way phosphorus, prussic acid, carbolic acid, chloroform, - chloral hydrate, nitrobenzol, aniline,[44] and alcohol may be - separated and identified by the reactions given in the sections of - this work describing those substances. - -[44] Aniline is a weak base, so that, although a solution be acid, some -of the aniline distils over on heating. - - -II. ORGANIC POISONS NOT VOLATILE IN ACID SOLUTION. - - Part No. II. is mixed with double its volume of absolute alcohol, - tartaric acid added to distinct acid reaction and placed in a flask - connected with an inverted Liebig's condenser; it is then warmed for - 15 to 20 minutes on the water-bath. After cooling, the mixture is - filtered, the residue well washed with alcohol and evaporated to a - thin syrup in a porcelain dish over the water-bath. The dish is then - allowed to cool and digested with 100 c.c. of water; fat and - resinous matters separate, the watery solution is filtered through - Swedish paper previously moistened: if the fluid filtrate is clear - it may be at once shaken up with ether, but if not clear, and - especially if it is more or less slimy, it is evaporated again on - the water-bath to the consistence of an extract: the extract treated - with 60 to 80 c.c. of absolute alcohol (which precipitates mucus and - dextrin-like substances), the alcohol evaporated off and the residue - taken up with from 60 to 80 c.c. of distilled water; it is then - shaken up with ether, as in Dragendorff's process, and such - substances as digitalin, picric acid, salicylic acid, antipyrin and - others separated in this way and identified. - - After this treatment with ether, and the separation of the ether - extract, the watery solution is strongly alkalised with caustic soda - and shaken up again with ether, which dissolves almost every - alkaloid save morphine and apomorphine; the ethereal extract is - separated and any alkaloid left identified by suitable tests. - - The aqueous solution, now deprived of substances soluble in ether - both from acid and from solutions made alkaline by soda, is now - investigated for morphine and apomorphine; the apomorphine being - separated by first acidifying a portion of the alkaline solution - with hydrochloric acid, then alkalising with ammonia and shaking out - with ether. The morphine is separated from the same solution by - shaking out with warm chloroform.[45] - -[45] Hot amyl alcohol would be better (see "Morphine"). - - -III. METALS. - - The substances are placed in a porcelain dish and diluted with a - sufficient quantity of water to form a thin soup and 20 to 30 c.c. - of pure hydrochloric acid added; the dish is placed on the - water-bath and 2 grms. of potassic chlorate added. The contents are - stirred from time to time, and successive quantities of potassic - chlorate are again added, until the contents are coloured yellow. - The heating is continued, with, if necessary, the addition of more - acid, until all smell of chlorine has ceased. If there is - considerable excess of acid, this is to be evaporated away by - diluting with a little water and continuing to heat on the - water-bath. The dish with its contents is cooled, a little water - added, and the fluid is then filtered. - - The metals remaining on the filter are:-- - - Silver chloride, - Lead sulphate, - Barium sulphate; - - in the filtrate will be all the other metals. - - The filtrate is put in a flask and heated to from 60 to 80 degrees - and submitted to a slow stream of hydric sulphide gas; when the - fluid is saturated with the gas, the flask is securely corked and - allowed to rest for twelve hours; at the end of that time the fluid - is filtered and the filter washed with water saturated with hydric - sulphide. - - The still moist sulphides remaining on the filter are treated with - yellow ammonium sulphide containing some free ammonia and washed - with sulphide of ammonium water. Now remaining on the filter, if - present at all, will be:-- - - Mercury sulphide, - Lead sulphide, - Copper sulphide, - Cadmium sulphide; - - in the filtrate may be:-- - - Arsenic sulphide, - Antimony sulphide, - Tin sulphide, - - and there may also be a small portion of copper sulphide, because - the latter is somewhat soluble in a considerable quantity of - ammonium sulphide. - - The filtrate from the original hydric sulphide precipitate will - contain, if present, the sulphides of zinc and chromium in solution. - - -INVESTIGATION OF THE SULPHIDES SOLUBLE IN AMMONIUM SULPHIDE, VIZ., -ARSENIC, ANTIMONY, TIN. - - The ammonium sulphide solution is evaporated to dryness in a - porcelain dish, strong nitric acid added and again dried. To this - residue a little strong caustic soda solution is added, and then it - is intimately mixed with three times its weight of a mixture - composed of 2 of potassic nitrate to 1 of dry sodium hydrate. This - is now cast, bit by bit, into a red-hot porcelain crucible. The - whole is heated until it has melted into a colourless fluid. - - Presuming the original mass contained arsenic, antimony, and tin, - the melt contains sodic arseniate, sodic pyro-antimonate, sodic - stannate, and tin oxide; it may also contain a trace of copper - oxide. - - The melt is cooled, dissolved in a little water, and sodium - bicarbonate added so as to change any caustic soda remaining into - carbonate, and to decompose the small amount of sodic stannate; the - liquid is then filtered. - - The filtrate will contain the arsenic as sodic arseniate; while on - the filter there will be pyro-antimonate of soda, tin oxide, and, - possibly, a little copper oxide. - - The recognition of these substances now is not difficult (see the - separate articles on _Antimony_, _Tin_, _Zinc_, _Arsenic_, - _Copper_). - - -INVESTIGATION OF THE SULPHIDES INSOLUBLE IN SULPHIDE OF AMMONIUM, VIZ., -MERCURY, LEAD, COPPER, CADMIUM. - - If the precipitate is contaminated with organic matter, it is - treated with hydrochloric acid and potassic chlorate in the manner - already described, p. 51. - - Afterwards it is once more saturated with hydric sulphide, the - precipitate is collected on a filter, well washed, and the sulphides - treated with moderately concentrated nitric acid (1 vol. nitric - acid, 2 vols. water). The sulphides are best treated with this - solvent on the filter; all the sulphides mentioned, save mercury - sulphide, dissolve and pass into the filtrate. This mercury sulphide - may be dissolved by nitro-muriatic acid, the solution evaporated to - dryness, the residue dissolved in water acidified with hydrochloric - acid and tested for mercury (see "Mercury"). - - The filtrate containing, it may be, nitrates of lead, copper and - cadmium is evaporated nearly to dryness and taken up in a very - little water. The lead is separated as sulphate by the addition of - dilute sulphuric acid. - - The filtered solution, freed from lead, is treated with ammonia to - alkaline reaction; if copper be present, a blue colour is produced, - and this may be confirmed by other tests (see "Copper"). To detect - cadmium in the presence of copper, potassic cyanide is added to the - blue liquid until complete decolorisation, and the liquid treated - with SH_{2}; if cadmium be present, it is thrown down as a yellow - sulphide, while potassic cupro-cyanide remains in solution. - - -SEARCH FOR ZINC AND CHROMIUM. - - The filtrate from the hydric sulphide precipitate is divided into - two parts; the one half is used in the search for zinc, the other - half is used for chromium. - - =Search for Zinc.=--The liquid is alkalised with ammonia and then - ammonium sulphide is added. There will always be a precipitate of a - dark colour; the precipitate will contain earthy phosphates, iron - and, in some cases, manganese. The liquid with the precipitate is - treated with acetic acid to strong acid reaction and allowed to - stand for several hours. The portion of the precipitate remaining - undissolved is collected on a filter, washed, dried and heated to - redness in a porcelain crucible. The residue thus heated is cooled - and dissolved in a little dilute sulphuric acid. To the acid - solution ammonia is added, and any precipitate formed is treated - with acetic acid; should the precipitate not completely dissolve, - phosphate of iron is present; this is filtered off, and if SH_{2} be - added to the filtrate, white zinc sulphide will come down (see - "Zinc"). - - =Search for Chromium.=--The second part of the SH_{2} filtrate is - evaporated to a thin extract, mixed with double its weight of sodic - nitrate, dried and cast, little by little, into a red-hot porcelain - crucible. When the whole is fully melted, the crucible is removed - from the flame, cooled, and the mass dissolved in water and - filtered. Any chromium present will now be in solution in the easily - recognised form of potassic chromate (see "Chromium"). - - -INVESTIGATION OF THE RESIDUE (p. 52) AFTER THE TREATMENT OF THE ORIGINAL -SUBSTANCE WITH HYDROCHLORIC ACID AND POTASSIC CHLORATE FOR PRESENCE OF -SILVER CHLORIDE, LEAD AND BARIUM SULPHATES. - - The residue is dried and intimately mixed with three times its - weight of a mixture containing 2 parts of sodic nitrate and 1 part - of sodium hydrate, This is added, little by little, into a red-hot - porcelain crucible. The melted mass is cooled, dissolved in a little - water, a current of CO_{2} passed through the solution to convert - any caustic soda into carbonate, and the solution boiled. The result - will be an insoluble portion consisting of carbonates of lead and - baryta, and of metallic silver. The mixture is filtered; the - insoluble residue on the filter is warmed for some time with dilute - nitric acid; the solution of nitrates of silver, lead and barium are - concentrated on the water-bath nearly to dryness so as to get rid of - any excess of acid, and the nitrates dissolved in water; then the - silver is precipitated by hydrochloric acid, the lead by SH_{2}, and - the barium by sulphuric acid. - - -VII.--The Spectroscope as an aid to the Identification of certain -Poisons. - -Sec. 33. The spectra of many of the metals, of phosphine, of arsine and of -several other inorganic substances are characteristic and easily -obtained. - -It is, however, from the employment of the _micro-spectroscope_ that the -toxicologist is likely to get most assistance. - -[Illustration] - -Oscar Brasch[46] has within the last few years studied spectroscopy in -relation to the alkaloids and organic poisons. Some of these, when mixed -with Froehde's reagent, or with sulphuric acid, or with sulphuric acid -and potassic dichromate, or with nitric acid, give characteristic -colours, and the resulting solutions, when examined by a spectroscope, -for the most part show absorption bands; these bands may, occasionally, -assist materially in the identification of a poison. By far the best -apparatus is a micro-spectroscope of the Sorby and Browning type, to -which is added an apparatus for measuring the position on a scale of the -lines and bands. Seibert and Kraft of Wetzlar make an excellent -instrument, in which a small bright triangle is projected on the -spectrum; this can be moved by a screw, so that the apex may be brought -exactly in the centre of any line or band, and its position read on an -outside scale. The first thing to be done with such an instrument is to -determine the position on the scale of the chief Fraunhofer lines or of -the more characteristic lines of the alkalies and alkaline earths,[47] -the wave lengths of which are accurately known. If, now, the scale -divisions are set out as abscissae, and the wave lengths in millionths of -a millimetre are made the ordinates of a diagram, and an equable curve -plotted out, as fully explained in the author's work on "Foods," it is -easy to convert the numbers on the scale into wave lengths, and so make -the readings applicable to any spectroscope. For the purpose of -graphical illustration the curve method is convenient, and is adopted in -the preceding diagrams, all taken from Oscar Brasch's monograph. Where -the curve is highest there the absorption band is thickest; where the -curve is lowest there the band is weak. The fluid to be examined is -simply placed in a watch-glass, the watch-glass resting on the -microscope stand. - -[46] _Ueber Verwendbarkeit der Spectroscopie zur Unterscheidung der -Farbenreactionen der Gifte im Interesse der forensischen Chemie_, -Dorpat, 1890. - -[47] The alkalies and earths used for this purpose, with their wave -lengths, are as follows: KCl, a line in the red [lambda] 770, in the -violet [lambda] 404. Lithium chloride, red line, 670.5; sodium chloride, -yellow, 589; strontium chloride, line in the blue, 461. It is also -useful to measure the green line of thallium chloride = 535. - -[Illustration: CURVES INDICATING THE POSITION OF ABSORPTION BANDS ON -TREATING CERTAIN ALKALOIDS WITH REAGENTS. - -NOTES TO CURVES INDICATING ABSORPTION BANDS. - - 1. Strychnine, treated with sulphuric acid and potassic dichromate - (violet). - 2. Brucine, treated with potassic nitrate and sulphuric acid (clear - red). - 3. Quebrachine, treated with vanadium sulphate (dark blue). - 4. Quinine, Vogel's reaction (red). - 5. Caffein, Murexid reaction (violet-red). - 6. Dephinoidin, Froehde's reagent (cherry-red). - 7. Veratrine, treated with sulphuric acid (straw-yellow). - 8. " " " (cherry-red). - 9. " " " (carmine-red). - 10. Veratrine, Furfurol reaction (blue-violet). - 11. Sabadillin, treated with sulphuric acid (red). - 12. Veratroidine, " " (brown-red). - 13. Jervine, Furfurol reaction (blue). - 14. Sabadine, " " (blue). - 15. Sabadine, treated with sulphuric acid (cherry-red). - 16. Physostigmine, " " (grass-green). - 17. Morphine, treated with Froehde's reagent and sugar (dark-green). - 18. Narcotine, treated with a mixture of sulphuric acid and nitric - acid (30 drops of sulphuric to 1 drop of nitric), (red). - 19. Codeine, treated with Froehde's reagent and sugar (dark violet). - 20. Papaverine, treated with Froehde's reagent (green-blue). - 21. Sanguinarin, " " (violet-red). - 22. Chelidonin, " sulphate of vanadium (dark green). - 23. Solanin, " sulphuric acid and allowed to stand 4 - hours (brown-red). - 24. Digitalin, " Erdmann's reagent (red). - 25. Aniline, " sulphuric acid and potassic dichromate - (blue).] - -The wave lengths corresponding to the numbers on the scale in the -diagram are as follows:-- - - W.L. - 0 732 - 1 656 - 2 589.2 - 3 549.8 - 4 510.2 - 5 480.0 - 6 458 - 7 438 - - -Examination of Blood, or of Blood-Stains. - -Sec. 34. Spots, supposed to be blood--whether on linen, walls, or -weapons--should, in any important case, be photographed before any -chemical or microscopical examination is undertaken. Blood-spots, -according to the nature of the material to which they are adherent, have -certain naked eye peculiarities--_e.g._, blood on fabrics, if dry, has -at first a clear carmine-red colour, and part of it soaks into the -tissue. If, however, the tissue has been worn some time, or was -originally soiled, either from perspiration, grease, or filth, the -colour may not be obvious or very distinguishable from other stains; -nevertheless, the stains always impart a certain stiffness, as from -starch, to the tissue. If the blood has fallen on such substances as -wood or metal, the spot is black, has a bright glistening surface, and, -if observed by a lens, exhibits radiating fissures and a sort of -pattern, which, according to some, is peculiar to each species; so that -a skilled observer might identify occasionally, from the pattern alone, -the animal whence the blood was derived. The blood is dry and brittle, -and can often be detached, or a splinter of it, as it were, obtained. -The edges of the splinter, if submitted to transmitted light, are -observed to be red. Blood upon iron is frequently very intimately -adherent; this is specially the case if the stain is upon rusty iron, -for haematin forms a compound with iron oxide. Blood may also have to be -recovered from water in which soiled articles have been washed, or from -walls, or from the soil, &c. In such cases the spot is scraped off from -walls, plaster, or masonry, with as little of the foreign matters as may -be. It is also possible to obtain the colouring-matter of blood from its -solution in water, and present it for farther examination in a -concentrated form, by the use of certain precipitating agents (see p. -61). - -In the following scheme for the examination of blood-stains, it is -presumed that only a few spots of blood, or, in any case, a small -quantity, is at the analyst's disposal. - -(1) The dried spot is submitted to the action of a cold saturated -solution of borax. This medium (recommended by Dragendorff)[48] does -certainly dissolve out of linen and cloth blood-colouring matter with -great facility. The best way to steep the spots in the solution is to -scrape the spot off the fabric, and to digest it in about a cubic -centimetre of the borax solution, which must not exceed 40 deg.; the -coloured solution may be placed in a little glass cell, with parallel -walls, .5 centimetre broad, and .1 deep, and submitted to spectroscopic -examination, either by the ordinary spectroscope or by the -micro-spectroscope; if the latter is used, a very minute quantity can be -examined, even a single drop. In order to interpret the results of this -examination properly, it will be necessary to be intimately acquainted -with the spectroscopic appearances of both ancient and fresh blood. - -[48] _Untersuchungen von Blutspuren_ in Maschka's _Handbuch_, Bd. i. -Halfband 2. - -Sec. 35. =Spectroscopic Appearances of Blood.=--If defibrinated blood[49] -be diluted with water until it contains about .01 per cent. of -oxyhaemoglobin, and be examined by a spectroscope, the layer of liquid -being 1 centimetre thick, a single absorption band between the wave -lengths 583 and 575 is observed, and, under favourable circumstances, -there is also to be seen a very weak band from 550 to 532. With -solutions so dilute as this, there is no absorption at either the violet -or the red end of the spectrum. A solution containing .09 per cent. of -oxyhaemoglobin shows very little absorption in the red end, but the -violet end is dark up to about the wave length 428. Two absorption bands -may now be distinctly seen. A solution containing .37 per cent. of -oxyhaemoglobin shows absorption of the red end to about W.L. 720; the -violet is entirely, the blue partly, absorbed to about 453. The bands -are considerably broader, but the centre of the bands occupies the same -relative position. A solution containing as much as .8 per cent. of -oxyhaemoglobin is very dark; the two bands have amalgamated, the red end -of the spectrum is absorbed nearly up to Fraunhofer's line a; the green -is just visible between W.L. 498 and 518. Venous blood, or arterial -blood, which has been treated with reducing agents, such, for example, -as an alkaline sulphide, gives the spectrum of reduced haemoglobin. If -the solution is equivalent to about .2 per cent., a single broad band, -with the edges very little defined, is seen to occupy the space between -W.L. 595 and 538, the band being darkest about 550; both ends of the -spectrum are more absorbed than by a solution of oxyhaemoglobin of the -same strength. In the blood of persons or animals poisoned with hydric -sulphide--to the spectrum of reduced haemoglobin, there is added a weak -absorption band in the red, with its centre nearly corresponding with -the Fraunhofer line C. Blood which has been exposed to carbon oxide has -a distinct spectrum, due, it would seem, to a special combination of -this gas with haemoglobin; in other words, instead of oxygen, the oxygen -of oxyhaemoglobin has been displaced by carbon oxide, and crystals of -carbon oxide-haemoglobin, isomorphous with those of oxyhaemoglobin, may be -obtained by suitable treatment. The spectrum of carbon oxide-haemoglobin, -however, differs so little from that of normal blood, that it is only -comparison with the ordinary spectrum, or careful measurements, which -will enable any person, not very familiar with the different spectra of -blood, to detect it; with careful and painstaking observation the two -spectra are seen to be distinct. The difference between the carbon oxide -and the normal spectrum essentially consists in a slight moving of the -bands nearer to E. According to the measurements of Gamgee, the band -[alpha] of CO-haemoglobin has its centre approximately at W.L. 572, and -the band [beta] has for its centre W.L. from 534 to 538, according to -concentration. If a small quantity of an ammoniacal solution of ferrous -tartrate or citrate be added to blood containing carbon oxide, the bands -do not wholly fade, but persist more or less distinctly; whereas, if the -same solution is added to bright red normal blood, the two bands vanish -instantly and coalesce to form the spectrum of reduced haemoglobin. When -either a solution of haemoglobin or blood is exposed to the air for some -time, it loses its bright red colour, becomes brownish-red, and presents -an acid reaction. On examining the spectrum, the two bands have become -faint, or quite extinct; but there is a new band, the centre of which -(according to Gamgee) occupies W.L. 632, but (according to Preyer) 634. -In solutions of a certain strength, four bands may be seen, but in a -strong solution only one. This change in the spectrum is due to the -passing of the haemoglobin into _methaemoglobin_, which may be considered -as an intermediate stage of decomposition, prior to the breaking up of -the haemoglobin into haematin and proteids. - -[49] In this brief notice of the spectroscopic appearances of the blood, -the measurements in wave lengths are, for the most part, after -Gamgee.--_Text-Book of Physiological Chemistry_, London, 1880. - -A spectrum very similar to that of methaemoglobin is obtained by treating -ancient blood-stains with acetic acid--viz., the spectrum of _acid -haematin_, but the band is nearer to its centre, according to Gamgee, -corresponding to W.L. 640 (according to Preyer, 656.6). The portion of -the band is a little different in alkaline solution, the centre being -about 592. Haematin is one of the bodies into which haemoglobin splits up -by the addition of such agents as strong acetic acid, or by the -decomposing influence of exposure; the view most generally accepted -being that the colouring-matter of the blood is haematin in combination -with one or more albuminoid bodies. The haematin obtained by treating -blood with acetic acid may be dissolved out by ether, and the ethereal -solution then exhibits a remarkable distinctive spectrum. Hence, in the -spectroscopic examination of blood, or solutions of blood, for -medico-legal purposes, if the blood is fresh, the spectrum likely to be -seen is either that of oxyhaemoglobin or haemoglobin; but, if the -blood-stain is not recent, then the spectrum of either haematin or -methaemoglobin. - -The colouring-matter of cochineal, to which alum, potassic carbonate, -and tartrate have been added, gives a spectrum very similar to that of -blood (see "Foods," p. 82); but this is only the case when the solution -is fresh. The colour is at once discharged by chlorine, while the colour -of blood, although changed in hue, remains. The colouring-matter of -certain red feathers, purpurin-sulphuric acid, and a few other reds, -have some similarity to either the haematin or the haemoglobin spectrum, -but the bands do not strictly coincide; besides, no one would trust to a -single test, and none of the colouring-matters other than blood yield -haematin. - -The blood in CO poisoning has also other characteristics. It is of a -peculiar florid vermilion colour, a colour that is very persistent, -lasting for days and even weeks. - -Normal blood mixed with 30 per cent. potash solution forms _greenish_ -streaky clots, while blood charged with CO forms red streaky clots. - -Normal blood diluted to 50 times its volume of water, and then treated -successively with yellow ammonium sulphide in the proportion of 2 to 25 -c.c. of blood, followed by three drops of acetic acid, gives a grey -colour, while CO blood remains bright red. CO blood shaken with 4 times -its volume of lead acetate remains red, but normal blood becomes -brown.[50] - -[50] M. Rubner, _Arch. Hyg._, x. 397. - -Solutions of platinum chloride or zinc chloride give a bright red colour -with CO blood; normal blood is coloured brown or very dark brown. - -Phospho-molybdic acid or 5 per cent. phenol gives a carmine-coloured -precipitate with CO blood, but a reddish-brown precipitate with normal -blood (sensitive to 16 per cent.). - -A mixture of 2 c.c. of dilute acetic acid and 15 c.c. of 20 per cent. -potassic ferrocyanide solution added to 10 c.c. of CO blood produces an -intense bright red; normal blood becomes dark brown. - -Four parts of CO blood, diluted with 4 parts of water and shaken with 3 -vols. of 1 per cent. tannin solution, become at first bright red with a -bluish tinge, and remain so persistently. Normal blood, on the other -hand, also strikes bright red at first, but with a yellowish tinge; at -the end of 1 hour it becomes brownish, and finally in 24 hours grey. -This is stated to be delicate enough to detect 0.0023 per cent. in air. - -If blood be diluted with 40 times its volume of water, and 5 drops of -phenylhydrazin solution be added, CO blood strikes rose-red; normal -blood grey-violet.[51] - -[51] A. Welzel, _Centr. med. Wiss._, xxvii. 732-734. - -Gustave Piotrowski[52] has experimented on the length of time blood -retains CO. The blood of dogs poisoned by this agent was kept in flasks, -and then the gas pumped out by means of a mercury pump on the following -dates:-- - -[52] _Compt. Rend. Soc. de Biol._, v. 433. - - Date. Content of gas in CO. - Jan. 12, 1892, 24.7 per cent. - " 20, " 23.5 " - " 28, " 22.2 " - Feb. 8, " 20.3 " - " 16, " 15.5 " - " 26, " 10.2 " - March 3, " 6.3 " - " 14, " 4.6 " - " 22, " 1.2 " - -The same dog was buried on the 12th of January, and exhumed on March -28th, and the gas pumped out from some of the blood; this gas gave 11.7 -per cent. of CO; hence it is clear that burial preserves CO blood from -change to a certain extent. - -N. Grehant[53] treated the poisoned blood of a dog with acetic acid, and -found it evolved 14.4 c.c. CO from 100 c.c. of blood. - -[53] _Compt. Rend._, cvi. 289. - -Stevenson, in one of the cases detailed at p. 67, found the blood in the -right auricle to contain 0.03 per cent. by weight of CO. - -(2) =Preparation of Haematin Crystals=--(Teichmann's crystals).--A -portion of the borax solution is diluted with 5 or 6 parts of water, and -one or more drops of a 5 or 6 per cent. solution of zinc acetate added, -so long as a brownish-coloured precipitate is thrown down. The -precipitate is filtered off by means of a miniature filter, and then -removed on to a watch-glass. The precipitate may now be dissolved in 1 -or 2 c.c. of acetic acid, and examined by the spectroscope it will show -the spectrum of haematin. A minute crystal of sodic chloride being then -added to the acetic acid solution, it is allowed to evaporate to dryness -at the ordinary temperature, and crystals of haematin hydrochlorate -result. There are other methods of obtaining the crystals. When a drop -of fresh blood is simply boiled with glacial acetic acid, on -evaporation, prismatic crystals are obtained. - -Haematin is insoluble in water, alcohol, chloroform, and in cold dilute -acetic and hydrochloric acids. It may, however, be dissolved in an -alcoholic solution of potassic carbonate, in solutions of the caustic -alkalies, and in boiling acetic and hydrochloric acids. Hoppe-Seyler -ascribes to the crystals the formula C_{68}H_{70}N_{8}Fe_{2}O_{10}2HCl. -Thudichum considers that the pure crystals contain no chlorine, and are -therefore those of haematin. It is the resistance of the haematin to -decomposition and to ordinary solvents that renders it possible to -identify a certain stain to be that of blood, after long periods of -time. Dr. Tidy seems to have been able to obtain blood reactions from a -stain which was supposed to be 100 years old. The crystals are of a -dark-red colour, and present themselves in three forms, of which that of -the rhombic prism is the most common (see fig.). But crystals like _b_, -having six sides, also occur, and also crystals similar to _c_. - -[Illustration] - -If the spot under examination has been scraped off an iron implement the -haematin is not so easily extracted, but Dragendorff states that borax -solution at 50 deg. dissolves it, and separates it from the iron. Felletar -has also extracted blood in combination with iron rust, by means of warm -solution of caustic potash, and, after neutralisation with acetic acid, -has precipitated the haemin by means of tannin, and obtained from the -tannin precipitate, by means of acetic acid, Teichmann's crystals. A -little of the rust may also be placed in a test tube, powdered ammonium -chloride added, also a little strong ammonia, and after a time filtered; -a small quantity of the filtrate is placed on a slide with a crystal of -sodium chloride and evaporated at a gentle heat, then glacial acetic -acid added and allowed to cool; in this way haemin crystals have been -obtained from a crowbar fifty days after having been blood-stained.[54] - -[54] _Brit. Med. Journ._, Feb. 17, 1894. - -(3) =Guaiacum Test.=--This test depends upon the fact that a solution of -haemoglobin develops a beautiful blue colour, if brought into contact -with fresh tincture of guaiacum and peroxide of hydrogen. The simplest -way to obtain this reaction is to moisten the suspected stain with -distilled water; after allowing sufficient time for the water to -dissolve out some of the blood constituents, moisten a bit of -filter-paper with the weak solution thus obtained; drop on to the moist -space a single drop of tincture of guaiacum which has been prepared by -digesting the inner portions of guaiacum resin in alcohol, and which has -been already tested on known blood, so as to ascertain that it is really -good and efficient for the purpose; and, lastly, a few drops of peroxide -of hydrogen. Dragendorff uses his borax solution, and, after a little -dilution with water, adds the tincture and then Heunefeld's turpentine -solution, which is composed of equal parts of absolute alcohol, -chloroform, and French turpentine, to which one part of acetic acid has -been added. The chloroform separates, and, if blood was present, is of a -blue colour. - -Sec. 36. To prove by chemical and physical methods that a certain stain is -that of blood, is often only one step in the inquiry, the next question -being whether the blood is that of man or of animals. The -blood-corpuscles of man are larger than those of any domestic animal -inhabiting Europe. The diameter of the average red blood-corpuscle is -about the 1/126 of a millimetre, or 7.9 [mu].[55] The corpuscles of man -and of mammals, generally speaking, are round, those of birds and -reptiles oval, so that there can be no confusion between man and birds, -fishes or reptiles; if the corpuscles are circular in shape the blood -will be that of a mammal. By careful measurements, Dr. Richardson, of -Pennsylvania, affirms that it is quite possible to distinguish human -blood from that of all common animals. He maintains, and it is true, -that, by using very high magnifying powers and taking much trouble, an -expert can satisfactorily identify human blood, if he has some -half-dozen drops of blood from different animals--such as the sheep, -goat, horse, dog, cat, &c., all fresh at hand for comparison, and _if -the human blood is normal_. However, when we come to the blood of -persons suffering from disease, there are changes in the diameter and -even the form of the corpuscles which much complicate the matter; while, -in blood-stains of any age, the blood-corpuscles, even with the most -artfully-contrived solvent, are so distorted in shape that he would be a -bold man who should venture on any definite conclusion as to whether the -blood was certainly human, more especially if he had to give evidence in -a criminal case. - -[55] 1/3200 of an inch; the Greek letter [mu] is the micro-millimetre, -or 1000th of a millimetre, .00003937 inch. - -Neumann affirms that the pattern which the fibrin or coagulum of the -blood forms is peculiar to each animal, and Dr. Day, of Geelong, has -independently confirmed his researches: this very interesting -observation perhaps has not received the attention it merits. - -When there is sufficient of the blood present to obtain a few milligrms. -of ash, there is a means of distinguishing human blood from that of -other common mammals, which has been neglected by authorities on the -subject, and which may be found of real value. Its principle depends -upon the relative amounts of potassium and sodium in the blood of man as -compared with that in the blood of domestic animals. In the blood of the -cow, sheep, fowl, pig, and horse, the sodium very much exceeds the -potassium in the ash; thus the proportion of sodium oxide to that of -potassium oxide in the blood of the sheep is as K_{2}O .1 : Na_{2}O .6; -in that of the cow, as 1 : 8; in that of the domestic fowl, as 1 : 16; -while the same substances in human blood are sometimes equal, and vary -from 1 : 1 to 1 : 4 as extremes, the mean numbers being as 1 : 2.2. The -potassium is greater in quantity in the blood-corpuscles than in the -blood serum; but, even in blood serum, the same marked differences -between the blood of man and that of many animals is apparent. Thus, the -proportion of potash to soda being as 1 : 10 in human blood, the -proportion in sheep's blood is 1 to 15.7; in horse's serum as 1 to 16.4; -and in the ox as 1 to 17. Since blood, when burnt, leaves from 6 to 7 -per thousand of ash, it follows that a quantitative analysis of the -relative amounts of potassium and sodium can only be satisfactorily -effected when sufficient of the blood is at the analyst's disposal to -give a weighable quantity of mineral matter. On the other hand, much -work requires to be done before this method of determining that the -blood is either human, or, at all events, not that of an herbivorous -animal, can be relied on. We know but little as to the effect of the -ingestion of sodium or potassium salts on either man or animals, and it -is possible--nay, probable--that a more or less entire substitution of -the one for the other may, on certain diets, take place. Bunge seems in -some experiments to have found no sodium in the blood of either the cat -or the dog. - -The source from which the blood has emanated may, in a few cases, be -conjectured from the discovery, by microscopical examination, of hair or -of buccal, nasal, or vaginal epithelium, &c., mixed with the -blood-stain. - - - - -PART III.--POISONOUS GASES: CARBON MONOXIDE--CHLORINE--HYDRIC SULPHIDE. - - -I.--Carbon Monoxide. - -Sec. 37. Carbon monoxide, CO, is a colourless, odourless gas of 0.96709 sp. -gravity. A litre weighs 1.25133 grm. It is practically insoluble in -water. It unites with many metals, forming gaseous or volatile -compounds, _e.g._, nickel carbon oxide, Ni(CO)_{4}, is a fluid -volatilising at 40 deg. These compounds have, so far as is known, the same -effects as CO. - -Whenever carbon is burned with an insufficient supply of air, CO in a -certain quantity is produced. It is always present in ordinary domestic -products of combustion, and must be exhaled from the various chimneys of -a large city in considerable volumes. A "smoky" chimney or a defective -flue will therefore introduce carbon monoxide into living-rooms. The -vapour from burning coke or burning charcoal is rich in carbon monoxide. -It is always a constituent of coal gas, in England the carbon monoxide -in coal gas amounting to about 8 per cent. Poisoning by coal gas is -practically poisoning by carbon monoxide. Carbon monoxide is also the -chief constituent in water gas. - -Carbon monoxide poisoning occurs far more frequently in France and -Germany than in England; in those countries the vapour evolved from -burning charcoal is a favourite method of suicide, on account of the -supposed painlessness of the death. It has also occasionally been used -as an instrument of murder. In this country carbon monoxide poisoning -mainly takes place accidentally as the effect of breathing coal gas; -possibly it is the secret and undetected cause of ill health where -chimneys "smoke"; and it may have something to do with the sore throats -and debility so often noticed when persons breathe for long periods air -contaminated by small leakages of coal gas. - -The large gas-burners (geysers) emit in burning under certain conditions -much carbon monoxide. It has been proved by Grehant[56] that a bunsen -burner "lit below" also evolves large quantities of the same poisonous -gas. - -[56] _Compt. Rend. Soc. de Biol._, ix. 779-780. - -Sec. 38. =Symptoms.=--Nearly all the experience with regard to the symptoms -produced by carbon monoxide is derived from breathing not the pure gas, -but the gas diluted by air, by hydrogen or by carburetted hydrogen, as -in coal gas, or mixed with large quantities of carbon dioxide. Two -assistants of Christison breathed the pure gas: the one took from two to -three inhalations; he immediately became giddy, shivered, had headache -and then became unconscious. The second took a bigger dose, for, after -emptying his lungs as much as possible, he took from three to four -inhalations; he fell back paralysed, became unconscious and remained -half-an-hour insensible and had the appearance of death, the pulse being -almost extinguished. He was treated with inhalations of oxygen, but he -remained for the rest of the day extremely ill; he had convulsive -muscular movements, stupor, headache, and quick irregular pulse; on this -passing away he still suffered from nausea, giddiness, alternate feeling -of heat and chilliness, with some fever, and in the night had a restless -kind of sleep. The chemist Chenot was accidentally poisoned by the pure -gas, and is stated to have fell as if struck by lightning after a single -inspiration, and remained for a quarter of an hour unconscious. Other -recorded cases have shown very similar symptoms. - -The pulse is at the onset large, full and frequent; it afterwards -becomes small, slow and irregular. The temperature sinks from 1 deg. to 3 deg. -C. The respiration at first slow, later becomes rattling. As vomiting -occurs often when the sufferer is insensible, the vomited matters have -been drawn by inspiration into the trachea and even into the bronchi, so -that death takes place by suffocation. - -The fatal coma may last even when the person has been removed from the -gas from hours to days. Coma for three, four and five days from carbon -monoxide has been frequently observed. The longest case on record is -that of a person who was comatose for eight days, and died on the -twelfth day after the fatal inhalation. Consciousness in this case -returned, but the patient again fell into stupor and died. - -The slighter kinds of poisoning by carbon monoxide, as in the -Staffordshire case recorded by Dr. Reid, in which for a long time a much -diluted gas has been breathed, produce pronounced headache and a general -feeling of ill health and _malaise_, deepening, it may be, into a fatal -slumber, unless the person is removed from the deadly atmosphere. To the -headache generally succeeds nausea, a feeling of oppression in the -temples, a noise in the ears, feebleness, anxiety and a dazed condition -deepening into coma. It is probably true that charcoal vapour is -comparatively painless, for when larger amounts of the gas are breathed -the insensibility comes on rapidly and the faces of those who have -succumbed as a rule are placid. Vomiting, without being constant, is a -frequent symptom, and in fatal cases the faeces and urine are passed -involuntarily. There are occasional deviations from this picture; -tetanic strychnine-like convulsions have been noticed and a condition of -excitement in the non-fatal cases as if from alcohol; in still rarer -cases temporary mania has been produced. - -In non-fatal but moderately severe cases of poisoning sequelae follow, -which in some respects imitate the sequelae seen on recovery from the -infectious fevers. A weakness of the understanding, incapacity for -rational and connected thought, and even insanity have been noticed. -There is a special liability to local inflammations, which may pass into -gangrene. Various paralyses have been observed. Eruptions of the skin, -such as herpes, pemphigus and others. Sugar in the urine is an almost -constant concomitant of carbon monoxide poisoning. - -Sec. 39. The poisonous action of carbon monoxide is, without doubt, due to -the fact that it is readily absorbed by the blood, entering into a -definite chemical compound with the haemoglobin; this combination is more -stable than the similar compound with oxygen gas, and is therefore slow -in elimination. - -Hence the blood of an animal remaining in an atmosphere containing -carbon monoxide is continually getting poorer in oxygen, richer in -carbon monoxide. Grehant has shown that if an animal breathes for one -hour a mixture of 0.5 carbon monoxide to 1000 oxygen, the blood contains -at the end of that time one-third less oxygen than normal, and contains -152 times more carbon monoxide than in the mixture. An atmosphere of 10 -per cent. carbon monoxide changes the blood so quickly, that after from -10 to 25 seconds the blood contains 4 per cent. of carbon monoxide, and -after from 75 to 90 seconds 18.4 per cent. Breathing even for half an -hour an atmosphere containing from 0.07 to 0.12 per cent. carbon -monoxide renders a fourth part of the red corpuscles of the blood -incapable of uniting with oxygen. - -The blood is, however, never saturated with carbon monoxide, for the -animal dies long before this takes place. - -The characteristics of the blood and its spectroscopic appearances are -described at p. 58. - -Besides the action on the blood there is an action on the nervous -system. Kobert,[57] in relation to this subject, says:--"That CO has a -direct action on the nervous system is shown in a marked manner when an -atmosphere of oxygen, with at least 20 per cent. carbon oxide, is -breathed; for in the first minute there is acute cramp or total -paralysis of the limbs, when the blood in no way attains the saturation -sufficiently great to account for such symptoms. Geppert has, through a -special research, shown that an animal suffocated by withdrawal of -oxygen, increases the number and depth of the respirations; but when the -animal is submitted to CO, in which case there is quite as much a -withdrawal of oxygen as in the former case, yet the animal is not in a -condition to strengthen its respiratory movements; Geppert hence rightly -concludes that CO must have a primary specific injurious action on the -nerve centres. I (Kobert) am inclined to go a step further, and, on the -ground of unpublished researches, to maintain that CO not only affects -injuriously the ganglion cells of the brain, but also the peripheral -nerves (_e.g._, the phrenic), as well as divers other tissues, as -muscles and glands, and that it causes so rapidly such a high degree of -degeneration as not to be explained through simple slow suffocation; -even gangrene may be caused." - -[57] _Lehrbuch der Intoxicationen_, 526. - -It is this rapid degeneration which is the cause of the enormous -increase of the products of the decomposition of albumin, found -experimentally in animals. - -Sec. 40. =Post-mortem Appearances.=--The face, neck, chest, abdomen are -frequently covered with patches of irregular form and of clear rose-red -or bluish-red colour; these patches are not noticed on the back, and -thus do not depend upon the gravitation of the blood to the lower or -most dependent part of the body; similar red patches have been noticed -in poisoning by prussic acid; the cause of this phenomenon is ascribed -to the paralysis of the small arteries of the skin, which, therefore, -become injected with the changed blood. The blood throughout is -generally fluid, and of a fine peculiar red colour, with a bluish tinge. -The face is mostly calm, pale, and there is seldom any foam about the -lips. Putrefaction is mostly remarkably retarded. There is nearly always -a congestion of some of the internal organs; sometimes, and indeed -usually, the membranes of the brain are strongly injected; sometimes the -congestion is mainly in the lungs, which may be [oe]dematous with -effusion; and in a third class of cases the congestion is most marked in -the abdominal cavity. - -The right heart is commonly filled with blood, and the left side -contains only a little blood. - -Poisoning by a small dose of carbon monoxide may produce but few -striking changes, and then it is only by a careful examination of the -blood that evidence of the real nature of the case will be obtained. - -Sec. 41. =Mass poisonings by Carbon Monoxide.=--An interesting series of -cases of poisoning by water gas occurred at Leeds in 1889, and have been -recorded by Dr. Thos. Stevenson.[58] - -[58] _Guy's Hospital Reports_, 1889. - -Water gas is made by placing coke in a vertical cylinder and heating the -coke to a red heat. Through the red-hot coke, air is forced up from -below for ten minutes; then the air is shut off and steam passes from -above downwards for four minutes; the gas passes through a scrubber, and -then through a ferric oxide purifier to remove SH_{2}. It contains about -50 per cent. of hydrogen and 40 per cent. of carbon monoxide, that is, -about five times more carbon monoxide than coal gas. - -On November 20, 1889, two men, R. French and H. Fenwick, both -intemperate men, occupied a cabin at the Leeds Forge Works; the cabin -was 540 c. feet in capacity, and was lighted by two burners, each -burning 5.5 c. feet of water gas per hour; the cabin was warmed by a -cooking stove, also burning water gas, the products of combustion -escaping into the cabin. Both men went into the cabin after breakfast -(8.30 A.M.). French was seen often going to and fro, and Fenwick was -seen outside at 10.30 A.M. At 11.30 the foreman accompanied French to -the cabin, and found Fenwick asleep, as he thought. At 12.30 P.M. -French's son took the men their dinner, which was afterwards found -uneaten. At that time French also appeared to be asleep; he was shaken -by his son, upon which he nodded to his son to leave. The door of the -cabin appears to have been shut, and all through the morning the lights -kept burning; no smell was experienced. At 2.30 P.M. both the men were -discovered dead. It was subsequently found that the stove was unlighted, -and the water gas supply turned on. - -What attracted most attention to this case was the strange incident at -the _post-mortem_ examination. The autopsies were begun two days after -the death, November 22, in a room of 39,000 c. feet capacity. There were -present Mr. T. Scattergood (senior), Mr. Arthur Scattergood (junior), -Mr. Hargreaves, three local surgeons, Messrs. Brown, Loe and Jessop, and -two assistants, Pugh and Spray. Arthur Scattergood first fainted, Mr. -Scattergood, senior, also had some peculiar sensations, viz., tingling -in the head and slight giddiness; then Mr. Pugh became faint and -staggered; and Mr. Loe, Mr. Brown, and Mr. Spray all complained. - -These symptoms were not produced, as was at first thought, by some -volatile gas or vapour emanating from the bodies of the poisoned men, -but, as subsequently discovered, admitted of a very simple explanation; -eight burners in the room were turned partly on and not lighted, and -each of the eight burners poured water gas into the room. - -In 1891 occurred some cases of poisoning[59] by CO which are probably -unique. The cases in question happened in January in a family at -Darlaston. The first sign of anything unusual having happened to the -family most affected was the fact that up to 9 A.M., Sunday morning, -January 18, none of the family had been seen about. The house was broken -into by the neighbours; and the father, mother, and three children were -found in bed apparently asleep, and all efforts to rouse them utterly -failed. The medical men summoned arrived about 10 A.M. and found the -father and mother in a state of complete unconsciousness, and two of the -children, aged 11 and 14 years, suffering from pain and sickness and -diarrh[oe]a; the third child had by this time been removed to a -neighbouring cottage. - -[59] "Notes on cases of poisoning by the inhalation of carbon monoxide," -by Dr. George Reid, Medical Officer of Health, County of Stafford. -_Public Health_, vol. iii. 364. - -Dr. Partridge, who was in attendance, remained with the patients three -hours, when he also began to suffer from headache; while others, who -remained in the house longer, suffered more severely and complained of -an indefinite feeling of exhaustion. These symptoms pointed to some -exciting cause associated with the surroundings of the cottage; -consequently, in the afternoon the two children were removed to another -cottage, and later on the father and mother also. All the patients, with -the exception of the mother, who was still four days afterwards -suffering from the effects of an acute attack, had completely recovered. -The opinion that the illness was owing to some local cause was -subsequently strengthened by the fact that two canaries and a cat had -died in the night in the kitchen of the cottage; the former in a cage -and the latter in a cupboard, the door of which was open. Also in the -same house on the opposite side of the road, the occupants of which had -for some time suffered from headache and depression, two birds were -found dead in their cage in the kitchen. It is important to notice that -all these animals died in the respective kitchens of the cottages, and, -therefore, on the ground floor, while the families occupied the first -floor. - -The father stated that for a fortnight or three weeks previous to the -serious illness, he and the whole family had complained of severe -frontal headache and a feeling of general depression. This feeling was -continuous day and night in the case of the rest of the family, but in -his case, during the day, after leaving the house for his work, it -gradually passed off, to return again during the night. The headaches -were so intense that the whole family regularly applied vinegar rags to -their heads, on going to bed each night during this period, for about -three weeks. About two o'clock on Sunday morning the headaches became so -severe that the mother got out of bed and renewed the application of -vinegar and water all round, after which they all fell asleep, and, so -far as the father and mother were concerned, remained completely -unconscious until Monday morning. - -A man who occupied the house opposite the house tenanted by the -last-mentioned family informed the narrator (Dr. Reid) that on Sunday -morning the family, consisting of four, were taken seriously ill with a -feeling of sickness and depression accompanied by headache; and he also -stated that for some time they had smelt what he termed a "fire stink" -issuing from the cellar. - -The cottage in which the family lived that had suffered so severely was -situated about 20 or 30 yards from the shaft of a disused coal mine, and -was the end house of a row of cottages. It had a cellar opening into the -outer air, but this opening was usually covered over by means of a piece -of wood. The adjoining house to this, the occupants of which had for -some time suffered from headache, although to a less extent, had a -cellar with a similar opening, but supplied with an ill-fitting cover. -The house on the opposite side of the road, in which the two birds were -found dead, had a cellar opening both at the front and the back; but -both these openings, until a little before the occurrence detailed, had -been kept closed. The cellars in all cases communicated with the houses -by means of doors opening into the kitchens. According to the general -account of the occupants, the cellars had smelled of "fire stink," -which, in their opinion, proceeded from the adjoining mine. - -The shaft of the disused mine communicated with a mine in working order, -and, to encourage the ventilation in this mine, a furnace had for some -weeks been lit and suspended in the shaft. This furnace had set fire to -the coal in the disused mine and smoke had been issuing from the shaft -for four weeks previously. Two days previous to the inquiry the opening -of the shaft had been closed over with a view to extinguish the fire. - -Dr. Reid considered, from the symptoms and all the circumstances of the -case, that the illness was due to carbon monoxide gas penetrating into -the cellars from the mine, and from thence to the living- and -sleeping-rooms. A sample of the air yielded 0.015 per cent. of carbon -monoxide, although the sample had been taken after the cellar windows -had been open for twenty-four hours. - -Sec. 42. =Detection of Carbon Monoxide.=--It may often be necessary to -detect carbon monoxide in air and to estimate its amount. The detection -in air, if the carbon monoxide is in any quantity, is easy enough; but -traces of carbon monoxide are difficult. Where amounts of carbon -monoxide in air from half a per cent. upwards are reasonably presumed to -exist, the air is measured in a gas measuring apparatus and passed into -an absorption pipette charged with alkaline pyrogallic acid, and when -all the oxygen has been abstracted, then the residual nitrogen and gases -are submitted to an ammoniacal solution of cuprous chloride. - -The solution of cuprous chloride is prepared by dissolving 10.3 grms. of -copper oxide in 150 c.c. of strong hydrochloric acid and filling the -flask with copper turnings; the copper reduces the cupric chloride to -cuprous chloride; the end of the reduction is known by the solution -becoming colourless. The colourless acid solution is poured into some -1500 c.c. of water, and the cuprous chloride settles to the bottom as a -precipitate. The supernatant fluid is poured off as completely as -possible and the precipitate washed into a quarter litre flask, with 100 -to 150 c.c. of distilled water and ammonia led into the solution until -it becomes of a pale blue colour. The solution is made up to 200 c.c. so -as to contain about 7.3 grms. per cent. of cuprous chloride. - -Such a solution is an absorbent of carbon monoxide; it also absorbs -ethylene and acetylene. - -A solution of cuprous chloride which has absorbed CO gives it up on -being treated with potassic bichromate and acid. It has been proposed by -Wanklyn to deprive large quantities of air of oxygen, then to absorb any -carbon monoxide present with cuprous chloride, and, lastly, to free the -cuprous chloride from the last gas by treatment with acid bichromate, so -as to be able to study the properties of a small quantity of pure gas. - -By far the most reliable method to detect small quantities of carbon -monoxide is, however, as proposed by Hempel, to absorb it in the lungs -of a living animal. - -A mouse is placed between two funnels joined together at their mouths by -a band of thin rubber; one of the ends of the double funnel is connected -with an aspirator, and the air thus sucked through, say for half an hour -or more; the mouse is then killed by drowning, and a control mouse, -which has not been exposed to a CO atmosphere, is also drowned; the -bodies of both mice are cut in two in the region of the heart, and the -blood collected. Each sample of blood is diluted in the same proportion -and spectroscopically examined in the manner detailed at p. 58. - -Winkler found that, when large volumes of gas were used (at least 10 -litres), 0.05 per cent. of carbon monoxide could be readily detected. - - -II.--Chlorine. - -Sec. 43. Chlorine is a yellow-green gas, which may, by cold and pressure, -be condensed into a liquid. Its specific gravity is, as compared with -hydrogen, 35.37; as compared with air, 2.45; a litre under standard -conditions weighs 3.167 grms. It is soluble in water. - -The usual method of preparation is the addition of hydrochloric acid to -bleaching powder, which latter substance is hypochlorite of lime mixed -with calcic chloride and, it may be, a little caustic lime. Another -method is to treat manganese dioxide with hydrochloric acid or to act on -manganese dioxide and common salt with sulphuric acid. - -Accidents are liable to occur with chlorine gas from its extensive use -as a disinfectant and also in its manufacture. In the "Weldon" process -of manufacturing bleaching powder, a thick layer of lime is placed on -the floor of special chambers; chlorine gas is passed into these -chambers for about four days; then the gas is turned off; the unabsorbed -gas is drawn off by an exhaust or absorbed by a lime distributor and the -doors opened. Two hours afterwards the men go in to pack the powder. The -packers, in order to be able to work in the chambers, wear a respirator -consisting of about thirty folds of damp flannel; this is tightly bound -round the mouth with the nostrils free and resting upon it. The men are -obliged to inhale the breath through the flannel and exhale through the -nostril, otherwise they would, in technical jargon, be "gassed." Some -also wear goggles to protect their eyes. Notwithstanding these -precautions they suffer generally from chest complaints. - -Sec. 44. =Effects.=--Free chlorine, in the proportion of 0.04 to 0.06 per -thousand, taken into the lungs is dangerous to life, since directly -chlorine attacks a moist mucous membrane, hydrochloric acid is formed. -The effects of chlorine can hardly be differentiated from hydrochloric -acid gas, and Lehmann found that 1.5 per thousand of this latter gas -affected animals, causing at once uneasiness, evidence of pain with -great dyspn[oe]a, and later coma. The eyes and the mucous membrane of -the nose were attacked. Anatomical changes took place in the cornea, as -evidenced by a white opacity. - -In cases that recovered, a purulent discharge came from the nostrils -with occasional necrosis of the mucous membrane. The symptoms in man are -similar; there is great tightness of the breath, irritation of the nose -and eyes, cough and, with small repeated doses, bronchitis with all its -attendant evils. Bleaching powder taken by the mouth is not so deadly. -Hertwig has given 1000 grms. to horses, 30 grms. to sheep and goats, and -15 grms. to dogs without producing death. The symptoms in these cases -were quickening of the pulse and respiration, increased peristaltic -action of the bowels and a stimulation of the kidney secretion. The -urine smelt of chlorine. - -Sec. 45. =Post-mortem Appearances.=--Hyperaemia of the lungs, with -ecchymoses and pneumonic patches with increased secretion of the -bronchial tubes. In the mucous membrane of the stomach, ecchymoses. The -alkalescence of the blood is diminished and there may be external signs -of bleaching. Only exceptionally has any chlorine smell been perceived -in the internal organs. - -Sec. 46. =Detection of Free Chlorine.=--The usual method of detection is to -prepare a solution of iodide of potassium and starch and to soak strips -of filter-paper in this solution. Such a strip, when moistened and -submitted to a chlorine atmosphere, is at once turned blue, because -chlorine displaces iodine from its combination with potassium. -Litmus-paper, indigo blue or other vegetable colours are at once -bleached. - -To estimate the amount of chlorine a known volume of the air is drawn -through a solution of potassium iodide, and the amount of iodine set -free, determined by titration with sodic hyposulphite, as detailed at p. -74. - - -III.--Hydric Sulphide (Sulphuretted Hydrogen). - -Sec. 47. Hydric sulphide, SH_{2}, is a colourless transparent gas of sp. -gravity 1.178. It burns with a blue flame, forming water and sulphur -dioxide, and is soluble in water; water absorbing about three volumes -at ordinary temperatures. It is decomposed by either chlorine gas or -sulphur dioxide. - -It is a common gas as a constituent of the air of sewers or cesspools, -and emanates from moist slag or moist earth containing pyrites or -metallic sulphides; it also occurs whenever albuminous matter putrefies; -hence it is a common constituent of the emanations from corpses of -either man or animals. It has a peculiar and intense odour, generally -compared to that of rotten eggs; this is really not a good comparison, -for it is comparing the gas with itself, rotten eggs always producing -SH_{2}; it is often associated with ammonium sulphide. - -Sec. 48. =Effects.=--Pure hydric sulphide is never met with out of the -chemist's laboratory, in which it is a common reagent either as a gas or -in solution; so that the few cases of poisoning by the pure gas, or -rather the pure gas mixed with ordinary air, have been confined to -laboratories. - -The greater number of cases have occurred accidentally to men working in -sewers, or cleaning out cesspools and the like. In small quantities it -is always present in the air of towns, as shown by the blackening of any -silver ornament not kept bright by frequent use. - -It is distinctly a blood poison, the gas uniting with the alkali of the -blood, and the sulphide thus produced partly decomposing again in the -lung and breathed out as SH_{2}. Lehmann[60] has studied the effects on -animals; an atmosphere containing from 1 to 3 per thousand of SH_{2} -kills rabbits and cats within ten minutes; the symptoms are mainly -convulsions and great dyspn[oe]a. An atmosphere containing from 0.4 to -0.8 per thousand produces a local irritating action on the mucous -membranes of the respiratory tract, and death follows from an -inflammatory [oe]dema of the lung preceded by convulsions; there is also -a paralysis of the nervous centres. Lehmann has recorded the case of -three men who breathed 0.2 per thousand of SH_{2}: within from five to -eight minutes there was intense irritation of the eyes, nose, and -throat, and after thirty minutes they were unable to bear the atmosphere -any longer. Air containing 0.5 per thousand of SH_{2} is, according to -Lehmann, the utmost amount that can be breathed; this amount causes in -half an hour smarting of the eyes, nasal catarrh, dyspn[oe]a, cough, -palpitation, shivering, great muscular weakness, headache and faintness -with cold sweats. 0.7 to 0.8 per thousand is dangerous to human life, -and from 1 to 1.5 per thousand destroys life rapidly. The symptoms may -occur some little time after the withdrawal of the person from the -poisonous atmosphere; for example, Cahn records the case of a student -who prepared SH_{2} in a laboratory and was exposed to the gas for two -hours; he then went home to dinner and the symptoms first commenced in -more than an hour after the first breathing of pure air. Taylor[61] -records an unusual case of poisoning in 1857 at Cleator Moor. Some -cottages had been built upon iron slag, the slag contained sulphides of -calcium and iron; a heavy storm of rain washed through the slag and -considerable volumes of SH_{2} with, no doubt, other gases diffused -during the night through the cottages and killed three adults and three -children. - -[60] K. B. Lehmann, _Arch. f. Hygiene_, Bd. xiv., 1892, 135. - -[61] _Principles and Practice of Medl. Jurisp._, vol. ii. 122. - -Sec. 49. =Post-mortem Appearances.=--The so-called apoplectic form of -SH_{2} poisoning, in which the sufferer dies within a minute or two, -shows no special change. The most frequent change in slower poisoning -is, according to Lehmann, [oe]dema of the lungs. A green colour of the -face and of the whole body is sometimes present, but not constant. A -spectroscopic examination of the blood may also not lead to any -conclusion, the more especially as the spectrum of sulphur methaemoglobin -may occur in any putrid blood. The pupils in some cases have been found -dilated; in others not so. - -=Chronic poisoning.=--Chronic poisoning by SH_{2} is of considerable -interest in a public health point of view. The symptoms appear to be -conjunctivitis, headache, dyspepsia and anaemia. A predisposition to -boils has also been noted. - -Sec. 50. =Detection.=--Both ammonium and hydric sulphides blacken silver -and filter-paper moistened with acetate of lead solution. To test for -hydric sulphide in air a known quantity may be aspirated through a -little solution of lead acetate. To estimate the quantity a decinormal -solution of iodine in potassium iodide[62] solution is used, and its -exact strength determined by d.n. sodic hyposulphite solution[63]; the -hyposulphite is run in from a burette into a known volume, _e.g._, 50 -c.c., of the d.n. iodine solution, until the yellow colour is almost -gone; then a drop or two of fresh starch solution is added and the -hyposulphite run in carefully, drop by drop, until the blue colour of -the starch disappears. If now a known volume of air is drawn through 50 -c.c. of the d.n. iodine solution, the reaction I_{2} + SH_{2} = 2HI + S -will take place, and for every 127 parts of iodine which have been -converted into hydriodic acid 17 parts by weight of SH_{2} will be -necessary; hence on titrating the 50 c.c. of d.n. iodine solution, -through which air containing SH_{2} has been passed, less hyposulphite -will be used than on the previous occasion, each c.c. of the -hyposulphite solution being equal to 1.11 c.c. or to 1.7 mgrm. of -SH_{2}. - -[62] 12.7 grms. of iodine, 16.6 grms. of potassium iodide, dissolved in -a litre of water. - -[63] 24.8 grms. of sodic hyposulphite, dissolved in a litre of water. - - - - -PART IV.--ACIDS AND ALKALIES. - - SULPHURIC ACID--HYDROCHLORIC ACID--NITRIC ACID--ACETIC - ACID--AMMONIA--POTASH--SODA--NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM - SALTS. - - -I.--Sulphuric Acid. - -Sec. 51. Sulphuric acid (hydric sulphate, oil of vitriol, H_{2}SO_{4}) -occurs in commerce in varying degrees of strength or dilution; the -strong sulphuric acid of the manufacturer, containing 100 per cent. of -real acid (H_{2}SO_{4}), has a specific gravity of 1.850. The ordinary -brown acid of commerce, coloured by organic matter and holding in -solution metallic impurities, chiefly lead and arsenic, has a specific -gravity of about 1.750; and contains 67.95 of anhydrous SO_{3} = 85.42 -of hydric sulphate. - -There are also weaker acids used in commerce, particularly in -manufactories in which sulphuric acid is made, for special purposes -without rectification. The British Pharmacop[oe]ia sulphuric acid is -directed to be of 1.843 specific gravity, which corresponds to 78.6 per -cent. sulphuric anhydride, or 98.8 per cent. of hydric sulphate. The -dilute sulphuric acid of the pharmacop[oe]ia should have a specific -gravity of 1.094, and is usually said to correspond to 10.14 per cent. -of anhydrous sulphuric acid; but, if Ure's Tables are correct, such -equals 11.37 per cent. - -The general characters of sulphuric acid are as follows:--When pure, it -is a colourless, or, when impure, a dark brown to black, oily liquid, -without odour at common temperatures, of an exceedingly acid taste, -charring most organic tissues rapidly, and, if mixed with water, -evolving much heat. If 4 parts of the strong acid are mixed with 1 part -of water at 0 deg., the mixture rises to a heat of 100 deg.; a still greater -heat is evolved by mixing 75 parts of acid with 27 of water. - -Sulphuric acid is powerfully hygroscopic--3 parts will, in an ordinary -atmosphere, increase to nearly 4 in twenty-four hours; in common with -all acids, it reddens litmus, yellows cochineal, and changes all -vegetable colours. There is another form of sulphuric acid, extensively -used in the arts, known under the name of "Nordhausen sulphuric acid," -"fuming acid," formula H_{2}S_{2}O_{4}. This acid is produced by the -distillation of dry ferrous sulphate, at a nearly white heat--either in -earthenware or in green glass retorts; the distillate is received in -sulphuric acid. As thus manufactured, it is a dark fuming liquid of 1.9 -specific gravity, and boiling at 53 deg. When artificially cooled down to -0 deg., the acid gradually deposits crystals, which consist of a definite -compound of 2 atoms of anhydrous sulphuric acid and 1 atom of water. -There is some doubt as to the molecular composition of Nordhausen acid; -it is usually considered as hydric sulphate saturated with sulphur -dioxide. This acid is manufactured chiefly in Bohemia, and is used, on a -large scale, as a solvent for alizarine. - -Sec. 52. =Sulphur Trioxide, or Sulphuric Anhydride= (SO_{3}), itself may be -met with in scientific laboratories, but is not in commerce. Sulphur -trioxide forms thin needle-shaped crystals, arranged in feathery groups. -Seen in mass, it is white, and has something the appearance of asbestos. -It fuses to a liquid at about 18 deg., boils at 35 deg., but, after this -operation has been performed, the substance assumes an allotropic -condition, and then remains solid up to 100 deg.; above 100 deg. it melts, -volatilises, and returns to its normal condition. Sulphuric anhydride -hisses when it is thrown into water, chemical combination taking place -and sulphuric acid being formed. Sulphur trioxide is excessively -corrosive and poisonous. - -Besides the above forms of acid, there is an officinal preparation -called "Aromatic Sulphuric Acid," made by digesting sulphuric acid, -rectified spirit, ginger, and cinnamon together. It contains 10.19 per -cent. of SO_{3}, alcohol, and principles extracted from cinnamon and -ginger. - -Sec. 53. Sulphuric acid, in the free state, may not unfrequently be found -in nature. The author has had under examination an effluent water from a -Devonshire mine, which contained more than one grain of free sulphuric -acid per gallon, and was accused, with justice, of destroying the fish -in a river. It also exists in large quantities in volcanic springs. In a -torrent flowing from the volcano of Parce, in the Andes, Boussingault -calculated that 15,000 tons of sulphuric acid and 11,000 tons of -hydrochloric acid were yearly carried down. In the animal and vegetable -kingdom, sulphuric acid exists, as a rule, in combination with bases, -but there is an exception in the saliva of the _Dolium galea_, a -Sicilian mollusc. - -Sec. 54. =Statistics.=--When something like 900,000 tons of sulphuric acid -are produced annually in England alone, and when it is considered that -sulphuric acid is used in the manufacture of most other acids, in the -alkali trade, in the manufacture of indigo, in the soap trade, in the -manufacture of artificial manure, and in a number of technical -processes, there is no cause for surprise that it should be the annual -cause of many deaths. - -The number of deaths from sulphuric acid will vary, other things being -equal, in each country, according to the manufactures in that country -employing sulphuric acid. The number of cases of poisoning in England -and Wales for ten years is given in the following table:-- - -DEATHS FROM SULPHURIC ACID IN ENGLAND AND WALES FOR THE TEN YEARS ENDING -1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, 1-5 5-15 15-25 25-65 65 & Total - upwards - Males, 11 4 2 14 2 33 - Females, 4 ... 2 3 ... 9 - --------------------------------------------- - Totals, 15 4 4 17 2 42 - --------------------------------------------- - - SUICIDE. - - Ages, 15-25 25-65 Total - Males, 4 25 29 - Females, 5 19 24 - --------------------------------- - Totals 9 44 53 - --------------------------------- - -During the ten years, no case of murder through sulphuric acid is on -record; hence the total deaths, as detailed in the tables, amount to 95, -or a little over 9 a year. - -Falck,[64] in comparing different countries, considers the past -statistics to show that in France sulphuric acid has been the cause of -4.5 to 5.5 per cent. of the total deaths from poison, and in England 5.9 -per cent. In England, France, and Denmark, taken together, 10.8, Prussia -10.6; while in certain cities, as Berlin and Vienna, the percentages are -much higher--Vienna showing 43.3 per cent., Berlin 90 per cent. - -[64] _Lehrbuch der praktischen Toxicologie_, p. 54. - -Sec. 55. =Accidental, Suicidal, and Criminal Poisoning.=--Deaths from -sulphuric acid are, for the most part, accidental, occasionally -suicidal, and, still more rarely, criminal. In 53 out of 113 cases -collected by Boehm, in which the cause of the poisoning could, with fair -accuracy, be ascertained, 45.3 per cent. were due to accident, 30.2 were -suicidal, and 24.5 per cent. were cases of criminal poisoning, the -victims being children. - -The cause of the comparatively rare use of sulphuric acid by the -poisoner is obvious. First of all, the acid can never be mixed with food -without entirely changing its aspect; next, it is only in cases of -insensibility or paralysis that it could be administered to an adult, -unless given by force, or under very exceptional circumstances; and -lastly, the stains on the mouth and garments would at once betray, even -to uneducated persons, the presence of something wrong. As an agent of -murder, then, sulphuric acid is confined in its use to young children, -more especially to the newly born. - -There is a remarkable case related by Haagan,[65] in which an adult man, -in full possession of his faculties, neither paralysed nor helpless, was -murdered by sulphuric acid. The wife of a day-labourer gave her husband -drops of sulphuric acid on sugar, instead of his medicine, and finally -finished the work by administering a spoonful of the acid. The spoon was -carried well to the back of the throat, so that the man took the acid at -a gulp. 11 grms. (171 grains) of sulphuric acid, partly in combination -with soda and potash, were separated from his stomach. - -[65] Gross: _Die Strafrechtspflege in Deutschland_, 4, 1861, Heft I. S. -181. - -Accidental poisoning is most common among children. The oily, -syrupy-looking sulphuric acid, when pure, may be mistaken for glycerin -or for syrup; and the dark commercial acid might, by a careless person, -be confounded with porter or any dark-looking medicine. - -Serious and fatal mistakes have not unfrequently arisen from the use of -injections. Deutsch[66] relates how a midwife, in error, administered to -mother and child a sulphuric acid clyster; but little of the fluid could -in either case have actually reached the rectum, for the mother -recovered in eight days, and in a little time the infant was also -restored to health. Sulphuric acid has caused death by injections into -the vagina. H. C. Lombard[67] observed a case of this kind, in which a -woman, aged thirty, injected half a litre of sulphuric acid into the -vagina, for the purpose of procuring abortion. The result was not -immediately fatal, but the subsequent inflammation and its results so -occluded the natural passage that the birth became impossible, and a -Caesarean section extracted a dead child, the mother also dying. - -[66] _Preuss. Med. Vereins-Zeitung_, 1848, No. 13. - -[67] _Journ. de Chim. Med._, tom. vii., 1831. - -An army physician prescribed for a patient an emollient clyster. Since -it was late at night, and the apothecary in bed, he prepared it himself; -but not finding linseed oil, woke the apothecary, who took a bottle out -of one of the recesses and placed it on the table. The bottle contained -sulphuric acid; a soldier noticed a peculiar odour and effervescence -when the syringe was charged, but this was unheeded by the doctor. The -patient immediately after the operation suffered the most acute agony, -and died the following day; before his death, the bedclothes were found -corroded by the acid, and a portion of the bowel itself came away.[68] - -[68] Maschka's _Handbuch_, p. 86; _Journal de Chimie Medicale_, t. i. -No. 8, 405, 1835. - -Sec.56. =Fatal Dose.=--The amount necessary to kill an adult man is not -strictly known; fatality so much depends on the concentration of the -acid and the condition of the person, more especially whether the -stomach is full or empty, that it will be impossible ever to arrive at -an accurate estimate. Christison's case, in which 3.8 grms. (60 grains) -of concentrated acid killed an adult, is the smallest lethal dose on -record. Supposing that the man weighed 68-1/2 kilo. (150 lbs.), this -would be in the proportion of .05 grm. per kilo. There is also the case -of a child of one year, recorded by Taylor, in which 20 drops caused -death. If, however, it were asked in a court of law what dose of -concentrated sulphuric acid would be dangerous, the proper answer would -be: so small a quantity as from 2 to 3 drops of the strong undiluted -acid might cause death, more especially if conveyed to the back of the -throat; for if it is improbable that on such a supposition death would -be sudden, yet there is a possibility of permanent injury to the gullet, -with the result of subsequent contraction, and the usual long and -painful malnutrition thereby induced. It may be laid down, therefore, -that all quantities, even the smallest, of the _strong undiluted acid_ -come under the head of hurtful, noxious, and injurious. - -Sec. 57. =Local Action of Sulphuric Acid.=--The action of the acid on -living animal tissues has been studied of late by C. Ph. Falck and L. -Vietor.[69] Concentrated acid precipitates albumen, and then redissolves -it; fibrin swells and becomes gelatinous; but if the acid is weak -(_e.g._, 4 to 6 per cent.) it is scarcely changed. Muscular fibre is at -first coloured amber-yellow, swells to a jelly, and then dissolves to a -red-brown turbid fluid. When applied to the mucous membrane of the -stomach, the mucous tissue and the muscular layer beneath are coloured -white, swell, and become an oily mass. - -[69] _Deutsche Klinik_, 1864, Mo. 1-32, and Vietor's -_Inaugur.-Dissert._, Marburg, 1803. - -When applied to a rabbit's ear,[70] the parenchyma becomes at first pale -grey and semi-transparent at the back of the ear; opposite the drop of -acid appear spots like grease or fat drops, which soon coalesce. The -epidermis with the hair remains adherent; the blood-vessels are narrowed -in calibre, and the blood, first in the veins, and then in the arteries, -is coloured green and then black, and fully coagulates. If the drop, -with horizontal holding of the ear, is dried in, an inflammatory zone -surrounds the burnt spot in which the blood circulates; but there is -complete stasis in the part to which the acid has been applied. If the -point of the ear is dipped in the acid, the cauterised part rolls -inwards; after the lapse of eighteen hours the part is brown and -parchment-like, with scattered points of coagulated blood; then there is -a slight swelling in the healthy tissues, and a small zone of redness; -within fourteen days a bladder-like greenish-yellow scab is formed, the -burnt part itself remaining dry. The vessels from the surrounding zone -of redness gradually penetrate towards the cauterised spot, the fluid -in the bleb becomes absorbed, and the destroyed tissues fall off in the -form of a crust. - -[70] Samuel, _Entzuendung u. Brand, in Virchow's Archiv f. Path. Anat._, -Bd. 51, Hft. 1 u. 2, S. 41, 1870. - -The changes that sulphuric acid cause in blood are as follows: the -fibrin is at first coagulated and then dissolved, and the colouring -matter becomes of a black colour. These changes do not require the -strongest acid, being seen with an acid of 60 per cent. - -Sec. 58. The action of the acid on various non-living matters is as -follows: poured on all vegetable earth, there is an effervescence, -arising from decomposition of carbonates; any grass or vegetation -growing on the spot is blackened and dies; an analysis of the layer of -earth, on which the acid is poured, shows an excess of sulphates as -compared with a similar layer adjacent; the earth will only have an acid -reaction, if there has been more than sufficient acid to neutralise all -alkalies and alkaline earths. - -Wood almost immediately blackens, and the spot remains moist. - -Spots on paper become quickly dark, and sometimes exhibit a play of -colours, such as reddish-brown; ultimately the spot becomes very black, -and holes may be formed; even when the acid is dilute, the course is -very similar, for the acid dries in, until it reaches a sufficient -degree of concentration to attack the tissue. I found small drops of -sulphuric acid on a brussels carpet, which had a red pattern on a dark -green ground with light green flowers, act as follows: the spots on the -red at the end of a few hours were of a dark maroon colour, the green -was darkened, and the light green browned; at the end of twenty-four -hours but little change had taken place, nor could any one have guessed -the cause of the spots without a close examination. Spots of the strong -acid on thin cotton fabrics rapidly blackened, and actual holes were -formed in the course of an hour; the main difference to the naked eye, -between the stains of the acid and those produced by a red-hot body, lay -in the moistness of the spots. Indeed, the great distinction, without -considering chemical evidence, between recent burns of clothing by -sulphuric acid and by heat, is that in the one case--that of the -acid--the hole or spot is very moist; in the other very dry. It is easy -to imagine that this distinction may be of importance in a legal -investigation. - -Spots of acid on clothing fall too often under the observation of all -those engaged in practical chemical work. However quickly a spot of acid -is wiped off, unless it is immediately neutralised by ammonia, it -ultimately makes a hole in the cloth; the spot, as a rule, whatever the -colour of the cloth, is of a blotting-paper red. - -Sulphuric acid dropped on iron, attacks it, forming a sulphate, which -may be dissolved out by water. If the iron is exposed to the weather -the rain may wash away all traces of the acid, save the corrosion; but -it would be under those circumstances impossible to say whether the -corrosion was due to oxidation or a solvent. - -To sum up briefly: the characters of sulphuric acid spots on organic -matters generally are black, brown, or red-coloured destructions of -tissue, moisture, acid-reaction (often after years), and lastly the -chemical evidence of sulphuric acid or sulphates in excess. - -=Caution necessary in judging of Spots, &c.=--An important case, related -by Maschka, shows the necessity of great caution in interpreting -results, unless all the circumstances of a case be carefully collated. A -live coal fell on the bed of a weakly infant, five months old. The child -screamed, and woke the father, who was dozing by the fire; the man, in -terror, poured a large pot of water on the child and burning bed. The -child died the following day. - -A _post-mortem_ examination showed a burn on the chest of the infant 2 -inches in length. The tongue, pharynx, and gullet were all healthy; in -the stomach a patch of mucous membrane, about half an inch in extent, -was found to be brownish, friable, and very thin. A chemical examination -showed that the portion of the bed adjacent to the burnt place contained -free sulphuric acid. Here, then, was the following evidence: the sudden -death of a helpless infant, a carbonised bed-cover with free sulphuric -acid, and, lastly, an appearance in the stomach which, it might be said, -was not inconsistent with sulphuric acid poisoning. Yet a careful -sifting of the facts convinced the judges that no crime had been -committed, and that the child's death was due to disease. Afterwards, -experiment showed that if a live coal fall on to any tissue, and be -drenched with water, free sulphuric acid is constantly found in the -neighbourhood of the burnt place. - -Sec. 59. =Symptoms.=--The symptoms may be classed in two divisions, -viz.:--1. External effects of the acid. 2. Internal effects and symptoms -arising from its interior administration. - -1. =External Effects.=--Of late years several instances have occurred in -which the acid has been used criminally to cause disfiguring burns of -the face. The offence has in all these cases been committed by women, -who, from motives of revengeful jealousy, have suddenly dashed a -quantity of the acid into the face of the object of their resentment. In -such cases, the phenomena observed are not widely different from those -attending scalds or burns from hot neutral fluids. There is destruction -of tissue, not necessarily deep, for the acid is almost immediately -wiped off; but if any should reach the eye, inflammation, so acute as to -lead to blindness, is the probable consequence. The skin is coloured at -first white, at a later period brown, and part of it may be, as it were, -dissolved. If the tract or skin touched by the acid is extensive, death -may result. The inflammatory processes in the skin are similar to those -noticed by Falck and Vietor in their experiments, already detailed (p. -79). - -=Internal Effects of Acids generally.=--It may not be out of place, -before speaking of the internal effects of sulphuric acid, to make a few -remarks upon the action of acids generally. This action differs -according to the kind of animal; at all events, there is a great -difference between the action of acids on the herb-eating animals and -the carnivora; the latter bear large doses of acids well, the former -ill. For instance, the rabbit, if given a dose of any acid not -sufficient to produce local effects but sufficient to affect its -functions, will soon become paralysed and lie in a state of stupor, as -if dead; the same dose per kilo. will not affect the dog. The reason for -this is that the blood of the dog is able to neutralise the acid by -ammonia, and that the blood of the rabbit is destitute of this property. -Man is, in this respect, nearer to the dog than to the plant-eaters. -Stadelmann has shown that a man is able to ingest large relative doses -of oxybutyric acid, to neutralise the acid by ammonia, and to excrete it -by means of the kidneys as ammonium butyrate. - -Acids, however, if given in doses too great to be neutralised, alike -affect plant- and flesh-eaters; death follows in all cases before the -blood becomes acid. Salkowsky[71] has, indeed, shown that the effect of -lessening the alkalinity of the blood by giving a rabbit food from which -it can extract no alkali produces a similar effect to the actual dosing -with an acid. - -[71] Virchow's _Archiv_, Bd. 58, 1. - -2. =Internal Effects of Sulphuric Acid.=--When sulphuric acid is taken -internally, the acute and immediate symptom is pain. This, however, is -not constant, since, in a few recorded cases, no complaint of pain has -been made; but these cases are exceptional; as a rule, there will be -immediate and great suffering. The tongue swells, the throat is also -swollen and inflamed, swallowing of saliva even may be impossible. If -the acid has been in contact with the epiglottis and vocal apparatus, -there may be spasmodic croup and even fatal spasm of the glottis. - -The acid, in its passage down the gullet, attacks energetically the -mucous membrane and also the lining of the stomach; but the action does -not stop there, for Lesser found in eighteen out of twenty-six cases (69 -per cent.) that the corrosive action extended as far as the duodenum. -There is excessive vomiting and retching; the matters vomited are acid, -bloody, and slimy; great pieces of mucous membrane may be in this way -expelled, and the whole of the lining membrane of the gullet may be -thrown up entire. The bowels are, as a rule, constipated, but -exceptionally there has been diarrh[oe]a; the urine is sometimes -retained; it invariably contains an excess of sulphates and often -albumen, with hyaline casts of the uriniferous tubes. The pulse is small -and frequent, the breathing slow, the skin very cold and covered with -sweat; the countenance expresses great anxiety, and the extremities may -be affected with cramps or convulsions. Death may take place within from -twenty-four to thirty-six hours, and be either preceded by dyspn[oe]a or -by convulsions; consciousness is, as a rule, maintained to the end. - -There are also more rapid cases than the above; a large dose of -sulphuric acid taken on an empty stomach may absolutely dissolve it, and -pass into the peritoneum; in such a case there is really no difference -in the symptoms between sudden perforation of the stomach from disease, -a penetrating wound of the abdomen, and any other sudden fatal lesion of -the organs in the abdominal cavity (for in all these instances the -symptoms are those of pure collapse); the patient is ashen pale, with -pulse quick and weak, and body bathed in cold sweat, and he rapidly -dies, it may be without much complaint of local pain. - -If the patient live longer than twenty-four hours, the symptoms are -mainly those of inflammation of the whole mucous tract, from the mouth -to the stomach; and from this inflammation the patient may die in a -variable period, of from three to eleven days, after taking the poison. -In one case the death occurred suddenly, without any immediately -preceding symptoms rendering imminent death probable. If this second -stage is passed, then the loss of substance in the gullet and in the -stomach almost invariably causes impairment of function, leading to a -slow and painful death. The common sequence is stricture of the gullet, -combined with feeble digestion, and in a few instances stricture of the -pylorus. A curious sequel has been recorded by Mannkopf, viz., obstinate -intercostal neuralgia; it has been observed on the fourth, seventh, and -twenty-second day. - -Sec. 60. =Treatment of Acute Poisoning by the Mineral Acids.=--The -immediate indication is the dilution and neutralisation of the acid. For -this purpose, finely-divided chalk, magnesia, or sodic carbonate may be -used, dissolved or suspended in much water. The use of the stomach-pump -is inadvisable, for the mucous membrane of the gullet may be so corroded -by the acid that the passage of the tube down will do injury; unless the -neutralisation is _immediate_, but little good is effected; hence it -will often occur that the bystanders, if at all conversant with the -matter, will have to use the first thing which comes to hand, such as -the plaster of a wall, &c.; and lastly, if even these rough antidotes -are not to be had, the best treatment is enormous doses of water, which -will dilute the acid and promote vomiting. The treatment of the -after-effects belongs to the province of ordinary medicine, and is based -upon general principles. - -Sec. 61. =Post-mortem Appearances.=[72]--The general pathological -appearances to be found in the stomach and internal organs differ -according as the death is rapid or slow; if the death takes place within -twenty-four hours, the effects are fairly uniform, the differences being -only in degree; while, on the other hand, in those cases which terminate -fatally from the more remote effects of the acid, there is some variety. -It may be well to select two actual cases as types, the one patient -dying from acute poisoning, the other surviving for a time, and then -dying from ulceration and contraction of the digestive tract. - -[72] It has been observed that putrefaction in cases of death from -sulphuric acid is slow. Casper suggests this may be due to the -neutralisation of ammonia; more probably it is owing to the antiseptic -properties all mineral acids possess. - -A hatter, early in the morning, swallowed a large mouthful of strong -sulphuric acid, a preparation which he used in his work--(whether the -draught was taken accidentally or suicidally was never known). He died -within two hours. The whole tongue was sphacelated, parts of the mucous -membrane being dissolved; the inner surface of the gullet, as well as -the whole throat, was of a grey-black colour; the mucous membrane of the -stomach was coal-black, and so softened that it gave way like -blotting-paper under the forceps, the contents escaping into the cavity -of the abdomen. The peritoneum was also blackened as if burnt; probably -there had been perforation of the stomach during life; the mucous -membrane of the duodenum was swollen, hardened, and looked as if it had -been boiled; while the blood was of a cherry-red colour, and of the -consistence of a thin syrup. The rest of the organs were healthy; a -chemical research on the fluid which had been collected from the -stomach, gullet, and duodenum showed that it contained 87.25 grains of -free sulphuric acid.[73] - -[73] Casper, vol. ii. case 194. - -This is, perhaps, the most extreme case of destruction on record; the -cause of the unusually violent action is referable to the acid acting on -an empty stomach. It is important to note that even with this extensive -destruction of the stomach, life was prolonged for two hours. - -The case I have selected to serve as a type of a chronic but fatal -illness produced from poisoning by sulphuric acid is one related by -Oscar Wyss. A cook, thirty-four years of age, who had suffered many -ailments, drank, on the 6th of November 1867, by mistake, at eight -o'clock in the morning, two mouthfuls of a mixture of 1 part of -sulphuric acid and 4 of water. Pain in the stomach and neck, and -vomiting of black masses, were the immediate symptoms, and two hours -later he was admitted into the hospital in a state of collapse, with -cold extremities, cyanosis of the face, &c. Copious draughts of milk -were given, and the patient vomited much, the vomit still consisting of -black pultaceous matters, in which, on a microscopical examination, -could be readily detected columnar epithelium of the stomach and mucous -tissue elements. The urine was of specific gravity 1.033, -non-albuminous; on analysis it contained 3.388 grms. of combined -sulphuric acid. - -On the second day there was some improvement in the symptoms; the urine -contained 1.276 grm. of combined sulphuric acid; on the third day 2.665 -grms. of combined sulphuric acid; and on the tenth day the patient -vomited up a complete cast of the mucous membrane of the gullet. The -patient remained in the hospital, and became gradually weaker from -stricture of the gullet and impairment of the digestive powers, and -died, two months after taking the poison, on the 5th of January 1868. - -The stomach was found small, contracted, with many adhesions to the -pancreas and liver; it was about 12 centimetres long (4.7 inches), and -from 2 to 2.5 centimetres (.7 to .9 inch) broad, contracted to somewhat -the form of a cat's intestine; there were several transverse rugae; the -walls were thickened at the small curvature, measurements giving 5 mm. -(.19 inch) in the middle, and beyond about 2.75 mm. (.11 inch); in the -upper two-thirds the lumen was so contracted as scarcely to admit the -point of the little finger. The inner surface was covered with a layer -of pus, with no trace of mucous tissue, and was everywhere pale red, -uneven, and crossed by cicatricial bands. In two parts, at the greater -curvature, the mucous surface was strongly injected in a ring-like form, -and in the middle of the ring was a deep funnel-shaped ulcer; a part of -the rest of the stomach was strongly injected and scattered over with -numerous punctiform, small, transparent bladders. The gullet was -contracted at the upper part (just below the epiglottis) from 20 to 22 -mm. (.78 to .86 inch) in diameter; it then gradually widened to measure -about 12 mm. (.47 inch) at the diaphragm; in the neighbourhood of the -last contraction the tissue was scarred, injected, and ulcerated; there -were also small abscesses opening into this portion of the gullet. - -E. Fraenkel and F. Reiche[74] have studied the effects of sulphuric acid -on the kidney. In rapid cases they find a wide-spread coagulation of the -epithelium in the convoluted and straight urinary canaliculi, with -destruction of the kidney parenchyma, but no inflammation. - -[74] Virchow's _Archiv_, Bd. 131, f. 130. - -Sec. 62. The museums of the different London hospitals afford excellent -material for the study of the effects of sulphuric acid on the pharynx, -gullet, and stomach; and it may be a matter of convenience to students -if the more typical examples at these different museums be noticed in -detail, so that the preparations themselves may be referred to. - - _In St. Bartholomew's Museum_, No. 1942, is an example of excessive - destruction of the stomach by sulphuric acid. The stomach is much - contracted, and has a large aperture with ragged edges; the mucous - membrane is thickened, charred, and blackened. - - No. 1941, in the same museum, is the stomach of a person who died - from a large dose of sulphuric acid. When recent, it is described as - of a deep red colour, mottled with black; appearances which, from - long soaking in spirit, are not true at the present time; but the - rough, shaggy state of the mucous tissue can be traced; the gullet - and the pylorus appear the least affected. - - _St. George's Hospital_, ser. ix., 146, 11 and 43, e.--The pharynx - and [oe]sophagus of a man who was brought into the hospital in a - state of collapse, after a large but unknown dose of sulphuric acid. - The lips were much eroded, the mucous membrane of the stomach, - pharynx, and [oe]sophagus show an extraordinary shreddy condition; - the lining membrane of the stomach is much charred, and the action - has extended to the duodenum; the muscular coat is not affected. - - _Guy's Hospital_, No. 1799.--A preparation showing the mucous - membrane of the stomach entirely denuded. The organ looks like a - piece of thin paper. - - No. 1799^{20}. The stomach of a woman who poisoned herself by - drinking a wine-glassful of acid before breakfast. She lived eleven - days. The main symptoms were vomiting and purging, but there was no - complaint of pain. There is extensive destruction of mucous membrane - along the lesser curvature and towards the pyloric extremity; a - portion of the mucous membrane is floating as a slough. - - No. 1799^{25} is the gullet and stomach of a man who took about 3 - drachms of the strong acid. He lived three days without much - apparent suffering, and died unexpectedly. The lining membrane of - the [oe]sophagus has the longitudinal wrinkles or furrows so often, - nay, almost constantly, met with in poisoning by the acids. The - mucous tissue of the stomach is raised in cloudy ridges, and - blackened. - - No. 1799^{35} is a wonderfully entire cast of the gullet from a - woman who swallowed an ounce of sulphuric acid, and is said, - according to the catalogue, to have recovered. - - _University College._--In this museum will be found an exquisite - preparation of the effects of sulphuric acid. The mucous membrane of - the [oe]sophagus is divided into small quadrilateral areas by - longitudinal and transverse furrows; the stomach is very brown, and - covered with shreddy and filamentous tissue; the brown colour is - without doubt the remains of extravasated and charred blood. - - No. 6201 is a wax cast representing the stomach of a woman who died - after taking a large dose of sulphuric acid. A yellow mass was found - in the stomach; there are two perforations, and the mucous membrane - is entirely destroyed. - -Sec. 63. =Chronic Poisoning by Sulphuric Acid.=--Weiske[75] has -experimentally proved that lambs, given for six months small doses of -sulphuric acid, grow thin, and their bones, with the exception of the -bones of the head and the long bones, are poor in lime salts, the -muscles also are poor in the same constituents. Kobert[76] thinks that -drunkards on the continent addicted to "Schnaps," commonly a liquid -acidified with sulphuric acid to give it a sharp taste, often show -typical chronic sulphuric acid poisoning. - -[75] H. Weiske, _Journ. f. Landwirthsch._, 1887, 417. - -[76] _Lehrbuch der Intoxicationen_, S. 210. - - -Detection and Estimation of Free Sulphuric Acid. - -Sec. 64. The general method of separating the mineral acids is as follows: -the tissues, or matters, are soaked in distilled water for some time. If -no free acid is present, the liquid will not redden litmus-paper, or -give an acid reaction with any of the numerous tinctorial agents in use -by the chemist for the purposes of titration. After sufficient digestion -in water, the liquid extract is made up to some definite bulk and -allowed to subside. Filtration is unnecessary. A small fractional part -(say, for example, should the whole be 250 c.c., 1/100th or 2.5 c.c.) is -taken, and using as an indicator cochineal or phenolphthalein, the total -acidity is estimated by a decinormal solution of soda. By this -preliminary operation, some guide for the conduct of the future more -exact operations is obtained. Should the liquid be very acid, a small -quantity of the whole is to be now taken, but if the acidity is feeble, -a larger quantity is necessary, and sufficient quinine then added to fix -the acid--100 parts of sulphuric acid are saturated by 342 parts of -quinine monohydrate. Therefore, on the supposition that all the free -acid is sulphuric, it will be found sufficient to add 3.5 parts of -quinine for every 1 part of acid, estimated as sulphuric, found by the -preliminary rough titration; and as it is inconvenient to deal with -large quantities of alkaloid, a fractional portion of the liquid extract -(representing not more than 50 mgrms. of acid) should be taken, which -will require 175 mgrms. of quinine. - -On addition of the quinine, the neutralised liquid is evaporated to -dryness, or to approaching dryness, and then exhausted by strong -alcohol. The alcoholic extract is, after filtration, dried up, and the -quinine sulphate, nitrate, or hydrochlorate, as the case may be, -filtered off and extracted by boiling water, and precipitated by -ammonia, the end result being quinine hydrate (which may be filtered off -and used again for similar purposes) and a sulphate, nitrate or chloride -of ammonia in solution. It therefore remains to determine the nature and -quantity of the acids now combined with ammonia. The solution is made up -to a known bulk, and portions tested for chlorides by nitrate of silver, -and for nitrates by the copper or the ferrous sulphate test. If -sulphuric acid is present, there will be a precipitate of barium -sulphate, which, on account of its density and insolubility in nitric or -hydrochloric acids, is very characteristic. For estimating the sulphuric -acid thus found, it will only be necessary to take a known bulk of the -same liquid, heat it to boiling after acidifying by hydrochloric acid, -and then add a sufficient quantity of baric chloride solution. Unless -this exact process is followed, the analyst is likely to get a liquid -which refuses to filter clear, but if the sulphate be precipitated from -a hot liquid, it usually settles rapidly to the bottom of the vessel, -and the supernatant fluid can be decanted clear; the precipitate is -washed by decantation, and ultimately collected on a filter, dried, and -weighed. - -The sulphate of baryta found, multiplied by .3434, equals the sulphuric -anhydride. - -The older process was to dissolve the free sulphuric acid out by -alcohol. As is well known, mineral sulphates are insoluble in, and are -precipitated by, alcohol, whereas sulphuric acid enters into solution. -The most valid objection, as a quantitative process, to the use of -alcohol, is the tendency which all mineral acids have to unite with -alcohol in organic combination, and thus, as it were, to disappear; and, -indeed, results are found, by experiment, to be below the truth when -alcohol is used. This objection does not hold good if either merely -qualitative evidence, or a fairly approximate quantation, is required. -In such a case, the vomited matters, the contents of the stomach, or a -watery extract of the tissues, are evaporated to a syrup, and then -extracted with strong alcohol and filtered; a little phenolphthalein -solution is added, and the acid alcohol exactly neutralised by an -alcoholic solution of clear decinormal or normal soda. According to the -acidity of the liquid, the amount used of the decinormal or normal soda -is noted, and then the whole evaporated to dryness, and finally heated -to gentle redness. The alkaline sulphate is next dissolved in very -dilute hydrochloric acid, and the solution precipitated by chloride of -barium in the usual way. The quantitative results, although low, would, -in the great majority of cases, answer the purpose sufficiently. - -A test usually enumerated, Hilger's test for mineral acid, may be -mentioned. A liquid, which contains a very minute quantity of mineral -acid, becomes of a blue colour (or, if 1 per cent. or above, of a green) -on the addition of a solution of methyl aniline violet; but this test, -although useful in examining vinegars (see "Foods," p. 519), is not of -much value in toxicology, and the quinine method for this purpose meets -every conceivable case, both for qualitative and quantitative purposes. - -Sec. 65. =The Urine.=--Although an excess of sulphates is found constantly -in the urine of persons who have taken large doses of sulphuric acid, -the latter has never been found in that liquid in a free state, so that -it will be useless to search for free acid. It is, therefore, only -necessary to add HCl to filter the fluid, and precipitate direct with an -excess of chloride of barium. It is better to operate in this manner -than to burn the urine to an ash, for in the latter case part of the -sulphates, in the presence of phosphates, are decomposed, and, on the -other hand, any organic sulphur combinations are liable to be estimated -as sulphates. - -It may also be well to pass chlorine gas through the same urine which -has been treated with chloride of barium, and from which the sulphate -has been filtered off. The result of this treatment will be a second -precipitate of sulphate derived from sulphur, in a different form of -combination than that of sulphate. - -The greatest amount of sulphuric acid as mineral and organic sulphate is -separated, according to Mannkopf[77] and Schultzen,[78] within five -hours after taking sulphuric acid; after three days the secretion, so -far as total sulphates is concerned, is normal. - -[77] "Toxicologie der Schwefelsaeure," _Wiener med. Wochen._, 1862, 1863. - -[78] _Archiv. f. Anatom. u. Physiol._, 1864. - -The normal amount of sulphuric acid excreted daily, according to -Thudichum, is from 1.5 to 2.5 grms., and organic sulphur up to .2 grm. -in the twenty-four hours, but very much more has been excreted by -healthy persons. - -Lehmann made some observations on himself, and found that, on an animal -diet, he excreted no less than 10.399 grms. of sulphuric acid per day, -while on mixed food a little over 7 grms.; but, as Thudichum justly -observes, this great amount must be referred to individual peculiarity. -The amount of sulphates has a decided relation to diet. Animal food, -although not containing sulphates, yet, from the oxidation of the -sulphur-holding albumen, produces a urine rich in sulphate. Thus Vogel -found that a person, whose daily average was 2.02 grms., yielded 7.3 on -a meat diet. The internal use of sulphur, sulphides, and sulphates, -given in an ordinary medicinal way, is traceable in the urine, -increasing the sulphates. In chronic diseases the amount of sulphates is -decreased, in acute increased. - -Finally, it would appear that the determination of sulphates in the -urine is not of much value, _save when the normal amount that the -individual secretes is primarily known_. On the other hand, a low amount -of sulphates in the urine of a person poisoned by sulphuric acid has not -been observed within three days of the taking of the poison, and one can -imagine cases in which such a low result might have forensic importance. - -The presence of albumen in the urine has been considered by some a -constant result of sulphuric acid poisoning, but although when looked -for it is usually found, it cannot be considered constant. O. -Smoler,[79] in eighteen cases of various degrees of sulphuric acid -poisoning, found nothing abnormal in the urine. Wyss[80] found in the -later stages of a case indican and pus. E. Leyden and Ph. Munn[81] -always found blood in the urine, as well as albumen, with casts and -cellular elements. Mannkopf[82] found albuminuria in three cases out of -five; in two of the cases there were fibrinous casts; in two the albumen -disappeared at the end of the second or third day, but in one it -continued for more than twenty days. Bamberger[83] has observed an -increased albuminuria, with separation of the colouring matter of the -blood. In this case it was ascribed to the action of the acid on the -blood. - -[79] _Archiv der Heilkunde red. v._ E. Wagner, 1869, Hft. 2, S. 181. - -[80] _Wiener Medicinal-Halle_, 1861, Jahr. 6, No. 46. - -[81] Virchow's _Archiv f. path. Anat._, 1861. Bd. 22, Hft. 3 u. 4, S. -237. - -[82] _Wien. med. Wochenschrift_, 1862, Nro. 35; 1863, Nro. 5. - -[83] _Wien. Med.-Halle_, 1864, Nro. 29, 30. - -Sec. 66. =The Blood.=--In Casper's case, No. 193, the vena cava of a child, -who died within an hour after swallowing a large dose of sulphuric acid, -was filled with a cherry-red, strongly acid-reacting blood. Again, -Casper's case, No. 200, is that of a young woman, aged 19, who died from -a poisonous dose of sulphuric acid. At the autopsy, four days after -death, the following peculiarities of the blood were thus noted:--"The -blood had an acid reaction, was dark, and had (as is usual in these -cases) a syrupy consistence, while the blood-corpuscles were quite -unchanged. The blood was treated with an excess of absolute alcohol, -filtered, the filtrate concentrated on a water-bath, the residue -exhausted with absolute alcohol, &c. It yielded a small quantity of -sulphuric acid." - -Other similar cases might be noted, but it must not for a moment be -supposed that the mass of the blood contains any free sulphuric acid -during life. The acidity of the blood in the vena cava may be ascribed -to _post-mortem_ endosmosis, the acid passing through the walls of the -stomach into the large vessel. - -Sec. 67. =Sulphates.=--If the acid swallowed should have been entirely -neutralised by antidotes, such as chalk, &c., it becomes of the first -importance to ascertain, as far as possible, by means of a microscopical -examination, the nature of the food remaining in the stomach, and then -to calculate the probable contents in sulphates of the food thus known -to be eaten. It will be found that, with ordinary food, and under -ordinary circumstances, only small percentages of combined sulphuric -acid can be present. - -As an example, take the ordinary rations of the soldier, viz.:--12 oz. -of meat, 24 oz. of bread, 16 oz. of potatoes, 8 oz. of other vegetables; -with sugar, salt, tea, coffee, and water. Now, if the whole quantity of -these substances were eaten at a meal, they would not contain more than -from 8 to 10 grains (.5 to .6 grm.) of anhydrous sulphuric acid, in the -form of sulphates. - -So far as the contents of the stomach are concerned, we have only to do -with sulphates introduced in the food, but when once the food passes -further along the intestinal canal, circumstances are altered, for we -have sulphur-holding secretions, which, with ordinary chemical methods, -yield sulphuric acid. Thus, even in the newly-born infant, according to -the analyses of Zweifler, the mineral constituents of meconium are -especially sulphate of lime, with a smaller quantity of sulphate of -potash. The amount of bile which flows into the whole tract of the -intestinal canal is estimated at about half a litre in the twenty-four -hours; the amount of sulphur found in bile varies from .89 to 3 per -cent., so that in 500 c.c. we might, by oxidising the sulphur, obtain -from 2.2 to 7.5 grms. of sulphuric anhydride. - -It is therefore certain that large quantities of organic -sulphur-compounds may be found in the human intestinal canal, for with -individuals who suffer from constipation, the residues of the biliary -secretion accumulate for many days. Hence, if the analyst searches for -sulphates in excretal matters, all methods involving destruction of -organic substances, whether by fire or by fluid-oxidising agents, are -wrong in principle, and there is nothing left save to separate soluble -sulphates by dialysis, or to precipitate direct out of an aqueous -extract. - -Again, sulphate of magnesia is a common medicine, and so is sodic -sulphate; a possible medicinal dose of magnesia sulphate might amount to -56.7 grms. (2 oz.), the more usual dose being half that quantity. -Lastly, among the insane there are found patients who will eat -plaster-of-Paris, earth, and similar matters, so that, in special cases, -a very large amount of combined sulphuric acid may be found in the -intestinal tract, without any relation to poisoning by the free acid; -but in such instances it must be rare, indeed, that surrounding -circumstances or pathological evidence will not give a clue to the real -state of affairs. - - -II.--Hydrochloric Acid. - -Sec. 68. _General Properties._--Hydrochloric acid, otherwise called -_muriatic acid_, _spirit of salt_, is, in a strictly chemical sense, a -pure gas, composed of 97.26 per cent. of chlorine, and 2.74 per cent. of -hydrogen; but, in an ordinary sense, it is a liquid, being a solution of -the gas itself. - -Hydrochloric acid is made on an enormous scale in the United Kingdom, -the production being estimated at about a million tons annually. - -The toxicology of hydrochloric acid is modern, for we have no evidence -that anything was known of it prior to the middle of the seventeenth -century, when Glauber prepared it in solution, and, in 1772, Priestley, -by treating common salt with sulphuric acid, isolated the pure gas. - -The common liquid hydrochloric acid of commerce has a specific gravity -of from 1.15 to 1.20, and contains usually less than 40 parts of -hydrochloric acid in the 100 parts. The strength of pure samples of -hydrochloric acid can be told by the specific gravity, and a very close -approximation, in default of tables, may be obtained by simply -multiplying the decimal figures of the specific gravity by 200. For -example, an acid of 1.20 gravity would by this rule contain 40 per cent. -of real acid, for .20 x 200 = 40. - -The commercial acid is nearly always a little yellow, from the presence -of iron derived from metallic retorts, and usually contains small -quantities of chloride of arsenic,[84] derived from the sulphuric acid; -but the colourless hydrochloric acid specially made for laboratory and -medicinal use is nearly always pure. - -[84] Some samples of hydrochloric acid have been found to contain as -much as 4 per cent. of chloride of arsenic, but this is very unusual. -Glenard found as a mean 2.5 grammes, As_{2}O_{3} per kilogramme. - -The uses of the liquid acid are mainly in the production of chlorine, as -a solvent for metals, and for medicinal and chemical purposes. Its -properties are briefly as follows:-- - -It is a colourless or faintly-yellow acid liquid, the depth of colour -depending on its purity, and especially its freedom from iron. The -liquid is volatile, and can be separated from fixed matters and the less -volatile acids by distillation; it has a strong attraction for water, -and fumes when exposed to the air, from becoming saturated with aqueous -vapour. If exposed to the vapour of ammonia, extremely dense clouds -arise, due to the formation of the solid ammonium chloride. The acid, -boiled with a small quantity of manganese binoxide, evolves chlorine. -Dioxide of lead has a similar action; the chlorine may be detected by -its bleaching action on a piece of paper dipped in indigo blue; a little -zinc foil immersed in the acid disengages hydrogen. These two -tests--viz., the production of chlorine by the one, and the production -of hydrogen by the other--separate and reveal the constituent parts of -the acid. Hydrochloric acid, in common with chlorides, gives a dense -precipitate with silver nitrate. The precipitate is insoluble in nitric -acid, but soluble in ammonia; it melts without decomposition. Exposed to -the light, it becomes of a purple or blackish colour. Every 100 parts of -silver chloride are equal to 25.43 of hydrochloric acid, HCl, and to -63.5 parts of the liquid acid of specific gravity 1.20. - -The properties of pure hydrochloric acid gas are as follows:--Specific -gravity 1.262, consisting of equal volumes of hydrogen and chlorine, -united without condensation. 100 cubic inches must therefore have a -weight of 39.36 grains. The gas was liquefied by Faraday by means of a -pressure of 40 atmospheres at 10 deg.; it was colourless, and had a less -refractive index than water. - -Water absorbs the gas with avidity, 100 volumes of water absorbing -48,000 volumes of the gas, and becoming 142 volumes. The solution has -all the properties of strong hydrochloric acid, specific gravity 1.21. -The dilute hydrochloric acid of the Pharmacop[oe]ia should have a -specific gravity of 1.052, and be equivalent to 10.58 per cent. of HCl. - -Sec.69. =Statistics of Poisoning by Hydrochloric Acid.=--The following -tables give the deaths, with age and sex distribution, due to -hydrochloric acid for ten years (1883-92):-- - -DEATHS FROM HYDROCHLORIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS -ENDING 1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, Under 1-5 5-15 15-25 25-65 65 and Total - 1 above - Males, 1 16 2 ... 26 3 48 - Females, ... 8 ... ... 9 1 18 - ---------------------------------------------------- - Totals, 1 24 2 ... 35 4 66 - ---------------------------------------------------- - - SUICIDE. - - Ages, 5-15 15-25 25-65 65 and Total - above - Males, ... 2 73 8 83 - Females, 1 8 42 65 116 - --------------------------------------- - Totals, 1 10 115 73 199 - --------------------------------------- - -In 1889 a solitary case of the murder of a child is on record from -hydrochloric acid; hence, with that addition, the total deaths from -hydrochloric acid amount to 266 in the ten years, or about 26 a year. - -Sec. 70. =Fatal Dose.=--The dose which destroys life is not known with any -accuracy. In two cases, adults have been killed by 14 grms. (half an -ounce) of the commercial acid; but, on the other hand, recovery is -recorded when more than double this quantity has been taken. A girl, -fifteen years of age, died from drinking a teaspoonful of the acid.[85] - -[85] _Brit. Med. Journ._, March, 1871. - -Sec. 71. =Amount of Free Acid in the Gastric Juice.=--Hydrochloric acid -exists in the gastric juice. This was first ascertained by Prout[86] in -1824; he separated it by distillation. The observation was afterwards -confirmed by Gmelin,[87] Children,[88] and Braconnot.[89] On the other -hand, Lehmann[90] pointed out that, as the stomach secretion contained, -without doubt, lactic acid, the act of distillation, in the presence of -this lactic acid, would set free hydrochloric acid from any alkaline -chlorides. Blondlot and Cl. Bernard also showed that the gastric juice -possessed no acid which would dissolve oxalate of lime, or develop -hydrogen when treated with iron filings; hence there could not be free -hydrochloric acid which, even in a diluted state, would respond to both -these tests. Then followed the researches of C. Schmidt,[91] who showed -that the gastric secretion of men, of sheep, and of dogs contained more -hydrochloric acid than would satisfy the bases present; and he -propounded the view that the gastric juice does not contain absolutely -free hydrochloric acid, but that it is in loose combination with the -pepsin. - -[86] _Philosophical Transactions_, 1824, p. 45. - -[87] P. Tiedmann and L. Gmelin, _Die Verdauung nach Versuchen_, -Heidelberg u. Leipsic, 1826, i. - -[88] _Annals of Philosophy_, July, 1824. - -[89] _Ann. de Chim._ t. lix. p. 348. - -[90] _Journal f. prakt. Chemie_, Bd. xl. 47. - -[91] Bidder u. Schmidt, _Verdauungs-Saefte_, &c. - -The amount of acid in the stomach varies from moment to moment, and -therefore it is not possible to say what the average acidity of gastric -juice is. It has been shown that in the total absence of _free_ -hydrochloric acid digestion may take place, because hydrochloric acid -forms a compound with pepsin which acts as a solvent on the food. The -amount of physiologically active acid varies with the food taken. It is -smallest when carbohydrates are consumed, greatest with meat. The -maximum amount that Jaksch found in his researches, when meat was -ingested, was .09 per cent. of hydrochloric acid. It is probable that -anything above 0.2 per cent. of hydrochloric acid is either abnormal or -owing to the recent ingestion of hydrochloric acid. - -Sec. 72. =Influence of Hydrochloric Acid on Vegetation.=--Hydrochloric acid -fumes, if emitted from works on a large scale, injure vegetation much. -In former years, before any legal obligations were placed upon -manufacturers for the condensing of the volatile products, the nuisance -from this cause was great. In 1823, the duty on salt being repealed by -the Government, an extraordinary impetus was given to the manufacture of -hydrochloric acid, and since all the volatile products at that time -escaped through short chimneys into the air, a considerable area of land -round the works was rendered quite unfit for growing plants. The present -law on the subject is, that the maximum quantity of acid escaping shall -not exceed 2 grains per cubic foot of the air, smoke, or chimney gases; -and, according to the reports of the alkali inspectors, the condensation -by the improved appliances is well within the Act, and about as perfect -as can be devised. - -It appears from the reports of the Belgian Commission in 1855, when -virtually no precautions were taken, that the gases are liable to injure -vegetation to the extent of 2000 metres (2187 yards) around any active -works; the more watery vapour the air contains, the quicker is the gas -precipitated and carried to the earth. If the action of the vapour is -considerable, the leaves of plants dry and wither; the chlorophyll -becomes modified, and no longer gives the normal spectrum, while a -thickening of the rind of trees has also been noticed. The cereals -suffer much; they increase in stalk, but produce little grain. The -leguminosae become spotted, and have an air of dryness and want of -vigour; while the potato, among plants utilised for food, appears to -have the strongest resistance. Vines are very sensitive to the gas. -Among trees, the alder seems most sensitive; then come fruit-trees, and -last, the hardy forest-trees--the poplar, the ash, the lime, the elm, -the maple, the birch, and the oak.[92] - -[92] Those who desire to study more closely the effect of acids -generally on vegetation may consult the various papers of the alkali -inspectors contained in the Local Government Reports. See also -Schubarth, _Die saueren Gase, welche Schwefelsaeure- und Soda-Fabriken -verbreiten_. _Verhandlungen des Vereins zur Befoerderung des -Gewerbefleisses in Preussen_, 1857, S. 135. Dingler's _Journal_, Bd. -145, S. 374-427. - -Christel, _Ueber die Einwirkung von Saeuren-Daempfen auf die Vegetation_. - -_Arch. f. Pharmacie_, 1871, p. 252. - -_Vierteljahrsschrift fuer gerichtliche Medicin_, 17 Bd. S. 404, 1872. - -Sec.73. =Action upon Cloth and Manufactured Articles.=--On black cloth the -acid produces a green stain, which is not moist and shows no corrosion. -On most matters the stain is more or less reddish; after a little time -no free acid may be detected, by simply moistening the spot; but if the -stain is cut out and boiled with water, there may be some evidence of -free acid. The absence of moisture and corrosion distinguishes the stain -from that produced by sulphuric acid. - -Sec.74. =Poisonous Effects of Hydrochloric Acid Gas.=--Eulenberg[93] has -studied the effects of the vapour of this acid on rabbits and pigeons. -One of these experiments may be cited in detail. Hydrochloric acid gas, -prepared by heating together common salt and sulphuric acid, was passed -into a glass shade supported on a plate, and a rabbit was placed in the -transparent chamber thus formed. On the entrance of the vapour, there -was immediate blinking of the eyes, rubbing of the paws against the -nostrils, and emission of white fumes with the expired breath, while the -respiration was irregular (40 to the minute). After the lapse of ten -minutes, the gas was again introduced, until the atmosphere was quite -thick; the symptoms were similar to those detailed above, but more -violent; and in fourteen minutes from the commencement, the rabbit sank -down on its right side (respirations 32). When twenty-two minutes had -elapsed, the gas was again allowed to enter. The rabbit now lay quiet, -with closed eyes and laboured respiration, and, finally, after -half-an-hour of intermittent exposure to the gas, the animal was -removed. - -[93] _Gewerbe Hygiene_, Berlin, 1876, S. 51. - -The cornea were opalescent, and the eyes filled with water; there was -frequent shaking of the head and working of the forepaws. After three -minutes' exposure to the air, the respirations were found to be 128 per -minute; this quickened respiration lasted for an hour, then gave place -to a shorter and more superficial breathing. On the second day after the -experiment, the rabbit suffered from laboured respiration (28 to the -minute) and pain, and there was a rattling in the bronchial tubes. The -animal died on the third day, death being preceded by slow respiration -(12 to the minute). - -The appearances twenty-four hours after death were as follows:--The eyes -were coated with a thick slime, and both cornea were opalescent; there -was strong rigidity of the body. The pia mater covering the brain was -everywhere hyperaemic, and at the hinder border of both hemispheres -appeared a small clot, surrounded by a thin layer of bloody fluid. The -_plex. venos spin._ was filled with coagulated blood, and there was also -a thin extravasation of blood covering the medulla and pons. The lungs -were mottled bright brown-red; the middle lobe of the right lung was -dark brown, solid, and sank in water; the lower lobe of the same lung -and the upper lobe of the left lung were nearly in a similar condition, -but the edges were of a bright red. The parenchyma in the darker places -on section did not crepitate. On the cut surface was a little dark, -fluid, weakly-acid blood; the tracheal mucous membrane was injected. The -heart was filled with thick coagulated blood; the liver was congested, -of a reddish-brown colour, and rich in dark, fluid blood: in the vena -cava inferior was coagulated blood. The kidneys were not hyperaemic; the -intestines were superficially congested. - -I think there can be little doubt that the symptoms during life, and the -appearances after death, in this case are perfectly consistent with the -following view:--The vapour acts first as a direct irritant, and is -capable of exciting inflammation in the lung and bronchial tissues; but -besides this, there is a secondary effect, only occurring when the gas -is in sufficient quantity, and the action sufficiently prolonged--viz., -a direct coagulation of the blood in certain points of the living -vessels of the lungs. The consequence of this is a more or less general -backward engorgement, the right side of the heart becomes distended with -blood, and the ultimate cause of death is partly mechanical. The -hyperaemia of the brain membranes, and even the haemorrhages, are quite -consistent with this view, and occur in cases where the obstruction to -the circulation is of a coarser and more obvious character, and can -therefore be better appreciated. - -Sec. 75. =Effects of the Liquid Acid.=--There is one distinction between -poisoning by hydrochloric and the other mineral acids--namely, the -absence of corrosion of the skin. Ad. Lesser[94] has established, by -direct experiment, that it is not possible to make any permanent mark on -the skin by the application even of the strongest commercial acid (40 -per cent.). Hence, in any case of suspected poisoning by acid, should -there be stains on the lips and face as from an acid, the presumption -will be rather against hydrochloric. The symptoms themselves differ very -little from those produced by sulphuric acid. The pathological -appearances also are not essentially different, but hydrochloric is a -weaker acid, and the extensive disorganisation, solution, and -perforation of the viscera, noticed occasionally with sulphuric acid, -have never been found in hydrochloric acid poisoning. We may quote here -the following case:-- - -[94] Virchow's _Archiv f. path. Anat._, Bd. 83, Hft. 2, S. 215, 1881. - -A woman, under the influence of great and sudden grief--not unmixed with -passion--drew a bottle from her pocket, and emptied it very quickly. She -immediately uttered a cry, writhed, and vomited a yellow-green fluid. -The abdomen also became enlarged. Milk was given her, but she could not -swallow it, and death took place, in convulsions, two hours after the -drinking of the poison. - -The _post-mortem_ appearances were briefly as follows:--Mouth and tongue -free from textural change: much gas in the abdomen, more especially in -the stomach; the membranes of the brain congested; the lungs filled with -blood. The stomach was strongly pressed forward, of a dark brown-red, -and exhibited many irregular blackish spots, varying from two lines to -half an inch in diameter (the spots were drier and harder than the rest -of the stomach); the mucous membrane, internally, was generally -blackened, and changed to a carbonised, shaggy, slimy mass, while the -organ was filled with a blackish homogeneous pulp, which had no odour. -The gullet was also blackened. A considerable quantity of hydrochloric -acid was separated from the stomach.[95] - -[95] _Preuss. Med. Vereinszeit. u. Friederichs Blaetter f. gerichtl. -Anthropologie_, 1858, Hft. 6, S. 70. - -The termination in this instance was unusually rapid. In a case detailed -by Casper,[96] in which a boy drank an unknown quantity of acid, death -took place in seven hours. In Guy's Hospital museum, the duodenum and -stomach are preserved of a patient who is said to have died in nine and -a half hours from half an ounce of the acid. The same quantity, in a -case related by Taylor, caused death in eighteen hours. From these and -other instances, it may be presumed that death from acute poisoning by -hydrochloric acid will probably take place within twenty-four hours. -From the secondary effects, of course, death may take place at a remote -period, _e.g._, in a case recorded by Dr. Duncan (_Lancet_, April 12, -1890), a man drank about 1 oz. of HCl accidentally, was admitted to -Charing Cross Hospital the same day, and treated with small quantities -of sodium carbonate, and fed by the rectum. On the eighth day he brought -up 34 oz. of blood; in a month he left apparently perfectly well, but -was admitted again in about six weeks, and died of contraction of the -stomach and stricture of the pylorus on the ninety-fourth day. - -[96] Case 230.--_Gerichtliche Medicin_, 6th Ed., Berlin, 1876. - -Sec.76. =Post-mortem Appearances.=--The pathological appearances are very -similar to those found in the case already detailed; though the skin of -the face may not be eroded in any way by the acid, yet the more delicate -mucous membrane of the mouth, gullet, &c., appears mostly to be changed, -and is usually white or whitish-brown. There is, however, in the museum -of the Royal College of Surgeons the stomach and gullet (No. 2386c.) of -an infant thirteen months old; the infant drank a tea-cupful of strong -hydrochloric acid, and died nine hours after the dose. The pharynx and -the upper end of the gullet is quite normal, the corrosive action -commencing at the lower end, so that, although the acid was -concentrated, not the slightest effect was produced on the delicate -mucous membrane of the throat and upper part of the gullet. The lower -end of the gullet and the whole of the stomach were intensely congested; -the rugae of the latter were ecchymosed and blackened by the action of -the acid. There were also small haemorrhages in the lungs, which were -ascribed to the action of the acid on the blood. Perforation of the -stomach has not been noticed in hydrochloric acid poisoning. - -In Guy's Hospital museum (prep. 1799^{10}), the stomach and duodenum of -the case mentioned exhibit the mucous membrane considerably injected, -with extravasations of blood, which, at the time when the preparation -was first arranged, were of various hues, but are now somewhat altered, -through long keeping in spirit. In St. George's Hospital museum (ser. x. -43, d. 200) are preserved the stomach and part of the duodenum of a -person who died from hydrochloric acid. The case is detailed in the -_Medical Times and Gazette_ for 1853, vol. ii. p. 513. The whole inner -surface appears to be in a sloughing state, and the larynx and lung were -also inflamed. - -A preparation, presented by Mr. Bowman to King's College Hospital -museum, exhibits the effects of a very large dose of hydrochloric acid. -The gullet has a shrivelled and worm-eaten appearance; the stomach is -injected with black blood, and was filled with an acid, grumous -matter.[97] - -[97] A drawing of parts of the gullet and stomach is given in Guy and -Ferrier's _Forensic Medicine_. - -Looking at these and other museum preparations illustrating the effects -of sulphuric and hydrochloric acids, I was unable (in default of the -history of the cases) to distinguish between the two, by the naked eye -appearances, save in those cases in which the disorganisation was so -excessive as to render hydrochloric acid improbable. On the other hand, -the changes produced by nitric acid are so distinctive, that it is -impossible to mistake its action for that of any other acid. The nitric -acid pathological preparations may be picked out at a glance. - - -Detection and Estimation of Free Hydrochloric Acid. - -Sec. 77. (1) =Detection.=--A large number of colouring reagents have been -proposed as tests for the presence of free mineral acid; among the best -is _methyl-aniline violet_ decolorised by a large amount of hydrochloric -acid; the violet turns to green with a moderate quantity, and to blue -with a small quantity. - -=Tropaeolin= (00), in the presence of free mineral acid, strikes a -ruby-red to a dark brown-red. - -=Congo-red= is used in the form of paper dyed with the material; large -amounts of free hydrochloric acid strike blue-black, small quantities -blue. - -=Guenzburg's test= is 2 parts phloroglucin and 1 part vanillin, dissolved -in 100 parts of alcohol. Fine red crystals are precipitated on the -addition of hydrochloric acid. To test the stomach contents for free -hydrochloric acid by means of this reagent, equal parts of the fluid and -the test are evaporated to dryness in the water-bath in a porcelain -dish. If free hydrochloric acid be present, the evaporated residue shows -a red colour; 1 mgrm. of acid can by this test be detected. The reaction -is not interfered with by organic acids, peptones, or albumin. - -Jaksch speaks highly of _benzopurpurin_ as a test. Filter-paper is -soaked in a saturated aqueous solution of benzopurpurin 6 B (the variety -1 or 4 B is not so sensitive), and the filter-paper thus prepared -allowed to dry. On testing the contents of the stomach with the reagent, -if there is more than 4 parts per 1000 of hydrochloric acid the paper is -stained intensely blue-black; but if the colour is brown-black, this is -from butyric or lactic acids, or from a mixture of these acids with -hydrochloric acid. If the paper is washed with pure ether, and the -colour was due only to organic acids, the original hue of the paper is -restored; if the colour produced was due to a mixture of mineral and -organic acids, the brown-black colour is weakened; and, lastly, if due -to hydrochloric acid alone, the colour is not altered by washing with -ether. Acid salts have no action, nor is the test interfered with by -large amounts of albumins and peptones. - -A. Villiers and M. Favolle[98] have published a sensitive test for -hydrochloric acid. The test consists of a saturated aqueous solution of -colourless aniline, 4 parts; glacial acetic acid, 1 part; 0.1 mgrm. of -hydrochloric acid strikes with this reagent a blue colour, 1 mgrm. a -black colour. The liquid under examination is brought by evaporation, or -by the addition of water, to 10 c.c. and placed in a flask; to this is -added 5 c.c. of a mixture of equal parts of sulphuric acid and water, -then 10 c.c. of a saturated solution of potassic permanganate, and -heated gently, conveying the gases into 3 to 5 c.c. of the reagent -contained in a test-tube immersed in water. If, however, bromine or -iodine (one or both) should be present, the process is modified as -follows:--The hydracids are precipitated by silver nitrate; the -precipitate is washed, transferred to a small flask, and treated with 10 -c.c. of water and 1 c.c. of pure ammonia. With this strength of ammonia -the chloride of silver is dissolved easily, the iodide not at all, and -the bromide but slightly. The ammoniacal solution is filtered, boiled, -and treated with SH_{2}; the excess of SH_{2} is expelled by boiling, -the liquid filtered, reduced to 10 c.c. by boiling or evaporation, -sulphuric acid and permanganate added as before, and the gases passed -into the aniline. The process is inapplicable to the detection of -chlorides or hydrochloric acid if cyanides are present, and it is more -adapted for traces of hydrochloric acid than for the quantities likely -to be met with in a toxicological inquiry. - -[98] _Comptes Rend._, cxviii. - -(2) =Quantitative estimation of Free Hydrochloric Acid.=--The contents -of the stomach are diluted to a known volume, say 250 or 500 c.c. A -fractional portion is taken, say 10 c.c., coloured with litmus or -phenol-phthalein, and a decinormal solution of soda added drop by drop -until the colour changes; this gives total acidity. Another 10 c.c. is -shaken with double its volume of ether three times, the fluid separated -from ether and titrated in the same way; this last titration will give -the acidity due to mineral acids and acid salts;[99] if the only mineral -acid present is hydrochloric acid the results will be near the truth if -reckoned as such, and this method, although not exact for physiological -research, is usually sufficient for the purpose of ascertaining the -amount of hydrochloric acid or other mineral acids in a case of -poisoning. It depends on the fact that ether extracts free organic -acids, such as butyric and lactic acids, but does not extract mineral -acids. - -[99] To distinguish between acidity due to free acid and acid salts, or -to acidity due to the combined action of acid salts and free acids, the -method of Leo and Uffelmann is useful. A fractional portion of the -contents of the stomach is triturated with pure calcium carbonate; if -all the acidity is due to free acid, the fluid in a short time becomes -neutral to litmus; if, on the other hand, the acidity is due entirely to -acid salts, the fluid remains acid; or, if due to both acid and acid -salts, there is a proportionate diminution of acidity due to the -decomposition of the lime carbonate by the free acid. A quantitative -method has been devised upon these principles. See Leo, _Diagnostik der -Krankheiten der Verdauungsorgane_, Hirschwald, Berlin, 1890. - -The free mineral acid, after extracting the organic acid by ether, can -also be saturated with cinchonine; this hydrochlorate of cinchonine is -extracted by chloroform, evaporated to dryness, and the residue -dissolved in water acidified by nitric acid and precipitated by silver -nitrate; the silver chloride produced is collected on a small filter, -washed, and the filter, with its contents, dried and ignited in a -porcelain crucible; the silver chloride, multiplied by 0.25426, equals -HCl. - -The best method of estimating free hydrochloric acid in the stomach is -that of Sjokvist as modified by v. Jaksch;[100] it has the disadvantage -of its accuracy being interfered with by phosphates; it also does not -distinguish between actual free HCl and the loosely bound HCl with -albuminous matters,--this in a toxicological case is of small -importance, because the quantities of HCl found are likely to be large. - -[100] _Klinische Diagnostik_, Dr. Rudolph v. Jaksch, Wien u. Leipzig, -1892. _Clinical Diagnosis_. English Translation, by Dr. Cagney. Second -Edition. London: Charles Griffin & Co., Limited. - -The method is based upon the fact that if carbonate of baryta be added -to the contents of the stomach, the organic acids will decompose the -barium carbonate, forming butyrate, acetate, lactate, &c., of barium; -and the mineral acids, such as hydrochloric acid, will combine, forming -salts of barium. - -On ignition, chloride of barium will be unaffected, while the organic -salts of barium will be converted into carbonate of barium, practically -insoluble in carbonic acid free water. - -The contents of the stomach are coloured with litmus, and barium -carbonate added until the fluid is no longer acid (as shown by the -disappearance of the red colour); then the contents are evaporated to -dryness in a platinum dish, and ignited at a dull red heat; complete -burning to an ash is not necessary. After cooling, the burnt mass is -repeatedly exhausted with boiling water and filtered; the chloride of -barium is precipitated from the filtrate by means of dilute sulphuric -acid; the barium sulphate filtered off, washed, dried, and, after -ignition, weighed; 233 parts of barium sulphate equal 73 parts of HCl. - -A method somewhat quicker, but depending on the same principles, has -been suggested by Braun.[101] A fractional part, say 10 c.c., of the -fluid contents is coloured by litmus and titrated with decinormal soda. -To the same quantity is added 2 or 3 more c.c. of decinormal soda than -the quantity used in the first titration; this alkaline liquid is -evaporated to dryness and ultimately ignited. To the ash is now added -exactly the quantity of decinormal sulphuric acid as the decinormal soda -last used to make it alkaline--that is to say, if the total acidity was -equal to 3.6 d.n. soda, and 5.0 d.n. soda was added to the 10 c.c. -evaporated to dryness and burned, then 5.6 c.c. of d.n. sulphuric acid -is added to the ash. The solution is now warmed to get rid of carbon -dioxide, and, after addition of a little phenolphthalein, titrated with -d.n. soda solution until the change of colour shows saturation, the -number of c.c. used, multiplied by 0.00365, equals the HCl. - -[101] _Op. cit._, S. 157. - -Sec.78. In investigating the stains from hydrochloric acid on fabrics, or -the leaves of plants, any free hydrochloric acid may be separated by -boiling with water, and then investigating the aqueous extract. Should, -however, the stain be old, all free acid may have disappeared, and yet -some of the chlorine remain in organic combination with the tissue, or -in combination with bases. Dr. Angus Smith has found weighed portions of -leaves, &c., which had been exposed to the action of hydrochloric acid -fumes, richer in chlorides than similar parts of the plants not thus -exposed. - -The most accurate method of investigation for the purpose of separating -chlorine from combination with organic matters is to cut out the -stained portions, weigh them, and burn them up in a combustion-tube, -the front portion of the tube being filled with caustic lime known to be -free from chlorides; a similar experiment must be made with the -unstained portions. In this way a considerable difference may often be -found; and it is not impossible, in some instances, to thus detect, -after the lapse of many years, that certain stains have been produced by -a chlorine-holding substance. - - -III.--Nitric Acid. - -Sec. 79. =General Properties.=--Nitric acid--commonly known in England as -_aqua fortis_, chemically as _nitric acid_, _hydric nitrate_, or _nitric -monohydrate_--is a mono-hydrate of nitrogen pentoxide (N_{2}O_{5}), two -equivalents, or 126 parts, of nitric acid containing 108 of N_{2}O_{5}, -and 18 of H_{2}O. Anhydrous nitric acid, or nitrogen pentoxide, can be -obtained by passing, with special precautions, dry chlorine over silver -nitrate; the products are free oxygen and nitrogen pentoxide, according -to the following equation:-- - - Silver Chlorine. Silver Nitrogen Oxygen. - Nitrate. Chloride. Pentoxide. - Ag_{2}O,N_{2}O_{5} + 2Cl = 2AgCl + N_{2}O_{5} + O - -By surrounding the receiver with a freezing mixture, the acid is -condensed in crystals, which dissolve in water, with emission of much -heat, forming nitric acid. Sometimes the crystals, though kept in sealed -tubes, decompose, and the tube, from the pressure of the liberated -gases, bursts with a dangerous explosion. - -Pure nitric acid has a specific gravity of 1.52, and boils at 98 deg. Dr. -Ure examined the boiling point and other properties of nitric acid very -fully. An acid of 1.5 specific gravity boils at 98.8 deg.; of specific -gravity 1.45, at 115.5 deg.; specific gravity 1.40, at 118.8 deg.; of specific -gravity 1.42, at 122.8 deg. The acid of specific gravity 1.42 is the -standard acid of the British Pharmacop[oe]ia. It can always be obtained -by distilling either strong or moderately weak nitric acid; for, on the -one hand, the acid on distillation gets weaker until the gravity of 1.42 -is reached, or, on the other, it becomes stronger. - -There is little doubt that acid of 1.42 gravity is a definite hydrate, -consisting of 1 atom of dry acid and 4 atoms of water; it corresponds to -75 per cent.[102] of the liquid acid HNO_{3}. There are also at least -two other hydrates known--one an acid of 1.485 specific gravity, -corresponding to 1 atom of dry acid and 2 of water, and an acid of -specific gravity 1.334, corresponding to 1 atom of dry acid and 7 atoms -of water. - -[102] The British Pharmacop[oe]ia states that the 1.42 acid equals 70 -per cent. of HNO_{3}; but this is not in accordance with Ure's Tables, -nor with the facts. - -In Germany the officinal acid is of 1.185 specific gravity, -corresponding to about 30 per cent. of HNO_{3}. The dilute nitric acid -of the Pharmacop[oe]ia is a colourless liquid, of specific gravity -1.101, and should contain about 17.4 per cent. of acid. The acids used -in various industries are known respectively as _dyers'_ and -_engravers'_ acid. _Dyers'_ acid has a specific gravity of 1.33 to 1.34 -(66 deg. to 68 deg. Twad.), that is, strength from 56 to 58 per cent. of -HNO_{3}. _Engravers'_ acid is stronger; being of 1.40 specific gravity -(80 deg. Twad.); and contains 70 per cent. of HNO_{3}. Although the _pure_ -acid of commerce is (and should be) almost colourless, most commercial -specimens are of hues from yellow up to deep red. An acid saturated with -red oxides of nitrogen is often known as "fuming nitric acid." - -Sec. 80. =Use in the Arts.=--Nitric acid is employed very extensively in -the arts and manufactures. The dyer uses it as a solvent for tin in the -preparation of valuable mordants for calico and other fabrics; the -engraver uses it for etching copper. It is an indispensable agent in the -manufacture of gun-cotton, nitro-glycerin, picric acid, and sulphuric -acid; it is also used in the manufacture of tallow, in preparing the -felt for hats, and in the gilding trades. It is said to be utilised to -make yellowish or fawn-coloured spots on cigar leaves, so as to give -them the appearance of age and quality. It is also used as a medicine. - -Sec. 81. =Statistics of Poisoning by Nitric Acid.=--In the ten years -1883-1892 no case of murder was ascribed to nitric acid, but it caused -accidentally 25 deaths, and was used in 27 cases of suicide. - -The following tables give the age and sex distribution of these -deaths:-- - -DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS ENDING 1892 FROM NITRIC -ACID. - - ACCIDENT OR NEGLIGENCE. - - Ages, 1-5 5-15 15-25 25-65 65 and Total - above - Males, 6 2 1 9 ... 18 - Females, 3 ... ... 4 ... 7 - -------------------------------------- - Totals, 9 2 1 13 ... 25 - -------------------------------------- - - SUICIDE. - - Ages, 15-25 25-65 65 and Total - above - Males, 3 14 1 18 - Females, 1 8 ... 9 - ---------------------------- - Totals, 4 22 1 27 - ---------------------------- - -Sec. 82. =Fatal Dose.=--The dose which causes death has not been -ascertained with any exactness. As in the case of sulphuric acid, we may -go so far as to say that it is possible for a few drops of the strong -acid to be fatal, for if brought into contact with the vocal apparatus, -fatal spasm of the glottis might be excited. The smallest dose on record -is 7.7 grms. (2 drachms), which killed a child aged 13. - -Sec. 83. =Action of Nitric Acid on Vegetation.=--Nitric acid acts on plants -injuriously in a two-fold manner--viz., by direct corrosive action, and -also by decomposing the chlorides which all plants contain, thus setting -free chlorine, which decomposes and bleaches the chlorophyll. The action -is most intense on soft and delicate leaves, such as those of clover, -the cabbage, and all the cruciferae. The tobacco plant is particularly -injured by nitric acid. Next to all herbaceous plants, trees, such as -the apple, pear, and fruit trees, generally suffer. The coniferae, -whether from their impregnation with resin, or from some other cause, -possess a considerable resisting-power against nitric acid vapours, and -the same is true as regards the cereals; in the latter case, their -siliceous armour acts as a preserving agent. - -Sec. 84. =Nitric Acid Vapour.=--The action of nitric acid in a state of -vapour, as evolved by warming potassic nitrate and sulphuric acid -together, has been studied by Eulenberg. A rabbit was placed under a -shade into which 63 grains of nitric acid in a state of vapour were -introduced. From the conditions of the experiment, some nitric peroxide -must also have been present. Irritation of the external mucous membranes -and embarrassment in breathing were observed. The animal in forty-five -minutes was removed, and suffered afterwards from a croupous bronchitis, -from which, however, it completely recovered in eleven days. A second -experiment with the same animal was followed by death. On inspection, -there was found strong injection of the cerebral membranes, with small -extravasations of blood; the lungs were excessively congested; the right -middle lobe especially was of a liver-brown colour, and empty of air: it -sank in water. - -O. Lassar[103] has also made a series of researches on the influence of -nitric acid vapour, from which he concludes that the acid is not -absorbed by the blood, but acts only by its mechanical irritation, for -he could not trace, by means of an examination of the urine, any -evidence of such absorption. - -[103] Hoppe-Seyler's _Zeitschrift f. physiol. Chemie_, Bd. i. S. -165-173, 1877-78. - -There are a few instances on record of the vapour having been fatal to -men; for example, the well-known case of Mr. Haywood, a chemist of -Sheffield, may be cited. In pouring a mixture of nitric and sulphuric -acids from a carboy of sixty pounds capacity, the vessel broke, and for -a few minutes he inhaled the mixed fumes. He died eleven hours after -the accident, although for the first three hours there were scarcely any -symptoms of an injurious effect having been produced. On inspection, -there was found intense congestion of the windpipe and bronchial tubes, -with effusion of blood in the latter. The lining membrane of the heart -and aorta was inflamed; unfortunately, the larynx was not examined.[104] - -[104] _Lancet_, April 15, 1854, p. 430. - -A very similar case happened in Edinburgh in 1863.[105] Two young men -were carrying a jar of nitric acid; the jar broke, and they attempted to -wipe up the acid from the floor. The one died ten hours after the -accident, the other in less than twenty-four hours. The symptoms were -mainly those of difficult breathing, and it is probable that death was -produced from suffocation. Dr. Taylor relates also, that having -accidentally inhaled the vapour in preparing gun-cotton, he suffered -from severe constriction of the throat, tightness in the chest, and -cough, for more than a week.[106] - -[105] _Chemical News_, March 14, 1863, p. 132. - -[106] _Principles and Practice of Medical Jurisprudence_, vol. i., 1873, -p. 218. - -Sec. 85. =Effects of Liquid Nitric Acid.=--Poisoning by nitric acid, though -still rare, is naturally more frequent than formerly. At the beginning -of this century, Tartra[107] wrote a most excellent monograph on the -subject, and collated all the cases he could find, from the first -recorded instances related by Bembo[108] in Venetian history, down to -his own time. The number of deaths in those 400 years was but -fifty-five, while, in our century, at least fifty can be numbered. Most -of these (74 per cent.) are suicidal, a very few homicidal, the rest -accidental. In one of Tartra's cases, some nitric acid was placed in the -wine of a drunken woman, with fatal effect. Osenbrueggen[109] relates the -case of a father murdering his six children by means of nitric acid; and -C. A. Buechner[110] that of a soldier who poured acid into the mouth of -his illegitimate infant. A curious case is one in which a man poisoned -his drunken wife by pouring the acid into her right ear; she died after -six weeks' illness. All these instances prove again, if necessary, that -the acid is only likely to be used with murderous intent in the case of -young children, or of sleeping, drunken, or otherwise helpless people. - -[107] Tartra, A. E., Dr., _Traite de l'Empoisonnement par l'Acide -Nitrique_, Paris, An. 10 (1802), pp. 300. - -[108] _Bembo Cardinalis, Rerum Venetarium Historiae_, lib. xii., lib. i. -p. 12, Paris Ed., 1551. - -[109] _Allgem.-Deutsche Strafrechtszeitung, herausgeg. v. Frz. v. -Holtzendorff_, 5 Jahrg., 1865, Hft. 5, S. 273. - -[110] Friederich's _Blaetter f. ger. Med._, 1866, Hft. 3, S. 187. - -As an example of the way in which accidents are brought about by -heedlessness, may be cited the recent case of a woman who bought a small -quantity of aqua fortis for the purpose of allaying toothache by a -local application. She attempted to pour the acid direct from the bottle -into the cavity of the tooth; the acid went down her throat, and the -usual symptoms followed. She threw up a very perfect cast of the gullet -(preserved in University College museum), and rapidly died. Nitric acid -has been mistaken for various liquids, and has also been used by -injection as an abortive, in every respect having a toxicological -history similar to that of sulphuric acid. - -Sec. 86. =Local Action.=--When strong nitric acid comes in contact with -organic matters, there is almost constantly a development of gas. The -tissue is first bleached, and then becomes of a more or less intense -yellow colour. Nitric acid spots on the skin are not removed by ammonia, -but become of an orange-red when moistened with potash and a solution of -cyanide of potassium. The yellow colour seems to show that picric acid -is one of the constant products of the reaction; sulphide of ammonium -forms a sort of soap with the epidermis thus attacked, and detaches it. - -Sec. 87. =Symptoms.=--The symptoms and course of nitric acid poisoning -differ in a few details only from those of sulphuric acid. There is the -same instant pain and frequent vomiting, destruction of the mucous -membranes, and, in the less severe cases, after-contraction of the -gullet, &c. - -One of the differences in the action of nitric and sulphuric acids is -the constant development of gas with the former. This, without doubt, -adds to the suffering. Tartra made several experiments on dead bodies, -and showed that very considerable distension of the intestinal canal, by -gaseous products, was the constant result; the tissues were corroded and -almost dissolved, being transformed, ultimately, into a sort of greasy -paste. The vomited matters are of a yellow colour, unless mixed with -blood, when they are of a dirty-brown hue, with shreds of yellow mucus, -and have the strong acid reaction and smell of nitric acid. The teeth -may be partially attacked from the solvent action of the acid on the -enamel. The fauces and tongue, at first blanched, soon acquire a -citron-yellow, or even a brown colour; the whole cavity may swell and -inflame, rendering the swallowing of liquids difficult, painful, and -sometimes impossible. The air passages may also become affected, and in -one case tracheotomy was performed for the relief of the breathing.[111] -The stomach rejects all remedies; there are symptoms of collapse; quick, -weak pulse, frequent shivering, obstinate constipation, and death (often -preceded by a kind of stupor) in from eighteen to twenty-four hours. The -intellectual faculties remain clear, save in a few rare instances. - -[111] Arnott, _Med. Gaz._, vol. xii. p. 220. - -C. A. Wunderlich has recorded an unusual case, in which the symptoms -were those of dysentery, and the large intestine was found acutely -inflamed, while the small one was little affected. The kidneys had the -same appearance as in Bright's disease.[112] The smallest fatal dose -given by Taylor is from 2 drachms, which killed a child aged 13 years. -Should the dose of nitric acid be insufficient to kill at once, or, what -amounts to the same thing, should the acid be immediately diluted with -water, or in some way be neutralised, the patient, as in the case of -sulphuric acid, may yet die at a variable future time from stenosis of -the gullet, impaired digestion, &c. For example, in an interesting case -related by Tartra,[113] a woman, who had swallowed 42 grms. (1.5 oz.) of -nitric acid, feeling acute pain, took immediately a quantity of water, -and three hours afterwards was admitted into hospital, where she -received appropriate treatment. At the end of a month she left, -believing herself cured; but in a little while returned, and was -re-admitted, suffering from marasmus, extreme weakness, and constant -vomiting; ultimately she died. The _post-mortem_ examination revealed -extreme contraction of the intestinal canal throughout. The lumen would -hardly admit a penholder. The stomach was no larger than an ordinary -intestine, and adherent to adjacent organs; on its internal surface -there were spots, probably cicatrices; there were also changes in the -gullet, but not so marked. A somewhat similar case is related by the -same author in his thirteenth observation. In the Middlesex Hospital -there is preserved the stomach (No. 1363) of a man who died forty days -after swallowing 2 ozs. of nitric acid diluted in a tumbler of water. -The stomach is contracted, the mucous membrane of the lower part of the -gullet, the lesser curvature, and the pyloric end of the stomach is -extensively corroded, showing ulcerated patches commencing to cicatrize. - -[112] _De Actionibus quibusdam Acidi Nitrici Caustico in Corpus Humanum -immissi. Programma Academ._, Lipsiae, 1857, 4. - -[113] _Op. cit._ - -Sec. 88. =Post-mortem Appearances.=--The pathological changes in the -tongue, gullet, and stomach can be readily studied from the preparations -in the different museums. The staining by the nitric acid appears -unchanged to the naked eye for many years; hence, most of the nitric -acid preparations are in an excellent state of preservation. A very good -example of the pathological changes is to be found in Nos. 1049 and -1050, University College museum. - - No. 1049 presents the tongue, pharynx, and larynx of a man who had - swallowed a tea-cupful of nitric acid. The epithelium of the - [oe]sophagus is for the most part wanting, and hangs in shreds; the - dorsum of the tongue, in front of the circumvallate papillae, is - excavated, and over its central part superficially ulcerated; in - other places the tongue is encrusted with a thick, loose, - fawn-coloured layer, formed probably of desquamated epithelium. The - whole of the mucous surface is stained of a dirty yellow. - - No. 1050 is a preparation showing the tongue, gullet, and stomach of - a person who died from the effects of nitric acid. The tongue in - places is smooth and glazed; in others, slightly depressed and - excavated. On the anterior wall and lower portion of the gullet two - large sloughs exist. - - Although perforation of the stomach is not so common with nitric as - with sulphuric acid, such an accident may occur, as shown in a - preparation at Guy's Hospital, in which there is a perforation at - the cardiac end. All the mucous membrane has disappeared, and the - inner surface is for the most part covered with flocculent shreds. - Three ounces of nitric acid are said to have been swallowed, and the - patient lived seventeen hours. There is the usual staining. There is - also in the Middlesex Hospital (No. 1364) the [oe]sophagus and - stomach of a woman aged 30, who died six hours after swallowing 2 to - 3 ozs. of strong nitric acid. The inner coats of the mucous membrane - of the gullet and stomach are in part converted into opaque yellow - and black eschars, and in part to a shreddy pulpy condition. At the - most depending part of the stomach is a large ragged perforation, - with pulpy margins, which allowed the contents of the stomach to - escape into the peritoneal cavity. - - In St. Bartholomew's museum, there is a very good specimen (No. - 1870) of the appearances in the gullet and stomach after poisoning - by nitric acid. The case is detailed in _St. Bartholomew's Hospital - Reports_, vol. v. p. 247. A male died in fifteen hours after - swallowing 1 oz. of nitric acid. The whole mucous membrane is - wrinkled, or rather ploughed, into longitudinal furrows, the yellow - discoloration stops abruptly, with an irregular border, at the - commencement of the stomach, the epithelial and mucous coats of - which are wanting--its surface being rough and of a brownish-red - colour. - - The following preparations are to be found in the museum of the - London Hospital:--A. b. 1. and A. b. 8.--A. b. 1. shows the pharynx, - [oe]sophagus, larynx, and stomach of a young woman, who, after - taking half an ounce of nitric acid, died in eight hours. The - staining is very intense; as an unusual feature, it may be noted - that the larynx is almost as yellow as the [oe]sophagus. The - abrasion or solution of the epithelium on the dorsum of the tongue - has dissected out the circumvallate and fungiform papillae, so that - they project with unusual distinctness. The lining membrane of the - gullet throughout is divided into minute squares by longitudinal and - transverse furrows. The mucous membrane of the stomach appears - wholly destroyed, and presents a woolly appearance. - - A. b. 8. shows a very perfect cast of the [oe]sophagus. The case was - that of a woman, aged 35, who swallowed half an ounce of nitric - acid. The symptoms for the first four days were the usual pain in - the throat and stomach, which might be expected; the bowels were - freely open, and the stools dark and offensive. On the sixth day, - there was constant vomiting with offensive breath; on the ninth, the - appearance of the patient was critical, and she threw up the cast - preserved. She died on the tenth day after the taking of the acid. - The gullet, stomach, trachea, and larynx were found after death much - inflamed. - - The following preparations are in St. Thomas' Hospital:--P. 5.--a - stomach with gullet attached. The stomach is covered with - yellowish-green patches of false membrane and deposit; the gullet - has the usual longitudinal furrows so characteristic of corrosive - fluids. - - P. 6. is also from a case of nitric acid poisoning. It shows the - lining membrane of the stomach partly destroyed and shreddy, yet but - little discoloured, the hue being a sort of delicate fawn. - - To these may be added a case described and figured by Lesser; to a - baby, a few days old, an unknown quantity of fuming nitric acid was - given; the child made a gurgling, choking sound, and died in a few - minutes. The corpse, nine days after death, showed no signs of - decomposition. The tongue and gums were yellow, the gullet less so, - the stomach still less, and the small intestine had no yellow tint; - the whole of the mouth, gullet, and stomach showed the corrosive - action of the acid. The graduation of tint, Lesser remarks, is what - is not seen when the yellow colour is due to poisoning by chromic - acid or by strong solution of ferric perchloride; in such cases, - wherever the liquid has gone, there is a yellowness.[114] - -[114] A. Lesser, _Atlas der gerichtlichen Medicin_, Berlin, 1884, Tafel -i. fig. 2. - -Sec. 89. =Detection and Estimation of Nitric Acid.=--The detection either -of free nitric acid or of its salts is not difficult. Free nitric acid, -after preliminary estimation of the total acidity by decinormal soda, -may be separated by the cinchonine process given at p. 100. On -precipitation by ammonia or soda solution, the nitrate of ammonia or -soda (and, it may be, other similarly combined acids) remain in -solution. If free nitric acid is present in small quantity only, it may -be necessary to evaporate the filtrate from the quinine nearly to -dryness, and to test the concentrated liquid for nitric acid. The -ordinary tests are as follows:-- - -(1.) Nitrates, treated with mercury or copper and strong sulphuric acid, -develop nitric oxide, recognised by red fumes, if mixed with air or -oxygen. - -(2.) A nitrate dissolved in a small quantity of water, with the addition -of a crystal of ferrous sulphate (allowed to partially dissolve), and -then of strong sulphuric acid--poured through a funnel with a long tube -dipping to the bottom of the test-tube, so as to form a layer at the -bottom--strikes a brown colour at the junction of the liquid. When the -test is properly performed, there will be three layers--the uppermost -being the nitrate solution, the middle ferrous sulphate, and the lowest -sulphuric acid; the middle layer becomes of a smoky or black hue if a -nitrate is present. Organic matter interferes much with the reaction. - -(3.) Nitrates in solution, treated in the cold with a zinc copper -couple, are decomposed first into nitrites, and then into ammonia. The -nitrites may be detected by a solution of metaphenyldiamine, which -strikes a red colour with an infinitesimal quantity. Hence, a solution -which gives no red colour with metaphenyldiamine, when submitted to the -action of a zinc copper couple, and tested from time to time, cannot -contain nitrites; therefore, no nitrates were originally present. - -(4.) Nitrates, on being treated with strong sulphuric acid, and then a -solution of indigo carmine dropped in, decolorise the indigo; this is a -useful test--not conclusive in itself, but readily applied, and if the -cinchonine method of separation has been resorted to, with few sources -of error. - -There is a process of separating nitric acid direct from any organic -tissue, which may sometimes be useful:--Place the substance in a strong, -wide-mouthed flask, closed by a caoutchouc cork, and in the flask put a -small, short test-tube, charged with a strong solution of ferrous -chloride in hydrochloric acid. The flask is connected to the mercury -pump (see fig. p. 47), and made perfectly vacuous by raising and -lowering the reservoir. When this is effected, the tube SS'P is adjusted -so as to deliver any gas evolved into a eudiometer, or other -gas-measuring apparatus. By a suitable movement of the flask, the acid -ferrous chloride is allowed to come in contact with the tissue, a gentle -heat applied to the flask, and gases are evolved. These may be carbon -dioxide, nitrogen, and nitric oxide. On the evolution of gas ceasing, -the carbon dioxide is absorbed by passing up under the mercury a little -caustic potash. When absorption is complete, the gas, consisting of -nitrogen and nitric oxide, may be measured. A bubble or two of oxygen is -now passed into the eudiometer; if nitric oxide is present, red fumes at -once develop. On absorbing the excess of oxygen and the nitric peroxide -by alkaline pyrogallate, and measuring the residual gas, it is easy to -calculate how much nitric oxide was originally present, according to the -principles laid down in "Foods," p. 587. - -It is also obvious that, by treating nitric oxide with oxygen, and -absorbing the nitric peroxide present by an alkaline liquid of known -strength and free from nitrates or ammonia, the resulting solution may -be dealt with by a zinc copper couple, and the ammonia developed by the -action of the couple directly estimated by titration by a decinormal -hydrochloric acid, if large in quantity, or by "_nesslerising_," if -small in quantity. Crum's method of estimating nitrates ("Foods," p. -568) in the cases of minute stains on fabrics, &c., with a little -modification, may be occasionally applicable. - - -IV.--Acetic Acid. - - Sec. 90. In the ten years ending 1893 nine deaths (four males and five - females) occurred in England and Wales from drinking, by mistake or - design, strong acetic acid. - - A few cases only have been recorded in medical literature although - there have been many experiments on animals. - - The symptoms in the human subject consist of pain, vomiting, and - convulsions. - - In animals it causes colic, paralysis of the extremities, bloody - urine, and [oe]dema of the lungs. The lethal dose for plant-eating - animals is about 0.49 gramme per kilo. - - There should be no difficulty in recognising acetic acid; the odour - alone is, in most cases, strong and unmistakable. Traces are - detected by distilling, neutralising the distillate by soda, - evaporating to dryness, and treating the residue as follows:--A - portion warmed with alcohol and sulphuric acid gives a smell of - acetic ether. Another portion is heated in a small tube of hard - glass with arsenious acid; if acetic acid is present, or an acetate, - a smell of kakodyl is produced. - - -V.--Ammonia. - -Sec. 91. Ammonia, (NH_{3}), is met with either as a vapour or gas, or as a -solution of the pure gas in water. - -=Properties.=--Pure ammonia gas is colourless, with a strong, -irritating, pungent odour, forming white fumes of ammonic chloride, if -exposed to hydric chloride vapour, and turning red moist litmus-paper -strongly blue. By intense cold, or by a pressure of 6-1/2 atmospheres at -the ordinary temperature, the gas is readily liquefied; the liquid -ammonia boils at 38 deg.; its observed specific gravity is .731; it freezes -at -57.1 deg. Ammonia is readily absorbed by water; at 0 deg. water will take -up 1000 times its own volume, and at ordinary temperatures about 600 -times its volume. Alcohol also absorbs about 10 per cent. Ammonia is a -strong base, and forms a number of salts. Ammonia is one of the constant -products of the putrefaction of nitrogenous substances; it exists in the -atmosphere in small proportions, and in everything that contains water. -Indeed, water is the only compound equal to it in its universality of -diffusion. The minute quantities of ammonia thus diffused throughout -nature are probably never in the free state, but combinations of ammonia -with hydric nitrate, carbon dioxide, &c. - -Sec. 92. =Uses.=[115]--A solution of ammonia in water has many applications -in the arts and industries; it is used in medicine, and is an -indispensable laboratory reagent. - -[115] Sir B. W. Richardson has shown that ammonia possesses powerful -antiseptic properties.--_Brit. Med. Journal_, 1862. - -The officinal caustic preparations of ammonia are--_ammoniae liquor -fortior_ (_strong solution of ammonia_), which should contain 32.5 per -cent. of ammonia, and have a specific gravity of .891. - -_Liquor ammoniae_ (_solution of ammonia_), specific gravity .959, and -containing 10 per cent. of ammonia. There is also a _liniment of -ammonia_, composed of olive oil, 3 parts, and ammonia, 1 part. - -_Spiritus Ammoniae F[oe]tidus_ (_f[oe]tid spirit of ammonia_).--A -solution of assaf[oe]tida in rectified spirit and ammonia solution, 100 -parts by measure, contains 10 of strong solution of ammonia. - -Strong solution of ammonia is an important ingredient in the -"_linimentum camphorae composita_" (_compound liniment of camphor_), the -composition of which is as follows:--camphor, 2.5 parts; oil of -lavender, .125; strong solution of ammonia, 5.0; and rectified spirit, -15 parts. Its content of strong solution of ammonia is then about 22.6 -per cent. (equivalent to 7.3 of NH_{3}).[116] - -[116] There is a common liniment for horses used in stables, and -popularly known as "white oil." It contains 1 part of ammonia, and 4 -parts of olive or rape oil; not unfrequently turpentine is added. -Another veterinary liniment, called "egg oil," contains ammonia, oil of -origanum, turpentine, and the yelks of eggs. - -_The carbonate of ammonia_ is also caustic; it is considered to be a -compound of acid carbonate of ammonium, NH_{4}HCO_{3}, with carbamate of -ammonium, NH_{4}NH_{2}CO_{2}. It is in the form of colourless, -crystalline masses; the odour is powerfully ammoniacal; it is strongly -alkaline, and the taste is acrid. It completely volatilises with heat, -is soluble in water, and somewhat soluble in spirit. - -The officinal preparation is the "_spiritus ammoniae aromaticus_," or -aromatic spirit of ammonia. It is made by distilling in a particular way -ammonic carbonate, 4 ozs.; strong solution of ammonia, 8 ozs.; rectified -spirit, 120 ozs.; water, 60 ozs.; volatile oil of nutmeg, 4-1/2 drms.; -and oil of lemon, 6-1/2 drms. Aromatic spirit of ammonia is a solution -in a weak spirit of neutral carbonate, flavoured with oil of lemon and -nutmeg; the specific gravity should be 0.896. - -_Smelling salts_ (_sal volatile_) are composed of carbonate of ammonia. - -Sec. 93. =Statistics.=--Falck has found throughout literature notices of -thirty cases of poisoning by ammonia, or some of its preparations. In -two of these it was used as a poison for the purpose of murder, and in -eight with suicidal intent; the remainder were all accidental. The two -criminal cases were those of children, who both died. Six out of eight -of the suicidal, and twelve of the twenty accidental cases also -terminated fatally. - -Ammonia was the cause of 64 deaths (39 male, 25 female) by accident and -of 34 (18 male, 16 female) by suicide, making a total of 98 during the -ten years 1883-1892 in England and Wales. At present it occupies the -seventh place among poisons as a cause of accident, the ninth as a means -of suicide. - -Sec. 94. =Poisoning by Ammonia Vapour.=--Strong ammoniacal vapour is fatal -to both animal and vegetable life. There are, however, but few instances -of poisoning by ammonia vapour; these few cases have been, without -exception, the result of accident. Two cases of death are recorded, due -to an attempt to rouse epileptics from stupor, by an injudicious use of -strong ammonia applied to the nostrils. In another case, when -hydrocyanic acid had been taken, there was the same result. An instance -is also on record of poisonous effects from the breaking of a bottle of -ammonia, and the sudden evolution in this way of an enormous volume of -the caustic gas. Lastly, a man employed in the manufacture of ice, by -means of the liquefaction of ammonia (Carre's process), breathed the -vapour, and had a narrow escape for his life. - -Sec. 95. =Symptoms.=--The symptoms observed in the last case may well serve -as a type of what may be expected to occur after breathing ammonia -vapour. The man remained from five to ten minutes in the stream of gas; -he then experienced a feeling of anxiety, and a sense of constriction in -the epigastrium, burning in the throat, and giddiness. He vomited. The -pulse was small and frequent, the face pale, the mouth and throat -strongly reddened, with increased secretion. Auscultation and percussion -of the chest elicited nothing abnormal, although during the course of -four days he had from time to time symptoms of suffocation, which were -relieved by emetics. He recovered by the eighth day.[117] - -[117] Schmidt's _Jahrbuch_, 1872, i. S. 30. - -In experiments on animals, very similar symptoms are produced. There is -increased secretion of the eyes, nose, and mouth, with redness. The cry -of cats becomes remarkably hoarse, and they generally vomit. Great -difficulty in breathing and tetanic convulsions are present. When the -animal is confined in a small closed chamber, death takes place in about -a quarter of an hour. - -_On section_, the bronchial tubes, to the finest ramifications, are -found to be filled with a tenacious mucus, and the air passages, from -the glottis throughout, reddened. The lungs are emphysematous, but have -not always any special colour; the heart contains but little coagulated -blood; the blood has a dark-red colour. - -Sec. 96. The chronic effects of the gas, as shown in workmen engaged in -manufactures in which the fumes of ammonia are frequent, appear to be an -inflammation of the eyes and an affection of the skin. The latter is -thought to be due to the ammonia uniting to form a soap with the oil of -the lubricating skin glands. Some observers have also noticed deafness, -and a peculiar colour of the skin of the nose and forehead, among those -who work in guano manufactories. Its usual action on the body appears to -be a diminution of the healthy oxidation changes, and a general lowering -of bodily strength, with evident anaemia. - -Sec. 97. =Ammonia in Solution.--Action on Plants.=--Solutions of strong -ammonia, or solutions of the carbonate, act injuriously on vegetable -life, while the neutral salts of ammonia are, on the contrary, excellent -manures. A 30 per cent. solution of ammonic carbonate kills most plants -within an hour, and it is indifferent whether the whole plant is watered -with this solution, or whether it is applied only to the leaves. If, -after this watering of the plant with ammonic carbonate water, the -injurious salt is washed out as far as possible by distilled water, or -by a weakly acidulated fluid, then the plant may recover, after having -shed more or less of its leaves. These facts sufficiently explain the -injurious effects noticed when urine is applied direct to plants, for -urine in a very short time becomes essentially a solution of ammonic -carbonate. - -Sec. 98. =Action on Human Beings and Animal Life.=--The violence of the -action of caustic solutions of ammonia almost entirely depends on the -state of concentration. - -The local action of the strong solution appears to be mainly the -extraction of water and the saponifying of fat, making a soluble soap. -On delicate tissues it has, therefore, a destructive action; but S. -Samuel[118] has shown that ammonia, when applied to the unbroken -epidermis, does not have the same intense action as potash or soda, nor -does it coagulate albumen. Blood, whether exposed to ammonia gas, or -mixed with solution of ammonia, becomes immediately dark-red; then, -later, through destruction of the blood corpuscles, very dark, even -black; lastly, a dirty brown-red. The oxygen is expelled, the haemoglobin -destroyed, and the blood corpuscles dissolved. - -[118] Virchow's _Archiv f. path. Anat._, Bd. 51, Hft. 1 u. 2, S. 41, -&c., 1870. - -The albumen of the blood is changed to alkali-albuminate, and the blood -itself will not coagulate. A more or less fluid condition of the blood -has always been noticed in the bodies of those poisoned by ammonia. - -Blood exposed to ammonia, when viewed by the spectroscope, shows the -spectra of alkaline haematin, a weak absorption-band, in the -neighbourhood of D; but if the blood has been acted on for some time by -ammonia, then all absorption-bands vanish. These spectra, however, are -not peculiar to ammonia, the action of caustic potash or soda being -similar. The muscles are excited by ammonia, the functions of the nerves -are destroyed. - -When a solution of strong ammonia is swallowed, there are two main -effects--(1) the action of the ammonia itself on the tissues it comes -into contact with, and (2) the effects of the vapour on the -air-passages. There are, therefore, immediate irritation, redness, and -swelling of the tongue and pharynx, a burning pain reaching from -the mouth to the stomach, with vomiting, and, it may be, nervous -symptoms. The saliva is notably increased. In a case reported by -Fonssagrives,[119] no less than 3 litres were expelled in the -twenty-four hours. Often the glands under the jaw and the lymphatics of -the neck are swollen. - -[119] _L'Union Medicale_, 1857, No. 13, p. 49, No. 22, p. 90. - -Doses of from 5 to 30 grammes of the strong solution of ammonia may kill -as quickly as prussic acid. In a case recorded by Christison,[120] death -occurred in four minutes from a large dose, doubtless partly by -suffocation. As sudden a result is also recorded by Plenk: a man, bitten -by a rabid dog, took a mouthful of spirits of ammonia, and died in four -minutes. - -[120] Christison, 167. - -If death does not occur rapidly, there may be other symptoms--dependent -not upon its merely local action, but upon its more remote effects. -These mainly consist in an excitation of the brain and spinal cord, and, -later, convulsive movements deepening into loss of consciousness. It has -been noticed that, with great relaxation of the muscular system, the -patients complain of every movement causing pain. With these general -symptoms added to the local injury, death may follow many days after the -swallowing of the fatal dose. - -Death may also occur simply from the local injury done to the throat and -larynx, and the patient may linger some time. Thus, in a case quoted by -Taylor,[121] in which none of the poison appears actually to have been -swallowed, the man died nineteen days after taking the poison from -inflammation of the throat and larynx. As with the strong acids, so with -ammonia and the alkalies generally, death may also be caused many weeks -and even months afterwards from the effects of contraction of the -gullet, or from the impaired nutrition consequent upon the destruction, -more or less, of portions of the stomach or intestinal canal. - -[121] _Principles of Jurisprudence_, i. p. 235. - -Sec. 99. =Post-mortem Appearances.=--In recent cases there is an intense -redness of the intestinal canal, from the mouth to the stomach, and even -beyond, with here and there destruction of the mucous membrane, and even -perforation. A wax preparation in the museum of University College (No. -2378) shows the effects on the stomach produced by swallowing strong -ammonia; it is ashen-gray in colour, and most of the mucous membrane is, -as it were, dissolved away; the cardiac end is much congested. - -The contents of the stomach are usually coloured with blood; the -bronchial tubes and glottis are almost constantly found inflamed--even a -croup-like (or diphtheritic) condition has been seen. [OE]dema of the -glottis should also be looked for: in one case this alone seems to have -accounted for death. The blood is of a clear-red colour, and fluid. A -smell of ammonia may be present. - -If a sufficient time has elapsed for secondary effects to take place, -then there may be other appearances. Thus, in the case of a girl who, -falling into a fainting fit, was treated with a draught of undiluted -spirits of ammonia, and lived four weeks afterwards, the stomach -(preserved in St. George's Hospital museum, 43 b, ser. ix.) is seen to -be much dilated and covered with cicatrices, and the pylorus is so -contracted as hardly to admit a small bougie. It has also been noticed -that there is generally a fatty degeneration of both the kidneys and -liver. - -It need scarcely be observed that, in such cases, no free ammonia will -be found, and the question of the cause of death must necessarily be -wholly medical and pathological. - -Sec. 100. =Separation of Ammonia.=--Ammonia is separated in all cases by -distillation, and if the organic or other liquid is already alkaline, -it is at once placed in a retort and distilled. If neutral or acid, a -little burnt magnesia may be added until the reaction is alkaline. It is -generally laid down that the contents of the stomach in a putrid -condition cannot be examined for ammonia, because ammonia is already -present as a product of decomposition; but even under these -circumstances it is possible to give an opinion whether ammonia _in -excess_ is present. For if, after carefully mixing the whole contents of -the stomach, and then drying a portion and reckoning from that weight -the total nitrogen (considering, for this purpose, the contents to -consist wholly of albumen, which yields about 16 per cent. of -nitrogen)--under these conditions, the contents of the stomach yield -more than 16 per cent. of nitrogen as ammonia reckoned on the dry -substance, it is tolerably certain that ammonia not derived from the -food or the tissues is present. - -If, also, there is a sufficient evolution of ammonia to cause white -fumes, when a rod moistened with hydrochloric acid is brought near to -the liquid, this is an effect never noticed with a normal decomposition, -and renders the presence of extrinsic ammonia probable. - -An alkaline-reacting distillate, which gives a brown colour with the -"nessler" reagent, and which, when carefully neutralised with sulphuric -acid, on evaporation to dryness by the careful heat of a water-bath, -leaves a crystalline mass that gives a copious precipitate with platinic -chloride, but is hardly at all soluble in absolute alcohol, can be no -other substance than ammonia. - -Sec. 101. =Estimation.=--Ammonia is most quickly estimated by distilling, -receiving the distillate in decinormal acid, and then titrating back. It -may also be estimated as the double chloride of ammonium and platinum -(NH_{4}Cl)_{2}PtCl_{4}. The distillate is exactly neutralised by HCl, -evaporated to near dryness, and an alcoholic solution of platinic -chloride added in sufficient quantity to be always in slight excess, as -shown by the yellow colour of the supernatant fluid. The precipitate is -collected, washed with a little alcohol, dried, and weighed on a tared -filter; 100 parts of the salt are equal to 7.6 of NH_{3}. - - -VI.--Caustic Potash and Soda. - -Sec. 102. There is so little difference in the local effects produced by -potash and soda respectively, that it will be convenient to treat them -together. - -=Potash= (=potassa caustica=).--Hydrate of potassium (KHO), atomic -weight 56, specific gravity 2.1. - -=Properties.=--Pure hydrate of potassium is a compact, white solid, -usually met with in the form of sticks. When heated to a temperature a -little under redness, it melts to a nearly colourless liquid; in this -state it is intensely corrosive. It rapidly absorbs moisture from the -air, and moist potash also absorbs with great avidity carbon dioxide; it -is powerfully alkaline, changing red litmus to blue. It is soluble in -half its weight of cold water, great heat being evolved during solution; -it forms two definite hydrates--one, KHO + H_{2}O; the other, KHO + -2H_{2}O. It is sparingly soluble in ether, but is dissolved by alcohol, -wood-spirit, fusel oil, and glycerin. - -Sec. 103. =Pharmaceutical Preparations.=--Potassium hydrate, as well as the -solution of potash, is officinal in all pharmacop[oe]ias. The _liquor -potassae_, or solution of potash, of the British Pharmacop[oe]ia, is a -strongly alkaline, caustic liquid, of 1.058 specific gravity, and -containing 5.84 per cent. by weight of KHO. It should, theoretically, -not effervesce, when treated with an acid, but its affinity for CO_{2} -is so great that all solutions of potash, which have been in any way -exposed to air, contain a little carbonate. Caustic sticks of potash and -lime used to be officinal in the British Pharmacop[oe]ia. Filho's -caustic is still in commerce, and is made by melting together two parts -of potassium hydrate and one part of lime in an iron ladle or vessel; -the melted mass is now moulded by pouring it into leaden moulds. Vienna -paste is composed of equal weights of potash and lime made into a paste -with rectified spirit or glycerin. - -Sec. 104. =Carbonate of Potash= (K_{2}CO_{3} + 1-1/2H_{2}O), when pure, is -in the form of small white crystalline grains, alkaline in taste and -reaction, and rapidly deliquescing when exposed to moist air; it gives -all the chemical reactions of potassium oxide, and carbon dioxide. -Carbonate of potash, under the name of _salt of tartar_, or potashes, is -sold by oilmen for cleansing purposes. They supply it either in a fairly -pure state, or as a darkish moist mass containing many impurities. - -Sec. 105. =Bicarbonate of Potash= (KHCO_{3}) is in the form of large -transparent rhombic prisms, and is not deliquescent. The effervescing -solution of potash (_liquor potassae effervescens_) consists of 30 grains -of KHCO_{3} in a pint of water (3.45 grms. per litre), and as much -CO_{2} as the water will take up under a pressure of seven atmospheres. - -Sec. 106. =Caustic Soda--Sodium Hydrate= (NaHO).--This substance is a white -solid, very similar in appearance to potassium hydrate; it absorbs -moisture from the air, and afterwards carbon dioxide, becoming solid -again, for the carbonate is not deliquescent. In this respect, then, -there is a great difference between potash and soda, for the former is -deliquescent both as hydrate and carbonate; a stick of potash in a -semi-liquid state, by exposure to the air, continues liquid, although -saturated with carbon dioxide. Pure sodium hydrate has a specific -gravity of 2.0; it dissolves in water with evolution of heat, and the -solution gives all the reactions of sodium hydrate, and absorbs carbon -dioxide as readily as the corresponding solution of potash. The _liquor -sodae_ of the B.P. should contain 4.1 per cent. of NaHO. - -Sec. 107. =Sodae Carbonas--Carbonate of Soda=--(Na_{2}CO_{3}10H_{2}O).--The -pure carbonate of soda for medicinal use is in colourless and -transparent rhombic octahedrons; when exposed to air, the crystals -effloresce and crumble. The _sodae carbonas exsiccata_, or dried -carbonate of soda, is simply the ordinary carbonate, deprived of its -water of crystallisation, which amounts to 62.93 per cent. - -Sec. 108. =Bicarbonate of Soda= (NaHCO_{3}) occurs in the form of minute -crystals, or, more commonly, as a white powder. The _liquor sodae -effervescens_ of the B.P. is a solution of the bicarbonate, 30 grains of -the salt in 20 ozs. of water (3.45 grms. per litre), the water being -charged with as much carbonic acid as it will hold under a pressure of -seven atmospheres. _The bicarbonate of soda lozenges_ (_trochisci sodae -bicarbonatis_) contain in each lozenge 5 grains (327 mgrms.) of the -bicarbonate. The carbonate of soda sold for household purposes is of two -kinds--the one, "seconds," of a dirty white colour and somewhat impure; -the other, "best," is a white mass of much greater purity. _Javelle -water_ (_Eau de Javelle_) is a solution of hypochlorite of soda; its -action is poisonous, more from the caustic alkali than from the -chlorine, and may, therefore, be here included. - -Sec. 109. =Statistics.=--Poisoning by the fixed alkalies is not so frequent -as poisoning by ammonia. Falck has collected, from medical literature, -27 cases, 2 of which were the criminal administering of _Eau de -Javelle_, and 5 were suicidal; 22, or 81.5 per cent., died--in 1 of the -cases after twenty-four hours; in the others, life was prolonged for -days, weeks, or months--in 1 case for twenty-seven months. In the ten -years 1883-1892, in England and Wales, there were 27 deaths from -poisoning by the fixed alkalies; 2 were suicidal (1 from potash, the -other from soda); the remaining 25 were due to accident; of these, 7 (3 -males and 4 females) were from caustic soda, and 18 (8 males and 10 -females) from caustic potash. - -Sec. 110. =Effects on Animal and Vegetable Life.=--The fixed alkalies -destroy all vegetable life, if applied in strong solution or in -substance, by dehydrating and dissolving the tissues. The effects on -animal tissues are, in part, due also to the affinity of the alkalies -for water. They extract water from the tissues with which they come in -contact, and also attack the albuminous constituents, forming -alkali-albuminate, which swells on the addition of water, and, in a -large quantity, even dissolves. Cartilaginous and horny tissues are also -acted upon, and strong alkalies will dissolve hair, silk, &c. The action -of the alkali is by no means restricted to the part first touched, but -has a remarkable faculty of spreading in all directions. - -Sec. 111. =Local Effects.=--The effects of strong alkali applied to the -epidermis are similar to, but not identical with, those produced by -strong acids. S. Samuel[122] has studied this experimentally on the ear -of the rabbit; a drop of a strong solution of caustic alkali, placed on -the ear of a white rabbit, caused stasis in the arteries and veins, with -first a greenish, then a black colour of the blood; the epidermis was -bleached, the hair loosened, and there quickly followed a greenish -coloration on the back of the ear, opposite to the place of application. -Around the burned spot appeared a circle of anastomising vessels, a -blister rose, and a slough separated in a few days. The whole thickness -of the ear was coloured yellowish-green, and, later, the spot became of -a rusty brown. - -[122] Virchow's _Archiv. f. path. Anat._, Bd. 51, Hft. 1 u. 2, 1870. - -Sec. 112. =Symptoms.=--The symptoms observed when a person has swallowed a -dangerous dose of caustic (fixed) alkali are very similar to those -noticed with ammonia, with the important exception that there is no -respiratory trouble, unless the liquid has come into contact with the -glottis; nor has there been hitherto remarked the rapid death which has -taken place in a few ammonia poisonings, the shortest time hitherto -recorded being three hours, as related by Taylor, in a case in which a -boy had swallowed 3 ozs. of a strong solution of carbonate of potash. - -There is instant pain, extending from the mouth to the stomach, and a -persistent and unpleasant taste; if the individual is not a determined -suicide, and the poison (as is mostly the case) has been taken -accidentally, the liquid is immediately ejected as much as possible, and -water, or other liquid at hand, drunk freely. Shock may at once occur, -and the patient die from collapse; but this, even with frightful -destruction of tissue, appears to be rare. Vomiting supervenes; what is -ejected is strongly alkaline, and streaked with blood, and has a soapy, -frothy appearance. There may be diarrh[oe]a, great tenderness of the -abdomen, and quick pulse and fever. With caustic potash, there may be -also noticed its toxic effects (apart from local action) on the heart; -the pulse, in that case, is slow and weak, and loss of consciousness and -convulsions are not uncommon. If the collapse and after-inflammation are -recovered from, then, as in the case of the mineral acids, there is all -the horrid sequence of symptoms pointing to contractions and strictures -of the gullet or pylorus, and the subsequent dyspepsia, difficulty of -swallowing, and not unfrequently actual starvation. - -Sec. 113. =Post-mortem Appearances.=--In cases of recent poisoning, spots -on the cheeks, lips, clothing, &c., giving evidence of the contact of -the alkali, should be looked for; but this evidence, in the case of -persons who have lived a few days, may be wanting. The mucous membrane -of the mouth, throat, gullet, and stomach is generally more or less -white--here and there denuded, and will be found in various stages of -inflammation and erosion, according to the amount taken, and the -concentration of the alkali. Where there is erosion, the base of the -eroded parts is not brown-yellow, but, as a rule, pale red. The gullet -is most affected at its lower part, and it is this part which is mostly -subject to stricture. Thus Boehm[123] found that in 18 cases of -contraction of the gullet, collected by him, 10 of the 18 showed the -contraction at the lower third. - -[123] _Centralblatt fuer die Med. Wiss._, 1874. - -The changes which the stomach may present if the patient has lived some -time, are well illustrated by a preparation in St. George's museum (43 -a. 264, ser. ix.). It is the stomach of a woman, aged 44, who had -swallowed a concentrated solution of carbonate of potash. She vomited -immediately after taking it, and lived about two months, during the -latter part of which she had to be nourished by injections. She died -mainly from starvation. The gullet in its lower part is seen to be much -contracted, its lining membrane destroyed, and the muscular coats -exposed. The coats of the stomach are thickened, but what chiefly -arrests the attention is a dense cicatrix at the pylorus, with an -aperture so small as only to admit a probe. - -The colour of the stomach is generally bright red, but in that of a -child, preserved in Guy's Hospital museum (No. 1798^{24}), the mucous -membrane is obliterated, the rugae destroyed, and a dark-brown stain is a -noticeable feature. The stomach is not, however, necessarily affected. -In a preparation in the same museum (No. 1798^{20}) the mucous membrane -of the stomach of a child who swallowed soap-lees is seen to be almost -healthy, but the gullet is much discoloured. The action on the blood is -to change it into a gelatinous mass; the blood corpuscles are destroyed, -and the whole colour becomes of a dirty blackish-red; the spectroscopic -appearances are identical with those already described (see p. 114). - -The question as to the effects of chronic poisoning by the alkalies or -their carbonates may arise. Little or nothing is, however, known of the -action of considerable quantities of alkalies taken daily. In a case -related by Dr. Tunstall,[124] a man for eighteen years had taken daily 2 -ozs. of bicarbonate of soda for the purpose of relieving indigestion. He -died suddenly, and the stomach was found extensively diseased; but since -the man, before taking the alkali, had complained of pain, &c., it is -hardly well, from this one case, to draw any conclusion. - -[124] _Med. Times_, Nov. 30, 1850, p. 564. - -It is important to observe that the contents of the stomach may be acid, -although the death has been produced by caustic alkali. A child, aged 4, -drank from a cup some 14 per cent. soda lye. He vomited frequently, and -died in fifteen hours. The stomach contained 80 c.c. of sour-smelling -turbid fluid, the reaction of which was acid. There were haemorrhagic -patches in the stomach, and signs of catarrhal inflammation; there was -also a similarly inflamed condition of the duodenum.[125] - -[125] Lesser, _Atlas d. gericht. Med._, Tafel ii. - -Sec. 114. =Chemical Analysis.=--The tests for potassium or sodium are too -well known to need more than enumeration. The intense yellow flame -produced when a sodium salt is submitted to a Bunsen flame, and the -bright sodium-line at D when viewed by the spectroscope, is a delicate -test; while potassium gives a dull red band in the red, and a faint but -very distinct line in the violet. Potassium salts are precipitated by -tartaric acid, while sodium salts do not yield this precipitate; -potassium salts also give a precipitate with platinic chloride insoluble -in strong alcohol, while the compound salt with sodium is rapidly -dissolved by alcohol or water. This fact is utilised in the separation -and estimation of the two alkalies. - -Sec. 115. =Estimation of the Fixed Alkalies.=--To detect a fixed alkali in -the contents of the stomach, a convenient process is to proceed by -dialysis, and after twenty-four hours, to concentrate the outer liquid -by boiling, and then, if it is not too much coloured, to titrate -directly with a decinormal sulphuric acid. After exact neutralisation, -the liquid is evaporated to dryness, carbonised, the alkaline salts -lixiviated out with water, the sulphuric acid exactly precipitated by -baric chloride, and then, after separation of the sulphate, the liquid -treated with milk of lime. The filtrate is treated with a current of -CO_{2} gas, boiled, and any precipitate filtered off; the final filtrate -will contain only alkalies. The liquid may now be evaporated to dryness -with either hydrochloric or sulphuric acids, and the total alkalies -weighed as sulphates or chlorides. Should it be desirable to know -exactly the proportion of potassium to sodium, it is best to convert the -alkalies into chlorides--dry gently, ignite, and weigh; then dissolve in -the least possible quantity of water, and precipitate by platinic -chloride, which should be added so as to be a little in excess, but not -much. The liquid thus treated is evaporated nearly to dryness, and then -extracted with alcohol of 80 per cent., which dissolves out any of the -double chloride of platinum and sodium. Finally, the precipitate is -collected on a tared filter and weighed, after drying at 100 deg. In this -way the analyst both distinguishes between the salts of sodium and -potassium, and estimates the relative quantities of each. It is hardly -necessary to observe that, if the double chloride is wholly soluble in -water or alcohol, sodium alone is present. This, however, will never -occur in operating on organic tissues and fluids, for both alkalies are -invariably present. A correction must be made when complex organic -fluids are in this way treated for alkalies which may be naturally in -the fluid. Here the analyst will be guided by his preliminary -titration, which gives the total free alkalinity. In cases where the -alkali has been neutralised by acids, of course no free alkali will be -found, but the corresponding salt. - - -VII.--Neutral Sodium, Potassium, and Ammonium Salts. - - Sec. 116. The neutral salts of the alkalies are poisonous, if - administered in sufficient doses, and the poisonous effect of the - sulphate, chloride, bromide, iodide, tartrate, and citrate appears - to depend on the specific action of the alkali metal, rather than on - the acid, or halogen in combination. According to the researches of - Dr. Ringer and Dr. Harrington Sainsbury,[126] with regard to the - relative toxicity of the three, as shown by their effect on the - heart of a frog--first, the potassium salts were found to exert the - most poisonous action, next come the ammonium, and, lastly, the - sodium salts. The highest estimate would be that sodium salts are - only one-tenth as poisonous as those of ammonium or potassium; the - lowest, that the sodium salts are one-fifth: although the - experiments mainly throw light upon the action of the alkalies on - one organ only, yet the indications obtained probably hold good for - the organism as a whole, and are pretty well borne out by clinical - experience. - -[126] _Lancet_, June 24, 1882. - - There appear to be four cases on record of poisoning by the above - neutral salts; none of them belong to recent times, but lie between - the years 1837-1856. Hence, the main knowledge which we possess of - the poisonous action of the potassium salts is derived from - experiments on animals. - - Sec. 117. =Sodium Salts.=--Common salt in such enormous quantity as - half a pound to a pound has destroyed human life, but these cases - are so exceptional that the poisonous action of sodium salts is of - scientific rather than practical interest. - - Sec. 118. =Potassium Salts.=--Leaving for future consideration the - nitrate and the chlorate of potassium, potassic sulphate and - tartrate are substances which have destroyed human life. - - =Potassic Sulphate= (K_{2}SO_{4}) is in the form of colourless - rhombic crystals, of bitter saline taste. It is soluble in 10 parts - of water. - - =Hydropotassic Tartrate= (KHC_{4}H_{4}O_{6}), when pure, is in the - form of rhombic crystals, tasting feebly acid. It is soluble in 210 - parts of water at 17 deg. - - Sec. 119. =Action on the Frog's Heart.=--Both excitability and - contractility are affected to a powerful degree. There is a - remarkable slowing of the pulsations, irregularity, and, lastly, - cessation of pulsation altogether. - - Sec. 120. =Action on Warm-Blooded Animals.=--If a sufficient quantity - of a solution of a potassic salt is injected into the blood-vessels - of an animal, there is almost immediate death from arrest of the - heart's action. Smaller doses, subcutaneously applied, produce - slowing of the pulse, dyspn[oe]a, and convulsions, ending in death. - Small doses produce a transitory diminution of the force of arterial - pressure, which quickly passes, and the blood-pressure rises. There - is at first, for a few seconds, increase in the number of - pulsations, but later a remarkable slowing of the pulse. The rise in - the blood-pressure occurs even after section of the spinal cord. - Somewhat larger doses cause rapid lowering of the blood-pressure, - and apparent cessation of the heart's action; but if the thorax be - then opened, the heart is seen to be contracting regularly, making - some 120-160 rhythmic movements in the minute. If the respiration be - now artificially maintained, and suitable pressure made on the walls - of the chest, so as to empty the heart of blood, the blood-pressure - quickly rises, and natural respiration may follow. An animal which - lay thirty-six minutes apparently dead was in this way brought to - life again (_Boehm_). The action of the salts of potassium on the - blood is the same as that of sodium salts. The blood is coloured a - brighter red, and the form of the corpuscles changed; they become - shrivelled through loss of water. Voluntary muscle loses quickly its - contractility when a solution of potash is injected into its - vessels. Nerves also, when treated with a 1 per cent. solution of - potassic chloride, become inexcitable. - - Sec. 121. =Elimination.=--The potassium salts appear to leave the body - through the kidneys, but are excreted much more slowly than the - corresponding sodium salts. Thus, after injection of 4 grms. of - potassic chloride--in the first sixteen hours .748 grm. of KCl was - excreted in the urine, and in the following twenty-four hours 2.677 - grms. - - Sec. 122. =Nitrate of Potash= (KNO_{3}).--Pure potassic nitrate - crystallises in large anhydrous hexagonal prisms with dihedral - summits; it does not absorb water, and does not deliquesce. Its - fusing point is about 340 deg.; when melted it forms a transparent - liquid, and loses a little of its oxygen, but this is for the most - part retained by the liquid given off when the salt solidifies. At a - red-heat it evolves oxygen, and is reduced first to nitrite; if the - heat is continued, potassic oxide remains. The specific gravity of - the fused salt is 2.06. It is not very soluble in cold water, 100 - parts dissolving only 26 at 15.6 deg.; but boiling water dissolves it - freely, 100 parts dissolving 240 of the salt. - - A solution of nitrate of potash, when treated with a zinc couple - (see "Foods," p. 566), is decomposed, the nitrate being first - reduced to nitrite, as shown by its striking a red colour with - metaphenylene-diamine, and then the nitrite farther decomposing, and - ammonia appearing in the liquid. If the solution is alkalised, and - treated with aluminium foil, hydrogen is evolved, and the same - effect produced. As with all nitrates, potassic nitrate, on being - heated in a test-tube with a little water, some copper filings, and - sulphuric acid, evolves red fumes of nitric peroxide. - - Sec. 123. =Statistics.=--Potassic nitrate, under the popular name of - "_nitre_," is a very common domestic remedy, and is also largely - used as a medicine for cattle. There appear to be twenty cases of - potassic nitrate poisoning on record--of these, eight were caused by - the salts having been accidentally mistaken for magnesic sulphate, - sodic sulphate, or other purgative salt; two cases were due to a - similar mistake for common salt. In one instance, the nitrate was - used in strong solution as an enema, but most of the cases were due - to the taking of too large an internal dose. - - Sec. 124. =Uses in the Arts=, &c.--Both sodic and potassic nitrates are - called "nitre" by the public indiscriminately. Sodic nitrate is - imported in large quantities from the rainless districts of Peru as - a manure. Potassic nitrate is much used in the manufacture of - gunpowder, in the preservation of animal substances, in the - manufacture of gun cotton, of sulphuric and nitric acids, &c. The - maximum medicinal dose of potassium nitrate is usually stated to be - 30 grains (1.9 grm.). - - Sec. 125. =Action of Nitrates of Sodium and Potassium.=--Both of these - salts are poisonous. Potassic nitrate has been taken with fatal - result by man; the poisonous nature of sodic nitrate is established - by experiments on animals. The action of the nitrates of the - alkalies is separated from that of the other neutral salts of - potassium, &c., because in this case the toxic action of the - combined nitric acid plays no insignificant part. Large doses, 3-5 - grms. (46.3-77.2 grains), of potassic nitrate cause considerable - uneasiness in the stomach and bowels; the digestion is disturbed; - there may be vomiting and diarrh[oe]a, and there is generally - present a desire to urinate frequently. Still larger doses, 15-30 - grms. (231.5-463 grains), rapidly produce all the symptoms of acute - gastro-enteritis--great pain, frequent vomiting (the ejected matters - being often bloody), with irregularity and slowing of the pulse; - weakness, cold sweats, painful cramps in single muscles (especially - in the calves of the legs); and, later, convulsions, aphonia, quick - collapse, and death. - - In the case of a pregnant woman, a handful of "nitre" taken in - mistake for Glauber's salts produced abortion after half-an-hour. - The woman recovered. Sodic nitrate subcutaneously applied to frogs - kills them, in doses of .026 grm. (.4 grain), in about two hours; - there are fibrillar twitchings of single groups of muscles and - narcosis. The heart dies last, but after ceasing to beat may, by a - stimulus, be made again to contract. Rabbits, poisoned similarly by - sodic nitrate, exhibit also narcotic symptoms; they lose - consciousness, lie upon their side, and respond only to the sharpest - stimuli. The breathing, as well as the heart, is "slowed," and death - follows after a few spasmodic inspirations. - - =Sodic nitrite= was found by Barth to be a more powerful poison, - less than 6 mgrms. (.1 grain) being sufficient to kill a rabbit of - 455.5 grms. (7028 grains) weight, when subcutaneously injected. The - symptoms were very similar to those produced by the nitrate. - - Sec. 126. The _post-mortem_ appearances from potassic nitrate are as - follows:--An inflamed condition of the stomach, with the mucous - membrane dark in colour, and readily tearing; the contents of the - stomach are often mixed with blood. In a case related by Orfila, - there was even a small perforation by a large dose of potassic - nitrate, and a remarkable preservation of the body was noted. - - It is believed that the action of the nitrates is to be partly - explained by a reduction to nitrites, circulating in the blood as - such. To detect nitrites in the blood, the best method is to place - the blood in a dialyser, the outer liquid being alcohol. The - alcoholic solution may be evaporated to dryness, extracted with - water, and then tested by metaphenylene-diamine. - - Sec. 127. =Potassic Chlorate= (KClO_{3}).--Potassic chlorate is in the - form of colourless, tabular crystals with four or six sides. About 6 - parts of the salt are dissolved by 100 of water at 15 deg., the - solubility increasing with the temperature, so that at 100 deg. nearly - 60 parts dissolve; if strong sulphuric acid be dropped on the - crystals, peroxide of chlorine is evolved; when rubbed with sulphur - in a mortar, potassic chlorate detonates. When the salt is heated - strongly, it first melts, and then decomposes, yielding oxygen gas, - and is transformed into the perchlorate. If the heat is continued, - this also is decomposed, and the final result is potassic chloride. - - Sec. 128. =Uses.=--Potassic chlorate is largely used as an oxidiser in - calico printing, and in dyeing, especially in the preparation of - aniline black. A considerable quantity is consumed in the - manufacture of lucifer matches and fireworks; it is also a - convenient source of oxygen. Detonators for exploding dynamite are - mixtures of fulminate of mercury and potassic chlorate. It is - employed as a medicine both as an application to inflamed mucous - membranes, and for internal administration; about 2000 tons of the - salt for these various purposes are manufactured yearly in the - United Kingdom. - - Sec. 129. =Poisonous Properties.=--The facility with which potassic - chlorate parts with its oxygen by the aid of heat, led to its very - extensive employment in medicine. No drug, indeed, has been given - more recklessly, or on a less scientific basis. Wherever there were - sloughing wounds, low fevers, and malignant sore throats, especially - those of a diphtheritic character, the practitioner administered - potassic chlorate in colossal doses. If the patient died, it was - ascribed to the malignity of the disease--if he recovered, to the - oxygen of the salt; and it is possible, from the light which of - recent years has been thrown on the action of potassic chlorate, - that its too reckless use has led to many unrecorded accidents. - - Sec. 130. =Experiments on Animals.=--F. Marchand[127] has studied the - effects of potassic chlorate on animals, and on blood. If either - potassic chlorate or sodic chlorate is mixed with fresh blood, it - shows after a little while peculiar changes; the clear red colour at - first produced passes, within a few hours, into a dark red-brown, - which gradually becomes pure brown. This change is produced by a 1 - per cent. solution, in from fifteen to sixteen hours; and a 4 per - cent. solution at 15 deg. destroys every trace of oxyhaemoglobin within - four hours. Soon the blood takes a syrupy consistence, and, with a - 2-4 per cent. solution of the salt, passes into a jelly-like mass. - The jelly has much permanence, and resists putrefactive changes for - a long time. - -[127] _Virchow's Archiv. f. path. Anat._, Bd. 77, Hft. 3, S. 455, 1879. - - Marchand fed a dog of 17 kilos. in weight with 5 grms. of potassic - chlorate for a week. As there were no apparent symptoms, the dose - was doubled for two days; and as there was still no visible effect, - lastly, 50 grms. of sodic chlorate were given in 5 doses. In the - following night the dog died. The blood was found after death to be - of a sepia-brown colour, and remained unaltered when exposed to the - air. The organs were generally of an unnatural brown colour; the - spleen was enormously enlarged; the kidneys were swollen, and of a - dark chocolate brown--on section, almost black-brown, the colour - being nearly equal, both in the substance and in the capsule. A - microscopical examination of the kidney showed the canaliculi to be - filled with brownish cylinders consisting of altered blood. A - spectroscopic examination of the blood showed weak haemoglobin bands, - and a narrow band in the red. With farther dilution, the haemoglobin - bands vanished, but the band in the red remained. The diluted blood, - when exposed to the light, still remained of a coffee-brown colour; - and on shaking, a white-brown froth was produced on the surface. - - A second experiment in which a hound of from 7-8 kilos. in weight - was given 3-5 grm. doses of potassic chlorate in sixteen hours, and - killed by bleeding seven to eight hours after the last dose, showed - very similar appearances. The kidneys were intensely congested, and - the peculiar brown colour was noticeable. - - Sec. 131. =Effects on Man.=--I find in literature thirty-nine cases - recorded, in which poisonous symptoms were directly ascribed to the - action of chlorate of potassium; twenty-eight of these terminated - fatally. A quadruple instance of poisoning, recorded by Brouardel - and L'Hote,[128] illustrates many of the points relative to the time - at which the symptoms may be expected to commence, and the general - aspect of potassic chlorate poisoning. The "_superieure_" of a - religious institution was in the habit of giving, for charitable - purposes, a potion containing 15 grms. (3.8 drms.) of potassic - chlorate, dissolved in 360 c.c. (about 12-1/2 ozs.) of a vegetable - infusion. - -[128] _Annales d'Hygiene publique_, 1881, p. 232. - - This potion was administered to four children--viz., David, aged - 2-1/2; Cousin, aged 3-1/2; Salmont, 2-1/2; and Guerin, 2-1/2. David - took the whole in two and a half hours, the symptoms commenced after - the potion was finished, and the child died five and a half hours - after taking the first dose; there were vomiting and diarrh[oe]a. - Cousin took the medicine in seven hours; the symptoms also commenced - after the last spoonful, and the death took place eight and a half - hours from the first spoonful. The symptoms were mainly those of - great depression; the lips were blue, the pulse feeble, there was no - vomiting, no diarrh[oe]a. Salmont took the medicine in nine hours, - and died in twelve. There was some diarrh[oe]a, the stools were of a - green colour. Guerin took the whole in two hours, the symptoms - commenced in four hours; the lips were very pale, the gums blue. - Death took place in four days. - - There was an autopsy in the case of David only. The stomach showed a - large ecchymosis on its mucous membrane, as if it had been burnt by - an acid; the spleen was gorged with blood, and its tissue friable; - the kidneys do not seem to have been thoroughly examined, but are - said to have been tumefied. Potassic chlorate was discovered by - dialysis. In the cases of the children just detailed, the symptoms - appear to be a mixture of the depressing action of the potassium, - and irritant action of the chlorate. - - Sec. 132. In adults, the main symptoms are those of nephritis, and the - fatal dose for an adult is somewhere about an ounce (28.3 grms.), - but half this quantity would probably be dangerous, especially if - given to a person who had congestion or disease of the kidneys. - - Dr. Jacobi[129] gives the following cases. - -[129] _Amer. Med. Times_, 1860. - - Dr. Fountain in 1858, experimenting on himself, took 29.2 grms. (8.7 - drms.) of potassic chlorate; he died on the seventh day from - nephritis. A young lady swallowed 30 grms. (8.5 drms.), when using - it as a gargle; she died in a few days from nephritis. A man, thirty - years of age, died in four days after having taken 48 grms. (12.3 - drms.) of sodic chlorate in six hours. The _shortest time_ in which - I can find the salt to have been fatal, is a case related by Dr. - Manouvriez, in which a woman took 45 grms., and died in five hours. - The _smallest dose_ which has proved fatal is one in which an infant - three years old was killed by 3 grms. (46.3 grains). - - Jacobi considers that the maximum dose to be given in divided doses - during the twenty-four hours, to infants under three, should be from - 1-1.5 grm. (15.4-23.1 grains), to children from three years old, up - to 2 grms. (30.8 grains); and adults from 6-8 grms. (92.6-123.4 - grains). - - Sec. 133. =Elimination.=--Potassic chlorate is quickly absorbed by - mucous membranes, and by the inflamed skin, and rapidly separated - from the body by the action of the kidneys. Woehler, as early as - 1824, recognised that it in great part passed out of the body - unchanged, and, lately, Isambert, in conjunction with Hirne,[130] - making quantitative estimations, recovered from the urine no less - than 95 per cent. of the ingested salts. Otto Hehner has also made - several auto-experiments, and taking 2-1/2 drms., found that it - could be detected in the urine an hour and a half afterwards. At - that time 17.23 per cent. of the salt had been excreted, and, by the - end of eleven hours, 93.8 per cent. was recovered. It is then - difficult to believe that the salt gives any oxygen to the tissues, - for though it is true that in all the investigations a small - percentage remains to be accounted for, and also that Binz,[131] - making experiments by mixing solutions of potassic chlorate with - moist organic substances, such as pus, yeast, fibrin, &c., has - declared that, at a blood heat the chlorate is rapidly reduced, and - is no longer recognisable as chlorate--yet it may be affirmed that - potassic chlorate is recovered from the urine as completely as - anything which is ever excreted by the body, and that deductions - drawn from the changes undergone by the salt in solutions of fibrin, - &c., have only an indirect bearing on the question. - -[130] _Gaz. Med. de Paris_, 1875, Nro. 17, 35, 41, 43. - -[131] _Berlin klin. Wochenschr._, xi. 10, S. 119, 1874. - - Sec. 134. The essential action of potassic chlorate seems to be that it - causes a peculiar change in the blood, acting on the colouring - matter and corpuscles; the latter lose their property as oxygen - carriers; the haemoglobin is in part destroyed; the corpuscles - dissolved. The decomposed and altered blood-corpuscles are crowded - into the kidneys, spleen, &c.; they block up the uriniferous - canaliculi, and thus the organs present the curious colouring seen - after death, and the kidneys become inflamed. - - -Detection and Estimation of Potassic Chlorate. - - Sec. 135. Organic fluids are best submitted to dialysis; the dialysed - fluid should then be concentrated and qualitative tests applied. One - of the best tests for the presence of a chlorate is, without doubt, - that recommended by Fresenius. The fluid to be tested is acidulated - with a few drops of sulphuric acid; sulphate of indigo added - sufficient to colour the solution blue, and finally a few drops of - sulphurous acid. In presence of potassic or sodic chlorate, the blue - colour immediately vanishes. This method is capable of detecting 1 - part in 128,000; provided the solution is not originally coloured, - and but little organic matter is present. - - The urine can be examined direct, but if it contain albumen, the - blue colour may disappear and yet chlorate be present; if too much - sulphurous acid be also added, the test may give erroneous results. - These are but trivial objections, however, for if the analyst - obtains a response to the test, he will naturally confirm or - disprove it by the following process:-- - - The liquid under examination, organic or otherwise, is divided into - two equal parts. In the one, all the chlorine present is - precipitated as chloride by silver nitrate in the usual way, and the - chloride of silver collected and weighed. In the other, the liquid - is evaporated to dryness and well charred by a dull red heat, the - ash dissolved in weak nitric acid, and the chlorides estimated as in - the first case. If chlorates were present, there will be a - difference between the two estimations, proportionate to the amount - of chlorates which have been converted into chlorides by the - carbonisation, and the first silver chloride subtracted from the - second will give an argentic chloride which is to be referred to - chlorate. In this way also the amount present may be quantitatively - estimated, 100 parts of silver chloride equalling 85.4 of potassic - chlorate. - - -Toxicological Detection of Alkali Salts. - -(See also _ante_, p. 121.) - - Sec. 136. Sodium, in combination, especially with chlorine, and also - with sulphuric, carbonic, and phosphoric acids, is found in the - plasma of the blood, in the urinary secretion, in the pancreatic - juice, in human bile, and in serous transudations, &c. Potassium, in - combination, is especially found in the red blood-corpuscles, in the - muscles, in the nervous tissues, and in milk. Ammonia, in - combination with acids, is naturally found in the stomach, in the - contents of the intestine; it is also a natural constituent of the - blood in small traces, and in a corpse is copiously evolved from - putrefactive changes. - - It hence follows, that mere qualitative tests for these elements in - the tissues or fluids of the body are of not the slightest use, for - they are always present during the life of the healthiest - individual, and can be found after death in persons dying from any - malady whatever. To establish the fact of a person having taken an - unusual dose of any of the alkali salts, by simply chemical - evidence, it must be proved that the alkalies are present in unusual - quantities or in an abnormal state of combination. - - In cases of rapid death, caused by sodic or potassic salts, they - will be found in such quantity in the contents of the stomach, or in - matters vomited, that there will probably be no difficulty in coming - to a direct conclusion; but if some time has elapsed, the analyst - may not find a sufficient ground for giving a decided judgment, the - excretion of the alkali salts being very rapid. - - In most cases, it will be well to proceed as follows:--The contents - of the stomach are, if necessary, diluted with distilled water, and - divided into three parts, one of which is submitted to dialysis, and - then the dialysed liquid evaporated to a small bulk and examined - qualitatively, in order to ascertain whether a large amount of the - alkaline salts is present, and in what form. In this way, the - presence or absence of nitrate of potassium or sodium may be proved, - or the iodide, bromide, sulphate, and chlorate detected. - - To find, in this way, nitrate of potassium, a coarse test is - preferable to the finer tests dependent upon conversion of the - nitrate into nitrites or into ammonia, for these tests are so - delicate, that nitrates may be detected in traces; whereas, in this - examination, to find traces is of no value. Hence, the old-fashioned - test of treating the concentrated liquid in a test-tube with copper - filings and then with sulphuric acid, and looking for the red fumes, - is best, and will act very well, even should, as is commonly the - case, some organic matters have passed through the dialyser. - - Chlorates are indicated if the liquid is divided into two parts and - tested in the manner recommended at p. 127. If present in any - quantity, chlorates or nitrates may be indicated by the brilliant - combustion of the organic matter when heated to redness, as also by - the action of strong sulphuric acid on the solid substances--in the - one case, yellow vapours of peroxide of chlorine being evolved--in - the other, the red fumes already mentioned of nitric peroxide. - - With regard to a substance such as the hydro-potassic tartrate, its - insolubility in water renders it not easy of detection by dialysis; - but its very insolubility will aid the analyst, for the contents of - the stomach may be treated with water, and thus all soluble salts of - the alkalies extracted. On now microscopically examining the - insoluble residue, crystals of bitartrate, if present, will be - readily seen. They may be picked up on a clean platinum wire and - heated to redness in a Bunsen flame, and spectroscopically examined. - After heating, the melted mass will have an alkaline reaction, and - give a precipitate with platinic chloride. All other organic salts - of potassium are soluble, and a white crystal giving such reaction - must be hydro-potassic tartrate. - - =Ammonium Salts.=--If the body is fresh, and yet the salts of - ammonium present in large amount, it is safe to conclude that they - have an external origin; but there might be some considerable - difficulty in criminal poisoning by a neutral salt of ammonium, and - search for it in a highly putrid corpse. Probably, in such an - exceptional case, there would be other evidence. With regard to the - quantitative separation and estimation of the fixed alkalies in the - ash of organic substances, the reader is referred to the processes - given in "Foods," p. 99, _et seq._, and in the present work, p. 121. - - - - -PART V.--MORE OR LESS VOLATILE POISONOUS SUBSTANCES CAPABLE OF BEING -SEPARATED BY DISTILLATION FROM NEUTRAL OR ACID LIQUIDS. - - HYDROCARBONS--CAMPHOR--ALCOHOL--AMYL NITRITE--ETHER--CHLOROFORM AND - OTHER ANAESTHETICS--CHLORAL--CARBON DISULPHIDE--CARBOLIC - ACID--NITRO-BENZENE--PRUSSIC ACID--PHOSPHORUS. - - -I.--Hydrocarbons. - - -1. PETROLEUM. - - Sec. 137. Petroleum is a general term for a mixture of hydrocarbons of - the paraffin series, which are found naturally in certain parts of - the world, and are in commerce under liquid and solid forms of - various density. Crude petroleum is not imported into England, the - original substance having previously undergone more or less - rectification. The lighter and more volatile portions are known - under the name of cymogene, rhigolene, gasolene, and naphtha. - - Sec. 138. =Cymogene= has a specific gravity of .590, and boils at 0 deg. - It has been employed in refrigerating machines. It appears to - consist chiefly of butane (C_{4}H_{10}). - - Sec. 139. =Rhigolene= is now used in medicine in the form of spray to - produce local anaesthesia. It boils at 18 deg., and has a density of - .650. - - Sec. 140. =Gasolene= has a density of .680-.688; it has received - technical applications in the "naphthalising" of air and gas. - - Sec. 141. =Benzoline= (=mineral naphtha=, =petroleum naphtha=, - =petroleum spirit=, =petroleum ether=) is a mixture of the lighter - series of hydro-carbons; the greater part consists of heptane, and - there is also a considerable quantity of pentane (C_{7}H_{16}) - present. The specific gravity varies from .69 to .74. It is very - inflammable, and is used in sponge lamps, and also as a solvent for - gutta-percha, naphthalene, paraffin, wax, and many other bodies. By - the practical chemist it is much employed. - - The similarity of the terms _benzoline_ and _benzene_ has caused - benzoline to be often confused with _benzol_ or _benzene_, the - leading constituent of coal-tar naphtha (C_{6}H_{6}). Mr Allen[132] - gives in the following table a summary of the chief points of - distinction, both between petroleum naphtha, shale naphtha, and - coal-tar naphtha. The table is founded upon the examination of - particular samples, and commercial samples may present a few minor - deviations. - -[132] _Commercial Organic Analysis_, vol. ii. p. 31. - -TABLE OF THE VARIETIES OF NAPHTHA. - - +---------------------+----------------------+----------------------+ - | Petroleum Naphtha. | Shale Naphtha. | Coal-tar Naphtha. | - +---------------------+----------------------+----------------------+ - |Contains at least 75 |Contains at least 60 |Consists almost wholly| - |per cent. of heptane,|to 70 per cent. of |of benzene, | - |C_{7}H_{16}, and |heptylene, |C_{6}H_{6}, and other | - |other hydrocarbons of|C_{7}H_{14}, and other|homologous hydro- | - |the marsh gas or |hydrocarbons of the |carbons, with a small | - |paraffin series; the |olefin series; the |percentage of light | - |remainder apparently |remainder paraffins. |hydrocarbons in some | - |olefins, C_{n}H_{2n},|No trace of benzene or|samples. | - |with distinct traces |its homologues. | | - |of benzene and its | | | - |homologues. | | | - | | | | - |Specific gravity at |Specific gravity at |Specific gravity .876.| - |15 deg., .600. |15 deg., .718. | | - | | | | - |Distils between 65 deg. |Distils between 65 deg. |Distils between 80 deg. | - |and 100 deg. |and 100 deg. |and 120 deg. | - | | | | - |Dissolves coal-tar |Behaves similarly to |Readily dissolves | - |pitch, but slightly; |petroleum naphtha with|pitch, forming a deep | - |liquid, but little |regard to the solution|brown solution. | - |coloured even after |of pitch. | | - |prolonged contact. | | | - | | | | - |On shaking three |When treated with |The liquids form a | - |measures of the |fused carbolic acid |homogeneous mixture | - |sample with one |crystals, the liquids |when treated with | - |measure of fused |mix perfectly. |fused carbolic acid | - |crystals of absolute | |crystals. | - |carbolic acid, no | | | - |solution. Liquids not| | | - |miscible. | | | - | | | | - |Combines with 10 per |Combines with upwards |Combines slowly with | - |cent. of its weight |of 90 per cent. of its|30-40 per cent. of its| - |of bromine in the |weight of bromine. |weight of bromine. | - |cold. | | | - +---------------------+----------------------+----------------------+ - - Sec. 142. =Paraffin Oil= (or =kerosine, mineral oil, photogen=, &c.) is - the chief product resulting from the distillation of American - petroleum--the usual specific gravity is about .802--it is a mixture - of hydrocarbons of the paraffin series. It should be free from the - more volatile constituents, and hence should not take fire when a - flame is applied near the surface of the cold liquid. - - Sec. 143. =Effects of Petroleum.=--Since we have here to deal with a - commercial substance of such different degrees of purity, and - various samples of which are composed of such various proportions of - different hydrocarbons, its action can only be stated in very - general terms. Eulenberg[133] has experimented with the lighter - products obtained from the distillation of Canadian petroleum. This - contained sulphur products, and was extremely poisonous, the vapour - killing a rabbit in a short time, with previous insensibility and - convulsions. The autopsy showed a thin extravasation of blood on the - surface of each of the bulbi, much coagulated blood in the heart, - congested lungs, and a bloody mucus covering the tracheal mucous - membrane. An experiment made on a cat with the lighter petroleum - (which had no excess of sulphur) in the state of vapour, showed that - it was an anaesthetic, the anaesthesia being accompanied by - convulsions, which towards the end were tetanic and violent. The - evaporation of 1.5 grm. in a close chamber killed the animal in - three hours. The lungs were found congested, but little else was - remarkable. Much petroleum vapour is breathed in certain factories, - especially those in which petroleum is refined.[134] From this cause - there have been rather frequent toxic symptoms among the workmen. - Eulenberg[135] describes the symptoms as follows:--A person, after - breathing an overdose of the vapour, becomes very pale, the lips are - livid, the respiration slow, the heart's action weak and scarcely to - be felt. If he does not immediately go into the open air away from - the poisonous vapour, these symptoms may pass on to insensibility, - convulsions, and death. It often occasions a condition of the - voluntary muscles similar to that induced by drunkenness, and on - recovery the patient is troubled by singing in the ears and noises - in the head. The smell and taste of the poison may remain for a long - time. - -[133] _Gewerbe-Hygiene._ - -[134] The vapour most likely to rise at the ordinary temperature, and -mix with the atmosphere, is that of the lighter series, from cymogene to -benzoline. - -[135] _Op. cit._ - - Sec. 144. Poisoning by taking light petroleum into the stomach is not - common. In a case recorded by Taylor,[136] a woman, for the purpose - of suicide, swallowed a pint of petroleum, There followed a slight - pain in the stomach, and a little febrile disturbance, and a - powerful smell of petroleum remained about the body for six days; - but she completely recovered. In August 1870 a sea-captain drank a - quantity of paraffin, that is, lighting petroleum, and died in a few - hours in an unconscious state. A child, 2 years old, was brought to - King's College Hospital within ten minutes after taking a - teaspoonful of paraffin. It was semi-comatose and pale, with - contracted pupils; there was no vomiting or purging. Emetics of - sulphate of zinc were administered, and the child recovered in - twenty-four hours. In another case treated at the same hospital, a - child had swallowed an unknown quantity of paraffin. It fell into a - comatose state, which simulated tubercular meningitis, and lasted - for nearly three weeks.[137] In a case recorded by Mr Robert - Smith,[138] a child, 4 years of age, had swallowed an unknown - quantity of paraffin. A few minutes afterwards, the symptoms - commenced; they were those of suffocation, with a constant cough; - there was no expectoration; the tongue, gums, and cheeks were - blanched and swollen where the fluid touched them; recovery - followed. A woman, aged 32, who had taken a quarter of a pint of - paraffin, was found unconscious and very cold; the stomach-pump was - used, and she recovered.[139] Hence it is tolerably certain, from - the above instances, that should a case of petroleum poisoning - occur, the expert will not have to deal with infinitesimal - quantities; but while the odour of the oil will probably be - distinctly perceptible, there will be also a sufficient amount - obtained either from matters vomited, or the contents of the - stomach, &c., so that no difficulty will be experienced in - identifying it. - -[136] _Poisons_, p. 656 - -[137] _Brit. Med. Journ._, Sept. 16, 1876, p. 365. - -[138] _Brit. Med. Journ._, Oct. 14, 1876. - -[139] _Pharm. Journ._, Feb. 12, 1875; also for other cases see _Brit. -Med. Journ._, Nov. 4, 1876; and Koehler's _Physiol. Therap._, p. 437. - - Sec. 145. In order to separate petroleum from any liquid, the - substances under examination must be carefully distilled in the - manner recommended under "_Ether_." The lighter petroleums will - distil by the aid of a water-bath; but the heavier require a - stronger heat; redistillation of the distillate may be necessary. - The odour of the liquid, its inflammable character, and its other - properties, will be sufficient for identification. - - -2. COAL-TAR-NAPHTHA--BENZENE. - - Sec. 146. Coal-tar-naphtha in its crude state, is an extremely complex - liquid, of a most disagreeable smell. Much benzene (C_{6}H_{6}) is - present with higher homologues of the benzene series. Toluene - (C_{7}H_{8}), naphthalene (C_{10}H_{8}), hydrocarbons of the - paraffin series, especially hexane (C_{6}H_{14}), and hydrocarbons - of the olefin series, especially pentylene, hexylene, and heptylene - (C_{5}H_{10}, C_{6}H_{12} and C_{7}H_{14}). Besides these, there are - nitrogenised bases, such as aniline, picoline, and pyridine; - phenols, especially carbolic acid; ammonia, ammonium sulphide, - carbon disulphide, and probably other sulphur compounds; acetylene - and aceto-nitrile. By distillation and fractional distillation are - produced what are technically known "_once run_" _naphtha_, _90 per - cent. benzol_, _50 and 90 per cent. benzol_,[140] _30 per cent. - benzol_, _solvent naphtha_, and residue known as "_last runnings_." - -[140] Or 50/90 benzol, this indicates that 50 per cent. distils over -below 100 deg.; and 40, making in all 90, below 120 deg. - - Sec. 147. Taylor[141] records a case in which a boy, aged 12, swallowed - about 3 ozs. of naphtha, the kind usually sold for burning in lamps, - and died with symptoms of narcotic poisoning. The child, after - taking it, ran about in wild delirium, he then sank into a state of - collapse, breathing stertorously, and the skin became cold and - clammy. On vomiting being excited, he rejected about two - tablespoonfuls of the naphtha, and recovered somewhat, but again - fell into collapse with great muscular relaxation. The breathing was - difficult; there were no convulsions; the eyes were fixed and - glassy, the pupils contracted; there was frothing at the mouth. In - spite of every effort to save him, he died in less than three hours - after taking the poison. The body, examined three days after death, - smelt strongly of naphtha, but the _post-mortem_ appearances were in - no way peculiar, save that the stomach contained a pint of - semi-fluid matter, from which a fluid, having the characteristics of - impure benzene, was separated. - -[141] _Op. cit._, p. 657. - - Sec. 148. The effects of the vapour of benzene have been studied by - Eulenberg in experiments on cats and rabbits, and there are also - available observations on men[142] who have been accidentally - exposed to its influence. From these sources of information, it is - evident that the vapour of benzene has a distinctly narcotic effect, - while influencing also in a marked degree the spinal cord. There - are, as symptoms, noises in the head, convulsive trembling and - twitchings of the muscles, with difficulty of breathing. - -[142] Dr. Stone, _Med. Gaz._, 1848, vol. xii. p. 1077. - - -DETECTION AND SEPARATION OF BENZENE. - - Sec. 149. Benzene is separated from liquids by distillation, and may be - recognised by its odour, and by the properties described at p. 130. - The best process of identification, perhaps, is to purify and - convert it into nitro-benzene, and then into aniline, in the - following manner:-- - - 1. =Purification.=--The liquid is agitated with a solution of - caustic soda; this dissolves out of the benzene any bodies of an - acid character, such as phenol, &c. The purified liquid should again - be distilled, collecting that portion of the distillate which passes - over between 65 deg. and 100 deg.; directly the thermometer attains nearly - the 100 deg., the distillation should be stopped. The distillate, which - contains all the benzene present, is next shaken with concentrated - sulphuric acid in the cold; this will dissolve out all the - hydrocarbons of the ethylene and acetylene series. On removing the - layer of benzene from the acid, it must be again shaken up with - dilute soda, so as to remove any trace of acid. The benzene is, by - this rather complicated series of operations, obtained in a very - fair state of purity, and may be converted into nitro-benzene, as - follows:-- - - 2. =Conversion into Nitro-Benzene.=--The oily liquid is placed in a - flask, and treated with four times its volume of fuming nitric acid. - The flask must be furnished with an upright condenser; a vigorous - action mostly takes place without the application of heat, but if - this does not occur, the flask may be warmed for a few minutes. - - After the conversion is over, the liquid, while still warm, must be - transferred into a burette furnished with a glass tap, or to a - separating funnel, and all, except the top layer, run into cold - water; if benzene was originally present, either oily drops of - nitro-benzene will fall, or if the benzene was only in small - quantity, a fine precipitate will gradually settle down to the - bottom of the vessel, and a distinct bitter-almond smell be - observed; but, if there be no benzene in the original liquid, and, - consequently, no nitro-benzene formed, no such appearance will be - observed. - - 3. =Conversion into Aniline.=--The nitro-benzene may itself be - identified by collecting it on a wet filter, dissolving it off the - filter by alcohol, acidifying the alcoholic solution by hydrochloric - acid, and then boiling it for some time with metallic zinc. In this - way aniline is formed by reduction. On neutralising and diluting the - liquid, and cautiously adding a little clear solution of - bleaching-powder, a blue or purple colour passing to brown is in a - little time produced. - - -3. TERPENES--ESSENTIAL OILS--OIL OF TURPENTINE. - - Sec. 150. The terpenes are hydrocarbons of the general formula - C_{n}H_{2n-4}. The natural terpenes are divided into three - classes:-- - - 1. =The true terpenes=, _formula_ (C_{10}H_{16})--a large number of - essential oils, such as those of turpentine, orange peel, nutmeg, - caraway, anise, thyme, &c., are mainly composed of terpenes. - - 2. =The cedrenes=, _formula_ (C_{15}H_{24})--the essential oil of - cloves, rosewood, cubebs, calamus, cascarilla, and patchouli belong - to this class. - - 3. =The colophene hydrocarbons=, _formula_ (C_{20}H_{32}), - represented by colophony. - - Of all these, oil of turpentine alone has any toxicological - significance; it is, however, true that all the essential oils, if - taken in considerable doses, are poisonous, and cause, for the most - part, vascular excitement and complex nervous phenomena, but their - action has not been very completely studied. They may all be - separated by distillation, but a more convenient process for - recovering an essential oil from a liquid is to shake it up with - petroleum ether, separating the petroleum and evaporating - spontaneously; by this means the oil is left in a fair state of - purity. - - -4. OIL OF TURPENTINE--SPIRIT OF TURPENTINE--"TURPS." - - Sec. 151. Various species of pine yield a crude turpentine, holding in - solution more or less resin. The turpentine may be obtained from - this exudation by distillation, and when the first portion of the - distillate is treated with alkali, and then redistilled, the final - product is known under the name of "rectified oil of turpentine," - and is sometimes called "camphene." It mainly consists of - terebenthene. Terebenthene obtained from French turpentine differs - in some respects from that obtained from English or American - turpentine. They are both mobile, colourless liquids, having the - well-known odour of turpentine and highly refractive; but the French - terebenthene turns a ray of polarised light to the left -40.3 deg. for - the sodium ray, and the English to the right +21.5 deg.; the latter - terebenthene is known scientifically as austra-terebenthene. This - action on polarised light is retained in the various compounds and - polymers of the two turpentine oils. - - The specific gravity of turpentine oil is .864; its boiling point, - when consisting of pure terebenthene, 156 deg., but impurities may raise - it up to 160 deg.; it is combustible and burns with a smoky flame. Oil - of turpentine is very soluble in ether, petroleum ether, carbon - disulphide, chloroform, benzene, fixed and essential oils, and by - the use of these solvents it is conveniently separated from the - contents of the stomach. It is insoluble in water, glycerin, and - dilute alkaline and acid solutions; and very soluble in absolute - alcohol, from which it may be precipitated by the addition of water. - - It is polymerised by the action of strong sulphuric acid, the - polymer, of course, boiling at a higher temperature than the - original oil. With water it forms a crystalline hydrate - (C_{10}H_{20}O_{2},H_{2}O). On passing nitrosyl chloride gas into - the oil, either pure or diluted with chloroform or alcohol, the - mixture being cooled by ice, a white crystalline body is deposited, - of the formula C_{10}H_{16}(NOCl). By treating this compound with - alcoholic potash, the substitution product (C_{10}H_{16}NO) is - obtained. By treating turpentine with an equal bulk of warm water, - and shaking it in a large bottle with air, camphoric acid and - peroxide of hydrogen are formed. When turpentine oil is left in - contact with concentrated hydrochloric acid, there is formed - terebenthene dihydrochloride (C_{10}H_{16}2HCl), which forms rhombic - plates, insoluble in water, and decomposable by boiling alcoholic - potash, with formation of terpinol, (C_{10}H_{17})_{2}O. The - dihydrochloride gives a colour-reaction with ferric chloride. This - is an excellent test--not, it is true, confined to oil of - turpentine--but common to the dihydrochlorides of all the terpenes. - A few drops of the oil are stirred in a porcelain capsule with a - drop of hydrochloric acid, and one of ferric chloride solution; on - gently heating, there is produced first a rose colour, then a - violet-red, and lastly a blue. - - Sec. 152. =Effects of the Administration of Turpentine.=--L. W. - Liersch[143] exposed animals to the vapour of turpentine, and found - that a cat and a rabbit died within half an hour. There was observed - uneasiness, reeling, want of power in the limbs (more especially in - the hinder extremities), convulsions partial, or general, difficulty - of respiration; and the heart's action was quickened. Death took - place, in part, from asphyxia, and in part was attributable to a - direct action on the nervous centres. The autopsy showed congestion - of the lungs, ecchymoses of the kidney, and much blood in the liver - and spleen. Small doses of turpentine-vapour cause (according to Sir - B. W. Richardson)[144] giddiness, deficient appetite, and anaemia. - From half an ounce to an ounce is frequently prescribed in the - country as a remedy for tape-worm; in smaller quantities it is found - to be a useful medicine in a great variety of ailments. The larger - doses produce a kind of intoxication with giddiness, followed often - by purging and strangury, not unfrequently blood and albumen (or - both) is found in the urine. When in medical practice I have given - the oil, and seen it given by others, in large doses for tape-worm - to adults, in perhaps 40 cases, but in no one instance were the - symptoms severe; the slight intoxication subsided quickly, and in a - few hours the patients recovered completely. Nevertheless it has - been known to destroy the lives of children, and cause most serious - symptoms in adults. Two fatal cases are mentioned by Taylor; one was - that of a child who died fifteen hours after taking half an ounce of - the oil; in another an infant, five months old, died rapidly from a - teaspoonful. The symptoms in these fatal cases were profound coma - and slight convulsions; the pupils were contracted, and there was - slow and irregular breathing. Turpentine is eliminated in a changed - form by the kidneys, and imparts an odour of violet to the urine; - but the nature of the odoriferous principle has not yet been - investigated. - -[143] Clarus in Schmidt's _Jahrbuecher_, Bd. cxvii., i. 1863; and -_Vierteljahrsschr. fuer ger. Med._, xxii., Oct. 1862. - -[144] _Brit. and For. Med.-Chir. Review_, April 1863. - - -II.--Camphor. - - Sec. 153. A great many essential oils deposit, after exposure to air, - camphors produced by oxidation of their terpenes. Ordinary camphor - is imported in the rough state from China and Japan, and is prepared - by distilling with water the wood of _Camphora officinarum_; it is - resublimed in England. The formula of camphor is C_{10}H_{16}O; it - has a density of .986 to .996; melts at 175 deg., and boils at 205 deg. It - is readily sublimed, especially in a vacuum, and is indeed so - volatile at all temperatures, that a lump of camphor exposed to the - air wastes away. It is somewhat insoluble in water (about 1 part in - 1000), but this is enough to impart a distinct taste to the water; - it is insoluble in chloroform, ether, acetone, acetic acid, carbon - disulphide, and oils. It has a fragrant odour and a burning taste. A - 10 per cent. solution in alcohol turns a ray of polarised light to - the right +42.8 deg. By distillation with zinc chloride, cymene and - other products are produced. By prolonged treatment with nitric - acid, camphor is oxidised to camphoric acid (C_{10}H_{16}O_{4}). - Camphor unites with bromine to form a crystalline, unstable - dibromide, which splits up on distillation into hydrobromic acid and - monobrom-camphor (C_{10}H_{15}BrO). The latter is used in medicine; - it crystallises in prisms fusible at 76 deg., and is readily soluble in - alcohol. - - Sec. 154. =Pharmaceutical Preparations.=--The preparations officinal in - the British Pharmacop[oe]ia are _camphor water_--water saturated - with camphor, containing about one part per thousand. - - =Camphor Liniment.=--A solution of camphor in olive oil, strength 25 - per cent. - - =Compound Camphor Liniment.=--Composed of camphor, oil of lavender, - strong solution of ammonia and alcohol; strength in camphor about 11 - per cent. - - =Spirit of Camphor.=--A solution of camphor in spirit; strength, 10 - per cent. - - Camphor is also a constituent of the _compound tincture of camphor_; - but in this case it may be considered only a flavouring agent. There - is a hom[oe]opathic solution of camphor in spirit (Rubini's Essence - of Camphor). The solution is made by saturating alcohol with - camphor; it is, therefore, very strong--about half the bulk - consisting of camphor. Camphor is used in veterinary medicine, both - externally and internally. - - Sec. 155. =Symptoms.=--Camphor acts energetically on the brain and - nervous system, especially if it is given in strong alcoholic - solution, and thus placed under conditions favouring absorption. - Some years ago, Dr. G. Johnson[145] published a series of cases - arising from the injudicious use of "hom[oe]opathic solution of - camphor," from 7 to 40 drops of Rubini's hom[oe]opathic camphor - taken for colds, sore throat, &c., having produced coma, foaming at - the mouth, convulsions, and partial paralysis. All the patients - recovered, but their condition was for a little time alarming. - -[145] _Brit. Med. Journ._, Feb. 27, 1878, p. 272; see also _ibid._, Feb. -1875. - - The cases of fatal poisoning by camphor are very rare. A woman, aged - 46, pregnant four months, took 12 grms. (about 184 grains) in a - glass of brandy for the purpose of procuring abortion. In a very - short time the symptoms commenced; she had intolerable headache, the - face was flushed, and there was a sensation of burning in the - stomach. In eight hours after taking the dose, she had strangury and - vomiting, and the pain in the epigastrium was intense. These - symptoms continued with more or less severity until the third day, - when she became much worse. Her face was pale and livid, the eyes - hollow, the skin cold and insensible, pulse weak and thready, - breathing laboured. There were violent cramps in the stomach and - retention of urine for twenty-four hours, and then coma. The patient - lingered on yet another three days, aborted, and died.[146] - -[146] _Journ. de Chim. Med._, May 1860. - - Dr. Schaaf[147] has recorded three cases of poisoning--one of which - was fatal. A woman gave about half a teaspoonful of a camphor - solution to each of her three children, the ages being respectively - five and three years and fifteen months. The symptoms noted were - pallor of the face, a burning pain in the throat, thirst, vomiting, - purging, convulsions, and afterwards coma. The youngest child died - in seven hours; the others recovered. The smallest dose known to - have produced violent symptoms in an adult is 1.3 grm. (20 grains); - the largest dose known to have been recovered from is 10.4 grms. - (160 grains).[148] - -[147] _Journ. de Chim. Med._, 1850, p. 507. - -[148] Taylor on _Poisons_, 3rd ed., 661. - - Sec. 156. =Post-mortem Appearances.=--The bodies of animals or persons - dying from poisoning by camphor, smell strongly of the substance. - The mucous membrane of the stomach has been found inflamed, but - there seem to be no characteristic lesions. - - Sec. 157. =Separation of Camphor from the Contents of the - Stomach.=--The identification of camphor would probably in no case - present any difficulty. It may be readily dissolved out from organic - fluids by chloroform. If dissolved in fixed oils, enough for the - purposes of identification may be obtained by simple distillation. - It is precipitated from its alcoholic solution by the addition of - water. - - -III.--Alcohols. - - -1. ETHYLIC ALCOHOL. - -Sec. 158. The chemical properties of ordinary alcohol are fully described, -with the appropriate tests, in "Foods," pp. 369-384, and the reader is -also referred to the same volume for the composition and strength of the -various alcoholic drinks. - -=Statistics.=--If we were to include in one list the deaths indirectly -due to chronic, as well as acute poisoning by alcohol, it would stand -first of all poisons in order of frequency, but the taking of doses so -large as to cause death in a few hours is rare. The deaths from alcohol -are included by the English registrar-general under two heads, viz., -those returned as dying from _delirium tremens_, and those certified as -due directly to intemperance. - -During the twenty-five years, from 1868 to 1892, 30,219 deaths have been -registered as due to intemperance, which gives an average of 1209 per -year. The rate per million has varied during the period from 29 to 71; -and the figures taken as a whole show that deaths from intemperance -appear to be increasing; the increase may be only apparent, not real, -for it is a significant circumstance that deaths registered under liver -diseases show a corresponding decrease; it is, therefore, not unlikely -that deaths which formerly would be ascribed to liver disease, are more -often now stated to be the effects of intemperance. - -Deaths directly due to large doses of alcohol are not uncommon; during -the ten years ending 1892, 105 deaths (81 males and 24 females) were -ascribed under the head of "accident or negligence" directly to alcohol. - -[Illustration: CHART SHEWING DEATHS PER MILLION PERSONS LIVING, FROM -INTEMPERANCE & FROM LIVER DISEASES. - - THE MEDICAL "OFFICERS OF HEALTH" CHART. - - ENT. AT STA. HALL. - - Notes. - _Intemperance_ -------------- - _Liver disease_ .............. - _The Scale for Intemperance is as printed._ - _That for Liver diseases is 10 times larger._] - -Sec. 159. =Criminal or Accidental Alcoholic Poisoning.=--Suicide by -alcohol, in the common acceptation of the term, is rare, and murder -still rarer, though not unknown. In the ten years ending 1892, only -three deaths from alcohol (1 male and 2 females) are recorded as -suicidal. Perhaps the most common cause of fatal acute poisoning by -alcohol is either a foolish wager, by which a man bets that he can drink -so many glasses of spirits without bad effect; or else the drugging of a -person already drunk by his companions in a sportive spirit. - -Sec. 160. =Fatal Dose.=--It is difficult to say what would be likely to -prove a lethal dose of alcohol, for a great deal depends, without doubt, -on the dilution of the spirit, since the mere local action of strong -alcohol on the mucous membranes of the stomach, &c., is severe (one may -almost say corrosive), and would aid the more remote effects. In -Maschka's case,[149] a boy of nine years and a girl of five, died from -about two and a half ounces of spirit of 67 per cent. strength, or 48.2 -c.c. (1.7 oz.) of absolute alcohol. - -[149] Recorded by Maschka (_Gutachten der Prager Facultaet_, iv. 239; see -also Maschka's _Handbuch der gericht. Medicin_, Band. ii. p. 384). The -following is a brief summary:--Franz. Z., nine years old, and Caroline -Z., eight years old, were poisoned by their stepfather with spirit of 67 -per cent. strength taken in small quantities by each--at first by -persuasion, and the remainder administered by force. About one-eighth of -a pint is said to have been given to each child. Both vomited somewhat, -then lying down, stertorous breathing at once came on, and they quickly -died. The autopsy, three days after death, showed dilatation of the -pupils; _rigor mortis_ present in the boy, not in the girl; and the -membranes of the brain filled with dark fluid blood. The smell of -alcohol was perceptible on opening the chest; the mucous membrane of the -bronchial tubes and gullet was normal, both lungs [oe]dematous, the fine -tubes gorged with a bloody frothy fluid, and the mucous membrane of the -whole intestinal canal was reddened. The stomach was not, unfortunately, -examined, being reserved for chemical analysis. The heart was healthy; -the pericardium contained some straw-coloured fluid. Chemical analysis -gave an entirely negative result, which must have been from insufficient -material having been submitted to the analyst, for I cannot see how the -vapours of alcohol could have been detected by the smell, and yet have -evaded chemical processes. - -In a case related by Taylor, a child, seven years old, died from some -quantity of brandy, probably about 113.4 c.c. (4 ozs.), which would be -equal to at least 56.7 c.c. (2 ozs.) of absolute alcohol. From other -cases in which the quantity of absolute alcohol can be, with some -approximation to the truth, valued, it is evident that, for any child -below ten or twelve, quantities of from 28.3 to 56.6 c.c. (1-2 ozs.) of -absolute alcohol contained in brandy, gin, &c., would be a highly -dangerous and probably fatal dose; while the toxic dose for adults is -somewhere between 71.8-141.7 c.c. (2.5-5 ozs.). - -Sec. 161. =Symptoms.=--In the cases of rapid poisoning by a large dose of -alcohol, which alone concern us, the preliminary, and too familiar -excitement of the drunkard, may be hardly observable; but the second -stage, that of depression, rapidly sets in; the unhappy victim sinks -down to the ground helpless, the face pale, the eyes injected and -staring, the pupils dilated, acting sluggishly to light, and the skin -remarkably cold. Fraentzel[150] found, in a case in which the patient -survived, a temperature of only 24.6 deg. in the rectum, and in that of -another person who died, a temperature of 23.8 deg. The mucous membranes -are of a peculiar dusky blue; the pulse, which at first is quick, soon -becomes slow and small; the respiration is also slowed, intermittent, -and stertorous; there is complete loss of consciousness and motion; the -breath smells strongly of the alcoholic drink, and if the coma continues -there may be vomiting and involuntary passing of excreta. Death -ultimately occurs through paralysis of the respiratory centres. -Convulsions in adults are rare, in children frequent. Death has more -than once been immediately caused, not by the poison, but by accidents -dependent upon loss of consciousness. Thus food has been sucked into the -air-tubes, or the person has fallen, so that the face was buried in -water, ordure, or mud; here suffocation has been induced by mechanical -causes. - -[150] _Temperaturerniedrigung durch Alcoholintoxication, Charite -Annalen_, i. 371. - -A remarkable course not known with any other narcotic is that in which -the symptoms remit, the person wakes up, as it were, moves about and -does one or more rational acts, and then suddenly dies. In this case -also, the death is not directly due to alcohol, but indirectly--the -alcohol having developed [oe]dema, pneumonia, or other affection of the -lungs, which causes the sudden termination when the first effect of the -poison has gone off. The time that may elapse from the commencement of -coma till death varies from a few minutes to days; death has occurred -after a quarter of an hour, half an hour, and an hour. It has also been -prolonged to three, four, and six days, during the whole of which the -coma has continued. The average period may, however, be put at from six -to ten hours. - -Sec. 162. =Post-mortem Appearances.=--Cadaveric rigidity lasts tolerably -long. Casper has seen it still existing nine days after death, and -Seidel[151] seven days (in February). Putrefaction is retarded in those -cases in which a very large dose has been taken, but this is not a very -noticeable or constant characteristic. The pupils are mostly dilated. -The smell of alcohol should be watched for; sometimes it is only present -in cases where but a short time has elapsed between the taking of the -poison and death; putrefaction may also conceal it, but under favourable -circumstances, especially if the weather is cold, the alcoholic smell -may remain a long time. Alcohol may cause the most intense redness and -congestion of the stomach. The most inflamed stomach I ever saw, short -of inflammation by the corrosive poisons, was that of a sailor, who died -suddenly after a twenty-four hours' drinking bout: all the organs of the -body were fairly healthy, the man had suffered from no disease; analysis -could detect no poison but alcohol; and the history of the case, -moreover, proved clearly that it was a pure case of alcoholic poisoning. - -[151] Seidel, Maschka's _Handbuch_, Bd. ii. p. 380. - -In a case related by Taylor, in which a child drank 4 ozs. of brandy and -died, the mucous membrane of the stomach presented patches of intense -redness, and in several places was thickened and softened, some portions -being actually detached and hanging loose, and there were evident signs -of extravasations of blood. The effect may not be confined to the -stomach, but extend to the duodenum and even to the whole intestinal -canal. The blood is generally dark and fluid, and usually the contents -of the skull are markedly hyperaemic, the pia very full of blood, the -sinuses and plexus gorged; occasionally, the brain-substance shows signs -of unusual congestion; serum is often found in the ventricles. The great -veins of the neck, the lungs, and the right side of the heart, are very -often found full of blood, and the left side empty. [OE]dema of the -lungs also occurs with tolerable frequency. The great veins of the -abdomen are also filled with blood, and if the coma has been prolonged, -the bladder will be distended with urine. A rare phenomenon has also -been noticed--namely, the occurrence of blebs on the extremities, &c., -just as if the part affected had been burnt or scalded. Lastly, with the -changes directly due to the fatal dose may be included all those -degenerations met with in the chronic drinker, provided the case had a -history of previous intemperance. - -Sec. 163. =Excretion of Alcohol.=--Alcohol, in the diluted form, is quickly -absorbed by the blood-vessels of the stomach, &c., and circulates in the -blood; but what becomes of it afterwards is by no means settled. I think -there can be little doubt that the lungs are the main channels through -which it is eliminated; with persons given up to habits of intemperance, -the breath has constantly a very peculiar ethereal odour, probably -dependent upon some highly volatile oxidised product of alcohol. - -Alcohol is eliminated in small proportion only by the kidneys. -Thudichum, in an experiment[152] by which 4000 grms. of absolute alcohol -were consumed by thirty-three men, could only find in the collected -urine 10 grms. of alcohol. The numerous experiments by Dupre also -establish the same truth, that but a fraction of the total alcohol -absorbed is excreted by the kidneys. According to Lallemand, Perrin, and -Duroy the content of the brain in alcohol is more than that of the -other organs. I have found also that the brain after death has a -wonderful attraction for alcohol, and yields it up at a water-heat very -slowly and with difficulty. In one experiment, in which a finely-divided -portion of brain, which had been soaking in alcohol for many weeks, was -submitted to a steam heat of 100 deg., twenty-four hours' consecutive -heating failed to expel every trace of spirit. - -[152] See Thudichum's _Pathology of the Urine_, London, 1877, in which -both his own and Dr. Dupre's experiments are summarised. - -It is probable that true alcoholates of the chemical constituents of the -brain are formed. In the case of vegetable colloidal bodies, such, for -example, as the pulp of cherries, a similar attraction has been -observed, the fruit condensing, as it were, the alcohol in its own -tissues, and the outer liquid being of less alcoholic strength than that -which can be expressed from the steeped cherries. Alcohol is also -excreted by the sweat, and minute fractions have been found in the -faeces. - -Sec. 164. =Toxicological Detection of Alcohol= (see "Foods," pp. -406-419).--The living cells of the body produce minute quantities of -alcohol, as also some of the bacteria normally inhabiting the small -intestine produce small quantities of alcohol, and it is often found in -traces in putrefying fluids. Hence, mere qualitative proofs of the -presence of alcohol are insufficient on which to base an opinion as to -whether alcohol had been taken during life or not, and it will be -necessary to estimate the quantity accurately by some of the processes -detailed in "Foods," p. 409, _et seq._ In those cases in which alcohol -is found in quantity in the stomach, there can, of course, be no -difficulty; in others, the whole of the alcohol may have been absorbed, -and chemical evidence, unless extremely definite, must be supplemented -by other facts. - - -2. AMYLIC ALCOHOL. - - Sec. 165. =Amylic Alcohol=--_Formula_, C_{5}H_{11}HO.--There is more - than one amylic alcohol according to theory; eight isomers are - possible, and seven are known. The amylic alcohols are identical in - their chemical composition, but differ in certain physical - properties, primary amylic alcohol boiling at 137 deg., and iso-amyl - alcohol at 131.6 deg. The latter has a specific gravity of .8148, and - is the variety produced by fermentation and present in fusel oil. - - Sec. 166. The experiments of Eulenberg[153] on rabbits, Cross[154] on - pigeons, Rabuteau[155] on frogs, and Furst on rabbits, with those of - Sir B. W. Richardson[156] on various animals, have shown it to be a - powerful poison, more especially if breathed in a state of vapour. - -[153] _Gewerbe Hygiene_, 1876, p. 440. - -[154] _De l'Alcohol Amylique et Methyl sur l'Organisme (These)_, -Strasburg, 1863. - -[155] "Ueber die Wirkung des Aethyl, Butyl u. Amyl Alcohols," _L'Union_, -Nos. 90, 91, 1870. Schmidt's _Jahrb._, Bd. 149, p. 263. - -[156] _Trans. Brit. Association_, 1864, 1865, and 1866. Also, _Brit. and -Foreign Med. Chir. Rev._, Jan. 7, 1867, p. 247. - - Richardson, as the result of his investigations, considers that amyl - alcohol when breathed sets up quite a peculiar class of symptoms - which last for many hours, and are of such a character, that it - might be thought impossible for the animal to recover, although they - have not been known to prove fatal. There is muscular paralysis with - paroxysms of tremulous convulsions; the spasms are excited by - touching the animal, breathing upon it, or otherwise subjecting it - to trifling excitation. - - Sec. 167. Hitherto, neither the impure fusel oil, nor the purer - chemical preparation, has had any toxicological importance. Should - it be necessary at any time to recover small quantities from organic - liquids, the easiest way is to shake the liquid up with chloroform, - which readily dissolves amylic alcohol, and on evaporation leaves it - in a state pure enough to be identified. Amyl alcohol is identified - by the following tests:--(1) Its physical properties; (2) if warmed - with twice its volume of strong sulphuric acid, a rose or red colour - is produced; (3) heated with an acetate and strong sulphuric acid, - _amyl acetate_, which has the odour of the jargonelle pear, is - formed; (4) heated with sulphuric acid and potassic dichromate, - valeric aldehyde is first produced, and then valeric acid is formed; - the latter has a most peculiar and strong odour. - - Sec. 168. =Amyl Nitrite, Iso-amyl Ester Nitrite= - (C_{5}H_{11}NO_{2}).--Boiling point 97 deg. to 99 deg., specific gravity - .877. Amyl nitrite is a limpid, and, generally, slightly yellow - liquid; it has a peculiar and characteristic odour. On heating with - alcoholic potash, the products are nitrite of potash and amylic - alcohol; the amylic alcohol may be distilled off and identified. The - presence of a nitrite in the alkaline solution is readily shown by - the colour produced, by adding a few drops of a solution of - meta-phenylenediamine. - - Sir B. W. Richardson and others have investigated the action of amyl - nitrite, as well as that of the acetate and iodide; they all act in - a similar manner, the nitrite being most potent. After absorption, - the effects of amyl nitrite are especially seen on the heart and - circulation: the heart acts violently, there is first dilatation of - the capillaries, then this is followed by diminished action of the - heart and contraction of the capillaries. - - According to Richardson, it suspends the animation of frogs. No - other substance known will thus suspend a frog's animation for so - long a time without killing it. Under favourable circumstances, the - animal will remain apparently dead for many days, and yet recover. - Warm-blooded animals may be thrown by amyl nitrite into a cataleptic - condition. It is not an anaesthetic, and by its use consciousness is - not destroyed, unless a condition approaching death be first - produced. When this occurs there is rarely recovery, the animal - passes into actual death. - - =Post-Mortem Appearances.=--If administered quickly, the lungs and - all the other organs are found blanched and free from blood, the - right side of the heart gorged with blood, the left empty, the brain - being free from congestion. If administered slowly, the brain is - found congested, and there is blood both on the left and right sides - of the heart. - - -IV.--Ether. - -Sec. 169. =Ether, Ethylic Ether, Ethyl Oxide,= (C_{2}H_{5})_{2}O.--Ethylic -ether is a highly mobile liquid of peculiar penetrating odour and -sweetish pungent taste. It is perfectly colourless, and evaporates so -rapidly, that when applied in the form of spray to the skin, the latter -becomes frozen, and is thus deprived of sensibility. - -Pure ether has a density of .713, its boiling-point is 35 deg., but -commercial samples, which often contain water (1 part of water is -soluble in 35 of ether), may have a higher gravity, and also a higher -boiling-point. The readiest way to know whether an ether is anhydrous or -not, is to shake it up with a little carbon disulphide. If it is -hydrous, the mixture is milky. Methylated ether is largely used in -commerce; its disagreeable odour is due to contamination by methylated -compounds; otherwise the ether made from methylated spirit is ethylic -ether, for methylic ether is a gas which escapes during the process. -Hence the term "methylated" ether is misleading, for it contains no -methylic ether, but is essentially a somewhat impure ethylic ether. - -Sec. 170. =Ether as a Poison.=--Ether has but little toxicological -importance. There are a few cases of death from its use as an -anaesthetic, and a few cases of suicide. Ether is used by some people as -a stimulant, but ether drinkers are uncommon. It causes an intoxication -very similar to that of alcohol, but of brief duration. In a case of -chronic ether-taking recorded by Martin,[157] in which a woman took -daily doses of ether for the purpose of allaying a gastric trouble, the -patient suffered from shivering or trembling of the hands and feet, -muscular weakness, cramp in the calves of the legs, pain in the breast -and back, intermittent headaches, palpitation, singing in the ears, -vomitings, and wakefulness; the ether being discontinued, the patient -recovered. In one of Orfila's experiments, half an ounce of ether was -administered to a dog. The animal died insensible in three hours. The -mucous membrane of the stomach was found highly inflamed, the -inflammation extending somewhat into the duodenum; the rest of the canal -was healthy. The lungs were gorged with fluid blood. - -[157] Virchow's _Jahresber._, 1870. - -Sec. 171. =Fatal Dose.=--The fatal dose of ether, when taken as a liquid, -is not known. 4 grms. (1.28 drms.) cause toxic symptoms, but the effect -soon passes. Buchanan has seen a brandy-drinker consume 25 grms. (7 -drms.) and yet survive. It is probable that most adults would be killed -by a fluid ounce (28.4 c.c.). - -Sec. 172. =Ether as an Anaesthetic.=--Ether is now much used as an -anaesthetic, and generally in conjunction with chloroform. Anaesthesia by -ether is said to compare favourably with that produced by chloroform. In -92,000 cases of operations performed under ether, the proportion dying -from the effects of the anaesthetic was only .3 per 10,000 (Morgan), -while chloroform gives a higher number (see p. 149). The mortality in -America, again, from a mixture of chloroform and ether in 11,000 cases -is reckoned at 1.7 per 10,000; but this proportion is rather above some -of the calculations relative to the mortality from pure chloroform, so -that the question can hardly be considered settled. The symptoms of -ether narcosis are very similar to those produced by chloroform. The -chief point of difference appears to be its action on the heart. Ether, -when first breathed, stimulates the heart's action, and the -after-depression that follows never reaches so high a grade as with -chloroform. Ether is said to kill by paralysing the respiration, and in -cases which end fatally the breathing is seen to stop suddenly: -convulsions have not been noticed. The _post-mortem_ appearances, as in -the case of chloroform, are not characteristic. - -Sec. 173. =Separation of Ether from Organic Fluids, &c.=--Despite the low -boiling-point of ether, it is by no means easy to separate it from -organic substances _so as to recover the whole of the ether present_. -The best way is to place the matters in a flask connected with an -ordinary Liebig's condenser, the tube of the latter at its farther end -fitting closely into the doubly perforated cork of a flask. Into the -second perforation is adapted an upright tube about 2 feet long, which -may be of small diameter, and must be surrounded by a freezing mixture -of ice and salt. The upper end of this tube is closed by a thistle-head -funnel with syphon, and in the bend of the syphon a little mercury -serves as a valve. Heat is now applied to the flask by means of a -water-bath, and continued for several hours; the liquid which has -distilled over is then treated with dry calcic chloride and redistilled -exactly in the same way. To this distillate again a similar process may -be used, substituting dry potassic carbonate for the calcic chloride. It -is only by operating on these principles that the expert can recover in -an approximate state of anhydrous purity such a volatile liquid. Having -thus obtained it pure, it may be identified (1) by its smell, (2) by its -boiling-point, (3) by its inflammability, and (4) by its reducing -chromic acid. The latter test may be applied to the vapour. An asbestos -fibre is soaked in a mixture of strong sulphuric acid and potassic -dichromate, and then placed in the tube connected with the flask--the -ethereal (or alcoholic) vapour passing over the fibre, immediately -reduces the chromic acid to chromic oxide, with the production of a -green colour. - - -V.--Chloroform. - -CHLOROFORM, TRICHLOROMETHANE OR METHENYL CHLORIDE (CHCl_{3}). - -Sec. 174. Chloroform appears to have been discovered independently by -Soubeiran and Liebig, about 1830. It was first employed in medicine by -Simpson, of Edinburgh, as an anaesthetic. Pure chloroform has a density -of 1.491 at 17 deg., and boils at 60.8 deg.; but commercial samples have -gravities of from 1.47 to 1.491. It is a colourless liquid, strongly -refracting light; it cannot be ignited by itself, but, when mixed with -alcohol, burns with a smoky flame edged with green. Its odour is heavy, -but rather pleasant; the taste is sweet and burning. - -Chloroform sinks in water, and is only slightly soluble in that fluid -(.44 in 100 c.c.), it is perfectly neutral in reaction, and very -volatile. When rubbed on the skin, it should completely evaporate, -leaving no odour. Pure absolute chloroform gives an opaline mixture if -mixed with from 1 to 5 volumes of alcohol, but with any quantity above 5 -volumes the mixture is clear; it mixes in all proportions with ether. -Chloroform coagulates albumen, and is an excellent solvent for most -organic bases--camphor, caoutchouc, amber, opal, and all common resins. -It dissolves phosphorus and sulphur slightly--more freely iodine and -bromine. It floats on hydric sulphate, which only attacks it at a -boiling heat. - -Chloroform is frequently impure from faulty manufacture or -decomposition. The impurities to be sought are alcohol, methylated -chloroform,[158] dichloride of ethylene (C_{2}H_{4}Cl_{2}), chloride of -ethyl (C_{2}H_{5}Cl), aldehyde, chlorine, hydrochloric, hypochlorous, -and traces of sulphuric acid: there have also been found chlorinated -oils. One of the best tests for contamination by alcohol, wood spirit, -or ether, is that known as Roussin's; dinitrosulphide of iron[159] is -added to chloroform. If it contain any of these impurities, it acquires -a dark colour, but if pure, remains bright and colourless. - -[158] Methylated chloroform is that which is prepared from methylated -spirit. It is liable to more impurities than that made from pure -alcohol, but, of course, its composition is the same, and it has -recently been manufactured from this source almost chemically pure. - -[159] Made by slowly adding ferric sulphate to a boiling solution of -ammonic sulphide and potassic nitrite, as long as the precipitate -continues to redissolve, and then filtering the solution. - -The presence of alcohol or ether, or both, may also be discovered by the -bichromate test, which is best applied as follows:--A few milligrammes -of potassic bichromate are placed at the bottom of a test-tube with four -or five drops of sulphuric acid, which liberates the chromic acid; next, -a very little water is added to dissolve the chromic acid; and lastly, -the chloroform. The whole is now shaken, and allowed to separate. If the -chloroform is pure, the mass is hardly tinged a greenish-yellow, and no -layer separates. If, however, there is anything like 5 per cent. of -alcohol or ether present, the deep green of chromium chloride appears, -and there is a distinct layer at the bottom of the tube. - -Another way to detect alcohol in chloroform, and also to make an -approximate estimation of its quantity, is to place 20 c.c. of -chloroform in a burette, and then add 80 c.c. of water. On shaking -violently, pure chloroform will sink to the bottom in clear globules, -and the measurement will be as nearly as possible the original quantity; -but if anything like a percentage of alcohol be present, the chloroform -is seen to be diminished in quantity, and its surface is opalescent, the -diminution being caused by the water dissolving out the alcohol. The -addition of a few drops of potash solution destroys the meniscus, and -allows of a close reading of the volume. The supernatant water may be -utilised for the detection of other impurities, and tested for sulphuric -acid by baric chloride, for free chlorine and hypochlorous acid by -starch and potassic iodide, and for hydrochloric acid by silver -nitrate.[160] Fuchsine, proposed by St[oe]deler, is also a delicate -reagent for the presence of alcohol in chloroform, the sample becoming -red in the presence of alcohol, and the tint being proportionate to the -quantity present. The most delicate test for alcohol is, however, the -iodoform test fully described in "Foods," p. 375.[161] Dichloride of -ethylene is detected by shaking up the chloroform with dry potassic -carbonate, and then adding metallic potassium. This does not act on pure -chloroform, but only in presence of ethylene dichloride, when the -gaseous chlor-ethylene (C_{2}H_{3}Cl) is evolved. Ethyl-chloride is -detected by distilling the chloroform and collecting the first portions -of the distillate; it will have a distinct odour of ethyl-chloride -should it be present. Methyl compounds and empyreumatic oils are roughly -detected by allowing the chloroform to evaporate on a cloth. If present, -the cloth, when the chloroform has evaporated, will have a peculiar -disagreeable odour. Aldehyde is recognised by its reducing action on -argentic nitrate; the mineral acids by the reddening of litmus paper, -and the appropriate tests. Hypochlorous acid first reddens, and then -bleaches, litmus-paper. - -[160] Neither an alcoholic nor an aqueous solution of silver nitrate -causes the slightest change in pure chloroform. - -[161] An attempt has been made by Besnou to estimate the amount of -alcohol by the specific gravity. He found that a chloroform of 1.4945 -gravity, mixed with 5 per cent. of alcohol, gave a specific gravity of -1.4772; 10 per cent., 1.4602; 20 per cent., 1.4262; and 25 per cent., -1.4090. It would, therefore, seem that every percentage of alcohol -lowers the gravity by .0034. - -Dr. Dott, _Pharm. Journ._, 1894, p. 629, gives the following -tests:--Specific gravity, 1.490 to 1.495. On allowing 1/2 fluid drm. to -evaporate from a clean surface, no foreign odour is perceptible at any -stage of the evaporation. When 1 fluid drm. is agitated with an equal -volume of solution of silver nitrate, no precipitate or turbidity is -produced after standing for five minutes. On shaking up the chloroform -with half its volume of distilled water, the water should not redden -litmus-paper. When shaken with an equal volume of sulphuric acid, little -or no colour should be imparted to the acid. - -Sec. 175. The ordinary method of manufacturing chloroform is by distilling -alcohol with chlorinated lime; but another mode is now much in -use--viz., the decomposition of chloral hydrate. By distilling it with a -weak alkali, this process yields such a pure chloroform, that, for -medicinal purposes, it should supersede every other. - - -Poisonous Effects of Chloroform. - - -1. AS A LIQUID. - -Sec. 176. =Statistics.=--Falck finds recorded in medical literature 27 -cases of poisoning by chloroform having been swallowed--of these 15 were -men, 9 were women, and 3 children. Eighteen of the cases were suicidal, -and 10 of the 18 died; the remainder took the liquid by mistake. - -Sec. 177. =Local Action of Chloroform.=--When applied to the skin or mucous -membranes in such a way that the fluid cannot evaporate--as, for -example, by means of a cloth steeped in chloroform laid on the bare -skin, and covered over with some impervious material--there is a burning -sensation, which soon ceases, and leaves the part anaesthetised, while -the skin, at the same time, is reddened and sometimes even blistered. - -Sec. 178. Chloroform added to blood, or passed through it in the state of -vapour, causes it to assume a peculiar brownish colour owing to -destruction of the red corpuscles and solution of the haemoglobin in the -plasma. The change does not require the presence of atmospheric air, but -takes place equally in an atmosphere of hydrogen. It has been shown by -Schmiedeberg that the chloroform enters in some way into a state of -combination with the blood-corpuscles, for the entire quantity cannot be -recovered by distillation; whereas the plasma, similarly treated, yields -the entire quantity which has in the first place been added. -Schmiedeberg also asserts that the oxygen is in firmer combination with -the chloroformised blood than usual, as shown by its slow extraction by -stannous oxide. Muscle, exposed to chloroform liquid by arterial -injection, quickly loses excitability and becomes rigid. Nerves are -first stimulated, and then their function for the time is annihilated; -but on evaporation of the chloroform, the function is restored. - -Sec. 179. =General Effects of the Liquid.=--However poisonous in a state of -vapour, chloroform cannot be considered an extremely active poison when -taken into the stomach as a liquid, for enormous quantities, relatively, -have been drunk without fatal effect. Thus, there is the case recorded -by Taylor, in which a man, who had swallowed 113.4 grms. (4 ozs.), -walked a considerable distance after taking the dose. He subsequently -fell into a state of coma, with dilated pupils, stertorous breathing, -and imperceptible pulse. These symptoms were followed by convulsions, -but the patient recovered in five days. - -In a case related by Burkart,[162] a woman desired to kill herself with -chloroform, and procured for that purpose 50 grms. (a little less than -one ounce and a half); she drank some of it, but the burning taste and -the sense of heat in the mouth, throat, and stomach, prevented her from -taking the whole at once. After a few moments, the pain passing off, she -essayed to drink the remainder, and did swallow the greater portion of -it, but was again prevented by the suffering it caused. Finally, she -poured what remained on a cloth, and placing it over her face, soon sank -into a deep narcosis. She was found lying on the bed very pale, with -blue lips, and foaming a little at the mouth; the head was rigidly bent -backwards, the extremities were lax, the eyes were turned upwards and -inwards, the pupils dilated and inactive, the face and extremities were -cold, the body somewhat warmer, there was no pulse at the wrist, the -carotids beat feebly, the breathing was deep and rattling, and after -five or six inspirations ceased. By the aid of artificial respiration, -&c., she recovered in an hour. - -[162] _Vierteljahrsschr. fuer ger. Med._, 1876. - -A still larger dose has been recovered from in the case of a young man, -aged 23,[163] who had swallowed no less than 75 grms. (2.6 ozs.) of -chloroform, but yet, in a few hours, awoke from the stupor. He -complained of a burning pain in the stomach; on the following day he -suffered from vomiting, and on the third day symptoms of jaundice -appeared,--a feature which has been several times noticed as an effect -of chloroform. - -[163] _Brit. Med. Journ._, 1879. - -On the other hand, even small doses have been known to destroy life. In -a case related by Taylor, a boy, aged 4, swallowed 3.8 grms. (1 drm.) of -chloroform and died in three hours, notwithstanding that every effort -was used for his recovery. - -Sec. 180. The smallest dose that has proved fatal _to an adult_ is 15 grms. -(a little over 4 drms.). - -From twenty-two cases in which the quantity taken had been ascertained -with some degree of accuracy, Falck draws the following conclusions:--In -eight of the cases the dose was between 4 and 30 grms., and one death -resulted from 15 grms. As for the other fourteen persons, the doses -varied from 35 to 380 grms., and eight of these patients died--two after -40, two after 45, one after 60, 90, 120, and 180 grms. respectively. -Hence, under conditions favouring the action of the poison, 15 grms. -(4.3 drms.) may be fatal to an adult, while doses of 40 grms. (11.3 -drms.) and upwards will almost certainly kill. - -Sec. 181. =Symptoms.=--The symptoms can be well gathered from the cases -quoted. They commence shortly after the taking of the poison; and, -indeed, the local action of the liquid immediately causes first a -burning sensation, followed by numbness. - -Often after a few minutes, precisely as when the vapour is administered, -a peculiar, excited condition supervenes, accompanied, it may be, by -delirium. The next stage is narcosis, and the patient lies with pale -face and livid lips, &c., as described at p. 147; the end of the scene -is often preceded by convulsions. Sometimes, however, consciousness -returns, and the irritation of the mucous membranes of the -gastro-intestinal canal is shown by bloody vomiting and bloody stools, -with considerable pain and general suffering. In this way, a person may -linger several days after the ingestion of the poison. In a case -observed by Pomeroy, the fatal malady was prolonged for eight days. -Among those who recover, a common _sequela_, as before mentioned, is -jaundice. - -A third form of symptoms has been occasionally observed, viz.:--The -person awakes from the coma, the breathing and pulse become again -natural, and all danger seems to have passed, when suddenly, after a -longer or shorter time, without warning, a state of general depression -and collapse supervenes, and death occurs. - -Sec. 182. =Post-mortem Appearances.=--The _post-mortem_ appearances from a -fatal dose of liquid chloroform mainly resolve themselves into redness -of the mucous membrane of the stomach, though occasionally, as in -Pomeroy's case, there may be an ulceration. In a case recorded by -Hoffman,[164] a woman, aged 30, drank 35 to 40 grms. of chloroform and -died within the hour. Almost the whole of the chloroform taken was found -in the stomach, as a heavy fluid, coloured green, through the bile. The -epithelium of the pharynx, epiglottis, and gullet was of a dirty colour, -partly detached, whitened, softened, and easily stripped off. The mucous -membrane of the stomach was much altered in colour and consistence, and, -with the duodenum, was covered with a tenacious grey slime. There was no -ecchymosis. - -[164] _Lehrbuch der ger. Medicin_, 2te Aufl. - - -2. THE VAPOUR OF CHLOROFORM. - -Sec. 183. =Statistics.=--Accidents occur far more frequently in the use of -chloroform vapour for anaesthetic purposes than in the use of the liquid. - -Most of the cases of death through chloroform vapour, are those caused -accidentally in surgical and medical practice. A smaller number are -suicidal, while for criminal purposes, its use is extremely infrequent. - -The percentage of deaths caused by chloroform administered during -operations is unaccountably different in different years, times, and -places. The diversity of opinion on the subject is partly (though not -entirely) explicable, by the degrees of purity in the anaesthetic -administered, the different modes of administration, the varying lengths -of time of the anaesthesia, and the varying severity of the operations. - -During the Crimean War, according to Baudens and Quesnoy, 30,000 -operations were done under chloroform, but only one death occurred -attributable to the anaesthetic. Sansom[165] puts the average mortality -at .75 per 10,000, Nussbaum at 1.3, Richardson at 2.8,[166] Morgan[167] -at 3.4. In the American war of secession, in 11,000 operations, there -were seven deaths--that is, 6.3 per 10,000, the highest number on a -large scale which appears to be on record. In the ten years 1883-1892, -103 deaths are attributed to chloroform in England and Wales, viz., 88 -deaths (57 males, 31 females) from accidents (no doubt in its use as a -general anaesthetic), 14 (9 males, 5 females) from suicide, and a -solitary case of murder. - -[165] _Chloroform: its Action, &c._, London, 1865. - -[166] _Med. Times and Gazette_, 1870. - -[167] _Med. Soc. of Virginia_, 1872. - -Sec. 184. =Suicidal and Criminal Poisoning by Chloroform.=--Suicidal -poisoning by chloroform will generally be indicated by the surrounding -circumstances; and in no case hitherto reported has there been any -difficulty or obscurity as to whether the narcosis was self-induced or -not. An interesting case is related by Schauenstein,[168] in which a -physician resolved to commit suicide by chloroform, a commencing -amaurosis having preyed upon his mind, and his choice having been -determined by witnessing an accidental death by this agent. He -accordingly plugged his nostrils, fitted on to the face an appropriate -mask, and fastened it by strips of adhesive plaster. In such an -instance, there could be no doubt of the suicidal intent, and the -question of accident would be entirely out of the question. - -[168] Maschka: _Handbuch der gerichtlich. Medicin_, p. 787, Tuebingen, -1882. - -A dentist in Potsdam,[169] in a state of great mental depression from -embarrassed circumstances, killed his wife, himself, and two children by -chloroform. Such crimes are fortunately very rare. - -[169] Casper: _Handbuch der ger. Med._ - -There is a vulgar idea that it is possible, by holding a cloth saturated -with chloroform to the mouth of a sleeping person (or one, indeed, -perfectly awake), to produce _sudden_ insensibility; but such an -occurrence is against all experimental and clinical evidence. It is true -that a nervous person might, under such circumstances, faint and become -insensible by mere nervous shock; but a true sudden narcosis is -impossible. - -Dolbeau has made some interesting experiments in order to ascertain -whether, under any circumstances, a sleeping person might be -anaesthetised. The main result appears to answer the question in the -affirmative, at least with certain persons; but even with these, it can -only be done by using the greatest skill and care, first allowing the -sleeper to breathe very dilute chloroform vapour, and then gradually -exhibiting stronger doses, and taking the cloth or inhaler away on the -slightest symptom of approaching wakefulness. In 75 per cent. of the -cases, however, the individuals awoke almost immediately on being -exposed to the vapour. This cautious and scientific narcosis, then, is -not likely to be used by the criminal class, or, if used, to be -successful. - -Sec. 185. =Physiological Effects.=--Chloroform is a protoplasmic poison. -According to Jumelle, plants can even be narcotised, ceasing to -assimilate and no longer being sensitive to the stimulus of light. -Isolated animal cells, like leucocytes, lose through chloroform vapour -their power of spontaneous movement, and many bacteria cease to multiply -if in contact with chloroform water. According to Binx, chloroform -narcosis in man is to be explained through its producing a weak -coagulation of the cerebral ganglion cells. As already mentioned, -chloroform has an affinity for the red blood-corpuscles. Chloroform -stimulates the peripheral ends of the nerves of sensation, so that it -causes irritation of the skin or mucous membranes when locally applied. -Flourens considers that chloroform first affects the cerebrum, then the -cerebellum, and finally the spinal cord; the action is at first -stimulating, afterwards paralysing. Most anaesthetics diminish equally -the excitability of the grey and the white nervous substance of the -brain, and this is the case with chloroform, ether, and morphine; but -apparently this is not the case with chloral hydrate, which only -diminishes the conductivity of the cortical substance of the brain, and -leaves the grey substance intact. Corresponding to the cerebral -paralysis, the blood pressure sinks, and the heart beats slower and -weaker.[170] The Hyderabad Commission made 735 researches on dogs and -monkeys, and found that in fatal narcosis, so far as these animals are -concerned, the respiration ceased before the heart, and this may be -considered the normal mode of death; but it is probably going too far to -say that it is the exclusive form of death in man, for there have been -published cases in which the heart failed first. - -[170] Kobert's _Lehrbuch der Intoxicationen_. - -Sec. 186. =Symptoms.=--There is but little outward difference between man -and animals, in regard to the symptoms caused by breathing chloroform; -in the former we have the advantage that the sensations preceding -narcosis can be described by the individual. - -The action of chloroform is usually divided into three more or less -distinct stages. In the _first_ there is a "drunken" condition, changes -in the sense of smell and taste, and it may be hallucinations of vision -and hearing; there are also often curious creeping sensations about the -skin, and sometimes excessive muscular action, causing violent -struggles. I have also seen epileptiform convulsions, and delirium is -almost always present. The face during this stage is generally flushed, -covered with perspiration, and the pupils contracted. The first stage -may last from one minute to several, and passes into the _second stage_, -or that of depression. Spontaneous movements cease, sensibility to all -external stimuli vanishes, the patient falls into a deep sleep, the -consciousness is entirely lost, and reflex movements are more and more -annihilated. The temperature is less than normal, the respirations are -slow, and the pulse is full and slow. The pupils in this stage are -usually dilated, all the muscles are relaxed, and the limbs can be bent -about in any direction. If now the inhalation of chloroform is -intermitted, the patient wakes within a period which is usually from -twenty to forty minutes, but may be several hours, after the last -inhalation. - -The _third stage_ is that of paralysis; the pulse becomes irregular, the -respirations superficial, there is a cyanotic colouring of the lips and -skin, while the pupils become widely dilated. Death follows quickly -through paralysis of the respiratory centre, the respirations first -ceasing, then the pulse; in a few cases, the heart ceases first to beat. - -According to Sansom's facts,[171] in 100 cases of death by chloroform, -44.6 per cent. occurred before the full narcosis had been attained, that -is in the first stage, 34.7 during the second stage, and 20.6 shortly -after. So, also, Kappeler has recorded that in 101 cases of death from -chloroform, 47.7 per cent. occurred before the full effect, and 52.2 -during the full effect. This confirms the dictum of Billroth, that in -all stages of anaesthesia by chloroform, death may occur. The _quantity_ -of chloroform, which, when inhaled in a given time, will produce death, -is unknown; for all depends upon the greater or less admixture of air, -and probably on other conditions. It has been laid down, that the -inhalation of chloroform should be so managed as to insure that the air -breathed shall never contain more than 3.9 per cent. of chloroform. -Fifteen drops have caused death, but Taylor, on the other hand, records -a case of tetanus, treated at Guy's Hospital, in which no less a -quantity than 700 grms. (22.5 ozs.) was inhaled in twenty-four hours. -Frequent breathing of chloroform in no way renders the individual safe -from fatal accident. A lady[172] having repeatedly taken chloroform, was -anaesthetised by the same agent merely for the purpose of having a tooth -extracted. About 6 grms. (1.5 drm.) were poured on a cloth, and after -nine to ten inspirations, dangerous symptoms began--rattling breathing -and convulsive movements--and, despite all remedies, she died. - -[171] _Op. cit._ - -[172] _Edin. Med. Journ._, 1855. - -Sec. 187. Chronic chloroform poisoning is not unknown. It leads to various -ailments, and seems to have been in one or two instances the cause of -insanity. - -Buchner records the case of an opium-eater, who afterwards took to -chloroform; he suffered from periodic mania. In a remarkable case -related by Meric, the patient, who had also first been a morphine-eater, -took 350 grms. of chloroform in five days by inhalation; as often as he -woke he would chloroform himself again to sleep. In this case, there was -also mental disturbance, and instances in which chloroform produced -marked mental aberration are recorded by Boehm[173] and by Vigla.[174] - -[173] Ziemssen's _Handbuch_, Bd. 15. - -[174] _Med. Times_, 1855. - -Sec. 188. =Post-mortem Appearances.=--The lesions found on section are -neither peculiar to, nor characteristic of, chloroform poisoning. It has -been noted that bubbles of gas are, from time to time, to be observed -after death in the blood of those poisoned by chloroform, but it is -doubtful whether the bubbles are not merely those to be found in any -other corpse--in 189 cases, only eighteen times were these gas-bubbles -observed,[175] so that, even if they are characteristic, the chances in -a given case that they will _not_ be seen are greater than the reverse. -The smell of chloroform may be present, but has been noticed very -seldom. - -[175] Schauenstein (_Op. cit._). - -Sec. 189. =The detection and estimation of chloroform= from organic -substances is not difficult, its low boiling-point causing it to distil -readily. Accordingly (whatever may be the ultimate modifications, as -suggested by different experimenters), the first step is to bring the -substances, unless fluid, into a pulp with water, and submit this pulp -to distillation by the heat of a water-bath. If the liquid operated upon -possesses no particular odour, the chloroform may in this way be -recognised in the distillate, which, if necessary, may be redistilled in -the same manner, so as to concentrate the volatile matters in a small -compass. - -There are four chief tests for the identification of chloroform:-- - -(1.) The final distillate is tested with a little aniline, and an -alcoholic solution of soda or potash lye; either immediately, or upon -gently warming the liquid, there is a peculiar and penetrating odour of -phenylcarbylamine, C_{6}H_{5}NC; it is produced by the following -reaction:-- - - CHCl_{3} + 3KOH + C_{6}H_{5}NH_{2} = C_{6}H_{5}NC + 3KCl + 3H_{2}O. - -Chloral, trichloracetic acid, bromoform and iodoform also give the same -reaction; on the other hand, ethylidene chloride does not yield under -these circumstances any carbylamine (isonitrile). - -(2.) Chloroform reduces Fehling's alkaline copper solution, _when -applied to a distillate_, thus excluding a host of more fixed bodies -which have the same reaction; it is a very excellent test, and may be -made quantitative. The reaction is as follows:-- - - CHCl_{3} + 5KHO + 2CuO = Cu_{2}O + K_{2}CO_{3} + 3KCl + 3H_{2}O; - -thus, every 100 parts of cuprous oxide equals 83.75 of chloroform. - -(3.) The fluid to be tested (which, if acid, should be neutralised), is -distilled in a slow current of hydrogen, and the vapour conducted -through a short bit of red-hot combustion-tube containing platinum -gauze. Under these circumstances, the chloroform is decomposed and -hydrochloric acid formed; hence, the issuing vapour has an acid reaction -to test-paper, and if led into a solution of silver nitrate, gives the -usual precipitate of argentic chloride. Every 100 parts of silver -chloride equal 27.758 of chloroform. - -(4.) The fluid is mixed with a little thymol and potash; if chloroform -be present, a reddish-violet colour is developed, becoming more distinct -on the application of heat.[176] - -[176] S. Vidali in _Deutsch-Amerikan. Apoth.-Zeitung_, vol. iij., Aug. -15, 1882. - -Sec. 190. For the quantitative estimation of chloroform the method -recommended by Schmiedeberg[177] is, however, the best. A -combustion-tube of 24 to 26 cm. long, and 10 to 12 mm. in diameter, open -at both ends, is furnished at the one end with a plug of asbestos, while -the middle part, to within 5-6 cm. of the other end, is filled with -pieces of caustic lime, from the size of a lentil to that of half a pea. -The lime must be pure, and is made by heating a carbonate which has been -precipitated from calcic nitrate. The other end of the tube is closed by -a cork, carrying a silver tube, 16-18 cm. long, and 4 mm. thick. The end -containing the asbestos plug is fitted by a cork to a glass tube. The -combustion-tube thus prepared is placed in the ordinary -combustion-furnace; the flask containing the chloroform is adapted, and -the distillation slowly proceeded with. It is best to add a tube, bent -at right angles and going to the bottom of the flask, to draw air -continuously through the apparatus. During the whole process, the tube -containing the lime is kept at a red heat. The chloroform is decomposed, -and the chlorine combines with the lime. The resulting calcic chloride, -mixed with much unchanged lime, is, at the end of the operation, cooled, -dissolved in dilute nitric acid, and precipitated with silver nitrate. -Any silver chloride is collected and weighed and calculated into -chloroform.[178] - -[177] _Ueber die quantitative Bestimmung des Chloroforms im Blute._ -Inaug. Dissert., Dorpat, 1866. - -[178] S. Vidali has made the ingenious suggestion of developing hydrogen -in the usual way, by means of zinc and sulphuric acid, in the liquid -supposed to contain chloroform, to ignite the hydrogen, as in Marsh's -test, when it issues from the tube, and then to hold in the flame a -clean copper wire. Since any chloroform is burnt up in the hydrogen -flame to hydrochloric acid, the chloride of copper immediately -volatilises and colours the flame green. - - -VI.--Other Anaesthetics. - - Sec. 191. When chlorine acts upon marsh-gas, the hydrogen can be - displaced atom by atom; and from the original methane (CH_{4}) can - be successively obtained chloromethane or methyl chloride - (CH_{3}Cl), dichloromethane, or methene dichloride, methylene - dichloride (CH_{2}Cl_{2}), trichloromethane, or chloroform - (CHCl_{3}), already described, and carbon tetrachloride (CCl_{4}). - All these are, more or less, capable of producing anaesthesia; but - none of them, save chloroform, are of any toxicological importance. - - Methene dichloride, recommended by Sir B. W. Richardson as an - anaesthetic, has come somewhat into use. It is a colourless, very - volatile liquid, of specific gravity 1.360, and boiling at 41 deg. It - burns with a smoky flame, and dissolves iodine with a brown colour. - - Sec. 192. =Pentane= (C_{5}H_{12}).--There are three isomers of pentane; - that which is used as an anaesthetic is normal pentane, - CH_{3}-CH_{2}-CH_{2}-CH_{2}-CH_{3}; its boiling-point is 37-38 deg. It - is one of the constituents of petroleum ether. - - Under the name of "Pental" it is used in certain hospitals - extensively, for instance, at the Kaiser Friederich's Children's - Hospital, Berlin.[179] It is stated to have no action on the heart. - -[179] _Zeit. f. Kinderheilk._, Bd. iii.-iv., 1893. - - One death[180] has been recorded from its use:--A lad, aged 14, was - put under pental for the purpose of having two molars painlessly - extracted. He was only a minute or two insensible, and 4-5 grms. of - pental was the quantity stated to have been inhaled. The boy spat - out after the operation, then suddenly fainted and died. The - _post-mortem_ showed [oe]dema of the lungs; the right side of the - heart was empty. The organs of the body smelled strongly of pental. - -[180] Dr. Bremme, _Vierteljahrsschr. f. gerichtliche Medicin_, Bd. v., -1893. - - Sec. 193. =Aldehyde= (Acetaldehyde), C_{2}H_{4}O = - - O - // - CH_{3}-C , - \ - H - - a fluid obtained by the careful oxidation of alcohol (boiling-point, - 20.8 deg.), is in large doses toxic; in smaller, it acts as a narcotic. - - =Metaldehyde= (C_{2}H_{4}O_{2})_{2}, obtained by treating - acetaldehyde at a low temperature with hydrochloric acid. It occurs - in the form of prisms, which sublime at about 112 deg.; it is also - poisonous. - - Sec. 194. =Paraldehyde= (C_{6}H_{12}O_{3}) is a colourless fluid, - boiling at 124 deg.; specific gravity .998 at 15 deg. By the action of cold - it may be obtained in crystals, the melting point of which is 10.5 deg. - It is soluble in eight parts of water at 13 deg.; in warm water it is - less soluble; hence, on warming a solution, it becomes turbid. - Paraldehyde acts very similarly to chloral; it causes a deep sleep, - and (judging by experiments on animals) produces no convulsive - movements. - - -VII.--Chloral. - -Sec. 195. =Chloral Hydrate= (C_{2}H_{3}Cl_{3}O_{2}) is made by mixing -equivalent quantities of anhydrous chloral[181] and water. The purest -chloral is in the form of small, granular, sugar-like crystals. When -less pure, the crystals are larger. These melt into a clear fluid at -from 48 deg. to 49 deg., and the melted mass solidifies again at 48.9 deg. Chloral -boils at 97.5 deg.; it is not very soluble in cold chloroform, requiring -four times its weight. The only substance with which chloral hydrate may -well be confused is chloral alcoholate (C_{4}H_{7}Cl_{3}O_{2}), but -chloral alcoholate melts at a lower temperature (45 deg.), and boils at a -higher (113.5 deg.); it is easily soluble in cold chloroform, and inflames -readily, whereas chloral scarcely burns. - -[181] Anhydrous chloral (C_{2}HCl_{3}O) is an oily liquid, of specific -gravity 1.502 at 18 deg.; it boils at 97.7 deg. It is obtained by the prolonged -action of chlorine on absolute alcohol. - -Chloral hydrate completely volatilises, and can be distilled in a vacuum -without change. If, however, boiled in air, it undergoes slow -decomposition, the first portions of the distillate being overhydrated, -the last underhydrated; the boiling-point, therefore, undergoes a -continuous rise. The amount of hydration of a commercial sample is of -practical importance; if too much water is present, the chloral -deliquesces, especially in warm weather; if too little, it may become -acid, and in part insoluble from the formation of meta-chloral -(C_{6}H_{3}Cl_{9}O_{3}). Chloral hydrate, by the action of the volatile -or fixed alkalies, is decomposed, an alkaline formiate and chloroform -resulting thus-- - - C_{2}HCl_{3}O,H_{2}O + NaHO = NaCHO_{2} + H_{2}O + CHCl_{3}. - -Trichlor-acetic acid is decomposed in a similar manner. - -=Statistics.=--Chloral caused, during the ten years 1883-1892 in England -and Wales, 127 deaths--viz., 111 (89 males, 22 females) accidentally, 15 -(14 males, 1 female) from suicide, and a case in which chloral was the -agent of murder. - -Sec. 196. =Detection.=--It is, of course, obvious that after splitting up -chloral into chloroform, the latter can be detected by distillation and -applying the tests given at p. 152 and _seq._ Chloral hydrate is soluble -in one and a half times its weight of water; the solution should be -perfectly neutral to litmus. It is also soluble in ether, in alcohol, -and in carbon disulphide. It may be extracted from its solution by -shaking out with ether. There should be no cloudiness when a solution is -tested with silver nitrate in the cold; if, however, to a boiling -solution nitrate of silver and a little ammonia are added, there is a -mirror of reduced silver. - -Sec. 197. The assay of chloral hydrate in solutions is best effected by -distilling the solution with slaked lime; the distillate is received in -water contained in a graduated tube kept at a low temperature. The -chloroform sinks to the bottom, and is directly read off; the number of -c.c. multiplied by 2.064 equals the weight of the chloral hydrate -present. - -Another method, accurate but only applicable to the fairly pure -substance, is to dissolve 1 to 2 grms. in water, remove any free acid by -baric carbonate, and then treat the liquid thus purified by a known -volume of standard soda. The soda is now titrated back, using litmus as -an indicator, each c.c. of normal alkali neutralised by the sample -corresponds to 0.1655 grm. of chloral hydrate. Small quantities of -chloral hydrate may be conveniently recovered from complex liquids by -shaking them up with ether, and removing the ethereal layer, in the tube -represented in the figure.[182] The ether must be allowed to evaporate -spontaneously; but there is in this way much loss of chloral. The best -method of estimating minute quantities is to alkalise the liquid, and -slowly distil the vapour through a red-hot combustion-tube charged with -pure lime, as in the process described at p. 153. A dilute solution of -chloral may also be treated with a zinc-copper couple, the nascent -hydrogen breaks the molecule up, and the resulting chloride may be -titrated, as in water analyses, by silver nitrate and potassic chromate. - -[Illustration] - -[182] The figure is from "Foods"; the description may be here -repeated:--A is a tube of any dimensions most convenient to the analyst. -Ordinary burette size will perhaps be the most suitable for routine -work; the tube is furnished with a stopcock and is bent at B, the tube -at K having a very small but not quite capillary bore. The lower end is -attached to a length of pressure-tubing, and is connected with a small -reservoir of mercury, moving up and down by means of a pulley. To use -the apparatus: Fill the tube with mercury by opening the clamp at H, and -the stopcock at B, and raising the reservoir until the mercury, if -allowed, would flow out of the beak. Now, the beak is dipped into the -liquid to be extracted with the solvent, and by lowering the reservoir, -a strong vacuum is created, which draws the liquid into the tube; in the -same way the ether is made to follow. Should the liquid be so thick that -it is not possible to get it in by means of suction, the lower end of -the tube is disconnected, and the syrupy mass worked in through the wide -end. When the ether has been sucked into the apparatus, it is emptied of -mercury by lowering the reservoir, and then firmly clamped at H, and the -stopcock also closed. The tube may now be shaken, and then allowed to -stand for the liquids to separate. When there is a good line of -demarcation, by raising the reservoir after opening the clamp and -stopcock, the whole of the light solvent can be run out of the tube into -a flask or beaker, and recovered by distillation. For heavy solvents -(such as chloroform), which sink to the bottom, a simple burette, with a -fine exit tube is preferable; but for petroleum ether, ordinary ether, -&c., the apparatus figured is extremely useful. - -Sec. 198. =Effects of Chloral Hydrate on Animals.=--Experiments on animals -have taught us all that is known of the physiological action of -chloral. It has been shown that the drug influences very considerably -the circulation, at first exciting the heart's action, and then -paralysing the automatic centre. The heart, as in animals poisoned by -atropine, stops in diastole, and the blood-pressure sinks in proportion -to the progressive paralysis of the cardiac centre. At the same time, -the respiration is slowed and finally ceases, while the heart continues -to beat. The body temperature of the warm-blooded animals is very -remarkably depressed, according to Falck, even to 7.6 deg. Vomiting has -been rather frequently observed with dogs and cats, even when the drug -has been taken into the system by subcutaneous injection. - -The secretion of milk, according to Roehrig, is also diminished. Reflex -actions through small doses are intensified; through large, much -diminished. .025-.05 grm. (.4-.7 grain), injected subcutaneously into -frogs, causes a slowing of the respiration, a diminution of reflex -excitability, and lastly, its complete cessation; this condition lasts -several hours; at length the animal returns to its normal state. If the -dose is raised to .1 grm. (1.5 grain) after the cessation of reflex -movements, the heart is paralysed--and a paralysis not due to any -central action of the vagus, but to a direct action on the cardiac -ganglia. Rabbits of the ordinary weight of 2 kilos. are fully narcotised -by the subcutaneous injection of 1 grm.; the sleep is very profound, and -lasts several hours; the animal wakes up spontaneously, and is -apparently none the worse. If 2 grms. are administered, the narcotic -effects, rapidly developed, are much prolonged. There is a remarkable -diminution of temperature, and the animal dies, the respiration ceasing -without convulsion or other sign. Moderate-sized dogs require 6 grms. -for a full narcosis, and the symptoms are similar; they also wake after -many hours, in apparent good health.[183] - -[183] C. Ph. Falck has divided the symptoms into (1) Preliminary -hypnotic; (2) an adynamic state; and (3) a comatose condition. - -Sec. 199. Liebreich considered that the action of chloral was due to its -being broken up by the alkali of the blood, and the system being thus -brought into a state precisely similar to its condition when -anaesthetised by chloroform vapour. This view has, however, been proved -to be erroneous. Chloral hydrate can, it is true, be decomposed in some -degree by the blood at 40 deg.; but the action must be prolonged for several -hours. A 1 per cent. solution of alkali does not decompose chloral at a -blood-heat in the time within which chloral acts in the body; and since -narcotic effects are commonly observed when, in the fatty group, -hydrogen has been displaced by chlorine, it is more probable that -chloral hydrate is absorbed and circulates in the blood as such, and is -not broken up into chloroform and an alkaline formiate. - -Sec. 200. =Effects of Chloral Hydrate on Man.=--Since the year 1869, in -which chloral was first introduced to medicine, it has been the cause -of a number of accidental and other cases of poisoning. I find, up to -the year 1884, recorded in medical literature, thirty-one cases of -poisoning by chloral hydrate. This number is a small proportion only of -the actual number dying from this cause. In nearly all the cases the -poison was taken by the mouth, but in one instance the patient died in -three hours, after having injected into the rectum 5.86 grms. of chloral -hydrate. There is also on record a case in which, for the purpose of -producing surgical anaesthesia, 6 grms. of chloral were injected into the -veins; the man died in as many minutes.[184] - -[184] This dangerous practice was introduced by M. Ore. In a case of -traumatic tetanus, in which M. Ore injected into the veins 9 grms. of -chloral in 10 grms. of water, there was profound insensibility, lasting -eleven hours, during which time a painful operation on the thumb was -performed. The next day 10 grms. were injected, when the insensibility -lasted eight hours; and 9 grms. were injected on each of the two -following days. The man recovered. In another case, Ore anaesthetised -immediately a patient by plunging the subcutaneous needle of his syringe -into the radial vein, and injected 10 grms. of chloral hydrate with 30 -of water. The patient became insensible before the whole quantity was -injected with "_une immobilite rappellant celle du cadavre_." On -finishing the operation, the patient was roused immediately by the -application of an electric current, one pole on the left side of the -neck, the other on the epigastrium. _Journ. de Pharm. et de Chimie._, t. -19, p. 314. - -Sec. 201. =Fatal Dose.=--It is impossible to state with any exactness the -precise quantity of chloral which may cause death. Children bear it -better, in proportion, than adults, while old persons (especially those -with weak hearts, and those inclined to apoplexy) are likely to be -strongly affected by very small doses. A dose of .19 grm. (3 grains) has -been fatal to a child a year old in ten hours. On the other hand, -according to Bouchut's observations on 10,000 children, he considers -that the full therapeutic effect of chloral can be obtained safely with -them in the following ratio:-- - - Children of 1 to 3 years, dose 1 to 1.5 grm. (15.4 to 23.1 grains) - " 3 " 5 " " 2 " 3 " (30.8 " 46.3 " ) - " 5 " 7 " " 3 " 4 " (46.3 " 61.7 " ) - - These quantities being dissolved in 100 c.c. of water. - -These doses are certainly too high, and it would be dangerous to take -them as a guide, since death has occurred in a child, aged 5, from a -dose of 3 grms. (46.3 grains). Medical men in England consider 20 grains -a very full dose for a child of four years old, and 50 for an adult, -while a case is recorded in which a dose of 1.9 grm. (30 grains) proved -fatal in thirty-five hours to a young lady aged 20. On the other hand, -we find a case[185] in which, to a patient suffering from epileptic -mania, a dose of 31.1 grms. (1.1 oz.) of chloral hydrate was -administered; she sank into a deep sleep in five minutes. Subcutaneous -injections of strychnine were applied, and after sleeping for -forty-eight hours, there was recovery. On the third day a vivid -scarlatinal rash appeared, followed by desquamation. The examples -quoted--the fatal dose of 1.9 grm., and recovery from 31 grms.--are the -two extremes for adults. From other cases, it appears tolerably plain -that most people would recover, especially with appropriate treatment, -from a single dose under 8 grms., but anything above that quantity taken -at one time would be very dangerous, and doses of 10 grms. and above, -almost always fatal. If, however, 8 grms. were taken in divided doses -during the twenty-four hours, it could (according to Sir B. W. -Richardson) be done with safety. The time from the taking of the poison -till death varies considerably, and is in part dependent on the dose. - -[185] _Chicago Medical Review_, 1882. - -In seven cases of lethal poisoning, three persons who took the small -doses of 1.25, 2.5, and 1.95 grms. respectively, lived from eight to ten -hours; two, taking 4 and 5 grms. respectively, died very shortly after -the administration of the chloral. In a sixth case, related by Brown, in -which 3.12 grms. had been taken, the patient lived an hour; and in -another, after a dose of 5 grms., recorded by Jolly, death took place -within a quarter of an hour. - -Sec. 202. =Symptoms.=--With moderate doses there are practically no -symptoms, save a drowsiness coming on imperceptibly, and followed by -heavy sleep. With doses up to 2 grms. (30.8 grains), the hypnotic state -is perfectly under the command of the will, and if the person chooses to -walk about or engage in any occupation, he can ward off sleep; but with -those doses which lead to danger, the narcosis is completely -uncontrollable, the appearance of the sleeper is often strikingly like -that of a drunken person. There is great diminution of temperature -commencing in from five to twenty minutes after taking the -dose--occasionally sleep is preceded by a delirious state. During the -deep slumber the face is much flushed, and in a few cases the sleep -passes directly into death without any marked change. In others, -symptoms of collapse appear, and the patient sinks through exhaustion. - -Sec. 203. With some persons doses, which, in themselves, are insufficient -to cause death, yet have a peculiar effect on the mental faculties. A -case of great medico-legal interest is described by the patient himself, -Dr. Manjot.[186] He took in three doses, hourly, 12 grms. of chloral -hydrate. After the first dose the pain, for which he had recourse to -chloral, vanished; but Manjot, although he had all the appearance of -being perfectly conscious, yet had not the slightest knowledge of what -he was doing or speaking. He took the other two doses, and sank into a -deep sleep which lasted twelve hours. He then awoke and answered -questions with difficulty, but could not move; he lay for the next -twelve hours in a half slumber, and the following night slept -soundly--to wake up recovered. - -[186] _Gaz. des Hop._, 1875. - -Sec. 204. The treatment of acute chloral poisoning which has been most -successful is that by strychnine injections, and the application of -warmth to counteract the loss of temperature which is so constant a -phenomenon. As an illustration of the treatment by strychnine, an -interesting case recorded by Levinstein[187] may be quoted. - -[187] _Vierteljahrsschr. f. ger. Med._, Bd. xx., 1874. - -A man, thirty-five years old, took at one dose, for the purpose of -suicide, 24 grms. of chloral hydrate. In half an hour afterwards he was -found in a deep sleep, with flushed face, swollen veins, and a pulse 160 -in the minute. After a further half hour, the congestion of the head was -still more striking; the temperature was 39.5 deg.; the pulse hard and -bounding 92; the breathing laboured, at times intermittent. - -Artificial respiration was at once commenced, but in spite of this, in -about another half hour, the face became deadly pale, the temperature -sank to 32.9 deg. The pupils contracted, and the pulse was scarcely to be -felt; 3 mgrms. (.04 grain) of strychnine were now injected -subcutaneously; this caused tetanic convulsions in the upper part of the -body and trismus. The heart's action again became somewhat stronger, the -temperature rose to 33.3 deg., and the pupils dilated; but soon followed, -again, depression of the heart's action, and the respiration could only -be kept going by faradisation. Two mgrms. (.03 grain) of strychnine were -once more injected, and the heart's action improved. During the -succeeding six hours the respiration had to be assisted by faradisation. -The temperature gradually rose to 36.5 deg.; ten hours after taking the dose -the patient lay in a deep sleep, breathing spontaneously and reacting to -external stimuli with a temperature of 38.5 deg. Eighteen hours from the -commencement, the respiration again became irregular, and the galvanic -current was anew applied. The last application aroused the sleeper, he -took some milk and again slept; after twenty-seven hours he could be -awakened by calling, &c., but had not full consciousness; he again took -some milk and sank to sleep. It was not until thirty-two hours had -elapsed from the ingestion of the poison that he awoke spontaneously; -there were no after effects. - -Sec. 205. =Chronic Poisoning by Chloral Hydrate.=--An enormous number of -people habitually take chloral hydrate. The history of the habit is -usually that some physician has given them a chloral prescription for -neuralgia, for loss of sleep, or other cause, and finding that they can -conjure sleep, oblivion, and loss (it may be) of suffering whenever they -choose, they go on repeating it from day to day until it becomes a -necessity of their existence. A dangerous facility to chloral-drinking -is the existence of patent medicines, advertised as sleep-producers, and -containing chloral as the active ingredient. A lady, aged 35, died in -1876, at Exeter, from an overdose of "Hunter's solution of chloral, or -sedative draught and sleep producer." Its strength was stated at the -inquest to be 25 grains to the drachm (41.6 per cent.).[188] - -[188] _Exeter and Plymouth Gazette_, Jan. 12, 1876. - -The evil results of this chloral-drinking are especially to be looked -for in the mental faculties, and the alienists have had since 1869 a new -insanity-producing factor. In the asylums may usually be found several -cases of melancholia and mania referred rightly (or wrongly) to -chloral-drinking. Symptoms other than cerebral are chilliness of the -body, inclination to fainting, clonic convulsions, and a want of -co-ordination of the muscles of the lower extremities. In a case -recorded by Husband,[189] a lady, after twelve days' treatment by -chloral hydrate, in doses of from 1 to 2 grms. (15.4 to 30.8 grains), -suffered from a scarlatina-like rash, which was followed by -desquamation. Among the insane, it has also been noticed that its use -has been followed by nettle-rash and petechiae (Reimer and others). - -[189] _Lancet_, 1871. - -Sec. 206. =Excretion of Chloral.=--Chloral hydrate is separated in the -urine partly as urochloral acid (C_{8}H_{11}Cl_{3}O_{7}). Butylchloral -is separated as butyl urochloral acid (C_{10}H_{15}Cl_{2}O_{7}). -Urochloral acid is crystalline, soluble in water, in alcohol, and in -ether, reduces copper from Fehling's solution, and rotates a ray of -polarised light to the left. Urochloral acid, on boiling with either -dilute sulphuric or hydrochloric acid, splits up into trichlorethyl -alcohol and glycuronic acid-- - - C_{8}H_{11}Cl_{3}O_{7} + H_{2}O = C_{2}H_{3}Cl_{3}O + - C_{6}H_{10}O_{7}. - -Trichloralcohol is an oily fluid (boiling-point 150 deg.-152 deg.); it yields by -oxidation trichloracetic acid. - -Urobutyl chloral acid gives on treatment with mineral acids -trichlorbutyl alcohol and glycuronic acid. - -To separate urochloral acid from the urine the following process has -been found successful:-- - -The urine is evaporated to a syrup at the heat of the water-bath, and -then strongly acidulated with sulphuric acid and repeatedly shaken out -in a separating tube with a mixture of 3 vols. of ether and 1 vol. of -alcohol. The ether-alcohol is separated and distilled off, the acid -residue is neutralised with KHO, or potassic carbonate, and evaporated; -the dry mass is then taken up with 90 per cent. alcohol, the filtrate -precipitated with ether, and the precipitate washed with ether and -absolute alcohol. - -Next the precipitate is boiled with absolute alcohol and filtered hot. -On cooling, the potassium salt of urochloral acid separates out in tufts -of silky needles. The crystals are dried over sulphuric acid and again -washed several times with absolute alcohol and ether to remove -impurities. - -To obtain the free acid, the potassium salt is dissolved in a little -water and acidulated with hydrochloric acid; the liquid is then shaken -out in a separating tube, with a mixture of 8 vols. of ether and 1 of -alcohol. The ether-alcohol is distilled off, the residue treated with -moist silver oxide until no farther separation of silver chloride -occurs, the silver chloride is separated by filtration, the soluble -silver salt decomposed by SH_{2}, and the filtrate carefully evaporated -to a syrup; after a few hours, the acid crystallises in stars of -needles. - -Urobutylchloral acid can be obtained in quite a similar way.[190] - -[190] V. Mering u. Musculus, _Ber._, viii. 662; v. Mering, _ibid._, xv. -1019; E. Kulz, _Ber._, xv., 1538. - -Sec. 207. =Separation of Chloral from Organic Matters.=--It will be most -convenient to place the organic fluid or pulped-up solid, mixed with -water, in a retort, to acidify with tartaric acid, and to distil. - -Chloral hydrate distils over from a liquid acidified with tartaric acid; -to obtain the whole of the chloral requires distillation in a vacuum -almost to dryness. - -The distillation will, unless there is also some partly decomposed -chloral, not smell of chloroform, and yet give chloroform reactions. - -To identify it, to the distillate should be added a little burnt -magnesia, and the distillate thus treated boiled for half an hour in a -flask connected with an inverted condenser; in this way the chloral -hydrate is changed into chloroform and magnesium formate-- - - 2CCl_{3}CH(OH)_{2} + MgO = 2CHCl_{3} + (HCOO)_{2}Mg + H_{2}O. - -The fluid may now be tested for formic acid: it will give a black -precipitate with solution of silver nitrate-- - - (HCOO)_{2}Mg + 4AgNO_{3} = 4Ag + Mg(NO_{3})_{2} + 2CO_{2} + 2HNO_{3}. - -It will give a white precipitate of calomel when treated with mercuric -chloride solution-- - - (HCOO)_{2}Mg + 4HgCl_{2} = 2Hg_{2}Cl_{2} + MgCl_{2} + 2HCl + 2CO_{2}. - -Chloral (or chloroform), when boiled with resorcinol and the liquid made -strongly alkaline with NaHO, gives a red colour, which disappears on -acidifying and is restored by alkalies. If, on the other hand, there is -an excess of resorcinol and only a very small quantity of NaHO used, the -product shows a yellowish-green fluorescence; 1/10 of a milligramme of -chloral hydrate gives this reaction distinctly when boiled with 50 -mgrms. of resorcinol and 5 drops of a normal solution of sodium -hydrate.[191] - -[191] C. Schwarz, _Pharm. Zeit._, xxxiii. 419. - -Dr. Frank Ogston[192] has recommended sulphide of ammonium to be added -to any liquid as a test for chloral. The contents of the stomach are -filtered or submitted to dialysis, and the test applied direct. If -chloral is present, there is first an orange-yellow colour; on standing, -the fluid becomes more and more brown, then troubled, an amorphous -precipitate falls to the bottom, and a peculiar odour is developed. With -10 mgrms. of chloral in 1 c.c. of water, there is an evident -precipitate, and the odour can readily be perceived; with 1 mgrm. -dissolved in 1 c.c. of water, there is an orange-yellow colour, and also -the odour, but no precipitate; with .1 mgrm. in 1 c.c. of water, there -is a weak, pale, straw-yellow colour, which can scarcely be called -characteristic. The only substance giving in neutral solutions the same -reactions is antimony; but, on the addition of a few drops of acid, the -antimony falls as an orange-yellow precipitate, while, if chloral alone -is present, there is a light white precipitate of sulphur. - -[192] _Vierteljahrsschrift f. gerichtl. Medicin_, 1879, Bd. xxx. Hft. 1, -S. 268. - - -VIII.--Bisulphide of Carbon. - -Sec. 208. Bisulphide of carbon--_carbon disulphide_, _carbon sulphide_ -(CS_{2})--is a colourless, volatile fluid, strongly refracting light. -Commercial samples have a most repulsive and penetrating odour, but -chemically pure carbon sulphide has a smell which is not disagreeable. -The boiling-point is 47 deg.; the specific gravity at 0 deg. is 1.293. It is -very inflammable, burning with a blue flame, and evolving sulphur -dioxide; is little soluble in water, but mixes easily with alcohol or -ether. Bisulphide of carbon, on account of its solvent powers for -sulphur, phosphorus, oils, resins, caoutchouc, gutta-percha, &c., is in -great request in certain industries. It is also utilised for -disinfecting purposes, the liquid being burnt in a lamp. - -Sec. 209. =Poisoning by Carbon Bisulphide.=--In spite of the cheapness and -numerous applications of this liquid, poisoning is very rare. There -appears to be a case on record of attempted self-destruction by this -agent, in which a man took 2 ozs. (56.7 c.c.) of the liquid, but without -a fatal result. The symptoms in this case were pallor of the face, wide -pupils, frequent and weak pulse, lessened bodily temperature, and -spasmodic convulsions. Carbon disulphide was detected in the breath by -leading the expired air through an alcoholic solution of -triethyl-phosphin, with which it struck a red colour. It could also be -found in the urine in the same way. An intense burning in the throat, -giddiness, and headache lasted for several days. - -Sec. 210. Experiments on animals have been frequent, and it is found to be -fatal to all forms of animal life. There is, indeed, no more convenient -agent for the destruction of various noxious insects, such as moths, the -weevils in biscuits, the common bug, &c., than bisulphide of carbon. It -has also been recommended for use in exterminating mice and rats.[193] -Different animals show various degrees of sensitiveness to the vapour; -frogs and cats being less affected by it than birds, rabbits, and -guinea-pigs. It is a blood poison; methaemoglobin is formed, and there is -disintegration of the red blood corpuscles. There is complete anaesthesia -of the whole body, and death occurs through paralysis of the respiratory -centre, but artificial respiration fails to restore life. - -[193] Cloez, _Compt. Rend._, t. 63, 85. - -Sec. 211. =Chronic Poisoning.=--Of some importance is the chronic poisoning -by carbon disulphide, occasionally met with in manufactures -necessitating the daily use of large quantities for dissolving -caoutchouc, &c. When taken thus in the form of vapour daily for some -time, it gives rise to a complex series of symptoms which may be divided -into two principal stages--viz., a stage of excitement and one of -depression. In the first phase, there is more or less permanent -headache, with considerable indigestion, and its attendant loss of -appetite, nausea, &c. The sensitiveness of the skin is also heightened, -and there are curious sensations of creeping, &c. The mind at the same -time in some degree suffers, the temper becomes irritable, and singing -in the ears and noises in the head have been noticed. In one factory a -workman suffered from an acute mania, which subsided in two days upon -removing him from the noxious vapour (_Eulenberg_). The sleep is -disturbed by dreams, and, according to Delpech,[194] there is -considerable sexual excitement, but this statement has in no way been -confirmed. Pains in the limbs are a constant phenomenon, and the French -observers have noticed spasmodic contractions of certain groups of -muscles. - -[194] _Memoire sur les Accidents que developpe chez les ouvrieres en -caoutchouc du sulfure de carb. en vapeur_, Paris, 1856. - -The stage of depression begins with a more or less pronounced anaesthesia -of the skin. This is not confined to the outer skin, but also affects -the mucous membranes; patients complain that they feel as if the tongue -were covered with a cloth. The anaesthesia is very general. In a case -recorded by Bernhardt,[195] a girl, twenty-two years old, who had worked -six weeks in a caoutchouc factory, suffered from mental weakness and -digestive troubles; there was anaesthesia and algesis of the whole skin. -In these advanced cases the mental debility is very pronounced, and -there is also weakness of the muscular system. Paralysis of the lower -limbs has been noted, and in one instance a man had his right hand -paralysed for two months. It seems uncertain how long a person is likely -to suffer from the effects of the vapour after he is removed from its -influence. If the first stage of poisoning only is experienced, then -recovery is generally rapid; but if mental and muscular weakness and -anaesthesia of the skin have been developed, a year has been known to -elapse without any considerable improvement, and permanent injury to the -health may be feared. - -[195] _Ber. klin. Wochenschrift_, No. 32, 1866. - -Sec. 212. =Post-mortem Appearances.=--The pathological appearances found -after sudden death from disulphide of carbon are but little different to -those found after fatal chloroform breathing. - -Sec. 213. =Detection and Separation of Carbon Disulphide.=--The extreme -volatility of the liquid renders it easy to separate it from organic -liquids by distillation with reduced pressure in a stream of CO_{2}. -Carbon disulphide is best identified by (1) Hofman's test, viz., passing -the vapour into an ethereal solution of triethyl-phosphin, -(C_{2}H_{5})_{3}P. Carbon disulphide forms with triethyl-phosphin a -compound which crystallises in red scales. The crystals melt at 95 deg. C., -and have the following formula--P(C_{2}H_{5})_{3}CS_{2}. This will -detect 0.54 mgrm. Should the quantity of bisulphide be small, no -crystals may be obtained, but the liquid will become of a red colour. -(2) CS_{2} gives, with an alcoholic solution of potash, a precipitate of -potassic xanthate, CS_{2}C_{2}H_{5}OK. - - Sec. 214. =Xanthogenic acid or ethyloxide-sulphocarbonate= - (CS_{2}C_{2}H_{5}OH) is prepared by decomposing potassic - xanthogenate by diluted hydrochloric or sulphuric acid. It is a - colourless fluid, having an unpleasant odour, and a weakly acid and - rather bitter taste. It burns with a blue colour, and is easily - decomposed at 24 deg., splitting up into ethylic alcohol and hydric - sulphide. It is very poisonous, and has an anaesthetic action similar - to bisulphide of carbon. Its properties are probably due to CS_{2} - being liberated within the body. - - Sec. 215. =Potassic xanthogenate= (CS_{2}C_{2}H_{5}OK) and =potassic - xanthamylate= (CS_{2}C_{5}H_{11}OK) (the latter being prepared by - the substitution of amyl alcohol for ethyl alcohol), both on the - application of a heat below that of the body, develop CS_{2}, and - are poisonous, inducing symptoms very similar to those already - detailed. - - -IX.--The Tar Acids--Phenol--Cresol. - -Sec. 216. =Carbolic Acid. Syn. Phenol, Phenyl Alcohol, Phenylic Hydrate; -Phenic Acid; Coal-Tar Creasote.=--The formula for carbolic acid is -C_{6}H_{5}HO. The pure substance appears at the ordinary temperature as -a colourless solid, crystallising in long prisms; the fusibility of the -crystals is given variously by different authors: from my own -observation, the pure crystals melt at 40 deg.-41 deg., any lower melting-point -being due to the presence of cresylic acid or other impurity; the -crystals again become solid about 15 deg. Melted carbolic acid forms a -colourless limpid fluid, sinking in water. It boils under the ordinary -pressure at 182 deg., and distils without decomposition; it is very readily -and completely distilled in a vacuum at about the temperature of 100 deg. -After the crystals have been exposed to the air, they absorb water, and -a hydrate is formed containing 16.07 per cent. of water. The hydrate -melts at 17 deg., any greater hydration prevents the crystallisation of the -acid; a carbolic acid, containing about 27 per cent. of water, and -probably corresponding to the formula C_{6}H_{6}O,2H_{2}O, is obtained -by gradually adding water to carbolic acid so long as it continues to be -dissolved. Such a hydrate dissolves in 11.1 times its measure of water, -and contains 8.56 per cent. of real carbolic acid. Carbolic acid does -not redden litmus, but produces a greasy stain on paper, disappearing on -exposure to the air; it has a peculiar smell, a burning numbing taste, -and in the fluid state it strongly refracts light. Heated to a high -temperature it takes fire, and burns with a sooty flame. - -When an aqueous solution of carbolic acid is shaken up with ether, -benzene, carbon disulphide, or chloroform, it is fully dissolved by the -solvent, and is thus easily separated from most solutions in which it -exists in the free state. Petroleum ether, on the other hand, only -slightly dissolves it in the cold, more on warming. Carbolic acid mixes -in all proportions with glycerin, glacial or acetic acid, and alcohol. -It coagulates albumen, the precipitate being soluble in an excess of -albumen; it also dissolves iodine, without changing its properties. It -dissolves many resins, and also sulphur, but, on boiling, sulphuretted -hydrogen is disengaged. Indigo blue is soluble in hot carbolic acid, and -may be obtained in crystals on cooling. Carbolic acid is contained in -castoreum, a secretion derived from the beaver, but it has not yet been -detected in the vegetable kingdom. The source of carbolic acid is at -present coal-tar, from which it is obtained by a process of -distillation. There are, however, a variety of chemical actions in the -course of which carbolic acid is formed. - -Sec. 217. The common disinfecting carbolic acid is a dark reddish liquid, -with a very strong odour; at present there is very little phenol in it; -it is mainly composed of meta- and para-cresol. It is officinal in -Germany, and there must contain at least 50 per cent. of the pure -carbolic acid. The pure crystallised carbolic acid is officinal in our -own and all the continental pharmacop[oe]ias. In the British -Pharmacop[oe]ia, a solution of carbolic acid in glycerin is officinal; -the proportions are 1 part of carbolic acid and 4 parts of glycerin, -that is, strength by measure = 20 per cent. The Pharmacop[oe]ia -Germanica has a _liquor natri carbolici_, made with 5 parts carbolic -acid, 1 caustic soda, and 4 of water; strength in carbolic acid = 50 per -cent. There is also a strongly alkaline crude sodic carbolate in use as -a preservative of wood. - -There are various disinfecting fluids containing amounts of carbolic -acid, from 10 per cent. upwards. Many of these are somewhat complex -mixtures, but, as a rule, any poisonous properties they possess are -mainly due to their content of phenol or cresol. A great variety of -disinfecting powders, under various names, are also in commerce, -deriving their activity from carbolic acid. Macdougall's disinfecting -powder is made by adding a certain proportion of impure carbolic acid to -a calcic sulphite, which is prepared by passing sulphur dioxide over -ignited limestone. - -=Calvert's carbolic acid powder= is made by adding carbolic acid to the -siliceous residue obtained from the manufacture of aluminic sulphate -from shale. There are also various carbolates which, by heating or -decomposing with sulphuric acid, give off carbolic acid. - -=Carbolic acid soaps= are also made on a large scale--the acid is free, -and some of the soaps contain as much as 10 per cent. In the inferior -carbolic acid soaps there is little or no carbolic acid, but cresylic -takes its place. Neither the soaps nor the powders have hitherto -attained any toxicological importance, but the alkaline carbolates are -very poisonous. - -Sec. 218. =The chief uses= of carbolic acid are indicated by the foregoing -enumeration of the principal preparations used in medicine and commerce. -The bulk of the carbolic acid manufactured is for the purposes of -disinfection. It is also utilised in the preparation of certain -colouring matters or dyes, and during the last few years has had another -application in the manufacture of salicylic acid. In medicine it is -administered occasionally internally, while the antiseptic movement in -surgery, initiated by Lister, has given it great prominence in surgical -operations. - -Sec. 219. =Statistics.=--The tar acids, _i.e._, pure carbolic acid and the -impure acids sold under the name of carbolic acid, but consisting (as -stated before) mainly of cresol, are, of all powerful poisons, the most -accessible, and the most recklessly distributed. We find them at the -bedside of the sick, in back-kitchens, in stables, in public and private -closets and urinals, and, indeed, in almost all places where there are -likely to be foul odours or decomposing matters. It is, therefore, no -wonder that poisoning by carbolic acid has, of late years, assumed large -proportions. The acid has become vulgarised, and quite as popularly -known, as the most common household drugs or chemicals.[196] This -familiarity is the growth of a very few years, since it was not -discovered until 1834, and does not seem to have been used by Lister -until about 1863. It was not known to the people generally until much -later. At present it occupies the third place in fatality of all -poisons in England. The following table shows that, in the past ten -years, carbolic acid has killed 741 people, either accidentally or -suicidally; there is also one case of murder by carbolic acid within the -same period, bringing the total up to 742:-- - -[196] Although this is so, yet much ignorance still prevails as to its -real nature. In a case reported in the _Pharm. Journ._, 1881, p. 334, a -woman, thirty years of age, drank two-thirds of an ounce of liquid -labelled "_Pure Carbolic Acid_" by mistake, and died in two hours. She -read the label, and a lodger also read it, but did not know what it -meant. - -DEATHS FROM CARBOLIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS -ENDING 1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total - above - Males, 2 39 13 5 83 8 150 - Females, 2 21 7 13 51 7 101 - ------------------------------------------- - Totals, 4 60 20 18 134 15 251 - ------------------------------------------- - - SUICIDE. - - Ages, 15-25 25-65 65 and Total - above - Males, 26 186 7 219 - Females, 72 194 5 271 - ---------------------------- - Totals, 98 380 12 490 - ---------------------------- - -Falck has collected, since the year 1868, no less than 87 cases of -poisoning from carbolic acid recorded in medical literature. In one of -the cases the individual died in nine hours from a large dose of -carbolate of soda; in a second, violent symptoms were induced by -breathing for three hours carbolic acid vapour; in the remaining 85, the -poisoning was caused by the liquid acid. Of these 85 persons, 7 had -taken the poison with suicidal intent, and of the 7, 5 died; 39 were -poisoned through the medicinal use of carbolic acid, 27 of the 39 by the -antiseptic treatment of wounds by carbolic acid dressings, and of these -8 terminated fatally; in 8 cases, symptoms of poisoning followed the -rubbing or painting of the acid on the skin for the cure of scabies, -favus, or psoriasis, and 6 of these patients died. In 4 cases, carbolic -acid enemata, administered for the purpose of dislodging ascarides, gave -rise to symptoms of poisoning, and in one instance death followed. - -The substitution of carbolic acid for medicine happened as follows:-- - - Cases. - Taken instead of Tincture of Opium, 1 - " " Infusion of Senna, 3 - " " Mineral Water, 2 - " " other Mixtures, 3 - " inwardly instead of applied outwardly, 3 - -- - 12 - -Of these 12, 8 died. - -Again, 10 persons took carbolic acid in mistake for various alcoholic -drinks, such as schnapps, brandy, rum, or beer, and 9 of the 10 -succumbed; 17 persons drank carbolic acid simply "by mistake," and of -these 13 died. Thus, of the whole 85 cases, no less than 51 ended -fatally--nearly 60 per cent. - -It must be always borne in mind that, with regard to statistics -generally, the term "carbolic acid" is not used by coroners, juries, or -medical men, in a strictly chemical sense, the term being made to -include disinfecting fluids which are almost wholly composed of the -cresols, and contain scarcely any phenol. In this article, with regard -to symptoms and pathological appearances, it is only occasionally -possible to state whether the pure medicinal crystalline phenol or a -mixture of tar-acids was the cause of poisoning. - -Sec. 220. =Fatal Dose.=--The minimum fatal dose for cats, dogs, and -rabbits, appears to be from .4 to .5 grm. per kilogram. Falck has put -the minimum lethal dose for man at 15 grms. (231.5 grains), which would -be about .2 per kilo., basing his estimate on the following reasoning. -In 33 cases he had a fairly exact record of the amount of acid taken, -and out of the 33, he selects only those cases which are of use for the -decision of the question. Among adults, in 5 cases the dose was 30 -grms., and all the 5 cases terminated by death, in times varying from -five minutes to an hour and a half. By other 5 adults a dose of 15 grms. -was taken; of the 5, 3 men and a woman died, in times varying from -forty-five minutes to thirty hours, while 1 woman recovered. Doses of -11.5, 10.8, and 9 grms. were taken by different men, and recovered from; -on the other hand, a suicide who took one and a half teaspoonful (about -6 grms.) of the concentrated acid, died in fifty minutes. Doses of .3 to -3 grms. have caused symptoms of poisoning, but the patients recovered, -while higher doses than 15 grms. in 12 cases, with only one exception, -caused death. Hence, it may be considered tolerably well established, -that 15 grms. (231.5 grains) may be taken as representing the minimum -lethal dose. - -The largest dose from which a person appears to have recovered is, I -believe, that given in a case recorded by Davidson, in which 150 grms. -of crude carbolic acid had been taken. It must, however, be remembered -that, as this was the impure acid, probably only half of it was really -carbolic acid. The German Pharmacop[oe]ia prescribes as a maximum dose -.05 grm (.7 grain) of the crystallised acid, and a daily maximum -quantity given in divided doses of .15 grm. (2.3 grains). - -Sec. 221. =Effects on Animals.=--Carbolic acid is poisonous to both animal -and vegetable life. - -=Infusoria.=--One part of the acid in 10,000 parts of water rapidly -kills ciliated animalcules,--the movements become sluggish, the sarcode -substance darker, and the cilia in a little time cease moving. - -=Fish.=--One part of the acid in 7000 of water kills dace, minnows, -roach, and gold fish. In this amount of dilution the effect is not -apparent immediately; but, at the end of a few hours, the movements of -the fish become sluggish, they frequently rise to the surface to -breathe, and at the end of twenty-four hours are found dead. Quantities -of carbolic acid, such as 1 part in 100,000 of water, appear to affect -the health of fish, and render them more liable to be attacked by the -fungus growth which is so destructive to fish-life in certain years. - -=Frogs.=--If .01 to .02 grm. of carbolic acid be dissolved in a litre of -water in which a frog is placed, there is almost immediately signs of -uneasiness in the animal, showing that pain from local contact is -experienced; a sleepy condition follows, with exaltation of reflex -sensibility; convulsions succeed, generally, though not always; then -reflex sensibility is diminished, ultimately vanishes, and death occurs; -the muscles and nerves still respond to the electric current, and the -heart beats, but slowly and weakly, for a little after the respiration -has ceased. - -Sec. 222. =Warm-blooded Animals.=--For a rabbit of the average weight of 2 -kilos., .15 grm. is an active dose, and .3 a lethal dose (that is .15 -per kilo.). The sleepy condition of the frog is not noticed, and the -chief symptoms are clonic convulsions with dilatation of the pupils, the -convulsions passing into death, without a noticeable paralytic stage. -The symptoms observed in poisoned dogs are almost precisely similar, the -dose, according to body-weight, being the same. It has, however, been -noticed that with doses large enough to produce convulsions, a weak -condition has supervened, causing death in several days. There appears -to be no cumulative action, since equal toxic doses can be given to -animals for some time, and the last dose has no greater effect than the -first or intermediate ones. The pathological appearances met with in -animals poisoned by the minimum lethal doses referred to are not -characteristic; but there is a remarkable retardation of putrefaction. - -Sec. 223. =Symptoms in Man, external application.=--A 5 per cent. solution -of carbolic acid, applied to the skin, causes a peculiar numbness, -followed, it may be, by irritation. Young subjects, and those with -sensitive skins, sometimes exhibit a pustular eruption, and concentrated -solutions cause more or less destruction of the skin. Lemaire[197] -describes the action of carbolic acid on the skin as causing a slight -inflammation, with desquamation of the epithelium, followed by a very -permanent brown stain, but this he alone has observed. Applied to the -mucous membrane, carbolic acid turns the epithelial covering white; the -epithelium, however, is soon thrown off, and the place rapidly heals; -there is the same numbing, aconite-like feeling before noticed. The -vapour of carbolic acid causes redness of the conjunctivae, and -irritation of the air-passages. If the application is continued, the -mucous membrane swells, whitens, and pours out an abundant secretion. - -[197] Lemaire, Jul., "_De l'Acide phenique_," Paris, 1864. - -Dr. Whitelock, of Greenock, has related two instances in which children -were treated with carbolic acid lotion (strength 2-1/2 per cent.) as an -application to the scalp for ringworm; in both, symptoms of poisoning -occurred--in the one, the symptoms at once appeared; in the other they -were delayed some days. In order to satisfy his mind, the experiment was -repeated twice, and each time gastric and urinary troubles followed. - -Nussbaum, of Munich, records a case[198] in which symptoms were induced -by the forcible injection of a solution of carbolic acid into the cavity -of an abscess. - -[198] _Leitfaden zur antiseptischer Wundbehandlung_, 141. - -Macphail[199] gives two cases of poisoning by carbolic acid from -external use. In the one, a large tumour had been removed from a woman -aged 30, and the wound covered with gauze steeped in a solution of -carbolic acid, in glycerin, strength 10 per cent.; subsequently, there -was high fever, with diminished sulphates in the urine, which smelt -strongly of carbolic acid, and was very dark. On substituting boracic -acid, none of these troubles were observed. The second case was that of -a servant suffering from axillary abscess; the wound was syringed out -with carbolic acid solution, of strength 2-1/2 per cent., when effects -were produced similar to those in the first case. It was noted that in -both these cases the pulse was slowed. Scattered throughout surgical and -medical literature, there are many other cases recorded, though not all -so clear as those cited. Several cases are also on record in which -poisonous symptoms (and even death) have resulted from the application -of carbolic acid lotion as a remedy for scabies or itch. - -[199] "Carbolic Acid Poisoning (Surgical)," by S. Rutherford Macphail, -M.B., _Ed. Med. Journal_, cccxiv., Aug. 1881, p. 134. - -A surgeon prescribed for two joiners who suffered from scabies a lotion, -which was intended to contain 30 grms. of carbolic acid in 240 c.c. of -water; but the actual contents of the flasks were afterwards from -analysis estimated by Hoppe-Seyler to be 33.26 grms., and the quantity -used by each to be equal to 13.37 grms. (206 grains) of carbolic acid. -One of the men died; the survivor described his own symptoms as -follows:--He and his companion stood in front of the fire, and rubbed -the lotion in; he rubbed it into his legs, breast, and the front part of -his body; the other parts were mutually rubbed. Whilst rubbing his right -arm, and drying it before the fire, he felt a burning sensation, a -tightness and giddiness, and mentioned his sensations to his companion, -who laughed. This condition lasted from five to seven minutes, but he -did not remember whether his companion complained of anything, nor did -he know what became of him, nor how he himself came to be in bed. He was -found holding on to the joiner's bench, looking with wide staring eyes, -like a drunken man, and was delirious for half an hour. The following -night he slept uneasily and complained of headache and burning of the -skin. The pulse was 68, the appearance of the urine, appetite, and sense -of taste were normal; the bowels confined. He soon recovered. - -The other joiner seems to have died as suddenly as if he had taken -prussic acid. He called to his mother, "_Ich habe einen Rausch_," and -died with pale livid face, after taking two deep, short inspirations. - -The _post-mortem_ examination showed the sinuses filled with much fluid -blood, and the vessels of the pia mater congested. Frothy, dark, fluid -blood was found in the lungs, which were hyperaemic; the mucous tissues -of the epiglottis and air-tubes were reddened, and covered with a frothy -slime. Both ventricles--the venae cavae and the vessels of the spleen and -kidneys--were filled with dark fluid blood. The muscles were very red; -there was no special odour. Hoppe-Seyler recognised carbolic acid in the -blood and different organs of the body.[200] - -[200] R. Koehler, _Wuertem. Med. Corr. Bl._, xlii., No. 6, April 1872; H. -Abelin, _Schmidt's Jahrbuecher_, 1877, Bd. 173, S. 163. - -In another case, a child died from the outward use of a 2 per cent. -solution of carbolic acid. It is described as follows:--An infant of -seven weeks old suffered from varicella, and one of the pustules became -the centre of an erysipelatous inflammation. To this place a 2 per cent. -solution of carbolic acid was applied by means of a compress steeped in -the acid; the following morning the temperature rose from 36.5 deg. (97.7 deg. -F.) to 37 deg. (98.6 deg. F.), and poisonous symptoms appeared. The urine was -coloured dark. There were sweats, vomitings, and contracted pupils, -spasmodic twitchings of the eyelids and eyes, with strabismus, slow -respiration, and, lastly, inability to swallow. Under the influence of -stimulating remedies the condition temporarily improved, but the child -died twenty-three and a half hours after the first application. An -examination showed that the vessels of the brain and the tissue of the -lungs were abnormally full of blood. The liver was softer than natural, -and exhibited a notable yellowishness in the centre of the acini. -Somewhat similar appearances were noticed in the kidneys, the -microscopic examination of which showed the _tubuli contorti_ enlarged -and filled with fatty globules. In several places the epithelium was -denuded, in other places swollen, and with the nuclei very visible. - -In an American case,[201] death followed the application of carbolic -acid to a wound. A boy had been bitten by a dog, and to the wound, at -one o'clock in the afternoon, a lotion, consisting of nine parts of -carbolic acid and one of glycerin, was applied. At seven o'clock in the -evening the child was unconscious, and died at one o'clock the following -day. - -[201] _American Journal of Pharmacy_, vol. li., 4th Ser.; vol. ix., -1879, p. 57. - -Sec. 224. =Internal Administration.=--Carbolic acid may be taken into the -system, not alone by the mouth, but by the lungs, as in breathing -carbolic acid spray or carbolic acid vapour. It is also absorbed by the -skin when outwardly applied, or in the dressing or the spraying of -wounds with carbolic acid. Lastly, the ordinary poisonous effects have -been produced by absorption from the bowel, when administered as an -enema. When swallowed undiluted, and in a concentrated form, the -symptoms may be those of early collapse, and speedy death. Hence, the -course is very similar to that witnessed in poisoning by the mineral -acids. - -If lethal, but not excessive doses of the diluted acid are taken, the -symptoms are--a burning in the mouth and throat, a peculiarly unpleasant -persistent taste, and vomiting. There is faintness with pallor of the -face, which is covered by a clammy sweat, and the patient soon becomes -unconscious, the pulse small and thready, and the pupils sluggish to -light. The respiration is profoundly affected; there is dyspn[oe]a, and -the breathing becomes shallow. Death occurs from paralysis of the -respiratory apparatus, and the heart is observed to beat for a little -after the respiration has ceased. All these symptoms may occur from the -application of the acid to the skin or to mucous membranes, and have -been noticed when solutions of but moderate strength have been -used--e.g., there are cases in gynaecological practice in which the -mucous membrane (perhaps eroded) of the uterus has been irrigated with -carbolic acid injections. Thus, Kuester[202] relates a case in which, -four days after confinement, the uterus was washed out with a 2 per -cent. solution of carbolic acid without evil result. Afterwards a 5 per -cent. solution was used, but it at once caused violent symptoms of -poisoning, the face became livid, clonic convulsions came on, and at -first loss of consciousness, which after an hour returned. The patient -died on the ninth day. There was intense diphtheria of the uterus and -vagina. Several other similar cases (although not attended with such -marked or fatal effects) are on record.[203] - -[202] _Centralblatt. f. Gynaekologie_, ii. 14, 1878. - -[203] A practitioner in Calcutta injected into the bowel of a boy, aged -5, an enema of diluted carbolic acid, which, according to his own -statement, was 1 part in 60, and the whole quantity represented 144 -grains of the acid. The child became insensible a few minutes after the -operation, and died within four hours. There was no _post-mortem_ -examination; the body smelt strongly of carbolic acid.--_Lancet_, May -19, 1883. - -Sec. 225. The symptoms of carbolic acid poisoning admit of considerable -variation from those already described. The condition is occasionally -that of deep coma. The convulsions may be general, or may affect only -certain groups of muscles. Convulsive twitchings of the face alone, and -also muscular twitchings only of the legs, have been noticed. In all -cases, however, a marked change occurs in the urine. Subissi[204] has -noted the occurrence of abortion, both in the pig and the mare, as a -result of carbolic acid, but this effect has not hitherto been recorded -in the human subject. - -[204] _L'Archivio della Veterinaria Ital._, xi., 1874. - -It has been experimentally shown by Kuester, that previous loss of blood, -or the presence of septic fever, renders animals more sensitive to -carbolic acid. It is also said that children are more sensitive than -adults. - -The course of carbolic acid poisoning is very rapid. In 35 cases -collected by Falck, in which the period from the taking of the poison to -the moment of death was accurately noted, the course was as follows:--12 -patients died within the first hour, and in the second hour 3; so that -within two hours 15 died. Between the third and the twelfth hour, 10 -died; between the thirteenth and the twenty-fourth hour, 7 died; and -between the twenty-fifth and the sixtieth hour, only 3 died. Therefore, -slightly over 71 per cent. died within twelve hours, and 91.4 per cent. -within the twenty-four hours. - -Sec. 226. =Changes in the Urine.=--The urine of patients who have absorbed -in any way carbolic acid is dark in colour, and may smell strongly of -the acid. It is now established--chiefly by the experiments and -observations of Baumann[205]--that carbolic acid, when introduced into -the body, is mainly eliminated in the form of phenyl-sulphuric acid, -C_{6}H_{5}HSO_{4}, or more strictly speaking as potassic -phenyl-sulphate, C_{6}H_{5}KSO_{4}, a substance which is not -precipitated by chloride of barium until it has been decomposed by -boiling with a mineral acid. Cresol is similarly excreted as -cresol-sulphuric acid, C_{6}H_{4}CH_{3}HSO_{4}, ortho-, meta-, or para-, -according to the kind of cresol injected; a portion may also appear as -hydro-tolu-chinone-sulphuric acid. Hence it is that, with doses of -phenol or cresol continually increasing, the amount of sulphates -naturally in the urine (as estimated by simply acidifying with -hydrochloric acid, and precipitating in the cold with chloride of -barium) continually decreases, and may at last vanish, for all the -sulphuric acid present is united with the phenol. On the other hand, the -precipitate obtained by prolonged boiling of the strongly acidified -urine, after filtering off any BaSO_{4} thrown down in the cold, is ever -increasing. - -[205] _Pflueger's Archiv_, 13, 1876, 289. - -Thus, a dog voided urine which contained in 100 c.c., .262 grm. of -precipitable sulphuric acid, and .006 of organically-combined sulphuric -acid; his back was now painted with carbolic acid, and the normal -proportions were reversed, the precipitable sulphuric acid became .004 -grm., while the organically-combined was .190 in 100 c.c. In addition to -phenyl-sulphuric acid, it is now sufficiently established[206] that -hydroquinone - - ( OH) - (C_{6}H_{4} ) - ( OH) - -(paradihydroxyl phenol) and pyrocatechin - - ( OH) - (C_{6}H_{4} ) - ( OH) - -(orthodihydroxyl phenol) are constant products of a portion of the -phenol. The hydroquinone appears in the urine, in the first place, as -the corresponding ether-sulphuric acid, which is colourless; but a -portion of it is set free, and this free hydroquinone (especially in -alkaline urine) is quickly oxidised to a brownish product, and hence the -peculiar colour of urine. Out of dark coloured carbolic acid urine the -hydroquinone and its products of decomposition can be obtained by -shaking with ether; on separation of the ether, an extract is obtained, -reducing alkaline silver solution, and developing quinone on warming -with ferric chloride. - -[206] E. Baumann and C. Preuss, _Zeitschrift f. phys. Chemie_, iii. 156; -_Anleitung zur Harn-Analyse_, W. F. Loebisch, Leipzig, 1881, pp. 142, -160; Schmiedeberg, _Chem. Centrbl._ (3), 13, 598. - -To separate pyro-catechin, 200 c.c. of urine may be evaporated to an -extract, the extract treated with strong alcohol, the alcoholic liquid -evaporated, and the extract then treated with ether. On separation and -evaporation of the ether, a yellowish mass is left, from which the -pyro-catechin may be extracted by washing with a small quantity of -water. This solution will reduce silver solution in the cold, or, if -treated with a few drops of ferric chloride solution, show a marked -green colour, changing on being alkalised by a solution of sodic -hydro-carbonate to violet, and then on being acidified by acetic acid, -changing back again to green. According to Thudichum,[207] the urine of -men and dogs, after the ingestion of carbolic acid, contains a blue -pigment. - -[207] _On the Pathology of the Urine_, Lond., 1877, p. 198. - -Sec. 227. =The Action of Carbolic Acid considered -physiologically.=--Researches on animals have elucidated, in a great -measure, the mode in which carbolic acid acts, and the general sequence -of effects, but there is still much to be learnt. - -E. Kuester[208] has shown that the temperature of dogs, when doses of -carbolic acid in solution are injected subcutaneously, or into the -veins, is immediately, or very soon after the operation, raised. With -small and moderate doses, this effect is but slight--from half to a -whole degree--on the day after the injection the temperature sinks below -the normal point, and only slowly becomes again natural. With doses that -are just lethal, first a rise and then a rapid sinking of temperature -are observed; but with those excessive doses which speedily kill, the -temperature at once sinks without a preliminary rise. The action on the -heart is not very marked, but there is always a slowing of the cardiac -pulsations; according to Hoppe-Seyler the arteries are relaxed. The -respiration is much quickened; this acceleration is due to an -excitement of the vagus centre, since Salkowsky has shown that section -of the vagus produces a retardation of the respiratory wave. Direct -application of the acid to muscles or nerves quickly destroys their -excitability without a previous stage of excitement. The main cause of -the lethal action of carbolic acid--putting on one side those cases in -which it may kill by its local corrosive action--appears to be paralysis -of the respiratory nervous centres. The convulsions arise from the -spinal cord. On the cessation of the convulsions, the superficial nature -of the breathing assists other changes by preventing the due oxidation -of the blood. - -[208] _Archiv f. klin. Chirurgie_, Bd. 23, S. 133, 1879. - -Sec. 228. Carbolic acid is separated from the body in the forms already -mentioned, a small portion is also excreted by the skin. Salkowsky -considers that, with rabbits, he has also found oxalic acid in the urine -as an oxidation product. According to the researches of Binnendijk,[209] -the separation of carbolic acid by the urine commences very quickly -after its ingestion; and, under favourable circumstances, it may be -completely excreted within from twelve to sixteen hours. It must be -remembered that normally a small amount of phenol may be present in the -animal body, as the result of the digestion of albuminous substances or -of their putrefaction. The amount excreted by healthy men when feeding -on mixed diet, Engel,[210] by experiment, estimates to be in the -twenty-four hours 15 mgrms. - -[209] _Journal de Pharmacie et de Chimie._ - -[210] _Annal. de Chimie et de Physique_, 5 Ser. T. 20, p. 230, 1880. - -Sec. 229. =Post-mortem Appearances.=--No fact is better ascertained from -experiments on animals than the following:--That with lethal doses of -carbolic acid, administered by subcutaneous injection, or introduced by -the veins, no appearances may be found after death which can be called -at all characteristic. Further, in the cases in which death has occurred -from the outward application of the acid for the cure of scabies, &c., -no lesion was ascertained after death which could--apart from the -history of the case and chemical evidence--with any confidence be -ascribed to a poison. - -On the other hand, when somewhat large doses of the acid are taken by -the mouth, very coarse and appreciable changes are produced in the upper -portion of the alimentary tract. There may be brownish, wrinkled spots -on the cheek or lips; the mucous membrane of the mouth, throat, and -gullet is often white, and if the acid was concentrated, eroded. The -stomach is sometimes thickened, contracted, and blanched, a condition -well shown in a pathological preparation (ix. 206, 43 _f_) in St. -George's Hospital. The mucous membrane, indeed, may be quite as much -destroyed as if a mineral acid had been taken. Thus, in Guy's Hospital -museum (1799^{40}), there is preserved the stomach of a child who died -from taking accidentally carbolic acid. It looks like a piece of paper, -and is very white, with fawn-coloured spots; the rugae are absent, and -the mucous membrane seems to have entirely vanished. Not unfrequently -the stomach exhibits white spots with roundish edges. The duodenum is -often affected, and the action is not always limited to the first part -of the intestine. - -The respiratory passages are often inflamed, and the lungs infiltrated -and congested. As death takes place from an asphyxiated condition, the -veins of the head and brain, and the blood-vessels of the liver, kidney -and spleen, are gorged with blood, and the right side of the heart -distended, while the left is empty. On the other hand, a person may die -of sudden nervous shock from the ingestion of a large quantity of the -acid, and in such a case the _post-mortem_ appearances will not then -exhibit precisely the characters just detailed. Putrefaction is retarded -according to the dose, and there is often a smell of carbolic acid.[211] -If any urine is contained in the bladder, it will probably be dark, and -present the characters of carbolic urine, detailed at p. 174. - -[211] In order to detect this odour, it is well to open the head first, -lest the putrefaction of the internal viscera be so great as to mask the -odour. - - -Tests for Carbolic Acid. - -Sec. 230. 1. =The Pinewood Test.=--Certain pinewood gives a beautiful blue -colour when moistened first with carbolic acid, and afterwards with -hydrochloric acid, and exposed to the light. Some species of pine give a -blue colour with hydrochloric acid alone, and such must not be used; -others do not respond to the test for carbolic acid. Hence it is -necessary to try the chips of wood first, to see how they act, and with -this precaution the test is very serviceable, and, in cautious hands, no -error will be made. - -2. =Ammonia and Hypochlorite Test.=--If to a solution containing even so -small a quantity as 1 part of carbolic acid in 5000 parts of water, -first, about a quarter of its volume of ammonia hydrate be added, and -then a small quantity of sodic hypochlorite solution, avoiding excess, a -blue colour appears, warming quickens the reaction: the blue is -permanent, but turns to red with acids. If there is a smaller quantity -than the above proportion of acid, the reaction may be still produced -feebly after standing for some time. - -3. =Ferric Chloride.=--One part of phenol in 3000 parts of water can be -detected by adding a solution of ferric chloride; a fine violet colour -is produced. This is also a very good test, when applied to a -distillate; but if applied to a complex liquid, the disturbing action of -neutral salts and other substances may be too great to make the -reaction under those circumstances of service. - -4. =Bromine.=--The most satisfactory test of all is treatment of the -liquid by bromine-water. A precipitate of tri-bromo-phenol -(C_{6}H_{3}Br_{3}O) is rapidly or slowly formed, according to the -strength of the solution; in detecting very minute quantities the -precipitate must be given time to form. According to Allen,[212] a -solution containing but 1/60000 of carbolic acid gave the reaction after -standing twenty-four hours. - -[212] _Commercial Organic Analysis_, vol. i. p. 306. - -The properties of the precipitate are as follows:--It is crystalline, -and under the microscope is seen to consist of fine stars of needles; -its smell is peculiar; it is insoluble in water and acid liquids, but -soluble in alkalies, ether, and absolute alcohol; a very minute quantity -of water suffices to precipitate it from an alcoholic solution; it is -therefore essential to the success of the test that the watery liquid to -be examined is either neutral or acid in reaction. - -Sec. 231. Tri-bromo-phenol may be used for the quantitative estimation of -carbolic acid, 100 parts of tri-bromo-phenol are equal to 29.8 of -carbolic acid; by the action of sodium amalgam, tri-bromo-phenol is -changed back into carbolic acid. - -That bromine-water precipitates several volatile and fixed alkaloids -from their solutions is no objection to the bromine test, for it may be -applied to a distillation product, the bases having been previously -fixed by sulphuric acid. Besides, the properties of tri-bromo-phenol are -distinct enough, and therefore there is no valid objection to the test. -It is the best hitherto discovered. There are also other reactions, such -as that Millon's reagent strikes a red--molybdic acid, in concentrated -sulphuric acid, a blue--and potassic dichromate, with sulphuric acid, a -brown colour--but to these there are objections. Again, we have the -_Euchlorine_ test, in which the procedure is as follows:--A test-tube is -taken, and concentrated hydrochloric acid is allowed to act therein upon -potassic chlorate. After the gas has been evolved for from 30 to 40 -seconds, the liquid is diluted with 1-1/2 volume of water, the gas -removed by blowing through a tube, and solution of strong ammonia poured -in so as to form a layer on the top; after blowing out the white fumes -of ammonium chloride, a few drops of the sample to be tested are added. -In the presence of carbolic acid, a rose-red, blood-red, or red-brown -tint is produced, according to the quantity present. Carbolic acid may -be confounded with _cresol_ or with _creasote_, but the distinction -between pure carbolic acid, pure cresol, and creasote is plain. - -Sec. 232. =Cresol (Cresylic Acid, Methyl-phenol)=, - - OH - / - C_{6}H_{4} . - \ - CH_{3} - ---There are three cresols--ortho-, meta-, and para-. Ordinary -commercial cresol is a mixture of the three, but contains but little -ortho-cresol; the more important properties of the pure cresols are set -out in the following table:-- - - +--------+-----------------+----------------+---------------------+ - | | Melting-point. | Boiling-point. | Converted by fusion | - | | | | with Potash into-- | - +--------+-----------------+----------------+---------------------+ - |Ortho-, | 31-31.5 deg. C. | 188.0 deg. | Salicylic Acid | - | | | | (Ortho-oxybenzoic | - | | | | acid). | - | | | | | - |Meta-, |Fluid at ordinary| 201.0 deg. | Meta-oxybenzoic | - | | temperature. | | acid. | - | | | | | - |Para-, | 36 deg. | 198 deg. |Para-oxybenzoic acid.| - +--------+-----------------+----------------+---------------------+ - -Pure ortho-, meta-, or para-cresol have been obtained by synthetical -methods; they cannot be said to be in ordinary commerce. - -=Commercial cresol= is at ordinary temperatures a liquid, and cannot be -obtained in a crystalline state by freezing. Its boiling-point is from -198 deg. to 203 deg.; it is almost insoluble in strong ammonia, and, when 16 -volumes are added, it then forms crystalline scales. On the other hand, -carbolic acid is soluble in an equal volume of ammonia, and is then -precipitated by the addition of 1-1/2 volume of water. Cresol is -insoluble in small quantities of pure 6 per cent. soda solution; with a -large excess, it forms crystalline scales; while carbolic acid is freely -soluble in small or large quantities of alkaline solutions. - -Cold petroleum spirit dissolves cresol, but no crystalline scales can be -separated out by a freezing mixture. Carbolic acid, on the contrary, is -but sparingly soluble in cold petroleum, and a solution of carbolic acid -in hot petroleum, when exposed to sudden cold produced by a freezing -mixture, separates out crystals from the upper layer of liquid. Cresol -is miscible with glycerin of specific gravity 1.258 in all proportions; -1 measure of glycerin mixed with 1 measure of cresol is completely -precipitated by 1 measure of water. Carbolic acid, under the same -circumstances, is not precipitated. The density of cresol is about -1.044. It forms with bromine a tri-bromo-cresol, but this is liquid at -ordinary temperatures, while tri-bromo-phenol is solid. On the other -hand, it resembles carbolic acid in its reactions with ferric chloride -and with nitric and sulphuric acid. - - Sec. 233. =Creasote= or =Kreozote= is a term applied to the mixture of - crude phenols obtained from the distillation of wood-tar. It - consists of a mixture of substances of which the chief are guaiacol - or oxycresol (C_{7}H_{8}O_{2}), boiling at 200 deg., and creasol - (C_{8}H_{10}O_{2}), boiling at 217 deg.; also in small quantities - phlorol (C_{8}H_{10}O), methyl creasol (C_{9}H_{12}O_{2}), and other - bodies. Morson's English creasote is prepared from Stockholm tar, - and boils at about 217 deg., consisting chiefly of creasol; it is not - easy, by mere chemical tests, to distinguish creasote from cresylic - acid. Creasote, in its reactions with sulphuric and nitric acid, - bromine and gelatin, is similar to carbolic and cresylic acids, and - its solubility in most solvents is also similar. It is, however, - distinguished from the tar acids by its insolubility in Price's - glycerin, specific gravity 1.258, whether 1, 2, or 3 volumes of - glycerin be employed. But the best test is its action on an ethereal - solution of nitro-cellulose. Creasote mixes freely with the B.P. - collodium, while cresylic acid or carbolic acid at once coagulates - the latter. With complicated mixtures containing carbolic acid, - cresol, and creasote, the only method of applying these tests with - advantage is to submit the mixture to fractional distillation. - - Flueckiger[213] tests for small quantities of carbolic acid in - creasote, by mixing a watery solution of the sample with one-fourth - of its volume of ammonia hydrate, wetting the inside of a porcelain - dish with this solution, and then carefully blowing bromine fumes on - to the surface. A fine blue colour appears if carbolic acid is - present, but if the sample consists of creasote only, then it is - dirty green or brown. Excess of bromine spoils the reaction.[214] - -[213] _Arch. der Pharmacie_, cxiii. p. 30. - -[214] Creasote is, without doubt, poisonous, though but little is known -of its action, and very few experiments are on record in which pure -creasote has been employed. Eulenberg has studied the symptoms in -rabbits, by submitting them to vaporised creasote--_i.e._, the vapour -from 20 drops of creasote diffused through a glass shade under which a -rabbit was confined. There was at once great uneasiness, with a watery -discharge from the eyes, and after seven minutes the rabbit fell on its -side, and was slightly convulsed. The cornea was troubled, and the eyes -prominent; a white slime flowed from the mouth and eyes. After fifteen -minutes there was narcosis, with lessened reflex action; the temperature -was almost normal. There was rattling breathing, and in half an hour the -animal died, the respiration ceasing, and fluid blood escaping from the -nose. Section after death showed the brain to be hyperaemic, the mucous -membranes of the air-passages to be covered with a thin layer of fluid -blood, and the lungs to be congested; the right side of the heart was -gorged with fluid blood. - -The _post-mortem_ appearances and the symptoms generally are, therefore, -closely allied to those produced by carbolic acid. A dark colour of the -urine has also been noticed. - -Sec. 234. =Carbolic Acid in Organic Fluids or in the Tissues of the -Body.=--If the routine process given at page 51, where the organic fluid -is distilled in a vacuum after acidifying with tartaric acid, is -employed, phenol or cresol, if present, will certainly be found in the -distillate. If, however, a special search be made for the acids, then -the fluid must be well acidified with sulphuric acid, and distilled in -the usual way. The distillation should be continued as long as possible, -and the distillate shaken up with ether in the apparatus figured at page -156. On separation and evaporation of the ether, the tar acids, if -present, will be left in a pure enough form to show its reactions. The -same process applies to the tissues, which, in a finely-divided state, -are boiled and distilled with dilute sulphuric acid, and the distillate -treated as just detailed. - -Like most poisons, carbolic acid has a selective attraction for certain -organs, so that, unless all the organs are examined, it is by no means -indifferent which particular portion is selected for the inquiry. -Hoppe-Seyler applied carbolic acid to the abdomen and thighs of dogs, -and when the symptoms were at their height bled them to death, and -separately examined the parts. In one case, the blood yielded .00369 per -cent.; the brain, .0034 per cent.; the liver, .00125; and the kidneys, -.00423 per cent. of their weight of carbolic acid. The liver then -contains only one-third of the quantity found in an equal weight of -blood, and, therefore, the acid has no selective affinity for that -organ. On the other hand, the nervous tissue, and especially the -kidneys, appear to concentrate it. - -Sec. 235. =Examination of the Urine for Phenol or Cresol.=--It has been -previously stated (see p. 174) that the urine will not contain these as -such, but as compounds--viz., phenyl or cresyl sulphate of potassium. By -boiling with a mineral acid, these compounds may be broken up, and the -acids obtained, either by distillation or by extraction with ether. To -detect very minute quantities, a large quantity of the urine should be -evaporated down to a syrup, and treated with hydrochloric acid and -ether. On evaporating off the ether, the residue should be distilled -with dilute sulphuric acid, and this distillate then tested with -bromine-water, and the tri-bromo-phenol or cresol collected, identified, -and weighed. - -Thudichum[215] has separated crystals of potassic phenyl-sulphate itself -from the urine of patients treated endermically by carbolic acid, as -follows:-- - -[215] _Pathology of the Urine_, p. 193. - -The urine was evaporated to a syrup, extracted with alcohol of 90 per -cent., treated with an alcoholic solution of oxalic acid as long as this -produced a precipitate, and then shaken with an equal volume of ether. -The mixture was next filtered, neutralised with potassic carbonate, -evaporated to a small bulk, and again taken up with alcohol. Some -oxalate and carbonate of potassium were separated, and, on evaporation -to a syrup, crystals of potassic phenyl-sulphate were obtained. They -gave to analysis 46.25 per cent. H_{2}SO_{4}, and 18.1 K--theory -requiring 46.2 of H_{2}SO_{4} and 18.4 of K. Alkaline phenyl-sulphates -strike a deep purple colour with ferric chloride. To estimate the amount -of phenyl-sulphate or cresol-sulphate in the urine, the normal sulphates -may be separated by the addition of chloride of barium in the cold, -first acidifying with hydrochloric acid. On boiling the liquid a second -crop of sulphate is obtained, due to the breaking up of the compound -sulphate, and from this second weight the amount of acid can be -obtained, _e.g._, in the case of phenol--C_{6}H_{5}HSO_{4} : BaSO_{4} :: -174 : 233. - - Sec. 236. =Assay of Disinfectants, Carbolic Acid Powders, &c.=--For the - assay of crude carbolic acid, Mr. Charles Lowe[216] uses the - following process:--A thousand parts of the sample are distilled - without any special condensing arrangement; water first comes over, - and is then followed by an oily fluid. When a hundred parts of the - latter, as measured in a graduated tube, have been collected, the - receiver is changed. The volume of water is read off. If the oily - liquid floats on the water, it contains light oil of tar; if it is - heavier than the water, it is regarded as hydrated acid, containing - 50 per cent. of real carbolic acid. The next portion consists of - anhydrous cresylic and carbolic acids, and 625 volumes are distilled - over; the remainder in the retort consists wholly of cresylic acid - and the higher homologues. The relative proportions of carbolic and - cresylic acids are approximately determined by taking the - solidifying point, which should be between 15.5 deg. and 24 deg., and having - ascertained this temperature, imitating it by making mixtures of - known proportions of carbolic and cresylic acids. - -[216] _Allen's Commercial Organic Analysis_, vol. i. p. 311. - - E. Waller[217] has recommended the following process for the - estimation of carbolic acid. It is based on the precipitation of the - tar acids by bromine, and, of course, all phenols precipitated in - this way will be returned as carbolic acid. The solutions necessary - are-- - -[217] _Chem. News_, April 1, 1881, p. 152. - - 1. A solution containing 10 grms. of pure carbolic acid to the - litre; this serves as a standard solution. - - 2. A solution of bromine in water. - - 3. Solution of alum in dilute sulphuric acid. A litre of 10 per - cent. sulphuric acid is shaken with alum crystals until saturated. - - The actual process is as follows:--10 grms. of the sample are - weighed out and run into a litre flask, water added, and the mixture - shaken. The flask being finally filled up to the neck, some of the - solution is now filtered through a dry filter, and 10 c.c. of this - filtrate is placed in a 6 or 8-ounce stoppered bottle, and 30 c.c. - of the alum solution added. In a similar bottle 10 c.c. of the - standard solution of carbolic acid are placed, and a similar - quantity of alum solution is added, as in the first bottle. The - bromine-water is now run into the bottle containing the standard - solution of carbolic acid from a burette until there is no further - precipitate; the bottle is stoppered and shaken after every - addition. Towards the end of the reaction the precipitate forms but - slowly, and when the carbolic acid is saturated, the slight excess - of bromine-water gives the solution a pale yellow tint. The solution - from the sample is treated in the same way, and from the amount of - bromine-water used, the percentage of the sample is obtained by - making the usual calculations. Thus, supposing that 5 c.c. of the - standard required 15 c.c. of the bromine-water for precipitation, - and 10 c.c. of the solution of the sample required 17 c.c., the - calculation would be 15 x 2 : 17 = 100 : _x_ per cent. With most - samples of crude carbolic acid, the precipitate does not readily - separate. It is then best to add a little of the precipitate already - obtained by testing the standard solution, which rapidly clears the - liquid. - - =Koppeschaar's volumetric method= is more exact, but also more - elaborate, than the one just described. Caustic normal soda is - treated with bromine until permanently yellow, and the excess of - bromine is then driven off by boiling. The liquid now contains 5NaBr - + NaBrO_{3}, and on adding this to a solution containing carbolic - acid, and a sufficient quantity of hydrochloric acid to combine with - the sodium, the following reactions occur:-- - - (1.) 5NaBr + NaBrO_{3} + 6HCl = 6NaCl + 6Br + 3H_{2}O; - - and - - (2.) C_{6}H_{6}O + 6Br = C_{6}H_{3}Br_{3}O + 3HBr. - - Any excess of bromine liberated in the first reaction above that - necessary for the second, will exist in the free state, and from the - amount of bromine which remains free the quantity of carbolic acid - can be calculated, always provided the strength of the bromine - solution is first known. The volumetric part of the analysis, - therefore, merely amounts to the determination of free bromine, - which is best found by causing it to react on potassium iodide, and - ascertaining the amount of free iodine by titration with a standard - solution of sodium thiosulphate. In other words, titrate in this way - the standard alkaline bromine solution, using as an indicator starch - paste until the blue colour disappears. Another method of indicating - the end of the reaction is by the use of strips of paper first - soaked in starch solution, and dried, and then the same papers - moistened with zinc iodide, and again dried; the least excess of - bromine sets free iodine, and strikes a blue colour. - - =Colorimetric Method of Estimation.=--A very simple and ever-ready - way of approximately estimating minute quantities of the phenols - consists in shaking up 10 grms. of the sample with water, allowing - any tar or insoluble impurities to subside. Ten c.c. of the clear - fluid are then taken, and half a c.c. of a 5 per cent. solution of - ferric chloride added. The colour produced is imitated by a standard - solution of carbolic acid, and a similar amount of the reagent, on - the usual principles of colorimetric analysis. - - Sec. 237. =Carbolic Acid Powders.=--Siliceous carbolic acid powders are - placed in a retort and distilled. Towards the end the heat may be - raised to approaching redness. The distillate separates into two - portions--the one aqueous, the other consisting of the acids--and - the volume may be read off, if the distillate be received in a - graduated receiver. Carbolic acid powders, having lime as a basis, - may be distilled in the same way, after first decomposing with - sulphuric acid. The estimation of the neutral tar oils in the - distillate is easily performed by shaking the distillate with - caustic soda solution, which dissolves completely the tar acids. The - volume of the oils may be directly read off if the receiver is a - graduated tube. Allen[218] has suggested the addition of a known - volume of petroleum to the distillate, which dissolves the tar oils, - and easily separates, and thus the volume may be more accurately - determined, a correction being of course made by subtracting the - volume of petroleum first added. - -[218] _Op. cit._, i. p. 310. - - Sec. 238. =Carbolic Acid Soap.=--A convenient quantity of soap is - carefully weighed, and dissolved in a solution of caustic soda by - means of heat. A saturated solution of salt is next added, - sufficient to precipitate entirely the soap, which is filtered off; - the filtrate is acidified with hydrochloric acid, and bromine water - added. The precipitated tribromo-phenol is first melted by heat, - then allowed to cool, and the mass removed from the liquid, dried, - and weighed. - - -X.--Nitro-Benzene. - -Sec. 239.--Nitro-benzene is the product resulting from the action of strong -nitric acid on benzene. Its chemical formula is C_{6}H_{5}NO_{2}. When -pure, it is of a pale yellow colour, of a density of 1.186, and boils at -from 205 deg. to 210 deg. It may be obtained in prismatic crystals by exposure -to a temperature of 3 deg. Its smell is exactly the same as that from the -oil or essence of bitter almonds; and it is from this circumstance, -under the name of "essence of mirbane," much used in the preparation of -perfumes and flavouring agents. - -In commerce there are three kinds of nitro-benzene--the purest, with the -characters given above; a heavier nitro-benzene, boiling at 210 deg. to -220 deg.; and a very heavy variety, boiling at 222 deg. to 235 deg. The last is -specially used for the preparation of aniline, or aniline blue. -Nitro-benzene has been used as an adulterant of bitter almond oil, but -the detection is easy (see "Foods," p. 551). Nitro-benzene was first -discovered by Mitscherlich in 1834, and its poisonous properties were -first pointed out by Casper[219] in 1859. Its technical use in perfumes, -&c., dates from about 1848, and in the twenty-eight years intervening -between that date and 1876, Juebell[220] has collected 42 cases of -poisoning by this agent, 13 of which were fatal. One of these cases was -suicidal, the rest accidental. - -[219] _Vierteljahrsschrift fuer ger. Med._, 1859, Bd. xvi. p. 1. - -[220] _Die Vergiftungen mit Blausaeure u. Nitro-benzol in forensischer -Beziehung_, Erlangen, 1876. - -Sec. 240. =Effects of Poisoning by Nitro-benzene.=--Nitro-benzene is a very -powerful poison, whether taken in the form of vapour or as a liquid. The -action of the vapour on animals has been studied by Eulenberg[221] and -others. One experiment will serve as an illustration. Fifteen grms. of -nitro-benzene were evaporated on warm sand under a glass shade, into -which a cat was introduced. There was immediately observed in the animal -much salivation, and quickened and laboured breathing. After thirty -minutes' exposure, on removing the shade to repeat the dose of 15 grms., -the cat for the moment escaped. On being put back there was again -noticed the salivation and running at the eyes, with giddiness, and -repeated rising and falling. The animal at last, about one hour and -forty minutes after the first dose, succumbed with dyspn[oe]a, and died -with progressive paralysis of the respiration. The membranes of the -brain were found gorged with blood, the lungs liver-coloured, the mucous -membrane of the trachea--to the finest sub-divisions of the -bronchia--reddened, inflamed, and clothed with a fine frothy mucus. The -left side of the heart was filled with thick black blood. The bladder -contained 8 grms. of clear urine, in which aniline was discovered. There -was a notable smell of bitter almonds. - -[221] _Gewerbe Hygiene_, S. 607, Berlin, 1876. - -Sec. 241. The effects of the vapour on man are somewhat different in their -details to those just described. In a remarkable case related by Dr. -Letheby, a man, aged 42, had spilt some nitro-benzene over his clothes. -He went about several hours breathing an atmosphere of nitro-benzene, he -then became drowsy, his expression was stupid, and his gait unsteady, -presenting all the appearances of intoxication. The stupor suddenly -deepened into coma, and the man died; the fatal course being altogether -about nine hours--viz., four hours before coma, and five hours of total -insensibility. - -An interesting case of poisoning by the vapour is recorded by -Taylor.[222] A woman, aged 30, tasted a liquid used for flavouring -pastry, which was afterwards chemically identified as pure -nitro-benzene. She immediately spat it out, finding that it had an acrid -taste, and probably did not swallow more than a drop. In replacing the -bottle, however, she spilt about a tablespoonful, and allowed it to -remain for some minutes; it was a small room, and the vapour rapidly -pervaded it, and caused illness in herself as well as in a -fellow-servant. She had a strange feeling of numbness in the tongue, and -in three hours and a quarter after the accident was seen by a medical -man; she then presented all the appearances of prussic acid poisoning. -The eyes were bright and glassy, the features pale and ghastly, the lips -and nails purple, as if stained with blackberries, the skin clammy, and -the pulse feeble, but the mind was then clear. An emetic was -administered, but she suddenly became unconscious; the emetic acted, and -brought up a fluid with an odour of nitro-benzene. The stomach-pump was -also used, but the liquid obtained had scarcely any odour of -nitro-benzene. In about eleven hours consciousness returned, and in -about seventeen hours she partially recovered, but complained of flashes -of light and strange colours before her eyes. Recovery was not complete -for weeks. In this case the small quantity swallowed would probably of -itself have produced no symptoms, and the effects are to be mainly -ascribed to the breathing of the vapour. - -[222] _Poisons_, Third Edition, p. 665. - -Sec. 242. The liquid, when swallowed, acts almost precisely in the same way -as the vapour, and the symptoms resemble very much those produced by -prussic acid. The great distinction between prussic acid and -nitro-benzene poisoning is that, in the latter, there is an interval -between the taking of the poison and its effects. This is, indeed, one -of the strangest phenomena of nitro-benzene poisoning, for the person, -after taking it, may appear perfectly well for periods varying from a -quarter of an hour to two or three hours, or even longer, and then there -may be most alarming symptoms, followed by rapid death. Poisoning by -nitro-benzene satisfies the ideal of the dramatist, who requires, for -the purposes of his plot, poisons not acting at once, but with an -interval sufficiently prolonged to admit of lengthy rhapsodies and a -complicated _denouement_. On drinking the poison there is a burning -taste in the mouth, shortly followed by a very striking blueness or -purple appearance of the lips, tongue, skin, nails, and even the -conjunctivae. This curious colour of the skin has, in one or two -instances, been witnessed an hour before any feeling of illness -manifested itself; vomiting then comes on, the vomited matter smelling -of nitro-benzene. The skin is cold, there is great depression, and the -pulse is small and weak. The respiration is affected, the breathing -being slow and irregular, the breath smelling strongly of the liquid, -and the odour often persisting for days. A further stage is that of loss -of consciousness, and this comes on with all the suddenness of a fit of -apoplexy. The coma is also similar in appearance to apoplectic coma, -but there have frequently been seen trismus and convulsions of the -extremities. The pupils are dilated and do not react to light, and -reflex sensibility is sometimes completely extinguished. Cases vary a -little in their main features; in a few the blue skin and the deep sleep -are the only symptoms noted. Death, for the most part, occurs after a -period of from eight to twenty-four hours (occasionally as soon as four -or five hours) after taking the poison. - -From the following remarkable train of symptoms in a dog, it is -probable, indeed, that nitro-benzene, taken by a human being, might -produce death, after a rather prolonged period of time, by its secondary -effects:--To a half-bred greyhound[223] were administered 15 grms. of -nitro-benzene, when shortly after there were noticed much salivation, -shivering, and muscular twitchings. The same dose was repeated at the -end of five, of seven, and of eight hours respectively, so that the dog -altogether took 60 grms., but with no other apparent symptom than the -profuse salivation. On the following day, the dog voided a tapeworm; -vomiting supervened; the heart's action was quickened, and the breathing -difficult; convulsions followed, and the pupils were seen to be dilated. -For eight days the dog suffered from dyspn[oe]a, quickened pulse, -shivering of the legs or of the whole body, tetanic spasms, bloody -motions, great thirst and debility. The temperature gradually sank under -25 deg., and the animal finally died. The autopsy showed, as the most -striking change, the whole mucous membrane of the intestinal tract -covered with a yellow layer, which chemical analysis proved to be caused -by picric acid, and in the urine, liver, and lungs, aniline was -discovered. - -[223] Eulenberg, _Gewerbe Hygiene_, S. 607. - -Sec. 243. =Fatal Dose.=--It is probable, from recorded cases, that 1 grm. -(15.4 grains) would be quite sufficient to kill an adult, and, under -favourable circumstances, less than that quantity. It would seem that -spirituous liquids especially hasten and intensify the action of -nitro-benzene, so that a drunken person, _caeteris paribus_, taking the -poison with spirits, would be more affected than taking it under other -conditions. - -In a case related by Stevenson,[224] in which so small a quantity as -1.74 grm. was taken in seven doses, spread over more than forty-eight -hours; there were yet extremely alarming symptoms, and the patient seems -to have had a narrow escape. On the other hand, a woman admitted into -the General Hospital, Vienna, took 100 grms. (about 3-1/2 ozs.) and -recovered; on admission she was in a highly cyanotic condition, with -small pulse, superficial respiration, and dribbling of urine, which -contained nitro-benzol. Artificial respiration was practised, and -camphor injections were administered. Under this treatment consciousness -was restored, and the patient recovered. On the fourth day the urine -resembled that of a case of cystitis (_Lancet_, Jan. 16, 1894). The -quantity of nitro-benzene which would be fatal, if breathed, is not -known with any accuracy. - -[224] This case is not uninteresting. Through a mistake in reading an -extremely illegible prescription, M. S. S., aet. 21, was supplied by a -druggist with the following mixture;-- - - [Rx]. Benzole-Nit., [dr]iij. - Ol. Menth, pep., [dr]ss. - Ol. Olivae, [dr]x. - gutt. xxx., t. ds. - -He took on sugar seven doses, each of 20 minims, equalling in all 23 -min. (or by weight 27.1 grains, 1.74 grm.) of nitro-benzene--viz., three -doses on the first day, three on the second, and one on the morning of -the third day. The first two days he was observed to be looking pale and -ill, but went on with his work until the seventh dose, which he took on -the third day at 9 A.M. About 2 P.M. (or six hours after taking the -seventh dose), he fell down insensible, the body pale blue, and with all -the symptoms already described in the text, and usually seen in -nitro-benzene poisoning. With suitable treatment he recovered. The next -morning, from 8 ounces of urine some nitro-benzene was extracted by -shaking with chloroform.--Thos. Stevenson, M.D., in _Guy's Hospital -Reports_, MS., vol. xxi., 1876. - -Sec. 244. =Pathological Appearances.=--The more characteristic appearances -seem to be, a dark brown or even black colour of the blood, which -coagulates with difficulty (an appearance of the blood that has even -been noticed during life), venous hyperaemia of the brain and its -membranes, and general venous engorgement. In the stomach, when the -fluid has been swallowed, the mucous membrane is sometimes reddened -diffusely, and occasionally shows ecchymoses of a punctiform character. - -Sec. 245. =The essential action of nitro-benzene= is of considerable -physiological interest. The blood is certainly in some way changed, and -gives the spectrum of acid haematin.[225] Filehne has found that the -blood loses, in a great degree, the power of carrying and imparting -oxygen to the tissues, and its content of carbon dioxide is also -increased. Thus, the normal amount of oxygen gas which the arterial -blood of a hound will give up is 17 per cent.; but in the case of a dog -which had been poisoned with nitro-benzene, it sank to 1 per cent. -During the dyspn[oe]a from which the dog suffered, the carbon dioxide -exhaled was greater than the normal amount, and the arterial blood (the -natural content of which should have been 30 per cent. of this gas), -only gave up 9 per cent. Filehne seeks to explain the peculiar colour of -the skin by the condition of the blood, but the explanation is not -altogether satisfactory. Some part of the nitro-benzene, without doubt, -is reduced to aniline in the body--an assertion often made, and as often -contradicted--but it has been found in too many cases to admit of -question. It would also seem from the experiment on the dog (p. 186), -that a conversion into picric acid is not impossible. A yellow colour -of the skin and conjunctivae, as if picric-acid-stained, has been noticed -in men suffering under slow poisoning by nitro-benzene. - -[225] Filehne, W., "_Ueber die Gift-Wirkungen des Nitrobenzols_," _Arch. -fuer exper. Pathol. u. Pharm._, ix. 329. - -Sec. 246. =Detection and Separation of Nitro-Benzene from the Animal -Tissues.=--It is evident from the changes which nitro-benzene may -undergo that the expert, in any case of suspected nitro-benzene -poisoning, must specially look (1) for nitro-benzene, (2) for aniline, -and (3) for picric acid. The best general method for the separation of -nitro-benzene is to shake up the liquid (or finely-divided solid) with -light benzoline (petroleum ether), which readily dissolves -nitro-benzene. On evaporation of the petroleum ether, the nitro-benzene -is left, perhaps mixed with fatty matters. On treating with cold water, -the fats rise to the surface, and the nitro-benzene sinks to the bottom; -so that, by means of a separating funnel, the nitro-benzene may be -easily removed from animal fats. The oily drops, or fine precipitate -believed to be nitro-benzene, may be dissolved in spirit and reduced to -aniline by the use of nascent hydrogen, developed from iron filings by -hydrochloric acid, and the fluid tested with bleaching powder, or, the -aniline itself may be recovered by alkalising the fluid, and shaking up -with ether in the separation-tube (p. 156), the ether dissolves the -aniline, and leaves it, on spontaneous evaporation, as an oily yellowish -mass, which, on the addition of a few drops of sodic hypochlorite, -strikes a blue or violet-blue--with acids, a rose-red--and with bromine, -a flesh-red. It gives alkaloidal reactions with such general reagents as -platinum chloride, picric acid, &c. Aniline itself may be extracted from -the tissues and fluids of the body by petroleum ether, but in any -special search it will be better to treat the organs as in Stas' -process--that is, with strong alcohol, acidified with sulphuric acid. -After a suitable digestion in this menstruum, filter, and then, after -evaporating the alcohol, dissolve the alcoholic extract in water; -alkalise the aqueous solution, and extract the aniline by shaking it up -with light benzoline. On separating the benzoline, the aniline will be -left, and may be dissolved in feebly-acid water, and the tests before -enumerated tried. - -Malpurgo[226] recommends the following test for nitro-benzene:--2 drops -of melted phenol, 3 drops of water, and a fragment of caustic potash are -boiled in a small porcelain dish, and to the boiling liquid the aqueous -solution to be tested is added. On prolonged boiling, if nitro-benzene -is present, a crimson ring is produced at the edges of the liquid; this -crimson colour, on the addition of a little bleaching powder, turns -emerald-green. - -[226] _Zeit. anal. Chem._, xxxii. 235. - -Oil of bitter almonds may be distinguished from nitro-benzene by the -action of manganese dioxide and sulphuric acid; bitter almond oil -treated in this way loses its odour, nitro-benzene is unaltered. To -apply the test, the liquid must be heated on the water-bath for a little -time. - - -XI.--Dinitro-benzol. - -Sec. 247. =Dinitro-benzol=, C_{6}H_{4}(NO_{2})_{2} (ortho-, meta-, -para-).--The ortho-compound is produced by the action of nitric acid on -benzol, aided by heat in the absence of strong sulphuric acid to fix -water. Some of the para-dinitro-benzol is at the same time produced. The -meta-compound is obtained by the action of fuming nitric acid on -nitro-benzol at a boiling temperature. - -The physical properties of the three dinitro-benzols are briefly as -follows:-- - -Ortho-d. is in the form of needles; m.p. 118 deg. - -Meta-d. crystallises in plates; m.p. 90 deg. - -Para-d. crystallises, like the ortho-compound, in needles, but the -melting-point is much higher, 171 deg. to 172 deg. - -Just as nitro-benzol by reduction yields aniline, so do the -nitro-benzols on reduction yield ortho-, meta-, or para-phenylene -diamines. - -Meta-phenylene diamine is an excellent test for nitrites; and, since the -commercial varieties of dinitro-benzol either consist mainly or in part -of meta-dinitro-benzol, the toxicological detection is fairly simple, -and is based upon the conversion of the dinitro-benzol into -meta-phenylene-diamine. - -Dinitro-benzol is at present largely employed in the manufacture of -explosives, such as roburite, sicherheit, and others. It has produced -much illness among the workpeople in the manufactures, and amongst -miners whose duty it has been to handle such explosives. - -Sec. 248. =Effects of Dinitro-benzol.=--Huber[227] finds that if -dinitro-benzol is given to frogs by the mouth in doses of from 100 to -200 mgrms., death takes place in a few hours. Doses of from 2.5 to 5 -mgrms. cause general dulness and ultimately complete paralysis, and -death in from one to six days. - -[227] "_Beitraege zur Giftwirkung des Dinitrobenzols_," A. Huber, -Virchow's _Archiv_, 1891, Bd. 126, S. 240. - -Rabbits are killed by doses of 400 mgrms., in time varying from -twenty-two hours to four days. - -In a single experiment on a small dog, the weight of which was 5525 -grms., the dog died in six hours after a dose of 600 mgrms. - -It is therefore probable that a dose of 100 mgrms. per kilo would kill -most warm-blooded animals. - -A transient exposure to dinitro-benzol vapours in man causes serious -symptoms; for instance, in one of Huber's cases, a student of chemistry -had been engaged for one hour and a half only in preparing -dinitro-benzol, and soon afterwards his comrades remarked that his face -was of a deep blue colour. On admission to hospital, on the evening of -the same day, he complained of slight headache and sleeplessness; both -cheeks, the lips, the muscles of the ear, the mucous membrane of the -lips and cheeks, and even the tongue, were all of a more or less intense -blue-grey colour. The pulse was dicrotic, 124; T. 37.2 deg. The next -morning the pulse was slower, and by the third day the patient had -recovered. - -Excellent accounts of the effects of dinitro-benzol in roburite -factories have been published by Dr. Ross[228] and Professor White,[229] -of Wigan. Mr. Simeon Snell[230] has also published some most interesting -cases of illness, cases which have been as completely investigated as -possible. As an example of the symptoms produced, one of Mr. Snell's -cases may be here quoted. - -[228] _Medical Chronicle_, 1889, 89. - -[229] _Practitioner_, 1889, ii. 15. - -[230] _Brit. Med. Journ._, March 3, 1894. - -[Illustration: Diagram of Visual Field.] - -C. F. W., aged 38, consulted Mr. Snell for his defective sight on April -9, 1892. He had been a mixer at a factory for the manufacture of -explosives. He was jaundiced, the conjunctiva yellow, and the lips blue. -He was short of breath, and after the day's work experienced aching of -the forearms and legs and tingling of the fingers. The urine was black -in colour, of sp. gr. 1024; it was examined spectroscopically by Mr. -MacMunn, who reported the black colour as due neither to indican, nor to -blood, nor bile, but to be caused by some pigment belonging to the -aromatic series. The patient's sight had been failing since the previous -Christmas. Vision in the right eye was 6/24, left 6/36, both optic -papillae were somewhat pale. In each eye there was a central scotoma for -red, and contraction of the field (see diagram). The man gradually gave -up the work, and ultimately seems to have recovered. It is, however, -interesting to note that, after having left the work for some weeks, he -went back for a single day to the "mixing," and was taken very ill, -being insensible and delirious for five hours. - -Sec. 249. =The Blood in Nitro-benzol Poisoning.=--The effect on the blood -has been specially studied by Huber.[231] The blood of rabbits poisoned -by dinitro-benzol is of a dark chocolate colour, and the microscope -shows destruction of the red corpuscles; the amount of destruction may -be gathered from the following:--the blood corpuscles of a rabbit before -the experiment numbered 5,588,000 per cubic centimetre; a day after the -experiment 4,856,000; a day later 1,004,000; on the third day the rabbit -died. - -[231] _Op. cit._ - -In one rabbit, although the corpuscles sank to 1,416,000, yet recovery -took place. - -Dr. MacMunn[232] has examined specimens of blood from two of Mr. Snell's -patients; he found a distinct departure from the normal; the red -corpuscles were smaller than usual, about 5 or 6 [mu] in diameter, and -the appearances were like those seen in pernicious anaemia. Huber, in -some of his experiments on animals, found a spectroscopic change in the -blood, viz., certain absorption bands, one in the red between C and D, -and two in the green between D and E; the action of reducing agents on -this dinitro-benzol blood, as viewed in a spectroscope provided with a -scale in which C = 48, D = 62, and E = 80.5, was as follows:-- - -[232] _Op. cit._ - - Dinitro-Bands. - In Red. In Green. - -----/\----- - 50-52 62-66 70-77 - After NH_{4}SO_{4}, 53-55 62-66 70-77 - " NH_{3}, 54-58 60-65 70-77 - " NH_{4}SO_{4} + NH_{3}, 52-55 60-65 70-77 - -Taking the symptoms as a whole, there has been noted:--a blue colour of -the lips, not unfrequently extending over the whole face, and even the -conjunctivae have been of a marked blue colour, giving the sufferer a -strange livid appearance. In other cases there have been jaundice, the -conjunctivae and the skin generally being yellow, the lips blue. -Occasionally gastric symptoms are present. Sleeplessness is common, and -not unfrequently there is some want of muscular co-ordination, and the -man staggers as if drunk. In more than one case there has been noticed -sudden delirium. There is in chronic cases always more or less anaemia, -and the urine is remarkable in its colour, which ranges from a slightly -dark hue up to positive blackness. In a large proportion of cases there -is ophthalmic trouble, the characteristics of which (according to Mr. -Snell) are "failure of sight, often to a considerable degree, in a more -or less equal extent on the two sides; concentric attraction of visual -field with, in many cases, a central colour scotoma; enlargement of -retinal vessels, especially the veins; some blurring, never extensive, -of edges of disc, and a varying degree of pallor of its surface--the -condition of retinal vessels spoken of being observed in workers with -the dinitro-benzol, independently of complaints of defective sight. -Cessation of work leads to recovery." - -Sec. 250. =Detection of Dinitro-benzol.=--Dinitro-benzol may be detected in -urine, in blood, and in fluids generally, by the following -process:--Place tinfoil in the fluid, and add hydrochloric acid to -strong acidity, after allowing the hydrogen to be developed for at least -an hour, make the fluid alkaline by caustic soda, and extract with ether -in a separating tube; any metaphenylene-diamine will be contained in the -ether; remove the ether into a flask, and distil it off; dissolve the -residue in a little water. - -Acidify a solution of sodium nitrite with dilute sulphuric acid; on -adding the solution, if it contains metaphenylene-diamine, a yellow to -red colour will be produced, from the formation of Bismarck brown -(triamido-phenol). - - -XII.--Hydrocyanic Acid. - -Sec. 251. =Hydrocyanic Acid= (=hydric cyanide=)--specific gravity of liquid -0.7058 at 18 deg. C., boiling-point 26.5 deg. (80 deg. F.), HCy = 27.--The anhydrous -acid is not an article of commerce, and is only met with in the -laboratory. It is a colourless, transparent liquid, and so extremely -volatile that, if a drop fall on a glass plate, a portion of it freezes. -It has a very peculiar peach-blossom odour, and is intensely poisonous. -It reddens litmus freely and transiently, dissolves red oxide of mercury -freely, forms a white precipitate of argentic cyanide when treated with -silver nitrate, and responds to the other tests described hereafter. - -Sec. 252. =Medicinal Preparations of Prussic Acid.=--The B.P. acid is a -watery solution of prussic acid; its specific gravity should be 0.997, -and it should contain 2 per cent. of the anhydrous acid, 2 per cent. is -also the amount specified in the pharmacop[oe]ias of Switzerland and -Norway, and in that of Borussica (VI. ed.); the latter ordains, however, -a spirituous solution, and the Norwegian an addition of 1 per cent. of -concentrated sulphuric acid. The French prussic acid is ordered to be -prepared of a strength equalling 10 per cent. - -The adulterations or impurities of prussic acid are hydrochloric, -sulphuric,[233] and formic acids. Traces of silver may be found in the -French acid, which is prepared from cyanide of silver. Tartaric acid is -also occasionally present. Hydrochloric acid is most readily detected by -neutralising with ammonia, and evaporating to dryness in a water-bath; -the ammonium cyanide decomposes and volatilises, leaving as a saline -residue chloride of ammonium. This may easily be identified by the -precipitate of chloride of silver, which its solution gives on testing -with silver nitrate, and the deep brown precipitate with Nessler -solution. Sulphuric acid is, of course, detected by chloride of barium; -formic acid by boiling a small quantity with a little mercuric oxide; if -present, the oxide will be reduced, and metallic mercury fall as a grey -precipitate. Silver, tartaric acid, and any other fixed impurities are -detected by evaporating the acid to dryness, and examining any residue -which may be left. It may be well to give the various strengths of the -acids of commerce in a tabular form:-- - -[233] A trace of sulphuric or hydrochloric acid should not be called an -_adulteration_, for it greatly assists the preservation, and therefore -makes the acid of greater therapeutic efficiency. - - Per cent. - - British Pharmacop[oe]ia, Switzerland, and Bor. (vj), 2 - France, 10 - Vauquelin's Acid, 3.3 - Scheele's " 4 to 5[234] - Riner's " 10 - Robiquet's " 50 - Schraeder's " 1.5 - Duflos' " 9 - Pfaff's " 10 - Koller's " 25 - -[234] Strength very uncertain. - -In English commerce, the analyst will scarcely meet with any acid -stronger than Scheele's 5 per cent. - -Impure oil of bitter almonds contains hydric cyanide in variable -quantity, from 5 per cent. up to 14 per cent. There is an officinal -preparation obtained by digesting cherry-laurel leaves in water, and -then distilling a certain portion over. This _Aqua Lauro-cerasi_ belongs -to the old school of pharmacy, and is of uncertain strength, but varies -from .7 to 1 per cent. of HCN. - -Sec. 253. =Poisoning by Prussic Acid.=--Irrespective of suicidal or -criminal poisoning, accidents from prussic acid may occur-- - -1. From the use of the cyanides in the arts. - -2. From the somewhat extensive distribution of the acid, or rather of -prussic-acid producing substances in the vegetable kingdom. - -1. =In the Arts.=--The galvanic silvering[235] and gilding of metals, -photography, the colouring of black silks, the manufacture of Berlin -blue, the dyeing of woollen cloth, and in a few other manufacturing -processes, the alkaline cyanides are used, and not unfrequently fumes of -prussic acid developed. - -[235] The preparation used for the silvering of copper vessels is a -solution of cyanide of silver in potassic cyanide, to which is added -finely powdered chalk. Manipulations with this fluid easily develop -hydrocyanic acid fumes, which, in one case related by Martin (_Aerztl. -Intelligenzbl._, p. 135, 1872), were powerful enough to produce symptoms -of poisoning. - -2. =In the Animal Kingdom.=--One of the myriapods (_Chilognathen_) -contains glands at the roots of the hairs, which secrete prussic acid; -when the insect is seized, the poisonous secretion is poured out from -the so-called _foramina repugnatoria_. - -3. =In the Vegetable Kingdom.=--A few plants contain cyanides, and many -contain amygdalin, or bodies formed on the type of amygdalin. In the -presence of emulsin (or similar principles) and water, this breaks up -into prussic acid and other compounds--an interesting reaction usually -represented thus-- - - C_{20}H_{27}NO_{11} + 2H_{2}O = CNH + C_{7}H_{6}O + 2C_{6}H_{12}O_{6}. - -1 equivalent of amygdalin--_i.e._, 457 parts--yielding 1 equivalent of -CNH or 27 parts; in other words, 100 parts of amygdalin yield -theoretically 5.909 parts of prussic acid,[236] so that, the amount of -either being known, the other can be calculated from it. - -[236] According to Liebig and Woehler, 17 grms. of amygdalin yield 1 of -prussic acid (_i.e._, 5.7 per cent.) and 8 of oil of bitter almonds. -Thirty-four parts of amygdalin, mixed with 66 of emulsin of almonds, -give a fluid equalling the strength of acid of most pharmacop[oe]ias, -viz., 2 per cent. - -Greshoff[237] has discovered an amygdalin-like glucoside in the two -tropical trees _Pygeum parriflorum_ and _P. latifolium_. The same author -states that the leaves of _Gymnema latifolium_, one of the Asclepiads, -yields to distillation benzaldehyde hydrocyanide. Both _Lasia_ and -_Cyrtosperma_, plants belonging to the natural family of the Orontads, -contain in their flowers potassic cyanide. _Pangium edule_, according to -Greshoff, contains so much potassic cyanide that he was able to prepare -a considerable quantity of that salt from one sample of the plant. An -Indian plant (_Hydnocarpus inebrians_) also contains a cyanide, and has -been used for the purpose of destroying fish. Among the Tiliads, -Greshoff found that _Echinocarpus Sigun_ yielded hydrocyanic acid on -distillation. Even the common linseed contains a glucoside which breaks -up into sugar, prussic acid, and a ketone. - -[237] M. Greshoff--_Erster Bericht ueber die Untersuchung von -Pflanzenstoffen Niederlaendisch-Indiens. Mittheilungen aus dem -chemisch-pharmakologischen Laboratorium des botan. Gartens des Staates_, -vii., Batavia, 1890, Niederlaendisch. Dr. Greshoff's research indicates -that there are several other cyanide-yielding plants than those -mentioned in the text. - -The following plants, with many others, all yield, by appropriate -treatment, more or less prussic acid:--Bitter almonds (_Amygdalus -communis_); the _Amygdalus persica_; the cherry laurel (_Prunus -laurocerasus_); the kernels of the plum (_Prunus domestica_); the bark, -leaves, flowers, and fruit of the wild service-tree (_Prunus padus_); -the kernels of the common cherry and the apple; the leaves of the -_Prunus capricida_; the bark of the _Pr. virginiana_; the flowers and -kernels of the _Pr. spinosa_; the leaves of the _Cerasus acida_; the -bark and almost all parts of the _Sorbus aucuparia_, _S. hybrida_, and -_S. torminalis_; the young twigs of the _Crataegus oxyacantha_; the -leaves and partly also the flowers of the shrubby _Spiraeaceae_, such as -_Spiraea aruncus_, _S. sorbifolia_, and _S. japonica_;[238] together with -the roots of the bitter and sweet _Cassava_. - -[238] The bark and green parts of the _Prunus avium_, L., _Prunus -mahaleb_, L., and herbaceous _Spiraeae_ yield no prussic acid. - -In only a few of these, however, has the exact amount of either prussic -acid or amygdalin been determined; 1 grm. of bitter almond pulp is about -equal to 2-1/2 mgrms. of anhydrous prussic acid. The kernels from the -stones of the cherry, according to Geiseler, yield 3 per cent. of -amygdalin; therefore, 1 grm. equals 1.7 mgrm. of HCN. - -Sec. 254. The wild service-tree (_Prunus padus_) and the cherry-laurel -(_Prunus Laurocerasus_) contain, not amygdalin but a compound of -amygdalin with amygdalic acid; to this has been given the name of -laurocerasin. It was formerly known as amorphous amygdalin; its formula -is C_{40}H_{55}NO_{24}; 933 parts are equivalent to 27 of hydric -cyanide--that is, 100 parts equal to 2.89. - -In the bark of the service-tree, Lehmann found .7 per cent. of -laurocerasin (= .02 HCN), and in the leaves of the cherry-laurel 1.38 -per cent. (= 0.39 HCN). - -Francis,[239] in a research on the prussic acid in cassava root, gives -as the mean in the sweet cassava .0168 per cent., in the bitter .0275 -per cent., the maximum in each being respectively .0238 per cent., and -.0442 per cent. The bitter-fresh cassava root has long been known as a -very dangerous poison; but the sweet has hitherto been considered -harmless, although it is evident that it also contains a considerable -quantity of prussic acid. - -[239] "On Prussic Acid from Cassava," _Analyst_, April 1877, p. 5. - -The kernels of the peach contain about 2.85 per cent. amygdalin (= .17 -HCN); those of the plum .96 per cent. (= .056 HCN); and apple pips .6 -per cent. (= .035 per cent. HCN). - -It is of great practical value to know, even approximately, the quantity -of prussic acid contained in various fruits, since it has been adopted -as a defence in criminal cases that the deceased was poisoned by prussic -acid developed in substances eaten. - -Sec. 255. =Statistics.=--Poisoning by the cyanides (prussic acid or -cyanide of potassium) occupies the third place among poisons in order -of frequency in this country, and accounts for about 40 deaths annually. - -In the ten years ending 1892 there were recorded no less than 395 cases -of accidental, suicidal, or homicidal poisoning by prussic acid and -potassic cyanide. The further statistical details may be gathered from -the following tables:-- - -DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS 1883-1892 FROM PRUSSIC -ACID AND POTASSIC CYANIDE. - - PRUSSIC ACID (ACCIDENT OR NEGLIGENCE). - - Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total - above - Males, ... 1 1 1 12 1 16 - Females, 1 1 ... 2 7 ... 11 - -------------------------------------------- - Totals, 1 2 1 3 19 1 27 - -------------------------------------------- - - CYANIDE OF POTASSIUM (ACCIDENT OR NEGLIGENCE). - - Ages, 1-5 5-15 15-25 25-65 65 and Total - above - Males, 1 1 4 1 ... 7 - Females, 1 ... ... 3 ... 4 - --------------------------------------- - Totals, 2 1 4 4 ... 11 - --------------------------------------- - - PRUSSIC ACID (SUICIDE). - - Ages, 15-25 25-65 65 and Total - above - Males, 23 156 23 202 - Females, 5 13 1 19 - ---------------------------- - Totals, 28 169 24 221 - ---------------------------- - - POTASSIUM CYANIDE (SUICIDE). - - Ages, 5-15 15-25 25-65 65 and Total - above - Males, 1 6 88 5 100 - Females, ... 6 15 1 22 - ---------------------------------- - Totals, 1 12 103 6 122 - ---------------------------------- - -To these figures must be added 10 cases of murder (2 males and 8 -females) by prussic acid, and 4 cases of murder (3 males and 1 female) -by potassic cyanide. - -In order to ascertain the proportion in which the various forms of -commercial cyanides cause death, and also the proportion of accidental, -suicidal, and criminal deaths from the same cause, Falck collated twelve -years of statistics from medical literature with the following result:-- - -In 51 cases of cyanide poisoning, 29 were caused by potassic cyanide, 9 -by hydric cyanide, 5 by oil of bitter almonds, 3 by peach stones (these -3 were children, and are classed as "domestic," that is, taking the -kernels as a food), 3 by bitter almonds (1 of the 3 suicidal and -followed by death, the other 2 "domestic"), 1 by tartaric acid and -potassic cyanide (a suicidal case, an apothecary), and 1 by -ferro-cyanide of potassium and tartaric acid. Of the 43 cases first -mentioned, 21 were suicidal, 7 criminal, 8 domestic, and 7 medicinal; -the 43 patients were 24 men, 14 children, and 5 women. - -The cyanides are very rarely used for the purpose of murder: a poison -which has a strong smell and a perceptible taste, and which also kills -with a rapidity only equalled by deadly bullet or knife-wounds, betrays -its presence with too many circumstances of a tragic character to find -favour in the dark and secret schemes of those who desire to take life -by poison. In 793 poisoning cases of a criminal character in France, 4 -only were by the cyanides. - -Hydric and potassic cyanides were once the favourite means of -self-destruction employed by suicidal photographers, chemists, -scientific medical men, and others in positions where such means are -always at hand; but, of late years, the popular knowledge of poisons has -increased, and self-poisoning by the cyanides scarcely belongs to a -particular class. A fair proportion of the deaths are also due to -accident or unfortunate mistakes, and a still smaller number to the -immoderate or improper use of cyanide-containing vegetable products. - -Sec. 256. =Accidental and Criminal Poisoning by Prussic Acid.=--The poison -is almost always taken by the mouth into the stomach, but occasionally -in other ways--such, for example, as in the case of the illustrious -chemist, Scheele, who died from inhalation of the vapour of the acid -which he himself discovered, owing to the breaking of a flask. There is -also the case related by Tardieu, in which cyanide of potassium was -introduced under the nails; and that mentioned by Carriere,[240] in -which a woman gave herself, with suicidal intent, an enema containing -cyanide of potassium. It has been shown by experiments, in which every -care was taken to render it impossible for the fumes to be inhaled, that -hydrocyanic acid applied to the eye of warm-blooded animals may destroy -life in a few minutes.[241] - -[240] "_Empoisonnement par le cyanure de potassium,--guerison_," -_Bullet. general de Therap._, 1869, No. 30. - -[241] N. Grehant, _Compt. rend. Soc. Biol._ [9], xi. 64, 65. - -With regard to errors in dispensing, the most tragic case on record is -that related by Arnold:[242]--A pharmaceutist had put in a mixture for a -child potassic cyanide instead of potassic chlorate, and the child died -after the first dose: the chemist, however, convinced that he had made -no mistake, to show the harmlessness of the preparation, drank some of -it, and there and then died; while Dr. Arnold himself, incautiously -tasting the draught, fell insensible, and was unconscious for six hours. - -[242] Arnold, A. B., "Case of Poisoning by the Cyanide of Potassium," -_Amer. Journ. of Med. Scien._, 1869. - -Sec. 257. =Fatal Dose.=--Notwithstanding the great number of persons who in -every civilised country fall victims to the cyanides, it is yet somewhat -doubtful what is the minimum dose likely to kill an adult healthy man. -The explanation of this uncertainty is to be sought mainly in the -varying strength of commercial prussic acid, which varies from 1.5 -(Schraeder's) to 50 per cent. (Robiquet's), and also in the varying -condition of the person taking the poison, more especially whether the -stomach be full or empty. In by far the greater number, the dose taken -has been much beyond that necessary to produce death, but this -observation is true of most poisonings. - -The dictum of Taylor, that a quantity of commercial prussic acid, -equivalent to 1 English grain (65 mgrm.) of the anhydrous acid, would, -under ordinary circumstances, be sufficient to destroy adult life, has -been generally accepted by all toxicologists. The minimum lethal dose of -potassic cyanide is similarly put at 2.41 grains (.157 grm.). As to -bitter almonds, if it be considered that as a mean they contain 2.5 per -cent. of amygdalin, then it would take 45 grms., or about 80 almonds, to -produce a lethal dose for an adult; with children less--in fact, 4 to 6 -bitter almonds are said to have produced poisoning in a child. - -Sec. 258. =Action of Hydric and Potassic Cyanides on Living -Organisms.=--Both hydric cyanide and potassic cyanide are poisonous to -all living forms, vegetable or animal, with the exception of certain -fungi. The cold-blooded animals take a larger relative dose than the -warm-blooded, and the mammalia are somewhat more sensitive to the -poisonous action of the cyanides than birds; but all are destroyed in a -very similar manner, and without any essential difference of action. The -symptoms produced by hydric and potassic cyanide are identical, and, as -regards general symptoms, what is true as to the one is also true as to -the other. There is, however, one important difference in the action of -these two substances, if the mere local action is considered, for -potassic cyanide is very alkaline, possessing even caustic properties. I -have seen, _e.g._, the gastric mucous membrane of a woman, who had taken -an excessive dose of potassic cyanide on an empty stomach, so inflamed -and swollen, that its state was similar to that induced by a moderate -quantity of solution of potash. On the other hand, the acid properties -of hydric cyanide are very feeble, and its effect on mucous membranes or -the skin in no way resembles that of the mineral acids. - -It attacks the animal system in two ways: the one, a profound -interference with the ordinary metabolic changes; the other, a paralysis -of the nervous centres. Schoenbein discovered that it affected the blood -corpuscles in a peculiar way; normal blood decomposes with great ease -hydrogen peroxide into oxygen and water. If to normal venous blood a -little peroxide of hydrogen be added, the blood at once becomes bright -red; but if a trace of prussic acid be present, it is of a dark brown -colour. The blood corpuscles, therefore, lose their power of conveying -oxygen to all parts of the system, and the phenomena of asphyxia are -produced. Geppert[243] has proved that this is really the case by -showing, in a series of researches, that, under the action of hydric -cyanide, less oxygen is taken up, and less carbon dioxide formed than -normal, even if the percentage of oxygen in the atmosphere breathed is -artificially increased. The deficiency of oxygen is in part due to the -fact that substances like lactic acid, the products of incomplete -combustion, are formed instead of CO_{2}. - -[243] Geppert, _Ueber das Wesen der CNH-Vergift; mit einer Tafel_, -Berlin, 1889; _Sep.-Abdr. aus Ztschr. f. klin. Med._, Bd. xv. - -At the same time the protoplasm of the tissues is paralysed, and unable -to take up the loosely bound oxygen presented. This explains a striking -symptom which has been noticed by many observers, that is, if -hydrocyanic acid be injected into an animal, the venous blood becomes of -a bright red colour; in warm-blooded animals this bright colour is -transitory, but in cold-blooded animals, in which the oxidation process -is slower, the blood remains bright red. - -Sec. 259. =Symptoms observed in Animals.=--The main differences between the -symptoms induced in cold-blooded and warm-blooded animals, by a fatal -dose of hydric cyanide, are as follows:-- - -The respiration in frogs is at first somewhat dyspn[oe]ic, then much -slowed, and at length it ceases. The heart, at first slowed, later -contracts irregularly, and at length gradually stops; but it may -continue to beat for several minutes after the respiration has ceased. -But all these progressive symptoms are without convulsion. Among -warm-blooded animals, on the contrary, convulsions are constant, and the -sequence of the symptoms appears to be--dyspn[oe]a, slowing of the -pulse, giddiness, falling down, then convulsions with expulsion of the -urine and faeces; dilatation of the pupils, exophthalmus, and finally -cessation of the pulse and breathing. The convulsions also frequently -pass into general paralysis, with loss of reflex movements, weak, -infrequent breathing, irregular, quick, and very frequent pulse, and -considerable diminution of temperature. - -The commencement of the symptoms in animals is extremely rapid, the -rapidity varying according to the dose and the concentration of the -acid. It was formerly thought that the death from a large dose of the -concentrated acid followed far more quickly than could be accounted for -by the blood carrying the poison to the nervous centres; but Blake was -among the first to point out that this doubt was not supported by facts -carefully observed, since there is always a sufficient interval between -the entry of the poison into the body and the first symptoms, to support -the theory that the poison is absorbed in the usual manner. Even when -Preyer injected a cubic centimetre of 60 per cent. acid into the jugular -vein of a rabbit, twenty-nine seconds elapsed before the symptoms -commenced. Besides, we have direct experiments showing that the -acid--when applied to wounds in limbs, the vessels of which are tied, -while the free nervous communication is left open--only acts when the -ligature is removed. Magendie describes, in his usual graphic manner, -how he killed a dog by injecting into the jugular vein prussic acid, and -"_the dog died instantly, as if struck by a cannon ball_," but it is -probable that the interval of time was not accurately noted. A few -seconds pass very rapidly, and might be occupied even by slowly pressing -the piston of the syringe down, and in the absence of accurate -measurements, it is surprising how comparatively long intervals of time -are unconsciously shortened by the mind. In any case, this observation -by Magendie has not been confirmed by the accurate tests of the more -recent experimenters; and it is universally acknowledged that, although -with strong doses of hydric cyanide injected into the circulation--or, -in other words, introduced into the system--in the most favourable -conditions for its speediest action, death occurs with appalling -suddenness, yet that it takes a time sufficiently long to admit of -explanation in the manner suggested. This has forensic importance, which -will be again alluded to. Experiments on animals show that a large dose -of a dilute acid kills quite as quickly as an equivalent dose of a -stronger acid, and in some cases it even seems to act more rapidly. If -the death does not take place within a few minutes, life may be -prolonged for hours, and even, in rare cases, days, and yet the result -be death. Coullon poisoned a dog with prussic acid; it lived for -nineteen days, and then died; but this is quite an exceptional case, and -when the fatal issue is prolonged beyond an hour, the chance of recovery -is considerable. - -Sec. 260. The length of time dogs poisoned by fatal doses survive, -generally varies from two to fifteen minutes. The symptoms are -convulsions, insensibility of the cornea, cessation of respiration, and, -finally, the heart stops--the heart continuing to beat several minutes -after the cessation of the respirations.[244] When the dose is short of -a fatal one, the symptoms are as follows:--Evident giddiness and -distress; the tongue is protruded, the breath is taken in short, hurried -gasps, there is salivation, and convulsions rapidly set in, preceded, it -may be, by a cry. The convulsions pass into paralysis and insensibility. -After remaining in this state some time, the animal again wakes up, as -it were, very often howls, and is again convulsed; finally, it sinks -into a deep sleep, and wakes up well. - -[244] N. Grehant, _Compt. rend._, t. 109, pp. 502, 503. - -Preyer noticed a striking difference in the symptoms after section of -the vagus in animals, which varied according to whether the poison was -administered by the lungs, or subcutaneously. In the first case, if the -dose is small, the respirations are diminished in frequency; then this -is followed by normal breathing; if the dose is larger, there is an -increase in the frequency of the respirations. Lastly, if a very large -quantity is introduced into the lungs, death quickly follows, with -respirations diminished in frequency. On the other hand, when the poison -is injected subcutaneously, small doses have no influence on the -breathing; but with large doses, there is an increase in the frequency -of the respirations, which sink again below the normal standard. - -Sec. 261. =Symptoms in Man.=--When a fatal but not excessive dose of either -potassic or hydric cyanide is taken, the sequence of symptoms is as -follows:--Salivation, with a feeling of constriction in the throat, -nausea, and occasionally vomiting. After a few minutes a peculiar -constricting pain in the chest is felt, and the breathing is distinctly -affected. Giddiness and confusion of sight rapidly set in, and the -person falls to the ground in convulsions similar to those of epilepsy. -The convulsions are either general, or attacking only certain groups of -muscles; there is often true trismus, and the jaws are so firmly closed -that nothing will part them. The respiration is peculiar, the -inspiration is short, the expiration prolonged,[245] and between the two -there is a long interval ever becoming more protracted as death is -imminent. The skin is pale, or blue, or greyish-blue; the eyes are -glassy and staring, with dilated pupils; the mouth is covered with foam, -and the breath smells of the poison; the pulse, at first quick and -small, sinks in a little while in frequency, and at length cannot be -felt. Involuntary evacuation of faeces, urine, and semen is often -observed, and occasionally there has been vomiting, and a portion of the -vomit has been aspirated into the air-passages. Finally, the convulsions -pass into paralysis, abolition of reflex sensibility, and gradual -ceasing of the respiration. With large doses these different stages may -occur, but the course is so rapid that they are merged the one into the -other, and are undistinguishable. The shortest time between the taking -of the acid and the commencement of the symptoms may be put at about ten -seconds. If, however, a large amount of the vapour is inhaled at once, -this period may be rather lessened. The interval of time is so short -that any witnesses generally unintentionally exaggerate, and aver that -the effects were witnessed _before_ the swallowing of the liquid--"As -the cup was at his lips"--"He had hardly drunk it," &c. There is -probably a short interval of consciousness, then come giddiness, and, it -may be, a cry for assistance; and lastly, there is a falling down in -convulsions, and a speedy death. Convulsions are not always present, the -victim occasionally appears to sink lifeless at once. Thus, in a case -related by Hufeland, a man was seen to swallow a quantity of acid, -equivalent to 40 grains of the pure acid--that is, about forty times -more than sufficient to kill him. He staggered a few paces, and then -fell dead, without sound or convulsion. - -[245] In a case quoted by Seidel (Maschka's _Handbuch_, p. 321), a man, -36 years of age, four or five minutes after swallowing 150 mgrms. -anhydrous HCN in spirits, lay apparently lifeless, without pulse or -breathing. After a few minutes was noticed an extraordinary deep -expiration, by which the ribs were drawn in almost to the spine, and the -chest made quite hollow. - -Sec. 262. The very short interval that may thus intervene between the -taking of a dose of prussic acid and loss of consciousness, may be -utilised by the sufferer in doing various acts, and thus this interval -becomes of immense medico-legal importance. The question is simply -this:--What can be done by a person in full possession of his faculties -in ten seconds? I have found from experiment that, after drinking a -liquid from a bottle, the bottle may be corked, the individual can get -into bed, and arrange the bedclothes in a suitable manner; he may also -throw the bottle away, or out of the window; and, indeed, with practice, -in that short time a number of rapid and complicated acts may be -performed. This is borne out both by experiments on animals and by -recorded cases. - -In Mr. Nunneley's numerous experiments on dogs, one of the animals, -after taking poison, "went down three or four steps of the stairs, saw -that the door at the bottom was closed, and came back again." A second -went down, came up, and went again down the steps of a long winding -staircase, and a third retained sufficient vigour to jump over another -dog, and then leap across the top of a staircase. - -In a remarkable case related by Dr. Guy,[246] in which a young man, -after drinking more wine than usual, was seized by a sudden impulse to -take prussic acid, and drank about 2 drachms, producing symptoms which, -had it not been for prompt treatment, would, in all probability, have -ended fatally--the interval is again noteworthy. After taking the poison -in bed, he rose, walked round the foot of a chest of drawers, standing -within a few yards of the bedside, placed the stopper firmly in the -bottle, and then walked back to bed with the intention of getting into -it; but here a giddiness seized him, and he sat down on the edge, and -became insensible. - -[246] _Forensic Medicine_, 4th ed., p. 615. - -A case related by Taylor is still stronger. A woman, after swallowing a -fatal dose of essence of almonds, went to a well in the yard, drew -water, and drank a considerable quantity. She then ascended two flights -of stairs and called her child, again descended a flight of stairs, fell -on her bed, and died within half an hour from the taking of the poison. - -Nevertheless, these cases and similar ones are exceptional, and only -show what is possible, not what is usual, the rule being that after -fatal doses no voluntary act of significance--save, it may be, a cry -for assistance--is performed.[247] - -[247] Dr. J. Autal, a Hungarian chemist, states that cobalt nitrate is -an efficacious antidote to poisoning by either HCN or KCN. The brief -interval between the taking of a fatal dose and death can, however, be -rarely utilised.--_Lancet_, Jan. 16, 1894. - -Sec. 263. =Chronic poisoning by hydric cyanide= is said to occur among -photographers, gilders, and those who are engaged daily in the -preparation or handling of either hydric or potassic cyanides. The -symptoms are those of feeble poisoning, headache, giddiness, noises in -the ears, difficult respiration, pain over the heart, a feeling of -constriction in the throat, loss of appetite, nausea, obstinate -constipation, full pulse, with pallor and offensive breath. -Koritschoner[248] has made some observations on patients who were made -to breathe at intervals, during many weeks, prussic acid vapour, with -the idea that such a treatment would destroy the tubercle bacilli. -Twenty-five per cent. of those treated in this way suffered from redness -of the pharynx, salivation, headache, nausea, vomiting, slow pulse, and -even albuminuria. - -[248] _Wiener klin. Woch._, 1891. - -Sec. 264. =Post-mortem Appearances.=[249]--If we for the moment leave out -of consideration any changes which may be seen in the stomach after -doses of potassic cyanide, then it may be affirmed that the pathological -changes produced by hydric and potassic cyanides mainly coincide with -those produced by suffocation. The most striking appearance is the -presence of bright red spots; these bright red spots or patches are -confined to the surface of the body, the blood in the deeper parts being -of the ordinary venous hue, unless, indeed, an enormous dose has been -taken; in that case the whole mass of blood may be bright red; this -bright colour is due, according to Kobert, to the formation of -cyanmethaemoglobin. The lungs and right heart are full of blood, and -there is a backward engorgement produced by the pulmonic block. The -veins of the neck and the vessels of the head generally are full of -blood, and, in like manner, the liver and kidneys are congested. In the -mucous membrane of the bronchial tubes there is a bloody foam, the lungs -are gorged, and often [oe]dematous in portions; ecchymoses are seen in -the pleura and other serous membranes; and everywhere, unless concealed -by putrefaction, or some strong-smelling ethereal oil, there is an odour -of hydric cyanide. - -[249] Hydric cyanide has, according to C. Brame, a remarkable antiseptic -action, and if administered in sufficient quantity to animals, preserves -them after death for a month. He considers that there is some more or -less definite combination with the tissues. - -Casper has rightly recommended the head to be opened and examined first, -so as to detect the odour, if present, in the brain. The abdominal and -chest cavities usually possess a putrefactive smell, but the brain is -longer conserved, so that, if this course be adopted, there is a greater -probability of detecting the odour. - -The stomach in poisoning by hydric cyanide is not inflamed, but if -alcohol has been taken at the same time, or previously, there may be -more or less redness. - -In poisoning by potassic cyanide, the appearances are mainly the same as -those just detailed, with, it may be, the addition of caustic local -action. I have, however, seen, in the case of a gentleman who drank -accidentally a considerable dose of potassic cyanide just after a full -meal, not the slightest trace of any redness, still less of corrosion. -Here the contents of the stomach protected the mucous membrane, or -possibly the larger amount of acid poured out during digestion -sufficiently neutralised the alkali. Potassic cyanide, in very strong -solution, may cause erosions of the lips, and the caustic effect may be -traced in the mouth, throat, gullet, to the stomach and duodenum; but -this is unusual, and the local effects are, as a rule, confined to the -stomach and duodenum. The mucous membrane is coloured blood-red, reacts -strongly alkaline,[250] is swollen, and it may be even ulcerated. The -upper layers of the epithelium are also often dyed with the -colouring-matter of the blood, which has been dissolved out by the -cyanide. This last change is a _post-mortem_ effect, and can be imitated -by digesting the mucous membrane of a healthy stomach in a solution of -cyanide. The intensity of these changes are, of course, entirely -dependent on the dose and emptiness of the stomach. If the dose is so -small as just to destroy life, there may be but little redness or -swelling of the stomach, although empty at the time of taking the -poison. In those cases in which there has been vomiting, and a part of -the vomit has been drawn into the air-passages, there may be also -inflammatory changes in the larynx. If essence of almonds has been -swallowed, the same slight inflammation may be seen which has been -observed with other essential oils, but no erosion, no strong alkaline -reaction, nor anything approaching the effects of the caustic cyanide. - -[250] The following case came under my own observation:--A stout woman, -35 years of age, the wife of a French polisher, drank, in a fit of rage, -a solution of cyanide of potassium. It was estimated that about 15 -grains of the solid substance were swallowed. She died within an hour. -The face was flushed, the body not decomposed; the mouth smelt strongly -of cyanide; the stomach had about an ounce of bloody fluid in it, and -was in a most intense state of congestion. There was commencing fatty -degeneration of the liver, the kidneys were flabby, and the capsule -adherent. The contents of the stomach showed cyanide of potassium, and -the blood was very fluid. The woman was known to be of intemperate -habits. - -In poisoning by bitter almonds no inflammatory change in the mucous -membrane of the coats of the stomach would be anticipated, yet in one -recorded case there seems to have been an eroded and inflamed patch. - -Sec. 265. =Tests for Hydrocyanic Acid and Cyanide of Potassium.=--(1.) The -addition of silver nitrate to a solution containing prussic acid, or a -soluble cyanide,[251] produces a precipitate of argentic cyanide. 100 -parts of argentic cyanide are composed of 80.60 Ag and 19.4 CN, -equivalent to 20.1 HCN. It is a white anhydrous precipitate, soluble -either in ammonia or in a solution of cyanide of potassium. It is -soluble in hot dilute nitric acid, but separates on cooling. A particle -of silver cyanide, moistened with strong ammonia, develops needles; -silver chloride treated similarly, octahedral crystals. It is insoluble -in water. Upon ignition it is decomposed into CN and metallic silver, -mixed with a little paracyanide of silver. - -[251] In the case of testing in this way for the alkaline cyanides, the -solution must contain a little free nitric acid. - -A very neat process for the identification of cyanide of silver is the -following:--Place the perfectly dry cyanide in a closed or sealed tube, -containing a few crystals of iodine. On heating slightly, iodide of -cyanogen is sublimed in beautiful needles. These crystals again may be -dissolved in a dilute solution of potash, a little ferrous sulphate -added, and hydrochloric acid, and in this way Prussian blue produced. If -the quantity to be tested is small, the vapour of the acid may be -evolved in a very short test-tube, the mouth of which is closed by the -ordinary thin discs of microscopic glass, the under surface of which is -moistened with a solution of nitrate of silver; the resulting crystals -of silver cyanide are very characteristic, and readily identified by the -microscope. - -(2.) If, instead of silver nitrate, the disc be moistened with a -solution of sulphate of iron (to which has been added a little potash), -and exposed to the vapour a short time, and then some dilute -hydrochloric acid added, the moistened surface first becomes yellow, -then green, lastly, and permanently, blue. No other blue compound of -iron (with the exception of Prussian blue) is insoluble in dilute -hydrochloric acid. - -(3.) A third, and perhaps the most delicate of all, is the so-called -sulphur test. A yellow sulphide of ammonium, containing free sulphur, is -prepared by saturating ammonia by SH_{2}, first suspending in the fluid -a little finely-precipitated sulphur (or an old, ill-preserved solution -of sulphide of ammonium may be used). Two watch-glasses are now taken; -in the one the fluid containing prussic acid is put, and the second -(previously moistened with the sulphide of ammonium described) is -inverted over it. The glasses are conveniently placed for a few minutes -in the water-oven; the upper one is then removed, the moist surface -evaporated to dryness in the water-bath, a little water added, and then -a small drop of solution of chloride of iron. If hydrocyanic acid is -present, the sulphocyanide of iron will be formed of a striking -blood-red colour. - -(4.) The reaction usually called Schoenbein's, or Pagenstecher and -Schoenbein's[252] (but long known,[253] and used before the publication -of their paper), consists of guaiacum paper, moistened with a very -dilute solution of sulphate of copper (1 : 2000). This becomes blue if -exposed to the vapour of hydrocyanic acid. Unfortunately, the same -reaction is produced by ammonia, ozone, nitric acid, hypochlorous acid, -iodine, bromine, chromate of potash, and other oxidising agents, so that -its usefulness is greatly restricted. - -[252] _Neues Repert. de Pharm._, 18, 356. - -[253] This reaction (with tincture of guaiacum and copper) has been long -known. "I remember a pharmaceutist, who attended my father's laboratory, -showing me this test in 1828 or 1829."--Mohr's _Toxicologie_, p. 92. - -(5.) A very delicate test for prussic acid is as follows:--About -one-half centigrm. of ammonia, ferrous sulphate (or other pure ferrous -salt), and the same quantity of uranic nitrate, are dissolved in 50 c.c. -of water, and 1 c.c. of this test-liquid is placed in a porcelain dish. -On now adding a drop of a liquid containing the smallest quantity of -prussic acid, a grey-purple colour, or a distinct purple precipitate is -produced.[254] - -[254] M. Carey Lea, _Amer. Journ. of Science_ [3], ix. pp. 121-123; _J. -C. Society_, 1876, vol. i. p. 112. - -(6.) A hot solution of potassic cyanide, mixed with picric acid, assumes -a blood-red colour, due to the formation of picro-cyanic acid. Free HCN -does not give this reaction, and therefore must first be neutralised by -an alkali. - -(7.) =Schoenbein's Test.=--To a few drops of defibrinated ox-blood are -added a few drops of the carefully-neutralised distillate supposed to -contain prussic acid, and then a little neutral peroxide of hydrogen is -added. If the distillate contains no prussic acid, then the mixture -becomes of a bright pure red and froths strongly; if, on the other hand, -a trace of prussic acid be present, the liquid becomes brown and does -not froth, or only slightly does so. - -(8.) =Kobert's Test.=--A 1-4 per cent. solution of blood, to which a -trace of ferridcyanide of potassium is added, is prepared, and the -neutralised distillate added to this solution. If hydric cyanide be -present, then the liquid becomes of a bright red colour, and, examined -spectroscopically, instead of the spectrum of methaemoglobin, will be -seen the spectrum of cyanmethaemoglobin. Kobert proposes to examine the -blood of the poisoned, for the purpose of diagnosis, during life. A drop -of blood from a healthy person, and a drop of blood from the patient, -are examined side by side, according to the process just given. - -Sec. 266. =Separation of Hydric Cyanide or Potassic Cyanide from Organic -Matters, such as the Contents of the Stomach, &c.=--It is very -necessary, before specially searching for hydric cyanide in the contents -of the stomach, to be able to say, by careful and methodical -examination, whether there are or are not any fragments of bitter -almonds, of apples, peaches, or other substance likely to produce hydric -cyanide. If potassic cyanide has been taken, simple distillation will -always reveal its presence, because it is found partly decomposed into -hydric cyanide by the action of the gastric acids. Nevertheless, an acid -should always be added, and if, as in the routine process given at p. -48, there is reasonable doubt for suspecting that there will be no -cyanide present, it will be best to add tartaric acid (for this organic -acid will in no way interfere with subsequent operations), and distil, -as recommended, in a vacuum. If, however, from the odour and from the -history of the case, it is pretty sure to be a case of poisoning by -hydric or potassic cyanide, then the substances, if fluid, are at once -placed in a retort or flask, and acidified with a suitable quantity of -sulphuric acid, or if the tissues or other solid matters are under -examination, they are finely divided, or pulped, and distilled, after -acidifying with sulphuric acid as before. It may be well here, as a -caution, to remark that the analyst must not commit the unpardonable -error of first producing a cyanide by reagents acting on animal matters, -and then detecting as a poison the cyanide thus manufactured. If, for -example, a healthy liver is carbonised by nitric acid, saturated with -potash, and then burnt up, cyanide of potassium is always one of the -products; and, indeed, the ashes of a great variety of nitrogenous -organic substances may contain cyanides--cyanides not pre-existing, but -manufactured by combination. By the action of nitric acid even on -sugar,[255] hydric cyanide is produced. - -[255] _Chemical News_, 68, p. 75. - -The old method of distillation was to distil by the gentle heat of a -water-bath, receiving the distillate in a little weak potash water, and -not prolonging the process beyond a few hours. The experiments of -Sokoloff, however, throw a grave doubt on the suitability of this simple -method for quantitative results. - -N. Sokoloff[256] recommends the animal substances to be treated by water -strongly acidified with hydric sulphate, and then to be distilled in the -water-bath for from two to three days; or to be distilled for -twenty-four hours, by the aid of an oil-bath, at a high temperature. He -gives the following example of quantitative analysis by the old process -of merely distilling for a few hours, and by the new:-- - -[256] _Ber. d. deutsch. chem. Gesellsch._, Berlin, ix. p. 1023. - -=Old Process.=--(1.) Body of a hound--age, 2 years; weight, 5180 grms.; -dose administered, 57 mgrms. HCN; death in fifteen minutes. After five -days there was found in the saliva 0.6 mgrm., stomach 3.2 mgrms., in the -rest of the intestines 2.6 mgrms., in the muscles 4.1--total, 10.5. - -(2.) Weight of body, 4000 grms.; dose given, 38 mgrms.; death in eleven -minutes. After fifteen days, in the saliva 0.8, in the stomach 7.2, in -the rest of the intestines 2.2, in the muscles 3.2--total, 13.4. - -=New Process.=--Weight of body, 5700 grams; dose, 57 mgrms.; death in -twenty-four minutes. After fifteen days, in the saliva 1.1 mgrm., in the -stomach 2.6, in the rest of the intestines 9.6, in the muscles 31.9, and -in the whole, 45.2 mgrms. Duration of process, thirteen hours. - -From a second hound, weighing 6800 grms.; dose, 67 mgrms.; 25.1 mgrms. -were separated three days after death. - -From a third hound, weighing 5920 grms.; dose, 98 mgrms.; after forty -days, by distillation on a sand-bath, there were separated 2.8 mgrms. -from the saliva, 4.8 from the stomach, 16.8 from the intestines, 23.6 -from the muscles--total, 48 mgrms. - -It would also appear that he has separated 51.2 mgrms. of anhydrous acid -from the corpse of a dog which had been poisoned by 57 mgrms. of acid, -and buried sixty days.[257] - -[257] Without wishing to discredit the statements of M. Sokoloff, we may -point out that a loss of half-a-dozen mgrms. only appears rather -extraordinary. - -From another canine corpse, three days laid in an oven, and left for -twenty-seven days at the ordinary temperature, 5.1 mgrms. were recovered -out of a fatal dose of 38 mgrms. - -The estimation was in each case performed by titrating the distillate -with argentic nitrate, the sulphur compounds having been previously got -rid of by saturating the distillate with KHO, and precipitating by lead -acetate. - -Venturoli[258] has, on the contrary, got good quantitative results -without distillation at all. A current of pure hydrogen gas is passed -through the liquid to be tested and the gas finally made to bubble -through silver nitrate. He states that the whole of the hydric cyanide -present is carried over in an hour. Metallic cyanides must be decomposed -by sulphuric acid or tartaric acid. Mercury cyanide must be decomposed -with SH_{2}, the solution acidified with tartaric acid, neutralised with -freshly precipitated calcic carbonate to fix any ferro- or -ferri-cyanides present, and hydrogen passed in and the issuing gases led -first through a solution of bismuth nitrate to remove SH_{2} and then -into the silver solution. - -[258] L'Orosi. xv. 85-88. - -Sec. 267. =How long after Death can Hydric or Potassic Cyanides be -Detected?=--Sokoloff appears to have separated prussic acid from the -body of hounds at very long periods after death--in one case sixty days. -Dragendorff recognised potassic cyanide in the stomach of a hound after -it had been four weeks in his laboratory,[259] and in man eight days -after burial. Casper also, in his 211th case, states that more than 18 -mgrms. of anhydrous prussic acid were obtained from a corpse eight days -after death.[260] Dr. E. Tillner[261] has recognised potassic cyanide in -a corpse four months after death. Lastly, Struve[262] put 300 grms. of -flesh, 400 of common water, and 2.378 of KCy in a flask, and then opened -the flask after 547 days. The detection was easy, and the estimation -agreed with the amount placed there at first. So that, even in very -advanced stages of putrefaction, and at periods after death extending -beyond many months, the detection of prussic acid cannot be pronounced -impossible. - -[259] Dragendorff, G., _Beitr. zur gericht. Chem._, p. 59. - -[260] Casper's _Pract. Handbuch der gerichtlichen Medicin_, p. 561. - -[261] _Vierteljahr. f. gerichtl. Med._, Berlin, 1881, p. 193. - -[262] _Zeitschrift f. anal. Chemie_, von Fresenius, 1873, xii. p. 4. - -Sec. 268. =Estimation of Hydrocyanic Acid or Potassic Cyanide.=--In all -cases, the readiest method of estimating prussic acid (whether it be in -the distillate from organic substances or in aqueous solution) is to -saturate it with soda or potash, and titrate the alkaline cyanide thus -formed with nitrate of silver. The process is based on the fact that -there is first formed a soluble compound (KCy, AgCy), which the -slightest excess of silver breaks up, and the insoluble cyanide is at -once precipitated. If grains are used, 17 grains of nitrate of silver -are dissolved in water, the solution made up to exactly 1000 grain -measures, each grain measure equalling .0054 grain of anhydrous -hydrocyanic acid. If grammes are employed, the strength of the nitrate -of silver solution should be 1.7 grm. to the litre, each c.c. then = -.0054 hydrocyanic acid, or .01302 grm. of potassic cyanide. - -Essential oil of bitter almonds may also be titrated in this way, -provided it is diluted with sufficient spirit to prevent turbidity from -separation of the essential oil. If hydrocyanic acid is determined -gravimetrically (which is sometimes convenient, when only a single -estimation is to be made), it is precipitated as cyanide of silver, the -characters of which have been already described. - - Sec. 269. =Case of Poisoning by Bitter Almonds.=--Instances of - poisoning by bitter almonds are very rare. The following interesting - case is recorded by Maschka:-- - - A maid-servant, 31 years of age, after a quarrel with her lover, ate - a quantity of bitter almonds. In a few minutes she sighed, - complained of being unwell and faint; she vomited twice, and, after - about ten minutes more had elapsed, fell senseless and was - convulsed. An hour afterwards, a physician found her insensible, the - eyes rolled upwards, the thumb clenched within the shut fists, and - the breathing rattling, the pulse very slow. She died within an - hour-and-a-half from the first symptoms. - - The autopsy showed the organs generally healthy, but all, save the - liver, exhaling a faint smell of bitter almonds. The right side of - the heart was full of fluid dark blood, the left was empty. Both - lungs were rich in blood, which smelt of prussic acid. The stomach - was not inflamed--it held 250 grms. of a yellow fluid, containing - white flocks smelling of bitter almond oil. In the most dependent - portion of the stomach there was a swollen patch of mucous membrane, - partially denuded of epithelium. The mucous membrane of the duodenum - was also swollen and slightly red. The contents of the stomach were - acid, and yielded, on distillation, hydride of benzole and hydric - cyanide. Residues of the almonds themselves were also found, and - the whole quantity taken by the woman from various data was - calculated to be 1200 grains of bitter almonds, equal to 43 grains - of amygdalin, or 2.5 grains of pure hydric cyanide. - - -Poisonous Cyanides other than Hydric and Potassic Cyanides. - - Sec. 270. The action of both _sodic and ammonic cyanides_ is precisely - similar to that of potassic cyanide. With regard to ammonic cyanide, - there are several experiments by Eulenberg,[263] showing that its - vapour is intensely poisonous. - -[263] _Gewerbe Hygiene_, p. 385. - - A weak stream of ammonic cyanide vapour was passed into glass - shades, under which pigeons were confined. After a minute, symptoms - of distress commenced, then followed convulsions and speedy death. - The _post-mortem_ signs were similar to those produced by prussic - acid, and this substance was separated from the liver and lungs. - - Sec. 271. With regard to the _double cyanides_, all those are poisonous - from which hydric cyanide can be separated through dilute acids, - while those which, like potassic ferro-cyanide, do not admit of this - decomposition, may be often taken with impunity, and are only - poisonous under certain conditions. - - Sonnenschein records the death of a colourist, after he had taken a - dose of potassic ferro-cyanide and then one of tartaric acid; and - Volz describes the death of a man, who took potassic ferro-cyanide - and afterwards equal parts of nitric and hydrochloric acids. In this - latter case, death took place within the hour, with all the symptoms - of poisoning by hydric cyanide; so that it is not entirely true, as - most text-books declare, that ferro-cyanide is in no degree - poisonous. Carbon dioxide will decompose potassic ferro-cyanide at - 72 deg.-74 deg., potass ferrous cyanide being - precipitated--K_{2}Fe_{2}(CN)_{6}. A similar action takes place if - ferro-cyanide is mixed with a solution of peptone and casein, and - digested at blood heat[264] (from 37 deg. to 40 deg. C.), so that it is - believed that when ferro-cyanide is swallowed HCN is liberated, but - the quantity is usually so small at any given moment that no injury - is caused: but there are conditions in which it may kill - speedily.[265] - -[264] Autenrieth, _Arch. Pharm._, 231, 99-109. - -[265] The presence of ferro-cyanide is easily detected. The liquid is, -if necessary, filtered and then acidified with hydrochloric acid and a -few drops of ferric chloride added; if the liquid contains -ferro-cyanide, there is immediate production of Prussian blue. It may -happen that potassic or sodic cyanide has been taken as well as -ferro-cyanide, and it will be necessary then to devise a process by -which only the prussic acid from the simple cyanide is distilled over. -According to Autenrieth, if sodium hydrocarbonate is added to the liquid -in sufficient quantity and the liquid distilled, the hydric cyanide that -comes over is derived wholly from the sodium or potassium cyanide. -Should mercury cyanide and ferro-cyanide be taken together, then this -process requires modification; bicarbonate of soda is added as before, -and then a few c.c. of water saturated with hydric sulphide; under these -circumstances, only the hydric cyanide derived from the mercury cyanide -distils over. If the bicarbonate of soda is omitted, the distillate -contains hydric cyanide derived from the ferro-cyanide. - - =Mercuric cyanide=, it has been often said, acts precisely like - mercuric chloride (corrosive sublimate), and a poisonous action is - attributed to it not traceable to cyanogen; but this is erroneous - teaching. Bernard[266] declares that it is decomposed by the gastric - juice, and hydric cyanide set free; while Pelikan puts it in the - same series as ammonic and potassic cyanides. Lastly, - Tolmatscheff,[267] by direct experiment, has found its action to - resemble closely that of hydric cyanide.[268] - -[266] _Substances Toxiques_, pp. 66-103. - -[267] "_Einige Bemerkungen ueber die Wirkung von Cyanquecksilber_," in -Hoppe-Seyler's _Med. Chem. Untersuchungen_, 2 Heft, p. 279. - -[268] Mercury cyanide may be detected in a liquid after acidifying with -tartaric acid, and adding a few c.c. of SH_{2} water and then -distilling. S. Lopes suggests another process: the liquid is acidified -with tartaric acid, ammonium chloride added in excess, and the liquid is -distilled. A double chloride of ammonium and mercury is formed, and HCN -distils over with the steam.--_J. Pharm._, xxvii. 550-553. - - =Silver cyanide= acts, according to the experiments of Nunneley, - also like hydric cyanide, but very much weaker. - - =Hydric sulphocyanide= in very large doses is poisonous. - - =Potassic sulphocyanide=, according to Dubreuil and Legros,[269] if - subcutaneously injected, causes first local paralysis of the - muscles, and later, convulsions. - -[269] _Compt. rend._, t. 64, 1867, p. 561. - - =Cyanogen chloride= (CNCl) and also the compound - (C_{3}N_{3}Cl_{3})--the one a liquid, boiling at 15 deg., the other a - solid, which may be obtained in crystals--are both poisonous, acting - like hydric cyanide. - - =Methyl cyanide= is a liquid obtained by distillation of a mixture - of calcic methyl sulphate and potassic cyanide. It boils at 77 deg., and - is intensely poisonous. Eulenberg[270] has made with this substance - several experiments on pigeons. An example of one will suffice:--A - young pigeon was placed under a glass shade, into which methyl - cyanide vapour, developed from calcic methyl sulphate and potassic - cyanide, was admitted. The pigeon immediately became restless, and - the faeces were expelled. In forty seconds it was slightly convulsed, - and was removed after a few minutes' exposure. The pupils were then - observed not to be dilated, but the respiration had ceased; the legs - were feebly twitching; the heart still beat, but irregularly; a - turbid white fluid dropped out of the beak, and after six minutes - life was extinct. - -[270] _Gewerbe Hygiene_, p. 392. - - The pathological appearances were as follows:--In the beak much - watery fluid; the membranes covering the brain weakly injected; the - _plexus venosus spinalis_ strongly injected; in the region of the - cervical vertebra a small extravasation between the dura mater and - the bone; the right lung of a clear cherry-red colour, and the left - lung partly of the same colour, the parenchyma presented the same - hue as the surface; on section of the lungs a whitish froth exuded - from the cut surface. In the cellular tissue of the trachea, there - were extravasations 5 mm. in diameter; the mucous membrane of the - air-passages was pale; the right ventricle and the left auricle of - the heart were filled with coagulated and fluid dark red blood; - liver and kidneys normal; the blood dark red and very fluid, - becoming bright cherry-red on exposure to the air; blood corpuscles - unchanged. Cyanogen was separated, and identified from the lungs and - the liver. - - =Cyanuric acid= (C_{3}O_{3}N_{3}H_{3}), one of the decomposition - products obtained from urea, is poisonous, the symptoms and - pathological effects closely resembling those due to hydric cyanide. - In experiments on animals, there has been no difficulty in detecting - prussic acid in the lungs and liver after poisoning by cyanuric - acid. - - -XIII.--Phosphorus. - -Sec. 272. =Phosphorus.=--Atomic weight 31, specific gravity 1.77 to 1.840. -Phosphorus melts at from 44.4 deg. to 44.5 deg. to a pale yellow oily fluid. The -boiling-point is about 290 deg. - -The phosphorus of commerce is usually preserved under water in the form -of waxy, semi-transparent sticks; if exposed to the air white fumes are -given off, luminous in the dark, with a peculiar onion-like odour. On -heating phosphorus it readily inflames, burning with a very white flame. - -At 0 deg. phosphorus is brittle; the same quality may be imparted to it by a -mere trace of sulphur. Phosphorus may be obtained in dodecahedral -crystals by slowly cooling large melted masses. It may also be obtained -crystalline by evaporating a solution in bisulphide of carbon or hot -naphtha in a current of carbon dioxide. It is usually stated to be -absolutely insoluble in water, but Julius Hartmann[271] contests this, -having found in some experiments that 100 grms. of water digested with -phosphorus for sixty-four hours at 38.5 deg. dissolved .000127 grm. He also -investigated the solvent action of bile, and found that 100 grms. of -bile under the same conditions, dissolved .02424 grm., and that the -solubility of phosphorus rose both in water and bile when the -temperature was increased. Phosphorus is somewhat soluble in alcohol and -ether, and also, to some extent, in fatty and ethereal oils; but the -best solvent is carbon disulphide. - -[271] _Zur acuten Phosphor-Vergiftung_, Dorpat, 1866. - -The following is the order of solubility in certain menstrua, the -figures representing the number of parts by weight of the solvent -required to dissolve 1 part of phosphorus:-- - - Carbon Disulphide, 4 - Almond Oil, 100 - Concentrated Acetic Acid,[272] 100 - Ether, 250 - Alcohol, specific gravity .822, 400 - Glycerin, 588 - -[272] Phosphorus is very little soluble in cold acetic acid, and the -solubility given is only correct when the boiling acid acts for some -time on the phosphorus. - -Phosphorus exists in, or can be converted into, several allotropic -modifications, of which the red or amorphous phosphorus is the most -important. This is effected by heating it for some time, in the absence -of air, from 230 deg. to 235 deg. It is not poisonous.[273] Commercial red -phosphorus does, however, contain very small quantities of unchanged or -ordinary phosphorus--according to Fresenius, from .6 per cent. -downwards; it also contains phosphorous acid, and about 4.6 per cent. of -other impurities, among which is graphite.[274] - -[273] A hound took 200 grms. of red phosphorus in twelve days, and -remained healthy.--Sonnenschein. - -[274] Schrotter, _Chem. News_, vol. xxxvi. p. 198. - -Sec. 273. =Phosphuretted Hydrogen.=--=Phosphine= (PH_{3}), mol. weight 34, -specific gravity 1.178, percentage composition, phosphorus 91.43, -hydrogen 8.57 by weight. The absolutely pure gas is not spontaneously -inflammable, but that made by the ordinary process is so. It is a -colourless, highly poisonous gas, which does not support combustion, but -is itself combustible, burning to phosphoric acid (PH_{3} + 2O_{2} = -PO_{4}H_{3}). Extremely dangerous explosive mixtures may be made by -combining phosphine and air or oxygen. Phosphine, when quite dry, burns -with a white flame, but if mixed with aqueous vapour, it is green; hence -a hydrogen flame containing a mixture of PH_{3} possesses a green -colour. - -If sulphur is heated in a stream of phosphine, hydric sulphide and -sulphur phosphide are the products. Oxides of the metals, heated with -phosphine, yield phosphides with formation of water. Iodine, warmed in -phosphine, gives white crystals of iodine phosphonium, and biniodide of -phosphorus, 5I + 4PH_{3} = 3PIH_{4} + PI_{2}. Chlorine inflames the gas, -the final result being hydric chloride and chloride of phosphorus, -PH_{3} + 8Cl = 3ClH + PCl_{5}. One of the most important decompositions -for our purpose is the action of phosphine on a solution of nitrate of -silver; there is a separation of metallic silver, and nitric and -phosphoric acids are found in solution, thus--8AgNO_{3} + PH_{3} + -4OH_{2} = 8Ag + 8HNO_{3} + PO_{4}H_{3}. This is, however, rather the end -reaction; for, at first, there is a separation of a black precipitate -composed of phosphor-silver. The excess of silver can be separated by -hydric chloride, and the phosphoric acid made evident by the addition of -molybdic acid in excess. - -Sec. 274. =The medicinal preparations of phosphorus= are not numerous; it -is usually prescribed in the form of pills, made by manufacturers of -coated pills on a large scale. The pills are composed of phosphorus, -balsam of Tolu, yellow wax, and curd soap, and 3 grains equal 1/30 grain -of phosphorus. There is also a _phosphorated oil_, containing about 1 -part of phosphorus in 100; that of the French Pharmacop[oe]ia is made -with 1 part of dried phosphorus dissolved in 50 parts of warm almond -oil; that of the German has 1 part in 80; the strength of the former is -therefore 2 per cent., of the latter 1.25 per cent. The medicinal dose -of phosphorus is from 1/100 to 1/30 grain. - -Sec. 275. =Matches and Vermin Pastes.=--An acquaintance with the percentage -of phosphorus in the different pastes and matches of commerce will be -found useful. Most of the vermin-destroying pastes contain from 1 to 2 -per cent. of phosphorus. - -A phosphorus paste that was fatal to a child,[275] and gave rise to -serious symptoms in others, was composed as follows:-- - -[275] Casper's 204th case. - - Per cent. - Phosphorus, 1.4 - Flowers of sulphur, 42.2 - Flour, 42.2 - Sugar, 14.2 - ------ - 100.00 - -Three common receipts give the following proportions:-- - - Per cent. - Phosphorus, 1.5 - Lard, 18.4 - Sugar, 18.4 - Flour, 61.7 - ------ - 100.00 - - Per cent. - Phosphorus, 1.2 - Warm water, 26.7 - Rye flour, 26.7 - Melted butter, 26.7 - Sugar, 18.7 - ------ - 100.00 - - Per cent. - Phosphorus, 1.6 - Nut oil, 15.7 - Warm water, 31.5 - Flour, 31.5 - Sugar, 19.7 - ------ - 100.00 - -A very common phosphorus paste, to be bought everywhere in England, is -sold in little pots; the whole amount of phosphorus contained in these -varies from .324 to .388 grm. (5 to 6 grains), the active constituent -being a little over 4 per cent. Matches differ much in composition. Six -matchheads, which had been placed in an apple for criminal purposes, and -were submitted to Tardieu, were found to contain 20 mgrms. of -phosphorus--_i.e._, .33 grm. in 100. Mayet found in 100 matches 55 -mgrms. of phosphorus. Gonning[276] analysed ten different kinds of -phosphorus matches with the following result:--Three English samples -contained in 100 matches 34, 33, and 32 mgrms. of phosphorus: a Belgian -sample, 38 mgrms.; and 5 others of unknown origin, 12, 17, 28, 32, and -41 mgrms. respectively. Some of the published formularies are as -follows:-- - -[276] _Nederlandsch Tijdschr. voor Geneesk._, Afl. i., 1866. - - (1.) Glue, 6 parts. - Phosphorus, 4 " or 14.4 per cent. - Nitre, 10 " - Red ochre, 5 " - Blue smalts, 2 " - - (2.) Phosphorus, 9 parts, or 16.3 per cent. - Gum, 16 " - Nitre, 14 " - Smalts, 16 " - - (3.) Phosphorus, 4 parts, or 14.4 per cent. - Glue, 6 " - Nitre, 10 " - Red lead, 5 " - Smalts, 2 " - - (4.) Phosphorus, 17 parts, or 17 per cent. - Glue, 21 " - Nitre, 38 " - Red lead, 24 " - -Phosphorus poisoning by matches will, however, shortly become very rare, -for those containing the ordinary variety of phosphorus are gradually -being superseded by matches of excellent quality, which contain no -phosphorus whatever. - -Sec. 276. =Statistics.=--The following table gives the deaths for ten years -from phosphorus poisoning in England and Wales:-- - -DEATHS FROM PHOSPHORUS IN ENGLAND AND WALES DURING THE TEN YEARS ENDING -1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, 1-5 5-15 15-25 25-65 65 and Total - above - Males, 11 1 2 8 ... 22 - Females, 15 2 11 5 ... 33 - ------------------------------------------- - Totals, 26 3 13 13 ... 55 - ------------------------------------------- - - SUICIDE. - - Ages, 5-15 15-25 25-65 65 and Total - above - Males, 1 6 20 1 28 - Females, 6 33 24 1 64 - ------------------------------------- - Totals, 7 39 44 2 92 - ------------------------------------- - -Phosphorus as a cause of death through accident or negligence occupies -the eighth place among poisons, and as a cause of suicide the ninth. - -A far greater number of cases of poisoning by phosphorus occur yearly in -France and Germany than in England. Phosphorus may be considered as the -favourite poison which the common people on the Continent employ for the -purpose of self-destruction. It is an agent within the reach of anyone -who has 2 sous in his pocket, wherewith to buy a box of matches, but to -the educated and those who know the horrible and prolonged torture -ensuing from a toxic dose of phosphorus, such a means of exit from life -will never be favoured. - -Otto Schraube[277] has collected 92 cases from Meischner's work,[278] -and added 16 which had come under his own observation, giving in all 108 -cases. Seventy-one (or 65 per cent.) of these were suicidal--of the -suicides 24 were males, 47 females (12 of the latter being prostitutes); -21 of the cases were those of murder, 11 were accidental, and in 3 the -cause was not ascertained. The number of cases in successive years, and -the kind of poison used, is given as follows:-- - -[277] Schmidt's _Jahrbuch der ger. Med._, 1867, Bd. 186, S. 209-248. - -[278] _Die acute Phosphorose und einige Reflexionen ueber die acute gelbe -Leberatrophie, &c., Inaug. Diss._, Leipzig, 1864. - - Phosphorus in Phosphorus - Number of Cases. In the Years Substance, Matches. - or as Paste. - - 15 1798-1850 13 2 - 36 1850-1860 15 21 - 41 1860-1864 6 35 - 16 1864-1867 5 11 - -Of the 108 cases, 18 persons recovered and 90 (or 83.3 per cent.) died. - -Falck also has collected 76 cases of poisoning from various sources -during eleven years; 55 were suicidal, 5 homicidal[279] (murders), and -the rest accidental. Of the latter, 2 were caused by the use of -phosphorus as a medicine, 13 by accidents due to phosphorus being in the -house; in 1 case phosphorus was taken intentionally to try the effects -of an antidote.[280] With regard to the form in which the poison was -taken, 2 of the 76, as already mentioned, took it as prescribed by -physicians, the remaining 74 were divided between poisonings by -phosphorus paste (22) and matches (52) = 70 per cent. Of the 76 cases, 6 -were children, 43 adult males, 13 adult females, and 14 adults, sex not -given. Of the 76 cases, 42, or 55.3 per cent., died--a much smaller rate -of mortality than that shown by Schraube's collection. - -[279] Dr. Dannenberg has shown by direct experiment that a poisonous -dose of phosphorus may be introduced into spirits or coffee, and the -mixture have but little odour or taste of phosphorus.--Schuchardt in -Maschka's _Handbuch_. - -[280] Gery, "_Ueber Terpentinessenz als Gegenmittel gegen Phosphor_," in -_Gaz. Hebd. de Med._, 2 ser., x. 2, 1873. - -Sec. 277. =Fatal Dose.=--The smallest dose on record is that mentioned by -Lobenstein Lobel, of Jena, where a lunatic died from taking 7.5 mgrms. -(.116 grain). There are other cases clearly indicating that this small -quantity may produce dangerous symptoms in a healthy adult. - -Sec. 278. =Effects of Phosphorus.=--Phosphorus is excessively poisonous, -and will destroy life, provided only that it enters the body in a fine -state of division, but if taken in coarse pieces no symptoms may follow, -for it has been proved that single lumps of phosphorus will go the whole -length of a dog's intestinal canal without causing appreciable loss of -weight, and without destroying life.[281] Magendie injected _oleum -phosphoratum_ into the veins, and although the animals experimented on -exhaled white fumes, and not a few died asphyxiated, yet no symptoms of -phosphorus poisoning resulted--an observation confirmed by others--the -reason being that the phosphorus particles in a comparatively coarse -state of division were arrested in the capillaries of the lung, and may -be said to have been, as it were, outside the body. On the other hand, -A. Brunner,[282] working in L. Hermann's laboratory, having injected -into the veins phosphorus in such a fine emulsion that the phosphorus -could pass the lung capillaries, found that there were no exhalations of -white fumes, but that the ordinary symptoms of phosphorus poisoning soon -manifested themselves. Phosphorus paste, by the method of manufacture, -is in a state of extreme sub-division, and hence all the phosphorus -pastes are extremely poisonous. - -[281] Reveil, _Ann. d'Hygiene Publ._ (3), xii. p. 370. - -[282] _Arch. f. d. Ges. Physiologie_, iii. p. 1. - -Sec. 279. In a few poisons there is a difference, more or less marked, -between the general symptoms produced on man, and those noticeable in -the different classes of animals; but with phosphorus, the effects on -animals appear to agree fairly with those witnessed most frequently in -man. Tardieu (who has written perhaps the best and most complete -clinical record of phosphorus poisoning extant) divides the cases under -three classes, and to use his own words:--"I think it useful to -establish that poisoning by phosphorus in its course, sometimes rapid, -sometimes slow, exhibits in its symptoms three distinct forms--a common -form, a nervous form, and a haemorrhagic form. I recognise that, in -certain cases, these three forms may succeed each other, and may only -constitute periods of poisoning; but it is incontestable that each of -them may show itself alone, and occupy the whole course of the illness -produced by the poison."[283] Premising that the common form is a -blending of irritant, nervous, and haemorrhagic symptoms, I adopt here in -part Tardieu's division. The name of "haemorrhagic form" may be given to -that in which haemorrhage is the predominant feature, and the "nervous" -to that in which the brain and spinal cord are from the first affected. -There yet remain, however, a few cases which have an entirely anomalous -course, and do not fall under any of the three classes. - -[283] _Etude Medico-Legale et Clinique sur l'Empoisonnement_, Paris, -1875, p. 483. - -From a study of 121 recorded cases of phosphorus poisoning, I believe -the relative frequency of the different forms to be as follows:--The -common form 83 per cent., haemorrhagic 10 per cent., nervous 6 per cent., -anomalous 1 per cent. The "anomalous" are probably over-estimated, for -the reason that cases presenting ordinary features are not necessarily -published, but others are nearly always chronicled in detail. - -Sec. 280. =Common Form.=--At the moment of swallowing, a disagreeable taste -and smell are generally experienced, and there may be immediate and -intense pain in the throat, gullet, and stomach, and almost immediate -retching and vomiting. The throat and tongue also may become swollen and -painful; but in a considerable number of cases the symptoms are not at -once apparent, but are delayed from one to six hours--rarely longer. The -person's breath may be phosphorescent before he feels in any way -affected, and he may go about his business and perform a number of acts -requiring both time and mental integrity. Pain in the stomach (which, in -some of the cases, takes the form of violent cramp and vomiting) -succeeds; the matters vomited may shine in the dark, and are often -tinged with blood. Diarrh[oe]a is sometimes present, sometimes absent; -sleeplessness for the first night or two is very common. The pulse is -variable, sometimes frequent, sometimes slow; the temperature in the -morning is usually from 36.0 deg. to 36.5 deg., in the evening 37 deg. to 38 deg. - -The next symptom is jaundice. I have notes of the exact occurrence of -jaundice in 23 cases, as follows:--In 1 within twenty-four hours, in 3 -within thirty-six hours, in 3 within two days, in 11 within three days, -in 1 within four days, in 1 within five days, in 1 within nine days, in -1 within eighteen days, and in 1 within twenty-seven days; so that in -about 78 per cent. jaundice occurred before the end of the third day. -Out of 26 cases, in which the patients lived long enough for the -occurrence of jaundice, in 3 (or 11 per cent.) it was entirely absent. -In 132 cases recorded by Lewin, Meischner, and Heisler, jaundice -occurred in 65, or about 49 per cent., but it must be remembered, that -in many of these cases the individual died before it had time to -develop. The jaundice having thoroughly pronounced itself, the system -may be considered as not only under the influence of the toxic action of -phosphorus, but as suffering in addition from all the accidents -incidental to the retention of the biliary secretion in the blood; nor -is there from this point any special difference between phosphorus -poisoning and certain affections of the liver--such, for example, as -acute yellow atrophy. There is retention of urine, sleeplessness, -headache, frequent vomiting, painful and often involuntary evacuations -from the bowels, and occasionally skin affections, such as urticaria or -erythema. The case terminates either by acute delirium with fever, -followed by fatal coma, or, in a few instances, coma comes on, and the -patient passes to death in sleep without delirium. In this common form -there is in a few cases, at the end of from twenty-four to thirty hours, -a remission of the symptoms, and a non-medical observer might imagine -that the patient was about to recover without further discomfort; but -then jaundice supervenes, and the course is as described. Infants often -do not live long enough for the jaundiced stage to develop, but die -within twenty-four hours, the chief symptoms being vomiting and -convulsions. - -Sec. 281. =Haemorrhagic Form.=--The symptoms set in as just detailed, and -jaundice appears, but accompanied by a new and terrible train of -events--viz., great effusion of blood. In some cases the blood has been -poured out simultaneously from the nose, mouth, bladder, kidneys, and -bowels. Among women there is excessive haemorrhagia. The liver is found -to be swollen and painful; the bodily weakness is great. Such cases are -usually of long duration, and a person may die months after taking the -poison from weakness, anaemia, and general cachexia. In many of its -phases the haemorrhagic form resembles scurvy, and, as in scurvy, there -are spots of purpura all over the body. - -Sec. 282. =The nervous form= is less common than the two forms just -described. From the beginning, there are strange creeping sensations -about the limbs, followed by painful cramps, repeated faintings, and -great somnolence. Jaundice, as usual, sets in, erythematous spots appear -on the skin, and, about the fifth day, delirium of an acute character -breaks out, and lock-jaw and convulsions close the scene. - -The following are one or two brief abstracts of anomalous cases in which -symptoms are either wanting, or run a course entirely different from any -of the three forms described:-- - -A woman, aged 20, took about 3 grains of phosphorus in the form of -rat-paste. She took the poison at six in the evening, behaved according -to her wont, and sat down and wrote a letter to the king. During the -night she vomited once, and died the next morning at six o'clock, -exactly twelve hours after taking the poison. There appear to have been -no symptoms whatever, save the single vomiting, to which may be added -that in the course of the evening her breath had a phosphorus odour and -was luminous.[284] - -[284] Casper's 205th case. - -A girl swallowed a quantity of phosphorus paste, but there were no -marked symptoms until the fifth day, on which there was sickness and -purging. She died on the seventh day. A remarkable blueness of the -finger nails was observed a little before death, and was noticeable -afterwards.[285] - -[285] Taylor on _Poisons_, p. 277. - -Sec. 283. =Sequelae.=--In several cases in which the patients have recovered -from phosphorus poisoning, there have been observed paralytic -affections.[286] O. Bollinger has recorded a case in which paralysis of -the foot followed;[287] in another, published by Bettelheim,[288] there -were peculiar cerebral and spinal symptoms. Most of these cases are to -be explained as disturbance or loss of function from small haemorrhages -in the nervous substance. - -[286] See Gallavardin, _Les Paralyses Phosphoriques_, Paris, 1865. - -[287] _Deutsches Archiv f. klin. Med._, Bd. 6, Hft. 1, S. 94, 1869. - -[288] _Wiener Med. Presse_, 1868, No. 41. - -Sec. 284. =Period at which the first Symptoms commence.=--The time when the -symptoms commence is occasionally of importance from a forensic point of -view. I find that out of 28 cases in which the commencement of evident -symptoms--_i.e._, pain, or vomiting, or illness--is precisely recorded, -in 8 the symptoms were described as either immediate or within a few -minutes after swallowing the poison; in 6 the symptoms commenced within -the hour; in 3 within two hours; in other 3 within four hours; and in 1 -within six hours. One was delayed until the lapse of twelve hours, 1 -from sixteen to eighteen hours, 1 two, and another five days. We may, -therefore, expect that in half the cases which may occur, the symptoms -will commence within the hour, and more than 80 per cent. within six -hours. - -Sec. 285. =Period of Death.=--In 129 cases death took place as follows:--In -17 within twenty-four hours, in 30 within two days, in 103 within seven -days. Three patients lived eight days, 6 nine days, 13 ten days, 1 -eleven days, 1 sixteen days, 1 seventeen days, and 1 survived eight -months. It hence follows that 79.8 per cent. of the fatal cases die -within the week. - -Sec. 286. =Phosphorus Vapour.=--There are one or two cases on record of -acute poisoning by phosphorus in the form of vapour. The symptoms are -somewhat different from the effects produced by the finely-divided -solid, and in general terms it may be said that phosphorus vapour is -more apt to produce the rarer "nervous" form of poisoning than the solid -phosphorus. - -Bouchardat[289] mentions the case of a druggist who, while preparing a -large quantity of rat-poison in a close room, inhaled phosphorus vapour. -He fainted repeatedly, fell into a complete state of prostration, and -died within a week. - -[289] _Annuaire de Therap._, 1874, p. 109; Schuchardt in Maschka's -_Handbuch_; also Schmidt's _Jahrbuch_, 1846, Bd. 51, S. 101. - -The following interesting case came under the observation of Professor -Magnus Huss:--A man, thirty-nine years old, married, was admitted into -the Seraphin-Lazareth, Stockholm, on the 2nd of February 1842. He had -been occupied three years in the manufacture of phosphorus matches, and -inhabited the room in which the materials were preserved. He had always -been well-conducted in every way, and in good health, until a year -previously, when a large quantity of the material for the manufacture of -the matches accidentally caught fire and exploded. In his endeavours to -extinguish the flames, he breathed a large quantity of the vapour, and -he fell for a time unconscious. The spine afterwards became so weak that -he could not hold himself up, and he lost, in a great measure, power -over his legs and arms. On admission, his condition was as follows:--He -could make a few uncertain and staggering steps, his knees trembled, his -arms shook, and if he attempted to grasp anything when he lay in bed, -there were involuntary twitchings of groups of muscles. There was no -pain; the sensibility of the skin was unchanged; he had formication in -the left arm; the spine was neither sensitive to pressure, nor unusually -sensitive to heat (as, _e.g._, to the application of a hot sponge); the -organs of special sense were not affected, but his speech was somewhat -thick. He lived to 1845 in the same condition, but the paralysis became -worse. There does not seem to have been any autopsy. - -The effects of phosphorus vapour may be still further elucidated by one -of Eulenberg's[290] experiments on a rabbit. The vapour of burning -phosphorus, mixed with much air, was admitted into a wooden hutch in -which a strong rabbit sat. After 5 mgrms. of phosphorus had been in this -manner consumed, the only symptoms in half an hour were salivation, and -quickened and somewhat laboured respiration. After twenty-four hours had -elapsed there was sudden indisposition, the animal fell as if lifeless, -with the hind extremities stretched out, and intestinal movements were -visible; there was also expulsion of the urine. These epileptiform -seizures seem to have continued more or less for twelve days, and then -ceased. After fourteen days the experiment was repeated on the same -rabbit. The animal remained exposed to the vapour for three-quarters of -an hour, when the epilepsy showed itself as before, and, indeed, almost -regularly after feeding. Between the attacks the respiration was slowed. -Eight weeks afterwards there was an intense icterus, which disappeared -at the end of ten weeks. - -[290] _Gewerbe Hygiene_, p. 255. - -Sec. 287. =Chronic phosphorus poisoning= has frequently been noticed in -persons engaged either in the manufacture of phosphorus or in its -technical application. Some have held that the symptoms are due to an -oxidation product of phosphorus rather than to phosphorus itself; but in -one of Eulenberg's experiments, in which a dove was killed by breathing -phosphorus fumes evolved by phosphorus oil, phosphorus was chemically -recognised in the free state in the lungs. The most constant and -peculiar effect of breathing small quantities of phosphorus vapour is a -necrosis of the lower jaw. There is first inflammation of the periosteum -of the jaw, which proceeds to suppuration and necrosis of a greater or -smaller portion. The effects may develop with great suddenness, and end -fatally. Thus Fournier and Olliver[291] relate the case of a girl, -fourteen years old, who, after working four years in a phosphorus -manufactory, was suddenly affected with periostitis of the upper jaw, -and with intense anaemia. An eruption of purpuric spots ensued, and she -died comatose. There is now little doubt, that minute doses of -phosphorus have a specific action on the bones generally, and more -especially on the bones of the jaw. Wegner[292] administered small daily -doses to young animals, both in the state of vapour, and as a -finely-divided solid. The condition of the bones was found to be more -compact than normal, the medullary canals being smaller than in healthy -bone, the ossification was quickened. The formation of callus in -fractured limbs was also increased. - -[291] _Gaz. hebd. de Med._, 29, p. 461, 1868. - -[292] Virchow's _Arch. f. path. Anat._, lv. 11. - -Sec. 288. =Changes in the Urinary Secretion.=--It has been before stated -that, at a certain period of the illness, the renal secretion is -scantier than in health, the urine diminishing, according to Lebert and -Wyss's[293] researches, to one-half on the third, fourth, or fifth day. -It frequently contains albumen, blood, and casts. When jaundice is -present, the urine has then all the characters noticed in icterus; -leucin and tyrosin, always present in acute yellow atrophy of the liver, -have been found in small quantity in jaundice through phosphorus; lactic -acid is also present. The urea is much diminished, and, according to -Schultzen and Riess,[294] may be towards death entirely absent. Lastly, -it is said that there is an exhalation of either phosphorus vapour or -phosphine from such urine. In some cases the urine is normal, _e.g._, in -a case recorded by E. H. Starling, M.D., and F. G. Hopkins, B.Sc. -(_Guy's Hospital Report_, 1890), in which a girl, aged 18, died on the -fifth day after taking phosphorus paste, the liver was fatty, and there -was jaundice; but the urine contained neither leucin nor tyrosin, and -was stated to be generally normal. - -[293] _Archiv Generale de Med._, 6 Ser., Tom. 12, 1868, p. 709. - -[294] _Annalen der Charite_, Berlin. - -Sec. 289. =Changes in the blood= during life have been several times -observed. In a case attended by M. Romellaere of Brussels,[295] in which -a man took the paste from 300 matches, and under treatment by turpentine -recovered, the blood was frequently examined, and the leucocytes found -much increased in number. There is a curious conflict of evidence as to -whether phosphorus prevents coagulation of the blood or not. Nasse -asserted that phosphorated oil given to a dog fully prevented -coagulation; P. I. Liebreck[296] also, in a series of researches, found -the blood dark, fluid, and in perfect solution. These observations were -also supported by V. Bibra and Schuchardt.[297] Nevertheless, Lebert and -Wyss found the blood, whether in the veins or in extravasations, in a -normal condition. Phosphorus increases the fatty contents of the blood. -Ritter found that phosphorus mixed with starch, and given to a dog, -raised the fatty content from the normal 2 per 1000 up to 3.41 and 3.47 -per 1000. Eug. Menard[298] saw in the blood from the jugular and portal -veins, as well as in extravasations, microscopic fat globules and fine -needle-shaped crystals soluble in ether. - -[295] Tardieu, _op. cit._, Case 31. - -[296] _Diss. de Venefico Phosphoreo Acuto_, Upsal, 1845. - -[297] V. Bibra u. Geist, _Die Krankheiten der Arbeiter in den -Phosphorzundholz Fabriken_, 1847, S. 59, &c.; Henle u. v. Pfeuffer's -_Zeitschr. f. ration. Med._, N. F., Bd. 7, Hft. 3, 1857. - -[298] _Etude Experimentale sur quelques lesions de l'Empoisonnement aigu -par le Phosphore (These)_, Strasbourg, 1869. - -Sec. 290. =Antidote--Treatment.=--After emptying the stomach by means of -emetics or by the stomach-pump, oil of turpentine in full medicinal -doses, say 2.5 c.c. (about 40 min.), frequently administered, seems to -act as a true antidote, and a large percentage of cases treated early in -this way recover. - -Sec. 291. =Poisonous Effects of Phosphine (phosphuretted -hydrogen).=--Experiments on pigeons, on rats, and other animals, and a -few very rare cases among men, have shown that phosphine has an exciting -action on the respiratory mucous membranes, and a secondary action on -the nervous system. Eulenberg[299] exposed a pigeon to an atmosphere -containing 1.68 per cent. of phosphine. There was immediate unrest; at -the end of three minutes, quickened and laboured breathing (100 a -minute); after seven minutes, the bird lay prostrate, with shivering of -the body and wide open beak; after eight minutes, there was vomiting; -after nine minutes, slow breathing (34 per minute); after twelve -minutes, convulsive movements of the wings; and after thirteen minutes, -general convulsions and death. - -[299] _Gewerbe Hygiene_, p. 273. - -The membranes of the brain were found strongly injected, and there were -extravasations. In the mucous membrane of the crop there was also an -extravasation. The lungs externally and throughout were of a dirty -brown-red colour; the entire heart was filled with coagulated blood, -which was weakly acid in reaction. - -In a second experiment with another pigeon, there was no striking -symptom save that of increased frequency of respiration and loss of -appetite; at the end of four days it was found dead. There was much -congestion of the cerebral veins and vessels, the mucous membrane of the -trachea and bronchi were weakly injected, and the first showed a thin, -plastic, diphtheritic-like exudation. - -Dr. Henderson's[300] researches on rats may also be noticed here. He -found that an atmosphere consisting entirely of phosphine killed rats -within ten minutes, an atmosphere with 1 per cent. in half an hour. The -symptoms observed were almost exactly similar to those noticed in the -first experiment on the pigeon quoted above, and the _post-mortem_ -appearances were not dissimilar. With smaller quantities of the gas, the -first symptom was increased frequency of the respiration; then the -animals showed signs of suffering intense irritation of the skin, -scratching and biting at it incessantly; afterwards they became drowsy, -and assumed a very peculiar attitude, sitting down on all-fours, with -the back bent forward, and the nose pushed backwards between the -forepaws, so as to bring the forehead against the floor of the cage. -When in this position, the rat presented the appearance of a curled-up -hedgehog. Phosphine, when injected into the rectum, is also fatal; the -animals exhale some of the gas from the lungs, and the breath, -therefore, reduces solutions of silver nitrate.[301] - -[300] _Journ. Anat. and Physiol._, vol. xiii. p. 19. - -[301] Dybskowsky, _Med. Chem. Untersuchungen aus Hoppe-Seyler's Labor. -in Tuebingen_, p. 57. - -Brenner[302] has recorded the case of a man twenty-eight years old, a -pharmaceutist, who is supposed to have suffered from illness caused by -repeated inhalations of minute quantities of phosphine. He was engaged -for two and a half years in the preparation of hypophosphites; his -illness commenced with spots before the eyes, and inability to fix the -attention. His teeth became very brittle, and healthy as well as carious -broke off from very slight causes. Finally, a weakness of the arms and -limbs developed in the course of nine months into complete locomotor -ataxy. - -[302] _St. Petersburg Med. Zeitschr._, 4 Hft., 1865. - -Sec. 292. Blood takes up far more phosphine than water. Dybskowsky found -that putting the coefficient of solubility of phosphine in pure water at -.1122 at 15 deg., the coefficient for venous blood was .13, and for arterial -26.73; hence the richer the blood is in oxygen the more phosphine is -absorbed. It seems probable that the poisonous gas reacts on the -oxyhaemoglobin of the blood, and phosphorous acid is formed. This is -supported by the fact that a watery extract of such blood reduces silver -nitrate, and has been also found feebly acid. The dark blood obtained -from animals poisoned by phosphine, when examined spectroscopically, has -been found to exhibit a band in the violet. - -Sec. 293. =Post-mortem Appearances.=--There are a few perfectly well -authenticated cases showing that phosphorus may cause death, and yet no -lesion be discovered afterwards. Thus, Tardieu[303] cites a case in -which a woman, aged 45, poisoned herself with phosphorus, and died -suddenly the seventh day afterwards. Dr. Mascarel examined the viscera -with the greatest care, but could discover absolutely no abnormal -conditions; the only symptoms during life were vomiting, and afterwards -a little indigestion. It may, however, be remarked that the microscope -does not seem to have been employed, and that probably a close -examination of the heart would have revealed some alteration of its -ultimate structure. The case quoted, by Taylor[304] may also be -mentioned, in which a child was caught in the act of sucking phosphorus -matches, and died ten days afterwards in convulsions. None of the -ordinary _post-mortem_ signs of poisoning by phosphorus were met with, -but the intestines were reddened throughout, and there were no less than -ten invaginations; but the case is altogether a doubtful one, and no -phosphorus may actually have been taken. It is very difficult to give in -a limited space anything like a full picture of the different lesions -found after death from phosphorus, for they vary according as to whether -the death is speedy or prolonged, whether the phosphorus has been taken -as a finely-divided solid, or in the form of vapour, &c. It may, -however, be shortly said, that the most common changes are fatty -infiltration of the liver and kidneys, fatty degeneration of the heart, -enlargement of the liver, ecchymoses in the serous membranes, in the -muscular, in the fatty, and in the mucous tissues. When death occurs -before jaundice supervenes, there may be little in the aspect of the -corpse to raise a suspicion of poison; but if intense jaundice has -existed during life, the yellow staining of the skin, and it may be, -spots of purpura, will suggest to the experienced pathologist the -possibility of phosphorus poisoning. In the mouth and throat there will -seldom be anything abnormal. In one or two cases of rapid death among -infants, some traces of the matches which had been sucked were found -clinging to the gums. The stomach may be healthy, but the most common -appearance is a swelling of the mucous membrane and superficial -erosions. Virchow,[305] who was the first to call attention to this -peculiar grey swelling of the intestinal mucous membrane under the name -of _gastritis glandularis_ or _gastradenitis_, shows that it is due to a -fatty degeneration of the epithelial cells, and that it is by no means -peculiar to phosphorus poisoning. The swelling may be seen in -properly-prepared sections to have its essential seat in the glands of -the mucous membrane; the glands are enlarged, their openings filled with -large cells, and each single cell is finely granular. Little centres of -haemorrhage, often microscopically small, are seen, and may be the -centres of small inflammations; their usual situation is on the summit -of the rugae. Very similar changes are witnessed after death from -septicaemia, pyaemia, diphtheria, and other diseases. The softening of the -stomach, gangrene, and deep erosions, recorded by the earlier authors, -have not been observed of late years, and probably were due to -_post-mortem_ changes, and not to processes during life. The same -changes are to be seen in the intestines, and there are numerous -extravasations in the peritoneum. - -[303] _L'Empoisonnement_, p. 520. - -[304] _Poisons_, 3rd ed., p. 276. - -[305] Virchow's _Archiv. f. path. Anat._, Bd. 31, Hft. 3, 399. - -The liver shows of all the organs the most characteristic signs; a more -or less advanced fatty infiltration of its structure takes place, which -was first described as caused by phosphorus by Hauff in 1860.[306] It -is the most constant pathological evidence both in man and animal, and -seems to occur at a very early period, Munk and Leyden having found a -fatty degeneration in the liver far advanced in twenty-four hours[307] -after poisoning. In rats and mice poisoned with paste, I have found this -evident to the naked eye twelve hours after the fatal dose. The liver is -mostly large, but in a case[308] recorded in the _Lancet_, July 14, -1888, the liver was shrunken; it has a pale yellow (or sometimes an -intense yellow) colour; on section the cut surface presents a mottled -appearance; the serous envelopes, especially along the course of the -vessels, exhibit extravasations of blood. The liver itself is more -deficient in blood than in the normal condition, and the more bloodless -it is, the greater the fatty infiltration. - -[306] Hauff collected 12 cases, and found a fatty liver in -11.--_Wuertemb. Med. Corresp. Bl._, 1860, No. 34. - -[307] _Die acute Phosphor-Vergiftung_, Berlin, 1865. - -[308] This case, from the similarity of the pathological appearances to -those produced by yellow atrophy, deserves fuller notice:--"Frances A. -Cowley, aged 20, on her own admission, took some rat paste on Tuesday, -June 19th. Death ensued eleven days later. The initial symptoms were not -very marked. Nausea and vomiting continued with moderate severity for a -few days and then ceased. There ensued a feeling of depression. Towards -the end insensibility, icterus, and somewhat profuse metrorrhagia -supervened. At the necropsy the skin and conjunctivae were observed of a -bright yellow colour. There was no organic disease save of a recent -nature, and entirely attributable to the action of the poison ingested. -The stomach contained about three-quarters of a pint of dark -claret-coloured fluid, consisting largely of blood derived from -capillary haemorrhage from the mucous membrane. There was no solution of -continuity of the mucous membrane, which showed traces of recent -irritation. The whole surface presented a yellow icteric tint, except -the summits of some of the rugae, which were of a bright pink colour. -There was also faint wrinkling of the mucous membrane. The upper part of -the small intestine was affected in much the same manner as the stomach. -The large intestine contained a quantity of almost colourless faeces. The -liver was shrunken, weighing only 26 ozs., and both on its outer and -sectional surface exactly resembled the appearances produced by acute -yellow atrophy, except that there were greater congestion and -interstitial haemorrhage in patches. The lobules of the liver were in -many places unrecognisable; in others they stood in bold relief as -brilliant canary-yellow patches, standing in strong contrast to the deep -dark-red areas of congestion and extravasation. The gall-bladder -contained about 2 drachms of thin greyish fluid, apparently all but -devoid of bile. The urinary bladder was empty; the kidneys were -enlarged; the cortex was very pale and bile-stained, of greater depth -than natural, and of softer consistence. The spleen was not enlarged, -nor was it in the least degree softened. In addition to the bleeding -from the uterus noticed during life, there was capillary haemorrhage into -the right lung and pleura, into the pericardium, and, as already -mentioned, into the stomach. The brain was healthy." - -In the Museum of the Royal College of Surgeons there is a preparation -(No. 2737) of the section of a liver derived from a case of phosphorus -poisoning. - -A girl, aged 18, after two days' illness, was admitted into Guy's -Hospital. She confessed to having eaten a piece of bread coated with -phosphorus paste. She had great abdominal pain, and died on the seventh -day after taking the phosphorus. A few hours before her death she was -profoundly and suddenly collapsed. The liver weighed 66 ozs. The -outlines of the hepatic lobules were very distinct, each central vein -being surrounded by an opaque yellowish zone; when fresh the hue was -more uniform, and the section was yellowish-white in colour. A -microscopical examination of the hepatic cells showed them laden with -fat globules, especially in the central parts of the liver. - -The microscopic appearances are also characteristic. In a case of -suicidal poisoning by phosphorus, in which death took place on the -seventh day, the liver was very carefully examined by Dr. G. F. Goodart, -who reported as follows:-- - - "Under a low power the structure of the liver is still readily - recognisable, and in this the specimen differs from slides of three - cases of acute yellow atrophy that I have in my possession. The - hepatic cells are present in large numbers, and have their natural - trabecular arrangement. The columns are abnormally separated by - dilated blood or lymph-spaces, and the individual cells are cloudy - and ill-defined. The portal channels are everywhere characterised by - a crowd of small nuclei which stain with logwood deeply. The - epithelium of the smaller ducts is cloudy, and blocks the tubes in - many cases. Under a high power (one-fifth) it is seen that the - hepatic cells are exceedingly ill-defined in outline, and full of - granules and even drops of oil. But in many parts, even where the - cells themselves are hazy, the nucleus is still fairly visible. It - appears to me that, in opposition to what others have described, the - nuclei of the cells have in great measure resisted the degenerative - process. The change in the cells is uniform throughout each lobule, - but some lobules are rather more affected than others. The - blood-spaces between the cells are empty, and the liver appears to - be very bloodless. The portal canals are uniformly studded with - small round nuclei or cells, which are in part, and might be said in - great part, due to increase of the connective tissue or to a - cirrhotic process. But I am more disposed to favour the view that - they are due to migration from the blood-vessels, because they are - so uniform in size, and the hepatic cells and connective tissue in - their neighbourhood are undergoing no changes in the way of growth - whatever. I cannot detect any fatty changes in the vessels, but some - of the smaller biliary ducts contain some cloudy albuminous - material, and their nucleation is not distinct. No retained biliary - pigment is visible."[309] - -[309] "A Recent Case of Suicide," by Herbert J. Capon, M.D.--_Lancet_, -March 18, 1882. - -Oscar Wyss,[310] in the case of a woman twenty-three years old, who died -on the fifth day after taking phosphorus, describes, in addition to the -fatty appearance of the cells, a new formation of cells lying between -the lobules and in part surrounding the gall-ducts and the branches of -the portal vein and hepatic artery. - -[310] Virchow's _Archiv. f. path. Anat._, Bd. 33, Hft. 3, S. 432, 1865. - -Salkowsky[311] found in animals, which he killed a few hours after -administering to them toxic doses of phosphorus, notable hyperaemia of -the throat, intestine, liver, and kidneys--both the latter organs being -larger than usual. The liver cells were swollen, and the nuclei very -evident, but they contained no fat, fatty drops being formed afterwards. - -[311] _Ibid._, Bd. 34, Hft. 1 u. 2, S. 73, 1865. - -Sec. 294. =The kidneys= exhibit alterations very similar and analogous to -those of the liver. They are mostly enlarged, congested, and flabby, -with extravasations under the capsule, and show microscopic changes -essentially consisting in a fatty degeneration of the epithelium. In -cases attended with haemorrhage, the tubuli may be here and there filled -with blood. The fatty epithelium is especially seen in the contorted -tubes, and the walls of the vessels, both of the capsule and of the -malpighian bodies, also undergo the same fatty change. In cases in which -death has occurred rapidly, the kidneys have been found almost healthy, -or a little congested only. The pancreas has also been found with its -structure in part replaced by fatty elements. - -Of great significance are also the fatty changes in the general muscular -system, and more especially in the heart. The muscular fibres of the -heart quickly lose their transverse striae, which are replaced by drops -of fat. Probably this change is the cause of the sudden death not -unfrequently met with in phosphorus poisoning. - -=In the lungs=, when the phosphorus is taken in substance, there is -little "naked-eye" change, but Perls,[312] by manometric researches, has -shown that the elasticity is always decreased. According to experiments -on animals, when the vapour is breathed, the mucous membrane is red, -congested, swollen, and has an acid reaction. - -[312] Deutsch. _Archiv f. klin. Med._, vi. Hft. 1, S. 1, 1869. - -=In the nervous system= no change has been remarked, save occasionally -haemorrhagic points and extravasations. - -Sec. 295. =Diagnostic Differences between Acute Yellow Atrophy of the Liver -and Fatty Liver produced by Phosphorus.=--O. Schultzen and O. L. Riess -have collected and compared ten cases of fatty liver from phosphorus -poisoning, and four cases of acute yellow atrophy of the liver, and, -according to them, the chief points of distinction are as follows:--In -phosphorus poisoning the liver is large, doughy, equally yellow, and -with the acini well marked; while in acute yellow atrophy the liver is -diminished in size, tough, leathery, and of a dirty yellow hue, the -acini not being well mapped out. The "phosphorus" liver, again, presents -the cells filled with large fat drops, or entirely replaced by them; but -in the "atrophy" liver, the cells are replaced by a finely-nucleated -detritus and through newly-formed cellular tissue. Yellow atrophy seems -to be essentially an inflammation of the intralobular connective tissue, -while in phosphorus poisoning the cells become gorged by an infiltration -of fat, which presses upon the vessels and lessens the blood supply, -and the liver, in consequence, may, after a time, waste. - -There is also a clinical distinction during life, not only in the -lessening bulk of the liver in yellow atrophy, in opposition to the -increase of size in the large phosphorus liver, but also in the -composition of the renal secretion. In yellow atrophy the urine contains -so much leucine and tyrosin, that the simple addition of acetic acid -causes at once a precipitate. Schultzen and Riess also found in the -urine, in cases of yellow atrophy, _oxymandelic acid_ (C_{8}H_{8}O_{4}), -but in cases of phosphorus poisoning a nitrogenised acid, fusing at 184 deg. -to 185 deg. - -According to Maschka, grey-white, knotty, faecal masses are found in the -intestines in yellow atrophy, but never in cases of phosphorus -poisoning. In the latter, it is more common to find a slight intestinal -catarrh and fluid excreta. - -Sec. 296. =The Detection of Phosphorus=.--The following are the chief -methods in use for the separation and detection of phosphorus:[313]-- - -[313] It has been recommended to dissolve the phosphorus out from -organic matters by carbon disulphide. On evaporation of the latter the -phosphorus is recognised by its physical properties. Such a method is of -but limited application, although it may sometimes be found useful. I -have successfully employed it in the extraction of phosphorus from the -crop of a fowl; but on this occasion it happened to be present in large -quantity. - -1. =Mitscherlich's Process=.--The essential feature of this process is -simply distillation of free phosphorus, and observation of its luminous -properties as the vapour condenses in the condensing tube. The -conditions necessary for success are--(1) that the apparatus should be -in total darkness;[314] and (2) that there should be no substance -present, such as alcohol or ammonia,[315] which, distilling over with -the phosphorus-vapour, could destroy its luminosity. A convenient -apparatus, and one certain to be in all laboratories, is an ordinary -Florence flask, containing the liquid to be tested, fitted to a glass -Liebig's condenser, supported on an iron sand-bath (which may, or may -not, have a thin layer of sand), and heated by a Fletcher's low -temperature burner. The distillate is received into a flask. This -apparatus, if in darkness, works well; but should the observer wish to -work in daylight, the condenser must be enclosed in a box perfectly -impervious to light, and having a hole through which the luminosity of -the tube may be seen, the head of the operator and the box being covered -with a cloth. If there be a stream of water passing continuously -through the condenser, a beautiful luminous ring of light appears in the -upper part of the tube, where it remains fixed for some time. Should, -however, the refrigeration be imperfect, the luminosity travels slowly -down the tube into the receiver. In any case, the delicacy of the test -is extraordinary.[316] If the organic liquid is alkaline, or even -neutral, there will certainly be some evolution of ammonia, which will -distil over before the phosphorus, and retard (or, if in sufficient -quantity, destroy) the luminosity. In such a case it is well, as a -precaution, to add enough sulphuric acid to fix the ammonia, omitting -such addition if the liquid to be operated upon is acid. - -[314] Any considerable amount of phosphorescence can, however, be -observed in twilight. - -[315] Many volatile substances destroy the luminous appearance of -phosphorus vapour, _e.g._, chlorine, hydric sulphide, sulphur dioxide, -carbon disulphide, ether, alcohol, petroleum, turpentine, creasote, and -most essential oils. On the other hand, bromine, hydrochloric acid, -camphor, and carbonate of ammonia do not seem to interfere much with the -phosphorescence. - -[316] Fresenius states that he and Neubauer, with 1 mgrm. of phosphorus -in 200,000, recognised the light, which lasted for half an -hour.--_Zeitschr. f. anal. Chem._, i. p. 336. - -2. =The Production of Phosphine= (PH_{3}).--Any method which produces -phosphine (phosphuretted hydrogen), enabling that gas to be passed -through nitrate of silver solution, may be used for the detection of -phosphorus. Thus, Sonnenschein states that he has found phosphorus in -extraordinary small amount, mixed with various substances, by heating -with potash in a flask, and passing the phosphine into silver nitrate, -separating the excess of silver, and recognising the phosphoric acid by -the addition of molybdate of ammonia.[317] - -[317] Sonnenschein, _Handbuch der gerichtlichen Chemie_, Berlin, 1869. - -The usual way is, however, to produce phosphine by means of the action -on free phosphorus of nascent hydrogen evolved on dissolving metallic -zinc in dilute sulphuric acid. Phosphine is formed by the action of -nascent hydrogen on solid phosphorus, phosphorous acid, and -hypophosphorous acid; but no phosphine can be formed in this way by the -action of hydrogen on phosphoric acid. - -Since it may happen that no free phosphorus is present, but yet the -first product (phosphorous acid) of its oxidation, the production of -phosphine becomes a necessary test to make on failure of Mitscherlich's -test; if no result follows the proper application of the two processes, -the probability is that phosphorus has not been taken. - -Blondlot and Dusart evolve hydrogen from zinc and dilute sulphuric acid, -and pass the gas into silver nitrate; if the gas is pure, there is of -course no reduction; the liquid to be tested is then added to the -hydrogen-generating liquid, and if phosphorous or hypophosphorous acids -be present, a black precipitate of phosphor-silver will be produced. To -prove that this black precipitate is neither that produced by SH_{2}, -nor by antimony nor arsenic, the precipitate is collected and placed in -the apparatus to be presently described, and the spectroscopic -appearances of the phosphine flame observed. - -3. =Tests Dependent on the Combustion of Phosphine= (PH_{3}).--A -hydrogen flame, containing only a minute trace of phosphorus, or of the -lower products of its oxidation, acquires a beautiful green tint, and -possesses a characteristic _spectrum_. In order to obtain the latter in -its best form, the amount of phosphine must not be too large, or the -flame will become whitish and livid, and the bands lose their defined -character, rendering the spectrum continuous. Again, the orifice of the -tube whence the gas escapes must not be too small; and the best result -is obtained when the flame is cooled. - -M. Salet has proposed two excellent methods for the observation of -phosphine by the spectroscope:-- - -(1) He projects the phosphorus-flame on a plane vertical surface, -maintained constantly cold by means of a thin layer of running water; -the green colour is especially produced in the neighbourhood of the cool -surface. - -(2) At the level of the base of the flame, there is an annular space, -through which a stream of cold air is continually blown upwards. Thus -cooled, the light is very pronounced, and the band [delta], which is -almost invisible in the ordinary method of examination, is plainly -seen.[318] - -[318] Consult _Spectres Lumineux_, par M. Lecoq de Boisbaudran, Paris, -1874. See also Christofle and Beilstrom's "Abhandlung," in _Fresenius' -Zeitschr. f. anal. Chem._, B. 2, p. 465, and B. 3, p. 147. - -An apparatus (devised by Blondlot, and improved by Fresenius) for the -production of the phosphine flame in medico-legal research, is -represented in the following diagram:-- - -[Illustration] - -Several of the details of this apparatus may be modified at the -convenience of the operator. A is a vessel containing sulphuric acid; B -is partly filled with granulated zinc, and hydrogen may be developed at -pleasure; _c_ contains a solution of nitrate of silver; _d_ is a tube at -which the gas can be lit; _e_, a flask containing the fluid to be -tested, and provided with a tube _f_, at which also the gas issuing can -be ignited. The orifice should be provided with a platinum nozzle. When -the hydrogen has displaced the air, both tubes are lit, and the two -flames, being side by side, can be compared. Should any phosphorus come -over from the zinc (a possibility which the interposed silver nitrate -ought to guard against), it is detected; the last flask is now gently -warmed, and if the flame is green, or, indeed, in any case, it should be -examined by the spectroscope.[319] - -[319] F. Selmi has proposed the simple dipping of a platinum loop into a -liquid containing phosphoric acid, and then inserting it into the tip of -a hydrogen flame. - -Sec. 297. The spectrum, when fully developed, shows one band in the orange -and yellow between C and D, but very close to D, and several bands in -the green. But the bands [delta], [gamma], [alpha], and [beta] are the -most characteristic. The band [delta] has its centre about the -wave-length 599.4; it is easily distinguished when the slit of the -spectroscope is a little wide, but may be invisible if the slit is too -narrow. It is best seen by M. Salet's second process, and, when cooled -by a brisk current of air, it broadens, and may extend closer to D. The -band [gamma] has a somewhat decided border towards E, while it is -nebulous towards D, and it is, therefore, very difficult to say where it -begins or where it ends; its centre may, however, be put at very near -109 of Boisbaudran's scale, corresponding to W. L. 560.5, if the flame -is free. This band is more distinct than [beta], but with a strong -current of air the reverse is the case. The middle of the important band -[alpha] is nearly marked by Fraunhofer's line E. Boisbaudran gives it as -coinciding with 122 of his scale W. L. 526.3. In ordinary conditions -(that is, with a free uncooled flame) this is the brightest and most -marked of all the bands. The approximate middle of the band [beta] is W. -L. 510.6 (Boisbaudran's scale 129.00). - -=Lipowitz's Sulphur Test.=--Sulphur has the peculiar property of -condensing phosphorus on its surface, and of this Lipowitz proposed to -take advantage. Pieces of sulphur are digested some time with the liquid -under research, subsequently removed, and slightly dried. When examined -in the dark, should phosphorus be present, they gleam strongly if rubbed -with the finger, and develop a phosphorus odour. The test is wanting in -delicacy, nor can it well be made quantitative; it has, however, an -advantage in certain cases, _e.g._, the detection of phosphorus in an -alcoholic liquid. - -Scherer's test, as modified by Hager,[320] is a very delicate and -almost decisive test. The substances to be examined are placed in a -flask with a little lead acetate (to prevent the possibility of any -hydric sulphide being evolved), some ether added, and a strip of -filter-paper soaked in a solution of silver nitrate is then suspended in -the flask; this is conveniently done by making a slit in the bottom of -the cork, and in the slit securing the paper. The closed flask is placed -in the dark, and if phosphorus is present, in a few minutes there is a -black stain. It may be objected that arsine will cause a similar -staining, but then arsine could hardly be developed under the -circumstances given. It is scarcely necessary to observe that the paper -must be wet. - -[320] _Pharm. Central-halle_, 20, 353. - -Sec. 298. =Chemical Examination of the Urine.=--It may be desirable, in any -case of suspected phosphorus poisoning, to examine the renal secretion -for leucin and tyrosin, &c. Leucin may be found as a deposit in the -urine. Its general appearance is that of little oval or round discs, -looking like drops of fat. It can be recognised by taking up one or more -of these little bodies and placing them in the author's subliming cell -(see Sec. 314). By careful heating it will sublime wholly on to the upper -cover. On now adding a little nitric acid to the sublimed leucin, and -drying, and then to the dried residue adding a droplet of a solution of -sodium hydrate, leucin forms an oily drop. Tyrosin also may occur as a -sediment of little heaps of fine needles. The best test for tyrosin is -to dissolve in hot water, and then add a drop of a solution of mercuric -nitrate and mercurous nitrate, when a rose colour is at once developed, -if the tyrosin is in very minute quantity; but if in more than traces, -there is a distinct crimson precipitate. To separate leucin and tyrosin -from the urine, the best process is as follows:--The urine is filtered -from any deposit, evaporated to a thin syrup, and decanted from the -second deposit that forms. The two deposits are mixed together and -treated with dilute ammonia, which will dissolve out any tyrosin and -leave it in needles, if the ammonia is spontaneously evaporated on a -watch-glass. The urine is then diluted and treated with neutral and -basic acetates of lead, filtered, and the lead thrown out of the -filtrate by hydric sulphide. The filtrate is evaporated to a syrup, and -it then deposits leucin mixed with some tyrosin. If, however, the syrup -refuses to crystallise, it is treated with cold absolute alcohol, and -filtered, the residue is then boiled up with spirit of wine, which -extracts leucin, and deposits it on cooling in a crystalline form. To -obtain oxymandelic acid, the mother liquor, from which leucin and -tyrosin have been extracted, is precipitated with absolute alcohol, -filtered, and then the alcoholic solution evaporated to a syrup. This -syrup is acidified by sulphuric acid, and extracted with ether; the -ether is filtered off and evaporated to dryness; the dry residue will be -in the form of oily drops and crystals. The crystals are collected, -dissolved in water, and the solution precipitated by lead acetate to -remove colouring-matters; after filtration it is finally precipitated -by basic acetate. On decomposition of the basic acetate, by suspending -in water and saturating with hydric sulphide, the ultimate filtrate on -evaporation deposits colourless, flexible needles of oxymandelic acid. -The nitrogenised acid which Schultzen and Riess obtained from urine in a -case of phosphorus poisoning, was found in an alcohol and ether -extract--warts of rhombic scales separating out of the syrupy residue. -These scales gave no precipitate with basic acetate, but formed a -compound with silver nitrate. The silver compound was in the form of -shining white needles, and contained 33.9 per cent. of silver; the acid -was decomposed by heat, and with lime yielded aniline. Its melting-point -is given at from 184 deg. to 185 deg. The occurrence of some volatile substance -in phosphorus urine, which blackens nitrate of silver, and which is -probably phosphine, was first noticed by Selmi.[321] Pesci and Stroppa -have confirmed Selmi's researches. It is even given off in the cold. - -[321] _Giornale Internaz. della Scienza Med._, 1879, Nro. 5, p. 645. - -Sec. 299. =The quantitative estimation of phosphorus= is best carried out -by oxidising it into phosphoric acid, and estimating as ammon. magnesian -phosphate. To effect this, the substances are distilled in an atmosphere -of CO_{2} into a flask with water, to which a tube containing silver -nitrate is attached; the latter retains all phosphine, the former solid -phosphorus. If necessary, the distillate may be again distilled into -AgNO_{3}; and in any case the contents of the [U]-tube and flask are -mixed, oxidised with nitromuriatic acid, filtered from silver chloride, -and the phosphoric acid determined in the usual way. - -In the case of a child poisoned by lucifer matches, Sonnenschein -estimated the free phosphorus in the following way:--The contents of the -stomach were diluted with water, a measured part filtered, and the -phosphoric acid estimated. The other portion was then oxidised by HCl -and potassic chlorate, and the phosphoric acid estimated--the difference -being calculated as free phosphorus. - -Sec. 300. =How long can Phosphorus be recognised after Death?=--One of the -most important matters for consideration is the time after death in -which free phosphorus, or free phosphoric acids, can be detected. Any -phosphorus changed into ammon. mag. phosphate, or into any other salt, -is for medico-legal purposes entirely lost, since the expert can only -take cognisance of the substance either in a free state, as phosphine, -or as a free acid. - -The question, again, may be asked in court--Does the decomposition of -animal substances rich in phosphorus develop phosphine? The answer to -this is, that no such reaction has been observed. - -A case is related[322] in which phosphorus was recognised, although the -body had been buried for several weeks and then exhumed. - -[322] _Pharm. Zeitsch. f. Russl._, Jahrg. 2, p. 87. - -The expert of pharmacy of the Provincial Government Board of Breslau has -also made some experiments in this direction, which are worthy of -note:--Four guinea-pigs were poisoned, each by 0.023 grm. of phosphorus; -they died in a few hours, and were buried in sandy-loam soil, 0.5 metre -deep. Exhumation of the first took place four weeks after. The -putrefying organs--heart, liver, spleen, stomach, and all the -intestines--tested by Mitscherlich's method of distillation, showed -characteristic phosphorescence for nearly one hour. - -The second animal was exhumed after eight weeks in a highly putrescent -state. Its entrails, on distillation, showed the phosphorescent -appearance for thirty-five minutes. - -The third animal was taken from the earth after twelve weeks, but no -free phosphorus could be detected, although there was evidence of the -lower form of oxidation (PO_{3}) by Blondlot's method. - -The fourth animal was exhumed after fifteen weeks, but neither free -phosphorus nor PO_{3} could be detected.[323] - -[323] _Vierteljahrsschrift fuer gerichtliche Medicin_, Jan. 7, 1876; see -also _Zeitschr. f. anal. Chemie_, 1872. - -A man, as well as a cat, was poisoned by phosphorus. On analysis, -twenty-nine days after death, negative results were alone -obtained.--_Sonnenschein._ - -It will thus be evident that there is no constant rule, and that, even -when decomposition is much advanced, an examination _may_ be -successful. - - - - -PART VI.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE -MOST PART BY ALCOHOLIC SOLVENTS. - - -DIVISION I.--VEGETABLE ALKALOIDS. - - -I.--General Methods of Testing and Extracting Alkaloids. - -Sec. 301. =General Tests for Alkaloids.=--In order to ascertain whether an -alkaloid is present or not, a method of extraction must be pursued -which, while disposing of fatty matters, salts, &c., shall dissolve as -little as possible of foreign substances--such a method, _e.g._, as the -original process of Stas, or one of its modern modifications. - -If to the acid aqueous solution finally obtained by this method a dilute -solution of soda be added, drop by drop, until it is rendered feebly -alkaline, _and no precipitate appear_, whatever other poisonous -plant-constituents may be present, all ordinary alkaloids[324] are -absent. - -[324] In the case of morphine tartrate, this test will not answer. See -the article on Morphine. - -In addition to this negative test, there are also a number of substances -which give well-marked crystalline or amorphous precipitates with -alkaloids. - -Sec. 302. These may be called "group reagents." The chief members of the -group-reagents are--Iodine dissolved in hydriodic acid, iodine dissolved -in potassic iodide solution, bromine dissolved in potassic bromide -solution, hydrargo-potassic iodide, bismuth-potassic iodide, cadmic -potassic iodide; the chlorides of gold, of platinum, and mercury; picric -acid, gallic acid, tannin, chromate of potash, bichromate of potash, -phospho-molybdic acid, phospho-tungstic acid, silico-tungstic acid, and -Froehde's reagent. It will be useful to make a few general remarks on -some of these reagents. - -=Iodine in hydriodic acid= gives either crystalline or amorphous -precipitates with nearly all alkaloids; the compound with morphine, for -example, is in very definite needles; with dilute solutions of -atropine, the precipitate is in the form of minute dots, but the -majority of the precipitates are amorphous, and all are more or less -coloured. - -=Iodine dissolved in a solution of potassic iodide= gives with alkaloids -a reddish or red-brown precipitate, and this in perhaps a greater -dilution than almost any reagent. When added to an aqueous solution, the -precipitates are amorphous, but if added to an alcoholic solution, -certain alkaloids then form crystalline precipitates; this, for example, -is the case with berberine and narceine. By treating the precipitate -with aqueous sulphurous acid, a sulphate of the alkaloid is formed and -hydriodic acid, so that by suitable operations the alkaloid may readily -be recovered from this compound. A solution of bromine in potassic -bromide solution also gives similar precipitates to the above, but it -forms insoluble compounds with phenol, orcin, and other substances. - -=Mercuric potassic iodide= is prepared by decomposing mercuric chloride -with potassic iodide in excess. The proportions are 13.546 grms. of -mercuric chloride and 49.8 of potassic iodide, and water sufficient to -measure, when dissolved, 1 litre. The precipitates from this reagent are -white and flocculent; many of them become, on standing, crystalline. - -=Bismuthic potassic iodide= in solution precipitates alkaloids, and the -compounds formed are of great insolubility, but it also forms compounds -with the various albuminoid bodies. - -=Chloride of gold= forms with the alkaloids compounds, many of which are -crystalline, and most admit of utilisation for quantitative -determinations. Chloride of gold does not precipitate amides or ammonium -compounds, and on this account its value is great. The precipitates are -yellow, and after a while are partly decomposed, when the colour is of a -reddish-brown. - -=Platinic chloride= also forms precipitates with most of the alkaloids, -but since it also precipitates ammonia and potassic salts, it is -inferior to gold chloride in utility. - -Sec. 303. (1.) =Phosphomolybdic Acid as a Reagent for -Alkaloids.=--_Preparation_; Molybdate of ammonia is precipitated by -phosphate of soda; and the well-washed yellow precipitate is suspended -in water and warmed with carbonate of soda, until it is entirely -dissolved. This solution is evaporated to dryness, and the ammonia fully -expelled by heating. If the molybdic acid is fairly reduced by this -means, it is to be moistened by nitric acid, and the heating repeated. -The now dry residue is warmed with water, nitric acid added to strong -acid reaction, and the mixture diluted with water, so that 10 parts of -the solution contain 1 of the dry salt. The precipitates of the -alkaloids are as follows:-- - - Aniline, Bright-yellow, flocculent. - Morphine, " " - Narcotine, Brownish-yellow, " - Quinine, Whitish-yellow, " - Cinchonine, " " - Codeine, Brownish-yellow, voluminous. - Strychnine, White-yellow, " - Brucine, Yelk-yellow, flocculent. - Veratrine, Bright-yellow, " - Jervine, " " - Aconitine, " " - Emetine, " " - Theine, Bright-yellow, voluminous. - Theobromine, " " - Solanine, Citron-yellow, pulverulent. - Atropine, Bright-yellow, flocculent. - Hyoscyamine, " " - Colchicine, Orange-yellow, " - Delphinine, Grey-yellow, voluminous. - Berberine, Dirty-yellow, flocculent. - Coniine, Bright-yellow, voluminous. - Nicotine, " " - Piperine, Brownish-yellow, flocculent. - -(2.) =Silico-Tungstic Acid as a Reagent for Alkaloids.=--Sodium -tungstate is boiled with freshly precipitated gelatinous silica. To the -solution is added mercurous nitrate, which precipitates the yellow -mercurous silico-tungstate. This is filtered, well-washed, and -decomposed by an equivalent quantity of hydrochloric acid; -silico-tungstic acid then goes into solution, and mercurous chloride -(calomel) remains behind. The clear filtrate is evaporated to drive off -the excess of hydrochloric acid, and furnishes, on spontaneous -evaporation, large, shining, colourless octahedra of silico-tungstic -acid, which effloresce in the air, melt at 36 deg., and are easily soluble -in water or alcohol. - -This agent produces no insoluble precipitate with any metallic salt. -Caesium and rubidium salts, even in dilute solutions, are precipitated by -it; neutral solutions of ammonium chloride give with it a white -precipitate, soluble with difficulty in large quantities of water. It -precipitates solutions of the salts of quinine, cinchonine, morphine, -atropine, &c.; if in extremely dilute solution, an opalescence only is -produced: for instance, it has been observed that cinchonine -hydrochlorate in 1/200000, quinia hydrochlorate in 1/20000, -morphia hydrochlorate in 1/15285 dilution, all gave a distinct -opalescence.--_Archiv der Pharm._, Nov., Dr. Richard Godeffroy. - -(3.) =Scheibler's Method for Alkaloids: Phospho-Tungstic -Acid.=--Ordinary commercial sodium tungstate is digested with half its -weight of phosphoric acid, specific gravity 1.13, and the whole allowed -to stand for some days, when the acid separates in crystals. A solution -of these crystals will give a distinct precipitate with the most minute -quantities of alkaloids, 1/200000 of strychnine, and 1/100000 of -quinine. The alkaloid is liberated by digestion with barium hydrate (or -calcium hydrate); and if volatile, may be distilled off, if fixed, -dissolved out by chloroform. In complex mixtures, colouring-matter may -be removed by plumbic acetate, the lead thrown out by SH_{2}, and -concentrated, so as to remove the excess of SH_{2}. - -Sec. 304. =Schulze's reagent= is phospho-antimonic acid. It is prepared by -dropping a strong solution of antimony trichloride into a saturated -solution of sodic phosphate. The precipitation of the alkaloids is -effected by this reagent in a sulphuric acid solution. - -Sec. 305. =Dragendorff's reagent= is a solution of potass-bismuth iodide; -it is prepared by dissolving bismuth iodide in a hot solution of -potassium iodide, and then diluting with an equal volume of iodide of -potassium solution. On the addition of an acid solution of an alkaloid, -a kermes-red precipitate falls down, which is in many cases crystalline. - -=Marm's reagent= is a solution of potass-cadmium iodide. It is made on -similar principles. - -=Potass-zinc iodide= in solution is also made similarly. The -precipitates produced in solutions of narceine and codeine are -crystalline and very characteristic. - -Sec. 306. =Colour Tests.=--=Froehde's reagent= is made by dissolving 1 part -of sodic molybdate in 10 parts of strong sulphuric acid; it strikes -distinctive colours with many alkaloids. - -=Mandelin's reagent= is a solution of meta-vanadate of ammonia in mono- -or dihydrated sulphuric acid. The strength should be 1 part of the salt -to 200 of the acid. This reagent strikes a colour with many alkaloids, -and aids to their identification. It is specially useful to supplement -and correct other tests. The following table gives the chief colour -reactions, with the alkaloids. (See also p. 55 for the spectroscopic -appearances of certain of the colour tests.) - - -METHODS OF SEPARATION. - -Sec. 307. =Stas's Process.=--The original method of Stas[325] (afterwards -modified by Otto)[326] consisted in extraction of the organic matters by -strong alcohol, with the addition of tartaric acid; the filtered -solution was then carefully neutralised with soda, and shaken up with -ether, the ethereal solution being separated by a pipette. Subsequent -chemists proposed chloroform instead of ether,[327] the additional use -of amyl-alcohol,[328] and the substitution of acetic, hydrochloric, and -sulphuric for tartaric acid. - -[325] _Annal d. Chem. u. Pharm._, 84, 379. - -[326] _Ib._, 100, 44. _Anleitung zur Ausmittel. d. Gifte._ - -[327] Rodgers and Girwood, _Pharm. Journ. and Trans._, xvi. 497; -Prollin's _Chem. Centralb._, 1857, 231; Thomas, _Zeitschr. fuer analyt. -Chem._, i. 517, &c. - -[328] Erdmann and v. Ushlar, _Ann. Chem. Pharm._, cxx. pp. 121-360. - - -COLOUR REACTIONS[329] OF CERTAIN ALKALOIDS. - -[329] Caustic potash also gives characteristic colours with certain -alkaloids. Out of seventy-two alkaloids (using 0.5 mgrm.), the following -alone gave characteristic colours when fused with KHO:--Quinine, -grass-green, and peculiar odour; quinidine, becoming yellower and -finally brown; cinchonine, at first brownish-red to violet, with green -edges, later, bluish-green; cinchonidine, blue passing into grey; -cocaine, greenish-yellow, turning to blue, and then dirty red on strong -heating.--W. Lenz, _Zeit. f. anal. Chem._, 25, 29-32. - - +-----------+-----------------+------------------+-------------------+ - | Name of |Strong Sulphuric |Froehde's Reagent.|Mandelin's Reagent.| - |Substance. | Acid. | | | - +-----------+-----------------+------------------+-------------------+ - | | | | | - |Strychnine.| ... | ... |Violet-blue, then | - | | | |lastly cinnabar- | - | | | |red. | - | | | | | - |Brucine. |Pale red. |Red, then yellow. |Yellow-red to | - | | | |orange, afterwards | - | | | |blood-red. | - | | | | | - |Curarine. |Fine red. | ... | ... | - | | | | | - |Quinine. | ... |Greenish. |Weak orange, then | - | | | |blue-green, lastly | - | | | |green-brown. | - | | | | | - |Atropine. | ... | ... |Red, then yellow- | - | | | |red, and lastly | - | | | |yellow. | - | | | | | - |Aconitine. | ... | ... | ... | - | | | | | - |Veratrine. |Yellow, then |Gamboge-yellow, |Yellow, orange, | - | |orange, blood- |then cherry-red. |blood-red, lastly | - | |red, lastly | |carmine-red. | - | |carmine-red. | | | - | | | | | - |Morphine. | ... |Violet, green, |Reddish, then | - | | |blue-green, and |blue-violet. | - | | |yellow. | | - | | | | | - |Narcotine. |Yellow, then |Green, then brown-|Cinnabar-red, then | - | |raspberry colour.|green, yellow, |carmine-red. | - | | |lastly red. | | - | | | | | - |Codeine. | ... |Dirty green, then |Green-blue to blue.| - | | |blue, lastly | | - | | |yellow. | | - | | | | | - |Papaverine.| ... |Green, then blue- |Blue-green to blue.| - | | |violet, lastly | | - | | |cherry-red. | | - | | | | | - |Thebaine. |Blood-red, then |Orange, then |Red to orange. | - | |yellow-red. |colourless. | | - | | | | | - |Narceine. |Grey-brown, then |Brown, green, red,|Violet, then | - | |blood-red. |lastly blue. |orange. | - | | | | | - |Nicotine. | ... |Yellowish, then |Transitory dark | - | | |red. |colour. | - | | | | | - |Coniine. | ... |Yellow. | ... | - | | | | | - |Colchicine.|Intense yellow. |Yellow to |Blue-green, then | - | | |green-yellow. |brown. | - | | | | | - |Delphini- |Red. |Red-brown. |Red-brown to brown.| - |dine. | | | | - | | | | | - |Solanine. |Red-yellow, then |Cherry-red, |Yellow-orange, | - | |brown. |red-brown, yellow,|cherry-red, and | - | | |yellow-green. |lastly violet. | - +-----------+-----------------+------------------+-------------------+ - -Sec. 308. =Selmi's Process for Separating Alkaloids.=--A method of -separating alkaloids from an ethereal solution has been proposed by -Selmi.[330] The alcoholic extract of the viscera, acidified and -filtered, is evaporated at 65 deg.; the residue taken up with water, -filtered, and decolorised by basic acetate of lead. The lead is thrown -out by sulphuretted hydrogen; the solution, after concentration, -repeatedly extracted with ether; and the ethereal solution saturated -with dry CO_{2}, which generally precipitates some of the alkaloids. The -ethereal solution is then poured into clean vessels, and mixed with -about half its volume of water, through which a current of CO_{2} is -passed for twenty minutes; this may cause the precipitation of other -alkaloids not thrown down by dry CO_{2}. If the whole of the alkaloids -are not obtained by these means, the solution is dehydrated by agitation -with barium oxide, and a solution of tartaric acid in ether is added -(care being taken to avoid excess); this throws down any alkaloid still -present. The detection of any yet remaining in the viscera is effected -by mixing with barium hydrate and a little water, and agitating with -_purified_ amylic alcohol; from the alcohol the alkaloids may be -subsequently extracted by agitation with very dilute sulphuric acid. - -[330] F. Selmi, _Gazett. Chim. Ital._, vj. 153-166, and _Journ. Chem. -Soc._, i., 1877, 93. - -Another ingenious method (also the suggestion of Selmi) is to treat the -organic substance with alcohol, to which a little sulphuric acid has -been added, to filter, digest with alcohol, and refilter. The filtrates -are united, evaporated down to a smaller bulk, filtered, concentrated to -a syrup, alkalised by barium hydrate, and, after the addition of freshly -ignited barium oxide and some powdered glass, exhausted with dry ether; -the ether filtered, the filtrate digested with lead hydrate; the -ethereal solution filtered, evaporated to dryness, and finally again -taken up with ether, which, this time, should leave on evaporation the -alkaloid almost pure. - -Sec. 309. =Dragendorff's Process.=--To Dragendorff we owe an elaborate -general method of separation, since it is applicable not only to -alkaloids, but to glucosides, and other active principles derived from -plants. His process is essentially a combination of those already known, -and its distinctive features are the shaking up--(1) of the acid fluid -with the solvent, thus removing colouring matters and certain -non-alkaloidal principles; and (2) of the same fluid made alkaline. The -following is his method in full. It may be advantageously used when the -analyst has to search generally for vegetable poison, although it is, of -course, far too elaborate for every case; and where, from any -circumstance, there is good ground for suspecting the presence of one or -two particular alkaloids or poisons, the process may be much shortened -and modified.[331] - -[331] Dragendorff's _Gerichtlich-chemische Ermittelung von Giften_, St. -Petersburg, 1876, p. 141. - -I. The substance, in as finely-divided form as possible, is digested for -a few hours in water acidified with sulphuric acid, at a temperature of -40 deg. to 50 deg., and this operation is repeated two or three times, with -filtering and pressing of the substances; later, the extracts are -united. This treatment (if the temperature mentioned is not exceeded) -does not decompose the majority of alkaloids or other active substances; -but there are a few (_e.g._, solanine and colchicine) which would be -altered by it; and, if such are suspected, maceration at the common -temperature is necessary, with substitution of acetic for sulphuric -acid.[332] - -[332] When blood is to be examined, it is better to dry it, and then -powder and extract with water acidified with dilute sulphuric acid. -However, if the so-called volatile alkaloids are suspected, this -modification is to be omitted. - -II. The extract is next evaporated until it begins to be of a syrupy -consistence; the residue mixed with three to four times its volume of -alcohol, macerated for twenty-four hours at about 34 deg., allowed to become -quite cool, and filtered from the foreign matters which have separated. -The residue is washed with alcohol of 70 per cent. - -III. The filtrate is freed from alcohol by distillation, the watery -residue poured into a capacious flask, diluted (if necessary) with -water, and filtered. Acid as it is, it is extracted at the common -temperature, with frequent shaking, by freshly-rectified petroleum -ether; and, after the fluids have again separated, the petroleum ether -is removed, carrying with it certain impurities (colouring matter, &c.), -which are in this way advantageously displaced. By this operation -ethereal oils, carbolic acid, picric acid, &c., which have not been -distilled, besides piperin, may also be separated. The shaking up with -petroleum ether is repeated several times (as long as anything remains -to be dissolved), and the products are evaporated on several -watch-glasses. - -RESIDUE OF PETROLEUM ETHER FROM THE ACID SOLUTION. - - 1. IT IS CRYSTALLINE. 2. IT IS AMORPHOUS. 3. IT IS VOLATILE, - with a powerful - odour; - _ethereal oil, - carbolic acid, &c._ - - A. _It is yellowish_, A. It is fixed. - and with difficulty - volatilised. - - [alpha]. The crystals [alpha]. Concentrated - are dissolved by con- sulphuric acid dis- - centrated sulphuric solves it immediately-- - acid, with the violet, and later - production of a clear greenish-blue. - yellow colour, _Constituents of the - passing into brown black hellebore._ - and greenish-brown. - _Piperin._ - - [beta]. The solution in sulphuric [beta]. It dissolves with a - acid remains yellow; potassic yellow colour, changing into - cyanide and caustic potash colour fallow-brown. - it, on warming, blood-red. _Constituents of aconite plant - _Picric acid._ and products of the decomposition - of Aconitine._ - - B. IT IS COLOURLESS, LIQUEFIES B. IT IS WHITE, SHARP-TASTING, - EASILY, AND SMELLS STRONGLY. AND REDDENS THE SKIN. - _Camphor and similar matters._ _Capsicin._ - -It may be expected that the substances mentioned under the heads 1, 2, -and 3 will be, in general, fully obtained by degrees. This is not the -case, however, as regards piperin and picric acid. - -IV. The watery fluid is now similarly shaken up with benzene, and the -benzene removed and evaporated. Should the evaporated residue show signs -of an alkaloid (and especially of theine), the watery fluid is treated -several times with a fresh mixture of benzene, till a little of the -last-obtained benzene extraction leaves on evaporation no residue. The -benzene extracts are now united, and washed by shaking with distilled -water; again separated and filtered, the greater part of the benzene -distilled from the filtrate, and the remainder of the fluid divided and -evaporated on several watch-glasses. - -The evaporated residue may contain theine, colchicine, cubebin, -digitalin, cantharidin, colocynthin, elaterin, caryophylline, absinthin, -cascarillin, populin, santonin, &c., and traces of veratrine, -delphinine, physostigmine, and berberine. - -A remnant of piperin and picric acid may remain from the previous -treatment with petroleum ether. - -THE BENZENE RESIDUE FROM THE ACID SOLUTION. - - 1. IT IS CRYSTALLINE. 2. IT IS AMORPHOUS. - - A. WELL-FORMED, COLOURLESS A. COLOURLESS OR PALE YELLOW - CRYSTALS. RESIDUE. - - [alpha]. Sulphuric acid dissolves [alpha]. Sulphuric acid dissolves - the hair-like crystals without it at first yellow; the solution - change of colour; evaporation with becoming later red. Froehde's re- - chlorine water, and subsequent agent does not colour it violet. - treatment with ammonia, gives a _Elaterin._ - murexide reaction. _Theine._ - - [beta]. Sulphuric acid leaves the [beta]. Sulphuric acid dissolves - rhombic crystals uncoloured. The red; Froehde's reagent violet- - substance, taken up by oil, and red;[333] tannic acid does not - applied to the skin, produces a precipitate. _Populin._ - blister. _Cantharidin._ - - [gamma]. Sulphuric acid leaves the [gamma]. Sulphuric acid dissolves - scaly crystals at first un- it with a red colour; Froehde's - coloured, then slowly develops a reagent[334] a beautiful cherry- - reddening. It does not blister. red; tannic acid precipitates a - Warm alcoholic potash-lye colours yellowish-white. _Colocynthin._ - it a transitory red. _Santonin._ - - [delta]. Sulphuric acid colours [delta]. Sulphuric acid colours - the crystals almost black, whilst it gradually a beautiful red, - it takes itself a beautiful red whilst tannin does not precipi- - colour. _Cubebin._ tate. _Constituents of the - Pimento._ - - B. CRYSTALS PALE TO CLEAR YELLOW. B. PURE YELLOW RESIDUE. - - [alpha]. _Piperin._ [alpha]. Sulphuric acid dis- - solves it yellow; on the addition - of nitric acid, this solution is - green, quickly changing to blue - and violet. _Colchicine._ - - [beta]. _Picric Acid._ [beta]. Sulphuric acid dissolves - with separation of a violet - powder; caustic potash colours it - red; sulphide of ammonia violet, - and, by heating, indigo-blue. - _Chrysammic acid._ - - [gamma]. Caustic potash dissolves - it purple. _Aloetin._ - - C. MOSTLY UNDEFINED COLOURLESS C. A GREENISH BITTER RESIDUE, - CRYSTALS. which dissolves brown in concen- - trated sulphuric acid; in - Froehde's reagent, likewise, at - first brown, then at the edge - green, changing into blue-violet, - and lastly violet. _Constituents - of wormwood, with absynthin, - besides quassiin, menyanthin, - ericolin, daphnin, cnicin, and - others._ - - [alpha]. Sulphuric acid dissolves - it green-brown; bromine colours - this solution red; dilution with - water again green. The substance - renders the heart-action of a - frog slower. _Digitalin._ - - [beta]. Sulphuric acid dissolves - it orange, then brown, lastly red- - violet. Nitric acid dissolves it - yellow, and water separates as a - jelly out of the latter solution. - Sulphuric acid and bromine do not - colour it red. _Gratiolin._ - - [gamma]. Sulphuric acid dissolves - it red-brown. Bromine produces in - this solution red-violet - stripes. It does not act on - frogs. _Cascarillin._ - - D. GENERALLY UNDEFINED YELLOW CRYSTALLISATION.--Sulphuric acid dis- - solves it olive-green. The alcoholic solution gives with potassic - iodide a colourless and green crystalline precipitate. _Berberin._ - -[333] Froehde's reagent is described at page 239. - -[334] Froehde's reagent is described at page 239. - -V. As a complete exhaustion of the watery solution is not yet attained -by the benzene agency, another solvent is tried. - -THE WATERY SOLUTION IS NOW EXTRACTED IN THE SAME WAY BY CHLOROFORM. - -In chloroform the following substances are especially taken -up:--Theobromine, narceine, papaverine, cinchonine, jervine, besides -picrotoxin, syringin, digitalin, helleborin, convallamarin, saponin, -senegin, smilacin. Lastly, portions of the bodies named in Process IV., -which benzene failed to extract entirely, enter into solution, as well -as traces of brucine, narcotine, physostigmine, veratrine, delphinine. -The evaporation of the chloroform is conducted at the ordinary -temperature in four or five watch-glasses. - -THE CHLOROFORM RESIDUE FROM THE ACID SOLUTION.[335] - -[335] Chloroform removes small portions of acetate of aconitine from -acid solution, Dunstan and Umney, _J. C. S._, 1892, p. 338. - - 1. THE RESIDUE IS MORE OR LESS 2. THE RESIDUE IS AMORPHOUS. - MARKEDLY CRYSTALLINE. - - A. _It gives in the sulphuric A. _In acetic acid solution it - acid solution evidence of an renders the action of the frog's - alkaloid by its action towards heart slower, or produces local - iodine and iodide of potassium._ anaesthesia._ - - _aa_. It does not produce local - anaesthesia. - - [alpha]. Sulphuric acid dissolves [alpha]. Sulphuric acid dissolves - it without the production of it red-brown, bromine produces a - colour, and chlorine and ammonia beautiful purple colour, water - give no murexide reaction. changes it into green, hydro- - _Cinchonine._ chloric acid dissolves it - greenish-brown. _Digitalin._ - - [beta]. Sulphuric acid dissolves [beta]. Sulphuric acid dissolves - it without colour, chlorine and it yellow, then brown-red; on ad- - ammonia give, as with theine, a dition of water this solution be- - murexide reaction. _Theobromine._ comes violet. Hydrochloric acid, - on warming, dissolves it red. - _Convallamarin._ - - _bb_. It produces local anaesthe- - sia. - - [alpha]. Sulphuric acid dissolves - it brown. The solution becomes, - by extracting with water, violet, - and can even be diluted with two - volumes of water without losing - its colour. _Saponin._ - - [beta]. Sulphuric acid dissolves - it yellow. On diluting with water - the same reaction occurs as in - the previous case, but more - feebly. _Senegin._ - - [gamma]. Sulphuric acid does not [gamma]. Sulphuric acid dissolves - colour in the cold; on warming, brown, and the solution becomes - the solution becomes a blue red by the addition of a little - violet. _Papaverine._ water. The action is very weak. - _Smilacin._ - - _cc_. Sulphuric acid dissolves it - with the production of a dirty - red, hydrochloric acid, in the - cold, with that of a reddish- - brown colour, and the last solu- - tion becomes brown on boiling. - _Constituents of the hellebore, - particularly Jervine._ - - [delta]. Sulphuric acid dissolves - it in the cold with the production - of a blue colour. _Unknown - impurities, many commercial - samples of Papaverine._ - - [epsilon]. Sulphuric acid dis- - solves it at first grey-brown; the - solution becomes in about twenty- - four hours blood-red. Iodine water - colours it blue. _Narceine._ - - B. IT GIVES NO ALKALOID REACTION. B. Is inactive, and becomes blue - by sulphuric acid; by Froehde's - reagent[336] dark cherry-red. - Hydrochloric acid dissolves it - red. The solution becomes, by - boiling, colourless. _Syringin._ - - [alpha]. Sulphuric acid dissolves - it with a beautiful yellow colour; - mixed with nitre, then moistened - with sulphuric acid, and lastly - treated with concentrated soda- - lye, it is coloured a brick-red. - _Picrotoxin._ - - [beta]. Sulphuric acid dissolves - it with the production of a - splendid red colour. The substance - renders the heart-action of a frog - slower. _Helleborin._ - -[336] Described at p. 239. - -VI. THE WATERY FLUID IS NOW AGAIN SHAKEN UP WITH PETROLEUM ETHER, - -in order to take up the rest of the chloroform, and the watery fluid is -saturated with ammonia. The watery solution of _aconitine_ and _emetine_ -is liable to undergo, through free ammonia, a partial decomposition; -but, on the other hand, it is quite possible to obtain, with very small -mixtures of the substances, satisfactory reactions, even out of -ammoniacal solutions. - -VII. THE AMMONIACAL WATERY FLUID WITH PETROLEUM ETHER. - -In the earlier stages Dragendorff advises the shaking up with petroleum -ether at about 40 deg., and the removal of the ether as quickly as possible -whilst warm. This is with the intention of separating by this fluid -strychnine, brucine, emetine, quinine, veratrine, &c. Finding, however, -that a full extraction by petroleum ether is either difficult or not -practicable, he prefers, as we have seen, to conclude the operation by -other agents, coming back again upon the ether for certain special -cases. Such are the volatile alkaloids; and here he recommends -treatment of the fluid by _cold_ petroleum ether, taking care _not_ to -hasten the removal of the latter. Strychnine and other fixed alkaloids -are then only taken up in small quantities, and the greater portion -remains for the later treatment of the watery fluid by benzene. - -A portion of the petroleum ether, supposed to contain in solution -volatile alkaloids, is evaporated in two watch-glasses; to the one, -strong hydrochloric acid is added, the other being evaporated without -this agent. On the evaporation of the petroleum ether, it is seen -whether the first portion is crystalline or amorphous, or whether the -second leaves behind a strongly-smelling fluid mass, which denotes a -volatile alkaloid. If the residue in both glasses is without odour and -fixed, the absence of volatile acids and the presence of fixed -alkaloids, strychnine, emetine, veratrine, &c., are indicated. - -THE PETROLEUM ETHER RESIDUE FROM AMMONIACAL SOLUTION. - - 1. IT IS FIXED AND 2. IT IS FIXED AND 3. IT IS FIXED AND - CRYSTALLINE. AMORPHOUS. ODOROUS. - - A. _The crystals are A. _On adding to the - volatilised with watch-glass a little - difficulty._ hydrochloric acid, - crystals are left - behind._ - - _aa._ Sulphuric acid _aa._ Its solution is - dissolves it without not precipitated by - colour. platin chloride. - - [alpha]. Potassic [alpha]. The purest [alpha]. The crystals - chromate colours this sulphuric acid dis- of the hydrochloric - solution a transitory solves it almost with- compound act on - blue, then red. out colour; sulphuric polarised light; and - _Strychnine._ acid containing nitric are mostly needle- - acid, red quickly be- shaped and columnar. - coming orange. _Coniine and - _Brucine._ Methyl-Coniine._ - - [beta]. Potassic [beta]. Sulphuric acid [beta]. The crystals - chromate does not dissolves it yellow, are cubical or tetra- - colour it blue; with becoming deep red. hedral. _Alkaloid - chlorine water and _Veratrine._ from Capsicum._ - ammonia it gives a - green colour. - _Quinine._ - - [gamma]. Sulphuric acid - dissolves it brown- - green; Froehde's reagent - red, changing into - green. _Emetine._ - - _bb_. The solution of - the hydrochlorate of - the alkaloid is pre- - cipitated by platin - chloride. - _Sarracinin._ - - [gamma]. Sulphuric B. The residue of the - acid dissolves it hydrochlorate of the - yellow, and the solu- alkaloid is amor- - tion becomes gradual- phous, or, by further - ly a beautiful deep additions of HCl, - red. _Sabadilline._ becomes crystalline. - - [delta]. The crystals - are easily volatil- - ised. _Coniine._ - - _aa._ Its diluted - aqueous solution is - precipitated by - platin chloride. - - [alpha]. The hydro- - chlorate salt, being - quickly treated with - Froehde's reagent, - gives after about two - minutes a violet - solution which - gradually fades. - _Lobeliin._ - - [beta]. The hydro- - chlorate smells like - nicotine, and becomes - by Froehde's reagent - yellow, and after - twenty-four hours - pale red. _Nicotine._ - - [gamma]. The hydro- - chlorate is without - odour, the free base - smells faintly like - aniline. _Sparteine._ - - _bb._ The substance - is not precipitated - from a diluted solu- - tion by platin - chloride. - - [alpha]. Its petro- - leum ether solution - produces no turbidity - with a solution of - picric acid in petro- - leum ether; but it - leaves behind, when - mixed with the above, - crystals mostly of - three-sided plates. - _Trimethylamine._ - - [beta]. The petroleum - ether solution gives, - on evaporation, when - treated similarly, - moss-like crystals. - The substance is made - blue by chloride of - lime, as well as by - diluted sulphuric - acid and bichromate - of potash. _Aniline._ - - [gamma]. The alkaloid - does not smell like - methylamine, and is - not coloured by chlo- - ride of lime, sul- - phuric acid, or chro- - mate of potash. - _Volatile alkaloid of - the Pimento._ - -VIII. THE AMMONIACAL SOLUTION IS SHAKEN UP WITH BENZENE. - -In most cases petroleum ether, benzene, and chloroform are more easily -separated from acid watery fluids than from ammoniacal, benzene and -chloroform causing here a difficulty which has perhaps deterred many -from using this method. Dragendorff, however, maintains that he has -never examined a fluid in which he could not obtain a complete -separation of the benzene and water. If the upper benzene layer is fully -gelatinous and emulsive, the under layer of water is to be removed with -a pipette as far as possible, and the benzene with a few drops of -absolute alcohol and filtration. As a rule, the water goes through first -alone, and by the time the greater part has run through, the jelly in -the filter, by dint of stirring, has become separated from the benzene, -and, finally, the jelly shrinks up to a minimum, and the clear benzene -filters off. Dragendorff filters mostly into a burette, from which -ultimately the benzene and the water are separated. - -The principal alkaloids which are dissolved in benzene are--strychnine, -methyl and ethyl strychnine, brucine, emetine, quinine, cinchonine, -atropine, hyoscyamine, physostigmine, aconitine, nepalin, the alkaloid -of the _Aconitum lycoctonum_, aconellin, napellin, delphinine, -veratrine, sabatrin, sabadilline, codeine, thebaine, and narcotine. - -THE BENZENE RESIDUE DERIVED FROM THE AMMONIACAL SOLUTION. - - 1. IT IS FOR THE MOST PART CRYS- 2. IT IS FOR THE MOST PART AMOR- - TALLINE. PHOUS. - - _a._ Sulphuric acid dissolves it _a._ Pure sulphuric acid dis- - without colour, the solution solves it either whitish-red or - being coloured neither on stand- yellowish. - ing nor on the addition of nitric - acid. - - _aa._ It dilates the pupil of a - cat. - - [alpha]. Platin chloride does not [alpha]. The solution becomes by - precipitate the aqueous solution. nitric acid immediately red, then - The sulphuric acid solution gives, quickly orange. _Brucine._ - on warming, a peculiar smell. - _Atropine._ - - [beta]. Platin chloride applied to [beta]. The solution becomes by - the solution precipitates. little and little brownish-red. - _Hyoscyamine._ The substance is coloured red by - chloride of lime solution, and it - contracts the pupil. - _Physostigmine._ - - _bb._ It does not dilate the - pupil. - - [alpha]. The sulphuric acid - solution becomes blue by chromate - of potash. - - [alpha][alpha]. The substance - applied to a frog produces - tetanus. _Strychnine._ - - [beta][beta]. It lowers the number - of respirations in a frog. _Ethyl - and Methyl Strychnine._ - - [beta]. Sulphuric acid and bi- - chromate of potash do not colour - it blue. - - [alpha][alpha]. The sulphuric acid - watery solution is fluorescent, - and becomes green on the addition - of chlorine water and ammonia. - _Quinine and Cinchonine._ - - (The last is more difficult to - dissolve in petroleum ether than - quinine.) - - [beta][beta]. The solution is not - fluorescent. _Cinchonine._ - - _b._ Sulphuric acid dissolves it _b._ Pure sulphuric acid dis- - at first colourless; the solution solves it yellow, and the solu- - takes on standing a rose or tion becomes later beautiful red - violet-blue; on addition of (with delphinine, more quickly a - nitric acid, a blood-red or brown darker cherry-red.) - coloration. - - [alpha]. A solution in diluted [alpha]. The hydrochloric acid - sulphuric acid becomes, on solution gradually becomes red on - heating, deep blood-red, and, when heating. - cooled, violet, with nitric acid. - The aqueous solution is precipi- - tated by ammonia. _Narcotine._ - - [alpha][alpha]. The substance - acts on a frog, causing, in large - doses, tetanus. _Veratrine._ - - [beta][beta]. It is almost with- - out action on frogs. _Sabatrin._ - - [beta]. The solution in diluted [beta]. The hydrochloric acid so- - sulphuric acid becomes, on heat- lution does not, on heating, - ing, a beautiful blue. Excess of become red. _Delphinine._ - ammonia does not precipitate in - a diluted watery solution. - _Codeine._ - - _c._ Sulphuric acid dissolves it _c._ Pure sulphuric acid dis- - with the production of a yellow solves it yellow, and the solu- - colour. tion becomes later red-brown, and - gradually violet-red. - - [alpha]. The solution remains [alpha]. The substance even in - yellow on standing. _Acolyctin._ small doses paralyses frogs, and - dilates the pupil of a cat's eye. - Ether dissolves it with diffi- - culty. _Nepalin._ - - [beta]. It becomes beautifully [beta]. It is easily soluble in - red. _Sabadilline._ ether, its effects are not so - marked, and it does not dilate - the pupil. _Aconitine._ - - [gamma]. Its effects are still - feeble; it does not dilate the - pupil, and is with difficulty - dissolved by ether. _Napellin._ - - _d._ Sulphuric acid dissolves it _d._ Sulphuric acid dissolves it - with an immediate deep red-brown with a dark green colour, and the - colour. _Thebaine._ solution becomes, even after a - few seconds, a beautiful blood- - red. _Alkaloidal substances out - of the Aconitum lycoctonum._ - - _e._ Sulphuric acid dissolves it _e._ Sulphuric acid dissolves it - immediately blue. _Substances brown-green, and Froehde's reagent - accompanying the Papaverins._ red, becoming beautifully green. - _Emetine._ - -IX. SHAKING OF THE AMMONIACAL WATERY SOLUTION WITH CHLOROFORM. - -This extracts the remainder of the cinchonine and papaverine, narceine, -and a small portion of morphine, as well as an alkaloid from the -celandine. - -THE RESIDUE FROM THE CHLOROFORM. - - _aa._ The solution, on warming, is only slightly coloured. - - [alpha]. But, after it is again cooled, it strikes with nitric acid a - violet-blue; chloride of iron mixed with the substance gives a blue - colour; Froehde's reagent also dissolves it violet. _Morphine._ - - [beta]. It is not coloured by nitric acid; it is also indifferent to - chloride of iron. _Cinchonine._ - - _bb._ The solution becomes by warming violet-blue. _Papaverine._ - - [gamma]. Sulphuric acid dissolves it greenish-brown, and the solution - becomes, on standing, blood-red. _Narceine._ - - [delta]. Sulphuric acid dissolves it a violet-blue. _Alkaloidal - constituent of the Celandine._ - -X. SHAKING UP OF THE WATERY FLUID WITH AMYL ALCOHOL. - -From this process, besides morphine and solanine, as well as salicin, -the remnants of the convallamarin, saponin, senegin, and narceine are -also to be expected. - -THE AMYL ALCOHOL RESIDUE. - - _a._ Sulphuric acid dissolves it without colour in the cold. - _Morphine_ (see above). - - _b._ Sulphuric acid dissolves it with the production of a clear - yellow-red and the solution becomes brownish. Iodine water colours it - a deep brown. The alcoholic solution gelatinises. _Solanine._ - - _c._ Sulphuric acid dissolves it green-brown, becoming red. - _Narceine_ (see above). - - _d._ Sulphuric acid dissolves it yellow, then brown-red, becoming - violet on dilution with water. Hydrochloric acid dissolves it, and it - becomes red on warming. It stops the heart-action in the systole. - _Convallamarin._ - - _e._ Hydrochloric acid dissolves it for the most part without colour. - _Saponin._ - - _f._ As the foregoing, but acting more feebly. _Senegin._ - - _g._ Sulphuric acid dissolves it immediately a pure red. On warming - with sulphuric acid and bichromate of potash, a smell of salicylic - acid is developed. _Salicin._ - -XI. DRYING THE WATERY FLUID WITH THE ADDITION OF POWDERED GLASS, AND -EXTRACTION OF THE FINELY-DIVIDED RESIDUE BY CHLOROFORM. - -The residue of the first chloroform extract lessens the number of -respirations of a frog; the residue of the second and third chloroform -extract becomes, by sulphuric acid and bichromate of potash, blue, -passing into a permanent red. - - Another portion of this residue becomes red on warming with diluted - sulphuric acid. _Curarine._ - - -SHORTER PROCESS FOR SEPARATING SOME OF THE ALKALOIDS. - -Sec. 310. A shorter process, recommended conditionally by Dragendorff, for -brucine, strychnine, quinine, cinchonine, and emetine, is as follows:-- - -The substance, if necessary, is finely divided, and treated with -sulphuric acid (dilute) until it has a marked acid reaction. To every -100 c.c. of the pulp (which has been diluted with distilled water to -admit of its being filtered later), at least 5 to 10 c.c. of diluted -sulphuric acid (1 : 5) are added. It is digested at 50 deg. for a few hours, -filtered, and the residue treated again with 100 c.c. of water at 50 deg. -This extract is, after a few hours, again filtered; both the filtrates -are mixed and evaporated in the water-bath to almost the consistency of -a thin syrup. The fluid, however, must not be concentrated too much, or -fully evaporated to dryness. The residue is now placed in a flask, and -treated with three to four times its volume of alcohol of 90 to 95 per -cent.; the mixture is macerated for twenty-four hours, and then -filtered. The filtrate is distilled alcohol-free, or nearly so, but a -small amount of alcohol remaining is not objectionable. The watery fluid -is diluted to about 50 c.c., and treated with pure benzene; the mixture -is shaken, and after a little time the benzene removed--an operation -which is repeated. After the removal the second time of the benzene, the -watery fluid is made alkaline with ammonia, warmed to 40 deg. or 50 deg., and -the free alkaloid extracted by twice shaking it up with two different -applications of benzene. On evaporation of the latter, if the alkaloid -is not left pure, it can be dissolved in acid, precipitated by ammonia, -and again extracted by benzene. - - Sec. 311. =Scheibler's Process=.--A method very different from those - just described is one practised by Scheibler. This is to precipitate - the phosphotungstate of the alkaloid, and then to liberate the - latter by digesting the precipitate with either hydrate of barium or - hydrate of calcium, dissolving it out by chloroform, or, if - volatile, by simple distillation. The convenience of Scheibler's - process is great, and it admits of very general application. In - complex mixtures, it will usually be found best to precede the - addition of phosphotungstic acid[337] by that of acetate of lead, in - order to remove colouring matter, &c.; the excess of lead must in - its turn be thrown out by SH_{2}, and the excess of SH_{2} be got - rid of by evaporation. Phosphotungstic acid is a very delicate test - for the alkaloids, giving a distinct precipitate with the most - minute quantities (1/200000 of strychnine and 1/100000 of quinine). - A very similar method is practised by Sonnenschein and others with - the aid of phospho-molybdic acid. The details of Scheibler's process - are as follows:-- - -[337] The method of preparing this reagent is as follows:--Ordinary -commercial sodium tungstate is treated with half its weight of -phosphoric acid, specific gravity, 1.13, and then allowed to stand for -some days. Phosphotungstic acid separates in crystals. - - The organic mixture is repeatedly extracted by water strongly - acidified with sulphuric acid; the extract is evaporated at 30 deg. to - the consistence of a thin syrup; then diluted with water, and, after - several hours' standing, filtered in a cool place. To the filtered - fluid phosphotungstic acid is added in excess, the precipitate - filtered, washed with water to which some phosphotungstic acid - solution has been added, and, whilst still moist, rinsed into a - flask. Caustic baryta or carbonate of potash is added to alkaline - reaction, and after the flask has been connected with bulbs - containing HCl, it is heated at first slowly, then more strongly. - Ammonia and any volatile alkaloids are driven over into the acid, - and are there fixed, and can be examined later by suitable methods. - The residue in the flask is carefully evaporated to dryness (the - excess of baryta having been precipitated by CO_{2}), and then - extracted by strong alcohol. On evaporation of the alcohol, the - alkaloid is generally sufficiently pure to be examined, or, if not - so, it may be obtained pure by re-solution, &c. - -The author has had considerable experience of Scheibler's process, and -has used it in precipitating various animal fluids, but has generally -found the precipitate bulky and difficult to manage. - - Sec. 312. =Grandval and Lajoux's Method=.[338]--The alkaloids are - precipitated from a solution slightly acidified by hydrochloric or - sulphuric acid by a solution of hydrarg-potassium iodide. The - precipitate is collected on a filter, washed and then transferred to - a flask; drop by drop, a solution of sodium sulphide is added; after - each addition the suspended precipitate is shaken and allowed to - stand for a few minutes, and a drop of the liquid taken out and - tested with lead acetate; directly a slight brown colour appears, - sufficient sodic sulphide has been added. The liquid is now left for - half-an-hour, with occasional shaking. Then sulphuric acid is added - until it is just acid, and the liquid is filtered and the mercury - sulphide well washed. In the filtrate will be the sulphate of any - alkaloid in solution; this liquid is now made alkaline with soda - carbonate and shaken up, as in Dragendorff's process, with - appropriate solvents; such, for example, as ether, or chloroform, or - acetone, or amylic alcohol, according to the particular alkaloid the - analyst is searching for, and the solvent finally separated and - allowed to evaporate, when the alkaloid is found in the residue. - -[338] "Dosage des alcaloides a l'aide de l'iodure double de mercure et -de potassium," par MM. A. Grandval et Henri Lajoux, _Journ. de -Pharmacie_, 5 ser. t. xxviii. 152-156. - - Sec. 313. =Identification of the Alkaloids=.--Having obtained, in one - way or other, a crystalline or amorphous substance, supposed to be - an alkaloid, or, at all events, an active vegetable principle, the - next step is to identify it. If the tests given in Dragendorff's - process have been applied, the observer will have already gone a - good way towards the identification of the substance; but it is, of - course, dangerous to trust to one reaction. - - In medico-legal researches there is seldom any considerable quantity - of the material to work upon. Hence the greatest care must be taken - from the commencement not to waste the substance in useless tests, - but to study well at the outset what--by the method of extraction - used, the microscopic appearance, the reaction to litmus paper, and - the solubility in different menstrua--it is likely to be. However - minute the quantity may be, it is essential to divide it into - different parts, in order to apply a variety of tests; but as any - attempt to do this on the solid substance will probably entail loss, - the best way is to dissolve it in a watch-glass in half a c.c. of - alcohol, ether, or other suitable solvent. Droplets of this solution - are then placed on watch-glasses or slips of microscopic glass, and - to these drops, by the aid of a glass rod, different reagents can be - applied, and the changes watched under the microscope as the drops - slowly evaporate. - -Sec. 314. =Sublimation of the Alkaloids.=--A very beautiful and elegant aid -to the identification of alkaloids, and vegetable principles generally, -is their behaviour towards heat. - -Alkaloids, glucosides, the organic acids, &c., when carefully heated, -either--(1) sublime wholly without decomposition (like theine, cytisin, -and others); or (2) partially sublime with decomposition; or (3) are -changed into new bodies (as, for example, gallic acid); or (4) melt and -then char; or (5) simply char and burn away. - -Many of these phenomena are striking and characteristic, taking place at -different temperatures, subliming in characteristic forms, or leaving -characteristic residues. - -One of the first to employ sublimation systematically, as a means of -recognition of the alkaloids, &c., was Helwig.[339] His method was to -place a small quantity (from 1/2 to 1/4000 of a mgrm.) in a depression -on platinum foil, cover it with a slip of glass, and then carefully heat -by a small flame. After Helwig, Dr. Guy[340] greatly improved the -process by using porcelain discs, and more especially by the adoption of -a convenient apparatus, which may be termed "the subliming cell." It is -essentially composed of a ring of glass from 1/8 to 2/3 of an inch in -thickness, such as may be obtained by sections of tubing, the cut -surfaces being ground perfectly smooth. This circle is converted into a -closed cell by resting it on one of the ordinary thin discs of glass -used as a covering for microscopic purposes, and supporting a similar -disc. The cell was placed on a brass plate, provided with a nipple, -which carried a thermometer, and was heated by a small flame applied -midway between the thermometer and the cell; the heat was raised very -gradually, and the temperature at which any change took place was noted. -In this way Dr. Guy made determinations of the subliming points of a -large number of substances, and the microscopic appearances of the -sublimates were described with the greatest fidelity and accuracy. On -repeating with care Dr. Guy's determinations, however, I could in no -single instance agree with his subliming points, nor with the apparatus -he figures and describes could two consecutive observations exactly -coincide. Further, on examining the various subliming temperatures of -substances, as stated by different authors, the widest discrepancies -were found--differences of 2 or even 3 degrees might be referred to -errors of observation, a want of exact coincidence in the thermometers -employed, and the like; but to what, for example, can we ascribe the -irreconcilable statements which have been made with regard to theine? -According to Strauch, this substance sublimes at 177 deg.; according to -Mulder, at 184.7 deg. But that both of these observations deviate more than -70 deg. from the truth may be proved by any one who cares to place a few -mgrms. of theine, enclosed between two watch-glasses, over the -water-bath; in a few minutes a distinct sublimate will condense on the -upper glass, and, in point of fact, theine will be found to sublime -several degrees below 100 deg. - -[339] _Das Mikroskop in der Toxicologie_. - -[340] _Pharm. Journ. Trans_. (2), viij. 719; ix. 10, 58. _Forensic -Medicine_, London, 1875. - -Since this great divergency of opinion is not found either in the -specific gravity, or the boiling-points, or any of the like -determinations of the physical properties of a substance, it is -self-evident that the processes hitherto used for the determination of -subliming points are faulty. The sources of error are chiefly-- - -(1.) Defects in the apparatus employed--the temperature read being -rather that of the metallic surface in the immediate vicinity of the -thermometer than of the substance itself. - -(2.) The want of agreement among observers as to what should be called a -sublimate--one considering a sublimate only that which is evident to the -naked eye, another taking cognisance of the earliest microscopic film. - -(3.) No two persons employing the same process. - -With regard to the apparatus employed, I adopt Dr. Guy's subliming cell; -but the cell, instead of resting on a metallic solid, floats on a -metallic fluid. For any temperature a little above 100 deg. this fluid is -mercury, but for higher temperatures fusible metal is preferable. - -[Illustration: SUBLIMING CELL.] - -The exact procedure is as follows:--A porcelain crucible (_a_ in fig.), -about 3 inches in diameter, is nearly filled with mercury or fusible -metal, as the case may be; a minute speck (or two or three crystals of -the substance to be examined) is placed on a thin disc of microscopic -covering glass, floated on the liquid, and the cell is completed by the -glass ring and upper disc. The porcelain crucible is supported on a -brass plate (_b_), fixed to a retort-stand in the usual way, and -protected from the unequal cooling effects of currents of air by being -covered by a flask (_c_), from which the bottom has been removed. The -neck of the flask conveniently supports a thermometer, which passes -through a cork, and the bulb of the thermometer is immersed in the bath -of liquid metal. In the first examination of a substance the temperature -is raised somewhat rapidly, taking off the upper disc with a forceps at -every 10 deg. and exchanging it for a fresh disc, until the substance is -destroyed. The second examination is conducted much more slowly, and the -discs exchanged at every 4 deg. or 5 deg., whilst the final determination is -effected by raising the temperature with great caution, and exchanging -the discs at about the points of change (already partially determined) -at every half degree. All the discs are examined microscopically. The -most convenient definition of a sublimate is this--the most minute -films, dots, or crystals, which can be observed by 1/4-inch power, and -which are obtained by keeping the subliming cell at a definite -temperature for 60 seconds. The commencement of many sublimates assumes -the shape of dots of extraordinary minuteness, quite invisible to the -unaided eye; and, on the other hand, since the practical value of -sublimation is mainly as an aid to other methods for the recognition of -substances, if we go beyond _short_ intervals of time, the operation, -otherwise simple and speedy, becomes cumbersome, and loses its general -applicability. - -There is also considerable discrepancy of statement with regard to the -melting-point of alkaloidal bodies; in many instances a viscous state -intervenes before the final complete resolution into fluid, and one -observer will consider the viscous state, the other complete fluidity, -as the melting-point. - -In the melting-points given below, the same apparatus was used, but the -substance was simply placed on a thin disc of glass floating on the -metallic bath before described (the cell not being completed), and -examined from time to time microscopically, for by this means alone can -the first drops formed by the most minute and closely-adherent crystals -to the glass be discovered. - -=Cocaine= melts at 93 deg., and gives a faint sublimate at 98 deg.; if put -between two watch-glasses on the water-bath, in fifteen minutes there is -a good cloud on the upper glass. - -=Aconitine= turns brown, and melts at 179 deg. C.; it gives no -characteristic sublimate up to 190 deg. - -=Morphine=, at 150 deg., clouds the upper disc with nebulae; the nebulae are -resolved by high magnifying powers into minute dots; these dots -gradually become coarser, and are generally converted into crystals at -188 deg.; the alkaloid browns at or about 200 deg. - -=Thebaine= sublimes in theine-like crystals at 135 deg.; at higher -temperatures (160 deg. to 200 deg.), needles, cubes, and prisms are observed. -The residue on the lower disc, if examined before carbonisation, is -fawn-coloured with non-characteristic spots. - -=Narcotine= gives no sublimate; it melts at 155 deg. into a yellow liquid, -which, on raising the temperature, ever becomes browner to final -blackness. On examining the residue before carbonisation, it is a rich -brown amorphous substance; but if narcotine be heated two or three -degrees above its melting-point, and then cooled slowly, the residue is -crystalline--long, fine needles radiating from centres being common. - -=Narceine= gives no sublimate; it melts at 134 deg. into a colourless -liquid, which undergoes at higher temperatures the usual transition of -brown colours. The substance, heated a few degrees above its -melting-point, and then allowed to cool slowly, shows a straw-coloured -residue, divided into lobes or drops containing feathery crystals. - -=Papaverine= gives no sublimate; it melts at 130 deg. The residue, heated a -little above its melting-point, and then slowly cooled, is amorphous, of -a light-brown colour, and in no way characteristic. - -=Hyoscyamine= gives no crystalline sublimate; it melts at 89 deg., and -appears to volatilise in great part without decomposition. It melts into -an almost colourless fluid, which, when solid, may exhibit a network not -unlike vegetable parenchyma; on moistening the network with water, -interlacing crystals immediately appear. If, however, hyoscyamine be -kept at 94 deg. to 95 deg. for a few minutes, and then slowly cooled, the edges -of the spots are arborescent, and the spots themselves crystalline. - -=Atropine= (daturine) melts at 97 deg.; at 123 deg. a faint mist appears on the -upper disc. Crystals cannot be obtained; the residue is not -characteristic. - -=Solanine.=--The upper disc is dimmed with nebulae at 190 deg., which are -coarser and more distinct at higher temperatures; at 200 deg. it begins to -brown, and then melts; the residue consists of amber-brown, -non-characteristic drops. - -=Strychnine= gives a minute sublimate of fine needles, often disposed in -lines, at 169 deg.; about 221 deg. it melts, the residue (at that temperature) -is resinous. - -=Brucine= melts at 151 deg. into a pale yellow liquid, at higher -temperatures becoming deep-brown. If the lower disc, after melting, be -examined, no crystals are observed, the residue being quite transparent, -with branching lines like the twigs of a leafless tree; light mists, -produced rather by decomposition than by true sublimation, condense on -the upper disc at 185 deg., and above. - -=Saponin= neither melts nor sublimes; it begins to brown about 145 deg., is -almost black at 185 deg., and quite so at 190 deg. - -=Delphinine= begins to brown about 102 deg.; it becomes amber at 119 deg., and -melts, and bubbles appear. There is no crystalline sublimate; residue -not characteristic. - -=Pilocarpine= gives a distinct crystalline sublimate at 153 deg.; but thin -mists, consisting of fine dots, may be observed as low as 140 deg. -Pilocarpine melts at 159 deg.; the sublimates at 160 deg. to 170 deg. are in light -yellow drops. If these drops are treated with water, and the water -evaporated, feathery crystals are obtained; the residue is resinous. - -=Theine= wholly sublimes; the first sublimate is minute dots, at 79 deg.; at -half a degree above that very small crystals may be obtained; and at -such a temperature as 120 deg., the crystals are often long and silky. - -=Theobromine= likewise wholly sublimes; nebulae at 134 deg., crystals at -170 deg., and above. - -=Salicin= melts at 170 deg.; it gives no crystalline sublimate. The melted -mass remains up to 180 deg. almost perfectly colourless; above that -temperature browning is evident. The residue is not characteristic. - -=Picrotoxin= gives no crystalline sublimate. The lowest temperature at -which it sublimes is 128 deg.; the usual nebulae then make their appearance; -between 165 deg. and 170 deg. there is slight browning; at 170 deg. it melts. The -residue, slowly cooled, is not characteristic. - -=Cantharidin= sublimes very scantily between 82 deg. and 83 deg.; at 85 deg. the -sublimate is copious. - -The active principles of plants may, in regard to their behaviour to -heat, be classed for practical purposes into-- - - 1. Those which give a decided crystalline sublimate: - (_a._) Below 100 deg., _e.g._, cocaine, theine, thebaine, cantharidin. - (_b._) Between 100 deg. and 150 deg., _e.g._, quinetum. - (_c._) Between 150 deg. and 200 deg., _e.g._, strychnine, morphine, - pilocarpine. - 2. Those which melt, but give no crystalline sublimate: - (_a._) Below 100 deg., _e.g._, hyoscyamine, atropine. - (_b._) Between 100 deg. and 150 deg., _e.g._, papaverine. - (_c._) Between 150 deg. and 200 deg., _e.g._, salicin. - (_d._) Above 200 deg., _e.g._, solanine. - 3. Those which neither melt nor give a crystalline sublimate, _e.g._, - saponin. - -Sec. 315. =Melting-point.=--The method of sublimation just given also -determines the melting-point; such a determination will, however, seldom -compare with the melting-points of the various alkaloids as given in -text-books, because the latter melting-points are not determined in the -same way. The usual method of determining melting-points is to place a -very small quantity in a glass tube closed at one end; the tube should -be almost capillary. The tube is fastened to a thermometer by means of -platinum wire, and then the bulb of the thermometer, with its attached -tube, is immersed in strong sulphuric acid or paraffin, contained in a -flask. The thermometer should be suspended midway in the liquid and heat -carefully applied, so as to raise the temperature gradually and equably. -It will be found that rapidly raising the heat gives a different -melting-point to that which is obtained by slowly raising the heat. -During the process careful watching is necessary: most substances change -in hue before they actually melt. A constant melting-point, however -often a substance is purified by recrystallisation, is a sign of purity. - -Sec. 316. =Identification by Organic Analysis.=--In a few cases (and in a -few only) the analyst may have sufficient material at hand to make an -organic analysis, either as a means of identification or to confirm -other tests. By the vacuum process described in "Foods," in which carbon -and nitrogen are determined by measuring the gases evolved by burning -the organic substance in as complete a vacuum as can be obtained, very -minute quantities of a substance can be dealt with, and the carbon and -nitrogen determined with fair accuracy. It is found in practice that the -carbon determinations appear more reliable than those of the nitrogen, -and there are obvious reasons why this should be so. - -Theoretically, with the improved gas-measuring appliances, it is -possible to measure a c.c. of gas; but few chemists would care to create -a formula on less than 10 c.c. of CO_{2}. Now, since 10 c.c. of CO_{2} -is equal to 6.33 mgrms. of carbon, and alkaloids average at least half -their weight of carbon, it follows that 12 mgrms. of alkaloid represent -about the smallest quantity with which a reliable single combustion can -be made. - -The following table gives a considerable number of the alkaloids and -alkaloidal bodies, arranged according to their content in carbon:-- - -TABLE SHOWING THE CONTENT OF CARBON AND NITROGEN IN VARIOUS ALKALOIDAL -BODIES. - - Carbon. Nitrogen. - - Asparagin, 36.36 21.21 - Methylamine, 38.71 45.17 - Betaine, 44.44 10.37 - Theobromine, 46.67 31.11 - Theine, 49.48 28.86 - Indican, 49.60 2.22 - Muscarine, 50.42 11.77 - Lauro-cerasin, 52.47 1.53 - Amanitine, 57.69 13.46 - Narceine, 59.63 3.02 - Colchicine, 60.53 4.15 - Oxyacanthine, 60.57 4.42 - Solanine, 60.66 1.68 - Trimethylamine, 61.02 23.73 - Jervine, 61.03 5.14 - Sabadilline, 61.29 3.46 - Aconitine, 61.21 2.16 - Nepaline, 63.09 2.12 - Colchicein, 63.44 4.38 - Veratroidine, 63.8 3.1 - Narcotine, 63.92 3.39 - Veratrine, 64.42 2.91 - Delphinine, 64.55 3.42 - Physostigmine, 65.49 15.27 - Rh[oe]adine, 65.79 3.65 - Cocaine, 66.44 4.84 - Gelsemine, 67.00 7.10 - Conhydrine, 67.12 9.79 - Staphisagrine, 67.5 3.6 - Chelidonine, 68.06 12.34 - Atropine, Hyoscyamine, 70.58 4.84 - Sanguinarine, 70.59 4.33 - Papaverine, 70.79 4.13 - Delphinoidine, 70.9 3.9 - Morphine and Piperine, 71.58 4.91 - Berberine, 71.64 4.18 - Codeine, 72.24 4.68 - Thebaine, 73.31 4.50 - Cytisine, 73.85 12.92 - Nicotine, 74.08 17.28 - Quinine, 75.02 8.64 - Coniine, 76.81 11.20 - Strychnine, 77.24 8.92 - Curarine, 81.51 5.28 - -Sec. 317. =Quantitative Estimation of the Alkaloids.=--For medico-legal -purposes the alkaloid obtained is usually weighed directly, but for -technical purposes other processes are used. One of the most convenient -of these is titration with normal or decinormal sulphuric acid, a method -applicable to a few alkaloids of marked basic powers--_e.g._, quinine is -readily and with accuracy estimated in this way, the alkaloid being -dissolved in a known volume of the acid, and then titrated back with -soda. If a large number of observations are to be made, an acid may be -prepared so that each c.c. equals 1 mgrm. of quinine. A reagent of -general application is found in the so-called _Mayer's reagent_, which -consists of 13.546 grms. of mercuric chloride, and 49.8 grms. of iodide -of potassium in a litre of water. Each c.c. of such solution -precipitates-- - - Of Strychnine, .0167 grm. - " Brucine, .0233 " - " Quinine, .0108 " - " Cinchonine, .0102 " - " Quinidine, .0120 " - " Atropine, .0145 " - " Aconitine, .0268 " - " Veratrine, .0269 " - " Morphine, .0200 " - " Narcotine, .0213 " - " Nicotine, .00405 " - " Coniine, .00416 " - -The final reaction is found by filtering, from time to time, a drop on -to a glass plate, resting on a blackened surface, and adding the test -until no precipitate appears. The results are only accurate when the -strength of the solution of the alkaloid is about 1 : 200; so that it is -absolutely necessary first to ascertain approximatively the amount -present, and then to dilute or concentrate, as the case may be, until -the proportion mentioned is obtained. - -A convenient method of obtaining the sulphate of an alkaloid for -quantitative purposes, and especially from organic fluids, is that -recommended by Wagner. The fluid is acidulated with sulphuric acid, and -the alkaloid precipitated by a solution of iodine in iodide of -potassium. The precipitate is collected and dissolved in an aqueous -solution of hyposulphite of soda. The filtered solution is again -precipitated with the iodine reagent, and the precipitate dissolved in -sulphurous acid, which, on evaporation, leaves behind the pure sulphate -of the base. - -It is also very useful for quantitative purposes to combine an alkaloid -with gold or platinum, by treating the solution with the chlorides of -either of those metals--the rule as to selection being to give that -metal the preference which yields the most insoluble and the most -crystallisable compound. - -The following table gives the percentage of gold or platinum left on -ignition of the double salt:-- - - Gold. Platinum. - - Atropine, 31.57 ... - Aconitine 20.0 ... - Amanitine, 44.23 ... - Berberine, 29.16 18.11 - Brucine, ... 16.52 - Cinchonine, ... 27.36 - Cinchonidine, ... 27.87 - Codeine, ... 19.11 - Coniine, ... 29.38 - Curarine, ... 32.65 - Delphinine, 26.7 ... - Delphinoidine, 29.0 15.8 - Emetine, ... 29.7 - Hyoscyamine, 34.6 ... - Morphine, ... 19.52 - Muscarine, 43.01 ... - Narcotine, 15.7 15.9 - Narceine, ... 14.52 - Nicotine, ... 34.25 - Papaverine, ... 17.82 - Pilocarpine, 35.5 23.6 to 25.2. - Piperine, ... 12.7 - Quinine, 40.0 26.26 - Strychnine, 29.15 18.16 - Thebaine, ... 18.71 - Theine, 37.02 24.58 - Theobromine, ... 25.55 - Veratrine, 21.01 ... - - -II.--Liquid Volatile Alkaloids. - -THE ALKALOIDS OF HEMLOCK--NICOTINE--PITURIE--SPARTEINE. - - -1. THE ALKALOIDS OF HEMLOCK (CONIUM). - -Sec. 318. The _Conium maculatum_, or spotted hemlock, is a rather common -umbelliferous plant, growing in waste places, and flowering from about -the beginning of June to August. The stem is from three to five feet -high, smooth, branched, and spotted with purple; the leaflets of the -partial involucres are unilateral, ovate, lanceolate, with an attenuate -point shorter than the umbels; the seeds are destitute of vittae, and -have five prominent crenate wavy ridges. The whole plant is f[oe]tid and -poisonous. Conium owes its active properties to a volatile liquid -alkaloid, _Coniine_, united with a crystalline alkaloid, _Conhydrine_. - -Sec. 319. =Coniine= (=conia=, =conicine=), (C_{8}H_{17}N)--specific gravity -0.862 at 0 deg.; melting-point, -2.5 deg.; boiling-point, 166.6 deg. Pure -coniine has been prepared synthetically by Ladenburg, and found -to be propyl-piperidine C_{5}H_{10}NC_{3}H_{7}, but the -synthetically-prepared piperidine has no action on polarised light. By -uniting it with dextro-tartaric acid, and evaporating, it is possible to -separate the substance into dextro-propyl-piperidine and -laevo-propyl-piperidine. The former is in every respect identical with -coniine from hemlock; it is a clear, oily fluid, possessing a peculiarly -unpleasant, mousey odour. One part is soluble in 150 parts of -water,[341] in 6 parts of ether, and in almost all proportions of amyl -alcohol, chloroform, and benzene. It readily volatilises, and, provided -air is excluded, may be distilled unchanged. It ignites easily, and -burns with a smoky flame. It acts as a strong base, precipitating the -oxides of metals and alkaline earths from their solutions, and it -coagulates albumen. Coniine forms salts with hydrochloric acid -(C_{8}H_{15}N.HCl), phosphoric acid, iodic acid, and oxalic acid, which -are in well-marked crystals. The sulphate, nitrate, acetate, and -tartrate are, on the other hand, non-crystalline. - -[341] The saturated watery solution of coniine at 15 deg., becomes cloudy if -gently warmed, and clears again on cooling. - -If coniine is oxidised with nitric acid, or bichromate of potash, and -diluted sulphuric acid, butyric acid is formed; and since the latter has -an unmistakable odour, and other characteristic properties, it has been -proposed as a test for coniine. This may be conveniently performed -thus:--A crystal of potassic bichromate is put at the bottom of a -test-tube, and some diluted sulphuric acid with a drop of the supposed -coniine added. On heating, the butyric acid reveals itself by its odour, -and can be distilled into baryta water, the butyrate of baryta being -subsequently separated in the usual way, and decomposed by sulphuric -acid, &c. - -Another test for coniine is the following:--If dropped into a solution -of alloxan, the latter is coloured after a few minutes an intense -purple-red, and white needle-shaped crystals are separated, which -dissolve in cold potash-lye into a beautiful purple-blue, and emit an -odour of the base.[342] Dry hydrochloric acid gives a purple-red, then -an indigo-blue colour, with coniine; but if the acid is not dry, there -is formed a bluish-green crystalline mass. This test, however, is of -little value to the toxicologist, the pure substance alone responding -with any definite result. - -[342] Schwarzenbach, _Vierteljahrsschr. f. prakt. Pharm._, viij. 170. - -The ordinary precipitating agents, according to Dragendorff, act as -follows:-- - - Potass bismuth iodide. - 1 : 2000, a strong orange precipitate. - 1 : 3000. The drop of the reagent is surrounded with a muddy border. - 1 : 4000. The drop of the reagent is surrounded with a muddy border. - 1 : 5000, still perceptible. - 1 : 6000. The last limit of the reaction. - -Phosphomolybdic acid gives a strong yellow precipitate; limit, 1 : 5000. - -Potass. mercuric iodide gives a cheesy precipitate; limit, 1 : 1000 in -neutral, 1 : 800 in acid, solutions. - -Potass. cadmic iodide gives an amorphous precipitate, 1 : 300. The -precipitate is soluble in excess of the precipitant. (Nicotine, under -similar circumstances, gives a crystalline precipitate.) - -Flueckiger recommends the following reaction:[343]--"Add to 10 drops of -ether in a shallow glass crystallising dish 2 drops of coniine, and -cover with filter paper. Set upon the paper a common-sized watch-glass -containing bromine water, and invert a beaker over the whole -arrangement. Needle-shaped crystals of coniine hydro-bromine soon form -in the dish as well as in the watch-glass." Hydrochloric acid, used in -the same way, instead of bromine water, forms with coniine microscopic -needles of coniine hydrochlorate; both the hydro-bromide and the -hydrochlorate doubly refract light. Nicotine does not respond to this -reaction. - -[343] _Reactions_, by F. A. Flueckiger, Detroit, 1893. - -Coniine forms with carbon disulphide a thiosulphate and a sulphite. If -carbon disulphide, therefore, be shaken with an aqueous solution of -coniine, the watery solution gives a brown precipitate with copper -sulphate, colours ferric chloride solution dark brown red, and gives a -milky opalescence with dilute acids. If coniine itself is added to -carbon disulphide, there is evolution of heat, separation of sulphur, -and formation of thiosulphate. Nicotine does not respond to this -reaction. - -Sec. 320. =Other Coniine Bases.=--Methyl- and ethyl-coniine have been -prepared synthetically, and are both similar in action to coniine, but -somewhat more like curarine. By the reduction of coniine with zinc dust -conyrine (C_{8}H_{11}N) is formed; between coniine and conyrine stands -coniceine (C_{8}H_{15}NO). De Coninck has made synthetically by the -addition of 6 atoms of hydrogen to [beta] collidine, a new fluid -alkaloid (C_{8}H_{11}N + 6H = C_{8}H_{17}N), which he has called -_isocicutine_: it has the same formula as coniine. Paraconiine Schiff -prepared synthetically from ammonia and normal butyl aldehyde; it has -the formula C_{8}H_{15}N, and therefore differs from coniine in -containing two atoms less of hydrogen. All the above have a similar -physiological action to coniine. [alpha]-stillbazoline (C_{11}H_{19}N), -prepared by Baurath from benzaldehyde and picoline, is analogous to -coniine, and according to Falck has similar action, but is more -powerful. - -Sec. 321. =Pharmaceutical Preparations.=--The percentage of coniine in the -plant itself, and in pharmaceutical preparations, can be approximately -determined by distilling the coniine over, in a partial vacuum,[344] -and titrating the distillate with Mayer's reagent, each c.c. = about -.00416 grm. of coniine. It appears to be necessary to add powdered -potassic chloride and a small quantity of diluted sulphuric acid before -titrating, or the precipitate does not separate. In any case, the end of -the reaction is difficult to observe.[345] - -[344] This is easily effected by uniting a flask containing the -alkaloidal fluid, air-tight, with a Liebig's condenser and a receiver, -the latter being connected with Bunsen's water-pump, or one of the -numerous exhausting apparatuses now in use in every laboratory. - -[345] Dragendorff, _Die Chemische Werthbestimmung einiger starkwirkender -Droguen_, St. Petersb., 1874. - -The fresh plant is said to contain from about .04 to .09 per cent., and -the fruit about 0.7 per cent. of coniine. - -The officinal preparations are--the leaves, the fruit, a tincture of the -fruit, an extract of the leaves, the juice of the leaves (_Succus -conii_), a compound hemlock pill (composed of extract of hemlock, -ipecacuanha, and treacle), an inhalation of coniine (_Vapor conii_), and -a poultice (_Cataplasma conii_) made with the leaves. - -Sec. 322. =Statistics of Coniine Poisoning.=--F. A. Falck[346] has been -able to collect 17 cases of death recorded in medical literature, up to -the year 1880, from either coniine or hemlock. Two of these cases were -criminal (murders), 1 suicidal, 2 cases in which coniine had been used -medicinally (in one instance the extract had been applied to a cancerous -breast; in the other, death was produced from the injection of an -infusion of hemlock leaves). The remaining 12 were cases in which the -root, leaves, or other portions of the plant had been ignorantly or -accidentally eaten. - -[346] _Prakt. Toxicologie_, p. 273. - -Sec. 323. =Effects on Animals.=--It destroys all forms of animal life. The -author made some years ago an investigation as to its action on the -common blow-fly. Droplets of coniine were applied to various parts of -blow-flies, which were then placed under glass shades. The symptoms -began within a minute by signs of external irritation, there were rapid -motions of the wings, and quick and aimless movements of the legs. -Torpor set in speedily, the buzz soon ceased, and the insects lay on -their sides, motionless, but for occasional twitching of the legs. The -wings, as a rule, became completely paralysed before the legs, and death -occurred at a rather variable time, from ten minutes to two hours. If -placed in a current of air in the sun, a fly completely under the -influence of coniine may recover. Coniine causes in frogs, similar to -curarine, peripheral paralysis of the motor nerves, combined with a -transitory stimulation, and afterwards a paralysis of the motor centres; -in frogs the paralysis is not preceded by convulsions. Dragendorff -experimented on the action of coniine when given to five cats, the -quantities used being .05 to .5 grm. The symptoms came on almost -immediately, but with the smaller dose given to a large cat, no effect -was witnessed until twenty-five minutes afterwards; this was the longest -interval. One of the earliest phenomena was dilatation of the pupil, -followed by weakness of the limbs passing into paralysis, the hinder -legs being affected prior to the fore. The respiration became troubled, -and the frequency of the breathing diminished; the heart in each case -acted irregularly, and the sensation generally was blunted; death was -preceded by convulsions. In the cases in which the larger dose of .4 to -.5 grm. was administered, death took place within the hour, one animal -dying in eight minutes, a second in eighteen minutes, a third in twenty -minutes, and a fourth in fifty-eight minutes. With the smaller dose of -.051 grm. given to a large cat, death did not take place until eight -hours and forty-seven minutes after administration. - -Sec. 324. =Effects on Man.=--In a case recorded by Bennet,[347] and quoted -in most works on forensic medicine, the symptoms were those of general -muscular weakness deepening into paralysis. The patient had eaten -hemlock in mistake for parsley; in about twenty minutes he experienced -weakness in the lower extremities, and staggered in walking like a -drunken man; within two hours there was perfect paralysis of both upper -and lower extremities, and he died in three and a quarter hours. In -another case, related by Taylor, the symptoms were also mainly those of -paralysis, and in other instances stupor, coma, and slight convulsions -have been noted. - -[347] _Edin. Med. and Surg. Journ._, July 1845, p. 169. - -Sec. 325. =Physiological Action.=--It is generally agreed that coniine -paralyses, first the ends of the motor nerves, afterwards their trunks, -and lastly, the motor centre itself. At a later period the sensory -nerves participate. In the earlier stage the respiration is quickened, -the pupils contracted, and the blood-pressure increased; but on the -development of paralysis the breathing becomes slowed, the capillaries -relaxed, and the blood-pressure sinks. Death takes place from cessation -of the respiration, and not primarily from the heart, the heart beating -after the breathing has stopped. Coniine is eliminated by the urine, and -is also in part separated by the lungs, while a portion is, perhaps, -decomposed in the body. - -Sec. 326. =Post-mortem Appearances.=--There is nothing characteristic in -the appearances after death. - -=Fatal Dose.=--The fatal dose of coniine is not accurately known; it is -about 150 mgrms. (2.3 grains). In the case of Louise Berger, 10 to 15 -drops appear to have caused death in a few minutes. The auto-experiments -of Dworzak, Heinrich, and Dillaberger would indicate that one drop may -cause unpleasant symptoms. Albers, in the treatment of a woman suffering -from cancer of the breast, witnessed convulsions and loss of -consciousness from a third dose of 4 mgrms. (.06 grain); and Eulenberg, -its full narcotic effects on a child after subcutaneous injection of 1 -mgrm. (.015 grain). - -Sec. 327. =Separation of Coniine from Organic Matters or Tissues.=--The -substances are digested with water, acidulated with H_{2}SO_{4}, at a -temperature not exceeding 40 deg., and then filtered. If the filtrate should -be excessive, it must be concentrated; alcohol is then added, the liquid -refiltered, and from the filtrate the alcohol separated by distillation. - -On cooling, the acid fluid is agitated with benzene, and the latter -separated in the usual way. The fluid is now alkalised with ammonia, and -shaken up once or twice with its own volume of petroleum ether; the -latter is separated and washed with distilled water, and the alkaloid is -obtained almost pure. If the petroleum ether leaves no residue, it is -certain that the alkaloid was not present in the contents of the stomach -or intestine. - -The affinity of coniine with ether or chloroform is such, that its -solution in either of these fluids, passed through a _dry_ filter, -scarcely retains a drop of water. In this way it may be conveniently -purified, the impurities dissolved by water remaining behind. - -In searching for coniine, the stomach, intestines, blood, urine, liver, -and lungs are the parts which should be examined. According to -Dragendorff, it has been discovered in the body of a cat six weeks after -death. - -Great care must be exercised in identifying any volatile alkaloid as -coniine, for the sources of error seem to be numerous. In one case[348] -a volatile coniine-like ptomaine, was separated from a corpse, and -thought to be coniine; but Otto found that in its behaviour to platinic -chloride, it differed from coniine; it was very poisonous--.07 was fatal -to a frog, .44 to a pigeon, in a few minutes. In the seeds of _Lupinus -luteus_ there is a series of coniine-like substances,[349] but they do -not give the characteristic crystals with hydrochloric acid. - -[348] Otto, _Anleitung z. Ausmittlung d. Gifte_, 1875. - -[349] Sievert, _Zeitschrift fuer Naturwissenschaften_. - - -2. TOBACCO--NICOTINE. - -Sec. 328. The different forms of tobacco are furnished by three species of -the tobacco plant, viz., _Nicotianum tabacum_, _N. rustica_, and _N. -persica_. - -Havanna, French, Dutch, and the American tobaccos are in the main -derived from _N. tabacum_; Turkish, Syrian, and the Latakia tobaccos are -the produce of _N. rustica_. There seems at present to be little of _N. -persica_ in commerce. - -All the species of tobacco contain a liquid, volatile, poisonous -alkaloid (_Nicotine_), probably united in the plant with citric and -malic acids. There is also present in tobacco an unimportant camphor -(_nicotianin_). The general composition of the plant may be gathered -from the following table:-- - -TABLE SHOWING THE COMPOSITION OF FRESH LEAVES OF TOBACCO (POSSELT AND -RIENMANN). - - Nicotine, 0.060 - Concrete volatile oil, 0.010 - Bitter extractive, 2.870 - Gum with malate of lime, 1.740 - Chlorophyl, 0.267 - Albumen and gluten, 1.308 - Malic acid, 0.510 - Lignine and a trace of starch, 4.969 - Salts (sulphate, nitrate, and malate of potash, } - chloride of potassium, phosphate and malate } 0.734 - of lime, and malate of ammonia,) } - Silica, 0.088 - Water, 88.280 - ------- - 100.836 - -Sec. 329. =Quantitative Estimation of Nicotine in Tobacco.=--The best -process (although not a perfectly accurate one) is the following:--25 -grms. of the tobacco are mixed with milk of lime, and allowed to stand -until there is no odour of ammonia; the mixture is then exhausted by -petroleum ether, the ether shaken up with a slight excess of normal -sulphuric acid, and titrated back by baryta water; the sulphate of -baryta may be collected and weighed, so as to control the results. With -regard to the percentage of nicotine in commercial tobacco, Kosutany -found from 1.686 to 3.738 per cent. in dry tobacco; Letheby, in six -samples, from 1.5 to 3.2 per cent.; whilst Schloessing gives for Havanna -2 per cent., Maryland 2.29 per cent., Kentucky 6.09 per cent., Virginian -6.87 per cent., and for French tobacco, quantities varying from 3.22 to -7.96 per cent. Again, Lenoble found in Paraguay tobacco from 1.8 to 6 -per cent.; and Wittstein, in six sorts of tobacco in Germany, 1.54 to -2.72 per cent. - -Mr. Cox[350] has recently determined the amount of nicotine in a number -of tobaccos. The results are tabulated in the following table as -follows:-- - -[350] _Pharm. Journ._, Jan. 20, 1894. - -TABLE OF RESULTS, ARRANGED ACCORDING TO PER CENT. OF NICOTINE. - - Variety examined. Nicotine - per cent. - - 1. Syrian leaves (_a_), .612 - 2. American chewing, .935 - 3. Syrian leaves (_b_), 1.093 - 4. Chinese leaves, 1.902 - 5. Turkish (coarse cut), 2.500 - 6. Golden Virginia (whole strips), 2.501 - 7. Gold Flake (Virginia), 2.501 - 8. "Navy-cut" (light coloured), 2.530 - 9. Light returns (Kentucky), 2.733 - 10. "Navy-cut" (dark "all tobacco"), 3.640 - 11. Best "Birds-eye," 3.931 - 12. Cut Cavendish (_a_), 4.212 - 13. "Best Shag" (_a_), 4.907 - 14. "Cut Cavendish" (_b_), 4.970 - 15. "Best Shag" (_b_), 5.000 - 16. French tobacco, 8.711 - 17. Algerian tobacco (_a_), 8.813 - 18. Algerian tobacco (_b_), 8.900 - -It is therefore obvious that the strength of tobacco in nicotine varies -between wide limits. - -Twenty-five grammes (or more or less, according to the amount of the -sample at disposal) of the dried and powdered tobacco were intimately -mixed with slaked lime, and distilled in a current of steam until the -condensed steam was no longer alkaline; the distillate was slightly -acidulated with dilute H_{2}SO_{4}, and evaporated to a conveniently -small bulk. This was made alkaline with soda, and agitated repeatedly -with successive portions of ether. The separated batches of ethereal -solution of nicotine were then mixed and exposed to the air in a cool -place. This exposure to the air carries away ammonia, if any be present, -as well as ether. - -Water was added to the ethereal residue, and the amount of nicotine -present determined by decinormal H_{2}SO_{4}, using methyl-orange as an -indicator. One c.c. of decinormal H_{2}SO_{4} represents 0.0162 gramme -of nicotine (C_{10}H_{14}N_{2}). - -Sec. 330. =Nicotine= (C_{10}H_{14}N_{2}).--Hexahydro dipyridyl -(C_{5}H_{4}N)_{2}H_{6}, when pure, is an oily, colourless fluid, of -1.0111, specific gravity at 15 deg.[351] It evaporates under 100 deg. in white -clouds, and boils at about 240 deg., at which temperature it partly distils -over unchanged, and is partly decomposed--a brown resinous product -remaining. It volatilises with aqueous and amyl alcohol vapour notably, -and is not even fixed at -10 deg. It has a strong alkaline reaction, and -rotates a ray of polarised light to the right. Its odour, especially on -warming, is strong and unpleasantly like tobacco, and it has a sharp -caustic taste. It absorbs water exposed to the air, and dissolves in -water in all proportions, partly separating from such solution on the -addition of a caustic alkali. The aqueous solution acts in many respects -like ammonia, saturating acids fully, and may therefore be in certain -cases estimated with accuracy by titration, 49 parts of H_{2}SO_{4} -corresponding to 162 of nicotine. It gives on oxidation nicotinic acid = -m([beta]) pyridincarbo acid C_{5}H_{4}N(COOH), and by oxidation with -elimination of water dipyridyl (C_{5}H_{4}N)_{2}, and through reduction -dipiperydil (C_{5}H_{10}N)_{2}. - -[351] J. Skalweit, _Ber. der. deutsch. Chem. Gesell._, 14, 1809. - -Alcohol and ether dissolve nicotine in every proportion; if such -solutions are distilled, nicotine goes over first. The salts which it -forms with hydrochloric, nitric, and phosphoric acids crystallise with -difficulty; tartaric and oxalic acid form white crystalline salts, and -the latter, oxalate of nicotine, is soluble in alcohol, a property which -distinguishes it from the oxalate of ammonia. The best salts are the -oxalate and the acid tartrate of nicotine, from which to regenerate -nicotine in a pure state. - -Hydrochloride of nicotine is more easily volatilised than the pure base. -Nicotine is precipitated by alkalies, &c., also by many oxyhydrates, -lead, copper, &c. By the action of light, it is soon coloured yellow and -brown, and becomes thick, in which state it leaves, on evaporation, a -brown resinous substance, only partly soluble in petroleum ether. - -A very excellent test for nicotine, as confirmatory of others, is the -beautiful, long, needle-like crystals obtained by adding to an ethereal -solution of nicotine a solution of iodine in ether. The crystals require -a few hours to form. - -Chlorine gas colours nicotine blood-red or brown; the product is soluble -in alcohol, and separates on evaporation in crystals. - -Cyanogen also colours nicotine brown; the product out of alcohol is not -crystalline. Platin chloride throws down a reddish crystalline -precipitate, soluble on warming; and gallic acid gives a flocculent -precipitate. A drop of nicotine poured on dry chromic acid blazes up, -and gives out an odour of tobacco camphor; if the ignition does not -occur in the cold, it is produced by a gentle heat. It is scarcely -possible to confound nicotine with ammonia, by reason of its odour; and, -moreover, ammonia may always be excluded by converting the base into the -oxalate, and dissolving in absolute alcohol. - -On the other hand, a confusion between coniine and nicotine is apt to -occur when small quantities only are dealt with. It may, however, be -guarded against by the following tests:-- - -(1.) If coniine be converted into oxalate, the oxalate dissolved in -alcohol, and coniine regenerated by distillation (best in _vacuo_) with -caustic lye, and then hydrochloric acid added, a crystalline -hydrochlorate of coniine is formed, which doubly refracts light, and is -in needle-shaped or columnar crystals, or dendritic, moss-like forms. -The columns afterwards become torn, and little rows of cubical, -octahedral, and tetrahedral crystals (often cross or dagger-shaped) grow -out of yellow amorphous masses. Crystalline forms of this kind are rare, -save in the case of dilute solutions of chloride of ammonium (the -presence of the latter is, of course, rendered by the treatment -impossible); and nicotine does not give anything similar to this -reaction. - -(2.) Coniine coagulates albumen; nicotine does not. - -(3.) Nicotine yields a characteristic crystalline precipitate with an -aqueous solution of mercuric chloride; the similar precipitate of -coniine is amorphous. - -(4.) Nicotine does not react with CS_{2} to form thiosulphate (see p. -266). - -Sec. 331. =Effects on Animals.=--Nicotine is rapidly fatal to all animal -life--from the lowest to the highest forms. That tobacco-smoke is -inimical to insect-life is known to everybody; very minute quantities in -water kill infusoria. Fish of 30 grms. weight die in a few minutes from -a milligram of nicotine; the symptoms observed are rapid movements, then -shivering and speedy paralysis, with decreased motion of the gills, and -death. With frogs, if doses not too large are employed, there is first -great restlessness, then strong tetanic convulsions, and a very peculiar -position of the limbs; the respiration after fatal doses soon ceases, -but the heart beats even after death. Birds also show tetanic -convulsions followed by paralysis and speedy death. The symptoms -witnessed in mammals poisoned by nicotine are not essentially -dissimilar. With large doses the effect is similar to that of prussic -acid--viz., a cry, one or two shuddering convulsions, and death. If the -dose is not too large, there is trembling of the limbs, excretion of -faeces and urine, a peculiar condition of stupor, a staggering gait, and -then the animal falls on its side. The respiration, at first quickened, -is afterwards slowed, and becomes deeper than natural; the pulse, also, -with moderate doses, is first slowed, then rises in frequency, and -finally, again falls. Tetanic convulsions soon develop, during the -tetanus the pupils have been noticed to be contracted, but afterwards -dilated, the tongue and mouth are livid, and the vessels of the ear -dilated. Very characteristic of nicotine poisoning as witnessed in the -cat, the rabbit, and the dog, is its peculiarly violent action, for -after the administration of from one to two drops, the whole course from -the commencement of symptoms to the death may take place in five -minutes. F. Vas has drawn the smoke of tobacco from an immense pipe, and -condensed the products; he finds the well-washed tarry products without -physiological action, but the soluble liquid affected the health of -rabbits,--they lost weight, the number of the blood corpuscles was -decreased, and the haemoglobin of the blood diminished.[352] - -[352] _Archiv. f. Exper. Pathol. u. Pharm._, Bd. 33. - -The larger animals, such as the horse, are affected similarly to the -smaller domestic animals. A veterinary surgeon, Mr. John Howard, of -Woolwich,[353] has recorded a case in which a horse suffered from the -most violent symptoms of nicotine-poisoning, after an application to his -skin of a strong decoction of tobacco. The symptoms were trembling, -particularly at the posterior part of the shoulders, as well as at the -flanks, and both fore and hind extremities; the superficial muscles were -generally relaxed and felt flabby; and the pupils were widely dilated. -There was also violent dyspn[oe]a, the respirations being quick and -short, pulse 32 per minute, and extremely feeble, fluttering, and -indistinct. When made to walk, the animal appeared to have partly lost -the use of his hind limbs, the posterior quarter rolling from side to -side in an unsteady manner, the legs crossing each other, knuckling -over, and appearing to be seriously threatened with paralysis. The anus -was very prominent, the bowels extremely irritable, and tenesmus was -present. He passed much flatus, and at intervals of three or four -minutes, small quantities of faeces in balls, partly in the liquid state, -and coated with slimy mucus. There was a staring, giddy, intoxicated -appearance about the head and eyes, the visible mucous membrane being of -a dark-red colour. A great tendency to collapse was evident, but by -treatment with cold douches and exposure to the open air, the horse -recovered. - -[353] _Veter. Journal_, vol. iii. - -In a case occurring in 1863, in which six horses ate oats which had been -kept in a granary with tobacco, the symptoms were mainly those of -narcosis, and the animals died.[354] - -[354] _Annales Veterinaires_, Bruxelles, 1868. - -Sec. 332. =Effects on Man.=--Poisoning by the pure alkaloid nicotine is so -rare that, up to the present, only three cases are on record. The first -of these is ever memorable in the history of toxicology, being the first -instance in which a pure alkaloid had been criminally used. The -detection of the poison exercised the attention of the celebrated -chemist Stas. I allude, of course, to the poisoning of M. Fougnies by -Count Bocarme and his wife. For the unabridged narrative of this -interesting case the reader may consult Tardieu's _Etude Medico-Legale -sur L'Empoisonnement_. - -Bocarme actually studied chemistry in order to prepare the alkaloid -himself, and, after having succeeded in enticing his victim to the -chateau of Bitremont, administered the poison forcibly. It acted -immediately, and death took place in five minutes. Bocarme now attempted -to hide all traces of the nicotine by pouring strong acetic acid into -the mouth and over the body of the deceased. The wickedness and cruelty -of the crime were only equalled by the clumsy and unskilful manner of -its perpetration. The quantity of nicotine actually used in this case -must have been enormous, for Stas separated no less than .4 grm. from -the stomach of the victim. - -The second known case of nicotine-poisoning was that of a man who took -it for the purpose of suicide. The case is related by Taylor. It -occurred in June 1863. The gentleman drank an unknown quantity from a -bottle; he stared wildly, fell to the floor, heaving a deep sigh, and -died quietly without convulsion. The third case happened at -Cherbourg,[355] where an officer committed suicide by taking nicotine, -but how much had been swallowed, and what were the symptoms, are equally -unknown, for no one saw him during life. - -[355] _Ann. d'Hygiene_, 1861, x. p. 404. - -Poisoning by nicotine, pure and simple, then is rare. Tobacco-poisoning -is very common, and has probably been experienced in a mild degree by -every smoker in first acquiring the habit. Nearly all the fatal cases -are to be ascribed to accident; but criminal cases are not unknown. -Christison relates an instance in which tobacco in the form of snuff was -put into whisky for the purpose of robbery. In 1854, a man was accused -of attempting to poison his wife by putting snuff into her ale, but -acquitted. In another case, the father of a child, ten weeks old, killed -the infant by putting tobacco into its mouth. He defended himself by -saying that it was applied to make the child sleep. - -In October 1855,[356] a drunken sailor swallowed (perhaps for the -purpose of suicide) his quid of tobacco, containing from about half an -ounce to an ounce. He had it some time in his mouth, and in half an hour -suffered from frightful tetanic convulsions. There was also diarrh[oe]a; -the pupils were dilated widely; the heart's action became irregular; and -towards the end the pupils again contracted. He died in a sort of -syncope, seven hours after swallowing the tobacco. - -[356] _Edin. Med. Journ._, 1855. - -Sec. 333. In 1829 a curious instance of poisoning occurred in the case of -two girls, eighteen years of age, who suffered from severe symptoms of -tobacco-poisoning after drinking some coffee. They recovered; and it was -found that tobacco had been mixed with the coffee-berries, and both -ground up together.[357] - -[357] Barkhausen, _Pr. Ver. Ztg._, v. 17, p. 83, 1838. - -Accidents have occurred from children playing with old pipes. In -1877[358] a child, aged three, used for an hour an old tobacco-pipe, and -blew soap bubbles with it. Symptoms of poisoning soon showed themselves, -and the child died in three days. - -[358] _Pharm. Journ._ [3], 377, 1877. - -Tobacco-juice, as expressed or distilled by the heat developed in the -usual method of smoking, is very poisonous. Sonnenschein relates the -case of a drunken student, who was given a dram to drink, into which his -fellows had poured the juice from their pipes. The result was fatal. -Death from smoking is not unknown.[359] Helwig saw death follow in the -case of two brothers, who smoked seventeen and eighteen German pipefuls -of tobacco. Marshall Hall[360] records the case of a young man, nineteen -years of age, who, after learning to smoke for two days, attempted two -consecutive pipes. He suffered from very serious symptoms, and did not -completely recover for several days. Gordon has also recorded severe -poisoning from the consecutive smoking of nine cigars. The external -application of the leaf may, as already shown in the case of the horse, -produce all the effects of the internal administration of nicotine. The -old instance, related by Hildebrand, of the illness of a whole squadron -of hussars who attempted to smuggle tobacco by concealing the leaf next -to their skin, is well known, and is supported by several recent and -similar cases. The common practice of the peasantry, in many parts of -England, of applying tobacco to stop the bleeding of wounds, and also as -a sort of poultice to local swellings, has certainly its dangers. The -symptoms--whether nicotine has been taken by absorption through the -broken or unbroken skin, by the bowel, by absorption through smoking, or -by the expressed juice, or the consumption of the leaf itself--show no -very great difference, save in the question of time. Pure nicotine acts -with as great a rapidity as prussic acid; while if, so to speak, it is -entangled in tobacco, it takes more time to be separated and absorbed; -besides which, nicotine, taken in the concentrated condition, is a -strong enough base to have slight caustic effects, and thus leaves some -local evidences of its presence. In order to investigate the effects of -pure nicotine, Dworzak and Heinrich made auto-experiments, beginning -with 1 mgrm. This small dose produced unpleasant sensations in the mouth -and throat, salivation, and a peculiar feeling spreading from the region -of the stomach to the fingers and toes. With 2 mgrms. there was -headache, giddiness, numbness, disturbances of vision, torpor, dulness -of hearing, and quickened respirations. With 3 to 4 mgrms., in about -forty minutes there was a great feeling of faintness, intense -depression, weakness, with pallid face and cold extremities, sickness, -and purging. One experimenter had shivering of the extremities and -cramps of the muscles of the back, with difficult breathing. The second -suffered from muscular weakness, fainting, fits of shivering, and -creeping sensations about the arms. In two or three hours the severer -effects passed away, but recovery was not complete for two or three -days. It is therefore evident, from these experiments and from other -cases, that excessive muscular prostration, difficult breathing, tetanic -cramps, diarrh[oe]a, and vomiting, with irregular pulse, represent both -tobacco and nicotine poisoning. The rapidly-fatal result of pure -nicotine has been already mentioned; but with tobacco-poisoning the case -may terminate lethally in eighteen minutes. This rapid termination is -unusual, with children it is commonly about an hour and a half, although -in the case previously mentioned, death did not take place for two days. - -[359] The question as to whether there is much nicotine in tobacco-smoke -cannot be considered settled; but it is probable that most of the -poisonous symptoms produced are referable to the pyridene bases of the -general formula (C_{n}H_{2n-5}N). Vohl and Eulenberg (_Arch. Pharmac._, -2, cxlvi. p. 130) made some very careful experiments on the smoke of -strong tobacco, burnt both in pipes and also in cigars. The method -adopted was to draw the smoke first through potash, and then through -dilute sulphuric acid. The potash absorbed prussic acid, hydric -sulphide, formic, acetic, propionic, butyric, valeric, and carbolic -acids; while in the acid the bases were fixed, and these were found to -consist of the whole series of pyridene bases, from pyridene -(C_{5}H_{5}N), boil. point 117 deg., picoline (C_{6}H_{7}N), boil. point -133 deg., lutidine (C_{7}H_{9}N), boil. point 154 deg., upwards. When smoked in -pipes, the chief yield was pyridene; when in cigars, collidine -(C_{8}H_{11}N); and in general, pipe-smoking was found to produce a -greater number of volatile bases. The action of these bases has been -investigated by several observers. They all have a special action on the -organism, and all show an increase in physiological activity as the -series is ascended. The lowest produce merely excitement from irritation -of the encephalic nervous centres, and the highest, paralysis of those -centres. Death proceeds from gradual failure of the respiratory -movements, leading to asphyxia--(Kendrick and Dewar, _Proc. Roy. Soc._, -xxii. 442; xxiii. 290). The most recent experimental work is that of A. -Gautier; he found that tobacco smoked in a pipe produced basic -compounds, a large quantity of nicotine, and a higher homologue of -nicotine, C_{11}H_{16}N_{2}, which pre-exists in tobacco leaves, and a -base C_{6}H_{9}NO, which seems to be a hydrate of picoline--(_Compt. -Rend._, t. cxv. p. 992, 993). The derivatives of the pyridene series are -also active. The methiodides strongly excite the brain and paralyse the -extremities. A similar but more energetic action is exerted by the ethyl -and allyl derivatives; the iodyallyl derivatives are strong poisons. -Methylic pyridene carboxylate is almost inactive, but the corresponding -ammonium salt gives rise to symptoms resembling epilepsy--(Ramsay, -_Phil. Mag._, v. 4, 241). One member of the pyridene series -[beta]-lutidine has been elaborately investigated by C. Greville -Williams and W. H. Waters--(_Proc. Roy. Soc._, vol. xxxii. p. 162, -1881). They conclude that it affects the heart profoundly, causing an -increase in its tonicity, but the action is almost confined to the -ventricles. The auricles are but little affected, and continue to beat -after the ventricles have stopped. The rate of the heart's beat is -slowed, and the inhibitory power of the vagus arrested. By its action on -the nervous cells of the spinal cord, it in the first place lengthens -the time of reflex action, and then arrests that function. Finally, they -point out that it is antagonistic to strychnine, and may be successfully -employed to arrest the action of strychnine on the spinal cord. - -[360] _Edin. Med. and Surg. Jour._, xii., 1816. - -Sec. 334. =Physiological Action.=--Nicotine is absorbed into the blood and -excreted unchanged, in part by the kidneys and in part by the saliva -(_Dragendorff_). According to the researches of Rosenthal and -Krocker,[361] nicotine acts energetically on the brain, at first -exciting it, and then lessening its activity; the spinal marrow is -similarly affected. The convulsions appear to have a cerebral origin; -paralysis of the peripheral nerves follows later than that of the nerve -centres, whilst muscular irritability is unaffected. The convulsions are -not influenced by artificial respiration, and are therefore to be -considered as due to the direct influence of the alkaloid on the nervous -system. Nicotine has a striking influence on the respiration, first -quickening, then slowing, and lastly arresting the respiratory -movements: section of the vagus is without influence on this action. -The cause of death is evidently due to the rapid benumbing and paralysis -of the respiratory centre. Death never follows from heart-paralysis, -although nicotine powerfully influences the heart's action, small doses -exciting the terminations of the vagus in the heart, and causing a -slowing of the beats. Large doses paralyse both the controlling and -exciting nerve-centres of the heart; the heart then beats fast, -irregularly, and weakly. The blood-vessels are first narrowed, then -dilated, and, as a consequence, the blood-pressure first rises, then -falls. Nicotine has a special action on the intestines. As O. Nasse[362] -has shown, there is a strong contraction of the whole tract, especially -of the small intestine, the lumen of which may be, through a continuous -tetanus, rendered very small. This is ascribed to the peripheral -excitation of the intestinal nerves and the ganglia. The uterus is also -excited to strong contraction by nicotine; the secretions of the bile -and saliva are increased. - -[361] _Ueber die Wirkung des Nicotines auf den thierischen Organismus_, -Berlin, 1868. - -[362] _Beitraege zur Physiologie der Darmbewegung, Leipsic_, 1866. - -Sec. 335. =Fatal Dose.=--The fatal dose for dogs is from 1/2 to 2 drops; -for rabbits, a quarter of a drop; for an adult not accustomed to tobacco -the lethal dose is probably 6 mgrms. - -Sec. 336. =Post-mortem Appearances.=--There seem to be no appearances so -distinctive as to be justly ascribed to nicotine or tobacco-poisoning -and no other. - -A more or less fluid condition of the blood, and, generally, the signs -of death by the lungs, are those most frequently found. In -tobacco-poisoning, when the leaves themselves have been swallowed, there -may be some inflammatory redness of the stomach and intestine. - -Sec. 337. =Separation of Nicotine from Organic Matters, &c.=--The process -for the isolation of nicotine is precisely that used for coniine (see p. -269). It appears that it is unaltered by putrefaction, and may be -separated and recognised by appropriate means a long time after death. -Orfila detected it in an animal two or three months after death; Melsens -discovered the alkaloid unmistakably in the tongues of two dogs, which -had been buried in a vessel filled with earth for seven years; and it -has been found, by several experiments, in animals buried for shorter -periods. Nicotine should always be looked for in the tongue and mucous -membrane of the mouth, as well as in the usual viscera. The case may be -much complicated if the person supposed to be poisoned should have been -a smoker; for the defence would naturally be that there had been either -excessive smoking or chewing, or even swallowing accidentally a quid of -tobacco.[363] A ptomaine has been discovered similar to nicotine. -Wolckenhaar separated also an alkaloid not unlike nicotine from the -corpse of a woman addicted to intemperate habits; but this base was not -poisonous, nor did it give any crystals when an ethereal solution was -added to an ether solution of iodine. It will be well always to support -the chemical evidence by tests on animal life, since the intensely -poisonous action of nicotine seems not to be shared by the nicotine-like -ptomaines. - -[363] In an experiment of Dragendorff's, nicotine is said to have been -detected in 35 grms. of the saliva of a person who had half an hour -previously smoked a cigar. - - -3. PITURIE.[364] - -[364] See "The Alkaloid from Piturie," by Prof. Leversidge, _Chem. -News_, March 18 and 25, 1881. - - Sec. 338. Piturie (C_{6}H_{8}N) is a liquid, nicotine-like alkaloid, - obtained from the _Duboisia hopwoodii_, a small shrub or tree - belonging to the natural order _Solanaceae_, indigenous in Australia. - The natives mix piturie leaves with ashes from some other plant, and - chew them. Piturie is obtained by extracting the plant with boiling - water acidified with sulphuric acid, concentrating the liquid by - evaporation, and then alkalising and distilling with caustic soda, - and receiving the distillate in hydrochloric acid. The solution of - the hydrochlorate is afterwards alkalised and shaken up with ether, - which readily dissolves out the piturie. The ether solution of - piturie is evaporated to dryness in a current of hydrogen, and the - crude piturie purified by distillation in hydrogen, or by changing - it into its salts, and again recovering, &c. It is clear and - colourless when pure and fresh, but becomes yellow or brown when - exposed to air and light. It boils and distils at 243 deg. to 244 deg. It - is soluble in all proportions in alcohol, water, and ether; its - taste is acrid and pungent; it is volatile at ordinary temperatures, - causing white fumes with hydrochloric acid; it is very irritating to - the mucous membranes, having a smell like nicotine at first, and - then, when it becomes browner, like pyridine. It forms salts with - acids, but the acetate, sulphate, and hydrochlorate are varnish-like - films having no trace of crystallisation; the oxalate is a - crystalline salt. Piturie gives precipitates with mercuric chloride, - cupric sulphate, gold chloride, mercur-potassic iodide, tannin, and - an alcoholic solution of iodine. If an ethereal solution of iodine - is added to an ethereal solution of piturie, a precipitate of - yellowish-red needles, readily soluble in alcohol, is deposited. The - iodine compound melts at 110 deg., while the iodine compound of nicotine - melts at 100 deg. Piturie is distinguished from coniine by its aqueous - solution not becoming turbid either on heating or on the addition of - chlorine water; it differs from picoline in specific gravity, - picoline being .9613 specific gravity at 0 deg., and piturie sinking in - water; it differs from aniline by not being coloured by chlorinated - lime. From nicotine it has several distinguishing marks, one of the - best being that it does not change colour on warming with - hydrochloric acid and the addition to the mixture afterwards of a - little nitric acid. The physiological action seems to be but little - different from that of nicotine. It is, of course, poisonous, but as - yet has no forensic importance. - - -4. SPARTEINE. - - Sec. 339. In 1851 Stenhouse[365] separated a poisonous volatile - alkaloid from _Spartium scoparium_, the common broom, to which he - gave the name of sparteine. At the same time a crystalline - non-poisonous substance, _scoparin_, was discovered. - -[365] _Phil. Trans._, 1851. - - Sparteine is separated from the plant by extraction with sulphuric - acid holding water, and then alkalising the acid solution and - distilling: it has the formula (C_{15}H_{26}N_{2}), and belongs to - the class of tertiary diamines. It is a clear, thick, oily - substance, scarcely soluble in water, to which it imparts a strong, - alkaline reaction; it is soluble in alcohol, in ether, and - chloroform; insoluble in benzene and in petroleum; it boils at - 288 deg. Sparteine neutralises acids fully, but the oxalate is the only - one which can be readily obtained in crystals. It forms crystalline - salts with platinic chloride, with gold chloride, with mercuric - chloride, and with zinc chloride. The picrate is an especially - beautiful salt, crystallising in long needles, which, when dried and - heated, explode. On sealing sparteine up in a tube with ethyl iodide - and alcohol, and heating to 100 deg. for an hour, ethyl sparteine iodide - separates in long, needle-like crystals, which are somewhat - insoluble in cold alcohol. - - =Effect on Animals.=--A single drop kills a rabbit; the symptoms are - similar to those produced by nicotine, but the pupils are - dilated.[366] - -[366] To the nicotine group, gelsemine (C_{24}H_{28}N_{2}O_{4}) and -oxalathylin (C_{6}H_{10}N_{2}) also belong, in a physiological sense, -but gelsemine, like sparteine, dilates the pupil. - - -5. ANILINE. - - Sec. 340. =Properties.=--Aniline or amido-benzol (C_{6}H_{5}NH_{2}) is - made by the reduction of nitro-benzol. It is an oily fluid, - colourless when quite pure, but gradually assuming a yellow tinge on - exposure to the air. It has a peculiar and distinctive smell. It - boils at 182.5 deg., and can be congealed by a cold of 8 deg. It is - slightly soluble in water, 100 parts of water at 16 deg. retaining about - 3 of aniline, and easily soluble in alcohol, ether, and chloroform. - It does not blue red-litmus paper, but nevertheless acts as a weak - alkali, for it precipitates iron from its salts. It forms a large - number of crystalline salts. The hydrochloride crystallises in white - plates, and has a melting-point of 192 deg. The platinum compound has - the formula of (C_{6}H_{5}NH_{2}HCl)_{2}PtCl_{4}, and crystallises - in yellow needles. - - Sec. 341. =Symptoms and Effects.=--Aniline, like picric acid, - coagulates albumin. Aniline is a blood poison; it produces, even - during life, in some obscure way, methaemoglobin, and it - disintegrates the red blood corpuscles; both these effects lessen - the power of the blood corpuscles to convey oxygen to the tissues, - hence the cyanosis observed so frequently in aniline poisoning is - explained. Engelhardt[367] has found that aniline black is produced; - in every drop of blood there are fine black granules, the total - effect of which produce a pale blue or grey-blue colour of the skin. - Aniline has also an action on the central nervous system, at first - stimulating, and then paralysing. Schmiedeberg finds that - para-amido-phenol-ether-sulphuric acid is produced, and appears in - the urine as an alkali salt; a small quantity of fuchsine is also - produced, and has been found in the urine. Some aniline may be - excreted unchanged. - -[367] _Beitraege zur Tox. des Anilins. Inaug.-Diss._, Dorpat, 1888. - - The symptoms are giddiness, weakness, cyanosis, blueness of the - skin, sinking of the temperature, and dilatation of the pupil. The - pulse is small and frequent, the skin moist and cold. The patient - smells of aniline. Towards the end coma and convulsions set in. The - urine may be brown to brown-black, and may contain hyaline - cylinders. The blood shows the spectrum of methaemoglobin, and has - the peculiarities already mentioned. Should the patient recover, - jaundice often follows. The outward application of aniline produces - eczema. - - Chronic poisoning by aniline is occasionally seen among workers in - the manufacture of aniline. Headache, loss of muscular power, - diminished sensibility of the skin, vomiting, loss of appetite, - pallor, eruptions on the skin, and general malaise are the chief - symptoms. The perspiration has been noticed to have a reddish - colour. - - Cases of aniline poisoning are not common; Dr. Fred. J. Smith has - recorded one in the _Lancet_ of January 13, 1894.[368] The patient, - a woman, 42 years of age, of alcoholic tendencies, swallowed, 13th - December 1893, at 1.40 P.M., about 3 ounces of marking ink, the - greatest part of which consisted of aniline; in a very little while - she became unconscious, and remained so until death. At 3 P.M. her - lips were of a dark purple, the general surface of the skin was - deadly white, with a slight bluish tinge; the pupils were small and - sluggish, the breathing stertorous, and the pulse full and slow--60 - per minute. The stomach was washed out, ether injected, and oxygen - administered, but the patient died comatose almost exactly twelve - hours after the poison had been taken. - -[368] See also a case reported by K. Dehio, in which a person drank 10 -grms. and recovered, _Ber. klinis. Wochen._, 1888, Nr. 1. - - The _post-mortem_ examination showed slight congestion of the lungs; - the heart was relaxed in all its chambers, and empty of blood; it - had a peculiar green-blue appearance. All the organs were healthy. - The blood was not spectroscopically examined. - - Sec. 342. =Fatal Dose.=--This is not known, but an adult would probably - be killed by a single dose of anything over 6 grms. Recovery under - treatment has been known after 10 grms.; the fatal dose for rabbits - is 1-1.5 grms., for dogs 3-5 grms. - - Sec. 343. =Detection of Aniline.=--Aniline is easily separated and - detected. Organic fluids are alkalised by a solution of potash, and - distilled. The organs, finely divided, are extracted with water - acidulated with sulphuric acid, the fluid filtered, and then - alkalised and distilled. The distillate is shaken up with ether, the - ether separated and allowed to evaporate spontaneously. Any aniline - will be in the residue left after evaporation of the ether, and may - be identified by the following tests:--An aqueous solution of - aniline or its salts is coloured blue by a little chloride of lime - or hypochlorite of soda; later on the mixture becomes red. The blue - colour has an absorption band, when examined spectroscopically, - extending from W.L. 656 to 560, and therefore in the red and yellow - from Fraunhofer's line C, and overlapping D. Another test for - aniline is the addition of kairine, hydrochloric acid, and sodium - nitrite, which strikes a blue colour. - - -III.--The Opium Group of Alkaloids. - -Sec. 344. =General Composition.=--Opium contains a larger number of basic -substances than any plant known. The list reaches at present to 18 or 19 -nitrogenised bases, and almost each year there have been additions. Some -of these alkaloids exist in very small proportion, and have been little -studied. Morphine and narcotine are those which, alone, are -toxicologically important. Opium is a gummy mass, consisting of the -juice of the incised unripe fruit of the _Papaver somniferum_ hardened -in the air. The following is a nearly complete list of the constituents -which have been found in opium:-- - - Morphine, C_{17}H_{19}NO_{3}. - Narcotine, C_{22}H_{23}NO_{7}. - Narceine, C_{23}H_{29}NO_{9}. - Apomorphine, C_{17}H_{17}NO_{2} } By dehydration of morphine and - Apocodeine, C_{18}H_{19}NO_{2} } codeine respectively. - Pseudomorphine, C_{17}H_{19}NO_{4}. - Codamine, C_{20}H_{25}NO_{4}. - Ladanine, C_{20}H_{25}NO_{4}. - Ladanosine, C_{21}H_{27}NO_{4}. - Protapine, C_{20}H_{19}NO_{5}. - Cryptopine, C_{21}H_{23}NO_{5}. - Lanthopine, C_{23}H_{25}NO_{4}. - Hydrocotarnine, C_{12}H_{15}NO_{3}. - Opianine, C_{21}H_{21}NO_{7}. - Cnoscopine, C_{34}H_{36}N_{2}O_{11}. - Rh[oe]adine, C_{20}H_{21}NO_{7}. - Codeine, C_{18}H_{21}NO_{3}. - Thebaine, C_{19}H_{21}NO_{3}. - Papaverine, C_{20}H_{21}NO_{4}. - Meconidine, C_{21}H_{23}NO_{4}. - Meconin, C_{10}H_{10}O_{4}. - Meconic acid, C_{7}H_{4}O_{7}. - Thebolactic acid. - Fat. - Resin. - Caoutchouc. - Gummy matters--Vegetable mucus. - Ash, containing the usual constituents. - -The various opiums differ, the one from the other, in the percentages of -alkaloids, so that only a very general statement of the mean composition -of opium can be made. The following statement may, however, be accepted -as fairly representative of these differences:-- - - Per cent. - Morphine, 6 to 15 - Narcotine, 4 to 8 - Other alkaloids, 5 to 2 - Meconin, Under 1 - Meconic acid, 3 to 8 - Peculiar resin and caoutchouc, 5 to 10 - Fat, 1 to 4 - Gum and soluble humoid acid matters, 40 to 50 - Insoluble matters and mucus, 18 to 20 - Ash, 4 to 8 - Water, 8 to 30 - -The general results of the analysis of 12 samples of Turkey opium, -purchased by Mr. Bott,[369] from leading druggists in London, Dublin, -and Edinburgh, are as follows:-- - -[369] _Year Book of Pharmacy_, 1876. - -=Water.=--Highest, 31.2; lowest, 18.4; mean, 22.4 per cent. - -=Insoluble Residue.=--Highest, 47.9; lowest, 25.45; mean, 32.48 per -cent. - -=Aqueous Extract.=--Highest, 56.15; lowest, 20.90; mean, 45.90 per cent. - -=Crude Morphine= (containing about 7/10 of pure morphine).--Highest, -12.30; lowest, 6.76; mean, 9.92 per cent., which equals 12.3 per cent. -of the dried drug. - -=Persian Opium=, examined in the same way, varied in crude morphine from -2.1 to 8.5 per cent.; Malwa, from 5.88 to 7.30. In 18 samples of -different kinds of opium, the mean percentage of crude morphine was 8.88 -per cent. (11 per cent. of the dried opium). According to Guibourt, -Smyrna opium, dried at 100 deg., yields 11.7 to 21.46 per cent., the mean -being 12 to 14 per cent.; Egyptian, from 5.8 to 12 per cent.; Persian, -11.37 per cent. In East Indian Patna opium, for medical use, he found -7.72; in a sample used for smoking, 5.27 per cent.; in Algerian opium, -12.1 per cent.; in French opium, 14.8 to 22.9 per cent. - -Sec. 345. =Action of Solvents on Opium.=--The action of various solvents on -opium has been more especially studied by several scientists who are -engaged in the extraction of the alkaloids. - -=Water= dissolves nearly everything except resin, caoutchouc, and woody -fibre. Free morphine would be left insoluble; but it seems always to be -combined with meconic and acetic acids. The solubility of free narcotine -in water is extremely small. - -=Alcohol= dissolves resin and caoutchouc, and all the alkaloids and -their combinations, with meconic acid, &c. - -=Amylic Alcohol= dissolves all the alkaloids, if they are in a free -state, and it also takes up a little of the resin. - -=Ether, Benzene, and Carbon Sulphide= do not dissolve the resin, and -only slightly morphine, if free; but they dissolve the other free -alkaloids as well as caoutchouc. - -=Acids= dissolve all the alkaloids and the resin. - -=Fixed Alkalies=, in excess, dissolve in part resin; they also dissolve -morphine freely; narcotine remains insoluble. - -=Lime Water= dissolves morphine, but is a solvent for narcotine only in -presence of morphine. - -=Ammonia= dissolves only traces of morphine; but narceine and codeine -readily. It does not dissolve the other alkaloids, nor does it dissolve -the resin. - -Sec. 346. =Assay of Opium.=--The following processes may be described:-- - -=Process of Teschemacher and Smith.=--This process, with a few -modifications, is as follows:--10 grms. of opium are as completely -exhausted with proof spirit at a boiling temperature as possible. The -resulting alcoholic extract is treated with a few drops of ammonium -oxalate solution, and the solution is almost neutralised with ammonia. -The solution is concentrated to one-third, cooled, and filtered. The -filtrate is farther concentrated to 5 c.c., and transferred to a small -flask, it is washed into this flask by 4 c.c. of water, and 3 c.c. of 90 -per cent. alcohol; next 2 c.c. solution of ammonia (sp. gr. 0.960) and -25 c.c. of dry ether are added. The flask is corked, shaken, and then -allowed to rest over-night. - -The ether is decanted as completely as possible. Two filter papers are -taken and counterpoised--that is to say, they are made precisely the -same weight. The filters are placed one inside the other, and the -precipitate collected on the inner one; the precipitate is washed with -morphinated water--that is to say, water in which morphine has been -digested for some days. The filter papers with their contents are washed -with benzene and dried, the outer paper put on the pan of the balance -carrying the weights, and the inner filter with the precipitate weighed. -The precipitate is now digested with a known volume of decinormal acid, -and then the excess of acid ascertained by titration with decinormal -alkali, using either litmus or methyl orange; each c.c. of decinormal -acid is equal to 30.3 mgrms. of morphine.[370] - -[370] _Pharm. Journal_, xix. 45, 82; xxii. 746. Wright and Farr, -_Chemist and Druggist_, 1893, i. 78. - -=Dott's Process.=--Dott has recently proposed a new process, which he -states has given good results. The process is as follows:--10 grammes -of powdered opium are digested with 25 c.c. water; 1.8 gramme barium -chloride dissolved in about 12 c.c. water is then added, the solution -made up to 50 c.c., well mixed, and after a short time filtered. 22 c.c. -(representing 5 grammes opium) are mixed with dilute sulphuric acid in -quantity just sufficient to precipitate the barium. About 1 c.c. is -required, and the solution should be warmed to cause the precipitate to -subside, and the solution to filter clear. To this filtered solution a -little dilute ammonia, about 0.5 c.c. is added to neutralise the free -acid, and the solution concentrated to 6 or 7 c.c., and allowed to cool. -1 c.c. spirit and 1 c.c. ether are then added, and next ammonia in -slight excess. The ammonia should be added gradually until there is no -further precipitation, and a perceptible odour of ammonia remains after -well stirring and breaking down any lumps with the stirring rod. After -three hours the precipitate is collected on counterpoised filters and -washed. Before filtering, it should be noted that the solution has a -faint odour of ammonia: if not, one or two drops of ammonia solution -should be added. The dried precipitate is washed with benzene or -chloroform, dried, and weighed. It is then titrated with _n_/10 acid, -until the morphine is neutralised, as indicated by the solution -reddening litmus paper.[371] - -[371] Other methods of opium assay have been published: see Mr. A. B. -Prescott's method (_Proceedings of Amer. Pharm. Assoc._, 1878); Allen -(_Commercial Org. Analysis_, vol. ii. p. 473); E. R. Squibb's -modification of Flueckiger's method (_Pharm. Journ._ (3), xii. p. 724); a -rapid mode of opium assay, MM. Portes and Lanjlois (_Journ. de Pharm. et -de Chim._, Nov. 1881); _Year Book of Pharmacy_, 1882. - -To the above may be added--(1.) _Schacht's Method._--5 to 10 grms. of -dry, finely-powdered opium are digested with sufficient distilled water -to make a thin pulp. After twenty-four hours the whole is thrown on a -weighed filter, and washed until the washings are almost colourless and -tasteless. The portion insoluble in water is dried at 100 deg. and weighed; -in good opium this should not exceed 40 per cent. The filtrate is -evaporated until it is about one-fifth of the weight of the opium taken -originally; cooled, filtered, and treated with pure animal charcoal, -until the dark brown colour is changed into a brownish-yellow. The -liquid is then refiltered, precipitated with a slight excess of ammonia, -allowed to stand in an open vessel until all odour of ammonia -disappears, and at the same time frequently stirred, in order that the -precipitate may not become crystalline--a form which is always more -difficult to purify. The precipitate is now collected on a tared filter, -washed, dried, and weighed. With an opium containing 10 per cent. of -morphine, its weight is usually 14 per cent. A portion of the -precipitate is then detached from the filter, weighed, and exhausted, -first with ether, and afterwards with boiling alcohol (0.81 specific -gravity). Being thus purified from narcotine, and containing a little -colouring-matter only, it may now be dried and weighed, and the amount -of morphine calculated, on the whole, from the data obtained. - -(2.) _Fleury_ has proposed a titration by oxalic acid as follows:--2 -grms. of the powdered opium are macerated a few hours with 8 c.c. of -aqueous oxalate of ammonia, brought on a filter, and washed with 5 c.c. -of water. To the filtrate an equal volume of 80 per cent. alcohol and -ammonia to alkaline reaction is added; and, after standing twenty-four -hours in a closed flask, it is filtered, and the flask rinsed out with -some c.c. of 40 per cent. alcohol. The filter, with its contents, after -drying, is placed in the same flask (which should not be cleansed), a -few drops of alcoholic logwood solution are added, with an excess of -oxalic acid solution of known strength, the whole being made up to 100 -c.c. This is divided into two parts, and the excess of acid titrated -back with diluted soda-lye. If the oxalic acid solution is of the -strength of 4.42 grms. to the litre, every c.c. of the oxalic acid -solution which has become bound up with morphine, corresponds to 0.02 -grm. of morphine. - -Sec. 347. =Medicinal and other Preparations of Opium.=--The chief mixtures, -pills, and other forms, officinal and non-officinal, in which opium may -be met with, are as follows:-- - - -(1.) OFFICINAL. - -=Compound Tincture of Camphor=, P. B. (Paregoric).--Opium, camphor, -benzoic acid, oil of anise, and proof spirit: the opium is in the -proportion of about 0.4 per cent., or 1 grain of opium in 240 minims. - -=Ammoniated Tincture of Opium= (Scotch paregoric).--Strong solution of -ammonia, rectified spirit, opium, oil of anise, saffron, and benzoic -acid. Nearly 1 per cent. or 1 grain of opium in every 96 minims. - - =The Compound Powder of Kino=, P. B. - Opium, 5 per cent. - Cinnamon, 20 " - Kino, 75 " - - =The Compound Powder of Opium=, P. B. - Opium, 10.00 per cent. - Black Pepper, 13.33 " - Ginger, 33.33 " - Caraway Fruit, 40.00 " - Tragacanth, 3.33 " - - =Pill of Lead and Opium=, P. B. - Acetate of Lead, 75.0 per cent. - Opium, 12.5 " - Confection of Roses, 12.5 " - -=Tincture of Opium= (=Laudanum=).--Opium and proof spirit. One grain of -opium in 14.8 min.--that is, about 6.7 parts by weight in 100 by -measure. - -The amount of opium actually contained in laudanum has been investigated -by Mr. Woodland,[372] from fourteen samples purchased from London and -provincial chemists. The highest percentage of extract was 5.01, the -lowest 3.21, the mean being 4.24; the highest percentage of morphine was -.70 per cent., the lowest .32, the mean being .51 per cent. It is, -therefore, clear that laudanum is a liquid of very uncertain strength. - -[372] _Year Book of Pharmacy_, 1882. - -=Aromatic Powder of Chalk and Opium.=--Opium 2.5 per cent., the rest of -the constituents being cinnamon, nutmeg, saffron, cloves, cardamoms, and -sugar. - -=Compound Powder of Ipecacuanha= (Dover's Powder). - - Opium, 10 per cent. - Ipecacuanha, 10 " - Sulphate of Potash, 80 " - -=Confection of Opium= (=Confectio opii=) is composed of syrup and -compound powder of opium; according to its formula, it contains 2.4 per -cent. of opium by weight. - -=Extract of Opium= contains the solid constituents capable of extraction -by water; it should contain 20 per cent. of morphine, and is therefore -about double the strength of dry powdered opium. - -=Liquid Extract of Opium= has been also examined by Mr. Woodland:[373] -ten samples yielded as a mean 3.95 per cent. of dry extract, the highest -number being 4.92 per cent., the lowest 3.02. The mean percentage of -morphine was .28 per cent., the highest amount being .37, and the lowest -.19 per cent. - -[373] _Op. cit._ - -=Liniment of Opium= is composed of equal parts of laudanum and soap -liniment; it should contain about 0.0375 per cent. morphine. - -=The Compound Soap-pill= is made of soap and opium, one part of opium in -every 5.5 of the mass--_i.e._, about 18 per cent. - -=Ipecacuanha and Morphine Lozenges=, as the last, with the addition of -ipecacuanha; each lozenge contains 1/36 grain (1.8 mgrms.) morphine -hydrochlorate, 1/12 grain (5.4 mgrms.) ipecacuanha. - -=Morphia Suppositories= are made with hydrochlorate of morphine, -benzoated lard, white wax, and oil of theobroma; each suppository -contains 1/2 grain (32.4 mgrms.) of morphine salt. - -=Opium Lozenges= are composed of opium extract, tincture of tolu, sugar, -gum, extract of liquorice, and water. Each lozenge contains 1/10 grain -(6.4 mgrms.) of extract of opium, or about 1/50 grain (1.3 mgrm.) -morphine. - -=The Ointment of Galls and Opium= contains one part of opium in 14.75 -parts of the ointment--_i.e._, opium 6.7 per cent. - -=Opium Wine=, P. B.--Sherry, opium extract, cinnamon, and cloves. About -5 of opium extract by weight in 100 parts by measure (22 grains to the -ounce). - -=Solutions of Morphine=, both of the acetate and hydrochlorate, P. B., -are made with a little free acid, and with rectified spirit. The -strength of each is half a grain in each fluid drachm (.0324 grm. in -3.549), or .91 part by weight in 100 by measure. - -=Solution of Bimeconate of Morphine.=--One fluid oz. contains 5-1/2 -grains of bimeconate of morphine. - -=Morphia Lozenges= are made with the same accessories as opium lozenges, -substituting morphine for opium; each lozenge contains 1/36 grain of -hydrochlorate of morphia (1.8 mgrm.). - -=Syrup of Poppies.=--The ordinary syrup of poppies is sweetened -laudanum. It should, however, be what it is described--viz., a syrup of -poppy-heads. As such, it is said to contain one grain of extract of -opium to the ounce. - - -(2.) PATENT AND OTHER NON-OFFICINAL PREPARATIONS OF OPIUM. - - =Godfrey's Cordial= is made on rather a large scale, and is variable - in strength and composition. It usually contains about 1-1/2 grains - of opium in each fluid ounce,[374] and, as other constituents: - sassafras, molasses or treacle, rectified spirit, and various - flavouring ingredients, especially ginger, cloves, and coriander; - aniseed and caraways may also be detected. - -[374] If made according to Dr. Paris' formula, 1-1/6 grains in an ounce. - - =Grinrod's Remedy for Spasms= consists of hydrochlorate of morphine, - spirit of sal-volatile, ether, and camphor julep; strength, 1 grain - of the hydrochlorate in every 6 ounces. - - =Lemaurier's Odontalgic Essence= is acetate of morphine dissolved in - cherry-laurel water; strength, 1 grain to the ounce. - - =Nepenthe= is a preparation very similar to _Liq. Opii sedativ._, - and is of about the same strength as laudanum.[375] - -[375] It may be regarded as a purified alcoholic solution of meconate of -morphia, with a little excess of acid, and of about the same strength as -laudanum.--_Taylor._ - - =Black Drop= (known also by various names, such as Armstrong's Black - Drop) is essentially an acetic acid solution of the constituents of - opium. It is usually considered to be of four times the strength of - laudanum. The wholesale receipt for it is: Laudanum, 1 oz., and - distilled vinegar 1 quart, digested for a fortnight. The original - formula proposed by the Quaker doctor of Durham, Edward Tunstall, - is--Opium, sliced, 1/2 lb.; good verjuice,[376] 3 pints; and nutmeg, - 1-1/2 oz.; boiled down to a syrup thickness; 1/4 lb. of sugar and 2 - teaspoonfuls of yeast are then added. The whole is set in a warm - place for six or eight weeks, after which it is evaporated in the - open air until it becomes of the consistence of a syrup. It is - lastly decanted and filtered, a little sugar is added, and the - liquid made up to 2 pints. - -[376] Verjuice is the juice of the wild crab. - - ="Nurse's Drops"= seem to be composed of oil of caraway and - laudanum. - - =Powell's Balsam of Aniseed=, according to evidence in the case of - _Pharmaceutical Society v. Armson_ (_Pharm. Journ._, 1894), contains - in every oz. 1/10 grain of morphine. - - =Dalby's Carminative=-- - - Carbonate of magnesia, 40 grains. - Tincture of castor, and compound tincture of cardamoms, - of each 15 drops. - Laudanum, 5 " - Oil of aniseed, 3 " - Oil of nutmeg, 2 " - Oil of peppermint, 1 " - Peppermint water, 2 fl. ounces - - Dose, from a half to one teaspoonful. Another recipe has no - laudanum, but instead syrup of poppies. - - =Chlorodyne=--Brown's Chlorodyne is composed of-- - - Chloroform, 6 drachms. - Chloric ether, 1 " - Tincture of capsicum, 1/2 " - Hydrochlorate of morphine, 8 grains. - Scheele's prussic acid, 12 drops - Tincture of Indian hemp, 1 drachm. - Treacle, 1 " - - =Atkinson's Infant Preserver=-- - - Carbonate of magnesia, 6 drachms. - White sugar, 2 ounces - Oil of aniseed, 20 drops. - Spirit of sal-volatile, 2-1/2 drachms. - Laudanum, 1 " - Syrup of saffron, 1 ounce. - Caraway water, to make up, 1 pint. - - =Boerhave's Odontalgic Essence=-- - - Opium, 1/2 drachm. - Oil of cloves, 2 " - Powdered camphor, 5 " - Rectified spirit, 1-1/2 fl. ounce. - -Sec. 348. =Statistics.=--During the ten years 1883-1892 no less than 1424 -deaths in England and Wales were attributed to some form or other of -opium or its active constituents; 45 of these deaths were ascribed to -various forms of soothing syrup or to patent medicines containing opium -or morphine; 876 were due to accident or negligence; 497 were suicidal -and 6 were homicidal deaths. The age and sex distribution of the deaths -ascribed to accident and those ascribed to suicide are detailed in the -following tabular statement:-- - -DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS 1883-1892 FROM OPIUM, -LAUDANUM, MORPHINE, &c. - - ACCIDENT. - - Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total - above - Males, 72 27 1 16 302 85 503 - Females, 50 23 4 21 189 86 373 - -------------------------------------------- - Total, 122 50 5 37 491 171 876 - -------------------------------------------- - - SUICIDE. - - Ages, 5-15 15-25 25-65 65 and Total - above - Males, 1 26 269 34 330 - Females, ... 24 126 17 167 - ---------------------------------- - Total, 1 50 395 51 497 - ---------------------------------- - -Of European countries, England has the greatest proportional number of -opium poisonings. In France, opium or morphine poisoning accounts for -about 1 per cent. of the whole; and Denmark, Sweden, Switzerland, -Germany, all give very small proportional numbers; arsenic, phosphorus, -and the acids taking the place of opiates. The more considerable -mortality arises, in great measure, from the pernicious practice--both -of the hard-working English mother and of the baby-farmer--of giving -infants various forms of opium sold under the name of "_soothing -syrups_," "_infants' friends_," "_infants' preservatives_," "_nurses' -drops_" and the like, to allay restlessness, and to keep them during the -greater part of their existence asleep. Another fertile cause of -accidental poisoning is mistakes in dispensing; but these mistakes seem -to happen more frequently on the Continent than in England. This is in -some degree due to the decimal system, which has its dangers as well as -its advantages, _e.g._:--A physician ordered .5 decigrm. of morphine -acetate in a mixture for a child, but omitted the decimal point, and the -apothecary, therefore, gave ten times the dose desired, with fatal -effect. Again, morphine hydrochlorate, acetate, and similar soluble -salts are liable to be mistaken for other white powders, and in this way -unfortunate accidents have occurred--accidents that, with proper -dispensing arrangements, should be impossible. - -Sec. 349. =Poisoning of Children by Opium.=--The drugging of children by -opium--sometimes with a view to destroy life, sometimes merely for the -sake of the continual narcotism of the infant--is especially rife in -India.[377] A little solid opium is applied to the roof of the mouth, or -smeared on the tongue, and some Indian mothers have been known to -plaster the nipples with opium, so that the child imbibes it with the -milk. Europeans, again and again, have discovered the native nurses -administering opiates to the infants under their care, and it is feared -that in many cases detection is avoided. - -[377] See Dr. Chevers's _Jurisprudence_, 3rd ed., 232 _et seq._ - -The ignorant use of poppy-tea has frequently caused the death of young -children; thus in 1875 an inquest was held at Chelsea on the body of a -little boy two years and a half old. He had been suffering from -whooping-cough and enlargement of the bowels, and poppy-tea was by the -advice of a neighbour given to him. Two poppy-heads were used in making -a quart of tea, and the boy, after drinking a great portion of it, fell -into a deep sleep, and died with all the symptoms of narcotic poisoning. - -Sec. 350. =Doses of Opium and Morphia.=--Opium in the solid state is -prescribed for adults in quantities not exceeding 3 grains, the usual -dose being from 16.2 mgrms. to 64.8 mgrms. (1/4 to 1 grain). The extract -of opium is given in exactly the same proportions (special -circumstances, such as the habitual use of opium, excepted); the dose of -all the compounds of opium is mainly regulated by the proportion of -opium contained in them. - -The dose for children (who bear opium ill) is usually very small; single -drops of laudanum are given to infants at the breast, and the dose -cautiously increased according to age. Most practitioners would consider -half a grain a very full dose, and, in cases requiring it, would seldom -prescribe at first more than 1/16 to 1/4 grain. - -The dose of solid opium for a horse is from 1.77 grm. to 7.08 grms. (1/2 -drachm to 2 drachms); in extreme cases, however, 4 drachms (14.16 grms.) -have been given. - -The dose for large cattle is from .648 grm. to 3.88 grms. (10 to 60 -grains); for calves, .648 grm. (10 grains); for dogs it is greatly -regulated by the size of the animal, 16.2 to 129.6 mgrms. (1/4 grain to -2 grains). - -=Fatal Dose.=--Cases are recorded of infants dying from extremely small -doses of opium, _e.g._, .7, 4.3, and 8.1 mgrms. (1/90, 1/15, and 1/8 of -a grain); but in such instances one cannot help suspecting some mistake. -It may, however, be freely conceded that a very small quantity might be -fatal to infants, and that 3 mgrms. given to a child under one year -would probably develop serious symptoms. - -The smallest dose of solid opium known to have proved fatal to adults -was equal to 259 mgrms. (4 grains) of crude opium (_Taylor_), and the -smallest dose of the tincture (laudanum), 7.0 c.c. (2 drachms), -(_Taylor_); the latter is, however, as already shown, uncertain in its -composition. - -A dangerous dose (save under special circumstances) is:--For a horse, -14.17 grms. (4 drachms); for cattle, 7.04 grms. (2 drachms); for a dog -of the size and strength of a foxhound, 204 mgrms. (3 grains). - -Enormous and otherwise fatal doses may be taken under certain conditions -by persons who are not opium-eaters. I have seen 13 cgrms. (2 grains) of -morphine acetate injected hypodermically in a strong man suffering from -rabies with but little effect. Tetanus, strychnine, convulsions, and -excessive pain all decrease the sensibility of the nervous system to -opium. - -Sec. 351. =General Method for the Detection of Opium.=--It is usually laid -down in forensic works that, where poisoning by opium is suspected, it -is sufficient to detect the presence of meconic acid in order to -establish that of opium. In a case of adult poisoning there is generally -substance enough available to obtain one or more alkaloids, and the -presence of opium may, without a reasonable doubt, be proved, if meconic -acid (as well as either morphine, narcotine, thebaine, or other opium -alkaloid) has been detected. Pills containing either solid opium or the -tincture usually betray the presence of the drug by the odour, and in -such a case there can be no possible difficulty in isolating morphine -and meconic acid, with probably one or two other alkaloids. The method -of extraction from organic fluids is the same as before described, but -it may, of course, be modified for any special purpose. If opium, or a -preparation of opium, be submitted to Dragendorff's process (see p. -242), the following is a sketch of the chief points to be noticed. - -If the solution is _acid_-- - -(1.) =Benzene= mainly extracts _meconin_, which dissolves in sulphuric -acid very gradually (in twenty-four to forty-eight hours), with a green -colour passing into red. Meconin has no alkaloidal reaction. - -(2.) =Amyl alcohol= dissolves small quantities of _meconic acid_, -identified by striking a blood-red colour with ferric chloride. - -If now the amyl alcohol is removed with the aid of petroleum ether, and -the fluid made alkaline by ammonia-- - -(1.) =Benzene= extracts _narcotine_, _codeine_, and _thebaine_. On -evaporation of the benzene the alkaloidal residue may be dissolved in -water, acidified with sulphuric acid, and after filtration, on adding -ammonia _in excess_, _thebaine and narcotine_ are precipitated, -_codeine_ remaining in solution. The dried precipitate, if it contain -thebaine, becomes blood-red when treated with cold concentrated -sulphuric acid, while narcotine is shown by a violet colour developing -gradually when the substance is dissolved in dilute sulphuric acid 1 : -5, and gently warmed. The codeine in the ammoniacal solution can be -recovered by shaking up with benzene, and recognised by the red colour -which the solid substance gives when treated with a little sugar and -sulphuric acid. - -(2.) =Chloroform= especially dissolves the _narceine_, which, on -evaporation of the chloroform, may be identified by its general -characters, and by its solution in Froehde's reagent becoming a beautiful -blue colour. Small quantities of morphine may be extracted with codeine. - -(3.) =Amyl alcohol= extracts from the alkaline solution morphine, -identified by its physical characters, by its forming a crystalline -precipitate with iodine and hydriodic acid, and the reaction with iodic -acid to be described. - -Sec. 352. =Morphine= (C_{17}H_{17}NO(OH)_{2} + H_{2}O).--Morphine occurs in -commerce as a white powder, sp. gr. 1.205, usually in the form of more -or less perfect six-sided prisms, but sometimes in that of white silky -needles. When heated in the subliming cell (described at pp. 257-8), -faint nebulae, resolved by high microscopic powers into minute dots, -appear on the upper disc at 150 deg. As the temperature is raised the spots -become coarser, and at 188 deg. distinct crystals may be obtained, the best -being formed at nearly 200 deg., at which temperature morphine begins -distinctly to brown, melt, and carbonise. At temperatures below 188 deg., -instead of minute dots, the sublimate may consist of white circular -spots or foliated patterns. One part of morphine, according to P. -Chastaing, is soluble at a temperature of 3 deg. in 33,333 parts of water; -at 22 deg., in 4545 parts; at 42 deg., 4280; and at 100 deg., 4562. It is scarcely -soluble in ether or benzene. Absolute alcohol, according to Pettenkofer, -dissolves in the cold one-fortieth of its weight; boiling, -one-thirtieth. Amyl alcohol, in the cold, dissolves one-fourth per -cent., and still more if the alkaloid be thrown out of an aqueous acid -solution by ammonia in the presence of amyl alcohol; for under such -circumstances the morphine has no time to become crystalline. According -to Schlimpert, 1 part of morphine requires 60 of chloroform for -solution; according to Pettenkofer, 175. - -Morphine is easily soluble in dilute acids, as well as in solutions of -the caustic alkalies and alkaline earths; carbonated alkalies and -chloride of ammonium also dissolve small quantities. The acid watery, -and the alcoholic solutions, turn the plane of polarisation to the left; -for sulphuric, nitric, and hydrochloric acids [[alpha]]_r_ = 89.8 deg.; in -alkaline solution the polarisation is less, [[alpha]]_r_ = 45.22 deg. It is -alkaline in reaction, neutralising acids fully; and, in fact, a -convenient method of titrating morphine is by the use of a centinormal -sulphuric acid--each c.c. equals 2.85 mgrms. of anhydrous morphine. - -Sec. 353. The salts of morphine are for the most part crystalline, and are -all bitter, neutral, and poisonous. They are insoluble in amylic -alcohol, ether, chloroform, benzene, or petroleum ether. - -=Morphine meconate= is one of the most soluble of the morphine salts; it -is freely soluble in water. Of all salts this is most suitable for -subcutaneous injection; it is the form in which the alkaloid exists in -opium. - -=Morphine hydrochlorate= (C_{17}H_{19}NO_{3}HCl) crystallises in silky -fibres; it is readily soluble in alcohol, and is soluble in cold, more -freely in boiling water. The purest morphine hydrochlorate is -colourless, but that which is most frequently met with in commerce is -fawn or buff-coloured. - -=Morphine acetate= is a crystallisable salt, soluble in water or -alcohol; it is in part decomposed by boiling the aqueous solution, some -of the acetic acid escaping. - -=Morphine Tartrates.=--These are readily soluble salts, and it is -important to note that the morphine might escape detection, if the -expert trusted alone to the usual test of an alkaloidal salt giving a -precipitate when the solution is alkalised by the fixed or volatile -alkalies; for the tartrates of morphine do not give this reaction, nor -do they give any precipitate with calcic chloride. By adding a solution -of potassium acetate in spirit, and also alcohol and a little acetic -acid to the concentrated solution, the tartrate is decomposed, and acid -tartrate of potassium is precipitated in the insoluble form; the -morphine in the form of acetate remains in solution, and then gives the -usual reactions. - -The solubility of morphine salts in water and alcohol has been -investigated by Mr. J. U. Lloyd. His results are as follows:-- - - =Morphine Acetate.= - - 11.70 parts of water by weight at 15.0 deg. dissolve 1 part of morphine - acetate. - 61.5 parts of water by weight at 100 deg. dissolve 1 part of morphine - acetate. - 68.30 parts of alcohol by weight (.820 specific gravity) at 15.0 deg. - dissolve 1 part of morphine acetate. - 13.30 parts of alcohol by weight (.820 specific gravity) at 100 deg. - dissolve 1 part of morphine acetate. - - =Morphine Hydrochlorate.= - - 23.40 parts of water dissolve at 15 deg. 1 morphine hydrochlorate. - .51 part of water dissolves at 100 deg. 1 morphine hydrochlorate. - 62.70 parts of alcohol (.820 specific gravity) dissolve at 15 deg. 1 - morphine hydrochlorate. - 30.80 parts of alcohol (.820 specific gravity) dissolve at 100 deg. 1 - morphine hydrochlorate. - - =Morphine Sulphate.= - - 21.60 parts of water at 15 deg. dissolve 1 morphine sulphate. - .75 part of water at 100 deg. dissolves 1 morphine sulphate. - 701.5 parts of alcohol (.820) at 15 deg. dissolve 1 morphine sulphate. - 144.00 parts of alcohol (.820) at 100 deg. dissolve 1 morphine sulphate. - -Sec. 354. =Constitution of Morphine.=--The chief facts bearing on the -constitution of morphine are as follows:-- - -It certainly contains two hydroxyl groups, because by the action of -acetic anhydride, acetyl morphine and diacetyl morphine, -C_{17}H_{18}(CH_{3}CO)NO_{3} and C_{17}H_{17}(CH_{3}CO)_{2}NO_{3} are -produced. The formation of the monomethyl ether of morphine (codeine), -C_{17}H_{17}(OH)(OCH_{3})NO, is also a testimony to the existence of -hydroxyl groups. One of the hydroxyl groups has phenolic functions, the -other alcoholic functions. By suitable oxidation morphine yields -trinitrophenol (picric acid), and by fusion with an alkali, -protocatechuic acid; both of these reactions suggest a benzene ring. On -distilling with zinc dust phenanthrene, pyridine, pyrrol, -trimethylamine, and ammonia are formed; evidence of a pyridine nucleus. -If morphine is mixed with 10 to 15 times its weight of a 20 per cent. -solution of potash, and heated at 180 deg. for from four to six hours, air -being excluded, a phenol-like compound is formed, and a volatile amine, -ethylmethylamine (the amine boils at 34 deg. to 35 deg., and its hydrochloride -melts at 133 deg.). This reaction is interpreted by Z. H. Skrauk[378] and L. -Wiegmann to indicate that the nitrogen is directly connected with two -alkyl groups--that is, ethyl and methyl. - -[378] _Monatsb._, x. 110-114. - -G. N. Vis,[379] after a careful review of the whole of the reactions of -morphine, has proposed the following constitutional formula as the one -that agrees best with the facts:-- - - CH--CH--CH--CH--CH-------------------C--CH--CH - | | | | | | - CH--CH--CH--O NMe--CH_{2}--CH(OH)--C--CH--CH - -[379] _J. pr. Chemie_ (2), xlvii. 584. Knorr's formula is-- - - CHOH----CHO---CH_{2} - / | \ - OH.C_{10}H_{5} | > - \ | / - CH_{2}--CH.NMeCH_{2} - -_Ber._, xxii. 1113-1119. - -Sec. 355. =Tests for Morphine.=--(1.) One hundredth of a milligrm. of pure -morphine gives a blue colour to a paste of ammonium molybdate in -sulphuric acid; 20 mgrms. of ammonium molybdate are rubbed with a glass -rod in a porcelain dish, and well mixed with 5 drops of pure strong -sulphuric acid and the morphine in a solid form applied; titanic acid -and tungstates give similar reactions. - -(2.) Morphine possesses strong reducing properties; a little solid -morphine dissolved in a solution of ferric chloride gives a Prussian -blue precipitate when ferridcyanide solution is added. A number of -ptomaines and other substances also respond to this test, so that in -itself it is not conclusive. - -(3.) =Iodic Acid Test.=--The substance supposed to be morphine is -converted into a soluble salt by adding to acid reaction a few drops of -hydrochloric acid, and then evaporating to dryness. The salt thus -obtained is dissolved in as little water as possible--this, as in -toxicological researches only small quantities are recovered, will -probably be but a few drops. A little of the solution is now mixed with -a very small quantity of starch paste, and evaporated to dryness at a -gentle heat in a porcelain dish. After cooling, a drop of a solution of -1 part of iodic acid in 15 of water is added to the dry residue; and if -even the 1/20000 of a grain of morphine be present, a blue colour will -be developed. - -Another way of working the iodic acid test is to add the iodic acid -solution to the liquid in which morphine is supposed to be dissolved, -and then shake the liquid up with a few drops of carbon disulphide. If -morphine be present, the carbon disulphide floats to the top distinctly -coloured pink. Other substances, however, also set free iodine from -iodic acid, and it has, therefore, been proposed to distinguish morphine -from these by the after addition of ammonia. If ammonia is added to the -solution, which has been shaken up with carbon disulphide, the pink or -red colour of the carbon disulphide is deepened, if morphine was -present; on the contrary, if morphine was _not_ present, it is either -discharged or much weakened. - -=Other Reactions.=--There are some very interesting reactions besides -the two characteristic tests just mentioned. If a saturated solution of -chloride of zinc be added to a little solid morphine, and heated over -the water-bath for from fifteen minutes to half-an-hour, the liquid -develops a beautiful and persistent green colour. This would be an -excellent test for morphine were it not for the fact that the colour is -produced with only pure morphine. For example, I was unable to get the -reaction from morphine in very well-formed crystals precipitated from -ordinary laudanum by ammonia, the least trace of resinous or -colouring-matter seriously interfering. By the action of nitric acid on -morphine, the liquid becomes orange-red, and an acid product of the -formula C_{10}H_{9}NO_{9} is produced, which, when heated in a closed -tube with water at 100 deg., yields trinitrophenol or picric acid. This -interesting reaction points very decidedly to the phenolic character of -morphine. On adding a drop of sulphuric acid to solid morphine in the -cold, the morphine solution becomes of a faint pink; on gently warming -and continuing the heat until the acid begins to volatilise, the colour -changes through a series of brownish and indefinite hues up to black. On -cooling and treating the black spot with water, a green solution is -obtained, agreeing in hue with the same green produced by chloride of -zinc. Vidali[380] has proposed the following test:--Morphine is -dissolved in strong sulphuric acid, and a little arsenate of sodium is -added; on gently warming, a passing blue colour develops; on raising the -temperature higher, the liquid changes into green, then into blue, and -finally again into green. Codeine acts very similarly. The following -test originated with Siebold (_American Journal of Pharmacy_, 1873, p. -544):--The supposed morphine is heated gently with a few drops of -concentrated sulphuric acid and a little pure potassic perchlorate. If -morphine be present the liquid immediately takes a pronounced brown -colour--a reaction said to be peculiar to morphine, and to succeed with -1/10 of a mgrm. In order to obtain absolutely pure perchlorate, potassic -perchlorate is heated with hydrochloric acid so long as it disengages -chlorine; it is then washed with distilled water, dried, and preserved -for use. There is also a test known as "Pellagri's"; it depends on the -production of apomorphine. The suspected alkaloid is dissolved in a -little strong hydrochloric acid, and then a drop of concentrated -sulphuric acid is added, and the mixture heated for a little time from -100 deg. to 120 deg., until it assumes a purple-black colour. It is now cooled, -some hydrochloric acid again added, and the mixture neutralised with -sodic carbonate. If morphine be present, on the addition of iodine in -hydriodic acid, a cherry-red colour is produced, passing into green. -Morphine and codeine are believed alone to give this reaction. - -[380] D. Vidali, _Bull. Farmaceut._, Milano, 1881, p. 197; D. E. Dott, -_Year Book of Pharmacy_, 1882. - -The acetate of morphine, and morphine itself, when added to ferric -chloride solution, develop a blue colour. When 1 molecule of morphine is -dissolved in alcohol, containing 1 molecule of sodium hydroxide, and 2 -vols. of methyl iodide are added, and the mixture gently heated, a -violent reaction sets in and the main product is codeine methiodide -(C_{17}H_{18}NO_{2}OCH,MeI). If only half the quantity of methyl iodide -is added, then free codeine is in small quantity produced; if ethyl -iodide be substituted for methyl, a new base is formed homologous with -codeine--codeine is therefore the methyl ether of morphine. If morphine -is heated with iodide of methyl and absolute alcohol in a closed tube -for half an hour at 100 deg., methyl iodide of morphine is obtained in -colourless, glittering, quadratic crystals, easily soluble in water -(C_{17}H_{19}NO_{3}MeI + H_{2}O); similarly the ethyl iodide compound -can be produced. - -If morphine is heated for from two to three hours in a closed tube with -dilute hydrochloric acid, water is eliminated-- - - (C_{17}H_{19}NO_{3} = C_{17}H_{17}NO_{2} + H_{2}O), - -and the hydrochlorate of apomorphine is produced. This succeeds when -even 1/2 mgrm. is heated with 1/10 c.c. of strong HCl, and the tests for -apomorphine applied. - -If concentrated sulphuric acid be digested on morphine for twelve to -fifteen hours (or heated for half an hour at 100 deg.), on adding to the -cooled violet-coloured solution either a crystal of nitrate of potash or -of chlorate of potash, or a drop of dilute nitric acid, a beautiful -violet-blue colour is produced, which passes gradually into a dark -blood-red. 1/100 of a mgrm. will respond distinctly to this test. -Froehde's reagent strikes with morphine a beautiful violet colour, -passing from blue into dirty green, and finally almost vanishing. 1/200 -of a mgrm. will respond to the test, but it is not itself conclusive, -since papaverine and certain glucosides give an identical reaction. - -Sec. 356. =Symptoms of Opium and Morphine Poisoning.=--The symptoms of -opium and morphine poisoning are so much alike, that clinically it is -impossible to distinguish them; therefore they may be considered -together. - -=Action on Animals--Frogs.=--The action of morphine or opium on frogs is -peculiar: the animal at first springs restlessly about, and then falls -into a condition extremely analogous to that seen in strychnine -poisoning, every motion or external irritation producing a tetanic -convulsion. This condition is, however, sometimes not observed. The -tetanic stage is followed by paralysis of reflex movements and cessation -of breathing, the heart continuing to beat. - -=Dogs.=--0.2 to 0.5 grm. of morphine meconate, or acetate, injected -directly into the circulation of a dog, shows its effects almost -immediately. The dog becomes uneasy, and moves its jaws and tongue as if -some peculiar taste were experienced; it may bark or utter a whine, and -then in a minute or two falls into a profound sleep, which is often so -deep that while it lasts--usually several hours--an operation may be -performed. In whatever attitude the limbs are placed, they remain. The -respiration is rapid and stertorous, and most reflex actions are -extinguished. Towards the end of the sleep, any sudden noise may startle -the animal, and when he wakes his faculties are evidently confused. A -partial paralysis of the hind legs has often been noticed, and then the -dog, with his tail and pelvis low, has something the attitude of the -hyena. Hence this condition (first, I believe, noticed by Bernard) has -been called the "hyenoid" state. If the dose is larger than 2 to 3 grms. -(31 to 46 grains), the symptoms are not dissimilar, save that they -terminate in death, which is generally preceded by convulsions.[381] - -[381] MM. Grasset and Amblard have studied the action of morphine in -causing convulsions in the mammalia. They found that if small doses of -hydrochlorate of morphine (from 1 to 15 centigrammes) are administered -to dogs, the brief sleep which is produced may be accompanied by partial -muscular contractions (in one paw, for instance), which are renewed at -variable intervals. Then occur true convulsive shocks in the whole body -or in the hind limbs. After an interval, the phenomena recur in more -intense degree, and are followed by true convulsions. Regularly, ten or -sixteen times a minute, at each inspiration, the hind limbs present a -series of convulsive movements, which may become general. Sometimes they -are excited by external stimulation, but they are usually spontaneous. -The sleep may continue profound during this convulsive period, or it may -become distinctly lighter. These convulsive phenomena may continue, with -intervals, for an hour. Differences are observed with different animals; -but the chief characters of the phenomena are as described. In certain -animals, and with small doses, there may be a brief convulsive phase at -the commencement of the sleep, but it is much less constant than the -later period of spasm. These convulsions, the authors believe, have not -previously been described, except as a consequence of very large doses, -amounting to grammes. The period of cerebral excitement, described by -Claude Bernard as occurring at the commencement of the sleep from -morphine, is a phenomenon of a different order. The conclusions drawn -from the experiments are--(1) That morphia is not diametrically opposed -to thebaine, as is often stated, since it has, to a certain degree, the -convulsive properties of the latter alkaloid. (2) That the excitomotor -action of opium cannot be exclusively attributed to the convulsive -alkaloids, but is, in fact, due to those which are soporific. According -to the ordinary composition of opium, 5 centigrammes of morphine -represent about a milligramme of thebaine. But these experiments show -that the quantity of morphine has a much more powerful convulsive action -than a milligramme of thebaine. (3) There is not the supposed antagonism -between the action of morphine on the frog and on the mammalia. (4) The -researches hitherto undertaken on the antagonism between morphine and -other agents need to be repeated, and a separate study made of the -substances which antagonise the convulsive and soporific action. - -=Goats.=--According to Guinard, goats are proof against the narcotic -influence of morphine. Large doses kill goats, but death is caused by -interference with the respiratory function. A young goat weighing 30 -kilos, showed little effect beyond a slightly increased cerebral -excitability after two doses of 8 and 8.5 grms. respectively of morphine -hydrochlorate had been administered by intravenous injection, the second -being given an hour and a half after the first. To the same animal two -days afterwards 195 grms. were administered in the same way, yet the -goat recovered. The lethal dose for a goat seems to be no less than 1000 -times that which will produce narcotism in man, and lies somewhere -between 0.25 to 0.30 per kilo. of the body weight.[382] - -[382] _Compt. Rend._, t. cxvi. pp. 520-522. - -=Cats and the Felidae.=--According to Guinard,[383] morphine injected -subcutaneously or intravenously into cats, in doses varying from 0.4 -mgrm. to 90 mgrms. per kilo., never produces sleep or narcotic -prostration. On the contrary, it causes a remarkable degree of -excitement, increasing in intensity with the dose given. This excitement -is evidently accompanied by disorder in the functions of the brain, and -if the dose is large convulsions set in, ending in death. According to -Milne-Edwards, the same symptoms are produced in lions and tigers. - -[383] _Compt. Rend._, t. cxi. pp. 981-983. The _bovine_ animals also get -excited, and no narcotic effect is produced by dosing them with -morphine.--_Compt. Rend. Soc. de Biologie_, t. iv., v. - -=Birds=, especially pigeons, are able to eat almost incredible -quantities of opium. A pigeon is said[384] to have consumed 801 grains -of opium, mixed with its food, in fourteen days. The explanation of this -is that the poison is not absorbed; for subcutaneous injections of salts -of morphine act rapidly on all birds hitherto experimented upon. - -[384] Hermann's _Lehrbuch der exper. Toxicologie_, p. 374. - -Sec. 357. =Physiological Action.=--From experiments on animals, the -essential action of morphine on the nervous and arterial systems has in -some measure been examined. There is no very considerable action on the -heart. The beats are first accelerated, then diminished in frequency; -but very large doses introduced directly into the circulation at once -diminish the pulsations, and no acceleration is noticed. The slowing may -go on to heart-paralysis. The slowing is central in its origin, for on -the vagi being cut, morphine always quickens. With regard to the -peripheric ends of the vagi, small doses excite, large paralyse. If all -the nerves going to the heart are divided, there is first a considerable -acceleration, and then a slowing and weakening of the pulsations. The -arterial blood-pressure, at first increased, is afterwards diminished. -This increase of blood-pressure is noticed during the acceleration of -the pulse, and also during some portion of the time during which the -pulse is slowed. Stockman and D. B. Dott,[385] experimenting on rabbits -and frogs, consider that a medium dose of morphine first of all -depresses the spinal cord and then excites it, for tetanus follows. If -morphine is in sufficient quantity thrown into the circulation then -tetanus at once occurs. It would thus appear that depression and -stimulation is entirely a matter of dosage. Gescheidlen, in his -researches on the frog, found the motor nerves at first excited, and -then depressed. When the doses were large, there was scarcely any -excitement, but the reverse effect, in the neighbourhood of the place of -application. According to other observers, the function of the motor -nerves may be annihilated.[386] According to Meihuizen, reflex action, -at first much diminished, is later, after several hours, normal, and -later still again increased. The intestinal movements are transitorily -increased. In the dog there has been noticed a greater flow of saliva -than usual, and the flow of bile from the gall-bladder is diminished. -The pupils in animals are mostly contracted, but, if convulsions occur -towards death, they are dilated. - -[385] _Brit. Med. Journ._ (2), 1890, 189-192. - -[386] _Arch. f. d. Ges. Physiol._, vii. p. 201. - -Sec. 358. =Physiological Effect of Morphine Derivatives.=--By introducing -methyl, or amyl, or ethyl, into the morphine molecule, the narcotic -action is diminished, while the tetanic effects are increased. Acetyl, -diacetyl, benzoyl, and dibenzoyl morphine, morphine sulphuric ether, and -nitrosomorphine are all weaker narcotics than morphine, but, on the -other hand, they depress the functions of the spinal cord and bring on, -in large doses, tetanus. - -The introduction of two methyl groups into morphine, as in -metho-codeine, C_{17}H_{17}MeNO(OH)-Me, entirely alters the -physiological effect. This compound has an action on voluntary muscle -causing gradual paralysis. - -The chlorine derivatives, trichlormorphine and chlorcodeine, have the -characteristic action of the morphine group on the central nervous -system and, in addition, act energetically as muscle poisons, soon -destroying the contractile power of the voluntary muscles with which -they first come into contact at the place of injection, and more -gradually affecting the other muscles of the body.[387] - -[387] R. Stockman and Dott, _Brit. Med. Journ._ (2), 1890, 189-192. - -Sec. 359. =Action on Man.=--There are at least three forms of opium -poisoning:--(1) _The common form_, as seen in about 99 per cent. of -cases; (2) A very _sudden form_, in which death takes place with fearful -rapidity (the _foudroyante_ variety of the French);[388] and (3) a very -rare entirely _abnormal form_, in which there is no coma, but -convulsions. - -[388] Tardieu, _Etude Med. Legale sur l'Empoisonnement._ - -In the _common form_ there are three stages, viz.:--(1) Excitement; (2) -Narcosis; (3) Coma. In from half an hour to an hour[389] the first -symptoms commence, the pulse is quickened, the pupils are contracted, -the face flushes, and the hands and feet reddened,--in other words, the -capillary circulation is active. This stage has some analogy to the -action of alcohol; the ideas mostly flow with great rapidity, and -instead of a feeling of sleepiness, the reverse is the case. It, -however, insensibly, and more or less rapidly, passes into the next -stage of heaviness and stupor. There is an irresistible tendency to -sleep; the pulse and the respiration become slower; the conjunctivae are -reddened; the face and head often flushed. In some cases there is great -irritability of the skin, and an eruption of nettle-rash. If the poison -has been taken by the mouth, vomiting may be present. The bowels are -usually--in fact almost invariably--constipated. There is also some loss -of power over the bladder. - -[389] In a remarkable case related by Taylor, a lady took a large dose -(supposed to be 1-1/2 oz.) of laudanum, and there were no symptoms for -four and a half hours. She died in twenty-two hours. - -In the next stage, the narcosis deepens into dangerous coma; the patient -can no longer be roused by noises, shaking, or external stimuli; the -breathing is loud and stertorous; the face often pale; the body covered -with a clammy sweat. The pupils are still contracted, but they may in -the last hours of life dilate: and it is generally agreed that, if a -corpse is found with the pupils dilated, this circumstance, taken in -itself, does not contra-indicate opium or morphine poisoning. Death -occasionally terminates by convulsion. - -The _sudden form_ is that in which the individual sinks into a deep -sleep almost immediately--that is, within five or ten minutes--and dies -in a few hours. In these rapid cases the pupils are said to be -constantly dilated. - -Examples of the _convulsive form_ are to be sought among opium-eaters, -or persons under otherwise abnormal conditions. - -A man, forty years old, who had taken opiates daily since his -twenty-second year--his dose being 6 grms. (92.4 grains) of solid -opium--when out hunting, of which sport he was passionately fond, took -cold, and, as a remedy, administered to himself three times his -accustomed dose. Very shortly there was contraction of the left arm, -disturbance of vision, pain in the stomach, faintness, inability to -speak, and unconsciousness which lasted half an hour. Intermittent -convulsions now set in, and pains in the limbs. There was neither -somnolence nor delirium, but great agitation; repeated vomiting and -diarrh[oe]a followed. After five hours these symptoms ceased; but he was -excessively prostrate.[390] There was complete recovery. - -[390] Demontporcellet, _De l'Usage Quotidien de l'Opium_, Paris, 1874. - -One may hazard a surmise that, in such a case, tolerance has been -established for morphine, but not for other morphine alkaloids in the -same degree, and that the marked nervous symptoms were in no small -degree the effect of some of the homologous alkaloids, which, in such an -enormous dose, would be taken in sufficient quantity to have a -physiological action. - -There are several instances of a relapsing or remittent form of -poisoning--a form in which the patient more or less completely recovers -consciousness, and then sinks back into a fatal slumber. One of the best -known is the case of the Hon. Mrs Anson (January 1859), who swallowed an -ounce and a half of laudanum by mistake. After remaining in a comatose -condition for more than nine hours, she revived. The face became -natural, the pulse steady. She was able to recognise her daughter, and -in a thick voice to give an account of the mistake. But this lasted only -ten minutes, when she again became comatose, and died in fourteen -hours.[391] - -[391] Taylor, _op. cit._ - -In a Swedish case quoted by Maschka,[392] a girl, nine years old, in -weak health and suffering from slight bronchitis, had been given a -non-officinal acetate of morphia lozenge, which was supposed to contain -5 mgrms. (.075 grain) of morphine acetate. She took the lozenge at eight -in the evening; soon slept, woke at ten, got out of bed, laughed, -talked, and joked with the nurse, again got into bed, and very quickly -fell asleep. At four A.M. the nurse came and found her breathing with a -rattling sound, and the physician, who arrived an hour later, found the -girl in a state of coma, with contracted pupils, breathing stertorously, -and the pulse scarcely to be felt. Despite all attempts to rouse the -patient, she died at eight in the morning, twelve hours after taking the -lozenge. - -[392] Maschka's _Handbuch_, Band ii. p. 438; also Svenska, _Laek-Saellsk. -Foerhandl._, Apr. 1, p. 90; Apr. 8, p. 160, 1873. For other cases see -Nasmyth, _Edin. Med. Journ._, Dec. 1878; Kirby, _Dub. Med. Press_, Dec. -24, 1845; W. Boyd Muschet, _Med. Times and Gaz._, March 20, 1858. - -The _post-mortem_ examination showed some hyperaemia of the brain and -serous effusion in the ventricles, and there was also tubercle in the -pleura. Three lozenges similar to the one taken by the patient were -chemically investigated by Hamberg, who found that the amount of acetate -was very small, and that the lozenges, instead of morphine acetate, -might be considered as prepared with almost pure morphine; the content -in the three of morphine being respectively 35, 37, and 42 mgrms. (that -is, from half a grain to three-fifths of a grain). There was a -difference of opinion among the experts as to whether in this case the -child died from morphine poisoning or not--a difference solely to be -attributed to the waking up of the child two hours after taking the -poison. Now, considering the great probability that a large dose for a -weakly child of that age had been taken, and that this is not the only -case in which a relapse has occurred, it seems just to infer that it was -really a case of poisoning. - -As unusual symptoms (or rather sequelae) may be noted in a few cases, -hemiplegia, which soon passes off; a weakness of the lower extremities -may also be left, and inability to empty the bladder thoroughly; but -usually on recovery from a large dose of opium, there is simply -heaviness of the head, a dry tongue, constipation, and loss of appetite. -All these symptoms in healthy people vanish in a day or two. There have -also been noticed slight albuminuria, eruptions on the skin, loss of -taste, and numbness of parts of the body. - -Opium, whether taken in substance, or still more by subcutaneous -injection, in some individuals constantly causes faintness. In my own -case, I have several times taken a single grain of opium to relieve -either pain or a catarrh; almost invariably within an hour afterwards -there has been great coldness of the hands and feet, lividity of the -face, a feeling of deadly faintness followed by vomiting; this stage -(which has seldom lasted more than half an hour) passed, the usual -narcotic effects have been produced. - -Some years ago I injected one-sixth of a grain of morphine hydrochlorate -subcutaneously into an old gentleman, who was suffering from acute -lumbago, but was otherwise healthy, and had no heart disease which could -be detected; the malady was instantly relieved, and he called out, "I am -well; it is most extraordinary." He went out of the front door, and -walked some fifty yards, and then was observed to reel about like a -drunken man. He was supported back and laid in the horizontal posture; -the face was livid, the pulse could scarcely be felt, and there was -complete loss of consciousness. This state lasted about an hour, and -without a doubt the man nearly died. Medical men in practice, who have -been in the habit of using hypodermic injections of morphine, have had -experiences very similar to this and other cases, and although I know of -no actual death, yet it is evident that morphine, when injected -hypodermically even in a moderate dose, may kill by syncope, and within -a few minutes.[393] Absorption by hypodermic administration is so rapid -that by the time, or even before the needle of the syringe is withdrawn, -a contraction of the pupil may be observed. - -[393] See a case of morphia poisoning by hypodermic injection, and -recovery, by Philip E. Hill, M.R.C.S., _Lancet_, Sept. 30, 1882. In this -instance a third of a grain introduced subcutaneously caused most -dangerous symptoms in a gardener, aged 48. - -Opium or morphine is poisonous by whatever channel it gains access to -the system, the intestinal mucous membrane absorbs it readily, and -narcotic effects may be produced by external applications, whether a -wound is present or not. A case of absorption of opium by a wound is -related in Chevers's _Jurisprudence_.[394] A Burman boy, about nine or -ten years of age, was struck on the forehead by a brick-bat, causing a -gaping wound about an inch long; his parents stuffed the wound with -opium. On the third day after the accident, and the opium still -remaining in the wound, he became semi-comatose, and, in short, had all -the symptoms of opium narcosis; with treatment he recovered. The -unbroken skin also readily absorbs the drug. Tardieu states that he had -seen 30 grms. of laudanum, applied on a poultice to the abdomen, produce -death. Christison has also cited a case in which a soldier suffered from -erysipelas, and died in a narcotic state, apparently produced from the -too free application of laudanum to the inflamed part. - -[394] Third ed., p. 228. - -To these cases may be added the one cited by Taylor, in which a druggist -applied 30 grains of morphine to the surface of an ulcerated breast, and -the woman died with all the symptoms of narcotic poisoning ten hours -after the application--an event scarcely surprising. It is a curious -question whether sufficient of the poison enters into the -secretions--_e.g._, the milk--to render it poisonous. An inquest was -held in Manchester, Nov. 1875, on the body of a male child two days old, -in which it seemed probable that death had occurred through the mother's -milk. She was a confirmed opium-eater, taking a solid ounce per week. - -Sec. 360. =Diagnosis of Opium Poisoning.=--The diagnosis is at times -between poisoning by opium or other narcotic substances, at others, -between opium and disease. Insensibility from chloral, from alcohol, -from belladonna or atropine, and from carbon oxide gas, are all more or -less like opium poisoning. With regard to chloral, it may be that only -chemical analysis and surrounding circumstances can clear up the matter. -In alcohol poisoning, the breath commonly smells very strongly of -alcohol, and there is no difficulty in separating it from the contents -of the stomach, &c., besides which the stomach is usually red and -inflamed. Atropine and belladonna invariably dilate the pupil, and -although just before death opium has the same effect, yet we must hold -that mostly opium contracts, and that a widely-dilated pupil during life -would, _per se_, lead us to suspect that opium had not been used, -although, as before mentioned, too much stress must not be laid upon the -state of the pupils. In carbon oxide, the peculiar rose-red condition of -the body affords a striking contrast to the pallor which, for the most -part, accompanies opium poisoning. In the rare cases in which -convulsions are a prominent symptom, it may be doubtful whether opium or -strychnine has been taken, but the convulsions hitherto noticed in opium -poisoning seem to me to have been rather of an epileptiform character, -and very different from the effects of strychnine. No rules can be laid -down for cases which do not run a normal course; in medicine such are -being constantly met with, and require all the care and acumen of the -trained observer. Cases of disease render a diagnosis often extremely -difficult, and the more so in those instances in which a dose of -laudanum or other opiate has been administered. In a case under my own -observation, a woman, suffering from emphysema and bronchitis, sent to a -chemist for a sleeping draught, which she took directly it arrived. A -short time afterwards she fell into a profound slumber, and died within -six hours. The draught had been contained in an ounce-and-a-half bottle; -the bottle was empty, and the druggist stated in evidence that it only -contained 20 minims of laudanum, 10 grains of potassic bromide, and -water. On, however, diluting the single drop remaining in the bottle, -and imitating its colour with several samples of laudanum diluted in the -same way, I came to the conclusion that the quantity of laudanum which -the bottle originally contained was far in excess of that which had been -stated, and that it was over 1 drachm and under 2 drachms. The body was -pallid, the pupils strongly contracted, the vessels of the brain -membranes were filled with fluid blood, and there was about an ounce of -serous fluid in each ventricle. The lungs were excessively -emphysematous, and there was much secretion in the bronchi; the liver -was slightly cirrhotic. The blood, the liver, and the contents of the -stomach were exhaustively analysed with the greatest care, but no trace -of morphine, narcotine, or meconic acid could be separated, although the -woman did not live more than six hours after taking the draught. I gave -the opinion that it was, in the woman's state, improper to prescribe a -sedative of that kind, and that probably death had been accelerated, if -not directly caused, by opium. - -Deaths by apoplexy will only simulate opium-poisoning during life; a -_post-mortem_ examination will at once reveal the true nature of the -malady. In epilepsy, however, it is different, and more than once an -epileptic fit has occurred and been followed by coma--a coma which -certainly cannot be distinguished from that produced by a narcotic -poison. Death in this stage may follow, and on examining the body no -lesion may be found. - -Sec. 361. =Opium-eating.=--The consumption of opium is a very ancient -practice among Eastern nations, and the picture, drawn by novelist and -traveller, of poor, dried-up, yellow mortals addicted to this vice, with -their faculties torpid, their skin hanging in wrinkles on their wasted -bodies, the conjunctivae tinged with bile, the bowels so inactive that -there is scarcely an excretion in the course of a week, the mental -faculties verging on idiocy and imbecility, is only true of a percentage -of those who are addicted to the habit. In the _British Medical Journal_ -for 1894, Jan. 13 and 20, will be found a careful digest of the -evidence collated from 100 Indian medical officers, from which it -appears that opium is taken habitually by a very large number of the -population throughout India, those who are accustomed to the drug taking -it in quantities of from 10 to 20 grains in the twenty-four hours; so -long as this amount is not exceeded they do not appear to suffer -ill-health or any injurious effect. The native wrestlers even use it -whilst training. The habitual consumption of opium by individuals has a -direct medico-legal bearing. Thus in India, among the Rajpoots, from -time immemorial, infused opium has been the drink both of reconciliation -and of ordinary greeting, and it is no evidence of death by poison if -even a considerable quantity of opium be found in the stomach after -death, for this circumstance taken alone would, unless the history of -the case was further known, be considered insufficient proof. So, again, -in all climates, and among all races, it is entirely unknown what -quantity of an opiate should be considered a poisonous dose for an -opium-eater. Almost incredible quantities have, indeed, been consumed by -such persons, and the commonly-received explanation, that the drug, in -these cases, passes out unabsorbed, can scarcely be correct, for Hermann -mentions the case of a lady of Zurich who daily injected subcutaneously -1 to 2 grms. (15-31 grains) of a morphine salt. In a case of uterine -cancer, recorded by Dr. W. C. Cass,[395] 20 grains of morphine in the -twelve hours were frequently used subcutaneously; during thirteen months -the hypodermic syringe was used 1350 times, the dose each time being 5 -grains. It is not credible that an alkaloid introduced into the body -hypodermically should not be absorbed. - -[395] _Lancet_, March 25, 1882. See also Dr. Boulton's case, _Lancet_, -March 18, 1882. - -Opium-smoking is another form in which the drug is used, but it is an -open question as to what poisonous alkaloids are in opium smoke. It is -scarcely probable that morphine should be a constituent, for its -subliming point is high, and it will rather be deposited in the cooler -portion of the pipe. Opium, specially prepared for smoking, is called -"Chandoo"; it is dried at a temperature not exceeding 240 deg. H. -Moissan[396] has investigated the products of smoking chandoo, but only -found a small quantity of morphine. N. Grehant and E. Martin[397] have -also experimented with opium smoke; they found it to have no appreciable -effect on a dog; one of the writers smoked twenty pipes in succession, -containing altogether 4 grms. of chandoo. After the fourth pipe there -was some headache, at the tenth pipe and onwards giddiness. Half an hour -after the last pipe the giddiness and headache rapidly went off. In any -case, opium-smoking seems to injure the health of Asiatics but little. -Mr. Vice-Consul King, of Kew-Kiang, in a tour through Upper Yangtse and -Stechnan, was thrown much into the company of junk sailors and others, -"almost every adult of whom smoked more or less." He says:--"Their work -was of the hardest and rudest, rising at four and working with hardly -any intermission till dark, having constantly to strip and plunge into -the stream in all seasons, and this often in the most dangerous parts. -The quantity of food they eat was simply prodigious, and from this and -their work it seems fairly to be inferred that their constitution was -robust. The two most addicted to the habit were the pilot and the ship's -cook. On the incessant watchfulness and steady nerve of the former the -safety of the junk and all on board depended, while the second worked so -hard from 3 A.M. to 10 P.M., and often longer, and seemed so independent -of sleep or rest, that to catch him seated or idle was sufficient cause -for good-humoured banter. This latter had a conserve of opium and sugar -which he chewed during the day, as he was only able to smoke at night." - -[396] _Compt. Rend._, cxv. 988-992. - -[397] _Compt. Rend._, 1012-1014. - -Sec. 362. =Treatment of Opium or Morphine Poisoning.=--The first thing to -be done is doubtless to empty the stomach by means of the flexible -stomach tube; the end of a sufficiently long piece of indiarubber tubing -is passed down into the pharynx and allowed to be carried into the -stomach by means of the natural involuntary movements of the muscles of -the pharynx and gullet; suction is then applied to the free end and the -contents syphoned out; the stomach is, by means of a funnel attached to -the tube, washed out with warm water, and then some coffee administered -in the same way. - -Should morphine have been taken, and permanganate of potash be at hand, -it has been shown that under such circumstances potassic permanganate is -a perfect antidote, decomposing at once any morphine remaining in the -stomach, but it, of course, will have no effect upon any morphine which -has already been absorbed. In a case of opium poisoning, reported in the -_Lancet_ of June 2, 1894, by W. J. C. Merry, M.B., inhalations of -oxygen, preceded by emptying the stomach and other means, appeared to -save a man, who, three hours before the treatment, had drank 2 ozs. of -chlorodyne. It is also the received treatment to ward off the fatal -sleep by stimulation; the patient is walked about, flicked with a towel, -made to smell strong ammonia, and so forth. This stimulation must, -however, be an addition, but must never replace the measures first -detailed. - -Sec. 363. =Post-mortem Appearances.=--There are no characteristic -appearances after death save hyperaemia of the brain and blood-vessels of -the membranes, with generally serous effusion into the ventricles. The -pupils are sometimes contracted, sometimes dilated, the dilatation -occurring, as before mentioned, in the act of dying. The external -surface of the body is either livid or pale. The lungs are commonly -hyperaemic, the bladder full of urine; still, in not a few cases, there -is nothing abnormal, and in no single case could a pathologist, from the -appearance of the organs only, declare the cause of death with -confidence. - -Sec. 364. =Separation of Morphine from Animal Tissues and -Fluids.=--Formerly a large proportion of the opium and morphine cases -submitted to chemical experts led to no results; but owing to the -improved processes now adopted, failure, though still common, is less -frequent. The constituents of opium taken into the blood undergo partial -destruction in the animal body, but a portion may be found in the -secretions, more especially in the urine and faeces. First -Bouchardat[398] and then Lefort[399] ascertained the excretion of -morphine by the urine after medicinal doses; Dragendorff and Kauzmann -showed that the appearance of morphine in the urine was constant, and -that it could be easily ascertained and separated from the urine of men -and animals; and Levinstein[400] has also shown that the elimination -from a single dose may extend over five or six days. The method used by -Dragendorff to extract morphine from either urine or blood is to shake -the liquid (acidified with a mineral acid) several times with amyl -alcohol, which, on removal, separates urea and any bile acids. The -liquid thus purified is then alkalised, and shaken up with amyl alcohol, -and this amyl alcohol should contain any morphine that was present. On -evaporation it may be pure enough to admit of identification, but if -not, it may be redissolved and purified on the usual principles. -Considerable variety of results seems to be obtained by different -experimenters. Landsberg[401] injected hypodermically doses of .2 to .4 -grm. of morphine hydrochlorate into dogs, making four experiments in -all, but failed to detect morphine in the urine. A large dose with 2.4 -mgrms. of the salt gave the same result. On the other hand, .8 grm. of -morphine hydrochlorate injected direct into the jugular vein, was partly -excreted by the kidneys, for 90 c.c. of the urine yielded a small -quantity of morphine. Voit, again, examined the urine and faeces of a man -who had taken morphine for years; he could detect none in the urine, but -separated morphine from the faeces.[402] Morphine may occasionally be -recognised in the blood. Dragendorff[403] found it in the blood of a cat -twenty-five minutes after a subcutaneous dose, and he also separated it -from the blood of a man who died of morphine poisoning in six hours. -Haidlen[404] recognised morphine in the blood of a suicide who had taken -opium extract. - -[398] _Bull. Gen. de Therap._, Dec. 1861. - -[399] _Journ. de Chim._, xi. 93, 1861. - -[400] _Berl. klin. Wochenschr._, 1876, 27. - -[401] _Pflueger's Archiv._, 23, 433, 413-433. _Chem. Soc. Journ._, May -1882, 543. - -[402] _Arch. Pharm._, pp. [3], vii. pp. 23-26. - -[403] Kauzmann, _Beitraege fuer den gerichtlich-chemischen Nachweis des -Morphia u. Narcotins_, Dissert., Dorpat, 1868. Dragendorff, _Pharm. -Zeitschr. f. Russland_, 1868, Hft. 4. - -[404] _Wuertbg. Correspondenzbl._, xxxiv. 16, 1863. - -On the other hand, in a case recorded at p. 304, where a woman died in -six hours from a moderate dose, probably of laudanum, although the -quantity of blood operated upon was over a pound in weight, and every -care was taken, the results were entirely negative. In poisoning by -laudanum there may be some remaining in the stomach, and also if large -doses of morphine have been taken by the mouth; but when morphine has -been administered hypodermically, and in all cases in which several -hours have elapsed, one may almost say that the organ in which there is -the least probability of finding the poison is the stomach. It may, in -some cases, be necessary to operate on a very large scale;--to examine -the faeces, mince up the whole liver, the kidney, spleen, and lungs, and -treat them with acid alcohol. The urine will also have to be examined, -and as much blood as can be obtained. In cases where all the evidence -points to a minute quantity (under a grain) of morphine, it is decidedly -best to add these various extracts together, to distil off the alcohol -at a very gentle heat, to dry the residue in a vacuum, to dissolve again -in absolute alcohol, filter, evaporate again to dryness, dissolve in -water, and then use the following process:-- - -Sec. 365. =Extraction of Morphine.=--To specially search for morphine in -such a fluid as the urine, it is, according to the author's experience, -best to proceed strictly as follows:--The urine is precipitated with -acetate of lead, the powdered lead salt being added to the warm urine -contained in a beaker on the water-bath, until a further addition no -longer produces a precipitate; the urine is then filtered, the lead -precipitate washed, and the excess of lead thrown down by SH_{2}; the -lead having been filtered off, and the precipitate washed, the urine is -concentrated down to a syrup in a vacuum. The syrup is now placed in a -separating tube (if not acid, it is acidified with hydrochloric acid), -and shaken up successively with petroleum ether, chloroform, ether, and, -lastly, with amylic alcohol (the latter should be warm); finally, the -small amount of amylic alcohol left dissolved in the liquid is got rid -of by shaking it up with petroleum ether. To get rid of the last traces -of petroleum ether, it may be necessary to turn the liquid into an -evaporating dish, and gently heat for a little time over the water-bath. -The acid liquid is now again transferred to the separating tube, and -shaken up with ether, after being made alkaline with ammonia; this will -remove nearly all alkaloids save morphine,--under the circumstances, a -very small quantity of morphine may indeed be taken up by the ether, but -not the main bulk. After separating the ether, the liquid is again made -slightly acid, so as to be able to precipitate morphine in the presence -of the solvent; the tube is warmed on the water-bath, at least its own -bulk of hot amylic alcohol added and the liquid made alkaline, and the -whole well shaken. The amylic alcohol is removed in the usual way, and -shaken with a small quantity of decinormal sulphuric acid; this washes -out the alkaloid from the amyl alcohol, and the same amyl alcohol can be -used again and again. It is best to extract the liquid for morphine at -least thrice, and to operate with both the solution and the amyl hot. -The decinormal acid liquid is made slightly alkaline with ammonia, and -allowed to stand for at least twelve hours; any precipitate is collected -and washed with ether, and then with water; the alkaline liquid from -which the morphine has been separated is concentrated to the bulk of 5 -c.c. on the water bath, and again allowed to stand for twelve hours; a -little more morphine may often in this way be obtained. - -The author in some test experiments, in which weighed small quantities -of morphine (60-80 mgrms.) were dissolved in a little decinormal -sulphuric acid, and added to large quantities of urine, found the -process given to yield from 80 to 85 per cent. of the alkaloid added, -and it was always recovered in fine crystals of a slight brown tint, -which responded well to tests. - -Various other methods were tried, but the best was the one given; the -method not only separates the alkaloid with but little loss, but also in -a sufficiently pure state to admit of identification. - -From the tissues the alkaloid may be dissolved out by the general method -given at p. 239, and the ultimate aqueous solution, reduced to a bulk of -not more than 25 c.c., treated by the ethereal solvents in the way just -described. - -Sec. 366. =Narcotine= (C_{22}H_{23}NO_{7}) crystallises out of alcohol or -ether in colourless, transparent, glittering needles, or groups of -needles, belonging to the orthorhombic system. - -It is only slightly soluble in boiling, and almost insoluble in cold -water. One part requires 100 parts of cold, and 20 of boiling 84 per -cent. alcohol; 126 parts of cold, 48 of boiling ether (specific gravity -0.735); 2.69 parts of chloroform; 400 of olive oil; 60 of acetic ether; -300 of amyl alcohol; and 22 parts of benzene, for solution. The neutral -solution of narcotine turns the plane of polarisation to the left -[[alpha]]_r_ = 130.6; the acid solution to the right. Narcotine has no -effect on red litmus paper. - -Narcotine gives no crystalline sublimate; its behaviour in the subliming -cell is described at p. 259. Its melting-point, taken in a tube, is -about 176 deg. - -=Behaviour of Narcotine with Reagents.=--Narcotine, dissolved in dilute -hydrochloric acid, and then treated with a little bromine, gives a -yellow precipitate, which on boiling is dissolved; by gradually adding -solution of bromine and boiling, a fine rose colour is produced, -readily destroyed by excess of bromine. This is perhaps the best test -for the presence of narcotine. Concentrated sulphuric acid dissolves -narcotine; the solution in the cold is at first colourless, after a few -minutes yellow, and in the course of a day or longer the tints gradually -deepen. If the solution is warmed, it first becomes orange-red, then at -the margin violet-blue; and if heated until hydric sulphate begins to -volatilise, the colour is an intense red-violet. If the heating is not -carried so far, but the solution allowed to cool, a delicate cherry-red -hue slowly develops. If the sulphuric acid solution contains 1 : 2000 of -the alkaloid, this test is very evident; with 1 : 40,000, the colour is -only a faint carmine.--_A. Husemann._ - -A solution of narcotine in pure sulphuric acid, to which a drop of -nitric acid has been added, becomes of a red colour; if the solution is -warmed to 150 deg., hypochlorite of soda develops a carmine-red; and -chloride of iron, first a violet, then a cherry-red. The precipitants of -narcotine are--phosphomolybdic acid, picric acid, sulphocyanide of -potash, potassio cadmic iodide, mercuric chloride, platinic chloride, -auric chloride, and several other reagents. - -From the brown mass left after heating narcotine above 200 deg., -hydrochloric acid extracts a small portion of a base but little studied. -The residue consists of humopic acid (C_{40}H_{19}O_{14}), which can be -obtained by dissolving in caustic potash, precipitating with HCl, -dissolving the precipitate in boiling alcohol, and finally throwing it -down by water. - -Sec. 367. =Effects.=--Narcotine in itself has toxic action only in rather -large doses; from 1 to 2 grms. have been given to man, and slight -hypnotic effects have followed. It is poisonous in very large doses; an -ordinary-sized cat is killed by 3 grms. The symptoms are mainly -convulsions. - -Sec. 368. =Codeine= (=Codomethylene=), C_{17}H_{17}OCH_{3}(OH)NO + H_{2}O, -is the methyl of morphine; it is an alkaloid contained in opium in small -quantity only. Mulder, indeed, quotes .66 to .77 per cent. as present in -Smyrna opium, but Merck and Schindler give .25 per cent. Schindler found -in Constantinople, .5 per cent.; and Merck, in Bengal, .5 per cent. -also. - -Codeine crystallises out of dry ether in small, colourless, anhydrous, -crystals; but crystallised slowly from an aqueous solution, the crystals -are either in well-defined octahedra, or in prisms, containing one atom -of water, and melting in boiling-water to an oily fluid. The anhydrous -crystals have a melting-point of 150 deg., and solidify again on cooling. -Its watery solution is alkaline to litmus paper. - -It requires 80 parts of cold, 17 of boiling water, 10 parts of benzole, -and 7 parts of amyl alcohol respectively, for solution. Alcohol, -benzene, ether, carbon disulphide, and chloroform freely dissolve it, -but in petroleum ether it is almost insoluble. Further, it is also -soluble in aqueous ammonia, and in dilute acids, but insoluble in -excess of caustic potash or soda, and may thus be thrown out of an -aqueous solution. A solution of codeine turns the plane of polarisation -to the left, [[alpha]]_r_ = 118.2 deg. - -Concentrated sulphuric acid dissolves codeine without colour, but after -eight days the solution becomes blue; this reaction is quicker if the -acid contains a trace of nitric acid. If the sulphuric acid solution be -warmed to 150 deg., and a drop of nitric acid be added after cooling, a -blood-red colour is produced. Froehde's reagent produces a dirty green -colour, soon becoming Prussian blue, and terminating after twenty-four -hours in a pale yellow. - -Cyanogen gas, led into an alcoholic solution of codeine, gives first a -yellow and then a brown colour; lastly, a crystalline precipitate falls. -On warming with a little sulphuric acid and ferric chloride, a blue -colour is produced. This blue colour is apparently common to all ethers -of the codeine class. - -Of the group reagents, the following precipitate solutions of -codeine:--Mercuric potassium iodide, mercuric chloride, mercuric -bromide, picric acid, and tannin solutions. The following do not -precipitate:--Mercuric cyanide and potassium ferrocyanide solutions. -Potassium dichromate gives no immediate precipitate, but crystals form -on long standing. It does not give the reaction with iodic acid like -morphine; it is distinguished from narceine by dropping a small particle -of iodine into the aqueous solution, the iodine particle does not become -surrounded with fine crystals. - -Sec. 369. =Effects.=--The physiological action of codeine on animals has -been investigated by Claude Bernard, Magendie, Crum Brown and Fraser, -Falck, and a large number of others.[405] It has also been administered -to man, and has taken in some degree the place of morphine. Claude -Bernard showed that, when given to dogs in sufficient quantity to -produce sleep, the sleep was different in some respects to that of -morphine sleep, especially in its after-effects. Thus, in his usual -graphic way, he describes the following experiment:--"Two young dogs, -accustomed to play together, and both a little beyond the average size, -received in the cellular tissue of the axillae, by the aid of a -subcutaneous syringe, the one 5 centigrammes of morphine hydrochloride, -the other 5 centigrammes of codeine hydrochloride. At the end of a -quarter of an hour both dogs showed signs of narcosis. They were placed -on their backs in the experimental trough, and slept tranquilly for -three or four hours. When the animals woke, they presented the most -striking contrast. The morphine dog ran with a hyena-like gait -(_demarche hyenoid_), the eye wild, recognising no one, not even his -codeine comrade, who vainly bit him playfully, and jumped sportively on -his back. It was not until the next day that the morphine dog regained -his spirits and usual humour. A couple of days after, the two dogs being -in good health, I repeated the same experiment, but in an inverse -order--that is to say, I gave the codeine to that which previously had -the morphine, and _vice versa_. Both dogs slept about as long as the -first time; but on waking the attitudes were completely reversed, just -as the administration of the two substances had been. The dog which, two -days before, after having been codeinised, woke lively and gay, was now -bewildered and half paralysed at the end of his morphine sleep; whilst -the other was wide awake and in the best spirits." - -[405] _Ann. Chem. Phys._ [5], 27, pp. 273-288; also, _Journ. Chem. -Soc._, No. ccxliv., 1883, p. 358. - -Subsequent experimenters found what Bernard does not mention--viz., that -codeine produced epileptiform convulsions. Falck made some very careful -experiments on pigeons, frogs, and rabbits. To all these in high enough -doses it was fatal. Falk puts the minimum lethal dose for a rabbit at -51.2 mgrms. per kilo. Given to man, it produces a sleep very similar to -that described by Claude Bernard--that is, a sleep which is very -natural, and does not leave any after-effect. Therefore it is declared -to be the best alkaloid of a narcotic nature to give when lengthened -slumber is desired, more especially since it does not confine the -bowels, nor has it been found to produce any eruption on the skin. -Before it has a full narcotic effect, vomiting has often been excited, -and in a few cases purging. The maximum dose for an adult is about .1 -grm. (1.5 grain); three times this quantity, .3 grms. (4-5 grains), -would probably produce unpleasant, if not dangerous, symptoms.[406] - -[406] For further details as to the action of codeine, the reader is -referred to L. O. Wach's monograph, _Das Codein_ (1868), which contains -reference to the earlier literature. See also Harley, _The Old Vegetable -Neurotics_, London. - - Sec. 370. =Narceine=, C_{23}H_{27}NO_{8} + 3H_{2}O.--Two of the three - molecules of water are expelled at 100 deg., the other molecule requires - a higher temperature; anhydrous narceine is hygroscopic, and melts - in a tube at about 140 deg.; when exposed to air it unites with one - molecule of water, and then melts at about 160 deg. - - The constitution of narceine is probably that of a substituted - phenylbenzylketone, and the following structural formula has been - attributed to it:[407]-- - -[407] M. Freund and G. B. Frankforter, _Annalen_, 277, pp. 20-58. - - 3 I:2 4 1' 2' - COOH,C_{6}H_{2}-(OMe)_{2}CO-CH_{2}-C_{6}H(CH_{2}-CH_{2}NMe_{2}) - O - 3 or 6/ \ - OMe CH_{2} - \ / - O - - It therefore contains three methoxyl groups. - - Narceine forms good crystals, the form being that of long, - four-sided rhombic prisms or fine bushy united needles. - - Narceine hydrochloride crystallises with 5-1/2H_{2}O and with - 3H_{2}O; the anhydrous salt melts at 190 deg.-192 deg. The platinochloride - is a definite salt, m.p. 190 deg.-191 deg.; it decomposes at 195 deg.-196 deg. The - nitrate forms good crystals, which decompose at 97 deg. Narceine also - forms crystalline salts with potassium and sodium; these may be - obtained by heating the base at 60 deg.-70 deg. with a 33 per cent. of NaHO - or KHO. - - The potassium compound melts at 90 deg., the sodium at 159 deg.-160 deg. The - alkaloid is regenerated when the alkali salts are treated with acids - or with CO_{2}. Crude narceine may be purified by means of the - sodium salt; the latter is dissolved in alcohol and precipitated - with ether. - - It is soluble in alcohol, but almost insoluble in alcohol and ether, - or benzene and ether; it is slightly soluble in ether, carbon - disulphide, and chloroform. It has no reaction on moist litmus - paper. - - Benzole and petroleum ether extract narceine neither from acid nor - alkaline solutions; chloroform extracts narceine both from acid and - from alkaline solutions, the latter in small proportion only. - Narceine turns the plane of polarisation to the left, [[alpha]]_r_ = - 66.7 deg. Narceine may be separated from narcotine by the addition of - ammonia to the acid aqueous solution; narcotine is fully - precipitated by ammonia, but narceine is left in solution. - - In the subliming cell it melts at 134 deg., but gives no crystalline - sublimate. The tube melting-point of the trihydrate is 170 deg. The - melted substance is at first colourless; but on raising the - temperature, the usual transitions of colour through different - shades of brown to black are observed. If melted, and kept a few - degrees above its melting-point, and then cooled slowly, the residue - is straw-coloured, divided into lobes, most of which contain - feathery crystals. - - At high temperatures narceine develops a herring-like odour; the - residue becomes darkish blue with iron chloride. Concentrated nitric - acid dissolves it with a yellow colour; on heating, red vapours are - produced; the fluid contains crystals of oxalic acid, and develops - with potash a volatile base. Concentrated sulphuric acid colours - pure narceine brown; but if impure, a blood-red or blue colour may - be produced. It does not reduce iron salts. - - Froehde's reagent colours it first brown-green, then red, passing - into blue. Narceine forms precipitates with bichromate of potash, - chloride of gold, bichloride of platinum, and several other - reagents. The one formed by the addition of potassio zinc iodide is - in hair-like crystals, which after twenty-four hours become blue. - - Weak iodine solution colours narceine crystals a black-blue; they - dissolve in water at 100 deg. without colour, but on cooling again - separate with a violet or blue colour. If on a saturated solution of - narceine a particle of iodine is strewn, fine needle-like grey - crystals form around the iodine. A drop of "Nessler" solution, added - to solid narceine, at once strikes a brown colour; on diluting the - drop with a little water, beautiful little bundles of crystals - appear.--_Flueckiger._ - - The following group reagents precipitate narceine:--picric acid, - tannin solution, and potassium dichromate on long standing. The - following give no precipitate:--mercuric cyanide, mercuric potas. - iodide, mercuric chloride, mercuric bromide, and potas. ferrocyanide - solutions. - - Sec. 371. =Effects.=--The physiological action of narceine has been - variously interpreted by different observers. Claude Bernard[408] - thought it the most somniferous of the opium alkaloids. He said that - "the narceinic sleep was characterised by a profound calm and - absence of the excitability of morphine, the animals narcotised by - narceine on awaking returning to their natural state without - enfeeblement of the hind limbs or other sequelae." It has been amply - confirmed that narceine possesses somniferous properties, but - certainly not to the extent that Bernard's observations led - physiologists to expect. In large doses there is some irritation of - the stomach and intestines, and vomiting occurs, and even - diarrh[oe]a; moderate doses induce constipation. The maximum - medicinal dose may be put at .14 grm. (or 2.26 grains), and a - probably dangerous dose would be three times that quantity.[409] - -[408] _Compt. Rend._, lix. p. 406, 1864. - -[409] See J. Bouchardat, _La Narceine_, These, Paris, 1865; Harley, _The -Old Vegetable Neurotics_, Lond.; Ch. Line, _Etudes sur la Narceine et -son Emploi Therapeutique_, These, Paris, 1865; also, Husemann's -_Planzenstoffe_, in which these and other researches are summarised. - - Sec. 372. =Papaverine= (C_{21}H_{21}NO_{4}) crystallises from alcohol - in white needles or scales. It possesses scarcely any alkaline - reaction, but its salts have an acid reaction; it has but little - effect on a ray of polarised light. It is almost insoluble in water; - it is easily soluble in acetone, amyl alcohol, alcohol, and - chloroform. One part of the alkaloid is dissolved in 36.6 of - benzene, and in 76 parts of amyl alcohol. Petroleum ether dissolves - it by the aid of heat, but the alkaloid separates in crystals on - cooling. Chloroform extracts it from either acid or alkaline - solutions. Papaverine gives no crystalline sublimate. The - melting-point of pure samples in a tube is 147 deg., with scarcely any - colour; it solidifies again to crystals on cooling; in the subliming - cell it melts at 130 deg., and decomposes about 149 deg.; the vapours are - alkaline; the residue is amorphous, light brown, and is not - characteristic. Concentrated sulphuric acid colours it a deep - violet-blue, and dissolves it to a violet, slowly fading. This - solution, by permanganate of potash, is first green and then grey. - Froehde's reagent gives a beautiful violet colour, which becomes - blue, and vanishes after twenty-four hours. Diluted solutions of - salts of papaverine are not precipitated by phosphomolybdic acid. It - is precipitated by ammonia, by the caustic and carbonated alkalies, - by potassic-cadmic iodide, iodine in hydriodic acid, and by - alkaloidal reagents generally--save by the important exception - mentioned above. A solution in amyl alcohol is also precipitated by - bromine; the precipitate is crystalline. An alcoholic solution of - platinic chloride also separates papaverine platin chloride in - crystals. An alcoholic solution of iodine, added to an alcoholic - solution of papaverine, separates in a little time crystals of the - composition C_{21}H_{21}NO_{4}I_{3}. From the mother-liquor, by - concentration, can be obtained needles of another iodine - combination, C_{21}H_{21}NO_{4}I_{5}; the latter heated above 100 deg. - parts with free iodine. These compounds with iodine are decomposed - by ammonia and potash, papaverine separating. The decomposition may - be watched under the microscope. Nitric acid precipitates from a - solution of the sulphate a white nitrate soluble in excess; the - precipitate does not appear at once, but forms in the course of an - hour; it is at first amorphous, but subsequently crystalline; this, - with its physical properties, is a great assistance to - identification. - - Sec. 373. =Effects.=--Claude Bernard ranked papaverine with the - convulsants; probably the papaverine he had was impure. In any case, - subsequent observations have shown that it is to be classed rather - with the hypnotic principles of opium. Leidesdorf[410] administered - it to the insane, and noted slowness of the pulse, muscular - weakness, and drowsiness to follow. The doses were given - subcutaneously (.42 grm. of the hydrochloride). Baxt,[411] - experimenting with the frog, found that a milligramme caused deep - sleep and slowing of the heart's action. This action on the heart is - witnessed also on the recently-removed frog's heart. Guinea-pigs, - and other small animals poisoned by strychnine or thebaine, and then - given papaverine, did not seem to be so soon affected with tetanus - as when no such remedy was administered. The fatal dose of - papaverine for a man is unknown. I should conjecture that the least - quantity that would cause dangerous symptoms would be 1 grm. (15.4 - grains). - -[410] _Ztschr. d. Wien. Aerzte_, pp. 13, 115, 1868. - -[411] _Arch. Anat. Phys._, p. 70, 1869. - - Sec. 374. =Thebaine=, C_{17}H_{15}NO(OCH_{3})_{2}.--Opium seldom - contains much more than 1 per cent. of this alkaloid. It usually - forms needles or short crystals. It is alkaline, and by rubbing - becomes negatively electric. It is almost insoluble in water, - aqueous ammonia, and solutions of the alkalies. It requires 10 - parts of cold alcohol for solution, and dissolves readily in hot. - Ether, hot or cold, is also a good solvent. 100 parts of benzene are - required for 5.27 parts of thebaine, and 100 of amyl alcohol for - 1.67 parts. Chloroform dissolves thebaine with difficulty out of - both acid and alkaline solutions; petroleum ether extracts it from - neither. Thebaine melts in a tube at 193 deg., sublimes at 135 deg. The - sublimate is in minute crystals, similar to theine; at higher - temperatures (160 deg. to 200 deg.) needles, cubes, and prisms are obtained. - The residue is fawn coloured. Froehde's reagent (as well as - concentrated sulphuric acid) dissolves it, with the production of a - blood-red colour, passing gradually into yellow. The precipitate - with picric acid is yellow and amorphous; with tannic acid yellow; - with gold chloride, red-yellow; and with platinic chloride, - citron-yellow, gradually becoming crystalline. A concentrated - alcoholic solution of thebaine, just neutralised with HCl, deposits - well-formed rhombic crystals of the composition - C_{19}H_{21}NO_{3}HCl + H_{2}O. - - If 200 mgrms. of thebaine are heated to boiling with 1.4 c.c. of HCl - and 2.8 c.c. of water, and the solution diluted, after boiling, with - 4 c.c. of water, crystals of thebaine hydrochloride form in the - yellow fluid in the course of a few hours.--_Flueckiger._ - - Sec. 375. =Effects.=--There is no disagreement of opinion as to the - action of thebaine. By the united testimony of all who have - experimented with it, the alkaloid belongs to those poisons which - produce tetanus, and the symptoms can scarcely be differentiated - from strychnia. In Baxt's experiments on frogs he showed that there - was some considerable difference in details in the general course of - the symptoms, according to the dose of the poison. A small dose - (such, for example, as .75 mgrm.) injected into a frog - subcutaneously produces immediate excitement, the animal jumping - about, and this stage lasting for about a minute; it then becomes - quieter, and has from three to six minutes' sleep; in a little time - this comatose state is followed by reflex tetanic spasms and then - spontaneous tetanic spasms. With three times the dose, the tetanic - convulsions commence early, and death takes place in from two to six - hours. Baxt[412] found 6 to 7 mgrms. kill rabbits with tetanic - convulsions in from fifteen to twenty-five minutes. Crum Brown and - Fraser also found that 12 mgrms. injected into rabbits were fatal; - it may then be presumed that the lethal dose for a rabbit is about 5 - mgrms. per kilo. A frog's heart under the action of thebaine, and - removed from the body, beats quicker and ceases earlier than one in - distilled water. Thebaine has been administered to the insane - subcutaneously in doses of from 12 to 40 mgrms., when a rise of - temperature and an increase in the respiratory movements and in the - circulation were noticed.[413] - -[412] _Sitzungsber. d. Wien. Akadem._, lvi. pp. 2, 89, 1867; _Arch. f. -Anat. u. Physiol._, Hft. 1, p. 112, 1869. - -[413] F. W. Mueller, _Das Thebaine, eine Monographie_, Diss., Marburg -1868. - - The fatal dose for a man is not known; .5 grm., or about 8 grains, - would probably be a poisonous quantity. - - Sec. 376. =Cryptopine= (C_{21}H_{23}NO_{5}) was discovered by T. & H. - Smith in 1867.[414] It is only contained in very minute traces in - opium--something like .003 per cent. It is a crystalline substance, - the crystals being colourless, six-sided prisms, without odour, but - with a bitter taste, causing an after-sensation like peppermint. The - crystals melt at 217 deg., and congeal in a crystalline form again at - 171 deg.; at high temperatures they are decomposed with evolution of - ammoniacal vapour. Cryptopine is insoluble, or almost so, in ether, - water, and oil of turpentine; it is soluble in acetone, benzene, and - chloroform; the latter is the best solvent, or hot alcohol; it is - insoluble in aqueous ammonia and in solutions of the caustic - alkaloids. Cryptopine is strongly basic, neutralising fully mineral - acids. Concentrated sulphuric acid colours cryptopine pure blue, the - tint gradually fading from absorption of water from the atmosphere. - On a crystal of potassic nitrate being added, the colour changes - into a permanent green. With ferric chloride cryptopine gives no - colour--thus distinguishing it from morphine. The physiological - properties of cryptopine have been investigated by Dr. Harley;[415] - it has a narcotic action, about double as strong as narceine, and - four times weaker than morphine. Munk and Sippell[416] found that it - gave rise in animals to paralysis of the limbs, and occasionally - asphyxic convulsions before death. - -[414] _Pharm. Journ. Trans._ [2], viii. pp. 495 and 716. - -[415] _The Old Vegetable Neurotics._ - -[416] Munk, _Versuche ueber die Wirkung des Cryptopins_, Berlin, 1873. -Sippell, _Beitraege zur Kentniss des Cryptopins_, Marburg, 1874. - - Sec. 377. =Rh[oe]adine= (C_{21}H_{21}NO_{6}).--Rh[oe]adine was - separated from _Papaver rh[oe]as_ by Hesse, and has also been found - in _Papaver somniferum_ and in opium. Rh[oe]adine is in the form of - small anhydrous tasteless prisms, melting at 230 deg. and partly - subliming. In a vacuum sublimation is almost complete, and at a much - lower temperature. It is a very insoluble substance, and is scarcely - dissolved, when crystalline, by water, alcohol, ether, chloroform, - benzene, and solutions of the fixed or volatile alkalies. When in an - amorphous state it is rather soluble in ether, and may be dissolved - out of any substance by treating with dilute acetic acid, and - neutralising by ammonia, and shaking up with ether before the - precipitate becomes crystalline. Rh[oe]adine is easily recognised by - its striking a red colour with hydrochloric acid. Either - spontaneously or on gentle warming, the colour is produced--one part - of rh[oe]adine will colour in this way 10,000 parts of acid water - blue or purple-red, 200,000 rose-red, and 800,000 pale red. The - reaction depends on a splitting up of the rh[oe]adine into a - colourless substance, _rh[oe]adin_, and a red colouring-matter. - Rh[oe]adine is not poisonous. - - Sec. 378. =Pseudomorphine= (C_{17}H_{19}NO_{4}).--Pseudomorphine was - discovered by Pelletier and Thiboumery in 1835. As precipitated by - ammonia out of the hot solution, pseudomorphine falls as a white - crystalline precipitate; but if the solution is cold, the - precipitate is gelatinous. It possesses no taste, and has no action - on vegetable colours. On heating, it decomposes and then melts. It - dissolves easily in caustic alkalies and in milk of lime, but is - insoluble in all the ordinary alcoholic and ethereal solvents, as - well as in diluted sulphuric acid. The most soluble salt is the - hydrochlorate (C_{17}H_{19}NO_{4}HCl + H_{2}O), and that requires 70 - parts of water at 20 deg. for solution. Various salts, such as the - sulphate, oxalate, &c., may be prepared from the hydrochlorate by - double decomposition. Concentrated sulphuric acid dissolves - pseudomorphine gradually, with the production of an olive-green - colour. - - Sec. 379. =Opianine= (C_{66}H_{72}N_{4}O_{21}).--Opianine crystallises - in colourless, glittering ortho-rhombic needles. Ammonia - precipitates it from its solution in hydrochloric acid as a fine - white powder. It is without odour, and has a bitter taste. It is a - strong base, and is soluble in cold, but slightly soluble in boiling - water. It is also but little soluble in boiling alcohol. - - An alcoholic solution of the alkaloid gives a voluminous precipitate - with mercuric chloride; after standing a little time, the - precipitate becomes crystalline, the crystals being in the shape of - fine needles. They have the following - composition--C_{66}H_{72}N_{4}O_{21}, 2HCl, 2HgCl--and are with - difficulty soluble in water or alcohol. - - Opianine, administered to cats in doses of .145 grm., produces - complex symptoms--_e.g._, dilated pupils, foaming at the mouth, - uncertain gait, paralysis of the hinder extremities, and stupor--but - the alkaloid is rare, and few experiments have been made with it. - - Sec. 380. =Apomorphine= (C_{17}H_{19}NO_{3}).--Apomorphine is a - derivative of morphine, and is readily prepared by saponifying - morphine by heating it with dilute hydrochloric acid in sealed - tubes. The result is apomorphine hydrochloride, the morphine losing - one molecule of water, according to the equation C_{17}H_{19}NO_{3} - = C_{17}H_{17}NO_{2} + H_{2}O. - - To extract apomorphine, the bases are precipitated by sodic - bicarbonate, and the precipitate extracted by ether or chloroform, - either of which solvents leaves morphine undissolved. The - apomorphine is again converted into hydrochloride, and once more - precipitated by sodic bicarbonate, and is lastly obtained as a - snow-white substance, rapidly becoming green on exposure to the air. - The mass dissolves with a beautiful green colour in water, and also - in alcohol, whilst it colours ether purple-red, and chloroform - violet. - - A test for apomorphine is the following:--The chloride is dissolved - in a little acetic acid and shaken with a crystal of potassic iodate - (KIO_{3}); this immediately turns red from liberated iodine on - shaking it up with a little chloroform; on standing, the chloroform - sinks to the bottom, and is coloured by the alkaloid a beautiful - blue colour; on now carefully pouring a little CS_{2} on the surface - of the liquid at the point of junction it is coloured amethyst owing - to dissolved iodine, and apocodeine gives a similar reaction. - - Apomorphine is the purest and most active emetic known: whether - injected beneath the skin or taken by the mouth, the effect is the - same--there is considerable depression, faintness, and then - vomiting. The dose for an adult is about 6 mgrms. (.092 grain) - subcutaneously administered. - - Sec. 381. The reactions of some of the rarer alkaloids of opium with - sulphuric acid and ferric chloride are as follows: none of them have - at present any toxicological importance:-- - -TABLE SHOWING SOME OF THE REACTIONS OF THE RARER ALKALOIDS OF OPIUM. - - +------------+--------------------+----------------------+---------+ - | | | |Reaction | - | Alkaloid. | Formula. | Reaction with Warm | with | - | | | Sulphuric Acid. | Ferric | - | | | |Chloride.| - +------------+--------------------+----------------------+---------+ - |Codamine, |C_{20}H_{25}NO_{4} {|Dirty red-violet |} | - | | {|colour, turning dark |} Dark | - |Landamine, |C_{20}H_{25}NO_{4} {|violet on the |} green. | - | | {|addition of HNO_{3}. |} | - | | | | | - |Landanosine,|C_{20}H_{27}NO_{4} }|Dirty green to |} No co- | - | | }|brownish-green. |} lour. | - |Protapine, |C_{20}H_{19}NO_{5} }| |} | - | | | | | - |Lanthopine, |C_{23}H_{25}NO_{4} |Dark brown or black. | No co- | - | | | | lour. | - | | | | | - |Hydro- |C_{12}H_{15}NO_{3} {|Dirty red-violet; |} No co- | - |cotarnine, | {|not changed by |} lour. | - | | {|trace of HNO_{3}. |} | - +------------+--------------------+----------------------+---------+ - - Sec. 382. =Tritopine= (C_{42}H_{54}N_{2}O_{7}).--This is a rare - alkaloid that has been found in small quantities in opium. It is - crystalline, separating in transparent prisms. Melting-point 182 deg. - It is soluble in alcohol and chloroform, and slightly soluble in - ether.[417] - -[417] E. Kander, _Arch. Pharm._, 228, pp. 419-431. - - Sec. 383. =Meconin (Opianyl)= (C_{10}H_{10}O_{4}) is in the form of - white glittering needles, which melt under water at 77 deg. and in air - at 90 deg., again coagulating at 75 deg. It may be sublimed in beautiful - crystals. It is soluble in 22 parts of boiling, and 700 of cold - water; dissolves easily in alcohol, ether, acetic acid, and ethereal - oil, and is not precipitated by acetate of lead. Its solution in - concentrated sulphuric acid becomes, on warming, purple, and gives, - on the addition of water, a brown precipitate. Meconin may be - prepared by treating narcotine with nitric acid. Meconin, in large - doses, is a feeble narcotic; 1.25 grm. (20 grains) has been given to - man without result. - - Sec. 384. =Meconic Acid= (C_{7}H_{4}O_{7}) crystallises in white - shining scales or small rhombic prisms, with three atoms of water - (C_{7}H_{4}O_{7} + 3H_{2}O), but at 100 deg. this is lost, and it - becomes an opaque white mass. It reddens litmus, and has a sourish - taste. It is soluble in 115 parts of cold, but dissolves in 4 parts - of boiling water; it dissolves easily in alcohol, less so in ether. - It forms well-marked salts; the barium and calcium salt crystallise - with one atom of water, the former having the composition - BaH_{4}(C_{7}HO_{7})_{2}; the latter, if ammonium meconate is - precipitated by calcium chloride, CaH_{4}(C_{7}HO_{7})_{2}; but if - calcium chloride is added to the acid itself, the salt has the - composition C_{7}H_{2}CaO_{7} + H_{2}O. If meconic acid is gently - heated, it decomposes into carbon dioxide and comenic acid - (C_{6}H_{4}O_{5}). If the heat is stronger, pyromeconic acid - (C_{5}H_{4}O_{3})--carbon dioxide, water, acetic acid, and benzole - are formed. Pyromeconic acid is readily sublimed in large - transparent tables. Chloride of iron, and soluble iron salts - generally, give with meconic acid (even in great dilution) a lively - red colour, which is not altered by heat, nor by the addition of HCl - nor by that of gold chloride. Sugar of lead and nitrate of silver - each give a white precipitate; and mercurous and mercuric nitrates - white and yellow precipitates. In any case where the analyst has - found only meconic acid, the question may be raised in court as to - whether it is a poison or not. The early experiments of - Sertuerner,[418] Langer, Vogel, Soemmering, and Grape[419] showed - that, in comparatively speaking large doses, it had but little, if - any, action on dogs or men. Albers[420] has, however, experimented - on frogs, and found that in doses of .1 to .2 grm. there is, first, - a narcotic action, and later, convulsions and death. According to - Schroff,[421] there is a slight narcotic action on man. - -[418] _Ann. Phys._, xxv. 56; xxvii. 183. - -[419] _De opio et de illis quibus constat partibus_, Berol., 1822. - -[420] _Arch. Path. Anat._, xxvi. 248. - -[421] _Med. Jahresb._, 1869. - -The most generally accepted view at the present time is that the -physiological action of meconic acid is similar to that of lactic -acid--viz., large doses cause some depression and feeble narcosis. - -In a special research amongst organic fluids for meconic acid, the -substances are extracted by alcohol _feebly_ acidulated with nitric -acid; on filtration the alcohol, after the addition of a little water, -is distilled off, and to the remaining fluid a solution of acetate of -lead is added, and the whole filtered. The filtrate will contain any -alkaloids, whilst meconic acid, if present, is bound up with the lead on -the filter. The meconate of lead may be either washed or digested in -strong acetic acid to purify it, suspended in water, and freed from lead -by SH_{2}; the filtrate from the lead sulphide may be tested by ferric -chloride, or preferably, at once evaporated to dryness, and weighed. -After this operation it is identified. If the quantity is so small that -it cannot be conveniently weighed, it may be estimated colorimetrically, -by having a standard solution of meconic acid, containing 1 mgrm. in -every c.c. A few drops of neutral ferric chloride are added in a Nessler -cylinder to the liquid under examination; and the tint thus obtained is -imitated in the usual way, in another cylinder, by means of ferric -chloride, the standard solution, and water. It is also obvious that the -weight of the meconic acid may be increased by converting it -into the barium salt--100 parts of anhydrous baric meconate, -(Ba_{2}C_{7}H_{2}O_{7}), being equivalent to 42.3 of meconic acid -(C_{7}H_{4}O_{7}). - - -IV.--The Strychnine or Tetanus-Producing[422] Group of Alkaloids. - -[422] To this group also belong some of the opium alkaloids. See -"Thebaine," "Landamine," "Codeine," "Hydrocotarnine." - - -1. NUX VOMICA GROUP--STRYCHNINE--BRUCINE--IGASURINE. - -Sec. 385. Nux vomica is found in commerce both in the entire state and as a -powder. It is the seed of the _Strychnos nux vomica_, or Koochla tree. -The seed is about the size of a shilling, round, flattened, -concavo-convex, of a yellowish-grey or light-brown colour, covered with -a velvety down of fine, radiating, silky hairs, which are coloured by a -solution of iodine beautiful gold-yellow; the texture is tough, -leathery, and not easily pulverised; the taste is intensely bitter. The -powder is not unlike that of liquorice, and, if met with in the pure -state, gives a dark orange-red colour with nitric acid, which is -destroyed by chloride of tin; the aqueous infusion gives a precipitate -with tincture of galls, is reddened by nitric acid, and gives an -olive-green tint with persulphate of iron. The best method, however, of -recognising quickly and with certainty that the substance under -examination is nux vomica powder, is to extract strychnine from it by -the following simple process:--The powder is completely exhausted by -boiling alcohol (90 per cent.), the alcoholic extract evaporated to -dryness, and then treated with water; the aqueous solution is passed -through a wet filter, and concentrated by evaporation to a small bulk. -To this liquid a drop or so of a concentrated solution of picric acid is -added, and the yellow precipitate of picrates thus obtained is -separated, treated with nitric acid, the picric acid removed by ether, -and the pure alkaloid precipitated by soda, and shaken out by -chloroform. - -Sec. 386. =Chemical Composition.=--Nux vomica contains at least four -distinct principles:-- - - (1.) Strychnine. - (2.) Brucine. - (3.) Igasurine. - (4.) Strychnic or igasuric acid. - -Sec. 387. =Strychnine= (C_{21}H_{22}N_{2}O_{2}) is contained in the bean of -S. _ignatius_, in the bark (_false angustura bark_) and seeds of the -_Strychnos nux vomica_, in the _Strychnos colubrina_, L., in the -_Strychnos tieute_, Lesch, and probably in various other plants of the -same genus. - -Commercial strychnine is met with either in colourless crystals or as a -white powder, the most usual form being that of the alkaloid itself; but -the nitrate, sulphate, and acetate are also sold to a small extent. - -The _microscopical appearance_ of strychnine, as thrown down by the -solution of vapour of ammonia, may be referred to three leading -forms--the long rectangular prism, the short hexagonal prism, or the -regular octahedron. If obtained from the slow evaporation of an -alcoholic solution, it is usually in the form of four-sided pyramids or -long prisms; but if obtained by speedy evaporation or rapid cooling, it -appears as a white granular powder. If obtained from a benzene solution, -the deposit is usually crystalline, but without a constant form, though -at times the crystals are extremely distinct, the short six-sided prism -prevailing; but triangular plates, dodecahedral, rhomboidal, and -pentagonal, may also be met with. An ethereal solution on evaporation -assumes dendritic forms, but may contain octahedra and four-sided -prisms. A chloroform solution deposits rosettes, veined leaves, stellate -dotted needles, circles with broken radii, and branched and reticulated -forms of great delicacy and beauty.--_Guy._ - -Strychnine is very insoluble in water, although readily dissolved by -acidulated water. According to Wormley's repeated experiments, one part -of strychnine dissolves in 8333 parts of cold water; and, according to -Pelletier and Cahours, it dissolves in 6667 parts of cold, and 2500 -parts of boiling water. It may be convenient, then, to remember that a -gallon of cold water would hardly dissolve more than 10 grains (.142 -grm. per litre); the same amount, if boiling, about 30 grains (.426 grm. -per litre) of strychnine. The solubility of one part of strychnine in -other menstrua is as follows:--Cold alcohol, 0.833 specific gravity, -120, boiling, 10 parts (_Wittstein_); cold alcohol, 0.936 specific -gravity, 240 parts (_Merck_); cold alcohol, 0.815 specific gravity, 107 -parts (_Dragendorff_); amyl alcohol, 181 parts; benzene, 164; -chloroform, 6.9 (_Schlimpert_), 5 (_Pettenkofer_); ether, 1250 parts; -carbon disulphide, 485 parts; glycerin, 300 parts. Creosote and -essential and fixed oils also dissolve strychnine. - -Of all the above solvents, it is evident that chloroform is the best for -purposes of separation, and next to chloroform, benzene. - -If a speck of strychnine be placed in the subliming cell, it will be -found to sublime usually in a crystalline form at 169 deg. A common form at -this temperature, according to the writer's own observations, is minute -needles, disposed in lines; but, as Dr. Guy has remarked, the sublimate -may consist of drops, of waving patterns, and various other forms; and, -further, while the sublimates of morphia are made up of curved lines, -those of strychnine consist of lines either straight or slightly -curved, with parallel feathery lines at right angles. On continuing the -heat, strychnine melts at about 221 deg., and the lower disc, if removed and -examined, is found to have a resinous residue; but it still continues to -yield sublimates until reduced to a spot of carbon. The melting-point -taken in a tube is 268 deg. - -Strychnine is so powerfully bitter, that one part dissolved in 70,000 of -water is distinctly perceptible; it is a strong base, with a marked -alkaline reaction, neutralising the strongest acids fully, and -precipitating many metallic oxides from their combinations, often with -the formation of double salts. Most of the salts of strychnine are -crystalline, and all extremely bitter. Strychnine, in the presence of -oxygen, combines with SH_{2} to form a beautiful crystalline compound:-- - - 2C_{21}H_{22}N_{2}O_{2} + 6H_{2}S + O_{3} = - 2C_{21}H_{22}N_{2}O_{2}3H_{2}S_{2} + 3H_{2}O. - -On treatment with an acid this compound yields H_{2}S_{2}.--Schmidt, -_Ber. Deutsch. Chem. Ges._, 8, 1267. - -An alcoholic solution of strychnine turns the plane of polarisation to -the left, [[alpha]]_r_ = -132.08 deg. to 136.78 deg. (_Bouchardat_); but acid -solutions show a much smaller rotatory power. - -The salts used in medicine are--the _sulphate_, officinal only in the -French pharmacop[oe]ia; the _nitrate_, officinal in the German, -Austrian, Swiss, Norse, and Dutch pharmacop[oe]ias; and the _acetate_, -well known in commerce, but not officinal. - -The commercial =Sulphate= (C_{21}H_{22}N_{2}O_{2}H_{2}SO_{4} + 2H_{2}O) -is an acid salt crystallising in needles which lose water at 150 deg., the -neutral sulphate (2C_{21}H_{22}N_{2}O_{2},H_{2}SO_{4} + 7H_{2}O) -crystallises in four-sided, orthorhombic prisms, and is soluble in about -50 parts of cold water. - -The =Nitrate= (C_{21}H_{22}N_{2}O_{2},HNO_{3}) crystallises on -evaporation from a warm solution of the alkaloid in dilute nitric acid, -in silky needles, mostly collected in groups. The solubility of this -salt is considerable, one part dissolving in 50 of cold, in 2 of boiling -water; its solubility in boiling and cold alcohol is almost the same, -taking 60 of the former and 2 of the latter. - -The =Acetate= crystallises in tufts of needles; as stated, it is not -officinal in any of the European pharmacop[oe]ias. - -The chief precipitates or sparingly soluble crystalline compounds of -strychnine are-- - -(1.) =The Chromate of Strychnine= (C_{21}H_{22}N_{2}O_{2}CrHO_{2}), -formed by adding a neutral solution of chromate of potash to a solution -of a strychnine salt, crystallises out of hot water in beautiful, very -insoluble, orange-yellow needles, mixed with plates of various size and -thickness. The salt is of great practical use to the analyst; for by its -aid strychnine may be separated from a variety of substances, and in -part from brucine--the colour tests being either applied direct to the -strychnine chromate, or the chromate decomposed by ammonia, and the -strychnine recovered from the alkaline liquid by chloroform. - -(2.) =Sulphocyanide of Strychnine= (C_{21}H_{22}N_{2}O_{2}CNHS) is a -thick, white precipitate, produced by the addition of a solution of -potassic sulphocyanide to that of a strychnine salt; on warming it -dissolves, but on cooling reappears in the form of long silky needles. - -(3.) =Double Salts.=--The platinum compound obtained by adding a -solution of platinic chloride to one of strychnine chloride has the -composition C_{21}H_{22}N_{2}O_{2}HClPtCl_{2}, and crystallises out of -weak boiling alcohol (in which it is somewhat soluble) in gold-like -scales. The similar palladium compound (C_{21}H_{22}N_{2}O_{2}HCl,PdCl) -is in dark brown needles, and the gold compound -(C_{21}H_{22}N_{2}O_{2}HClAuCl_{3}) in orange-coloured needles. - -(4.) =Strychnine Trichloride.=--The action of chlorine on strychnine--by -which chlorine is substituted for a portion of the hydrogen--has been -proposed as a test. The alkaloid is dissolved in very dilute HCl, so as -to be only just acid; on now passing through chlorine gas, a white -insoluble precipitate is formed, which may be recrystallised from ether; -it has probably the composition C_{21}H_{19}Cl_{3}N_{2}O_{2}, and is -extremely insoluble in water. - -(5.) =The Iodide of Strychnine= (C_{21}H_{22}N_{2}O_{2}HI_{3}) is -obtained by the action of iodine solution on strychnine sulphate; on -solution of the precipitate in alcohol, and evaporation, it forms -violet-coloured crystals, very similar to those of potassic -permanganate. - -Sec. 388. =Pharmaceutical and other Preparations of Nux Vomica and -Strychnine, with Suggestions for their Valuation.= - -=An aqueous extract of nux vomica=, officinal in the German -pharmacop[oe]ia, appears to contain principally brucine, with a small -percentage of strychnine; the proportion of brucine to strychnine being -about four-fifths to one-fifth. Blossfield found in a sample 4.3 per -cent. of total alkaloid, and two samples examined by Grundmann consisted -(No. 1) of strychnine, 0.6 per cent.; brucine, 2.58 per cent.--total, -3.18 per cent.; (No. 2) strychnine, 0.68 per cent.; brucine, 2.62 per -cent.--total, 3.3 per cent. A sample examined by Dragendorff -yielded--strychnine, 0.8 per cent.; brucine, 3.2 per cent.--total, 4 per -cent. The maximum medicinal dose is put at .6 grm. (9-1/14 grains). - -=The spirituous extract of nux vomica=, officinal in the British and all -the Continental pharmacop[oe]ias, differs from the aqueous in containing -a much larger proportion of alkaloids, viz., about 15 per cent., and -about half the total quantity being strychnine. The medicinal dose is -21.6-64.8 mgrms. (1/3 grain to a grain). - -There is also an =extract of St. Ignatius bean= which is used in the -United States; nearly the whole of its alkaloid may be referred to -strychnine. - -=The tincture of nux vomica=, made according to the British -Pharmacop[oe]ia, contains in 1 fl. oz. 1 grain of alkaloids, or 0.21 -part by weight in 100 by volume, but the strength of commercial samples -often varies. Lieth found in one sample 0.122 per cent. of strychnine -and 0.09 per cent. brucine; and two samples examined by Wissel consisted -respectively of 0.353 per cent. and 0.346 per cent. of total alkaloids. -Dragendorff found in two samples .2624 per cent. and .244 per cent. of -total alkaloids, about half of which was strychnine. - -=Analysis.=--Either of the extracts may be treated for a few hours on -the water-bath, with water acidulated by sulphuric acid, filtered, the -residue well washed, the acid liquid shaken up with benzene to separate -impurities, and, on removal of the benzene, alkalised with ammonia, and -shaken up two or three times with chloroform; the chloroform is then -evaporated in a tared vessel, and the total alkaloids weighed. The -alkaloids can then be either (_a_) treated with 11 per cent. of nitric -acid on the water-bath until all the brucine is destroyed, and then (the -liquid being neutralised) precipitated by potassic chromate; or (_b_) -the alkaloids may be converted into picrates. Picrate of strychnine is -very insoluble in water, 1 part requiring no less than 10,000 of -water.[423] The tincture is analysed on precisely similar principles, -the spirit being got rid of by distillation, and the residue treated by -acidified water, &c. - -[423] Dolzler, _Arch. Pharm._ [3], xxiv. 105-109. - -The nux vomica powder itself may be valued as follows:--15 to 20 grms., -pulverised as finely as possible, are treated three times with 150 to -300 c.c. of water, acidified with sulphuric acid, well boiled, and, -after each boiling, filtered and thoroughly pressed. The last exhaustion -must be destitute of all bitter taste. The united filtrates are then -evaporated to the consistence of a thick syrup, which is treated with -sufficient burnt magnesia to neutralise the acid. The extract is now -thoroughly exhausted with boiling alcohol of 90 per cent.; the alcoholic -extract, in its turn, is evaporated nearly to dryness, and treated with -acidulated water; this acid solution is freed from impurities by shaking -up with benzene, and lastly alkalised with ammonia, and the alkaloids -extracted by shaking up with successive portions of chloroform. The -chloroformic extract equals the total alkaloids, which may be separated -in the usual way. - -In four samples of nux vomica examined by Dragendorff, the total -alkaloids ranged from 2.33 to 2.42 per cent. Grate found in two samples -2.88 per cent. and 2.86 per cent. respectively; while Karing from one -sample separated only 1.65 per cent. The strychnine and brucine are in -about equal proportions, Dragendorff[424] finding 1.187 per cent. -strychnine and 1.145 per cent. brucine.[425] - -[424] Dragendorff, _Die chemische Werthbestimmung einiger starkwirkenden -Droguen_, St. Petersburg, 1874. - -[425] These details are very necessary, as bearing on the question of -the fatal dose of nux vomica, which Taylor tells us (_Med. Jurisprud._, -i. 409) was of some importance in _Reg._ v. _Wren_, in which 47 grains -were attempted to be given in milk. The fatal dose of nux vomica must be -ruled by its alkaloidal content, which may be so low as 1 per cent., and -as high as nearly 3 per cent. 30 grains have proved fatal (_Taylor_); if -the powder in this instance was of the ordinary strength, the person -died from less than a grain (.0648 grm.) of the united alkaloids. - -The =vermin-killers= in use in this country are those of Miller, Battle, -Butler, Clift, Craven, Floyd, Gibson, Hunter, Stenier, and Thurston. Ten -samples from these various makers were examined recently by Mr. Allen -(_Pharm. Journal_, vol. xii., 1889), and the results of the analyses are -embodied in the following table:-- - - +-----+----------+------+-------------------+-------+--------------+ - |Name |Weight of | | Strychnine. |Nature | | - | or | Powder |Price.+---------+---------+ of | Colouring | - |Mark.|in Grains.| |Weight in| Per- |Starch.| Matter. | - | | | |Grains. |centage. | | | - +-----+----------+------+---------+---------+-------+--------------+ - | | | | | | | | - | 1 | 5.6 | 3_d._| 0.61 | 10.9 | Wheat | ? | - | 2 | 11.8 | 3_d._| 0.80 | 6.7 | Wheat | Ultramarine. | - | 3 | 13.1 | 3_d._| 1.12 | 8.7 | Rice | Ultramarine. | - | 4 | 11.6 | 3_d._| 1.28 | 11.1 | Rice | Ultramarine. | - | 5 | 13.1 | 3_d._| 1.70 | 13.0 | Rice | Ultramarine. | - | 6 | 21.5 | 6_d._| 2.42 | 11.2 | Wheat |Prussian blue.| - | 7 | 49.2 | 3_d._| 2.85 | 5.8 | Wheat | Soot. | - | 8 | 30.5 | 3_d._| 3.45 | 11.3 | Wheat |Prussian blue.| - | 9 | 16.6 | 3_d._| 3.81 | 19.4 | Rice | Carmine. | - | 10 | 10.0 | 3_d._| 4.18 | 41.8 | Rice | Ultramarine. | - +-----+----------+------+---------+---------+-------+--------------+ - -Sec. 389. =Statistics.=--In England, during the ten years 1883-92, out of -6666 total deaths from poison, strychnine, nux vomica, and vermin-killer -account for 325. Out of these deaths, 118 were ascribed to -"vermin-killer." "Vermin-killer" may be presumed to include not only -strychnine mixtures, but also phosphorus and arsenic pastes and powders, -so that there are no means of ascertaining the number of strychnine -cases comprised under this heading. Taking the deaths actually -registered as due to strychnine or nux vomica, they are about 4.7 per -cent. of the deaths from all sorts of poison. Of these deaths, 268, or -82.4 per cent., were suicidal, 8 were homicidal, and 49 only were -accidental. - -Schauenstein has collected from literature 130 cases of poisoning by -strychnine, but most of these occurred during the last twenty-five -years; 62 of the 130, or about one-half, were fatal, and 15 were -homicidal. It has been stated that strychnine is so very unsuitable for -the purpose of criminal poisoning as to render it unlikely to be often -used. Facts, however, do not bear out this view; for, allowing its -intensely bitter taste, yet it must be remembered that bitter liquids, -such as bitter ale, are in daily use, and a person accustomed to drink -any liquid rapidly might readily imbibe sufficient of a toxic liquid to -produce death before he was warned by its bitterness. It is, indeed, -capable of demonstration, that taste is more vivid _after_ a substance -has been taken than just in the act of swallowing, for the function of -taste is not a rapid process, and requires a very appreciable interval -of time. - -The series of murders by Thomas Neill, or, more correctly, Thomas Neill -Cream, is an example of the use of strychnine for the purposes of -murder. Thomas Neill Cream was convicted, October 21, 1892, for the -murder of Matilda Clover on October 20, 1891; there was also good -evidence that the same criminal had murdered Ellen Dunworth, October 13, -1891; Alice Marsh, April 12, 1892; Emma Shrivell, April 12, 1892, and -had attempted the life of Louie Harvey. The agent in all these cases was -strychnine. There was no evidence as to what form of the poison was -administered in the case of Clover, but Ellen Dunworth, who was found -dying in the streets at 7.45 P.M., and died less than two hours -afterwards, stated that a gentleman gave her "two drops" of white stuff -to drink. - -In the cases of Marsh and Shrivell, Neill Cream had tea with them on the -night of April 11, and gave them both "three long pills;" half an hour -after Neill Cream left them they were found to be dying, and died within -six hours. From Marsh 7 grains, from Shrivell nearly 2 grains of -strychnine were separated; the probability is that each pill contained -at least 3 grains of strychnine. The criminal met Louie Harvey on the -Embankment, and gave her "some pills" to take; she pretended to do so, -but threw them away. Hence it seems probable that Neill Cream took -advantage of the weakness that a large number of the population have for -taking pills, and mostly poisoned his victims in this manner. Clover's -case was not diagnosed during life, but strychnine was found six or -seven months after burial in the body. It may be mentioned incidentally -that the accused himself furnished the clue which led to his arrest, by -writing letters charging certain members of the medical profession with -poisoning these poor young prostitutes with strychnine. - -Sec. 390. =Fatal Dose.=--In a research, which may, from its painstaking -accuracy, be called classical, F. A. Falck has thrown much light upon -the minimum lethal dose of strychnine for various animals. It would seem -that, in relation to its size, the frog is by no means so sensible to -strychnine as was believed, and that animals such as cats and rabbits -take a smaller dose in proportion to their body-weight. The method used -by Falck was to inject subcutaneously a solution of known strength of -strychnine nitrate, and, beginning at first with a known lethal dose, a -second experiment was then made with a smaller dose, and if that proved -fatal, with a still smaller, and so on, until such a quantity was -arrived at, that the chances as determined by direct observation were as -great of recovery as of death. Operating in this way, and making no less -than 20 experiments on the rabbit, he found that the least fatal dose -for that animal was .6 mgrm. of strychnine nitrate per kilogramme. Cats -were a little less susceptible, taking .75 mgrm. Operating on fowls, he -found that strychnine taken into the crop in the usual way was very -uncertain; 50 mgrms. per kilo, taken with the food had no effect, but -results always followed if the poison was introduced into the -circulation by the subcutaneous needle--the lethal dose for fowls being, -under those circumstances, 1 to 2 mgrms. per kilo. He made 35 -experiments on frogs, and found that to kill a frog by strychnine -nitrate, at least 2 mgrms. per kilo, must be injected. Mice take a -little more, from 2.3 to 2.4 mgrms. per kilo. In 2 experiments on the -ring adder, in one 62.5 mgrms. per kilo. of strychnine nitrate, injected -subcutaneously, caused death in seven hours; in the second, 23.1 mgrms. -per kilo. caused death in five days; hence the last quantity is probably -about the least fatal dose for this particular snake. - -These observations may be conveniently thrown into the following table -(see next page), placing the animals in order according to their -relative sensitiveness.[426] - -[426] According to Christison's researches, 0.2 grm. (about 1/3 grain) -is fatal to swine; .03 grm. (1/2 grain) to bears, if injected into the -pleura. 1 to 3 grains (.0648 to .1944 grm.) is given to horses in cases -of paralysis, although 3 grains cannot but be considered a dangerous -dose, unless smaller doses have been previously administered without -effect; 10 grains would probably kill a horse, and 15 grains (.972 grm.) -have certainly done so. - -Now, the important question arises, as to the place in this series -occupied by man--a question difficult to solve, because so few cases are -recorded in which strychnine has been administered by subcutaneous -injection with fatal result. Eulenberg has observed poisonous symptoms, -but not death, produced by 6 mgrms. (1/11 grain) and by 10 mgrms. (about -1/6 grain). Bois observed poisonous symptoms from the similar -subcutaneous administrations of 8 mgrms. to a child six years old, and 4 -mgrms. to another child four years old--the latter dose, in a case -recorded by Christison, actually killing a child of three years of age. -On the other hand, the smallest lethal dose taken by an adult was -swallowed in solution. Dr. Warner took 32 mgrms. (1/2 grain) of -strychnine sulphate, mistaking it for morphine sulphate, and died in -twenty minutes. In other cases 48 mgrms. (7/10 grain) have been fatal. -It will be safe to conclude that these doses by the stomach would have -acted still more surely and energetically if injected subcutaneously. -The case of Warner is exceptional, for he was in weak health; and, if -calculated out according to body-weight, presuming that Dr. Warner -weighed 68 kilos., the relative dose as strychnine nitrate would be .24 -per kilo.--a smaller dose than for any animal hitherto experimented -upon. There is, however, far more reason for believing that the degree -of sensitiveness in man is about the same as that of cats or dogs, and -that the least fatal dose for man is .70 per kilo., the facts on record -fairly bearing out this view. It is, therefore, probable that death -would follow if 38 mgrms. (7/10 grain) were injected subcutaneously into -a man of the average weight of 68 kilos. (150 lbs.). Taylor estimates -the fatal dose of strychnine for adults as from 32.4 to 129.6 mgrms. (.5 -to 2 grains); Guy puts the minimum at 16.2 mgrms. (.25 grain). - -TABLE SHOWING THE ACTION OF STRYCHNINE ON ANIMALS. - - +------------+----------------------+--------------------------------+ - | | | Reckoned on 1 Kilo. of | - | | | Body-weight. | - | | +-----------------|--------------+ - | | Manner of | Lowest | Highest | - | Animal. | Application. | Experimental | Experimental | - | | | Lethal Dose | Lethal Dose. | - | | +-----------------+--------------+ - | | | Dose of Strychnine Nitrate in | - | | | Mgrms. | - +------------+----------------------+-----------------+--------------+ - | Rabbit, | Subcutaneous. | 0.50 | 0.60 | - | Cat, | " | ... | 0.75 | - | Dog, | " | ... | 0.75 | - | " | Taken by the Stomach.| 2.0 | 3.90 | - | " | " Rectum. | ... | 2.00 | - | " | " Bladder.| 5.50 | ... | - | Fox, | Subcutaneous. | ... | 1.00 | - | Hedgehog, | " | 1.00 | 2.00 | - | Fowl, | " | ... | 2.00 | - | Frog, | " | 2.00 | 2.10 | - | Mouse, | " | 2.36 | 2.36 | - | Ring Adder,| " | ... | 23.10 | - +------------+----------------------+-----------------+--------------+ - -Large doses of strychnine may be recovered from if correct medical -treatment is sufficiently prompt. Witness the remarkable instances on -record of duplex poisonings, in which the would-be-suicide has -unwittingly defeated his object by taking strychnine simultaneously with -some narcotic, such as opium or chloral. In a case related by -Schauenstein,[427] a suicidal pharmacist took .48 grm. or .6 grm. (7.4 -to 9.25 grains) of strychnine nitrate dissolved in about 30 c.c. of -bitter-almond water, and then, after half an hour, since no symptoms -were experienced, .6 grm. (9.25 grains) of morphine acetate, which he -likewise dissolved in bitter-almond water and swallowed. After about ten -minutes, he still could walk with uncertain steps, and poured some -chloroform on the pillow-case of his bed, and lay on his face in order -to breathe it. In a short time he lost consciousness, but again awoke, -and lay in a half-dreamy state, incapable of motion, until some one -entered the room, and hearing him murmur, came to his bedside. At that -moment--two and a quarter hours after first taking the strychnine--the -pharmacist had a fearful convulsion, the breathing was suspended, and he -lost consciousness. Again coming to himself, he had several convulsions, -and a physician who was summoned found him in general tetanus. There -were first clonic, then tonic convulsions, and finally opisthotonus was -fully developed. The treatment consisted of emetics, and afterwards -tannin and codeine were given separately. The patient slept at short -intervals; in ten hours after the taking of the poison the seizures were -fewer in number and weaker in character, and by the third day recovery -was complete. Dr. Macredy[428] has also placed on record an interesting -case, in which the symptoms, from a not very large dose of strychnine, -were delayed by laudanum for eight hours. A young woman, twenty-three -years of age, pregnant, took at 10 A.M. a quantity of strychnine -estimated at 1.5 grain, in the form of Battle's vermin-killer, and -immediately afterwards 2 ounces of laudanum. She was seen by Dr. Macredy -in four hours, and was then suffering from pronounced narcotic symptoms. -A sulphate of zinc emetic was administered. In eight hours after taking -the strychnine, there were first observed some clonic convulsive -movements of the hands, and, in a less degree, the legs. These -convulsions continued, at times severe, for several hours, and were -treated with chloral. Recovery was speedy and complete. - -[427] Maschka's _Handbuch_, from Tschepke, _Deutsche Klinik_, 1861. - -[428] _Lancet_, November 28, 1882. - -In a similar case related by Dr. Harrison,[429] a man, aged 54, took a -packet of Battle's vermin-killer, mixed with about a drachm and a half -of laudanum and some rum. At the time he had eaten no food for days, and -had been drinking freely; yet fifty minutes elapsed before the usual -symptoms set in, and no medical treatment was obtained until four hours -after taking the dose. He was then given chloral and other remedies, and -made a rapid recovery. - -[429] _Lancet_, May 13, 1882. - -Sec. 391. =Action on Animals.=--The action of strychnine has been -experimentally studied on all classes of animals, from the infusoria -upwards. The effects produced on animal forms which possess a nervous -system are strikingly alike, and even in the cephalopoda, tetanic -muscular spasm may be readily observed. Of all animals the frog shows -the action of strychnine in its purest form, especially if a dose be -given of just sufficient magnitude to produce toxic effects. The frog -sits perfectly still and quiet, unless acted upon by some external -stimuli, such as a breath of air, a loud noise, or the shaking of the -vessel which contains it, then an immediate tetanic convulsion of all -the muscles is witnessed, lasting a few seconds only, when the animal -again resumes its former posture. This heightened state of reflex action -has its analogue in hydrophobia as well as in idiopathic tetanus. If the -frog thus poisoned by a weak dose is put under a glass shade, kept -moist, and sheltered from sound, or from other sources of irritation, no -convulsions occur, and after some days it is in its usual health. If, on -the other hand, by frequent stimuli, convulsions are excited, the animal -dies. M. Richet[430] has contributed a valuable memoir to the Academy of -Sciences on the toxic action of strychnine. He has confirmed the -statement of previous observers that, with artificial respiration, much -larger doses of strychnine may be taken without fatal result than under -normal conditions, and has also recorded some peculiar phenomena. -Operating on dogs and rabbits, after first securing a canula in the -trachea, and then injecting beneath the skin or into the saphena vein 10 -mgrms. of strychnine hydrochlorate, the animal is immediately, or within -a few seconds, seized with tetanic convulsions, and this attack would be -mortal, were it not for artificial respiration. Directly this is -practised the attack ceases, and the heart, after a period of hurried -and spasmodic beats, takes again its regular rhythm. Stronger and -stronger doses may then be injected without causing death. As the dose -is thus augmented, the symptoms differ. M. Richet distinguishes the -following periods:--(1.) A period of tetanus. (2.) A period of -convulsion, characterised by spasmodic and incessant contraction of all -the muscles. (3.) A little later, when the quantity exceeds 10 mgrms. -per kilo., a choreic period, which is characterised by violent rhythmic -shocks, very sudden and short, repeated at intervals of about three to -four seconds; during these intervals there is almost complete -relaxation. (4.) A period of relaxation; this period is attained when -the dose exceeds 40 mgrms. per kilo. Reflex action is annihilated, the -spontaneous respiratory movements cease, the heart beats tumultuously -and regularly in the severe tetanic convulsions at first, and then -contracts with frequency but with regularity. The pupils, widely dilated -at first, become much contracted. The arterial pressure, enormously -raised at the commencement, diminishes gradually, in one case from 0.34 -mm. to 0.05 mm. The temperature undergoes analogous changes, and during -the convulsions is extraordinarily elevated; it may even attain 41 deg. or -42 deg., to sink in the period of relaxation to 36 deg. Dogs and rabbits which -have thus received enormous quantities of strychnine (_e.g._, 50 mgrms. -per kilo.), may, in this way, live for several hours, but the slightest -interruption to the artificial respiration, in the relaxed state, is -followed by syncope and death. - -[430] _De l'Action de la Strychnine a tres forte dose sur les -Mammiferes. Comptes Rend._, t. xcl. p. 131. - -Sec. 392. =Effects on Man: Symptoms.=--The commencement of symptoms may be -extremely rapid, the rapidity being mainly dependent on the form of the -poison and the manner of application. A soluble salt of strychnine -injected subcutaneously will act within a few seconds;[431] in a case of -amaurosis, related by Schuler,[432] 5.4 mgrms. of a soluble strychnine -salt were introduced into the punctum lachrymale;--in less than four -minutes there were violent tetanic convulsions. In a case related by -Barker, the symptoms commenced in three minutes from a dose of .37 grm. -(5.71 grains).[433] Here the poison was not administered subcutaneously. -Such short periods, to a witness whose mind was occupied during the -time, might seem immediate. On the other hand, when nux vomica powder -has been taken, and when strychnine has been given in the form of pill, -no such rapid course has been observed, or is likely to occur, the usual -course being for the symptoms to commence within half an hour. It is, -however, also possible for them to be delayed from one to two hours, and -under certain circumstances (as in the case related by Macredy) for -eight hours. In a few cases, there is first a feeling of uneasiness and -heightened sensibility to external stimuli, a strange feeling in the -muscles of the jaw, and a catching of the respiration; but generally -the onset of the symptoms is as sudden as epilepsy, and previous to -their appearance the person may be pursuing his ordinary vocation, when, -without preliminary warning, there is a shuddering of the whole frame, -and a convulsive seizure. The convulsions take the form of violent -general tetanus; the limbs are stretched out involuntarily, the hands -are clenched, the soles of the feet incurved, and, in the height of the -paroxysm, the back may be arched and rigid as a board, the sufferer -resting on head and heels, and the abdomen tense. In the grasp of the -thoracic muscles the walls of the chest are set immovable, and from the -impending suffocation the face becomes congested, the eyes prominent and -staring. The muscles of the lower jaw--in "disease tetanus" the first to -be affected--are in "strychnos tetanus," as a rule, the last; a -distinction, if it were more constant, of great clinical value. The -convulsions and remissions recur until death or recovery, and, as a -rule, within two hours from the commencement of the symptoms the case in -some way or other terminates. The number of the tetanic seizures noted -has varied--in a few cases the third spasm has passed into death, in -others there have been a great number. The duration of the spasm is also -very different, and varies from thirty seconds to five or even eight -minutes, the interval between lasting from forty-five seconds[434] to -one or even one and a half hours.[435] - -[431] In one of M. Richet's experiments, a soluble strychnine salt -injected into a dog subcutaneously acted in fourteen seconds. - -[432] Quoted by Taylor from _Med. Times and Gazette_, July, 1861. - -[433] A non-fatal dose may show its effects rapidly, _e.g._, there is a -curious case of symptoms of poisoning caused by the _last_ dose of a -mixture which is recorded in _Pharm. Journ._, 1893, 799. A medical -practitioner prescribed the following mixture:-- - - [Rx]. Tr. strophanthi, [dr]i. - Liq. strychni hydrochlorici, [dr]iiss. - Sol. bismuthi et pepsin. (Richardson's), [oz]iss. - Sp. ammon. aromat., ... - Sp. chloroformi, aa. [oz]iss. - Aquam ad, [oz]vi. - ft. mist. - Shake the bottle. - Two teaspoonfuls when the attack threatens, and repeat in an hour if - necessary. - -Richardson's liquor bismuth contains 1/20 grain of strychnine in each -drachm. The mixture was alkaline; it contained 1.7 grain of strychnine -and 38.25 minims of chloroform. - -The patient, a woman, 54 years of age, had taken the previous doses with -considerable relief; but ten minutes after the last dose, which she -described as far more bitter than those she had taken previously, she -was seized with the usual symptoms of strychnine poisoning, but -recovered after five hours. - -The explanation is pretty obvious; the mixture was alkaline, so that the -strychnine was not in the form of a salt, but in the free state, and was -therefore dissolved by the chloroform; the amount of strychnine taken in -each dose wholly depended on whether or not the mixture was shaken -violently and poured out into the teaspoon immediately after shaking; if -allowed to repose the globules of chloroform saturated with strychnine -would settle at the bottom, and there form a stratum rich in strychnine; -so that the last dose would certainly contain an excess. - -[434] White, _Brit. Med. Journ._, 1867. - -[435] Folkes, _Med. Times_, 1869. - -Sec. 393. =Diagnosis of Strychnine Poisoning.=--However striking and well -defined the picture of strychnine tetanus may be, mistakes in diagnosis -are rather frequent, especially when a medical man is hastily summoned, -has never seen a case of similar poisoning, and has no suspicion of the -possible nature of the seizure. If a young woman, for instance, is the -subject, he may put it down to hysteria, and certainly hysteria not -unfrequently affects somewhat similar convulsions. In a painful case in -which the author was engaged, a young woman either took or was given -(for the mystery was never cleared up fully) a fatal dose of strychnine, -and though the symptoms were well marked, the medical attendant was so -possessed with the view that the case was due to hysteria, that, even -after making the _post-mortem_ examination, and finding no adequate -lesion, he theorised as to the possibility of some fatal hysteric spasm -of the glottis, while there was ample chemical evidence of strychnine, -and a weighable quantity of the alkaloid was actually separated from the -contents of the stomach. The medical attendant of Matilda Clover, one of -Neill's victims, certified that the girl died from _delirium tremens_ -and syncope, although the symptoms were typically those produced by -strychnine. Such cases are particularly sad, for we now know that, with -judicious treatment, a rather large dose may be recovered from. - -If the case is a male, a confusion with epilepsy is possible, though -hardly to be explained or excused; while in both sexes idiopathic -tetanus is so extremely similar as to give rise to the idea that all -cases of idiopathic tetanus are produced by poison, perhaps secreted by -the body itself. As for the distinction between idiopathic and strychnic -tetanus, it is usually laid down (1) that the intervals in the former -are characterised by no relaxation of the muscles, but that they -continue contracted and hard; and (2) that there is a notable rise of -temperature in disease tetanus proper, and not in strychnine tetanus. -Both statements are misleading, and the latter is not true, for in -strychnic poisoning the relaxation is not constant, and very high -temperatures in animals have been observed. - -Sec. 394. =Physiological Action.=--The tetanic convulsions are essentially -reflex, and to be ascribed to a central origin; the normal reflex -sensibility is exaggerated and unnaturally extended. If the ischiatic -plexus supplying the one leg of an animal is cut through, that leg takes -no part in the general convulsions, but if the artery of the leg alone -is tied, then the leg suffers from the muscular spasm, as well as the -limbs in which the circulation is unrestrained. In an experiment by Sir -B. W. Richardson, a healthy dog was killed, and, as soon as practicable, -a solution of strychnine was injected through the systemic vessels by -the aorta--the whole body became at once stiff and rigid as a board. -These facts point unmistakably to the spinal marrow as the seat of the -toxic influence. Strychnine is, _par excellence_, a spinal poison. On -physiological grounds the grey substance of the cord is considered to -have an inhibitory action upon reflex sensibility, and this inhibitory -power is paralysed by strychnine. The spinal cord, it would appear, has -the power of collecting strychnine from the circulation and storing it -up in its structure.[436] - -[436] R. W. Lovett, _Journ. Physiol._, ix. 99-111. - -Much light has been thrown upon the cause of death by Richet's -experiments.[437] It would seem that, in some cases, death takes place -by a suffocation as complete as in drowning, the chest and diaphragm -being immovable, and the nervous respiratory centres exhausted. In such -a case, immediate death would be averted by a tracheal tube, by the aid -of which artificial respiration might be carried on; but there is -another asphyxia due to the enormous interstitial combustion carried on -by muscles violently tetanised. "If," says Richet, "after having -injected into a dog a mortal dose of strychnine, and employed artificial -respiration according to the classic method twenty or thirty times a -minute, the animal dies (sometimes at the end of ten minutes, and in -every case at the end of an hour or two), and during life the arterial -blood is examined, it will be ascertained that it is black, absolutely -like venous blood." - -[437] _Op. cit._ - -This view is also supported by the considerable rise of temperature -noticed: the blood is excessively poor in oxygen, and loaded with carbon -dioxide. That this state of the blood is produced by tetanus, is proved -by the fact that an animal poisoned by strychnine, and then injected -subcutaneously with curare in quantity just sufficient to paralyse the -muscular system, does not exhibit these phenomena. By the aid of -artificial respiration, together with the administration of curare, an -animal may live after a prodigious dose of strychnine. - -Meyer[438] has investigated carefully the action of strychnine on the -blood-pressure--through a strong excitement of the vaso-motor centre, -the arteries are narrowed in calibre, and the blood-pressure much -increased; the action of the heart in frogs is slowed, but in the -warm-blooded animals quickened. - -[438] _Wiener Akad. Sitzungsber._, 1871. - -Sec. 395. =Post-mortem Appearances.=--There is but little characteristic in -the _post-mortem_ appearances from strychnine poisoning. The body -becomes very stiff a short time after death, and this rigidity remains -generally a long time. In the notorious Palmer case, the body was rigid -two months after death, but, on the other hand, the _rigor mortis_ has -been known to disappear within twenty-four hours. If the convulsions -have been violent, there may be minute haemorrhages in the brain and -other parts. I have seen considerable haemorrhage in the trachea from -this cause. When death occurs from asphyxia, the ordinary signs of -asphyxia will be found in the lungs, &c. The heart mostly has its right -side gorged with blood, but in a few cases it is empty and contracted. - -In a case which Schauenstein has recorded[439] he found strychnine still -undissolved, coating the stomach as a white powder; but this is very -unusual, and I believe unique. The bladder often contains urine, which, -it need scarcely be said, should be preserved for chemical -investigation. - -[439] _Op. cit._ - -Sec. 396. =Treatment.=--From the cases detailed, and from the experiments -on animals, the direction which treatment should take is very clear. As -a matter of course, if there is the slightest probability of any of the -poison remaining in the stomach, it should be removed. It is doubtful -whether the stomach pump can be ever applied with benefit in strychnine -poisoning, the introduction of the tube is likely to aggravate the -tetanus, but apomorphine can be injected subcutaneously. Large and -frequent doses of chloral should be administered in order to lessen the -frequency of convulsions, or prevent their occurrence, and it may be -necessary in a few cases, where death threatens by suffocation, to -perform tracheotomy, and to use artificial respiration. Where chloral or -chloroform is not at hand, and in cases of emergency, where this may -easily happen, the medical man must administer in full doses the nearest -narcotic at hand.[440] - -[440] It is certain that lutidine would be a valuable antidote for -strychnine. C. G. Williams found that lutidine injected into frogs -already under the influence of strychnine, arrested the convulsions, or -if given first, and then followed by a fatal dose of strychnine, it -prevented the appearance of the tetanus. (See _ante_, p. 276, footnote.) - -Sec. 397. =Separation of Strychnine from Organic Matters.=--The separation -of strychnine from organic matters, &c., is undertaken strictly on the -general principles already detailed. It may happen, however, that in -cases of poisoning there is the strongest evidence from symptoms in the -person or animal that strychnine alone is to be sought for. In an -instance of the kind, if a complex organic liquid (such as the contents -of the stomach) is under examination, it is best to remove the solid -substances by filtration through glass, wool, or linen, and evaporate -nearly to dryness over the water-bath, acidifying with acetic acid, and -then exhausting the residue repeatedly with boiling alcohol of 80 per -cent. The alcoholic extract is in its turn evaporated to dryness, and -taken up with water; the aqueous solution is passed through a wet -filter, and then shaken up with the usual succession of fluids, viz., -petroleum ether, benzene, chloroform, and amyl alcohol, which will -remove a great number of impurities, but will not dissolve the -strychnine from the acid solution. The amyl alcohol may lastly be -removed by petroleum ether; and on removal of the final extractive -(which should be done as thoroughly as possible) chloroform is added, -and the fluid is alkalised by ammonia, which precipitates the alkaloid -in the presence of the solvent. Should the reverse process be -employed--that is, ammonia added first, and then chloroform--the -strychnine is not so perfectly dissolved, since it has time to assume a -crystalline condition. On separation and evaporation of the chloroform, -the residue (if much discoloured, or evidently impure) may be dissolved -in alcohol or benzene, and recrystallised several times. Cushman has -published an improved method of separating strychnine, which, according -to test experiments, appears to give good results. He describes the -method as follows:[441]-- - -[441] "The _post-mortem_ Detection and Estimation of Strychnine," by -Allerton S. Cushman--_Chem. News_, vol. lxx. 28. - - "The stomach contents or viscera properly comminuted are weighed, - and an aliquot part taken for analysis. The mass is digested in a - beaker over night, at a warm temperature, with water acidulated with - acetic acid. The contents of the beaker are filtered by pressing - through muslin, and then passing through paper. The clear filtrate - is evaporated on the water-bath to soft dryness, an excess of - ordinary 80 per cent. alcohol added, and boiled ten minutes with - stirring, and allowed to stand one half hour at a warm temperature. - This extraction is repeated, the alcohol extracts united, filtered, - evaporated to soft dryness, and the residue taken up with a little - water acidulated with acetic acid, and shaken out with pure acetic - ether in a separating funnel. Successive fresh portions of acetic - ether are used until the solvent shows by its colour, and by the - evaporation of a few drops, that it does not contain extractive - matter. As many as twelve extractions are sometimes necessary to - accomplish this. Care should be taken in each case to allow time for - as complete separation as possible between the two layers. The - purified acid aqueous liquid, which need not exceed in bulk 50 c.c., - is now returned to the separator, an equal quantity of fresh acetic - ether added, and enough sodic carbonate in solution to render the - mixture slightly alkaline, and the separator is then thoroughly - shaken for several minutes. All the alkaloid should now be in - solution in the acetic ether, but a second shaking of the alkaline - liquid, with acetic ether, is always made, the two extracts united, - and evaporated in a glass dish over hot water to dryness. It will - now be found that the residue shows the alkaloid fairly pure, but - not pure enough for quantitative results. The residue is dissolved - in a few drops of dilute acetic acid, warmed to complete solution, - filtered if necessary, diluted to about 30 c.c., and the solution - transferred to a small separating funnel; 30 c.c. of - ether-chloroform (1-1) are now added, and the separator shaken. - After separation the heavier ether-chloroform is allowed to run off, - another lot of 30 c.c. of ether-chloroform is added, the separator - shaken, and immediately enough ammonia-water added to render the - mixture alkaline, and the whole vigorously agitated for several - minutes. After separation is complete, the ether-chloroform layer is - run out into a clean 50 c.c. glass-stoppered burette. The alkaline - water solution is agitated with 20 c.c. more of the - ether-chloroform, separated, and this extract added to that in the - burette. The burette is now supported over a small weighed glass - dish, which is kept warm on a water-bath, and the liquid allowed to - evaporate gently, drop by drop, until a sufficient quantity of the - pure alkaloid has collected in the centre of the dish to render an - accurate weighing possible, or else all of the alkaloid may be - collected and weighed at once. After all possible tests have been - made upon the weighed alkaloid, the remainder is re-dissolved in a - drop or two of acetic acid, a little water added, and the dish - exposed under a bell-glass to the fumes of ammonia. After standing - some time all the strychnine is found crystallised out in the - beautiful characteristic needle-formed crystals. The mother-liquor - is drawn off with a small fine-pointed tube and rubber bulb, the - crystals carefully washed with a little water and dried over - sulphuric acid. The glass dish containing these crystals is kept as - the final exhibit, and is shown in evidence. Another convenient - exhibit may be prepared by moistening a small filter-paper with a - solution of the alkaloid in dilute acetic acid, then moistening with - a solution of potassium dichromate: this paper, on being dried, may - be kept indefinitely. On moistening it, and touching it at any time - with a drop of strong sulphuric acid, a violet film, changing to - cherry-red, is formed at the place of contact." - -Should search be made for minute portions of strychnine in the tissues, -considering the small amount of the poison which may produce death, it -is absolutely necessary to operate on a very large quantity of material. -It would be advisable to take the whole of the liver, the brain, spinal -cord, spleen, stomach, duodenum, kidneys, all the blood that can be -obtained, and a considerable quantity of muscular tissue, so as to make -in all about one-eighth to one-tenth of the whole body; this may be cut -up into small pieces, and boiled in capacious flasks with alcohol, -acidified with acetic acid. Evaporation must be controlled by adapting -to the cork an upright condenser. - -Should the analyst not have apparatus of a size to undertake this at -one operation, it may be done in separate portions--the filtrate from -any single operation being collected in a flask, and the spirit -distilled off in order to be used for the next. In this way, a large -quantity of the organs and tissues can be exhausted by half a gallon of -alcohol. Finally, most of the alcohol is distilled off, and the -remainder evaporated at a gentle heat in a capacious dish, the final -extract being treated, evaporating to a syrup, and using Cushman's -process (_ante_, p. 334) as just described. It is only by working on -this large scale that there is any probability of detecting absorbed -strychnine in those cases where only one or two grains have destroyed -life, and even then it is possible to miss the poison. - -Strychnine is separated by the kidneys rapidly. In a suicidal case -recorded by Schauenstein,[442] death took place in an hour and a half -after taking strychnine, yet from 200 c.c. of the urine, Schauenstein -was able to separate nitrate of strychnine in well-formed crystals. Dr. -Kratter[443] has made some special researches on the times within which -strychnine is excreted by the kidneys. In two patients, who were being -treated by subcutaneous injection, half an hour after the injection of -7.5 mgrms. of strychnine nitrate the alkaloid was recognised in the -urine. The strychnine treatment was continued for eight to ten days, and -then stopped; two days after the cessation, strychnine was found in the -urine, but none on the third day, and the inference drawn is that the -elimination was complete within forty-eight hours. - -[442] Maschka's _Handbuch_, Band 2, p. 620. - -[443] _Ibid._ - -Strychnine has been detected in the blood of dogs and cats in researches -specially undertaken for that purpose, but sometimes a negative result -has been obtained, without apparent cause. Dragendorff[444] gave dogs -the largest possible dose of strychnine daily. On the first few days no -strychnine was found in the urine, but later it was detected, especially -if food was withheld. M'Adam was the first who detected the absorbed -poison, recognising it in the muscles and urine of a poisoned horse, and -also in the urine of a hound. Dragendorff has found it in traces in the -kidneys, spleen, and pancreas; Gay, in different parts of the central -nervous system, and in the saliva. So far as the evidence goes, the -liver is the best organ to examine for strychnine; but all parts -supplied with blood, and most secretions, may contain small quantities -of the alkaloid. At one time it was believed that strychnine might be -destroyed by putrefaction, but the question of the decomposition of the -poison in putrid bodies may be said to be settled. So far as all -evidence goes, strychnine is an extremely stable substance, and no -amount of putrescence will destroy it. M'Adam found it in a horse a -month after death, and in a duck eight weeks after; Nunneley in 15 -animals forty-three days after death, when the bodies were much -decomposed; Roger in a body after five weeks' interment; Richter in -putrid tissues exposed for eleven years to decomposition in open -vessels; and, lastly, W. A. Noyes[445] in an exhumed body after it had -been buried 308 days. - -[444] In an animal rapidly killed by a subcutaneous injection of acetate -of strychnine, no strychnine was detected either in the blood or -liver.--_Dragendorff._ - -[445] _Journ. Americ. Chem. Soc._, xvi. 2. - -It would appear from Ibsen's[446] experiments that strychnine gets -dissolved in the fluids of the dead body--so that whether strychnine -remains or not, greatly depends as to whether the fluids are retained or -are allowed to soak away; it is, therefore, most important in -exhumations to save as much of the fluid as possible. - -[446] _Viertel. f. gericht. Med._, Bd. viii. - -Sec. 398. =Identification of the Alkaloid.=--A residue containing -strychnine, or strychnine mixed with brucine, is identified-- - -(1.) By its alkaline reaction and its bitter taste. No substance can -possibly be strychnine unless it tastes remarkably bitter. - -(2.) By the extremely insoluble chromate of strychnine, already -described.[447] A fluid containing 1 : 1000 of strychnine gives with -chromate of potash (if allowed to stand over-night) a marked -precipitate, dissimilar to all others, except those of lead and baryta -chromates, neither of which can possibly occur if any of the processes -described are followed. - -[447] 1 grm. of strychnine gave 1.280 grms. of the chromate, = 78.1 per -cent. of strychnine; 3 gave 3.811 of the chromate, = 78.77 per cent. of -strychnine.--_Mohr._ - -(3.) If the chromate just described is treated on a porcelain plate with -a drop of pure strong sulphuric acid, a deep rich blue colour, passing -through purple into red, rapidly makes its appearance. This colour -possesses an absorption spectrum (figured at p. 55). Dr. Guy, neglecting -intermediate colours, aptly compares the succession--(1) to the rich -blue of the Orleans plum; (2) to the darker purple of the mulberry; and -(3) to the bright clear red of the sweet orange. These characters--viz., -alkalinity, bitterness, and the property of precipitation by potassic -chromate in a definite crystalline form, the crystals giving the -colours detailed--belong to no other substance known save strychnine, -and for all purposes sufficiently identify the alkaloid. The -same colour is obtained by mixing a drop of sulphuric acid with -strychnine and a crystal, or speck, of any one of the following -substances:--Ferridcyanide of potash, permanganate of potash, peroxide -of lead, peroxide of manganese, and cerous hydroxide. - -Potassic permanganate and sulphuric acid is the most delicate, and will -detect 0.001 mgrm. of strychnine; cerous hydroxide is, on the other -hand, most convenient, for cerous hydroxide is white; all the others -have colours of their own. Cerous hydroxide is prepared strychnine; 3 -gave 3.811 of the chromate, = 78.77 per cent. of strychnine.--_Mohr._ -by dissolving cerium oxalate in dilute sulphuric acid and precipitating -with ammonia, filtering and well washing the precipitate; and the latter -may be used while moist, and responds well to 1/100 mgrm. of strychnine. - -The influence of mixtures on the colour reactions of strychnine have -been studied by Flueckiger, who states:-- - -"No strychnine reaction appears with sulphuric acid containing chromic -acid (made by dissolving 0.02 grm. of pot. bichromate in 10 c.c. of -water, and then adding 30 grms. strong sulphuric acid) when brucine and -strychnine mixed in equal parts are submitted to the test; it succeeds, -however, in this proportion with sulphuric acid containing potassium -permanganate (.02 grm. pot. permanganate in 10 c.c. of water, and 30 -grms. of strong sulphuric acid). - -"If the brucine is only one-tenth of the mixture, the blue-violet colour -is obtained. A large excess of atropine does not prevent or obscure the -strychnine reaction. A solution of 1 milligrm. atropine sulphate -evaporated to dryness, together with 5 c.c. of a solution of strychnine -(1 : 100,000) has no influence on the reaction, neither in the -proportion of 1 mgrm. to 1 c.c. of the same solution; neither has -cinchonine nor quinine any effect. - -"Morphine obscures the reaction in the following proportions:-- - -"A solution of 0.01 mgrm. strychnine evaporated with a solution of 1 -mgrm. of morphine sulphate on a water-bath, yields a blurred strychnine -reaction when the residue is dissolved in sulphuric acid, and a crystal -of potassic permanganate added. But still there is evidence whereby to -_suspect_ the presence of strychnine. - -"A solution of 2 mgrms. of morphine sulphate treated in like manner with -0.01 mgrm. of strychnine yields like results. - -"A solution of 3 mgrms. of morphine sulphate evaporated to dryness, with -a solution of 0.01 mgrm. strychnine yielded results with the potassic -permanganate test the same as if no strychnine was present. - -"A solution of 1 mgrm. of morphine sulphate, treated as above, with a -solution of 0.1 mgrm. strychnine, offered positive proof of the presence -of the latter."[448] - -[448] Flueckiger's _Reactions_, translated by Nagelvoort, Detroit, 1893. - -Dragendorff was able to render evident .025 mgrm. mixed with twenty -times its weight of quin. sulphate; the same observer likewise -recognised .04 mgrm. of strychnine in thirty-three times its weight of -caffeine. Veratrine is likewise not injurious. - -=The physiological test= consists in administering the substance to some -small animal (preferably to a frog), and inducing the ordinary tetanic -symptoms. It may be at once observed that if definite chemical evidence -of strychnine has been obtained, the physiological test is quite -unnecessary; and, on the other hand, should the application of a liquid -or substance to a frog induce tetanus, while chemical evidence of the -presence of strychnine was wanting, it would be hazardous to assert that -strychnine was present, seeing that caffeine, carbolic acid, picrotoxin, -certain of the opium alkaloids, hypaphorine, some of the ptomaines, and -many other substances induce similar symptoms. The best method (if the -test is used at all) is to take two frogs,[449] and insert under the -skin of the one the needle of a subcutaneous syringe, previously charged -with a solution of the substance, injecting a moderate quantity. The -other frog is treated similarly with a very dilute solution of -strychnine, and the two are then placed under small glass shades, and -the symptoms observed and compared. It is not absolutely necessary to -inject the solution under the skin, for if applied to the surface the -same effects are produced; but, if accustomed to manipulation, the -operator will find the subcutaneous application more certain, especially -in dealing with minute quantities of the alkaloid.[450] - -[449] A very practical disadvantage of the physiological test is the -great difficulty of obtaining frogs exactly when wanted. - -[450] Methyl strychnine, as well as methyl brucine, has been shown by -Brown and Fraser to have an effect exactly the opposite to that of -strychnine, paralysing the muscles like curare. In the case, therefore, -of the methyl compounds, a physiological test would be very valuable, -since these compounds do not respond to the ordinary tests. - - Sec. 399. =Hypaphorine.=--One substance is known which neither - physiological test nor the colour reactions suffice to distinguish - from strychnine, viz., hypaphorine,[451] the active matter of a - papilionaceous tree growing in Java--the _Hypaphorus subumbrans_; a - small quantity of the alkaloid is in the bark, a larger quantity is - in the seed. - -[451] Dr. C. Plugge, _Arch. f. exp. Path. u. Ph._, Bd. xxxii. 313. - - Hypaphorine forms colourless crystals which brown, without melting, - above 220 deg., and exhale a vapour smelling like napththylamine. The - free alkaloid is soluble in water, but has no action on litmus. The - salts are less soluble than the free alkaloid, so that acids, such - as nitric or hydrochloric, produce in a short time precipitates on - standing. Solutions of the salts are not precipitated by alkalies; - chloroform, ether, benzene, all fail to extract it from either - alkaline or acid solutions. It gives no precipitate with potassic - chromate, but most general alkaloidal reagents precipitate. - - It gives a precipitate with iodine trichloride, and has therefore - probably a pyridine nucleus, it may be an acid anilide.[452] It - gives the same colours as strychnine with sulphuric acid and - potassic permanganate or potassic chromate; it causes in frogs - tetanus, but the dose has to be much larger than that of strychnine. - The duration of life in doses of 15 mgrms. may extend to five days, - and frogs may even recover after 50 mgrms. - -[452] Julius Tafel (_Ber._, 1890, 412) has shown that the colour -reactions with H_{2}SO_{4} and oxidising agents are the characteristic -tests of an acid anilide. - - The distinction between strychnine and hypaphorine is therefore - easy; besides it will not occur in a chloroform extract, and it will - not give a precipitate with potassic chromate. - - Sec. 400. =Quantitative Estimation of Strychnine.=--The best process of - estimating the proportion of each alkaloid in a mixture of - strychnine and brucine, is to precipitate them as picrates, and to - destroy the brucine picrate by nitric acid after obtaining the - combined weight of the mixed picrates; then to weigh the undestroyed - strychnine picrate. - - To carry out the process, the solution of the mixed alkaloids must - be as neutral as possible. A saturated solution of picric acid is - added drop by drop to complete precipitation. A filter paper is - dried and weighed, and the precipitate collected on to this filter - paper; the precipitate is washed with cold water, dried at 105 deg., and - weighed. This weight gives the combined weight of both strychnine - and brucine picrates. - - The precipitate is now detached from the filter, washed into a small - flask, and heated on the water-bath for some time with nitric acid - diluted to 1.056 gravity (about 11 per cent. HNO_{3}). This process - destroys the brucine picrate, but leaves the strychnine picrate - untouched. The acid liquid is now neutralised with ammonia or soda, - and a trace of acetic acid added; the precipitate of strychnine - picrate is now collected and weighed. The weight of this subtracted - from the first weight, of course, gives that of the brucine picrate. - - One part of strychnine picrate is equal to 0.5932 strychnine; and - one part of brucine picrate is equal to 0.6324 brucine. - - From the strychnine picrate the picric acid may be recovered and - weighed by dissolving the picrate in a mineral acid and shaking out - with ether; from the acid liquid thus deprived of picric acid the - alkaloid may be separated by alkalising with ammonia and shaking out - with chloroform. - -Sec. 401. =Brucine= (C_{23}H_{26}N_{2}O_{4} + 4H_{2}O)[453] occurs -associated with strychnine in the plants already mentioned; its best -source is the so-called _false angustura_ bark, which contains but -little strychnine. Its action is similar to that of strychnine. If -crystallised out of dilute alcohol it contains 4 atoms of water, easily -expelled either in a vacuum over sulphuric acid or by heat. Crystallised -thus, it forms transparent four-sided prisms, or arborescent forms, like -boric acid. If thrown down by ammonia from a solution of the acetate, it -presents itself in needles or in tufts. - -[453] Sonnenschein has asserted that brucine may be changed into -strychnine by the action of NO_{3}. This statement has been investigated -by A. J. Cownley, but not confirmed.--_Pharm. Journ._ (3), vi. p. 841. - -The recently-crystallised alkaloid has a solubility different from that -which has effloresced, the former dissolving in 320 parts of cold, and -150 parts of boiling water; whilst the latter (according to Pelletier -and Caventou) requires 500 of boiling, and 850 parts of cold water for -solution. Brucine is easily soluble in absolute, as well as in ordinary -alcohol; 1 part dissolves in 1.7 of chloroform, in 60.2 of benzene. -Petroleum ether, the volatile and fatty oils and glycerine, dissolve the -alkaloid slightly, amyl alcohol freely; it is insoluble in _anhydrous_ -ether. The behaviour of brucine in the subliming cell is described at p. -260. Anhydrous brucine melts in a tube at 178 deg. The alcoholic solution -of brucine turns the plane of polarisation to the left [[alpha]]_r_ = --11.27 deg. The taste is bitter and acrid. Soubeiran maintains that it can -be recognised if 1 part is dissolved in 500,000 parts of water. If -nitric trioxide be passed into an alcoholic solution of brucine, first -brucine nitrate is formed; but this passes again into solution, from -which, after a time, a heavy, granular, blood-red precipitate separates: -it consists of dinitro-brucine (C_{23}H_{24}(NO_{2})_{2}N_{2}O_{4}). -Brucine fully neutralises acids, and forms salts, which -are for the most part crystalline. The neutral sulphate -(C_{23}H_{25}N_{2}O_{4}SH_{2}O_{4} + 3-1/2H_{2}O) is in long needles, -easily soluble in water. The acetate is not crystalline, that of -strychnine is so (p. 321). - -Brucine is precipitated by ammonia, by the caustic and carbonated -alkalies, and by most of the group reagents. Ammonia does not -precipitate brucine, if in excess; on the other hand, strychnine comes -down if excess of ammonia is added immediately. This has been proposed -as a method of separation; if the two alkaloids are present in acid -solution, ammonia in excess is added, and the solution is immediately -filtered; the quantitative results are, however, not good, the -strychnine precipitate being invariably contaminated by brucine. - -Chromate and dichromate of potassium give no precipitate with neutral -salts of brucine; on the other hand, strychnine chromate is at once -formed if present. It might, therefore, be used to separate strychnine -from brucine. The author has attempted this method, but the results were -not satisfactory. - -Sec. 402. =Physiological Action.=--The difference between the action of -strychnine and that of brucine on man or animals is not great. Mays -states that strychnine affects more the anterior, brucine the posterior -extremities. In strychnine poisoning, convulsions occur early, and -invariably take place before death; but death may occur from brucine -without any convulsions, and in any case they develop late. Brucine -diminishes local sensibility when applied to the skin; strychnine does -not.[454] In a physiological sense, brucine may be considered a diluted -strychnine. The lethality of brucine, especially as compared with -strychnine, has been investigated by F. A. Falck.[455] He experimented -on 11 rabbits, injecting subcutaneously brucine nitrate, in doses of -varying magnitude, from 100 mgrms. down to 20 mgrms. per kilogram of -body-weight. He found that brucine presented three stages of symptoms. -In the first, the respiration is quickened; in 3 of the 11 cases a -strange injection of the ear was noticed; during this period the pupils -may be dilated. In the second stage, there are tetanic convulsions, -trismus, opisthotonus, oppressed respiration, and dilated pupils. In the -third stage, the animal is moribund. Falck puts the minimum lethal dose -for rabbits at 23 mgrms. per kilo. Strychnine kills 3.06 times more -quickly than brucine, the intensity of the action of strychnine relative -to that of brucine being as 1 : 117.4. Falck has also compared the -minimum lethal dose of strychnine and brucine with the tetanising opium -alkaloids, as shown in the following table:-- - -[454] _Journ. Physiol._, viii. 391-403. - -[455] _Brucin u. Strychnin; eine toxikologische Parallele_, von Dr. F. -A. Falck. _Vierteljahrsschr. f. gerichtl. Med._, Band xxiii. p. 78. - -TABLE SHOWING THE LETHAL DOSES OF VARIOUS TETANISING POISONS. - - +-----------------------+---------------+------------+ - | |Minimum Lethal | | - | |Dose for every |Proportional| - | |Kilogram Weight| Strength. | - | | of Rabbit. | | - +-----------------------+---------------+------------+ - | | Mgrms. | | - | | | | - |Strychnine nitrate, | 0.6 | ... | - |Thebaine nitrate, | 14.4 | 24.0 | - |Brucine nitrate, | 23.0 | 38.33 | - |Landanine nitrate, | 29.6 | 49.33 | - |Codeine nitrate, | 51.2 | 85.33 | - |Hydrocotarnine nitrate,| 203.8 | 339.66 | - +-----------------------+---------------+------------+ - -If these views are correct, it follows that the least fatal dose for an -adult man would be 1.64 grm. (about 24.6 grains) of brucine nitrate. - -[Illustration: Brucine Crystals. (_From a Photograph._)] - -Sec. 403. Tests.--If to a solution of brucine in strong alcohol a little -methyl iodide is added, at the end of a few minutes circular rosettes of -crystal groups appear (see fig.): they are composed of methyl brucine -iodide (C_{23}H_{25}(CH_{3})N_{2}O_{4}HI). Crystals identical in shape -are also obtained if an alcoholic solution of iodine, or hydriodic acid -with iodine, is added to an alcoholic solution of brucine. A solution of -strychnine gives with methyl iodide no similar reaction. Strychnine in -alcoholic solution, mixed with, brucine in no way interferes with the -test. The methyl iodide test may be confirmed by the action of nitric -acid. With that reagent it produces a scarlet colour, passing into -blood-red, into yellow-red, and finally ending in yellow. This can be -made something more than a mere colour test, for it is possible to -obtain a crystalline body from the action of nitric acid on brucine. If -a little of the latter be put in a test-tube, and treated with nitric -acid of 1.4 specific gravity (immersing the test-tube in cold water to -moderate the action), the red colour is produced. On spectroscopic -examination of the blood-red liquid a broad, well-marked absorption band -is seen, the centre of which (_see_ page 55) is between E. & F. [W. L. -about 500]. There is also a development of nitric oxide and carbon -dioxide, and the formation of methyl nitrite, oxalic acid, and kakotelin -(C_{23}H_{26}N_{2}O_{4} + 5NHO_{3} = C_{20}H_{22}N_{4}O_{9} + -N(CH_{3})O_{2} + C_{2}H_{2}O_{4} + 2NO + 2H_{2}O). On diluting -abundantly with water, the kakotelin separates in yellow flocks, and may -be crystallised out of dilute hydrochloric or dilute nitric acid in the -form of yellow or orange-red crystals, very insoluble in water, but -dissolving readily in dilute acid. On removal by dilution of the product -just named, neutralisation with ammonia, and addition of a solution of -chloride of calcium, the oxalate of lime is thrown down. The nitric acid -test is, therefore, a combined test, consisting of--the production by -the action of nitric acid (1) of a red colour; (2) of yellow scales or -crystals insoluble in water; (3) of oxalic acid. No alkaloid save -brucine is known to give this reaction. - -There are other methods of producing the colour test. If a few drops of -nitric acid are mixed with the substance in a test-tube, and then -sulphuric acid cautiously added, so as to form a layer at the bottom, at -the junction of the liquids a red zone, passing into yellow, is seen. - -A solution of brucine is also coloured red by chlorine gas, ammonia -changing the colour into yellow. - -Flueckiger[456] has proposed as a test mercurous nitrate, in aqueous -solution with a little free nitric acid. On adding this reagent to a -solution of brucine salt, and gently warming, a fine carmine colour is -developed. - -[456] _Archiv f. Pharm._ (3), vi. 404. - -In regard to the separation of brucine from organic fluids or tissues, -the process already detailed for strychnine suffices. It is of very -great importance to ascertain whether both strychnine and brucine are -present or not--the presence of both pointing to nux vomica or one of -its preparations. The presence of brucine may, of course, be owing to -impure strychnine; but if found in the tissues, that solution of the -question is improbable, the commercial strychnine of the present day -being usually pure, or at the most containing so small a quantity of -brucine as would hardly be separated from the tissues. - - Sec. 404. =Igasurine= is an alkaloid as yet but little studied; it - appears that it can be obtained from the boiling-hot watery extract - of nux vomica seeds, through precipitating the strychnine and - brucine by lime, and evaporation of the filtrate. According to - Desnoix,[457] it forms white crystals containing 10 per cent. of - water of crystallisation. - -[457] _Journ. Pharm._ (3), xxv. 202. - - It is said to be poisonous, its action being similar to that of - strychnine and brucine, and in activity standing midway between the - two. - - Sec. 405. _Strychnic Acid._--Pelletier and Caventou obtained by boiling - with spirit small, hard, warty crystals of an organic acid, from _S. - ignatius_, as well as from nux vomica seeds. The seeds were first - exhausted by ether, the alcohol solution was filtered and - evaporated, and the extract treated with water and magnesia, - filtered, and the residue first washed with cold water, then with - hot spirit, and boiled lastly with a considerable quantity of water. - The solution thus obtained was precipitated with acetate of lead, - the lead thrown out by SH_{2}, and the solution evaporated, the acid - crystallising out. It is a substance as yet imperfectly studied, and - probably identical with malic acid. - - -2. THE QUEBRACHO GROUP OF ALKALOIDS. - - Sec. 406. The bark of the _Quebracho Blanco_[458] (_Aspidosperma - quebracho_) contains, according to Hesse's researches, no fewer than - six alkaloids--Quebrachine, Aspidospermine, Aspidospermatine, - Aspidosamine, and Hypoquebrachine. The more important of these are - _Aspidospermine_ and _Quebrachine_. - -[458] See Liebig's _Annal._, 211, 249-282; _Ber. der deutsch. Chem. -Gesellsch._, 11, 2189; 12, 1560. - - =Aspidospermine= (C_{22}H_{30}N_{2}O_{2}) forms colourless needles - which melt at 206 deg. They dissolve in about 6000 parts of water at - 14 deg.--48 parts of 90 per cent. alcohol, and 106 parts of pure ether. - The alkaloid gives a fine magenta colour with perchloric acid. - - =Quebrachine= (C_{21}H_{26}N_{2}O_{3}) crystallises in colourless - needles, melting-point (with partial decomposition) 215 deg. The - crystals are soluble in chloroform, with difficulty soluble in cold - alcohol, but easily in hot. The alkaloid, treated with sulphuric - acid, and peroxide of lead, strikes a beautiful blue colour. It also - gives with sulphuric acid and potassic chromate the strychnine - colours. Quebrachine, dissolved in sulphuric acid containing iron, - becomes violet-blue, passing into brown. The alkaloid, treated with - strong sulphuric acid, becomes brown; on adding a crystal of - potassic nitrate, a blue colour is developed; on now neutralising - with caustic soda no red coloration is perceived. Dragendorff has - recently studied the best method of extracting these alkaloids for - toxicological purposes. He recommends extraction of the substances - with sulphuric acid holding water, and shaking up with solvents. - Aspidospermine is not extracted by petroleum ether or benzene from - an acid watery extract, but readily by chloroform or by amyl - alcohol. It is also separated from the same solution, alkalised by - ammonia, by either amyl alcohol or chloroform; with difficulty by - petroleum ether; some is dissolved by benzene. Quebrachine may be - extracted from an acid solution by chloroform, but not by petroleum - ether. Alkalised by ammonia, it dissolves freely in chloroform and - in amyl alcohol. Traces are taken up by petroleum, somewhat more by - benzene. Aspidospermine is gradually decomposed in the body, but - Quebrachine is more resistant, and has been found in the stomach, - intestines, blood, and urine. The toxicological action of the bark - ranks it with the tetanic class of poisons. In this country it does - not seem likely to attain any importance as a poison. - - -3. PEREIRINE. - - Sec. 407. =Pereirine=--an alkaloid from pereira bark--gives a play of - colours with sulphuric acid and potassic bichromate similar to but - not identical with that of strychnine. Froehde's reagent strikes - with it a blue colour. On dissolving pereirine in dilute sulphuric - acid, and precipitating by gold chloride, the precipitate is a - beautiful red, which, on standing and warming, is deepened. - Pereirine may be extracted from an acid solution, after alkalising - with ammonia, by ether or benzene. - - -4. GELSEMINE. - - Sec. 408. Gelsemine (C_{22}H_{28}N_{2}O_{4}) is an alkaloid[459] which - has been separated from _Gelsemium sempervirens_, the Carolina - jessamine, a plant having affinities with several natural orders, - and placed by De Candolle among the _Loganiaceae_, by Chapman among - the _Rubiaceae_ and by Decaisne among the _Apocynaceae_. It grows wild - in Virginia and Florida.[460] Gelsemine is a strong base; it is - yellowish when impure, but a white amorphous powder when pure. It - fuses below 100 deg. into a transparent vitreous mass, at higher - temperatures it condenses on glass in minute drops; its taste is - extremely bitter; it is soluble in 25 parts of ether, in chloroform, - bisulphide of carbon, benzene, and in turpentine; it is not very - soluble in alcohol, and still less soluble in water, but it freely - dissolves in acidulated water. The caustic alkalies precipitate it, - the precipitate being insoluble in excess; it is first white, but - afterwards brick-red. Tannin, picric acid, iodised potassic iodide, - platinic chloride, potassio-mercuric iodide, and mercuric chloride - all give precipitates. Froehde's reagent gives with gelsemine a brown - changing to green. - -[459] Dr. T. G. Wormley separated, in 1870, a non-nitrogenised -remarkably fluorescent body, which he named gelsemic acid (_Amer. Journ. -of Pharm._, 1870), but Sonnenschein and C. Robbins afterwards found -gelsemic acid to be identical with aesculin (_Ber. der deutsch. Chem. -Ges._, 1876, 1182). Dr. Wormley has, however, contested this, stating -that there are differences. (_Amer. Journ. of Pharm._, 1882, p. 337. -_Yearbook of Pharmacy_, 1882, p. 169.) - -[460] The following are its botanical characters:--Calyx five-parted, -corolla funnel-shaped, five-lobed, somewhat oblique, the lobes almost -equal, the posterior being innermost in bud; stamens five; anthers -oblong sagittate, style long and slender; stigmas two, each two-parted, -the divisions being linear; fruit elliptical, flattened contrary to the -narrow partition, two-celled, septicidally two-valved, the valves -keeled; seeds five to six in each cell, large, flat, and winged; embryo -straight in fleshy albumen; the ovate flat, cotyledons much shorter than -the slender radicle; stem smooth, twining and shrubby; leaves opposite, -entire, ovate, or lanceolate, shining on short petioles, nearly -persistent; flowers large, showy, very fragrant, yellow, one to five in -the axil of the leaves. - - Sulphuric acid dissolves gelsemine with a reddish or brownish - colour; after a time it assumes a pinkish hue, and if warmed on the - water-bath, a more or less purple colour; if a small crystal of - potassic bichromate be slowly stirred in the sulphuric acid - solution, reddish purple streaks are produced along the path of the - crystal; ceric oxide exhibits this better and more promptly, so - small a quantity as .001 grain showing the reaction. This reaction - is something like that of strychnine, but nitric acid causes - gelsemine to assume a brownish-green, quickly changing to a deep - green--a reaction which readily distinguishes gelsemine from - strychnine and other alkaloids. - - Sec. 409. =Fatal Dose.=--10 mgrms. killed a frog within four hours, and - 8 mgrms. a cat within fifteen minutes. A healthy woman took an - amount of concentrated tincture, which was equivalent to 11 mgrms. - (1/6 grain), and died in seven and a half hours. - - Sec. 410. =Effects on Animals--Physiological Action.=--Gelsemine acts - powerfully on the respiration; for example, Drs. Sydney Ringer and - Murrell[461] found, on operating on the frog, that in two minutes - the breathing had become distinctly slower; in three and a half - minutes, it had been reduced by one-third; and in six minutes, by - one-half; at the expiration of a quarter of an hour, it was only - one-third of its original frequency; and in twenty minutes, it was - so shallow and irregular that it could no longer be counted with - accuracy. In all their experiments they found that the respiratory - function was abolished before reflex and voluntary motion had become - extinct. In several instances the animals could withdraw their legs - when their toes were pinched, days after the most careful - observations had failed to detect the existence of any respiratory - movement. The heart was seen beating through the chest wall long - after the complete abolition of respiration. - -[461] _Lancet_, vol. i., 1876, p. 415. - - In their experiments on warm-blooded animals (cats), they noticed - that in a few minutes the respirations were slowed down to 12 and - even to 8, and there was loss of power of the posterior extremities, - while at short intervals the upper half of the body was convulsed. - In about half an hour paralysis of the hind limbs was almost - complete, and the respiratory movements so shallow that they could - not be counted. In the case of a dog, after all respiration had - ceased tracheotomy was performed, and air pumped in: the animal - recovered. - - Ringer and Murrell consider that gelsemine produces no primary - quickening of the respiration, that it has no direct action on - either the diaphragm or intercostal muscles, that it paralyses - neither the phrenic nor the intercostal nerves, and that it - diminishes the rate of respiration after both vagi have been - divided. They do not consider that gelsemine acts on the cord - through Setschenow's inhibitory centre, but that it destroys reflex - power by its direct action on the cord, and that probably it has no - influence on the motor nerves. Dr. Burdon Sanderson has also - investigated the action of gelsemine on the respiration, more - especially in relation to the movements of the diaphragm. He - operated upon rabbits; the animal being narcotised by chloral, a - small spatula, shaped like a teaspoon, was introduced into the - peritoneal cavity through an opening in the linea alba, and passed - upwards in front of the liver until its convex surface rested - against the under side of the centrum tendineum. The stem of the - spatula was brought into connection with a lever, by means of which - its to-and-fro movements (and consequently that of the diaphragm) - were inscribed. The first effect is to augment the depth but not the - frequency of the respiratory movements; the next is to diminish the - action of the diaphragm both in extent and frequency. This happens - in accordance with the general principle applicable to most cases of - toxic action--viz., that paresis of a central organ is preceded by - over-action. The diminution of movement upon the whole is - progressive, but this progression is interrupted, because the blood - is becoming more and more venous, and, therefore, the phenomena of - asphyxia are mixed up with the toxical effects. Dr. Sanderson - concludes that the drug acts by paralysing the automatic respiratory - centre; the process of extinction, which might be otherwise expected - to be gradual and progressive, is prevented from being so by the - intervention of disturbances of which the explanation is to be found - in the imperfect arterialisation of the circulating blood. Ringer - and Murrell have also experimented upon the action of gelsemine on - the frog's heart. In all cases it decreased the number of beats; a - small fatal dose produced a white contracted heart, a large fatal - dose, a dark dilated heart; in either case arrest of the circulation - of course followed. - - Sec. 411. =Effects on Man.=--The preparations used in medicine are the - fluid extract and the tincture of gelsemine; the latter appears to - contain the resin of the root as well as the active principle. There - are several cases on record of gelsemine, or the plant itself, - having been taken with fatal effect.[462] Besides a marked effect on - the respiration, there is an effect upon the eye, better seen in man - than in the lower animals; the motor nerves of the eye are attacked - first, objects cannot be fixed, apparently dodging their position, - the eyelids become paralysed, droop, and cannot be raised by an - effort of the will; the pupils are largely dilated, and at the same - time a feeling of lightness has been complained of in the tongue; it - ascends gradually to the roof of the mouth, and the pronunciation is - slurred. There is some paresis of the extremities, and they refuse - to support the body; the respiration becomes laboured, and the pulse - rises in frequency to 120 or 130 beats per minute, but the mind - remains clear. The symptoms occur in about an hour and a half after - taking an overdose of the drug, and, if not excessive, soon - disappear, leaving no unpleasantness behind. If, on the other hand, - the case proceeds to a fatal end, the respiratory trouble increases, - and there may be convulsions, and a course very similar to that seen - in experimenting on animals. Large doses are especially likely to - produce tetanus, which presents some clinical differences - distinguishing it from strychnine tetanus. Gelsemine tetanus is - always preceded by a loss of voluntary reflex power, respiration - ceases before the onset of convulsions, the posterior extremities - are most affected, and irritation fails to excite another paroxysm - till the lapse of some seconds, as if the exhausted cord required - time to renew its energy; finally, the convulsions only last a short - time. - -[462] See _Lancet_, 1873, vol. ii. p. 475; _Brit. Med. and Surg. -Journ._, April 1869; _Phil. Med. and Surg. Reporter_, 1861. - - Sec. 412. _Extraction from Organic Matters, or the Tissues of the - Body._--Dragendorff states that, from as little as half a grain of - the root, both gelsemine and gelsemic acid may be extracted with - acid water, and identified. On extracting with water acidified with - sulphuric acid, and shaking up the acid liquid with chloroform, the - gelsemic acid (aesculin?) is dissolved, and the gelsemine left in the - liquid. The chloroform on evaporation leaves gelsemic acid in little - micro-crystals; it may be identified by (1) its crystallising in - little tufts of crystals; (2) its strong fluorescent properties, one - part dissolved in 15,000,000 parts of water showing a marked - fluorescence, which is increased by the addition of an alkali; and - (3) by splitting up into sugar and another body on boiling with a - mineral acid. After separation of gelsemic acid, the gelsemine is - obtained by alkalising the liquid, and shaking up with fresh - chloroform; on separation of the chloroform, gelsemine may be - identified by means of the reaction with nitric acid, and also the - reaction with potassic bichromate and sulphuric acid. - - -5. COCAINE. - - Sec. 413. =Cocaine= (C_{17}H_{21}NO_{4}).--There are two cocaines--the - one rotating a ray of polarised light to the left, the other to the - right. The left cocaine is contained in the leaves of _Erythroxylon - coca_ with other alkaloids, and is in commerce. - - Cocaine has been used most extensively in medicine since the year - 1884--its chief use being as a local anaesthetic. Chemically cocaine - is a derivative of ecgonin, being ecgonin-methyl-ester. It has a - pyridine nucleus, and may be written - C_{5}H_{4}N(CH_{3})--H_{3}CHO--(COC_{6}H_{5})--CH_{2}COOCH_{3}, or - expressed graphically as follows:-- - - CH_{2} - /\ - CH / \CH_{2} - || | - ||Py| H - || | / - CH \ /C--CHO(C_{6}H_{5}CO)--CH_{2}COOCH_{3}. - \/ - NCH_{3} - - =Properties.=--Cocaine is in the form of four- to six-sided prisms - of the monoclinic system. It is one of the few alkaloids which melt - under the temperature of boiling water, the melting-point being as - low as 85 deg. in water. It readily furnishes a sublimate at 100 deg., - partially decomposing. On boiling with hydrochloric acid cocaine is - decomposed into methyl alcohol, ecgonin, and benzoic acid, according - to the following reaction:-- - - Benzoic - Cocaine. acid. Ecgonin. - C_{17}H_{21}NO_{4} + 2H_{2}O = C_{6}H_{5}COOH + C_{9}H_{15}NO_{3} + - - Methyl - Alcohol. - CH_{3}OH. - - Cocaine is but little soluble in water, but easily dissolves in - ether, alcohol, benzene, chloroform, and carbon disulphide; an - aqueous solution is alkaline to methyl-orange, but not to - phenol-phthalein. It can be made synthetically by the reaction of - ecgonin-methyl-ester with benzoyl chloride. - -Sec. 414. =Cocaine Hydrochlorate= (C_{17}H_{21}NO_{4}HCl).--Crystallised -from alcohol, cocaine hydrochlorate appears in prismatic crystals; these -crystals, according to Hesse,[463] when perfectly pure, should melt at -186 deg., although the melting-point is generally given as 200 deg. or even -202 deg. Cocaine hydrochlorate is soluble in half its weight of water, -insoluble in dry ether, but readily soluble in alcohol, amyl alcohol, or -chloroform. - -[463] O. Hesse, _Annalen_, 276, 342-344. - -Sec.415. =Pharmaceutical Preparations.=--Cocaine hydrochlorate is -officinal. Gelatine discs, weighing 1.31 mgrms. (1/50 grain), and each -containing 0.33 mgrm. (1/200 grain) of the salt are officinal, and used -by ophthalmic surgeons. A solution of the hydrochlorate, containing 10 -per cent. of cocaine hydrochlorate and (for the purposes of preserving -the solution) 0.15 per cent. of salicylic acid is also officinal. -Stronger solutions may also be met with; for instance, a 20 per cent. -solution in oil of cloves for external application in cases of -neuralgia. - -Sec.416. =Separation of Cocaine and Tests.=--Cocaine may be shaken out of -solutions made slightly alkaline by ammonia by treatment with benzene; -it also passes into petroleum ether under the same circumstances. The -best method is to extract a solution, made feebly alkaline, thoroughly -by ether, and then shake it out by benzene and evaporate the separated -benzene at the ordinary air temperature. The property of the alkaloid to -melt at or below the temperature of boiling water, and the ready -decomposition into benzoic acid and other products, render cocaine easy -of identification. If, for instance, a small particle of cocaine is put -in a tube, a drop of strong sulphuric acid added and warmed by the -water-bath, colourless crystals of benzoic acid sublime along the tube, -and an aromatic odour is produced. - -Flueckiger has recommended the production of benzoate of iron as a useful -test both for cocaine and for cocaine hydrochlorate. - -One drop of a dilute solution of ferric chloride added to a solution of -20 mgrms. of cocaine hydrochlorate in 2 c.c. of water, gives a yellow -fluid, which becomes red on boiling from the production of iron -benzoate. This reaction is of little use unless a solution of the same -strength of ferric chloride, but to which the substance to be tested has -not been added, is boiled at the same time for comparison, because all -solutions of ferric chloride deepen in colour on heating. - -A solution of the alkaloid evaporated to dryness on the water-bath, -after being acidulated with nitric acid, and then a few drops of -alcoholic solution of potash or soda added, develops an odour of benzoic -ethyl-ester. Cocaine hydrochlorate, when triturated with calomel, -blackens by the slightest humidity or by moistening it with alcohol. -Cocaine in solution is precipitated by most of the group reagents, but -is not affected by mercuric chloride, picric acid, nor potassic -bichromate. - -Added to the tests above mentioned, there is the physiological action; -cocaine dilates the pupil, tastes bitter, and, for the time, arrests -sensation; hence the after-effect on the tongue is a sensation of -numbness. - -Sec. 417. =Symptoms.=--A large number of accidents occur each year from the -external application of cocaine; few, however, end fatally. Cocaine has -thus produced poisonous symptoms when applied to the eye, to the rectum, -to the gums, to the urethra, and to various other parts. There have been -a few fatal cases, both from its external and internal administration; -Mannheim, for example, has collected eleven of such instances. - -The action of cocaine is twofold; there is an action on the central and -the peripheral nervous system. In small doses cocaine excites the spinal -cord and the brain; in large it may produce convulsions and then -paralysis. The peripheral action is seen in the numbing of sensation. -There is always interference with the accommodation of vision, and -dilatation of the pupil. The eyelids are wider apart than normal, and -there may be some protrusion of the eyeball. - -The usual course of an acute case of poisoning is a feeling of dryness -in the nose and throat, difficulty of swallowing, faintness, and there -is often vomiting; the pulse is quickened; there is first cerebral -excitement, followed usually by great mental depression. Occasionally -there is an eruption on the skin. Hyperaesthesia of the skin is followed -by great diminution of sensation, the pupils, as before stated, are -dilated, the eyes protruding, the eyelids wide open, the face is pale, -and the perspiration profuse. Convulsions and paralysis may terminate -the scene. Death takes place from paralysis of the breathing centre; -therefore the heart beats after the cessation of respiration. As an -antidote, nitrite of amyl has apparently been used with success. - -There is a form of chronic poisoning produced from the taking of small -doses of cocaine daily. The symptoms are very various, and are referable -to disturbance of the digestive organs, and to the effect on the nervous -system. The patients become extremely emaciated, and it seems to produce -a special form of mania. - -Sec. 418. =Post-mortem Appearances.=--The appearances found in acute cases -of poisoning have been hyperaemia of the liver, spleen, and kidneys, as -well as of the brain and spinal cord. - -In the experimental poisoning of mice with cocaine Ehrlich[464] found a -considerable enlargement of the liver. - -[464] _Deutsche med. Wochens._, 1890, No. 32. - -Sec. 419. =Fatal Dose.=--The fatal dose, according to Mannheim,[465] must -be considered as about 1 grm. (15.4 grains); the smallest dose known to -have been fatal is 0.08 grm. (1.2 grain) for an adult, and 0.05 grm. -(0.7 grain) for a child. - -[465] _Deutsch. Arch. f. klin. Med._, Bd. viii., 1891, 380. - - -6. CORYDALINE. - - Sec. 420. =Corydaline= (C_{22}H_{28}NO_{4}) is an alkaloid discovered - by Wackenroder (1826) in the tubers of _Corydalis tuberosa_; - crystallised in the cold and away from light, out of a mixture of - absolute alcohol and ether, corydaline forms colourless, flat, - prismatic crystals, which quickly turn yellow on exposure to light - or heat. Pure corydaline changes colour at about 125 deg., softens at - about 133 deg., and melts finally at 134 deg. to 135 deg. It dissolves in - ether, chloroform, carbon disulphide, and benzene, but not so - readily in alcohol. It is almost insoluble in cold water, and but - slightly soluble in boiling water. Water precipitates it from a - solution in alcohol. It is also soluble in dilute hydrochloric and - sulphuric acids. It gives a precipitate with potassium iodide if a - solution of the hydrochloride be used. The precipitate crystallises - out of hot water in clusters of short lemon-yellow prismatic - crystals, and has the formula of C_{22}H_{28}NO_{4}HI. Corydaline - platinochloride has the composition of - (C_{22}H_{28}NO_{4})_{2}H_{2}PtCl_{6}, containing Pt 16.94 per - cent., and 2.44 per cent. of N.--Dobbie & Lauder, _Journ. Chem. - Soc._, March 1892, 244. - - Corydaline in large doses causes epileptiform convulsions. Death - takes place from respiratory paralysis. - - -V.--The Aconite Group of Alkaloids. - -Sec. 421. The officinal aconite is the _Aconitum napellus_--monkshood or -wolfsbane--a very common garden plant in this country, and one -cultivated for medicinal purposes. Many varieties of aconite exist in -other regions, which either are, or could be, imported. Of these the -most important is the _Aconitum ferox_, a native of the Himalayan -mountains, imported from India. - -All the aconites, so far as known, are extremely poisonous, and it -appears probable that different species contain different alkaloids. The -root of _A. napellus_ is from 2 to 4 inches long, conical in shape, -brown externally, and white internally. The leaves are completely -divided at the base into five wedge-shaped lobes, each of the five lobes -being again divided into three linear segments. The numerous seeds are -three-sided, irregularly twisted, wrinkled, of a dark-brown colour, in -length one-sixth of an inch, and weighing 25 to the grain (_Guy_). The -whole plant is one of great beauty, from 2 to 6 feet high, and having a -terminal spike of conspicuous blue flowers. The root has been fatally -mistaken for horse-radish, an error not easily accounted for, since no -similarity exists between them. - -Sec. 422. =Pharmaceutical Preparations of Aconite.=--The preparations of -aconite used in medicine are-- - -=Aconitine=, officinal in all the pharmacop[oe]ias. - -=Aconite liniment= (=linimentum aconiti=), made from the root with -spirit, and flavoured with camphor; officinal in the British -Pharmacop[oe]ia. It may contain about 2.0 per cent. of aconitine. - -=Aconite tincture=, officinal in all the pharmacop[oe]ias. - -=Aconite ointment=, 8 grains of aconitine to the oz. (_i.e._, 1.66 per -cent.); officinal in the British Pharmacop[oe]ia. - -=Aconite extract=, the juice of the leaves evaporated; officinal in most -of the pharmacop[oe]ias. The strength in alkaloid of the extract varies; -in six samples examined by F. Casson, the least quantity was 0.16 per -cent., the maximum 0.28 per cent.[466] - -[466] _Pharm. Journ._, 1894, 901. - -=Fleming's tincture of aconite= is not officinal, but is sold largely in -commerce. It is from three to four times stronger than the B.P. -tincture. - -Sec. 423. =The Alkaloids of Aconite.=--The researches of Dr. Alder Wright -and Luff, and especially those of Professor Dunstan,[467] have -established that in the root of the true aconite there exist four -alkaloids, one only of which has been as yet crystallised. - -[467] Various papers in _Journ. Chem. Soc._, 1892-1894. - -Three of the alkaloids have been fairly well worked out; the fourth -homo-napelline has not yet been satisfactorily investigated. - -The three alkaloids are aconitine, aconine and benzoyl-aconine; besides -which pyraconitine and pyraconine can be obtained by suitable treatment -from aconitine and aconine. - -The formulae of the alkaloids and their derivatives are as follows:-- - - Aconitine - (acetyl-benzoyl-aconine), m.p., 188.60 deg., C_{33}H_{45}NO_{12} - Benzoyl-aconine, m.p., 268.0 deg., C_{31}H_{43}NO_{11} - Pyraconitine - (anhydro-benzoyl-aconine), m.p., 188-190 deg., C_{31}H_{41}NO_{10} - Aconine, m.p., 132 deg., C_{24}H_{39}NO_{10} - Pyraconine (anhydro-aconine), C_{24}H_{37}NO_{9} - -Sec. 424. =Aconitine=, C_{33}H_{45}NO_{12}.--This base has been shown by -Dunstan to be acetyl-benzoyl-aconine; one molecule of the base breaking -up, on complete hydrolysis, into one molecule of aconine, one of acetic -acid, and one of benzoic acid-- - - Acetic Benzoic - Acid. Acid. - C_{33}H_{45}NO_{12} + 2H_{2}O = C_{2}H_{4}O_{2} + C_{7}H_{6}O_{2} + - - Aconine. - C_{24}H_{39}NO_{10}. - -That is to say that 100 parts of aconitine, according to theory, should -yield:-- - -Acetic acid, 9.37 per cent.; benzoic acid, 18.85 per cent.; and aconine, -77.52 per cent. - -Pure aconitine has a tube melting-point of 188.6 deg. The behaviour of a -sample of Merck's aconitine in the subliming cell, which had a -melting-point of 184 deg., was as described at page 259. - -Aconitine dissolves in water at 22 deg. in the proportion of 1 in 4431 -(_Dunstan_); it is soluble in 37 of absolute alcohol, 64 of anhydrous -ether, 5.5 parts of chloroform and benzene (_A. Jurgens_); it has basic -properties, and a cold watery solution has an alkaline reaction to -cochineal, but not to litmus nor to phenol-phthalein. Aconitine is not -precipitated by mercuric potassium iodide, but gives a voluminous -precipitate with an aqueous solution of iodine in potassium iodide. - -It gives a crystalline yellow gold compound with gold chloride, which -has a melting-point of 135.5 deg., and according to its composition, -C_{33}H_{45}NO_{12}HAuCl_{4}, should give 19.9 per cent. of gold. - -Aconitine is best extracted from the plant, or from organic matters -generally, by a 1 per cent. sulphuric acid; this strength is stated not -to hydrolyse aconitine if acting in the cold; after purifying the acid -liquid by shaking it with amyl alcohol, and then with chloroform, -_always operating in the cold_, the liquid is precipitated by ammonia in -very slight excess, and the liquid shaken with ether; the ether is -removed, dehydrated by standing over calcium chloride, and then -evaporated spontaneously; should the aconitine be mixed with the other -alkaloids, advantage can be taken of the method of separating -aconitine by converting it into hydrobromide, as described under -"Benzoyl-aconine." - -Sec. 425. =Tests for Aconitine.=--The most satisfactory and the most -delicate is the physiological test; the minutest trace of an -aconite-holding liquid, applied to the tongue or lips, causes a peculiar -numbing, tingling sensation which, once felt, can readily be remembered. - -An alkaloidal substance which, heated in a tube, melts approximately -near the melting-point of aconitine, and gives off an acid vapour, would -render one suspicious of aconitine, for most alkaloids give off alkaline -vapours. Aconitine also may, by heating with dilute acids, be made to -readily yield benzoic acid, an acid easy of identification. Aconitine -dissolved in nitric acid, evaporated to dryness, and then treated with -alcoholic potash, gives off an unmistakable odour of benzoic ester. - -Should there be sufficient aconitine recovered to convert it into the -gold salt, the properties of the gold salt (that is, its melting-point, -and the percentage of gold left after burning) assist materially in the -identification. - -A minute quantity of aconitine dissolved in water, acidified with -acetic acid, and a particle of KI added and the solution allowed to -evaporate, gives crystals of aconitine hydriodide, from which water will -dissolve out the KI. Iodine water gives a precipitate of a reddish-brown -colour in a solution of 1 : 2000.[468] - -[468] A. Jurgens, _Arch. Pharm._ (3), xxiv. 127, 128. - -The chemical tests are supplementary to the physiological; if the -alkaloidal extract does not give the tingling, numbing sensation, -aconitine cannot be present. - -Sec. 426. =Benzoyl-aconine ("isaconitine")=, C_{31}H_{43}NO_{11}, is -obtained from aconitine by heating an aqueous solution of the sulphate -or hydrochloride in a closed tube at 120 deg.-130 deg. for two or three hours, a -molecule of acetic acid (9.27 per cent.) being split off, and -benzoyl-aconine left. - -It may be separated from the mixed alkaloids of the _Aconitum napellus_ -by dissolving in a 5 per cent. solution of hydrobromic acid (excess of -acid being avoided), precipitating with a slight excess of ammonia, and -shaking out with ether. The residue left after the ether is evaporated -chiefly consists of aconitine; it is dissolved in just sufficient -hydrobromic acid and the exactly neutral hydrobromate solution allowed -to evaporate spontaneously in a desiccator; crystals of aconitine -hydrobromide separate out, the mother liquor containing some -benzoyl-aconine and "homonapelline." The aqueous solution which has been -exhausted with ether is now shaken out with chloroform. This chloroform -solution contains most of the benzoyl-aconine, and on separation the -residue is dissolved in just sufficient hydrochloric acid to form a -neutral solution; this solution is concentrated on the water-bath with -constant stirring, crystals of the hydrochloride form, and are filtered -off from time to time and washed with a little cold water, the washings -being added to the original liquid; the different fractions are mixed -together, and the process repeated until they have a melting-point of -268 deg. Benzoyl-aconine is obtained from the hydrochloride by -precipitating the aqueous solution by the addition of dilute ammonia, -and extracting the solution with ether; the solution in ether is washed -with water, dried by means of calcium chloride, and then distilled off. -Benzoyl-aconine is left as a transparent colourless non-crystalline -varnish of a melting-point near 125 deg. - -The solution in water is alkaline to litmus. The base is readily soluble -in alcohol, in chloroform, and in ether. The alcoholic solution is -dextrorotatory. The solutions are bitter, but do not give the tingling -sensation characteristic of aconitine. The hydrochloride, the -hydrobromide, the hydriodide, and the nitrate have been obtained in a -crystalline state. The most characteristic salt is, however, the -aurochlor derivative. When aqueous solutions of benzoyl-aconine chloride -and auric chloride are mixed, a yellow precipitate is thrown down, -which (dissolved in alcohol, after being dried over calcium chloride, -and slowly evaporated in a desiccator) deposits colourless crystals -entirely different from the yellow crystals of aconitine gold chloride. -These crystals have the composition C_{31}H_{42}(AuCl_{2})NO_{11}, and -therefore, by theory, should yield 22.6 per cent. of gold, and 8.2 per -cent. of chlorine. - -By hydrolysis benzoyl-aconine yields benzoic acid, which can be shaken -out of an acid solution by ether and identified; one molecule of benzoic -acid is formed from one molecule of benzoyl-aconine. Twenty per cent. of -benzoic acid should, according to the formula, be obtained; Professor -Dunstan found only 18.85 per cent.[469] - -[469] Professor Dunstan found, as a means of two determinations, 21.6 -per cent. of gold, and 7.8 per cent. of chlorine, which comes nearer his -old formula of C_{33}H_{44}(AuCl_{2})NO_{12}.--_Journ. Chem. Soc._, -April 1893. - -Benzoic acid in the subliming cell begins to give a cloud at about -77 deg.-80 deg., and at or near 100 deg. sublimes most rapidly. - -Benzoic acid, recovered from an acid solution by shaking out with -ether, may be recognised as follows:--To the film left on evaporating -off the ether add a drop of H_{2}SO_{4}, and a few crystals of sodic -nitrate, and heat gently for a short time; pour the clear liquid -into ammonia water, and add a drop of ammonium sulphide. A red-brown -colour indicates benzoic acid. The _rationale_ of the test is as -follows:--Dinitro-benzoic acid is first formed, and next, by the action -of ammonium sulphide, this is converted into the red-brown ammonium -diamidobenzoate.--E. Mohler, _Bull. Soc. Chem._ (3), iii. 414-416. - -Sec. 427. =Pyraconitine=, C_{31}H_{41}NO_{10}, is anhydro-benzoyl-aconine; -it differs from benzoyl-aconine by a molecule of water; picraconitine is -obtained by keeping aconitine at its melting-point (188 deg.-190 deg.) for some -time, when acetic acid distils over and pyraconitine is left. -Pyraconitine is an amorphous varnish, sparingly soluble in water, but -readily dissolving in alcohol, chloroform, and ether; it gives a pale -yellow precipitate with gold chloride, and forms crystalline salts with -hydriodic, hydrobromic, and hydrochloric acids. Pyraconitine readily -undergoes hydrolysis by the action of dilute acids, or by potash or -soda, or with water in a closed tube; the products are benzoic acid and -an alkaloid, to which the name of pyraconine has been given. - -Sec. 428. =Pyraconine=, C_{24}H_{37}NO_{9}.--This base is anhydro-aconine, -the formula differing from aconine by one atom of water. It is -amorphous, closely resembling aconine; it is soluble in water and ether; -the aqueous solution has a somewhat sweet taste, and is laevorotatory; it -combines with acids to form crystalline salts, which are very soluble in -water. - -Sec. 429. =Aconine=, C_{24}H_{39}NO_{10}, m.p. 132 deg.--Aconine does not -crystallise. Its aqueous solution is decidedly alkaline, and, like -aconitine, it is laevorotatory, although to a less degree. Its taste is -bitter, but causes no tingling sensation. Aconine is very soluble in -water or alcohol, and slightly in chloroform, but insoluble in ether or -in petroleum ether. It does, however, dissolve, in the presence of -aconitine, slightly in ether. The aqueous solutions reduce the salts of -gold and silver, and also Fehling's solution. A solution of aconine -gives precipitates with the general alkaloidal reagents; with mercuric -chloride it gives a copious yellow precipitate, which darkens on -standing. - -Aconine hydrochloride, the hydriodide, the hydrobromide, and the -sulphate, have all been crystallised; solutions of these salts are -laevorotatory. - -Sec. 430. =Commercial Aconitine and the Lethal Dose of -Aconitine.=--Commercial aconitine has in the past varied in appearance -from that of a gummy amorphous mass up to a purer kind in white -crystals. - -Professor Dunstan[470] has recently examined fourteen samples, some of -them of considerable age, and only found two samples (one of English, -another of German make) which approached in melting-point and -crystalline appearance pure aconitine; the one, the English, melted at -186 deg.-187 deg., and contained about 3 per cent. of benzoyl-aconine; the -other, a German specimen, was almost pure; the melting-point was 187.5 deg. -At the present time it is, however, not difficult to obtain fairly pure -crystalline aconitine, and to assay it accurately by determining the -proportion of acetic and benzoic acids. The physiological action of -commercial aconitine is, however, in all cases the same, the difference -being in quantitative not qualitative action; in the small doses usually -administered, the physiological action depends wholly upon the true -aconitine present, the other bases being practically without toxic -action. Professor Plugge[471] has made some researches on the fatal dose -(for the lower animals) of Petit's, Merck's, and Friedlaender's aconitine -nitrate, which in 1882 were the purest in commerce. He administered the -following doses to the animals mentioned:-- - -[470] _Journ. Chem. Soc. Trans._, 1893, 491. - -[471] _Archiv de Pharm._, Jan. 7, 1882. - -TABLE SHOWING FATAL DOSES (FOR ANIMALS) OF ACONITINE. - -PETIT'S CRYSTALLINE ACONITINE NITRATE. - - +--------------+------------+-----------+----------------------+ - | Animals | Dose | Dose | | - |Experimented | Given. | per | Result. | - | upon. | | Kilogrm. | | - +--------------+------------+-----------+----------------------+ - | A Frog, | .4 mgrm. | 16.0 | Death in 60 Minutes. | - | A Rabbit, | .8 " | .5-.6 | " 30 " | - | A Dog, | 1.6 " | .21 | " 20 " | - | " | .45 " | .10 | " 140 " | - | " | .50 " | .054 | Recovered. | - | " | .60 " | .075 | Recovered. | - | A Pigeon, | .07 " | .22 | Death in 21 Minutes. | - +--------------+------------+-----------+----------------------+ - -MERCK'S ACONITINE NITRATE. - - +--------------+------------+-----------+----------------------+ - | Animals | Dose | Dose | | - |Experimented | Given. | per | Result. | - | upon. | | Kilogrm. | | - +--------------+------------+-----------+----------------------+ - | A Frog, | .4 mgrm. | 16 | Recovered. | - | " | 1.0 " | 40 | Died in 110-360 Min. | - | " | 2.0 " | 80 | " 75-130 " | - | " | 4.0 " | 160 | " 50 " | - | A Rabbit, | 3.5 " | 2 | " 75 " | - | " | 10 " | 6.50 | " 15 " | - | A Dog, | 10 " | 1.65 | " 15 " | - | A Pigeon, | ... | 1.65 | Recovered. | - +--------------+------------+-----------+----------------------+ - -FRIEDLAeNDER'S ACONITINE NITRATE. - - +--------------+------------+-----------+----------------------+ - | Animals | Dose | Dose | | - |Experimented | Given. | per | Result. | - | upon. | | Kilogrm. | | - +--------------+------------+-----------+----------------------+ - | A Frog, | 4 mgrms. | 160 | Recovered. | - | | | | | - | " | 10 " | 400 } | Death in | - | " | 20 " | 800 } | more than | - | " | 40 " | 1600 } | 60 minutes. | - | | | | | - | A Rabbit, | 6 " | 4.11 | Recovered. | - | " | 24 " | 18.00 | " | - | " | 50 " | 85.50 | " | - | A Dog, | 28 " | 6.00 | " | - | A Pigeon, | 10 " | 33.4 | " | - +--------------+------------+-----------+----------------------+ - -The conclusions Plugge draws from his researches are that Petit's -aconitine was at least eight times stronger than that of Merck, and -seventy times more toxic than that of Friedlaender, while Merck's -"aconitine again was twenty to thirty times stronger than -Friedlaender's." He was inclined to put seven commercial samples which he -has examined in the following diminishing order of toxicity:--(1) -Petit's crystalline aconitine nitrate; (2) Morson's aconitine nitrate; -(3) Hottot's aconitine nitrate; (4) Hopkins & Williams' pseudaconitine; -(5) Merck's aconitine nitrate; (6) Schuchart's aconitine sulphate; and -(7) Friedlaender's aconitine nitrate. - -From a study of Dr. Harley's experiments,[472] however, made a few years -ago, there would appear to have been but little difference between the -activity of Petit's and Morson's aconitine. Dr. Harley experimented on a -young cat, 3 lbs. in weight, and nearly killed it with a 1/1000 of a -grain of Morson's aconitine; two other cats, also weighing 3 lbs. each, -died in seven and a half hours and three-quarters of an hour -respectively, killed from a subcutaneous dose of of a grain. Reducing -these values to the ordinary equivalents, the dose, after which the cat -recovered with difficulty, is equal to about .048 mgrm. per kilo., -while a certainly fatal dose is .092 mgrm. per kilo.; therefore, it -seems likely that the least fatal dose for Morson's, as for Petit's, is -some number between .075 and .09 mgrm. per kilo. - -[472] "On the Action and Use of Aconitine," _St. Thos. Hosp. Report_, -1874. - -Man is evidently more sensitive to aconitine than any of the dogs or -cats experimented upon, since, in the German cases to be recorded, 1.6 -mgrm. of Petit's aconitine nitrate, taken by the mouth, gave rise to -symptoms so violent that it was evidently a dangerous dose, while 4 -mgrms. were rapidly fatal; but if man took the same amount per kilo. as -dogs or cats, he would require a little over 6 mgrms. to be certainly -fatal. It seems, then, from the evidence obtainable, that .03 grain (2 -mgrms.) is about the least fatal dose for an adult man of standard -weight. This dose is equal to .028 mgrm. per kilo., and, of course, -refers either to Morson's aconitine or French aconitine, the alkaloid -being taken by the mouth. If given by subcutaneous injection, probably -1.5 mgrm. would kill, for the whole of the poison is then thrown on the -circulation at one time, and there is no chance of its elimination by -vomiting. - -The lethal dose of the pure alkaloid being even approximately settled, -it is possible to get a more exact idea as to the suitable medicinal -dose of the tincture and extract, and also to study more profitably the -"quantitative toxicity." The English officinal tincture, although -variable in strength, may for our purposes be regarded as averaging 1 -per cent. of alkaloid--that is, in every 100 parts by volume there will -be 1 part of the alkaloid by weight, and Fleming's tincture may be -considered as one-third stronger, containing in every 100 parts 1.3 part -of alkaloid. The medicinal dose of the P.B. tincture is laid down as -from 5 to 15 min.--equal to from .005 to .015 grain of aconitine. The -German pharmacop[oe]ia gives the maximum single dose as 1 c.c. (say 15 -mins.), and the maximum quantity to be taken in the twenty-four hours as -four times that quantity. As before stated, 2 mgrms. (.030 grain) of -aconitine being considered a fatal dose, this is equivalent to about 2 -c.c. (30 mins.) of the P.B. tincture, or to 1.2 c.c. (20 mins.) of -Fleming's tincture in a single dose; and on these theoretical grounds I -should consider this dose dangerous, and in the absence of prompt -treatment likely to be fatal to an adult man. The usual least fatal dose -laid down in medical toxicological works, however, is greater than -this--viz., 3.75 c.c. (a drachm). - -In 1863 a woman took 70 minims of Fleming's tincture, and a grain of -acetate of morphine, and died in about four hours; but as this was a -complex case of poisoning, it is not of much value. Fifteen minims of -the tincture caused very serious symptoms in the case of a woman under -the care of Dr. Topham,[473] the effects lasting many hours. Probably -the smallest quantity of the tincture recorded as having destroyed life -is in the case of Dr. Male, of Birmingham.[474] He died from the -effects of 80 drops taken in ten doses, extending over a period of four -days--the largest dose at any one time being 10 drops, the total -quantity would perhaps equal .08 grain of aconitine. - -[473] _Lancet_, July 19, 1851, p. 56. - -[474] _Med. Gaz._, vol. xxxvi. p. 861, quoted by Taylor, _Prin. of Med. -Juris._, vol. i. p. 426. - -The P.B. extract is not a very satisfactory preparation, varying much in -strength. It may be taken to average about .6 per cent., and if so, -applying the same reasoning as before, from .26 to .32 grm. (4 to 5 -grains) would be a fatal dose.[475] On the other hand, there is an -alcoholic extract which is very powerful, and averages 5 per cent. of -aconitine: 40 mgrms. (.6 grain) of this extract would be likely to be -fatal. With regard to the root itself, 3.8 grms. (60 grains) have been -known to produce death, and from the average alkaloidal contents it is -probable that .648 grm. (10 grains) would be a highly dangerous dose. -Dunstan's researches will now alter probably the whole of the pharmacy -of aconite, and the tendency will be to make the preparations of greater -activity, and, consequently, to make the dangerous doses smaller than -formerly. - -[475] But there is a case reported by Dr. Vachell, of Cardiff, in which -2 grains of extract of aconite taken in pills proved fatal. Now 2 grains -is the medicinal dose, laid down as a maximum in the pharmacop[oe]ia; a -complete revolution is, therefore, necessary in the use of these active -remedies. No extract or tincture should be used until its approximate -strength in active principles is determined. - -Sec. 431. =Effects of Aconitine on Animal Life.=--There are few substances -which have been experimented upon in such a variety of ways and upon so -many classes of animals as aconitine in different forms; but there does -not seem to be any essential difference in the symptoms produced in -different animals save that which is explained by the organisation of -the life-form under experiment. - -=Insects.=--The author has made experiments with the active principles -of aconite upon blow-flies. An extract was made by allowing the ordinary -tincture to evaporate spontaneously at the temperature of the -atmosphere. If a minute dot of this is placed upon the head of a -blow-fly, absorption of the active principle takes place in from fifteen -to thirty minutes, and marked symptoms result. The symptoms consist -essentially of muscular weakness, inability to fly, and to walk up -perpendicular surfaces; there is also, in all cases, a curious -entanglement of the legs, and very often extrusion of the proboscis; -trembling of the legs and muscular twitchings are frequent. A -progressive paralysis terminates in from four to five hours in death; -the death is generally so gradual that it is difficult to know when the -event occurs, but in one case there were violent movements of the body, -and sudden death.[476] - -[476] It may be well to quote in full a typical experiment. Six P.M., a -little extract smeared on the head of a blow-fly. Forty-five minutes -after--makes no attempt to fly, great muscular weakness, no trembling or -convulsive movements. Fifty minutes after--partial paralysis of right -half of body, so that the fly, on moving, goes in a circular direction, -the second pair of legs are curiously bent forward and useless; the -wings seem fairly strong. Seventy-five minutes--fly very dull, always in -one spot, without movement; when placed on a horizontal glass surface, -and the glass then very slowly inclined, until it is at last quite -perpendicular, the fly falls. There is now a strange entanglement of the -legs. 125 minutes--perfectly paralysed; 145 minutes--dead. - -=Fish.=--The action on fish has been studied by Schulz and Praag. There -is rapid loss of power and diminished breathing; the respiration seems -difficult, and the fish rapidly die. - -=Reptiles--Frogs.=--The most recent experiments on frogs are those of -Plugge, and although his interpretation of the phenomena in some points -is different from that of previous observers, the symptoms themselves -are, as might have been expected, not different from those described by -Achscharumow, L. v. Praag, and others. Plugge found no qualitative -difference in the action of any of the commercial samples of aconitine. -This fact gives the necessary value to all the old experiments, for we -now know that, although they were performed with impure or weak -preparations, yet there is no reason to believe that the symptoms -described were due to any other but the alkaloid aconitine in varying -degrees of purity or dilution. Frogs show very quickly signs of weakness -in the muscular power; the respiration invariably becomes laboured, and -ceases after a few minutes; the heart's action becomes slowed, -irregular, and then stops in diastole. The poisoned heart, while still -pulsating, cannot be arrested either by electrical stimulation of the -vagus or by irritation of the sinus, nor when once arrested can any -further contraction be excited in it. Opening of the mouth and apparent -efforts to vomit, Plugge observed both with _Rana esculenta_ and _Rana -temporaria_. He considers them almost invariable signs of aconitine -poisoning. A separation of mucus from the surface of the body of the -frog is also very constantly observed. Dilatation of the pupils is -frequent, but not constant; there may be convulsions, both of a clonic -and tonic character, before death, but fibrillar twitchings are seldom. -(With regard to the dose required to affect frogs, see _ante_, pp. 355 -and 356.) - -=Birds.=--There is a discrepancy in the descriptions of the action of -aconitine on birds. L. v. Praag thought the respiration and circulation -but little affected at first; while Achscharumow witnessed in pigeons -dyspn[oe]a, dilatation of the pupils, vomiting, shivering, and paresis. -It may be taken that the usual symptoms observed are some difficulty in -breathing, a diminution of temperature, a loss of muscular power -generally (but not constantly), dilatation of the pupils, and -convulsions before death. - -=Mammals.=--The effects vary somewhat, according to the dose. Very large -doses kill rabbits rapidly. They fall on their sides, are violently -convulsed, and die in an asphyxiated condition; but with smaller doses -the phenomena first observed are generally to be referred to the -respiration. Thus, in an experiment on the horse, Dr. Harley found that -the subcutaneous administration of .6 mgrm. (.01 grain) caused in a -weakly colt some acceleration of the pulse and a partial paralysis of -the dilator narium. Double the quantity given to the same animal some -time after, caused, in six hours and a half, some muscular weakness, and -an evident respiratory trouble. The horse recovered in eighteen hours. -2.7 mgrms. (1/24 grain) given in the same way, after a long interval of -time, caused, at the end of an hour, more pronounced symptoms; the -pulse, at the commencement 50, rose in an hour and a half to 68, then -the respiration became audible and difficult. In an hour and -three-quarters there were great restlessness and diminution of muscular -power. Two hours after the injection the muscular weakness increased so -much that the horse fell down; he was also convulsed. After eight hours -he began to improve. In another experiment, 32.4 mgrms. (1/2 grain) -killed a sturdy entire horse in two hours and twenty minutes, the -symptoms commencing within the hour, and consisting of difficulty of -breathing, irregularity of the heart's action, and convulsions. - -The general picture of the effects of fatal, but not excessive, doses -given to dogs, cats, rabbits, &c., resembles closely that already -described. The heart's action is at first slowed, then becomes quick and -irregular, there is dyspn[oe]a, progressive paralysis of the muscular -power, convulsions, and death in asphyxia. Vomiting is frequently -observed, sometimes salivation, and very often dilatation of the pupil. -Sometimes the latter is abnormally active, dilating and contracting -alternately. Diarrh[oe]a also occurs in a few cases. Vomiting is more -frequent when the poison is taken by the mouth than when administered -subcutaneously.[477] - -[477] The more important physiological researches on the action of -aconite are contained in the following works and papers:-- - - FLEMING, A.--_An Inquiry into the Physiological and Medicinal - Properties of the Aconitum napellus_, to which are added - observations on several other species of aconite, 8vo, Lond., 1845. - - SCHULZ, F. W.--_De Aconitini Effectu in Organismum Animalium._ - - V. PRAAG.--_Arch. f. Path. Anat._, vii. p. 438, 1854. - - HOTTOT, E.--_De l'Aconitine et de ses Effets Physiologiques_, 4to, - Paris, 1863. - - ACHSCHARUMOW.--_Arch. f. Anatom. u. Physiol._, 1866. - - BOeHN.--_Herzgifte_, 1871. - - EWERS, C.--_Ueber die physiologischen Wirkungen des aus Aconitum - ferox dargestellten Aconitins_ (_Pseudoaconitin, Aconitinum - anglicum, Nepalin_), 8vo, Dorpat, 1873. - - GUILAUD.--_De l'Aconite et de l'Aconitine_, 4to, Montpellier, 1874. - - FRANCHESCHINI, M. A.--_Contribution a l'Etude de l'Action - Physiologique et Therapeutique de l'Aconitine_, 4to, Paris, 1875. - - LEWIN.--_Exp. Untersuch. ueber die Wirkung d. Aconitins auf's Herz. - Diss._, Berlin, 1875. - - GIULINI, P.--_Experimentelle Untersuchungen ueber die Wirkung des - Aconitins auf das Nervensystem, das Herz, u. die Athmung_, 8vo, - Erlangen, 1876. - - HARLEY, DR. JOHN.--"On the Action and Uses of Aconitia," _St. Thos. - Hosp. Reports_, 1874. - - V. SCHROFF, C. Jr.--_Beitrag zur Kenntniss des Aconit._, 8vo, Wien, - 1876. - - PLUGGE, P. C.--"Untersuchungen ueber die physiologische Wirkung - verschiedener Handelssorten von Aconitin, u. Pseudoaconitin auf - Muskeln u. Nerven," _Virch. Archiv_, Bd. 87, 1882, S. 410. - - -Sec. 432. =Statistics.=--During the ten years, 1883-92, there were recorded -in England and Wales, 40 accidental deaths from the various forms of -aconite (19 males, 21 females); and 19 suicidal deaths (9 males, 10 -females) from the same cause, which makes a total of 59. - -Sec. 433. =Effects on Man.=--I have collected from European medical -literature, 87 cases of poisoning by aconite in some form or other. -These comprise only 2 cases of murder, 7 of suicide, and 77 which were -more or less accidental. Six of the cases were from the use of the -alkaloid itself; 10 were from the root; in two cases children eat the -flowers; in 1, the leaves of the plant were cooked and eaten by mistake; -in 7, the tincture was mistaken for brandy, sherry, or liqueur; the -remainder were caused by the tincture, the liniment, or the extract. - -Sec. 434. =Poisoning by the Root.=--A case of murder which occurred some -years ago in America, and also the Irish case which took place in 1841 -(_Reg._ v. _M'Conkey_), were, until the recent trial of Lamson, the only -instances among English-speaking people of the use of aconite for -criminal purposes; but if we turn to the Indian records, we find that it -has been largely used from the earliest times as a destroyer of human -life. In 1842 a tank of water destined for the use of the British army -in pursuit of the retreating Burmese, was poisoned by intentional -contamination with the bruised root of _Aconitum ferox_; it was -fortunately discovered before any harm resulted. A preparation of the -root is used in all the hill districts of India to poison arrows for the -destruction of wild beasts. A Lepcha described the root to a British -officer as being "useful to sportsmen for destroying elephants and -tigers, useful to the rich for putting troublesome relations out of the -way, and useful to jealous husbands for the purpose of destroying -faithless wives." From the recorded cases, the powdered root, mixed with -food, or the same substance steeped in spirituous liquor, is usually the -part chosen for administration. In M'Conkey's case, the man's wife -purchased powdered aconite root, mixed it with pepper, and strewed it -over some greens, which she cooked and gave to him. The man complained -of the sharp taste of the greens, and soon after the meal vomited, and -suffered from purging, became delirious with lock-jaw, and clenching of -the hands; he died in about three hours. The chief noticeable -_post-mortem_ appearance was a bright red colour of the mucous membrane -of the stomach. - -The symptoms in this case were, in some respects, different from those -met with in other cases of poisoning by the root. A typical case is -given by Dr. Chevers (_op. cit._), in which a man had taken by mistake a -small portion of aconite root. Immediately after chewing it he felt a -sweetish taste, followed immediately by tingling of the lips and tongue, -numbness of the face, and severe vomiting. On admission to hospital he -was extremely restless, tossing his limbs about in all directions and -constantly changing his position. He complained of a burning sensation -in the stomach, and a tingling and numbness in every part of the body, -excepting his legs. The tingling was specially marked in the face and -tongue--so much so that he was constantly moving the latter to and fro -in order to scratch it against the teeth. Retching and vomiting occurred -almost incessantly, and he constantly placed his hand over the cardiac -region. His face was anxious, the eyes suffused, the lips pale and -exsanguine, the eyelids swollen, moderately dilated, and insensible to -the stimulus of light; the respiration was laboured, 64 in a minute; the -pulse 66, small and feeble. There was inability to walk from loss of -muscular power, but the man was perfectly conscious. The stomach-pump -was used, and albumen and milk administered. Three and three-quarter -hours after taking the root the symptoms were increased in severity. The -tongue was red and swollen, the pulse intermittent, feeble, and slower. -The tingling and numbness had extended to the legs. On examining the -condition of the external sensibility with a pair of scissors, it was -found that, on fully separating the blades and bringing the points in -contact with the skin over the arms and forearms, he felt them as one, -although they were 4 inches apart. But the sensibility of the thighs and -legs was less obtuse, for he could feel the two points distinctly when -they were 4 inches apart, and continued to do so until the distance -between the points fell short of 2-3/4 inches. He began to improve about -the ninth hour, and gradually recovered, although he suffered for one or -two days from a slight diarrh[oe]a. As in the case detailed (p. 363), no -water was passed for a long time, as if the bladder early lost its -power. - -Sec. 435. =Poisoning by the Alkaloid Aconitine.=--Probably the earliest -instance on record is the case related by Dr. Golding Bird in 1848.[478] -What kind of aconitine was then in commerce I know not, and since -apparently a person of considerable social rank was the subject of the -poisoning, the case has been imperfectly reported. It seems, however, -that, whether for purposes of suicide, or experiment, or as a medicine, -two grains and a half of aconitine were swallowed. The symptoms were -very violent, consisting of vomiting, collapse, and attacks of muscular -spasm; the narrator describes the vomiting as peculiar. "It, perhaps, -hardly deserved that title; the patient was seized with a kind of -general spasm, during which he convulsively turned upon his abdomen, -and with an intense contraction of the abdominal muscles, he jerked out, -as it were, with a loud shout the contents of his stomach, dependent -apparently on the sudden contraction of the diaphragm." On attempting to -make him swallow any fluid, a fearful spasm of the throat was produced; -it reminded his medical attendants of hydrophobia. The patient recovered -completely within twenty-four hours. - -[478] _Lancet_, vol. i. p. 14. - -One of three cases reported by Dr. Albert Busscher,[479] of poisoning by -aconitine nitrate, possesses all the exact details of an intentional -experiment, and is of permanent value to toxicological literature. - -[479] _Intoxicationsfaelle durch Aconitin Nitricum Gallicum, nebst -Sections Bericht_, von Dr. Albert Busscher; _Berl. klinische -Wochenschrift_, 1880, No. 24, pp. 338, 356. - -A labourer of Beerta, sixty-one years of age, thin, and of somewhat weak -constitution, suffered from neuralgia and a slight intermittent fever; -Dr. Carl Meyer prescribed for his ailment:-- - - [Rx]. Aconiti Nitrici, 2 grm. - Tr. Chenopodii Ambrosioid., 100 grms. M.D.S. - -Twenty drops to be taken four times daily. The patient was instructed -verbally by Dr. Meyer to increase the dose until he attained a maximum -of sixty drops per day. - -The doses which the man actually took, and the time of taking them, are -conveniently thrown into a tabular form as follows:-- - - No. 1. March 14, 7 P.M., 5 drops equal to aconitine nitrate, .4 mgrm. - " 2. " 9 P.M., 20 " " " 1.6 " - " 3. March 15, 8 A.M., 20 " " " 1.6 " - " 4. " 11 A.M., 20 " " " 1.6 " - " 5. " 4 P.M., 20 " " " 1.6 " - " 6. " 9 P.M., 20 " " " 1.6 " - " 7. March 16, 10 P.M., 10 " " " .8 " - -In the whole seven doses, which were distributed over forty-eight hours, -he took 9.2 mgrms. (.14 grain) of aconitine nitrate. - -On taking dose No. 1, he experienced a feeling of constriction -(_Zusammenziehung_), and burning spreading from the mouth to the -stomach, but this after a little while subsided. Two hours afterwards he -took No. 2, four times the quantity of No. 1. This produced the same -immediate symptoms, but soon he became cold, and felt very ill. He had -an anxious oppressive feeling about the chest, with a burning feeling -about the throat; the whole body was covered with a cold sweat, his -sight failed, he became giddy, there was excessive muscular weakness, he -felt as if he had lost power over his limbs, he had great difficulty in -breathing. During the night he passed no water, nor felt a desire to do -so. About half an hour after he had taken the medicine, he began to -vomit violently, which relieved him much; he then fell asleep. - -Dose No. 3, equal as before to 1.6 mgrm., he took in the morning. He -experienced almost exactly the same symptoms as before, but convulsions -were added, especially of the face; the eyes were also prominent; twenty -minutes after he had taken the dose, vomiting came on, after which he -again felt better. - -He took dose No. 4, and had the same repetition of symptoms, but in the -interval between the doses he felt weaker and weaker; he had no energy, -and felt as if paralysed. No. 5 was taken, and produced, like the -others, vomiting, after which he felt relieved. Neither he nor his wife -seemed all this time to have had any suspicion that the medicine was -really doing harm, but thought that the effects were due to its constant -rejection by vomiting, so, in order to prevent vomiting with No. 6, he -drank much cold water. After thus taking the medicine, the patient -seemed to fall into a kind of slumber, with great restlessness; about an -hour and a half afterwards he cried, "I am chilled; my heart, my heart -is terribly cold. I am dying; I am poisoned." His whole body was covered -with perspiration; he was now convulsed, and lost sight and hearing; his -eyes were shut, his lips cracked and dry, he could scarcely open his -mouth, and he was extremely cold, and thought he was dying. The -breathing was difficult and rattling; from time to time the muscular -spasms came on. His wife now made a large quantity of hot strong black -tea, which she got him to drink with great difficulty; although it was -hot, he did not know whether it was hot or cold. About five minutes -afterwards he vomited, and did so several times; this apparently -relieved him, and he sank into a quiet sleep; during the night he did -not urinate. In the morning the wife went to Dr. Carl Meyer, described -the symptoms, and accused the medicine. So convinced was Dr. Meyer that -the medicine did not cause the symptoms, that he poured out a quantity -of the same, equal to 4 mgrms. of aconitine nitrate, and took it himself -in some wine, to show that it was harmless, and ordered them to go on -with it. The unhappy physician died of aconitine poisoning five hours -after taking the medicine.[480] In the meantime, the woman went home, -and her husband actually took a seventh, but smaller dose, which -produced similar symptoms to the former, but of little severity; no more -was taken. - -[480] The symptoms suffered by Dr. Meyer are to be found in _Neder. -Tijdschrift van Geneeskunde_, 1880, No. 16. - -The absence of diarrh[oe]a, and of the pricking sensations so often -described, is in this case noteworthy. Both diarrh[oe]a and formication -were also absent in a third case reported by Dr. Busscher in the same -paper. - -Sec. 436. The most important criminal case is undoubtedly that of -Lamson:--At the Central Criminal Court, in March, 1882, George Henry -Lamson, surgeon, was convicted of the murder of his brother-in-law, -Percy Malcolm John. The victim was a weakly youth of eighteen years of -age, paralysed in his lower limbs from old standing spinal disease. The -motive for perpetrating the crime was that Lamson, through his wife -(Malcolm John's sister), would receive, on the death of his -brother-in-law, a sum of L1500, and, according to the evidence, it is -probable that there had been one or more previous attempts by Lamson on -the life of the youth with aconitine given in pills and in powders. -However this may be, on November 24, 1880, Lamson purchased 2 grains of -aconitine, came down on Dec. 3 to the school where the lad was placed, -had an interview with his brother-in-law, and, in the presence of the -head-master, gave Malcolm John a capsule, which he filled then and there -with some white powder, presumed at the time to be sugar. Lamson only -stayed altogether twenty minutes in the house, and directly after he saw -his brother-in-law swallow the capsule, he left. Within fifteen minutes -Malcolm John became unwell, saying that he felt as if he had an attack -of heart-burn, and then that he felt the same as when his brother-in-law -had on a former occasion given him a quinine pill. Violent vomiting soon -set in, and he complained of pains in his stomach, a sense of -constriction in his throat, and of being unable to swallow. He was very -restless--so much so that he had to be restrained by force from injuring -himself. There was delirium a few minutes before death, which took place -about three hours and three-quarters after swallowing the fatal dose. -The _post-mortem_ appearances essentially consisted of redness of the -greater curvature of the stomach, and the posterior portion of the same -organ. In one part there was a little pit, as if a blister had broken; -the rest of the viscera were congested, and the brain also slightly -congested.[481] - -[481] To these cases of poisoning by the alkaloid aconitine may be added -one recorded in Bouchardat's _Annuaire de Therapeutie_, 1881, p. 276. -The case in itself is of but little importance, save to illustrate the -great danger in permitting the dispensing of such active remedies of -varying strength. A gentleman suffering from "angina pectoris" was -prescribed "Hottot's aconitine" in granules, and directed carefully to -increase the dose up to four granules, according to the effect produced. -The prescription was taken to a pharmacist, who, instead of supplying -Hottot's aconitine, supplied some other of unknown origin. The medicine -was taken daily, and the dose raised to four granules, which were taken -with benefit until the whole was exhausted. He then went to Hottot's -establishment, and had a fresh supply, presumably of the same substance, -but a very little time after he had taken his usual dose of four -granules, he suffered from symptoms of aconitine poisoning, headache, -vertigo, feebleness of the voice, and muscular weakness, and was -alarmingly ill. He recovered after some hours of medical treatment. - -Sec. 437. The symptoms of poisoning by the tincture, extract, or other -preparation, do not differ from those detailed. As unusual effects, -occasionally seen, may be noted profound unconsciousness lasting for -two hours (Topham's case), violent twitching of the muscles of the -face, opisthotonos, and violent convulsions. It is important to -distinguish the symptoms which are not constant from those which are -constant, or nearly so. The tingling and creeping sensations about the -tongue, throat, lips, &c., are not constant; they certainly were not -present in the remarkable German case cited at p. 363. Speaking -generally, they seem more likely to occur after taking the root or the -ordinary medicinal preparations. A dilated state of the pupil is by no -means constant, and not to be relied upon. Diarrh[oe]a is seen after -taking the root or tincture by the stomach, but is often absent. In -short, the only constant symptoms are difficulty of breathing, -progressive muscular weakness, generally vomiting, and a weak -intermittent pulse. - -Sec. 438. =Physiological Action.=--Aconitine, according to Dr. S. Ringer, -is a protoplasmic poison, destroying the functions of all nitrogenous -tissue--first of the central nervous system, next of the nerves, and -last of the muscles. Aconitine without doubt acts powerfully on the -heart, ultimately paralysing it; there is first a slowing of the pulse, -ascribed to a central excitation of the vagus; then a quickening, due to -paralysis of the peripheral termination of the vagus in the heart; -lastly, the heart's action becomes slow, irregular, and weak, and the -blood-pressure sinks. The dyspn[oe]a and convulsions are the usual -result, seen among all warm-blooded animals, of the heart affection. -Plugge found that the motor nerves, and more especially their -intra-muscular terminations, were always paralysed; but if the dose was -small the paralysis might be incomplete. B[oe]hm and Wartmann, on the -other hand, considered that the motor paralysis had a central origin, a -view not supported by recent research. The action of aconitine in this -way resembles curare. The muscles themselves preserve their -irritability, even after doses of aconitine which are five to ten times -larger than those by which the nerve terminations are paralysed. - -Sec. 439. =Post-mortem Appearances.=--Among animals (mammals) the -appearances most constantly observed have been hyperaemia of the cerebral -membranes and brain, a fulness of the large veins, the blood generally -fluid--sometimes hyperaemia of the liver, sometimes not. When aconitine -has been administered subcutaneously, there have been no inflammatory -appearances in the stomach and bowels. - -In the case of Dr. Carl Meyer, who died in five hours from swallowing 4 -mgrms. of aconitine nitrate, the corpse was of a marble paleness, the -pupils moderately dilated. The colour of the large intestine was pale; -the duodenum was much congested, the congestion being most intense the -nearer to the stomach; the mucous membrane of the stomach itself was -strongly hyperaemic, being of an intense red colour; the spleen was -enlarged, filled with much dark blood. The liver and kidneys were -deeply congested, the lungs also congested; the right ventricle of the -heart was distended with blood; in the pericardium there was a quantity -of bloody serum. The brain was generally blood-red; in the cerebral -hemispheres there were several large circumscribed subarachnoid -extravasations. The substance of the brain on section showed many red -bloody points. - -In a case recorded by Taylor, in which a man died in three hours from -eating a small quantity of aconitine root, the only morbid appearance -found was a slight reddish-brown patch on the cardiac end of the -stomach, of the size of half a crown; all the other organs being -healthy. - -Sec. 440. =Separation of Aconitine from the Contents of the Stomach or the -Organs.=--It would appear certain that in all operations for the -separation of aconite alkaloids (whether from the organic matters which -make up the plant, or from those constituting animal tissues), mineral -acids and a high heat should be avoided. A 1 per cent. sulphuric acid -does not, however, hydrolyse, if acting in the cold, so that the process -already given, p. 352, may be followed. - -The chemical examination in the Lamson case was entrusted to Dr. -Stevenson, assisted by Dr. Dupre, and was conducted on the principles -detailed. The contents of the stomach were treated with alcohol, and -digested at the ordinary temperature of the atmosphere; the contents -were already acid, so no acid in this first operation was added. The -mixture stood for two days and was then filtered. The insoluble portion -was now exhausted by alcohol, faintly acidulated by tartaric acid, and -warmed to 60 deg.; cooled and filtered, the insoluble part being washed -again with alcohol. The two portions--that is, the spirituous extract -acid from acids pre-existing in the contents of the stomach, and the -alcohol acidified by tartaric acid--were evaporated down separately, -exhausted by absolute alcohol, the solutions filtered, evaporated, and -the residue dissolved in water. The two aqueous solutions were now -mixed, and shaken up with ether, which, as the solution was acid, would -not remove any alkaloid, but might remove various impurities; the -residue, after being thus partially purified by ether, was alkalised by -sodic carbonate, and the alkaloid extracted by a mixture of chloroform -and ether. On evaporation of the chloroform and ether, the resulting -extract was tested physiologically by tasting, and also by injections -into mice. By means analogous to those detailed, the experts isolated -aconitine from the vomit, the stomach, liver, spleen, and urine, and -also a minute quantity of morphine, which had been administered to the -patient to subdue the pain during his fatal attack. When tasted, the -peculiar numbing, tingling sensation lasted many hours. These extracts -were relied upon as evidence, for their physiological effect was -identical with that produced by aconitine. For example, the extract -obtained from the urine caused symptoms to commence in a mouse in two -minutes, and death in thirty minutes, and the symptoms observed by -injecting a mouse with known aconitine coincided in every particular -with the symptoms produced by the extraction from the urine. - -With regard to the manner of using "_life tests_," since in most cases -extremely small quantities of the active principle will have to be -identified, the choice is limited to small animals, and it is better to -use mice or birds, rather than reptiles. In the Lamson case, -subcutaneous injections were employed, but it is a question whether -there is not less error in administering it by the mouth. If two healthy -mice are taken, and the one fed with a little meal, to which a weighed -quantity of the extract under experiment has been added, while to the -other some meal mixed with a supposed equal dose of aconitine is given, -then the symptoms may be compared; and several objections to any -operative proceeding on such small animals are obviated. It is certain -that any extract which causes distinct numbness of the lips will contain -enough of the poison to kill a small bird or a mouse, if administered in -the ordinary way.[482] - -[482] Dr. A. Langaard has described a species of aconite root, named by -the Japanese _K[)u]sa-[=u]s[=u]_. From his experiments on frogs and -rabbits, its physiological action seems not to differ from that of -aconitine generally.--_Ueber eine Art Japanische Akonit-knollen, -K[)u]sa-[=u]s[=u] genannt, u. ueber das in denselben vorkommende -Akonitin. Virchow's Archiv_, B. 79, 1880, p. 229. - - -VI.--The Mydriatic Group of -Alkaloids--Atropine--Hyoscyamine--Solanine--Cytisine. - - -1. ATROPINE. - -Sec. 441. =Atropine= (=Daturine=), C_{17}H_{23}NO_{3}.--This important -alkaloid has been found in all parts of the _Atropa belladonna_, or -deadly nightshade, and in all the species of _Datura_. - -The _Atropa belladonna_ is indigenous, and may be found in some parts of -England, although it cannot be said to be very common. It belongs to the -_Solanaceae_, and is a herbaceous plant with broadly ovate entire leaves, -and lurid-purple axillary flowers on short stalks; the berries are -violet-black, and the whole of the plant is highly poisonous. The juice -of the leaves stains paper a purple colour. The seeds are very small, -kidney-shaped, weighing about 90 to the grain; they are covered closely -with small, round projections, and are easily identified by an expert, -who may be supposed to have at hand (as is most essential) samples of -different poisonous seeds for comparison. The nightshade owes its -poisonous properties to _atropine_. - -The yield of the different parts of belladonna, according to -Gunther,[483] is as follows:-- - -[483] _Pharm. Zeitschr. f. Russl._, Feb., 1869; Dragendorff, _Die -chemische Werthbestimmung einiger starkwirkenden Droguen_, St. -Petersburg, 1874. - -TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE BELLADONNA -PLANT. - - +-------------+----------------------+----------------------+ - | |Quantity of Alkaloids |Quantity of Alkaloids | - | | in the Fresh | in the Dry | - | | Substance, per cent. | Substance, per cent. | - | +-----------+----------+-----------+----------+ - | | (_a._) By |(_b._) By | (_a._) By |(_b._) By | - | | Weighing. |Titration.| Weighing. |Titration.| - +-------------+-----------+----------+-----------+----------+ - |Leaves, | 0.2022 | 0.20072 | 0.838 | 0.828 | - |Stalk, | 0.0422 | ... | 0.146 | ... | - |Ripe fruit, | 0.2128 | 0.20258 | 0.821 | 0.805 | - |Seed, | 0.26676 | ... | 0.407 | ... | - |Unripe fruit,| 0.1870 | 0.1930 | 0.955 | 0.955 | - |Root, | 0.0792 | ... | 0.210 | ... | - +-------------+-----------+----------+-----------+----------+ - -Atropine appears to exist in the plant in combination with malic acid. -According to a research by Ladenburg, hyoscyamine is associated with -atropine, both in the Belladonna and Datura plants.[484] - -[484] _Ber. der deutsch. Chem. Ges._, Bd. 13. - -From a research by W. Schuette,[485] it appears that the younger roots of -wild belladonna contain hyoscyamine only, whilst the older roots contain -atropine as well as hyoscyamine, but only in small proportion; the same -was observed to be the case in the older cultivated roots. - -[485] _Arch. Pharm._, ccxxix., 492-531; _Journ. Chem. Soc._ (abstract), -February 1892, 231. - -The ripe berries of cultivated _Atropa belladonna nigra_ contain -atropine and hyoscyamine; those of the wild plant contain atropine only; -the ripe fruit of _Atropa belladonna lutea_ contains only atropine and -another base, perhaps identical with atropamine; the unripe fruit of -wild _Atropa belladonna nigra_ contains hyoscyamine, with only a small -quantity of atropine. - -The leaves of the yellow and black-fruited wild _Atropa belladonna_ -contain hyoscyamine and atropine, the latter being in small quantity -only. - -Fresh and old seeds of _Datura Stramonium_ contain chiefly hyoscyamine; -small quantities of atropine and scopolamine are also present. - -Sec. 442. =The Datura Stramonium or Thorn-apple= is also indigenous in the -British Islands, but, like belladonna, it cannot be considered a common -plant. Datura belongs to the Solanaceae; it grows from 1 to 2 feet in -height, and is found in waste places. The leaves are smooth, the flowers -white; the fruit is densely spinous (hence the name thorn-apple), and is -divided into four dissepiments below, two at the top, and containing -many seeds. - -The _Datura_, or the _Dhatura_-plants, of India have in that country a -great toxicological significance, the white-flowered datura, or _Datura -alba_, growing plentifully in waste places, especially about Madras. The -purple-coloured variety, or _Datura fastuosa_, is also common in certain -parts. There is a third variety, the _Datura atrox_, found about the -coast of Malabar. The seeds of the white datura have been mistaken in -India for those of capsicum. The following are some of the most marked -differences:-- - - SEEDS OF THE COMMON OR WHITE SEEDS OF CAPSICUM. - DATURA. - - (1.) Outline angular. Outline rounded. - - (2.) Attached to the placenta by a Attached to the placenta by a - large, white, fleshy mass separ- cord from a prominence on the - ating easily, leaving a deep concave border of the seed. - furrow along half the length of - the seed's concave border. - - (3.) Surface scabrous, almost re- Uniformly scabrous, the sides - ticulate, except on the two com- being equally rough with the - pressed sides, where it has borders. - become almost glaucous from - pressure of the neighbouring - seeds. - - (4.) Convex border thick and Convex border thickened, but - bulged with a longitudinal depres- uniformly rounded. - sion between the bulgings, caused - by the compression of the two - sides. - - (5.) A suitable section shows the The embryo, exposed by a suitable - embryo curved and twisted in the section, is seen to resemble in - fleshy albumen. outline very closely the figure - 6. - - (6.) The taste of the datura seeds The taste of capsicum is pungent; - is very feebly bitter. The watery a decoction irritates the eye - decoction causes dilatation of the much, but does not cause dilata- - pupil. tion of the pupil. - -The identity of the active principle in both the datura and belladonna -tribes is now completely established.[486] - -[486] See a research by Ernst Schmidt, "Ueber die Alkaloide der -Belladonna-Wurzel u. des Stechapfel-Samens," _Lieb. Annl._, Bd. 208, -1881. - -Sec. 443. =Pharmaceutical Preparations.=--(_a._) _Of the leaves. Extract -of Belladonna._--This contains, according to Squire,[487a] from 0.73 to -1.7 per cent. of total alkaloids. _Belladonna Juice_ (_succus -belladonnae_).--Strength in alkaloid about 0.05 per cent. _Tincture of -Belladonna._--Half the strength of the juice, and therefore yielding -about 0.025 per cent. of alkaloid. - -[487a] _Companion to the British Pharmacop[oe]ia_, 1894. - -(_b._) _Belladonna Root.--Belladonna plaster_ contains 20 per -cent. of alcoholic extract of belladonna. _Alcoholic Extract of -Belladonna._--This extract, according to Squire,[487b] contains from 1.6 -to 4.45 per cent. of alkaloid. _Belladonna liniment_ is an alcoholic -extract with the addition of camphor; its strength is about equal to 0.2 -per cent. of alkaloid. _Belladonna ointment_ contains about 10 per cent. -of the alcoholic extract. - -[487b] _Companion to the British Pharmacop[oe]ia_, 1894. - -(_c._) _The Alkaloid.--Atropine Discs_ (_lamellae atropinae_).--These are -discs of gelatin, each weighing about 1/50 grain, and containing for -ophthalmic use 1/5000 grain of atropine sulphate. Similar discs are made -for hypodermic use, but stronger; each containing 1/120 grain. _Solution -of Atropine Sulphate._--Strength about 1 per cent. _Atropine -Ointment._--Strength about 1 in 60, or 1.60 per cent. of atropine. - -(_d._) _Stramonium._--An extract of the seeds is officinal in Britain; -the alkaloidal content is from 1.6 to 1.8 per cent. There is also a -tincture which contains about 0.06 per cent. of alkaloid. - -Sec. 444. =Properties of Atropine=, C_{17}H_{23}NO_{3}.--Atropine, -hyoscyamine, and hyoscine have all the same formula, but differ in their -molecular constitution. Atropine by hydrolysis, either by heating it -with hydrochloric acid or baryta water, is decomposed into tropine and -tropic acid:-- - - C_{17}H_{23}NO_{3} + H_{2}O = C_{8}H_{15}NO + C_{9}H_{10}O_{3}. - Atropine. Tropine. Tropic - acid. - -On the other hand, by heating tropic acid and tropine together, -atropine is regenerated. Hence it is proved by analysis and -synthesis, that atropine is tropic acid-tropine, just as aconitine -is benzoyl-aconine. Tropic acid has been produced synthetically by -boiling [beta]-chlorphenyl-propionic acid with potash, which at once -shows its constitutional formula, viz.:-- - - CH_{2}OH - / - C_{6}H_{5}CH . - \ - COOH - -Tropic acid has a melting-point of 117 deg. to 118 deg. Tropine is a four-fold -hydrated oxethyl-methyl-pyridine, and has the constitutional formula of -C_{5}H_{3}(H_{4})(C_{2}H_{4}OH)N(CH_{3}); hence the constitutional -formula of atropine is-- - - CH_{2}(OH) - / - C_{6}H_{5}--CH . - \ - CO--O(C_{2}H_{4}--C_{5}H_{7}==N--CH_{3}) - -Tropine is a white, crystalline, strongly alkaline mass, melting at 60 deg., -and volatilising at 230 deg. undecomposed. It is soluble in water, alcohol, -and ether, and gives precipitates with tannic acid, iodised hydriodic -acid, Mayer's reagent, gold chloride, and mercuric chloride. Tropine -gold chloride melts at 210 deg. to 212 deg. Atropic acid (C_{9}H_{8}O_{2}), -melting-point 198 deg. to 200 deg., and isatropic acid (C_{9}H_{8}O_{2}), may -also be obtained by the action of hydrochloric acid--the first, in -radiating crystals, melting at 106 deg., and capable of distillation; the -second, in thin rhombic plates, melting about 200 deg., and not volatile. -Picric acid also gives a precipitate of beautiful plates. To obtain this -the carbazotic acid must be in excess, and time must be given for the -precipitate to form. - -Atropine forms colourless crystals (mostly in groups or tufts of needles -and prisms), which are heavier than water, and possess no smell, but an -unpleasant, long-enduring, bitter taste. The experiments of E. Schmidt -place the melting-point between 115 deg. and 115.5 deg. It is said to sublime -scantily in a crystalline form, but the writer has been unable to obtain -any crystals by sublimation; faint mists collect on the upper disc, at -about 123 deg., but they are perfectly amorphous. - -Its reaction is alkaline; one part requires, of cold water, 300; of -boiling, 58; of ether, 30; of benzene, 40; and of chloroform, 3 parts -for solution. In alcohol and amyl alcohol it dissolves in almost every -proportion. It turns the plane of polarisation weakly to the left. - -Sec. 445. =Tests.=--Atropine mixed with nitric acid exhibits no change of -colour. The same is the case with concentrated sulphuric acid in the -cold; but on heating, there ensues the common browning, with development -of a peculiar odour, likened by Gulielmo to orange flowers, by -Dragendorff to the flowers of the _Prunus padus_, and by Otto to the -_Spiraea ulmaria_--a sufficient evidence of the untrustworthiness of this -as a distinctive test. The odour, indeed, with small quantities, is -certainly not powerful, nor is it strongly suggestive of any of the -plants mentioned. A far more intense odour is given off if a speck of -atropine is evaporated to dryness with a few drops of strong solution of -baryta, and heated strongly; the scent is decidedly analogous to that of -hawthorn-blossom, and unmistakably agreeable. - -By boiling a small quantity of atropine, say 1 mgrm., with 2 mgrms. of -calomel and a very little water, the calomel blackens, and crystals may -be obtained of a double salt; this reaction is, however, given also by -hyoscyamine and homatropine. Mercuric potassium iodide solution, and -mercuric bromide solution give amorphous precipitates, which, after a -time, become crystalline, and have characteristic forms. - -A solution of iodine in potassium iodide gives a precipitate with -acidulated solutions of atropine in even a dilution of 1 : 10,000. -Tannin precipitates, and the precipitate is soluble in excess of the -reagent. If atropine be dissolved in dilute hydrochloric acid, and a 5 -per cent. of gold chloride solution be added, a precipitate of a gold -compound (C_{17}H_{23}NO_{3}HClAuCl_{3}) separates. The precipitate is -in the form of rosettes or needles; melting-point 137 deg. On boiling it -with water, however, it melts into oily drops, and this peculiar -behaviour distinguishes it from the analogous salt of hyoscyamine, which -does not melt in boiling water. The percentage of gold left on a -combustion of atropine gold chloride is 31.35 per cent. 100 parts of the -gold salt are equal to 46.2 of atropine. A platinum salt may also be -obtained, (C_{17}H_{23}NO_{3}HCl)_{2},PtCl_{4}, containing 29.5 per -cent. of platinum. - -Vitali's test is important; it consists in the production of a violet -colour with alcoholic potash after oxidation. - -The test may be applied as follows:--Equal parts, say 1 mgrm., of -nitrate of sodium and of the substance to be tested, are rubbed together -with a glass rod on a porcelain slab, and to this mixture 1 drop of -sulphuric acid is added; the mixture is spread out in a thin film; upon -this is strewn a little powdered potassium hydrate, and finally 1 drop -of alcohol added; a violet colour is produced which passes into a fine -red; according to the author of the test, 0.001 mgrm. of atropine -sulphate can by this test be detected. Strychnine obscures this -reaction. - -Atropine, homatropine, and hyoscyamine show an alkaline reaction with -phenolphthalein: atropine and homatropine give a precipitate with -HgCl_{2}. Hyoscyamine, not cocaine, precipitates HgCl_{2}, and is -alkaline to litmus, but not to phenolphthalein. Atropine behaves as -follows:--(1) Sodium nitrate, sulphuric acid, and afterwards sodium -hydroxide, gives a violet colour; (2) the test as before, but with -nitrite instead of nitrate, gives orange colour, which, on dilution with -sodium hydroxide solution, changes to red, violet, or lilac; (3) when -heated with glacial acetic acid and sulphuric acid for a sufficient -time, a greenish-yellow fluorescence is produced.--_Flueckiger, Pharm. -Journ. Trans._ (3), vol. xvi. p. 601-602. - -The two alkaloids, strychnine and atropine, are not likely to be often -together in the human body, but that it may sometimes occur is shown by -a case recorded by L. Fabris.[488] A patient in the hospital at Padua -had for some time been treated with daily injections of 3 mgrms. of -strychnine nitrate; unfortunately, one day, instead of the 3 mgrms. of -strychnine, the same quantity of atropine sulphate was injected, and the -patient died after a few hours, with symptoms of atropine poisoning. - -[488] _Gazzetta_, xxii., i. 347-350. - -On chemical treatment of the viscera, a mixture of alkaloids was -obtained which did not give either the reactions of strychnine or of -atropine. To test the possibility of these alkaloids obscuring each -other's reactions, mixtures of 3 per cent. solutions (the strength of -the injections) of atropine sulphate and strychnine nitrate were mixed -together, and strychnine tested for by the dichromate and sulphuric acid -test. - -A mixture of equal parts gave the strychnine reaction very clearly, but -the atropine reaction not at all; 1 strychnine with 3 of atropine gave -strychnine reaction, but not that of atropine; 1 strychnine with 4 -atropine gave indistinct reaction for both alkaloids; 1 of strychnine -with 5 of atropine gave a momentary atropine reaction, the violet was, -however, almost immediately replaced by a red colour. Vitali's reaction -was not clearly shown until the mixture was in the proportion of 9 of -atropine to 1 of strychnine, but mixtures in the proportion of 3 -strychnine and 1 atropine will give distinct mydriasis. - -In such a case, of course, the strychnine should be separated from the -atropine; this can be effected by precipitating the strychnine as -chromate, filtering and recovering from the filter the atropine by -alkalising and shaking it out with ether. - -The atropine may be farther purified by converting it into oxalate, -dissolving the oxalate in as small a quantity of alcohol as possible, -and precipitating the oxalate out with ether; the precipitate is -collected, dissolved in as small a quantity of water as possible, the -water made alkaline, and the base shaken out with ether. - -The most reliable test for atropine, or one of the mydriatic alkaloids, -is its action on the iris; a solution of atropine, even so weak as 1 : -130,000, causing dilatation.[489] This action on the iris has been -studied by Ruyter,[490] Donders, and von Graefe. - -[489] _De Actione Atropae Belladonnae in Iridem_, Traj. ad Rhen., 1852. - -[490] _Arch. Ophthal._, ix. 262, 1864. - -The action is local, taking effect when in dilute solution only on the -eye to which it has been applied; and it has been produced on the eyes -of frogs, not only in the living subject, but after the head has been -severed from the body and deprived of brain. The thinner the cornea, the -quicker the dilatation; therefore, the younger the person or animal, the -more suitable for experiment. In frogs, with a solution of 1 : 250, -dilatation commences in about five minutes; in pigeons, seven minutes; -and in rabbits, ten minutes. In man, a solution of 1 : 120 commences to -act in about six to seven minutes, reaches its highest point in from ten -to fifteen minutes, and persists more or less for six to eight days. A -solution of 1 : 480 acts first in fifteen to twenty minutes, and reaches -its greatest point in twenty minutes; a solution of 1 : 48,000 requires -from three-quarters of an hour to an hour to show its effect. Dogs and -cats are far more sensible to its influence than man, and therefore more -suitable for experiment. If the expert chooses, he may essay the proof -upon himself, controlling the dilatation by Calabar bean; but it is -seldom necessary or advisable to make personal trials of this -nature.[491] - -[491] A. Ladenburg (_Compt. Rend._, xc. 92), having succeeded in -reproducing atropine by heating tropine and tropic acid with -hydrochloric acid, by substituting various organic acids for the tropic -acid, has obtained a whole series of compounds to which he has given the -name of _tropeines_. One of these, hydroxytoluol (amygdalic) tropeine, -he has named _homatropine_. It dilates the pupil, but is less poisonous -than atropine. - -Sec. 446. =Statistics of Atropine Poisoning.=--Since atropine is the active -principle of belladonna and datura plants, and every portion of -these--root, seeds, leaves, and fruit--has caused toxic symptoms, -poisoning by any part of these plants, or by their pharmaceutical or -other preparations, may be considered with strict propriety as atropine -poisoning. Our English death statistics for the ten years ending 1892, -record 79 deaths (50 males and 29 females) from atropine (for the most -part registered under the head of belladonna); 29 (or 36.7 per cent.) -were suicidal, the rest accidental. - -The greatest number of the accidental cases arise from mistakes in -pharmacy; thus, belladonna leaves have been supplied for ash leaves; the -extract of belladonna has been given instead of extract of juniper; the -alkaloid itself has been dispensed in mistake for theine;[492] a more -curious and marvellously stupid mistake is one in which it was dispensed -instead of assaf[oe]tida (Schauenstein, _op. cit._, p. 652). Further, -valerianate of atropine has been accidentally substituted for quinine -valerianate, and Schauenstein relates a case in which atropine sulphate -was administered subcutaneously instead of morphine sulphate; but the -result was not lethal. Many other instances might be cited. The extended -use of atropine as an external application to the eye naturally gives -rise to a few direct and indirect accidents. Serious symptoms have -arisen from the solution reaching the pharynx through the lachrymal duct -and nose. A curious indirect poisoning, caused by the use of atropine as -a collyrium, is related by Schauenstein.[493] A person suffered from all -the symptoms of atropine poisoning; but the channel by which it had -obtained access to the system was a great mystery, until it was traced -to some coffee, and it was then found that the cook had strained this -coffee through a certain piece of linen, which had been used months -before, soaked in atropine solution, as a collyrium, and had been cast -aside as of no value. - -[492] Hohl, _De Effectu Atropini. Diss. Halle_, 1863. - -[493] Maschka's _Handbuch_. - -Sec. 447. =Accidental and Criminal Poisoning by Atropine.=--External -applications of atropine are rapidly absorbed, _e.g._, if the foot of a -rat be steeped for a little while in a solution of the alkaloid, and the -eyes watched, dilatation of the pupils will soon be observed. If the -skin is broken, enough may be absorbed to cause death. A case is on -record in which .21 grm. of atropine sulphate, applied as an ointment to -the abraded skin, was fatal.[494] Atropine has also been absorbed from -the bowel; in one case, a clyster containing the active principles of -5.2 grms. (80 grains) of belladonna root was administered to a woman -twenty-seven years of age, and caused death. Allowing the root to have -been carefully dried, and to contain .21 per cent. of alkaloid, it would -seem that so little as 10.9 mgrms. (.16 grain) may even prove fatal, if -left in contact with the intestinal mucous membrane. Belladonna berries -and stramonium leaves and seeds are eaten occasionally by children. A -remarkable series of poisonings by belladonna berries occurred in London -during the autumn of 1846. - -[494] Ploss, _Zeitschr. f. Chir._, 1863. - -Criminal poisoning by atropine in any form is of excessive rarity in -Europe and America, but in India it has been frightfully prevalent. In -all the Asiatic cases the substance used has been one of the various -species of datura, and mostly the bruised or ground seeds, or a -decoction of the seeds. In 120 cases recorded in papers and works on -Indian toxicology, I find no less than 63 per cent. of the cases -criminal, 19 per cent. suicidal, and 18 per cent. accidental. In noting -these figures, however, it must be borne in mind that known criminal -cases are more certain to be recorded than any other cases. The drug has -been known under the Sanscrit name of _dhatoora_ by the Hindoos from -most remote times. It was largely used by the Thugs, either for the -purpose of stupefying their victim or for killing him; by loose wives to -ensure for a time the fatuity of their husbands; and, lastly, it seems -in Indian history to have played the peculiar _role_ of a state agent, -and to have been used to induce the idiocy or insanity of persons of -high rank, whose mental integrity was considered dangerous by the despot -in power. The Hindoos, by centuries of practice, have attained such -dexterity in the use of the "datura" as to raise that kind of poisoning -to an art, so that Dr. Chevers, in his _Medical Jurisprudence for -India_,[495] declares that "there appears to be no drug known in the -present day which represents in its effects so close an approach to the -system of slow poisoning, believed by many to have been practised in the -Middle Ages, as does the datura." - -[495] Dr. Chevers's work contains a very good history of datura criminal -poisoning. - -Sec. 448. =Fatal Dose.=--It is impossible to state with precision the exact -quantity which may cause death, atropine being one of those substances -whose effect, varying in different cases, seems to depend on special -constitutional tendencies or idiosyncracies of the individual. Some -persons take a comparatively large amount with impunity, while others -scarcely bear a very moderate dose without exhibiting unpleasant -symptoms. Eight mgrms. (1/8 grain) have been known to produce poisonous -symptoms, and .129 grm. (2 grains) death. We may, therefore, infer that -about .0648 grm. (1 grain) would, unchecked by remedies, probably act -fatally; but very large doses have been recovered from, especially when -treatment has been prompt. - -Atropine is used in veterinary practice, from 32.4 to 64.8 mgrms. (1/2 -to 1 grain) and more being administered subcutaneously to horses; but -the extent to which this may be done with safety is not yet established. - -Sec. 449. =Action on Animals.=--The action of atropine has been studied on -certain beetles, on reptiles (such as the salamander, triton, frogs, and -others), on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs, -and cats. Among the mammalia there is no essential difference in the -symptoms, but great variation in the relative sensibility; man seems the -most sensitive of all, next to man come the carnivora, while the -herbivora, and especially the rodents, offer a considerable resistance. -According to Falck the lethal dose for a rabbit is at least .79 mgrm. -per kilo. It is the general opinion that rabbits may eat sufficient of -the belladonna plant to render their flesh poisonous, and yet the -animals themselves may show no disturbance in health; but this must not -be considered adequately established. Speaking very generally, the -higher the animal organisation the greater the sensibility to atropine. -Frogs are affected in a peculiar manner. According to the researches of -Fraser,[496] the animal is first paralysed, and some hours after the -administration of the poison lies motionless, the only signs of life -being the existence of a slight movement of the heart and muscular -irritability. After a period of from forty-eight to seventy-two hours, -the fore limbs are seized with tetanic spasms, which develop into a -strychnine-like tetanus. - -[496] _Transact. of Edin. Roy. Soc._, vol. xxv. p. 449. _Journ. of Anat. -and Physiol._, May 1869, p. 357. - -Sec. 450. =Action on Man.=--When atropine is injected subcutaneously, the -symptoms, as is usually the case with drugs administered in this manner, -may come on immediately, the pupil not unfrequently dilating almost -before the injection is finished. This is in no way surprising; but -there are instances in which decoctions of datura seeds have been -administered by the stomach, and the commencement of symptoms has been -as rapid as in poisoning by oxalic or even prussic acid. In a case tried -in India in July 1852, the prosecutor declared that, while a person was -handing him a _lota_ of water, the prisoner snatched it away on pretence -of freeing the water from dirt or straws, and then gave it to him. He -then drank only two mouthfuls, and, complaining of the bitter taste, -fell down insensible within forty yards of the spot where he had drunk, -and did not recover his senses until the third day after. In another -case, a man was struck down so suddenly that his feet were scalded by -some hot water which he was carrying.--_Chevers._ - -When the seeds, leaves, or fruit of atropine-holding plants are eaten, -there is, however, a very appreciable period before the symptoms -commence, and, as in the case of opium poisoning, no very definite rule -can be laid down, but usually the effects are experienced within half -an hour. The first sensation is dryness of the mouth and throat; this -continues increasing, and may rise to such a degree that the swallowing -of liquids is an impossibility. The difficulty in swallowing does not -seem to be entirely dependent on the dry state of the throat, but is -also due to a spasmodic contraction of the pharyngeal muscles. -Tissore[497] found in one case such constriction that he could only -introduce emetics by passing a catheter of small diameter. The mucous -membrane is reddened, and the voice hoarse.[498] The inability to -swallow, and the changed voice, bear some little resemblance to -hydrophobia--a resemblance heightened to the popular mind by an -inclination to bite, which seems to have been occasionally observed; the -pupils are early dilated, and the dilatation may be marked and extreme; -the vision is deranged, letters and figures often appear duplicated; the -eyeballs are occasionally remarkably prominent, and generally congested; -the skin is dry, even very small quantities of atropine arresting the -cutaneous secretion; in this respect atropine and pilocarpine are -perfect examples of antagonism. With the dryness of skin, in a large -percentage of cases, occurs a scarlet rash over most of the body. This -is generally the case after large doses, but Stadler saw the rash -produced on a child three months old by .3 mgrm. of atropine sulphate. -It appeared three minutes after the dose, lasted five hours, and was -reproduced by a renewed dose.[499] The temperature of the body with -large doses is raised; with small, somewhat lowered. The pulse is -increased in frequency, and is always above 100--mostly from 115 to 120, -or even 150, in the minute. The breathing is at first a little slowed, -and then very rapid. Vomiting is not common; the sphincters may be -paralysed so that the evacuations are involuntary, and there may be also -spasmodic contractions of the urinary bladder. The nervous system is -profoundly affected; in one case there were clonic spasms,[500] in -another,[501] such muscular rigidity, that the patient could with -difficulty be placed on a chair. The lower extremities are often partly -paralysed, there is a want of co-ordination, the person reels like a -drunken man, or there may be general jactitation. The disturbance of -the brain functions is very marked; in about 4 per cent. only of the -recorded cases has there been no delirium, or very little--in the -majority delirium is present. In adults this generally takes a -garrulous, pleasing form, but every variety has been witnessed. Dr. H. -Giraud describes the delirium from datura (which it may be necessary to -again repeat is _atropine_ delirium) as follows:--"He either vociferates -loudly or is garrulous, and talks incoherently; sometimes he is -mirthful, and laughs wildly, or is sad and moans, as if in great -distress; generally he is observed to be very timid, and, when most -troublesome and unruly, can always be cowed by an angry word, frequently -putting up his hands in a supplicating posture. When approached he -suddenly shrinks back as if apprehensive of being struck, and frequently -he moves about as if to avoid spectra. But the most invariable -accompaniment of the final stage of delirium, and frequently also that -of _sopor_, is in the incessant picking at real or imaginary objects. At -one time the patient seizes hold of parts of his clothes or bedding, -pulls at his fingers and toes, takes up dirt and stones from the ground, -or as often snatches at imaginary objects in the air, on his body, or -anything near him. Very frequently he appears as if amusing himself by -drawing out imaginary threads from the ends of his fingers, and -occasionally his antics are so varied and ridiculous, that I have seen -his near relatives, although apprehensive of danger, unable to restrain -their laughter."[502] This active delirium passes into a somnolent state -with muttering, catching at the bedclothes, or at floating spectra, and -in fatal cases the patient dies in this stage. As a rule, the sleep is -not like opium coma; there is complete insensibility in both, but in the -one the sleep is deep, without muttering, in the other, from atropine, -it is more like the stupor of a fever. The course in fatal cases is -rapid, death generally taking place within six hours. If a person live -over seven or eight hours, he usually recovers, however serious the -symptoms may appear. On waking, the patient remembers nothing of his -illness; mydriasis remains some time, and there may be abnormality of -speech and weakness of the limbs, but within four days health is -re-established. In cases where the seeds have been swallowed, the -symptoms may be much prolonged, and they seem to continue until all the -seeds have been voided--perhaps this is due to the imperfect but -continuous extraction of atropine by the intestinal juices. - -[497] _Gaz. hebd._, 1856. - -[498] A friend of the author's was given, by a mistake in dispensing, 16 -minims of a solution of atropine sulphate, equivalent to 1/7 grain of -atropine (or 9.3 mgrms). Ten minutes after taking the dose there was -dilatation of the pupil, indistinctness of vision, with great dryness of -the throat and difficulty in swallowing; he attempted to eat a biscuit, -but, after chewing it, he was obliged to spit it out, as it was not -possible to swallow; the throat was excessively sore, and there was a -desire to pass urine, but only a few drops could be voided. In -forty-five minutes he was unable to stand or walk. There was a bright -rash on the chest. In two hours he became insensible, and was taken to -the Middlesex Hospital, recovering under treatment in about eight hours. - -[499] _Med. Times_, 1868. - -[500] _Lancet_, vol. i., 1881, p. 414. - -[501] _Ibid._, vol. i., 1876, p. 346. - -[502] In an English case of belladonna poisoning, the patient, a tailor, -sat for four hours, moving his hands and arms as if sewing, and his lips -as if talking, but without uttering a word. - -Chronic poisoning by atropine may, from what has been stated, be of -great importance in India. It is probable that its continuous effect -would tend to weaken the intellect, and there is no reason for any -incredulity with regard to its power as a factor of insanity. Rossbach -has ascertained that if dogs are, day after day, dosed with atropine, -they become emaciated; but a certain tolerance is established, and the -dose has to be raised considerably after a time to produce any marked -physiological effect. - -Sec. 451. =Physiological Action of Atropine.=--From the numerous -experiments on animals which have been performed for the purpose of -elucidating the action of atropine, it is clear that the terminations of -the vagus in the heart muscle are first excited, and then paralysed. The -excitor-motor ganglion is also paralysed, and finally the heart itself; -death resulting from heart paralysis. The respiratory disturbance is -also to be ascribed to the vagus; the terminations in the lung are -paralysed, and, at the same time, the poison circulating through the -respiratory nervous centre stimulates it first, and then it also becomes -finally paralysed. The small vessels are generally widened after a -previous transitory narrowing. Organs containing unstriped muscular -fibre are generally paralysed, as well as the ends of the nerves -regulating secretion--hence the dryness of the skin. The action on the -iris is not thoroughly elucidated. - -Sec. 452. The _diagnosis_ of atropine poisoning may be very difficult -unless the attention of the medical man be excited by some suspicious -circumstance. A child suffering from belladonna rash, with hot dry skin, -quick pulse, and reddened fauces, looks not unlike one under an attack -of scarlet fever. Further, as before mentioned, some cases are similar -to rabies; and again, the garrulous delirium and the hallucinations of -an adult are often very similar to those of _delirium tremens_, as well -as tomania. - -Sec. 453. =Post-mortem Appearances.=--The _post-mortem_ appearances do not -seem to be characteristic, save in the fact that the pupils remain -dilated. The brain is usually hyperaemic, and in one case the absence of -moisture seems to have been remarkable. The stomach and intestines may -be somewhat irritated if the seeds, leaves, or other parts of the plant -have been eaten; but the irritation is not constant if the poisoning has -been by pure atropine, and still less is it likely to be present if -atropine has been administered subcutaneously. - -Sec. 454. =Treatment.=--The great majority of cases recover under -treatment. In 112 cases collected by F. A. Falck, 13 only were fatal -(11.6 per cent.). The greater portion of the deaths in India are those -of children and old people--persons of feeble vitality. The Asiatic -treatment, which has been handed down by tradition, is the application -of cold water to the feet; but the method which has found most favour in -England is treatment by pilocarpine, a fifth of a grain or more being -injected from time to time. Pilocarpine shows as perfect antagonism as -possible; atropine dries, pilocarpine moistens the skin; atropine -accelerates, pilocarpine slows the respiration. Dr. Sydney Ringer and -others have published a remarkable series of cases showing the efficacy -of this treatment, which, of course, is to be combined where necessary -with emetics, the use of the stomach-pump, &c.[503] - -[503] See, for Dr. Ringer's cases, _Lancet_, vol. i., 1876, p. 346. -Refer also to _Brit. Med. Journ._, vol. i., 1881, p. 594; _ib._, p. 659. - -Sec. 455. =Separation of Atropine from Organic Tissues, &c.=--From the -contents of the stomach, atropine may be separated by acidulating -strongly with sulphuric acid (15 to 20 c.c. of dilute H_{2}SO_{4} to 100 -c.c.), digesting for some time at a temperature not exceeding 70 deg., and -then reducing any solid matter to a pulp by friction, and filtering, -which can generally be effected by the aid of a filter-pump. The liver, -muscles,[504] and coagulated blood, &c., may also be treated in a -precisely similar way. The acid liquid thus obtained, is first, to -remove impurities, shaken up with amyl alcohol, and after the separation -of the latter in the usual manner, it is agitated with chloroform, which -will take up any of the remaining amyl alcohol,[505] and also serve to -purify further. The chloroform is then removed by a pipette (or the -separating flask before described), and the fluid made alkaline, and -shaken up with ether, which, on removal, is allowed to evaporate -spontaneously. The residue will contain atropine, and this may be -farther purified by converting it into oxalate, as suggested, page 374. - -[504] Neither amyl alcohol nor chloroform removes atropine from an -_acid_ solution. - -[505] Atropine goes into the blood, and appears to be present in the -different organs in direct proportion to the quantity of blood they -contain. Dragendorff has found in the muscles of rabbits fed upon -belladonna sufficient atropine for quantitative estimation. - -From the urine,[506] atropine may be extracted by acidifying with -sulphuric acid, and agitation with the same series of solvents. Atropine -has been separated from putrid matters long after death, nor does it -appear to suffer any decomposition by the ordinary analytical operations -of evaporating solutions to dryness at 100 deg. In other words, there seems -to be no necessity for operations _in vacuo_, in attempts at separating -atropine. - -[506] Dragendorff has found atropine in the urine of rabbits fed with -belladonna; the separation by the poison is so rapid that it often can -only be recognised in the urine during the first hour after the poison -has been taken. - -TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE HENBANE -PLANT. - - +----------------------------+-------+-------+-------+-------+ - | | Seeds,|Leaves,| Stalk,| Root, | - +----------+---------+-------+-------+-------+-------+-------+ - | Plant | Hyosc.- | 1868. | ... | 0.588 | 0.012 | 0.128 | - | Desti- | Albus. | 1869. | ... | 0.469 | ... | 0.176 | - | tute +---------+-------+-------+-------+-------+-------+ - | of | Hyosc.- | 1868. | ... | 0.154 | 0.070 | 0.027 | - | Flowers. | Niger. | 1869. | ... | 0.192 | 0.017 | 0.080 | - +----------+---------+-------+-------+-------+-------+-------+ - | | Hyosc.- | 1868. | ... | 0.359 | 0.036 | 0.146 | - | Plant | Albus. | 1869. | ... | 0.329 | 0.048 | 0.262 | - | in +---------+-------+-------+-------+-------+-------+ - | Flower. | Hyosc.- | 1868. | ... | 0.147 | 0.032 | 0.127 | - | | Niger. | 1869. | ... | 0.206 | 0.030 | 0.138 | - +----------+---------+-------+-------+-------+-------+-------+ - | | Hyosc.- | 1868. | 0.162 | 0.211 | 0.027 | 0.106 | - | Plant | Albus. | 1869. | 0.172 | 0.153 | 0.029 | 0.086 | - | in +---------+-------+-------+-------+-------+-------+ - | Fruit. | Hyosc.- | 1868. | 0.075 | 0.065 | 0.009 | 0.028 | - | | Niger. | 1869. | 0.118 | 0.110 | 0.010 | 0.056 | - +----------+---------+-------+-------+-------+-------+-------+ - - -2. HYOSCYAMINE. - -Sec. 456. This powerful alkaloid is contained in small quantities in datura -and belladonna, and also is found in the common lettuce (.001 per -cent.),[507] and in _Scopola carmolica_, a solanaceous plant -indigenous to Austria and Hungary[508]; but its chief source is the -_Hyoscyamus niger_ and _Hyoscyamus alba_ (black and white henbane): it -is also found in the _Duboisia myoporoides_. The latter plant was -considered to contain a new alkaloid, "_Duboisine_," but duboisine is a -mixture of hyoscyamine and hyoscine. Ladenburg's hyoscine accompanies -hyoscyamine, and is an isomeride of both atropine and hyoscyamine; its -chemical reactions are similar to those of hyoscyamine, as well as its -physiological effects.[509] - -[507] T. S. Dymond, _Journ. Chem. Soc. Trans._, 1892, 90. - -[508] W. R. Dunstan and A. E. Chaston. _Pharm. Journ. Trans._ (3), xx. -461-464. - -[509] See _Ber. der deutsch. Chem. Gesell._, 13, 1549 to 1554. By -boiling hyoscine hydrochloride with animal charcoal, and then -precipitating with auric chloride, a good crystalline compound, melting -at 198 deg., can be obtained. - -=Hyoscyamine= (C_{17}H_{23}NO_{3}), as separated in the course of -analysis, is a resinoid, sticky, amorphous mass, difficult to dry, and -possessing a tobacco-like odour. It can, however, be obtained in -well-marked odourless crystals, which melt at 108 deg.-109 deg., a portion -subliming unchanged. It liquefies under boiling water without -crystallisation. According to Thorey,[510] hyoscyamine crystallises out -of chloroform in rhombic tables, and out of benzene in fine needles; but -out of ether or amyl alcohol it remains amorphous. When perfectly pure, -it dissolves with difficulty in cold, but more readily in hot, water; if -impure, it is hygroscopic, and its solubility is much increased. In any -case, it dissolves easily in alcohol, ether, chloroform, amyl alcohol, -benzene, and dilute acids. Hyoscyamine neutralises acids fully, and -forms crystallisable salts, which assume for the most part the form of -needles. It is isomeric with atropine, and is converted into atropine by -heating to 110 deg., or warming with alcoholic potash. The gold salt melts -at 159 deg., and does not melt in boiling water like the atropine gold salt. - -[510] _Pharm. Zeitschr. f. Russl._, 1869. - -Sec. 457. =Pharmaceutical and other Preparations of Henbane.=--The leaves -are alone officinal in the European pharmacop[oe]ias; but the seeds and -the root, or the flowers, may be met with occasionally, especially among -herbalists. The table[511] (p. 382) will give an idea of the alkaloidal -content of the different parts of the plant. - -[511] This table, taken from Dragendorff's _Chemische Werthbestimmung -einiger starkwirkenden Droguen_, embodies the researches of Thorey. - -In order to ascertain the percentage of the alkaloid in any part of the -plant, the process followed by Thorey has the merit of simplicity. The -substance is first exhausted by petroleum ether, which frees it from -fat; after drying, it is extracted with 85 per cent. alcohol at a -temperature not exceeding 40 deg. The alcoholic extracts are then united, -the alcohol distilled off, and the residue filtered. The filtrate is now -first purified by agitation with petroleum ether, then saturated by -ammonia, and shaken up with chloroform. The latter, on evaporation, -leaves the alkaloid only slightly impure, and, after washing with -distilled water, if dissolved in dilute sulphuric acid, a crystalline -sulphate may be readily obtained. - -=A tincture and an extract of henbane leaves and flowering tops= are -officinal in most pharmacop[oe]ias; an extract of the seeds in that of -France. - -=An oil of hyoscyamus= is officinal in all the Continental -pharmacop[oe]ias, but not in the British. - -=Henbane juice= is recognised by the British pharmacop[oe]ia; it is -about the same strength as the tincture. - -=An ointment=, made of one part of the extract to nine of simple -ointment, is officinal in the German pharmacop[oe]ia. - -The tincture (after distilling off the spirit) and the extracts (on -proper solution) may be conveniently titrated by Mayer's reagent (p. -263), which, for this purpose, should be diluted one-half; each c.c. -then, according to Dragendorff, equalling 6.98 mgrms. of hyoscyamine. -Kruse found 0.042 per cent. of hyoscyamine in a Russian tincture, and -.28 per cent. in a Russian extract. Any preparation made with extract of -henbane will be found to contain nitrate of potash, for Attfield has -shown the extract to be rich in this substance. The ointment will -require extraction of the fat by petroleum ether; this accomplished, the -determination of its strength is easy. - -=The oil of hyoscyamus= is poisonous, and contains the alkaloid. An -exact quantitative research is difficult; but if 20 grms. of the oil are -shaken up for some time with water acidified by sulphuric acid, the -fluid separated from the oil, made alkaline, shaken up with chloroform, -and the latter removed and evaporated, sufficient will be obtained to -test successfully for the presence of the alkaloid, by its action on the -pupil of the eye. - -Sec. 458. =Dose and Effects.=--The dose of the uncrystalline hyoscyamine is -6 mgrms. (1/10 grain), carefully increased. I have seen it extensively -used in asylums to calm violent or troublesome maniacs. Thirty-two -mgrms. (1/2 grain) begin to act within a quarter of an hour; the face -flushes, the pupils dilate, there is no excitement, all muscular motion -is enfeebled, and the patient remains quiet for many hours, the effects -from a single dose not uncommonly lasting two days. 64.8 mgrms. (1 -grain) would be a very large, and possibly fatal, dose. The absence of -delirium or excitement, with full doses of hyoscyamine, is a striking -contrast to the action of atropine, in every other respect so closely -allied; yet there are cases on record showing that the henbane root -itself has an action similar to that of belladonna, unless indeed one -root has been mistaken for another; _e.g._, Sonnenschein relates the -following ancient case of poisoning:--In a certain cloister the monks -ate by error the root of henbane. In the night they were all taken with -hallucinations, so that the pious convent was like a madhouse. One monk -sounded at midnight the matins, some who thereupon came into chapel -could not read, others read what was not in the book, others sang -drinking songs--in short, there was the greatest disturbance. - -Sec. 459. =Separation of Hyoscyamine from Organic Matters.=--The isolation -of the alkaloid from organic tissues or fluids, in cases where a -medicinal preparation of henbane, or of the leaves, root, &c., has been -taken, is possible, and should be carried out on the principles already -detailed. Hyoscyamine is mainly identified by its power of dilating the -pupil of the eye. It is said that so small a quantity as .0083 mgrm. -(1/4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is -true that atropine also dilates the pupil; but if sufficient of the -substance should have been isolated to apply other tests, it can be -distinguished from atropine by the fact that the latter gives no -immediate precipitate with platinic chloride, whilst hyoscyamine is -precipitated by a small quantity of platinic chloride, and dissolved by -a larger amount, and also by the characters of the gold salt. - - -3. HYOSCINE. - - Sec. 460. =Hyoscine=, C_{17}H_{23}NO_{3}.--According to E. Schmidt[512] - the formula is C_{17}H_{21}NO_{4} + H_{2}O, and the alkaloid is - identical with scopolamine. Scopolamine has a m.p. of 59 deg., gives an - aurochloride, crystallising in needles, the m.p. of which is 212 deg. to - 214 deg.; when boiled with baryta water, it splits up into atropic acid - and scopoline, a base (C_{8}H_{13}NO), m.p. 110 deg., boiling-point, - 241 deg. to 243 deg.; scopoline forms an aurochloride, m.p. 223 deg.-225 deg.; and a - platinochloride, m.p. 228 deg.-230 deg.; but Ladenburg,[513] in answer to - Schmidt, asserts that hyoscine exists, and is not identical with - scopolamine. A sample of commercial hyoscine hydrobromide Nagelvoort - found to melt, water-free, at 198 deg.; other commercial samples of - hydrobromide melted at 179 deg. and 186 deg.; the latter sample giving an - aurochloride which melted at 192 deg. Pure hyoscine gold chloride is - stated to melt at 198 deg. Its reactions are much the same as those of - atropine, but it does not blacken calomel. It is very poisonous. - -[512] _Arch. Pharm._, ccxxx. 207-231. - -[513] _Ber._, xxv. 2388-2394. - - According to experiments on animals, the heart is first slowed, then - quickened; the first effect being due to a stimulation of the - inhibitory nervous apparatus, the second to a paralysing action on - the same. The temperature is not altered. The pupils are dilated, - the saliva diminished. The irritability of the brain is - lessened.[514] - -[514] Parloff, _St Petersburg Med. Chem. Acad._, Dissert. No. 9, -1889-90. - - -4. SOLANINE. - - Sec. 461. =Distribution of Solanine.=--Solanine is a poisonous - nitrogenised glucoside found in all parts of the plants belonging to - the nightshade order. The English common plants in which solanine - occurs are the edible potato plant (_Solanum tuberosum_), the - nightshade (_Solanum nigrum_), and the _Solanum dulcamara_, or - bitter-sweet. The berries of the _Solanum nigrum_ and those of _S. - dulcamara_ contain about 0.3 per cent. Mature healthy potatoes - appear to contain no solanine, but from 150 grms. of diseased - potatoes G. Kassner[515] separated 30 to 50 mgrms. - -[515] _Arch. Pharm._ (3), xxv. 402, 403. - - R. Firbas,[516] in a research on the active substances or young - shoots of the _S. tuberosum_ found two products--one crystalline, - _Solanine_; the other amorphous, _Solaneine_. He gives the following - formula to solanine--C_{52}H_{93}NO_{18}4-1/2H_{2}O; when dried at - 100 deg. it becomes anhydrous. From a solution in 85 per cent. alcohol - it crystallises in colourless needles, m.p. 244 deg.; these are almost - insoluble in ether and alcohol, but are readily dissolved in dilute - hydrochloric acid. On hydrolysis solanine breaks up into solanidine - and a sugar, according to the equation-- - -[516] _Monatsh._, x. 541-560; _Journ. Chem. Soc._ (Abst.), Jan. 1890. - - C_{52}H_{93}NO_{18} = C_{40}H_{61}NO_{2} + 2C_{6}H_{12}O_{6} + - 4H_{2}O. - - Sec. 462. =Properties of Solanine.=--The reaction of the crystals is - weakly alkaline; the taste is somewhat bitter and pungent. Solanine - is soluble in 8000 parts of boiling water, 4000 parts of ether, 500 - parts of cold, and 125 of boiling alcohol. It dissolves well in hot - amyl alcohol, but is scarcely soluble in benzene. An aqueous - solution froths on shaking, but not to the degree possessed by - saponine solutions. - - The amyl alcohol solution has the property of gelatinising when - cold. It does this if even so little as 1 part of solanine is - dissolved in 2000 of hot amyl alcohol. The jelly is so firm that the - vessel may be inverted without any loss. This peculiar property is - one of the most important tests for the presence of solanine. The - hot ethylic alcohol solution will, on cooling, also gelatinise, but - a stronger solution is required. From very dilute alcoholic - solutions (and especially with slow cooling) solanine may be - obtained in crystals. In dilute mineral acids solanine dissolves - freely, and forms salts, which for the most part have an acid - reaction and are soluble in alcohol and in water, but with - difficulty in ether. The compounds with the acids are not very - stable, and several of them are broken up on warming the solution, - solanine separating out from the aqueous solutions of the solanine - salts. The alkaloid may be precipitated by the fixed and volatile - alkalies, and by the alkaline earths. Solanine will stand boiling - with strongly alkaline solutions without decomposition; but dilute - acids, on warming, hydrolyse. By heating solanine in alcoholic - solution with ethyl iodide in closed tubes, and then treating the - liquid with ammonia, ethyl solanine in well-formed crystals can be - obtained. Solanine is precipitated by phosphomolybdic acid, but by - very few other substances. It gives, for example, no precipitate - with the following reagents:--Platinic chloride, gold chloride, - mercuric chloride, potassic bichromate, and picric acid. Tannin - precipitates it only after a time. Sodic phosphate gives a - crystalline precipitate of solanine phosphate, if added to a - solution of solanine sulphate. Both solanine and solanidine give - with nitric acid at first a colourless solution, which, on gentle - warming, passes into blue, then into light red, and lastly becomes - weakly yellow. Solanine, dissolved in strong sulphuric acid, to - which a little Froehde's reagent is added, at first colours the fluid - light brown; after standing some time the edges of the drop becomes - reddish-yellow, and finally the whole a beautiful cherry-red, which - gradually passes into dark violet when violet-coloured flocks - separate. - - Sec. 463. =Solanidine.=--Solanidine has stronger basic properties than - solanine. Its formula is C_{40}H_{61}NO_{2}. It is obtained from an - alcoholic solution in amorphous masses interspersed with needles; - m.p. 191 deg. It dissolves readily in hot alcohol, with difficulty in - ether. With hydrochloric acid it forms a - hydrochloride--3(C_{40}H_{61}NO_{2}HCl)HCl + H_{2}O or 1-1/2H_{2}O. - This hydrochloride is a slightly yellow powder, only sparingly - soluble in water, and carbonising without melting when heated to - 287 deg. Solanidine also forms a sulphate, - 3(C_{40}H_{61}NO_{2}H_{2}SO_{4})H_{2}SO_{4} + 8H_{2}O; this salt is - in the form of scaly plates, melting at 247 deg.; it dissolves readily - in water. - - The sugar obtained from the hydrolysis of solanidine is a yellow - amorphous mass dissolving readily in water and wood spirit, and has - a specific rotatory power of [[alpha]]_{D} = + 28.623. With - Phenylhydrazine hydrochloride and sodium acetate in aqueous solution - it forms a glucosazone, melting at 199 deg. It is probably a mixture of - sugars. - - Solaneine is the name that has been given to the amorphous substance - accompanying solanine; on hydrolysis it yields solanidine and the - same sugar as solanine. Its formula is C_{52}H_{82}NO_{13} with - 4H_{2}O. - - Sec. 464. =Poisoning from Solanine.=--Poisoning from solanine has been, - in all recorded cases, induced, not by the pure alkaloid (which is - scarcely met with out of the laboratory of the scientific chemist), - but by the berries of the different species of _Solanum_, and has - for the most part been confined to children. The symptoms in about - twenty cases,[517] which may be found detailed in the medical - literature of this century, have varied so greatly that the most - opposite phenomena have been witnessed as effects of poisoning by - the same substance. The most constant phenomena are a quick pulse, - laboured respiration, great restlessness, and hyperaesthesia of the - skin. Albumen in the urine is common. Nervous symptoms, such as - convulsions, aphasia, delirium, and even catalepsy, have been - witnessed. In some cases there have been the symptoms of an irritant - poison--diarrh[oe]a, vomiting, and pain in the bowels: in many cases - dilatation of the pupil has been observed. - -[517] See "Death of Three Children by _S. nigrum_"; Hirtz., _Gaz. Med. -de Strasbourg_, 1842; Maury, _Gaz. des Hop._, 1864; J. B. Montane, -_Chim. Med._, 1862; Magne, _Gaz. des Hop._, 1869; Manners, _Edin. Med. -Journ._, 1867. Cases of poisoning by bitter-sweet berries are recorded -in _Lancet_, 1856; C. Bourdin, _Gaz des Hopitaux_, 1864; Bourneville, -the berries of _S. tuberosum_, _Brit. Med. Journ._, 1859. - - Rabbits are killed by doses of .1 grm. per kilo. The symptoms - commence in about ten minutes after the administration, and consist - of apathy and a low temperature; the breathing is much slowed. - Convulsions set in suddenly before death, and the pupils become - dilated. The _post-mortem_ appearances in animals are intense - redness and injection of the meninges of the cerebellum, of the - medulla oblongata, and the spinal cord. Dark red blood is found in - the heart, and the kidneys are hyperaemic. The intestinal mucous - membrane is normal. - - Sec. 465. =Separation of Solanine from the Tissues of the - Body.=--Dragendorff has proved the possibility of separating - solanine from animal tissues by extracting it from a poisoned pig. - The best plan seems to be to extract with cold dilute sulphuric acid - water, which is then made alkaline by ammonia, and shaken up with - warm amyl alcohol. This readily dissolves any solanine. The peculiar - property possessed by the alkaloid of gelatinising, and the play of - colours with Froehde's reagent, may then be essayed on the solanine - thus separated. - - -5. CYTISINE. - -Sec.466. =The Cytisus Laburnum.=--The laburnum tree, _Cytisus laburnum_, so -common in shrubberies, is intensely poisonous. The flowers, bark, wood, -seeds, and the root have all caused serious symptoms. The active -principle is an alkaloid, to which the name of Cytisine has been given. -The best source is the seeds. The seeds are powdered and extracted with -alcohol containing hydrochloric acid, the alcohol distilled off, the -residue treated with water and filtered through a wet filter to remove -any fatty oil, the filtrate treated with lead acetate; and, after -separating the precipitated colouring matter, made alkaline with caustic -potash, and shaken with amyl alcohol. The amyl alcohol is shaken with -dilute hydrochloric acid, the solution evaporated, the crude crystals -of hydrochloride thus obtained treated with alcohol to remove colouring -matters, and recrystallised several times from water; it then forms -well-developed, colourless, transparent prisms. From the hydrochloride -the free base is readily obtained. - -=Cytisine=, C_{11}H_{14}N_{2}O.--To cytisine used to be ascribed the -formula C_{20}H_{27}N_{3}O, but a study of the salt and new -determinations appear to prove that it is identical with ulexine.[518] -Cytisine is in the form of white radiating crystals, consisting, when -deposited from absolute alcohol, of anhydrous prisms, which melt at from -152 deg. to 153 deg. Cytisine has a strong alkaline reaction; it is soluble in -water, alcohol, and chloroform, less so in benzene and amyl alcohol, -almost insoluble in cold light petroleum, and insoluble in pure ether. -The specific rotatory power in solution is [[alpha]]_{D}17 deg. = -119.57. - -[518] A. W. Gerrard and W. H. Symons dispute this; they ascribe -to ulexine the formula of C_{11}H_{14}N_{2}O, to cytisine -C_{20}H_{27}N_{3}O. Ulexine is very hygroscopic, cannot be sublimed, -even in a vacuum, without decomposition, and dissolves readily in -chloroform; on the contrary, cytisine is not hygroscopic, sublimes -completely, and is almost insoluble in chloroform, _Pharm. J._ (3), xx. -1017. - -A. Partheil, _Ber._, xxiii. 3201-3203; _Arch. Pharm._, ccxxx. 448-498. - -It is capable of sublimation in a current of hydrogen at 154.5 deg.; the -sublimate is in the form of very long needles and small leaflets; at -higher temperatures it melts to a yellow oily fluid, again becoming -crystalline on cooling. Cytisine is a strong base; it precipitates the -earths and oxides of the heavy metals from solutions of the chlorides, -and, even in the cold, expels ammonia from its combinations. - -Cytisine forms numerous crystalline salts, among which may be mentioned -two platinochlorides, C_{11}H_{14}N_{2}OH_{2}PtCl_{6} + 2-1/2H_{2}O and -(C_{11}H_{14}N_{2}O)_{2}H_{2}PtCl_{6}, crystallising in golden yellow -needles, which are tolerably soluble in water; and the aurochloride, -C_{11}H_{14}N_{2}OHAuCl_{4}, crystallising in short, red-brown, -hook-shaped needles; m.p. 212 deg. to 213 deg., without evolution of gas. - -Sec. 467. =Reactions of Cytisine.=--Concentrated sulphuric acid dissolves -cytisine without colour; if to the solution is added a drop of nitric -acid, it becomes orange-yellow, and on addition of a crystal of potassic -bichromate, first yellow, then dirty brown, and lastly green. -Concentrated nitric acid dissolves the base in the cold without colour, -but, on warming, it becomes orange-yellow. Picric, tannic, and -phosphomolybdic acids, potassic, mercuric, and potass. cadmium iodides, -and iodine with potassic iodide, all give precipitates. Neither potassic -bichromate nor mercuric chloride precipitates cytisine, even though the -solution be concentrated. The best single test appears to be the -reaction discovered by Magelhaes; this consists in adding thymol to a -solution of cytisine in concentrated sulphuric acid, when a yellow -colour, finally passing into an intense red, is produced. - -Sec. 468. =Effects on Animals.=--W. Marme found subcutaneous doses of from -30 to 40 mgrms. fatal to cats; death was from paralysis of the -respiration, and could be avoided by artificial respiration. Cattle are -sometimes accidentally poisoned by laburnum. An instance of this is -recorded in the _Veterinarian_ (vol. lv. p. 92). In Lanark a storm had -blown a large laburnum tree down to the ground; it fell into a field in -which some young heifers were grazing, and they began to feed on the -leaves and pods. Two or three died, and three more were ill for some -time, but ultimately recovered. - -The laburnum, however, does not always have this effect, for there is a -case related in the _Gardeners' Chronicle_, in which five cows browsed -for some time on the branches and pods of an old laburnum tree that had -been thrown aside. Rabbits and hares are said to feed eagerly, and -without injury, on the pods and branches. - -Sec. 469. =Effects on Man.=--The sweet taste of many portions of the -laburnum tree, as well as its attractive appearance, has been the cause -of many accidents. F. A. Falck has been able to collect from medical -literature no less than 155 cases--120 of which were those of the -accidental poisoning of children: only 4 (or 2.6 per cent.), however, -died, so that the poison is not of a very deadly character. - -One of the earliest recorded cases is by Christison.[519] A servant-girl -of Inverness, in order to excite vomiting in her fellow-servant (the -cook), boiled some laburnum bark in soup; very soon after partaking of -this soup, the cook experienced violent vomiting, which lasted for -thirty-six hours; she had intense pain in the stomach, much diarrh[oe]a, -and great muscular weakness; she appears to have suffered from -gastro-intestinal catarrh for some time, but ultimately recovered. - -[519] _Ed. Med. Journ._, 1843. - -Vallance[520] has described the symptoms observed in the poisoning of -fifty-eight boys, who ate the root of an old laburnum tree, being -allured by its sweet taste. All were taken ill with similar symptoms, -differing only in severity; two who had eaten half an ounce (nearly 8 -grms.) suffered with especial severity. The symptoms were first -vomiting, then narcosis, with convulsive movements of the legs and -strange movements of the arms: the pupils were dilated. This dilatation -of the pupil Sedgwick also saw in the poisoning of two children who ate -the root. On the other hand, when the flower, seeds, or other portions -of the laburnum have been eaten, the symptoms are mainly referable to -the gastro-intestinal tract, consisting of acute pain in the stomach, -vomiting, and diarrh[oe]a. On these grounds it is therefore more than -probable that there is another active principle in the root, differing -from that which is in those portions of the tree exposed to the -influence of sunlight.[521] - -[520] _Brit. Med. Journ._, 1875. - -[521] See also a case related by Dr. Popham, in which ten children ate -laburnum seeds; the pupils were dilated. They all recovered. _B. and F. -Med. Chir. Review_, Ap. 1863; also a case reported by H. Usher, _Med. -Times and Gazette_, Sept. 15, 1862. - -The _post-mortem_ appearances are, so far as known, in no way -characteristic. - - -VII.--The Alkaloids of the Veratrums. - -Sec. 470. The alkaloids of the veratrums have been investigated by Dr. -Alder Wright, Dr. A. P. Luff, and several other chemists.[522] - -[522] "The Alkaloids of the Veratrums," by C. R. Alder Wright, D.Sc., -and A. P. Luff, _Journ. Chem. Soc._, July 1879; "The Alkaloids of -_Veratrum viride_," by C. Alder Wright, D.Sc., _ib._, 1879. - -The method which Wright and Luff adopted to extract and separate these -alkaloids from the root of _V. album_ and _V. viride_, essentially -consisted in exhausting with alcohol, to which a little tartaric acid -has been added, filtering, distilling off the alcohol, dissolving the -residue in water, alkalising with caustic soda, and shaking up with -ether. The ethereal solution was next separated, and then washed with -water containing tartaric acid, so as to obtain a solution of the bases -as tartrates: in this way the same ether could be used over and over -again. Ultimately a rough separation was made by means of the different -solubilities in ether, pseudo-jervine being scarcely soluble in this -medium, whilst jervine, veratralbine, veratrine, and cevadine are very -soluble in it. - -The yield of Wright and Luff's alkaloids was as follows:-- - -TABLE SHOWING THE ALKALOIDS IN THE VERATRUMS. - - +---------------+------------+---------------------+ - | | V. album. | V. viride. | - | | Per Kilo. | Per Kilo. | - | +------------+---------------------+ - |Jervine, | 1.3 grm. | .2 grm. | - |Pseudo-jervine,| .4 " | .15 " | - |Rubi-jervine, | .25 " | .02 " | - |Veratralbine, | 2.2 " | Traces. | - |Veratrine, | .05 " | Less than .004 grm. | - |Cevadine, | Absent. | " .43 " | - +---------------+------------+---------------------+ - -From whence it appears that _V. album_ has only a very small quantity of -veratrine, that it is almost absent in _V. viride_; on the other hand, -_V. viride_ contains a fair quantity of cevadine, an alkaloid absent in -_V. album_. - -Besides the six principles enumerated, G. Salzberger has recently -separated two other crystalline substances, to which he has given the -names of _protoveratrine_ and _protoveratridine_, and Pehkschen has also -separated a ninth substance, to which he has given the name of -_veratroidine_. - -The formulae of the nine bodies which have been separated from hellebore -root are as follows:-- - - Melting- - point. - 1. Veratrine, C_{37}H_{53}NO_{11}, ... - 2. Cevadine, C_{32}H_{49}NO_{9}, 205 deg.-206 deg. - 3. Protoveratrine, C_{32}H_{51}NO_{11}, 245 deg.-250 deg. - 4. Pseudo-jervine, { C_{29}H_{43}NO_{7} (_Wright_), 299 deg.-300 deg. - { C_{29}H_{49}NO_{12} (_Pehkschen_), ... - 5. Veratralbine, C_{28}H_{43}NO_{5}, ... - 6. Protoveratridine, C_{26}H_{45}NO_{8}, 265 deg. - 7. Rubi-jervine, { C_{26}H_{43}NO_{2} (_Wright_ and _Luff_), 236 deg. - { (_Salzberger_), 240 deg.-245 deg. - 8. Jervine, C_{26}H_{37}NO_{3}2H_{2}O, 237 deg.-239 deg. - 9. Veratroidine, C_{32}H_{53}NO_{9}, 149 deg. - -Three of these alkaloids possess powerful sternutatory properties, the -least quantity applied to the nostrils exciting sneezing; the three are -veratrine, cevadine, and protoveratrine. - -Protoveratrine, C_{32}H_{51}NO_{11}, has been obtained by G. -Salzberger[523] from powdered hellebore root, by the following -process:-- - -[523] _Arch. Pharm._, ccxxviii. 462-483. - -The powdered root is first freed from fatty and resinous matters by -treatment with ether, and then the fat-free powder is exhausted with -alcohol. The alcohol is evaporated off in a vacuum, the extract mixed -with much acetic acid water, filtered from the insoluble residue, and -treated with metaphosphoric acid; the voluminous precipitate contains -much amorphous matter, with insoluble compounds of jervine and -rubi-jervine. The precipitate is filtered off, and the filtrate treated -with excess of ammonia and shaken up with ether. On separating the ether -and distilling, protoveratrine crystallises out, and can be obtained -pure by recrystallisation from strong alcohol. - -Protoveratrine crystallises in four-sided plates, which melt with -charring at 245 deg. to 250 deg. The base is insoluble in water, benzene, and -light petroleum; chloroform and boiling 96 per cent. alcohol dissolve it -somewhat; cold ether scarcely touches it, boiling ether dissolves it a -little. - -Concentrated sulphuric acid dissolves the alkaloid slowly with the -production of a greenish colour, which passes to cornflower blue, and, -after some hours, becomes violet. Sulphuric acid and sugar gives a -different colour to that produced by commercial veratrine. There is -first a green colour which darkens into olive green, then becomes dirty -green, and finally dark brown. When warmed with strong sulphuric, -hydrochloric, or phosphoric acids, there is a strong odour of -isobutyric acid developed. Dilute solutions of the salts are -precipitated by ammonia, Nessler's reagent, gold chloride, potassium -mercury iodide, cadmium iodide, phosphotungstic acid, and picric acid; -no precipitate is produced by tannin, platinum chloride, or mercuric -chloride. - -Sec. 471. =Veratrine= (C_{37}H_{53}NO_{11}) is a crystallisable alkaloid, -which is a powerful irritant of the sensory nerves of the mucous -membrane, and excites violent sneezing. Treated with concentrated -sulphuric acid, it dissolves with a yellow colour, deepening into -orange, then into blood-red, and finally passing into carmine-red. If -the freshly-prepared sulphuric acid solution is now treated with bromine -water, a beautiful purple colour is produced. Concentrated hydrochloric -acid dissolves veratrine without the production of colour, but, with -careful warming, it becomes beautifully red. This reaction is very -delicate, occurring with .17 mgrm. On saponification veratrine yields -veratric acid. - -Veratric acid is procatechu-dimethylether acid, and has the -constitutional formula, - - COOH - / - C_{6}H_{3} . - \ - (OCH_{3})_{2} - -Veratric acid forms colourless needles and four-sided prisms which have -a marked acid reaction; it melts on heating to a colourless fluid, and -sublimes without decomposition; it is easily soluble in hot alcohol, but -insoluble in ether. If dissolved in nitric acid, water separates -nitro-veratric acid, C_{9}H_{9}(NO_{2})O_{4} which crystallises out of -alcohol in small yellow scales. Veratric acid unites with bases forming -crystalline salts; the silver salt has the composition of -C_{9}H_{9}AgO_{4} = 37.37 per cent. silver, and may assist in -identification. It is crystalline with a melting point of 205 deg. to 206 deg. - -=Cevadine=, C_{32}H_{49}NO_{9} (Merck's veratrine).--It has powerful -sternutatory properties, and, under the influence of alcoholic potash, -yields tiglic[524] acid and cevine, C_{27}H_{43}NO_{8}. - -[524] Tiglic acid, C_{5}H_{8}O_{2}, is a volatile acid, m.p. 64 deg., -boiling point, 198.5 deg.; it forms a soluble barium salt, and an insoluble -silver salt. - -According to Ahrens, angelic acid is first formed, and then converted -into tiglic acid. When the alkaloid is boiled with hydrochloric acid, -tiglic acid is formed, and a ruby red mass. Nitric acid oxidises -cevadine completely; with potassic permanganate it yields acetic and -oxalic acids; with chromic acid it forms acetaldehyde and carbon -dioxide.[525] - -[525] _Ber._, xxiii. 2700-2707. - -The Continental authorities always give to cevadine the name of -veratrine. Cevadine forms a crystalline aurochloride, a crystalline -mercurochloride, C_{32}H_{49}NO_{9}HHgCl_{3}, and a crystalline picrate, -C_{32}H_{49}NO_{9}C_{6}H_{3}N_{8}O_{7}. The mercury salt crystallises in -small silvery plates, and melts with decomposition at 172 deg. The picrate -forms stable crystals blackening at 225 deg.; both of the latter salts are -but little soluble in water, but are soluble in alcohol. Cevadine also -unites with bromine, forming a tetrabromide, an amorphous yellow powder -insoluble in water, but readily soluble in alcohol, ether, and -chloroform. - -Sec. 472. =Jervine=, (C_{26}H_{37}NO_{3}2H_{2}O) (_Wright_ and _Luff_), -C_{14}H_{22}NO_{2} (_Pehkschen_),[526] crystallises in white needles, -and, when anhydrous, melts at 237.7 deg. It is slightly laevorotatory. At -25 deg. one part of the base dissolves in 1658 benzene, 268 ether, 60 -chloroform, and 16.8 absolute alcohol. It is insoluble in light -petroleum, and but slightly soluble in ethyl acetate, water, or carbon -bisulphide. It forms a very insoluble sulphate, and a sparingly soluble -nitrate and hydrochloride. Jervine gives, with sulphuric acid and sugar, -a violet colour, passing to blue. Treated with strong sulphuric acid it -dissolves to a yellow fluid, which becomes successively dark yellow, -brownish yellow, and then greenish. The green shade is immediately -developed by diluting with water. Jervine does not produce sneezing. - -[526] _Jour. Pharm._ (5), xxii. 265-269. - -Sec. 473. =Pseudo-jervine=, C_{29}H_{43}NO_{7} (_Wright_), m.p. 299 deg.; -C_{29}H_{49}NO_{12}, m.p. 259 deg. (_Pehkschen_), may be obtained in a -crystalline state. One part is soluble in 10.9 parts of light petroleum, -372 parts of benzene, 1021 parts of ether, 4 of chloroform, and 185 of -absolute alcohol. The pure base gives no colour with sulphuric, nitric, -or hydrochloric acids. It does not produce sneezing. - -Sec. 474. =Protoveratridine=, C_{26}H_{45}NO_{8}, is probably derived from -protoveratrine. Salzberger[527] isolated it from powdered hellebore -roots by treating the powder with barium hydroxide and water, and -extracting with ether. The ether extract was separated and freed from -ether in a current of hydrogen at a low temperature. - -[527] _Arch. Pharm._, ccxxviii. 462-483. - -From the dark green syrup obtained jervine crystallised out, and from -the mother liquor ultimately protoveratridine was separated. - -Protoveratridine crystallises in colourless four-sided plates, which -melt at 265 deg. It is almost insoluble in alcohol, chloroform, methyl -alcohol, and acetone, and insoluble in benzene, light petroleum, and -ether. Concentrated sulphuric acid gives a violet, then a cherry-red -colour. Its solution in concentrated hydrochloric acid becomes light red -on warming, and there is an odour of isobutyric acid. It is readily -soluble in dilute mineral acids, and the solution, on the addition of -ammonia, yields the alkaloid in a crystalline condition. The sulphuric -acid solution gives precipitates with phosphotungstic, picric, and -tannic acids, and with potassium mercury iodide; but gives no -precipitate with platinum chloride, potassium-cadmium iodide, or with -Millon's reagent. - -It forms a platinum salt, (C_{26}H_{45}NO_{8})_{2}H_{2}PtCl_{6} + -6H_{2}O, which is precipitated in large six-sided plates on adding -alcohol to a mixed solution of platinum chloride and a salt of the base. - -Protoveratridine is not poisonous, and does not cause sneezing. Its -solutions are very bitter. - -Sec. 475. =Rubi-jervine=, C_{26}H_{43}NO_{2}, is a crystallisable base -wholly different from jervine, yet probably closely allied to it. It -forms a light yellow, indistinctly crystalline gold salt -(C_{26}H_{43}NO_{2},HCl,AuCl_{3}): it gives a different play of colours -from jervine with sulphuric acid. The concentrated acid dissolves -rubi-jervine to a clear yellow fluid, becoming successively dark yellow, -brownish yellow, and brownish blood-red, changing after several hours to -a brownish purple. On diluting slightly with water the brownish-red -liquid, it becomes successively crimson, purple, dark lavender, dark -violet, and ultimately light indigo. Its hydrochloride and sulphate are -both more soluble than either of the corresponding salts of jervine or -pseudo-jervine. - -Sec. 476. =Veratralbine=, C_{28}H_{43}NO_{5}, an amorphous non-sternutatory -base, gives, when a speck of the substance is dissolved in sulphuric -acid, a play of colours, becoming successively yellow, dark yellow, -brownish orange, and brownish blood-red, with a strong green -fluorescence. It yields no acid on saponification. - -Sec. 477. =Veratroidine=, C_{32}H_{53}NO_{9}, is another base which has -been separated by C. Pehkschen.[528] Its melting point is 149 deg. One part -dissolves in 13 of benzene, 59 of chloroform, and 9 of ether. It yields -amorphous salts with the mineral acids, and with oxalic and acetic -acids. It is precipitated by most of the group reagents. With 11 per -cent. solution of hydrochloric acid it gives a beautiful rose colour. - -[528] _Op. cit._ - -Sec. 478. =Commercial Veratrine.=--Commercial veratrine is a mixture of -alkaloids, and has usually fairly constant properties, one of which is -its intense irritant action on the nostrils. Placed on moist blue-red -litmus paper it gives a blue spot. It is but little soluble in water, -1 : 1500; but readily dissolves in alcohol and chloroform; it is but -little soluble in amyl alcohol, benzene, and carbon disulphide. - -When a very small quantity is treated with a drop of sulphuric acid, the -acid in the cold strikes a yellow colour; on warming, the colour becomes -violet, slowly changing to orange and cherry red. Sensible to 100th of -mgrm. If this test is performed in a test-tube, a green-yellow -fluorescence is also seen on the sides of the test-tube. - -Commercial veratrine strikes a pink-red colour with hydrochloric acid in -the cold if a long time is allowed to elapse, but it at once appears if -the acid is warmed, and is permanent. The solution becomes fluorescent -if two drops of acetic acid are added. - -If a small quantity of commercial veratrine is added to melted oxalic -acid and the warming continued, a blood-red colour is obtained. - -Veratrine, warmed with syrupy phosphoric acid, develops an odour of -butyric acid. - -A dark green colour, followed by reddish purple and blue colours, is -obtained by adding a sprinkling of finely-powdered sugar to a solution -of veratrine in sulphuric acid. This is best seen with a solution of 1 -to 10,000; if in dilution of 1 to 100,000 a grass-green colour is -produced, followed by purple and blue colours, quickly changing to brown -or black.[529] - -[529] _Flueckiger's Reactions_, 1893. - -When two or three drops of sulphuric acid and furfur aldehyde (5 drops -to 10 c.c. of acid) are added to minute particles of alkaloids, a more -or less characteristic colour makes its appearance; this is particularly -the case with veratrine. A few particles rubbed with a glass rod, and -moistened with the reagent, gives first a yellowish-green, then an -olive-green mixture, the edges afterwards becoming a beautiful blue. On -warming, the mixture gradually acquires a purple-violet colour. The blue -substance obtained in the cold is insoluble in alcohol, ether, or -chloroform. The least amount of water decolorises the solution, and, on -adding much water, a fairly permanent yellow solution is obtained.[530] - -[530] A. Wender, _Chem. Zeitung_, xvii. 950, 951. - -Sec. 479. =Pharmaceutical Preparations.=--The alkaloid is officinal in the -English, American, and Continental pharmacop[oe]ias. There is also an -_unguentum veratrinae_--strength about 1.8 per cent. In the London -pharmacop[oe]ia of 1851 there used to be a wine of white hellebore, the -active principle of 20 parts of the root by weight being contained in -100 parts by measure of the wine. Such a wine would contain about 0.084 -per cent. of total alkaloids. Of the green hellebore there is a tincture -(_tinctura veratri viridis_), to make which four parts by weight of the -root are exhausted by 20 parts by measure of spirits; the strength -varies, but the average is 0.02 per cent. of total alkaloids. - -Sec. 480. =Fatal Dose.=--The maximum dose of the commercial alkaloid is -laid down as 10 mgrms. (.15 grain), which can be taken safely in a -single dose, but nothing sufficiently definite is known as to what is a -lethal dose. 1.3 grm. of the powdered rhizome has caused death, and, on -the other hand, ten times that quantity has been taken with impunity, so -that at present it is quite an open question. - -Sec. 481. =Effects on Animals--Physiological Action.=--Experiments on -animals have proved that the veratrums act on the sensory nerves of the -skin, and those of the mucous membranes of the nose and intestinal -canal; they are first excited, afterwards paralysed. When administered -to frogs, sugar and lactic acid appear in the urinary excretion.[531] -It exercises a peculiar influence on voluntary muscle; the -contractility is changed, so that, when excited, there is a -long-continuing contraction, and from a single stimulus more heat is -disengaged than with healthy muscle; the motor nerves are also affected. -The respiration, at first quickened, is then slowed, and finally -paralysed. The heart's action is also first quickened, the -blood-pressure at the same time is raised, and the small arteries -narrowed in calibre; later follow sinking of the pressure, slowing of -the heart, and dilatation of the vessels, and the heart becomes finally -paralysed. - -[531] _Zeit. Phys. Chem._, xvi. 453-459. - -Sec. 482. =Effects on Man.=--Poisoning by veratrum, sabadilla, or -pharmaceutical preparations containing veratrine, is not common. Plenk -witnessed a case in which the external application of sabadilla powder -to the head caused delirium, and Lentin also relates a case in which an -infant at the breast seems to have died from an external application -made for the purpose of destroying lice. In both instances, however, -there is a possibility that some of the medicament was swallowed. - -Blas recorded, in 1861, the case of two children who drank a decoction -of white hellebore, the liquid being intended as an external application -to an animal. They showed serious symptoms, but ultimately recovered. - -A scientific chemist took 3.8 grms. (58 grains) of the tincture of green -hellebore for the purpose of experiment. There followed violent symptoms -of gastric irritation, vomiting, and diarrh[oe]a, but he also -recovered.[532] - -[532] _Med. Times and Gazette_, Jan. 3, 1863. - -Casper relates the poisoning of a whole family by veratrum; from the -stomach of the mother (who died) and the remains of the repast (a -porridge of lentils) veratrine was separated. - -Faber[533] recorded the poisoning of thirty cows by veratrum; eight -died, and it is noteworthy that violent poisonous symptoms were produced -in animals partaking of their flesh and milk. - -[533] _Zeitschr. f. Staatsarzneik._, 1862. - -Sec. 483. The symptoms appear soon after the ingestion, and consist of a -feeling of burning in the mouth, spreading downwards to the stomach, -increased secretion of saliva, and difficulty of swallowing; then follow -violent vomiting and diarrh[oe]a, with great pain in the bowels, often -tenesmus; there is also headache, giddiness, a feeling of anxiety, and -the pupils are dilated. The consciousness is ordinarily intact; the -pulse is weak and slow, and the breathing embarrassed; the skin is -benumbed. There may be also formicating feelings, and twitchings in the -muscles with occasionally the tetanic cramps, which are constantly seen -in frogs. In cases which end fatally, the disturbance of the breathing -and circulation increases, and death takes place in collapse. - -An important case of slow poisoning is on record,[534] in which two -brothers, aged twenty-one and twenty-two years, died after nine and -eleven weeks of illness, evidently from repeated small doses of the -powder of _Veratrum album_. They became very weak and thin, suffered -from diarrh[oe]a and bloody stools, sleeplessness, disturbance of the -intellect, and delirium. - -[534] Nivet and Geraud, _Gaz. Hebdom._, 1861. - -Sec. 484. The _post-mortem_ signs do not appear distinctive; even in the -case just mentioned--in which one would expect to find, at all events, -an extensive catarrh of the intestinal canal--the results seem to have -been negative. - -Sec. 485. =Separation from Organic Matters.=--The method of Stas (by which -the organic matters, whether the contents of the stomach or the tissues, -are treated with alcohol, weakly acidified by tartaric acid) is to be -recommended. After filtering, the alcoholic extract may be freed from -alcohol by careful distillation, and the extract taken up with water. By -now acidifying gently the watery extract, and shaking it up with ether -and chloroform, fatty matters, resinous substances, and other -impurities, are removed, and it may then be alkalised by soda or potash, -and the veratrine extracted by ether. The residue should be identified -by the hydrochloric acid and by the sulphuric acid and bromine -reactions; care should also be taken to ascertain whether it excites -sneezing. - -A ptomaine, discovered by Brouardel,[535] was described by him as both -chemically and physiologically analogous to veratrine. A. M. -Deleziniere[536] has since investigated this substance. Only when in -contact with air does the analogy to veratrine obtain, and Deleziniere, -to ascertain its reactions, studied it when in an atmosphere of -nitrogen. It appears to be a secondary monamine, C_{32}H_{31}N, and is -in the form of a colourless, oily liquid, with an odour like that of the -hawthorn. It is insoluble in water, but alcohol, ether, toluene, and -benzene dissolve it readily. It oxidises in the presence of air. The -salts are deliquescent. - -[535] _Moniteur Scient._ (3), 10, 1140. - -[536] _Bull. Soc. Chim._ (3), 1, 178-180. - - -VIII.--Physostigmine. - -Sec. 486. The ordeal bean of Calabar (_Physostigma faba_) is a large, all -but tasteless, kidney-shaped bean, about an inch in length, and half an -inch thick; its convex edge has a furrow with elevated ridges, and is -pierced by a small hole at one extremity. The integuments are -coffee-brown in colour, thin, hard, and brittle; they enclose two white -cotyledons, easily pulverisable, and weighing on an average 3.98 grms. -(61 grains). The seed contains at least one alkaloid, termed -_Physostigmine_ (first separated in 1864 by Jobst and Hesse), and -possibly a second, according to Harnack and Witkowsky, who have -discovered in association with physostigmine a new alkaloid, which they -call _Calabarine_, and which differs from physostigmine in being -insoluble in ether and soluble in water. It is also soluble in alcohol; -and further, the precipitate produced by potassium iodo-hydrargyrate in -calabarine solutions is insoluble in alcohol. - -Sec. 487. =Physostigmine=, or =eserine=, is not easily obtained in a -crystalline state, being most frequently extracted as a colourless -varnish, drying into brittle masses. It is, however, quite possible to -obtain it in the form of partially-crystalline crusts, or even rhombic -plates, by care being taken to perform the evaporation, and all the -operations, at as low a temperature as possible, and preferably in a -dimly-lit room; for, if the temperature rises to 40 deg., much of the -alkaloid will be decomposed. Hesse recommends that the beans be -extracted, alcohol by the alcoholic solution alkalised by sodic -carbonate, and the liquid shaken up with ether, which will retain the -alkaloid. The ether solution is now separated, and acidified slightly -with very dilute sulphuric acid; the fluid, of course, separates into -two layers, the lower of which contains the alkaloid as a sulphate, the -upper is the ether, which is withdrawn, and the acid fluid passed -through a moist filter. The whole process is then repeated as a -purification. - -Again, Vee, who has repeatedly obtained the alkaloid in a crystalline -condition, directs the extraction of the beans by alcohol, the alcoholic -solution to be treated as before with sodic carbonate, and then with -ether; the ethereal solution to be evaporated to dryness, dissolved in -dilute acid, precipitated by sugar of lead, and the filtrate from this -precipitate alkalised by potassic bicarbonate, and then shaken up with -ether. The ethereal solution is permitted to evaporate spontaneously, -the crystalline crusts are dissolved in a little dilute acid, and the -solution is lastly alkalised by potassic bicarbonate, when, after a few -minutes, crystalline plates are formed. - -The formula ascribed to physostigmine is C_{15}H_{21}N_{3}O_{2}. It is -strongly alkaline, fully neutralising acids and forming tasteless salts. -It is easily melted, and perhaps partly decomposed, at a temperature of -45 deg.; at 100 deg. it is certainly changed, becoming of a red colour, and -forming with acids a red solution. It dissolves easily in alcohol, -ether, chloroform, and bisulphide of carbon, but is not easily soluble -in water. - -The salts formed by the alkaloid with the acids are generally -hygroscopic and uncrystallisable, but an exception is met with in the -hydrobromide, which crystallises in stellate groups.[537] If CO_{2} is -passed into water containing the alkaloid in suspension, a clear -solution is obtained; but the slightest warmth decomposes the soluble -salt and reprecipitates the alkaloid. The hydrarg-hydroiodide -(C_{15}H_{21}N_{3}O_{2},HI,2HgI) is a white precipitate, insoluble in -water, becoming yellow on drying, soluble in ether and alcohol, and from -such solutions obtained in crystalline prismatic groups. A heat of 70 deg. -melts the crystals, and they solidify again in the amorphous condition. - -[537] M. Duquesnel, _Pharm. J. Trans._ (3), v. 847. - -It gives a precipitate with gold chloride, reducing the gold; also one -with mercuric chloride easily soluble in hydrochloric acid. It gives no -precipitate with platinum chloride. - -Sec. 488. =Tests.=--Da Silva's[538] test for eserine is as follows:--A -minute fragment of eserine or one of its salts is dissolved in a few -drops of fuming nitric acid; this makes a yellow solution, but -evaporated to complete dryness it is pure green. The green substance, -called by others chloreserine, dissolves to a non-fluorescent green -solution; in water and also in strong alcohol it shows a band in the red -between [lambda]670 and [lambda]688, a broader but more nebulous band in -the blue and violet between [lambda]400 and [lambda]418, and a very -feeble band in the orange. - -[538] S. J. Ferreira da Silva, _Compt. Rend._, cxvii. 330, 331. - -J. B. Nagelvoort[539] has recommended the following tests:--(_a_) An -amorphous residue of a permanent blue colour is obtained if a trace of -the alkaloid, or one of its salts, is evaporated in the presence of an -excess of ammonia; this blue alkaloid dissolves in dilute acids with a -red colour; sensitiveness 0.00001 gm. (1 : 100000). The solution has -beautiful red fluorescence in reflected light; when evaporated, it -leaves a residue that is green at first, changing to blue afterwards, -the blue residue being soluble in water, alcohol, and chloroform, but -not in ether. Chloroform extracts the blue colour from the watery -ammoniacal solution only partially. The blue solutions are reddened at -first by H_{2}S, and discoloured afterwards. The blue colour is restored -by expelling the H_{2}S on the water-bath. (_b_) A red fluid is obtained -when 0.010 gm. eserine or its salicylate, 0.050 gm. of slacked lime, and -1 c.c. of water are added together. Warmed in a water-bath, it turns -green, and a piece of red litmus-paper suspended in the test-tube turns -blue; a glass rod moistened with HCl gives off the well-known white -clouds characteristic of an ammonia reaction. The green solution does -not lose its colour by evaporation. Baryta water, added to an eserine -solution, gives a white precipitate that turns red when strongly -agitated, sensitive to 0.01 mgrm. (1 : 100000). - -[539] _Flueckiger's Reactions_, 1893. - -Sec. 489. =Pharmaceutical Preparations.=--The only preparations officinal -in this country are a spirituous extract (_Extractum physostigmatis_), -used principally for external application, the dose of which is not more -than 18.1 mgrms. (.18 grain), and gelatine discs for the purpose of the -ophthalmic surgeon, each disc weighing about 1/50th grain, and -containing 1/1000 gr. of the alkaloid. - -Sec. 490. =Effects on Animals.=--A large number of experiments have been -made upon animals with physostigmine, most of them with the impure -alkaloid, which is a mixture of calabarine and physostigmine. Now, the -action of calabarine seems to be the opposite to that of -physostigmine--that is, it causes tetanus. Hence, these experiments are -not of much value, unless the different proportions of the alkaloids -were known. Harnack and Witkowsky[540] made, however, some researches -with pure physostigmine, of which the following are the main -results:--The smallest fatal dose for rabbits is 3 mgrms. per kilo.; -cats about the same; while dogs take from 4 to 5 mgrms. per kilo. Frogs, -under the influence of the alkaloid, lie paralysed without the power of -spontaneous movement, and the sensibility is diminished; later, the -breathing ceases, and the reflex irritability becomes extinguished. The -activity of the heart is through .5 mgrm. slowed, but at the same time -strengthened. - -[540] _Arch. f. Pathol. u. Pharm._, 1876, Bd. v. - -The warm-blooded animals experimented upon show rapid paralysis of the -respiratory centre, but the animal by artificial respiration can be -saved. Fibrillar muscular twitching of all the muscles of the body are -observed. Death follows in all cases from paralysis of the respiration. -Experiments (first by Bexold, then by Fraser and Bartholow, and lastly -by Schroff) have amply shown that atropine is, to a certain extent, an -antidote for physostigmine poisoning. Fraser also maintains an -antagonism between strychnine and physostigmine, and Bennet that chloral -hydrate is antagonistic to physostigmine. - -=Effects on Man.=--The bean has long been used by the superstitious -tribes of the West Coast of Africa as an ordeal, and is so implicitly -believed in that the innocent, when accused of theft, will swallow it, -in the full conviction that their innocency will protect them, and that -they will vomit up the bean and live. In this way, no doubt, life has -often been sacrificed. Christison experimented upon himself with the -bean, and nearly lost his life. He took 12 grains, and was then seized -with giddiness and a general feeling of torpor. Being alarmed at the -symptoms, he took an emetic, which acted. He was giddy, faint, and -seemed to have lost all muscular power; the heart and pulse were -extremely feeble, and beat irregularly. He afterwards fell into a sleep, -and the next day he was quite well. - -In August 1864 forty-six children were poisoned at Liverpool by eating -some of the beans, which had been thrown on a rubbish heap, being part -of the cargo of a ship from the West Coast of Africa. A boy, aged six, -ate six beans, and died. In April of the same year, two children, aged -six and three years, chewed and ate the broken fragments of one bean; -the usual symptoms of gastric irritation and muscular weakness followed, -but both recovered. Physostigmine contracts the iris to a point; the -action is quite local, and is confined to the eye to which it is -applied. When administered internally, according to some, it has no -effect on the eyes, but according to others, it has a weak effect in -contracting the pupil. In any case, the difference of opinion shows that -the effect, when internally administered, is not one of a marked -character. - -Sec. 491. =Physiological Action.=--The physiological action of -physostigmine is strikingly like that of nicotine, which it resembles in -being a respiratory poison, first exciting, afterwards paralysing the -vagus. Like nicotine, also, it produces a great loss of muscular power; -it first excites, and then paralyses the intra-muscular terminations of -the nerves; and, again, like nicotine, it induces a tetanus of the -intestine. A difference between physostigmine and nicotine exists in the -constant convulsive effects of the former, and in the greater influence -on the heart of the latter. - -Sec. 492. =Post-mortem Appearances.=--But little is known relative to the -_post-mortem_ appearances likely to be found in human poisoning; redness -of the stomach and intestines is probably the chief sign. - -Sec. 493. =Separation of Physostigmine.=--For the extraction of -physostigmine from the fluids of the body, Dragendorff recommends -benzene: the alcoholic filtered extract (first acidified) may be -agitated with such solvents as petroleum and benzene, in order to remove -colouring matter; then alkalised and shaken up with benzene, and the -latter allowed to evaporate spontaneously--all the operations being, as -before stated, carried on under 40 deg. If much coloured, it may be -purified according to the principles before mentioned. In cases where -enough of the extract (or other medicinal preparation) has been taken to -destroy life, the analyst, with proper care, would probably not have -much difficulty in separating a small quantity of the active principle. -It is rapidly eliminated by the saliva and other secretions. In most -cases it will be necessary to identify physostigmine by its -physiological activity, as well as by its chemical characters. For this -purpose a small quantity of the substance should be inserted in the eye -of a rabbit; if it contains the alkaloid in question, in twenty minutes, -at the very latest, there will be a strong contraction of the pupil, and -a congested state of the conjunctival vessels. Further researches may be -made with a small quantity on a bird or frog. The chief symptoms -observed will be those of paralysis of the respiratory and voluntary -muscles, followed by death. If a solution is applied to the web of a -frog's foot, the blood-vessels become dilated. Physostigmine appears, -according to Dragendorff and Pander, to act as an irritant, for they -always observed gastro-enteritis as a result of the poison, even when -injected subcutaneously. The enhanced secretion from all mucous -surfaces, and the enlargement of the blood-vessels, are also very -constant symptoms. But of all these characteristics, the contraction of -the pupil is, for the purposes of identification, the principal. A -substance extracted from the tissue or other organic matters, in the -manner mentioned, strongly contracting the pupil and giving the bromine -reaction, would, in the present state of our knowledge, be indicative of -physostigmine, and of that alone. - -Sec. 494. =Fatal Dose of Physostigmine.=--One mgrm. (.015 grain) as -sulphate, given by Vee to a woman subcutaneously, caused vomiting, &c., -after half an hour. A disciple of Gubler's took 2 mgrms. without -apparent effect; but another mgrm., a little time after, caused great -contraction of the pupil and very serious symptoms, which entirely -passed off in four hours. It would thus seem that three times this -(_i.e._, 6 mgrms.) would be likely to be dangerous. If so, man is far -more sensitive to physostigmine than dogs or cats; and 3 mgrms. per -kilo.--that is, about 205 mgrms. (3 grains)--would be much beyond the -least fatal dose. - - -IX.--Pilocarpine. - -Sec. 495. From the leaves of the jaborandi, _Pilocarpus pennatafolius_ -(Nat. Ord. _Rutaceae_), two alkaloids have been separated--_jaborandi_ -and _pilocarpine_. - -=Jaborandi= (C_{10}H_{12}N_{2}O_{3}) is a strong base, differing from -pilocarpine in its sparing solubility in water, and more ready -solubility in ether; its salts are soluble in water and alcohol, but do -not crystallise. P. Ghastaing,[541] by treating pilocarpine with a large -quantity of nitric acid, obtained nitrate of jaborandi, and operating in -the same way with hydrochloric acid, obtained the hydrochlorate of -jaborandi; hence, it seems that jaborandi is derived from pilocarpine. - -[541] _Compt. Rend._, vol. xciv. p. 223. - -Sec. 496. =Pilocarpine= (C_{11}H_{16}N_{2}O_{2}) is a soft gelatinous mass, -but it forms with the mineral acids crystallisable salts. The solutions -are dextra-rotatory. On boiling with water, it decomposes into -trimethylamine and m-pyridine lactic acid, - - CH_{3} - / - C_{11}H_{16}N_{2}O_{2} + H_{2}O = N(CH_{3})_{3} + C_{5}H_{4}NCHO : - \ - COOH - -hence it is a pyridine derivative, and its graphic formula probably - - CO--O - | - C_{5}H_{4}N--C--N(CH_{3})_{3}. - | - CH_{3} - -The nitrate and hydrochloride are at present much used in pharmacy. -Pilocarpine gives a precipitate with phosphomolybdic acid, -potassio-mercuric iodide, and most general alkaloidal reagents, but none -that are very distinctive. When a solution of gold chloride is added to -one of pilocarpine, a salt falls, having the composition -C_{11}H_{16}N_{2}O_{2},HCl + AuCl_{3}. It is not very soluble in water -(about 1 in 4600), and has been utilised for the estimation of -pilocarpine. Pilocarpine fused with potash yields trimethylamine, carbon -dioxide, butyric, and traces of acetic acid. Pilocarpine dissolves -without the production of colour in sulphuric acid; but, with bichromate -of potash and sulphuric acid, a green colour is produced. It may be -extracted from an aqueous solution made alkaline by ammonia, by shaking -up with chloroform or benzene. - -Sec. 497. =Tests.=--When a little of the alkaloid is mixed with ten times -its weight of calomel, and rubbed, and moistened by the breath, the -calomel is blackened; cocaine also acts similarly; but the two could not -be mistaken for each other. If a solution of mercur-potassium iodide is -added to a solution of the hydrochloride, the amorphous precipitate -becomes, in the course of a day or two, oily drops. "A solution of -iodine in potassium iodide gives in pilocarpine solutions a brown -precipitate that often crystallises to feathery brown crystals -(microscopically), and of serrated form, something like the blade of a -scroll-saw, when the crystallisation is incomplete."--_Flueckiger's -Reactions._ - -Sec. 498. =Effects.=--Pilocarpine, given subcutaneously in doses of about -32 mgrms. (1/2 grain), causes within five minutes a profuse perspiration -and salivation, the face becomes flushed, and the whole body sweats; at -the same time, the buccal secretion is so much increased that in a few -hours over a pint may be secreted. The tears, the bronchial secretion, -and the intestinal secretions are also augmented; there are generally -headache and a frequent desire to pass water; the pulse is much -quickened, and the temperature falls from 1 deg.4 to 4 deg.: the symptoms last -from two to five hours. Langley has shown that the over-action of the -submaxillary gland is not affected by section either of the _chorda -tympani_ or of the sympathetic supplying the gland. Although pilocarpine -quickens the pulse of man, it slows, according to Langley,[542] the -heart of the warm-blooded animals, and that of the frog. With regard to -the frog, Dr. S. Ringer's researches are confirmatory. With large doses -the heart stops in diastole. If to the heart thus slowed, or even when -recently stopped, a minute quantity of atropine be applied, it begins to -beat again. There is also a most complete antagonism between atropine -and pilocarpine in other respects, atropine stopping the excessive -perspiration, and relieving the headache and pain about the pubes, &c. -Pilocarpine, given internally, does not alter the size of the pupil, -but the sight may, with large doses, be affected. If a solution is -applied direct to the eye, then the pupil contracts. No fatal case of -its administration has occurred in man. The probable dangerous dose -would be about 130 mgrms. (2 grains) administered subcutaneously. -Pilocarpine must be classed among the heart poisons. - -[542] "The Action of Jaborandi on the Heart," by J. N. Langley, B.A., -_Journ. Anat. and Physiol._, vol. x. p. 187. - - -X.--Taxine. - -Sec. 499. =Properties of Taxine.=--The leaves and berries, and probably -other portions of the yew tree (_Taxus baccata_), are poisonous. The -poison is alkaloidal, and was first separated by Marme. - -=Taxine= (C_{37}H_{52}O_{10}N).--Taxine cannot be obtained in crystals, -but as a snow-white amorphous powder, scarcely soluble in water, but -dissolving in alcohol, in ether, and in chloroform; insoluble in -benzene. It melts at 82 deg., gives an intense purple-red, with sulphuric -acid, and colours Froehde's reagent reddish-violet. - -A slightly acid aqueous solution of the alkaloid gives precipitates with -all the group reagents and with picric acid. - -The salts are soluble in water; the hydrochloride may be obtained by -passing gaseous HCl into anhydrous ether. The platinichloride forms a -yellow micro-crystalline powder (C_{37}H_{52}O_{10}N)_{2}H_{2}PtCl_{6}. -The salts are generally difficult to crystallise.[543] - -[543] A. Hilger and F. Brande, _Ber._, xxiii. 464-468. - -Sec. 500. =Poisoning by Yew.=--Falck has been able to collect no less than -32 cases of poisoning by different parts of the yew--9 were from the -berries, and the rest from the leaves. They were all accidental; 20 -persons died, or 62.5 per cent. - -Sec. 501. =Effects on Animals--Physiological Action.=--From the researches -of Marme-Borchers, it appears that taxine acts upon the nervous -centres--the nervous trunks themselves and the muscles remaining with -their excitability unimpaired, even some time after death. Taxine kills -through paralysis of the respiration, the heart beating after the -breathing has stopped. The leaves contain much formic acid, and their -irritant action on the intestine is referred to this cause. - -Sec. 502. =Effects on Man.=--Several deaths from yew have resulted in -lunatic asylums from the patients chewing the leaves. For example, a few -years ago, at the Cheshire County Asylum, a female, aged 41, was -suddenly taken ill, apparently fainting, her face pale, her eyes shut, -and pulse almost imperceptible. Upon the administration of stimulants, -she somewhat revived, but in a little while became quite unconscious. -The pupils were contracted, and there were epileptiform convulsions, -succeeded by stertorous breathing. These convulsions returned from time -to time, the action of the heart became weaker, and there was a -remarkable slowing of the respirations, with long intervals between the -breathing. The woman died within an hour from the time when her illness -was first observed, and within two hours of eating the leaves. Yew -leaves were found in her stomach. In another case that occurred at the -Parkside Asylum,[544] the patient died suddenly in a sort of epileptic -fit. Yew leaves were again found in the stomach. In a case quoted by -Taylor, in which a decoction of the leaves was drunk by a girl, aged 15, -for the purpose of exciting menstruation, she took the decoction on four -successive mornings. Severe vomiting followed, and she died eight hours -after taking the last dose. In another case there were also no symptoms -except vomiting, followed by rapid death. Mr. Hurt, of Mansfield, has -recorded a case of poisoning by the berries. The child died in -convulsions before it was seen by any medical man. - -[544] _Pharm. Journ._ (3), No. 294. - -From these and other recorded cases, the symptoms seem generally to be a -quick pulse, fainting or collapse, nausea, vomiting, convulsions, slow -respiration, and death, as a rule sudden and unexpected. We may suppose -that the sudden death is really due to a rapid paralysis of the -respiration, and suffocation. - -Sec. 503. =Post-Mortem Appearances.=--In the case of the girl who drank the -decoction, nothing unusual was observed in the stomach or organs of the -body; but when the leaves have been eaten, usually more or less -congestion of the mucous membrane of the stomach, as well as of the -bowels, is apparent. In the case of the child who ate the berries -(Hurt's case), the stomach was filled with mucous and half-digested pulp -of the berries and seeds. The mucous membrane was red in patches and -softened, and the small intestines were also inflamed. - - -XI.--Curarine. - -Sec. 504. Commercial curare is a black, shining, resinoid mass, about 83 -per cent. of which is soluble in water, and 79 in weak spirit. It is a -complicated mixture of vegetable extracts, from which, however, a -definite principle possessing basic characters (_curarine_) has been -separated. - -The extract is an arrow poison[545] prepared by different tribes of -Indians in South America, between the Amazon and the Orinoco; -therefore, samples are found to vary much in their poisoning properties, -although it is noticeable that qualitatively they are the same, and -produce closely analogous symptoms. It is supposed that some of the -curare is derived from different species of strychnos. This is the more -probable, because, as before stated, the South American strychnines -paralyse, and do not tetanise. It is not unlikely that the active -principles of curare (or woorari) may be methyl compounds similar to -those which have been artificially prepared, such as methyl strychnine -and methyl brucine, both of which have a curare-like action. - -[545] A constituent of the Borneo arrow poison is "derrid," a toxic -principle obtained from a leguminous plant, the _Derris elliptica_; it -is a resinous substance, which has not yet been obtained in the pure -state. It is said not to be a glucoside, nor to contain any nitrogen -(Greshoff, _Ber._, xxiii. 3537-3550). - -The Comalis on the east coast of Africa prepare an arrow poison from the -aqueous extract of the root of Oubaion, a tree closely related to -_Carissa Schimperii_. - -Oubain is prepared by treating the aqueous extract with lead acetate, -getting rid of excess of lead by SH_{2}, and concentrating in a vacuum. -The syrup is boiled with six times its volume of alcohol of 85 deg., and -allowed to cool in shallow vessels; crystals are obtained which are -recrystallised, first from alcohol, and afterwards from water. - -Oubain, C_{30}H_{46}O_{12}, forms thin white nacreous lamellae. It is -tasteless, odourless, and neutral, almost insoluble in cold water, and -soluble in boiling water; it dissolves readily in moderately -concentrated alcohol, is almost insoluble in absolute alcohol, and -insoluble in ether and chloroform. Its melting-point is 200 deg. The -solution of oubain in water is laevorotatory [[alpha]]_{D} = -340. It is -a glucoside, yielding on boiling with dilute acids a sugar. It is very -poisonous; 2 mgrms. will kill a dog of 12 kilos. weight in a few -minutes, if subcutaneously injected; but, taken by the stomach, it -produces no effect.--Arnaud, _Compt. Rend._, cvi. 1011-1014. - -=Curarine= was first separated by Preyer in a crystalline form in 1865. -He extracted curare with boiling alcohol, to which a few drops of soda -solution had been added, evaporated off the alcohol, took up the extract -with water, and, after filtration, precipitated by phosphomolybdic acid, -which had been acidified with nitric acid. The precipitate was dried up -with baryta water, exhausted with boiling alcohol, and curarine -precipitated from the alcoholic solution by anhydrous ether. It may also -be obtained by precipitating with mercuric chloride solution, and -throwing out the mercury afterwards by means of hydric sulphide, &c. - -Curarine, when pure, forms colourless, four-sided, very hygroscopic -prisms of bitter taste, and weakly alkaline reaction; soluble in water -and alcohol in all proportions, but with difficulty soluble in amyl -alcohol and chloroform, and not at all in anhydrous ether, bisulphide of -carbon, or benzene. The base forms crystallisable salts with -hydrochloric, nitric, and acetic acids. Curarine strikes a purple colour -with strong nitric acid. Concentrated solutions of curarine mixed with -dilute glycerin, give an amorphous precipitate with potassic bichromate, -and the precipitate treated with sulphuric acid strikes a beautiful blue -colour. Curarine chromate is distinguished from strychnine chromate by -its amorphous character, and by its comparatively easy solubility. If -the chromates of strychnine and curarine be mixed, and the mixed -chromates be treated with ammonia, strychnine will be precipitated, and -curarine pass into solution, thus forming a ready method of separating -them. - -Sec. 505. =Physiological Effects.=--According to Voisin and Liouville's -experiments, subcutaneous injections of curare on man cause, in small -doses, strong irritation at the place of application, swelling, and -pain. The temperature of the body is raised from 1 deg. to 2 deg., and the -number of respirations increased from 4 to 8 per minute. The pulse -becomes somewhat stronger and more powerful. The urine is increased, and -contains sugar. Large doses administered to warm-blooded animals cause, -after a short time, complete paralysis of voluntary motion and of reflex -excitability, and the animal dies in asphyxia, the heart continuing to -beat. - -This state is best produced for the purpose of experiment on frogs, and, -indeed, is the best test for the poison. A very minute dose injected -beneath the skin of a frog soon paralyses both the voluntary and -respiratory muscles; the animal continues to breathe by the skin; the -heart beats normally, or, perhaps, a little weakly, and the frog may -remain in this motionless condition for days and yet recover. Only -curare and its congeners have this effect. By tying the femoral artery -of one of the frog's legs before administering the poison, an insight -into the true action of the drug is obtained. It is then found that the -reflex excitability and power of motion in the leg are retained, -although all the rest of the body is paralysed. The only explanation of -this is that curare does not act centrally, but paralyses the -intramuscular ends of the motor nerves. Curare is eliminated partly -through the liver and partly through the kidneys. Dragendorff found it -in the faeces, while a striking proof that it is excreted by the kidneys -is given by the experiment of Bidder,[546] in which the urine of a frog -poisoned by curare was made to poison a second, and the urine of the -second, a third. The easy excretion of curare through the kidneys -furnishes an explanation of the relatively large dose of curare which -can be taken by the stomach without injury. A dose which, given by -subcutaneous injection, would produce violent symptoms, perhaps death, -may yet be swallowed, and no ill effects follow. It is hence presumed -that, in the first case, the poison is, comparatively speaking, slowly -absorbed, and almost as fast separated, and put, as it were, outside the -body by going into the urine; while, in the other case, the whole dose -is thrown suddenly into the circulation. - -[546] _Arch. f. Anat. u. Physiol._, 1879, p. 598. - -Sec. 506. =Separation of Curarine.=--It is hardly probable that the -toxicologist will have to look for curarine, unless it has entered the -body by means of a wound or by subcutaneous injection; so that in all -cases the absorbed poison alone must be sought for. The seat of entry, -the liver, the kidneys, and the urine are the only parts likely to be of -any use. Dragendorff recommends the extraction of the tissues with water -feebly acidulated with a mineral acid, to precipitate albuminous -matters, &c., by strong alcohol, and separate, by means of benzene, -fatty matters. The liquid is then made alkaline, and shaken up with -petroleum ether, which removes certain alkaloidal matters. It is now -evaporated to dryness, mixed with finely-powdered glass, and extracted -with absolute alcohol. The alcohol is evaporated to dryness, and any -curarine extracted from this residue with water. By very careful drying -up of this last extract, and taking it up in alcohol, the alkaloid is -said to be obtained so pure as to respond to chemical tests. The -identification may be by the colour reaction of sulphuric acid described -_ante_, in all cases supplemented by its physiological action on -frogs.[547] - -[547] It is known that curare may cause slight symptoms of excitation -before the paralysis comes on. M. Couty has succeeded in isolating these -symptoms by employing feeble extracts of _Strychnos triplinervia_, or -small doses of certain native preparations. By these means, in dogs, a -new phase of intoxication may be present for ten or even twenty minutes. -In the first instance the animal is agitated, jumping, scratching, -barking, as if in a state of general hyperaesthesia. Then it presents -half choreic shocks or tremors; the pupils dilate, and are alternately -dilated and contracted. The heart's action is increased or diminished in -frequency; sometimes there is vomiting, micturition, or defecation; and -there is always salivation. Finally, the central and peripheral -temperature are raised, and the excitability of the muscles and nerves -becomes highly increased. With the native preparation of curare, it is -impossible to prolong this stage, and symptoms of paralysis soon become -associated with those of excitement. The choreic shocks were found to be -arrested by section of the sciatic nerve. Other experiments proved that -the spasms originated from the spinal cord, and were influenced by its -preceding functional condition. If the cord was tied in the mid-dorsal -region, and the curare injected, the spasms were still produced in the -hind legs; but if, after the operation, the excitability of the -posterior segment became lowered, the spasm was no longer produced in -the hind legs. This dependence on a perfect functional activity is a -point of difference of these spasms from those produced by strychnine, -and by asphyxia. The action of small doses of curare is not, however, -limited to the spinal cord. The diminished frequency of the heart -continues after section of the pneumogastrics, and will even occur if -the pneumogastrics have been previously divided. From these facts M. -Couty considers that curare must not be regarded as entirely destitute -of a "convulsant" action, nor of an action on the central nervous -system. - - -XII.--Colchicine. - -Sec. 507. The whole of the _Colchicum autumnale_, or common meadow-saffron, -is poisonous, owing to the presence of an alkaloid (discovered by -Pelletier and Caventou) called _Colchicine_. - -According to Johannson's experiments, the dried colchicum seeds contain -1.15 per cent. of colchicine; the leaves, 1.459 per cent.; the bulbs, -from 1.4 to 1.58 per cent.; and the roots, 0.634 per cent. The frequent -poisoning of cattle in the autumn by colchicum, its use in quack pills -for rheumatism, and its supposed occasional presence in beer, give it -an analytical importance. - -Sec. 508. =Colchicine= (C_{22}H_{25}NO_{6}) may be extracted from the -seeds, &c., in the manner recommended by Huebler:--The seeds are treated, -without crushing, by hot 90 per cent. alcohol, and the alcoholic -solution evaporated to a syrup, which is diluted with twenty times its -bulk of water and filtered; the liquid is next treated with acetate of -lead, again filtered, and the lead thrown out by phosphate of soda. -Colchicine is now precipitated as a tannate.[548] The precipitation is -best fractional, the first and last portions being rejected as -containing impurities. The tannate is decomposed in the usual way with -litharge and extracted by alcohol. - -[548] The purest tannic acid must be used. The commercial tannin may be -purified by evaporating to dryness with litharge, exhausting the tannate -of lead repeatedly with boiling alcohol and water, and, lastly, -suspending in water, and separating the lead by SH_{2}. - -A simpler method is, however, extraction by chloroform from an aqueous -solution, feebly acidified, as recommended by Dragendorff. The parts of -the plant are digested in very dilute acid water, and the resulting -solution concentrated and shaken up with chloroform, which is best done -in a separating tube. - -Colchicine contains four methoxyl groups, and its constitutional formula -is considered to be C_{15}H_{9}[NH(CH_{3}CO)](COOCH_{3})(OCH_{3})_{3}. - -Its melting-point is 143 deg.-147 deg. It is usually a white, gummy mass. It is -easily soluble in cold water, in alcohol, and in chloroform. The -solutions are laevorotatory. It is hardly soluble in ether. Boiling with -dilute acids or alkalies in closed tubes yields colchiceine. - -Colchiceine contains three methoxyl groups. It melts at 150 deg., dissolves -but little in cold, copiously in boiling water. Colchiceine appears to -be an acid, forming salts with the alkalies. - -Zeisel[549] has formed acetotrimethylcolchicinamide -(NHAcC_{15}H_{9}(OMe)_{3}CONH_{3}) by heating colchicine with alcoholic -ammonia in closed tubes for four hours at 100 deg. The amide is -crystallised from hot alcohol; it is readily soluble in dilute HCl, -almost insoluble in water; when a strong hydrochloric acid solution of -the amide is treated with a small amount of potassium nitrite a splendid -violet colour is produced. - -[549] _Monatsh._, ix. 1-30. - -Sec. 509. =Tests.=--Ferric chloride, if added to an alcoholic solution of -the alkaloid, strikes a garnet red; if to an aqueous solution a green or -brownish-green; nitric acid added to the solid substance gives a violet -colour. Erdmann's reagent (nitrosulphuric acid) gives in succession -green, dark blue, and violet colours, ultimately turning yellow, -changed, on addition of an alkali, to raspberry-red. Mandelin's reagent -(1 grm. of ammonium vanadate in 200 grms. of sulphuric acid) gives a -green colour. - -Sec. 510. =Pharmaceutical Preparations.=--Colchicine itself is officinal in -Austria--the wine in the British, French, and Dutch, and the seeds -themselves in all the pharmacop[oe]ias. The wine of colchicum, officinal -in nearly all the pharmacop[oe]ias, is made with very different -proportions of seeds or bulbs. - -The tincture of colchicum is officinal in our own and in all the -Continental pharmacop[oe]ias; in the British, one part of seeds is -exhausted by eight parts of proof spirit. - -A tincture of colchicum seeds, examined by Johannson, contained .18 per -cent. of colchicine, and a tincture prepared from the bulbs .14 per -cent. - -Colchicum vinegar is not officinal in Britain, but one containing 5.4 -per cent. of acetic acid is so in the Netherlands, Germany, and France; -the strength appears to be about .095 per cent. of colchicine. - -An extract of colchicum is officinal in Britain and France; and an -acetic extract in Britain. The latter is the most active of all the -pharmaceutical preparations of colchicum. - -Lastly, an oxymel of colchicum is in use in Germany, France, and the -Netherlands. - -=Quack and Patent Medicines.=--In all specifics for gout the analyst -will naturally search for colchicum. Most gout pills contain the -extracts; and liquids, such as "Reynolds' gout specific," the wine or -the tincture, variously flavoured and disguised. - -The strength of the different pharmaceutical preparations may be -ascertained by dissolving in chloroform, evaporating off the chloroform, -dissolving in water (which is finally acidified by from 7 to 10 per -cent. of sulphuric acid), and titrating with Mayer's reagent (see p. -263). If the solution is diluted so that there is about one part of -colchicine in 600 of the solution, then each c.c. of Mayer's reagent -equals 31.7 mgrms. colchicine. - -Sec. 511. =Fatal Dose.=--In Taylor's _Principles of Medical Jurisprudence_ -is mentioned an instance in which 3-1/2 drachms of colchicum wine, taken -in divided doses, caused death on the fourth day. The quantity of the -active principle in the colchicum wine, as found by Johannson -(_Dragendorff_), being 0.18 per cent., it follows that 24.4 mgrms. (.378 -grain) were fatal, though not given as one dose, so that this quantity -may be considered as the least fatal one. Casper puts the lethal dose of -colchicine at from 25 to 30 mgrms. (.385 to .463 grain). It is, however, -incontestable that there are cases of recovery from as much as 70 mgrms. -(1.08 grain). The lethal dose of the pharmaceutical preparations of -colchicum may, on these grounds, be predicted from their alkaloidal -contents, and, since the latter is not constant, in any medico-legal -inquiry, it may be necessary, where facility is given, to ascertain the -strength of the preparation administered. - -Sec. 512. =Effects of Colchicine on Animals.=--The researches of Rossbach -show that the carnivorae are more sensitive to colchicine than any other -order of mammals. Frogs show a transitory excitement of the nervous -system, then there is loss of sensation, paralysis of motion, and of the -respiratory apparatus; the heart beats after the respiration has ceased. -Death follows from paralysis of the respiration. The mucous membrane of -the intestine is much congested and swollen. - -I have seen cattle die from the effects of eating the meadow-saffron; -the animals rapidly lose condition, suffer great abdominal pain, and are -generally purged. The farmers, in certain parts of the country, have had -extensive losses from want of care and knowledge with regard to -colchicum poisoning. - -Sec. 513. =Effects of Colchicum on Man.=--Colchicum poisoning in man[550] -is not very common: 2 deaths (accidental) are recorded in England and -Wales during the ten years ending 1892. F. A. Falck was able to collect -from medical literature, prior to 1880, 55 cases, and he gives the -following analysis of the cases:--In 2, colchicum was taken for suicidal -purposes; of the unintentional poisonings, 5 were from too large a -medicinal dose of colchicum wine, syrup, or extract, given in cases of -rheumatism; in 13 cases, colchicum was used as a purgative; 42 cases -were owing to mistaking different preparations for drinks, or -cordials--the tincture in 5, and the wine in 14, being taken instead of -orange tincture, quinine wine, schnapps or Madeira; in 1 case the corms -were added to mulled wine, in another, the leaves consumed with salad; -in 16 cases (all children), the seeds of colchicum were eaten. Forty-six -of the 55 died--that is, 83.7 per cent. - -[550] For the curious epidemic of diarrh[oe]a which broke out in the -Rhone Gorge in 1785, and was referred to colchicine, see "Foods," p. -287. - -In the remarkable trial at the Central Criminal Court, in 1862, of -Margaret Wilson (_Reg._ v. _Marg. Wilson_), who was convicted of the -murder of a Mrs. Somers, the evidence given rendered it fairly probable -that the prisoner had destroyed four people at different dates by -colchicum. The symptoms in all four cases were--burning pain in the -throat and stomach, intense thirst, violent vomiting and purging, -coldness and clamminess of the skin, excessive depression, and great -weakness. One victim died on the second day, another on the fifth, a -third on the eighth, and the fourth on the fourteenth day. Schroff -witnessed a case in which a man took 2 grms. (nearly 31 grains) of the -corms; in one and a half hours he experienced general _malaise_; on the -next day there were flying muscular pains, which at length were -concentrated in the diaphragm, and the breathing became oppressed; -there was also pain in the neighbourhood of the duodenum, the abdomen -was inflated with gas; there was a sickly feeling and faintness. Then -came on a sleepy condition, lasting several hours, followed by fever, -with excessive pain in the head, noises in the ears, and delirium; there -was complete recovery, but the abdomen continued painful until the fifth -day. - -In another instance, a gentleman, aged 50,[551] had taken twenty-eight -of Blair's gout-pills in four and a half days for the relief of a -rheumatic affection. He suffered from nausea, griping pains in the -belly, considerable diarrh[oe]a, vomiting, and hiccough; towards the end -there was stupor, convulsive twitchings of the muscles, paralysis, and -death. The fatal illness lasted fourteen days; he was seen by three -medical men at different dates--the first seems to have considered the -case one of diarrh[oe]a, the second one of suppressed gout; but Dr. C. -Budd was struck with the similarity of the symptoms to those from an -acrid poison, and discovered the fact that the pills had been taken. -These pills I examined; they were excessively hard, and practically -consisted of nothing else than the finely-ground colchicum corms; six -pills yielded 8 mgrms. of colchicine, so that the whole twenty-eight -would contain 39 mgrms. (3/5 grain). Dr. Budd considered that the whole -of the pills, which were of a stony hardness, remained in the bowels for -some time undigested, so that the ultimate result was the same as if the -whole had been taken in one dose. - -[551] See _Lancet_, vol. i., 1881, p. 368. - -Sec. 514. The general symptoms produced by colchicum are--more or less -burning pain in the whole intestinal tract, vomiting, diarrh[oe]a, with -not unfrequently bloody stools; but sometimes diarrh[oe]a is absent. In -single cases tenesmus, dysuria, and, in one case, haematuria have been -noted. The respiration is usually troubled, the heart's action slowed, -the pulse small and weak, and the temperature sinks. In a few cases -there have been pains in the limbs; cerebral disturbance is rare; but in -two cases (one described _ante_) there was stupor. Muscular weakness has -been observed generally. In a few cases there have been cramps in the -calves and in the foot, with early collapse and death. - -=Post-mortem Appearances.=--Schroff found in rabbits poisoned with from -.1 to 1.0 grm. of colchicine, tolerably constantly enteritis and -gastritis, and always a thick, pitch-like blood in the heart and veins. -Casper has carefully recorded the _post-mortem_ appearances in four -labourers, ages ranging from fifteen to forty years, who, finding a -bottle of colchicum-wine, and supposing it to be some kind of brandy, -each drank a wine-glassful. They all died from its effects. In all four -there was great hyperaemia of the brain membranes and of the kidneys. The -large veins were filled with thick, dark, cherry-red blood, very similar -to that seen in sulphuric acid poisoning. There was an acid reaction of -the contents of the stomach. The lungs were moderately congested. The -mucous membrane of the stomach of the one who died first was swollen and -scarlet with congestion; with the second there was some filling of the -vessels at the small curvature; while the stomachs of the third and -fourth were quite normal. In 5 cases described by Roux there was also -hyperaemia of the brain and kidneys, but no gastritis or enteritis. It -is, therefore, evident that there are in man no constant pathological -changes from colchicine poisoning. - -Sec. 515. =Separation of Colchicine from Organic Matters.=--W. -Obolonski[552] has recommended the following process:--The finely -divided viscera are triturated with powdered glass and digested for -twelve hours with alcohol. The liquid is squeezed out and the dry -residue washed with alcohol. The extract is concentrated at a -temperature not exceeding 80 deg., and the cooled residue made up to the -original volume with alcohol. The filtered liquid is evaporated as -before, and this operation repeated until no more clots separate on -addition of water. The residue is then dissolved in water, the solution -purified by shaking with light petroleum, and the colchicine finally -extracted with chloroform. - -[552] _Zeit. anal. Chem._, xxix. 493. - -In cases of poisoning by colchicum at Berlin, Wittstock used the -following process:--The contents of the stomach were mixed with a large -amount of alcohol, a few drops of HCl added, and the whole well shaken; -the fluid was then filtered, and the filtrate evaporated to a syrupy -consistence at 37 deg. The resulting residue was dissolved in distilled -water, the fat, &c., filtered off, and the liquid carefully evaporated. -From the extract foreign matter was again separated by treatment with -alcohol and filtration, and the last filtrate was evaporated to a syrupy -consistence. The syrupy fluid was taken up by distilled water, filtered, -evaporated to 30 grms., and 2 grms. of calcined magnesia with 90 grms. -of ether were added. After a time, the ether was removed, and allowed to -evaporate spontaneously. The residue was once more taken up with water, -filtered from fat, &c., and evaporated. This final residue gave all the -reactions of colchicine. In medico-legal researches, it must be -remembered that colchicine is absorbed but slowly, a not insignificant -portion remaining in the bowels, with the faeces. - - -XIII.--Muscarine and the Active Principles of Certain Fungi. - -Sec. 516. =The Amanita Muscaria=, or fly-blown agaric, is a very -conspicuous fungus, common in fir-plantations, about the size and shape -of the common mushroom; but the external surface of the pileus is of a -bright red, or sometimes of a yellowish cast, and studded over with -warts. The common name of the fungus denotes that it was used in former -times as a popular insecticide; the fungus was bruised, steeped in milk, -and the milk exposed, in the same way as we now expose arsenical -fly-papers. - -Some peculiar properties of the agaric have long been known to the -natives of Kamschatka, and of the north-eastern part of Asia generally. -They collect the fungi in the hottest months, and hang them up to dry. -The fungus is then rolled up in a kind of bolus, and swallowed without -chewing. One large, or two small, fungi will produce a kind of -intoxication, which lasts a whole day. It comes on in about two hours' -time, and is very similar to that of alcohol. There is a giddy feeling, -the spirits are exalted, the countenance becomes flushed, involuntary -actions and words follow, and sometimes loss of consciousness. It -renders some persons remarkably active, and proves highly stimulant to -muscular exertion; by too large a dose violent spasmodic effects are -produced. "So very exciting to the nervous system in many individuals is -this fungus, that the effects are often very ludicrous. If a person -under its influence wishes to step over a straw or small stick, he takes -a stride or a jump sufficient to clear the trunk of a tree. A talkative -person cannot keep silence or secrets, and one fond of music is -perpetually singing. The most singular effect of the amanita is the -influence which it has over the urine. It is said that from time -immemorial the inhabitants have known that the fungus imparts an -intoxicating quality to that secretion, which continues for a -considerable time after taking it. For instance, a man moderately -intoxicated to-day will, by the next morning, have slept himself sober, -but (as is the custom) by taking a teacup of his urine he will be more -powerfully intoxicated than he was the preceding day. It is, therefore, -not uncommon for confirmed drunkards to preserve their urine as a -precious liquor against a scarcity of the fungus. The intoxicating -property of the urine is capable of being propagated; for every one who -partakes of it has his urine similarly affected. Thus, with a very few -amanitas, a party of drunkards may keep up their debauch for a week. Dr. -Langsdorf mentions that by means of the second person taking the urine -of the first, the third of the second, and so on, the intoxication may -be propagated through five individuals."[553] - -[553] Lindley's _Vegetable Kingdom_. - -Sec. 517. A few cases of poisoning by the fly-blown agaric from time to -time have occurred in Europe, where it has been eaten in mistake for the -edible fungi, or taken by children allured by the bright attractive -colours. In these cases the poisonous symptoms noticed have been those -of gastro-intestinal irritation, as shown by vomiting and diarrh[oe]a, -_dilated_[554] pupils, delirium, tetanic convulsions, slow pulse, -stertorous breathing, collapse, and death. In a few cases epileptic -attacks and trismus have been observed. The course is usually a rapid -one, the death occurring within twelve hours. In cases of recovery, -convalescence has been prolonged. - -[554] This is the more curious, for muscarine strongly contracts the -pupil. It, however, tends to prove what is stated in the text--viz., -that there is more than one poisonous substance in _Amanita_. - -=The post-mortem characteristics are not distinctive=, a fluid condition -of the blood, hyperaemia of the brain, liver, and kidneys has been -noticed. - -Sec. 518. =Muscarine.=--These effects are partly due to an undiscovered, -toxic substance--which seems to be destroyed at the temperature of -boiling water, and is probably of rather easy destructibility--and of a -very definite poisonous alkaloid (_muscarine_) first separated by a -complex process by Schmiedeberg and Koppe in 1869.[555] It is a -trimethylammonium base, and has lately been formed synthetically by -Schmiedeberg and Harnack,[556] by treating cholin with nitric acid. -Muscarine is isomeric with betain and oxycholin, from which it is -separated by its fluorescence and poisonous properties. - -[555] _Das Muscarin, das giftige Alkaloid des Fliegenpilzes._ Leipzig, -1869. - -[556] _Arch. f. exper. Path._, Bd. 4 u. 5. - -The structural formula of muscarine, and its connection with choline, is -as follows:-- - - CH_{2}OH - | - CH_{2} - | - N(CH_{3})_{3}OH - - _Choline._ - - CH_{2}OH - | - CHOH - | - N(CH_{3})_{3}OH - - _Muscarine._ - - -An atom of hydrogen from the choline, CH_{2}, group, being replaced by -hydroxyl. - -Muscarine is a colourless, strongly alkaline, syrupy fluid, which, if -allowed to stand over sulphuric acid, becomes gradually crystalline, but -liquefies again on exposure to the atmosphere. It dissolves in water in -every proportion, and also in alcohol, but is very little soluble in -chloroform, and insoluble in ether. It is not precipitated by tannin: it -forms salts with acids, and gives precipitates with auric chloride, -phosphotungstic, and phosphomolybdic acids, and also with -potassio-mercuric iodide. The last precipitate is at first amorphous, -but it gradually becomes crystalline. This was the compound used by the -discoverers to separate the base. With many other general alkaloidal -reagents muscarine forms no compound that is insoluble, and therefore -gives no precipitate, such, _e.g._, as iodine with potassic iodide, -picric acid, and platinic chloride. Muscarine is a stronger base than -ammonia, and precipitates copper and iron oxides from solutions of -their salts. Muscarine is very poisonous; 2 to 4 mgrms. are sufficient -in subcutaneous injection to kill cats in from two to twelve -hours--larger doses in a few minutes; but with rabbits the action is -less intense. Cats become salivated, their pupils contract, they vomit, -and are purged, the breathing becomes frequent, and there is marked -dyspn[oe]a. At a later stage the respirations are slower, and there are -convulsions, and death. - -The alkaloid has also been tried on man. Doses of from 3 to 5 mgrms., -injected subcutaneously, cause, after a few minutes' profuse salivation, -increased frequency of the pulse, nausea, giddiness, confusion of -thought and myosis, but no vomiting, and no diarrh[oe]a. Small -quantities applied to the eye cause, after a few minutes, a derangement -of the accommodation, but no change in the size, of the pupil; larger -quantities cause also myosis, which depends upon an excitement of the -sphincter iridis, or of the oculomotorius. - -Sec. 519. The actions of muscarine and atropine are to a great extent -antagonistic. This is especially and beautifully demonstrated by the -effects of the two substances on the frog's heart. The action of -muscarine upon the heart is to excite the inhibitory nerve apparatus, -while the action of atropine is to paralyse the same system. One mgrm. -of muscarine, injected subcutaneously into a frog, arrests the heart _in -diastole_, but if a suitable dose of atropine is applied to the heart -thus arrested, it begins to beat again; or, if atropine is first given, -and then muscarine, the heart does not stop. The muscarine heart, when -it has ceased to beat, may be successfully stimulated by galvanism. -Muscarine at first excites the respiratory centre, and then paralyses -it. - -Sec. 520. =Detection of Muscarine in the Body.=--Muscarine itself is not -likely to be taken as a poison or administered; but if it is sought for -in the fly-blown agaric, or in the tissues or organs of persons who have -been poisoned by the fungus, the process of Brieger appears the best. -The process depends upon the fact that muscarine gives a soluble -mercuric chloride compound, and is not precipitated by chloride of -platinum, whilst most other substances accompanying it give more or less -insoluble precipitates. The substances are treated with water acidulated -with hydrochloric acid, and the acidulated extract concentrated (best in -a vacuum) to a syrup. The syrupy residue is now treated with water, and -the solution precipitated by means of mercuric chloride solution and any -precipitate filtered off; the filtrate is freed from mercury by SH_{2}, -and evaporated to a syrup; the syrup is repeatedly extracted with -alcohol, and the alcoholic solution precipitated with platinum chloride -and any precipitate filtered off. The filtrate is freed from alcohol, -and all the platinum thrown out of solution by SH_{2}; the aqueous -filtrate is now concentrated to a small volume, and again platinum -chloride added, any precipitate which forms is filtered off, and the -final filtrate allowed to crystallise. If muscarine be present, a -crystalline compound of muscarine platinum chloride will form. - -The crystals are usually octahedral in form, and have the composition -(C_{5}H_{14}NO_{2}Cl)_{2}PtCl_{4}; the percentage of platinum is 30.41. - -It would probably be necessary to identify farther, by the action of the -poison on a frog. - -Sec. 521. =The Agaricus phalloides=, a common autumn fungus, has been -several times mistaken for mushrooms, and has proved fatal; of some 53 -cases collected by Falck, no less than 40, or 75 per cent., were fatal; -the real mortality is much lower than this, for it is only such cases -that are pronounced and severe which are likely to be recorded. The -fungus contains a toxalbumin which has been named "phallin." The action -of this toxalbumin is to dissolve the blood corpuscles; according to -Kobert, even one 250,000th dilution produces "polycholie," with all its -consequences, such as the escape of haemoglobin and its decomposition -products in the blood and urine, multiple blood coagulation through the -fibrin ferment becoming free, and serious cerebral disturbance. If into -a dog, cat, or rabbit, only 0.5 mgrm. of phallin be injected -intravenously, within from twenty to thirty minutes blood from a vein -shows that the serum has a red colour. - -The symptoms in man first appear in from three to forty-eight hours; -there is mostly diarrh[oe]a, violent vomiting, with cramp in the legs, -cyanosis, and collapse. There are also nervous phenomena, convulsions, -trismus, and, in a few cases, tetanic spasms. The pulse, in seven cases -described by Maschka, was very small, thready, and quick, but in others, -again, small and slow. The pupils have in some cases been dilated, in -others unchanged. Death is generally rapid. In two of Maschka's cases -from sixty to sixty-eight hours after the investigation, but in the rest -from twelve to eighteen hours. Life may, however, be prolonged for -several days. In a case recorded by Plowright,[557] in which a boy had -eaten a piece of the pileus, death occurred on the fourth day. - -[557] _Lancet_, 1879. - -Sec. 522. =The post-mortem appearances= observed in Maschka's seven cases -were--absence of cadaveric rigidity, dilatation of the pupil, a dark red -fluid condition of the blood, numerous ecchymoses in the pleura, in the -substance of the lungs, the pericardium, the substance of the heart, the -liver, kidneys, and spleen. The mucous membrane of the digestive canal -presented nothing characteristic. In two cases there were a few -ecchymoses, and in one the mucous membrane of the stomach was softened, -red, and easily detached. In one case only were any remnants of the -fungus found, by which the nature of the substance eaten could be -determined. The bladder in each case was full. In three cases a fatty -degeneration of the liver had commenced. The same appearance was met -with in some of the older cases related by Orfila. - -Sec. 523. =The Agaricus pantherinus= is said to be poisonous, although -Hertwig found it to have no action when given to dogs. - -=The Agaricus ruber=, a bright-hued fungus, growing profusely on the -Hampshire coast, of a purple-red colour--the colouring-matter not only -covering the pileus, but also extending down the stipe--is poisonous, -and has recently been chemically investigated by Phipson,[558] who has -identified a colouring-matter _ruberine_, and an alkaloid _agarythrine_. -Agarythrine is separated by macerating the fungus (from which the skin -containing the colouring-matter has been removed) as completely as -possible in water acidulated with 8 per cent. of hydrochloric acid. The -filtered solution is neutralised by sodic carbonate, and the alkaloid -shaken up with ether. On evaporation the ether leaves a white, somewhat -greasy-looking substance, having a bitter burning taste, and easily -fusible into yellow globules, giving forth an odour like quinoleine; it -is soluble in alcohol and ether. From Phipson's observations it would -appear probable that the red colouring-matter is derived from a -decomposition of this alkaloidal substance. A rose-red colour is -produced by the action of nitric acid, and chlorinated lime first -reddens and then bleaches it. Buchwald[559] has recorded three cases of -poisoning by this fungus; the patients were labourers, who, after eating -the fungus, suffered from vomiting, thirst, a "drunken" condition, -cramp, albuminuria, and disturbance of the sensory functions. The fungus -causes in cats myosis, but is said not to affect rabbits. - -[558] _Chem. News_, p. 199, 1882. - -[559] _Industr. Bl._, 1876. - -Sec. 524. =The Soletus satanas, or luridus= (=Lenz=), is poisonous; very -small quantities of the uncooked fungus caused in Lenz, who experimented -upon its properties, violent vomiting. In cases in which this fungus has -been eaten accidentally, the symptoms have been very similar to cholera. - -Sec. 525. =The Common Morelle= seems under certain conditions to be -poisonous. From six to ten hours after ingestion there have appeared -depression, nausea, jaundice, dilated pupils, and in the worst cases at -the end of the first day, delirium, somnolence, and muscular cramps, -followed by collapse and death. In a case observed by Kromholz, the -_post-mortem_ appearances were jaundice, a dark fluid state of the -blood, and hyperaemia of the brain and liver. Bostroem fed a dog with 100 -grms. of the fresh young morelle; the animal died on the third day, and -the canaliculi of the kidney were found filled with haemoglobin, partly -amorphous, and partly crystalline.[560] - -[560] See Casper's _Viertelj._, 1844; Keber, _Preuss. Vereinszeitg._ -1846; Bostroem, _Ber. d. Phys. Med. Soc._, Erlangen, 1880; Schauenstein, -"Giftige Schwaemme" in Maschka's _Handbuch_, &c. - - -DIVISION II.--GLUCOSIDES. - - -I.--Digitalis Group. - -Sec. 526. =The Digitalis purpurea=, or foxglove, is a plant extremely -common in most parts of England, and poisoning may occur from the -accidental use of the root, leaves, or seeds. The seeds are very small -and pitted; they weigh 1126 to a grain (_Guy_), are of a light brown -colour, and in form somewhat egg-shaped. The leaves are large, ovate, -crenate, narrowed at the base, rugous, veined, and downy, especially on -the under surface. Their colour is a dull green, and they have a faint -odour and a bitter, nauseous taste. The leaf is best examined in -section. Its epidermis, when fresh, is seen to consist of transparent, -hexagonal, colourless cells, beneath which, either singly or in groups, -there are round cells of a magenta tint, and beneath these again a layer -of columnar cells, and near the lower surface a loose parenchyma. The -hairs are simple, appearing scantily on the upper, but profusely on the -lower, surface; each is composed of from four to five joints or cells, -and has at its base a magenta-coloured cell. The small leaves just below -the seed-case, and the latter itself, are studded with glandular hairs. -The root consists of numerous long slender fibres. - -Sec. 527. =Chemical Composition.=--It is now generally accepted that there -exist in the foxglove, at least, four distinct principles--_digitalin_, -_digitonin_, _digitoxin_, and _digitalein_. Besides these there are -several others of more or less definite composition, which are all -closely related, and may be derived from a complex glucoside by -successive removals of hydrogen in the form of water. - -The following is the theoretical percentage composition of the -digitalins, the identity of which has been fairly established. They are -arranged according to their percentage in carbon:-- - -TABLE SHOWING THE COMPOSITION OF THE DIGITALINS. - - +------------------+--------------------+--------------------+ - | Name. | Formula. | Percentage | - | | | Composition. | - +------------------+--------------------+--------------------+ - | Digitalein, | C_{21}H_{46}O_{11} | C. 53.16 per cent. | - | | | H. 8.08 " | - | Digitonin,[561] | C_{31}H_{52}O_{17} | C. 53.44 " | - | | | H. 7.46 " | - | Digitalin, | C_{54}H_{84}O_{27} | C. 58.16 " | - | | | H. 3.65 " | - | Digitaletin, | C_{44}H_{30}O_{18} | C. 62.41 " | - | | | H. 3.54 " | - | Digitoxin, | C_{21}H_{32}O_{7} | C. 63.63 " | - | | | H. 8.08 " | - | Digitaleretin, | C_{44}H_{38}O_{18} | C. 66.05 " | - | | | H. 4.58 " | - | Paradigitaletin, | C_{44}H_{34}O_{14} | C. 67.17 " | - | | | H. 4.3 " | - +------------------+--------------------+--------------------+ - -[561] According to Kiliani, digitonin has the composition of -C_{27}H_{44}O_{13}, and it breaks up, when heated with hydrochloric -acid, as follows:-- - - C_{27}H_{44}O_{13} + 2H_{2}O = C_{16}H_{24}O_{3} + 2C_{6}H_{12}O_{6}. - Digitonin. Digitogenin. Dextrose. - ---_Ber._, xxiii. 1555-1568. - - Sec. 528. =Digitalein= is a colourless, amorphous body, easily soluble - in water and in cold absolute alcohol. It may be precipitated from - an alcoholic solution by the addition of much ether. It is with - difficulty soluble in chloroform, and insoluble in ether. It is - precipitated from a watery solution by tannin, or by basic lead - acetate; saponification by dilute acids splits it up into glucose - and digitaleretin. It has a sharp, acrid taste, and the watery - solution froths on shaking. - - Sec. 529, =Digitonin=, a white amorphous body, has many of the - characters of saponin. Like saponin, it is easily soluble in water, - and the solution froths, and, like saponin again, it is precipitated - by absolute alcohol, by baryta water, and by basic lead acetate. It - may be readily distinguished from saponin by treating a watery - solution with sulphuric or hydrochloric acid. On saponifying, it is - split up into digitogenin, galactose, and dextrose. On heating, a - beautiful red colour develops. It does not give the bromine - reaction. - -=Digitogenin= is insoluble in water and aqueous alkalies; it is somewhat -soluble in alcohol, chloroform, and glacial acetic acid; it forms a -crystalline compound with alcoholic potash, which is strongly alkaline, -and not very soluble in alcohol. - -Sec. 530. =Digitalin=, when perfectly pure, forms fine, white, glittering, -hygroscopic needles, or groups of crystalline tufts; it is without -smell, but possesses a bitter taste, which is at once of slow -development and of long endurance. On warming, it becomes soft under -100 deg., and, above that temperature, is readily decomposed with evolution -of white vapours. It is insoluble in water, in dilute soda solution, in -ether, and in benzene. It is soluble in chloroform, especially in -chloroform and alcohol, and dissolves easily in warm acetic acid; twelve -parts of cold and six of boiling alcohol of 90 per cent. dissolve one of -digitalin. Dilute hydrochloric or sulphuric acid decompose it into -glucose and digitaletin (C_{44}H_{30}O_{18}); if the action is -prolonged, digitaleretin (C_{44}H_{38}O_{18}), and finally dehydrated -digitaleretin, are formed. Concentrated sulphuric acid dissolves it with -the production of a green colour, which by bromine passes into -violet-red, but on the addition of water becomes green again. -Hydrochloric acid dissolves it with the production of a greyish-yellow -colour, passing gradually into emerald green; water precipitates from -this solution a resinous mass. - - Sec. 531. =Digitaletin.=--A substance obtained by Walz on treating his - digitalin by dilute acids. It is crystalline, and its watery - solution tastes bitter. It melts at 175 deg., and decomposes, evolving - an acid vapour at about 206 deg. It dissolves in 848 parts of cold, and - 222 of boiling, water; in 3.5 parts of cold, and in from 2 to 4 of - boiling, alcohol. It is with difficulty soluble in ether. It - dissolves in concentrated sulphuric acid, developing a red-brown - colour, which, on the addition of water, changes to olive-green. On - boiling with dilute acids, it splits up into sugar and - digitaleretin. - -Sec. 532. =Digitoxin= always accompanies digitalin in the plant, and may by -suitable treatment be obtained in glittering needles and tabular -crystals. It is insoluble in water and in benzene. It dissolves with -some difficulty in ether, and is readily dissolved by alcohol or by -chloroform. On boiling with dilute acids, it is decomposed into an -amorphous, readily soluble body,--_Toxiresin_. Digitoxin, according to -Schmiedeberg, only exists in the leaves of the digitalis plant, and that -in the proportion of 1 part in 10,000. Digitalin and digitoxin are _par -excellence_ the poisonous principles of the plant. Toxiresin is also -intensely poisonous. It may be obtained in crystals by extracting the -dry exhausted leaves with alcohol of 50 per cent., precipitating with -lead acetate, and washing the precipitate first with a dilute solution -of sodium carbonate (to remove colouring-matter), and then with ether, -benzene, and carbon disulphide, in all of which it is insoluble; on -decomposing the lead compound, digitoxin may be obtained in colourless -scales or needle-shaped crystals. - - Sec. 533. =Digitaleretin=, the origin of which has been already alluded - to, is a yellowish-white, amorphous powder, possessing no bitter - taste, melting at 60 deg., soluble in ether or in alcohol, but insoluble - in water. - - =Paradigitaletin= is very similar to the above, but it melts at - 100 deg., and is insoluble in ether. - -Sec. 534. Several other derivatives have been obtained and described, such -as the inert _digitin_, _digitalacrin_, _digitalein_, and others, but -their properties are, as yet, insufficiently studied. Digitalin, as well -as digitoxin, may now be obtained pure from certain firms, but the -ordinary digitalin of commerce is, for the most part, of two kinds, -which may be distinguished as French and German digitalin. The French -digitalin, or the digitalin of Homolle, is prepared by treating an -aqueous extract of the digitalis plant with lead acetate, and freeing -the filtrate from lead, lime, and magnesia, by successive additions of -alkaline carbonate, oxalate, and phosphate, and then precipitating with -tannin. The tannin precipitate is treated with litharge, and the -digitalins boiled and extracted from the mass by means of alcohol, and -lastly, purifying with animal charcoal. Crystals are in this way -obtained, and by removing all substances soluble in ether by that -solvent, digitalin may be separated. The German digitalin is prepared -according to the process of Walz, and is extracted from the plant by -treatment with alcohol of .852. The alcohol is removed by evaporation, -and the alcoholic extract taken up with water; the watery extract is -treated with lead acetate and litharge, filtered, the filtrate freed -from lead by hydric sulphate, and the excess of acid neutralised by -ammonia, and then tannin added to complete precipitation. The -precipitate is collected and rubbed with hydrated oxide of lead, and the -raw digitalin extracted by hot alcohol. The alcohol, on evaporation, -leaves a mixture of digitalin mixed with other principles and fatty -matter. If sold in this state, it may contain from 2 to 3 per cent. of -digitalein and digitonin. On treating the mixture with ether, digitalin -with some digitaletin is left behind, being almost insoluble in ether. -Since, however, digitaletin is very insoluble in cold water, by -treating the mixture with eight parts of its weight of cold water, -digitalin is dissolved out in nearly a pure state. It may be further -purified by treating the solution with animal charcoal, -recrystallisation from spirit, &c. - -Sec. 535. =Reactions of the Digitalins.=--Digitonin is dissolved by dilute -sulphuric acid (1 : 3) without colour, and the same remark applies to -hydrochloric acid; on warming with either of these acids, a violet-red -colour appears; this reaction thus serves to distinguish digitonin from -the three other constituents, as well as from saponin. - -Sulphuric and gallic acids colour the glucosides of digitalin, -digitalein, and digitonin, red, but not digitoxin, which can be -identified in this way. - -Sulphuric acid and bromine give with digitalin a red, and with -digitalein a violet coloration, which, on the addition of water, change -respectively into emerald and light green. This, the most important -chemical test we possess, is sometimes called _Grandeau's test_; it is -not of great delicacy, the limit being about .1 mgrm. - -Sec. 536. =Pharmaceutical Preparations of Digitalin.=--Digitalin itself is -officinal in the French, Belgium, Portuguese, Russian, Spanish, and -Austrian pharmacop[oe]ias. It is prepared in our own by making a strong -tincture of the leaves at 120 deg. F.; the spirit is then evaporated off, -and the extract heated with acetic acid, decolorised by animal charcoal, -and filtered. After neutralisation with ammonia, the digitalin is -precipitated with tannin, and the tannate of digitalin resolved into -tannate of lead and free digitalin, by rubbing it with oxide of lead and -spirit. - -Digitalis leaf is officinal in most of the pharmacop[oe]ias. - -Tincture of digitalis is officinal in our own and all the Continental -pharmacop[oe]ias, and an ethereal tincture is used in France and -Germany. - -An _Acetum digitalis_ is officinal in the Netherlands and Germany; an -extract and infusion are also used to some extent. - -With regard to the nature of the active principle in these different -preparations, according to Dragendorff, digitonin and digitalein are -most plentiful in the acetic and aqueous preparations; whilst in the -alcoholic, digitalin, digitoxin, and digitalein are present. - -According to Schmiedeberg, commercial digitalin contains, in addition to -digitoxin, digitonin, digitalin, and digitalein; of these, digitonin is -greatest in amount.[562] - -[562] H. Kiliani, _Ber._, xxiii. - -Sec. 537. =Fatal Dose.=--The circumstance of commercial digitalin -consisting of varying mixtures of digitoxin, digitalin, and digitalein, -renders it difficult to be dogmatic about the dose likely to destroy -life. Besides, with all heart-poisons, surprises take place; and very -minute quantities have a fatal result when administered to persons with -disease of the heart, or to such as, owing to some constitutional -peculiarity, have a heart easily affected by toxic agents. Digitoxin, -according to Kopp's[563] experiments, is from six to ten times stronger -than digitalin or digitalein. Two mgrms. caused intense poisonous -symptoms. Digitoxin is contained in larger proportions in Nativelle's -digitalin than in Homolle's, or in the German digitalin. The digitalin -of Homolle is prescribed in 1 mgrm. (.015 grain) doses, and it is -thought dangerous to exceed 6 mgrms. - -[563] _Archiv f. exp. Pathol. u. Pharm._, vol. iii. p. 284, 1875. - -Lemaistre has, indeed, seen dangerous symptoms arise from 2 mgrms. (.03 -grain), when administered to a boy fifteen years old. It may be -predicated from recorded cases and from experiment, that digitoxin would -probably be fatal to an adult man in doses of 4 mgrms. (1/16 grain), and -digitalin, or digitalein, in doses of 20 mgrms. (.3 grain). With regard -to commercial digitalin, as much as from 10 to 12 mgrms. (.15 to .18 -grain) have been taken without a fatal result; on the other hand, 2 -mgrms. gave rise to poisonous symptoms in a woman (Battaille). Such -discrepancies are to be explained on the grounds already mentioned. It -is, however, probable that 4 mgrms. (or 1/16 grain) of ordinary -commercial digitalin would be very dangerous to an adult. - -It must also, in considering the dose of digitalin, be ever remembered -that it is a cumulative poison, and that the same dose--harmless if -taken once--yet, frequently repeated, becomes deadly: this peculiarity -is shared by all poisons affecting the heart. When it is desired to -settle the maximum safe dose for the various tinctures, extracts, and -infusions of digitalis used in pharmacy, there is still greater -difficulty, a difficulty not arising merely from the varying strength of -the preparations, but also from the fact of the vomiting almost -invariably excited by large doses. Individuals swallow quantities -without death resulting, simply because the poison is rapidly expelled; -whereas, if the [oe]sophagus was ligatured (as in the experiments on the -lower animals formerly favoured by the French school of toxicologists), -death must rapidly ensue. The following table is a guide to the maximum -single dose, and also the amount safe to administer in the twenty-four -hours in divided doses. As a general rule, it may be laid down that -double the maximum dose is likely to be dangerous:-- - -TABLE SHOWING THE MAXIMUM SINGLE DOSE, AND MAXIMUM QUANTITY OF THE -DIFFERENT PREPARATIONS OF DIGITALIS, WHICH CAN BE ADMINISTERED IN A DAY. - - +----------------+----------------------+--------------------------+ - | | Single Dose. | Per Day. | - | +----------+-----------+-------------+------------+ - | |Grains or | Grammes | Grains or |Grammes | - | | Minims. | or c.c's. | Minims. |or c.c's. | - +----------------+----------+-----------+-------------+------------+ - |Powdered Leaves,| 4-1/2 | .3 grm. | 15.4 grns. | 1.0 grm. | - | | grns. | | | | - |Infusion, | 480 m. |28.3 c.c. | 1440 m. | 84.9 c.c. | - |Tincture, | 45 m. | 3 c.c. | 135 m. | 9 c.c. | - |Digitalin, | .03 grn. | .002 grm.| .09 grn. | .006 grm. | - |Extract, | 3.0 " | .2 " | 12.0 " | .8 " | - +----------------+----------+-----------+-------------+------------+ - -Sec. 538. =Statistics.=--The main knowledge which we possess of the action -of digitalis is derived from experiments on animals, and from occasional -accidents in the taking of medicines; but in comparison with certain -toxic agents more commonly known, the number of cases of death from -digitalis is very insignificant. Of 42 cases of digitalis-poisoning -collected by Husemann, 1 was criminal (murder); 1 the result of -mistaking the leaves for those of borage; 42 were caused in medicinal -use--in 33 of these last too large a dose had been given, in 3 the drug -was used as a domestic remedy, in 2 of the cases the prescription was -wrongly read, and in 1 digitalis was used as a secret remedy. Twenty-two -per cent. of the 45 were fatal. - -Sec. 539. =Effects on Man.=--It was first distinctly pointed out by Tardieu -that toxic doses of digitalis, or its active principles, produced not -only symptoms referable to an action on the heart, but also, in no small -degree, gastric and intestinal irritation, similar to that produced by -arsenic. Tardieu also attempted to distinguish the symptoms produced by -the pharmaceutical preparations of digitalis (the tincture, extract, -&c.), and the glucoside digitalin; but there does not appear a -sufficient basis for this distinction. The symptoms vary in a -considerable degree in different persons, and are more or less tardy or -rapid in their development, according to the dose. Moderate doses -continued for some time (as, for example, in the persistent use of a -digitalis medicine) may produce their first toxic effects even at the -end of many days; but when a single large dose is taken, the symptoms -are rarely delayed more than three hours. They may commence, indeed, in -half an hour, but have been known to be retarded for more than -twenty-four hours, and the longer periods may be expected if digitalis -is given in hard, not easily soluble pills. There is commonly a feeling -of general _malaise_, and then violent retching and vomiting. The pulse -at first may be accelerated, but it soon is remarkably slowed--it sinks -commonly down to 50, to 40, and has even been known as low as 25. To -these symptoms, referable to the heart and to the digestive tract, are -added nervous troubles; there are noises in the ears, and disturbances -of vision. In a case related by Taylor, a red-coal fire seemed to the -patient to be of a blue colour; in another, related by Lersch,[564] -there was blindness for eighteen hours, and for some time a confusion in -the discrimination in colours; quiet delirium has also been noticed. As -the case proceeds, the gastric symptoms also increase in severity; the -tongue Christison, in one case, noticed to be enormously swollen, and -the breath f[oe]tid. Diarrh[oe]a is commonly present, although also -sometimes absent. The action of the kidneys is suppressed. Hiccough and -convulsions close the scene. - -[564] _Rhen. West. Corr. Bl._, 15, 1848; Husemann in Maschka's -_Handbuch_. - -In the cumulative form, the symptoms may suddenly burst out, and the -person pass into death in a fainting-fit without any warning. As a rare -effect, hemiplegia may be mentioned. - -This brief _resume_ of the symptoms may be further illustrated by the -following typical cases:--A recruit, aged 22, desiring to escape from -military service, went to a so-called "_Freimacher_" who gave him 100 -pills, of which he was to take eight in two doses daily. Eleven days -after the use of the pills, he became ill, and was received into -hospital, where he suddenly died after three weeks' treatment. His -malady was at first ascribed to gastric catarrh; for he suffered from -loss of appetite, nausea, and constipation. He complained of pain in the -head, and giddiness. His breath smelled badly, and the region of the -stomach was painful on pressure. The pulse was slow (56), the -temperature of the body normal. Towards the end, the pulse sank to 52; -he suffered from vomiting, noise in the ears, troubles of vision, great -weakness, and later, hiccough and swelling in the neck. The mere act of -standing up in order to show his throat caused him to faint; on the same -day on which this occurrence took place, he suddenly died on the way to -the nightstool. Thirteen of the pills were found in the patient's -clothes, and from a chemical and microscopical examination it was found -that they contained digitalis leaf in fine powder. The quantity which -the unfortunate man took in the four weeks was estimated at 13.7 grms. -(= about 211 grains). - -Two of his comrades had also been to the "_Freimacher_," and had -suffered from the same symptoms, but they had left off the use of the -medicine before any very serious effect was produced.[565][566] - -[565] Koehnhorn, _Vierteljahrsschr. f. ger. Med._, 1876, n. F. xxiv. p. -402. - -[566] There is an interesting case on record, in which a woman died from -the expressed juice of digitalis. She was twenty-seven years of age, and -took a large unknown quantity of the freshly expressed juice for the -purpose of relieving a swelling of the limbs. The symptoms came on -almost immediately, she was very sick, and was attacked by a -menorrhagia. These symptoms continued for several days with increasing -severity, but it was not until the fifth day that she obtained medical -assistance. She was then found semi-comatose, the face pale, pulse slow, -epigastrium painful on pressure, diarrh[oe]a, and hiccough were -frequent. She died on the twelfth day. The _post-mortem_ appearances -showed nothing referable to digitalis save a few spots of inflammation -on the stomach.--Causse, _Bull. de Therapeutique_, vol. lvi. p. 100; -_Brit. and For. Med. Chir. Review_, vol. xxvi., 1860, p. 523. - -An instructive case of poisoning by digitoxin occurred in the person of -Dr. Koppe, in the course of some experiments on the drug. He had taken -1.5 mgrm. in alcohol without result; on the following day (May 14) he -took 1 mgrm. at 9 A.M., but again without appreciable symptoms. Four -days later he took 2 mgrms. in alcoholic solution, and an hour -afterwards felt faint and ill, with a feeling of giddiness; the pulse -was irregular, of normal frequency, 80 to 84. About three hours after -taking the digitoxin, Dr. Koppe attempted to take a walk, but the -nausea, accompanied with a feeling of weakness, became so intense that -he was obliged to return to the house. Five hours after the dose, his -pulse was 58, intermittent after about every 30 to 50 beats. Vomiting -set in, the matters he threw up were of a dark green colour; after -vomiting he felt better for a quarter of an hour, then he again vomited -much bilious matter; the pulse sank to 40, and was very intermittent, -stopping after every 2 or 3 beats. Every time there was an intermission, -he felt a feeling of constriction and uneasiness in the chest. Six and a -quarter hours after the dose there was again violent vomiting and -retching, with paleness of the face. The muscular weakness was so great -that he could not go to bed without assistance. He had a disorder of -vision, so that the traits of persons well-known to him were changed, -and objects had a yellow tint. He had a sleepless night, the nausea and -vomiting continuing. During the following day the symptoms were very -similar, and the pulse intermittent, 54 per minute. He passed another -restless night, his short sleep being disturbed by terrible dreams. On -the third day he was somewhat better, the pulse was 60, but irregular -and still intermittent; the nausea was also a little abated. The night -was similar in its disturbed sleep to the preceding. He did not regain -his full health for several days.[567] - -[567] _Arch. f. exp. Path. u. Pharm._, vol. iii. p. 289, 1875. - -A third case may be quoted, which differs very markedly from the -preceding, and shows what a protean aspect digitalin poisoning may -assume. A woman, twenty-three years old, took on June 26th, at 7 A.M., -for the purpose of suicide, 16 granules of digitalin. Two hours later -there was shivering and giddiness, so that she was obliged to go to bed. -In the course of the day she had hallucinations. In the evening at 8 -P.M., after eating a little food, she had a shivering fit so violent -that her teeth chattered; there was cold sweat, and difficulty in -breathing; she became gradually again warm, but could not sleep. At 1 -A.M. the difficulty of breathing was so great that she dragged herself -to the window, and there remained until 3 A.M., when she again went back -to bed, slept until 7 A.M., and woke tolerably well. Since this attempt -of self-destruction had failed, she took 40 granules. After one hour she -became giddy, had hallucinations, chilliness, cold sweats, copious -vomiting, and colicky pains; there was great muscular weakness, but no -diarrh[oe]a. Towards evening the vomiting became worse. There was no -action of the bowels, nor was any urine passed; she felt as if her eyes -were prominent and large. The sufferings described lasted during the -whole night until five o'clock the following day, when the vomiting -ceased, whilst the hallucinations, chilliness, and cold sweat continued; -and the thirst, sick feeling, and weakness increased. The next morning, -a physician found her motionless in bed, with pale face, notable double -exophthalmus, dilated pupils, and cold skin, covered with sweat; the -pulse was small and intermittent, sometimes scarcely to be felt (46 to -48 per minute); the epigastrium was painful on pressure. She passed this -second night without sleep, and in the morning the pulse had risen from -56 to 58 beats, but was not quite so intermittent. There was some action -of the bowels, but no urine was passed, nor had any been voided from the -commencement; the bladder was not distended. The following (third) day -some red-coloured, offensive urine was passed; the skin was warmer, and -the pulse from 60 to 64, still somewhat intermittent--from this time she -began to improve, and made a good recovery.[568] - -[568] Related by Ducroix: _De l'Empoisonnement par la Digitale et la -Digitaline._ Paris, 1864. - -Sec. 540. =Physiological Action of the Digitalins.=--Whatever other -physiological action this group may have, its effect on the heart's -action is so prominent and decided, that the digitalins stand as a type -of _heart poisons_. The group of heart poisons has been much extended of -late years, and has been found to include the following:--Antiarin, an -arrow poison; helleborin, a glucoside contained in the hellebore family; -a glucoside found in the _Apocynaceae_, _Thevatii neriifolia_, and -_Thevatia iccotli_; the poisonous principle of the _Nerium oleander_ and -_N. odorum_; the glucoside of _Tanghinia venenifera_; convallamarin, -derived from the species of _Convallaria_; scillotoxin, from the squill; -superbin, from the Indian lily; and the alkaloid erythrophl[oe]in from -the _Erythrophl[oe]um judiciale_ (see p. 432 _et seq._). This list is -yearly increasing. - -Sec. 541. =Local Action.=--The digitalins have an exciting or stimulating -action if applied to mucous membranes--_e.g._, if laid upon the nasal -mucous surface, sneezing is excited; if applied to the eye, there is -redness of the conjunctivae with smarting; if to the tongue, there is -much irritation and a bitter taste. The leaves, the extract, and the -tincture all have this directly irritating action, for they all redden -and inflame mucous membranes. - -Sec. 542. =Action on the Heart.=--The earlier experimenters on the -influence of digitalis on the heart were Stannius and Traube. -Stannius[569] experimented on cats, and found strong irregularity, and, -lastly, cessation in diastole, in which state it responded no longer to -stimuli. Rabbits and birds--especially those birds which lived on -plants--were not so susceptible, nor were frogs. - -[569] _Arch. f. Physiol._ - -Traube[570] made his researches on dogs, using an extract, and -administering doses which corresponded to from .5 to 4.0 grms. He -divided the symptoms witnessed into four stages:-- - -[570] _Ann. d. Charite-Krankenhauses_, vol. ii. p. 785. - -_1st Stage._--The pulse frequently diminishes, while the pressure of the -blood rises. - -_2nd Stage._--Not seen when large doses are employed; pulse frequency, -as well as blood pressure, abnormally low. - -_3rd Stage._--Pressure low, pulse beats above the normal frequency. - -The slowing of the heart[571] is attributed to the stimulus of the -inhibitory nerves, but the later condition of frequency to their -paralysis. After the section of the vagi the slow pulse frequently -remains, and this is explained by the inhibitory action of the cardiac -centre. The vagus, in point of time, is paralysed earlier than the -muscular substance of the heart. - -[571] Slowing of the pulse was mentioned first by Withering (_An Account -of the Foxglove_, Lond., 1785). Beddoes afterwards observed that -digitalis increased the force of the circulation, the slowing of the -pulse not being always observed; according to Ackermann, if the -inhibitory apparatus is affected by atropine, or if the patient is under -deep narcosis, the slowing is absent. - -The increased blood pressure Traube attributed to increased energy of -the heart's contraction, through the motor centre being stimulated -later; the commencing paralysis explains the abnormally low pressure. - -There is, however, also an influence on vaso-motor nerves. What Dr. -Johnson has described as the "stop-cock" action of the small arteries -comes into play, the small arteries contract and attempt, as it were, to -limit the supply of poisoned blood. Ackermann,[572] indeed, witnessed -this phenomenon in a rabbit's mesentery, distinctly seeing the arteries -contract, and the blood pressure rise after section of the spinal cord. -This observation, therefore, of Ackermann's (together with experiments -of Boehm[573] and L. Brunton[574]) somewhat modifies Traube's -explanation, and the views generally accepted respecting the cause of -the increased blood pressure may be stated thus:--The pressure is due to -prolongation of the systolic stroke of the cardiac pump, and to the -"stop-cock" action of the arteries; in other words, there is an increase -of force from behind (_vis a tergo_), and an increased resistance in -front (_vis a fronte_). - -[572] _Deutsch. Arch. f. klin. Med._, vol. xix. p. 125. - -[573] _Archiv f. d. Ges. Phys._, vol. v. p. 153. - -[574] _On Digitalis, with Some Observations on the Urine_, Lond., 1868. - -Sec. 543. =Action of the Digitalins on the Muco-Intestinal Tract and other -Organs.=--In addition to that on the heart, there are other actions of -the digitalins; for example, by whatever channel the poison is -introduced, vomiting has been observed. Even in frogs this, in a -rudimentary manner, occurs. The diuretic action which has been noticed -in man is wanting in animals, nor has a lessened diminution of urea been -confirmed. - -Ackermann found the temperature during the period of increased blood -pressure raised superficially, but lowered internally. According to -Boeck[575] there is no increase in the decomposition of the albuminoids. - -[575] _Intoxication_, p. 404. - - Sec. 544. =The Action of Digitalin on the Common Blow-fly.=--The author - has studied the effects of digitalin, made up into a thin paste with - water, and applied to the head of the common blow-fly. There are at - once great signs of irritation, the sucker is extruded to its full - length, and the fly works its fore feet, attempting to brush or - remove the irritating agent. The next symptom is a difficulty in - walking up a perpendicular glass surface. This difficulty increases, - but it is distinctly observed that weakness and paralysis occur in - the legs before they are seen in the wings. Within an hour the wings - become paralysed also, and the fly, if jerked from its support, - falls like a stone. The insect becomes dull and motionless, and - ultimately dies in from ten to twenty-four hours. A dose, in itself - insufficient to destroy life, does so on repetition at intervals of - a couple of hours. The observation is not without interest, inasmuch - as it shows that the digitalins are toxic substances to the muscular - substance of even those life-forms which do not possess a heart. - -Sec. 545. =Action of the Digitalins on the Frog's Heart.=--The general -action of the digitalins is best studied on the heart of the frog. Drs. -Fagge and Stevenson have shown[576] that, under the influence of -digitalin, there is a peculiar form of irregularity in the beats of the -heart of the frog; the ventricle ultimately stops in the white -contracted state, the voluntary power being retained for fifteen to -twenty minutes afterwards; in very large doses there is, however, at -once paralysis. Lauder Brunton[577] considers the action on the heart to -essentially consist in the prolongation of the systole. - -[576] _Guy's Hospl. Reports_, 3rd ver., vol. xii. p. 37. - -[577] _On Digitalis, with Some Observations on the Urine_, Lond., 1868. - -Atropine or curare have no influence on the heart thus poisoned. If the -animal under the influence of digitalin be treated with muscarine, it -stops in diastole instead of systole. On the other hand, the heart -poisoned by muscarine is relieved by digitalin, and a similar influence -appears to be exercised by atropine. The systolic stillness of the -heart is also removed by substances which paralyse the heart, as -delphinin, saponin, and apomorphin. - -Large doses of digitalin, thrown suddenly on the circulation by -intravenous injection, cause convulsions and sudden death, from quick -palsy of the heart. With frogs under these circumstances there are no -convulsions, but a reflex depression, which, according to Weil[578] and -Meihuizen,[579] disappears on decapitation. The central cerebral -symptoms are without doubt partly due to the disturbance of the -circulation, and there is good ground for attributing them also to a -toxic action on the nervous substance. The arteries are affected as well -as the heart, and are reduced in calibre; the blood pressure is also -increased.[580] This is essentially due to the firm, strong contraction -of the heart, and also to the "stop-cock" action of the small -arteries.[581] - -[578] _Archiv f. Anat. u. Physiol._, 1871, p. 282. - -[579] _Archiv f. d. Ges. Physiol._, vol. vii. p. 201. - -[580] The following is a brief summary of observations on the blood -pressure; four stages may be noticed--(1) Rise of normal blood pressure, -not necessarily accompanied with a diminution of pulse frequency; (2) -continuation of heightened blood pressure, the pulse being raised beyond -the normal rate; (3) continued high pressure, with great irregularity of -the heart and intermittent pulse; (4) quick depression of pressure, -sudden stopping of the heart, and death. - -[581] According to Boehm (_Arch. f. d. Ges. Physiol._, Bd. v. S. 189) -and to Williams (_Arch. f. exper. Pathol._, Bd. xiii. S. 2), the rise of -pressure is due entirely to the heart, and not to the contractions of -the small arteries; but I fail to see how the small arteries can -contract, and yet not heighten the pressure. - -Sec. 546. =Post-mortem Appearances.=--In the case of the recruit poisoned -by digitalis leaf (p. 425), the blood was found dark and fluid; the -right ventricle and auricle of the heart were filled with blood, the -left empty; the brain and its membranes were anaemic; the stomach and -mucous membrane of the intestines were in parts ecchymosed, and there -were patches of injection. In the case of the widow De Pauw, poisoned -with digitalin by the hom[oe]opath (Conty de la Pommerais), the only -abnormality discovered was a few hyperaemic points in the mucous membrane -of the stomach and small intestines. It is then certain that although -more or less redness of the lining membrane of the intestine track may -be present, yet, on the other hand, the active principle of the -digitalis may destroy life, and leave no appreciable sign. - -Sec. 547. =Separation of the Digitalins from Animal Tissues, &c.=--It is -best to make an alcoholic extract after the method of Stas, the alcohol -being feebly acidulated by acetic acid, and all operations being carried -on at a temperature below 60 deg. The alcoholic extract is dissolved in -water feebly acidulated by acetic acid, and shaken up, first with -petroleum ether to remove impurities (the ether will not dissolve any of -the digitalins), then with benzene, and, lastly, with chloroform. The -benzene dissolves digitalein, and the chloroform, digitalin and -digitoxin. On allowing these solvents to evaporate spontaneously, -residues are obtained which will give the reactions already detailed. -Neither the bromine nor any other chemical test is sufficient to -identify the digitalins; it is absolutely necessary to have resource to -physiological experiment. The method used by Tardieu in the classical -Pommerais case may serve as a model, more especially the experiments on -frogs. Three frogs were properly secured, the hearts exposed, and the -beats counted. The number of beats was found to be fairly equal. Frog -No. 1 was placed under such conditions that the heart was constantly -moist. Frog No. 2 was poisoned by injecting into the pleura 6 drops of a -solution in which 10 mgrms. of digitalin were dissolved in 5 c.c. of -water. The third frog was poisoned by a solution of the suspected -extract. The number of beats per minute were now counted at definite -intervals of time as follows:-- - -TABLE SHOWING THE ACTION OF DIGITALIN ON THE FROG'S HEART. - - +----------------------+--------------------+----------------------+ - | Frog No. 1. | Frog No. 2. | Frog No. 3. | - | Unpoisoned. | Poisoned by a | Poisoned by the | - | | known quantity | suspected | - | | of digitalin. | extract. | - +----------------------+--------------------+----------------------+ - | No. of beats | No. of beats | No. of beats | - | per minute. | per minute. | per minute. | - +----------------------+--------------------+----------------------+ - | After 6 minutes, 42 | 20 | 26 | - | " 10 " 40 | 16 irregular. | 24 irregular. | - | " 20 " 40 | 15 | 20 " | - | " 28 " 38 | 0 | 12 very irregular. | - | " 31 " 36 | 0 | 0 | - +----------------------+--------------------+----------------------+ - -In operating in this way--which is strictly comparative, and, with care, -has few sources of error--if the heart of the frog poisoned with the -unknown extract behaves in the number and irregularity of its -contractions similarly to that of the digitalin-poisoned heart, it is a -fair inference that, at all events, a "heart-poison" has been separated; -but it is, of course, open to question whether this is a digitalin or -one of the numerous groups of glucosides acting in the same way. If -sufficient quantity has been separated, chemical reactions, especially -the bromine test (Grandeau's test), may decide, but with the larger -number (yearly increasing) of substances acting similarly on the heart, -great caution in giving an opinion will be necessary. - - -II.--Other Poisonous Glucosides Acting on the Heart. - -Sec. 548. Several members of these glucosides have been studied by -Schmiedeberg,[582] and his convenient divisions will be followed here:-- - -[582] _Beitraege zur Kentniss der pharmakol. Gruppe des Digitalins._ - - -1. CRYSTALLISABLE GLUCOSIDES. - - =Antiarin= (C_{14}H_{20}O_{5}).--Antiarin is an arrow poison - obtained from the milky juice of the _Antiaris toxicaria_ growing in - Java. Antiarin is obtained in crystals, by first treating the - inspissated milky juice with petroleum ether to remove fatty and - other matters, and then dissolving the active principle out with - absolute alcohol. The alcoholic extract is taken up with water, - precipitated with lead acetate, filtered, and from the filtrate - antiarin obtained by freeing the solution from lead, and then - evaporating. De Vry and Ludwig obtained about 4 per cent. from the - juice. Antiarin is crystalline, the crystals containing 2 atoms of - water. Its melting-point is given as 220.6 deg.; the crystals are - soluble in water (254 parts cold, 27.4 parts boiling), they are not - soluble in benzene, and with difficulty in ether; 1 part of antiarin - requiring 2792 parts of ether. - - The watery solution is not precipitated by metallic salts. On - warming with dilute mineral acids, antiarin splits up into a resin - and sugar. Concentrated sulphuric acid gives with antiarin a - yellow-brown solution, hydrochloric and nitric acids strike no - distinctive colours. - - Sec. 549. =Effects.=--Antiarin is essentially a muscular and a heart - poison. When given in a sufficient dose, it kills a frog in from - half an hour to an hour. Its most marked effect is on the cardiac - muscle, the heart beats more and more slowly, and at last stops, the - ventricle being firmly contracted. As with digitalin, there is a - very marked prolongation of the systole, and as with digitalin, - after the beats have ceased, a forcible dilatation of the ventricle - will restore them (Schmiedeberg). It is doubtful whether by - physiological experiment antiarin could be differentiated from - digitalin. - - Sec. 550. =Separation of Antiarin.=--In any case of poisoning by - antiarin, it would be best to extract with alcohol, evaporate, - dissolve the alcoholic extract in water, precipitate with lead - acetate, filter, free the filtrate from lead, and then, after - alkalising with ammonia, shake the filtrate successively with - petroleum ether, benzene, and a small quantity of ether in the - manner recommended at page 247, _et seq._ The liquid, now freed from - all fatty, resinous, and alkaloidal bodies, is neutralised and - evaporated to dryness in a vacuum, and the dry residue taken up with - absolute alcohol, filtered, the alcohol evaporated at a very low - temperature, and finally the extract dissolved in a small quantity - of water, and submitted to physiological tests. - -Sec. 551. =The Active Principles of the Hellebores.=--The Christmas rose -(_Helleborus niger_), as well as _H. viridis_, _H. f[oe]tidus_, and, in -short, all the species of hellebore, are poisonous, and if the root is -treated with alcohol, from the alcoholic extract may be separated two -glucosides, _helleborin_ and _helleborein_. - -=Helleborin= is in the form of white, glittering needles, which, if -placed on the tongue, are almost tasteless, but if dissolved in alcohol, -and then tasted, give a burning, numbing sensation. By boiling with zinc -chloride, helleborin splits up into sugar and a resin--_helleboresin_. -Concentrated sulphuric acid dissolves the crystals with the production -of a beautiful red colour; on standing, the solution after a while -becomes colourless, and a white powder separates. - -=Helleborein= forms colourless crystals, mostly consisting of fine -needles; they have a bitter taste, excite sneezing, and are very -hygroscopic. The crystals easily dissolve in water and dilute alcohol, -but are with difficulty soluble in absolute alcohol, and not soluble in -ether. They dissolve in fatty oils. Helleborein splits by the action of -mineral acids into sugar and amorphous _helleboretin_. - -=Helleboretin= is in the moist condition of a beautiful violet-blue -colour, becoming, when dried at 100 deg., dirty green. Concentrated -sulphuric acid dissolves it with the production of a brown-yellow -colour, which on standing passes into violet and then into brown. - -Marme separated from _H. f[oe]tidus_, in addition, a white, intensely -odorous substance, but too small in quantity to thoroughly investigate -its properties. - -Sec. 552. There is little doubt that hellebore owes its properties to the -glucosides just described. There are several instances of poisoning by -hellebore root,[583] and by the pharmaceutical preparations, but none of -poisoning by the pure active principles. Morgagni mentions a case in -which 2 grms. (nearly 31 grains) of the watery extract of _H. Niger_ -caused death within eight hours; and Ferrari saw, after the use of the -wine in which the root had been boiled, two persons poisoned with a like -result. A more recent case was recorded by Felletar, in 1875, in which a -person died from an infusion of hellebore; there was, however, old -standing heart-disease, so that there may be a doubt as to the real -cause of death in this instance. Schauenstein mentions a case in which -the roots of hellebore were accidentally used in soup, but the bitter -taste prevented any quantity being eaten. The physiological action, -especially of helleborein, is that of an intense heart poison, and the -symptoms produced by the hellebores are so strikingly like those of the -digitalins that it might be difficult to distinguish clinically between -them. In any case of poisoning, the active principle must be separated -in the form of an alcoholic extract, and identified as a heart poison by -physiological experiment. - -[583] There used to be a tincture officinal in our pharmacop[oe]ia; the -root of _H. viridis_ is officinal in the German pharmacop[oe]ia, maximum -single dose, .3 grm.; maximum total quantity in twenty-four hours, 1.2 -grm. The tincture is also officinal on the Continent. - - Sec. 553. =Euonymin= is found in a resin obtained from the _Euonymus - atropurpureus_; it is crystalline, crystallising in colourless, - cauliflower-like masses consisting of groups of stellate needles, - which are soluble in water, but with difficulty in alcohol. It is a - glucoside, and a powerful heart poison, 1 mgrm. causing the heart of - a frog to cease in diastole.[584] - -[584] Schmiedeberg, _op. cit._, from unpublished researches of Professor -H. Meyer, Dorpat. - - Sec. 554. =Thevetin= (C_{54}H_{48}O_{2}).--A glucoside which has been - separated from the Thevetia nereifolia, and perhaps also from the - _Cerbera Odallam_. It is soluble in 124 parts of water at 14 deg., and - is easily soluble in spirit, but not in ether. It is coloured by - sulphuric acid red-brown, passing into cherry-red, and then, in a - few hours, into violet. On boiling with diluted acids, it splits up - into sugar and theveresin. Both thevetin and theveresin are powerful - heart poisons.[585] - -[585] Husemann, _Archiv f. exper. Path. u. Pharmakol._, Bd. v., S. 228, -1876. - - -2. SUBSTANCES PARTLY CRYSTALLISABLE BUT WHICH ARE NOT GLUCOSIDES. - - Sec. 555. =Strophantin= is a very poisonous substance which belongs - physiologically to this group, but does not seem to be a glucoside. - It is soluble in water and in alcohol, less so in ether and - chloroform. It is found in the _kombe_, _manganja_, _inee_, or - _onaje_, a West African poison derived from the _Strophanthus - hispidus_ of the family of _Apocynaceae_. The poison has been - investigated by several observers.[586] - -[586] _Digitoxin_ (see _ante_, p. 420) belongs to this group. - - Dr. Fraser considers, from his experiments, (1) That strophantin - acts primarily on the heart, producing, as an end result, heart - paralysis, with permanence of the ventricular systole. (2) He found - the pulmonary respiration to continue in cold-blooded animals many - minutes after the heart was paralysed. (3) The striped muscles of - the body are affected, and twitches occur in them; their tonicity is - exaggerated, and finally their functional activity is destroyed. - This change is referred to an action on the muscular structure - itself, independent of that upon the heart, and also independent of - the cerebro-spinal nervous system. (4) The reflex action of the - spinal cord is suspended after the heart is paralysed, but the motor - conductivity of the spinal cord and of the nerve trunks continue - after the striped muscles of the body are paralysed. (5) The - lymph-hearts of the frog continue to contract for many minutes after - the blood-heart has been paralysed. - - Sec. 556. =Apocynin.=--In the root of _Apocynum cannabinum_ a - non-crystallisable substance, soluble in alcohol and ether, but not - soluble easily in water, has been separated and found to have a - physiological activity similar to that of the digitalins.[587] - -[587] Hardy et Callois, "_Sur la matiere active du Strophanthus Hispidus -ou Inee_," _Gaz. Med. de Paris_; Pelikan, _Compt. Rend._, t. 60, p. -1209, 1815; Sharpey,_ Proc. Roy. Soc._, May, 1865; Fagge and Stevenson, -_Pharm. Journ._, p. 11, 1865-66; Fraser, _Journ. of Anatom. and Phys._, -also _Proc. of Roy. Soc. of Edin._; Poillo and Carville, _Arch. de -Physiol. Norm. et Pathol._, 1872; G. Valentin, _Zeitschr. et. -Biologie._, x. 133, 1874. - - -3. NON-CRYSTALLISABLE GLUCOSIDES ALMOST INSOLUBLE IN WATER. - - Sec. 557. =Scillain, or Scillitin=, a glucoside which has been - separated from the bulbs of the common squill. It is insoluble or - nearly so in water, but easily dissolves in alcohol. It is little - soluble in ether. It acts upon the heart, and is poisonous. - - =Adonidin=, a very similar substance, has been separated from the - root of the _Adonis vernalis_ (Nat. Ord. _Ranunculaceae_), to which - the name of adonidin has been given.[588] It is an amorphous, - colourless substance, without odour; soluble in alcohol, but with - difficulty soluble in ether and water. It is precipitated by tannin, - and on saponification by mineral acids, splits up into sugar and a - substance soluble in ether. The effects on animals are identical - with those of digitalin. The root has been used recently in - medicine, and found to slow the heart and increase the urinary - secretion; in this also it is like digitalis. - -[588] Cervello, _Archiv fuer exp. Path. Pharm._, 1882, p. 338. - - Sec. 558. =Oleandrin.=--Oleander leaves contain two - chemically-different, nitrogen-free substances. The one is probably - identical with digitalein; but as this is not certain, Schmiedeberg - proposes to call it provisionally _neriin_. The other active - substance is essentially the same as the oleandrin of Lukomske[589] - and Betelli.[590] Oleandrin has basic properties, and is separated - in the form of an amorphous mass, soluble in alcohol, ether, and - chloroform, and slightly soluble in water. Schmiedeberg obtained a - third product from African leaves, which he calls _nerianthin_. - This, on treatment with sulphuric acid and bromine, gives a - beautiful colour peculiar to oleander leaves. It is very similar in - physiological and chemical properties to digitalin, and is probably - derived by decomposition from one of the principles already - described. There is also a product similar to digitaliresin. - -[589] _Repert. de Chimie de Wurtz et Bareswill_, t. iii. p. 77, 1861. - -[590] _Bull. Med. di Bologna_, t. xix. p. 321, 1865. - - The active principles of the oleander are separated by digestion of - the leaves with alcohol of 50 per cent., and precipitating the - alcoholic extract with lead acetate and ammonia. The first - precipitate is yellow, and is probably composed of a tannin-like - substance; the next precipitate is white, consisting of the lead - compound of neriin. The precipitates are filtered off, and the - filtrate concentrated; nerianthin, after a while, separates in light - flocks, and the filtrate from this contains some of the other - products. - - Sec. 559. =Neriin or Oleander Digitalin.=--Neriin is, in the presence - of much free mineral acid, precipitated by potass-bismuth iodide, a - reaction first pointed out by Marme,[591] as useful in the isolation - of the helleborins; or it may be precipitated by tannin, and then - the precipitate decomposed by dissolving in alcohol, and evaporating - it to dryness with zinc oxide on the water-bath. It is next - extracted by absolute alcohol, and precipitated by the addition of - much ether. The further purification consists of resolution in - alcohol, and fractional precipitation by ether. If, however, the - potass-bismuth iodide process is used, the liquid must be acidified - strongly with sulphuric acid, and the precipitate washed with - diluted sulphuric acid. The precipitate may be decomposed by baryta, - filtered, and the filtrate freed from baryta by carbon dioxide; the - filtrate from this contains neriin with baric iodide; it is - therefore treated with silver sulphate, then again with baryta, next - with carbon dioxide, and also with SH_{2} to get rid of the last - trace of silver. - - The filtrate will also contain some oleandrin which, by evaporating - slowly in a vacuum, separates gradually in the form of a clear, - resinous mass. It can be filtered off, and the neriin then may be - precipitated pure by fractional precipitation. Its physiological - action is the same as that of digitalein. - -[591] _Zeitschr. f. rat. Med._ (3 R.), Bd. xxvi., S. 1, 1866. - - Sec. 560. The nerium oleander has several times caused grave symptoms - of poisoning, and they have usually fairly agreed with those - produced by foxglove. For example, Maschka[592] relates the case of - a boy, two years old, who ate two handfuls of the nerium oleander. - The effects commenced in ten minutes, the child was uneasy, and - vomited. In six hours a sleepy condition came on; the face was pale, - the skin cold, the pupils contracted, and the pulse slow and - irregular. After the sickness the boy woke up, but again fell - asleep, and this occurred frequently; coffee was given, which - appeared to do good. The pulse was intermittent. On the following - day the child was still ill, with an intermittent pulse, frequent - vomiting, feebleness, sleeplessness, and dilatation of the pupil; - there was no diarrh[oe]a, on the contrary, the bowels were confined. - On the third day recovery followed. - -[592] _Vierteljahrsschrift f. gericht. Med._, Bd. ii., No. 17, 1860. -_Brit. and For. Med. Chir. Review_, vol. xxvi. p. 523, 1860. - - In an Indian case,[593] the symptoms were altogether peculiar, and - belonged rather to the convulsive order. A wood-cutter, aged - thirty-five, near Kholapore, took, for the purpose of suicide, a - little over an ounce of the expressed juice of the oleander. The - symptoms began so rapidly that he had not time to walk five yards - before he fell insensible; he was brought to the hospital in this - state; the face on his arrival was noticed to be flushed, the - breathing stertorous, there were violent spasmodic contractions of - the whole body, more marked on the left than on the right side. The - effect of this was remarkable. During the intervals of the spasm, - the patient lay evenly on his back, and when the convulsions - commenced the superior contraction of the left side threw him on to - the right, in which position he remained during the paroxysm, after - the subsidence of which he fell back into his old position. The - evacuations were involuntary and watery; the man was insensible, - with frequent convulsions of the kind described, for two days, but - on the third day became conscious, and made a good recovery. - -[593] _Transac. of Med. and Phys. Soc. of Bombay_, 1859. - - In any case of poisoning, the methods by which neriin and oleandrin - are separated from the plant can be applied to separate them from - the tissues with more or less success. Here, as in all the other - digitalin-like glucosides, physiological tests are alone of value in - the final identification. - - Sec. 561. =The Madagascar Ordeal Poison.=--To this group may also - belong the poison of the _Tanghinia venenifera_, a tree in the - Island of Madagascar, the fruit of which is used as an ordeal - poison. It may be obtained in crystals; it is insoluble in water, - and very poisonous. The upas of Singapore is also said to contain - with strychnine a glucoside similar to antiarin. - - -4. SUBSTANCES WHICH, WITH OTHER TOXIC EFFECTS, BEHAVE LIKE THE -DIGITALIS. - - Sec. 562. =Erythrophlein= is an alkaloid, not a glucoside, and is - obtained from the bark of the _Erythrophl[oe]um guineense_ (West - Africa). It acts on the heart like digitalis, and has also effects - similar to picrotoxin. - - -III.--Saponin--Saponin Substances. - -Sec. 563. The term "saponin" of late years has been applied to a class of -glucosides which possess the common property of being poisonous, and, -when dissolved in water, forming solutions which froth on shaking like -soap-suds. - -The substances which have these properties are not all of the -same series chemically, but those of the general formula, -C_{n}H_{2n-8}O_{10}, are most numerous, and the following is a list:-- - - Name. Formula. - - Saponin, senegin, } - Quillaja-sapotoxin, } - Sapindus-sapotoxin, } C_{17}H_{26}O_{10}. - Grypsophila-sapotoxin, } - Agrostemma-sapotoxin, } - Saponin II., digitonin, saporubrin, assamin, C_{18}H_{28}O_{10}. - Saponin III., quillajic acid, polygalic acid, } C_{19}H_{30}O_{10}. - Herniari-saponin, } - Cyclamin, sarsaparilla-saponin, C_{20}H_{32}O_{10}. - Sarsa-saponin, C_{22}H_{36}O_{10}. - Parillin, C_{26}H_{44}O_{10}. - Melanthin, C_{29}H_{50}O_{10}. - -Possibly also dulcamarin C_{22}H_{34}O_{10} and syringen -C_{17}H_{26}O_{10} may belong to this series. - -There are some 150 distinct plants which thus yield saponins; a few of -these plants are as follows:--_Saponaria officinalis_, _Gypsophila -struthium_, _Agrostemma githago_ (corn cockle), _Polygala senega_, -_Monimia polystachia_, the bark of _Quillaja saponaria_, and -_Chrysophyllum glycyphleum_. - -The saponin separated from _Saponaria_, and from the corn cockle will be -here described. - -Sec. 564. =Properties.=--Saponin is a white amorphous powder, very soluble -in water, to which it gives the curious property of frothing just like -soap solution. To obtain this effect there must be at least 1 mgrm. in 1 -c.c. of liquid. Saponin is neutral in reaction, it has no odour, but -causes sneezing if applied to the mucous membrane of the nose; the taste -is at first sweet, and then sharp and acrid. It is almost entirely -insoluble in absolute alcohol, but dissolves in hot alcohol of 83 deg. to -separate again nearly completely on cooling. It is precipitated by basic -lead acetate, and also by baryta water, but in each case it is advisable -to operate on concentrated solutions. Picric acid, mercuric chloride, -and alkaloidal "group reagents" give no precipitate. When a little of -the solid substance is treated with "Nessler" reagent, there is a -greenish or yellow colour produced. A drop of strong sulphuric acid, -mixed with a minute quantity of saponin, strikes slowly a bright red -colour, which, on heating, deepens to maroon-brown. Nordhausen sulphuric -acid shows this better and more rapidly. If saponin is boiled with -dilute acid it breaks up into sapogenin and sugar, and therefore the -liquid after neutralisation reduces "Fehling." This reaction is probably -after the following equation:-- - - 2C_{17}H_{26}O_{10} + 2H_{2}O = 2C_{8}H_{11}O_{2} + 3C_{6}H_{12}O_{6}. - -Sapogenin may be separated by evaporating the neutralised liquid to -dryness, treating the dry residue with ether, which dissolves out the -sapogenin, and finally recovering the substance from the ethereal -solution, and crystallising it from hot alcohol. Crystals are readily -obtained if the alcoholic solution is allowed to evaporate -spontaneously. A solution of saponin exposed to the air gets turbid, and -develops carbon dioxide; not unfrequently the solution becomes mouldy. - -Sec. 565. =Effects.=--Pelikan[594] has studied the effects of various -saponins on frogs. One to two drops of a saturated watery solution of -saponin applied subcutaneously to the leg, caused, in from five to six -minutes, great weakness, accompanied by a loss of sensibility; but -strong mechanical, chemical, or electrical stimuli applied to the foot -excited reflex action, for the ischiatic nerve still retained its -functions. Nevertheless, from the commencement, the excitability of the -poisoned muscles was much weakened, and just before death quite -disappeared. Section of the ischiatic nerve delayed the phenomena. -Curarine did not seem to have any effect on the poisonous action. A -concentrated solution applied to the heart of a frog soon arrests its -beats, but weaker doses first excite, and then retard.[595] - -[594] _Berl. klin. Wochschr._, 36, 186. - -[595] J. Hoppe, _Nervenwirkung der Heilmittel_, H. 4, 37. - -The author has studied the general action of saponin on kittens, -insects, and infusoria. Small doses, such as from 13 to 32 mgrms. (1/5 -to 1/2 grain), were injected beneath the loose skin of the back of the -neck of a kitten, when there were immediate symptoms of local pain. In -from five to ten minutes the respiration notably quickened, and the -animal fell into a lethargic state, with signs of general muscular -weakness; just before death the breathing became very rapid, and there -were all the signs of asphyxia. The pathological appearances after death -were fulness in the right side of the heart, and intense congestion of -the intestinal canal, the stomach generally being perfectly normal in -appearance, and the kidneys and other organs healthy. The least fatal -dose for a kitten seems to be 13 mgrms., or .04 grm. to a kilogram.[596] - -[596] The action of saponin when applied in concentrated solution to -flies is that of an intense irritant. There is protrusion of the sucker, -and progressive paralysis. The common infusoria live for some time in -dilute solutions of saponin--this is also true of some of the higher -forms; for example, a _Cyclops quadricornis_ seemed in no way affected -by a 2 per cent. solution. - -Sec. 566. =Action on Man.=--The effects of saponin on man have been but -little studied; it has been administered by the mouth in doses of from -.1 to .2 grm., and in those doses seems to have distinct physiological -effects. There is increased mucous secretion, and a feeling of nausea; -but neither diaphoresis nor diuresis has been observed. From the -foregoing study it may be predicated that 2.6 grms. (40 grains), if -administered subcutaneously to an adult, would endanger life. The -symptoms would be great muscular prostration, weakness of the heart's -action, and probably diarrh[oe]a. In fatal cases, some signs of an -irritant or inflammatory action on the mucous membranes of the stomach -and intestines would be probable. - -Sec. 567. =Separation of Saponin.=--Saponin is separated from bread, flour, -and similar substances by the process given at p. 153, "Foods." The -process essentially consists in extracting with hot spirit, allowing the -saponin to separate as the spirit cools, collecting the precipitate on -a filter, drying, dissolving in cold water, and precipitating with -absolute alcohol. In operating on animal tissues, a more elaborate -process is necessary. The author has successfully proceeded as -follows:--The finely divided organ is digested in alcohol of 80 to 90 -per cent. strength, and boiled for a quarter of an hour; the alcohol is -filtered hot and allowed to cool, when a deposit forms, consisting of -fatty matters, and containing any saponin present. The deposit is -filtered off, dried, and treated with ether to remove fat. The insoluble -saponin remaining is dissolved in the least possible quantity of water, -and precipitated with absolute alcohol. It is also open to the analyst -to purify it by precipitating with baryta water, the baryta compound -being subsequently decomposed by carbon dioxide. Basic lead acetate may -also be used as a precipitant, the lead compound being, as usual, -decomposed by hydric sulphide; lastly, a watery solution may be shaken -up with chloroform, which will extract saponin. By some one of these -methods, selected according to the exigencies of the case, there will be -no difficulty in separating the glucoside in a fairly pure state. The -organ best to examine for saponin is the kidney. In one of my own -experiments, in a cat poisoned with a subcutaneous dose of saponin (.2 -grm.), evidence of the glucoside was obtained from the kidney alone. The -time after death at which it is probable that saponin could be detected -is unknown; it is a substance easily decomposed, and, therefore, success -in separating it from highly putrid matters is not probable. - -Sec. 568. =Identification of Saponin.=--An amorphous white powder, very -soluble in water, insoluble in cold alcohol or ether, having glucosidal -reactions, striking a red colour with sulphuric acid, imparting a -soap-like condition to water, and poisonous to animals, is most probably -a saponin. - - -DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS. - - -I.--Santonin. - -Sec. 569. Santonin (C_{15}H_{18}O_{3}) is a neutral principle extracted -from the unexpanded heads of various species of _Artemisia_ (Nat. Ord. -_Compositae_). The seeds contain, according to Dragendorff, 2.03 to 2.13 -per cent. of santonin, and about 2.25 per cent. of volatile oil, with 3 -per cent. of fat and resin. Santonin forms brilliant, white, four-sided, -flat prisms, in taste feebly bitter. The crystals become yellow through -age and exposure to light; they melt at 169 deg., and are capable of being -sublimed; they are scarcely soluble in cold water, but dissolve in 250 -parts of boiling water, freely in alkaline water, in 3 parts of boiling -alcohol, and in 42 parts of boiling ether. Santonin is the anhydride of -santonic acid (C_{15}H_{20}O_{4}). Santonin unites with alkalies to form -santonates. Sodic santonate (C_{15}H_{19}NaO_{4} + 3-1/2H_{2}O) is -officinal on the Continent; it forms colourless rhombic crystals, -soluble in 3 parts of cold water. - -Sec. 570. =Poisoning by Santonin.=--Eighteen cases of poisoning, either by -santonin or santonin-holding substances, which F. A. Falck has been able -to collect, were nearly all occasioned by its use as a remedy for worms. -A few were poisonings of children who had swallowed it by accident. With -one exception those poisoned were children of from two to twelve years -of age; in five the flower heads, and in thirteen santonin itself was -taken. Of the eighteen cases, two only died (about 11 per cent.). - -Sec. 571. =Fatal Dose.=--So small a number of children have died from -santonin, that data are not present for fixing the minimum fatal dose. -.12 grm. of santonin killed a boy of five and a half years of age in -fifteen hours; a girl, ten years old, died from a quantity of flower -heads, equal to .2 grm. of santonin. The maximum dose for children is -from 65 to 194 mgrms. (1 to 3 grains), and twice the quantity for -adults. - -Sec. 572. =Effects on Animals.=--Experiments on animals with santonin have -been numerous. It has first an exciting action on the centres of nerves -from the second to the seventh pairs, and then follows decrease of -excitability. The medulla is later affected. There are tetanic -convulsions, and death follows through asphyxia. Artificial respiration -lessens the number and activity of the convulsions, and chloroform, -chloral hydrate, or ether, also either prevent or shorten the attacks. - -Sec. 573. =Effects on Man.=--One of the most constant effects of santonin -is a peculiar aberration of the colour-sense, first observed by Hufeland -in 1806. All things seem yellow, and this may last for twenty-four -hours, seldom longer. According to Rose, this apparent yellowness is -often preceded by a violet hue over all objects. If the lids are closed -while the "yellow sight" is present, the whole field is momentarily -violet. De Martiny,[597] in a few cases, found the "yellow sight" -intermit and pass into other colours, _e.g._, after .3 grm. there was -first the yellow perception, then giving the same individual .6 grm., -all objects seemed coloured red, after half an hour orange, and then -again yellow. In another patient the effect of the drug was to give -"green vision," and in a third blue. - -[597] _Gaz. des Hopit._, 1860. - -Hufner and Helmholtz explain this curious effect as a direct action on -the nervous elements of the retina, causing them to give the perception -of violet; they are first excited, then exhausted, and the eye is -"violet blind." On the other hand, it has been suggested that santonin -either colours the media of the eye yellow, or that there is an increase -in the pigment of the _macula lutea_. I, however, cannot comprehend how -the two last theories will account for the intermittency and the play of -colours observed in a few cases. To the affections of vision are also -often added hallucinations of taste and smell; there is headache and -giddiness, and in fourteen out of thirty of Rose's observations vomiting -occurred. The urinary secretion is increased. In large and fatal doses -there are shivering of the body, clonic, and often tetanic convulsions; -the consciousness is lost, the skin is cool, but covered with sweat, the -pupils dilated, the breathing becomes stertorous, the heart's action -weak and slow, and death occurs in collapse--in the case observed by -Grimm in fifteen hours, in one observed by Linstow in forty-eight hours. -In those patients who have recovered, there have also been noticed -convulsions and loss of consciousness. Sieveking[598] has recorded the -case of a child who took .12 grm. (1.7 grain) santonin; an eruption of -nettle rash showed itself, but disappeared within an hour. - -[598] _Brit. Med. Journ._, 1871. - -Sec. 574. =Post-mortem Appearances.=--The _post-mortem_ appearances are not -characteristic. - -Sec. 575. =Separation of Santonin from the Contents of the Stomach, -&c.=--It is specially important to analyse the faeces, for it has been -observed that some portion goes unchanged into the intestinal canal. The -urine, also, of persons who have taken santonin, possesses some -important peculiarities. It becomes of a peculiar yellow-green, the -colour appearing soon after the ingestion of the drug, and lasting even -sixty hours. The colour may be imitated, and therefore confused with -that which is produced by the bile acids; a similar colour is also seen -after persons have been taking rhubarb. Alkalies added to urine coloured -by santonin or rhubarb strike a red colour. If the urine thus reddened -is digested on zinc dust, santonin urine fades, rhubarb urine remains -red. Further, if the reddened urine is precipitated by excess of milk of -lime or baryta water and filtered, the filtrate from the urine reddened -by rhubarb is colourless, in that reddened by santonin the colour -remains. Santonin may be isolated by treating substances containing it -with warm alkaline water. The water may now be acidified and shaken up -with chloroform, which will dissolve out any santonin. On driving off -the chloroform, the residue should be again alkalised, dissolved in -water, and acidified with hydrochloric acid, and shaken up with -chloroform. In this way, by operating several times, it may be obtained -very pure. Santonin may be identified by its dissolving in alcoholic -potash to a transitory carmine-red, but the best reaction is to dissolve -it in concentrated sulphuric acid, to which a very little water has -been added, to warm on the water-bath, and then to add a few drops of -ferric chloride solution to the warm acid; a ring of a beautiful red -colour passing into purple surrounds each drop, and after a little time, -on continuing the heat, the purple passes into brown. A distinctive -reaction is also the production of "iso-santonin"; this substance is -produced by warming santonin on the water-bath with sulphuric acid for a -few hours, and then diluting with water; iso-santonin is precipitated, -and may be crystallised from boiling alcohol. Iso-santonin melts at -138 deg.; it has the same composition as santonin. It is distinguished from -santonin by giving no red colour when treated with sulphuric or -phosphoric acids. - - -II.--Mezereon. - - Sec. 576. =The Daphne Mezereum= (L.).--Mezereon, an indigenous shrub - belonging to the _Thymeleaceae_, is rather rare in the wild state, - but very frequent in gardens. The flowers are purple and the berries - red. Buckheim isolated by means of ether an acrid resin, which was - converted by saponifying agents into _mezereic acid_; the acrid - resin is the anhydride of the acid. The resin is presumed to be the - active poisonous constituent of the plant, but the subject awaits - further investigation. There are a few cases of poisoning on record, - and they have been mostly from the berries. Thus, Linne has recorded - an instance in which a little girl died after eating twelve berries. - The symptoms observed in the recorded cases have been burning in the - mouth, gastroenteritis, vomiting, giddiness, narcosis, and - convulsions, ending in death. The lethal dose for a horse is about - 30 grms. of powdered bark; for a dog, the [oe]sophagus being tied, - 12 grms.; but smaller doses of the fresh leaves may be deadly. - - -DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES--NOT ADMITTING OF -CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS. - - -I.--Ergot of Rye. - -Sec. 577. Ergot is a peculiar fungus attacking the rye and other -graminaceous plants;[599] it has received various names, _Claviceps -purpurea_ (Tulasne), _Sperm[oe]dia clavus_ (Fries), _Sclerotium clavus_ -(D.C.), &c. The peculiar train of symptoms arising from the eating of -ergotised grain (culminating occasionally in gangrene of the lower -limbs), its powerful action on the pregnant uterus, and its styptic -effects, are well known. - -[599] Some of the _Cyperaceae_ are also attacked. - -The very general use of the drug by accoucheurs has, so to speak, -popularised a knowledge of its action among all classes of society, and -its criminal employment as an abortive appears to be on the -increase.[600] - -[600] The Russian peasantry use the drug for the same purpose. _Vide_ -Mackenzie Wallace's "Russia," i. p. 117. - -The healthy grain of rye, if examined microscopically in thin sections, -is seen to be composed of the seed-coating, made up of two layers, -beneath which are the gluten-cells, whilst the great bulk of the seed is -composed of cells containing starch. In the ergotised grain, dark -(almost black) cells replace the seed-coat and the gluten-cells, whilst -the large starch-containing cells are filled with the small cells of the -fungus and numerous drops of oil. - -Sec. 578. =The chemical constituents of ergot= are a fixed oil, -trimethylamine, certain active principles, and colouring-matters. - -The =fixed oil= is of a brownish-yellow colour, of aromatic flavour and -acrid taste; its specific gravity is 0.924, and it consists chiefly of -palmitin and olein; it has no physiological action. - -=Trimethylamine= is always present ready formed in ergot; it can also be -produced by the action of potash on ergot. - -With regard to the =active principles of ergot= considerable confusion -still exists, and no one has hitherto isolated any single substance in -such a state of purity as to inspire confidence as to its formula or -other chemical characters. They may, however, be briefly described. - -C. Tamet[601] has separated an alkaloid, which appears identical with -Wenzel's _ergotinine_. To obtain this the ergot is extracted by alcohol -of 86 deg., the spirit removed by distillation, and the residue cooled; a -resin (which is deposited) and a fatty layer (which floats on the -surface) are separated from the extractive liquor and washed with ether; -the ethereal solution is filtered and shaken with dilute sulphuric acid, -which takes up the alkaloid; the aqueous solution of the substance is -then filtered, rendered alkaline by KHO, and agitated with chloroform. -The ergotinine is now obtained by evaporating the chloroform solution, -care being taken to protect it from contact with the air. It gives -precipitates with chloride of gold, potassium iodohydrargyrate, -phosphomolybdic acid, tannin, bromine water, and the chlorides of gold -and platinum. With moderately concentrated SO_{4}H_{2}, it gives a -yellowish-red coloration, changing to an intense violet, a reaction -which does not occur if the alkaloid has been exposed to the air. -The composition of the base is represented by the formula -C_{70}H_{40}N_{4}O_{12}, and a crystalline sulphate and lactate have -been obtained.[602] - -[601] _Compt. Rendus_, vol. xxxi. p. 896. - -[602] _Compt. Rendus_, April 1878. - -Wenzel's =Ecboline= is prepared by precipitating the cold watery extract -of ergot with sugar of lead, throwing out the lead in the usual way by -hydric sulphide, concentrating the liquid, and adding mercuric chloride, -which only precipitates the ecboline. The mercury salt is now decomposed -with hydric sulphide, and after the mercury precipitate has been -filtered off, the filtrate is treated with freshly precipitated -phosphate of silver, and refiltered; lastly, the liquid is shaken up -with milk of lime, again filtered, and the lime thrown out by CO_{2}. -The last filtrate contains ecboline only, and is obtained by evaporation -at a gentle heat. It is an amorphous, feebly bitter substance, with an -alkaline reaction, forming only amorphous salts. - -The most recent research by Dragendorff on ergot tends to show that -Wenzel's alkaloids, ergotinine and ecboline, are inactive. Dragendorff -describes also (_a._) _Scleromucin_, a slimy substance which goes into -solution upon extraction of the ergot with water, and which is again -precipitated by 40 to 45 per cent. alcohol. It is colloidal and soluble -with difficulty in water. It contains nitrogen, but gives no albuminoid -reaction, nor any reaction of an alkaloidal or glucosidal body; it -yields to analysis-- - - 8.26 per cent. Water. - 26.8 " Ash. - 39.0 " Carbon. - 6.44 " Hydrogen. - 6.41 " Nitrogen. - -(_b._) =Sclerotic Acid.=--A feebly-acid substance, easily soluble in -water and dilute and moderately concentrated alcohol. It passes, in -association with other constituents of the ergot extract, into the -diffusate, when the extract is submitted to dialysis; but after its -separation in a pure state it is, like scleromucin, colloidal. It is -precipitated by 85 to 90 per cent. alcohol, together with lime, potash, -soda, silica, and manganese; but after maceration with hydrochloric -acid, the greater part of the ash constituents can be separated by a -fresh precipitation with absolute alcohol. The sample gave 40.0 per -cent. of carbon, 5.2 per cent. hydrogen, 4.2 per cent. nitrogen, 50.6 -per cent. oxygen, with 3.4 per cent. of ash. Sclerotic acid forms with -lime a compound that is not decomposed by carbonic acid, and which upon -combustion leaves from 19 to 20 per cent. of calcium carbonate. Both -these substances are active, although evidently impure. Sclerotic acid -is sold in commerce, and has been employed subcutaneously in midwifery -practice in Russia and Germany for some time. - -The inert principles of ergot are--(1.) A red colouring matter, -_Sclererythrin_, insoluble in water, but soluble in dilute and strong -alcohol, ether, chloroform, dilute solutions of potash, ammonia, &c. It -can be obtained by dissolving in an alkali, neutralising with an acid, -and shaking up with ether. Alcoholic solution of sclererythrin gives -with aluminium sulphate, and with zinc chloride, a splendid red mixture; -with salts of calcium, barium, and many of the heavy metals, it gives a -blue precipitate; the yield is only .1 to .05 in a thousand parts. - -(2.) Another colouring-matter, dissolving in concentrated sulphuric acid -with the production of a fine blue violet colour, the discoverer has -named _Scleroidin_. This is not soluble in alcohol, ether, chloroform, -or water, but dissolves in alkaline solutions, potash producing a -splendid violet colour; yield about 1 per 1000. - -(3, 4.) Two crystalline substances, which may be obtained from ergot -powder, first treated with an aqueous solution of tartaric acid, and the -colouring-matters extracted by ether. One Dragendorff names -_Sclerocrystallin_ (C_{10}H_{10}O_{4}); it is in colourless needles, -insoluble in alcohol and water, with difficulty soluble in ether, but -dissolving in ammonia and potash solutions. The other crystalline -substance is thought to be merely a hydrated compound of -sclerocrystallin. Both are without physiological action. - -Kobert recognises two active substances in ergot, and two alone; the one -he calls _sphacelic acid_, the other _cornutin_. - -Sec. 579. =Detection of Ergot in Flour= (see "Foods").--The best process is -to exhaust the flour with boiling alcohol. The alcoholic solution is -acidified with dilute sulphuric acid, and the coloured liquid examined -by the spectroscope in thicker or thinner layers, according to the depth -of colour. A similar alcoholic solution of ergot should be made, and the -spectrum compared. If the flour is ergotised, the solution will be more -or less red, and show two absorption bands, one in the green, and a -broader and stronger one in the blue. On mixing the original solution -with twice its volume of water, and shaking successive portions of this -liquid with ether, amyl alcohol, benzene, and chloroform, the red -colour, if derived from ergot, will impart its colour to each and all of -these solvents. - -Sec. 580. =Pharmaceutical Preparations.=--Ergot itself is officinal in all -the pharmacop[oe]ias, and occurs in grains from 1/3 to 1 inch in length, -and about the same breadth, triangular, curved, obtuse at the ends, of a -purple colour, covered with a bloom, and brittle, exhibiting a pinkish -interior, and the microscopical appearances already detailed. Ergot may -also occur as a brown powder, possessing the unmistakable odour of the -drug. A liquid extract of the B.P. is prepared by digesting 16 parts of -ergot in 80 parts of water for twelve hours, the infusion is decanted or -filtered off, and the digestion repeated with 40 parts of water; this is -also filtered off, and the residue pressed, and the whole filtrate -united and evaporated down to 11 parts; when cold, 6 parts of rectified -spirit are added, and, after standing, the liquid is filtered and made -up to measure 16. A tincture and an infusion are also officinal; the -latter is very frequently used, but seldom sold, for it is preferable to -prepare it on the spot. The tincture experience has shown to be far -inferior in power to the extract, and it is not much used. Ergotin is a -purified extract of uncertain strength; it is used for hypodermic -injection; it should be about five times more active than the liquid -extract. - -Sec. 581. =Dose.=--The main difficulties in the statement of the medicinal -dose, and of the minimum quantity which will destroy life, are the -extreme variability of different samples of ergot, and its readiness to -decompose. A full medicinal dose of ergot itself, as given to a woman in -labour, is 4 grms. (61.7 grains), repeated every half hour. In this way -enormous doses may be given in some cases without much effect. On the -other hand, single doses of from 1 to 4 grms. have caused serious -poisonous symptoms. The extract and the tincture are seldom given in -larger doses than that of a drachm as a first dose, to excite uterine -contraction. In fact, the medical practitioner has in many cases to -experiment on his patient with the drug, in order to discover, not only -the individual susceptibility, but the activity of the particular -preparation used. From the experiments of Nikitin, it is probable that -the least fatal dose of sclerotic acid for an adult man is 20 mgrms. per -kilogrm. - -Sec. 582. =Ergotism.=--Ergotised cereals have played a great part in -various epidemics, probably from very early times, but the only accurate -records respecting them date from the sixteenth century. According to -Dr. Tissot,[603] the first recorded epidemic was in 1596, when a -strange, spasmodic, convulsive disease broke out in Hessia and the -neighbouring regions. It was probably due to spurred rye. In -Voigtlaender, the same disease appeared in 1648, 1649, and 1675; in 1702 -the whole of Freiberg was attacked. In Germany and in France successive -epidemics are described throughout the eighteenth century. In France, in -1710, Ch. Noel, physician at the _Hotel Dieu_, had no less than fifty -cases under treatment at the same time. - -[603] Dr. Tissot in _Phil. Trans._, vol. lv. p. 106, 1765. This is a -Latin letter by Dr. Baker, and gives a good history of the various -epidemics of ergotism. - -It is generally said that in 1630, Thuillier, in describing an ergot -epidemic which broke out in Cologne, first referred the cause of the -disease to spurred rye. - -It is interesting to inquire into the mortality from this disease. In -1770, in an epidemic described by Taube, in which 600 were affected, 16 -per cent. died. In a nineteenth-century epidemic (1855), in which, -according to Husemann, 30 were ill, 23.3 per cent. died. In other -epidemics, according to Heusinger, out of 102, 12 per cent. died; -according to Griepenkerl, out of 155, 25 or 16 per cent. died; and, -according to Meyer, of 283 cases, 6 per cent. died. - -There are two forms of chronic poisoning by ergot--one a spasmodic form, -the other the gangrenous form. - -Sec. 583. =The convulsive form of ergotism= mostly begins with some -cerebral disturbance. There are sparks before the eyes, giddiness, -noises in the ears, and a creeping feeling about the body. There is also -very commonly anaesthesia of the fingers and toes, and later of the -extremities, of the back, and even of the tongue. Diarrh[oe]a, vomiting, -colic, and other signs of intestinal irritation seldom fail to be -present; there are also tetanic spasms of the muscles, rising in some -cases to well-marked tetanus; epilepsy, faintings, aberrations of -vision, amaurosis, and amblyopia are frequent; the skin becomes of a -yellow or earthy colour, and is covered with a cold sweat; boils and -other eruptions may break out; blebs, like those caused by burns or -scalds, have in a few cases been noticed. Death may occur in from four -to twelve weeks after the eating of the spurred grain from exhaustion. -In those individuals who recover, there remain for some time weakness, -contractions of groups of muscles, anaemia, or affections of vision. - -Sec. 584. =The Gangrenous Form of Ergotism.=--In this form there is -generally acute pain in the limb or limbs which are to mortify; and -there may be prodromata, similar to those already described. The limb -swells, is covered with an erysipelatous blush, but at the same time -feels icy cold; the gangrene is generally dry, occasionally moist; the -mummified parts separate from the healthy by a moist, ulcerative -process; and in this way the toes, fingers, legs, and even the nose, may -be lost. During the process of separation there is some fever, and -pyaemia may occur with a fatal result. - -Fontenelle described a case in which a rustic lost all the toes of one -foot, then those of the other; after that, the remnant of the first -foot, and lastly the leg. But probably the most extraordinary case of -gangrene caused by the use of ergot is that which occurred at Wattisham, -Suffolk, in the family of a labouring man named John Downing. He had a -wife and six children of various ages, from fifteen years to four -months. On Monday, January 10, 1762, the eldest girl complained of a -pain in the calf of her left leg; in the evening, her sister, aged 10, -also experienced the same symptoms. On the following Monday, the mother -and another child, and on Tuesday, all the rest of the family except the -father became affected. The pain was very violent. The baby at the -breast lived a few weeks, and died of mortification of the extremities. -The limbs of the family now began to slough off, and the following are -the notes on their condition made by an observer, Dr. C. Wollaston, -F.R.S., on April 13:-- - -"The mother, aged 40. Right foot off at the ankle, the left leg -mortified; a mere bone left, but not off. - -"Elizabeth, aged 13. Both legs off below the knees. - -"Sarah, aged 10. One foot off at the ankle. - -"Robert, aged 8. Both legs off below the knees. - -"Richard, aged 4. Both feet off at the ankle. - -"Infant, four months old, dead." - -The father was also attacked a fortnight after the rest of the family, -and in a slighter degree--the pain being confined to the fingers of his -right hand, which turned a blackish colour, and were withered for some -time, but ultimately got better. - -As a remarkable fact, it is specially noted that the family were in -other respects well. They ate heartily, and slept soundly when the pain -began to abate. The mother looked emaciated. "The poor boy in particular -looked as healthy and florid as possible, and was sitting on the bed, -quite jolly, drumming with his stumps." They lived as the country people -at the time usually lived, on dried peas, pickled pork, bread and -cheese, milk, and small beer. Dr. Wollaston strictly examined the corn -with which they made the bread, and he found it "very bad; it was wheat -that had been cut in a rainy season, and had lain in the ground till -many of the grains were black and totally decayed."[604] - -[604] In the _Phil. Trans._ for 1762 there are two strictly concordant -accounts of this case; and in the parish church of Wattisham, there is -said to be a memorial tablet, which runs as follows:--"This inscription -serves to authenticate the truth of a singular calamity which suddenly -happened to a poor family in this parish, of which six persons lost -their feet by a mortification not to be accounted for. A full narrative -of their case is recorded in the Parish Register and _Philosophical -Transactions_ for 1762." - -Sec. 585. =Symptoms of Acute Poisoning by Ergot.=--In a fatal case of -poisoning by ergot of rye, recorded by Dr. Davidson,[605] in which a -hospital nurse, aged 28, took ergot, the symptoms were mainly vomiting -of blood, the passing of bloody urine, intense jaundice, and stupor. But -in other cases, jaundice and vomiting of blood have not been recorded, -and the general course of acute poisoning shows, on the one hand, -symptoms of intense gastro-intestinal irritation, as vomiting, colicky -pains, and diarrh[oe]a; and, on the other, of a secondary affection of -the nervous system, weakness of the limbs, aberrations of vision, -delirium, retention of urine, coma, and death. - -[605] _Lancet_, Sept. 30, 1882. - -Sec. 586. =Physiological Action as shown by Experiments on Animals.=--In -spite of numerous experiments on animals and man, the action of the -ergot principles remains obscure. It has been found in medicine to exert -a specific action on the uterus,[606] causing powerful contractions of -that organ, especially in labour. It is also a haemostatic, and is used -to check bleeding from the lungs and other internal organs of the body. -This haemostatic action, as well as the extraordinary property possessed -by ergot, of producing an arrest or disturbance of the circulation -inducing gangrene has naturally led to the belief that ergot causes a -narrowing in the calibre of the small arteries, but this has not -received the necessary experimental sanction. Holmes,[607] Eberty, -Koehler,[608] and Wernick,[609] all observed a contraction in the part to -which the ergot was applied, both in frogs and in warm-blooded animals; -but L. Hermann,[610] although he made many experiments, and used the -most different preparations, never succeeded in observing a contraction. -It would also seem reasonable to expect that with a narrowing of the -vessels, which means a peripheral obstruction, the blood-pressure would -rise, but on the contrary the pressure sinks, a fact on which there is -no division of opinion. - -[606] In a case in which the author was engaged, a dabbler in drugs, -having seduced a young woman, administered to her a dose of ergot which -produced a miscarriage, and for this offence he was convicted. The -defence raised was that ergot is a common medicine used by physicians in -the treatment of amenorrh[oe]a, and other uterine affections. Although -in itself this statement was perfectly true, as a defence it was -invalidated by the large dose given, the fact of the seduction, and the -other circumstances of the case. - -[607] _Archiv d. Physiol. Norm. u. Pathol._, iii. p. 384. - -[608] _Ueber die Wirkungen des Secale Cornutum_, Dissert. Halle, 1873. - -[609] _Arch. f. pathol. Anat._, lvi. p 505. - -[610] _Lehrbuch der exper. Toxicologie_, Berlin, 1874, p. 386. - -Nikitin has made some researches with pure sclerotic acid, which -certainly possesses the most prominent therapeutic effects of ergot; but -since it is not the only _toxic_ substance, it may not represent the -collective action of the drug, just in the same way that morphine is not -equivalent in action to opium. Cold-blooded animals are very sensitive -to sclerotic acid; of the warm-blooded the carnivorae are more sensitive -than the herbivorae. The toxic action is specially directed to the -central nervous system--with frogs, the reflex excitability is -diminished to full paralysis; with warm-blooded animals reflex -excitability is only diminished, and continues to exist even to death. - -The temperature falls, the breathing is slowed, and the respiration -stops before the heart ceases to beat; the peristaltic action of the -intestines is quickened, and the uterus (even of non-pregnant animals) -is thrown into contraction. The terminations of the sensory nerves are -paralysed by the direct action of sclerotic acid, but they remain intact -with general poisoning. The heart of frogs is slowed by sclerotic acid. -Eberty observed that this slowing of the heart (he used ergotin) was -produced even after destruction of the spinal cord; he therefore -considered it as acting on the inhibitory nerve apparatus of the heart -itself. Rossbach, using Wenzel's ecbolin, has also studied its action on -the heart of the frog, and observed that the slowing affected the -ventricles rather than the auricles, so that for one ventricle-systole -there were two contractions of the auricles; besides which, the -contractions themselves were peculiar and abnormal in character. The -cause of death from sclerotic acid seems to be paralysis of the -respiration. It is said not to affect animal f[oe]tal life. With regard -to the effects produced by feeding animals with ergotised grain, -experiments made during the last century have proved that it produces a -gangrenous disease, _e.g._, C. Salerne mixed one part of spurred rye -with two of good barley, and fed pigs with the mixture; a few days -afterwards the pigs perished with dilated, hard, and black bellies, and -offensively ulcerated legs; another pig fed entirely on the rye, lost -its four feet and both ears. - -Kobert[611] has investigated the effects produced on animals by -"sphacelic acid," and by "cornutin." Sphacelic acid appears to cause -gangrene, like ergot, and Kobert believes that in "sphacelic acid" is to -be found the gangrene-producing substance. In cases of death -putrefaction is rapid, the mucous membrane of the intestine is swollen, -and the spleen enlarged. If the mucous membrane of the intestine is -examined microscopically, a large quantity of micro-organisms are found -in the vessels, in the villi, between the muscular bundles and in the -deeper layers of the intestinal walls; this is evidence that the -protective epithelial cells have been destroyed. The mesentery of cats, -pigs, and fowls, contains numerous small extravasations of blood. The -organs generally, and especially the subcutaneous cellular tissue, are -tinged with the colouring matters of the bile; this Kobert considers as -evidence of weakened vitality of the red blood corpuscles. The walls of -the blood-vessels show hyaline degeneration, and give with iodine a -quasi-amyloid reaction. The vessels are often partly filled with a -hyaline mass, in which, at a later date, a fine black pigment appears. -These pigmented hyaline masses probably occlude the vessels, and hence -cause gangrene. - -[611] _Lehrbuch der Intoxicationen_, by Dr. Rudolph Kobert, Stuttgart, -1893. - -Cornutin, according to Kobert, first excites the vagus; consequently -there is slow pulse and heightened blood pressure; then it paralyses the -vaso-motor centre, and the pulse is accelerated. Severe convulsions, -preceded by formication, follow. Paralysis of the extensor muscles, with -permanent deformity, may result. Cornutin stimulates the uterus to -contraction, but it does not act so well in this respect alone as when -given with sphacelic acid. In animals poisoned with cornutin, no special -pathological changes of a distinctive nature have been described. - -Sec. 587. =Separation of the Active Principles of Ergot from Animal -Tissues.=--There has been no experience in the separation of the -constituents of ergot from the organs of the body; an attempt might be -made on the principles detailed in page 425, but success is doubtful. - - -II.--Picrotoxin, the Active Principle of the Cocculus indicus (Indian -Berry, Levant Nut). - -Sec. 588. The berries of the _Menispermum cocculus_ comprise at least three -definite crystalline principles: _menispermine_,[612] _paramenispermine_ -(nitrogen containing bases), and _picrotoxin_, which possesses some of -the characters of an acid. - -[612] _Menispermine_ (C_{18}H_{24}N_{2}O_{2}?), discovered in 1834 by -Pelletier and Courbe, is associated with a second named -_paramenispermine_. The powdered berries are extracted by alcohol of -36 deg.; the picrotoxin removed by hot water from the alcoholic extract; the -menispermine and paramenispermine dissolved out together by acidulated -water, and from this solution precipitated by ammonia. The brown -precipitate is dissolved by acetic acid, filtered, and again -precipitated by ammonia. This precipitate is dried, treated with cold -alcohol, to separate a yellow resinous substance, and lastly with ether, -which dissolves out the menispermine, but leaves the paramenispermine. - -Menispermine forms white semi-transparent, four-sided, truncated prisms, -melting at 120 deg., decomposed at a higher temperature, insoluble in water, -but dissolving in warm alcohol and ether. Combined with 8 atoms of water -it crystallises in needles and prisms. The crystals are without any -taste; in combination with acids, salts may be formed. - -_Paramenispermine_ forms four-sided prisms, or radiating crystalline -masses, melting at 250 deg., and subliming undecomposed. The crystals are -soluble in absolute ether, insoluble in water, and scarcely soluble in -ether. - -_Paramenispermine_ dissolves in acids, but apparently without forming -definite salts. - -Sec. 589. =Picrotoxin= (C_{30}H_{34}O_{13}) was discovered in 1820 by -Boullay. It is usually prepared by extracting the berries with boiling -alcohol, distilling the alcohol off, boiling the alcoholic residue with -a large quantity of water, purifying the watery extract with sugar of -lead, concentrating the colourless filtrate by evaporation, and -crystallising the picrotoxin out of water. - -Picrotoxin crystallises out of water, and also out of alcohol, in -colourless, flexible, four-sided prisms, often arborescent, and -possessing a silky lustre. They are unalterable in the air, soluble in -150 parts of cold, and 25 parts of boiling water, dissolving easily in -acidified water, in spirit, in ether, in amyl alcohol, and chloroform. -They are without smell, but have an extremely bitter taste. Caustic -ammonia is also a solvent. - -The crystals are neutral in reaction. They melt at 192 deg.-200 deg. C. to a -yellow mass; at higher temperatures giving off an acid vapour, with a -caramel-like odour, and lastly carbonising. Picrotoxin in cold -concentrated sulphuric acid dissolves with the production of a beautiful -gold-yellow to saffron-yellow colour, which becomes on the addition of a -trace of potassic bichromate, violet passing into brown. An alcoholic -solution turns a ray of polarised light to the left [[alpha]]_{D} = --28.1 deg. - -Picrotoxin behaves towards strong bases like a weak acid. Its compounds -with the alkalies and alkaline earths are gummy and not easily obtained -pure. Compounds with quinine, cinchonine, morphine, strychnine, and -brucine can be obtained in the crystalline condition. Dilute sulphuric -acid transforms it, with assimilation of water, into a weak gummy-like -acid, which corresponds to the formula C_{12}H_{16}O_{6}. Nitric acid -oxidises it to oxalic acid. Nitropicrotoxin and bromopicrotoxin, -C_{30}H_{33}(NO_{2})O_{13}, and C_{30}H_{32}Br_{2}O_{13}, can by -appropriate treatment be obtained. - -Concentrated aqueous solutions of alkalies and ammonia decompose -picrotoxin fully on warming. It reduces alkaline copper solution, and -colours bichromate of potash a beautiful green. The best test for its -presence is, however, as follows:--The supposed picrotoxin is carefully -dried, and mixed with thrice its bulk of saltpetre, the mixture -moistened with sulphuric acid, and then decomposed with soda-lye in -excess, when there is produced a transitory brick-red colour. For the -reaction to succeed, the picrotoxin should be tolerably pure. - -Solutions of picrotoxin are not precipitated by the chlorides of -platinum, mercury, and gold, iodide of potassium, ferro- and -ferri-cyanides of potassium, nor by picric nor tannic acids. - -Sec. 590. =Fatal Dose.=--Vossler killed a cat in two hours with a dose of -.12 grm. (1.8 grain); and another cat, with the same dose, died in 45 -minutes. Falck destroyed a young hound with .06 grm. (.92 grain) in 24 -to 26 minutes. Given by subcutaneous or intravenous injection, it is, as -might be expected, still more lethal and rapid in its effects. In an -experiment of Falck's, .03 grm. (.46 grain), injected into a vein, -destroyed a strong hound within 20 minutes; .016 grm. (.24 grain) -injected under the skin, killed a guinea-pig in 22 minutes; and .012 -grm. (.18 grain) a hare in 40 minutes. Hence it may be inferred that -from 2 to 3 grains (12.9 to 19.4 centigrms.) would in all probability, -be a dangerous dose for an adult person. - -Sec. 591. =Effects on Animals.=--The toxic action of picrotoxin on fish and -frogs has been proposed as a test. The symptoms observed in fish are -mainly as follows:--The fish, according to the dose, show uncertain -motions of the body, lose their balance, and finally float to the -surface, lying on one side, with frequent opening of the mouth and -gill-covers. These symptoms are, however, in no way distinguishable from -those induced by any poisonous substance in the water, or by many -diseases to which fish are liable. Nevertheless, it may be conceded that -in certain cases the test may be valuable--if, _e.g._, beer be the -matter of research, none of the methods used for the extraction of -picrotoxin will be likely to extract any other substance having the -poisonous action described on fish, so that, as a confirmatory test, -this may be of use. - -Frogs, under the influence of picrotoxin, become first uneasy and -restless, and then somewhat somnolent; but after a short time tetanic -convulsions set in, which might lead the inexperienced to imagine that -the animal was poisoned by strychnine. There is, however, one marked -distinction between the two--viz., that in picrotoxin poisoning an -extraordinary swelling of the abdomen has been observed, a symptom -which, so far as known, is due to picrotoxin alone. The frog is, -therefore, in this instance, the most suitable object for physiological -tests. - -Beer extract containing picrotoxin is fatal to flies; but no definite -conclusion can be drawn from this, since many bitter principles (notably -quassia) are in a similar manner fatal to insect life. - -Sec. 592. =Effects on Man.=--Only two fatal cases of poisoning by -picrotoxin are on record. In 1829 several men suffered from drinking rum -which had been impregnated with _Cocculus indicus_; one died, the rest -recovered. In the second case, a boy, aged 12, swallowed some of a -composition which was used for poisoning fish, the active principle of -which was _Cocculus indicus_; in a few minutes the boy experienced a -burning taste, he had pains in the gullet and stomach, with frequent -vomiting, and diarrh[oe]a. A violent attack of gastro-enteritis -supervened, with fever and delirium; he died on the nineteenth day. The -_post-mortem_ signs were those usual in peritonitis: the stomach was -discoloured, and its coats thinner and softer than was natural; there -were also other changes, but it is obvious that, as the death took place -so long after the event, any pathological signs found are scarcely a -guide for future cases. - -Sec. 593. =Physiological Action.=--The convulsions are considered to arise -from an excitation of the medulla oblongata; the vagus centre is -stimulated, and causes spasm of the glottis and slowing of the heart's -action during the attack. Roehrig also saw strong contraction of the -uterus produced by _picrotoxin_. According to the researches of Crichton -Browne, _chloral hydrate_ acts in antagonism to picrotoxin, and prevents -the convulsions in animals if the dose of picrotoxin is not too large. - -Sec. 594. =Separation from Organic Matters.=--Picrotoxin is extracted from -aqueous acid solutions by either chloroform, amyl alcohol, or ether; the -first is the most convenient. Benzene does not extract it, if employed -in the same manner. On evaporation of the solvent the crude picrotoxin -can be crystallised out of water, and its properties examined. - -R. Palm[613] has taken advantage of the fact that picrotoxin forms a -stable compound with freshly precipitated lead hydroxide, by applying -this property as follows:--the solution supposed to contain picrotoxin -is evaporated to dryness, and the extract then taken up in a very little -water, acidified and shaken out with ether. The ether is evaporated, -the ethereal extract dissolved in a little water, the aqueous solution -filtered through animal charcoal, and precipitated by means of lead -acetate, avoiding excess. The solution is filtered and shaken with -freshly prepared lead hydroxide. The lead hydroxide is dried and tested -direct for picrotoxin; if it does contain picrotoxin then on adding to -it concentrated H_{2}SO_{4} a beautiful saffron yellow is produced as -bright as if the substance was pure picrotoxin. - -[613] _J. Pharm._, (5), xvii. 19-20. - - -III.--The Poison of Illicium Religiosum--A Japanese Plant. - - Sec. 595. A new poison belonging to the picrotoxin class has been - described by Dr. A. Langaard. In 1880, 5 children in Japan were - poisoned by the seeds of the _Illicium religiosum_; 3 of the - children died. Dr. Langaard then made various experiments on animals - with an active extract prepared by exhaustion with spirit, and - ultimate solution of the extract in water. Eykmann has also - imperfectly examined the chemistry of the plant, and has succeeded - in isolating a crystalline body which is not a glucoside; it is - soluble in hot water, in chloroform, ether, alcohol, and acetic - acid, but it is insoluble in petroleum ether; it melts at 175 deg., and - above that temperature gives an oily sublimate. Langaard's - conclusions are that all parts of the plant are poisonous. The - poison produces excitation of the central apparatus of the medulla - oblongata and clonic convulsions analogous to those produced by - picrotoxin, toxiresin, and cicutoxin. Before the occurrence of - convulsions, the reflex excitability of frogs is diminished, the - respiratory centre is stimulated, hence frequency of the - respiration. Small doses cause slowing of the pulse through - stimulation of the vagus and of the peripheral terminations of the - vagus; in the heart the functional activity is later diminished. - Small doses kill by paralysing the respiratory centre, large by - heart paralysis. The proper treatment seems to be by chloral - hydrate, for when animals are poisoned by small lethal doses it - appears to save life, although when the dose is large it has no - effect.--_Ueber die Giftwirkung von Japanischem Sternanis_ - (_Illicium religiosum_, Sieb.), _Virch. Archiv_, Bd. lxxxvi., 1881, - S. 222. - - -IV.--Picric Acid and Picrates. - -Sec. 596. =Picric Acid=, - - OH - / - C_{6}H_{3}N_{3}O_{7}, or C_{6}H_{2} - \\\ - (NO_{2})_{3} - -is trinitrophenol; it forms a number of salts, all of which are more or -less poisonous. Picric acid is much used in the arts, especially as a -dye. The pure substance is in the form of pale yellow crystals, not very -soluble in cold water, but readily soluble in hot water, and readily -soluble in benzene, ether, and petroleum ether. The solution is yellow, -tastes bitter, and dyes animal fibres, such as wool; but it can be -washed out of plant fibres such as cotton. - -Sec. 597. =Effects of Picric Acid.=--Picric acid and its salts have a -tendency to decompose the elements of the blood, and to produce -methaemoglobin; picric acid is also an excitor of the nervous system, -producing convulsions. To these two effects must be added a third; in -acid solution it has a strong affinity for albumin, so that if it meets -with an acid tissue it combines with the tissue, and in this way local -necroses are set up. The action on albumin is somewhat weakened by the -reduction in the body of part of the picric acid to picraminic acid -C_{6}H_{2}(NO_{2})_{2}NH_{2}OH, a substance that does not so readily -form compounds with albuminous matters. Doses of 0.5 to 0.9 grm. (about -8 to 14 grains) may be taken several days in succession without marked -symptoms. Ultimately, however, what is known as "picric jaundice" -appears, the conjunctiva and the whole skin being stained more or less -yellow. The urine, at first of a dark yellow, is later of a red brown -colour. Dyspepsia, with flatulence and an inclination to diarrh[oe]a -have been noticed. A single dose of a gramme (15.4 grains) caused in a -case described by Adler[614] pain in the stomach, headache, weakness, -diarrh[oe]a, vomiting of yellow matters, quickening and afterwards -slowing of the pulse; the skin was of a brown yellow colour, and there -were nervous symptoms. The urine was ruby red. In both faeces and urine -picric acid could be recognised. The excretion of picric acid continued -for six days. A microscopical examination of the blood showed a -diminution of the red blood corpuscles, an increase in the white. -Cheron[615] has described a case in which the application of 0.45 grm. -(6.9 grains) to the vagina produced yellowness of the skin in an hour, -and the urine was also coloured red. Erythema, somnolence, burning and -smarting in the stomach and in the kidneys were also noticed. - -[614] _Wiener. med. Woch._, 1880, 819. - -[615] J. Cheron, _Journ. de Ther._, 1880, 121. - -Sec. 598. =Tests.=--Picric acid is easily separated from either tissues or -other organic matters. These are acidified with sulphuric acid and then -treated with 95 per cent. alcohol; the alcohol is filtered off, -distilled, and the residue treated with ether; this last ethereal -extract will contain any picric acid that may be present. - -If the ether extract contains much impurity, it may be necessary to -drive off the ether, and to take up the residue with a little warm -water, then to cool, filter through a moistened filter paper, and test -the aqueous solution. Picric acid, warmed with KCN and KHO gives a -blood-red colour, from the production of iso-purpurate of potash. -Ammoniacal copper sulphate forms with picric acid yellow-green crystals -which strongly refract the light. If a solution of picric acid be -reduced by the addition of a hydrochloric acid solution of stannous -chloride, the subsequent addition of ferric chloride produces a blue -colour, due to the formation of amidoimidophenol hydrochloride -C_{6}H_{2}OH(NH_{2})(NH)_{2}HCl. - - -V.--Cicutoxin. - -Sec. 599. The _Cicuta virosa_, a not very common umbelliferous plant -growing in moist places, is extremely poisonous. It is from 3 to 4 feet -in height, with white flowers; the umbels are large, the leaves are -tripartite, the leaflets linear lanceolate acute, serrate decurrent; the -calyx has five leaf-like teeth, the petals are obcordate with an inflex -point; the carpels have five equal broad flattened ridges with solitary -stripes. Boehm[616] succeeded, in 1876, in separating an active principle -from this plant. The root was dried, powdered, and exhausted with ether; -on evaporation of the ether the extract was taken up with alcohol, and -after several days standing the filtrate was treated with petroleum -ether; after removing the petroleum, the solution was evaporated to -dryness in a vacuum; it was found to be a resinous mass, to which was -given the name _cicutoxin_. It was fully soluble in alcohol, ether, or -chloroform, and was very poisonous, but what its exact chemical nature -may be is still unknown. - -[616] _Arch. f. exp. Path._, Bd. v., 1876. - -Sec. 600. =Effects on Animals.=--Subcutaneously injected into frogs, -cicutoxin acts something like picrotoxin, and something like the barium -compounds. Ten to fifteen minutes after the injection the animal assumes -a peculiar posture, holding the legs so that the thigh is stretched out -far from the trunk, and the leg at right angles with the thigh; -voluntary motion is only induced by the strongest stimuli, and when the -frog springs, he falls down plump with stiffly stretched-out limbs. The -frequency of breathing is increased, the muscles of the abdomen are -thrown into contraction, and the lungs being full of air, on mechanical -irritation there is a peculiar loud cry, depending upon the air being -forced under the conditions detailed through the narrow glottis. Tetanic -convulsions follow, gradually paresis of the extremities appears, and, -lastly, full paralysis and death; these symptoms are seen after doses of -from 1 to 2 mgrms. The lethal dose for cats is about 1 centigrm. per -kilo. Diarrh[oe]a, salivation, and frequent breathing are first seen, -and are followed by tonic and clonic convulsions, then there is an -interval, during which there is heightened excitability of reflex -action, so that noises will excite convulsions. Small doses by exciting -the vagus slow the pulse; larger doses quicken the pulse, and raise the -arterial pressure. Cicutoxin is supposed to act specially on the medulla -oblongata, while the spinal cord and the brain are only secondarily -affected. - -Sec. 601. =Effects on Man.=--F. A. Falck was able to collect thirty-one -cases of poisoning by cicuta; of these 14 or 45.2 per cent. died. The -symptoms are not dissimilar to those described in animals. There are -pain and burning in the stomach, nausea, vomiting, headache, and then -tetanic convulsions. These, in some cases, are very severe, and resemble -those induced by strychnine; but in a few cases there is early coma -without convulsions. There is also difficulty or absolute impossibility -of swallowing. In fatal cases the respiration becomes stertorous, the -pulse small, the pupils dilated, and the face cyanotic, and death occurs -within some four hours, and in a few cases later. The _fatal dose_ is -unknown. - -Sec. 602. =Separation of Cicutoxin from the Body.=--An attempt might be -made to extract cicutoxin from the tissues on the same principles as -those by which it has been separated from the plant, and identified by -physiological experiments. In all recorded cases, identification has -been neither by chemical nor physiological aids, but by the recognition -of portions of the plant. - - -VI.--AEthusa Cynapium (Fool's Parsley). - -Sec. 603. This plant has long been considered poisonous, and a number of -cases are on record in which it is alleged that death or illness -resulted from its use. Dr. John Harley,[617] however, in an elaborate -paper, has satisfactorily proved the innocence of this plant, and has -analysed the cases on record. He has experimented on himself, on -animals, and on men, with the expressed juice and with the tincture. The -results were entirely negative: some of the published cases he refers to -conium, and others to aconite. - -[617] _St. Thomas' Hospital Reports_, N.S., 1875. - - -VII.--[OE]nanthe Crocata. - -Sec. 604. =The Water Hemlock.=[618]--This, a poisonous umbelliferous plant, -indigenous to England, and growing in moist places such as ditches, &c., -is in flower in the month of August. It resembles somewhat celery, and -the root is something like the parsnip, for which it has been eaten. All -parts of the plant are said to be poisonous, but the leaves and stalks -only slightly so, while the root is very deadly. We unfortunately know -nothing whatever about the active principles of the plant, its -chemistry has yet to be worked out. M. Toulmouche (_Gaz. Med._, 1846) -has recorded, as the expert employed in the case, an attempt to murder -by using the _[oe]nanthe_ as a poison; a woman scraped the root into her -husband's soup with evil intent, but the taste was unpleasant, and led -to the detection of the crime. The root has been mistaken several times -for parsnip and other edible roots, and has thus led to poisonings. The -case of 36 soldiers poisoned in this way, in 1758, has been recorded by -Orfila; there was one death. In 1803 three soldiers were poisoned at -Brest--1 died. In Woolwich Bossey witnessed the poisoning of 21 convicts -who ate the roots and leaves of the plant--6 died. In 1858 there were -several sailors poisoned in a similar way--2 died; while there have been -numerous cases in which the plant has been partaken of by children. - -[618] The earliest treatise on poisoning by the water-hemlock is by -Wepfer. _Cicutae Aquat. Historia et Noxae_, 1679; for cases see -Trojanowsky, _Dorp. med. Ztg._, 1875; Meyer, _Med. Zeitg. f. Preussen_, -1842; Schlesier in Casper's _Wochenschrift_, 1843; Maly, _[OE]ster. med -Wochenschr._, 1844; Badgeley, _Montreal med. Gaz._, 1844; Lender, -_Viertelj. f. ger. Med._, 1865; Gampf, _Coeln. Pharm. Zeitg._, 1875; and -the treatises of Taylor and others. - -Sec. 605. The effects of the poison may be gathered from a case of -poisoning[619] which occurred in 1882 at Plymouth; a Greek sailor, aged -thirty, found on the coast what he considered "wild celery," and ate -part of the root and some of the stem. Two hours after this he ate a -good meal and felt perfectly well, but fifteen minutes later he suddenly -and violently vomited; the whole contents of the stomach were completely -evacuated. In five minutes he was completely unconscious, and had -muscular twitchings about the limbs and face. There was a copious flow -of a thick tenacious mucus from the mouth which hung about the lips and -clothing in viscid strings. Twenty-four hours after the poisoning he was -admitted into the South Devon Hospital apparently semi-comatose; his -legs dragged, and he had only feeble control of them; the extremities -were cold, but there was general free sweating. He could be roused only -with difficulty. There were no spasms, the pupils were dilated and -sluggish, the respiration only 14 per minute. Twelve hours after -admission he became warmer, and perspired freely; he slept continuously, -but could easily be roused. On the following day he was quite conscious, -and made a good recovery. Two companions who had also eaten a smaller -quantity of the hemlock dropwort, escaped with some numbing sensations, -and imperfect control over the extremities. In the Woolwich cases the -symptoms seem to have been something similar; in about twenty minutes, -one man, without any apparent warning, fell down in strong convulsions, -which soon ceased, although he looked wild; a little while afterwards -his face became bloated and livid, his breathing stertorous and -convulsive, and he died in five minutes after the first symptoms had set -in. A second died with similar symptoms in a quarter of an hour; a third -died in about an hour, a fourth in a little more than an hour; two other -cases also proved fatal, one in nine days, the other in eleven. In the -two last cases there were signs of intestinal irritation. The majority -of the others fell down in a state of insensibility with convulsions, -the after-symptoms being more or less irritation of the intestinal -canal. - -[619] _Lancet_, Dec. 18, 1882. - -Sec. 606. =Post-mortem Appearances.=--It was noticed in the Woolwich cases -that those who died quickly had congestion of the cerebral vessels, and, -in one instance, there was even extravasation of blood, but the man who -died first of all had no congestion of the cerebral vessels. The lining -membrane of the wind-pipe and air tubes was intensely injected with -blood, and the lungs were gorged with fluid blood; the blood in the -heart was black and fluid. The stomach and intestines were externally of -a pink colour. The mucous membrane of the stomach was much corrugated, -and the follicles particularly enlarged. In the two protracted cases the -stomach was not reddened internally, but the vessels of the brain were -congested. - - -VIII.--Oil of Savin. - -Sec. 607. The leaves of the _Sabina communis_ (_Juniperus Sabina_), or -common savin, an evergreen shrub to be found in many gardens, contains a -volatile oil, which has highly irritant properties. Savin leaves are -occasionally used in medicine, maximum dose 1 grm. (15.4 grains). There -is also a tincture--maximum dose 3 c.c. (about 45 mins.)--and an -ointment made by mixing eight parts of savin tops with three of yellow -wax and sixteen parts of lard, melting and digesting for twenty minutes, -and then straining through calico. The oil, a tincture, and an ointment, -are officinal pharmaceutical preparations. - -The oil of savin is contained to the extent of about 2 per cent. in the -leaves and 10 per cent. in the fruit. It has a peculiar odour, its -specific gravity is .89 to .94, and it boils at 155 deg. to 160 deg. An -infusion of savin leaves (the leaves being drunk with the liquid) is a -popular and very dangerous abortive. - -It is stated by Taylor that oil of savin has no abortive effect, save -that which is to be attributed to its general effect upon the system, -but this is erroneous. Roehrig found that, when administered to rabbits, -it had a very evident effect upon the pregnant uterus, throwing it into -a tetanic contraction. The action was evident after destruction of the -spinal cord. The plant causes great irritation and inflammation, whether -applied to the skin or taken internally. The symptoms are excruciating -pain, vomiting, and diarrh[oe]a, and the person dies in a kind of -collapse. - -In a case in which the author was engaged some years ago, a woman, -pregnant by a married man, took an unknown quantity of infusion of savin -tops. She was violently sick, suffered great pain, with diarrh[oe]a, and -died in about 26 hours. The pharynx was much reddened, and the gullet -even congested; the stomach was inflamed, and contained some greenish -matter, in which the author was able to detect savin tops, as well as to -separate by distillation a few drops of a strong savin-like smelling -oil. The time which would elapse between the swallowing of the poison -and the commencement of the pain was an important factor in this case, -for the man was accused of having supplied her with the infusion. From -the redness of the pharynx, and, generally, the rapid irritation caused -by ethereal oils, the author was of opinion that but a few minutes must -have passed between the taking of the liquid and the sensation of -considerable burning pain, although it is laid down in some works, as -for example Falck's _Toxicologie_, that commonly the symptoms do not -commence for several hours. Symptoms which have been noticed in many -cases are--some considerable irritation of the urinary organs, such as -strangury, bloody urine, &c.; in a few cases vomiting of blood, in -others anaesthesia, convulsions, and coma. Death may occur within 12 -hours, or may be postponed for two or three days. - -Sec. 608. =Post-mortem Appearances.=--More or less inflammation of the -bowels, stomach, and intestinal tract, with considerable congestion of -the kidneys, are the signs usually found. - -Sec. 609. =Separation of the Poison and Identification.=--Hitherto reliance -has been placed entirely on the finding of the savin tops, or on the -odour of the oil. There is no reliable chemical test. - - -IX.--Croton Oil. - -Sec. 610. Croton oil is an oil expressed from the seeds of _Croton -tiglium_, a plant belonging to the natural order _Euphorbiaceae_, growing -in the West Indies. The seeds are oval in shape, not unlike castor-oil -seeds, and about three-eighths of an inch in length. Both the seeds and -the oil are very poisonous. The chemical composition of croton oil can -scarcely be considered adequately settled. The most recent view, -however, seems to be that it contains a fixed oil (C_{9}H_{14}O_{2}) -with certain glycerides.[620] On saponifying and decomposing the soap a -series of volatile fatty acids can be distilled over, the principal of -which are methyl crotonic acid, with small quantities of formic, acetic, -iso-butyric, valeric, and perhaps propionic, and other acids.[621] The -peculiar properties of croton are due rather to the fixed oil than to -the volatile principles. The only officinal preparation in the British -pharmacop[oe]ia is a "_croton oil liniment_," containing one part of -croton oil to seven of equal parts of oil of cajuput and rectified -spirit. - -[620] G. Schmidt, _Arch. Pharm._ [3] 13, 213-229. Schlippe, Liebig's -_Annalen_, 105, 1. Geuther and Froehlich, _Zeitschrift f. Chem._, 1870, -26 and 549; _Journ. Chem. Society_, March 1879, p. 221. - -[621] Benedikt has found 0.55 per cent. of unsaponifiable matter in -croton oil. Lewkowitsch gives the iodine value 101.7 to 104.7, and -solidifying point as 18.6 deg.-19.0 deg. (_Cheml. Analysis of the Oils, Fats, -and Waxes_, by R. Benedikt, translated and enlarged by J. Lewkowitsch, -London, 1895.) - -Sec. 611. =Dose.=--The oil is given medicinally as a powerful purgative in -doses up to 65 mgrms. (about a grain). It is used externally as an -irritant or vesicant to the skin. A very dangerous dose would be from -fifteen to twenty times the medicinal dose. - -=Effects.=--Numerous cases of poisoning from large doses of croton oil -are recorded in medical literature, but the sufferers have mostly -recovered. The symptoms are pain, and excessive purging and vomiting. - -In the case of a chemist,[622] who took half an ounce of impure croton -oil instead of cod-liver oil, the purging was very violent, and he had -more than a hundred stools in a few hours; there was a burning pain in -the gullet and stomach, the skin was cyanosed, the pupils dilated, and -great faintness and weakness were felt, yet the man recovered. A child, -aged four, recovered from a teaspoonful of the oil given by mistake -directly after a full meal of bread and milk. In five minutes there were -vomiting and violent purging, but the child was well in two days. A -death occurred in Paris, in 1839, in four hours after taking two and a -half drachms of the oil. The symptoms of the sufferer, a man, were those -just detailed, namely, burning pain in the stomach, vomiting, and -purging. Singularly enough, no marked change was noticed in the mucous -membrane of the stomach when examined after death. An aged woman died in -3 days from a teaspoonful of croton-oil embrocation; in this case there -were convulsions. - -[622] _Revue de Therapeut._, May 1881. - -In the case of _Reg._ v. _Massey and Ferraud_,[623] the prisoners were -charged with causing the death of a man, by poisoning his food with -jalap and six drops of croton oil. The victim, with others who had -partaken of the food, suffered from vomiting and purging; he became -better, but was subsequently affected with inflammation and ulceration -of the bowels, of which he died. In this case it was not clear whether -the inflammation had anything to do with the jalap and croton oil or -not, and the prisoners were acquitted. In a criminal case in the United -States, a man, addicted to drink, was given, when intoxicated, 2 drachms -of croton oil in a glass of whisky. He vomited, but was not purged, and -in about twelve hours was found dead. The mucous membrane of the stomach -and small intestines proved to be much inflamed, and in some parts -eroded, and croton oil was separated from the stomach. - -[623] _Orfila_, t. i. p. 108. - -Sec. 612. =Post-mortem Appearances.=--Inflammation of the stomach and -intestines are the signs usually found in man and animals. - -Sec. 613. =Chemical Analysis.=--The oil may be separated from the contents -of the stomach by ether. After evaporation of the ether, the blistering -or irritant properties of the oil should be essayed by placing a droplet -on the inside of the arm. - - -X.--The Toxalbumins of Castor-Oil Seeds and of Abrus. - -Sec. 614. =The Toxalbumin of Castor-Oil Seeds.=--In castor-oil seeds, -besides the well-known purgative oil, there exists an albuminous body -intensely poisonous, which has been carefully investigated by -Stillmark,[624] under the direction of Kobert.[625] Injected into the -circulation it is more poisonous than strychnine, prussic acid, or -arsenic; and since the pressed seeds are without taste or smell, this -poison has peculiar dangers of its own. - -[624] H. Stillmark, _Dorp. Arb._, Bd. iii., 1889. - -[625] Kobert's _Lehrbuch_, 453-456. - -It is essentially a blood poison, coagulating the blood. - -The blood, if carefully freed from all fibrin, is yet again brought to -coagulation by a small amount of this body. - -If castor-oil seeds are eaten, a portion of the poison is destroyed by -the digestive processes; a part is not thus destroyed, but is absorbed, -and produces in the blood-vessels its coagulating property. Where this -takes place, ulcers naturally form, because isolated small areas are -deprived of their blood supply. These areas thus becoming dead, may be -digested by the gastric or intestinal fluids, and thus, weeks after, -death may be produced. The symptoms noted are nausea, vomiting, colic, -diarrh[oe]a, tenesmus, thirst, hot skin, frequent pulse, sweats, -headache, jaundice, and death in convulsions or from exhaustion. Animals -may be made immune by feeding them carefully with small doses, gradually -increased. - -The _post-mortem_ appearances are ulceration in the stomach and -intestines. In animals the appearances of haemorrhagic gastro-enteritis, -with diffuse nephritis, haemorrhages in the mesentery and so forth have -been found. - -Sec. 615. =Toxalbumin of Abrus.=--A toxalbumin is found in the _Abrus -precatorius_ (Jequirity) which causes quite similar effects and -symptoms. That it is not identical is proved by the fact that, -though animals may become immune by repeated doses of Jequirity -against "Abrin," the similar substance from castor-oil seeds only -confers immunity against the toxalbumin of those seeds, and not -against abrin; and similarly abrin confers no immunity against the -castor albumin. Either of these substances applied to the conjunctiva -produces coagulation in the vessels and a secondary inflammation, to -which in the case of jequirity has been given the name of -"jequirity-ophthalmia."[626] - -[626] Heinr. Hellin, _Der giftige Eiweisskorper-Abrin u. seine Wirkung -auf das Blut. Inaug.-Diss._, Dorpat., 1891. - -The general effect of these substances, and, above all, the curious fact -that a person may acquire by use a certain immunity from otherwise fatal -doses is so similar to poisonous products evolved in the system of -persons suffering from infectious fevers, that they have excited of late -years much interest, and a study of their methods of action will throw -light upon many diseased processes. - -At present there are no chemical means of detecting the presence of the -toxalbumins mentioned. Should they be ever used for criminal purposes, -other evidence will have to be obtained. - - -XI.--Ictrogen. - -Sec. 616. =Ictrogen.=--Various lupins, _e.g._, _Lupinus luteus_, _L. -angustifolius_, _L. thermis_, _L. linifolius_, _L. hirsutus_, contain a -substance of which nothing chemically is known, save that it may be -extracted by weakly alkaline water, and which has been named "ictrogen"; -this must not be confused with the alkaloid of lupins named "lupinine," -a bitter tasting substance. In large doses a nerve poison. Ictrogen has -the unusual property of acting much like phosphorus. It causes yellow -atrophy of the liver, and produces the following symptoms:--Intense -jaundice; at first enlargement of the liver, afterwards contraction; -somnolence, fever, paralysis. The urine contains albumen and the -constituents of the bile. After death there is found to be -parenchymatous degeneration of the heart, kidneys, muscles, and liver. -If the animal has suffered for some time the liver may be cirrhotic. - -Hitherto the cases of poisoning have been confined to animals. Many -thousands of sheep and a few horses and deer have, according to Kobert, -died in Germany from eating lupin seeds. Further information upon the -active principles of lupins may be obtained by referring to the -following treatises:--G. Schneidemuhl, _Die lupinen Krankheit der -Schafe_; _Vortraege f. Thieraerzte_. Ser. 6, Heft. 4, Leipzig, 1883. C. -Arnold and G. Schneidemuhl, _Vierter Beitrag zur Klarstellung der -Ursache u. des Wesens der Lupinose_, Luneburg, 1883; Julius Loewenthal, -_Ueber die physiol. u. toxicol. Wirkungen der Lupinenalkaloide, -Inaug.-Diss._, Koenigsberg, 1888. - - -XII.--Cotton Seeds. - -Sec. 617. Cotton seeds, used as an adulterant to linseed cake, &c., have -caused the death of sheep and calves. Cotton seeds contain a poison of -which nothing is chemically known, save that it is poisonous. It -produces anaemia and cachexia in animals when given in small repeated -doses. - -After death the changes are, under these circumstances, confined to the -kidney; these organs showing all the signs of nephritis. If, however, -the animal has eaten a large quantity of cotton seeds, then there is -gastro-enteritis, as well as inflammation of the kidneys. - - -XIII.--Lathyrus Sativus. - -Sec. 618. Various species of vetchlings, such as _L. sativus_, _L. cicera_, -_L. clymenum_, are poisonous, and have caused an epidemic malady in -parts of Spain, Africa, France, and Italy, among people who have eaten -the seeds. The symptoms are mainly referable to the nervous system, -causing a transverse myelitis and paraplegia. In this country it is -chiefly known as a poisonous food for horses; the last instance of -horse-poisoning by lathyrus was that of horses belonging to the Bristol -Tramways and Carriage Company.[627] The company bought some Indian peas; -these peas were found afterwards to consist mainly of the seeds of -_Lathyrus sativus_, for out of 335 peas no fewer than 325 were the seeds -of _Lathyrus_. The new peas were substituted for the beans the horses -had been having previously on the 2nd November, and the horses ate them -up to the 2nd December. Soon after the new food had been given, the -horses began to stumble and fall about, not only when at work, but also -in their stalls; to these symptoms succeeded a paralysis of the larynx; -this paralysis was in some cases accompanied by a curious weird -screaming, which once having been heard could never be forgotten; there -was also gasping for breath and symptoms of impending suffocation. A few -of the horses were saved by tracheotomy. Some died of suffocation; one -horse beat its brains out in its struggles for breath; 127 horses were -affected; 12 died. - -[627] Bristol Tramways and Carriage Company _v._ Weston & Co., _Times_, -July 17, 1894. - -The above train of symptoms has also been recorded in similar cases; -added to which paralysis of the lower extremities is frequent. After -death atrophy of the laryngeal muscles, wasting of the nervus recurrens, -and atrophy of the ganglion cells of the vagus nucleus as also of the -multipolar ganglion cells in the anterior horns of the spinal cord have -been found. - -The active principle of the seeds has not been satisfactorily isolated. -The symptoms suggest the action of a toxalbumin. Teilleux found a resin -acid; Louis Astier a volatile alkaloid, and he explains the fact that -the seeds, after being heated, are no longer poisonous by the -dissipation of this alkaloid. - - -XIV.--Arum--Bryony--Locust Tree--Male Fern. - -Sec. 619. =Arum maculatum=, the common cuckoo-pint, flowering in April and -May, and frequent in the hedges of this country, is extremely poisonous. -Bright red succulent attractive berries are seen on a single stalk, the -rest of the plant having rotted away, and these berries are frequently -gathered by children and eaten. The poison belongs to the class of acrid -irritants, but its real nature remains for investigation. - -Some of the species of the same natural order growing in the tropics are -far more intensely poisonous. - -Sec. 620. =The Black Bryony.=--_Tamus communis_, the black bryony, a common -plant by the wayside, flowering in May and June, possesses poisonous -berries, which have been known to produce death, with symptoms of -gastro-enteritis. In smaller doses the berries are stated to produce -paralysis of the lower extremities.[628] - -[628] Contagne, _Lyon med._, xlvi., 1884, 239. - -Sec. 621. =The Locust Tree.=--The _Robinia pseudo-acacia_, a papilionaceous -tree, contains a poison in the leaves and in the bark. R. Coltmann [629] -has recorded a case in China of a woman, twenty-four years of age, who, -at a time of famine, driven by hunger, ate the leaves of this tree. She -became ill within forty-eight hours, with high fever; the tongue swelled -and there was much erysipelatous-like infiltration of the tissues of the -mouth; later the whole body became swollen. There was constipation and -so much [oe]dema of the eyelids that the eyeballs were no longer -visible. Recovery took place without special treatment. Power and -Cambier[630] have separated from the bark an albumose, which is -intensely poisonous, and is probably the cause of the symptoms detailed. - -[629] _Medical and Surgical Reporter_, lxi., 1889. - -[630] _Pharm. Journ._, 1890, 711. - -Sec. 622. =Male Fern.=--An ethereal extract of _Aspidium Filix mas_ is used -as a remedy against tape worm. - -Poullson[631] has collected up to the year 1891 sixteen cases of -poisoning by male fern; from which it would appear that 7 to 10 grms. -(103 to 154 grains) of the extract may be fatal to a child, and 45 grms. -(rather more than 1-1/2 oz.) to an adult. The active principle seems to -be filicic acid and the ethereal oil. Filicic acid, under the influence -of saponifying agencies, breaks up into butyric acid and phloroglucin. - -[631] _Arch. exp. P._, Bd. 29. - -The symptoms produced are pain, heaviness of the limbs, faintness, -somnolence, dilatation of the pupil, albuminuria, convulsions, lock-jaw, -and collapse. In animals there have also been noticed salivation, -amaurosis, unsteady gait, dragging of the hind legs, dyspn[oe]a, and -paralysis of the breathing centres. The _post-mortem_ appearances which -have been found are as follows:--Redness and swelling with haemorrhagic -spots of the mucous membranes of the stomach and intestines; acute -[oe]dema of the brain and spinal cord with petechia in the meninges; the -kidneys inflamed, the liver and spleen congested, and the lungs -[oe]dematous. - -There is no characteristic reaction for male fern; the research most -likely to be successful is to attempt to separate from an ethereal -extract filicic acid, and to decompose it into butyric acid and -phloroglucin; the latter tinges red a pine splinter moistened with -hydrochloric acid. - - - - -PART VII.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL SUBSTANCES. - - -DIVISION I.--POISONS SECRETED BY LIVING ANIMALS. - - -I.--Poisonous Amphibia. - -Sec. 623. The glands of the skin of certain amphibia possess a secretion -that is poisonous; the animal is unable to empty the poison glands by -any voluntary act, but the secretion can readily be obtained by -pressure. Zalesky found the juice in the skin glands of the _Salamandra -maculosa_, milky, alkaline in reaction, and bitter in taste. He -isolated from it an organic base, which he named _Salamandrine_ -(C_{34}H_{60}N_{2}O_{5}), it is soluble in water and in alcohol, and -forms salts. Salamandrine is a strong poison; injected subcutaneously -into rabbits it causes shivering, epileptiform convulsions, and -salivation; then tetanus, followed by oppressed respiration, dilated -pupils, and anaesthesia. Death occurs after a kind of paralytic state. -When given to dogs, it causes vomiting. In frogs, tetanus occurs first -and then paralysis--the result of all the experiments being that -salamandrine acts on the brain and spinal cord, leaving the heart and -muscular substance unaffected. A similar secretion obtained from the -water salamander (_Triton cristatus_), causes, according to Vulpian, the -death of dogs in from three to eighteen hours; the symptoms being -progressive weakness, slowing of the respiration, and depression of the -heart's action. - -Sec. 624. The secretion of the skin of the common toad contains -methylcarbylaminic acid, carbylamine, and, according to Fornara, an -alkaloid which is soluble in alcohol, and to which the name of -_phrynine_ has been applied; its action is toxic on all animals -experimented upon, save toads. Administered subcutaneously to frogs, it -has a digitalis-like action, causing rapid paralysis of the heart, and -the breathing soon after ceases; the muscles become early rigid. - - -II.--The Poison of the Scorpion. - -Sec. 625. There are several species of scorpions. The small European -variety (_Scorpio europaeus_) is found in Italy, the south of France, and -the Tyrol; the African scorpion (_Bothus afer_, L.), which attains the -length of 16 cm., is found in Africa and the East Indies; _Androctonus -bicolor_ in Egypt; and the _Androctonus occitanus_ in Spain, Italy, -Greece, and North Africa. - -In the last joint of the tail the scorpion is provided with a poisonous -apparatus, consisting of two oval glands, the canal of which leads into -a round bladder, and this last is connected with a sting. When the sting -is inserted, the bladder contracts, and expels the poison through the -hollow sting into the wound. The smaller kinds of scorpion sting with as -little general effect as a hornet, but the large scorpion of Africa is -capable of producing death. There is first irritation about the wound, -and an erysipelatous inflammation, which may lead to gangrene. Vomiting -and diarrh[oe]a then set in, with general weakness and a fever, which -may last from one to one and a half days; in the more serious cases -there are fainting, delirium, coma, convulsions, and death. According to -G. Sanarelli[632] the blood corpuscles of birds, fishes, frogs, and -salamanders are dissolved by the poison; only the nucleus remaining -intact; the blood corpuscles of warm-blooded animals are not affected. - -[632] G. Sanarelli, _Bollet. della Soc. della sez. dei cult. delle -Scienze med._, v., 1888, 202. - -Valentin made some experiments on frogs with the _Androctonus -occitanus_. He found that soon after the sting the animal remains quiet, -but on irritation it moves, and is thrown into a transitory convulsion; -to this follow twitchings of single muscular bundles. The frog is -progressively paralysed, and the reflex irritability is gradually -extinguished from behind forwards; at first the muscles may be excited -by electrical stimuli to the nerves, but later they are only capable of -contraction by direct stimuli. - - -III.--Poisonous Fish. - -Sec. 626. A large number of fish possess poisonous properties; in some -cases the poison is local; in others the poison is in all parts of the -body. - -Many fish are provided with poison glands in connection with the fins or -special weapons, and such are used for purposes of defence; for example, -_Synanceia brachio_ is provided with a back fin consisting of 13 spines, -each of which has two poison reservoirs; the reservoirs are connected -with 10 to 12 tubular glands which secrete the poison, a clear feebly -acid bluish fluid, exciting in a concentrated condition, local gangrene; -in a diluted one, paralysis of the nervous centres. - -Another kind of localisation is the localisation in certain of the -internal organs. Remy states, that there are twelve varieties of -_Tetrodon_ in Japanese waters, all of which are poisonous. M. Minra and -K. Takesaki[633] find that the poison of the _Tetrodon_ is confined to -the sexual organs of the female, and at the time of activity of these -glands, the poisonous properties are most intense; but, even in winter, -when the glands are atrophied, Remy found the glands were so poisonous -that he could prepare from them a fluid, which, administered -subcutaneously, killed dogs within two hours. The symptoms in the dog -are restlessness, salivation, vomiting of slimy masses, dilatation of -the pupil, paralysis and great dyspn[oe]a. Death occurs by the lung. -After death the appearances are similar to those from asphyxia; in -addition to which there are small ecchymoses in the stomach and -intestines; the salivary glands and pancreas are also injected. The -symptoms observed in man are similar, there is headache, dilated pupils, -vomiting, sometimes haematamesis, convulsions, paralysis, dyspn[oe]a and -death. - -[633] Virchow's _Archiv_, 1890, Bd. 122. - -Some fishes are poisonous on account of the food they live upon; the -_Meletta venenosa_ is only poisonous when it feeds upon a certain green -monad; _Clupea thrissa_, _C. venenosa_ and certain species of _Scarus_, -neither possess poison glands nor poisonous ovaries; but also derive -their poisonous properties from their food. In the West Indies it is -well-known that fish caught off certain coral banks are unwholesome, -while the same species caught elsewhere may be eaten with safety. - -A good many shell-fish, especially mussels, occasionally cause intense -poisonous symptoms; those usually noticed are high fever, nettle rash, -dilated pupils, and diarrh[oe]a. It may be that in these cases a -ptomaine, the product of bacterial action, has been ingested. To the -agency of bacteria has been ascribed illness produced in Russia by a -good many fish of the sturgeon species. The symptoms are those of -cerebro-spinal paralysis. The "Icthyismus gastricus" of Germany may -belong to the same type. Prochorow[634] has described illness from -ingestion of _Petromyzon fluviatilis_ in Russia. Whether the fish was -eaten raw or cooked, the effect was the same, producing a violent -diarrh[oe]a, dysenteric in character. Even the broth in which the fish -had been boiled produced symptoms. Fresh blood of the eel is stated to -be intensely poisonous; this property is apparently due to a toxalbumin; -Pennavaria[635] relates the case of a man who took, in 200 c.c. of wine, -0.64 kilo. of fresh eel blood and suffered from diarrh[oe]a with -symptoms of collapse. - -[634] _Pharmac. Ztg._, 1885. - -[635] _Il Farmacista Italiano_, xii., 1888. - -In the _Linnean Transactions_ for November, 1860, is recorded a fatal -accident, which took place on board the Dutch ship "Postillion" at -Simon's Bay, Cape of Good Hope. The boatswain and purser's steward -partook of the liver of the _toad_ or _ball-bladder_ (_Diodon_); within -twenty minutes the steward died; in ten minutes the boatswain was -violently ill; the face flushed, the eyes glistening, and the pupils -contracted; there was cyanosis of the face, the pulse was weak and -intermittent, and swallowing was difficult, the breathing became -embarrassed, and the body generally paralysed. Death took place in -seventeen minutes. The liver of one fish only is said to have been -eaten. This might weigh 4 drachms. If the account given is literally -correct, the intensity of the poison equals that of any known substance. - -The poisonous nature of the goby has also led to several accidents, and -we possess a few experiments made by Dr. Collas,[636] who fed chickens -with different parts of the fish, and proved that all parts were alike -poisonous. The effects were slow in developing; they commenced in about -an hour or an hour and a half, and were well developed in five hours, -mainly consisting of progressive muscular weakness and prostration. -Death occurred without convulsions. - -[636] _Soc. Sci. Rev._, July 19, 1862; _Brit. and For. Med. Chir. Rev._, -Oct. 1862, p. 536. - - -IV.--Poisonous Spiders and Other Insects. - -Sec. 627. It is probable that all spiders are poisonous; the only species, -however, of which we have any definite information relative to their -poisonous properties, are _Lycosa tarantula_ and the _Latrodectus -malmignatus_, to which may be added the New Zealand _katipo_. These -spiders possess a poisonous gland connected with their masticatory -apparatus, which secretes a clear, oily, bitter acid-reacting fluid; the -acidity seems due to formic acid. - -Zangrilli has observed several cases of tarantula bite; soon after the -occurrence the part bitten is anaesthetic, after a few hours there are -convulsive shiverings of the legs, cramps of the muscles, inability to -stand, spasm of the pharyngeal muscles, quickening of the pulse, and a -three days' fever, with vomiting of yellow, bilious matter; recovery -follows after copious perspiration. In one case there was tetanus, and -death on the fourth day. The extraordinary effects attributed to the -bite of the tarantula, called _tarantism_ in the Middle Ages, are well -detailed by Hecker;[637] this excitement was partly hysterical and -partly delirious, and has not been observed in modern times. - -[637] "The Epidemics of the Middle Ages," by J. F. C. Hecker, translated -by B. G. Babington, M.D., F.R.S. (_The Dancing Mania_, chap, ii., &c.) - -Dax has described the effects of the bite of the _L. malmignatus_; it -occasioned headache, muscular weakness, pain in the back, cramps, and -dyspn[oe]a; the symptoms disappeared after several days. - -Sec. 628. The _katipo_ is a small poisonous spider confined to New Zealand. -Mr. W. H. Wright has recorded the case of a person who, in 1865, was -bitten by this spider on the shoulder. The part rapidly became swollen, -and looked like a large nettle-rash wheal; in an hour the patient could -hardly walk, the respiration and circulation were both affected, and -there was great muscular prostration; but he recovered in a few hours. -In other cases, if the accounts given are to be relied upon, the bite of -the spider has produced a chronic illness, accompanied by wasting of the -body, followed by death after periods varying from six weeks to three -months.[638] - -[638] _Transac. of the New Zealand Inst._, vol. ii., 1869; _Brit. and -For. Med. Chir. Review_, July 1871, p. 230. - -Sec. 629. =Ants.=--The various species of ants possess at the tail special -glands which secrete _formic acid_. Certain exotic species of ants are -provided with a sting, but the common ant of this country has no special -piercing apparatus. The insect bites, and then squirts the irritating -secretion into the wound, causing local symptoms of swelling and -inflammation. - -Sec. 630. =Wasps, &c.=--Wasps, bees, and hornets all possess a poison-bag -and sting. The fluid secreted is as clear as water, and of an acid -reaction; it certainly contains formic acid, with some other poisonous -constituent. An erysipelatous inflammation generally arises round the -sting, and in those cases in which persons have been attacked by a swarm -of bees, signs of general poisoning, such as vomiting, fainting, -delirium, and stupor, have been noticed. Death has occasionally -resulted. - -Sec. 631. =Cantharides.=--Commercial cantharides is either the dried -entire, or the dried and powdered blister-beetle, or Spanish fly -(_Cantharis vesicatoria_). The most common appearance is that of a -greyish-brown powder, containing shining green particles, from which -cantharidin is readily extracted by exhausting with chloroform, driving -off the chloroform by distillation or evaporation, and subsequently -treating the extract with bisulphide of carbon, which dissolves the -fatty matters only. Finally, the cantharidin may be recrystallised from -chloroform, the yield being .380 to .570 per cent. Ferrer found in the -wings and their cases, .082 per cent.; in the head and antennae, .088; in -the legs, .091; in the thorax and abdomen, .240; in the whole insect, -.278 per cent. Wolff found in the _Lytta aspera_, .815 per cent.; Ferrer -in _Mylabris cichorei_, .1 per cent.; in _M. punctum_, .193; and in _M. -pustulata_, .33 per cent. of _cantharidin_. - -Sec. 632. =Cantharidin= (C_{10}H_{12}O_{4}) has two crystalline forms--(1) -Right-angled four-sided columns with four surfaces, each surface being -beset with needles; and (2) flat tables. It is the anhydride of a ketone -acid (cantharidic acid), C_{8}H_{13}O_{2}-CO-COOH. It is soluble in -alkaline liquids, and can be recovered from them by acidifying and -shaking up with _ether_, _chloroform_, or _benzene_; it is almost -completely insoluble in water. 100 parts of alcohol (99 per cent.) -dissolve at 18 deg. 0.125 part; 100 of bisulphide of carbon, at the same -temperature, 0.06 part; ether, .11 part; chloroform, 1.2 part; and -benzene, .2 part. Cantharidin can be completely sublimed, if placed in -the subliming cell (described at p. 258), floating on mercury; a scanty -sublimate of crystals may be obtained at so low a temperature as 82.5 deg.; -at 85 deg., and above, the sublimation is rapid. If the cantharidin is -suddenly heated, it melts; but this is not the case if the temperature -is raised gradually. The tube melting-point is as high as 218 deg. Potassic -chromate with sulphuric acid decomposes cantharidin with the production -of the green oxide of chromium. An alkaline solution of permanganate, -iodic acid, and sodium amalgam, are all without influence on an -alcoholic solution of cantharidin. With bases, cantharidin forms -crystallisable salts, and, speaking generally, if the base is soluble in -water, the "_cantharidate_" is also soluble; the lime and magnesic salts -dissolve readily. From the soda or potash salt, mineral acid will -precipitate crystals of cantharidin; on heating with pentasulphide of -phosphorus, o-xylol is produced. - -Sec. 633. =Pharmaceutical Preparations of Cantharides.=--The P.B. -preparations of cantharides are--_Acetum cantharides_, or vinegar of -cantharides, containing about .04 per cent. of cantharidin. - -_Tincture of cantharides_, containing about .005 per cent. of -cantharidin. - -A solution of cantharides for blistering purposes, _Liquor -epispasticus_, a strong solution of the active principle in ether and -acetic acid, containing about .16 per cent. of cantharidin. - -There are also--An _ointment_; a blistering paper, _Charta epispastica_; -a blistering plaster, _Emplastrum cantharides_; and a warm plaster, -_Emplastrum calefaciens_. - -Sec. 634. =Fatal Dose.=--It is difficult to state the fatal dose of -cantharidin, the unassayed powder or tincture having mostly been taken. -A young woman died from 1.62 grm. (25 grains) of the powder, which is -perhaps equivalent to 6.4 mgrms. (1 grain) of cantharidin, whilst the -smallest dose of the tincture known to have been fatal is (according to -Taylor) an ounce. This would be generally equivalent to 15 mgrms. (.24 -grain). Hence the fatal dose of cantharidin may be approximately stated -as from 6 mgrms. upwards. But, on the other hand, recovery has taken -place from very large doses. - -Sec. 635. =Effects on Animals.=--Certain animals do not appear susceptible -to the action of cantharidin. For example, hedgehogs and swallows are -said to be able to take it with impunity. Radecki[639] found that -cantharidin might even be injected into the blood of fowls without any -injury, and frogs also seem to enjoy the same impunity; while dogs, -cats, and other animals are sensitive to the poison. Galippe ascertained -that after the injection of 5 mgrms. into the veins of a dog, there was -exaltation of the sexual desire; the pupils quickly dilated, the dog -sought a dark place, and became sleepy. Animals when poisoned die in -asphyxia from paralysis of the respiratory centre. Schachowa[640] made -some observations on the effect of cantharides on the renal excretion of -a dog fed daily with 1 grm. in powder. On the third day, pus corpuscles -were noticed; on the fifth, bacteria; on the thirteenth, the urine -contained a large quantity of fatty matters, and several casts; and on -the seventeenth, red shrivelled blood corpuscles were observed. - -[639] _Die Cantharidin Vergift._, Diss., Dorpat, 1806. - -[640] _Unters. ueber die Nieren_, Diss., Bern, 1877; Cornil, _Gaz. Med._, -1880. - -=Effects on Man.=--Heinrich[641] made the following experiments upon -himself:--Thirty living blister-beetles were killed, and digested, -without drying, in 35 grms. of alcohol for fourteen days, of this -tincture ten drops were taken. There ensued immediately a feeling of -warmth in the mouth and stomach, salivation, the pulse was more frequent -than in health, there was a pleasant feeling of warmth about the body, -and some sexual excitement lasting three hours. In half an hour there -was abdominal pain, diarrh[oe]a, and tenesmus, and frequent painful -micturition. These symptoms subsided in a few hours, but there was a -want of appetite, and pain about the kidneys lasting until the following -day. In the second experiment, on taking 1 cgrm. of cantharidin, there -were very serious symptoms of poisoning. Blisters formed on the tongue, -and there was salivation, with great difficulty in swallowing, and a -general feeling of illness. Seven hours after taking the poison, there -were frequent micturitions of bloody urine, diarrh[oe]a, and vomiting. -Twenty hours after the ingestion the face was red, the skin hot, the -pulse twenty beats beyond the normal pulsation, the tongue was denuded -to two-thirds of its extent of its epithelium, and the lips and mucous -membrane were red and swollen; there was great pain in the stomach, -intestines, and in the neighbourhood of the kidneys, continuous desire -to micturate, burning of the urethra, and swelling of the glands. There -was no sexual excitement whatever; the urine was ammoniacal, and -contained blood and pus; the symptoms gradually subsided, but recovery -was not complete for fourteen days. - -[641] Schroff, _Zeitschrift d. Ges. d. Aerzte in Wien_, 13, 56. - -Sec. 636. The foregoing is a fair picture of what may be expected in -cantharides poisoning. It is remarkable that the popular idea as to the -influence of cantharidin in exciting the sexual passion, holds good only -as to the entire cantharides, and not with cantharidin. It is very -possible that cantharidin is not the only poisonous principle in the -insect. The symptoms in other cases, fatal or not, have been as -follows:--Immediate burning in the mouth and throat, extending to the -stomach and alimentary canal, and increasing in intensity until there is -considerable pain. Then follow salivation, difficulty in swallowing, and -vomiting, and generally diarrh[oe]a, pain in the kidneys, irritation of -the bladder, priapism, and strangury, are all present. The pulse is -accelerated, the breathing disturbed, there are pains in the head, and -often mydriasis, giddiness, insensibility, delirium, and convulsions; -trismus has been noticed. The desire to micturate frequently is urgent, -the urine is generally bloody, and contains pus. Pregnant women have -been known to abort. In a few of the cases in which a different course -has been run, the nervous symptoms have predominated over those of -gastro-intestinal irritation, and the patient has sunk in a kind of -collapse. In a case of chronic poisoning by cantharides, extending over -three months, and recorded by Tarchioni Bonfanti,[642] after the first -dose appeared tetanic convulsions, which subsided in twenty-four hours, -there was later cystitis, and from time to time the tetanic convulsions -returned; gastro-enteritis followed with frequent vomiting, when, -cantharides being found in the matters ejected, the otherwise obscure -nature of the illness was shown. - -[642] _Gaz. Med. Ital. Lomb._, 1863. - -In a case recorded by Sedgwick,[643] following the gastro-enteric -symptoms, there were epileptic convulsions; in this instance also was -noticed an unpleasant smell, recalling the notion formerly held that -cantharides imparted a peculiar odour to the breath and urine. In a case -of chronic poisoning related by Tardieu, six students, during several -months, used what they thought was pepper with their food, but the -substance proved to be really powdered cantharides. The quantity taken -each day was probably small, but they suffered from pain about the -loins, and also irritation of the bladder. There was no sexual -excitement. - -[643] _Med. Times_, 1864. - -Sec. 637. =Post-mortem Appearances.=--In a French criminal case, in which a -man poisoned his step-brother by giving cantharides in soup, the -pathological signs of inflammation of the gastro-intestinal tract were -specially evident, the mouth was swollen, the tonsils ulcerated, the -gullet, stomach, and intestines were inflamed, and the mucous membrane -of the intestines covered with purulent matter. In another case there -was an actual perforation 3 inches from the pylorus. The inflammatory -appearances, however, are not always so severe, being confined to -swelling and inflammation without ulceration. In all cases there has -been noted inflammation of the kidneys and urinary passages, and this is -seen even when cantharidin is administered to animals by subcutaneous -injection. In the urine will be found blood and fatty epithelial casts, -as well as pus. The contents of the stomach or the intestines will -probably contain some remnants of powdered cantharides, if the powder -itself has been taken. - -Sec. 638. =Tests for Cantharidin, and its Detection in the Tissues, -&c.=--The tests for cantharidin are--(1.) Its form, (2.) its action in -the subliming cell, and (3.) its power of raising a blister. - -The most convenient method of testing its vesicating properties, is to -allow a chloroformic solution of the substance supposed to be -cantharidin to evaporate to dryness, to add to this a drop of olive oil -(or almond oil), and to take a drop up on the smallest possible quantity -of cotton wool, and apply the wool to the inside of the arm, covering it -with good oilskin, and strapping the whole on by the aid of -sticking-plaster. In about an hour or more the effect is examined. The -thin skin of the lips is far more easily blistered than that of the arm, -but the application there is inconvenient. - -Dragendorff has ascertained that cantharidin is not present in the -contents of a blister raised by a cantharides plaster, although it has -been found in the urine of a person treated by one; and Pettenkofer has -also discovered cantharidin in the blood of a boy to whose spine a -blister had been applied. - -The great insolubility of cantharidin in water has led to various -hypotheses as to its absorption into the system. It is tolerably easily -dissolved by potash, soda, and ammonia solutions, and is also taken up -in small proportion by sulphuric, phosphoric, and lactic acids. The -resulting compounds quickly diffuse themselves through animal membranes. -Even the salts with lime, magnesia, alumina, and the heavy metals, are -not quite insoluble. A solution of salt with cantharidin, put in a -dialysing apparatus, separates in twenty-four hours enough cantharidin -to raise a blister. - -Cantharidin has actually been discovered in the heart, brain, muscles, -contents of the stomach, intestines, and faeces (as well as in the blood -and urine) of animals poisoned by the substance. A urine containing -cantharidin is alkaline and albuminous. Cantharidin, although readily -decomposed by chemical agents, is so permanent in the body that it has -been detected in the corpse of a cat eighty-four days after death. - -In any forensic case, the defence will not improbably be set up that -some animal (_e.g._, a fowl poisoned by cantharides) has been eaten and -caused the toxic symptoms, for cantharides is an interesting example of -a substance which, as before stated, for certain animals (such as -rabbits, dogs, cats, and ducks), is a strong poison, whilst in others -(_e.g._, hedgehogs, fowls, turkeys, and frogs), although absorbed and -excreted, it appears inert. Experiment has shown that a cat may be -readily poisoned by a fowl saturated with cantharides; and in Algeria -the military surgeons meet with cystitis among the soldiers, caused by -eating frogs in the months of May and June, the frogs living in these -months almost exclusively on a species of cantharides. - -Dragendorff recommends the following process:--The finely-pulped -substance is boiled in a porcelain dish with potash-lye (1 part of -potash and 12 to 18 of water) until the fluid is of a uniform -consistence. The fluid, after cooling, is (if necessary) diluted with an -equal bulk of water, for it must not be too thick; then shaken with -chloroform in order to remove impurities; and after separation of the -chloroform, strongly acidified with sulphuric acid, and mixed with about -four times its volume of alcohol of 90 to 95 per cent. The mixture is -kept for some time at a boiling temperature, filtered hot, and the -alcohol distilled from the filtrate. The watery fluid is now again -treated with chloroform, as above described. The chloroform extract is -washed with water, the residue taken up on some hot almond oil, and its -blistering properties investigated. The mass, heated with potash in the -above way, can also be submitted to dialysis, the diffusate -supersaturated with sulphuric acid, and shaken up with chloroform. - -In order to test further for cantharidin, it can be dissolved in the -least possible potash or soda-lye. The solution, on evaporation in the -water-bath, leaves crystals of a salt not easily soluble in alcohol, and -the watery solution of which gives with chloride of calcium and baryta a -white precipitate; with sulphate of copper and sulphate of protoxide of -nickel, a green; with cobaltous sulphate, a red; with sugar of lead, -mercury chloride and argentic nitrate, a white crystalline precipitate. -With palladium chloride there occurs a yellow, hair-like, crystalline -precipitate; later crystals, which are isomorphous with the nickel and -copper salts. - -If the tincture of cantharides has been used in considerable quantity, -the urine may be examined; in such a case there will collect on the -surface drops of a green oil, which may be extracted by petroleum ether; -this oil is not blister-raising. Cantharides in powder may, of course, -be detected by its appearance. - -To the question whether the method proposed would extract any other -blister-producing substance, the answer is negative, since ethereal oil -of mustard would be decomposed, and the active constituents of the -_Euphorbias_ do not withstand the treatment with KHO. Oils of anemone -and anemonin are dissolved by KHO, and again separated out of their -solutions, but their blistering property is destroyed. They are -volatile, and found in anemone and some of the _Ranunculaceae_. In the -_Aqua pulsatilla_ there is an oil of anemone, which may be obtained by -shaking with ether; but this oil is not permanent, and if the _Aqua -pulsatilla_ stand for a little time, it splits up into anemonic acid and -anemonin, and then cannot be reobtained. A blistering substance, -obtained from the _Anacardia orientalia_ and the fruit of the -_Anacardium occidentale_ and _Semecarpus anacardium_, is not quite -destroyed by a short action with potash, but is by one of long duration; -this substance, however, cannot be confused with cantharidin, for it is -oily, yellow, easily soluble in alcohol and ether, and differs in other -respects. - - -V.--Snake Poison. - -Sec. 639. The poisonous snakes belong chiefly to two classes, the -_Proteroglypha_ and the _Solenoglypha_. - -Weir Mitchell and Ed. T. Reichert[644] have made some important -experiments on snake poison, using the venom of some 200 snakes. Most of -the snakes were rattlesnakes, a few were cobras and other species. They -came to the conclusion that the active constituents are contained in the -fluid part alone, the solid particles suspended in the fluid having no -action. The poison they considered to consist of two toxalbumins, one a -globulin, acting more particularly on the blood, the other, a peptone -(albumose?), acting more particularly on the tissues. Differences in -snake venom depend on the relative proportions of these two substances. -The peptone, which acts more especially locally on the tissues, -determines an inflammatory action, with much swelling and multiple -extravasation of blood, which may proceed to a moist gangrene. The -globulin has a paralysing influence on the heart, the vasomotor centres, -the peripheral ends of the splanchnic nerves, as well as on the -respiratory centres of both warm and cold-blooded animals. -Feoktisow's[645] researches show that although the heart continues to -beat after the respiration has ceased for a few minutes, it has no -force. The blood pressure sinks immediately after the injection. Whether -the globulin is injected subcutaneously or direct into the veins, there -is commonly considerable extravasation of blood in the chest and -abdomen; the intestine is often filled with blood as well as the -pericardium; and the urine is bloody. The poison of _Vipera ammodytes_ -in watery solution may be boiled for six minutes, and yet is as active -as before. According to Lewin, snake poison generally can be heated to -125 deg. and yet preserve its poisonous properties. These last observations -are not in accordance with the belief of some that the active principle -of snake venom is a ferment, or, indeed, in harmony with the idea that -it is a globulin or toxalbumin; for such bodies have not, so far as we -know, the stability to withstand so high a degree of heat. - -[644] _Smithsonian Contributions to Knowledge_, Washington, 1886. - -[645] _Exp. Unters. ueber Schlangengift. Inaug. Diss._, Dorpat, 1888. - -Sec. 640. =The Poison of the Cobra.=--The poison excreted from the salivary -glands of the cobra di capello is the most deadly animal fluid known. -When first ejected, it is an amber-coloured, rather syrupy, frothy -liquid, of specific gravity 1.046, and of feeble acid reaction; it dries -rapidly on exposure to air to a yellow film, which readily breaks up -into brilliant yellow granules, closely imitating crystals. The yellow -powder is very acrid and pungent to the nostrils, and excites a painful -(though transitory) inflammation, if applied to the mucous membrane of -the eye; the taste is bitter, and it raises little blisters on the -tongue. It is perfectly stable, and preserves its activity for an -indefinite time. The dried poison as described is perfectly soluble in -water, and if the water is added in proper proportions, the original -fluid is without doubt reproduced, the solution usually depositing a -sediment of epithelial _debris_, and often containing little white -threads. - -The poison has been examined by several chemists, but until of late -years with a negative result. The writer was the first to isolate, in -1876, a crystalline principle, which appears to be the sole acting -ingredient; the yellow granules were dissolved in water, the albumen -which the venom so copiously contains coagulated by alcohol, and -separated by filtration; the alcohol was then driven off at a gentle -heat, the liquid concentrated to a small bulk, and precipitated with -basic acetate of lead. The precipitate was separated, washed, and -decomposed in the usual way by SH_{2}, and on removing the lead -sulphide, crystals having toxic properties were obtained. - -Pedler,[646] precipitating the albumen by alcohol, and then to the -alcoholic solution adding platinic chloride, obtained a semi-crystalline -precipitate, which from an imperfect combustion he thinks may have -something like the composition PtCl_{4}(C_{17}H_{25}N_{4}O_{7}HCl)_{2}. -I have examined the platinum compound, and made several combustions of -different fractions, but was unable to obtain the compound in a -sufficient state of purity to deduce a formula. My analysis agreed with -those of Pedler for nitrogen--viz., 9.93 per cent. (Pedler, 9.69); -hydrogen 4.17 (Pedler, 4.28); but were higher for carbon, 41.8 per cent. -(Pedler, 33.42 per cent.); one fraction gave 7.3 per cent. of platinum, -another double that amount. Material was insufficient to thoroughly -investigate the compound, but it was evident that several double salts -were formed. The blood of the cobra is also poisonous. A. Calmette[647] -has found that 2 c.c. of fresh cobra blood, injected into the peritoneum -of a rabbit weighing 1.5 kilo., causes death in six hours; the same -dose of the defibrinated blood injected into the veins is fatal in three -minutes. - -[646] _Proc. Roy. Soc._, vol. xxvii. p. 17. - -[647] _Compt. Rend., Soc. de Biol._, 1894. - -Sec. 641. =Fatal Dose.=--From my experiments on cats, rabbits, and birds, -it seems probable that the least fatal dose for cats and rabbits, lies -between .7 and .9 mgrm. per kilo., and for birds somewhere about .7 -mgrm. per kilo. of the dried poison; the venom contains about 60 per -cent. of albuminous matter, and about 10 per cent. of poisonous -substance; therefore, the lethal power is represented by something like -.07 to .09 mgrm. per kilo., if the pure toxic principle free from -albumen and diluting impurities be considered. - -Sec. 642. =Effects on Animals.=--Almost immediately local pain or signs of -uneasiness at the seat of injection are observed. There is then a -variable interval, seldom exceeding 20 minutes (and generally much -less), but in one of my experiments half an hour elapsed after the -injection of a fatal dose before any effect was evident. The symptoms -once produced, the course is rapid, and consists, first, of acceleration -of the respirations, and then a progressive slowing, soon followed by -convulsions. The convulsions are probably produced by the interference -with the respiration and the deficient oxidation of the blood, and are -therefore, the so-called "carbonic acid convulsions." There is paresis -or paralysis of the limbs. Death seems to occur from asphyxia, and the -heart beats for one or more minutes after the respirations have ceased. -If the dose is so small as not to produce death, no after-effects have -been observed; recovery is complete. - -Sir J. Fayrer, and Dr. Lauder Brunton consider that the terminations of -the motor nerves suffer; on the other hand, Dr. Wall would explain the -phenomena by referring the action entirely to the central nervous -system, and concludes that the effects of the cobra poison consist in -the extinction of function extending from below upwards of the various -nerve centres constituting the cerebro-spinal system. In addition to -this, there is a special and rapid action on the respiratory and allied -nuclei, and this it is that causes death. - -Sec. 643. =Effects on Man.=--By far the best account hitherto published of -the effects of the cobra poison is a paper by Dr. Wall,[648] in which he -points out the very close similarity between the symptoms produced and -those of glosso-pharyngeal paralysis. This is well shown in the -following typical case:--A coolie was bitten on the shoulder about -twelve at midnight by a cobra; he immediately felt burning pain at the -spot bitten, which increased. In fifteen minutes afterwards he began, he -said, to feel intoxicated, but he seemed rational, and answered -questions intelligently. The pupils were natural, and the pulse normal; -the respirations were also not accelerated. He next began to lose power -over his legs, and staggered. In thirty minutes after the bite his lower -jaw began to fall, and frothy viscid mucous saliva ran from his mouth; -he spoke indistinctly, like a man under the influence of liquor, and the -paralysis of the legs increased. Forty minutes after the bite, he began -to moan and shake his head from side to side, and the pulse and -respirations were somewhat accelerated; but he was still able to answer -questions, and seemed conscious. There was no paralysis of the arms. The -breathing became slower and slower, and at length ceased one hour and -ten minutes after the bite, the heart beating for about one minute after -the respiration had stopped. - -[648] "On the Difference of the Physiological Effects Produced by the -Poison of Indian Venomous Snakes," by A. T. Wall, M.D., _Proc. Roy. -Soc._, 1881, vol. xxxii. p. 333. - -There is often very little sign of external injury, merely a scratch or -puncture being apparent, but the areolar tissue lying beneath is of a -purple colour, and infiltrated with a large quantity of coagulable, -purple, blood-like fluid. In addition, the whole of the neighbouring -vessels are intensely injected, the injection gradually diminishing as -the site of the poisoned part is receded from, so that a bright scarlet -ring surrounds a purple area, and this in its turn fades into the normal -colour of the neighbouring tissues. At the margin is also a purple -blood-like fluid, replaced by a pinkish serum, which may often be traced -up in the tissues surrounding the vessels that convey the poison to the -system, and may extend a considerable distance. These appearances are to -be accounted for in great part by the irritant properties of the cobra -venom. The local hyperaemia and the local pain are the first symptoms. In -man there follows an interval (which may be so short as a few minutes, -or so long as four hours) before any fresh symptoms appear; the average -duration of the interval is, according to Dr. Wall, about an hour. When -once the symptoms are developed, then the course is rapid, and, as in -the case quoted, a feeling like that of intoxication is first produced, -and then loss of power over the legs. This is followed by a loss of -power over the speech, over swallowing, and the movement of the lips; -the tongue becomes motionless, and hangs out of the mouth; the saliva is -secreted in large quantities, and runs down the face, the patient being -equally unable to swallow it or to eject it, and the glosso-pharyngeal -paralysis is complete. - -Sec. 644. =Antidotes and Treatment.=--Professor Halford some years ago -proposed ammonia, and M. Lacerda in recent times has declared potassic -permanganate an antidote to the cobra poison. The ammonia theory has -been long disproved, and before Lacerda had made his experiments I had -published the chemical aspect of some researches,[649] which showed that -mixing the cobra venom with an alkaline solution of potassic -permanganate destroyed its poisonous properties. Other experiments were -also made in every conceivable way with potassic permanganate, injecting -it separately, yet simultaneously, into different parts of the same -animal's body, but so long as it does not come into actual contact with -the poison it has no antidotal power whatever over the living subject. -Other observers, previous to the researches mentioned and since, all -agree that permanganate is no true antidote.[650] It only acts when it -comes directly into contact with the venom, but when the venom is once -absorbed into the circulation potassic permanganate, whether acid, -alkaline, or neutral, is powerless. That it is of great use when applied -to a bite is unquestionable, for it neutralises or changes any of the -venom hanging about the wound, and which, if allowed to remain, might -yet be absorbed; but here it is obvious that the venom is, so to speak, -outside the body. A. Galmette (_Annales de l'Institut Pasteur_, 25th -March 1892) has found that gold chloride forms an insoluble compound -with the cobra poison, which is not poisonous, and that animal living -tissues impregnated with gold chloride will not absorb the poison. He -even advances some evidence tending to show that gold chloride may -overtake, as it were, the venom in the circulation, and thus act as a -true antidote. This is improbable, and, until confirmed, the general -treatment most likely to be successful is the immediate sucking of the -wound, followed by the application of an alkaline solution of -permanganate; and lastly, if the symptoms should nevertheless develop, -an attempt should be made to maintain the breathing by galvanism and -artificial respiration.[651] - -[649] _Analyst_, Feb. 28, 1877. - -[650] See Note on the effect of various substances in destroying the -activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer, -_Proc. Roy. Soc._, vol. xxvii. p. 17. - -[651] Some of my experiments on the cobra poison may be briefly -detailed, illustrating the general statement in the text:-- - -1. A quantity equal to 1 mgrm. of the dried venom was injected -subcutaneously into a chicken. The symptoms began in two minutes with -loss of power over both legs. In eight minutes the legs were perfectly -paralysed. There were convulsive movements of the head and wings, -slowing of the respiration, and death in ten minutes. The same quantity -of poison was treated with a little tannin, and the clear liquid which -separated from the precipitate injected into another chicken. The -respiration became affected in ten minutes; in eighteen minutes the bird -had become very quiet, and lay insensible; in twenty minutes it was -dead, the respiration ceasing before the heart. - -2. In seven experiments with cobra poison, first rendered feebly -alkaline with an alkaline solution of potassic permanganate, no effect -followed. Three of the experiments were on chickens, four on rabbits. - -3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and -in the other simultaneously with a solution of potassic permanganate. -Death followed in sixteen minutes. Another chicken was treated in the -same way, but with injections of potassic permanganate solution every -few minutes. Death resulted in thirty-seven minutes. Four other similar -experiments were made--two with feebly alkaline permanganate, two with -permanganate made feebly acid with sulphuric acid--but death occurred -with the usual symptoms. - -4. Cobra poison was mixed with a weak solution of iodine, and a quantity -equal to half a mgrm. was injected into a chicken. The symptoms began -directly, were fully developed in ten minutes, and death took place in -twenty-one minutes. - -5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity -equivalent to 1 mgrm. of the cobra poison injected. The symptoms were -immediate paralysis and insensibility, and the respiration rapidly fell. -Death occurred in four minutes without convulsions. - -6. The cobra venom was mixed with a feebly alkaline solution of -pyrogallic acid, and injected subcutaneously into a chicken. In six -minutes the usual symptoms commenced, followed in thirteen minutes by -death. - -7. One mgrm. was injected into a chicken. The respirations at the -commencement were 120; in twenty-two minutes they sank to 96, in -twenty-five minutes to 84, in twenty-seven minutes to 18, and then to -occasional gasps, with slight movement of the wings and toes. There was -death in thirty-two minutes after the injection. - -8. A young rabbit was injected with .5 mg. (equal to 1 mgrm. per kilo.) -of cobra poison. In two hours it was apparently moribund, with -occasional short gasps. Artificial respiration was now attempted. There -was considerable improvement, but it was intermitted during the night, -and the animal was found dead in the morning, having certainly lived six -hours. - -9. A strong healthy kitten was injected with 1 mgrm. of cobra venom -(equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well -developed, and in an hour the animal was gasping--about twelve short -respirations per minute. Artificial respiration was kept up for two -hours, and the animal recovered, but there was great muscular weakness -lasting for more than twenty-four hours. - -10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms. -(6 per kilo.) of the cobra poison. The symptoms developed within ten -minutes; ammonia was injected, and also given by the nostril. The -heart's action, which, previous to the administration of the ammonia, -had been beating feebly, became accelerated, but death followed within -the hour, the heart beating two minutes after the respiration had -ceased. - -11. A brown rabbit, about 2 kilos. in weight, was injected with 1.5 -mgrms. of cobra poison (.75 per kilo.). There were no symptoms for -nearly an hour, then sudden convulsions, and death. - -12. Another rabbit of the same size was treated similarly, but -immediately after the injection made to breathe nitrous oxide; death -took place in thirty minutes. A rabbit, a little over 2 kilos. in -weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10 -mgrms. of monobromated camphor were administered. In fifteen minutes -there was general paralysis of the limbs, from which in a few minutes -the animal seemed to recover; thirty minutes after the injection there -were no very evident symptoms, but within forty minutes there was a -sudden accession of convulsions, and death. Experiments were also made -with chloroform, morphine, and many other substances, but none seemed to -exercise any true antidotal effect. - -Sec. 645. =Detection of the Cobra Venom.=--In an experiment on a rabbit, -the animal was killed by the subcutaneous injection of 8 mgrms. per -kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood -were injected into a small rabbit; in fifteen minutes there was slow -respiration with pains in the limbs; in thirty minutes this had, in a -great measure, passed off, and in a little time the animal was well. In -any case in which it is necessary to attempt to separate the cobra -venom, the most likely method of succeeding would be to make a cold -alcoholic extract, evaporate in a vacuum, take up the residue in a -little water, and test its effect on small animals. - -Sec. 646. =Duboia Russellii.=--The _Duboia russellii_ or _Russell's viper_ -is one of the best known and most deadly of the Indian vipers. The -effects of the poison of this viper are altogether different from those -of the cobra. The action commences by violent general convulsions, which -are often at once fatal, or may be followed by rapid paralysis and -death; or these symptoms, again, may be recovered from, and death follow -at a later period. The convulsions do not depend on asphyxia, and with a -small dose may be absent. The paralysis is general, and may precede for -some time the extinction of the respiration, the pupils are widely -dilated, there are bloody discharges, and the urine is albuminous. -Should the victim survive the first effects, then blood-poisoning may -follow, and a dangerous illness result, often attended with copious -haemorrhages. A striking example of this course is recorded in the -_Indian Med. Gaz._, June 1, 1872. - -A Mahommedan, aged 40, was bitten on the finger by Russell's viper; the -bitten part was soon after excised, and stimulants given. The hand and -arm became much swollen, and on the same day he passed blood by the -rectum, and also bloody urine. The next day he was sick, and still -passing blood from all the channels; in this state he remained eight -days, losing blood constantly, and died on the ninth day. Nothing -definite is known of the chemical composition of the poison; it is -probably qualitatively identical with "viperin." - -Sec. 647. =The Poison of the Common Viper.=--The common viper still abounds -in certain parts of Great Britain, as, for example, on Dartmoor. The -venom was analysed in a partial manner by Valentin. In 1843 Prince -Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and -transparent, which he called _echidnin_ or _viperin_; it was a neutral -nitrogenous body without taste, it arrested the coagulation of the -blood, and, injected into animals, produced all the effects of the bite -of the viper. Phisalix and G. Bertrand have studied the symptoms -produced in small animals after injection. A guinea-pig, weighing 500 -grms., was killed by 0.3 grm. of the dried venom dissolved in 5000 parts -of saline water; the symptoms were nausea, quickly passing into stupor. -The temperature of the body fell. The autopsy showed the left auricle -full of blood, the intestine, lungs, liver, and kidneys injected. The -blood of the viper is also poisonous, and produces the same symptoms as -the venom.[652] The same observers have shown (_Compt. rend._, cxviii., -Jan. 1894) that the blood of the water-snake (_Tropidonotus natrix_) and -of the Thuringian adder (_Tropidonotus viperinus_) is poisonous, -producing the same symptoms as that of the viper. - -[652] _Compt. rend. Soc. de Biol._, t. v. 997. - -=The Venom of Naja Haje= (=Cleopatra's Asp=).--It has been stated that -20,000 persons annually die in Ceylon from the bite of Cleopatra's asp. -Graziani (_Rif. Med._, October 7, 1893) has undertaken a physiological -study of the venom, which has already received attention at the hands of -Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The -venom, when dried, appears as transparent scales, easily soluble in -water, very slightly so in alcohol, ether, or chloroform; its aqueous -solution has an unpleasant odour, and is neutral to test paper. -Chemically it gives all the tests described by Weir Mitchell and others -as characteristic of the venom of _Naja tripudians_. The physiological -effects of this dried venom were tried on guinea-pigs, rabbits, and -frogs, to all of which it proved fatal in extremely minute doses. The -guinea-pig, a few seconds after injection, becomes paralysed in its hind -limbs, it foams at the mouth, and makes violent attempts at vomiting. -The eyes are half closed, but occasionally for short periods there is a -partial disappearance of the paralysis, and the animal makes feeble -attempts to support itself. Respiratory embarrassment is soon added to -the foregoing symptoms, and the animal lies perfectly prone, devoting -all its attention to breathing, which is rendered still more difficult -by the vomiting and frothy saliva which is secreted in abundance. -Finally death ensues from asphyxia. The _post-mortem_ examination -reveals the heart still feebly beating, the lungs pallid, and the blood -in the organs very dark. The liver and kidneys are hyperaemic, but the -brain and cord, with their coverings, are anaemic. In the rabbit the -course of the poisoning is practically identical with that described -above. Histologically, the following facts are made out in addition to -the foregoing. The red blood-corpuscles are in great measure broken -down, and there are also effusions into the muscular tissues. The -kidneys are very hyperaemic, and there is marked degeneration of the -epithelium lining the glomeruli and convoluted tubules. The glomerular -capsules are much distended, and numerous leucocytes are discernible -throughout the organ. The liver, also, is hyperaemic, and shows numerous -broken-down blood-corpuscles, and partial necrosis of many of the liver -cells. Examination of the central nervous system reveals no particular -changes. - - -DIVISION II.--PTOMAINES--TOXINES. - -Sec. 648. =Definition of a Ptomaine.=--A ptomaine may be considered as a -basic chemical substance derived from the action of bacteria on -nitrogenous substances. If this definition is accepted, a ptomaine is -not necessarily formed in the dead animal tissue; it may be produced by -the living, and, in all cases, it is the product of bacterial life. A -ptomaine is not necessarily poisonous; many are known which are, in -moderate doses, quite innocuous. - -When Selmi's researches were first published there was some anxiety lest -the existence of ptomaines would seriously interfere with the detection -of poison generally, because some were said to be like strychnine, -others like colchicine, and so forth. Farther research has conclusively -shown that at present no ptomaine is known which so closely resembles a -vegetable poison as to be likely in skilled hands to cause confusion. - - -Isolation of Ptomaines. - -Sec. 649. =Gautier's[653] Process.=--The liquid is acidified with oxalic -acid, warmed, filtered, and distilled in a vacuum. - -[653] _Ptomaines et Leucomaines_, E. J. A. Gautier, Paris, 1886. - -In this way pyrrol, skatol, phenol, indol, and volatile fatty acids are -separated and will be found in the distillate. The residue in the retort -is treated with lime, filtered from the precipitate that forms, and -distilled in a vacuum, the distillate being received in weak sulphuric -acid. The bases accompanied with ammonia distil over. The distillate is -now neutralised by sulphuric acid[654] and evaporated nearly to dryness, -separating the mother liquid from sulphate of ammonia, which -crystallises out. The mother liquids are treated with absolute alcohol, -which dissolves the sulphates of the ptomaines. The alcohol is got rid -of by evaporation, the residue treated with caustic soda, and the bases -shaken out by successive treatment with ether, petroleum ether, and -chloroform. The residue remaining in the retort with the excess of lime -is dried, powdered, and exhausted with ether; the ethereal extract is -separated, evaporated to dryness, the dry residue taken up in a little -water, slightly acidulated, and the bases precipitated by an alkali. - -[654] The first acid apparently is so dilute that the distillate more -than neutralises it, hence more sulphuric acid is added to complete -neutralisation. - -Sec. 650. =Brieger's Process.=--Brieger[655] thus describes his process:-- - -[655] _Untersuchungen ueber Ptomaine_, Theil iii., Berlin, 1886. - -"The matters are finely divided and boiled with water feebly acidulated -with hydrochloric acid. - -"Care must be taken that on boiling, the weak acid reaction must be -retained, and that this manipulation only lasts a few minutes. - -[Illustration] - -"The insoluble portion is filtered off, and the filtrate evaporated, -either in the gas-oven or on the water-bath, to syrupy consistency. If -the substances are offensive, as alcoholic and watery extracts of flesh -usually are, the use of Bocklisch's simple apparatus (see diagram) is to -be recommended. The filtrate to be evaporated is placed in a flask -provided with a doubly perforated caoutchouc cork carrying two bent -tubes; the tube _b_ terminates near the bottom of the flask, while the -tube _a_ terminates a little above the level of the fluid to be -evaporated. The tube _a_ is connected with a water pump which sucks away -the escaping steam. In order to avoid the running back of the condensed -water forming in the cooler part of the tube, the end of the tube _a_ is -twisted into a circular form. Through the tube _b_, which has a fine -capillary bore, a stream of air is allowed to enter, which keeps the -fluid in constant agitation, continually destroying the scum on the -surface, and avoiding sediments collecting at the bottom, which may -cause fracture of the flask. According to the regulation of the air -current, a greater or smaller vacuum can be produced. The fluid, -evaporated to the consistency of a syrup, is treated with 96 per cent. -alcohol, filtered, and the filtrate precipitated with lead acetate. - -"The lead precipitate is filtered off, the filtrate evaporated to a -syrup, and the syrup again treated with 96 per cent. alcohol. This is -again filtered, the alcohol got rid of by evaporation, water added, the -lead thrown down by SH_{2}, and the fluid, after the addition of a -little hydrochloric acid, evaporated to the consistence of a syrup; this -syrup is exhausted with 96 per cent. alcohol, and precipitated with an -alcoholic solution of mercury chloride. The mercury precipitate is -boiled with water, and by the different solubility of the mercury salts -of certain ptomaines some separation takes place. If it is suspected -that some of the ptomaines may have been separated with the lead -precipitate, this lead precipitate can be decomposed by SH_{2} and -investigated. I have only (says Brieger) in the case of mussels been -able to extract from the lead precipitate small quantities of ptomaines. - -"The mercury filtrate is freed from mercury and evaporated, the excess -of hydrochloric acid being carefully neutralised by means of soda (for -it must only be slightly acid); then it is again treated with alcohol, -so as to separate as much as possible the inorganic constituents. The -alcoholic extract is evaporated, dissolved in a little water, -neutralised with soda, acidulated with nitric acid, and precipitated -with phospho-molybdic acid. The phospho-molybdic acid precipitate is -decomposed with neutral lead acetate, which process may be facilitated -by heating on the water-bath. After getting rid of the lead by treatment -with SH_{2}, the fluid is evaporated to a syrup and alcohol added, by -which process many ptomaines may be eliminated as hydrochlorates; or -they can be converted into double salts (of platinum or gold) for the -purpose of separation. In the filtrate from phospho-molybdate, ptomaines -may also be found by treating with lead acetate to get rid of the -phospho-molybdic acid, and then adding certain reactives. Since it is -but seldom that the hydrochlorates are obtained in a state of purity, it -is preferable to convert the substance separated into a gold or platinum -salt or a picrate, since the greater or less solubility of these -compounds facilitates the purification of individual members; but which -reagent is best to add, must be learned from experience. The -melting-point of these salts must always be taken, so that an idea of -their purity may be obtained. It is also to be noted that many gold -salts decompose on warming the aqueous solution; this may be avoided by -the addition of hydrochloric acid. The hydrochlorates of the ptomaines -are obtained by decomposing the mercury, gold, or platinum combinations -by the aid of SH_{2}, while the picrates can be treated with -hydrochloric acid and shaken up with ether, which latter solvent -dissolves the picric acid. - -"Considerable difficulty in the purification of the ptomaines is caused -by a nitrogenous, amorphous, non-poisonous, albumin-like substance, -which passes into all solutions, and can only be got rid of by careful -precipitation with an alcoholic solution of lead acetate, in which it is -soluble in excess. This albuminoid forms an amorphous compound with -platinum, and acts as a strongly reducing agent (the platinum compound -contains 29 per cent. platinum). When this albuminoid is eliminated, -then the hydrochlorates or the double salts of the ptomaines -crystallise." - -Sec. 651. =The Benzoyl Chloride Method.=--The fatty diamines in dilute -aqueous solutions, shaken with benzoyl chloride and soda, are converted -into insoluble dibenzoyl derivatives; these may be separated from -benzamide and other nitrogenous products by dissolving the precipitate -in alcohol, and pouring the solution into a large quantity of -water.[656] Compounds which contain two amido groups combined with one -and the same carbon atom, do not yield benzoyl derivatives when shaken -with benzoyl chloride and soda. Hence this reaction can be utilised for -certain of the ptomaines only. The solution must be dilute, because -concentrated solutions of creatine, creatinine, and similar bodies also -give precipitates with benzoyl chloride; no separation, however, occurs -unless these bodies are in the proportion of five per thousand. - -[656] L. V. Udransky and Baumann, _Ber._, xxi. 2744. - -The process is specially applicable for the separation of -ethylenediamine, pentamethylenediamine (cadaverine), and -tetramethylenediamine (putrescine) from urine. In a case of -cystinuria Udransky and E. Baumann[657] have found 0.24 grm. of -benzoyltetramethylenediamine, 0.42 grm. of benzoylpentamethylenediamine -in a day. Diamines are absent in normal faeces and urine. Stadthagen and -Brieger[658] have also found, in a case of cystinuria diamines, chiefly -pentamethylenediamine. - -[657] L. V. Udransky and Baumann, _Zeit. f. physiol. Chem._, xiii. 562. - -[658] _Arch. pathol. Anatom._, cxv. p. 3. - -The operation is performed by making the liquid alkaline with soda, so -that the alkalinity is equal to about 10 per cent., adding benzoyl -chloride, shaking until the odour of benzoyl chloride disappears, and -then filtering; to the filtrate more benzoyl chloride is added, the -liquid shaken, and, if a precipitate appears, this is also filtered off, -and the process repeated until all diamines are separated. - -The precipitate thus obtained is dissolved in alcohol, and the alcoholic -solution poured into a considerable volume of water and allowed to stand -over night; the dibenzoyl compound is then usually found to be in a -crystalline condition. The compound is crystallised once or twice from -alcohol or ether, and its melting-point and properties studied. Mixtures -of diamines may be separated by their different solubilities in ether -and alcohol. - -A solution of 0.00788 grm. of pentamethylenediamine in 100 c.c. of water -gave 0.0218 grm. of the dibenzoyl-derivative when shaken with benzoyl -chloride (5 c.c.) and 40 c.c. of soda (10 per cent.) and kept for -twenty-four hours. In a second experiment with a similar solution only -0.0142 grm. of dibenzoyl-derivative was obtained;[659] hence the process -is not a good quantitative process, and, although convenient for -isolation, gives, so far as the total amount recovered is concerned, -varying results. - -[659] _Ber._, xxi. 2744. - -Sec. 652. =The Amines.=--The amines are bases originating from ammonia and -built on the same type. Those that are interesting as poisons are -monamines, diamines, and the quaternary ammonium bases. - -Considered as compound ammonias, the amines are divided into primary or -amide bases, secondary or imid bases, and tertiary or nitrile bases, -according as to whether one, two, or three atoms of hydrogen have been -displaced from the ammonia molecule by an alkyl; for instance, -methylamine NH_{2}CH_{3} is a primary or amide base, because only one of -the three atoms of H in NH_{3} has been replaced by methyl; similarly, -dimethylamine is a secondary or imid base, and trimethylamine is a -tertiary or nitrile base. - -The quaternary bases are derived from the hypothetical ammonium -hydroxide NH_{4}OH, as, for example, tetraethyl ammonium hydroxide -(C_{2}H_{5})_{4}N,OH. - -The diamines are derived from two molecules of NH, and therefore -contain, instead of one molecule of nitrogen, two molecules of nitrogen; -in two molecules of ammonia there are six atoms of hydrogen, two, four, -or six of which may be replaced by alkyls; as, for example, - - C_{2}H_{4} - / \ - / \ - N------HH------N - \ / - \ / - ----HH---- - - Ethylenediamine. - - C_{2}H_{4} - / \ - / \ - N--C_{2}H_{4}--N - \ / - \ / - ----HH---- - - Diethylenediamine. - - C_{2}H_{4} - / \ - / \ - N--C_{2}H_{4}--N - \ / - \ / - C_{2}H_{4} - - Triethylenediamine. - -The monamines are similar to ammonia in their reactions; some of them -are stronger bases; for instance, ethylamine expels ammonia from its -salts. The first members of the series are combustible gases of pungent -odour, and easily soluble in water; the higher homologues are fluids; -and the still higher members solids. - -The hydrochlorides are soluble in absolute alcohol, while chloride of -ammonium is insoluble; this property is taken advantage of for -separating amines from ammonia. The amines form double salts with -platinic chloride; this is also utilised for recognition, for the -purpose of separation, and for purification; for instance, -ammonium-platinum-chloride on ignition yields 43.99 per cent. of -platinum, and methylamine-platinum-chloride yields 47.4 of platinum. It -is comparatively easy to ascertain whether an amine is primary, -secondary, or tertiary. - -The primary and secondary amines react with nitrous acid, but not the -tertiary; the primary amines, for instance, are converted into alcohols, -and there is an evolution of nitrogen gas; thus methylamine is -decomposed into methyl alcohol, nitrogen, and water. - - CH_{3}NH_{2} + (OH)NO = CH_{3}(OH) + N_{2} + H_{2}O. - -The secondary amines, treated in the same way, evolve no nitrogen, but -are converted into nitrosamines; thus dimethylamine, when treated with -nitrous acid, yields nitrosodimethylamine, - - (CH_{3})_{2}NH + (OH)NO = (CH_{3})_{2}(NO)N + H_{2}O; - -and the nitrosamines respond to the test known as Lieberman's -nitroso-reaction, which is thus performed:--The substance is dissolved -in phenol and a few drops of concentrated sulphuric acid added. The -yellow colour at first produced changes into blue by adding to the acid -liquid a solution of potash. - -The primary amines, and the primary amines alone, treated with -chloroform and alcoholic potash, yield the peculiarly offensive smelling -carbylamine or isonitrile (Hofmann's test), - - V - NH_{2}(CH_{3}) + CHCl_{3} + 3KOH = C[=]N-CH_{3} + 3KCl + 3H_{2}O. - -Again the primary bases, when treated with corrosive sublimate and -carbon disulphide, evolve sulphuretted hydrogen, and mustard oil is -produced, _e.g._, - - NH_{2}(C_{2}H_{5}) + CS_{2} = CS=N-C_{2}H_{5} + H_{2}S. - Ethylamine. Ethylmustard - oil. - -Where a sufficient quantity of an amine is obtained, the primary, -secondary, or tertiary character of the amine may be deduced with -certainty by treating it with methyl or ethyl iodide. - -A molecule of the base is digested with a molecule of methyl iodide and -distilled with potash; the distillate is in the same manner again -treated with methyl iodide and again distilled; and the process is -repeated until an ammonium base is obtained, which will take up no more -iodide. If three methyl groups were in this way introduced, the original -substance was primary, if two, secondary, if one, tertiary. - -The quaternary bases, such as tetraethyl ammoniumoxhydrate, decompose, -on heating, into triethylamine and ethylene; the corresponding methyl -compound in like manner yields trimethylamine and methyl-alcohol. - -On the other hand, the primary, secondary, and tertiary bases do not -decompose on heating, but volatilise without decomposition. - -The chief distinctions between these various amines are conveniently put -into a tabular form as follows:-- - - +--------------------+-----------+-----------+-----------+-----------+ - | | Primary, |Secondary, | Tertiary, |Quaternary,| - | | NH_{2}R. | NHR_{2}. | NR_{3}. |NR_{4}(OH).| - +--------------------+-----------+-----------+-----------+-----------+ - |On treating with | 3 | 2 | 1 | ... | - |methyl iodide it | | | | | - |takes up the follow-| | | | | - |ing number of methyl| | | | | - |groups, | | | | | - | | | | | | - |Reaction with |Decomposes |Formation | | | - |nitrous acid, |with evolu-|of nitro- | ... | ... | - | |tion of |samine. | | | - | |nitrogen | | | | - | |gas. | | | | - | | | | | | - |Mustard oil, &c., on|Mustard oil| | | | - |treatment with |formed. | ... | ... | ... | - |CS_{2} and sub- | | | | | - |limate, | | | | | - | | | | | | - |Chloroform and |Formation | ... | ... | ... | - |alcoholic potash, |of carbyl- | | | | - | |amine. | | | | - | | | | | | - |Effect of strong |Sublimes. |Sublimes. |Sublimes. |Decomposes.| - |heat, | | | | | - | | | | | | - |On addition of |Combines to|Combines to|Combines to| ... | - |acids, |form salts.|form salts.|form salts.| | - +--------------------+-----------+-----------+-----------+-----------+ - - Sec. 653. =Methylamine,= CH_{3}NH_{2}.--This is a gas at ordinary - temperatures; it is inflammable, and possesses a strong ammoniacal - odour. It has been found in herring brine, and is present in - cultures of the comma bacillus; it has also been found in poisonous - sausages, but it is not in itself toxic. - - It forms crystalline salts, such as, for example, the hydrochloride, - the platinochloride (Pt = 41.4 per cent.), and the aurochloride (Au - = 53.3 per cent. when anhydrous). The best salt for estimation is - the platinochloride, insoluble in absolute alcohol and ether. - - Sec. 654. =Dimethylamine=, (CH_{3})_{2}NH.--Dimethylamine is also a - gas; it has been found in various putrefying substances. It forms - crystalline salts, such as the hydrochloride, the platinochloride - (Pt = 39.1 per cent.), and an aurochloride (Au = 51.35 per cent.). - It is not poisonous. - - In Brieger's process it may occur in both the mercuric chloride - precipitate and filtrate. From cadaverine it may be separated by - platinum chloride; cadaverine platinochloride is with difficulty - soluble in cold water and crystallises from hot water, while - dimethylamine remains in the mother liquor. From choline it may be - separated by recrystallising the mercuric precipitate from hot - water. From methylamine it may be separated by converting into - chloride and extracting with chloroform; dimethylamine chloride is - soluble, methylamine chloride insoluble in chloroform. - - Sec. 655. =Trimethylamine=, (CH_{3})_{3}N.--Trimethylamine in the free - state is an alkaline liquid with a fishy odour, boiling at 9.3 deg.; it - is not toxic save in large doses. - - It occurs in a great variety of plants, and is also found in - putrefying substances. It is a product of the decomposition of - choline, betaine, and neuridine, when these substances are distilled - with potash. - - In Brieger's process, if an aqueous solution of mercuric chloride is - used as the precipitant, trimethylamine (if present) will be almost - entirely in the filtrate, from which it can be obtained by getting - rid of the mercury by SH_{2}, filtering, evaporating to dryness, - extracting with alcohol, and precipitating the alcoholic solution - with platinic chloride. It forms crystalline salts with hydrochloric - acid, platinum chloride, and gold chloride; the platinum double salt - yields 37 per cent. of platinum, the gold salt 49.4 per cent. gold. - The gold salt is easily soluble, and this property permits its - separation from choline, which forms a compound with gold chloride - soluble with difficulty. - - Sec. 656. =Ethylamine=, C_{2}H_{5}NH_{2}.--Ethylamine is in the free - state an ammoniacal liquid boiling at 18.7 deg. It is a strong base, - miscible with water in every proportion. It has been found in - putrefying yeast, in wheat flour, and in the distillation of beet - sugar residues. It is not poisonous; the hydrochloride forms - deliquescent plates melting at 76 deg.-80 deg.; the platinochloride contains - 39.1 per cent. of platinum, and the gold salt 51.35 per cent. of - gold. In other words, the same percentages as the corresponding - salts of dimethylamine, with which, however, it cannot be confused. - - Sec. 657. =Diethylamine=, (C_{2}H_{5})_{2}NH, is an inflammable liquid - boiling at 57.5 deg.; it forms salts with hydrochloric acid, platinum - and gold, &c.; the gold salt contains 47.71 per cent. of gold, and - its melting-point is about 165 deg. - - Sec. 658. =Triethylamine=, (C_{2}H_{5})_{3}N, is an oily base but - slightly soluble in water, and boiling at 89 deg.-89.5 deg. It gives no - precipitate with mercuric chloride in aqueous solution; it forms a - platinochloride containing 31.8 per cent. of platinum. It has been - found in putrid fish. - - Sec. 659. =Propylamine.=--There are two propylamines; one, normal - propylamine, CH_{3}CH_{2}.CH_{2}.NH_{2}, boiling at 47 deg.-48 deg., and - iso-propylamine, (CH_{3})_{2}CH.NH_{2}, boiling at 31.5 deg.; both are - ammoniacal fish-like smelling liquids. The hydrochloride of normal - propylamine melts at 155 deg.-158 deg., and iso-propylamine chloride melts - at 139.5 deg. - - It has been found in cultures of human faeces on gelatin. None of the - above amines are sufficiently active in properties to be poisonous - in the small quantities they are likely to be produced in - decomposing foods. - - Sec. 660. =Iso-amylamine=, (CH_{3})_{2}CH.CH_{2}.CH_{2}.NH_{2}, is a - colourless alkaline liquid, possessing a peculiar odour. It boils at - 97 deg.-98 deg. It forms a deliquescent hydrochloride. The platinochloride - crystallises in golden yellow plates. - - Iso-amylamine occurs in the putrefaction of yeast, and is a normal - constituent of cod-liver oil. It is intensely poisonous, producing - convulsions. - - -Diamines. - -Sec. 661. =Rate of Formation of Diamines.=--Diamines are formed in -putrefactive processes, generally where there is abundance of nitrogen. -Garcia[660] has attempted to trace the rates at which they are formed by -allowing meat extracts to decompose, precipitating by benzoyl chloride -(see p. 487) the dibenzoyl compound, and weighing; the following were -the results obtained:-- - -[660] _Zeit. f. physiol. Chemie_, xvii. 6. 571. - - Time. Weight of benzoyl compound. - 24 hours, 0.56 grm. - 2 days, 0.75 " - 3 days, 0.82 " - 4 days, 0.73 " - 5 days, 0.57 " - 6 days, 0.58 " - - Sec. 662. =Ethylidenediamine.=--Brieger found in putrid haddock, in the - filtrate from the mercury chloride precipitate:--gadinine, - neuridine, a base isomeric with ethylenediamine C_{2}H_{8}N_{2} (but - which Brieger subsequently more or less satisfactorily identified - with ethylidenediamine), muscarine, and triethylamine; these bases - were separated as follows:-- - - The filtrate from the mercury chloride solution was freed from - mercury by SH_{2}, evaporated to a syrup, and then extracted with - alcohol. From the alcoholic solution platinum chloride precipitated - neuridine, this was filtered off, the filtrate freed from alcohol - and platinum, and the aqueous solution concentrated to a small - volume and precipitated with an aqueous solution of platinum - chloride; this precipitated ethylidene platinum chloride. The mother - liquor from this precipitate was concentrated on the water-bath, - and, on cooling, the platinochloride of muscarine crystallised out. - From the mother liquor (freed from the crystals), on standing in a - desiccator, the gadinine double salt crystallised out, and from the - mother liquor (freed from gadinine after removal of the platinum by - SH_{2}) distillation with KHO recovered trimethylamine. - - From the platinochloride of ethylenediamine, the chloride can be - obtained by treating with SH_{2}, filtering, and evaporating; by - distilling the chloride with a caustic alkali, the free base can be - obtained by distillation. - - Ethylidenediamine is isomeric with ethylenediamine, but differs from - it in the following properties:--ethylidenediamine is poisonous, - ethylenediamine is non-poisonous. - - Ethylenediamine forms a platinochloride almost insoluble in hot - water, while the ethylidene salt is more easily soluble. The - properties of the gold salts are similar, ethylenediamine forming a - difficultly soluble gold salt, ethylidene a rather soluble gold - salt. - - Ethylidenediamine forms a hydrochloride, C_{2}H_{8}N_{2}2HCl, - crystallising in long glistening needles, insoluble in absolute - alcohol, rather soluble in water. The hydrochloride gives - precipitates in aqueous solution with phospho-molybdic acid, - phospho-antimonic acid, and potassium bismuth iodide; the latter is - in the form of red plates. - - The platinochloride, C_{2}H_{8}N_{2}2HCl.PtCl (Pt = 41.5 per cent.), - is in the form of yellow plates, not very soluble in cold water. - -Ethylidenediamine, when subcutaneously injected into guinea-pigs, -produces an abundant secretion from the mucous membranes of the nose, -mouth, and eyes. The pupils dilate, and the eyeballs project. There is -acute dyspn[oe]a; death takes place after some twenty-four hours, and -the heart is stopped in diastole. - -Trimethylenediamine is believed to have been isolated by Brieger from -cultivations in beef broth of the comma bacillus. - -It occurs in small quantity in the mercuric chloride precipitate, and is -isolated by decomposing the precipitate with SH_{2}, evaporating the -filtrate from the mercury sulphide to dryness, taking up the residue -with absolute alcohol, and precipitating by an alcoholic solution of -sodium picrate. The precipitate contains the picrate of -trimethylenediamine, mixed with the picrates of cadaverine and -creatinine. Cadaverine picrate is insoluble in boiling absolute alcohol, -the other picrates soluble; so the mixed picrates are boiled with -absolute alcohol, and the insoluble cadaverine filtered off. Next, the -picrates of creatinine and trimethylenediamine are freed from alcohol, -the solution in water acidified with hydrochloric acid, the picric acid -shaken out by treatment with ether, and then the solution precipitated -with platinum chloride; the platinochloride of trimethylenediamine is -not very soluble, while creatinine easily dissolves; so that separation -is by this means fairly easy. - -It also gives a difficultly soluble salt with gold chloride. - -The picrate consists of felted needles, melting-point 198 deg. -Phospho-molybdic acid gives a precipitate crystallising in plates; -potassium bismuth iodide gives dark coloured needles. - -It produces in animals violent convulsions and muscular tremors; but the -substance has hitherto been obtained in too small a quantity to be -certain as to its identification and properties. - -Sec. 663. =Neuridine=, C_{5}H_{14}N_{2}.--Neuridine is a diamine, and is -apparently the most common basic product of putrefaction; it has been -obtained from the putrefaction of gelatin, of horseflesh, of fish, and -from the yelk of eggs. It is usually accompanied by choline, from which -it can be separated by converting the bases into hydrochlorides, choline -hydrochloride being soluble in absolute alcohol, neuridine scarcely so. -Brieger isolated neuridine from putrid flesh by precipitating the watery -extract with mercuric chloride. He decomposed the mercury precipitate -with SH_{2}, and, after having got rid of the sulphide of mercury by -filtration, he concentrated the liquid to a small bulk, when a substance -separated in crystals similar in form to urea; this was purified by -recrystallisation from absolute alcohol, and converted into the platinum -salt. - -Another method which may be used for the separation and purification of -neuridine is to dissolve it in alcohol and precipitate with an alcoholic -solution of picric acid; the picrate may be decomposed by treatment with -dilute mineral acid, and the picric acid removed by shaking with ether. - -The free base has a strong seminal odour. It is gelatinous, and has not -been crystallised. It is insoluble in ether and in absolute alcohol, and -not readily soluble in amyl alcohol. It gives white precipitates with -mercuric chloride, neutral and basic lead acetates. It does not give -Hofmann's isonitrile reaction. When distilled with a fixed alkali, it -yields di- and trimethylamine. - -The hydrochloride, C_{5}H_{14}N_{2}2HCl, crystallises in long needles, -which are insoluble in absolute alcohol, ether, benzol, chloroform, -petroleum ether, and amyl alcohol; but the hydrochloride is very soluble -in water and in dilute alcohol. - -The hydrochloride gives no precipitate with mercuric chloride, -potass-mercuric iodide, potass-cadmium iodide, iodine and iodide of -potassium, tannic acid, ferricyanide of potassium, ferric chloride, and -it does not give any colour with Froehde's reagent. - -On the other hand, phosphotungstic acid, phospho-molybdic acid, picric -acid, potass-bismuth iodide, platinum chloride, and gold chloride all -give precipitates. - -Neuridine hydrochloride is capable of sublimation, and at the same time -it is decomposed, for the sublimed needles show red or blue colours. - -Neuridine platinochloride, C_{5}H_{14}N_{2}2HCl.PtCl_{4}, yields 38.14 -per cent. of platinum; it crystallises in flat needles, soluble in -water, from which it is precipitated on the addition of alcohol. - -The aurochloride has the formula C_{5}H_{14}N_{2}2HCl2AuCl_{3}; it is -rather insoluble in cold water, and crystallises in bunches of yellow -needles. On ignition, it should yield 41.19 per cent. of gold. - -The picrate, C_{5}H_{14}N_{2},2C_{6}H_{2}(NO_{2})_{3}OH, is almost -insoluble in cold water, and crystallises in needles. It is not fusible, -but decomposes at about 230 deg. - -Neuridine is not poisonous. - -Sec. 664. =Cadaverine= (Pentamethylenediamine, C_{5}H_{14}N_{2} = -NH_{2}CH_{2}--CH_{2}--CH_{2}--CH_{2}CH_{2}NH_{2}) is formed in putrid -animal matters, and in cultures of the genus _Vibrio_. It has been found -in the urine and faeces in cases of cystinuria, and Roos[661] has -separated it by the benzoyl-chloride method from the faeces of a patient -suffering from tertian ague. It may be formed synthetically by -dissolving trimethylcyanide in absolute alcohol, and then reducing by -sodium (Mendius' reaction). - -[661] _Zeit. f. physiol. Chemie_, xvi., 1892. - -Cadaverine is a thick, clear, syrupy liquid, with a peculiar coniine- as -well as a semen-like odour. It absorbs eagerly CO_{2} from the air, and -ultimately is converted into a solid crystalline mass. It volatilises -with the steam when boiled with water, and may be distilled in the -presence even of the caustic alkalies and the alkaline earths without -decomposition. It does not give oil of mustard when treated with CS_{2} -and mercuric chloride, nor does it give with chloroform and alcoholic -potash, carbylamine (isonitrile). If dehydrated by KHO, it boils at from -115 deg.-120 deg. (_Brieger_).[662] - -[662] Brieger has also given to the pure base a boiling-point of 175 deg. - -When cadaverine is treated with methyl iodide, two atoms of hydrogen may -be replaced with methyl, forming the base C_{5}H_{12}(CH_{3})_{2}N_{2}; -the platinochloride of this last base crystallises in long red needles. - -Cadaverine forms well-defined crystalline salts as well as compounds -with metals. - -Cadaverine hydrochloride, C_{5}H_{14}N_{2}2HCl, crystallises in needles -which are deliquescent, or it may be obtained from an alcoholic solution -in plates. The crystals are insoluble in absolute alcohol, but readily -soluble in 96 per cent. alcohol. Putrescine hydrochloride, on the other -hand, is with difficulty soluble in alcohol of that strength; hence the -two hydrochlorides can be separated by taking advantage of their -difference in solubility in 96 per cent. alcohol; but the better -method for separation is the benzoyl-chloride process (p. 487). -On dry distillation, cadaverine hydrochloride decomposes into -NH_{3},HCl and piperidine C_{5}H_{11}N. The compound with mercury -chloride--C_{5}H_{14}N_{2}2HCl,4HgCl_{2} (Hg = 63.54 per cent.); -melting-point, 214 deg.-216 deg.--is insoluble in alcohol and in cold water; -this property is also useful to separate it from putrescine, the mercury -compound of which is soluble in cold water. The platinochloride, -C_{5}H_{14}N_{2}2HCl,PtCl_{4} (Pt = 38.08 per cent.), crystallises in -dirty red needles; but, by repeated crystallisation, it may be obtained -in clear chrome yellow, short, octahedral prisms; it is soluble with -difficulty in hot water, insoluble in cold water. The salt decomposes at -235 deg.-236 deg. - -The aurochloride--C_{5}H_{14}N_{2}2HCl2AuCl (Au = 50.41 per cent.), -melting-point 188 deg.--crystallises partly in cubes and partly in needles, -and is easily soluble in water. - -Other salts are the picrate, C_{5}H_{14}N_{2}2C_{6}H_{2}(NO_{2})_{3}OH, -melting-point 221 deg. with decomposition; with difficulty soluble in cold, -but dissolving in hot water, and insoluble in absolute alcohol. There -are also a neutral oxalate, C_{5}H_{14}N_{2},H_{2}C_{2}O_{4} + -2H_{2}O, melting-point 160 deg.; and an acid oxalate, -C_{5}H_{14}N_{2}2H_{2}C_{2}O_{4} + H_{2}O, melting-point 143 deg. with -decomposition; both these oxalates are insoluble in absolute alcohol. - -Cadaverine dibenzoyl--C_{5}H_{10}(NHCOC_{6}H_{5})_{2}, melting-point -129 deg.-130 deg.--crystallises in needles and plates, soluble in alcohol and -slightly soluble in ether, insoluble in water. - -It is not acted on by hot dilute acids or alkalis, and when dissolved in -concentrated hydrochloric acid and alcohol it is, only after prolonged -boiling, decomposed into benzoic acid and the free base. The benzoic -acid after getting rid of the alcohol by evaporation, can be removed by -shaking up with ether; then the hydrochloride can be decomposed by an -alkali and the free base obtained, or the platinum salt of cadaverine -may be formed by precipitation with platinum chloride. Should cadaverine -and putrescine be in the same liquid, the dibenzoyl compounds may be -separated as follows:--the crystalline precipitate is collected on a -filter, washed with water until the filtrate runs clear, and then -dissolved in warm alcohol; this solution is poured into twenty times its -volume of ether and allowed to stand; after a short time crystals form -of the putrescine compound, which are far less soluble in alcohol than -those of cadaverine dibenzoyl; these crystals are filtered off and -repeatedly crystallised from alcohol until the melting-point is about -175 deg.-176 deg. The filtrate contains the cadaverine compound; this latter is -recovered by evaporating off the ether-alcohol. - -Sec. 665. =Putrescine--Tetramethylenediamine=, - - C_{4}H_{12}N_{2}=NH_{2}CH_{2}CH_{2}CH_{2}CH_{2}NH_{2}. - -The free base is a clear liquid, with a semen-like odour, boiling-point -135 deg. It is a common base in putrefying animal substances, and also -occurs in the urine in cases of cystinuria. It can be obtained -synthetically by reducing ethylene cyanide by the action of sodium in -absolute alcohol. - -The best method of separating putrescine is the benzoyl chloride method -already given. - -Putrescine forms crystalline salts, of which the following are the most -important:-- - -Putrescine hydrochloride, C_{4}H_{12}N_{2}2HCl, forms long colourless -needles, insoluble in absolute alcohol, easily soluble in water. - -The platinochloride, C_{4}H_{12}N_{2}2HCl.PtCl_{4} (Pt = 39.2 per -cent.), is with difficulty soluble in cold water. When pure, the salt is -in the form of six-sided plates. - -The aurochloride, C_{4}H_{12}N_{2}2HCl.2AuCl_{3} + 2H_{2}O (Au = 51.3 -per cent.), is insoluble in cold water, in contradistinction to -cadaverine aurochloride, which easily dissolves. - -The picrate, C_{4}H_{12}N_{2}2C_{6}H_{2}(NO_{2})_{3}OH, is a salt of -difficult solubility. It crystallises in yellow plates. It browns at -230 deg., and melts with evolution of gas at 250 deg. - -Dibenzoylputrescine, C_{4}H_{8}(NHCOC_{6}H_{5})_{2}, forms silky plates -or long needles, melting-point 175 deg.-176 deg. By boiling it for twelve -hours with alcohol and strong hydrochloric acid the compound may be -broken up into hydrochloride of putrescine and free benzoic acid. As -stated before, it is less soluble in alcohol than the corresponding -compound of cadaverine. - -Putrescine is not poisonous. On the other hand, by repeated treatment -with methyl iodide, it takes up four methyl radicals, and the -tetramethyl compound, C_{4}H_{8}(CH_{3})_{4}N_{2}, produces symptoms -similar to those of muscarine poisoning. - -Sec. 666. =Metaphenylenediamine=, - - NH_{2}^{1} - / - C_{6}H_{4} , - \ - NH_{2}^{3} - -is a crystalline substance, melting-point 63 deg., boiling-point 276 deg.-277 deg. -The crystals are easily soluble in alcohol or ether, with difficulty in -water. The least trace of nitrous acid strikes a yellow colour from the -formation of triamidobenzol. - -Sec. 667. =Paraphenylenediamine=, - - NH_{2}^{1} - / - C_{6}H_{4} , - \ - NH_{2}^{4} - -is in the form of tabular crystals, melting-point 140 deg., boiling-point -267 deg. If this substance is oxidised with ferric chloride or manganese -binoxide and sulphuric acid, chinone is produced; if treated with SH_{2} -and ferric chloride, a violet sulphur-holding colouring matter, allied -to methylene blue, is formed; these reactions are tests for the presence -of the para-compound. - -Both these diamines are poisonous. Metaphenylenediamine produces, in the -dog, the symptoms of an aggravated influenza with continual sneezing and -hoarse cough, which, if the dose is large enough, ends in coma and -death. Paraphenylenediamine produces exophthalmia, the tissues of the -eye undergoing complete alteration.[663] - -[663] _Comptes Rend._, cvii. 533-535. - -Both compounds, in doses of 100 mgrms. per kilo., cause more or less -salivation, with diarrh[oe]a. The para-compound is more poisonous than -the meta-compound. So far as the author is aware, neither of these -diamines have been separated with certainty from the urine of sick -persons, nor from products of decomposition. - -Sec. 668. =Hexamethylenediamine=, C_{6}H_{16}N_{2}.--Hexamethylenediamine -has been found by A. Garcia[664] in a putrefying mixture of horse-flesh -and pancreas. - -[664] _Zeit. f. physiol. Chemie_, xvii. 543-555. - -Sec. 669. =Diethylenediamine=, C_{4}H_{10}N_{2}, is a crystalline -substance, melting-point 104 deg., boiling-point 145 deg.-146 deg. After melting, -it solidifies on cooling, forming a hard crystalline mass. It is -extremely soluble in water, and is deposited from alcohol in large -transparent crystals. A technical product called "spermin piperazidin" -or "piperazine" has been found by A. W. v. Hoffmann[665] to be -identical with diethylenediamine. The hydrochloride crystallises -in colourless needles, insoluble in alcohol, readily soluble in -water. The platinochloride, C_{4}H_{10}N_{2}H_{2}PtCl_{6}, is in -small yellow needles, and is fairly easily soluble in hot water, -but dissolves but slightly in hot alcohol. The mercuro-chloride, -C_{4}H_{10}N_{2}H_{2}HgCl_{4}, crystallises in concentrically grouped -needles, and is readily soluble in hot water, but is reprecipitated on -adding alcohol. The picrate, C_{4}H_{10}N_{2},C_{6}H_{2}(NO_{2})_{3}OH, -crystallises from water in yellow needles, almost insoluble in -alcohol.[666] - -[665] _Ber._, xxiii. 3297-3303. - -[666] Sieber, J., _Ber._, xxiii. 326-327. - -Sec. 670. =Mydaleine= is a poisonous base discovered by Brieger in putrid -animal matters. It is probably a diamine, but has not been obtained in -sufficient quantity for accurate chemical study. The platinochloride is -extremely soluble in water, and only comes down from an absolute alcohol -solution. It has been obtained in a crystalline form, giving on analysis -38.74 per cent. of platinum, C. 10.83 per cent., H. 3.23 per cent. - -Mydaleine is very poisonous. Small quantities injected into guinea-pigs -cause dilatation of the pupil, an abundant secretion from the nose and -eyes, and a rise of temperature. Fifty mgrms. cause death. The -_post-mortem_ appearances are not distinctive; the heart is arrested in -diastole; the intestines and bladder are contracted. In cats it causes -profuse diarrh[oe]a and vomiting. - -Sec. 671. =Guanidine.=--Guanidine may be considered to have a relation to -urea; for, if the oxygen of urea is replaced by the imide group NH, -guanidine originates thus:-- - - NH_{2} - / - Urea = O=C - \ - NH_{2} - - NH_{2} - / - Guanidine = NHC - \ - NH_{2} - -Hence guanidine from its structural formula is a carbodiamidimide. -Guanidine may be formed by the action of oxidising agents, such as -potassic chlorate and hydrochloric acid, on guanine; or by heating amide -cyanide with ammonium chloride, and so forming guanidine chloride. It is -also produced from the oxidation of albumin. When boiled with -baryta-water it decomposes into urea and ammonia. It combines with acids -to form salts; the gold salt, CH_{5}N_{3}HCl,AuCl_{3}, is in the form of -long yellow needles, with difficulty soluble in water. Guanidine -nitrate, CH_{5}N_{3}HNO_{3}, is also almost insoluble in cold water and -similar to urea nitrate. By dissolving equivalent parts of phenol and -guanidine in hot alcohol, triphenylguanidine is formed; on adding picric -acid to a solution of triphenylguanidine, phenylguanidine picrate, -CH_{2}Ph_{3}N_{3}C_{6}H_{2}(NO_{2})_{3}OH, is formed, and falls as a -precipitate of slender needles, melting-point 208 deg.; this picrate is -very slightly soluble, 1 part dissolving in 12,220 parts of water at -15 deg. Guanidine is poisonous.[667] - -[667] O. Prelinger, _Monatsb._, xiii. 97-100. - -A method of separating guanidine from urine has been worked out by -Gergers and Baumann.[668] The principle of the method is based upon the -fact that guanidine is precipitated by mercurous oxide. The urine is -precipitated by hydrate of baryta, the precipitate filtered off, the -alkaline filtrate neutralised by hydrochloric acid, and the neutral -filtrate evaporated to a syrup on the water-bath; the syrup is exhausted -by absolute alcohol, and the alcoholic solution filtered; this filtrate -is freed from alcohol by distillation, the alcohol-free residue -dissolved in a little water, shaken up with freshly precipitated mercury -oxide, and allowed to stand for two days in a warm place; the -precipitate formed is collected, acidulated with HCl and treated with -SH_{2}; the mercury sulphide thus obtained is separated by filtration, -the filtrate evaporated, and the residue dissolved in absolute alcohol. -This solution is precipitated by platinum chloride, filtered, separated -from any platinum ammonium salt, and evaporated to a small volume. After -long standing the guanidine salt crystallises out. The best method to -identify it appears to be, to ascertain the absence of ammonia and of -urea, and then to gently warm the supposed guanidine with an alkali, -which breaks guanidine up into ammonia and urea, according to the -following equation:-- - - NH=C(NH_{2})_{2} + H_{2}O = NH_{3} + CO(NH_{2})_{2}. - -[668] Pflueger's _Archiv_, xii. 205. - -The physiological effects of guanidine are as follows:-- - -A centigrm. of guanidine salt injected into the lymph sac in the back of -frogs produces, after a few minutes, muscular convulsions: first, there -are fibrillar twitchings of the muscles of the back; next, these spread -generally so that the whole surface of the frog seems to be in a -wave-like motion. Irritation of the limbs produces tetanus. There is, at -the same time, increased secretion from the skin. The breathing is -irregular. In large doses there is paralysis and death. The heart is -found arrested in diastole. The fatal dose for a frog is 50 mgrms.; but -1 mgrm. will produce symptoms of illness. In dogs there is paralysis, -convulsions, vomiting, and difficult breathing. - -Sec. 672. =Methylguanidine=, - - NH.CH_{3} - / - NH=C . - \ - NH_{2} - ---Methylguanidine has been isolated by Brieger from putrefying -horse-flesh; it has also been found in impure cultures in beef broth of -Finkler and Prior's _Vibrio proteus_. Bocklisch isolated it, working -with Brieger's process, from the mercuric chloride precipitate, after -removal of the mercury and concentration of the filtrate, by adding a -solution of sodium picrate. The precipitate contained the picrates of -cadaverine, creatinine, and methylguanidine; cadaverine picrate, -insoluble in boiling absolute alcohol, was separated by filtering from a -solution of the picrates of the bases in boiling absolute alcohol; the -alcohol was evaporated from the filtrate and the residue taken up with -water. From this aqueous solution the picric acid was removed and then -the solution precipitated with gold chloride; methylguanidine was -precipitated, while creatinine remained in solution. - -Methylguanidine aurochloride, C_{2}H_{7}N_{3}HCl.AuCl_{3} (Au = -47.7 per cent.), forms rhombic crystals easily soluble in alcohol -and ether; melting-point 198 deg. The hydrochloride, C_{2}H_{7}N_{3}HCl, -crystallises in needles insoluble in alcohol. The picrate, -C_{2}H_{7}N_{3}C_{6}H_{2}(NO_{2})_{3}OH, comes down at first as a -resinous mass, but, after boiling in water, is found to be in the form -of needles soluble in hot absolute alcohol; melting-point 192 deg. The -symptoms produced by methylguanidine are rapid respiration, dilatation -of the pupils, paralysis, and death, preceded by convulsions. The heart -is found arrested in diastole. - -Sec. 673. =Saprine=, C_{5}H_{14}N_{2}.--Saprine is isomeric with cadaverine -and neuridine; it was found by Brieger in human livers and spleens after -three weeks' putrefaction. Saprine occurs, in Brieger's process, in the -mercury precipitate. Its reactions are very similar to those of -cadaverine; the main difference being that cadaverine hydrochloride -gives a crystalline aurochloride, saprine does not; the platinum salt is -also more soluble in water than the cadaverine salt. It is not -poisonous. - -Sec. 674. =The Choline Group.=--The choline group consists of choline, -neurine, betaine, and muscarine. - -All these bodies can be prepared from choline; their relationship to -choline can be readily gathered from the following structural formulae:-- - - CH_{2}OH - | - CH_{2} - | - N(CH_{3})_{3}.OH - - Choline. - - CH_{2} - || - CH - | - N(CH_{3})_{3}.OH - - Neurine. - - CO_{2}H - | - CH_{2} - | - N(CH_{3})_{3}.OH - - Betaine. - - CH_{2}OH - | - CHOH - | - N(CH_{3})_{3}.OH - - Muscarine. - -Choline is a syrup with an alkaline reaction. On boiling with water, it -decomposes into glycol and trimethylamine. It gives, when oxidised, -muscarine. It forms salts. The hydrochloride is soluble in water and -absolute alcohol; neurine hydrochloride and betaine hydrochloride are -but little soluble in absolute alcohol, therefore this property can be -utilised for their separation from choline. The platinochloride is -insoluble in absolute alcohol; it melts at 225 deg. with effervescence, and -contains 31.6 per cent. of platinum. The mercurochloride is soluble with -difficulty even in hot water. The aurochloride (Au = 44.5 per cent.) is -crystalline, and with difficulty soluble in cold water; but is soluble -in hot water and in alcohol; melting-point 264 deg. with decomposition. - -Choline is only poisonous in large doses. - -Sec. 675. =Neurine= (Trimethyl-vinyl-ammonium hydrate), -C_{2}H_{3}N(CH_{3})_{3}OH.--Neurine is one of the products of -decomposition of choline. It is poisonous, and has been separated by -Brieger and others from decomposing animal matters. In Brieger's -process, neurine, if present, will be for the most part in the mercuric -chloride precipitate, and some portion will also be in the filtrate. The -mercury precipitate is decomposed by SH_{2}, the mercury sulphide -filtered off, and the filtrate, concentrated, treated with absolute -alcohol and then precipitated by platinum chloride. It is usually -accompanied by choline; the platinochloride of choline is readily -soluble in water, neurine platinochloride is soluble with difficulty; -this property is taken advantage of, and the platinochloride -crystallised from water until pure. Neurine has a strong alkaline -reaction. - -Neurine chloride, C_{5}H_{12}N.Cl, crystallises in fine needles. The -platinochloride, (C_{5}H_{12}NCl)_{2}PtCl_{4} (Pt = 33.6 per cent.), -crystallises in octahedra. The salt is soluble with difficulty in hot -water. - -The aurochloride, C_{5}H_{12}NClAuCl_{3} (Au = 46.37 per cent.), forms -flat prisms, which, according to Brieger, are soluble with difficulty in -hot water. - -Neurine is intensely poisonous, the symptoms being similar to those -produced by muscarine. - -Atropine is an antidote to neurine, relieving in suitable doses the -effects, and even rendering animals temporarily immune against the toxic -action of neurine. - -When a fatal dose of neurine is injected into a frog there is in a short -time paralysis of the extremities. The respiration stops first, and -afterwards the heart, the latter in diastole. - -The symptoms in rabbits are profuse nasal secretion and salivation with -paralysis, as in frogs. Applied to the eye, neurine causes contraction -of the pupil; to a less degree the same effect is produced by the -ingestion of neurine. - -=Trimethyloxyammonium= hydrochloride causes similar symptoms to neurine, -but the action is less powerful.--V. Cervello, _Arch. Ital. Biol._, vii. -232-233. - -Sec. 676. =Betaine.=--Betaine may be separated from a solution in alcohol -as large deliquescent crystals; the reaction of the crystals is neutral. -Distilled with potash, trimethylamine and other bases are formed. - -Betaine chloride, C_{5}H_{12}NO_{2}Cl, forms plates permanent in the air -and insoluble in absolute alcohol. A solution of the chloride in water -gives, with potassium mercuric iodide, a light yellow or whitish yellow -precipitate, soluble in excess; but, on rubbing the sides of the tube -with a glass rod, the oily precipitate crystallises as yellow needles; -probably this is characteristic. - -The aurochloride (Au = 43.1 percent.) forms fine cholesterine plates, -soluble in water; melting-point 209 deg. Betaine is not poisonous. - -Sec. 677. =Peptotoxine.=--Brieger submitted to the action of fresh gastric -juice moist fibrin for twenty-four hours at blood heat. The liquid was -evaporated to a syrup and boiled with ethylic alcohol, the ethylic -alcohol was evaporated, the residue digested with amylic alcohol, and -the amyl alcohol in its turn evaporated to dryness; the residue was a -brown amorphous mass that was poisonous. It was farther purified by -treating the extract with neutral lead acetate and then filtered; the -filtrate was freed from lead by SH_{2} and treated with ether, the -ethereal extract being then separated and evaporated to dryness; this -last residue was taken up with amyl alcohol, the alcohol evaporated to -dryness, and the residue finally taken up with water and filtered. The -filtrate is poisonous. The poisonous substance, to which Brieger gave -the provisional name of peptotoxine, is a very stable substance, -resisting the action of a boiling temperature, and even the action of -strong alkalies. It gives precipitates with alkaloidal group reagents, -and strikes a blue colour with ferric chloride and ferricyanide of -potassium. The most characteristic test seems to be its action with -Millon's reagent (a solution of mercury nitrate in nitric acid -containing nitrous acid); this gives a white precipitate which, on -boiling, becomes intensely red. - -It is poisonous, killing rabbits in doses of 0.5 grm. per kilogrm., with -symptoms of paralysis and coma. The nature of this substance requires -further elucidation. - -Sec. 678. =Pyridine Alkaloid from the Cuttle Fish.=--O. de Coninck[669] has -obtained, by Gautier's process, an alkaloid from the cuttle fish, of the -formula C_{8}H_{11}N, in the form of a yellow, mobile, strongly odorous -liquid, very soluble in alcohol, ether, and acetone, boiling-point 202 deg. -It quickly absorbs moisture from the air. It forms two mercuric -chlorides, one of which has the formula (C_{8}H_{11}N,HCl)_{2}HgCl_{2}; -this compound crystallises in small white needles, slightly soluble in -water and dilute alcohol, but insoluble in absolute alcohol, and -decomposing when exposed to moist air. The other salt is a sesqui-salt, -forming long yellowish needles, insoluble in ordinary solvents, and -decomposing when exposed to moist air. The alkaloid also forms -deliquescent very soluble salts with hydrochloric and hydrobromic acids. -A platinum salt is also formed, (C_{8}H_{11}N)_{2}H_{2}PtCl_{6}; -it is of a deep yellow colour, almost insoluble in cold, but soluble -in hot water; it is decomposed by boiling water, with the formation -of a very insoluble compound in the shape of a brown powder, -(C_{8}H_{11}N)_{2}PtCl_{4}. Coninck's alkaloid, on oxidation with -potassic permanganate, yields a gummy acid; this acid, on purifying it -by conversion into a potassium salt and then into a cupric salt, was -found to be nicotinic acid; so that the alkaloid is undoubtedly a -pyridine compound; indeed, the acid, distilled with lime, yields -pyridine. - -[669] _Comptes Rend._, cvi. 858, 861; cviii. 58-59, 809-810; cvi. -1604-1605. - -Sec. 679. =Poisons connected with Tetanus.=--Brieger, in 1887, isolated a -base of unknown composition, to which he gave the name of -"spasmotoxine." It was produced in cultures of the tetanus bacillus in -beef broth. - -Two more definite substances have also been discovered, viz., tetanine -and tetanotoxine. - -=Tetanine=, C_{13}H_{30}N_{2}O_{4}, is best isolated by the method of -Kitasato and Weyl.[670] Their method of treating broth cultures of the -tetanus bacillus is as follows:-- - -[670] _Zeit. f. Hygiene_, viii. 404. - -The broth is digested with 0.25 per cent. HCl for some hours at 460 deg., -then rendered feebly alkaline, and distilled in a vacuum. The residue in -the retort is then worked up for tetanine by Brieger's method; the -distillate contains tetanotoxine, ammonia, indol, hydrogen sulphide, -phenol, and butyric acid. On treating the contents of the retort by -Brieger's mercury chloride method, the filtrate contains most of the -poison. The mercury is removed by SH_{2}, the filtered solution -evaporated and exhausted by absolute alcohol, in which the tetanine -dissolves. Any ammonium chloride is thus separated, ammonium chloride -being insoluble in absolute alcohol. The alcoholic solution, filtered -from any insoluble substance, is next treated with an alcoholic solution -of platinum chloride, which precipitates creatinine (and any ammonium -salts), but does not precipitate tetanine. The platinum salt of tetanine -may, however, be precipitated by the addition of ether to the alcoholic -solution. The platinum salt, as obtained by precipitation from ether, is -very deliquescent; it has, therefore, to be rapidly filtered off and -dried in a vacuum. It can then be recrystallised from hot 96 per cent. -alcohol, forming clear yellow plates; these plates, if dried in a -vacuum, become with difficulty soluble in water. - -Tetanine may be obtained as a free base by treating the hydrochloride -with freshly precipitated moist silver oxide. It forms a strongly -alkaline yellow syrup, and is easily decomposed in acid solution, but is -permanent in alkaline solutions. - -The platinochloride, as before observed, is precipitable by ether from -alcoholic solution; it contains 28.3 per cent. of platinum, and -decomposes at 197 deg. - -The base produces tetanus. - -Sec. 680. =Tetanotoxine= may be distilled, and be found in the distillate -with other matters. It forms an easily soluble gold salt, melting-point -130 deg. The platinochloride is soluble with difficulty, and decomposes at -240 deg. The hydrochloride is soluble in alcohol and in water, -melting-point about 205 deg. - -Tetanotoxine produces tremor, then paralysis, and lastly, violent -convulsions. - -Sec. 681. =Mydatoxine=, C_{6}H_{13}NO_{2}.--A base obtained by Brieger from -horse-flesh in a putrefactive condition and other substances. It is -found in the mercury chloride precipitate. The free base is an alkaline -syrup, isomeric with the base separated by Brieger from tetanus -cultures. The hydrochloride is a deliquescent syrup, not forming any -compound with gold chloride, but uniting with phospho-molybdic acid in -forming a compound crystallising in cubes. It forms a double salt with -gold chloride, sparingly soluble in water. The platinochloride (Pt = 29 -per cent.) is very soluble in water, but not soluble in alcohol; -melting-point 193 deg. with decomposition. - -The base in large doses is poisonous, causing lachrymation, diarrh[oe]a, -and convulsions. - -Sec. 682. =Mytilotoxine=, C_{6}H_{15}NO_{2}.--This is believed to be the -poison of mussels. Brieger isolated it as follows:-- - -The mussels were boiled with water acidified by hydrochloric acid; the -liquid was filtered, and the filtrate evaporated to a syrup, and the -syrup was repeatedly extracted with alcohol. It was found advisable to -exhaust thoroughly with alcohol, otherwise much poison remained behind. -The alcoholic solution was treated with an alcoholic solution of lead -acetate. The filtrate was evaporated and the residue extracted with -alcohol. The lead was removed by SH_{2}, the alcohol distilled off, -water added to the remaining syrup, and the solution decolorised by -boiling with animal charcoal. The solution was neutralised by sodium -carbonate, acidulated with nitric acid, and precipitated with -phosphomolybdic acid. The precipitate was then decomposed by warming -with a neutral solution of lead acetate, and the filtrate (after the -removal of the lead by the action of SH_{2}) was acidulated with HCl and -evaporated to dryness. The residue was then extracted with absolute -alcohol, filtered from any insoluble chloride, _e.g._, betaine chloride, -and precipitated by mercury chloride in alcohol. - -The free base has a most peculiar odour, which disappears on exposure to -air; at the same time, the poisonous properties also diminish. The base -is destroyed by boiling with sodium carbonate; on the other hand, the -hydrochloride may be evaporated to dryness or be boiled without -decomposing. - -The hydrochloride crystallises in tetrahedra; the aurochloride -crystallises in cubes (Au=41.66 per cent.). Its melting-point is 182 deg. - -Sec. 683. =Tyrotoxicon= (Diazobenzol, C_{6}H_{5}N_{2}(OH)).--It appears, -from the researches of Vaughan and others, that diazobenzol is liable to -be formed in milk and milk products, especially in summer time. It is -confidently asserted by many that the summer diarrh[oe]a of infants is -due to this toxine; however that may be, it is well established that -diazobenzol is a violent poison, causing sickness, diarrh[oe]a, and, in -large doses, an acute malady scarcely distinguishable from cholera, and -which may end fatally. There will always be difficulty in detecting it, -because of its instability. The following is the best process of -extraction from milk. The milk will probably be acid from decomposition; -if so, the whey must be separated by dilution and filtration; without -dilution it may be found impracticable to get a clear filtrate. In order -to keep the bulk down, 25 c.c. of the milk may be diluted up to 100 -c.c., and, having obtained a clear filtrate from this 25 c.c. thus -diluted, the filtrate is used to dilute another 25 c.c. of milk and so -on. The acid filtrate is neutralised by sodium carbonate, agitated with -an equal volume of ether, allowed to stand in a stoppered vessel for -twenty-four hours, and the ether then separated and allowed to evaporate -spontaneously. The residue is acidified with nitric acid and then -treated with a saturated solution of potash, which forms a stable -compound with diazobenzol, and the whole concentrated on the water-bath. -On cooling, the tyrotoxicon compound forms six-sided plates. Before the -whole of this process is undertaken, it is well to make a preliminary -test of the milk as follows:--A little of the ether is allowed to -evaporate spontaneously. Place on a porcelain slab two or three drops of -a mixture of equal parts of sulphuric and carbolic acids, and add a few -drops of the aqueous solution; if tyrotoxicon be present, a yellow to -orange-red colour is produced. A similar colour is also produced by -nitrates or nitrites, which are not likely to be present under the -circumstances, milk having mere traces only of nitrates or nitrites; it -may also be due to butyric acid, which, in a decomposed milk, may -frequently be in solution. Therefore, if a colour occurs, this is not -absolutely conclusive; if, however, no colour is produced, then it is -certain that no diazobenzol has been separated. That is all that can be -said, for the process itself is faulty, and only separates a fractional -part of the whole. - -Sec. 684. =Toxines of Hog Cholera.=--Toxines have been isolated by F. G. -Novy[671] from a cultivation of Salmon's bacillus in pork broth. The -fluid possessed a strong alkaline reaction. For the isolation, Brieger's -method was used. The mercury chloride precipitate was amorphous and was -converted into a chlorine-free platinum compound, to which was assigned -the composition of C_{8}H_{14}N_{4}PtO_{8}. After separation of this -compound, the mother liquor still contained a platinum salt -crystallising in needles, and from this was obtained the chlorhydrate of -a new base, to which was given the name of _susotoxine_; it had the -composition of C_{10}H_{26}N_{2}2HCl,PtCl_{4}. Susotoxine gives general -alkaloidal reactions, and is very poisonous. - -[671] _Med. News_, September 1890. - -Sec. 685. =Other Ptomaines.=--Besides the ptomaines which have been already -described, there are a number of others; the following may be mentioned: -isoamylamine,[672] (CH_{3})_{2}CH.CH_{2}.CH_{2}NH_{2}; butylamine, -CH_{3}CH_{2}CH_{2}CH_{2}NH_{2}; dihydrolutidine,[673] C_{7}H_{11}N; -hydrocollidine,[674] C_{8}H_{13}N; C_{10}H_{15}N (a base isolated by -Guareschi and Mosso[675] from ox-fibrin in a state of putrefaction by -Gautier's method; it forms a crystalline hydrochloride and an insoluble -platinochloride; its action is like that of curare but weaker); -aselline,[676] C_{25}H_{32}N_{4}, isolated from cod-liver oil; -typhotoxine,[677] C_{7}H_{17}NO_{2}, isolated from cultures of Eberth's -bacillus. So far as the published researches go, it would appear that -other crystalline substances have been isolated from the urine, from the -tissues, and from the secretions of patients suffering from various -diseases; the quantity obtained in each case has, however, been, under -the most favourable circumstances, less than a gramme; often only a few -milligrms. To specifically declare that a few milligrms. of a substance -is a new body, requires immense experience and great skill; and, even -where those qualifications are present, this is too often impossible. -This being so, the long list of named ptomaines, such as erysipeline, -varioline, and others, must have their existence more fully confirmed by -more than one observer before they can be accepted as separate entities. - -[672] Hesse, _Chem. Jahresb._, 1857, 403. - -[673] Gautier, A., and Morgues, _Compt. Rend._, 1888. - -[674] Gautier et Etard, _Bull. Soc. Chim._, xxxvii., 1882. - -[675] Guareschi et Mosso, _Les ptomaines_, 1883. - -[676] Gautier, A., et Morgues, _Compt. Rend._, 1888. - -[677] Brieger, 1885, _Ptomaines_, iii. - - -DIVISION III.--FOOD POISONING. - -Sec. 686. A large number of cases of poisoning by food occur yearly; some -are detailed in the daily press; the great majority are neither recorded -in any journal, scientific or otherwise; nor, on account of their slight -and passing character, is medical aid sought. The greatest portion of -these cases are probably due to ptomaines existing in the food before -being consumed; others may be due to the action of unhealthy -fermentation in the intestinal canal itself; in a third class of cases, -it is probable that a true zymotic infection is conveyed and develops in -the sufferer; the latter class of cases, as, for instance, the -Middlesborough epidemic of pleuro-pneumonia, is outside the scope of -this treatise. - -Confining the attention to cases of food poisoning in which the symptoms -have been closely analysed and described, the reader is referred to -thirteen cases of food poisoning, investigated by the medical officers -of the Local Government Board between the years 1878 and 1891, as -follows:-- - -1878. =A Case of Poisoning at Whitchurch from eating Roast Pork.=--Only -the leg of pork was poisonous, other parts eaten without injury. Two -persons died after about thirty hours' illness. The pork itself, on a -particular Sunday, was innocuous; it became poisonous between the Sunday -and the Monday; the toxicity appeared to gradually increase, for those -who ate it for dinner on the Monday were not taken ill for periods of -from seven to nineteen hours, while two persons who ate of it in the -evening were attacked four hours after eating. - -1880. =The Welbeck Epidemic=, due to eating cold boiled ham. Over fifty -persons affected. Symptoms commenced in from twelve to forty-eight -hours. - -1881. =A Series of Poisoning from eating Baked Pork, -Nottingham.=--Probably the gravy was the cause and not the pork itself. -Many persons seriously ill. One died. - -1881. =Tinned American Sausage.=--A man in Chester died from eating -tinned American sausage. Poison found to be unequally distributed in the -sausage. - -1882. =Poisoning at Oldham by Tinned Pigs' Tongues.=--Two families -affected. Symptoms commenced in about four hours. All recovered. After a -few days' keeping it would appear that the poison had been decomposed. - -1882. =A Family Poisoned by Roast Beef at Bishop Stortford.=--Only a -particular piece of the ribs seemed to be poisonous, the rest of the -carcase being innocuous. Symptoms did not commence until several hours -after ingestion. - -1882. =Ten different Families at Whitchurch Poisoned by eating -Brawn.=--First symptoms after about four hours. - -1884. =Tinned Salmon at Wolverhampton.=--Five persons, two being -children, ate of tinned salmon at Wolverhampton. All suffered more or -less. The mother's symptoms began after twelve hours, and she died in -five days; the son died in three days, the symptoms commencing in ten -hours. The _post-mortem_ signs were similar to those from phosphorus -poisoning, viz., fatty degeneration. Mice fed on the material also -suffered, and their organs showed a similar degeneration. - -1886. =The Carlisle A Case.=--At a wedding breakfast in Carlisle -twenty-four persons were poisoned by food which had been kept in an -ill-ventilated cellar. The articles suspected were an American ham, an -open game pie, and certain jellies. The bride died. Symptoms commenced -in from six to forty-three hours. - -1886. =Poisoning by Veal Pie at Iron Bridge.=--Twelve out of fifteen ate -of the pie; all were taken ill in from six to twelve hours. - -1887. =Poisoning at Retford of Eighty Persons from eating Pork Pie or -Brawn.=--Symptoms commenced at various intervals, from eight to -thirty-six hours. - -1889. =The Carlisle B Case.=--Poisoning by pork pies or boiled salt -pork. Number of persons attacked, about twenty-five. - -1891. =Poisoning by a Meat Pie at Portsmouth.=--Thirteen persons -suffered from serious illness. Portions of the pies were poisonous to -mice. - -The symptoms in all these cases were not precisely alike; but they were -so far identical as to show as great a similarity as in cases when a -number of persons are poisoned by the same chemical substance. Arsenic, -for instance, produces several types of poisoning; so does phosphorus. - -Severe gastro-enteric disturbance, with more or less affection of the -nervous system, were the main characteristics. These symptoms commenced, -as before stated, at various intervals after ingestion of the food; but -they came on with extreme suddenness. Rigors, prostration, giddiness, -offensive diarrh[oe]a, followed by muscular twitchings, dilatation of -the pupil, drowsiness, deepening in bad cases to coma, were commonly -observed. The _post-mortem_ appearances were those of enteritis, with -inflammatory changes in the kidney and liver. Convalescence was slow; -sometimes there was desquamation of the skin. - -In many of these cases Dr. Klein found bacteria which, under certain -conditions, were capable of becoming pathogenic; but in no case does -there seem to have been at the same time an exhaustive chemical inquiry; -so that, although there was evidence of a poison passing through the -kidney, the nature of the poison still remains obscure. - -The deaths in England and Wales from unwholesome food during ten years -were as follows:-- - -DEATHS IN ENGLAND AND WALES FROM UNWHOLESOME FOOD DURING THE TEN YEARS -1883-1892. - - +----------+-----+---+-----+---+-----+---+-----+---+-----+----+----+ - | |1883.| |1885.| |1887.| |1889.| |1891.| |To- | - | | |1884.| |1886.| |1888.| |1890.| |1892.|tal.| - +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+ - |Diseased | 1 | ... |...| ... |...| ... |...| ... |...| ... | 1 | - |meat, | | | | | | | | | | | | - |Poisonous | 2 | 3 | 2 | 1 | 1 | 4 | 3 | 2 | 9 | 6 | 33 | - |fish, | | | | | | | | | | | | - |Unwholesome|...| 1 |...| ... |...| ... |...| ... |...| ... | 1 | - |brawn, | | | | | | | | | | | | - |Tinned |...| 2 |...| ... |...| ... |...| ... |...| ... | 2 | - |salmon, | | | | | | | | | | | | - |Putrid |...| 1 | 1 | 1 |...| ... | 1 | ... |...| ... | 4 | - |meat, | | | | | | | | | | | | - |Diseased |...| 1 |...| ... |...| ... |...| ... |...| ... | 1 | - |food, | | | | | | | | | | | | - |Mussels, |...| 1 |...| ... |...| ... | 1 | ... |...| ... | 2 | - |Tinned |...| ... |...| ... | 2 | ... |...| ... |...| ... | 2 | - |foods, | | | | | | | | | | | | - |Whelks, |...| ... |...| ... | 1 | ... |...| ... |...| ... | 1 | - |Winkles, |...| ... |...| ... |...| ... |...| 1 |...| ... | 1 | - |Ptomaines, |...| ... |...| ... |...| ... |...| ... | 1 | ... | 1 | - | +---+-----+---+-----+---+-----+---+-----+---+-----+----+ - | | 3 | 9 | 3 | 2 | 4 | 4 | 5 | 3 |10 | 6 | 49 | - +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+ - -Sec. 687. =German Sausage Poisoning.=--A series of cases may be picked out -from the accounts of sausage poisoning in Germany, all of which -evidently depend upon a poison producing the same symptoms, and the -essentially distinctive mark of which is extreme dryness of the skin and -mucous membranes, dilatation of the pupil, and paralysis of the upper -eyelids (ptosis). In an uncertain time after eating sausages or some -form of meat, from one to twenty-four hours, there is a general feeling -of uneasiness, a sense of weight about the stomach, nausea, and soon -afterwards vomiting, and very often diarrh[oe]a. The diarrh[oe]a is not -severe, never assumes a choleraic form, and is unaccompanied by cramps -in the muscles. After a considerable interval there is marked dryness of -the mucous membrane (a symptom which never fails), the tongue, pharynx, -and the mouth generally seem actually destitute of secretion; there is -also an absence of perspiration, the nasal mucous membrane participates -in this unnatural want of secretion, the very tears are dried up. In a -case related by Kraatzer,[678] the patient, losing a son, was much -troubled, but wept no tear. This dryness leads to changes in the mucous -membrane, it shrivels, and partly desquamates, aphthous swellings may -occur, and a diffuse redness and diphtheritic-like patches have been -noticed. There is obstinate constipation, probably from a dryness of the -mucous lining of the intestines. The breath has an unpleasant odour, -there is often a croupy cough, the urinary secretion alone is not -decreased but rather augmented. Swallowing may be so difficult as to -rise to the grade of aphagia, and the tongue cannot be manipulated -properly, so that the speech may be almost unintelligible. At the same -time, marked symptoms of the motor nerves of the face are present, the -patient's sight is disturbed, he sees colours or sparks before his eyes; -in a few cases there has been transitory blindness, in others diplopia. -The pupil in nearly all the cases has been dilated, also in exceptional -instances it has been contracted. The _levator palpebrae superioris_ is -paralysed, and the resulting ptosis completes the picture. Consciousness -remains intact almost to death, there is excessive weakness of the -muscles, perhaps from a general paresis. If the patient lives long -enough, he gets wretchedly thin, and dies from marasmus. In more rapidly -fatal cases, death follows from respiratory paralysis, with or without -convulsions. - -[678] Quoted by Husemann, _Vergiftung durch Wurstgift_ (Maschka's -_Handbook_). - -=The post-mortem appearances= which have been observed are--the mucous -membranes of the mouth, gullet, and throat are white, hard, and -parchment-like; that of the stomach is more or less injected with -numerous haemorrhages: the kidneys are somewhat congested, with some -effusion of blood in the tubuli; the spleen is large and very full of -blood, and the lungs are often [oe]dematous, pneumonic, or bronchitic. - - - - -PART VIII.--THE OXALIC ACID GROUP OF POISONS. - -Sec. 688. Oxalic acid is widely distributed both in the free state and in -combination with bases throughout the vegetable kingdom, and it also -occurs in the animal kingdom. In combination with potash it is found in -the _Geranium acetosum_ (L.), _Spinacia oleracea_ (L.), _Phytolacca -decandra_ (L.), _Rheum palmatum_ (L.), _Rumex acetosa_, _Atropa -belladonna_, and several others; in combination with soda in different -species of _Salsola_ and _Salicornia_; and in combination with lime in -most plants, especially in the roots and bark. Many lichens contain half -their weight of calcic oxalate, and oxalic acid, either free or -combined, is (according to the observations of Hamlet and -Plowright[679]) present in all mature non-microscopic fungi. Crystals of -oxalate of lime may be frequently seen by the aid of the microscope in -the cells of plants. According to Schmidt,[680] this crystallisation -only takes place in the fully mature cell, for in actively growing cells -the oxalate of lime is entirely dissolved by the albumen of the plant. - -[679] _Chem. News_, vol. xxxvi. p. 93. - -[680] _Ann. Chem. Pharm._, vol. lxi. p. 297. - -In the animal kingdom oxalic acid is always present in the intestinal -contents of the caterpillar. In combination with lime, it is constantly -found in the allantois liquor of the cow, the urine of man, swine, -horses, and cats. With regard to human urine, the presence or absence of -oxalate of lime greatly depends upon the diet, and also upon the -individual, some persons almost invariably secreting oxalates, whatever -their food may be. - -Sec. 689. =Oxalic Acid=, H_{2}C_{2}O_{4}2H_{2}O (90 + 36), specific gravity -1.64, occurs in commerce in prismatic crystals, very similar to, and -liable to be mistaken for, either magnesic or zincic sulphates. The -crystals are intensely acid, easily soluble in water (1 part requiring -at 14.5 deg. 10.46 parts of water); they are also soluble in parts of cold, -and readily in boiling, alcohol. Oxalic acid is slightly soluble in cold -absolute ether; but ether, although extracting most organic acids from -an aqueous solution, will not extract oxalic acid. - -Oxalic acid sublimes slowly at 100 deg., but rapidly and completely at -150 deg.; the best means of obtaining the pure anhydride is to put a -sufficient quantity of the acid into a strong flask, clamp it by -suitable connections to a mercury pump, and sublime in a vacuum; in this -way a sufficient quantity may be sublimed a little above 100 deg. It is -well to remember, not only its low subliming temperature, but also that -an aqueous solution, if kept at 100 deg., loses acid; hence all evaporating -or heating operations must not exceed 98 deg., or there will be some loss. -The effect of heat is first to drive off water, then, if continued up to -about 190 deg., there is decomposition into carbon monoxide, carbon dioxide, -water, and formic acid; the two reactions occurring simultaneously-- - - C_{2}H_{2}O_{4} = CO_{2} + CO + H_{2}O. - - C_{2}H_{2}O_{4} = CO_{2} + CH_{2}O_{2}. - -Heated with sulphuric acid to 110 deg., the following decomposition takes -place:-- - - H_{2}C_{2}O_{4} = H_{2}O + CO_{2} + CO. - -Oxalic acid decomposes fluor spar, the phosphates of iron, silver, zinc, -copper, and the arseniates of iron, silver, and copper. It may be used -to separate the sulphides of iron and manganese from the sulphides of -zinc, cadmium, uranium, cobalt, mercury, and copper--dissolving the -former, not the latter. Many minerals and other substances are also -attacked by this acid. - -If a solution of oxalic acid in water is boiled with ammonio or sodio -terchloride of gold (avoiding direct exposure to light) the gold is -precipitated-- - - 2AuCl_{3} + 3H_{2}C_{2}O_{4} = 6CO_{2} + 6HCl + Au_{2}. - -When black oxide of manganese (free from carbonate) is mixed with an -oxalate, and treated with dilute sulphuric acid, the oxalic acid is -decomposed, and carbon dioxide evolved-- - - MnO_{2} + H_{2}C_{2}O_{4} + H_{2}SO_{4} = MnSO_{4} + 2H_{2}O + - 2CO_{2}. - -A similar reaction occurs with permanganate of potash. - -If to a solution of oxalic acid, which may be neutralised with an -alkali, or may contain free acetic acid, a solution of acetate of lime -be added, oxalate of lime is thrown down. This salt, important in an -analytical point of view, it will be well to describe. - -Sec. 690. =Oxalate of Lime= (CaC_{2}O_{4}H_{2}O), 1 part .863 crystallised -oxalic acid. This is the salt which the analyst obtains for the -quantitative estimation of lime or oxalic acid; it is not identical with -that occurring in the vegetable kingdom, the latter containing 3H_{2}O. -Oxalate of lime cannot be precipitated for quantitative purposes from -solutions containing chromium, aluminium, or ferric iron, since somewhat -soluble salts are formed. It dissolves in solutions of magnesium and -manganese,[681] and citrate of soda, and is also decomposed by boiling -with solutions of copper, silver, lead, cadmium, zinc, nickel, cobalt, -strontium, or barium. It is insoluble in solutions of chlorides of the -alkalies and alkaline earths, and in water, in alkaline solutions, or in -acetic acid; and is soluble in mineral acid only when the acid is strong -and in considerable excess. It is unalterable in the air, and at 100 deg. -When carefully and slowly ignited it may be wholly converted into -carbonate of lime; if the heat is not properly managed (that is, if -excessive), caustic lime may be formed in greater or smaller quantity. - -[681] But it is reprecipitated unaltered by excess of alkaline oxalate. - -Sec. 691. =Use in the Arts.=--Oxalic acid is chiefly used by dyers and -calico-printers, but also by curriers and harness-makers for cleaning -leather, by marble masons for removing iron stains, by workers in straw -for bleaching, and it is applied to various household purposes,[682] -such as the whitening of boards, the removing of iron-mould from linen, -&c. The hydropotassic oxalate (binoxalate of potash), under the popular -names of "_essential salt of lemons_" and salts of sorrel, is used for -scouring metals and for removing ink-stains from linen. - -[682] A "Liquid Blue," used for laundry purposes, contains much free -oxalic acid. - -Sec. 692. =Hydropotassic Oxalate, Binoxalate of Potash=, -KHC_{2}O_{4}(H_{2}O), is a white salt, acid in reaction, soluble in -water, and insoluble in alcohol. Heated on platinum foil it leaves -potassic carbonate, which may be recognised by the usual tests. Its -aqueous solution gives, with a solution of acetate or sulphate of lime, -a precipitate of calcic oxalate insoluble in acetic acid. - -Sec. 693. =Statistics.=--Poisoning by oxalic acid is more frequent in -England than in any other European country. In the ten years 1883-92, -there were registered in England and Wales 222 deaths from oxalic -acid--of these 199, or 89.6 per cent., were suicidal, the remainder -accidental. The age and sex distribution of these cases is set out in -the following table:-- - -POISONING BY OXALIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS -1883-1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total - above - Males, 1 ... ... 2 ... 14 17 - Females, ... ... ... 1 5 ... 6 - --------------------------------------------- - Total, 1 ... ... 3 5 14 23 - --------------------------------------------- - - SUICIDE. - - Ages, 15-25 25-65 65 and Total - above - Males, 9 102 3 114 - Females, 21 62 2 85 - ---------------------------- - Total, 30 164 5 199 - ---------------------------- - -Sec. 694. =Fatal Dose.=--The smallest dose of oxalic acid known to have -destroyed life is, according to Dr. Taylor, 3.88 grms. (60 grains); but -recovery has taken place, on prompt administration of remedies, after -eight times this quantity has been swallowed. - -With regard to oxalate of soda, or binoxalate of potash, 14.2 grms. -(half an ounce) have been taken without fatal result, although the -symptoms were very serious; and it may be held that about that quantity -would usually cause death. Oxalic acid is not used in medicine, save as -a salt, _e.g._, oxalate of cerium. - -Sec. 695. =Effects of Oxalic Acid and Oxalates on Animals.=--The first -cases of poisoning by oxalic acid occurred early in the nineteenth -century, a little more than fifty years after its discovery. -Thompson[683] was the first who attempted, by experiment on animal life, -to elucidate the action of the poison; he noted the caustic action on -the stomach, and the effects on the heart and nervous system, which he -attributed simply to the local injury through the sympathetic nerves. -Orfila[684] was the next who took the matter up, and he made several -experiments; but it was Robert Christison[685] who distinctly recognised -the important fact that oxalic acid was toxic, quite apart from any -local effects, and that the soluble oxalates, such as sodic and potassic -oxalates, were violent poisons. - -[683] _Lond. Med. Rep._, vol. iii. p. 382. - -[684] _Traite de Toxicologie._ - -[685] _Edin. Med. and Surg. Journ._, 1823. - -Sec. 696. Kobert and Kuessner[686] have made some extended researches on the -effects of sodic oxalate on rabbits, cats, dogs, guinea-pigs, hedgehogs, -frogs, &c.--the chief results of which are as follows:--On injection of -sodic oxalate solution in moderate doses into the circulation, the -heart's action, and, therefore, the pulse, become arhythmic; and a -dicrotic or tricrotic condition of the pulse may last even half a day, -while at the same time the frequency may be uninfluenced. The -blood-pressure also with moderate doses is normal, and with small atoxic -doses there is no slowing of the respiration. On the other hand, toxic -doses paralyse the respiratory apparatus, and the animal dies -asphyxiated. With chronic and subacute poisoning the respiration becomes -slower and slower, and then ceases from paralysis of the respiratory -muscles. The first sign of poisoning, whether acute or chronic, is a -sleepy condition; dogs lie quiet, making now and then a noise as if -dreaming, mechanical irritations are responded to with dulness. The hind -extremities become weak, and then the fore. This paresis of the hind -extremities, deepening into complete paralysis, was very constant and -striking. Take, for example, from the paper (_op. cit._) the experiment -in which a large cat received in six days five subcutaneous injections -of 5 c.c. of a solution of sodic oxalate (strength 1 : 30), equalling -.16 grm.; the cat died, as it were, gradually from behind forwards, so -that on the sixth day the hinder extremities were fully motionless and -without feeling. The heart beat strongly. The temperature of the -poisoned animal always sinks below the normal condition. Convulsions in -acute poisoning are common, in chronic quite absent; when present in -acute poisoning, they are tetanic or strychnic-like. In all the -experiments of Kobert and Kuessner, lethal doses of soluble oxalates -caused the appearance of sugar in the urine. - -[686] _Exper. Wirkungen der Oxalsaeure, Virch. Archiv_, Bd. lxxvii. S. -209. - -J. Uppmann[687] made forty-nine experiments on dogs, in which he -administered relatively large doses by the stomach; no poisonous effect -followed. Emil Pfeiffer[688] gave a dog in three successive days .2, .5, -and lastly 1 grm. oxalic acid with meat, but no symptoms resulted. Yet -that oxalic acid, as sodic oxalate, is poisonous to dogs, if it once -gets into the circulation, cannot be disputed. The accepted explanation -is that the large amount of lime phosphates in the digestive canal of -dogs is decomposed by oxalic acid, and the harmless lime oxalate formed. - -[687] _Allg. Med. central Ztg._, 1877. - -[688] _Archiv der Pharm._ (3 R.), Bd. xiii. S. 544, 1878. - -Oxalic acid is absorbed into the blood, and leeches have been known to -die after their application to a person who had taken a large dose. Thus -Christison[689] quotes a case related by Dr. Arrowsmith, in which this -occurred:--"They were healthy, and fastened immediately; on looking at -them a few minutes after, I remarked that they did not seem to fill, and -on touching one it felt hard, and instantly fell off motionless and -dead; the others were in the same state. They had all bitten, and the -marks were conspicuous, but they had drawn scarcely any blood. They were -applied about six hours after the acid had been taken." - -[689] _Treatise on Poisons._ - -Sec. 697. =Effects of Vaporised Oxalic Acid.=--Eulenberg has experimented -on pigeons on the action of oxalic acid when breathed. In one of his -experiments, .75 grm. of the acid was volatilised into a glass shade, in -which a pigeon had been placed; after this had been done five times in -two minutes, there was uneasiness, shaking of the head, and cough, with -increased mucous secretion of the nasal membrane. On continuing the -transmission of the vapour, after eight minutes there was again -restlessness, shaking of the head, and cough; after eleven minutes the -bird fell and was convulsed. On discontinuing the sublimation, it got up -and moved freely, but showed respiratory irritation. On the second day -after the experiment, it was observed that the bird's note was hoarse, -on the fourth day there was slowness of the heart's action and refusal -of food, and on the sixth day the bird was found dead. Examination after -death showed slight injection of the cerebral membranes; the cellular -tissue in the neighbourhood of the trachea contained in certain places -extravasations of blood, varying from the size of a pea to that of a -penny; the mucous membrane of the larynx and trachea was swollen and -covered with a thick croupous layer; the lungs were partially hepatised, -and the pleura thickened; the crop as well as the true intestines still -contained some food.[690] - -[690] _Gewerbe Hygiene_, p. 423. - -Sec. 698. =The Effects of Oxalic Acid and Hydropotassic Oxalate on -Man.=--The cases of oxalic poisoning have been invariably due to either -oxalic acid or hydropotassic oxalate, the neutral sodic or potassic -oxalates having hitherto in no instance been taken. The symptoms, and -even the locally destructive action of oxalic acid and the acid oxalate, -are so similar that neither from clinical nor _post-mortem_ signs could -they be differentiated by anyone not having a previous knowledge of the -case. - -The external application of oxalic acid does not appear to cause -illness; workmen engaged in trades requiring the constant use of the -acid often have the nails white, opaque, and brittle; but no direct -injury to health is on record. - -A large dose of either causes a local and a remote effect; the local is -very similar to that already described as belonging to the mineral -acids, i.e., more or less destructive of the mucous membranes with which -the acid comes in contact. The remote effects may only be developed -after a little; they consist essentially of a profound influence on the -nervous system. Though more than 120 cases of oxalic acid poisoning have -occurred since Christison wrote his treatise, his graphic description -still holds good. "If," says he, "a person immediately after swallowing -a solution of a crystalline salt, which tasted purely and strongly acid, -is attacked with burning in the throat, then with burning in the -stomach, vomiting, particularly of bloody matter, imperceptible pulse, -and excessive languor, and dies in half an hour, or still more, in -twenty, fifteen, or ten minutes, I do not know any fallacy which can -interfere with the conclusion that oxalic acid was the cause of death. -No parallel disease begins so abruptly, and terminates so soon; and no -other crystalline poison has the same effect." The local action is that -of a solvent on the mucous tissues. If from 10 to 30 grms. are -swallowed, dissolved in water, there is an immediate sour taste, pain, -burning in the stomach, and vomiting. The vomit may be colourless, -greenish, or black, and very acid; but there is a considerable variety -in the symptoms. The variations may be partly explained by saying that, -in one class of cases, the remote or true toxic effects of the poison -predominate; in a second, the local and the nervous are equally divided; -while in a third, the local effects seem alone to give rise to symptoms. - -In a case at Guy's Hospital, in 1842, there was no pain, but vomiting -and collapse. In another case which occurred in 1870, a male (aged 48) -took 10.4 grms. (162 grains); he had threatening collapse, cold sweats, -white and red patches on the tongue and pharynx, difficulty in -swallowing, and contracted pupils. Blood was effused from the mouth and -anus; on the following day there were convulsions, coma, and death -thirty-six hours after taking the poison. In another case, there was -rapid loss of consciousness and coma, followed by death in five hours. -Death may be very rapid, _e.g._, in one case (_Med. Times and Gaz._, -1868) it took place in ten minutes; there was bleeding from the stomach, -which doubtless accelerated the fatal result. Orfila has recorded a -death almost as rapid from the acid oxalate of potash; a woman took 15 -grms.; there was no vomiting, but she suffered from fearful cramps, and -death ensued in fifteen minutes. In another case, also recorded by -Orfila, there was marked slowing of the pulse, and soporific tendencies. -With both oxalic acid and the acid oxalate of potash, certain nervous -and other sequelae are more or less constant, always provided time is -given for their development. From the experiments already detailed on -animals, one would expect some paresis of the lower extremities, but -this has not been observed in man. There is more or less inflammation of -the stomach, and often peritonitis; in one case (_Brit. Med. Journal_, -1873) there were cystitis and acute congestion of the kidneys with -albuminuria. - -In two cases quoted by Taylor, there was a temporary loss or -enfeeblement of voice; in one of the two, the aphonia lasted for eight -days. In the other, that of a man who had swallowed about 7 grms. (1/4 -oz.) of oxalic acid, his voice, naturally deep, became in nine hours low -and feeble, and continued so for more than a month, during the whole of -which time he suffered in addition from numbness and tingling of the -legs. As a case of extreme rarity may be mentioned that of a young -woman,[691] who took 12 grms. (185 grains) of the acid oxalate of -potash, and on the third day died; before death exhibiting delirium so -active and intense that it was described as "madness." - -[691] _Journ. de Chim. Med._, 1839, p. 564. - -Sec. 699. =Physiological Action.=--Putting on one side the _local_ effects -of oxalic acid, and regarding only its true toxic effects, there is some -difference of opinion as to its action. L. Hermann considers it one of -the heart poisons, having seen the frog's heart arrested by subcutaneous -doses of sodic oxalate, an observation which is borne out by the -experiments of Cyon,[692] and not negatived by those of Kobert and -Kuessner. The poison is believed to act on the extracardial ganglia. -Onsum[693] held at one time a peculiar theory of the action of oxalic -acid, believing that it precipitated as oxalate of lime in the lung -capillaries, causing embolic obstruction; but this view is not now -accepted--there are too many obvious objections to it. Kobert and -Kuessner do not consider oxalic acid a heart poison, but believe that its -action is directed to the central nervous system, as attested by sinking -of the blood-pressure, the arhythm and retardation of the pulse, the -slow breathing, the paralytic symptoms, and the fibrillary muscular -contraction; but, with regard to the latter, Locke[694] has observed -that a frog's sartorius, immersed in 0.75 sodium oxalate solution, -becomes in a few seconds violently active, much more so than in -Biederman's normal saline solution. After thirty to forty-five minutes -it loses its irritability, which, however, it partially recovers by -immersion in 0.6 sodium chloride solution. He thinks this may explain -the symptoms of fibrillary muscular contraction observed by Kobert and -Kuessner, which they ascribe to an action on the central nervous system. - -[692] _Virch. Archiv_, Bd. xx. S. 233. - -[693] Almen afterwards supported Onsum's view; he made a number of -microscopical observations, and appears to have been the first who -identified oxalate of lime in the kidneys (Upsala, _Laekarefoerenings -foerhandl._, Bd. ii. Hft. iv. S. 265). - -[694] F. S. Locke, _J. Phys._, xv. 119; _Journ. Chem. Soc._, 1893, 480. - -Sec. 700. =Pathological Changes.=--Kobert and Kuessner observed that when -oxalate of soda was subcutaneously injected into animals, there was -often abscess, and even gangrene, at the seat of the injection. If the -poison were injected into the peritoneal cavity, death was so rapid as -to leave little time for any coarse lesions to manifest themselves. They -were not able to observe a cherry-red colour of the blood, nor did they -find oxalate of lime crystals in the lung capillaries; there were often -embolic processes in the lung, but nothing typical. They came, -therefore, to the conclusion that the state of the kidneys and the urine -was the only typical sign. The kidneys were dark, full of blood, but did -not show any microscopic haemorrhages. Twelve hours after taking the -poison there is observed in the cortical substance a fine striping -corresponding to the canaliculi; in certain cases the whole boundary -layer is coloured white. If the poisoning lasts a longer time, the -kidneys become less blood-rich, and show the described white striping -very beautifully; this change persists several weeks. The cause of this -strange appearance is at once revealed by a microscopical examination; -it is due to a deposition of oxalate of lime; no crystals are met with -in the glomerules. Both by the microscope and by chemical means it may -be shown that the content of the kidney in oxalates is large.[695] So -far as the tissues generally are concerned, free oxalic acid is not -likely to be met with; there is always present sufficient lime to form -lime oxalate. The urine was always albuminous and contained a reducing -substance, which vanished about the second day after the dose. Hyaline -casts and deposits of oxalates in the urine never failed.[696] - -[695] The important fact of the oxalate-content of kidneys and urine, -and the expulsion of casts, was first observed by Mitscherlich in 1854. -He noticed in a rabbit, to which had been given 7.5 grms. of oxalic -acid, and which had died in thirteen minutes, "_renes paululum magis -sanguine replete videbantur, in urina multa corpora inveniebantur, quae -tubulos Bellenianos explese videntur_" (_De acidi acetici, oxalici, -tartarici, citrici, formici, et boracici, &c., Berlin_). - -[696] Rabuteau has discovered by experiment that even the oxalates of -iron and copper are decomposed and separated by the kidneys. _Gaz. Med. -de Paris_, 1874. - -Sec. 701. Observations of the pathological effects of the oxalates on man -have been confined to cases of death from the corrosive substances -mentioned, and hence the intestinal tract has been profoundly affected. - -In the museum of St. Thomas' Hospital is a good example of the effects -produced. The case was that of a woman who had taken a large, unknown -quantity of oxalic acid, and was brought to the hospital dead. The -mucous membrane of the gullet is much corrugated and divided into -numerous parallel grooves, these again by little transverse grooves, so -that the intersection of the two systems makes a sort of raised pattern. -It is noted that in the recent state the mucous membrane could be -removed in flakes; in the upper part it was whitish, in the lower -slate-coloured. The stomach has a large perforation, but placing the -specimen beside another in the same museum which illustrates the effect -of the gastric juice, in causing an after-death solution of a portion of -the stomach, I was unable to differentiate between the two. The mucous -membrane had the same shreddy flocculent appearance, and is soft and -pale. The pyloric end is said to have been of a blackish colour, and no -lymph was exuded. - -Sec. 702. The pathological changes by the acid oxalate of potash are -identical with those of oxalic acid, in both the gullet and stomach -being nearly always more or less inflamed or corroded; the inflammation -in a few cases has extended right through into the intestinal canal; -there are venous hyperaemia, haemorrhages, and swelling of the mucous -membrane of the stomach. The haemorrhages are often punctiform, but -occasionally larger, arranged in rows on the summits of the rugae; -sometimes there is considerable bleeding. In the greater number of cases -there is no actual erosion of the stomach, but the inner layer appears -abnormally transparent. On examining the mucous membrane under the -microscope, Lesser[697] has described it as covered with a layer which -strongly reflects light, and is to be considered as caused by a fine -precipitate of calcic oxalate. Lesser was unable to find in any case -oxalic acid crystals, or those of the acid oxalate of potash. There are -many cases of perforation on record, but it is questionable whether they -are not all to be regarded as _post-mortem_ effects, and not -life-changes; at all events, there is little clinical evidence to -support the view that these perforations occur during life. In the case -(mentioned _ante_) in which death took place by coma, the brain was -hyperaemic. The kidneys, as in the case of animals, show the white zone, -and are congested, and can be proved by microscopical and chemical -means to be rich in oxalates. - -[697] Virchow's _Archiv_, Bd. lxxxiii. S. 218, 1881. - -Sec. 703. =Separation of Oxalic Acid from Organic Substances, the Tissues -of the Body, &c.=--From what has been stated, no investigation as to the -cause of poison, when oxalic acid is suspected, can be considered -complete unless the analyst has an opportunity of examining both the -urine and the kidneys; for although, in most cases--when the acid -itself, or the acid potassic salt has been taken--there may be ample -evidence, both chemical and pathological, it is entirely different if a -case of poisoning with the neutral sodic salt should occur. In this -event, there may be no congested appearance of any portion of the -intestinal canal, and the evidence must mainly rest on the urine and -kidneys. - -Oxalic acid being so widely distributed in the vegetable kingdom, the -expert must expect, in any criminal case, to be cross-examined by -ingenious counsel as to whether or not it was possible that the acid -could have entered the body in a rhubarb-pie, or accidentally through -sorrel mixed with greens, &c. To meet these and similar questions it is -important to identify, if possible, any green matters found in the -stomach. In any case, it must be remembered, that although rhubarb has -been eaten for centuries, and every schoolboy has occasionally chewed -small portions of sorrel, no poisoning has resulted from these -practices. When oxalic acid has been taken into the stomach, it will -invariably be found partly in combination with lime, soda, ammonia, &c., -and partly free; or if such antidotes as chalk has been administered, it -may be wholly combined. Vomiting is nearly always present, and valuable -evidence of oxalic acid may be obtained from stains on sheets, carpets, -&c. In a recent case of probably suicidal poisoning, the writer found no -oxalic acid in the contents of the stomach, but some was detected in the -copious vomit which had stained the bed-clothes. The urine also -contained a great excess of oxalate of lime--a circumstance of little -value taken by itself, but confirmatory with other evidence. If a liquid -is strongly acid, oxalic acid may be separated by dialysis from organic -matters, and the clear fluid thus obtained precipitated by sulphate of -lime, the oxalate of lime being identified by its microscopic form and -other characters. - -The usual general method for the separation of oxalic acid from organic -substances or mixtures is the following:--Extract with boiling water, -filter (which in some cases must be difficult or even impossible), and -then precipitate with acetate of lead. The lead precipitate may contain, -besides oxalate of lead, phosphate, chloride, sulphate, and various -organic substances and acids. This is to be decomposed by sulphuretted -hydrogen, and on filtering off the sulphide of lead, oxalic acid is to -be tested for in the filtrate. This process can only be adopted with -advantage in a few cases, and is by no means to be recommended as -generally applicable. The best general method, and one which insures -the separation of oxalic acid, whether present as a free acid, as an -alkaline, or a calcic oxalate, is perhaps the following:--The substance -or fluid under examination is digested with hydrochloric acid until a -fluid capable of filtration is obtained; the free acid is neutralised by -ammonia in very slight excess, and permitted to deposit, and the fluid -is then carefully decanted, and the deposit thrown on a filter. The -filtrate is added to the decanted fluid, and precipitated with a slight -excess of acetate of lime--this precipitate, like the first, being -collected on a filter. The first precipitate contains all the oxalic -acid which was in combination with lime; the second, all that which was -in the free condition. Both precipitates should be washed with acetic -acid. The next step is to identify the precipitate which is supposed to -be oxalate of lime. The precipitate is washed into a beaker, and -dissolved with the aid of heat by adding, drop by drop, pure -hydrochloric acid; it is then reprecipitated by ammonia, and allowed to -subside completely, which may take some time. The supernatant fluid is -decanted, and the precipitate washed by subsidence; it is lastly dried -over the water-bath in a tared porcelain dish, and its weight taken. The -substance is then identified by testing the dried powder as follows:-- - -(_a_) It is whitish in colour, and on ignition in a platinum dish leaves -a grey carbonate of lime. All other organic salts of lime--viz., -citrate, tartrate, &c.--on ignition become coal-black. - -(_b_) A portion suspended in water, to which is added some sulphuric -acid, destroys the colour of permanganate of potash--the reaction being -similar to that on p. 511--a reaction by which, as is well known, oxalic -acid or an oxalate may be conveniently titrated. This reaction is so -peculiar to oxalic acid, that there is no substance with which it can be -confounded. It is true that uric acid in an acid solution equally -decolorises permanganate, but it does so in a different way; the -reaction between oxalic acid and permanganate being at first slow, and -afterwards rapid, while the reaction with uric acid is just the -reverse--at first quick, and towards the end of the process extremely -slow. - -(_c_) A portion placed in a test-tube, and warmed with concentrated -sulphuric acid, develops on warming carbon oxide and carbon dioxide; the -presence of the latter is easily shown by adapting a cork and bent tube -to the test-tube, and leading the evolved gases through baryta water. - -Alexander Gunn[698] has described a new method of both detecting and -estimating oxalic acid; it is based on the fact that a small trace of -oxalic acid, added to an acid solution of ferrous phosphate, strikes a -persistent lemon-yellow colour; the depth of colour being proportionate -to the amount of oxalic acid. - -[698] _Pharm. Journal_, 1893, 408. - -The reagents necessary for both quantitative and qualitative testing are -as follows:--A standard solution of oxalic acid, of which 100 c.c. equal -1 grm., and a solution of ferrous phosphate, containing about 12.5 per -cent. of Fe_{3}2PO_{4}, with excess of phosphoric acid. - -Into each of two Nessler graduated glasses 7.5 c.c. of the ferrous -phosphate solution are run and made up to 50 c.c. with distilled water; -both solutions should be colourless; 1, 2, or more c.c. of the solution -to be tested are then run into one of the Nessler glasses; if oxalic -acid be present, a more or less deep tint is produced; this must be -imitated by running the standard solution of oxalic acid into the second -Nessler cylinder--the calculation is the same as in other colorimetric -estimations. It does not appear to be reliable quantitatively, if alum -is present; and it is self-evident that the solution to be tested must -be fairly free from colour. - -Sec. 704. =Oxalate of Lime in the Urine.=--This well-known urinary sediment -occurs chiefly as octahedra, but hour-glass, contracted or dumbbell-like -bodies, compound octahedra, and small, flattened, bright discs, not -unlike blood discs, are frequently seen. It may be usually identified -under the field of the microscope by its insolubility in acetic acid, -whilst the ammonio mag. phosphate, as well as the carbonate of lime, are -both soluble in that acid. From urates it is distinguished by its -insolubility in warm water. A chemical method of separation is as -follows:--The deposit is freed by subsidence as much as possible from -urine, washed with hot water, and then dissolved in hydrochloric acid -and filtered; to the filtrate ammonia is added in excess. The -precipitate may contain phosphates of iron, magnesia, lime, and oxalate -of lime. On treatment of the precipitate by acetic acid, the phosphates -of the alkaline earths (if present) dissolve; the insoluble portion will -be either phosphate of iron, or oxalate of lime, or both. On igniting -the residue in a platinum dish, any oxalate will be changed to -carbonate, and the carbonate of lime may be titrated with d. n. HCl acid -and cochineal solution, and from the data thus obtained the oxalate -estimated. The iron can be tested qualitatively in the acid solution by -ferrocyanide of potassium, or it can be determined by the ordinary -methods. If the qualitative detection of oxalate of lime in the deposit -is alone required, it is quite sufficient evidence should the portion -insoluble in acetic acid, on ignition in a platinum dish, give a residue -effervescing on the addition of an acid. - -Sec. 705. =Estimation of Oxalic Acid.=--Oxalic acid is estimated in the -free state by direct weighing, or by titration either with alkali or by -potassic permanganate, the latter being standardised by oxalic acid. If -(as is commonly the case) oxalic acid is precipitated as oxalate of -lime, the oxalate may be-- - -(_a_) Dried at 100 deg. and weighed directly, having the properties already -described. - -(_b_) Titrated with dilate sulphuric acid and permanganate. - -(_c_) Ignited, and the resulting carbonate of lime weighed; or dissolved -in standard acid and titrated back--one part of calcic carbonate -corresponds to 1.26 part of crystallised oxalic acid, or 0.90 part of -H_{2}C_{2}O_{4}; similarly, 1 c.c. of standard acid equals .05 of calcic -carbonate (or .063 of crystallised oxalic acid). - -(_d_) The oxalate may be dissolved in the smallest possible amount of -hydrochloric acid, and boiled with ammonio chloride of gold, avoiding -exposure to light; every part of gold precipitated corresponds to .961 -part of crystallised oxalic acid. - -(_e_) The oxalate may be placed in Geissler's carbonic acid apparatus, -with peroxide of manganese and diluted sulphuric acid. The weight of the -gas which at the end of the operation has escaped, will have a definite -relation to that of the oxalate, and if multiplied by 1.4318 will give -the amount of crystallised oxalic acid. - - -CERTAIN OXALIC BASES--OXALMETHYLINE--OXALPROPYLINE. - - Sec. 706. Hugh Schulz[699] and Mayer have contributed the results of - some important researches bearing upon a more exact knowledge of the - effects of the oxalic group of poisons, and upon the relation - between chemical constitution and physiological effects. They - experimented upon _oxalmethyline_, _chloroxalmethyline_, and - _oxalpropyline_. - -[699] _Beitrag zur Kenntniss der Wirkung der Oxalbasen auf den -Thierkoerper. Arch. f. exper. Path. u Pharm._, 1882. - - =Chloroxalmethyline= (C_{6}H_{5}ClN_{2}) is a liquid, boiling at - 205 deg., with a weakly narcotic smell. A solution of the hydrochlorate - of the base was employed. Subcutaneous injections of .05 grm. into - frogs caused narcosis, and both this and the ethylic compound - deranged the heart's action, decreasing the number of beats. Thus - .05 grm. decreased the number of the beats of the heart of a frog in - the course of one and three-quarter hours as follows: 72, 60, 56, - 50, 44, 40, 35, 0. - - =Oxalmethyline= produces somewhat similar symptoms, but the nervous - system is more affected than in that which contains chlorine. - - =Oxalpropyline= also causes narcosis, and afterwards paralysis of - the hinder extremities and slowing of the heart. - - The difference between the chlorine-free and the chlorine-containing - oxalic bases are summarised as follows:-- - - FROGS. - - CHLORINE-HOLDING BASES. CHLORINE-FREE BASES. - - Notable narcosis; no heightened Narcosis occurs late, and is - reflex action, muscular cramps, little pronounced; a notable in- - nor spontaneous convulsions. crease of reflex excitability; - more and more muscular paralysis; - between times, muscular cramps. - - CATS. - - Notable narcosis and salivation; Great excitement; general - no mydriasis; convulsions and shivering, rising to pure clonic - paralysis; no change in the convulsions; paralysis of the - respirations. hind legs; notable mydriasis, - jerking, and superficial res- - piration; weak narcosis. - - DOGS. - - Notable narcosis; occasional Narcosis evident; the rest as in - vomiting; the rest as in cats. cats. - - - - -PART IX.--INORGANIC POISONS. - - -I.--PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC -SULPHIDE--PRECIPITATE YELLOW OR ORANGE.[700] - -Arsenic--Antimony--Cadmium. - -[700] Fresenius has pointed out that sulphur may mask small quantities -of arsenic, antimony, tin, &c., and he recommends that the turbid liquid -in which apparently nothing but sulphur has separated should be treated -as follows:--A test-tube is half filled with the liquid, and then a -couple of c.c. of petroleum ether or of benzene added, the tube closed -by the thumb, and the contents well shaken. The sulphur dissolves, and -is held in solution by the solvent, which latter forms a clear upper -layer. If traces of a metallic sulphide were mixed with the sulphur, -thin coloured films are seen at the junction of the two layers, and the -sulphides may also coat the tube above the level of the liquid with a -slight faintly-coloured pellicle (_Chem. News_, Jan. 4, 1895). - - -1. ARSENIC. - -Sec. 707. =Metallic Arsenic=, at. wt. 75, specific gravity of solid 5.62 to -5.96, sublimes without fusion in small quantities at 110 deg. (230 deg. F.) -_Guy_. It occurs in commerce in whitish-grey, somewhat brittle, -crystalline masses, and is obtained by subjecting arsenical pyrites to -sublimation in earthen retorts, the arsenic being deposited in suitable -receivers on sheet iron. Metallic arsenic is probably not poisonous, but -may be changed by the animal fluids into soluble compounds, and then -exert toxic effects--volatilised metallic arsenic is easily transformed -in the presence of air into arsenious acid, and is therefore intensely -poisonous. - -Sec. 708. =Arsenious Anhydride--Arsenious Acid--White Arsenic--Arsenic=, -As_{2}O_{3} = 198; specific gravity of vapour, 13.85; specific gravity -of opaque variety, 3.699; specific gravity of transparent variety, -3.7385. Composition in 100 parts, As 75.75, O 24.25; therefore one part -of metallic arsenic equals 1.32 of As_{2}O_{3}. It is entirely -volatilised at a temperature of 204.4 deg. - -In analysis it is obtained in brilliant octahedral crystals as a -sublimate on discs of glass, or within tubes, the result of heating a -film of metallic arsenic with access of air. It is obtained in commerce -on a very large scale from the roasting of arsenical pyrites. As thus -derived, it is usually in the form of a white cake, the arsenious acid -existing in two forms--an amorphous and a crystalline--the cake being -generally opaque externally, whilst in the centre it is transparent. -According to Kruger, this change from the crystalline to the amorphous -condition is dependent upon the absorption of moisture, no alteration -taking place in dry air. Both varieties of arsenious anhydride are acid -to test-paper. - -The solubility of arsenious acid is often a question involving chemical -legal matters of great moment. Unfortunately, however, no precisely -definite statement can be made on this point, the reason being that the -two varieties of arsenic occur in very different proportions in -different samples. Both the amorphous and crystalline varieties having -very unequal solubilities, every experimenter in succession has given a -different series of figures, the only agreement amid the general -discrepancy being that arsenic is very sparingly soluble in water. - -The statement of Taylor may, however, be accepted as very near the -truth, viz., that an ounce of cold water dissolves from half a grain to -a grain. According to M. L. A. Buchner,[701] one part of crystalline -arsenious acid dissolves after twenty-four hours' digestion in 355 parts -of water at 15 deg.; and the amorphous, under the same condition, in 108 of -water. A boiling solution of the crystalline acid, left to stand for -twenty-four hours, retains one part of acid in 46 of water; a similar -solution of the amorphous retains one of arsenic in 30 parts of water, -_i.e._, 100 parts of water dissolve from 2.01 to 3.3 parts of -As_{2}O_{3}. - -[701] _Bull. de la Societe Chem. de Paris_, t. xx. 10, 1873. - -Boiling water poured on the powdered substance retains in cooling a -grain and a quarter to the ounce; in other words, 100 parts of water -retain .10. Lastly, arsenious acid boiled in water for an hour is -dissolved in the proportion of 12 grains to the ounce, _i.e._, 100 parts -of water retain 2.5. - -K. Chodomisky[702] has investigated the solubility of recrystallised -arsenious acid in dilute acids, and his results are as follows:--100 -c.c. of 1.32 per cent. hydrochloric acid dissolves 1.15 grm. As_{2}O_{3} -at 18.5 deg. 100 c.c. of 6 per cent. hydrochloric acid dissolves 1.27 grm. -at 18.5 deg. 100 c.c. of pure hydrochloric acid of the ordinary commercial -strength dissolves 1.45 grm. As_{2}O_{3}. 100 c.c. of dilute sulphuric -acid at 18 deg. dissolves about 0.54 grm.; at 18.5 deg. from 0.65 to 0.72 grm.; -and at 80 deg. from 1.09 to 1.19 grm. - -[702] _Chem. Centrbl._, 1889, 569. - -Sec. 709. =Arsine--Arseniuretted Hydrogen=, H_{3}As.--Mol. weight, 78; vol. -weight, 39; specific gravity, 2.702; weight of a litre, 3.4944 grammes; -percentage composition, 95.69 As, 4.31 H; volumetric composition, 2 vol. -H_{3}As = half vol. As + 3 vol. H. A colourless inflammable gas, of a -f[oe]tid alliaceous odour, coercible into a limpid colourless liquid at -a temperature of from -30 deg. to -40 deg. The products of the combustion of -arseniuretted hydrogen are water and arsenious acid; thus, 2H_{3}As + 6O -= 3H_{2}O + As_{2}O_{3}. If supplied with air in insufficient quantity, -if the flame itself be cooled by (for example) a cold porcelain plate, -or if the gas pass through a tube any portion of which is heated to -redness, the gas is decomposed and the metal separated. Such a -decomposition may be compared to the deposit of carbon from ordinary -flames, when made to play upon a cooled surface. It may also be -decomposed by the electric spark,[703] _e.g._, if the gas is passed -slowly through a narrow tube 0.7 to 0.8 mm. internal diameter, provided -with wires 0.5 to 0.6 mm. apart, and a small induction coil used -connected with two large Bunsen's cells, then, under these conditions, -arsenic as a metal is deposited in the neighbourhood of the sparks. For -the decomposition to be complete, the gas should not be delivered at a -greater speed than from 10 to 15 c.c. per minute. The gas burns with a -blue-white flame, which is very characteristic, and was first observed -by Wackenroder. It cannot, however, be properly seen by using the -ordinary apparatus of Marsh, for the flame is always coloured from the -glass; but if the gas is made to stream through a platinum jet, and then -ignited, the characters mentioned are very noteworthy. - -[703] N. Klobrikow, _Zeit. Anal. Chem._, xxix. 129-133. - -Oxygen or air, and arsine, make an explosive mixture. Chlorine -decomposes the gas with great energy, combining with the hydrogen, and -setting free arsenic as a brown cloud; any excess of chlorine combines -with the arsenic as a chloride. Sulphur, submitted to arseniuretted -hydrogen, forms sulphuretted hydrogen, whilst first arsenic and then -sulphide of arsenic separate. Phosphorus acts in a similar way. -Arseniuretted and sulphuretted hydrogen may be evolved at ordinary -temperatures without decomposition; at the boiling-point of mercury -(350 deg.) they are decomposed, sulphide of arsenic and hydrogen being -formed; thus, 3H_{2}S + 2AsH_{3} = As_{2}S_{3} + 6H_{2}, a reaction -which is of some importance from a practical point of view. Many metals -have also the property of decomposing the gas at high temperatures, and -setting hydrogen free. Metallic oxides, again, in like manner combine -with arsenic, and set water free, _e.g._, 3CuO + 2H_{3}As = Cu_{3}As_{2} -+ 3H_{2}O. - -Arsine acts on solutions of the noble metals like phosphuretted -hydrogen, precipitating the metal and setting free arsenious acid; for -example, nitrate of silver is decomposed thus-- - - 12AgNO_{3} + 2H_{3}As + 3H_{2}O = As_{2}O_{3} + 12HNO_{3} + 12Ag. - -Vitali[704] thinks the reaction is in two stages, thus:-- - -[704] _L'Orosi_, 1892, 397-411. - - (1) 2AsH_{3} + 12AgNO_{3} = 2(Ag_{3}As3AgNO_{3}) + 6HNO_{3}. - - (2) 2(Ag_{3}As,3AgNO_{3}) + 6H_{2}O = 6HNO_{3} + 6Ag_{2} + - 2H_{3}AsO_{3}. - -This reaction admits of valuable practical application to the estimation -of arsenic; for the precipitated silver is perfectly arsenic-free; the -excess of nitrate of silver is easily got rid of by a chloride of sodium -solution, and the absorption and decomposition of the gas are complete. - -In cases of poisoning by arsine, the blood, when examined by the -spectroscope (a process the analyst should never omit where it is -possible), is of a peculiar inky colour, and the bands between D and C -are melted together, and have almost vanished. Such blood, exposed to -oxygen remains unaltered. - -Sec. 710. =Arsine in the Arts, &c.=--In the bronzing of brass, in the -desilverising of lead by zinc, and subsequent treatment of the silver -zinc with hydrochloric acid, in the tinning of sheet iron, and similar -processes, either from the use of acids containing arsenic as an -impurity, or from the application of arsenic itself, arsine is evolved. - -Sec. 711. =Effects on Animals and Man of Breathing Arsine.=--The most -general effect on mammals is to produce jaundice, bloody urine, and -bile. In the course of numerous experiments on dogs, Stadelmann[705] -found that by making them breathe a dose of arsine, which would not be -immediately fatal, icterus was always produced under these -circumstances, and could be always detected by the appearance of the -tissues. The bile is remarkably thickened, and the theory is, that in -such cases the jaundice is purely mechanical, the gall-duct being -occluded by the inspissated bile. Rabbits experimented upon similarly -showed increased biliary secretion, but no jaundice; while it was proved -that cats are not so sensitive to arsine as either rabbits or dogs. -There are not wanting instances of arsine having been breathed by -man--the discoverer of the gas, Gehlen, was in fact the first victim on -record. In order to discover a flaw in his apparatus he smelt strongly -at the joints, and died in eight days from the effects of the -inhalation. - -[705] _Die Arsenwasserstoff-Vergiftung, Archiv f. exper. Path. u. -Pharm._, Leipzig, 1882. - -Nine persons, workmen in a factory, were poisoned by arsine being -evolved during the treatment by hydrochloric acid of silver-lead -containing arsenic. Three of the nine died; their symptoms were briefly -as follows:-- - -(1) H. K., 22 years old; his duty was to pour hydrochloric acid on the -metal. Towards mid-day, after this operation, he complained of nausea, -giddiness, and _malaise_. In the afternoon he felt an uncommon weight of -the limbs, and an oppression in breathing. His fellow-workmen thought -that he looked yellow. On going home he lay down and passed into a -narcotic sleep. Next morning he went to his work as usual, but was not -capable of doing anything; he passed bloody urine several times -throughout the day, and fell into a deep sleep, from which he could -scarcely be roused. On the third day after the accident, a physician -called in found him in a deep sleep, with well-developed jaundice, the -temperature moderately high, pulse 100. On the fifth day the jaundice -diminished, but it was several months before he could resume his work. - -(2) J. T., aged 19, suffered from similar symptoms after five and a half -hours' exposure to the gas. He went home, vomited, was jaundiced, and -suffered from bloody urine; in six days became convalescent, but could -not go to work for many months. - -(3) C. E. was very little exposed, but was unwell for a few days. - -(4) L. M., 37 years old, was exposed two days to the gas; he vomited, -had bloody urine, passed into a narcotic sleep, and died in three days -from the date of the first exposure. - -(5) J. S., aged 40, was exposed for two days to the gas; the symptoms -were similar to No. 4, there was suppression of urine, the catheter -drawing blood only, and death in eight days. - -(6) M. E., 36 years old; death in three days with similar symptoms. - -(7), (8), and (9) suffered like Nos. 1 and 2, and recovered after -several months. - -The chief _post-mortem_ appearance was a dirty green colour of the -mucous membrane of the intestines, and congestion of the kidneys. -Arsenic was detected in all parts of the body.[706] - -[706] Trost, _Vergiftung durch Arsenwasserstoff bei der technischen -Gewinnung des Silbers, Vierteljahrsschrift f. gericht. Med._, xviii. -Bd., 2 Heft, S. 6, 1873. - -Two cases are detailed by Dr. Valette in Tardieu's _Etude_.[707] A -mistake occurred in a laboratory, by which a solution of arsenic -(instead of sulphuric acid) was poured on zinc to develop hydrogen. Of -the two sufferers, the one recovered after an illness of about a week or -ten days, the other died at the end of twenty-eight days. The main -symptoms were yellowness of skin, vomiting, bloody urine, great -depression, slight diarrh[oe]a, headache, and in the fatal case a -morbiliform eruption. In a case recorded in the _British Medical -Journal_, November 4, 1876, there were none of the usual symptoms of -gastric irritation, but loss of memory of recent acts, drowsiness, and -giddiness. - -[707] Ambroise Tardieu, _Etude Medico-legale sur l'Empoisonnement_, Obs. -xxv. p. 449. - -Sec. 712. =The Sulphides of Arsenic.=--Of the sulphides of arsenic, two -only, realgar and orpiment, are of any practical importance. _Realgar_, -As_{2}S_{2} = 214; specific gravity, 3.356; composition in 100 parts, As -70.01, S 29.91; average composition of commercial product, As 75, S 25. -Realgar is found native in ruby-red crystals, and is also prepared -artificially by heating together 9 parts of arsenic and 4 of sulphur, or -198 parts of arsenious anhydride with 112 parts of sulphur, 2As_{2}O_{3} -+ 7S = 2As_{2}S_{2} + 3SO_{2}. It is insoluble in water and in -hydrochloric acid, but is readily dissolved by potassic disulphide, by -nitric acid, and by aqua regia. It is decomposed by caustic potash, -leaving undissolved a brown sediment (As_{12}S), which contains 96.5 per -cent. of arsenic. The dissolved portion is readily converted into arsine -by aluminium. - -Sec. 713. =Orpiment, or Arsenic Trisulphide.=--As_{2}S_{3} = 246; specific -gravity, 3.48; composition in 100 parts, As 60.98, S 39.02; found native -in crystals, presents itself in the laboratory usually as a brilliant -yellow amorphous powder, on passing sulphuretted hydrogen through an -acid solution of arsenious acid or an arsenite. It is very insoluble in -water (about one in a million, _Fresenius_), scarcely soluble in boiling -concentrated hydrochloric acid, and insoluble generally in dilute acids. -Red fuming nitric acid dissolves it, converting it into arsenic and -sulphuric acids; ammonia and other alkaline sulphides, the alkalies -themselves, alkaline carbonates, bisulphide of potassium, and aqua -regia, all dissolve it readily. In the arts it is used as King's yellow -(see p. 532). Tanners also formerly employed a mixture of 90 parts of -orpiment and 10 of quicklime, under the name of _Rusma_, as a -depilatory; but the alkaline sulphides from gas-works are replacing this -to a great extent. - -Sec. 714. =Haloid Arsenical Compounds.--The Chloride of Arsenic=, AsCl_{3} -= 181.5; specific gravity liquid, 0 deg. 2.205; boiling-point 134 deg. -(273.2 deg.F.), is a heavy, colourless, oily liquid, which has been used as -an escharotic in cancerous affections (principally by quacks). In one -process of detecting and estimating arsenic, the properties of this -substance are utilised (see p. 575). It is immediately decomposed by -water into arsenious and hydrochloric acids. - -=The Iodide of Arsenic= (AsI_{3}) is used occasionally in skin diseases, -but is of little interest to the analyst; it is commonly seen in the -form of brick-red brilliant flakes. - -Sec. 715. =Arsenic in the Arts.=--The metal is used in various alloys; for -example, speculum metal is made of tin, copper, and a little arsenic; -white copper is an alloy of copper and arsenic; shot is composed of 1000 -parts of lead mixed with 3 of arsenic; the common Britannia metal used -for tea-pots, spoons, &c., often contains arsenic; and brass is bronzed -with a thin film of arsenic. It was formerly much employed in the -manufacture of glass, but is being gradually superseded. It is also now -used to some extent in the reduction of indigo blue, and in that of -nitro-benzole in the manufacture of aniline. - -In cases of suspected poisoning, therefore, and the finding of arsenic -in the stomach, or elsewhere, it may be set up as a defence that the -arsenic was derived from shot used in the cleansing of bottles, from the -bottles themselves, or from metal vessels, such as tea-pots, &c. - -The arsenic in all these alloys being extremely insoluble, any solution -to a poisonous extent is in the highest degree improbable. It may, -however, be necessary to treat the vessels with the fluid or fluids -which have been supposed to exert this prejudicial action, and test -them for arsenic. The treatment should, of course, be of a severe and -exhaustive character, and the fluids should be allowed to stand cold in -the vessels for twenty-four hours; then the effect of a gentle heat -should be studied, and, lastly, that of boiling temperatures. The -analysis of the alloy itself, or of the glass, it would seldom be of -value to undertake, for the crushed and finely divided substance is in a -condition very different from that of the article when entire, and -inferences drawn from such analytical data would be fallacious. - -Arsenious anhydride is also used for the preservation of wood, and is -thrown occasionally into the holds of vessels in large quantities to -prevent vegetable decomposition. In India, again, a solution of arsenic -is applied to the walls as a wash, in order to prevent the attacks of -insects. - -Sec. 716. =Pharmaceutical, Non-officinal, and other Preparations of -Arsenic.=--(1) =Pharmaceutical Preparations.=--The Liquor arsenicalis -(Fowler's solution), or solution of arsenic of the pharmacop[oe]ia, is -composed of:-- - - Carbonate of Potash, 87 grains (5.64 grms.) - Arsenious Acid, 87 " (5.64 " ) - Compound Tincture of Lavender, 5 drachms (17.72 c.c.) - -dissolved in 1 pint (567.9 c.c.) of water; every ounce, therefore, -contains 4.3 grains of arsenious acid (or 100 c.c. = .9As_{2}O_{3}); the -strength is therefore nearly 1 per cent. - -=Liquor Ammonii Arsenitis= (not officinal) is made of the same strength, -ammonium carbonate being substituted for potassic carbonate. - -The _hydrochloric solution of arsenic_ is simply arsenious acid -dissolved in hydrochloric acid; its strength should be exactly the same -as that of Fowler's solution. - -A solution of _arseniate of soda_[708] contains the _anhydrous_ salt in -the proportion of 4 grains to the ounce (.9 in 100 c.c.) of water. - -[708] The formula for arseniate of soda is Na_{2}HAsO_{4}7H_{2}O, but it -sometimes contains more water. - -=Liquor Arsenii et Hydrargyri Iodidi= (Donovan's Solution of -Arsenic).--This is not officinal, but is used to some extent in skin -diseases; it is a solution of the iodides of mercury and arsenic; -strength about 1 per cent. of each of the iodides. - -=Arseniate of Iron=, Fe_{3}As_{2}O_{8}, is an amorphous green powder, -used to some extent in medicine. It should contain 33.6 per cent. of -metallic arsenic. - -=Clemen's Solution.=--A solution of the bromide and arseniate of -potassium; strength equal to 1 per cent. arsenious acid. Officinal in -U.S., France, and Norway. - -=Pilula Asiatica= (not officinal) is composed of arsenious acid, extract -of gentian, and black pepper. There is 1/12th of a grain (5.4 -milligrams) of arsenious acid in each pill. - -=Dr. De Valanguis' Solutio solventes mineralis= is composed of 30 grains -of As_{2}O_{3} dissolved by 90 minims of HCl in 20 oz. of water; -strength = 0.034 per cent. As_{2}O_{3}. - -(2) =Veterinary Arsenical Medicine.=--Common veterinary preparations -containing arsenic are:--A ball for worms, containing in parts-- - - Calomel, 1.3 per cent. - Arsenious Acid, 1.3 " - Tin Filings, 77.9 " - Venice Turpentine,[709] 19.5 " - -[709] The Venice turpentine is rarely found in ordinary commerce, what -is sold under that name consisting of black resin and oil of turpentine. - -A common tonic ball:[710]-- - -[710] A similar preparation in common use has the addition of sulphate -of zinc. - - Arsenious Acid, 5 to 10 grains (.324 to .648 grm.) - Aniseed, 1/2 oz. (14.1744 grms.) - Opium, 30 grains ( 1.94 " ) - Treacle, q. s. - -An arsenical ball, often given by grooms to horses for the purpose of -improving their coats, contains in 100 parts:-- - - Arsenious Acid, 2.5 per cent. - Pimento, 19.2 " - Extract of Gentian, 78.3 " - -Another ball in use is composed of arsenic and verdigris (acetate of -copper), of each 8 grains (.518 grm.); cupric sulphate, 20 grains (1.3 -grm.); q. s. of linseed meal and treacle. - -(3) =Rat and Fly Poisons, &c.=--An arsenical paste sold for rats has the -following composition:-- - - Arsenious Acid, 5.0 per cent. - Lampblack, .6 " - Wheat Flour, 46.3 " - Suet, 46.3 " - Oil of Aniseed, a small quantity. - -Another rat poison is composed as follows:-- - - White Arsenic, 46.8 per cent. - Carbonate of Baryta, 46.8 " - Rose-pink,[711] 5.8 " - Oil of Aniseed, .2 " - Oil of Rhodium, .2 " - -[711] Alum and carbonate of lead coloured with Brazil and peach woods. - -Various arsenical preparations are used to kill flies; the active -principle of the brown "_papier moure_" is arsenious acid. A dark grey -powder, which used to be sold under the name of fly-powder, consisted of -metallic arsenic that had been exposed some time to the air. - -=Fly-water= is a strong solution of arsenious acid of uncertain -strength, sweetened with sugar, treacle, or honey. Another fly-poison -consists of a mixture of arsenious acid, tersulphide of arsenic, -treacle, and honey. - -(4) =Quack and other Nostrums.=--The analyst may meet with several quack -preparations for external use in cancer. A celebrated arsenical paste -for this purpose is composed of:-- - - Arsenious Acid, 8 per cent. - Cinnabar, 70 " - Dragon's Blood, 22 " - -=Freres Come's Cancer Paste= is composed of arsenious acid, 1; charcoal, -1; red mercury sulphide, 4; water, q. s. - -The tasteless "_ague drops_" used in the fen countries are simply a -solution of arsenite of potash. - -=Davidson's Cancer Remedy= consists, according to Dr. Paris, of equal -parts of arsenious acid and powdered hemlock. - -In India, arsenic given as a medicine by native practitioners, or -administered as a poison, may be found coloured and impure, from having -been mixed either with cow's urine, or with the juice of leaves, -&c.[712] - -[712] Chevers, _Med. Jurisprudence for India_, p. 116. - -Arsenious acid is used by dentists to destroy the nervous pulp of -decayed and painful teeth, about the twenty-fifth of a grain (2.5 -mgrms.) being placed in the cavity. A common formula is arsenious acid, -2; sulphate of morphine, 1; creasote, q. s. to make a stiff paste. There -is no record of any accident having resulted from this practice -hitherto; but since the dentist seldom weighs the arsenic, it is not -altogether free from danger. - -(5) =Pigments, &c.=--_King's yellow_ should be As_{2}S_{3}, the -trisulphide of arsenic or orpiment. It is frequently adulterated with 80 -to 90 per cent. of arsenious acid, and in such a case is, of course, -more poisonous. King's yellow, if pure, yields to water nothing which -gives any arsenical reaction. - -A blue pigment, termed _mineral blue_, consists of about equal parts of -arsenite of copper and potash, and should contain 38.7 per cent. of -metallic arsenic (= to 51.084 As_{2}O_{3}H) and 15.6 of copper. - -=Schweinfurt green= (Syn. _Emerald-green_), -(CuAs_{2}O_{4})_{3}Cu(C_{2}H_{3}O_{2})_{2} is a cupric arsenite and -acetate, and should contain 25 per cent. of copper and 58.4 per cent. of -arsenious acid. In analysis, the copper in this compound is readily -separated from the arsenic by first oxidising with nitric acid, and then -adding to the nitric acid solution ammonia, until the blue colour -remains undissolved. At this point ammonium oxalate is added in excess, -the solution is first acidified by hydrochloric or nitric acid, and, on -standing, the copper separates completely (or almost so) as Oxalate, the -arsenic remaining in solution. - -Another method is to pass SH_{2} to saturation, collect the sulphides on -a filter, and, after washing and drying the mixed sulphides, oxidise -with fuming nitric acid, evaporate to dryness, and again treat with -nitric acid. The residue is fused with soda and potassic nitrate, the -fused mass is dissolved in water, acidulated with nitric acid, and the -copper is precipitated by potash; the solution is filtered, and in the -filtrate the arsenic is precipitated as ammonio-magnesian arseniate or -as trisulphide.[713] - -[713] P. Gucci, _Chem. Centrbl._, 1887, 1528. - -=Scheele's green= (CuHAsO_{3}) is a hydrocupric arsenite, and contains -52.8 per cent. of arsenious anhydride and 33.8 per cent. of copper. - -(6) =External Application of Arsenic for Sheep, &c.=--Many of these are -simply solutions of arsenic, the solution being made by the farmer. Most -of the yellow sheep-dipping compounds of commerce are made up either of -impure carbonate of potash, or of soda ash, arsenic, soft soap, and -sulphur. The French _bain de Tessier_ is composed of:-- - - Arsenious Acid, 1.00 kgrm. - Ferrous Sulphate, 10.00 " - Peroxide of Iron, 0.40 " - Gentian Powder, 0.20 " - -This is to be added to 100 kgrms. of water. Another common application -consists of alum and arsenic (10 or 12 to 1), dissolved in two or three -hundred parts of water. - -(7) =Arsenical Soaps, &c.=--Arsenic is used in preserving the skins of -animals. One of the compounds for this purpose, known under the name of -_Becoeur's arsenical soap_, has the following composition:-- - - Camphor, 3.4 per cent. - Arsenic, 20.2 " - Carbonate of Potash, 56.2 " - Lime,[714] 20.2 " - -[714] The dust from the preserved skins of animals has caused, at least, -one case of poisoning. _Ann. d'Hyg. Pub. et de Med. Leg._, 2 ser., 1870, -t. xxxiii, p. 314. - -(8) =Arsenical compounds= used in pyrotechny:-- - - Parts. - Blue fires--(1) Realgar, 2 - Charcoal, 3 - Potassic Chlorate, 5 - Sulphur, 13 - Nitrate of Baryta, 77 - ----- - (2) Sulphur, 40.9 - Nitre, 36.8 - Sulphide of Antimony, 12.3 - " Arsenic, 5 - Charcoal, 5 - ----- - Green fires--Metallic Arsenic, 2 - Charcoal, 3 - Chlorate of Potash, 5 - Sulphur, 13 - Nitrate of Baryta, 7 - ------ - Light green fire--Charcoal, 1.75 - Sulphide of Arsenic, 1.75 - Sulphur, 10.50 - Chlorate of Potash, 23.25 - Nitrate of Baryta, 62.50 - ------ - White fire--(1) Arsenious Acid, .76 - Charcoal, 1.63 - Sulphide of Antimony, 12.27 - Nitrate of Potash, 36.59 - Sulphur, 48.75 - ------ - (2) Realgar, 6.1 - Sulphur, 21.2 - Nitrate of Potash, 72.7 - ------ - -Sec. 717. =Statistics.=--During the ten years 1883-92 there were registered -in England and Wales 113 deaths from arsenic; of these 57, or about -half, were suicidal deaths, and 5 were classed under the head of -"murder"; the rest were due to accident. The age and sex distribution of -persons dying from accidental or suicidal arsenical poisoning are -detailed in the following table:-- - -DEATHS FROM ARSENIC DURING THE TEN YEARS 1883-1892. - - ACCIDENT OR NEGLIGENCE. - - Ages, 1-5 5-15 15-25 25-65 65 and Total - above - Males, 1 4 3 23 6 37 - Females, 4 ... 3 4 3 14 - --------------------------------------- - Total, 5 4 6 27 9 51 - --------------------------------------- - - SUICIDE. - - Ages, 15-25 25-65 65 and Total - above - Males, 3 32 2 37 - Females, 5 12 3 20 - ---------------------------- - Total, 8 44 5 57 - ---------------------------- - -Sec. 718. =Law Relative to the Sale of Arsenic.=--By the 14th of Vict. c. -12, every person selling arsenic is bound to keep a written record of -every particular relative to each transaction, such as the name, abode, -and calling of the purchaser, the purpose for which the poison is -required, and the quantity sold, &c. These particulars are to be signed -also by the purchaser. No person (sec. 2) is allowed to sell arsenic to -any one unknown to the seller, unless in the presence of a witness whom -the seller is acquainted with. The arsenic sold (sec. 3) is to be mixed -with soot or indigo in the proportion of half an ounce of indigo to a -pound of arsenic. It, therefore, follows that the coloured substance -should not contain more than 70 per cent. of arsenious acid. The Act -applies to all the colourless preparations of arsenic: but it is not to -affect chemists in making up prescriptions for medical men, or in -supplying medical men; nor is it to affect the wholesale dealers in -supplying arsenic to retail shops, &c. The penalty for conviction is -L20, or less.[715] - -[715] Commercial arsenic is often much adulterated, especially with -gypsum, chalk, &c. These are most readily detected by subliming the -arsenic. The sublimed arsenic itself may not be entirely pure, sometimes -containing arsenical sulphides and antimonious oxide. - -Sec. 719. =Dose.=--The smallest dose of arsenic known to have proved fatal -to a human being is .16 grm. (2-1/2 grains). Farriers and grooms are in -the habit of giving as much as l.3 grm. (20 grains) a day to a horse, so -that the poisonous dose for this animal must be very large. - -The maximum dose for the horned cattle appears to be from .32 to .38 -grm. (5 to 6 grains); that for a dog is 16 mgrms. (1/4 grain), and even -this may, in the smaller kinds, cause illness. - -The following may be considered as _dangerous doses_ of arsenic:--.13 -grm. (2 grains) for an adult; 1.9 grm. (30 grains) for a horse; .64 grm. -(10 grains) for a cow; and 32 to 64 mgrms. (1/2 to 1 grain) for a dog. - -Sec. 720. =Effects of Arsenious Acid on Plants.=--If the root or stem of a -plant is immersed in a solution of arsenious acid, the hue of the leaves -soon alters in appearance, the green colour becomes of a whitish or -brownish hue, and the plant withers; the effect being very similar to -that produced by hot water. The toxic action may be traced from below -upwards, and analysis will detect minute quantities of arsenic in all -portions of the plant. - -It has, however, been shown by Gorup-Besanez,[716] that if arsenious -acid be mixed with earth, and plants grown in such earth, they only take -up infinitesimal quantities of arsenic. Hence, in cases of cattle -poisoning, any defence based upon the alleged presence of arsenic in the -pasture will be more ingenious than just. - -[716] _Annal. d. Chemie u. Pharmacie_, Bd. cxxvii., H. 2, 243. - -The influence of arsenical fumes as evolved from manufactories upon -shrubs and trees is in general insignificant. Pines and firs, five to -six years old, have been known to suffer from a disease in which there -is a shedding of the leaves, the more tender herbage being at the same -time affected. Whatever dangers the practice of steeping corn intended -for seed in a solution of arsenious acid, as a preventive of "smut," may -possess, it does not appear to influence deleteriously the growth of the -future plant. - -Superphosphate of manure is frequently rich in arsenic. Dr. Edmund Davy -asserts that plants to which such manure is applied take up arsenic in -their tissues, and M. Andonard has made a similar statement. Tuson[717] -has also undertaken some experiments, which confirm Andonard and Davy's -researches. The bearing of this with relation to the detection of -arsenic in the stomachs of the herbivora needs no comment. - -[717] Cooley's _Dictionary_, Art. "Arsenic." - -Sec. 721. =Effects on Animal Life--Animalcules.=--All infusoria and forms -of animalcule-life hitherto observed perish rapidly if a minute quantity -of arsenious acid is dissolved in the water in which they exist. - -=Insects.=--The common arsenical fly-papers afford numerous -opportunities for observing the action of arsenic on ordinary flies; -within a few minutes (five to ten after taking the poison into their -digestive organs) they fall, apparently from paralysis of the wings, and -die. Spiders and all insects into which the poison has been introduced -exhibit a similar sudden death. It is said that in the neighbourhood of -arsenical manufactories there is much destruction among bees and other -forms of insect life. - -=Annelids.=--If arsenious acid is applied to the external surface of -worms or leeches, the part which it touches perishes first, and life is -extinguished successively in the others. If a wound is made first, and -the arsenious acid then applied to it, the effects are only intensified -and hastened. There is always noticed an augmentation of the excretions; -the vermicular movements are at first made more lively, they then become -languid, and death is very gradual. - -=Birds.=--The symptoms with birds are somewhat different, and vary -according to the form in which the poison is administered, viz., whether -as a vapour or in solution. In several experiments made by Eulenberg on -pigeons, the birds were secured under glass shades, and exposed to the -vapour of metallic arsenic vaporised by heat. It is scarcely necessary -to remark that in operating in this way, the poisoning was not by -metallic arsenic vapour, but by that of arsenious acid. One of these -experiments may be cited:--A pigeon was made to breathe an atmosphere -charged with vapour from the volatilisation of metallic arsenic. The -bird was immediately restless; in thirty minutes it vomited repeatedly, -and the nasal apertures were noticed to be moist; after a little while, -the bird, still breathing the arsenious acid atmosphere, was much -distressed, shook its head repeatedly, and yawned; in fifty minutes the -respiration was laboured, and in fifty-nine minutes there was much -vomiting. On removing the bird, after it had been exposed an hour to the -vapour (.16 grm. of metallic arsenic having been evaporated in all), it -rapidly recovered. - -Six days after, the pigeon was again exposed in the same way to the -vapour, but this time .56 grm. of metallic arsenic was volatilised. In -fifteen minutes there was retching, followed by vomiting. On taking it -out after an hour it remained very quiet, ate nothing, and often puffed -itself out; the breathing was normal, movements free, but it had unusual -thirst. On the second and third day the excretions were frequent and -fluid; the cardiac pulsations were slowed, and the bird was disinclined -to move. On the fourth day it continued in one place, puffing itself -out; towards evening the respirations slowed, the beak gaping at every -inspiration. On attempting flight, the wings fluttered and the bird fell -on its head. After this it lay on its side, with slow, laboured -respiration, the heart-beats scarcely to be felt, and death took place -without convulsions, and very quietly. On examining the organs after -death, the brain and spinal cord were very bloodless; there were -ecchymoses in the lungs; but little else characteristic. The experiment -quoted has a direct bearing upon the breathing of arsenical dust; as, -for example, that which floats in the air of a room papered with an -easily detached arsenical pigment. Other experiments on birds generally -have shown that the symptoms produced by arsenious acid in solution, or -in the solid form, in a dose insufficient to destroy life, are languor, -loss of appetite, and the voidance of large quantities of liquid excreta -like verdigris. With fatal doses, the bird remains quiet; there are -fluid, sometimes bloody, excretions; spasmodic movements of the pharynx, -anti-peristaltic contraction of the [oe]sophagus, vomiting, general -trembling of the body, thirst, erection of the feathers, and laboured -respiration. The bird becomes very feeble, and the scene mostly closes -with insensibility and convulsions. - -=Mammals=, such as cats, dogs, &c., suffer from symptoms fairly -identical with those observed in man; but the nervous symptoms -(according to P. Hugo) do not predominate, while with rabbits and -guinea-pigs, nervous symptoms are more marked and constant.[718] There -are vomiting, purging, and often convulsions and paralysis before death. -It has been noticed that the muscles after death are in a great state of -contraction. The slow poisoning of a dog, according to Lolliot,[719] -produced an erythematous eruption in the vicinity of the joints, ears, -and other parts of the body; there were conjunctivitis, increased -lachrymal secretion, and photophobia; the hair fell off. - -[718] _Archiv f. exper. Path. u. Pharmakol_, Leipzig, 1882. - -[719] _Etude Physiol. d'Arsene_, These, Paris, 1868. - -Sec. 722. =Effects of Arsenious Acid on Man.=--The symptoms produced by -arsenious acid vary according to the form of the poison--whether solid, -vaporous, or soluble--according to the condition of bodily health of the -person taking it, and according to the manner in which it is introduced -into the animal economy, while they are also in no small degree modified -by individual peculiarities of organisation and by habit, as, for -instance, in the arsenic-eaters. - -=Arsenic-Eaters.=--In all European countries grooms and horse-dealers -are acquainted with the fact that a little arsenic given daily in the -corn improves the coat, increases, probably, the assimilation of the -food, and renders the horse plump and fat. On the Continent grooms have -been known to put a piece of arsenic, the size of a pea, in a little -oatmeal, make it into a ball, tie it up in a linen rag, and attach it to -the bit; the saliva dissolves, little by little, the poison, while both -the gentle irritation and physiological action excite a certain amount -of salivation, and the white foam at the mouth, and the champing of the -horse, are thought vastly to improve the appearance. Shot, which -contains a small quantity of arsenic, have been used for the same -purpose, and from half a pound to a pound of small shot has been given -to horses. When a horse has been for a long time dosed with arsenic, it -seems necessary to continue the practice; if this is not done, the -animal rapidly loses his condition. The explanation probably is, that -the arsenic stimulates the various cells and glands of the intestinal -tract to a superaction, the natural termination of which is an -enfeeblement of their secreting power--this especially in the absence of -the stimulus. Turning from equine involuntary arsenic-eaters, we find -the strange custom of arsenic-eating voluntarily pursued by the races of -lower Austria and Styria, especially by those dwelling on the mountains -separating Styria from Hungary. In India also (and especially in the -Punjaub) the same practice prevails, and here it is often taken as an -aphrodisiac. The mountaineers imagine that it increases the respiratory -power, nor is there wanting some evidence to show that this is actually -the fact, and medicinal doses of arsenic have been in use for some time -in cases of asthma and other diseases of the chest. The arsenic-eaters -begin with a very small dose, which is continued for several weeks or -months, until the system gets accustomed to it. The amount is then -slightly augmented until relatively large doses are taken with impunity. -In one case[720] it appears that a countryman, in good health, and sixty -years of age, took daily 4 grains of arsenious acid, a habit which he -had inherited from his father, and which he in turn bequeathed to his -son. - -[720] Tardieu, _op. cit._ - -The existence of such a custom as arsenic-eating, in its literal sense, -has more than once been doubted, but all who have travelled over Styria -and other places where the habit prevails have convinced themselves that -the facts have not been overstated. For example, Dr. Maclagan, in -company with Dr. J. T. Rutter,[721] visited Styria in 1865, and having -carefully weighed 5 or 6 grains of arsenic, saw these doses actually -swallowed by two men. On collecting their urine, about two hours -afterwards, abundant quantitative evidence of its presence was found; -but in neither of the men were there the slightest symptoms of -poisoning. It is obvious that the existence of such a habit might -seriously complicate any inquiry into arsenical poisoning in these -regions. - -[721] _Edin. Med. Journ._, April 1865; _Brit. and For. Med. Chir. -Journ._, Oct. 1865. - -Sec. 723. =Manner of Introduction of Arsenic.=--Arsenious acid exerts a -poisonous action, whether it is taken by the stomach, or introduced into -the system by any other channel whatever. The differences in the -symptoms produced by external application (as through a wound), and by -swallowing arsenious acid in substance or in solution, are not so marked -as might be expected. It was probably Hunter who first distinctly -recognised the fact that arsenic, even when introduced outwardly by -application to an abraded surface, exerts a specific effect on the -mucous membrane of the stomach. Brodie[722] states, "Mr. Home informed -me that in an experiment made by Mr. Hunter himself, in which arsenic -was applied to a wound in a dog, the animal died in twenty-four hours, -and the stomach was found to be considerably inflamed. I repeated this -experiment several times, taking the precaution of always applying a -bandage to prevent the animal licking the wound. The result was that the -inflammation of the stomach was commonly more violent and more immediate -than when the poison was administered internally, and that it preceded -in appearance the inflammation of the wound." - -[722] _Phil. Trans._, 1812. - -Sec. 724. =Cases of Poisoning by the External Application of Arsenic.=--A -mass-poisoning by the external use of arsenical violet powder to infants -occurred in England some years ago. Two deaths from this cause were -established by coroners' inquests.[723] Dr. Tidy found the violet -powders used in the two cases to have the following composition:-- - -[723] "Gleanings in Toxicology," by C. Meymott Tidy, M.B.--_Lancet_, -Aug. 21, 1878. - - 1. 2. - Per cent. Per cent. - Arsenious Acid, 38.5 38.3 - Starch (Potato), 54.8 55.4 - Magnesia, &c. 6.7 6.3[724] - -[724] Two recipes were handed in at the coroner's inquest which pretty -fairly represent the composition of ordinary commercial violet powder:-- - - _First Quality, sold at 7s. per gross._ - - Starch Powder, 28 lbs. - Magnesia, 1-1/2 lb. - Orris-root, 1 lb. - Violet Perfume, 1 oz. - Essence of Roses, 5 drops. - - _Second Quality, sold at 6s. per gross._ - - Terra Alba (Sulphate of Lime), 14 lbs. - Potato Starch, 21 lbs. - Magnesia, 3 lbs. - Orris-root, 1-1/2 lb. - Violet Perfume, 1-1/2 oz. - Essence of Roses, 5 drops. - - -Although the children were poisoned by absorption through the skin -(unless it is allowed that some may have found its way in the form of -arsenical dust into the throat, or, what is still more probable, that -the infants may from time to time have seized the puff-ball and _sucked_ -it), the large quantity of .421 grm. (6.5 grains) of arsenious acid was -separated in the one case, and .194 grm. (3 grains) in the other. In -these cases arose the question which is sure to recur in legal inquiries -into poisoning by absorption, viz., whether the poison lying on the -surface and folds of the skin could not have been mixed during the -_post-mortem_ examination with the organs of the body? In these -particular cases special care appears to have been taken, and the answer -was satisfactory. It is not amiss, however, to call attention to the -extreme precaution which such instances necessitate. - -A woman, aged 51, had used a solution of arsenious acid to cure the -itch; erysipelas of the body, however, followed, and she died after a -long illness--one of the symptoms noted being trembling and paresis of -the limbs.[725] In a case recorded by Desgranges,[726] a young -chambermaid had applied to the unwounded scalp an arsenical ointment for -the purpose of destroying vermin. She also suffered from a severe -erysipelas, and the hair fell off. Quacks have frequently applied -various arsenical pastes to ulcers and cancerous breasts with a fatal -result. Instances of this abound; in one, a charlatan applied to a -chronic ulcer of the leg an arsenical caustic; the patient showed -symptoms of violent poisoning, and died on the sixth day.[727] In -another, a lady suffering from some form of tumour of the breast, -applied to an unqualified practitioner, who made from fifteen to twenty -punctures with a lancet in the swelling, covered a piece of bread with -an arsenical compound, and applied the bread thus prepared to the -breast. Twelve hours afterwards symptoms of violent gastric irritation -commenced; and vomiting and a sanguinolent diarrh[oe]a followed, with -death on the fifth day. Arsenic was found in all the organs.[728] Such -examples might be multiplied. Arsenic has been in more than one case -introduced criminally into the vagina with a fatal result.[729] Fodere, -_e.g._, has recorded the case of a maid-servant who poisoned her -mistress by intentionally administering several arsenical enemata.[730] -Arsenious acid again has been respired in the form of vapour. One of the -best instances of this is recorded by Taylor, and was the subject of a -trial at the York Lent Assizes, 1864. The prisoner placed some burning -pyrites at the doorway of a small room, in which there were eight -children, including an infant in the cradle. The other children were -removed speedily, but the infant was exposed to the vapour for an hour; -it suffered from vomiting and diarrh[oe]a, and died in twenty-four -hours. There was slight inflammation of the stomach and intestines, the -brain and lungs were congested, and the lining membrane of the trachea -of a bright red colour. Arsenic was detected in the stomach, in the -lungs, and spleen. The pyrites contained arsenic, and the fatal fumes -were in effect composed of sulphurous and arsenious acids. - -[725] Belloc, _Med. Leg._, t. iv. p. 124. - -[726] _Recueil de la Soc. de Med. de Paris_, t. vi. p. 22, An. vii.; -also Tardieu, _Etude Med. Legale, sur l'Empoisonnement_, Obs. xxvii. p. -457. - -[727] Mean, _Bibliotheque Med._, t. lxxiv., 1821, p. 401. - -[728] Tardieu, _op. cit._, Obs. xxix.; Dr. Vernois, _Ann. d'Hyg. et de -Med. Leg._, t. xxxvi., 1st ser., p. 141, 1846. - -[729] Ansiaulx, _Clinique Chirurgicale_. Mangor (_Acta. Societ. Reg. -Hafniens_, iii. p. 178) gives the case of a man who poisoned his three -wives successively with arsenic--the two last by introducing into the -vagina a powder composed of flour and arsenic. Another similar case is -related by Brisken. Mangor made experiments on mares, showing that when -arsenic is applied to the vagina, death may result from inflammation. - -[730] _Med. Legale_, iv. - -Sec. 725. =Arsenic in Wall-Papers.=--It is now an accepted fact that -arsenical colours on wall-papers cause illness. The symptoms are those -of chronic poisoning, and present nothing distinctive from the effects -produced from small doses of arsenic. - -Kirschgasser[731] has described the symptoms in detail of twenty-six -cases. That arsenic is actually present in patients suffering is often -susceptible of proof, by examining skilfully and carefully a -considerable volume (from one to two days' collection) of the urine; in -most of the cases thus examined arsenic has been discovered. This -poisoning is produced, sometimes from the dust, at others from a -volatile compound of arsenic, which has the following properties:--It is -very volatile (perhaps a gas), it has a strong alliaceous odour, it is -not entirely decomposed by a solution of silver nitrate, but is -apparently decomposed by a boiling acid solution of potassic -permanganate. The author suggests that it may be a compound of CO and -As, but this is only a supposition. The existence of this volatile -substance has been settled beyond all question by the experiments of -Gosio,[732] confirmed by those of Charles Robert Sanger.[733] - -[731] _Vierteljahr. f. gericht Med._, N. F., ix. 96. - -[732] _Azione di alcune Muffe sui Compositi fissi d'Arsenico. Ministero -dell' Interno, Laboratori Scientifici della Direzione di Sanita_, Roma, -1892. - -[733] "On the Formation of Volatile Compounds of Arsenic from Arsenical -Wall-Papers," _American Academy of Arts and Sciences_, vol. xxix. - -This substance appears to be readily enough produced by the action of -the common moulds upon organic matter in the presence of small amounts -of arsenic; the moulds vary in this property: _Mucor_, _Mucedo_, and -_Aspergillum glaucum_ react well; on the contrary, _Penicillium -glaucum_, _Mucor ramosus_, and several others have either no action, or -the action is but slight. One mould, the _Penicillium brevicaule_, has -quite a special endowment in forming this peculiar arsenical compound; -so much so, that Gosio has proposed its use as a reagent for arsenic, -the garlic odour being perceived when the fungus is made to grow in -solutions containing organic matter and only traces of arsenic. - -Sec. 726. =Forms of Arsenical Poisoning.=--There are at least four distinct -forms of arsenical poisoning, viz., an acute, subacute, a nervous, and a -chronic form. - -=Acute Form.=--All those cases in which the inflammatory symptoms are -severe from the commencement, and in which the sufferer dies within -twenty-four hours, may be called acute. The commencement of the symptoms -in these cases is always within the hour; they have been known, indeed, -to occur within eight minutes, but the most usual time is from twenty -minutes to half an hour. There is an acrid feeling in the throat, with -nausea; vomiting soon sets in, the ejected matters being at first -composed of the substances eaten; later they may be bilious or even -bloody, or composed of a whitish liquid. Diarrh[oe]a follows and -accompanies the vomiting, the motions are sometimes like those met with -in ordinary diarrh[oe]a and English cholera, and sometimes bloody. There -is coldness of the extremities, with great feebleness, and the pulse is -small and difficult to feel. The face, at first very pale, takes a -bluish tint, the temperature falls still lower; the patient sinks in -collapse, and death takes place in from five to twenty hours after the -taking of the poison. - -There can scarcely be said to be any clinical feature which -distinguishes the above description from that of cholera; and supposing -that cholera were epidemic, and no suspicious circumstance apparently -present, there can be little doubt that a most experienced physician -might mistake the cause of the malady, unless surrounding circumstances -give some hint or clue to it. In the acute form diarrh[oe]a may be -absent, and the patient die, as it were, from "shock." This was probably -the cause of death in a case related by Casper,[734] that of Julius -Bolle, poisoned by his wife. He took an unknown quantity of arsenic in -solution at seven in the morning, and in about three-quarters of an hour -afterwards suffered from pain and vomiting, and died in little more than -three hours. There were no signs of inflammation in the stomach and -intestines, but from the contents of the stomach were separated .0132 -grm. of arsenious acid, and .00513 grm. from pieces of the liver, -spleen, kidneys, lung, and blood. The dose actually taken is supposed -not to have been less than .388 grm. (6 grains). - -[734] Case 188 in Casper's _Handbuch_. - -Sec. 727. =The Subacute Form.=--The subacute form is that which is most -common; it exhibits some variety of phenomena, and individual cases vary -much in the matter of time. The commencement of symptoms is, as in the -most acute form, usually within the hour, but exceptions to this rule -occur. In a case quoted by Taylor,[735] and recorded by M. Tonnelier, -the poison did not cause any marked illness for eight hours; it was -found, on _post-mortem_ examination, that a cyst had been formed in the -stomach which sheathed the arsenic over, and in some degree explained -this delay. In another case, again, ten hours elapsed, and this is -considered to be the maximum period yet observed. As with the acute -form, there is a feeling of nausea, followed by vomiting, which -continues although the stomach is quite empty; at first the ejected -matter is a watery fluid, but later it may be streaked with blood. The -tongue is thickly coated; there is great thirst, but the drinking of any -liquid (even of ice-cold water) increases the vomiting. Nearly always -pain is felt in the epigastrium, spreading all over the abdomen, and -extending to the loin (which is tense and tender on pressure). -Deglutition is often painful, and is accompanied by a sort of spasmodic -constriction of the pharyngeal muscles. Diarrh[oe]a follows the -vomiting, and has the same characters as that previously described; -occasionally, however, this feature is absent. In the case recorded by -Martineau,[736] a man, aged 25, was seized at 10 A.M. suddenly with -vomiting, which persisted all that day and the next, during which time -the bowels were obstinately confined. On the second day a purgative was -administered, whereupon diarrh[oe]a set in, and continued until his -death, which occurred in about two days and sixteen hours from the -commencement of the symptoms. This case is also remarkable from the -absence of pain or tenderness of the abdomen. - -[735] Taylor's _Principles and Practice of Jurisprudence_, vol. i. p. -251; Flandin, vol. i. p. 535. - -[736] Tardieu, _op. cit._, Obs. xix. - -In subacute cases the urine has several times been suppressed, and it is -generally scanty and red in colour. Irregularity of the heart's action -and feebleness are tolerably constant phenomena. As the end approaches, -there is excessive muscular weakness, the face is pale, the eyes hollow; -the mucous membranes first, and then the skin, take a bluish tint; the -skin itself is covered with perspiration, and there has been noticed a -peculiar odour, which has been likened to arsine (arseniuretted -hydrogen). The respiration is troubled, convulsive movements of the -limbs have been observed, and cramps in the calves of the legs; death -follows in a variable time--from twenty-four hours to several days. In -certain cases there is a curious remission after violent symptoms, the -patient rallies and seems to have recovered; but the appearance is -deceptive, for the symptoms recur, and death follows. Recovery may also -take place partially from the primary effects, and then inflammatory -changes in the stomach, &c., set in, with fever and the ordinary -symptoms which are common in all internal inflammation. - -A single dose of arsenious acid may cause a prolonged and fatal illness, -one of the best known examples being that of the suicide of the Duc de -Praslin,[737] who took, with suicidal intent, on Wednesday, August 18, -1847, a dose of arsenious acid. The exact time of the act could not be -ascertained, but the first effects appeared at 10 P.M.; there were the -usual signs of vomiting, followed on the next day by diarrh[oe]a, -fainting, and extreme feebleness of the pulse. On Friday there was a -remission of the symptoms, but great coldness of the limbs, -intermittency and feebleness of the heart's action, and depression. On -Saturday there was slight fever, but no pain or tenderness in the -abdomen, vomiting, or diarrh[oe]a; on this day no urine was passed. On -the Sunday he complained of a severe constriction of the throat, and -deglutition was extremely painful; thirst was extreme, the tongue -intensely red, as well as the mucous membrane of the mouth and pharynx, -and the patient had a sensation of burning from the mouth to the anus. -The abdomen was painful and distended, the heat of the skin was -pronounced, the pulse frequent and irregular,--sometimes strong, at -others feeble,--the bowels had to be relieved by injections, the urine -was in very small quantity; during the night there was no sleep. The -duke died at 4.35 A.M. on Tuesday the 24th, the sixth day; intelligence -was retained to the last. As the end approached, the respiration became -embarrassed, the body extremely cold, and the pulse very frequent. - -[737] Tardieu, "Relation Medico-Legale de l'Assassinat de la Duchesse de -Praslin," _Ann. d'Hyg. Pub. et de Medico-Leg._, 1847, t. xxxviii. p. -390; also _op. cit._, Obs. xi. - -Sec. 728. =In the nervous form= the ordinary vomiting and purging are -either entirely suppressed, or present in but feeble degree; and under -this heading are classed the rare cases in which, in place of the -ordinary symptoms, affections of the nervous system predominate. -Narcotism, paresis, deepening into paralysis, delirium, and even acute -mania, as well as epileptiform convulsions, have all been recorded. In -short, the symptoms show so much variety, that an idea of the malady -produced in this very rare form can only be obtained by studying the -clinical history of cases which have presented this aspect. In a case -recorded by Guilbert,[738] a man, thirty-five years of age, had -swallowed a solution of arsenic, half of which was immediately rejected -by vomiting. A little while afterwards his respiration became laborious; -the eyes were bathed with tears, which were so acrid as to inflame the -eyelids and the cheeks; the muscles of the face were from time to time -convulsed; he perspired much, and the perspiration had a f[oe]tid odour; -there was some diarrh[oe]a, the urine was suppressed, and from time to -time he was delirious. Afterwards the convulsions became general, and -the symptoms continued with more or less severity for five days. On the -sixth a copious miliary eruption broke out, and the symptoms became less -severe. The eruption during fifteen days every now and again reappeared, -and at the end of that time the patient was convalescent, but weak, -liable to ophthalmia, and had a universal trembling of the limbs. - -[738] _Journal de Van der Monde_, 1756, t. iv. p. 353; Tardieu, _op. -cit._, Obs. xiii. p. 430. - -In one of Brodie's[739] experiments on rabbits, 7 grains of arsenious -acid were inserted in a wound in the back; the effect of which was to -paralyse the hind legs. In other experiments on animals, paralysis of -the hind legs has been frequently noticed, but paralysis certainly is -rare in man; in the case, however, recorded by Barrier,[740] of the five -men who took by mistake a solution of arsenious acid, one of them was -found stretched on the ground with the inferior extremities paralysed. - -[739] "The Action of Poisons," _Phil. Trans._, 1812. - -[740] _Journ. de Medecine_, 1783, p. 353; Tardieu, _op. cit._, Obs. xiv. -p. 431. - -In a case of "mass" poisoning reported by Dr. Coqueret,[741] three -persons ate by mistake an unknown quantity of arsenious acid--two of -them only suffered slightly, but the third severely, vomiting occurring -almost immediately, and continuing with frequency until the end of the -fourth day. Two hours after swallowing the poison, the patient took the -hydrated oxide of iron as an antidote. On the sixth day there was stupor -and a semi-delirious state, with an eruption of a pustular character -compared to that of the small-pox. These symptoms continued more or less -until the fifteenth day, when they diminished, and ultimately the -patient recovered. In a case related by Tardieu,[742] in which a person -died on the eleventh day from the effects of the poison, towards the -end, as a specially marked symptom, there was noted hyperaesthesia of the -inferior extremities, so that the least touch was painful. - -[741] _Journ. de Connaiss. Med. Chirurg._, 1839, p. 155; Tardieu, _op. -cit._, Obs. xv. p. 482. - -[742] _Op. cit._, Obs. xvii. p. 434. - -Sec. 729. =Absence of Symptoms.=--In a few cases there have been a -remarkable absence of symptoms, and this both in man and animals. Seven -horses were fed with oats accidentally mixed with arseniate of soda. -The first succumbed three hours after taking the poison, without having -presented any symptom whatever; he fell suddenly, and in a short time -expired.[743] It is related by Orfila,[744] that a woman, aged 27, -expired in about twelve hours from a large dose of arsenious acid; there -were the usual _post-mortem_ appearances, but in life no sign of pain, -no vomiting, and but little thirst. - -[743] Bouley (Jeune), _Ann. d'Hyg. et de Medico-Leg._, 1834, t. xii. p. -393. - -[744] Tome i. Obs. iv. p. 314. - -Sec. 730. =Slow Poisoning.=--Slow poisoning has been caused accidentally by -arsenical wall-paper, in the manufacture of arsenical pigments, by the -admixture of small quantities of arsenic with salt or other condiments, -and repeated small doses have been used for criminally producing a fatal -illness intended to simulate disease from natural causes. The illness -produced by small intermittent doses may closely resemble in miniature, -as it were, those produced by large amounts; but, on the other hand, -they may be different and scarcely to be described otherwise than as a -general condition of ill-health and _malaise_. In such cases there is -loss of appetite, feebleness, and not unfrequently a slight yellowness -of the skin. A fairly constant effect seen, when a solution of arsenious -acid is given continuously for a long time, is an inflammation of the -conjunctivae, as well as of the nasal mucous membrane--the patient -complains of "always having a cold." This inflammatory action also -affects the pharynx, and may extend to the air-passages, and even to the -lung-tissue. At the same time there is often seen an exanthem, which has -received a specific name--"_eczema arsenicale_." Salivation is present, -the gums are sore, at times lacerated. In chronic poisoning by arsenic, -nervous symptoms are almost constant, and exhibit great variety; there -may be numbness, or the opposite condition, hyperaesthesia, in the -extremities. In certain cases fainting, paresis, paralysis, and -sometimes convulsions occur; towards the end a sort of hectic fever -supervenes, and the patient dies of exhaustion. - - Sec. 731. =The Maybrick Case.=[745]--The Maybrick case may be - considered an example of poisoning extending over a considerable - period of time:--Mr. James Maybrick, a Liverpool cotton-broker, aged - 49, married Florence Elizabeth, an American lady, aged 21. They had - two children. The marriage proved an unhappy one. Some two years - before his death in May 1889 they had occupied two separate rooms. - Seven weeks before the husband's death, Mrs. Maybrick went to London - on a false pretext, and lived for some days at an hotel, ostensibly - the wife of another man. Two days after her return, Mr. and Mrs. - Maybrick attended the Grand National race meeting, and there a - serious quarrel arose between them respecting the man with whom she - had cohabited in London; they returned from the race, each - separately, and she slept apart. Next day an apparent reconciliation - took place through the intervention of Dr. Fuller, the family - medical attendant. - -[745] "The Maybrick Trial and Arsenical Poisoning," by Thos. Stevenson, -M.D., _Guy's Hosp. Rep._, 1889. - - On or about April 12-19th, 1889, Mrs. Maybrick purchased arsenical - fly-papers. On April 13-20th Mr. Maybrick visited London, and - consulted Dr. Fuller for dyspepsia, who prescribed nux vomica, - acids, and mild remedies (but no arsenic); in one bottle of - medicine, ostensibly made according to Dr. Fuller's prescription, - arsenic was subsequently found. - - Up to Saturday, April 27th, Mr. Maybrick was in his usual health; he - was then sick, numbed, and in pain, and had cramps; he told his - clerk he had been an hour in the water-closet, but whether for - diarrh[oe]a or constipation does not appear; he ascribed the - symptoms to an overdose of Fuller's medicine. About this date - fly-papers were found by the servants soaking in Mrs. Maybrick's - bedroom in a sponge-basin, carefully covered up. On the 29th she - again purchased two dozen fly-papers from another chemist. On April - 28th Mr. Maybrick was sick and ill; at 11 A.M. Dr. R. Humphreys was - called in; Mr. Maybrick complained of a peculiar sensation about his - heart, and said he was in dread of paralysis. He attributed his - illness to a strong cup of tea taken before breakfast. On the - following day he was better, and on the 30th still improving. On May - 1st and 2nd Mr. Maybrick went to his office and lunched, both days, - off revalenta food, prepared at home and warmed at his office in a - new saucepan purchased for the occasion; on one of these days the - lunch was forgotten, and was sent to Mr. Maybrick by his wife; and - on one of the two days, it is not clear which, Mr. Maybrick - complained that his lunch did not agree with him, and he attributed - it to inferior sherry put into his food. - - In a jug found at the office, and in which food had been taken - there, a trace of the food still remained after Mr. Maybrick's - death, and arsenic was found therein. - - On May 3rd the last fatal illness set in. It is uncertain what food - he had after breakfast; he went to the office, and returned home - between 5 and 6 P.M. He had been seen by Dr. Humphreys in the - morning, and appeared then not quite so well; he found him at - midnight suffering from what he thought was severe sciatica; the - patient said he had been sick from revalenta. On May 4th he was - continually sick, nothing could be retained on the stomach, but the - sciatic pain was gone; on May 5th the vomiting continued, the - patient complained of the sensation of a hair sticking in the - throat, and of a filthy taste in the mouth. The throat and fauces - were only slightly reddened, the tongue was furred. - - On May 6th there was less vomiting, but otherwise the condition was - the same, and Fowler's solution ordered, but only a quantity equal - to 1/300 grain was actually taken. - - May 7th the condition was improved, but there was no increase of - power. Dr. W. Carter was called in consultation. The vomiting was - passing away, and diarrh[oe]a commencing. The throat was red, dry, - and glazed; there were incessant attempts to cough up an imaginary - hair. No cramps, no pain in the stomach or intestines, nor - conjunctivitis. On this day the first direct evidence of diarrh[oe]a - is recorded, the medical men actually seeing a loose motion. The - result of the consultation was that Mr. Maybrick must have taken - some irritant in his food or drink. - - On the 8th a professional nurse took charge. During the 8th and 9th - severe tenesmus set in with diarrh[oe]a, and blood was observed in - the faeces. Now arsenic was suspected, the urine was examined by Dr. - Humphreys, and a rough analysis was made of some Neaves' food which - the patient had been taking. - - The patient died on the 10th, at 8.30 P.M. - - The _post-mortem_ appearances were as follows:-- - - The tongue was dark, the top of the gullet slightly red, but - otherwise healthy, save at the lower end, where the mucous membrane - was gelatinous, and was dotted over with black dots, like frogs' - spawn. - - There was a small shallow ulcer in the mucous membrane of the larynx - at the back of the epiglottis. The free margin of the epiglottis was - rough and eroded; and on the posterior aspect of the ericoid - cartilage there were two small red patches. In the stomach were - from 5-6 ozs. of brownish fluid. At the cardiac end there was a - large vermilion-red patch, interspersed here and there with small - dark ecchymoses (spoken of by Dr. Humphreys as a flea-bitten - appearance); to this followed a non-inflamed space, and near the - pyloric orifice, and extending 2 inches from it, was another red - inflamed portion of mucous membrane. In the small intestine the - mucous membrane was red and inflamed, from 3 inches below the - pylorus to about 3 feet downwards. About 18 or 20 feet lower down, - _i.e._, a little below the ileo-caecal valve, the mucous membrane was - again inflamed to a lesser extent over a space of about 2 feet; the - lower end of the rectum was also red and inflamed. No arsenic was - found in the stomach or its contents, or in the spleen. Arsenic was - present in the liver, in the intestines, and in the kidneys. The - quantity separated altogether amounted to over 0.1 grain. The liver - weighed 48 ozs., and from 12 ozs. of the liver 0.076 grain of - arsenic, reckoned as As_{2}O_{3}, was separated. - - The whole course of the symptoms and the _post-mortem_ examination - showed that the deceased died from an irritant poison; and from the - fact of a small quantity of arsenic having been found in the body, - there can be little doubt but that the poison was arsenic. The - symptoms were somewhat anomalous, but not more so than in other - recorded cases of undoubted arsenical poisoning. The facts that - tended to connect the accused with the death were as follows:--On - the night of either May 9th or the 10th Mrs. Maybrick was observed - to remove from the table an opened bottle of Valentine's meat juice, - and take it into an inner dressing-room, and then replace it--the - acts being surreptitious. In replacing it, she was observed to take - it either from the pocket of her dressing-gown or from an inner - pocket. The lining of this pocket was found to be impregnated with - As_{2}O_{3}. The juice was found to contain 0.5 grain As_{2}O_{3}, - and the liquid was of lower gravity than commercial juice; it had - probably, therefore, been diluted. - - The following is a list of things containing arsenic:-- - - 1. Mrs. Maybrick's dressing-gown. - 2. " apron. - 3. A handkerchief wrapped around a bottle. - 4. Packet of arsenic "for cats." (Arsenious acid mixed with char- - coal.) Tumbler containing milk, with handkerchief soaking in it; - at least 20 grains of As_{2}O_{3} in the tumbler mixed with - charcoal. - 5. A portion of a handkerchief. - 6. A bottle containing a strong solution of arsenious acid and - several grains of undissolved arsenious acid. - 7. A bottle containing from 15-20 grains of solid arsenic and a few - drops of solution. - 8. A saturated solution of arsenious acid and some solid arsenious - acid. - 9. Valentine's meat juice. - 10. Price's glycerin; 2/3 grain in the whole bottle. - 11. A bottle containing 0.1 grain of arsenious acid. - 12. A bottle from Mr. Maybrick's office containing a few drops of - medicine prescribed by Dr. Fuller (decidedly arsenical). - 13. Jug from the office with remains of food. - 14. Sediment from trap of w.c. and lavatory drain containing - As_{2}O_{3}. - - Mrs. Maybrick was convicted, but afterwards the sentence was - commuted to penal servitude for life. - -Sec. 732. =Post-mortem Appearances in Animals.=--P. Hugo[746] has made some -minute researches as to the pathological appearances met with in -animals. His experiments were made on seven dogs, eight guinea-pigs, -five rabbits, two pigeons, and five cats--all poisoned by arsenious -acid. According to Hugo, so far as these animals were concerned, changes -were more constant in the intestine than in the stomach. - -[746] _Beitraege zur Pathologie der acuten Arsenikvergiftung., Archiv fuer -exper. Pathol. u. Pharmakol._, Leipzig, 1882. - -=Stomach.=--Changes in the mucous membrane were especially noticed in -the great curvature and towards the pylorus; the pylorus itself, and a -part of the cardiac portion, remained unchanged. The mucous membrane in -dogs and cats was red, with a tinge of blue--in many cases the redness -was in streaks, with injection of the capillaries. The stomach of -plant-eaters was less altered, and a microscopical examination of the -mucous tissues did not show any fatty change. - -=The Intestines.=--In dogs and cats changes were evident; in rabbits and -guinea-pigs they were not so marked, but the intestines of the last were -extremely tender and brittle, very moist, and filled with a slimy, -serous, grey-white fluid; nevertheless, the changes in all these animals -appear to be of essentially the same nature. The most striking effect is -the shedding of a pseudo-membrane; in quite recent cases there is a -layer of from 1 to 1-1/2 mm. wide of a transparent, frog-spawn-like -jelly streaking the intestine. In later stages it becomes thicker, while -occasionally it resembles a diphtheritic exudation. The mucous membrane -itself is deep purple-red, showing up by the side of the -pseudo-membrane. With regard to the villi, the epithelial layer is -detached, and the capillary network filled with blood and enlarged. - -=The Liver.=--Hugo met only occasionally with fatty degeneration of the -liver, but there was marked steatosis of the epithelium of the -gall-bladder of dogs. A fact not prominently noticed before, is (at all -events, in dogs) a serous transudation into the pleural sac and acute -[oe]dema of the lungs; the exudation may be excessive, so that more than -100 c.c. of serous fluid can be obtained from the thorax; there is also -usually much fluid in the pericardium. In two of Hugo's experiments -there was fluid in the cerebral ventricles; and in all there was -increased moisture of the brain substance with injection of the -capillary vessels, especially of the pia. - -Sec. 733. =Post-mortem Appearances.=--A remarkable preservation of the body -is commonly, but not constantly, observed. When it does occur it may -have great significance, particularly when the body is placed under -conditions in which it might be expected to decompose rapidly. In the -celebrated Continental case of the apothecary Speichert (1876), -Speichert's wife was exhumed eleven months after death. The coffin stood -partly in water, the corpse was mummified. The organs contained arsenic, -the churchyard earth no arsenic. R. Koch was unable to explain the -preservation of the body, under these conditions, in no other way than -from the effect of arsenic; and this circumstance, with others, was an -important element which led to the conviction of Speichert. - -When arsenious acid is swallowed in substance or solution, the most -marked change is that in the mucous membrane of the stomach and -intestines; and, even when the poison has been absorbed by the skin, or -taken in any other way, there may be a very pronounced inflammatory -action. On the other hand, this is occasionally absent. Orfila[747] -relates a case in which a man died in thirteen hours after having taken -12 grms. of arsenious acid:--"The mucous membrane of the stomach -presented in its whole extent no trace of inflammation, no redness, and -no alteration of texture." Many other similar cases are on record; and, -according to Harvey's statistics, in 197 cases, 36 (about 18.2 per -cent.) presented no lesion of the stomach. - -[747] Tome i. Obs. v. - -The usual changes produced by arsenious acid may be studied in the -museums of the London hospitals. In Guy's Hospital Museum there are -three preparations. In preparation 1798^{32} is seen a large stomach -with the mucous membrane at certain points abraded, and at the great -curvature the whole coats are thinned; it is also somewhat congested. In -preparation 1798^{64} is a portion of coagulated lymph, from the stomach -of a lad, aged 14, who had taken accidentally a piece of cheese charged -with arsenious acid, prepared for the purpose of destroying rats. He -lived twenty-eight hours, and presented the ordinary symptoms. The lymph -has a membranous appearance, and the rugae of the stomach are impressed -upon it. It is said when recent to have presented numerous bright bloody -spots, although there was no visible breach of substance on the surface -of the stomach. The mucous membrane of the stomach is stated to have -been injected, and there was also diffuse injection of the duodenum. -Preparation 1798^{80} is the stomach of a person who survived thirteen -hours after taking a fatal dose of arsenious acid; and in the same -museum there is a wax model of the appearances which the fresh -preparation exhibited, showing a large oval patch coated with mucus and -the poison. The stomach was intensely inflamed, the caecum injected. The -rest of the intestine was healthy. - -In the museum of University College there are two preparations, one[748] -exhibiting intense swelling and congestion of the gastric mucous -membrane, which is of a perfectly vermilion colour. Another preparation -(No. 2868) shows the effect of a small dose of arsenic on the stomach; -there are spots of arborescent extravasation, and slight congestion of -the summits of the rugae, but in other respects it is normal. There is -also a cast of Peyer's patches from the same case, showing great -prominence of the glands, with some injection of the intestinal mucous -membrane. - -[748] This preparation at the time of my visit had no number. - -In St. Thomas' Hospital there is an interesting preparation (No. 8) -showing the gastric mucous membrane dotted all over with minute ulcers, -none of which have an inflammatory zone.[749] I have not, however, seen -in any museum a preparation of the curious emphysematous condition of -the mucous membrane, which has more than once been met with. For -example, in a case related by Tardieu,[750] Schwann, a labourer, died -from the effects of arsenic in thirty-six hours. The autopsy showed that -the mucous membrane of the stomach and small intestine was covered with -a pasty coating, and was elevated in nearly its whole extent by bullae -filled with gas, forming true emphysematous swellings which encroached -upon the diameter of the intestine. There was neither redness nor -ulceration, but the mucous membrane was softened. - -[749] In a case related by Orfila, t. i. Obs. xv., death resulted from -the outward application of arsenic; the mucous membrane of the stomach -was natural in colour, but there were four ulcers, one of which was 50 -centimetres in diameter. - -[750] _Op. cit._, Obs. i. p. 468. - -The author saw, many years ago, at Barnard Castle, an autopsy made on a -gentleman who died from arsenic. In this case the mucous membrane of the -stomach presented a peculiar appearance, being raised here and there by -little blebs, and very slightly reddened. - -Sec. 734. The inflammatory and other changes rarely affect the gullet. -Brodie[751] never observed inflammation of the [oe]sophagus as an effect -of arsenic; but, when arsenic is swallowed in the solid state, as in the -suicide of Soufflard, graphically described by Orfila,[752] it may be -affected. In Soufflard's case there was a vivid injection of the pharynx -and gullet. - -[751] _Phil. Trans._, 1812. - -[752] T. i. p. 319. - -In many instances, when the arsenic has been taken in the solid form, -the crystals with mucus and other matters adhere to the lining membrane. -I have seen in the stomach of a horse, poisoned by an ounce of arsenic, -an exquisite example of this. The inflammatory changes may be recognised -many months after death owing to the antiseptic properties of arsenic; -nevertheless, great caution is necessary in giving an opinion, for there -is often a remarkable redness induced by putrefactive changes in healthy -stomachs. Casper,[753] on this point, very justly observes:--"If Orfila -quotes a case from Lepelletier, in which the inflammatory redness of the -mucous membrane of the stomach was to be recognised after nine months' -interment, and if Taylor cites two cases in which it was observed -nineteen and twenty-one months after death respectively, this is in -contradiction of all that I, on my part, have seen in the very numerous -exhumed corpses examined by me in relation to the gradual progress of -putrefaction and of saponification, and I cannot help here suspecting a -confusion with the putrefactive imbibition redness of the mucous -membrane." - -[753] _Handbuch_, vol. ii. p. 420. - -If examined microscopically, the liver and kidneys show no change, save -a fatty degeneration and infiltration of the epithelial cells. In the -muscular substance of the heart, under the endocardium, there is almost -constantly noticed ecchymosis. In the most acute cases, in which a -cholera-like diarrh[oe]a has exhausted the sufferer, the blood may be -thickened from loss of its aqueous constituents, and the whole of the -organs will present that singularly dry appearance found in all cases in -which there has been a copious draining away of the body fluids. In the -narcotic form of arsenical poisoning, the vessels of the brain have been -noted as congested, but this congestion is neither marked nor -pathognomonic. Among the rare pathological changes may be classed -glossitis, in which the whole tongue has swollen, and is found so large -as almost to fill the mouth. This has been explained, in one case, as -caused by solid arsenious acid having been left a little time in the -mouth before swallowing it. On the other hand, it has also been observed -when the poison has been absorbed from a cutaneous application. When -arsenic has been introduced into the vagina, the ordinary traces of -inflammatory action have been seen, and, even without direct contact, an -inflammation of the male and female sexual organs has been recorded, -extending so far as gangrene. As a rule, putrefaction is remarkably -retarded, and is especially slow in those organs which contain arsenic; -so that, if the poison has been swallowed, the stomach will retain its -form, and, even to a certain extent, its natural appearance, for an -indefinite period. In corpses long buried of persons dying from -arsenical poisoning, the ordinary process of decay gives place to a -saponification, and such bodies present a striking contrast to others -buried in the same graveyard. This retardation of putrefaction is what -might, _a priori_, be expected, for arsenic has been long in use as a -preservative of organic tissues. - -Sec. 735. =Physiological Action of Arsenic.=--The older view with regard to -the essential action of arsenic was, without doubt, that the effects -were mainly local, and that death ensued from the corrosive action on -the stomach and other tissues--a view which is in its entirety no longer -accepted; nevertheless, it is perfectly true that arsenic has a -corrosive local action; it will raise blisters on the skin, will inflame -the tongue or mucous membranes with which it comes in contact; and, in -those rapid cases in which extensive lesions have been found in the -alimentary canal, it can hardly be denied that instances of death have -occurred more from the local than the constitutional action. In the vast -majority of cases, however, there is certainly insufficient local action -to account for death, and we must refer the lethal result to a more -profound and intimate effect on the nervous centres. The curious fact, -that, when arsenic is absorbed from a cutaneous surface or from a -wound, the mucous membrane of the stomach inflames, is explained by the -absorption of the arsenic into the blood and its separation by the -mucous membrane, in its passage exerting an irritant action. The -diarrh[oe]a and hyperaemia of the internal abdominal organs have been -referred to a paralysis of the splanchnic nerves, but Esser considers -them due to an irritation of the ganglia in the intestinal walls. Binz -has advanced a new and original theory as to the action of arsenious -acid; he considers that the protoplasm of the cells of many tissues -possess the power of oxidising arsenious acid to arsenic acid, and this -arsenic acid is again, by the same agency, reduced to arsenious acid, in -this way, by the alternate oxidation and reduction of the arsenious -acid, the cells are decomposed, and a fatty degeneration takes place. -Thus arsenic causes fatty changes in the liver, kidney, and other cells -by a process analogous to the action of phosphorus. T. Araki[754] also -considers that both arsenic and phosphorus lessen oxidation, and points -out that lactic acid appears in the urine when either of these poisons -are taken, such acid being the result of insufficient oxidation. A -notable diminution of arterial pressure has been observed. In an -experiment by Hugo[755] .03 grm. of As_{2}O_{3} was injected -intravenously, the normal arterial pressure being 178 mm. Ten minutes -after injection the pressure sank to 47 mm.; in sixteen minutes it again -rose to 127 mm. Accumulative action of arsenic does not occur. Hebra has -given, in skin diseases, during many months, a total quantity of 12 -grms. without evil result. - -[754] _Zeit. physiol. Chem._, xvii. 311-339. - -[755] _Op. cit._ - -Sec. 736. =Elimination of Arsenic.=--Arsenic is separated especially by the -urine,[756] then through the bile, and by the perspiration. The eruption -often observed on the skin has been referred to the local action of -small quantities of arsenic in this way eliminated. It is found in the -urine first after from five to six hours, but the elimination from a -single dose is not finished till a period of from five to eight days; it -has often been looked for twelve days after taking it, but very seldom -found. According to Vitali, the arsenic in the urine is not free, but -probably displaces phosphorus in phospho-glyceric acid; possibly it may -also replace phosphorus in lecithin. - -[756] An old experiment of Orfila's has some practical bearings, and may -be cited here. A dog was treated by .12 grm. of arsenious acid, and -supplied plentifully with liquid to drink; his urine, analysed from time -to time during ten days, gave abundant evidences of arsenic. On killing -the animal by hanging on the tenth day, no arsenic could be detected in -any of the organs of the body; it had been, as it were, washed out. - -Sec. 737. =Antidote and Treatment.=--In any case in which there is -opportunity for _immediate_ treatment, ferric hydrate should be -administered as an antidote. Ferric hydrate converts the soluble -arsenious acid into the insoluble ferric arseniate, the ferric oxide -being reduced to ferrous oxide. It is necessary to use ferric hydrate -recently prepared, for if dried it changes into an oxyhydrate, or even -if kept under water the same change occurs, so that (according to the -experiments of Messrs. T. & H. Smith) after four months the power of the -moist mass is reduced to one-half, and after five months to one-fourth. - -It is obvious that ferric hydrate is not in the true sense of the word -an antidote, for it will only act when it comes in contact with the -arsenious acid; and, when once the poison has been removed from the -stomach by absorption into the tissues, the administration of the -hydrate is absolutely useless. Ferric hydrate may be readily prepared by -adding strong ammonia to the solution or tincture of ferric chloride, -found in every medical man's surgery and in every chemist's shop, care -being taken to add no caustic excess of ammonia; the liquid need not be -filtered, but should be at once administered. With regard to other -methods of medical treatment, they are simply those suggested by the -symptoms and well-known effects of the poison. When absorbed, the -drinking of water in excess cannot but assist its elimination by the -kidneys. - -Sec. 738. =Detection of Arsenic.=--The analyst may have to identify arsenic -in substance, in solution, in alloys, in wall-papers, in earth, and in -various animal, fatty, resinous, or other organic matters. - -=Arsenious Acid in Substance.=--The general characters of arsenious acid -have been already described, and are themselves so marked as to be -unmistakable. The following are the most conclusive tests:-- - -(1) A small fragment placed in the subliming cell (p. 258), and heated -to about the temperature of 137.7 deg. (286 deg. F.), at once sublimes in the -form of an amorphous powder, if the upper glass disc is cool; but if -heated (as it should be) to nearly the same temperature as the lower, -characteristic crystals are obtained, remarkable for their brilliancy -and permanency, and almost always distinct and separate. The prevailing -form is the regular octahedron, but the rhombic dodecahedron, the -rectangular prism, superimposed crystals, half crystals, deep triangular -plates like tetrahedra, and irregular and confused forms, all -occasionally occur. - -[Illustration] - -(2) A beautiful and well-known test is that of Berzelius:--A small -hard-glass tube is taken, and the closed end drawn out to the size of a -knitting needle. Within the extreme point of this fine part is placed -the fragment (which may be no more than a milligramme) and a splinter of -charcoal, fine enough to enter freely the narrow part, as shown in the -figure. The portion of the tube containing the charcoal (_e_) is first -heated until it glows, and then the extreme end; if arsenic is present, -a mirror-like coating is easily obtained in the broader portion of the -tube (_d_). That this coating is really arsenical can be established by -the behaviour of metallic crusts of arsenic towards solvents (as given -at p. 557). The portion of the tube containing the crust may also be -broken up, put in a very short, wide test-tube (the mouth of which is -occupied by a circle of thin microscopic glass) and heated, when the -arsenic will sublime on to the glass disc, partly as a metal and partly -as crystalline arsenious acid. - -(3) Arsenious acid, itself inodorous, when heated on coal, after mixing -it with moist oxalate of potash, evolves a peculiar garlic-like odour. -To this test oxide of antimony adulterated with arsenic will respond, if -there is only a thousandth part present. Simply projecting arsenious -acid on either red-hot charcoal or iron produces the same odour. - -(4) A little bit of arsenious acid, heated in a matrass with two or -three times its weight of acetate of potash, evolves the unsupportable -odour of kakodyl. - -=Arsenites and Arseniates=, mixed with oxalate of soda and heated in a -matrass, afford distinct mirrors, especially the arsenites of the earths -and silver; those of copper and iron are rather less distinct. - -=Sulphides of Arsenic= are reduced by any of the processes described on -p. 573 _et seq._ - -=In Solution.=--An acid solution of arsenious acid gives, when treated -with SH_{2}, a canary-yellow precipitate, soluble in ammonia, carbonate -of ammonia, and bisulphite of potash, and also a metallic sublimate when -heated in a tube with the reducing agents in the manner described at p. -575. By these properties the sulphide is distinguished and, indeed, -separated from antimony, tin, and cadmium. - -The sulphides of tin and cadmium are certainly also yellow, but the -latter is quite insoluble in ammonia, while the former gives no metallic -sublimate when heated with reducing substances. - -The sulphide of antimony, again, is orange, and quite insoluble in -potassic bisulphite, and scarcely dissolves in ammonia. - -A small piece of sodium amalgam placed in a test-tube or flask -containing an arsenic-holding liquid, or the liquid made alkaline with -soda or potash and a little bit of aluminium added, produces in a short -time arsine, which will blacken a piece of paper, soaked in nitrate of -silver, and inserted in the mouth of the flask. This is certainly the -most convenient test for arsenic. No antimoniuretted hydrogen -(_stibine_) is given off from an alkaline solution and no SH_{2}. - -=Marsh's Original Test for Arsenic= consisted in evolving nascent -hydrogen by zinc and sulphuric acid, and then adding the liquid to be -tested. The apparatus for Marsh's test, in its simplest form, consists -of a flask provided with a cork conveying two tubes, one a funnel -reaching nearly to the bottom of the flask; the other, a delivery tube, -which is of some length, is provided with a chloride of calcium -bulb,[757] and towards the end is turned up at right angles, the end -being narrowed. By evolving hydrogen from zinc and sulphuric acid, and -then adding portions of the liquid through the funnel, arseniuretted -hydrogen in a dry state is driven along the leading tube, can be ignited -on its issue, and on depressing a piece of cold porcelain, a dark -metallic spot of arsenic is obtained.[758] Or, if any portion of the -tube be made red-hot, the metal is deposited in the same way as a ring. -The apparatus admits of much complication and variety. One of the most -useful additions is, perhaps, the interposition of a small gasometer. -This consists of a cylindrical glass vessel with entrance and exit -tubes, open at the bottom, immersed in water in a larger vessel, and -counterpoised by weights and rollers, exactly like the large gasometers -used at gasworks; the exit tube must have a stop-cock, and the gas must -pass over calcic chloride in order to dry it thoroughly. - -[757] Otto recommends the first half of the drying tube connected with -the development flask to be filled with caustic potash, the latter half -with chloride of calcium (_Ausmittelung der Gifte_). Dragendorff -approves of this, but remarks that it should be used when arsenic alone -is searched for, since caustic potash decomposes stibine. The potash -fixes SH_{2}, and prevents the formation of chloride of arsenic; on the -other hand, it absorbs some little AsH_{3}. - -[758] For identification of arsenical films, see p. 557. - -M. Blondlot has observed[759] that if pure zinc, a weak solution of -arsenious acid, and a sulphuric acid containing nitric acid or nitrous -compounds, be mixed together, the arsenic passes into a solid hydrate, -which is deposited on the surface of the zinc; this is, however, -prevented by the addition of a little stannous chloride dissolved in -hydrochloric acid. - -[759] Blondlot, "Transformation de l'arsenic en hydrure solide par -l'hydrogene aissant sous l'influence des composes nitreux."--_Jour. de -Pharm. et de Chim._, 3e ser., t. xliv. p. 486. - -The precautions to be observed in Marsh's test are:-- - -(1) Absolute freedom of the reagents used from arsenic, antimony,[760] -and other impurities. - -[760] With regard to purity of reagents, Sonnenschein states that he has -once found chlorate of potash contaminated with arsenic.--Sonnenschein, -_Gericht. Chemie_, p. 139. - -(2) The sulphuric acid should be diluted with five times its weight of -water, and if freshly prepared should be cooled before use. Strong acid -must not be employed.[761] - -[761] M. A. Gautier uses sulphuric acid diluted with five times its -weight of water; when the hydrogen has displaced the air, he adds to the -arsenical matter 45 grms. of this acid and 5 grms. of pure sulphuric -acid.--_Bull. de la Societe Chim. de Paris_, 1875, t. xxiv. - -(3) The fluid to be tested should be poured in little by little. - -(4) Nitrous compounds, nitric acid, hydrochloric acid, chlorides, are -all more or less prejudicial. - -(5) The gas should come off regularly in not too strong a stream, nor -out of too small an opening. - -(6) The gas should pass through the red-hot tube at least one hour, if -no stain is at once detected. - -(7) Towards the end of the operation, a solution of stannous chloride in -hydrochloric acid is to be added to the contents of the flask. This -addition precipitates any arsenic present in a finely divided state, in -which it is readily attacked by nascent hydrogen.[762] - -[762] F. W. Schmidt, _Zeit. anorg. Chem._, i. 353-359. - -The characteristics of the metallic stains which may occur either on -glass or porcelain in the use of Marsh's test, may be noted as under:-- - - MIRROR OR CRUST OF ARSENIC MIRROR OR CRUST OF ANTIMONY - - Is deposited at a little distance Is deposited close to the flame, - from the flame. and on both sides of it, and is - therefore notched. - - An arsenical stain is in two The stain is tolerably homo- - portions, the one brownish, the geneous, and usually has a tin- - other a glittering black. like lustre. - - On heating, it is rapidly Volatilisation very slow; no - volatilised as arsenious acid. crystalline sublimate obtainable. - - On transmission of a stream of The same process applied in the - SH_{2}, whilst immediately behind case of antimony produces the - the stain a gentle heat is orange or black sulphide; and on - applied, the arsenic is changed passing dry ClH, chloride of - to yellow sulphide;[763] if dry antimony volatilises without the - ClH is now transmitted, the application of heat. - arsenical sulphide is unchanged. - - Chloride of lime dissolves the Antimony not affected. Dissolves - arsenic completely. slowly but completely the - antimony stain. - - Protochloride of tin has no action No precipitate with antimony. - on metallic arsenic. - - The arsenic stain, dissolved in - _aqua regia_, or ClH and chlorate - of potash, and then treated with - tartaric acid, ammonia, and - magnesia mixture, gives a - precipitate of ammonia magnesian - arseniate.[764] - -[763] It is desirable to dissolve away the free sulphur often deposited -with the arsenical sulphide by bisulphide of carbon. - -[764] Schoenbein has proposed ozone as an oxidiser of arsenical stains. -The substance containing the stain, together with a piece of moist -phosphorus, is placed under a shade, and left there for some time; the -oxidisation product is, of course, coloured yellow by SH_{2} if it is -arsenious acid, orange if antimony. The vapour of iodine colours -metallic arsenic pale yellow, and later a brownish hue; on exposure to -the air it loses its colour. Iodine, on the other hand, gives with -antimony a carmelite brown, changing to orange. - -An arsenical ring may be also treated as follows:--Precipitated zinc -sulphide is made into a paste with a little water, and introduced into -the end of the tube; the same end is then plunged into dilute sulphuric -acid, and the ring heated, when the arsenical sulphide will be -produced. - -The mirror or crust of arsenic is usually described and weighed as being -composed of the pure metal, but J. W. Rettgers has investigated the -matter, and the following is an abstract of his results:-- - -There is no amorphous form of arsenic, the variety generally thus called -being crystalline. Two modifications can be distinguished: the one being -a hexagonal silver-white variety possessed of metallic lustre, -specifically heavier and less volatile than the second kind, which is -black in colour, crystallises apparently in the regular system, and -constitutes the true arsenic mirror. The former modification corresponds -to red hexagonal phosphorus (red phosphorus having been recently proved -by the author to be crystalline), and the latter to yellow phosphorus, -which crystallises in the regular system. Both modifications of arsenic -are perfectly opaque; deposits which are yellow or brown, and more or -less transparent, consist of the suboxide and hydride, As_{2}O and AsH. -The brown spot on porcelain produced by contact with a flame of -arseniuretted hydrogen is not a thin film of As, but one of the brown -solid hydride AsH, formed by the decomposition of AsH_{3}. This view is -confirmed by the fact that arsenic sublimed in an indifferent gas -(_e.g._, CO_{2}) is deposited in one or other of the modifications -described above, the brown transparent product being obtained only in -the presence of H or O. Moreover, pure arsenic is insoluble in all -solvents, whereas the film on porcelain (AsH) is soluble in many -solvents, including hydrocarbons of the benzene series (_e.g._, xylene), -warm methylene iodide, and hot caustic potash. - -Hence quantitative results from weighing arsenical mirrors can never be -accurate, because the mirrors consist of mixtures of hydride and -suboxide. - -=Reinsch's Test.=--A piece of bright copper foil, boiled in an acid -liquid containing either arsenic or antimony, or both, becomes coated -with a dark deposit of antimony or arsenic, as the case may be. The -arsenical stain, according to Lippert, is a true alloy, consisting of 1 -arsenic to 5 copper.[765] Properly applied, the copper will withdraw -every trace of arsenic or antimony from a solution. Dr. John Clark[766] -has lately introduced some improvements in Reinsch's process. His -experiments have been directed to the means of proving the presence of -arsenic or antimony in the stain on the copper with greater certainty, -and at the same time estimating the amount when they occur together. - -[765] _Journ. f. pract. Chem._, xiii. 168. - -[766] _Journ. Chem. Soc._, June 1893, 886. - -The material to be tested is boiled gently in a porcelain vessel with -dilute hydrochloric acid and a small strip of copper about 1 inch long -by 1/4 inch broad, till the absence of arsenic or antimony has been -ascertained, or a coating has been produced. When the coating is -decided, the piece of copper is taken out, washed first with water, then -with a little alcohol to get rid of fatty matter, and finally with -water. It is then placed in a mixture of dilute caustic potash and -peroxide of hydrogen, and allowed to digest in the cold. At the same -time a second piece of copper is introduced into the material which has -given a deposit on the first piece, the washings of the first piece -being added, and the boiling continued. - -The treatment of the first piece of copper by caustic potash and -peroxide of hydrogen dissolves any antimony or arsenic and restores the -copper to its original brightness; when this is accomplished, the second -piece of copper is taken out and replaced by the first, and this second -piece, if stained, is digested with potash, peroxide of hydrogen, and -washed as in the former case. The process is repeated until the slips of -copper cease to be stained in the slightest degree--until, in short, the -whole arsenic or antimony has been withdrawn. - -The alkaline liquid contains the arsenic, as arsenate of potassium; the -antimony, if present, as antimonate; and the solution is also -contaminated by a little hydrated copper oxide; this latter separates on -boiling, and can be filtered off, and the filtrate is boiled down to a -small bulk. The liquid is washed into a small distillation-flask with -strong hydrochloric acid, ferrous chloride is added, the flask, fitted -with a safety tube, is connected with a condenser, and the arsenic -distilled into water. To obtain the last traces of arsenic it may be -necessary to distil it twice in this way, adding, each time, fresh -strong acid and distilling to dryness. The distillate is then tested for -arsenic by adding an equal bulk of saturated SH_{2} water. The sulphide -of arsenic may be dealt with as described (p. 573). - -The residue in the flask is now tested for antimony by saturating with -SH_{2}; should antimony be present, the precipitate by SH_{2} will -probably be dark coloured, because of a small quantity of copper. The -precipitate is collected, dissolved in dilute caustic soda, boiled, -filtered to remove copper sulphide, the filtrate acidified by -hydrochloric acid, and sulphuretted hydrogen water added. If antimony -was present, this time the precipitate will be of an orange colour, and -may be dealt with as described (p. 589). - -The test experiments with regard to this combined process appear -satisfactory. - -Sec. 739. =Arsenic in Glycerin.=--Arsenic has been frequently found in -commercial glycerin, the quantity varying from 0.1 to 1 mgrm. in 100 -c.c. The best method to detect the presence of arsenic in glycerin is as -follows:--A mixture of 5 c.c. of hydrochloric acid (1 : 7) and 1 grm. of -pure zinc is placed in a long test-tube, the mouth of which is covered -with a disc of filter-paper previously moistened with one or two drops -of mercuric chloride solution, and dried. If arsenic is present, a -yellow stain is produced upon the filter-paper within fifteen minutes, -and it subsequently becomes darker.[767] - -[767] "Arsenic in Glycerin," by Dr. H. B. H. Paul and A. J. Cownley, -_Pharm. Journ._, Feb. 24, 1894. - -Sec. 740. =Arsenic in Organic Matters.=--Orfila and the older school of -chemists took the greatest care, in searching for arsenic, to destroy -the last trace of organic matter. Orfila's practice was to chop up the -substance and make it into a paste with 400 to 700 grms. of water; to -this .010 grm. KHO in alcohol was added, and .020 grm. of potassic -nitrate. The substances were heated up to from 80 deg. to 90 deg. for some time, -until they were pretty well dissolved; the organic matter was then burnt -off in a Hessian crucible heated to redness, on which small quantities -of the matters were placed at a time. When the whole had thus been -submitted to red heat, the melted mass was run into an almost red-hot -porcelain basin, and allowed to cool. Afterwards, it was again heated -with concentrated sulphuric acid, until all nitric and nitrous fumes -were dissipated; on dissolving and filtering in water, the liquid was -introduced into a Marsh's apparatus. Orfila never seems to have failed -in detecting arsenic by this process. For an organ like the liver, he -considered that 100 grms. of potash and 86 of strong sulphuric acid were -necessary in order to destroy the organic matters. - -The liability of the various reagents used to impurity, and the -probability of loss in these operations, have tended to discredit -destruction of the organic matter by a red heat, and chemists generally -have preferred to oxidise animal matters by a moist process. The organic -substance is divided finely and digested with dilute hydrochloric acid, -and from time to time crystals of potassic chlorate are thrown in until -all the fluid is very thin and capable of passing through a filter. The -filtrate must now be submitted to the prolonged action of sulphuretted -hydrogen,[768] and the sulphide of arsenic separated from free sulphur -by dissolving in sodic sulphide. After filtering, the arsenic sulphide -may be again thrown down by the addition of hydrochloric acid, -collected on a filter, and still further purified by solution in ammonic -carbonate; once more precipitated by hydrochloric acid, and lastly -identified by conversion into magnesia pyro-arseniate (see p. 572). The -above process is a general and safe way of detecting arsenic in almost -any organic tissue, but the author prefers the distillation process -described p. 575 _et seq._ - -[768] The SH_{2} should be washed by passing it through two or more -washing bottles supplied with warm dilute HCl--a few samples of sulphide -of iron give off an arseniferous gas, so that this precaution is -necessary. - -From ordinary pills, quack extracts, and similar preparations, drying, -powdering, and exhaustion with boiling dilute HCl, will remove the whole -of the arsenic, if in a soluble state. - -Oils and matters consisting almost entirely of fat, suspected of -containing arsenic, are gently heated, and allowed to deposit any -insoluble matter they may contain; the oil is then decanted, and, if -necessary, filtered from any deposit; saponified by alcoholic potash, -the soap decomposed by HCl, the fatty acids separated, and the arsenic -looked for both in the first deposit and in the solution, now fairly -free from fat, and easy to treat. - -In searching for arsenic in the fluids or tissues of the body, the -analyst is generally at the mercy of the pathologist, and sometimes the -work of the chemist leads to a negative result, solely from not having -the proper organ sent to him.[769] - -[769] For example, in cases of poisoning by external application, more -than once merely the empty stomach and a piece of intestine have been -forwarded to the writer. - -Brodie long ago stated that when arsenious acid had been given in -solution to any animal capable of vomiting, no arsenic could be detected -in the stomach; this statement is too absolute, but in the majority of -cases true. - -In all cases the chemist should have portions of the brain, spinal cord, -liver, kidneys, lungs, and muscular tissue, as well as the stomach and -its contents. - -According to the experiments of Scolosuboff,[770] arsenic is generally -greatest in the marrow, then in the brain, next in the liver, and least -in the muscles, and the following may be taken as a fairly accurate -statement of the relative proportion in which arsenic is likely to be -found in the body, 100 grms. being taken of each:-- - -[770] _Bull. Soc. Chim._ (2), xxiv. p. 124. - - Muscles, 1 - Liver, 10.8 - Brain, 36.5 - Spinal Marrow, 37.3 - -But Ludwig's[771] experiments and conclusions are entirely opposed to -this, since both in acute and chronic cases he found as follows (per -cent. As_{2}O_{3}):-- - -[771] _Ueber die Verhaltung des Arsens im thierischen Organismus nach -Einverleibung von Arseniger Saeure. Med. Jahrbuch_, 1880. - - Brain, .0002 - Liver, .001 - Kidney, .0004 - Muscle, .00025 - -So that he detected in the liver five times more than in the brain. M. -P. Hamberg has also confirmed the fact, that more is found in the liver -and kidneys than in the nervous tissues. - -Chittenden[772] found in a body the following quantities of arsenic -estimated as arsenious acid:-- - -[772] _American Chemical Journal_, v. 8. - - Grain. - Stomach and gullet, 0.158 - Intestines, 0.314 - Liver, 0.218 - Kidney, 0.029 - Lungs and spleen, 0.172 - Heart, 0.112 - Brain, 0.075 - Diaphragm, 0.010 - -The whole arsenic present was estimated as equal to 3.1 grains of -arsenious acid, viz., 2.628 grains absorbed, and 0.472 unabsorbed; of -the absorbed portion 8.3 per cent. was found in the liver. - -With regard to the preliminary treatment of the stomach and fluids -submitted to the analyst, the careful noting of appearances, the -decantation, washing, and examination[773] (microscopical and chemical) -of any deposit, are precautions so obviously dictated by common sense, -that they need only be alluded to in passing. Of some considerable -moment is the question which may be put to the analyst in court, in -reference to the possible entrance of arsenic into the living body, by -accidental and, so to speak, _subtle_ means. Such are the inhaling of -the fumes from the burning of arsenical candles,[774] and of emanations -from papers (see p. 541),[775] as well as the possible entrance of -arsenic into the body after death from various sources, such as -arsenical earth, &c.[776] - -[773] From some observations of Fresenius in a recent number of the -_Zeitschrift f. anal. Chem._, it would seem necessary to test all glass -vessels used; for it is difficult at present to purchase arsenic-free -glass. - -[774] See a case of poisoning (non-fatal) of a lady by the use of -arsenical candles, _Med. Times and Gazette_, vol. iii., 1876, p. 367. - -[775] To solve this question, it has been at times considered necessary -to analyse an extraordinary number of things. In the "affaire Danval" -(_Journ. d'Hygiene_, 2e ser., No. 108, July 1878), more than sixty -different articles, comprising drugs, drinks, perfumes, bed-curtains, -wall-paper, and other matters, were submitted to the experts. - -[776] The following important case is related by Sonnenschein:-- - -Nicholas Nobel and his wife, Jerome, were buried two metres from each -other in the churchyard at Spinal, the earth of which notoriously -contained arsenic. A suspicion of poisoning arose. The bodies were -exhumed, and arsenic was found in the stomach and intestines of Nobel, -but not the slightest trace in the corpse of the wife. The remains of -the bodies were reinterred, and after six months, on a fresh suspicion -of poisoning arising, again exhumed. The corpse of the woman had been -put naked in the moist earth during a heavy shower, but this time also -no arsenic was detected in it. - -Sec. 741. =Imbibition of Arsenic after Death.=--The arguments which are -likely to be used, in favour of a corpse having become arsenical may be -gathered from a case related by Sonnenschein:--Certain bodies were -exhumed in two churchyards; the evidence went to show that they had been -poisoned by arsenic, and this substance was actually found in the -bodies, while at the same time it was discovered to exist also in traces -in the earth of the churchyard. The theory for the defence was, that -although the arsenic in the earth was in an insoluble state, yet that it -might combine with lime as an arsenite of lime; this arsenite would -become soluble by the action of carbonic acid set free by vegetation, -and filter down to the corpse. Sonnenschein suspended a quantity of this -earth in water, and passed CO_{2} through it for twelve hours; on -filtering, the liquid gave no evidence of arsenic. A similar result was -obtained when an artificial mixture of 1 grm. of arsenious acid and 1 -pound of earth were submitted to the same process. - -The fact would appear to stand thus: oxide of iron in ordinary earth -retains arsenic, and requires treatment with a concentrated acid to -dissolve it. It therefore follows that, if a defence of arsenical earth -is likely to be set up, and the analyst finds that by mere extraction of -the tissues by _water_ he can detect arsenic, the defence is in all -probability unsound. The expert should, of course, deal with this -question on its merits, and without prejudice. According to -Eulenberg,[777] in arsenical earth--if, after having been crushed and -washed, it lies for some time exposed to the disintegrating action of -the air--soluble arsenical salts are formed, which may find their way -into brooks and supplies of drinking water. We may infer that it is -hardly probable (except under very peculiar circumstances) for a corpse -to be contaminated internally with an estimable quantity of arsenic from -the traces of arsenic met with in a few churchyards. - -[777] _Gewerbe Hygiene_, p. 234. - -It occasionally happens that an exhumation is ordered a very long time -after death, when no organs or parts (save the bones) are to be -distinguished. In the case of a man long dead, the widow confessing that -she had administered poison, the bones were analysed by Sonnenschein, -and a small quantity of arsenic found. Conierbe and Orfila have both -asserted that arsenic is a normal constituent of the bones--a statement -which has been repeatedly disproved. Sonnenschein relates:[778]--"I -procured from a churchyard of this place (Berlin) the remnants of the -body of a person killed twenty-five years previously, and investigated -several others in a similar way, without finding the least trace of -arsenic. Similar experiments in great number were repeated in my -laboratory, but in no case was arsenic recognised." The opinion of the -expert, should he find arsenic in the bones, must be formed from the -amount discovered, and other circumstances. - -[778] _Gerichtl. Chem._, p. 212. - -A difficult case on which to form an opinion is one recorded by William -P. Mason,[779] as follows:-- - -[779] _Chem. News_, Feb. 23, 1894. - - The deceased, a farmer, bachelor, sixty-five years of age, and in - good health, was taken violently sick shortly after breakfast, with - vomiting and distress in the stomach. Although a physician was - summoned, the symptoms increased in severity, and a little after - midnight death ensued. The funeral took place three days later. - Certain very damaging pieces of circumstantial evidence having been - collected, the housekeeper was arrested on the charge of murder, it - having been shown, among other things, that on the day preceding the - death she had purchased an ounce of white arsenic. - - Thirty-five days after death (from March 20 to April 25) the body - was exhumed, and found in a state of remarkable preservation, and - free from cadaveric smell. The stomach presented evidences of - inflammation. - - Portions sent for analysis were the stomach, portion of intestine, - portion of liver, one kidney, and the heart. Arsenic was found in - all these parts. White octahedral crystals were found in the - contents of the stomach, which on separation gave arsenical - reaction. - - The arsenic found was:-- - - Stomach and intestine, 0.2376 grm. - Liver and kidney, 0.0032 " - Heart, 0.0007 " - ------ - Total as metallic arsenic, 0.2415 " - - The amount of arsenic recovered and produced in court was in - quantity sufficient to produce death. Some time after the analytical - report was made to the coroner, it was learned that an embalming - fluid, highly arsenical in character, had been used upon the body by - the undertaker at the time of preparation for burial. No injection - of this embalming fluid was practised, but cloths wrung out in the - fluid were laid upon the face and chest, and were kept constantly - wet therewith during a period of many hours. In all about two quarts - of embalming fluid were so used. Its composition appeared to be a - strongly acidified solution of sodium arsenite and zinc sulphate. - Only the arsenic and zinc were determined quantitatively, and they - were found to be, zinc (metallic), 1.978 per cent., and arsenic - (metallic), 1.365 per cent. by weight. An amount of this fluid - measuring 15.7 c.c. would thus contain a weight of arsenic equal to - that actually recovered from the body. - - Extended medical testimony was offered by the prosecution, tending - to show that, under the given circumstances, no fluid of any kind - could have reached the stomach through the nose or mouth after - death, thus anticipating what the defence afterwards claimed, that - the undertaker was responsible for the arsenic discovered in the - remains. - - In order to gather further light upon the possibility of cadaveric - imbibition of embalming fluid through the unbroken skin, test was - made for zinc in the heart and stomach, and distinct traces of the - metal were found in each instance. That at least a portion of the - arsenic found in the body was due to _post-mortem_ causes was thus - distinctly proven. A weighed portion (62 grms.) of the stomach and - contents was then most carefully analysed quantitatively for both - zinc and arsenic with the following results:--Arsenic, 0.0648 grm., - and zinc, 0.0079 grm. Bearing in mind the relative quantities of the - two metals in the embalming fluid, it will be seen that the arsenic - found in the 62 grms. of the stomach was nearly twelve times larger - than it should have been to have balanced the zinc which was also - present. This fact, together with the discovery of crystals of white - arsenic in the stomach, constituted the case for the prosecution, so - far as the chemical evidence was concerned. - - The defence made an unsuccessful effort to show that the crystals of - the tri-oxide originated from the spontaneous evaporation of the - embalming fluid. The prosecution met this point by proving that such - fluid had been abundantly experimented upon by exposure to a very - low temperature during an interval of several months, and also by - spontaneous evaporation with a view of testing that very question, - and that the results had in every case been negative. Special - importance was given these experiments, because of the well-known - separation of octahedral crystals during the spontaneous evaporation - of a hydrochloric acid solution of the white oxide, it having also - appeared that, in the manufacture of the embalming fluid, the - arsenic was used as white arsenic. - - A very strong point was finally raised for the defence by the - inability of the expert on the side of the prosecution to state - positively whether or not an embalming fluid of the above - composition would diffuse as a whole through dead tissue, or its - several parts would be imbibed at different rates of speed, the zinc - portion becoming arrested by albuminoid material and being therefore - outstripped by the arsenic, or _vice versa_. The prisoner was - ultimately acquitted. - -In a case which occurred in the Western States of America, there was -good reason for believing that arsenic had been introduced into the -corpse of a man _after_ his decease. With regard to the imbibition of -arsenic thus introduced, Orfila[780] says:--"I have often introduced -into the stomach (as well as the rectum) of the corpses of men and dogs -2 to 3 grms. of arsenious acid, dissolved in from 400 to 500 grms. of -water, and have examined the different viscera at the end of eight, ten, -or twenty days. Constantly I have recognised the effects of cadaveric -imbibition. Sections of the liver or other organs which touch the -digestive canal, carefully cut and analysed, furnished arsenic, which -could not be obtained sensibly (or not at all) from sections which had -not been in contact with this canal. If the corpse remained long on the -back after arsenious acid had been introduced into the stomach, I could -obtain this metal from the left half of the diaphragm and from the -inferior lobe of the left lung, whilst I did not obtain it from other -portions of the diaphragm nor from the right lung." Dr. Reece has also -made some experiments on the imbibition of arsenic after death. He -injected solutions of arsenious acid into the stomach of various -warm-blooded animals, and found at various periods arsenic, not alone in -the intestinal canal, but also in the spleen, liver, and kidneys. - -[780] _Op. cit._, t. i. p. 309. - -Sec. 742. =Analysis of Wall-Paper for Arsenic.=--The separation of arsenic -from paper admits of great variety of manipulation. A quick special -method is as follows:--The paper is saturated with chlorate of potash -solution, dried, set on fire in a suitable plate, and instantly covered -with a bell-glass. The ash is collected, pulverised, and exhausted with -cold water, which has previously thoroughly cleansed the plate and -bell-glass; the arsenic in combination with the potash is dissolved, -whilst oxides of chromium, copper, aluminium, tin, and lead remain in -the insoluble portion.[781] - -[781] Kapferschlaeger: _Rev. Universelle des Mines_, 1876. - -Fresenius and Hintz[782] have elaborated a method for the examination of -wall-papers, fabrics, yarns, and similar substances, which, provided the -reagents are pure, is accurate and easy. Twenty-five grms. of the -substance are placed in a half-litre distilling flask or retort, and 250 -c.c. of HCl, specific gravity 1.19, added; after digestion for an hour, -5 c.c. of a saturated solution of ferrous chloride are added, and the -liquid slowly distilled until frothing stops any farther distillation. A -further quantity of 100 c.c. HCl is then added, and distilled over. The -receiver, in each case, contains water, and must be kept cool. The -united distillates are diluted to 800 c.c. and saturated with SH_{2}. -The arsenious sulphide is collected on an asbestos filter. After partial -washing, it is heated with bromine in HCl of 1.9 specific gravity, and -the solution again distilled with ferrous chloride. The distillate, on -now being treated with SH_{2}, gives arsenious sulphide free from -organic matter. - -[782] _Zeit. anal. Chem._, xxvii. 179-182. - -Sec. 743. =Estimation of Arsenic.=--Most of the methods for the -quantitative determination of arsenic are also excellent tests for its -presence. It may be regarded, indeed, as an axiom in legal chemistry, -that the precise amount of every substance detected, if it can be -weighed or estimated by any process whatever, should be accurately -stated. Indefinite expressions, such as "a small quantity was found," -"traces were detected," &c., are most objectionable. The more perfect of -the methods of evolving arsenic can be made quantitative. For example, -the galvanic process introduced by Bloxam may be utilised as follows:--A -fractional part of the arsenical solution is taken for the experiment; -the bottom of a narrow-necked bottle of about 100 c.c. capacity is -removed, and replaced by a piece of vegetable parchment. The neck of the -bottle carries a cork, which is pierced by (1) a platinum wire, which is -attached to a platinum electrode; (2) a short tube, bent at right -angles, and connected by piping with a longer tube, which has also a -rectangular bend, and dips into a solution of silver nitrate; (3) an -ordinary funnel-tube, reaching nearly to the bottom. The bottle is -placed in a beaker of such a size as to leave a small interval between -the two, and the whole apparatus stands in a large vessel of cold water. -Dilute sulphuric acid is now put into the bottle, and also into the -beaker, so that the fluid reaches exactly the same level in each. The -positive platinum electrode of a battery of six of Grove's cells, or -other efficient combination, is immersed in the liquid outside the -bottle, connection with the negative plate is established, and hydrogen -very soon comes off, and passes over into the nitrate of silver -solution. When all the air is expelled, a portion of the rectangular -tube is heated to redness, and if there is no stain nor any reduction of -the silver, the acid is pure. If the gas is passed for a long time into -the silver solution, the silver will be reduced to some extent by the -hydrogen, although arsenic-free;[783] so that it is better to rely upon -the metallic ring or stain, which is certain to be formed on heating a -portion of the tube red-hot, and keeping it at that temperature for _at -least ten minutes_. The liquid is then passed through the funnel in -successive portions; if arsenic is present, there will be a decided -metallic ring on heating the tube as before, and if antimony is present, -there will also be a stain; the distinctions between these stains have -been described at p. 557. - -[783] Nitrate of silver solution is reduced by H_{2}, CH_{3}, PH_{3}, -and SbH_{3}; hence it is absolutely necessary in any qualitative -examination to prove that arsenious acid has actually been produced in -the silver solution. - -The tube is kept red-hot until the stain is very distinct; then the -source of heat is removed, and the gas allowed to bubble through the -argentic nitrate solution, which it decomposes, as before detailed (p. -526). This process is continued until, on placing the delivery tube in a -sample of clear nitrate of silver solution, there is no darkening of -colour. In certain cases this may take a long time, but the apparatus, -once set to work, requires little superintendence. At the conclusion, -the whole of the arsenic is separated,--part is in the silver solution -as arsenious acid, part in the tube as a ring of metallic arsenic. The -portion of the tube containing the metallic arsenic should be cut off -with a file and weighed, the arsenic then removed and re-weighed; the -loss is the metal approximately. Or, the weight of the film may be -estimated by having a set of similar deposits of known weight or -quantities, in tubes exactly corresponding to those used in the -analysis, and comparing or matching them. - -The arsenious acid in the nitrate of silver may be dealt with in several -ways. The equation given (p. 526) shows clearly that pure arsine, passed -into nitrate of silver solution, decomposes it in such a manner that, if -either the silver deposited or the free acid is estimated, the quantity -of arsenic can from such data be deduced. In operating on organic -liquids, ammonia and other products may be given off, rendering either -of the indirect processes inadvisable. A very convenient method, -applicable in many cases, is to throw out the silver by hydrochloric -acid, alkalise the filtrate by bicarbonate of soda, and titrate with -iodine solution. The latter is made by dissolving exactly 12.7 grms. of -pure dry iodine by the aid of 18 grms. of potassic iodide in one litre -of water, observing that the solution must take place in the cold, -without the application of heat. The principle of the titration is, that -arsenious acid, in the presence of water and free alkali, is converted -into arsenic acid-- - - As_{2}O_{3} + 4I + 2Na_{2}O = As_{2}O_{5} + 4NaI. - -The end of the reaction is known by adding a little starch-paste to the -solution; as soon as a blue colour appears, the process is finished. - -Another convenient way by which (in very dilute solutions of arsenious -acid) the arsenic may be determined, is a colorimetric method, which -depends on the fact that sulphuretted hydrogen, when arsenious acid is -present in small quantity, produces no precipitate at first, but a -yellow colour, proportionate to the amount of arsenic present. The -silver solution containing arsenious acid is freed from silver by -hydrochloric acid; a measured quantity of saturated SH_{2} water is -added to a fractional and, if necessary, diluted portion, in a Nessler -cylinder or colorimetric apparatus, and the colour produced exactly -imitated, by the aid of a dilute solution of arsenious acid, added from -a burette to a similar quantity of SH_{2} water in another cylinder, the -fluid being acidified with HCl. - -Sec. 744. =Destruction of the Organic Matter by Nitric Acid, and Subsequent -Reduction of the Arsenic Acid to Arsine (Arseniuretted Hydrogen), and -final Estimation as Metallic Arsenic.=--This process, which is -essentially a combination of several, has been much improved in its -details by R. H. Chittenden and H. H. Donaldson.[784] 100 grms. of the -suspected matters, cut up into small pieces, are heated in a porcelain -dish of suitable size, stirred by means of a glass rod with 23 c.c. of -pure concentrated nitric acid, and heated up to from 150 deg. to 160 deg. When -the matters assume a yellow or orange colour, the bath is removed from -the source of heat, and 3 c.c. of pure concentrated sulphuric acid -added, and the mixture stirred, when the mass becomes brown, swells up, -and evolves dense nitrous and other fumes. The vessel is again heated to -180 deg., and while hot 8 c.c. of pure concentrated nitric acid are added, -drop by drop, with continual stirring. After this addition, it is heated -to 200 deg. for fifteen minutes, and the result on cooling is a hard -carbonaceous residue wholly free from nitric acid. The arsenic is in -this way oxidised into arsenic acid, which is easily soluble in water. -The contents of the dish are, therefore, perfectly extracted by boiling -water, the aqueous extract filtered, and evaporated to dryness. The next -process is to obtain the arsenic in a metallic state:-- - -[784] _American Chem. Journ._, vol. ii., No. 4; _Chem. News_, Jan. 1881, -p. 21. - -The flask, a Bunsen's wash-bottle of 200 c.c. capacity, is provided with -a small separating funnel of 65 c.c. capacity, with glass stop-cock. -This is a very material aid to the obtaining of a slow and even -evolution of gas, an important desideratum when all loss is to be -avoided; for with only a funnel tube, every time a small portion of -fluid is added, a sudden rush of gas takes place, with probably a small, -but still more or less appreciable, loss. But the separating funnel, -filled with the acid mixture, can be so arranged as to give a constant -and regular supply of fluid at the rate of two or three drops per -minute, more or less. The gas generated is dried by a calcic chloride -tube, and then passes through a tube of hard glass, heated to a red heat -by a miniature furnace of three Bunsen lamps with spread burners, so -that a continuous flame of 6 inches is obtained, and with a proper -length of cooled tube not a trace of arsenic passes by. The glass tube -where heated is wound with a strip of wire gauze, both ends being -supported upon the edges of the lamp frame, so that the tube does not -sink down when heated. The small furnace is provided with two -appropriate side pieces of sheet metal, so that a steady flame is always -obtained. When the quantity of arsenic is very small, the tube is -naturally so placed that the mirror is deposited in the narrow portion; -but when the arsenic is present to the extent of 0.005 grm., the tube -should be 6 mm. in inner diameter, and so arranged that fully 2 inches -of this large tube are between the flame and the narrow portion. When -the quantity of arsenic is less, the tube can naturally be smaller. - -Acids of different strengths are made as follows:-- - - Acid No. 1. - - 545 c.c. pure conc. H_{2}SO_{4}. - 5000 c.c. H_{2}O. - - Acid No. 2. - - 109 c.c. pure conc. H_{2}SO_{4}. - 1640 c.c. Acid No. 1. - - Acid No. 3. - - 218 c.c. pure conc. H_{2}SO_{4}. - 1640 c.c. Acid No. 1. - - Acid No. 4. - - 530 c.c. pure conc. H_{2}SO_{4}. - 1248 c.c. H_{2}O. - -25 to 35 grms. of granulated zinc, previously alloyed with a small -quantity of platinum, are placed in the generator, and everything being -in position, the apparatus is filled with hydrogen by the use of a small -quantity of acid No. 2. After a sufficient time has elapsed, the gas is -lighted at the jet, and the glass tube heated to a bright redness. - -The arsenical solution in concentrated form is mixed with 45 c.c. of -acid No. 2, and the mixture passed into the separating funnel, from -which it is allowed to flow into the generator at such a rate that the -entire fluid is introduced in one hour or one and a half; 40 c.c. of -acid No. 3 are then added and allowed to flow slowly into the generator, -and, lastly, 45 c.c. of acid No. 4. The amount of time required will -vary with the amount of arsenic: 2 to 3 mgrms. of arsenic will require -about two to three hours for the entire decomposition, while 4 to 5 -mgrms. will need perhaps three to four hours. Where the amount of -arsenic is small, only 25 grms. of zinc are needed, and but 45 c.c. of -acid No. 2, 30 c.c. of acid No. 3, and 30 c.c. of acid No. 4; but when -4 to 5 mgrms. of arsenic are present, it is better to take the first -mentioned quantities of zinc and acids. - -The arsenic being thus collected as a large or small mirror of metal, -the tube is cut at a safe distance from the mirror, so that a tube of -perhaps 2 to 6 grms. weight is obtained. This is carefully weighed, and -then the arsenic removed by simple heating; or, if the arsenic is to be -saved (as in a toxicological case), dissolved out with strong nitric -acid. The tube is then cleaned, dried, and again weighed, the difference -giving the weight of metallic arsenic, from which, by a simple -calculation, the amount of arsenious oxide can be obtained. Some test -results are given as follows; they were obtained by introducing definite -quantities of arsenious oxide in the form of a solution mixed with 45 -c.c. of No. 2 acid, &c.:-- - - Quantity of Wt. of Metallic Theoretical Wt. of - Arsenic introduced. Arsenic found. Metallic Arsenic. - - 0.005 grm. As_{2}O_{3} 0.00373 0.00378 - 0.005 " " 0.00370 0.00378 - 0.004 " " 0.00300 0.00303 - 0.002 " " 0.00151 0.00151 - -Sanger estimates and tests for minute quantities of arsenic by the -Marsh-Berzelius process, and uses a generator of hydrogen; that is to -say, the hydrogen is evolved in the ordinary way from zinc and sulphuric -acid, and the issuing gas dried by calcic chloride; but into this flask -is also delivered from another flask, charged with sulphuric acid and -zinc, pure hydrogen, so that into the second flask, little by little, -may be added the solution to be tested; and, owing to the generating -flask, the gas may be made to give a uniform current, and at the end of -the operation all arsine swept out. To estimate the quantities of -arsenic in the gas, the reduction tube is heated, and a mirror or -mirrors obtained, and compared with a set of standard mirrors. The -standard mirrors are made as follows:--One grm. of arsenious oxide, -purified by repeated sublimation, is dissolved with the aid of a little -sodic bicarbonate, and, after acidification with dilute sulphuric acid, -made up to 1 litre. This standard solution contains 1 mgrm. of -As_{2}O_{3} in every c.c., and is used to make a second standard -solution, containing 0.01 mgrm., to every c.c., by diluting 10 c.c. to a -litre. Of this last solution, 1 c.c., 2 c.c., 3 c.c., and so on, are -measured and introduced into the reduction flask, and the standard -mirrors obtained. It is recommended, for obvious reasons, to make more -than one standard for each quantity, for the appearance of the mirrors -from the same amount of arsenic varies. The tubes are hermetically -sealed, and, when not in use, kept in the dark. - -This process is convenient for small amounts of arsenic; but, as stated -before, the results are given as metallic arsenic, whereas the films -appear never to be composed of pure metallic arsenic, but a mixture of -hydride and suboxide. Test experiments give, however, fair results.[785] - -[785] _Proc. American Academy of Arts and Sciences_, vol. xxvi. - -Sec. 745. =Arsine Developed from an Alkaline Solution.=--Fleitmann -discovered in 1851 that arsenic, mixed with finely divided zinc, and -excess of soda or potash added, evolved arsine; but no stibine was -evolved under the same conditions. In 1873 J. W. Gatehouse suggested the -use of aluminium and sodic hydrate as a modification of Fleitmann's -test, for the purpose of distinguishing between arsenic and antimony; -and this is now the usual process adopted. The hydrogen comes off -regularly even in the cold, but it is best to apply a little heat. This -test will evolve arsine from arsenious acid, and also from arsenic -trisulphide; but it is not available for the detection of arsenic, when -the arsenic is in the form of arsenic acid. According to Clark,[786] it -is not adapted for quantitative purposes, because, owing to the -formation of solid hydride, about one-fifth remains behind. - -[786] _Journ. Chem. Soc._, 1893, 884. - -E. W. Davy, in 1876, proposed the use of sodium amalgam for the -generation of arsine; on the whole, it is, however, not so convenient as -the aluminium process. - -The liquid to be tested is made strongly alkaline with pure sodic or -potassic hydrate placed in a flask connected with a tube dipping into a -4 per cent. solution of silver nitrate, a few pieces of sheet aluminium -added, and the flask gently heated; any arsine present will reduce the -silver. The silver solution thus blackened may be treated in the manner -described (p. 567). - -Sec. 746. =Precipitation as Tersulphide.=--Despite the advantages of some -of the processes described, which are (to a certain extent) easy and -accurate, not a few chemists still prefer the old method of -precipitation with hydric sulphide SH_{2}, because, although tedious, it -has stood the test of experience. If this be used, it is well in most -cases to pass sulphurous anhydride through the liquid until it smells -strongly of the gas, for by this means any arsenic acid present is -reduced, the sulphurous anhydride is quickly got rid of by a current of -carbonic anhydride, and then the liquid is saturated with hydric -sulphide. In the ordinary way, much time is often wasted in saturating -the liquid with this gas. Those, however, who have large laboratories, -and daily employ hydric sulphide, possess (or should possess) a water -saturated with the gas under pressure; such a liquid, added in equal -volume to an arsenical solution, is able to convert the whole of the -arsenic into sulphide in a very few minutes. Those who do not possess -this hydric sulphide water can saturate in an hour the liquid to be -tested, by passing the gas in under pressure.[787] A convenient method -is to evolve SH_{2} from sulphide of antimony and ClH; the gas passes -first into a wash-bottle, and then into a strong flask containing the -solution under trial. This flask is furnished with a safety-valve, -proportioned to the strength of the apparatus; the two tubes dipping -into the wash-bottle and the last flask are provided with Bunsen's -valves, which only allow the gas to pass in one direction. The hydric -sulphide is then driven over by heat, and when sufficient gas has in -this way passed into the liquid, the flame is withdrawn, and the -apparatus allowed to stand for some hours, the valves preventing any -backward flow of the liquid or gas. When the precipitate has settled to -the bottom, the supernatant fluid is carefully passed through a filter, -and the precipitate washed by decantation in the flask, without -transference to the filter, if it can be avoided. - -[787] Hydric sulphide gas has been liquefied, and is now an article of -commerce, being sold in iron bottles. - -The impure sulphide is washed with water, then with alcohol, then with -carbon disulphide, then, after having got rid of the lead, again with -alcohol, and finally with water; it is then dissolved in ammonia, the -ammonia solution filtered, and the filtrate evaporated to dryness on a -sand-bath, at a somewhat high temperature; in this way it is freed from -sulphur and, to a great extent, from organic matter; after weighing, it -may be purified or identified by some of the following methods:-- - -(_a_) =Solution in Ammonia and Estimation by Iodine.=[788]--The filter -is pierced, the sulphide washed into a flask by ammonia water (which -need not be concentrated), and dissolved by warming, filtered from any -insoluble matter, and estimated by iodine and starch. - -[788] P. Champion and H. Pellett, _Bull. Soc. Chim._ (2), xxvj. pp. -541-544. - -(_b_) =Oxidation of the Sulphide and Precipitation as Ammonia Magnesian -Arseniate, or Magnesia Pyro-Arseniate.=--The tersulphide, as before, is -dissolved in ammonia (not omitting the filter-paper, which should be -soaked in this reagent), the solution filtered, and evaporated to -dryness. The dry residue is now oxidised by fuming nitric acid, taking -care to protect the dish with a large watch-glass (or other cover) -during the first violent action; the dish is then heated in the -water-bath until all the sulphur has disappeared, and only a small bulk -of the liquid remains; it is then diluted and precipitated by "magnesia -mixture."[789] The fluid must stand for several hours, and, if the -arsenic is to be determined as the usual ammoniacal salt, it must be -passed through a weighed filter, and washed with a little ammoniacal -water (1 : 3). The solubility of the precipitate is considerable, and -for every 16 c.c. of the filtrate (not the washings) 1 mgrm. must be -allowed. The precipitate, dried at 100 deg., 2(NH_{4}MgAsO_{4})H_{2}O, -represents 39.47 per cent. metallic arsenic. - -[789] Magnesia Mixture:-- - - Sulphate of magnesia, 1 - Chloride of ammonium, 1 - Solution of ammonia, 4 - Water, 8 - -Dissolve; then allow to stand for several days; finally filter, and keep -for use. - -The solubility of the magnesium arseniate itself, and the general -dislike which chemists have to weighing in such hygroscopic material as -a filter, are, perhaps, the main reasons for the variation of this old -method, which has lately come into notice. Rose proposed some time ago -the conversion of the double salt into the pyro-arseniate--a method -condemned by Fresenius and Parnell, but examined and pronounced a -practicable and accurate process by Remol, Rammelsberg, Thorpe, Fuller, -Wittstein, Emerson, Macivor, Wood, and Brauner. The modification of -Rose's process, recommended by Wood,[790] and still further improved by -Brauner,[791] may be accepted. - -[790] _Zeitschrift fuer anal. Chem._, vol. xiv. p. 356. - -[791] _Ibid._, xvj. pp. 57, 58. - -The precipitation is effected by magnesia mixture, with the addition of -half its bulk of alcohol. The solution is allowed to stand for several -hours, until it is possible to decant the clear liquid from the -precipitate; the latter is now dissolved in ClH, reprecipitated as -before, thrown on a small filter, and washed with a mixture of one -volume of ammonia, two volumes of alcohol, and three of water. - -The precipitate is now dried, and transferred as completely as possible -from the filter into a small porcelain crucible, included in a larger -one made of platinum, moistened with nitric acid, covered and heated at -first gently, lastly to a bright redness; the filter is then treated -similarly, and the crucible with its contents weighed. Pyro-arseniate of -arsenic (Mg_{2}As_{2}O_{7}) contains 48.29 per cent. of metallic -arsenic. - -(_c_) =Conversion of the Trisulphide of Arsenic into the Arsenomolybdate -of Ammonia.=--The purified sulphide is oxidised by nitric acid, the acid -solution is rendered alkaline by ammonia, and then precipitated by a -molybdenum solution, made as follows:--100 grms. of molybdic acid are -dissolved in 150 c.c. of ordinary ammonia and 80 of water; this solution -is poured drop by drop into 500 c.c. of pure nitric acid and 300 c.c. of -water; it is allowed to settle, and, if necessary, filtered. The -molybdic solution must be mixed in excess with the liquid under -treatment, the temperature raised to 70 deg. or 80 deg., and nitric acid added -in excess until a yellow coloration appears; the liquid is then passed -through a tared filter, and dried at 100 deg. It contains 5.1 per cent. of -arsenic acid [3.3 As].[792] - -[792] Champion and Pellett, _Bull. Soc. Chim._, Jan. 7, 1877. - -(_d_) =Conversion of the Sulphide into Metallic Arsenic.=--If there -should be any doubt as to the nature of the precipitated substances, the -very best way of resolving this doubt is to reduce the sulphide to -metal; the easiest method of proving this is to dissolve in potash and -obtain arsine by the action of aluminium; or if it is desired to evolve -arsine from an acid solution with zinc in the usual way, then by -dissolving a slight excess of zinc oxide in potash or soda, and -dissolving in this the arsenic sulphide; the zinc combines with all the -sulphur, and converts the sulpharsenite into arsenite; the zinc sulphide -is filtered off, and the filtrate acidified and introduced into Marsh's -apparatus. The original process of Fresenius was to mix the sulphide -with carbonate of soda and cyanide of potassium, and place the mixture -in the wide part of a tube of hard German glass, drawn out at one end to -a capillary fineness. Carbonic anhydride, properly dried, was passed -through the tube, and the portion containing the mixture heated to -redness; in this way the arsenical sulphide was reduced, and the metal -condensed in the capillary portion, where the smallest quantity could be -recognised. A more elaborate and accurate process, based on the same -principles, has been advocated by Mohr.[793] - -[793] Mohr's _Toxicologie_, p. 57. - -A convenient quantity of carbonate of soda is added to the sulphide, and -the whole mixed with a very little water, and gently warmed. The yellow -precipitate is very soon dissolved, and then the whole is evaporated -carefully, until it is in a granular, somewhat moist, adhesive state. It -is now transferred to a glass tube, open at top and bottom, but the top -widened into a funnel; this tube is firmly held perpendicularly on a -glass plate, and the prepared sulphide hammered into a compact cylinder -by the aid of a glass rod, which just fits the tube. The cylinder is now -dried over a flame, until no more moisture is to be detected, and then -transferred into a glass tube 4 or 5 inches long, and with one end drawn -to a point (the weight of this tube should be first accurately taken). -The tube is connected with the following series:--(1) A chloride of -calcium tube; (2) a small bottle containing nitrate of silver solution; -(3) a hydrogen-generating bottle containing zinc and sulphuric acid. The -hydrogen goes through the argentic nitrate solution, leaving behind any -sulphur and arsenic it may contain; it is then dried by chloride of -calcium, and streams in a pure dry state over the cylinder of prepared -sulphide (no error with regard to impurities in the gas is likely to -occur; but in rigid inquiries it is advisable to heat a portion of the -tube, previous to the insertion of the cylinder, for some time, in order -to prove the absence of any external arsenical source); when it is -certain that pure hydrogen, unmixed with air, is being evolved, the -portion of the tube in which the cylinder rests is heated slowly to -redness, and the metallic arsenic sublimes at a little distance from the -source of heat. Loss is inevitable if the tube is too short, or the -stream of hydrogen too powerful. - -The tube after the operation is divided, the portion soiled by the soda -thoroughly cleansed, and then both parts weighed; the difference between -the weight of the empty tube and the tube + arsenic gives the metallic -arsenic. This is the process as recommended by Mohr; it may, however, be -pointed out that the glass tube itself loses weight when any portion of -it is kept red-hot for some little time; and, therefore, unless the -crust is required in the original tube, it is better to divide it, -carefully weigh the arsenical portion, remove the crust, and then -re-weigh. The method is not perfectly accurate. The mirror is not pure -metallic arsenic (see p. 571), and if the white alkaline residue be -examined, arsenic will be detected in it, the reason being that the -arsenical sulphide generally contains pentasulphide of arsenic as well -as free sulphur. Now the pentasulphide does not give up metallic arsenic -when treated as before detailed; nor, indeed, does the trisulphide, if -mixed with much sulphur, yield an arsenical crust. It is, therefore, of -great moment to free the precipitate as much as possible from sulphur, -before attempting the reduction. - -The development of a reducing gas from a special and somewhat -complicated apparatus is not absolutely necessary. The whole process of -reduction, from beginning to end, may take place in a single tube by any -of the following processes:--(1) The sulphide is mixed with oxalate of -soda (a salt which contains no water of crystallisation), and the dry -mixture is transferred to a suitable tube, sealed at one end. An -arsenical mirror is readily obtained, and, if the heat is continued long -enough, no arsenic remains behind--an excellent and easy method, in -which the reducing gas is carbonic oxide, in an atmosphere of carbonic -anhydride. (2) The sulphide is oxidised by _aqua regia_, and the -solution evaporated to complete dryness. The residue is then dissolved -in a few drops of water, with the addition of some largish grains of -good wood charcoal (which absorb most of the solution), and the whole -carefully dried. The mass is now transferred to a tube closed at one -end, a little charcoal added in the form of an upper layer, and heat -applied first to this upper layer, so as to replace the air with CO_{2}, -and then to bring the whole tube gradually to redness from above -downwards. In this case also the whole of the arsenic sublimes as a -metallic mirror. - -There are various other modifications, but the above are trustworthy, -and quite sufficient. Brugelmann's method of determining arsenic, -elsewhere described, would appear to possess some advantages, and to -promise well; but the writer has had no personal experience of it with -regard to arsenic. - -Sec. 747. =Conversion of Arsenic into Arsenious Chloride= (AsCl_{3}).--This -process, first employed by Schneider and Fyfe, and afterwards modified -by Taylor, differs from all the preceding, since an attempt is made to -separate by one operation volatile metallic chlorides, and to -destroy the organic matter, and thus obtain two liquids--one a -distillate--tolerably clear and free from solid particles, whilst the -mass in the retort retains such metals as copper, and is in every way -easy to deal with. - -Schneider and Fyfe employed sulphuric acid and common salt; but Taylor -recommends hydrochloric acid, which is in every respect preferable. As -recommended by Taylor, all matters, organic or otherwise, are to be -completely desiccated before their introduction into a retort, and on -these dried substances sufficient pure hydrochloric acid poured, and the -distillation pushed to dryness. Every one is well aware how tedious is -the attempt to dry perfectly the organs of the body (such as liver, &c.) -at any temperature low enough to ensure against volatilisation of such a -substance as, _e.g._, calomel. This drying has, therefore, been the -great stumbling-block which has prevented the general application of the -process. It will be found, however, that drying in the ordinary way is -by no means necessary. The writer cuts up the solid organ (such as -liver, brain, &c.) with scissors into small pieces, and transfers them -to a retort fitted by an air-tight joint to a Liebig condenser; the -condenser in its turn being connected with a flask by a tube passing -through an india-rubber stopper dipping into a little water. Another -tube from the same flask is connected with india-rubber piping, which is -connected with a water-pump, the fall tube of which terminates in the -basement of a house over a gully. The distillation is now carried on to -carbonisation; on cooling, a second quantity of hydrochloric acid is -added, and the last fraction of the distillate examined for arsenic. If -any is found, a third distillation is necessary. At the termination of -the operation the retort is washed with water, the solution filtered, -and this solution and the distillate are each separately examined for -arsenic. If properly performed, however, the second distillation brings -over the whole of the arsenical chloride,[794] and none will be found in -the retort. With the above arrangement there can be no odour, nor is -there any loss of substance. In the distillate the arsenic can hardly be -in the form of arsenious chloride, but rather arsenious acid and -hydrochloric acid; for the chloride easily splits up in the presence of -water into these substances. It is best to convert it into the -trisulphide. Taylor[795] recommends evolving arsine in the usual way, -and passing the arsine (AsH_{3}) into solution of silver nitrate, -finally estimating it as an arseniate of silver. Objections with regard -to the impurity of reagents should be met by blank experiments. -Kaiser[796] has proposed and practised a modification of this method, -which essentially consists in the use of sulphuric acid and sodic -chloride (as in Schneider and Fyfe's original process), and in passing -the distillate first into a flask containing a crystal or two of -potassium chlorate, and thence into an absorption bulb; in the latter -most of the arsenic is found in the form of arsenic acid, the chloride -having been oxidised in its passage. The apparatus is, however, -complicated in this way without a corresponding advantage.[797] Lastly, -E. Fischer[798] has shown that it is a considerable advantage to add -from 10 to 20 c.c. of a saturated solution of ferrous chloride before -distilling with HCl. In this way all the arsenic, whether as arsenic or -arsenious acids, is easily converted into chloride. - -[794] Dragendorff asserts to the contrary; but we may quote the -authority of Taylor, who has made several experiments, in which he -obtained all the arsenic as chloride. The writer has performed the -process many times, each time carefully testing the mass in the retort -for arsenic; but the result proved that it had entirely passed over. - -[795] _Principles of Medical Jurisprudence_, vol. i. p. 267. - -[796] _Zeitschr. f. anal. Chem._, xiv. pp. 250-281. - -[797] Selmi (_Atti dell. Accademia dei Lincei_, Fasc. ii., 1879) -proposed a modification of Schneider's process. The substances are -treated with hot, pure sulphuric acid, and at the same time the liquid -is traversed by a stream of hydrochloric acid gas. The resulting -distillate is tested for arsenic by Marsh's process. Selmi states that, -operating in this way, he has detected 1/400 of a mgrm. of As_{2}O_{3} -in 100 grms. of animal matter. - -[798] _Scheidung u. Bestimmung d. Arsens_; Liebig's _Annalen d. Chemie_, -Bd. ccvii. p. 182. - - -2. ANTIMONY. - -Sec. 748. =Metallic Antimony.=--Atomic weight, 120.3 (R. Schneider), 120.14 -(Cook[799]); specific gravity, 6.715; fusing-point about 621 deg. (1150 deg. -F.). In the course of analysis, metallic antimony may be seen as a black -powder thrown down from solutions; as a film deposited on copper or -platinum; and, lastly, as a ring on the inside of a tube from the -decomposition of stibine. At a bright red-heat it is volatilised slowly, -even when hydrogen is passed over it; chlorine, bromine, and iodine -combine with it directly. It may be boiled in concentrated ClH without -solution; but _aqua regia_, sulphides of potassium and sodium readily -dissolve it. The distinction between thin films of this metal and of -arsenic on copper and glass are pointed out at pp. 557 and 559. It is -chiefly used in the arts for purposes of alloy, and enters to a small -extent into the composition of fireworks (_vide_ pp. 534 and 581). - -[799] _Ann. Phys. Chem._ (2), v. pp. 255-281. - -Sec. 749. =Antimonious Sulphide.=--Sulphide of antimony = 336; composition -in 100 parts, Sb 71.76, S 28.24. The commercial article, known under the -name of black antimony, is the native sulphide, freed from silicious -matter by fusion, and afterwards pulverised. It is a crystalline -metallic-looking powder, of a steel-grey colour, and is often much -contaminated with iron, lead, copper, and arsenic. - -The amorphous sulphide (as obtained by saturating a solution of tartar -emetic with SH_{2}) is an orange-red powder, soluble in potash and in -ammonic, sodic, and potassic sulphides; and dissolving also in -concentrated hydrochloric acid with evolution of SH_{2}. It is insoluble -in water and dilute acid, scarcely dissolves in carbonate of ammonia, -and is quite insoluble in potassic bisulphite. If ignited gently in a -stream of carbonic acid gas, the weight remains constant. To render it -anhydrous, a heat of 200 deg. is required. - -The recognition of arsenic in the commercial sulphide is most easily -effected by placing 2 grms. or more in a suitable retort (with -condenser), adding hydrochloric acid, and distilling. The chloride of -arsenic passes over before the chloride of antimony; and by not raising -the heat too high, very little antimony will come over, even if the -distillation be carried almost to dryness. The arsenic is detected in -the distillate by the ordinary methods. - -Several lamentable accidents have happened through mistaking the -sulphide of antimony for oxide of manganese, and using it with potassic -chlorate for the production of oxygen. The addition of a drop of -hydrochloric acid, it is scarcely necessary to say, will distinguish -between the two. - -Antimony is frequently estimated as sulphide. An amorphous tersulphide -of mercury, containing a small admixture of antimonious oxide and -sulphide of potassium, is known under the name of _Kermes mineral_, and -has lately been employed in the vulcanising of india-rubber. Prepared in -this way, the latter may be used for various purposes, and thus become a -source of danger. It behoves the analyst, therefore, in searching for -antimony, to take special care not to use any india-rubber fittings -which might contain the preparation. - -A _pentasulphide of antimony_ (from the decomposition of Schleppe's salt -[Na_{3}Sb_{6}S_{4} + 9H_{2}O], when heated with an acid) is used in -calico-printing. - -Sec. 750. =Tartarated Antimony, Tartrate of Potash and Antimony, or Tartar -Emetic=, is, in a medico-legal sense, the most important of the -antimonial salts. Its formula is KSbC_{4}H_{4}O_{7}H_{2}O, and 100 -parts, theoretically, should contain 35.2 per cent. of metallic -antimony. The B.P. gives a method of estimation of tartar emetic not -free from error, and Professor Dunstan has proposed the -following:--Dissolve 0.3 grm. of tartar emetic in 80 c.c. of water, add -to this 10 c.c. of a 5 per cent. solution of sodium bicarbonate, and -immediately titrate with a decinormal solution of iodine, using starch -as an indicator. One c.c. of _n_/10 iodine = 0.0166 grm. tartar emetic; -therefore, if pure, the quantity used by 0.3 grm. should be 18 c.c. -Tartar emetic occurs in commerce in colourless, transparent, rhombic, -octahedral crystals, slightly efflorescing in dry air. - -A crystal, placed in the subliming cell (p. 258), decrepitates at 193.3 deg. -(380 deg. F.), sublimes at 248.8 deg. (480 deg. F.) very slowly and scantily, and -chars at a still higher temperature, 287.7 deg. (550 deg. F.). On evaporating a -few drops of a solution of tartar emetic, and examining the residue by -the microscope, the crystals are either tetrahedra, cubes, or branched -figures. 100 parts of cold water dissolve 5 of tartar emetic, whilst the -same quantity of boiling water dissolves ten times as much, viz., 50. -The watery solution decomposes readily with the formation of algae; it -gives no precipitate with ferrocyanide of potassium, chloride of barium, -or nitrate of silver, unless concentrated. - -Sec. 751. =Metantimonic Acid=, so familiar to the practical chemist from -its insoluble sodium salt, is technically applied in the painting of -glass, porcelain, and enamels; and in an impure condition, as antimony -ash, to the glazing of earthenware. - -Sec. 752. =Pharmaceutical, Veterinary, and Quack Preparations of -Antimony.=[800] - -[800] The history of antimony as a drug is curious. Its use was -prohibited in France in 1566, because it was considered poisonous, one -Besnier being actually expelled from the faculty for transgressing the -law on this point. The edict was repealed in 1650; but in 1668 there was -a fresh enactment, confining its use to the doctors of the faculty. - -(1) =Pharmaceutical Preparations=:-- - -=Oxide of Antimony= (Sb_{2}O_{3}) is a white powder, fusible at a low -red heat, and soluble without effervescence in hydrochloric acid, the -solution responding to the ordinary tests for antimony. Arsenic may be -present in it as an impurity; the readiest means of detection is to -throw small portions at a time on glowing charcoal, when very small -quantities of arsenic will, under such conditions, emit the peculiar -odour. Carbonate of lime appears also to have been found in the oxide of -commerce. - -=Antimonial Powder= is composed of one part of oxide of antimony and two -parts of phosphate of lime; in other words, it ought to give 33.3 per -cent. of Sb_{2}O_{3}. - -=Tartar Emetic= itself has been already described. The preparations used -in medicine are-- - -=The Wine of Antimony= (=Vinum antimoniale=), which is a solution of -tartar emetic in sherry wine, and should contain 2 grains of the salt in -each ounce of the wine (0.45 grm. in 100 c.c.). - -=Antimony Ointment= (=Unguentum antimonii tartarati=) is a mechanical -mixture of tartar emetic and lard, or simple ointment;[801] strength 20 -per cent. There is no recorded case of conviction for the adulteration -of tartar emetic; cream of tartar is the only probable addition. In such -a case the mixture is less soluble than tartar emetic itself, and on -adding a small quantity of carbonate of soda to a boiling solution of -the suspected salt, the precipitated oxide at first thrown down, becomes -redissolved. - -[801] Simple ointment is composed of white wax 2, lard 3, almond oil 3 -parts. - -=Solution of Chloride of Antimony= is a solution of the terchloride in -hydrochloric acid; it is a heavy liquid of a yellowish-red colour, -powerfully escharotic; its specific gravity is 1.47; on dilution with -water, the whitish-yellow oxychloride of antimony is precipitated. One -drachm (3.549 c.c.) mixed with 4 ounces (112 c.c.) of a solution of -tartaric acid (.25 : 4) gives a precipitate with SH_{2}, which weighs -_at least_ 22 grains (1.425 grm.). This liquid is used on very rare -occasions as an outward application by medical men; farriers sometimes -employ it in the foot-rot of sheep. - -=Purified Black Antimony= (=Antimonium nigrum purificatum=) is the -purified native sulphide Sb_{2}S_{3}; it should be absolutely free from -arsenic. - -=Sulphurated Antimony= (=Antimonium sulphuratum=) is a mixture of -sulphide of antimony, Sb_{2}S_{3}, with a small and variable amount of -oxide, Sb_{2}O_{3}. The P.B. states that 60 grains (3.888 grms.) -dissolved in ClH, and poured into water, should give a white precipitate -of oxychloride of antimony, which (properly washed and dried) weighs -about 53 grains (3.444 grms.). The officinal compound pill of -subchloride of mercury (_Pilula hydrargyri subchloridi composita_) -contains 1 grain (.0648 grm.) of sulphurated antimony in every 5 grains -(.324 grm.), _i.e._, 20 per cent. - -(2) =Patent and Quack Pills=:-- - - =Dr. J. Johnson's Pills.=--From the formula each pill should - contain:-- - - Grains. Grms. - Compound Extract of Colocynth, 2.5 = .162 - Calomel, .62 = .039 - Tartar Emetic, .04 = .002 - Oil of Cassia, .12 = .007 - ---- ---- - 3.28 = .210 - - The oil of cassia can be extracted by petroleum ether; the calomel - sublimed and identified by the methods given in the article on - "Mercury"; the antimony deposited in the metallic state on platinum - or tin; and the colocynth extracted by dissolving in water, - acidifying, and shaking up with chloroform. On evaporating the - chloroform the residue should taste extremely bitter; dissolved in - sulphuric acid it changes to a red colour, and dissolved in Froehde's - reagent to a cherry-red. It should also have the ordinary reactions - of a glucoside. - - =Mitchell's Pills= contain in each pill:-- - - Grains. Grms. - Aloes, 1.1 = .070 - Rhubarb, 1.6 = .103 - Calomel, .16 = .010 - Tartar Emetic, .05 = .003 - ---- ---- - 2.91 = .186 - - The mineral substances in this are easy of detection by the methods - already given; the aloes by the formation of chrysammic acid, and - the rhubarb by its microscopical characters. - - =Dixon's Pills= probably contain the following in each pill:-- - - Grains. Grms. - Compound Extract of Colocynth, 2.0 = .1296 - Rhubarb, 1.0 = .0648 - Tartar Emetic, .06 = .0038 - ---- ----- - 3.06 = .1982 - - -(3) =Antimonial Medicines, chiefly Veterinary=:[802]-- - -[802] There has long prevailed an idea (the truth of which is doubtful) -that antimony given to animals improves their condition; thus, the -_Encyclop. Brit._, 5th ed., art. "Antimony":--"A horse that is lean and -scrubby, and not to be fatted by any means, will become fat on taking a -dose of antimony every morning for two months together. A boar fed for -brawn, and having an ounce of antimony given him every morning, will -become fat a fortnight sooner than others put into the stye at the same -time, and fed in the same manner, but without the antimony." Probably -the writer means by the term _antimony_ the impure sulphide. To this may -be added the undoubted fact, that in Brunswick the breeders of fat geese -add a small quantity of antimonious oxide to the food, as a traditional -custom. - - =Liver of Antimony= is a preparation formerly much used by farriers. - It is a mixture of antimonious oxide, sulphide of potassium, - carbonate of potassium, and undecomposed trisulphide of antimony - (and may also contain sulphate of potassium), all in very - undetermined proportions. When deprived of the soluble potash salts, - it becomes the _washed saffron of antimony_ of the old pharmacists. - A receipt for a grease-ball, in a modern veterinary work, gives, - with liver of antimony, cream of tartar and guaiacum as ingredients. - - =Hind's Sweating-ball= is composed of 60 grains (3.888 grms.) of - tartar emetic and an equal portion of assaf[oe]tida, made up into a - ball with liquorice-powder and syrup. The assaf[oe]tida will be - readily detected by the odour, and the antimony by the methods - already recommended. - - =Ethiops of Antimony=, very rarely used now, is the mechanical - mixture of the sulphides of antimony and mercury--proportions, 3 of - the former to 2 of the latter. - - =The Flowers of Antimony= is an impure oxysulphide of antimony, with - variable proportions of trioxide and undecomposed trisulphide. - - =Diaphoretic Antimony= (=calcined antimony=) is simply antimoniate - of potash. - - =Glass of Antimony= is a mixture of sulphide and oxide of antimony, - contaminated with a small quantity of silica and iron. - - A quack pill, by name, =Ward's Red Pill=, is said to contain glass - of antimony and dragon's blood. - - =Antimonial Compounds used in Pyrotechny=:-- - - Blue Fire:-- - - Antimonious sulphide, 1 - Sulphur, 2 - Nitre, 6 - - This composition is used for the blue or Bengal signal-light at sea. - Bisulphide of carbon and water are solvents which will easily - separate the powder into its three constituents. - - Crimson Fire:-- - - Potassic Chlorate, 17.25 - Alder or Willow Charcoal, 4.5 - Sulphur, 18. - Nitrate of Strontia, 55. - Antimonious Sulphide, 5.5 - - The spectroscope will readily detect strontia and potassium, and the - analysis presents no difficulty. In addition to these a very great - number of other pyrotechnical preparations contain antimony. - - Sec. 753. =Alloys.=--Antimony is much used in alloys. The ancient - _Pocula emetica_, or everlasting emetic cups, were made of antimony, - and with wine standing in them for a day or two, they acquired - emetic properties. The principal antimonial alloys are Britannia and - type metal, the composition of which is as follows:-- - - Tin, Copper, Antimony, - per cent. per cent. per cent. - Britannia Metal, Best, 92.0 1.8 6.2 - Common, 92.1 2.0 5.9 - For Castings, 92.9 1.8 5.3 - For Lamps, 94.0 1.3 4.7 - - Tea Lead, Antimony, Block Tin, - per cent. per cent. per cent. - Type Metal, { (1.) 75 20 5 - { (2.) 70 25 5 - Metal for Stereotype, 84.2 13.5 2.3 - - There is also antimony in brass, concave mirrors, bell-metal, &c. - - Sec. 754. =Pigments.=--Cassella and Naples yellow are principally - composed of the antimoniate of lead. - - =Antimony Yellow= is a mixture of antimoniate of lead with basic - chloride of lead. - -Sec. 755. =Dose.=--A medicinal dose of a soluble antimonial salt should not -exceed 97.2 mgrms. (1-1/2 grain). With circumstances favouring its -action, a dose of 129.6 mgrms. (2 grains) has proved fatal;[803] but -this is quite exceptional, and few medical men would consider so small a -quantity dangerous for a healthy adult, especially since most -posological tables prescribe tartar emetic as an emetic in doses from -64.8 to 194.4 mgrms. (1 to 3 grains). The smallest dose which has killed -a child appears to be 48.5 mgrms. (3/4 grain).[804] The dose of tartar -emetic for horses and cattle is very large, as much as 5.832 grms. (90 -grains) being often given to a horse in his gruel three times a day. 3.8 -grms. (60 grains) are considered a full, but not an excessive, dose for -cattle; .38 grm. (6 grains) is used as an emetic for pigs, and half this -quantity for dogs. - -[803] Taylor, Guy's Hosp. Reports, Oct. 1857. - -[804] Op. cit. - -Sec. 756. =Effects of Tartar Emetic and of Antimony Oxide on -Animals.=--Large doses of tartar emetic act on the warm-blooded animals -as on man; whether the poison is taken by the mouth, or injected -subcutaneously, all animals able to vomit[805] do so. The heart's -action, at first quickened, is afterwards slowed, weakened, and lastly -paralysed. This action is noticed in cold as well as in warm-blooded -animals. It is to be ascribed to a direct action on the heart; for if -the brain and spinal cord of the frog be destroyed--or even if a -solution of the salt be applied direct to the frog's heart separated -from the body--the effect is the same. The weak action of the heart, of -course, causes the blood-pressure to diminish, and the heart stops in -diastole. The voluntary muscles of the body are also weakened; the -breathing is affected, partly from the action on the muscles. The -temperature of the body is depressed (according to F. A. Falck's -researches) from 4.4 deg. to 6.2 deg. - -[805] L. Hermann (_Lehrbuch der experimentellen Toxicologie_) remarks -that the vomiting must be considered as a reflex action from the -inflammatory excitement of the digestive apparatus, especially of the -stomach. It is witnessed if the poison is administered subcutaneously or -injected into the brain. Indeed, it is established that (at least, so -far as the muscles are concerned) the co-ordinated movements producing -vomiting are caused by excitement of the medulla oblongata. Giannussi -and others found that after section between the first and third vertebrae -of dogs, and subsequent administration of tartar emetic, no vomiting -took place; and Grimm's researches seem to show that the suspected -_vomit-centre_ is identical with the respiratory centre, so that the -vomiting movement is only an abnormal respiratory movement. L. Hermann, -however, considers the theory that when tartar emetic is introduced into -the vessels the _vomit-centre_ is directly excited, erroneous, for (1) -in introducing it by the veins much larger doses are required to excite -vomiting than by the stomach; and (2), after subcutaneous injection of -the salt, antimony is found in the first vomit. His explanation, -therefore, is that antimony is excreted by the intestinal tract, -and in its passage excites this action. Majendie's well-known -experiment--demonstrating that, after extirpation of the stomach, -vomiting movements were noticed--is not considered opposed to this view. - -The effect of small doses given repeatedly to animals has been several -times investigated. Dr. Nevin[806] experimented upon eleven rabbits, -giving them tartar emetic four times a day in doses of 32.4 mgrms. (1/2 -grain), 64.8 mgrms. (1 grain), and 129.6 mgrms. (2 grains). Five died, -the first after four, the last after seventeen days; three were killed -after one, three, and four days respectively, two after an interval of -fourteen days, and one thirty-one days after taking the last dose. There -was no vomiting; diarrh[oe]a was present in about half the number; one -of the rabbits, being with young, aborted. The chief symptoms were -general dulness, loss of appetite, and in a few days great emaciation. -Four of the five that died were convulsed before death, and several of -the animals exhibited ulcers of the mucous membrane of the mouth, in -places with which the powder had come in contact. Caillol and Livon have -also studied the action of small doses of the white oxide of antimony -given in milk to cats. A cat took in this way in 109 days .628 grm. The -animal passed gradually into a cachectic state, diarrh[oe]a supervened, -and it died miserably thin and exhausted. - -[806] Lever, _Med. Chir. Journ._, No. 1. - -Sec. 757. =Effects of Tartar Emetic on Man.=[807]--The analogy between the -symptoms produced by arsenic and antimony is striking, and in some acute -cases of poisoning by tartar emetic, there is but little (if any) -clinical difference. If the dose of tartar emetic is very large, there -may be complete absence of vomiting, or only a single evacuation of the -stomach. Thus, in a case mentioned by Taylor, in which a veterinary -surgeon swallowed by mistake 13 grms. (200 grains) of tartar emetic, -vomiting after fifteen minutes could only be induced by tickling the -throat. So, again, in the case reported by Mr. Freer, a man, aged 28, -took 7.77 grms. (120 grains) of tartar emetic by mistake for Epsom -salts; he vomited only once; half an hour after taking the poison he had -violent pain in the stomach and abdomen, and spasmodic contraction of -the abdomen and arms; the fingers were firmly contracted, the muscles -quite rigid, and there was involuntary aqueous purging. After six hours, -during which he was treated with green tea, brandy, and decoction of -oak-bark, he began to recover, but suffered for many nights from profuse -perspirations. - -[807] Antimony occasionally finds its way into articles of food through -obscure channels. Dr. Page has recorded the fact of antimonial lozenges -having been sold openly by an itinerant vendor of confectionery. Each -lozenge contained nearly a quarter of a grain (.16 mgrms.), and they -caused well-marked symptoms of poisoning in the case of a servant and -two children. How the antimony got in was unknown. In this case it -appears to have existed not as tartar emetic, but as an insoluble oxide, -for it would not dialyse in aqueous solution.--"On a remarkable instance -of Poisoning by means of Lozenges containing Antimony," by David Page, -M.D., Medical Officer of Health, _Lancet_, vol. i., 1879, p. 699. - -With more moderate and yet large doses, nausea and vomiting are very -prominent symptoms, and are seldom delayed more than half an hour. The -regular course of symptoms may therefore be summed up thus:--A metallic -taste in the mouth, repeated vomitings, which are sometimes bloody, -great faintness and depression, pains in the abdomen and stomach, and -diarrh[oe]a, which may be involuntary. If the case is to terminate -fatally, the urine is suppressed, the temperature falls, the face -becomes cyanotic, delirium and convulsions supervene, and death occurs -in from two to six days. Antimony, like arsenic, often produces a -pustular eruption. Solitary cases deviate more or less from the course -described, _i.e._, severe cramps affecting all the muscles, haemorrhage -from the stomach, kidney, or bowel, and death from collapse in a few -hours, have all been noticed. In a case recorded by Mr. Morley,[808] a -surgeon's daughter, aged 18, took by mistake an unknown quantity of -antimonial wine; she soon felt sleepy and powerless, and suffered from -the usual symptoms in combination with tetanic spasms of the legs. She -afterwards had enteritis for three weeks, and on recovery her hair fell -off. Orfila relates a curious case of intense spasm of the gullet from a -large dose of tartar emetic. - -[808] _Brit. Med. Journ._, Oct. 14, p. 70. - -Sec. 758. =Chronic Antimonial Poisoning.=--The cases of Palmer and J. P. -Cook, M. Mullen, Freeman, Winslow, Pritchard, and the remarkable Bravo -case have, in late years, given the subject of chronic antimonial -poisoning a considerable prominence. In the trials referred to, it was -shown that medical men might easily mistake the effects of small doses -of antimony given at intervals for the action of disease--the symptoms -being great nausea, followed by vomiting, chronic diarrh[oe]a, -alternating with constipation, small frequent pulse, loss of voice, -great muscular weakness, depression, with coldness of the skin and a -clammy perspiration. In the case of Mrs. Pritchard,[809] her face was -flushed, and her manner so excited as to give an ordinary observer the -idea that she had been drinking; and with the usual symptoms of vomiting -and purging, she suffered from cramps in the hands. Dr. Pritchard tried -to make it appear that she was suffering from typhoid fever, which the -symptoms in a few respects only resembled. - -[809] _Edin. Med. Journ._, 1865. - -According to Eulenberg, workmen, exposed for a long period to the vapour -of the oxide of antimony, suffer pain in the bladder and a burning -sensation in the urethra, and continued inhalation even leads to -impotence and wasting of the testicles.[810] - -[810] In the first operations of finishing printers' types, the workmen -inhale a metallic dust, which gives rise to effects similar to lead -colic; and probably in this case the lead is more active than the -associated antimony. - -Sec. 759. =Post-mortem Appearances.=--The effect of large doses of tartar -emetic is mainly concentrated upon the gastro-intestinal mucous -membrane. There is an example in the museum of University College -Hospital of the changes which resulted from the administration of tartar -emetic in the treatment of pneumonia. These are ascribed in the -catalogue, in part to the local action of the medicine, and in part to -the extreme prostration of the patient. In the preparation (No. 1052) -the mucous membrane over the fore border of the epiglottis and adjacent -part of the pharynx has been destroyed by sloughing; the ulceration -extends into the upper part of the [oe]sophagus. About an inch below its -commencement, the mucous membrane has been entirely removed by sloughing -and ulceration, the circular muscular fibres being exposed. Above the -upper limit of this ulcer, the mucous membrane presents several oval, -elongated, and ulcerated areas, occupied by strips of mucous membrane -which have sloughed. In other places, irregular portions of the mucous -membrane, of a dull ashen-gray colour, have undergone sloughing; the -edges of the sloughing portion are of colours varying from brown to -black. - -It is seldom that so much change is seen in the gullet and pharynx as -this museum preparation exhibits; but redness, swelling, and the -general signs of inflammation are seldom absent from the stomach and -some parts of the intestines. On the lining membrane of the mouth, -ulcers and pustules have been observed. - -In Dr. Nevin's experiments on the chronic poisoning of rabbits already -referred to, the _post-mortem_ appearances consisted in congestion of -the liver in all the rabbits; in nearly all there was vivid redness of -the stomach; in two cases there was ulceration; in some, cartilaginous -hardness of the pylorus; while, in others, the small intestines -presented patches of inflammation. In two of the rabbits the solitary -glands throughout the intestines were prominent, yellow in colour, and -loaded with antimony. The colon and rectum were healthy, the kidneys -congested; the lungs were in most congested, in some actually inflamed, -or hepatised and gorged with blood. Bloody extravasations in the chest -and abdomen were frequent. - -Saikowsky,[811] in feeding animals daily with antimony, found invariably -in the course of fourteen to nineteen days fatty degeneration of the -liver, and sometimes of the kidney and heart. In the experiment of -Caillol and Livon also all the organs were pale, the liver had undergone -fatty degeneration, and the lung had its alveoli filled with large -degenerated cells, consisting almost entirely of fat. The mesenteric -glands also formed large caseous masses, yellowish-white in colour, -which, under the microscope, were seen to be composed of fatty cells, so -that there is a complete analogy between the action of arsenic and -antimony on the body tissues. - -[811] Virchow's _Arch. f. path. Anat._, Bd. xxv.; also, _Centralblatt f. -Med. Wissen._, No. 23, 1865. - -Sec. 760. =Elimination of Antimony.=--Antimony is mainly eliminated by the -urine. In 1840, Orfila showed to the _Academie de Medecine_ metallic -antimony, which he had extracted from a patient who had taken .12 grm. -of tartar emetic in twenty-four hours. He also obtained antimony from an -old woman, aged 80, who twelve hours before had taken .6 grm. (9-1/4 -grains)--a large dose, which had neither produced vomiting nor purging. -In Dr. Kevin's experiments on rabbits, antimony was discovered in the -urine after the twelfth dose, and even in the urine of an animal -twenty-one days after the administration of the poison had been -suspended. - -Sec. 761. =Antidotes for Tartar Emetic.=--Any infusion containing tannin or -allied astringent principles, such as decoctions of tea, oak-bark, &c., -may be given with advantage in cases of recent poisoning by tartar -emetic, for any of the salt which has been expelled by vomiting may in -this way be decomposed and rendered harmless. The treatment of acute -poisoning which has proved most successful, has been the encouraging of -vomiting by tickling the fauces, giving strong green tea and stimulants. -(See Appendix.) - -Sec. 762. =Effects of Chloride or Butter of Antimony.=--Only a few cases of -poisoning by butter of antimony are on record: its action, generally -speaking, on the tissues is like that of an acid, but there has been -considerable variety in the symptoms. Five cases are recorded by Taylor; -three of the number recovered after taking respectively doses of 7.7 -grms. (2 drachms) and 15.5 grms. (4 drachms), and two died after taking -from 56.6 to 113 grms. (2 to 4 ounces). In one of these cases the -symptoms were more like those of a narcotic poison, in the other fatal -case there was abundant vomiting with purging. The autopsy in the first -case showed a black appearance from the mouth to the jejunum, as if the -parts had been charred, and extensive destruction of the mucous -membrane. In the other case there were similar changes in the stomach -and the upper part of the intestines, but neither the lips nor the lower -end of the gullet were eroded. In a case recorded by Mr. Barrington -Cooke,[812] a farmer's wife, aged 40, of unsound mind, managed to elude -the watchfulness of her friends, and swallowed an unknown quantity of -antimony chloride about 1.30 P.M. Shortly afterwards she vomited several -times, and had diarrh[oe]a; at 2.30 a medical man found her lying on her -back insensible, and very livid in the face and neck. She was retching, -and emitting from her mouth a frothy mucous fluid, mixed with ejected -matter of a grumous colour; the breathing was laboured and spasmodic; -the pulse could not be felt, and the body was cold and clammy. She -expired at 3.30, about one hour and a half from the commencement of -symptoms, and probably within two hours from the taking of the poison. -The autopsy showed no corrugation of the tongue or inner surface of the -lining membrane of the mouth, and no appearance of the action of a -corrosive upon the lips, fauces, or mucous membrane of the [oe]sophagus. -The whole of the mucous membrane of the stomach was intensely congested, -of a dark and almost black colour, the rest of the viscera were healthy. -Chemical analysis separated antimony equivalent to nearly a grm. (15 -grains) of the chloride, with a small quantity of arsenic, from the -contents of the stomach. - -[812] _Lancet_, May 19, 1883. - -Sec. 763. =Detection of Antimony in Organic Matters.=--In acute poisoning -by tartar emetic it is not impossible to find a mere trace only in the -stomach, the greater part having been expelled by vomiting, which nearly -always occurs early, so that the most certain method is, where possible, -to analyse the ejected matters. If it should be suspected that a living -person is being slowly poisoned by antimony, it must be remembered that -the poison is mainly excreted by the kidneys, and the urine should -afford some indication. The readiest way to test is to collect a -considerable quantity of the urine (if necessary, two or three days' -excretion), concentrate by evaporation, acidify, and then transfer the -liquid to a platinum dish, in which is placed a slip of zinc. The whole -of the antimony is in time deposited on the platinum dish, and being -thus concentrated, may be subsequently identified in any way thought -fit. - -Organic liquids are boiled with hydrochloric acid; organic solids are -extracted with the same acid in the manner described (p. 51); or, if the -distillation process given at p. 576 be employed, the antimony may be -found partly in the distillate, and partly in the retort. In any case, -antimony in solution may be readily detected in a variety of ways--one -of the most convenient being to concentrate on tin or platinum, to -dissolve out the antimonial film by sulphide of ammonium, and thus -produce the very characteristic orange sulphide. - -If a slip of pure tinfoil be suspended for six hours in a solution, -which should not contain more than one-tenth of its bulk of ClH, and -exhibit no stain or deposit, it is certain that antimony cannot be -present. It may also conveniently be deposited on a platinum dish,[813] -by filling the same with the liquid properly acidulated, and inserting a -rod of zinc; the metallic antimony can afterwards be washed, dried, and -weighed. - -[813] According to Fresenius (_Zeitschr. f. anal. Chem._, i. 445), a -solution which contains 1/10000 of its weight of antimony, treated in -this way, gives in two minutes a brown stain, and in ten a very notable -and strong dark brown film. When in the proportion of 1 to 20,000, the -reaction begins to be certain after a quarter of an hour; with greater -dilution it requires longer time, 1 to 40,000 giving a doubtful -reaction, and 1 to 50,000 not responding at all to this test. - -Reinsch's and Marsh's tests have been already described (pp. 558 and -559), and require no further notice. There is, however, a very beautiful -and delicate means of detecting antimony, which should not be omitted. -It is based upon the action of stibine (SbH_{3}) on sulphur.[814] When -this gas is passed over sulphur, it is decomposed according to equation, -2SbH_{3} + 6S = Sb_{2}S_{3} + 3SH_{2}, the action taking place slowly in -diffused daylight, but very rapidly in sunshine. An ordinary flask for -the evolution of hydrogen (either by galvanic processes or from zinc and -sulphuric acid), with its funnel and drying-tubes, is connected with a -narrow tube having a few fragments of sulphur, kept in place by plugs of -cotton wool. The whole apparatus is placed in sunshine; if no orange -colour is produced when the hydrogen has been passing for some time, the -liquid to be tested is poured in gradually through the funnel, and if -antimony should be present, the sulphur acquires a deep orange colour. -This is distinct even when so small a quantity as .0001 grain has been -added through the funnel. The sulphide of antimony thus mixed with -sulphur can, if it is thought necessary, be freed from the sulphur by -repeated exhaustion with bisulphide of carbon. The stibine does not, -however, represent all the antimony introduced, a very large proportion -remaining in the evolution flask;[815] hence it cannot be employed for -quantitative purposes. Moreover, the test can, of course, only be -conveniently applied on sunny days, and is, therefore, in England more -adapted for summer.[816] Often, however, as mentioned elsewhere, when -the analyst has no clue whatever to the nature of the poison, it is -convenient to pass SH_{2} in the liquid to saturation.[817] In such a -case, if antimony is present (either alone or in combination with other -sulphides), it remains on the filter, and must be separated and -identified as follows:--The sulphides are first treated with a solution -of carbonate of ammonia, which will dissolve arsenic, if present, and -next saturated _in situ_ with pure sulphide of sodium, which will -dissolve out sulphide of antimony, if present. The sulphide of antimony -will present the chemical characters already described, more -particularly-- - -[814] See Ernest Jones on "Stibine," _Journ. Chem. Soc._, vol. i., 1876. - -[815] Rieckter, _Jahresbericht_, 1865, p. 255. - -[816] The action of salts of caesium with chloride of antimony might be -used as a test for the latter. A salt of caesium gives a white -precipitate with chloride of antimony in concentrated ClH; it contains -30.531 per cent. of antimony, and corresponds to the formula -SbCl_{3}CsCl. Chloride of tin acts similarly.--E. Godeffroy, _Berichte -der deutschen Chem. Gesellschaft_, Berlin, 1874. - -[817] The solution must not be too acid. - -(1) It will evolve SH_{2} when treated with HCl, and at the same time -pass into solution.[818] - -[818] By adding chloride of tin to a solution of chloride of antimony in -sufficient quantity, and passing SO_{2} through the liquid, the whole of -the antimony can be thrown down as sulphide, whilst the tin remains in -solution. Thus,-- - - 9SnCl_{2} + 2SbCl_{3} + 3SO_{2} + 12ClH = Sb_{2}S_{3} + 9SnCl_{4} + - 6OH_{2}. - ---Federow, _Zeitschrift fuer Chemie_, 1869, p. 16. - -(2) The solution evaporated to get rid of free HCl gives with water a -thick cheesy precipitate of basic chloride of antimony. This may be seen -if only a drop or two of the solution be taken and tested in a -watch-glass. - -(3) If tartaric acid be added to the solution, this precipitation does -not occur. - -(4) The solution from (3) gives an orange precipitate with SH_{2}. - -Such a substance can only be sulphide of antimony. With regard to (2), -bismuth would act similarly, but under the circumstances could not be -present, for the sulphide of bismuth is insoluble in sodic sulphide. - -Sec. 764. =Quantitative Estimation.=--The quantitative estimation of -antimony is best made by some volumetric process, _e.g._, the sulphide -can be dissolved in HCl, some tartrate of soda added, and then carbonate -of soda to weak alkaline reaction. The strength of the solution of -tartarised antimony thus obtained can now be estimated by a decinormal -solution of iodine, the end reaction being indicated by the previous -addition of a little starch solution, or by a solution of permanganate -of potash, either of which should be standardised by the aid of a -solution of tartar emetic of known strength. - - -3. CADMIUM. - - Sec. 765. =Cadmium=, Cd = 112; specific gravity, 8.6 to 8.69; - fusing-point, 227.8 deg. (442 deg. F.); boiling-point, 860 deg. (1580 deg. - F.).--Cadmium in analysis is seldom separated as a metal, but is - estimated either as oxide or sulphide. - - Sec. 766. =Cadmium Oxide=, CdO = 128--cadmium, 87.5 per cent.; oxygen, - 12.5 per cent.--is a yellowish or reddish-brown powder, non-volatile - even at a white heat; insoluble in water, but dissolving in acids. - Ignited on charcoal, it is reduced to metal, which volatilises, and - is then deposited again as oxide, giving to the coal a distinct coat - of an orange-yellow colour in very thin layers; in thicker layers, - brown. - - Sec. 767. =Cadmium Sulphide=, CdS = 144--Cd, 77.7 per cent.; S, 22.3 - per cent.--known as a mineral termed Greenockite. When prepared in - the wet way, it is a lemon-yellow powder, which cannot be ignited in - hydrogen without loss, and is insoluble in water, dilute acids, - alkalies, alkaline sulphides, sulphate of soda, and cyanide of - potassium. The solution must not contain too much hydrochloric acid, - for the sulphide is readily soluble with separation of sulphur in - concentrated hydrochloric acid. It may be dried in the ordinary way - at 100 deg. without suffering any decomposition. - - Sec. 768. =Medicinal Preparations.=--_The Iodide of Cadmium_ (CdI_{2}) - occurs in white, flat, micaceous crystals, melting at about 215.5 deg. - (419.9 deg. F.), and at a dull red heat giving off violet vapour. In - solution, the salt gives the reactions of iodine and cadmium. The - ointment of iodide of cadmium (_Unguentum cadmii iodidi_) contains - the iodide in the proportion of 62 grains to the ounce, or 14 per - cent. - - =Cadmium Sulphate= is officinal in the Belgian, Portuguese, and - French pharmacop[oe]ias. - - Sec. 769. =Cadmium in the Arts, &c.=--Cadmium is used in various - alloys. The sulphide is found as a colouring ingredient in certain - toilet soaps, and it is much valued by artists as a pigment. The - iodide of cadmium is employed in photography, and an amalgam of - metallic cadmium to some extent in dentistry. - - Sec. 770. =Fatal Dose of Cadmium.=--Although no deaths from the use of - cadmium appear to have as yet occurred, its use in photography, &c., - may lead to accidents. There can be no question about the poisonous - action of cadmium, for Marme,[819] in his experiments on it with - animals, observed giddiness, vomiting, syncope, difficulty in - respiration, loss of consciousness, and cramps. The amount necessary - to destroy life can only be gathered from the experiments on - animals. A strong hound died after the injection of .03 grm. (.462 - grain) subcutaneously of a salt of cadmium; rabbits are poisoned if - from 19.4 to 38.8 mgrms. (.3 to .6 grain) are introduced into the - stomach. A watery solution of .5 grm. (7.5 grains) of the bromide - administered to a pigeon caused instant death, without convulsion; - the same dose of the chloride killed a second pigeon in six minutes; - .25 grm. (3.85 grains) of sulphite of cadmium administered to a - pigeon excited vomiting, and after two hours diarrh[oe]a; it died in - eight days. Another pigeon died from a similar dose in fourteen - days, and cadmium, on analysis, was separated from the liver. From - the above cases it would seem probable that 4 grms. (61.7 grains) - would be a _dangerous_ dose of a soluble salt of cadmium for an - adult, and that in a case of chronic poisoning it would most - probably be found in the liver. - -[819] _Zeitschr. f. rationelle Med._, vol. xxix. p. 1, 1867. - - Sec. 771. =Separation and Detection of Cadmium.=--If cadmium be in - solution, and the solution is not too acid, on the addition of - SH_{2} there is precipitated a yellow sulphide, which is - distinguished from antimony and arsenical sulphides by its - insolubility in ammonia and alkaline sulphides. Should all three - sulphides be on the filter (an occurrence which will seldom, perhaps - never, happen), the sulphide of arsenic can be dissolved out by - ammonia, the antimony by sulphide of sodium, leaving the sulphide of - cadmium as the residue.[820] - -[820] It is unnecessary to state that absence of sulphur is presupposed. - - The further tests of the sulphide are:-- - - (1) It dissolves in dilute nitric acid to a colourless fluid, with - separation of sulphur. - - (2) The solution, filtered and freed from excess of nitric acid by - evaporation, gives with a solution of ammonic carbonate a white - precipitate of carbonate of cadmium insoluble in excess. This - distinguishes it from zinc, which gives a similar white precipitate, - but is soluble in the excess of the precipitant. - - (3) The carbonate thus obtained, heated on platinum foil, is changed - into the brown-red non-volatile oxide. - - (4) The oxide behaves on charcoal as already detailed. - - (5) A metallic portion can be obtained by melting the oxide with - cyanide of potassium; it is between zinc and tin in brilliancy, and - makes a mark on paper like lead, but not so readily. There are many - other tests, but the above are conclusive. - - If cadmium in any case be specially searched for in the organs or - tissues, the latter should be boiled with nitric acid. The acid - solution is filtered, saturated with caustic potash, evaporated to - dryness, and ignited; the residue is dissolved in dilute - hydrochloric acid, and treated after filtration with SH_{2}. Cadmium - may also be estimated volumetrically by digesting the sulphide in a - stoppered flask with ferric chloride and hydrochloric acid; the - resulting ferrous compound is titrated with permanganate, each c.c. - of a d.n. solution of permanganate = .0056 grm. of cadmium. - - -II.--PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID -SOLUTION--BLACK. - -Lead--Copper--Bismuth--Silver--Mercury. - - -1. LEAD. - -Sec. 772. =Lead=, Pb = 207.--Lead is a well-known bluish-white, soft metal; -fusing-point, 325 deg.; specific gravity, 11.36. - -=Oxides of Lead.=--The two oxides of lead necessary to notice here -briefly are--litharge and minium. - -=Litharge, or Oxide of Lead=, PbO = 223; specific gravity, 9.2 to -9.5--Pb 92.82 per cent., O 7.18--is either in crystalline scales, a -fused mass, or a powder, varying in colour (according to its mode of -preparation) from yellow to reddish-yellow or orange. When prepared -below the temperature of fusion it is called "_massicot_." It may be -fused without alteration in weight; in a state of fusion it dissolves -silicic acid and silicates of the earths. It must not be fused in -platinum vessels. - -=Minium, or Red Lead=, 2PbO, PbO_{2}; specific gravity, 9.08, is a -compound of protoxide of lead with the dioxide. It is of a brilliant -red colour, much used in the arts, and especially in the preparation of -flint-glass. - -Sec. 773. =Sulphide of Lead=, PbS = 239; Pb, 86.61 per cent., S, 13.39 per -cent., occurring in the usual way, is a black precipitate insoluble in -water, dilute acids, alkalies, and alkaline sulphides. It dissolves in -strong nitric acid with separation of sulphur, and in strong -hydrochloric acid, with evolution of SH_{2}. Fuming nitric acid does not -separate sulphur, but converts the sulphide into sulphate. - -Sec. 774. =Sulphate of Lead=, PbSO_{4} = 303; specific gravity, 6.3; PbO, -73.61 per cent., SO_{3}, 26.39 per cent., when produced artificially is -a heavy white powder, of great insolubility in water, 22,800 parts of -cold water dissolving only one of lead sulphate; and if the water -contains sulphuric acid, no less than 36,500 parts of water are -required. The salts of ammonia (especially the acetate and tartrate) -dissolve the sulphate, and it is also soluble in hyposulphite of soda. -The sulphate can be readily changed into the carbonate of lead, by -boiling it with solutions of the alkaline carbonates. The sulphate of -lead, fused with cyanide of potassium, yields metallic lead; it may be -also reduced on charcoal, and alone it may be fused without -decomposition, provided reducing gases are excluded. - -Sec. 775. =Acetate of Lead=, =Sugar of Lead=, -Pb(C_{2}H_{3}O_{2})_{2}3OH_{2} = 379, is found in commerce in white, -spongy masses composed of acicular crystals. It may, however, be -obtained in flat four-sided prisms. It has a sweet metallic taste, is -soluble in water, and responds to the usual tests for lead. The P.B. -directs that 38 grains dissolved in water require, for complete -precipitation, 200 grain measures of the volumetric solution of oxalic -acid, corresponding to 22.3 grains of oxide of lead. - -Sec. 776. =Chloride of Lead=, PbCl_{2} = 278; specific gravity, 5.8; Pb, -74.48 per cent., Cl, 25.52 per cent., is in the form of brilliant -crystalline needles. It is very insoluble in cold water containing -hydrochloric or nitric acids. According to Bischof, 1635 parts of water -containing nitric acid dissolve one part only of chloride of lead. It is -insoluble in absolute alcohol, and sparingly in alcohol of 70 to 80 per -cent. It fuses below red heat without losing weight; at higher -temperatures it may be decomposed. - -=Carbonate of Lead.=--The commercial carbonate of lead (according to the -exhaustive researches of Wigner and Harland[821]) is composed of a -mixture of neutral carbonate of lead and hydrate of lead, the best -mixture being 25 per cent. of hydrate, corresponding to an actual -percentage of 12.3 per cent. carbonic acid. The nearer the mixture -approximates to this composition the better the paint; whilst samples -containing as much as 16.33 per cent., or as little as 10.39 per cent., -of CO_{2} are practically useless. - -[821] "On the Composition of Commercial Samples of White Lead," by G. W. -Wigner and R. H. Harland.--_Analyst_, 1877, p. 208. - -Sec. 777. =Preparations of Lead used in Medicine, the Arts, &c.= - -(1) =Pharmaceutical=:-- - -=Lead Plaster= (_Emplastrum plumbi_) is simply a lead soap, in which the -lead is combined with oleic and margaric acids, and contains some -mechanically included glycerin. - -=Lead Iodide=, PbI_{2}, is contained in the _Emplastrum plumbi iodidi_ -to the extent of 10 per cent., and in the _Unguentum plumbi iodidi_ to -the extent of about 12.5 per cent. - -=Acetate of Lead= is contained in a pill, a suppository, and an -ointment. The pill (_Pilula plumbi cum opio_) contains 75 per cent. of -lead acetate, and 12.5 per cent. of opium, the rest confection of roses. -The suppository (_Suppositoria plumbi composita_) contains 20 per cent. -of acetate of lead, and 6.6 per cent. of opium, mixed with oil of -theobroma. The ointment (_Unguentum plumbi acetatis_) contains 20.6 per -cent. of lead acetate, mixed with benzoated lard. - -The solution of subacetate of lead (_Liquor plumbi subacetatis_) is the -subacetate, Pb(C_{2}H_{3}O_{2})_{2}PbO, dissolved in water; it contains -nearly 27 per cent. of subacetate. - -A dilute solution of the stronger, under the name of _Liquor plumbi -subacetatis dilutus_, and commonly called Goulard water, is prepared by -mixing 1 part (by volume) of the solution and 1 part of spirit, and 78 -parts of distilled water; the strength is equal to 1.25 per cent. - -There is an ointment, called the _Compound Ointment of subacetate of -lead_, which contains the subacetate in about the proportion of 2 per -cent. of the oxide, the other constituents being camphor, white wax, and -almond oil. - -=Carbonate of Lead.=--The ointment (_Unguentum plumbi carbonatis_) -should contain about 12.5 per cent. of the carbonate, and the rest -simple ointment. - - (2) =Quack Nostrums, &c.=:-- - - The quack medicines composed of lead are not very numerous. - - Liebert's =Cosmetique Infaillible= is said to have for its basis - nitrate of lead. - - One of "=Ali Ahmed's Treasures of the Desert=," viz., the antiseptic - malagma, is a plaster made up of lead plaster 37.5 per cent., - frankincense 25 per cent., salad oil 25 per cent., beeswax 12.5 per - cent. - - =Lewis' Silver Cream= contains white precipitate and a salt of lead. - - =Goulard's Balsam= is made by triturating acetate of lead with hot - oil of turpentine. - - There are various ointments in use made up of litharge. Some - herbalists in the country (from cases that have come under the - writer's own knowledge) apply to cancerous ulcers, &c., a liniment - of linseed and other common oils mixed with litharge and acetate of - lead. - - Acetate of lead may also be found as a constituent of various - eye-waters. - - (3) =Preparations of Lead used in the Arts, &c.=:-- - - =Ledoyen's Disinfecting Fluid= has for its basis nitrate of lead. - - In various hair-dyes the following are all used:--Litharge, lime, - and starch; lime and carbonate of lead; lime and acetate of lead; - litharge, lime, and potassic bicarbonate. The detection of lead in - the hair thus treated is extremely easy; it may be dissolved out by - dilute nitric acid. - - =Lead Pigments.=--The principal pigments of lead are white, yellow, - and red. - - =White Pigments=:-- - - =White Lead=, =Flake White Ceruse=, =Mineral White=, are so many - different names for the carbonate of lead already described. - - =Newcastle White= is white lead made with molasses vinegar. - - =Nottingham White.=--White lead made with alegar (sour ale), often, - however, replaced by permanent white, _i.e._, sulphate of baryta. - - =Miniature Painters' White=, =White Precipitate of Lead=, is simply - lead sulphate. - - =Pattison's White= is an oxychloride of lead, PbCl_{2}PbO. - - =Yellow Pigments=:-- - - =Chrome Yellow= may be a fairly pure chromate of lead, or it may be - mixed with sulphates of lead, barium, and calcium. The pigment known - as "Cologne yellow" consists of 25 parts of lead chromate, 15 of - lead sulphate, and 60 of calcic sulphate. The easiest method of - analysing chrome yellow is to extract with boiling hydrochloric acid - in the presence of alcohol, which dissolves the chromium as - chloride, and leaves undissolved chloride of lead, sulphate of lead, - and other substances insoluble in ClH. Every grain of chromate of - lead should yield 0.24 grain of oxide of chromium, and 0.4 grain of - chloride of lead. - - =Turner's Yellow=, =Cassella Yellow=, =Patent Yellow=, is an - oxychloride of lead (PbCl_{2}7PbO) extremely fusible. - - =Dutch Pink= sometimes contains white lead. - - =Red Pigments=:-- - - =Chrome Red= is a bichromate of lead. - - =Red Lead= or =Minium= is the red oxide of lead. - - =Orange Red= is an oxide prepared by calcining the carbonate. - - The chief preparations of lead which may be met with in the arts, in - addition to the oxides and the carbonate, are-- - - The =Nitrate of Lead=, much used in calico-printing. - - The =Pyrolignite of Lead=, which is an impure acetate used in - dyeing; and - - The =Sulphate of Lead= is a by-product in the preparation of acetate - of aluminium for dyeing. - - The alloys containing lead are extremely numerous; but, according to - the experiments of Knapp,[822] the small quantity of lead in those - used for household purposes has no hygienic importance. - -[822] _Dingl. Polytech. Journ._, vol. ccxx. pp. 446-453. - -Sec. 778. =Statistics of Lead-Poisoning.=--In the ten years, 1883 to 1892, -no less than 1043 persons died from the effects of lead; of these, 3 -only were suicidal, the remaining 1040 were mainly from the manufacture -of white lead or from the use of lead in the arts or from the accidental -contamination of food or drink. - -The following table shows in what manner the 1040 were distributed as to -age and sex:-- - -DEATHS FROM LEAD-POISONING IN ENGLAND AND WALES DURING THE TEN YEARS -1883-1892. - - Ages, 0-1 1-5 5-15 15-25 25-65 65 and Total - above - Males, ... 4 14 44 733 36 831 - Females, 3 5 ... 68 129 4 209 - --------------------------------------------- - Total, 3 9 14 112 862 40 1040 - --------------------------------------------- - -Sec. 779. =Lead as a Poison.=--All the compounds of lead are said to be -poisonous; but this statement cannot be regarded as entirely correct, -for the sulphocyanide has been proved by experiment not to be so,[823] -and the sulphide is also probably inactive. In the treatment of cases of -lead-poisoning, the flowers of sulphur given internally appear to be -successful.[824] - -[823] Eulenberg, _Gewerbe Hygiene_, p. 712. - -[824] Mohr's _Toxicologie_, p. 78. - -Lead-poisoning, either in its obscure form (producing uric acid in the -blood, and, as a consequence, indigestion and other evils), or in the -acute form (as lead colic and various nervous affections), is most -frequent among those who are habitually exposed to the influence of the -metal in its different preparations, viz., workers of lead, -house-painters, artists, gilders, workers of arsenic, workers of gold, -calico-printers, colourists, type-founders, type-setters, shot-founders, -potters, faience makers, braziers, and many others.[825] In white-lead -factories so large a number of the employes suffer from poisoning that -it has excited more than once the attention of the Government.[826] - -[825] The attention which the use of lead in the arts has always excited -is evident from the fact that one of the oldest works on Trade Hygiene -(by Stockhausen) is entitled, _De lithargyrii fumo noxio, morbifico -ejusque metallico frequentiori morbo vulgo dicto huettenkatze_, Gaslar, -1556. - -[826] A departmental committee, appointed to inquire into the white lead -and allied industries, in a report presented to the Home Secretary -stated:-- - -"8. (_a_) It is known that if lead (in any form), even in what may be -called infinitesimal quantities, gains entrance into the system for a -lengthened period, by such channels as the stomach, by swallowing lead -dust in the saliva, or through the medium of food and drink; by the -respiratory organs, as by the inhalation of dust; or through the skin; -there is developed a series of symptoms, the most frequent of which is -colic. Nearly all the individuals engaged in factories where lead or its -compounds are manipulated look pale, and it is this bloodlessness and -the presence of a blue line along the margin of the gums, close to the -teeth, that herald the other symptoms of plumbism. (_b_) A form of -paralysis known as wrist-drop or lead-palsy occasionally affects the -hands of the operatives. There is, in addition, a form of acute -lead-poisoning, most frequently met with in young girls from 18 to 24 -years of age, which is suddenly developed and is extremely fatal. In it -the first complaint is headache, followed sooner or later by convulsions -and unconsciousness. Death often terminates such a case within three -days. In some cases of recovery from convulsions total blindness -remains. - -"9. There has been considerable doubt as to the channels by which the -poison enters the system. The committee have taken much evidence on this -subject, and have arrived at the conclusion (_a_) that carbonate of lead -may be absorbed through the pores of the skin, and that the chance of -this is much increased during perspiration and where there is any -friction between the skin and the clothing; (_b_) that minute portions -of lead are carried by the hands, under and round the nails, &c., on to -the food, and so into the stomach; (_c_) but that the most usual manner -is by the inhalation of lead dust. Some of this becomes dissolved in the -alkaline secretions of the mouth, and is swallowed by the saliva, thus -finding its way to the stomach. Other particles of dust are carried to -the lungs, where they are rendered soluble and absorbed by the -blood."--_Report of Chief Inspector of Factories for 1893._ - -Lead, again, has been found by the analyst in most of the ordinary -foods, such as flour, bread, beer, cider, wines, spirits, tea, vinegar, -sugar, confectionery, &c., as well as in numerous drugs, especially -those manufactured by the aid of sulphuric acid (the latter nearly -always containing lead), and those salts or chemical products which -(like citric and tartaric acids) are crystallised in leaden pans. Hence -it follows that in almost everything eaten or drunk the analyst, as a -matter of routine, tests for lead. The channels through which it may -enter into the system are, however, so perfectly familiar to practical -chemists, that a few _unusual_ instances of lead-poisoning only need be -quoted here. - -A cabman suffered from lead colic, traced to his taking the first glass -of beer every morning at a certain public-house; the beer standing in -the pipes all night, as proved by analysis, was strongly impregnated -with lead.[827] - -[827] _Chem. News._ - -The employment of red lead for repairing the joints of steam pipes has -before now caused poisonous symptoms from volatilisation of lead.[828] -The use of old painted wood in a baker's oven, and subsequent adherence -of the oxide of lead to the outside of the loaves, has caused the -illness of sixty-six people.[829] - -[828] Eulenberg, _Op. cit._, p. 708. - -[829] _Annales d'Hygiene._ - -Seven persons became affected with lead-poisoning through horse-hair -coloured with lead.[830] - -[830] Hitzig, _Studien ueber Bleivergiftung_. - -The manufacture of _American overland cloth_ creates a white-lead dust, -which has caused serious symptoms among the workmen (_Dr. G. Johnson_). -The cleaning of pewter pots,[831] the handling of vulcanised -rubber,[832] the wrapping up of various foods in tinfoil,[833] and the -fingering of lead counters covered with brine by fishmongers, have all -caused accidents in men. - -[831] _Med. Gazette_, xlviij. 1047. - -[832] _Pharm. Journ._, 1870, p. 426. - -[833] Taylor, _Prin. Med. Jurisprud._, i. - -The lead in glass, though in the form of an insoluble silicate, is said -to have been dissolved by vinegar and other acid fluids to a dangerous -extent. This, however, is hardly well established.[834] - -[834] See _Aerztl. Intelligenzbl. f. Baiern_, Jahrg., 1869; _Buchner's -Rep. Pharm._, Bd. xix. p. 1; _Med. Centrbl._, Jahrg., 1869, p. 40. - -Sec. 780. =Effects of Lead Compounds on Animals.=--Orfila and the older -school of toxicologists made a number of experiments on the action of -sugar of lead and other compounds, but they are of little value for -elucidating the physiological or toxic action of lead, because they -were, for the most part, made under unnatural conditions, the gullet -being ligatured to avoid expulsion of the salt by vomiting. Harnack, in -order to avoid the local and corrosive effects of sugar of lead, used an -organic compound, viz., plumbic triethyl acetate, which has no local -action. Frogs exhibited symptoms after subcutaneous doses of from 2 to -3 mgrms., rabbits after 40 mgrms.; there was increased peristaltic -action of the intestines, with spasmodic contraction rising to colic, -very often diarrh[oe]a, and death followed through heart paralysis. Dogs -given the ethyl compound exhibited nervous symptoms like chorea. -Gusserno[835] has also made experiments on animals as to the effects of -lead, using lead phosphate, and giving from 1.2 grm. to a rabbit and a -dog daily. Rosenstein[836] and Heubel[837] used small doses of acetate, -the latter giving dogs daily from .2 to .5 grm. The results arrived at -by Gusserno were, mainly, that the animals became emaciated, shivered, -and had some paralysis of the hinder extremities; while Rosenstein -observed towards the end epileptiform convulsions, and Heubel alone saw, -in a few of his cases, colic. A considerable number of cattle have been -poisoned from time to time with lead, and one instance of this fell -under my own observation. A pasture had been manured with refuse from a -plumber's yard, and pieces of paint were in this way strewn about the -field in every direction; a herd of fifteen young cattle were placed in -the field, and in two or three days they all, without exception, began -rapidly to lose condition, and to show peculiar symptoms--diarrh[oe]a, -loss of appetite; in two, blindness, the retina presenting an appearance -not unlike that seen in Bright's disease; in three, a sort of delirium. -Four died, and showed on _post-mortem_ examination granular conditions -of the kidneys, which was the most striking change observable. In the -fatal cases, paralysis of the hind extremities, coma, and convulsions -preceded death. In another case[838] seven cows and a bull died from -eating lead paint; the symptoms were loss of appetite, obstinate -constipation, suspension of rumination, dry muffle, quick breathing, and -coma. In other cases a marked symptom has been paralysis. Cattle[839] -have also several times been poisoned from eating grass which has been -splashed by the spray from bullets, as in pastures in the vicinity of -rifle butts; here we must allow that the intestinal juices have -dissolved the metal, and transformed it into compounds capable of being -taken into the system. - -[835] Virchow's _Archiv. f. path. Anat._, vol. xxi. p. 443. - -[836] _Ib._, vol. xxxix. pp. 1 and 74. - -[837] _Pathogenese u. Symptome der chronischen Bleivergiftung_, Berlin, -1871. - -[838] See a paper by Professor Tuson, _Veterinarian_, vol. xxxviii., -1861. - -[839] _Ib._; also Taylor, _Op. cit._ - -Sec. 781. =Effects of Lead Compounds on Man--Acute Poisoning.=--Acute -poisoning by preparations of lead is not common, and, when it does -occur, is seldom fatal. With regard to the common acetate, it would seem -that a large single dose is less likely to destroy life than smaller -quantities given in divided doses for a considerable period. The -symptoms produced by a considerable dose of sugar of lead usually -commence within a few minutes; there is immediately a metallic taste, -with burning, and a sensation of great dryness in the mouth and throat; -vomiting, which occurs usually within fifteen minutes, is in very rare -cases delayed from one to two hours. The retching and vomiting are very -obstinate, and continue for a long time; the matters thrown up are -sometimes streaked with blood; there is pain in the abdomen of a colicky -character--a pain relieved by pressure. The bowels are, as a rule, -constipated, but occasionally relaxed. The stools at a later date are -black from the presence of lead sulphide. The urine, as a rule, is -diminished. The breath has a foul odour, and the tongue is coated; the -skin is dry, and the pulse small and frequent. The full development of -the toxic action is completed by the appearance of various nervous -phenomena--headache, shooting pains in the limbs, cramps in the legs, -and local numbness. All the symptoms enumerated are not present in each -case; the most constant are the vomiting and the colic. If the sufferer -is to die, death occurs about the second or third day. If the patient -recovers, convalescence may be much retarded, as shown in the case of -two girls,[840] who had each swallowed an ounce of lead acetate by -mistake, and who suffered even after the lapse of a year from pain and -tenderness in the stomach and sickness. - -[840] Prov. _Med. Journal_, 1846. - -There are "mass-poisonings" by acetate of lead on record, which afford -considerable insight into the varying action of this salt on different -individuals. A case (_e.g._) occurred at Stourbridge in 1840,[841] in -which no less than 500 people were poisoned by thirty pounds of lead -acetate being accidentally mixed with eighty sacks of flour at a -miller's. The symptoms commenced after a few days; constriction of the -throat, cramping and twisting pains round the umbilicus, rigidity of the -abdominal muscles, dragging pains at the loins, cramps and paralysis of -the lower extremities. There was obstinate constipation; the urine was -scanty and of a deep red colour, and the secretions were generally -arrested; the pulse was slow and feeble; the countenance depressed, -often livid; and the gums showed the usual blue line. The temperature of -the skin was low. In only a few cases was there sickness, and in these -it soon ceased. It is curious that not one of the 500 cases proved -fatal, although some of the victims were extremely ill, and their -condition alarming. It was specially observed that, after apparent -convalescence, the symptoms, without any obvious cause, suddenly -returned, and this even in a more aggravated form. Remittance of this -kind is of medico-legal import; it might, for example, be wrongly -inferred that a fresh dose had been taken. In the 500 cases there were -no inflammatory symptoms; complete recovery took some time. On examining -the bread the poison was found so unequally distributed that no idea -could be formed as to the actual amount taken. - -[841] Recorded by Mr. Bancks, _Lancet_, May 5, 1849, p. 478. - -There is also recorded[842] an outbreak of lead-poisoning among 150 men -of the 7th Infantry at Tione, in the Southern Tyrol. One case proved -fatal, forty-five required treatment in hospital. The symptoms were -pallor, a blue line in the gums, metallic taste in the mouth, a peculiar -odour of the breath, a loaded tongue with a bluish tint, obstinate -constipation with loss of appetite whilst all complained, in addition, -of dragging of the limbs and of the muscles of the chest, and difficulty -of breathing. In the severer cases there were tetanic spasms, muscular -tremors, and anaesthesia of the fingers and toes. The pulse and -temperature were normal, save in a few cases in which there were fever -and sweats at night. _In none was there colic_, but the constipation was -obstinate. In two of the worst cases there was strangury. Acute cases -occur occasionally from poisoning by _the carbonate of lead_. Dr. Snow -recorded an instance (in 1844) of a child who had eaten a piece as big -as a marble, ground up with oil. For three days the child suffered from -pain in the abdomen and vomiting, and died ninety hours after taking the -poison. In another case, in which a young man took from 19 to 20 grms. -of lead carbonate in mistake for chalk as a remedy for heartburn, the -symptoms of vomiting, pain in the stomach, &c., commenced after a few -hours; but, under treatment with magnesic sulphate, he recovered. - -[842] Koenigschmied, _Centralbl. Allg. fuer Gesundheitspflege_, 2 Jahrg., -Heft 1. - -=The chromate of lead= is still more poisonous (see Art. "Chromium"). - -Sec. 782. =Chronic Poisoning by Lead.=--Chronic poisoning by lead--often -caused by strange and unsuspected channels, more frequently an incident, -nay, almost a necessity, of certain trades, and occasionally induced by -a cunning criminal for the purpose of simulating natural disease--is of -great toxicological and hygienic importance. In the white-lead trade it -is, as might be expected, most frequently witnessed; but also in all -occupations which involve the daily use of lead in almost any shape. The -chief signs of chronic poisoning are those of general ill-health; the -digestion is disturbed, the appetite lessened, the bowels obstinately -confined, the skin assumes a peculiar yellowish hue, and sometimes the -sufferer is jaundiced. The gums show a black line from two to three -lines in breadth, which microscopical examination and chemical tests -alike show to be composed of sulphide of lead; occasionally the teeth -turn black.[843] The pulse is slow, and all secretions are diminished. -Pregnant women have a tendency to abort. There are also special -symptoms, one of the most prominent of which is often lead colic. - -[843] The black line soon develops; Masazza has seen it in a dog, -exposed to the influence of lead, in so short a period as three days -(_Riforma med._, 1889, Nos. 248-257, 1). - -In 142 cases of lead-poisoning, treated between 1852 and 1862 at the -Jacob's Hospital, Leipzig, forty-four patients (or about 31 per cent.) -suffered from colic. Arthralgia--that is, pains in the joints--is also -very common; it seldom occurs alone, but in combination with other -symptoms. Thus, in seventy-five cases of lead-arthralgia treated at -Jacob's Hospital, in only seven were pain in the joints without other -complications, fifty-six being accompanied by colic, five by paralysis, -and seven by other affections of the nervous system. The total -percentage of cases of lead-poisoning, in which arthralgia occurs, -varies from 32 to 57 per cent. - -Paralysis, in some form or other, Tanqueril[844] found in 5 to 8 per -cent. of the cases, and noticed that it occurred as early as the third -day after working in lead. The muscles affected are usually those of the -upper extremity, then the legs, and still more rarely the muscles of the -trunk. It is only exceptionally that the paralysis extends over an -entire limb; it more usually affects a muscular group, or even a single -muscle. Its common seat is the extensors of the hand and fingers; hence -the expression "dropped-wrist," for the hands droop, and occasionally -the triceps and the deltoid are affected. The paralysis is usually -symmetrical on both sides. Although the extensors are affected most, the -flexors nearly always participate, and a careful investigation will show -that they are weakened. If the paralysis continues, there is a wasting -and degeneration of the muscle, but this is seen in paralysis from any -cause. The muscular affection may cause deformities in the hands, -shoulders, &c. Anaesthesia of portions of the skin is generally present -in a greater or less degree. A complete analgesia affecting the whole -body has been noticed to such an extent that there was absolute -insensibility to burns or punctures; but it is usually confined to the -right half of the body, and is especially intense in the right hand and -wrist. - -[844] Tanqueril des Planches, _Traite des Maladies de Plomb_, Paris, -1839. Tanqueril's monograph is a classical work full of information. - -Sec. 783. The older writers recognised the toxic effect of lead on the -nervous system. Thus Dioscorides speaks of delirium produced by lead, -Aretaeus of epilepsy, and Paul of AEgina refers to it as a factor of -epilepsy and convulsions. But in 1830, Tanqueril first definitely -described the production of a mental disease, which he called "_lead -encephalopathy_." This he divided into four forms--(1) a delirious form; -(2) a comatose; (3) a convulsive; and (4) a combined form, comprising -the delirious, convulsive, and comatose. Dr. Henry Rayner,[845] and a -few other English alienists, have directed their attention to this -question; and, according to Dr. Rayner's researches, the number of male -patients admitted into Hanwell Asylum, engaged in trades such as -plumbing, painting, and the like, is larger in proportion to the number -admitted from other trades than it should be, compared with the -proportion of the various trades in the county of Middlesex, as -ascertained from the census. Putting aside coarse lead-poisoning, which -may occasionally produce acute mania, the insanity produced by prolonged -minute lead intoxications possesses some peculiar features. It develops -slowly, and in nearly all cases there are illusions of the senses, of -hearing, taste, or smell, and especially of sight. Thus, in one of Dr. -Rayner's cases the patient saw round him "wind-bags blown out to look -like men," apparitions which made remarks to him, and generally worried -him. Besides this form, there is also another which closely resembles -general paralysis, and, in the absence of the history, might be mistaken -for it. - -[845] See an important paper, "Insanity from Lead-Poisoning," by Drs. H. -Rayner, Robertson, Savage, and Atkins, _Journ. of Mental Science_, vol. -xxvi. p. 222; also a paper by Dr. Barton, _Allgemeine Zeitschrift fuer -Psychiatrie_, Bd. xxxvij. H. 4, p. 9. - -Sec. 784. The degenerative influence on the organ of sight is shown in six -of Dr. Robertson's patients, whose insanity was ascribed to lead--four -of the six were either totally or partially blind. - -The amaurosis has been known to come on suddenly, and after a very brief -exposure to lead, _e.g._, a man, thirty-four years of age, after working -for three days in a white-lead factory, was seized with intense ciliary -neuralgia, had pains in his limbs and symptoms of lead-poisoning, and -the right eye became amaurotic.[846] This form of impairment or loss of -vision is different from the _Retinitis albuminurica_,[847] which may -also be produced as a secondary effect of the poison; the kidneys in -such cases being profoundly affected. The kind of diseased kidney -produced by lead is the granular contracted kidney. - -[846] Samelsohn, _Monatsbl. f. Augenheilk._, vol. xi. p. 246, 1873. See -also a case of lead amaurosis, described by Mr. W. Holder, _Pharm. -Journ._, Oct. 14, 1876. - -[847] Ran, _Arch. f. Ophthal._, vol. i. (2), p. 205, 1858, and Schmidt's -_Jahrbuch_, Bd. cxxxiii. p. 116; Bd. cxliii. p. 67. - -Eulenberg speaks of the sexual functions being weakened, leading to more -or less impotence. - -Lewy,[848] in 1186 patients suffering from lead-poisoning, has found -caries or necrosis in twenty-two cases, or about 1.8 per cent.; fifteen -were carious affections of the upper jaw, four of the fore-arm, two of -the thigh, and one of the rib and sternum. Epilepsy and epileptiform -convulsions occur in a few cases; it is very possible that the epilepsy -may be a result of the uraemic poisoning induced by diseased kidneys. - -[848] _Die Berufskrank. d. Bleiarbeiter_, Wien, 1873, S. 61. - -Five cases of fatal poisoning occurred between 1884-6 among the employes -of a certain white-lead factory in the east of London. The cases -presented the following common characters. They were all adult women, -aged from 18 to 33, and they had worked at the factory for short -periods, from three to twelve months. They all exhibited mild symptoms -of plumbism, such as a blue line round the gums, and more or less -ill-defined indisposition; paralyses were absent. They were all in their -usual state of health within a few hours or days preceding death. Death -was unexpected, mostly sudden. In four cases it was preceded by -epileptic fits and coma; but in the fifth case no convulsions were -noted, although they may have occurred in the night. - -The author[849] had an opportunity of investigating by chemical means -the distribution of lead in the fourth and fifth cases in the liver, -kidney, and brain. - -[849] "The Distribution of Lead in the Brains of two Lead Factory -Operatives," _Journ. of Mental Science_, Jan. 1888. - -In the fourth case, from 402 grms. of liver 24.26 mgrms. of lead -sulphate were separated. The right kidney (weighing 81 grms.) yielded -5.42 mgrms. of lead sulphate. The brain was dehydrated with alcohol, and -then treated with ether, hot alcohol, and chloroform until an albuminoid -residue remained; lead was extracted from each of these portions, viz., -the alcohol used for dehydration, the ethereal and chloroform extracts, -and the albuminoid residue, as follows:-- - - Mgrms. of Lead - Sulphate. - Soluble in cold alcohol, 1.11 - Soluble in ether and chloroform and hot alcohol, 25.47 - Albuminoid residue, 7.76 - 34.34 - -In the fifth case, the brain was examined more in detail, and the lead -present estimated in the following solutions and substances:-- - -1. Alcohol used for dehydration. This may be called "the watery -extract," for, after the brain has remained in strong alcohol for some -weeks, the result is that the alcohol contains much water and substances -extracted with water. - -2. White matter--(_a_) from cerebrum; (_b_) from cerebellum. - -3. Kephalin--(_a_) from cerebrum; (_b_) from cerebellum. - -4. Ether extract, kephalin-free--(_a_) from cerebrum; (_b_) from -cerebellum. - -5. Substances soluble in cold alcohol--(_a_) from cerebrum; (_b_) from -cerebellum. - -6. The albuminoid residue--(_a_) from cerebrum; (_b_) from cerebellum. - -The general results were as follows:-- - - Cerebrum, Cerebellum, - 460.8 grms. 156.2 grms. - Mgrms. of PbSO_{4}. Mgrms. of PbSO_{4}. - - White matter freed from kephalin - by ether, 0.0 5.0 - Kephalin, 1.5 6.0 - Ether extract, kephalin-free, 0.0 0.0 - Substances soluble in cold alcohol, 0.0 0.0 - Albuminoid residue, 40.0 6.0 - ---- ---- - 41.5 17.0 - -The aqueous extract contained 1.5 mgrm. of lead sulphate. In neither of -the cases did the pathologist ascertain the total weight of the brain, -but, presuming that the weight was an average weight, and that the lead -in the remainder of the brain was similarly distributed, the amount of -lead calculated as sulphate would amount to 117 mgrms. From these -results it appears to the author probable that lead forms a substitution -compound with some of the organic brain matters. This view would explain -the absence of changes apparent to the eye found in so many of the fatal -cases of lead encephalopathy. - -Sec. 785. Lead taken for a long time causes the blood to be impregnated -with uric acid. In 136 cases of undoubted gout, 18 per cent. of the -patients were found to follow lead occupations, and presented signs of -lead impregnation.[850] - -[850] "On Lead Impregnation in Relation to Gout," by Dyce Duckworth, -M.D., _St. Barth. Hosp. Reports_, vol. xvii., 1881. - -Ellenberger and Hofmeister[851] found that, with chronic poisoning of -sheep with lead, excretion of hippuric acid ceased, and the output of -uric acid was diminished. This may be explained by the formation of -glycocol being arrested. - -[851] _Arch. f. wiss. u. pract. Thierheilk._, Bd. x., 1884. - -Sec. 786. There are some facts on record which would seem to countenance -the belief that disease, primarily caused by an inorganic body like -lead, may be transmitted. M. Paul (_e.g._) has related the history of -the offspring (thirty-two in number) of seven men, who were suffering -from lead-poisoning--eleven were prematurely born and one still-born; of -the remaining twenty, eight died in the first year, four in the second, -and five in the third year, so that of the whole thirty-two, only three -survived three years. - -The influence of the poison on pregnant women is, indeed, very -deleterious. M. Paul noted that in four women who were habitually -exposed to the influence of lead, and had fifteen pregnancies, ten -terminated by abortion, two by premature confinement, three went the -full term, but one of the three children was born dead, a second only -lived twenty-four hours; so that, out of the whole fifteen, one only -lived fully. In another observation of M. Paul's, five women had two -natural confinements before being exposed to lead. After exposure, the -history of the thirty-six pregnancies of these women is as -follows:--there were twenty-six abortions (from two to five months), one -premature confinement, two infants born dead, and five born alive, four -of whom died in the first year. - -Chronic poisoning may be nearly always accounted for by the inhaling of -lead dust, or by the actual swallowing of some form of lead; but, if we -are to accept the fact narrated by the late Dr. Taylor, viz., that he -himself had an attack of lead colic from sitting in a room for a few -hours daily, in which there was a large canvas covered with white lead -and drying oil, and one or two other similar cases,[852] we must allow -that there is some subtle volatile organic compound of lead evolved. In -the present state of our knowledge, it seems more reasonable to account -for such cases by the suggestion that lead has entered the system by an -unsuspected channel. - -[852] The gate-keeper of a graveyard at Bordeaux continually used the -remnants of crosses, covered with lead paint, to replenish his fire; the -chimney smoked; gradually paralysis of the extensors of the right wrist -developed itself, and he suffered from colic and other signs of -lead-poisoning.--Marmisse, _Gaz. des Hopit._, No. 25, 1866. - -In 1882, a very interesting case occurred at Keighley, in which a -mechanic, aged 42, died from the supposed effects of lead-poisoning, -induced from drinking the town water, which was proved by Mr. Allen to -contain about 3/5 of a grain of lead per gallon. For six months he had -been out of health, and a week before his death he suffered from colic, -vomiting, constipation, and a blue line round the gums, and occasional -epileptiform seizures. After death the kidneys were found granular, and -the heart somewhat enlarged. The viscera were submitted to Mr. Allen for -analysis; no lead was found in the heart or brain, a slight, -non-estimable trace in the kidneys, and about a grain was separated from -the liver and spleen. Dr. Tidy, who was called in as an expert, gave a -very guarded opinion, rather against the theory of direct -lead-poisoning; and the verdict returned by the jury was to the effect -that the deceased died from granular kidney, accelerated by -lead-poisoning. Murder by the administration of doses of sugar of lead -is rare, but such a case has occurred. - -At the Central Criminal Court, in December 1882, Louisa Jane Taylor was -indicted for poisoning Mary Ann Tregillis at Plumstead, and convicted. -From the evidence it appeared that the prisoner, who was thirty-six -years of age, came to reside with Mr. and Mrs. Tregillis, an aged couple -of eighty-five and eighty-one years respectively. The prisoner was -proved to have purchased at different times an ounce and half an ounce -of sugar of lead, and to have added a white powder to the medicine of -Mrs. Tregillis. The illness of the latter extended from about August 23 -to October 23--a period of two months. It is difficult to say when the -first dose could have been given, but it was probably some time between -August 13 and 23, while the administration, without doubt, ceased on or -before October 6, for on that date different nursing arrangements were -made. The symptoms observed were nausea, vomiting, pain in the pit of -the stomach, burning in the throat, very dark teeth, a blue line round -the gums, and slight jaundice. There was great muscular weakness, with -trembling of the hands, and a week before death there was paralysis of -the right side. - -Lead was discovered in most of the viscera, which were in great part -normal, but the kidneys were wasted, and the mucous membrane blackened. -The actual quantity of lead recovered by analysis was small, viz., 16.2 -mgrms. (1/4 grain) from the liver; from 8 ounces of brain, 3.2 mgrms. -(1/20 grain); from half of the stomach, 16.2 mgrms. (1/4 grain); and -from the spleen, the kidneys, and the lungs, small quantities. It is, -therefore, probable that, if the whole body had been operated upon, the -yield would have been more than .15 grm. (a little over 2 grains); but -then, it must be remembered that the deceased lived, at least, seventeen -days after the last dose. - -Sec. 787. =Post-mortem Appearances.=--In acute cases of poisoning by the -acetate, there may sometimes be found a slight inflammatory appearance -of the mucous membrane of the stomach and intestines. Orfila considered -that streaks of white points adherent to the mucous membrane were -pathognomonic; but there have been several cases in which only negative -or doubtful signs of inflammatory or other action have presented -themselves. A general contraction of the intestines has often been -noticed, and is of considerable significance when present; so also is a -grey-black mucous membrane caused by deposited lead sulphide. Loen found -in dogs and guinea-pigs, poisoned by lead, local inflammation areas in -the lungs, liver, and kidneys; but in no case fatty degeneration of the -epithelial cells of the liver, kidneys, or intestines. As a rule, no -unabsorbed poison will be found in the stomach; the case related by -Christison, in which a person died on the third day after taking at a -single dose some large quantity of acetate of lead; and at the autopsy a -fluid was obtained from the stomach, which had a sweet metallic taste, -on evaporation smelt of acetic acid, and from which metallic lead was -obtained--is so very extraordinary in every respect, that its entire -accuracy is to be questioned. In death from chronic lead-poisoning, -there is but little that can be called diagnostic; a granular condition -of the kidneys, and all the pathological changes dependent on such a -condition, are most frequently seen. If the patient has suffered from -colic, a constriction of portions of the intestine has been noticed; -also, in cases in which there has been long-standing paralysis of groups -of muscles, these muscles are wasted, and possibly degenerated. In -instances, again, in which lead has induced gout, the pathological -changes dependent upon gout will be prominent. The blue line around the -gums, and sometimes a coloration by sulphide of lead of portions of the -intestines, may help a proper interpretation of the appearances seen -after death; but all who have given any attention to the subject will -agree that, simply from pathological evidence, it is impossible to -diagnose chronic lead-poisoning. - -Sec. 788. =Physiological Action of Lead.=--The action of lead is still -obscure, but it is considered to have an effect mainly on the nervous -centres. The paralysed muscles respond to the direct current, but not to -the induced, leading to the suspicion that the intramuscular -terminations of the nerves are paralysed, but that the muscular -substance itself is unattacked. On the other hand, the restriction of -the action to groups of muscles supports the theory of central action. - -The lead colic is due to a true spasmodic constriction of the bowel, the -exciting cause of which lies in the walls of the bowel itself; the -relief given by pressure is explained by the pressure causing an anaemia -of the intestinal walls, and thus lessening their sensibility. The -slowing of the pulse produced by small doses is explained as due to a -stimulation of the inhibitory nerves; and, lastly, many nervous -phenomena, such as epilepsy, &c., are in part due to imperfect -elimination of the urinary excreta, causing similar conditions to those -observed in uraemia. - -Sec. 789. =Elimination of Lead.=--When a large dose of acetate or carbonate -is taken, part is transformed into more or less insoluble -compounds--some organic, others inorganic; so that a great portion is -not absorbed into the body at all, but passes into the intestines, -where, meeting with hydric sulphide, part is changed into sulphide, -colouring the alvine evacuations black. Some of the lead which is -absorbed is excreted by the kidneys, but the search often yields only -traces. Thudichum[853] states that in fourteen cases of lead-poisoning, -in two only was obtained a weighable quantity from a day's urine; in the -remaining twelve lead was detected, but only by the brownish colour -produced in an acid solution of the ash by hydric sulphide. - -[853] _Pathology of the Urine_, p. 550. - -The elimination of lead by the kidneys is favoured by certain medicines, -such, for example, as potassic iodide. Annuschat found in dogs poisoned -by lead from 3.8 to 4.1 mgrms. in 100 c.c. of urine; but, after doses of -potassic iodide, the content of lead rose to 6.9 and even to 14 mgrms. -Lead appears to be eliminated by the skin, being taken up by the -epithelial cells, and minute, insoluble particles coming away with these -cells. If a person who has taken small doses of lead for a time be -placed in a sulphur water-bath, or have his skin moistened with a 5 per -cent. solution of sodium sulphide, the upper layer of the epidermis is -coloured dark; but the perspiration excited by pilocarpin or other -agency contains no lead. - -Sec. 790. =Fatal Dose=--(_a._) =Sugar of Lead.=--It may almost be said that -it is impossible to destroy human life with any single dose likely to be -taken or administered. In three cases an ounce (28.3 grms.) has been -taken without fatal result. Although it must be allowed that repeated -moderate doses, extending over some time, are more dangerous to health -and life than a single large dose, yet there seems to be in some -individuals a great tolerance of lead. Christison has given .18 grm. in -divided doses daily for a long time without any bad effect, save the -production of a slight colic. Swieten has also given daily 3.9 grms. (60 -grains) in ten days without observing toxic effects. That, in other -cases, less than a grain per gallon of some lead compound dissolved in -drinking-water, or in some way introduced into the economy, causes -serious illness, is most inexplicable. - -(_b._) =The Basic Acetate= in solution is more poisonous apparently than -the acetate--60 c.c. (1-1/2 drms.) have caused serious symptoms. - -(_c._) =The Carbonate of Lead.=--Doses of anything like 28 grms. (an -ounce) would probably be very dangerous to an adult; the only case of -death on record is that of a child who took some unknown quantity, -probably, from the description of the size of the lump, about 10 grms. -(2-1/2 drms.). - -Sec. 791. =Antidotes and Treatment.=--Soluble sulphates (especially -magnesic sulphate) have been given largely in both acute and chronic -cases; in the acute, it stands to reason that it is well to ensure the -presence of plenty of sulphates in the stomach and intestines, in order -to form the sparingly soluble lead sulphate, should any residue remain; -but to expect this double decomposition to go on in the blood and -tissues is not based upon sound observation. The chronic lead-poisoning -is best treated by removal from the source of mischief, the -administration of large quantities of distilled water, and medicinal -doses of potassic iodide. - -Sec. 792. =Localisation of Lead.=--In a dog, which was killed by chronic -lead-poisoning, Heubel found in the bones 0.18 to 0.27 per 1000 of lead; -in the kidneys, 0.17 to 0.20; liver, 0.10 to 0.33; spinal cord, 0.06 to -0.11; brain, 0.04 to 0.05; muscles, 0.02 to 0.04; in the intestines -traces, 0.01 to 0.02; in the spleen, the blood, and the bile, he also -only found traces. Ellenberger and Hofmeister found in the kidneys of -the sheep, 0.44 to 0.47; liver, 0.36 to 0.65; pancreas, 0.54; salivary -glands, 0.42; bile, 0.11 to 0.40; bones, 0.32; faeces, 0.22; spleen, -0.14; central nervous system, 0.07 to 0.18; blood, 0.05 to 0.12; flesh, -0.05 to 0.08; urine, 0.06 to 0.08; and in the unstriped muscles and the -lungs, 0.03 per 1000 of lead. - -Without going so far as to say that lead is a natural constituent of the -body, it is certain that it may be frequently met with in persons who -have been apparently perfectly healthy, and quite free from all symptoms -of lead-poisoning. Legrip found in the liver and spleen of a healthy -person, 5.4 mgrms. of lead oxide in every kilogram; Oidtmann, in the -liver of a man fifty-six years of age, 1 mgrm. of lead oxide per -kilogram, and in the spleen 3 mgrms. per kilogram. Hence, the analyst, -in searching for poison, must be very careful in his conclusions. Grave -and serious errors may also arise from complications; suppose, _e.g._, -that a deceased person previous to death had partaken of game, and -inadvertently swallowed a shot--if the analyst had not carefully -searched the contents of the stomach for _solid_ bodies, but merely -treated them at once with acid solvents, he would naturally get very -decided lead reactions, and would possibly conclude, and give evidence -to the effect, that a poisonous soluble salt of lead had been -administered shortly before death. - -Sec. 793. =Detection and Estimation of Lead.=--A great number of fluids -(such as beer, wines, vinegar, water, &c.), if they contain anything -like the amount of one-tenth of a milligramme in 100 c.c., will give a -very marked dark colour with SH_{2}. It is, however, usually safest in -the first place to concentrate the liquid, to add an acid, and deposit -the lead on platinum, in the way to be shortly described. Nearly all the -lead from oils and fatty matter may be dissolved out by shaking up the -fat with dilute nitric acid; if necessary, the fat should previously be -melted. - -If (in the usual course of routine research) a hydrochloric acid -solution is obtained from the treatment or destruction of organic -substances by that agent, and lead sulphide (mixed possibly with other -sulphides) is filtered off, any arsenical sulphide may first be -extracted from the filter by ammonia, and any antimonious sulphide by -sodic sulphide; then the sulphide may be extracted by warm hydrochloric -acid, which will leave undissolved such sulphides as those of copper and -mercury. On diluting the liquid, and filtration at a boiling -temperature, crystals of lead chloride will be deposited on cooling. - -If, however, organic matters are _specially_ searched for lead, -hydrochloric acid is not the best solvent, but nitric should always be -preferred; and, if there is reason to think that the lead exists in the -form of sulphate, then the proper solvent is either the acetate or the -tartrate of ammonia; but, in either case, the solution should contain an -excess of ammonia. It must, however, be remembered that organic matters -retain lead with great tenacity, and that in all cases where it can with -any convenience be effected, the substances should be not only -carbonised, but burnt to an ash; for Boucher has shown[854] that carbon -retains lead, and that the lead in carbon resists to a considerable -extent the action of solvents. - -[854] _Ann. d'Hygiene_, t. xli. - -In the case of sulphate of lead, which may be always produced in an ash -from organic substances by previous treatment with sufficient sulphuric -acid, a very excellent method of identification is to convert it into -sugar of lead. To do this, it is merely necessary to boil it with -carbonate of ammonia, which changes it into carbonate of lead; treatment -with acetic acid will now give the acetate; the solution may (if the -lead is in very small quantity) be concentrated in a watch-glass, a -drop evaporated to dryness on a circle of thin microscopic glass, and -the crystals examined by the microscope; the same film next exposed to -the fumes of SH_{2}, which will blacken it; and lastly, the solution -(which should be sweet) tasted. A crystalline substance, possessing a -sweet taste, and blackening when exposed to SH_{2}, can, under the -circumstances, be no other substance than acetate of lead. - -If the analyst does not care for this method, there is room for choice. -Lead in solution can be converted into sulphide; in this case it is, -however, absolutely necessary that there should be no great excess of -acid, since as little as 2.5 per cent. of free hydrochloric acid will -prevent all the lead going down. On obtaining the sulphide, the latter, -as already described, can be converted into chloride by hydrochloric -acid, and the crystalline chloride is extremely characteristic. - -From the solution of the chloride the metal may be obtained in a solid -state by inserting a piece of zinc in the solution contained in a -crucible; the lead will be deposited gradually, and can be then -collected, washed, and finally fused into a little globule on charcoal. -A lead bead flattens easily when hit with a hammer, and makes a mark on -paper. Solutions of the chloride also give a heavy precipitate of lead -sulphate, when treated with a solution of sodic sulphate. - -When lead is in very minute quantity, an electrolytic method is -generally preferable; the lead is precipitated on platinum by using -exactly the same apparatus as in Bloxam's test, described at p. 566; the -liquid to be tested being placed in the inner cell, the lead film may -now be identified, dissolved in nitric acid, and estimated by a -colorimetric process. For the estimation of the minute fractions of a -grain by a colour method, it is merely necessary to have a very dilute -solution of acetate of lead, to add a known volume of SH_{2} water to -the liquid to be tested in a Nessler cylinder, noting the colour, and -add to another a known quantity of the standard lead solution and the -same quantity of SH_{2} as was added to the first. - -The process has an advantage which is great, viz., that it either -detects copper, or proves its absence at the same time; and there are -few cases in which the analyst does not look for copper as well as for -lead. Lead, if in sufficient quantity, may be most conveniently -estimated as oxide, sulphate, or chloride; the chief properties of these -substances have been already described. - -Sec. 794. =The Detection of Lead in Tartaric Acid, in Lemonade, and Aerated -Waters.=--To detect lead in tartaric acid a convenient method is to burn -it to an ash, digest in a little strong sulphuric acid, and then add -either sodic chloride or a drop of HCl; lead, if present, is -precipitated as chloride, giving a pearly opalescence. Lemonades often -contain minute quantities of iron and copper as well as lead. Neither -copper nor iron are precipitated by ammonium sulphide in presence of -potassic cyanide. On the other hand, the sulphide of lead is not soluble -in the alkaline cyanides. Hence a liquid which, on the addition of -potassium cyanide and then ammonium sulphide, becomes dark coloured, or -from which a precipitate separates, contains lead.[855] - -[855] F. L. Teed, _Analyst_, xvii. 142-143. - - -2. COPPER. - -Sec. 795. =Copper=, Cu = 63.5; specific gravity, from 8.921 to 8.952; -fusing-point, 1091 deg. (1996 deg. F.). Copper in analysis occurs either as a -film or coating on such metals as platinum, iron, &c., or in a state of -fine division; or, finally, as a bead. In thin films, copper has a -yellowish or a yellowish-red colour; it dissolves readily in nitric, -slowly in hydrochloric acid. If air be excluded, hydrochloric acid fails -to dissolve copper, and the same remark applies to ammonia; but, if -there be free access of air, ammonia also acts as a slow solvent. -Metallic copper in a fine state of division can be fused at a white heat -to a bright bluish-green globule, which, on cooling, is covered with -black oxide. - -Sec. 796. =Cupric Oxide= (CuO = 79.5; specific gravity, 6.5, composition in -100 parts, Cu 79.85, O 20.15) is a brownish-black powder, which remains -in the absence of reducing gases unaltered at a red heat. It is nearly -insoluble in water, but soluble in ClH, NO_{3}H, &c.; it is hygroscopic, -and, as every one who has made a combustion knows, is readily reduced by -ignition with charcoal in the presence of reducing gases. - -Sec. 797. =Cupric Sulphide=, CuS = 95.5, produced in the wet way, is a -brownish powder so insoluble in water that, according to Fresenius, -950,000 parts of water are required to dissolve one part. It is not -quite insoluble in ClH, and dissolves readily in nitric acid with -separation of sulphur. By ignition in a stream of H it may be converted -into the subsulphide of copper. It must always be washed by SH_{2} -water. - -Sec. 798. =Solubility of Copper in Water and Various Fluids.=--The -solubility of copper in water and saline solutions has been very -carefully studied by Carnelley.[856] Distilled water exerts some solvent -action, the amount varying, as might be expected, according to the time -of exposure, the amount of surface exposed, the quantity of water acting -upon the copper, &c. It would appear that, under favourable -circumstances, 100 c.c. of distilled water may dissolve .3 mgrm. of -copper (.2 grain per gallon). - -[856] _Journ. Chem. Soc._, 1876, vol. ii. p. 4. - -With regard to salts, those of ammonium exert a solvent action on -copper more decided than that of any others known. With the others, -however, the nature of the base exerts little influence, the action of -the salt depending chiefly on the nature of its acid radical. Thus, -beginning with the least effective, the following is the order of -dissolving strength:--Nitrates, sulphates, carbonates, and chlorides. It -will then at once be evident that a water, contaminated by sewage, and -therefore containing plenty of ammonia and chlorides, might exert a very -considerable solvent action on copper. - -Almost all the oils and fats, as well as syrups, dissolve small -quantities of copper; hence its frequent presence in articles of food -cooked or prepared in copper vessels. In the very elaborate and careful -experiments of Mr. W. Thompson,[857] the only oils which took up no -copper, when digested on copper foil, were English neats'-foot oil, -tallow oil, one sample of olive oil, palm-nut oil, common tallow oil, -and white oil, which was protected from the air by a thick coating of -oxidised oil on its surface. - -[857] "Action of Fatty Oils on Metallic Copper," _Chem. News_, vol. -xxxiv. pp. 176, 200, 313. - -The formation of copper compounds with the fatty acids takes place so -readily that Jeannel[858] has proposed the green colouring of fats by -copper as a test for the presence of copper; and Bottger[859] recommends -a copper holding brandy to be shaken up with olive oil to free it from -copper. - -[858] _L'Union pharmac._, xvii. 81. - -[859] _Arch. de Pharm._, 1853, cxxvi. 67. - -Lehmann has made some useful researches on the amount of copper taken up -by fats under different conditions. 100 c.c. of strongly rancid fat -dissolved in fourteen days 8.7 mgrms. of copper; but when heated to 160 deg. -for one hour, and then allowed to stand, a similar amount was found. -Some rancid butter was rubbed into a brass bowl of 90 c.c. capacity, and -then allowed to stand for twenty-four hours; the butter became of a -blue-green colour. Into this dish, thus partially attacked by fatty -acids, 50 c.c. of rancid butter was poured in a melted condition, and -allowed to stand for twenty-four hours. The amount taken up was found to -be equal to 10 mgrms. of copper for every 100 c.c. of fluid butter. - -Hilger found a fatty soup, which had stood twelve hours in a clean -copper vessel, to contain 0.163 per cent. copper. According to Tschirch, -the easiest fatty salt to form is the oleate, hydrated copper oxide -dissolving in oleic acid with great ease, and even copper oxide -dissolving to some extent; the palmitate and the stearate are not so -readily produced; hence the amount of copper dissolved is greater in the -case of olive oil and butter (both rich in oleic acids) than in the case -of the firmer animal fats. Acid solutions, such as clarets, acetic acid, -vinegars, and so forth, as might be expected, dissolve more or less -copper. The amount likely to be dissolved in practice has been -investigated by Lehmann. He steeped 600 square metres of copper -sheeting or brass sheeting in vessels holding 2 litres of acid claret; -the sheets were in some of the experiments wholly immersed, in others -partly so. More copper was dissolved by the wine when the copper was -partly immersed than when it was wholly immersed; and more copper was -dissolved from brass sheeting than from pure copper sheeting. With a -sheet of copper, partly immersed, claret may contain as much as 56 -mgrms. per litre. Lehmann also investigated the amount of copper, as -acetate, which could be dissolved in wine before the taste betrayed its -presence: with 50 mgrms. per litre no copper taste; with 100 mgrms. -there was a weak after taste; with 150 mgrms. it was scarcely drinkable, -and there was a strong after taste; with 200 mgrms. per litre it was -quite undrinkable, and the colour was changed to bluish-green. Vinegar, -acting under the most favourable circumstances on sheet brass or copper, -dissolved, in seven days, 195 mgrms. of copper per litre from the copper -sheet, 195 from the brass sheet. - -Lehmann discusses the amount of copper which may be taken at a meal -under the circumstance that everything eaten or drank has been -artificially coppered, but none "coppered" to the extent by which the -presence of the metal could be betrayed by the taste; and the following -is, he thinks, possible:-- - - 300 c.c. of soup boiled in a copper vessel, 20 mgrms. Cu. - 1 litre of wine which has been standing in a - copper vessel, 50 " - 50 c.c. vinegar which has been kept in a copper - vessel, 10 " - 50 grms. of fat which has been used for frying in a - copper vessel, 5 " - 200 grms. of strongly coppered peas, 50 " - 500 grms. of strongly coppered bread, 60 " - -The total only amounts to 195 mgrms. of copper, which only slightly -exceeds a high medicinal dose. The metal is tasted more easily in -liquids, such as wine, than in bread; bread may be coppered so that at a -meal a person might eat 200 mgrms. of a copper compound without tasting -it. - -It is pretty well accepted that cooking in clean bright copper vessels -will not contaminate any ordinary food sufficiently to be injurious to -health. - -Sec. 799. =Copper in the Vegetable and Animal Kingdom and in -Foods.=--Copper is widely distributed in the vegetable kingdom, and is a -constant constituent of the chief foods we consume; the following -quantities, for example, have been separated from the chief cereals:-- - - Wheat, 5.2 to 10.8 mgrms. per kilo. - Rye, 5 mgrms. " - Oats, 8.5 " " - Barley, 11.8 " " - Rice, 1.6 " " - Bread, 1.5 to 4.4 mgrms. " - -It has also been found in vermicelli (2-10 mgrms. per kilo.), groats -(1.6-3 mgrms. per kilo.), potatoes (1.8 mgrm. per kilo.), beans (2-11 -mgrms. per kilo.). In similar small quantities it has also been found in -carrots, chicory, spinach, hazel-nuts, blackberries, peaches, pears, -figs, plums, tamarinds, black pepper, and many other fruits and spices. -The most common food which has a high copper content is cocoa, which -contains from 12 mgrms. to 29 mgrms. per kilo., the highest amount of -copper being in the outer husk; copper has also been found in many -supplies of drinking water, in aerated waters, in brandies, wines, and -many drugs. - -It has been calculated that the ordinary daily food of an average man -contains the following:-- - - Copper. - 900 grms. bread, 0.45 mgrm. - 260 grms. meat, 0.25 " - 200 grms. fruit and vegetables, 0.25 " - ---- - 0.95 mgrm. - -That is to say, that, neglecting altogether foods artificially -contaminated with copper, each of us eats daily about 1 mgrm. of copper -(0.015 grain). - -In the animal kingdom it is a constant and natural constituent of the -blood of the cephalopods, crustacea, and gasteropods, and is nearly -always present in the liver and kidneys of domestic animals, as well as -in men. Dr. Dupre[860] found .035 to .029 grain (1.8 to 2 mgrms.) in -human livers, or about 1 part in 500,000. Bergeron and L. L'Hote's -researches on fourteen bodies, specially examined for copper, fully -substantiate those of Dr. Dupre; in twelve the copper was found in -quantities of from .7 to 1.5 mgrm.; in the remaining two the amount of -copper was very minute, and was not estimated.[861] Copper is also found -normally in the kidneys, and Dupre [862] detected in human kidneys about -1 in 100,000 parts; it is also found in the bile, and in minute traces -in the blood.[863] - -[860] _Analyst_, No. 13, 1877. - -[861] _Compt. Rendus_, vol. lxxx. p. 268. - -[862] _Op. cit._ - -[863] Hoppe-Seyler, _Handbuch der physiologisch. Analyse_, p. 415. - -In the kidneys and livers of the ruminants copper may always be found, a -sheep's liver containing about 1 part in 20,000.[864] Church found -copper in the feathers of the wings of the turaco; melopsitt in the -feathers of a parroquet (_Melopsittacus undulatus_).[865] In these cases -the copper enters into the composition of the colouring matter to which -the name of "turacin" has been given. Turacin contains 7 per cent. of -copper, and gives to analysis numbers which agree with the formula of -C_{82}H_{81}Cu_{2}N_{9}O_{32}. - -[864] Dupre, _op. cit._ - -[865] _Chem. News_, xxviij. 212. - -Copper has been discovered in aerated waters, its presence being due to -the use of copper cylinders, the tin lining of which had been rendered -defective by corrosion.[866] - -[866] "On the Presence of Lead and Copper in Aerated Waters," by Dr. -James Milne, _Chem. News_, xxxi. p. 77. - -Accidents may also occur from the use of copper boilers. Mr. W. Thompson -found in one case[867] no less than 3.575 grains in a gallon (51 mgrms. -per litre) in water drawn from a kitchen boiler. - -[867] _Chem. News_, xxxi. No. 801. - -At Roubaix, in France, sulphide of copper had been deposited on the -roof, as a consequence of the use of copper flues; the sulphide was -changed into sulphate by the action of the air, and washed by the rain -into the water-tank.[868] - -[868] Author's _Dictionary of Hygiene_, p. 167. - -That preserved vegetables are made of a bright and attractive green -colour by impregnation with copper, from the deliberate use of copper -vessels for this purpose, is a fact long known. Green peas especially -have been coloured in this way, and a number of convictions for this -offence have taken place in England. - -Sec. 800. =The "Coppering" of Vegetables.=--The fact that green vegetables, -such as peas, beans, cucumbers, and so forth, preserve their green -colour, if boiled in copper vessels, has long been known. In this -"coppering" the French have been more active than the English traders; -the French operate in two different ways. One method is, to dip from 60 -to 70 litres of the green vegetables in 100 litres of 0.3 to 0.7 per -cent. of copper sulphate, to leave them there for from five to fifteen -minutes, then to remove them, wash and sterilise in an autoclave. A -second method is to put the vegetables into a copper vessel, the wall of -which is connected with the negative pole of an electric current, the -positive pole dips in a solution of salt in the same vessel, the current -is allowed to pass for three minutes, and the vegetables are afterwards -sterilised. Fruits are simply allowed to stand with water in copper -vessels, the natural acidity of the juice dissolving sufficient copper. - -The amount of copper taken up in this way is appreciable, but yet not so -much as might be expected; the prosecutions for selling "coppered" peas -in England have been based upon quantities varying from 1 to 3 grains -per lb.; the highest published amount of copper found in peas -artificially coloured is 0.27 per kilo., or 18.9 grains per lb. - -The reason why vegetables preserve their green colour longer when -treated with a copper salt has been proved by Tschirch[869] to be owing -to the formation of a phyllocyanate of copper. - -[869] _Das Kupfer_, Stuttgart, 1893. - -Phyllocyanic acid is a derivative of chlorophyll, and allied to it in -composition; the formula of C_{24}H_{28}N_{2}O_{4} has been ascribed to -it. Under the action of acids generally, mineral or organic, chlorophyll -splits up into this acid and other compounds. Copper phyllocyanate, -(C_{24}H_{27}N_{2}O_{4})_{2}Cu, contains 8.55 per cent. of copper; it -forms black lamellae, dissolving easily in strong alcohol and chloroform, -but insoluble in water; it is a little soluble in ether, insoluble in -petroleum ether, and dissolved neither by dilute acetic acid, nor by -dilute nor concentrated hydrochloric acid. The compound dissolves in -caustic alkali on warming. In alcohol it forms a beautiful -non-fluorescent solution. A solution of 1 : 100,000 is still coloured -strongly green. - -This solution, in a stratum of 25 mm. thick, gives four absorption bands -when submitted to spectroscopic observation, and Tschirch has worked out -a process of estimation of the amount of copper phyllocyanate based upon -the disappearance of these bands on dilution. - -Green substances, so carefully treated that they only contain -phyllocyanate of copper, would yield but small quantities of copper, and -probably they would not be injurious to health; but the coppering is -usually more extensive, and copper leguminate and other compounds are -formed; for the vegetables, when exhausted by alcohol, give a residue -which, successively exhausted by water, by soda-lye, and lastly by -hydrochloric acid, parts with copper into the three solvents mentioned. - -It might be argued that, from the insoluble character of the -phyllocyanate of copper, and especially seeing that it does not dissolve -in strong hydrochloric acid, that it would be perfectly innocuous; but -Tschirch has proved that, whether the tartrate of copper (dissolving -easily in water), or copper oxide (not dissolving at all in water, but -soluble in hydrochloric acid), or phyllocyanate of copper (insoluble -both in water and in hydrochloric acid) be used, the physiological -effect is the same. - -Copper may be found in spirits, owing to the use of copper condensers, a -remark which applies also to the essential oils, such as _oleum -cajepute_, _menthae_, &c.[870] In France, it has been added fraudulently -to absinthe, to improve its colour.[871] Green sweetmeats, green toys, -green papers, have all been found to contain definite compounds of -copper to a dangerous extent. - -[870] According to Eulenberg (_Gewerbe Hygiene_, p. 716), _Oleum -cajepute_, _Menth. pip._, _Melissae_, _Tanaceti_, &c., are almost always -contaminated with copper. - -[871] Tardieu, _Etude Med. Leg. sur l'Empoisonnement_. - -Sec. 801. =Preparations of Copper used in Medicine and the Arts.= - -(1) =Medicinal Preparations=:-- - -=Sulphate of Copper=, =Cupri Sulphas=, CuSO_{4}5H_{2}O.--This well-known -salt is soluble in water at ordinary temperature, 3 parts of water -dissolving 1 of the sulphate; but boiling water dissolves double its -weight; 1 part of copper sulphate dissolves in 2-1/2 of glycerin; it -reddens litmus, and is slightly efflorescent; its solution responds to -all the usual tests for copper and sulphuric acid. A watery solution of -the salt to which twice its volume of a solution of chlorine has been -added, gives, when treated with ammonia in excess, a clear sapphire-blue -solution, leaving nothing undissolved, and thus showing the absence of -iron. Besides iron, sulphate of copper has been found to contain zincic -sulphate. - -=Nitrate of Copper=, Cu(NO_{3})_{2}3H_{2}O, is officinal; it is very -soluble. - -=Cuprum Aluminatum.=--A preparation, called cuprum aluminatum (_Pierre -divine_), is in use in France and Germany, chiefly as an external wash. -It is composed of 16 parts cupric sulphate, 16 potassic nitrate, 16 -alum, fused in a crucible, a little camphor being afterwards added. - -Regular and irregular medical practitioners, veterinary surgeons, -farriers, and grooms, all use sulphate of copper (bluestone) as an -application to wounds. Copper as an _internal_ remedy is not in favour -either with quacks or vendors of patent medicines. The writer has not -yet found any patent pill or liquid containing it. - -(2) =Copper in the Arts.=--Copper is used very extensively in the arts; -it enters into the composition of a number of alloys, is one of the -chief constituents of the common bronzing powders, is contained in many -of the lilac and purple fires of the pyrotechnist, and in a great -variety of pigments. The last-mentioned, being of special importance, -will be briefly described:-- - -=Pigments=:-- - -=Schweinfurt and Scheele's Green=[872] are respectively the -aceto-arsenite and the arsenite of copper (see article "Arsenic"). - -[872] The synonyms for Schweinfurt green are extremely numerous:--Mitic -green, Viennic green, imperial green, emerald green, are the principal -terms in actual use. - -=Brighton Green= is a mixture of impure acetate of copper and chalk. - -=Brunswick Green=, originally a crude chloride of copper, is now -generally a mixture of carbonate of copper and chalk or alumina. - -=Mountain Green=, or =Mineral Green=, is the native green carbonate of -copper, either with or without a little orpiment. - -=Neuwieder Green= is either the same as mountain green, or Schweinfurt -green mixed with gypsum or sulphate of baryta. - -=Green Verditer= is a mixture of oxide and carbonate of copper with -chalk. - -=Verdigris= is an acetate of copper, or a mixture of acetates. Its -formula is usually represented as (C_{2}H_{3}O_{2})CuO. It is much used -in the arts, and to some extent as an external application in medicine. -Its most frequent impurities or adulterations are chalk and sulphate of -copper. - -Sec. 802. =Dose--Medicinal Dose of Copper.=--Since sulphate of copper is -practically the only salt administered internally, the dose is generally -expressed as so many grains of sulphate. This salt is given in -quantities of from .016 to .129 grm. (1/4 to 2 grains) as an astringent -or tonic; as an emetic, from .324 to .648 grm. (5 to 10 grains). - -The sulphate of copper is given to horses and cattle in such large -doses as from 30 up to 120 grains (1.9 to 7.7 grms.); to sheep, from -1.3 to 2.6 grms. (20 to 40 grains); rabbits, .0648 to .1296 grm. (1 to 2 -grains). - -Sec. 803. =Effects of Soluble Copper Salts on Animals.=--Harnack has made -some experiments on animals with an alkaline tartrate of copper, which -has no local action, nor does it precipitate albumin. 1/2 to 3/4 mgrm. -of copper oxide in this form, administered subcutaneously, was fatal to -frogs, .05 grm. to rabbits, .4 grm. to dogs. The direct excitability of -the voluntary muscles was gradually extinguished, and death took place -from heart paralysis. Vomiting was only noticed when the poison was -administered by the stomach.[873] The temperature of animals poisoned by -copper, sinks, according to the researches of F. A. Falck, many degrees. -These observations are in agreement with the effects of copper salts on -man, and with the experiments of Orfila, Blake, C. Ph. Falck, and -others. - -[873] On the other hand, Brunton and West have observed vomiting -produced in animals after injection of copper peptone into the jugular -vein.--_Barth. Hosp. Rep._, 1877, xii. - -Roger[874] experimented on the effect of copper leguminate which was -administered subcutaneously; he found gradual increasing paralysis of -the motor spinal tracts, which finally destroyed life by paralysis of -the breathing centre. The heart beat after the breathing had stopped. -The irritability and contractility of the muscles of frogs were lost, -while sensibility remained. He also found that, if the copper was -injected into the intestinal vessels, the dose had to be doubled in -order to destroy life; this is, doubtless, because the liver, as it -were, strained the copper off and excreted it through the bile. Roger -was unable to destroy life by large doses of copper given by the mouth, -for then vomiting supervened and the poison in great part was removed. - -[874] _Revue de Medecine_, 1877, xii. - -Bernatzic[875] considers that the poisonous properties of copper are -similar to those of zinc and silver. He says: "Silver, copper, and zinc -are, in their medicinal application, so much allied that, with regard to -their action, they graduate one into the other and show only minor -differences; copper, which is a little the more poisonous of the three -so far as its remote action is concerned, stands between the other two. -If taken, in not too small a quantity, for a long time, the functional -activity of the muscular and nervous systems is influenced injuriously, -the development of the animal cells is inhibited, the number of the red -blood corpuscles decreased, and therefore the oxidising process and -metabolism are likewise diminished, leading ultimately to a condition of -marked cachexia. . . . From a toxic point of view, the three metals -named also stand near each other, and their compounds differ from other -metals injurious to the organism in this, that they do not produce -notable changes of the tissues or coarse functional disturbances leading -to death as other poisonous metals, and therefore are not to be -considered poisons in the same sense as lead, mercury, arsenic, -antimony, phosphorus are considered poisons; for, on stopping the entry -of the poison, any injurious effect is completely recovered from and the -functions again become normal." - -[875] _Encycloped. d. ges. Heilkunde_, xi. S. 429. - -Lehmann[876] has also experimented on the effects of copper; his -experiments were made on both animals and men. He found that small -quantities were more thoroughly absorbed than medium or large doses; the -method of separation appeared to be different in different -animals--thus, the chief copper-excreting organ in dogs is the liver; in -rabbits, the intestine; and in man, the kidneys. Of 3 mgrms. of copper -taken by a man in three days, 1 mgrm., or a third, was recovered from -the urine. Lehmann experimented on 6 rabbits, 4 cats, and 1 dog. During -the first few days the animals were given 10 to 30 mgrms. of copper, in -the form of a salt, in their food; then the dose was raised to 50 mgrms. -or even to 100 mgrms., and the experiment continued for from two to four -months; in one case, six months. The sulphate, acetate, chloride, -oleate, butyrate, and lactate were all tried, but no essential -difference in action discovered. Apart from slight vomiting, and in a -few cases, as shown by _post-mortem_, a slight catarrh of the stomach, -the animals remained well. A few increased in weight. Nervous symptoms, -cramps, convulsions, diarrh[oe]a, or the reverse, were not observed. The -analysis of the organs showed considerable copper absorption; the liver -of the cats gave a mean amount of 12 mgrms. of copper, and in the other -organs there was more copper than is found in cases of acute poisoning. - -[876] _Muench. med. Wochenschrift_, 1891, Nr. 35 u. 36. - -Lehmann has also made experiments upon himself and his pupils on the -effect of the sulphate and the acetate when taken for a long time:-- - - One of the experimenters took for 50 days 10 mgrms. daily Cu as - sulphate. - " " " then for 30 " 20 " " - Another took for 3 days 5 mgrms. as acetate. - " then for 10 days 10 " " - " " 1 day 15 " " - " " 19 days 20 " " - " " 18 days 30 " " - -None of these daily doses had the least effect. - -Five farther experiments showed that 75 to 127 mgrms. of copper in peas -and beans, divided in two meals, could be taken daily without effect; -but if 127 mgrms. were taken at one meal in 200 grms. of peas, then, -after a few hours, there might be vomiting; and Lehmann concludes that -doses of copper in food of about 100 mgrms. may produce some transient -derangement in health, such as sickness, a nasty taste in the mouth, and -a general feeling of discomfort, but nothing more; some slight colicky -pains and one or two loose motions are also possible, but were not -observed in Lehmann's experiments. - -Sec. 804. =Toxic Dose of Copper Salts.=--This is a difficult question, -because copper salts generally act as an emetic, and therefore very -large doses have been taken without any great injury. In fact, it may be -laid down that a medium dose taken daily for a considerable time is far -more likely to injure health, or to destroy life, than a big dose taken -at once. In Tschirch's[877] careful experiments on animals, he found 10 -mgrm. doses of CuO given daily to rabbits, the weight of which varied -from 1200 to 1650 grms., caused injury to health, that is, about 3.5 -mgrms. per kilo. If man is susceptible in the same proportion, then -daily doses of 227.5 mgrms. (or about 3-1/2 grains) would cause serious -poisonous symptoms; although double or treble that quantity might in a -single dose be swallowed and, if thrown up speedily, no great harm -result. 120 grms. of sulphate of copper have been swallowed, and yet the -patient recovered after an illness of two weeks.[878] Lewin[879] -mentions the case of an adult who recovered after ten days' illness, -although the dose was 15 grms.; there is also on record the case of a -child, four and a half years old, who recovered after a dose of 16.5 -grms. (a little over half an ounce). On the other hand, 7.7 grms. have -been with difficulty recovered from.[880] A woman died in seventy-two -hours after taking 27 grms. (7 drms.) of copper sulphate mixed with 11.6 -grms. (3 drms.) of iron sulphide; 56.6 grms. (2 ozs.) of copper acetate -have caused death in three days; 14.2 grms. (0.5 oz.) in sixty -hours.[881] - -[877] _Das Kupfer_, Stuttgart, 1893. - -[878] Referred to by Bernatzic, on the authority of Ketli, in _Encycl. -d. ges. Heilkunde_, xi. S. 433. - -[879] _Toxicologie_, S. 133. - -[880] D Taylor, _op. cit._ - -[881] Sonnenschein, _op. cit._ - -Sec. 805. =Cases of Acute Poisoning.=--Acute poisoning by salts of copper -is rare; in the ten years ending 1892, there were registered in England -8 deaths from this cause--3 suicidal (2 males, 1 female) and 5 -accidental (4 males, 1 female). The symptoms produced by the sulphate of -copper are those of a powerful irritant poison: there is immediate and -violent vomiting; the vomited matters are of a greenish colour--a green -distinguished from bile by the colour changing to blue on the addition -of ammonia. There is pain in the stomach, and in a little time -affections of the nervous system, as shown by spasms, cramps, paralysis, -and even tetanus. Jaundice is a frequent symptom, if life is prolonged -sufficiently to admit of its occurrence. - -One of the best examples of acute poisoning by copper sulphate is -recorded by Maschka.[882] A youth, sixteen years old, took an unknown -large dose of powdered copper sulphate, mixed with water. Half an hour -afterwards there was violent vomiting, and he was taken to the hospital. -There was thirst, retching, constriction in the throat, a coppery taste -in the mouth, and pain in the epigastrium, which was painful on -pressure. The vomit was of a blue colour, and small undissolved crystals -of copper sulphate were obtained from it. The patient was pale, the -edges of the lips and the angles of the mouth were coloured blue, the -surface of the tongue had also a blue tint, the temperature was -depressed, the extremities cold, nails cyanotic, and the pulse small and -quick. Several loose greenish-yellow evacuations were passed; there was -no blood. The urine was scanty, but contained neither blood nor albumen. -During the night the patient was very restless; the next morning he had -violent headache, pain in the epigastrium, burning in the mouth and -gullet, but no vomiting. The urine was scanty, contained blood, albumen, -and colouring matter from the bile. On the fourth day there was marked -jaundice. The mucous membrane was very pale, the temperature low, pulse -frequent, and great weakness, cardiac oppression, and restlessness were -experienced. There were diarrh[oe]a and tenesmus, the motions being -streaked with blood; the urine also contained much blood. The liver was -enlarged. The patient died in a state of collapse on the seventh day. - -[882] _Wiener med. Wochenschr._, 1871, Nro. 26, p. 628. - -In 1836 a girl, sixteen months old, was given bluestone to play with, -and ate an unknown quantity; a quarter of an hour afterwards the child -was violently sick, vomiting a bluish-green liquid containing some -pieces of sulphate of copper. Death took place in four hours, without -convulsions, and without diarrh[oe]a. - -Sec. 806. =Subacetate of Copper, Subchloride, and Carbonate=, all act very -similarly to the sulphate when given in large doses. - -Sec. 807. =Post-mortem Appearances.=--In Maschka's case, the chief changes -noted were in the liver, kidneys, and stomach. The substance of the -liver was friable and fatty; in the gall-bladder there were but a few -drops of dark tenacious bile. The kidneys were swollen, the cortical -substance coloured yellow, the pyramids compressed and pale brown. In -the mucous membrane of the stomach there was an excoriation the size of -a shilling, in which the epithelium was changed into a dirty brown mass, -easily detached, laying bare the muscular substance beneath, but -otherwise normal. - -In a case of poisoning by verdigris (subacetate of copper) recorded by -Orfila,[883] the stomach was so much inflamed and thickened that -towards the pyloric end the opening into the intestine was almost -obliterated. The small intestines throughout were inflamed, and -perforation had taken place, so that part of the green liquid had -escaped into the abdomen. The large intestines were distended in some -parts, contracted in others, and there was ulceration of the rectum. In -other cases a striking discoloration of the mucous membrane, being -changed by the contact of the salt to a dirty bluish-green, has been -noticed, and, when present, will afford valuable indications. - -[883] _Toxicologie_, vol. i. p. 787 (5th ed.). - -Sec. 808. =Chronic Poisoning by Copper.=--Symptoms have arisen among -workers in copper or its salts, and also from the use of food -accidentally contaminated by copper, which lend support to the existence -of chronic poisoning. In the symptoms there is a very great resemblance -to those produced by lead. There is a green line on the margin of the -gums. Dr. Clapton[884] found the line very distinct in a sailor and two -working coppersmiths, and the two men were also seen by Dr. Taylor. -Cases of chronic poisoning among coppersmiths have also been treated by -Dr. Cameron,[885] but this symptom was not noticed. Corrigan speaks of -the line round the gums, but describes it as purple-red. Among workers -in copper, Lancereaux[886] has seen a black coloration of the mucous -membrane of the digestive canal; its chemical characters appear to agree -with those of carbon. - -[884] _Med. Times and Gazette_, June 1868, p. 658. - -[885] _Med. Times and Gazette_, 1870, vol. i. p. 581. - -[886] _Atlas of Pathological Anatomy._ - -Metallic copper itself is not poisonous. A Mr. Charles Reed has -published a letter in the _Chemical News_ of Jan. 12, 1894, stating that -he was, when a boy, wounded in the shin by a copper percussion-cap, and -the cap remained in the tissues; it was removed from the shin after a -sojourn thereof some twelve years; about the year 1873 he noticed that -whenever a piece of clean iron or steel came in contact with his -perspiration it was at once covered with a bright coating of copper, and -this continued until the percussion-cap was removed. Presuming the truth -of this, it shows conclusively that metallic copper deposited in the -tissues is in itself not poisonous, and farther, that one method of -elimination is by the skin. The experiments already cited throw doubt as -to whether repeated small doses of copper taken for a long time produce -in a scientific sense chronic poisoning; those which apparently support -the view that there is such a thing as chronic poisoning by copper, have -been produced by copper mixed with other metals; and there is the -possibility that these cases are really due to lead or arsenic, and not -to copper. The great use of late years of solutions of copper sulphate -as a dressing to plants, for the purpose of preventing the ravages of -various parasites, has provided, so far as animals are concerned, much -material for the judgment of this question. Sheep have been fed with -vines which have been treated with copper sulphate, oxen and pigs have -consumed for a long time grass treated with a 3 per cent. of copper -sulphate, without the least health disturbance. Mach[887] has fed cows -with green food coppered up to 200 mgrms. of copper sulphate, without -observing the slightest bad effect, for long periods of time; and -Tschirch[888] summarises the evidence as to chronic poisoning as -follows:--"So it appears the contention that there is no chronic -poisoning in men or animals is at present uncontradicted; it is farther -to be considered proved that the small amounts of copper naturally in -food, or carefully introduced into food, are not injurious to the health -of those that take such food, because the liver, kidneys, and other -organs excrete the copper through the urine and bile, and prevent a -pernicious accumulation." At the same time, Tschirch does not consider -the question is definitely settled; the experiments should, he thinks, -have been continued not for months, but for years, to obtain a -trustworthy judgment. - -[887] Mach, _Bericht ueber die Ergebnisse der im Jahre 1886 ausgefuehrten -Versuche zur Bekaempfung der Peronospora_, St. Michele, Tyrol. - -[888] _Op. cit._ - -It may also be remarked that, if we are to rely upon the separation of -copper by the kidneys and the liver, those organs are presumed to be in -a healthy state, which is not the case with a percentage of the -population; to persons whose liver or kidneys are unsound, even the -small amounts of copper found in "coppered" peas may act as a poison, -and the experiments previously detailed throw no light upon the action -of copper under such circumstances. - -Sec. 809. =Detection and Estimation of Copper.=--Copper may occur either in -the routine process of precipitating by SH_{2}, or it may, as is -generally the case, be searched for specially. If copper is looked for -in a precipitate produced by SH_{2}, it is taken for granted that the -precipitate has first been treated successively by carbonate of ammonia, -sulphide of sodium, and hydrochloric acid; in other words, arsenic, -antimony, and lead have been removed. The moist precipitate is now -treated with warm nitric acid, which dissolves out copper sulphide with -separation of sulphur; if there is sufficient copper, the fluid shows a -blue colour, which of itself is an indication of copper being present. -The further tests are--(1) Ammonia gives a deeper blue; (2) ferrocyanide -of potash a brown-red colour or precipitate; (3) a few drops mixed with -a solution of tartrate of soda, alkalised with sodic hydrate, and boiled -with a crystal or two of grape-sugar, gives quickly a red precipitate of -oxide of copper; (4) a needle or a clean iron wire, or any simple -galvanic combination, immersed in, or acting on, the liquid, soon -becomes coated with the very characteristic reddish metallic film. -Various other tests might be mentioned, but the above are ample. - - -Special Examinations for Copper. - -(1) =In Water and Liquids generally.=--The liquid may be concentrated, -and the copper separated by electrolysis. A simple method is to place -the liquid in a large platinum dish, and insert a piece of zinc, adding -a sufficient quantity of ClH to dissolve the zinc entirely; the copper -is found as an adherent film on the inner surface of the dish. It is -neater, however, and more accurate, to connect the platinum dish with -the negative plate of a battery, suspending in the liquid the positive -electrode. The modifications of this method are numerous; some chemists -use (especially for small quantities of copper) two small platinum -electrodes, either of foil or of wire, and on obtaining the film, weigh -the electrode, then dissolve the copper off by nitric acid, and -re-weigh. Such solid substances as peas are conveniently mashed up into -a paste with water and ClH; an aliquot part is carefully weighed and put -in a platinum dish, connected, as before described, with a battery; at -the end of from twelve to twenty-four hours all the copper is deposited, -and the dish with its film dried and weighed. The weight of the clean -dish, _minus_ the coppered dish, of course equals the copper. Fat and -oils are best thoroughly washed with hot acid water, which will, if -properly performed, extract all the copper. By the use of separating -funnels and wet filters, the fat or oil can be separated from the watery -liquid. - -A galvanic test has been proposed, which is certainly very delicate, -1/100 of a mgrm. in solution being recognised with facility. A zinc -platinum couple is made with two wires; on leaving this in an acid -liquid containing a mere trace of copper, after several hours the -platinum will be found discoloured. If the discoloration is from copper, -on exposing the wire to hydrobromic acid fumes (easily produced from the -action of potassic bromide and sulphuric acid) and bromine, the wire -will become of a violet colour. This colour is easily recognised by -rubbing the wire on a piece of porcelain.[889] - -[889] _Chem. News_, Nov. 30, 1877. - -(2) =Animal Matters=, such as the liver, brain, spinal cord, &c., are -best entirely burnt to an ash, and the copper looked for in the -latter.[890] The same remark applies to bread and substances consisting -almost entirely of starchy matters. Any injurious quantity of copper -can, however, be extracted with hydrochloric acid and water; and, -although this method of extraction is not quite so accurate, it is -quicker. - -[890] In exhumation of long buried bodies, it may be necessary to know -the composition of the soil. Sonnenschein mentions a skull, now in the -museum at Madrid, which was dug out of an old Roman mine, and is quite -green from copper compounds.--Sonnenschein's _Handbuch_, p. 83. - -Sec. 810. =Volumetric Processes for the Estimation of Copper.=--A number of -volumetric processes have been devised for the estimation of copper, but -for the purposes of this work it is unnecessary to detail them. When -copper is in too small a quantity to be weighed, it may then be -estimated by a colorimetric process. - -One of the best of these is based upon the brown colour which -ferrocyanide of potash produces in very dilute solutions of copper. A -standard copper solution is obtained by dissolving sulphate of copper in -a litre of water, so that each c.c. contains 0.1 mgrm. Cu, and a -solution of ferrocyanide of potash in water is prepared, strength 4 per -cent. It is also convenient to have a solution of nitrate of ammonia, -which is found to render the reaction much more delicate. - -The further details are on the well-known lines of colorimetric -estimations. - - -3. BISMUTH. - -Sec. 811. =Bismuth=, Bi = 210; sp. gr., 9.799; fusing-point, 264 deg. (507.2 deg. -F.).--Bismuth, as obtained in the course of analysis, is either a black -metallic powder or an extremely brittle bead of a reddish-white colour. -The compounds which it will be necessary to briefly notice are the -peroxide and tersulphide. - -Sec. 812. =The peroxide of bismuth=, Bi_{2}O_{3} = 468; sp. gr., 8.211; Bi, -89.64 per cent., O, 10.36 per cent., as prepared by igniting the -carbonate or nitrate, is a pale lemon coloured powder, which can be -fused without loss of weight, but is reduced on charcoal, or in a stream -of carbon dioxide, to the metallic state. It is also reduced by fusion -with potassic cyanide or by ignition with ammonium chloride. - -Sec. 813. =The Sulphide of Bismuth=, Bi_{2}S_{3} = 516; Bi, 81.25 per -cent., S, 18.75 per cent., occurs, in the course of analysis, as a -brownish-black or quite black precipitate, insoluble in water, dilute -acids, alkalies, alkaline sulphides, sulphate of soda, and cyanide of -potassium, but dissolving in moderately concentrated nitric acid with -separation of sulphur. It continually increases in weight when dried in -the ordinary way, and is completely reduced when fused with cyanide of -potassium. - -Sec. 814. =Preparations of Bismuth used in Medicine and the Arts.= - -(1) =Pharmaceutical Preparations=:-- - -=Bismuthi Subnitras=, BiONO_{3}.H_{2}O.--A heavy white powder, insoluble -in water, and responding to the usual tests for bismuth and nitric acid. -The formula should yield 77 per cent. of bismuth oxide. Commercial -preparations, however, vary from 79 to 82 per cent. - -=Bismuth Lozenges= (=Trochisci bismuthi=) are composed of subnitrate of -bismuth, magnesia carbonate, precipitated lime carbonate, sugar, and -gum, mixed with rose water. Each lozenge should contain 0.13 grm. (2 -grains) of subnitrate of bismuth. - -=Solution of Citrate of Bismuth and Ammonia= (=Liquor Bismuthi et -Ammoniae citratis=), a colourless neutral or slightly alkaline fluid, sp. -gr. 1.07, responding to the tests for bismuth and ammonia. As an -impurity lead may be present, citric acid being so frequently -contaminated with lead. Carbonate of bismuth (_Bismuthi carbonas_), -(Bi_{2}O_{2}CO_{3})_{2}H_{2}O is a fine white powder answering to the -tests for carbon dioxide and bismuth; it should yield 89.1 per cent. of -bismuth oxide. - -=A Nitrate of Bismuth=, Bi(NO_{3})_{3}, an oleate of bismuth, an oxide -of bismuth, a subgallate of bismuth (_dermatol_), and a subiodide of -bismuth are also used in medicine. - -(2) =Bismuth in the Arts.=[891] - -[891] Bismuth is contained in all copper coinage--from the Bactrian -coins to our own; in all cupreous ores, except the carbonates, and in -nearly all specimens of commercial copper.--Field, _Chem. News_, xxxvi. -261. - -The chief use of bismuth is in alloys and solders. The Chromate is -employed in calico-printing, and the subnitrate as a paint under the -name of pearl-white. - -The salts of bismuth also occur in washes for the hair, and pearl-white -is used as a cosmetic, but only to a small extent. - -Sec. 815. =Medicinal Doses of Bismuth.=--The subnitrate and carbonate are -prescribed in doses from .0648 to 1.296 grm. (1 to 20 grains); the -valerianate, from .1296 to .648 grm. (2 to 10 grains); and the solution, -from 1.7 c.c. to 5.2 c.c. (1/2 drachm to 1-1/2 drachm). - -Sec. 816. =Toxic Effects of Bismuth.=--From the researches of Meyer and -Steinfeld[892] on animals, it appears that if birds or mammals are -poisoned with bismuth salts introduced subcutaneously, or by direct -injection, into the veins, death follows in from twenty-four to -forty-eight hours, the fatal issue being preceded by convulsions; after -death, the colon is intensely blackened, and it may be ulcerated, while -the small intestines and the stomach are healthy. If, however, sulphur -preparations are given by the mouth, there is then blackening of the -stomach, and there may also be ulcers. Meyer is of the opinion that -SH_{2} precipitates bismuth in the parenchyma, and the particles -occluding the capillaries thus cause small local necroses; that which -escapes precipitation is mainly excreted by the kidneys. Poisonous -symptoms in man have been known to occur from the treatment of wounds -with bismuth preparations;[893] the symptoms have been somewhat similar -to mercurial poisoning; there have been noticed stomatitis with -salivation, loosening of the teeth, a black colour of the mucous -membrane of the mouth and ulceration, also catarrh of the intestines, -and the inflammatory condition of the kidneys usual when that organ has -to excrete metallic substances not natural to the body, the -"metallniere," or metal kidney, of the German writers. One case is -recorded of death in nine days of an adult after taking 7.7 grms. (2 -drms.) of bismuth subnitrate. The recorded symptoms were a metallic -taste in the mouth, pain in the throat, vomiting, purging, coldness of -the surface, and spasms of the arms and legs. A _post-mortem_ -examination showed inflammatory changes in the gullet, windpipe, and -throughout the intestinal canal. Recovery has, however, taken place from -a single dose three times the amount mentioned. It is possible that the -fatal case was due to impure bismuth. - -[892] L. Feder-Meyer, _Rossbach's pharmak. Unters._, iii., 1882, No. 23; -Steinfeld, _Wirkung des Wismut. Inaug. Diss._, Dorpat, 1884; _Arch. exp. -P._, Bd. xx. 1886. - -[893] _B. Med. Journal_, 1887, i. 749. - -Sec. 817. =Extraction and Detection of Bismuth in Animal Matters.=--Bismuth -appears to be excreted principally by the bowels as sulphide of bismuth; -but it has also been detected in the urine, spleen, and liver; and -Lubinsky has found it in the saliva and in the epithelium of the mouth -of persons taking one of its preparations. Without denying the -possibility of its existing in a soluble state in the saliva, its -presence in the mouth may, under such circumstances, be ascribed to the -lodgment of particles of subnitrate or subcarbonate of bismuth in the -interstices of the teeth, &c. It will then be evident that, if a person -is supposed to have been poisoned by a large dose of bismuth, and the -analyst fail to find it in the stomach, the contents of the bowels -should be next examined. - -The extraction of bismuth must be undertaken by nitric acid, and boiling -for at least two hours may be necessary to dissolve it out from the -tissues. Such organs as the liver and spleen are boiled in a finely -divided state with a litre of dilute nitric acid (strength, 5 per -cent.), for the time mentioned, filtered, and the filtrate evaporated to -dryness; the remainder is then carbonised by strong nitric acid; and, -finally, the charcoal is boiled with equal parts of nitric acid and -water, and the whole evaporated to dryness. By this method every trace -of bismuth is extracted. The dry residue may now be brought into -solution, and tested for bismuth. The best solvent for the nitrate of -bismuth is dilute nitric acid 50 per cent.; the dry residue is therefore -dissolved in 100 or 200 c.c. of the acid, and fractional parts taken for -examination:-- - -(1) The solution, poured into a large volume of warm distilled water, -gives a crystalline precipitate of subnitrate of bismuth. The only metal -giving a similar reaction is antimony, and this is excluded by the -method employed. - -(2) The filtered fluid gives on addition of sodic chloride a precipitate -of oxychloride. This, again, is distinguished from oxychloride of -antimony by its insolubility in tartaric acid. - -(3) Any bismuth precipitate, fused with soda on charcoal, gives a -brittle bead of bismuth; the coal is coated whilst warm a dark -orange-yellow, on cooling citron-yellow. - -(4) The bead may be identified by powdering it, placing it in a short -subliming tube, and passing over it dry chlorine. The powder first turns -black, then melts to an amber-yellow fluid, and finally, by prolonged -heating, sublimes as terchloride of bismuth. - -(5) A very delicate test proposed by Abel and Field, in 1862,[894] -specially for the detection of bismuth in copper (but by no means -confined to mineral analysis), utilises the fact that, if iodide of lead -be precipitated from a fluid containing the least trace of bismuth, -instead of the yellow iodide the scales assume a dark orange to a -crimson tint. A solution of nitrate of lead is used; to the nitric acid -solution ammonia and carbonate of ammonia added; the precipitate washed, -and dissolved in acetic acid; and, finally, excess of iodide of -potassium added. It is said that thus so small a quantity as .00025 grm. -may be detected in copper with the greatest ease, the iodide of lead -becoming dark orange; .001 grain imparts a reddish-brown tinge, and .01 -grain a crimson. - -[894] _Journ. Chem. Soc._, 1862, vol. xiv. p. 290; _Chem. News_, vol. -xxxvi. p. 261. - -(6) A solution of a bismuth salt, which must contain no free HCl, when -treated with 10 parts of water, 2 of potassium iodide, and 1 part of -cinchonine, gives a red orange precipitate of cinchonine -iod.-bismuth.[895] - -[895] E. Legar, _Bull. de la Soc. Chim._, vol. iv., 1888, 91. - -(7) Van Kobell's test, as modified by Hutchings,[896] and proposed more -especially for the detection of bismuth in minerals, is capable of being -applied to any solid compound suspected of containing the metal:--A -mixture of precipitated and purified cuprous iodide, with an equal -volume of flowers of sulphur, is prepared, and 2 parts of this mixture -are made into a paste with 1 part of the substance, and heated on a slip -of charcoal on an aluminium support by the blowpipe flame. If bismuth be -present, the red bismuth iodide will sublime, and on clean aluminium is -easily distinguishable. - -[896] _Chem. News_, vol. xxxvi. p. 249. - -There are many other tests, but the above are sufficient. - -Sec. 818. =Estimation of Bismuth.=--The estimation of bismuth, when in any -quantity easily weighed, is, perhaps, best accomplished by fusing the -sulphide, oxide, or other compound of bismuth, in a porcelain crucible -with cyanide of potassium; the bismuth is reduced to the metallic state, -the cyanide can be dissolved out, and the metallic powder washed (first -with water, lastly with spirit), dried, and weighed. - -Mr. Pattison Muir has shown[897] that bismuth may be separated from -iron, aluminium, chromium, and manganese, by adding ammonia to the acid -solutions of these metals. - -[897] Pattison Muir on "Certain Bismuth Compounds," _Journ. Chem. Soc._, -p. 7, 1876. - -This observation admits of many applications, and may be usefully taken -advantage of in the separation of bismuth from the nitric acid solution -of such animal matters as liver, &c. The acid liquid is partially -neutralised by ammonia, and, on diluting with warm water containing a -little sodium or ammonium chloride, the whole of the bismuth is -precipitated as oxychloride, which may be collected, and fused with -cyanide of potassium, as above. - -If the bismuth precipitate is in small quantity, or if a number of -estimations of bismuth are to be made, it is most convenient to use a -volumetric process. In the case first mentioned, the oxychloride could -be dissolved in nitric acid, sodium acetate added in excess, and -sufficient acetic acid to dissolve any precipitate which has been -produced, and then titrated by the following method, which we also owe -to Mr. Pattison Muir:-- - -=Estimation of Bismuth by Potassium Dichromate.=[898]--A solution of -recrystallised potassium dichromate (strength, 1 per cent.) is prepared. -A known weight of pure bismuthous oxide (Bi_{2}O_{3}) is dissolved in -excess of nitric acid, and a solution of sodium acetate is added to this -liquid until a copious white precipitate is thrown down; acetic acid is -then added in quantity sufficient to dissolve the precipitate -completely, and to insure that, when the liquid is made up with water to -a fixed volume, no precipitate shall be formed. A certain volume of this -liquid is withdrawn by means of a pipette, placed in a beaker, and -heated to boiling; the potassium dichromate is then gradually run in -from a burette, the liquid being boiled between each addition of the -solution, until a drop of the supernatant liquid gives a faint -reddish-brown coloration when spotted with silver nitrate on a white -slab. - -[898] Pattison Muir on "Certain Bismuth Compounds," _Journ. Chem. Soc._, -vol. i. p. 659, 1879. - -Another very generally applicable volumetric method for bismuth has been -proposed by Mr. Muir.[899] This depends on the fact (observed by Sonchay -and Leussen),[900] that normal bismuth oxalate splits up on boiling into -a basic oxalate of the composition Bi_{2}O_{3}2C_{2}O_{3} + OH_{2}, but -slightly soluble in nitric acid. The process is performed by -precipitating the bismuth by excess of oxalic acid, dissolving the -precipitate (first purified from free oxalic acid) in dilute -hydrochloric acid, and lastly, titrating by permanganate. The absence of -free hydrochloric acid before precipitating must be insured. - -[899] _Ibid._, 1877. - -[900] _Ann. Chem. Pharm._, vol. cv. p. 245. - - -4. SILVER. - -Sec. 819. =Silver= = 108; specific gravity, 10.5; fusing-point, 1023 deg. -(1873 deg. F.).--Silver, as separated in analysis, is either a very white, -glittering, metallic bead, or a dull grey powder. It does not lose -weight on ignition, and is soluble in dilute nitric acid. - -Sec. 820. =Chloride of Silver=, AgCl = 143.5; specific gravity, 5.552; Ag, -75.27 per cent., Cl, 24.73 per cent., is a dense, white, curdy -precipitate, when produced in the wet way. It is very insoluble in -water, dilute nitric acid, and dilute sulphuric acid; in many warm -solutions (especially aqueous solutions of the chlorides generally), the -alkaline and alkaline-earthy nitrates, and tartaric acid solutions, the -silver is dissolved to an appreciable extent, but deposited again on -diluting and cooling. The complete solvents of chloride of silver -are--ammonia, cyanide of potassium, and hyposulphite of soda. Chloride -of silver cannot be fused at a high heat without some slight loss by -volatilisation; on coal in the R.F., it fuses very easily to a globule. -It can with soda be reduced to metal, and can also readily be reduced by -ignition in a current of hydrogen, carbon oxide, or carburetted hydrogen -gas. - -Sec. 821. =Sulphide of Silver=, Ag_{2}S = 248; specific gravity, 7.2; Ag, -87.1 per cent., S, 12.9 per cent., when prepared in the wet way, is a -black precipitate, insoluble in water, dilute acids, and alkaline -sulphides. If ignited in hydrogen it may be reduced to the metallic -state; it is soluble in nitric acid, with separation of sulphur. - -Sec. 822. =Preparations of Silver used in Medicine and the Arts.= - -(1) =Medicinal Preparations=:-- - -=Nitrate of Silver=, AgNO_{3}; Ag, 63.51 per cent., N_{2}O_{5}, 36.49 -per cent. This salt is either sold crystallised in colourless rhombic -prisms, or in the form of small white pencils or sticks. It gives the -reactions for silver and nitric acid, and stains the skin black. 100 -parts, dissolved in distilled water, should give, with hydrochloric -acid, a precipitate which, when washed and dried, weighs 83.4 parts. The -silver is, however, far more quickly estimated by the blowpipe than in -the wet way. One grm. fused in a cavity on charcoal should give a little -globule of metallic silver, weighing about .6351 grm. The chief -adulterations of this substance are copper, lead, and nitrate of potash. -If all the silver is precipitated by hydrochloric acid, carefully -filtered off, and the filtrate evaporated to dryness, any residue will -denote adulteration or impurity. - -=Argenti Oxidum=, =Oxide of Silver=, Ag_{2}O = 232; Ag, 93.19 per -cent.--A dark olive-brown powder, soluble in ammonia and nitric acid. By -ignition it readily yields metallic silver. The P.B. directs that 29 -grains of the oxide should yield 27 of metallic silver. - -=Nitrate of Silver and Potash= (=Argentum nitricum cum kali nitrico=), -AgNO_{3} + KNO_{3}.--This preparation is in most of the -pharmacop[oe]ias, Austrian, German, Danish, Swedish, Russian, Swiss, and -the British; it is directed by the B.P. to be composed of 1 part of -silver nitrate and 1 part of potassic nitrate fused together. A -"toughened silver nitrate" is made by fusing together potassic nitrate -5, silver nitrate 95. Mild caustic points are used by oculists by fusing -1 of silver nitrate with 2, 3, 3-1/2, and 4 parts of potassic nitrate. - -(2) =Silver in the Arts.=--The uses of the metal in coinage, articles -for domestic purposes, for ornament, &c., are too well known to require -enumeration. The only forms in which silver is likely to give rise to -accident are the salts used in medicine, photography, in the dyeing of -hair, and in the manufacture of marking inks. - -=Hair-dyes.=--About one-half of the hair-dyes in use are made with -nitrate of silver. The following are only a few of the recipes:-- - -=Aqua Orientalis.=--Grain silver 2 drms., nitric acid 1 oz., steel -filings 4 drms., distilled water 1-1/2 oz.--the whole finally made up to -3-1/2 fluid ozs., and filtered. - -=Argentan Tincture.=--Nitrate of silver 1 drachm, rose water 1 fluid -oz., sufficient nitrate of copper to impart a greenish tint. - -=Eau d'Afrique.=--Two solutions--one of nitrate of silver, the other of -potash, containing ammonium sulphide. - -The photographer uses various salts of silver, the chief of which -are--the nitrate, iodide, bromide, cyanide, and chloride of silver. - -=Marking Inks.=--Some of the more important recipes for marking ink are -as follows:-- - -Nitrate of silver 1.0 part, hot distilled water 3.6 parts, mucilage, -previously rubbed with sap-green, 1.0 part. With this is sold a -"pounce," or preparation consisting of a coloured solution of sodic -carbonate. Another preparation is very similar, but with the addition of -ammonia and some colouring matter, such as indigo, syrup of buckthorn, -or sap-green. A third is made with tartaric acid and nitrate of silver, -dissolved in ammonia solution, and coloured. - -=Redwood's Ink= consists of equal parts of nitrate of silver and -potassic bitartrate, dissolved in ammonia, with the addition of archil -green and sugar; according to the formula, 100 parts should equal 16.6 -of silver nitrate. - -=Soubeiran's Ink= is composed of cupric nitrate 3, argentic nitrate 8, -sodic carbonate 4, and the whole made up to 100 parts, in solution of -ammonia. In one of Mr. Reade's inks, besides silver, an ammoniacal -solution of a salt of gold is used. - -Sec. 823. =Medicinal Dose of Silver Compounds.=--The nitrate and the oxide -of silver are given in doses from .0162 to .1296 grm. (1/4 grain to 2 -grains). Anything like .1944 to .2592 grm. (3 or 4 grains) would be -considered a large, if not a dangerous dose; but nothing definite is -known as to what would be a _poisonous_ dose. - -Sec. 824. =Effects of Nitrate of Silver on Animals.=--Nitrate of silver is -changed into chloride by the animal fluids, and also forms a compound -with albumen. Silver chloride and silver albumenate are both somewhat -soluble in solutions containing chlorides of the alkalies, which -explains how a metallic salt, so very insoluble in water, can be -absorbed by the blood. - -The action of soluble salts of silver on animals has been several times -investigated. There appears to be some difference between its effects on -warm and cold-blooded animals. In frogs there is quickly an exaltation -of the functions of the spinal cord, tetanic convulsions appear, similar -to those induced by strychnine; later, there is disturbance of the -respiration and cessation of voluntary motion. - -The first symptoms with dogs and cats are vomiting and diarrh[oe]a; -muscular weakness, paralysis, disturbance of the respiration, and weak -clonic convulsions follow. Rouget, as well as Curci, considers that the -action of silver is directed to the central nervous system; there is -first excitement, and then follows paralysis of the centres of -respiration and movement. Death occurs through central asphyxia. -According to the researches of F. A. Falck, subcutaneous injections of -silver nitrate into rabbits cause a fall of temperature of 6.7 deg. to -17.6 deg., the last being the greatest fall which, in his numerous -researches on the effect of poisons on temperature, he has seen. - -Chronic poisoning, according to the experiments of Bogoslowsky on -animals, produces emaciation, fatty degeneration of the liver, kidneys, -and also of the muscles--a statement confirmed by others. - -Sec. 825. =Toxic Effects of Silver Nitrate in Man=--(1) =Acute -Poisoning.=--This is very rare. Orfila relates an attempt at suicide; -but most of the cases have been accidental, and of these, in recent -times, about five are recorded, mostly children. The accident is usually -due to the application of the solid nitrate to the throat, as an -escharotic, the stick breaking or becoming detached, and being -immediately swallowed; such an accident is related by Scattergood.[901] -A piece of silver nitrate 3/4 inch long, slipped down the throat of a -child, aged fifteen months--vomiting immediately occurred, followed by -convulsions and diarrh[oe]a; chloride of sodium was administered, but -the child died in six hours. In other cases paralysis and an unconscious -state has been observed. - -[901] _Brit. Med. Journal_, May 1871. - -(2) =Chronic Poisoning.=--Salts of silver taken for a long period cause -a peculiar and indelible colour of the skin, the body becomes of a -greyish-blue to black colour, it begins first around the nails and -fingers, then patches of a similar hue appear in different parts of the -body, and gradually coalesce, being most marked in those parts exposed -to the light. The colour is not confined to the outer skin, but is also -seen in the mucous membranes. There is also a slight inflammation of the -gums, and a violet line around their edge. Ginpon observed this line -after two months' treatment of a patient by silver nitrate; the whole -quantity taken being 3.9 grms. (about 60 grains). The peculiar colour of -the skin is only seen after large dose; after 8 grms. taken in divided -doses Chaillon could not observe any change, but after 15 grms. had been -taken it was evident. So also Riemer has recorded a case, in which, -after a year's use of silver nitrate (total quantity 17.4 grms.) a -greyish-black colour of the face was produced, and, when nearly double -the quantity had been taken, the colour had invaded the whole body. - -Sec. 826. =Post-mortem Appearances.=--In the acute case recorded by -Scattergood, the mucous membranes of the gullet, of the great curvature -of the stomach, and parts of the duodenum and jejunum were eroded, and -particles of curd-like silver chloride adhered to the mucous membrane. - -In the case recorded by Riemer of the long-continued use of silver -nitrate, the serous and mucous membranes were coloured dark; the choroid -plexus was of a blue-black; the endocardium, the valves of the heart, -and the aorta pale to dark grey, as well as the rest of the vessels; the -colouring was confined to the intima. The liver and kidney also showed -similar pigmentation. The pigment (probably metallic silver) was in the -form of very fine grains, and, as regards the skin, was situate under -the _rete Malpighia_ in the upper layer of the corium, and also in the -deeper connective tissue and in the sweat glands. Liouville has also -found the kidneys of a woman similarly pigmented, who took silver -nitrate daily for 270 days, in all about 7 grms., five years before her -death. - -Sec. 827. =Detection and Estimation of Silver.=--The examination of the -solid salts of silver usually met with (viz., the nitrate, bromide, -iodide, cyanide, and chloride) is most speedy by the dry method on -charcoal; in this way in less than 120 seconds any practical chemist -could identify each compound. The nitrate, bromide, iodide, and -cyanide, all, if ignited on charcoal, yield buttons of metallic -silver--deflagration, bromine vapours, iodine vapours, and cyanogen -vapours being the respective phenomena observed. Chloride of silver -fuses to a pearl-grey, brown, or black globule on charcoal, according to -its purity; but is only in the R.F. gradually reduced to metal. With -soda, or fused in hydrogen or coal gas, the reduction is rapid enough. - -=Nitrate of Silver in solution= might be identified by a very large -number of tests, since it forms so many insoluble salts. In practice one -is, however, satisfied with three tests, viz.: (1) A curdy precipitate -of chloride, on the addition of hydrochloric acid or alkaline chlorides, -soluble only in ammonia, cyanide of potassium, or hyposulphite of soda; -(2) a yellow precipitate, but little soluble in ammonia, on the addition -of iodide of potassium; and (3) a blood-red precipitate on the addition -of chromate of potash. - -The separation of silver from the contents of the stomach is best -ensured by treating it with cyanide of potassium; for, unless a very -large quantity of silver nitrate has been taken, it is tolerably certain -that the whole of it has passed into chloride, and will, therefore, not -be attacked easily by acids. The contents of the stomach, then, or the -tissues themselves, are placed in a flask and warmed for some time with -cyanide of potassium, first, if necessary, adding ammonia. The fluid is -separated from the solid matters by subsidence (for an alkaline fluid of -this kind will scarcely filter), and then decomposed by hydrochloric -acid in excess. The flask containing this fluid is put on one side in a -warm place, and the clear fluid decanted from the insoluble chloride. -The latter is now collected on a filter, well washed with hot water, and -then dried and reduced on charcoal; or it may be put in a little -porcelain crucible with a rod of zinc and a few drops of hydrochloric -acid. The silver is soon deposited, and must be washed with water, then -with sulphuric acid. By the aid of a wash-bottle the particles of silver -are now collected on a small filter, again washed, and on the moist mass -a crystal of nitrate of potash and a little carbonate of soda laid. The -whole is then dried, and all the filter cut away, save the small portion -containing the silver. This small portion is now heated on charcoal -until a little button of pure silver is obtained, which may first be -weighed, then dissolved in nitric acid, and tested by the methods -detailed. - -In a similar way hair, suspected of being dyed with silver, can be -treated with chlorine gas, and the chloride dissolved in potassic -cyanide. - -Spots on linen, and, generally, very small quantities of silver, may be -detected by a simple galvanic process:--The substance is treated with -solution of cyanide of potassium, and submitted to a weak galvanic -current, using for the negative plate a slip of copper, for the -positive, platinum; the silver is deposited on the former. - - -5. MERCURY. - -Sec. 828. =Mercury=, Hg = 200; specific gravity, 13.596; boiling-point, -350 deg. (662 deg. F.); it becomes solid at -39.4 (-39 F.). This well known and -familiar fluid metal evaporates and sublimes to a minute extent at all -temperatures above 5 deg. - -When precipitated or deposited in a finely divided state, the metal can -be united into a single globule only if it is fairly pure; very slight -_fatty_ impurities especially will prevent the union. It is insoluble in -hydrochloric acid, soluble to a slight extent in dilute cold sulphuric -acid, and completely soluble in concentrated sulphuric and in nitric -acids. It combines directly with chlorine, bromine, and iodine, which, -in presence of free alkali, readily dissolve it. It is unalterable at -100 deg., and, when exposed to a high temperature, sublimes unchanged. - -=Mercurous Chloride= (Calomel, HgCl = 235.5; specific gravity, 7.178; -subliming temperature, 111.6 deg.; Hg, 84.94 per cent., Cl, 15.06 per -cent.), when prepared in the wet way is a heavy white powder, absolutely -insoluble in cold, but decomposed by boiling water. It may be converted -into the mercuric chloride by chlorine water and aqua regia. Chloride of -ammonium, potassium, and sodium, all decompose calomel into metallic -mercury and mercuric chloride. It is easily reduced to metal in a tube -with soda, potash, or burnt magnesia. - -Sec. 829. =Sulphide of Mercury= (HgS, Hg, 86.21 per cent., S, 13.79 per -cent.) is a black powder, dissolving in nitromuriatic acid, but very -insoluble in other acids or in water. It is also insoluble in alkaline -sulphides, with the exception of potassic sulphide. - -Sec. 830. =Medicinal Preparations of Mercury.=--Mercury in the liquid state -has been occasionally administered in constipation; its internal use is -now (or ought to be) obsolete. Gmelin has found samples contaminated -with metallic bismuth--a metal which only slightly diminishes the -fluidity of mercury; the impurity may be detected by shaking the mercury -in air, and thus oxidising the bismuth. Mercury may also contain various -mechanical impurities, which are detected by forcing the metal by means -of a vacuum pump through any dense filtering substance. Tin and zinc may -be dissolved out by hydrochloric acid, and all fixed impurities (such as -lead and bismuth) are at once discovered on subliming the metal. - -=Mercury and Chalk= (=Hydrargyrum cum creta=).--Mercury, 33.33 per -cent.; chalk, 66.67. - -=Blue Pill= (=Pilula hydrargyri=).--Mercury in a finely divided state, -mixed with confection of roses and liquorice root; the mercury should be -in the proportion of 33.33 per cent.[902] - -[902] The chemical composition of blue pill varies according to its age. -Harold Senier has made a careful series of analyses, with the following -result (_Pharm. Journ._, Feb. 5, 1876):-- - - +----+------------+---------+---------+-----------+--------+---------+ - | | Age. |Metallic |Mercuric | Mercurous | Ash. | Organic | - | | |Mercury. | Oxide. | Oxide. | | Matter. | - +----+------------+---------+---------+-----------+--------+---------+ - | 1 | 18 hours, | 32.49 | none. | a trace. | 1.20 | 66.31 | - | 2 | 3 weeks, | 32.26 | .09 | .25 | 1.20 | 66.20 | - | 3 | 3 months, | 32.60 | .24 | .62 | 1.18 | 66.36 | - | 4 | 3 " | 31.15 | .44 | 1.60 | 1.12 | 65.69 | - | 5 | 6 " | 32.44 | .50 | .80 | 1.70 | 64.56 | - | 6 | 14 " | 29.86 | .98 | 2.60 | 1.20 | 65.36 | - | 7 | 19 " | 31.59 | .50 | 2.50 | 1.00 | 64.41 | - | 8 | 2 years, | 28.40 | 1.80 | 4.22 | 2.10 | 63.48 | - | 9 | (?) | 30.23 | 1.06 | 3.24 | 1.05 | 64.44 | - +----+------------+---------+---------+-----------+--------+---------+ - - -=Mercury Plaster= (=Emplastrum hydrargyri=).--Made with mercury, olive -oil, sulphur, and lead plaster; it should contain Hg, 33 per cent.; -sulphur, 18 per cent. - -=Ammoniac and Mercury Plaster= (=Emplastrum ammoniaci cum -hydrargyro=).--Gum, ammonia, mercury, olive oil, and sulphur; it should -contain 20 per cent. of Hg, and .1 per cent. of sulphur. - -=Mercurial Ointment= (=Unguentum hydrargyri=).--Mercury mixed with lard -and suet, the strength should be nearly 50 per cent. mercury; commercial -samples often contain as little as 38 per cent. - -=Compound Mercury Ointment= (=Unguentum hydrargyri compositum=).--Made -with ointment of mercury, yellow wax, olive oil, and camphor; it should -contain 22.2 per cent. Hg. - -=Liniment of Mercury= (=Linimentum hydrargyri=) is made of mercurial -ointment, solution of ammonia, and liniment of camphor; it contains -about 16-1/2 per cent. of mercury. - -=Mercurial Suppositories= (=Suppositoria hydrargyri=).--Composed of -ointment of mercury and oil of theobroma. Each suppository should weigh -15 grains and contain 1/3 of its weight of mercurial ointment. - -=Acetate of Mercury= (=Mercurous acetate=) is not contained in the B.P., -but is officinal on the Continent. It is a salt occurring in white -micaceous scales, soluble in 133 parts of cold water, giving the -reactions of acetic acid and mercury, and very readily decomposed. - -=Mercuric Ethyl Chloride= (=Hydrargyrum aethylo-chloratum=) is used as a -medicine on the Continent. It occurs in white, glittering, crystalline -scales, which take on pressure a metallic appearance, and possess a -peculiar ethereal odour; it is but little soluble in water and ether, -with difficulty in cold alcohol, but copiously soluble on boiling, and -depositing crystals on cooling. It sublimes at about 40 deg. without -residue; on quick heating it burns with a weak flame, developing a -vapour of metallic taste and unpleasant odour. It gives no precipitate -with silver nitrate, nor with albumen. - -=Corrosive Sublimate= (=Mercuric chloride=), HgCl_{2} = 271; Hg, 73.8 -per cent., Cl, 26.1 per cent.--In commerce this salt occurs in -transparent, heavy, colourless masses, which have a crystalline -fracture; if placed in the subliming cell described at p. 258, it -sublimes at about 82.2 deg. (180 deg. F.), and melts at higher temperatures. The -sublimate is generally in groups of plates drawn to a point at both -ends, in crystalline needles, or in octahedra with a rectangular base. -It dissolves in 16 parts of cold water and about 3 of boiling, and is -very soluble in solutions of the alkaline chlorides; it dissolves also -in ether, and can be, to a great extent, withdrawn from aqueous -solutions by this agent. Alcohol dissolves nearly one-third its weight -of the salt, and its own weight when boiling. It combines with albumen; -gives, when in solution, a precipitate of mercuric oxide when tested -with solution of potash; a white precipitate with ammonia; a scarlet -with iodide of potassium; and a black precipitate of finely divided -mercury with protochloride of tin. If a crystal (when placed in the -subliming cell) gives a crystalline sublimate at about the temperature -mentioned, and this sublimate becomes of a red colour when treated with -a droplet of iodide of potassium, it can be no other substance than -corrosive sublimate. - -=Solution of Perchloride of Mercury= (=Liquor hydrargyri perchloridi=) -is simply 10 grains of perchloride of mercury and chloride of ammonium -in a pint of water; 100 c.c. therefore should contain 114 mgrms. -corrosive sublimate. - -=Yellow Mercurial Lotion= (=Lotio hydrargyri flava=).--Perchloride of -mercury, 18 grains, mixed with 10 ounces of solution of lime. - -=Calomel=[903] (=Hydrargyri subchloridum=).--The properties of calomel -have been already described. It sometimes contains as an impurity -corrosive sublimate, which may be dissolved out by ether. Carbonate of -lead, sulphate, and carbonate of baryta, gum, and starch, are the usual -adulterants mentioned. If on the application of heat calomel entirely -sublimes, it must be free from the substances enumerated. - -[903] It would appear that in America a cosmetic is in use, consisting -of calomel mixed into a paste with water.--_Vide_ "A Dangerous -Cosmetic," by C. H. Piesse, _Analyst_ (25), 1878, p. 241. - -=Oleate of Mercury= (=Hydrargyri oleatum=) is composed of 1 part of -yellow oxide and 9 parts of oleic acid. - -=Black Mercurial Lotion= (=Lotio hydrargyri nigra=).--Calomel, 30 -grains, mixed with 10 fluid ounces of lime-water. - -=Compound Pill of Subchloride of Mercury.=--Calomel and sulphurated -antimony, each 1 ounce, guiac resin 2 ounces, castor-oil 1 fluid ounce. -One grain (.0648 grm.) of calomel, and the same quantity of antimony -sulphide, are contained in every 5 grains (324 mgrms.) of the pill mass, -_i.e._, calomel 20 per cent. - -=Ointment of Subchloride of Mercury= (=Unguentum hydrargyri -subchloridi=).--Calomel mixed with benzoated lard; strength about 1 : -6-1/2. - -=White Precipitate= (=Hydrargyrum ammoniatum=, NH_{2}HgCl).--A white, -heavy powder, subliming by heat without residue, and insoluble in water, -alcohol, and ether. With soda, it yields a metallic sublimate. When -boiled with potash, ammonia is evolved, the yellow oxide of mercury -formed, and chloride of potassium passes into solution. It should -contain 79.5 per cent. of mercury. - -The fusible white precipitate of the pharmacop[oe]ia of the Netherlands -does not appear to be of constant composition, varying between 69.4 to -65.6 per cent. of mercury.[904] It melts on heating, and leaves as a -residue chloride of sodium. - -[904] Hirsch, _Die Pruefung der Arzeneimittel_. - -Commercial white precipitate is frequently adulterated; Barnes has found -carbonates of lead and lime, the latter to the extent of nearly 2 per -cent.[905] Calomel, according to Nickles,[906] has been substituted for -white precipitate, but this was several years ago. The methods for -detection are obvious. - -[905] _Proceed. Brit. Pharm. Conf._, 1867, p. 10. - -[906] _Journ. Pharm. et Chim._, le Serie, 1858, vol. viij. p. 399. - -=Ointment of Ammoniated Mercury= (=Unguentum hydrargyri ammoniati=).--1 -part of ammoniated mercury mixed with 9 parts of simple ointment. - -=Red Iodide of Mercury= (=Hydrargyrum iodidum rubrum=, HgI_{2}).--A -crystalline powder of a scarlet colour, becoming yellow on gentle -heating. It is very insoluble in water, one part requiring from 6000 to -7000 parts; soluble in 130 parts of cold, 150 of hot alcohol; and -dissolving freely in ether, or in aqueous solution of iodide of -potassium. - -=Ointment of Red Iodide of Mercury= (=Unguentum hydrargyri iodidi -rubri=).--16 grains of the substance mixed with an ounce of simple -ointment. - -=Green Iodide of Mercury= (=Hydrargyri iodidum viride=, HgI).--A dingy, -greenish-yellow powder, darkening on exposure to light, and easily -decomposed into the red iodide. - -=Red Oxide of Mercury= (=Hydrargyri oxidum rubrum=), HgO = 216; Hg, -92.12 per cent.; specific gravity, 11 to 11.3; small, red, shining, -crystalline scales, very insoluble in water, requiring about 20,000 -parts; entirely soluble in hydrochloric acid. By a heat below redness it -may be volatilised, and at the same time decomposed into mercury and -oxygen. Its principal impurity is nitric acid, readily detected by the -usual tests, or by heating in a test-tube, when, if nitric acid is -present, orange vapours will be evolved. Fixed red powders (such as -brick-dust and minium) are detected by being left as a residue, after -the application of heat sufficient to volatilise the mercury. An -ointment (strength 1 : 8) is officinal. - -=Sulphate of Mercury.=--A white crystalline powder, decomposed by water -into the very insoluble basic salt of mercury, known as _Turbith -mineral_, HgSO_{4}2HgO. - -=Turbith, or Turpeth, Mineral= is contained in the French -pharmacop[oe]ia, HgSO_{4}2HgO; Hg, 82.4 per cent.; specific gravity, -8.319. It requires for solution 2000 parts of cold, and 600 of boiling -water; but dissolves with tolerable ease in hydrochloric acid. - -=The Sulphide of Mercury=, known in commerce under the name of _Ethiops -mineral_, is officinal in France, the Netherlands, and Germany. Its -properties have been already described. The German and Dutch -pharmacop[oe]ias require in it 50, the French only 33-1/3 per cent. of -metallic mercury. - -=Hahnemann's Soluble Mercury= (=Hydrargyrum solubile Hahnemanni=) is -officinal in the Dutch pharmacop[oe]ia. As found in commerce it contains -metallic mercury, nitric acid, and ammonia. The mercury should be in the -proportion of 86.33 per cent., the ammonia 2.44 per cent. - -=Crystallised Nitrate of Mercury= (=Hydrargyrum nitricum oxidulatum=) is -officinal in the pharmacop[oe]ias of Germany, Switzerland, and France. -The salt is in white crystals, giving the reactions of nitric acid and -mercury, decomposed by the addition of water, but fully soluble in -water, if first moistened with nitric acid. The formula of the neutral -salt is Hg2NO_{3}HgO2H_{2}O, which requires 69.4 per cent. of mercury. -An acid solution of mercuric nitrate is officinal. - -=An Ointment of Nitrate of Mercury= (=Unguentum hydrargyri nitratis=) -(often called citrine ointment) is contained in the B.P.; it is made -with 4 parts of mercury, nitric acid 12, lard 15, olive oil, 32; the -strength is about 1 in 15-1/2. - -=A Chloride of Mercury and Quinine= exists in commerce, prepared by -mixing 1 part of corrosive sublimate in solution with 3 parts of quinine -chloride, evaporating, and crystallising. - -=Cyanide of Mercury=, HgCy, is contained in the French pharmacop[oe]ia. -It occurs in small, colourless, prismatic crystals, easily soluble in -water. If to the solution chloride of tin be added, a black precipitate -of reduced metal and stannous oxide is thrown down, and the odour of -prussic acid is developed. - -=Mercuric Sulphide= (=Sulphide of Mercury=, =Cinnabar=, =Vermilion=) is -officinal in Germany, the Netherlands, and France; HgS = 232; specific -gravity, solid, 8.2; Hg, 86.21 per cent., O, 13.79 per cent. For -medicinal purposes it is made artificially. It is a beautiful red -powder, insoluble in all alkaline and all acid liquids, with the -exception of aqua regia. The solution gives the reactions of a sulphide -and mercury. On heating, it must burn away entirely without residue; -adulterations or impurities are--minium, lead, copper, and other metals. -The detection of minium is conveniently executed in the dry way. Pure -cinnabar, when heated in a matrass, gives a black sublimate, which -becomes red on friction. If minium is present, sulphide of lead remains -as a residue, and may be recognised on coal; the same remark applies to -sulphide of antimony. If it be desired to take the percentage of mercury -in cinnabar, equal parts of oxalate and cyanide of potassium should be -well mixed with the cinnabar, and heated in the bent tube described at -p. 654; by this means the whole of the metallic mercury is readily -obtained.[907] - -[907] Dr. Sutro has published a case (quoted by Taylor), in which the -vapour of vermilion, applied externally, produced poisonous symptoms; -yet, according to Polak, the Persians inhale it medicinally, smoking it -with tobacco, catechu, mucilage, &c., the only bad effect being an -occasional stomatitis.--Eulenberg, _Gewerbe Hygiene_, p. 741. - -Sec. 831. =Mercury in the Arts.=--The use of mercury in the arts is so -extensive, that any one in analytical practice is almost certain -occasionally to meet with cases of accidental poisoning, either from the -vapour[908] or some of its combinations. - -[908] A singular case is cited by Tardieu (_Etude med.-legal sur -l'Empoisonnement_), in which a man, supposing he had some minerals -containing gold, attempted the extraction by amalgamation with mercury. -He used a portable furnace (for the purpose of volatilising the mercury) -in a small room, and his wife, who assisted him, suffered from a very -well-marked stomatitis and mercurial eruption. - -Quicksilver is used in the extraction of gold, the silvering of mirrors, -the construction of barometers, and various scientific instruments and -appliances; also for the preservation of insects, and occasionally for -their destruction.[909] An alloy with zinc and cadmium is employed by -dentists for stopping teeth; but there is no evidence that it has been -at all injurious, the mercury, probably, being in too powerful a state -of combination to be attacked by the fluids in the mouth.[910] Cinnabar -has also been employed to give a red colour to confections, and it may -be found in tapers, cigarette papers, and other coloured articles. The -nitrate of mercury in solution finds application in the colouring of -horn, in the etching of metals, in the colouring of the finer sorts of -wool, and in the hat manufacture. - -[909] Forty-three persons were salivated from fumigating rooms with -mercury for the purpose of destroying bugs (Sonnenschein's _Handbuch_, -p. 96). - -[910] More danger is to be apprehended from the vulcanised rubber for -artificial teeth; and, according to Dr. Taylor, accidents have occurred -from the use of such supports or plates. - -The sulphocyanide of mercury gives, when burnt, a most abundant ash, a -fact utilised in the toy known as Pharaoh's serpent; the products of -combustion are mercurial vapours and sulphurous anhydride. That the -substance itself is poisonous, is evident from the following -experiment:--.5 grm. was given to a pigeon without immediate result; but -ten hours afterwards it was indisposed, refused its food, and in forty -hours died without convulsions.[911] - -[911] Eulenberg, _Op. cit._, p. 472. - -Sec. 832. The more Common Patent and Quack Medicines containing Mercury. - - =Mordant's Norton's Drops.=--This patent medicine is a mixture of - the tincture of gentian and ginger, holding in solution a little - bichloride of mercury, and coloured with cochineal. - - =Solomon's Anti-impetigines= is a solution of bichloride of mercury, - flavoured and coloured. - - =Poor Man's Friend.=--An ointment of nitrate of mercury. - - =Brown's Lozenges.=--Each lozenge contains 1/2 grain of calomel, and - 3-1/2 grains of resinous extract of jalap; the rest is white sugar - and tragacanth. - - =Ching's Worm Lozenges.=--Each lozenge contains 1 grain of calomel; - the rest white sugar and tragacanth, with saffron as a colouring - matter. - - =Storey's Worm Cakes.=--Each cake 2 grains of calomel, 2 grains of - cinnabar, 6 grains of jalap, 5 grains of ginger, and the remainder - sugar and water. - - =Wright's Pearl Ointment= is said to be made up of 8 ozs. of white - precipitate rubbed to a cream in 1 pint of Goulard's extract, and to - the mixture is added 7 lbs. of white wax and 10 lbs. of olive oil. - - =Keyser's Pills.=--The receipt for these pills is--red oxide of - mercury 1-1/2 oz., distilled vinegar (dilute acetic acid) 1 pint; - dissolve, add to the resulting solution manna 2 lbs., and triturate - for a long time before the fire, until a proper consistence is - attained; lastly, divide the mass into pills of 1-1/2 grain each. - - =Mitchell's Pills.=--Each pill contains aloes .8 grain, rhubarb 1.6 - grain, calomel .16 grain, tartar emetic .05 grain. - - Many =Antibilious Pills= will be found to contain calomel, a few - mercury in a finely divided state. - -Sec. 833. =Mercury in Veterinary Medicine.=--Farmers and farriers use the -ointment (_blue ointment_) to a dangerous extent, as a dressing for the -fly, and wholesale poisoning of sheep has been in several instances the -consequence.[912] Ethiops mineral and Turpeth mineral are given to dogs -when affected by the distemper, worms, or the mange. Mercury, however, -is not very frequently given to cattle by veterinary surgeons, ruminants -generally appearing rather susceptible to its poisonous effects. - -[912] Twenty-five tons of blue ointment are said to have been sold to -farmers by a druggist in Boston, Lincolnshire, in the course of a single -year.--Taylor's _Medical Jurisprudence_, vol. i. p. 279. - -Sec. 834. =Medicinal and Fatal Dose--Horses.=--Cinnabar 14.2 grms, (1/2 -oz.), calomel 14.2 grms. (1/2 oz.) or more, corrosive sublimate .13 to -.38 grm. (2 to 6 grains), and as much as 1.3 grm. (20 grains) have been -given in farcy. - -=Cattle.=--Mercury with chalk 3.8 to 11.6 grms. (1 to 3 drms.), calomel -3.8 to 7.7 grms. (1 to 2 drms.) for worms; .65 to 1.3 grm. (10 to 20 -grains) as an alterative; Ethiops mineral, 7.7 to 15.5 grms. (2 to 4 -drms.). - -=Dogs.=--Ethiops or Turpeth mineral .13 to 1.3 grm. (2 to 20 grains), -according to the size. - -=Fowls.=--Mercury and chalk are given in fractions of a grain. - -=Hogs= are also treated with mercury and chalk; the dose usually given -does not exceed .32 grm. (5 grains). - -It may be remarked that many of the doses quoted appear very large; the -writer cannot but consider that 20 grains of corrosive sublimate -administered to a horse would be more likely to kill the animal than to -cure the disease. - -=Man.=--Corrosive sublimate has been fatal in a dose so small as .19 -grm. (3 grains); white precipitate has caused dangerous symptoms in -doses of from 1.9 to 2.6 grm. (30 to 40 grains); the cyanide of mercury -has killed a person in a dose of .64 grm. (10 grains)--_Christison_; and -Turpeth mineral has proved fatal in doses of 2.6 grms. (40 grains). - -Other preparations of mercury have also been fatal, but a doubt has -existed as to the precise quantity. Sometimes, also, there is probably a -chemical change in the substance, so that it is impossible to state the -fatal dose. For example, it is well known that calomel, under the -influence of alkaline chlorides, can be converted into the bichloride--a -fact which probably explains the extensive corrosive lesions that have -been found after death from large doses of calomel. - -Sec. 835. =Poisoning by Mercury--Statistics.=--In the Registrar-General's -death returns for the ten years ending 1892, it appears that in England -the deaths from mercurial poisoning[913] were 40 males, 19 females; of -these, 16 males and 18 females were cases of suicide, the remainder were -referred to accident. - -[913] The deaths are registered under the term "_Mercury_," but the -majority are poisonings by "_Corrosive Sublimate_." - -The effects of the different compounds of mercury may be divided into -two groups, viz., (1) Those caused by the finely divided metal and the -non-corrosive compounds; (2) the effects caused by the corrosive -compounds. - -Sec. 836. (1) Effects of Mercurial Vapour, and of the Non-Corrosive -Compounds of Mercury. - -(_a_) =Vegetable Life.=--Priestly and Boussingault have shown that -plants under a glass shade in which mercury is exposed in a saucer, -first exhibit black spots on the leaves; ultimately, the latter blacken -entirely, and the plants die. - -(_b_) =Animal Life.=--Mercury in the form of vapour is fatal to animal -life, but it is only so by repeated and intense application. -Eulenberg[914] placed a rabbit under a large glass shade, and for four -days exposed it daily for two hours to the volatilisation of 2 grms. of -mercury on warm sand; on the sixth and seventh day 1.5 grm. was -volatilised. On the fifteenth day there was no apparent change in the -aspect of the animal; 5 grms. of mercury were then heated in a retort, -and the vapour blown in at intervals of ten minutes. Fourteen days -afterwards the gums were reddened and swollen, and the appetite lost; -the conjunctivae were also somewhat inflamed. The following day these -symptoms disappeared, and the animal remained well. - -[914] _Op. cit._, p. 728. - -In another experiment 20 grms. of mercury were volatilised, and a rabbit -exposed to the vapour under a small glass shade. The following day the -conjunctivae were moist and reddened; two days afterwards 10 grms. of -mercury were volatilised in the same way; and in two days' interval -other 10 grms. were volatilised in three-quarters of an hour. There was -no striking change noticeable in the condition of the animal, but -within forty-eight hours it was found dead. The cause of death proved to -be an extravasation of blood at the base of the brain. The bronchia were -reddened throughout, and the lungs congested. Mercury, as with man, is -also readily absorbed by the broken or unbroken skin; hence thousands of -sheep have been poisoned by the excessive and ignorant external -application of mercurial ointment as a remedy against the attacks of -parasites. The sheep become emaciated, refuse food, and seem to be in -pain, breathing with short quick gasps. - -In experiments on rabbits, dogs, and warm-blooded animals generally, -salivation and stomatitis are found to occur as regularly as in man; so -also in animals and man, paralytic and other nervous affections have -been recorded. - -Sec. 837. (_c_) =Effects on Man.=--In 1810[915] an extraordinary accident -produced, perhaps, the largest wholesale poisoning by mercurial vapour -on record. The account of this is as follows:--H.M.S. "Triumph," of -seventy-four guns, arrived in the harbour of Cadiz in the month of -February 1810; and in the following March, a Spanish vessel, laden with -mercury for the South American mines, having been driven on shore in a -gale, was wrecked. The "Triumph" saved by her boats 130 tons of the -mercury, and this was stowed on board. The mercury was first confined in -bladders, the bladders again were enclosed in small barrels, and the -barrels in boxes. The heat of the weather, however, was at this time -considerable; and the bladders, having been wetted in the removal from -the wreck, soon rotted, and mercury, to the amount of several tons, was -speedily diffused as vapour through the ship, mixing more or less with -the bread and the other provisions. In three weeks 200 men were affected -with ptyalism, ulceration of the mouth, partial paralysis, and, in many -instances, with diarrh[oe]a. The "Triumph" was now ordered to Gibraltar, -the provisions were removed, and efforts were made to cleanse the -vessel. On restowing the hold, every man so employed was salivated. The -effects noted were not confined to the officers and ship's company, for -almost all the stock died from the fumes--mice, cats, a dog, and even a -canary bird shared the same fate, though the food of the latter was kept -in a bottle closely corked up. The vapour was very deleterious to those -having any tendency to pulmonic affections. Three men, who had never -complained before they were saturated with mercury, died of phthisis; -one, who had not had any pulmonic complaint, was left behind at -Gibraltar, where his illness developed into a confirmed phthisis. Two -died from gangrene of the cheeks and tongue. A woman, confined to bed -with a fractured limb, lost two of her teeth; and many exfoliations of -the jaw took place. - -[915] "An Account of the Effect of Mercurial Vapours on the Crew of His -Majesty's Ship 'Triumph,' in the year 1810."--_Phil. Trans._, 113, -1823. - -Accidents from the vapour of mercury, quite independently of its -applications in the arts, have also occurred, some of them under curious -circumstances; such, for example, is the case mentioned in the footnote -to p. 639. Witness, again, a case mentioned by Seidel,[916] in which a -female, on the advice of an old woman, inhaled for some affection or -other 2.5 grms. of mercury poured on red-hot coals, and died in ten days -with all the symptoms of mercurial poisoning. - -[916] Maschka's _Handbuch_, Bd. ii. 295. - -The metal taken in bulk into the stomach has been considered -non-poisonous, and, probably, when perfectly pure, it is so; we have, -however, the case of a girl who swallowed 4-1/2 ozs. by weight of the -liquid metal, for the purpose of procuring abortion--this it did not -effect; but, in a few days, she suffered from a trembling and shaking of -the body and loss of muscular power. These symptoms continued for two -months, but there was no salivation and no blue marks on the gums. This -case is a rare one, and a pound or more has been taken without injury. - -Sec. 838. =Absorption of Mercury by the Skin.=--Mercury in a finely divided -form, rubbed into the skin, is absorbed, and all the effects of -mercurialism result. This method of administering mercury for medicinal -purposes has long been in use, but, when the inunction is excessive, -death may occur. Thus, Leiblinger records a case in which three persons -were found dead in bed; the day before they had rubbed into the body, -for the purpose of curing the itch, a salve containing 270 grms. of -mercury finely divided. - -It is difficult to say in what proportion workers in mercury, such as -water-gilders, &c., suffer. According to Hirt, not only do 1.5 to 2.1 -per cent. of the workmen employed in smelting mercury ores suffer -acutely, but as high a proportion as 8.7 per cent. are slightly -affected. - -Sec. 839. =Symptoms of Poisoning by Mercury Vapour.=--The symptoms of -poisoning by mercury vapour, or by the finely divided metal, are the -same as those which arise from the corrosive salts, with the exception -of the local action. In mild cases there is pallor, languor, and sore -mouth (from slightly inflamed gums), f[oe]tid breath, and disorder of -the digestive organs. If the action is more intense, there is an -inflammation of the gums and, indeed, of the whole mouth, and -salivation, which is sometimes so profuse that as much as two gallons of -saliva have been secreted daily. The saliva is alkaline, has a bad -odour, and its specific gravity in the early stages is increased, but -ultimately becomes normal; the gums are raised into slight swellings, -which gradually enlarge and coalesce. The teeth that are already -carious, decay more rapidly; they become loose, and some may be shed; -the inflammatory action may extend to the jaw, and necrosis of portions -of the bone is no unusual occurrence. On recovery, the cheeks sometimes -form adhesions with the gums, and cicatrices always mark the loss of -substance which such an affection entails. With the stomatitis there are -disturbances of the gastro-intestinal tract--nausea and vomiting, pain -in the stomach, and diarrh[oe]a alternating with constipation. -Conjunctivitis is very common, both in man and animals, from exposure to -mercury vapours. The further action of the metal is shown in its -profound effects on the nervous system. The patient is changed in his -disposition, he is excitable, nervous, or torpid; there are -sleeplessness and bad dreams, at the same time headache, noises in the -ears, giddiness, faintings, &c. - -Sec. 840. =Mercurial Tremor.=--Mercurial tremor[917] may follow, or -accompany the above state, or it may be the chief and most prominent -effect. It specially affects the arms, partly withdrawing the muscles -from the control of the will, so that a person affected with mercurial -tremor is incapacitated for following any occupation, especially those -requiring a delicate and steady touch. In cases seriously affected, the -tremor spreads gradually to the feet and legs, and finally the whole -body may be invaded. The patient is no longer master of his muscles--the -muscular system is in anarchy, each muscle aimlessly contracting and -relaxing independently of the rest--the movement of the legs becomes -uncertain, the speech stuttering, the facial expressions are even -distorted into grimaces, and the sufferer sinks into a piteous state of -helplessness. The convulsive movements generally cease during sleep. The -tremors are accompanied by interference with the functions of other -organs: the respiration is weakened and difficult; dyspn[oe]a, or an -asthmatic condition, results; the pulse is small and slow; paresis, -deepening into paralysis of the extremities, or of a group of muscles, -follows; and, lastly, if the condition is not alleviated, the patient -becomes much emaciated and sinks from exhaustion. Pregnant women are -liable to abortion, and the living infants of women suffering from -tremor have also exhibited tremor of the limbs. - -[917] A case of mercurial tremor (in _Bericht. des K. K. Allgem. -Krankenhauses zu Wien im Jahre 1872_, Wien, 1873) is interesting, as -showing the influence of pregnancy. A woman, twenty years of age, -employed in making barometers, had, in 1869, mercurial tremor and -salivation. During a three months' pregnancy the tremor ceased, but -again appeared after she had aborted. She again became pregnant, and the -tremor ceased until after her confinement in November 1871. The tremor -was so violent that the patient could not walk; she also had stomatitis; -but ultimately, by treatment with galvanism and other remedies, she -recovered. - -In the case of the "mass poisoning" on board the "Triumph," it has been -mentioned that several of the sailors became consumptive, and the same -effect has been noticed among all workers in the metal; it is now, -indeed, an accepted fact that the cachexia induced by mercurialismus -produces a weak habit of body specially liable to the tuberculous -infection. - -The course of the poisoning is generally more rapid when it has -resulted from the taking of mercury internally as a medicine than when -inhaled by workers in the metal, _e.g._, a patient suffering from -mercurial tremor shown to the Medical Society by Mr. Spencer Watson in -1872, had resisted for seven years the influence of the fumes of -mercury; and then succumbed, exhibiting the usual symptoms. Idiosyncrasy -plays a considerable _role_; some persons (and especially those whose -kidneys are diseased) bear small doses of mercury ill, and are readily -salivated or affected; this is evidently due to imperfect elimination. - -Sec. 841. =Mercuric Methide=, Hg(CH_{3})_{2}.--This compound is obtained by -the action of methyl iodide on sodium amalgam in the presence of acetic -ether. It is a dense, stable liquid, of highly poisonous properties. In -1865, mercuric methide, in course of preparation in a London laboratory, -caused two cases of very serious slow poisoning.[918] One was that of a -German, aged 30, who was engaged in preparing this compound for three -months, and during this time his sight and hearing became impaired; he -was very weak, his gums were sore, and he was ultimately admitted into -St. Bartholomew's Hospital, February 3rd, 1865. His urine was found to -be albuminous, and his mental faculties very torpid. On the 9th he -became noisy, and had to be put under mechanical restraint. On the 10th -he was semi-comatose, but there was no paralysis; his breath was very -offensive, his pupils dilated; at intervals he raised himself and -uttered incoherent howls. There was neither sensation nor motion in the -left leg, which was extended rigidly; the knee and the foot were turned -slightly inward. On the 14th he died insensible. - -[918] _St. Barth. Hosp. Reports_, vol. i., 1866, p. 141. - -The only appearance of note seen at the autopsy was a congestion of the -grey matter in the brain; the kidneys and liver were also congested, and -there were ecchymoses in the kidneys. - -The second case--a young man, aged 23, working in the same -laboratory--was admitted into the hospital, March 28th, 1865. In the -previous January he had been exposed to the vapour of mercuric methide -for about a fortnight; during the illness of the other assistant he felt -ill and weak, and complained of soreness of the gums and looseness of -the teeth. He had also dimness of vision, pain and redness of the eyes, -giddiness, nausea and vomiting, the ejected matters being greenish and -watery. At the beginning of March his sight and taste became -imperfect--all things tasted alike; his tongue was numb and his gums -sore, he was also salivated slightly. A week before admission he lost -his hearing, and first his hands and then his feet became numb; on -admission his breath was very offensive, his pupils dilated; the sight -impaired; he was very deaf, and his powers of speech, taste, and smell -were deficient. There was anaesthesia of the body, and the movement of -the limbs was sluggish and difficult. He continued in the hospital for -nearly a month, with but little change. On April 24th, it was noticed -that he was getting thinner and slightly jaundiced; he moved his arms -aimlessly in an idiotic manner, and passed his urine involuntarily. On -April 27th he was more restless, and even violent, shrieking out and -making a loud, incoherent noise, or laughing foolishly; he passed his -motions and urine beneath him. On July 7th he was in a similar -state--perfectly idiotic. He died on April 7th, 1866, about a year and -three months from his first exposure to the vapour; the immediate cause -of death was pneumonia. The _post-mortem_ appearances of the brain and -membranes differed little from the normal state; the grey matter was -pink, but otherwise healthy; there was a considerable amount of -cerebro-spinal fluid; the arachnoid along the longitudinal fissure was -thickened; the total weight of the brain with medulla was 41 ozs. The -stomach was of enormous size; the pyramids of the kidneys were -congested, as was also the small intestine; the lungs showed the usual -signs of pneumonia.[919] - -[919] _St. Barth. Hosp. Reports_, vol. ii. p. 211. - -Sec. 842. =Effects of the Corrosive Salts of Mercury.=--The type of the -corrosive salts is mercuric chloride, or corrosive sublimate--a compound -which acts violently when administered, either externally or internally, -in large doses.[920] If the poison has been swallowed, the symptoms come -on almost immediately, and always within the first half hour; the whole -duration also is rapid. In 36 cases collected by F. A. Falck, 11 died on -the first or second day, and 11 on the fifth day; so that 61 per cent. -died in five days--the remainder lived from six to twenty-six days. The -shortest fatal case on record is one communicated to Dr. Taylor by Mr. -Welch; in this instance the man died from an unknown quantity within -half an hour. - -[920] The effects on animals are similar to those on man. Richard Mead -gave a dog with bread 3.8 grms. (60 grains) of corrosive -sublimate:--"Within a quarter of an hour he fell into terrible -convulsions, casting up frequently a viscid frothy mucus, every time -more and more bloody, till, tired and spent with this hard service, he -lay down quietly, as it were, to sleep, but died the next morning." - -In the very act of swallowing, a strong metallic taste and a painful -sensation of constriction in the throat are experienced. There is a -burning heat in the throat extending downwards to the stomach. All the -mucous membranes with which the solution comes in contact are attacked, -shrivelled, and whitened; so that, on looking into the mouth, the -appearance has been described as similar to that produced by the recent -application of silver nitrate. The local changes may be so intense as to -cause [oe]dema of the glottis, and death through asphyxia. In a few -minutes violent pain is felt in the stomach; so much so, that the -sufferer is drawn together, and is in a fainting condition; but there -are rare cases in which pain has been absent. There are nausea and -vomiting, the ejected matters being often streaked with blood; after -the vomiting there is purging; here also the motions are frequently -bloody.[921] The temperature of the body sinks, the respiration is -difficult, and the pulse small, frequent, and irregular. The urine is -generally scanty, and sometimes completely suppressed.[922] Sometimes -there is profuse haemorrhage from the bowel, stomach, or other mucous -membrane, and such cases are accompanied by a considerable diminution of -temperature. In a case recorded by L[oe]wy,[923] after a loss of blood -by vomiting and diarrh[oe]a, the temperature sank to 33.4 deg. The patient -dies in a state of collapse, or insensibility, and death is often -preceded by convulsions. - -[921] The mixture of blood with the evacuations is more constantly -observed in poisoning by corrosive sublimate than in poisoning by -arsenic, copper, or lead. - -[922] In a case recorded by Dr. Wegeler (Casper's _Wochenschrift_, -January 10, 1846, p. 30), a youth, aged 17, swallowed 11.6 grms. (3 -drachms) of the poison. No pain was experienced on pressure of the -abdomen; he died on the sixth day, and during the last three days of -life no urine was secreted. - -[923] _Vierteljahrsschr. fuer ger. Med._, 1864, vol. i. p. 187. - -Sec. 843. Two remarkable cases of death from the external use of corrosive -sublimate are recorded by Anderseck. An ointment, containing corrosive -sublimate, was rubbed into the skin of two girls, servants, in order to -cure the itch. The one, during the inunction, complained of a burning of -the skin; the other also, a little while after, suffered in the same -way. During the night the skin of each swelled, reddened, and became -acutely painful. There were thirst and vomiting, but no diarrh[oe]a, On -the following day there was an eruption of blebs or little blisters. On -the third day they had diarrh[oe]a, tenesmus, fever, and diminution of -the renal secretion; on the fourth day, f[oe]tid breath, stomatitis, -hyperaesthesia of the body, and a feeling of "pins and needles" in the -hands and feet were noted. The first girl died in the middle of the -fifth day, fully conscious; the other died on the sixth. So also -Taylor[924] gives the case of a girl, aged 9, who died from the effects -of an alcoholic solution of corrosive sublimate (strength, 80 grains to -the oz.) applied to the scalp as a remedy for ringworm. The same -author[925] further quotes the case of two brothers who died--the one on -the fifth, the other on the eleventh day--from the effects of absorbing -corrosive sublimate through the unbroken skin. - -[924] _Op. cit._ - -[925] _Poisons_, 1848, p. 394. - -Sec. 844. =The Nitrates of Mercury= are poisons, but little (if at all) -inferior in corrosive action to mercuric chloride. Death has resulted -from both the external and internal use. Application of the nitrate as -an escharotic to the _os uteri_, in one case,[926] produced all the -symptoms of mercurial poisoning, but the woman recovered; in another -case,[927] its use as a liniment caused death. - -[926] _Med. Gazette_, vol. 45, p. 1025. - -[927] _Edin. Monthly Journal_, 1864, p. 167. - -Sec. 845. When taken internally, the symptoms are scarcely different from -those produced by corrosive sublimate. It seems an unlikely vehicle for -criminal poisoning, yet, in the case of _Reg._ v. _E. Smith_ (Leicester -Summer Assizes, 1857), a girl was proved to have put a solution of -nitrate of mercury in some chamomile tea, which had been prescribed for -the prosecutrix. The nauseous taste prevented a fatal dose being taken; -but the symptoms were serious. - -Sec. 846. =Mercuric Cyanide= acts in a manner very similar to that of -corrosive sublimate, 1.3 grm. (about 20 grains) in one case,[928] and in -another[929] half the quantity, having destroyed life. - -[928] Orfila, i. p. 735. - -[929] Christison, p. 427. - -Sec. 847. =White Precipitate= (ammoniated mercury), as a poison, is weak. -Out of fourteen cases collected by Taylor, two only proved fatal; one of -these formed the subject of a trial for murder, _Reg._ v. _Moore_ (Lewes -Lent Assizes, 1860). The effects produced are vomiting, purging, &c., as -in corrosive sublimate.[930] Other preparations of mercury, such as the -red iodide, the persulphide, and even calomel,[931] have all a more or -less intense poisonous action, and have caused serious symptoms and -death. - -[930] See Dr. Th. Stevenson, "Poisoning by White Precipitate," _Guy's -Hospital Reports_, vol. xix. p. 415. - -[931] Seidel quotes a case from Hasselt, in which a father, for the -purpose of obtaining insurance money, killed his child by calomel. - -Sec. 848. =Treatment of Acute and Chronic Poisoning.=--In acute poisoning, -vomiting usually throws off some of the poison, if it has been -swallowed; and the best treatment seems to be, to give copious -albuminous drinks, such, for example, as the whites of eggs in water, -milk, and the like. The vomiting may be encouraged by subcutaneous -injections of apomorphine. The after-treatment should be directed to -eliminating the poison, which is most safely effected by very copious -drinks of distilled water (see "Appendix"). - -The treatment of slow poisoning is mainly symptomatic; medicinal doses -of zinc phosphide seem to have done good in mercurial tremors. Potassic -iodide is also supposed to assist the elimination of mercury. - -Sec. 849. =Post-mortem Appearances.=--The pathological effects seen after -chronic poisoning are too various to be distinctive. In the museum of -the Royal College of Surgeons there is (No. 2559) the portion of a colon -derived from a lady aged 74.[932] This lady had been accustomed for -forty-three years to take a grain of calomel every night; for many years -she did not suffer in health, but ultimately she became emaciated and -cachectic, with anasarca and albuminuria. The kidneys were found to be -granular, and the mucous membrane of a great part of the intestine of a -remarkable black colour, mottled with patches of a lighter hue, -presenting somewhat the appearance of a toad's back. From the portion of -colon preserved mercury was readily obtained by means of Reinsch's -test. The black deposit is in the submucosa, and it is, without doubt, -mercurial, and probably mercury sulphide. In acute poisoning (especially -by the corrosive salts) the changes are great and striking. After rapid -death from corrosive sublimate, the escharotic whitening of the mouth, -throat, and gullet, already described, will be seen. The mucous membrane -right throughout, from mouth to anus, is more or less affected and -destroyed, according to the dose and concentration of the poison. The -usual appearances in the stomach are those of intense congestion, with -ecchymoses, and portions of it may be destroyed. Sometimes the coats are -very much blackened; this is probably due to a coating of sulphide of -mercury. - -[932] _Path. Soc. Trans._, xviii. 111. - - In St. George's Hospital Museum (Ser. ix. 43, y. 337) there is a - stomach, rather large, with thickened mucous coats, and having on - the mucous surface a series of parallel black, or black-brown lines - of deposit; it was derived from a patient who died from taking - corrosive sublimate. With the severe changes mentioned, perforation - is rare.[933] In the intestines there are found hyperaemia, - extravasations, loosening of the mucous membrane, and other changes. - The action is particularly intense about the caecum and sigmoid - flexure; in one case,[934] indeed, there was little inflammatory - redness of the stomach or of the greater portion of the intestine, - but the whole surface of the caecum was of a deep black-red colour, - and there were patches of sloughing in the coats. The kidneys are - often swollen, congested, or inflamed; changes in the respiratory - organs are not constantly seen, but in a majority of the cases there - have been redness and swelling of the larynx, trachea, and bronchi, - and sometimes hepatisation of smaller or larger portions of the - lung. - -[933] There is only one case of perforation on record. - -[934] _Lancet_, 1845, p. 700. - - In St. George's Hospital Museum, there are (from a patient dying in - the hospital) preparations which well illustrate what pathological - changes may be expected in any case surviving for a few days. The - patient was Francis L----, aged 45, admitted to the hospital, - February 27, 1842. He took a quantity of corrosive sublimate spread - on bread and butter, was immediately sick, and was unable to take as - much as he had intended. The stomach-pump and other remedies were - used. On the following day his mouth was sore, and on March 1st his - vision was dim; his mouth was drawn over to the right side, and he - lost power over the left eyelid, but he had no pain; he passed some - blood from the bowel. On the 2nd he passed much blood, and was - salivated; still no pain. On March 4, on the evening of the sixth - day, he expired; he was drowsy during the last day, and passed - watery evacuations. - - Prep. 14a, Ser. ix., shows the pharynx, [oe]sophagus, and tongue; - there is ulceration of the tonsils, and fibrinous exudation on the - gullet. The stomach (43b, 199) shows a large dark slough, three - inches from the cardiac extremity; the margin surrounding the slough - is thickened, ulcerated, and irregular in shape, the submucous - tissue, to some extent, being also thickened; there is fibrine in - the ileum, pharynx, and part of the larynx. The action extended to - the whole intestine, the rectum in prep. 145a, 36, is seen to be - thickened, and has numerous patches of effused fibrine. - -It is a curious fact that the external application of corrosive -sublimate causes inflammatory changes in the alimentary canal of nearly -the same intensity as if the poison had been swallowed. Thus, in the -case of the two girls mentioned _ante_ (p. 647), there was found an -intense inflammation of the stomach and intestines, the mucous tissues -being scarlet-red, swollen, and with numerous extravasations. - -Sec. 850. The effects of the nitrate of mercury are similar to the -preceding; in the few cases which have been recorded, there has been -intense redness, and inflammation of the stomach and intestines, with -patches of ecchymosis. White precipitate, cyanide of mercury, mercuric -iodide, and mercurous sulphide (turpeth-mineral) have all caused -inflammation, more or less intense, of the intestinal tract. - -Sec. 851. =Elimination of Mercury.=--The question of the channels by which -mercury is eliminated is of the first importance. It would appear -certain that it can exist in the body for some time in an inactive -state, and then, from some change, be carried into the circulation and -show its effects.[935] Voit considers that mercury combines with the -albuminous bodies, separating upon their oxidation, and then becoming -free and active.[936] - -[935] Tuson gave a mare, first, 4 grains, and afterwards 5 grains of -corrosive sublimate twice a day; at the end of fourteen days, in a pint -of urine no mercury was detected, but at the end of three weeks it was -found. - -[936] _Voit, Physiol. chem. Unters._, Augsburg, 1857. - -Ullmann[937] found most mercury in the following order:--Kidneys, liver, -spleen, a small quantity in the stomach, no mercury in the small -intestine, but some in the large intestine; small weighable quantities -in the heart and skeletal muscles, also in the lungs; but no mercury, -when the dose was small, in brain, the salivary glands, abdominal -glands, thyroid glands, the bile, or the bones. - -[937] _Chem. Centr._, 1892, ii. 941. - -The main channel by which absorbed mercury passes out of the body is the -kidneys, whilst mercurial compounds of small solubility are in great -part excreted by the bowel. A. Bynssen,[938] after experimenting with -mercuric chloride (giving .015 to .15 grm., with a little morphine -hydrochlorate), came to the conclusion that it could be detected in the -urine about two hours, and in the saliva about four hours, after its -administration; he considered that the elimination was finished in -twenty-four hours. - -[938] _Journal de l'Anat. et de Physiol._, 1872, No. 5, p. 500. On the -separation of mercury by the urine, see also Salkowsky in Virchow's -_Archiv_, 1866. - -From the body of a hound that, in the course of thirty-one days, took -2.789 grms. of calomel (2.368 Hg) in eighty-seven doses, about 94 per -cent. of the substance was recovered on analysis:-- - - Mercurous - Sulphide. - Grms. - In the faeces, 2.1175 - " urine, 0.0550 - " brain, heart, lungs, spleen, pancreas, - kidneys, scrotum, and penis, 0.0090 - " liver, 0.0140 - " muscles, 0.0114 - ------ - 2.2069 - -This equals 1.9 of metallic mercury.[939] Thus, of the whole 2.2 grms. -of mercuric sulphide separated, over 95 per cent. was obtained from the -faeces. - -[939] Riederer, in Buchner's _Neues Repert. f. Pharm._, Bd. xvii. 3, -257, 1868. - -This case is of considerable interest, for there are recorded in -toxicological treatises a few cases of undoubted mercurial poisoning in -which no poison had been detected, although there was ample evidence -that it had been administered by the mouth. In such cases, it is -probable that the whole length of the intestinal canal had not been -examined, and the analysis failed from this cause. When (as not -unfrequently happens) the mercurial poison has entered by the skin, it -is evident that the most likely localities are the urine, the liver, and -the kidneys.[940] - -[940] A woman died from the effects of a corrosive sublimate lotion -applied by a quack to a wound in her leg. The writer found no poison in -the stomach, but separated a milligramme of metallic mercury from the -liver; the urine and intestines were not sent. - -In a case related by Vidal,[941] the _Liquor Bellostii_ (or solution of -mercuric nitrate) was ordered by mistake instead of a liniment. Although -externally applied, it caused salivation, profuse diarrh[oe]a, and death -in nine days. The whole of the intestinal tract was found inflamed with -extravasations, and mercury detected in the liver. - -[941] _Gaz. des Hop._, Juillet 1864. - -In any case of external application, if death ensues directly from the -poison, evidence of its presence will probably be found; but too much -stress must not be laid upon the detection of mercury, for, as Dr. -Taylor says, "Nothing is more common than to discover traces of mercury -in the stomach, bowels, liver, kidneys, or other organs of a dead -body."[942] - -[942] Taylor, _Medical Jurisprudence_, i. p. 288. - -Sec. 852. =Tests for Mercury.=--Mercury, in combination and in the solid -form, is most readily detected by mixing the substance intimately with -dry anhydrous sodic carbonate, transferring the mixture to a glass tube, -sealed at one end, and applying heat. If mercury be present, a ring of -minute globules condenses in the cool part of the tube. If the quantity -of mercury is likely to be very minute, it is best to modify the process -by using a subliming cell (p. 258), and thus obtain the sublimate on a -circle of thin glass in a convenient form for microscopical examination. -If there is any doubt whether the globules are those of mercury or not, -this may be resolved by putting a fragment of iodine on the lower disc -of the subliming cell, and then completing it by the disc which contains -the sublimate (of course, the supposed mercurial surface must be -undermost); on placing the cell in a warm, light place, after a time the -scarlet iodide is formed, and the identification is complete. Similarly, -a glass tube containing an ill-defined metallic ring of mercury can be -sealed or corked up with a crystal of iodine, and, after a few hours, -the yellow iodide, changing to scarlet, will become apparent. There are -few (if any) tests of greater delicacy than this. - -Mercury in solution can be withdrawn by acidulating the liquid, and then -inserting either simply a piece of gold foil, gold wire, or bright -copper foil; or else, by a galvanic arrangement, such as iron wire wound -round a gold coin, or gold foil attached to a rod of zinc; or, lastly, -by the aid of gold or copper electrodes in connection with a battery. By -any of these methods, mercury is obtained in the metallic state, and the -metal with its film can be placed in a subliming cell, and globules -deposited and identified, as before described. - -The =Precipitating Reagents= for mercury are numerous: a solution of -stannous chloride, heated with a solution of mercury, or any -combination, whether soluble or insoluble, reduces it to the metallic -state. - -=Mercurous Salts= in solution yield, with potash, soda, or lime, a black -precipitate of mercurous oxide. =Mercuric Salts=, a bright yellow -precipitate of mercuric oxide. - -=Mercurous Salts= yield black precipitates, with sulphides of ammonium -and hydrogen. =Mercuric Salts= give a similar reaction, but, with -sulphuretted hydrogen, first a whitish precipitate, passing slowly -through red to black. - -=Mercurous Salts=, with solutions of the chlorides, give a white -precipitate of calomel; the =Mercuric Salts= yield no precipitate under -similar circumstances. =Mercurous Salts=, treated with iodide of -potassium, give a green mercurous iodide; =Mercuric=, a scarlet. - -Sec. 853. =The Detection of Mercury in Organic Substances and -Fluids.=--Ludwig's process, previously described, is found in practice -the best. Fluids, such as urine, must be evaporated to dryness, and then -treated with hydrochloric acid. Such organs as the liver are cut up and -boiled in 20 per cent. HCl. Distinct evidence of mercury in the liver -has been obtained on a piece of copper gauze, in a case where a child -had been given 2 grains of calomel before death. "Four ounces of the -liver were treated with hydrochloric acid and water, and a small piece -of pure copper placed in the acid liquid while warm, and kept there for -about forty-eight hours. It acquired a slight silvery lustre, and -globules of mercury were obtained from it by sublimation." - -To detect the cyanide of mercury may require special treatment, and -Vitali[943] recommends the following process:--The fluid is acidified -with tartaric acid and neutralised by freshly precipitated CaCO_{3}; a -slight excess of hydric sulphide is added, and the flask allowed to rest -for twenty-four hours in the cold. Then a further quantity of SH_{2} is -added, and a current of hydrogen passed through the liquid; the effluent -gas is first made to bubble through a solution of bismuth nitrate in -dilute nitric acid (for the purpose of absorbing SH_{2}), and then -through aqueous potash (to absorb HCl); in the first flask the analyst -will separate and identify mercury sulphide, while in the last flask -there will be potassic cyanide, which will respond to the usual tests. - -[943] _L'Orosi_, xii. 181-196. - -In those cases where no special search is made for mercury, but an acid -(hydrochloric) solution is treated with sulphuretted hydrogen, mercury -is indicated by the presence of a black precipitate, which does not -dissolve in warm nitric acid. - -The further treatment of the black sulphide may be undertaken in two -ways:-- - -(1) It is collected on a porcelain dish, with the addition of a little -nitric acid, and evaporated to dryness in order to destroy organic -matter. Hydrochloric and a few drops of nitric acid are next added; the -action is aided by a gentle heat, the solution finally evaporated to -dryness on the water-bath, and the residue taken up by warm distilled -water. The solution is that of a persalt of mercury, and the mercury can -be separated by electrolysis, or indicated by the tests already -detailed. - -(2) The other method, and the most satisfactory, is to mix the sulphide -while moist with dry carbonate of soda, make it into a pellet which will -easily enter a reducing or subliming tube, dry it carefully, and obtain -a sublimate of metallic mercury. - -A neat method of recognising mercury when deposited as a film on copper -has been proposed by E. Brugnatelli:[944] the copper, after being -washed, is transferred to a glass vessel, and a porcelain lid, on which -a drop of gold chloride solution has been placed, adjusted over the -dish. The whole is heated by a water-bath. The mercury vapour reduces -the gold chloride, and gold is deposited as a bluish-violet stain; 1/10 -mgrm. mercury may by this test be identified. - -[944] _Gazzetta_, xix. 418-422. - -Of special methods for the separation and detection of mercury, -Ludwig's[945] is, without a doubt, the best when organic matters have to -be dealt with; the finely divided solid substances are boiled for some -hours with hydrochloric acid, strength 20 per cent.; then the liquid is -cooled to 60 deg., and potassic chlorate added in half gramme quantities -until the dark liquid becomes clear; the liquid is cooled and filtered, -and the substances on the filter washed with water. To the filtrate 5 -grms. of zinc dust are added, and the liquid is violently shaken from -time to time; a second portion is afterwards added, and also vigorously -shaken. After some hours the clear liquid is separated from the zinc and -the zinc washed, first with water, then with a little soda solution, and -finally, again with water. The zinc is now collected on a glass-wool -filter, treated with absolute alcohol to remove water, and dried by -suction in a stream of air. The zinc is put into a combustion-tube, the -tube being drawn out into a thin capillary extremity, and a combustion -made, the mercury collecting at the capillary part. It is a necessary -refinement, should the zinc be contaminated with a trace of organic -matter, to pack the combustion-tube as follows:--First, the zinc dust on -which any mercury present has been deposited, then a plug of asbestos; -next, some cupric oxide; and lastly, some pure zinc dust. -Bondzynski[946] prefers to use copper rather than zinc; for he says that -zinc so frequently contains cadmium, which latter metal also gives a -mirror, so that, unless the mercury is afterwards identified by turning -it into an iodide, error may be caused. - -[945] _Zeit. f. physiolog. Chemie_, 1882, i. 495; _Chem. Centrblt._, -1892, ii. 941. - -[946] _Zeit. f. anal. Chem._, xxxii. 302-305. - -[Illustration] - -Sec. 854. =Estimation of Mercury.=--All pharmaceutical substances -containing mercury, as well as the sulphide prepared in the wet way, and -minerals, are best dealt with by obtaining and weighing the metal in the -solid state. The assay is very simple and easy when carried out on the -method that was first, perhaps, proposed by Domeyko. A glass tube (which -should not be too thin), closed at one end, is bent, as shown in the -figure, the diameter should be about three lines, the length from 7 to 8 -inches, the shorter arm not exceeding 2 inches. The powdered substance -is mixed with two or three times its weight of litharge, and introduced -into the tube at _a_. The portion of the tube containing the mercury is -at first heated gently, but finally brought to a temperature sufficient -to fuse the substance and soften the glass. The mercury collects in an -annular film at _b_ in the cooler limb, and may now, with a little -management of the lamp, be concentrated in a well-defined ring; the -portion of the tube containing this ring is cut off, weighed, then -cleansed from mercury, and reweighed. Many of the pharmaceutical -preparations do not require litharge, which is specially adapted for -ores, and heating with sodic carbonate (in great excess) will suffice. -Mercury mixed with organic matter must be first separated as described, -by copper or gold, the silvered foil rolled up, dried, introduced into -the bent tube, and simply heated without admixture with any substance; -the weight may be obtained either by weighing the foil before and after -the operation, or as above. - -Sec. 855. =Volumetric Processes for the Estimation of Mercury.=--When a -great number of mercurial preparations are to be examined, a volumetric -process is extremely convenient. There are several of these processes, -some adapted more particularly for mercuric, and others for mercurous -compounds. For mercuric, the method of Personne[947] is the best. The -conversion of the various forms of mercury into corrosive sublimate may -be effected by evaporation with aqua regia, care being taken that the -bath shall not be at a boiling temperature, or there will be a slight -loss. - -[947] _Comptes Rendus_, lvi. 68; Sutton's _Vol. Anal._, 177. - -Personne prefers to heat with caustic soda or potash, and then pass -chlorine gas into the mixture; the excess of chlorine is expelled by -boiling, mercuric chloride in presence of an alkaline chloride not being -volatilised at 100 deg. The standard solutions required for this process -are:-- - -(1) 33.2 grms. of potassic iodide in 1 litre of water, 1 c.c. = 0.01 -grm. Hg, or 0.01355 grm. HgCl_{2}. - -(2) A solution of mercuric chloride containing 13.55 grms. to the litre, -1 c.c. = 0.1 grm. Hg. - -The process is founded on the fact that, if a solution of mercuric -chloride be added to one of potassic iodide, in the proportion of one of -the former to four of the latter, mercuric iodide is formed, and -immediately dissolved, until the balance is overstepped, when the red -colour is developed; the final reaction is very sharp, and with -solutions properly made is very accurate. The mercuric solution must -always be added to the alkaline iodide; a reversal of the process does -not answer. It therefore follows that the solution to be tested must be -made up to a definite bulk, and added to a known quantity of the -potassic iodide until the red colour appears. - -=Mercurous Salts= may be titrated with great accuracy by a decinormal -solution of sodic chloride. This is added to the cold solution in very -slight excess, the calomel filtered off, the filtrate neutralised by -pure carbonate of soda, and the amount of sodic chloride still unused -found by titration with nitrate of silver, the end reaction being -indicated by chromate of potash. Several other volumetric processes are -fully described in works treating upon this branch of analysis. - - -III.--PRECIPITATED BY HYDRIC SULPHIDE FROM A NEUTRAL SOLUTION. - -Zinc--Nickel--Cobalt. - - -1. ZINC. - -Sec. 856. =Zinc=--At. wt., 65; specific gravity, 6.8 to 7.1; fusing-point, -412 deg. (773 deg. F.)--is a hard, bluish-white, brittle metal, with a -crystalline fracture. Between 100 deg. and 150 deg. it becomes ductile, and may -be easily wrought, but at a little higher temperature it again becomes -brittle, and at a bright red heat it fuses, and then volatilises, the -fumes taking fire when exposed to the air. In analysis, zinc occurs -either as a metallic deposit on a platinum foil or dish, or as a brittle -bead, obtained by reducing a zinc compound with soda on charcoal. - -The salts of zinc to be briefly described here are the carbonate, the -oxide, and the sulphide,--all of which are likely to occur in the -separation and estimation of zinc, and the sulphate and chloride,--salts -more especially found in commerce, and causing accidents from time to -time. - -Sec. 857. =Carbonate of Zinc=, in the native form of calamine, contains, as -is well known, 64.8 per cent. of oxide of zinc; but the carbonate -obtained in the course of an analysis by precipitating the neutral hot -solution of a soluble salt of zinc by carbonate of potash or soda, is -carbonate of zinc _plus_ a variable quantity of hydrated oxide of zinc. -Unless the precipitation takes place at a boiling temperature, the -carbonic anhydride retains a portion of the oxide of zinc in solution. -By ignition of the carbonate, oxide of zinc results. - -Sec. 858. =Oxide of Zinc= (ZnO = 81; specific gravity, 5.612; Zn, 80.24, O, -19.76) is a white powder when cool, yellow when hot. If mixed with -sufficient powdered sulphur, and ignited in a stream of hydrogen, the -sulphide is produced; if ignited in the pure state in a rapid stream of -hydrogen gas, metallic zinc is obtained; but, if it is only a feeble -current, the oxide of zinc becomes crystalline, a portion only being -reduced. - -Sec. 859. =Sulphide of Zinc= (ZnS = 97; specific gravity, 4.1; Zn, 67.01, -S, 32.99).--The sulphide obtained by treating a neutral solution of a -soluble salt of zinc by hydric sulphide is hydrated sulphide, insoluble -in water, caustic alkalies, and alkaline sulphides, but dissolving -completely in nitric or in hydrochloric acid. When dry, it is a white -powder, and if ignited contains some oxide of zinc. The anhydrous -sulphide is produced by mixing the precipitated sulphide with sulphur, -and igniting in a crucible in a stream of hydrogen gas. - -=Pharmaceutical Preparations.=--The officinal compounds of zinc used in -medicine are the _acetate_, _carbonate_, _chloride_, _oxide_, -_sulphate_, _sulphocarbolate_, and _valerianate_. - -=Sulphate of Zinc= (ZnSO_{4}7H_{2}O 161 + 126; specific gravity, -crystals, 1.931).--This salt is officinal in all the pharmacop[oe]ias, -is used in calico-printing, and is commonly known as _white vitriol_. By -varying the temperature at which the crystals are allowed to be formed, -it may be obtained with 6, 5, 2, or 1 atoms of water. The commercial -sulphate is in crystals exactly similar to those of Epsom salts; it is -slightly efflorescent, and gives the reactions of zinc and sulphuric -acid. - -Sec. 860. =Chloride of Zinc= is obtained by dissolving zinc in hydrochloric -acid, or by direct union of zinc and chlorine. Chloride of zinc is the -only constituent in the well-known "Burnett's disinfectant fluid." A -solution of chloride of zinc may be heated until it becomes water-free; -when this takes place it still remains fluid, and makes a convenient -bath, for warmth may be applied to it above 370 deg. without its emitting -fumes to inconvenience; at a red heat it distils. A concentrated -solution of zinco-ammonic chloride (2H_{4}NClZnCl_{2}) is used for the -purpose of removing the film of oxide from various metals preparatory to -soldering. - -Sec. 861. =Zinc in the Arts.=--The use of zinc as a metal in sheeting -cisterns, articles for domestic use, alloys, &c., is well known; oxide -of zinc enters largely into the composition of india-rubber. Sulphide of -zinc has been employed as a substitute for white lead, and may possibly -supersede it. Zinc white is further employed as a pigment, and, mixed -with albumen, is an agent in calico-printing; it is also used in the -decoloration of glass, in the polishing of optical glasses, and in the -manufacture of artificial meerschaum pipes.[948] - -[948] Artificial meerschaum pipes are composed of zinc white, magnesia -usta, and caseine ammonium. - -=Chromate of Zinc= (ZnCrO_{4}) is used in calico-printing, and there is -also in commerce a basic chromate known as _zinc yellow_. Zinc green, or -Rinman's green, is a beautiful innocuous colour, formed by igniting a -mixture of dry zincic and cobaltous carbonates. - -The use of zinc vessels in the preparation of foods may occasionally -bring the metal under the notice of the analyst. When exposed to a moist -atmosphere, zinc becomes covered with a thin film of oxide, perfectly -insoluble in ordinary water; but, if the water should be charged with -common salt, a considerable quantity may be dissolved. It may generally -be laid down as a rule that the solvent power of water on zinc has a -direct relation to the chlorides present, whilst carbonate of lime -greatly diminishes this solubility.[949] - -[949] Ziurek, indeed, found in a litre of water contained in a zinc -cistern no less than 1.0104 grm. of zinc, and the same water showed only -0.074 grm. of common salt to the litre.--_Vierteljahrsschr. fuer gericht. -Medicin_, 1867, Bd. 6, p. 356. - -Milk may become contaminated by zinc; for, it is a matter of common -knowledge, that milk contained in zinc vessels does not readily turn -sour. This may be explained by the zinc oxide combining with the lactic -acid, and forming the sparingly soluble lactate of zinc -2(C_{3}H_{5}O_{3})Zn + 3H_{2}O, thus withdrawing the lactic acid as fast -as it is formed, preventing the coagulation of the casein. With regard -to this important practical subject, MM. Payne and Chevallier made -several experiments on the action of brandy, wine, vinegar, olive oil, -soup, milk, &c., and proved that zinc is acted on by all these, and -especially by alcoholic, acetic, and saline liquids. M. Schauffele has -repeated these experiments, and determined the amount of zinc dissolved -in fifteen days by different liquids from a galvanised iron as well as a -zinc vessel. - -The amount found was as follows:-- - - The liquid from - The liquid from the galvanised - the zinc vessel, iron vessel, - grms. per litre. grms. per litre. - Brandy, 0.95 0.70 - Wine, 3.95 4.10 - Orange-flower water, 0.50 0.75 - Vinegar, 31.75 60.75 - Fatty soup, 0.46 1.00 - Weak soup, 0.86 1.76 - Milk, 5.13 7.00 - Salt water, 1.75 0.40 - Seltzer water, 0.35 0.30 - Distilled water, traces. traces. - Ordinary water, traces. traces. - Olive oil, none. none. - -Sec. 862. =Effects of Zinc, as shown by Experiments on Animals.=--Harnack, -in experiments with sodium-zinc oxide pyrophosphate, has shown that the -essential action of zinc salts is to paralyse the muscles of the body -and the heart, and, by thus affecting the circulation and respiration, -to cause death; these main results have been fully confirmed by Blake, -Letheby, and C. Ph. Falck. For rabbits the lethal dose is .08 to .09 -grm. of zinc oxide, or about .04 per kilogrm. The temperature during -acute poisoning sinks notably--according to F. A. Falck's researches on -rabbits, from about 7.3 deg. to 13.0 deg. Zinc is eliminated mainly by the -urine, and has been recognised in that fluid four to five days after the -last dose. It has also been separated in small quantity from the milk -and the bile. - -Sec. 863. =Effects of Zinc Compounds on Man=--(=a=) =Zinc Oxide=.--The -poisonous action of zinc oxide is so weak that it is almost doubtful -whether it should be considered a poison. Dr. Marcett has given a pound -(453.6 grms.) during a month in divided doses without injury to a -patient afflicted with epilepsy; and the workmen in zinc manufactories -cover themselves from head to foot with the dust without very apparent -bad effects. It is not, however, always innocuous, for Popoff has -recorded it as the cause of headache, pain in the head, cramps in the -calves of the legs, nausea, vomiting, and diarrh[oe]a; and he also -obtained zinc from the urine of those suffering in this manner.[950] -Again, a pharmacy student[951] filled a laboratory with oxide of zinc -vapour, and suffered from well-marked and even serious poisonous -symptoms, consisting of pain in the head, vomiting, and a short fever. -It must be remembered that, as the ordinary zinc of commerce is seldom -free from arsenic, and some samples contain gallium, the presence of -these metals may possibly have a part in the production of the symptoms -described. - -[950] The so-called "zinc fever" has only been noticed in the founding -of brass; it is always preceded by well-marked shivering, the other -symptoms being similar to those described. - -[951] Rust's _Magazin_, Bd. xxi. Sec. 563. - -Sec. 864. (=b=) =Sulphate of Zinc.=--Sulphate of zinc has been very -frequently taken by accident or design, but death from it is rare. The -infrequency of fatal result is due, not to any inactivity of the salt, -but rather to its being almost always expelled by vomiting, which is so -constant and regular an effect, that in doses of 1.3 grm. (20 grains), -sulphate of zinc is often relied upon in poisoning from other substances -to quickly expel the contents of the stomach. In a case reported by Dr. -Gibb, an adult female swallowed 4.33 grms. (67 grains), but no vomiting -occurred, and it had to be induced by other emetics; this case is -unique. It is difficult to say what would be a fatal dose of zinc -sulphate, but the serious symptoms caused by 28 grms. (1 oz.) in the -case of a groom in the service of Dr. Mackenzie, leads to the view that, -although not fatal in that particular instance, it might be in others. -The man took it in mistake for Epsom salts: a few minutes after he was -violently sick and purged, and was excessively prostrated, so that he -had to be carried to his home; the following day he had cramps in the -legs, and felt weak, but was otherwise well. - -In a criminal case related by Tardieu and Roussin, a large dose of zinc -sulphate, put into soup, caused the death of an adult woman of sixty -years of age in about thirty hours.[952] The symptoms were violent -purging and vomiting, leading to collapse. From half of the soup a -quantity of zinc oxide, equal to 1.6 grm. of zinc sulphate, was -separated. Zinc was also found in the stomach, liver, intestines, and -spleen--(see also a case of criminal poisoning recorded by -Chevallier).[953] - -[952] Taylor notices this case, but adds that she died in three days. -This is a mistake, as the soup was taken on the 12th of June, probably -at mid-day, and the woman died on the 13th, at 8 P.M. - -[953] "Observations toxicologiques sur le zinc," _Annales d'Hygiene -Publique_, July 1878, p. 153. - -Sec. 865. (=c=) =Zinc Chloride.=--Chloride of zinc is a powerful poison, -which may kill by its primary or secondary effects; its local action as -a caustic is mainly to be ascribed to its intense affinity for water, -dehydrating any tissue with which it comes in contact. The common use of -disinfecting fluids containing zinc chloride, such as Burnett's fluid, -leads to more accidents in England than in any other European country. -Of twenty-six cases of poisoning by this agent, twenty-four occurred in -England, and only two on the Continent. Death may follow the external -use of zinc chloride. Some years ago, a quack at Barnstaple, Devon, -applied zinc chloride to a cancerous breast; the woman died with all -the general symptoms of poisoning by zinc, and that metal was found in -the liver and other organs. - -The symptoms observed in fatal cases of chloride of zinc poisoning -are--immediate pain in the throat, and burning of the lips, tongue, &c. -There is difficulty in swallowing, an increase in the secretion of -saliva, vomiting of bloody matters, diarrh[oe]a, collapse, coma, and -death. In some cases life has been prolonged for days; but, on the other -hand, death has been known to occur in a few hours. In those cases in -which either recovery has taken place, or in which death is delayed, -nervous symptoms rarely fail to make their appearance. In a case -recorded by Dr. R. Hassall, 3 ounces of Burnett's fluid were swallowed. -The usual symptoms of intense gastro-intestinal irritation ensued, but -there was no purging until the third day; after the lapse of a -fortnight, a train of nervous symptoms set in, indicated by a complete -perversion of taste and smell. In other cases, aphonia, tetanic -affections of groups of muscles, with great muscular weakness and -impairment of sight, have been noticed. Very large doses of zinc -chloride have been recovered from, _e.g._, a man had taken a solution -equivalent to about 13 grms. (200 grains) of the solid chloride. -Vomiting came on immediately, and there was collapse, but he recovered -in sixteen days. On the other hand, .38 grm. (6 grains) has destroyed -life after several weeks' illness. - -Sec. 866. =Post-mortem Appearances.=--In poisoning by sulphate of zinc, the -appearances usually seen are inflammation, more or less intense, of the -mucous membrane of the stomach and bowels. In the museums of the London -hospitals, I could only find (1882) a single specimen preserved -illustrating the effects of this poison. This preparation is in St. -George's Hospital Museum, and shows (ser. ix. 43 and 198) the stomach of -a man who died from zinc sulphate, and whose case is reported in the -_Lancet_, 1859. The mucous membrane is wrinkled all over like a piece of -tripe; when recent it was vascular and indurated, but uniformly of a -dirty grey colour; the lining membrane of the small intestine is very -vascular, and in the duodenum and upper part of the jejunum the colour -is similar to that of the stomach, but in a less marked degree; the -stomach and intestines are contracted. - -The pathological appearances after chloride of zinc vary according to -the period at which death takes place. When it has occurred within a few -hours, the lining membrane of the mouth and gullet shows a marked change -in texture, being white and opaque, the stomach hard and leathery, or -much corrugated or ulcerated. In cases in which life has been prolonged, -contractions of the gullet and stomach may occur very similar to those -caused by the mineral acids, and with a similar train of symptoms. In a -case which occurred under Dr. Markham's[954] observation, a person died -ten weeks after taking the fatal dose, the first symptoms subsiding in a -few days, and the secondary set of symptoms not commencing for three -weeks. They then consisted mainly of vomiting, until the patient sank -from exhaustion. The stomach was constricted at the pyloric end, so that -it would scarcely admit a quill. - -[954] _Med. Times and Gazette_, June 11, 1859, p. 595. - -In Guy's Hospital there is a good preparation, 1799^{35}, from the case -of S. R., aged 22; she took a tablespoonful of Burnett's fluid, and died -in about fourteen weeks. There were at first violent vomiting and -purging, but she suffered little pain, and in a day or two recovered -sufficiently to move about the house; but the vomiting after food -continued, everything being ejected about five minutes after swallowing. -Before death she suffered from pneumonia. The stomach is seen to be much -contracted--5 inches in length; it is ulcerated both near the pylorus -and near the gullet; at the latter part there is a pouch-like portion of -the mucous membrane of the stomach adherent to the spleen, which -communicates by a perforation with an abscess formed and bounded by the -stomach, diaphragm, and spleen; it contained 3 ozs. of dirty-looking -pus. At the pylorus, in the centre, there is a second perforation, but -extravasation of the contents is prevented by the adherent omentum and -transverse colon. The muscular coats are thickened. - -Sec. 867. =Detection of Zinc in Organic Liquids or Solids.=--In cases where -the poison has been expelled from the stomach by vomiting, the muscles -and bones would appear to be the best tissues to examine chemically; for -Matzkewitsch investigated very carefully a dog poisoned by 100 parts of -zinc, subcutaneously injected in the form of acetate, and found it -distributed over the several organs of the body in the following -ratios:--Muscles 60.5, bones 24.41, stomach and intestines 4.63, skin -3.70, place of injection 2.19, liver 1.75, lungs and heart 1.68, -kidneys, bladder, and urine 1.14. - -The only certain method of detection is to produce the sulphide of zinc, -best effected by saturating a neutral or feebly acid liquid with hydric -sulphide. If an organic liquid, which can be easily filtered, is -operated upon, it may be strongly acidulated with acetic acid, and at -once treated with hydric sulphide. If, however, zinc is sought for as a -part of a systematic examination (as will most likely be the case), the -solution will have been treated with hydrochloric acid, and already -tested for arsenic, antimony, lead, &c., and filtered from any -precipitate. In such a case the hydrochloric acid must first be replaced -by acetic, which is effected by adding a slight excess of sodic acetate; -the right quantity of the latter is easily known, if the hydrochloric -acid originally added was carefully measured, and its specific gravity -ascertained; 3.72 of crystallised sodic acetate saturating one of HCl. -Lastly, should the distillation process, given at p. 49, have been -adopted, the contents of the retort will only require to be treated -with water, filtered, and saturated with sulphuretted hydrogen. In any -of the above cases, should a white, dirty white or lightish-coloured -precipitate (which is not sulphur) be thrown down, zinc may be -suspected; it will, however, be absolutely necessary to identify the -sulphide, for there are many sources of error. The most satisfactory of -all identifications is the production of Rinman's green. The supposed -sulphide is dissolved off the filter with hot nitric acid, a drop or -more (according to the quantity of the original precipitate) of solution -of cobalt nitrate added, the solution precipitated with carbonate of -soda and boiled, to expel all carbonic anhydride; the precipitate is -then collected on a filter, washed, dried, and ignited in a platinum -dish. If zinc be present in so small a proportion as 1.100,000 part, the -mass will be permanently green. - -Sec. 868. Other methods of procedure are as follows:--The supposed zinc -sulphide (after being well washed) is collected in a porcelain dish, and -dissolved in a few drops of sulphuric acid, filtered, nitric acid added, -evaporated to dryness, and heated to destroy all organic matter. When -cool, the mass is treated with water acidulated by sulphuric acid, and -again filtered. The solution may contain iron as well as zinc, and if -the former (on testing a drop with ferrocyanide of potash) appears in -any quantity, it must be separated by the addition of ammonia in excess -to the ammoniacal filtrate; sodic carbonate is added in excess, the -liquid well boiled, and the precipitate collected on a filter and -washed. The carbonate of zinc thus obtained is converted into zinc oxide -by ignition, and weighed. If oxide of zinc, it will be yellow when hot, -white when cold: it will dissolve in acetic acid; give a white -precipitate with sulphuretted hydrogen; and, finally, if heated on -charcoal in the oxidising flame, and moistened with cobalt nitrate -solution, a green colour will result. Zinc may also be separated from -liquids by electrolysis. The simplest way is to place the fluid under -examination in a platinum dish of sufficient size, acidify, and insert a -piece of magnesium tape. The metallic film so obtained may be dissolved -by hydrochloric acid, and the usual tests applied. - - -2. NICKEL--COBALT. - -Sec. 869. The salts of nickel and cobalt have at present no toxicological -importance, although, from the experiments of Anderson Stuart,[955] both -may be classed as poisonous. The experiments of Gmelin had, prior to -Stuart's researches, shown that nickel sulphate introduced into the -stomach acted as an irritant poison, and, if introduced into the blood, -caused death by cardiac paralysis. Anderson Stuart, desiring to avoid -all local irritant action, dissolved nickel carbonate in acid citrate of -soda by the aid of a gentle heat; he then evaporated the solution, and -obtained a glass which, if too alkaline, was neutralised by citric acid, -until its reaction approximated to the feeble alkalinity of the blood; -the cobalt salt was produced in the same way. The animals experimented -on were frogs, fish, pigeons, rats, guinea-pigs, rabbits, cats, and -dogs--in all 200. The lethal dose of nickelous oxide, when -subcutaneously injected in the soluble compound described, was found to -be as follows:--frogs, .08 grm. per kilogram; pigeons, .06; guinea-pigs, -.030; rats, .025; cats, .01; rabbits, .009; and dogs, .007. The -cobaltous oxide was found to be much less active, requiring the above -doses to be increased about two-thirds. In other respects, its -physiological action seems to be very similar to that of nickelous -oxide. - -[955] "Nickel and Cobalt; their Physiological Action on the Animal -Organism," by T. P. Anderson Stuart, M.D., _Journ. of Anat. and -Physiol._, vol. xvii., Oct. 1882. - -Sec. 870. =Symptoms--Frogs.=--A large dose injected into the dorsal lymph -sac of the frog causes the following symptoms:--The colour of the skin -all over the body becomes darker and more uniform, and not infrequently -a white froth is abundantly poured over the integument. In an interval -of about twenty minutes the frog sits quietly, the eyes retracted and -shut; if molested, it moves clumsily. When quiet, the fore limbs are -weak, and the hind legs drawn up very peculiarly, the thighs being -jammed up so against the body, that they come to lie on the dorsal -aspect of the sides of the frog, and the legs are so much flexed that -the feet lie on the animal's back, quite internal to the plane of the -thighs. Soon fibrillary twitchings are observed in the muscles of the -abdominal wall, then feeble twitchings of the fingers, and muscles of -the fore limbs generally; lastly, the toes are seen to twitch, and then -the muscles of the hind limbs--this order is nearly always observed; now -spasmodic gaping and incoordinate movements are seen, and the general -aspect is not unlike the symptoms caused by picrotoxin. After this, -tetanus sets in, and the symptoms then resemble those of strychnine; the -next stage is stupefaction and voluntary motor paresis; the respiratory -movements become feeble, and the paresis passes into paralysis. The -heart beats more and more slowly and feebly, and death gradually and -imperceptibly supervenes. The _post-mortem_ appearances are well marked, -_i.e._, rigor mortis, slight congestion of the alimentary tract, the -heart with the auricle much dilated and filled with dark blood, the -ventricle mostly small, pale, and semi-contracted. For some time after -death, the nerve trunks and muscles react to the induction current. - -=Pigeons.=--In experiments on pigeons the symptoms were those of dulness -and stupor, jerkings of different sets of muscles, and then death -quietly. - -=Guinea-pigs.=--In guinea-pigs there were dulness and stupefaction, with -some weakness of the hind limbs. - -=Rats.=--The symptoms in rats were almost entirely nervous; they became -drowsy and apathetic, and there was paralysis of the hind legs. - -=Rabbits.=--In rabbits, also, the symptoms were mainly those caused by -an affection of the nervous system. There was paralysis, which affected -either the hind legs only, or all four limbs. The cervical muscles -became so weak that the animal was unable to hold its head up. -Diarrh[oe]a occurred and persisted until death. If the dose is not large -enough to kill rapidly, the reflex irritability is decidedly increased, -so that the slightest excitation may cause the animal to cower and -tremble all over. Now appear twitchings and contractions of single -groups of muscles, and this excitement becomes general. The respirations -also become slower and more difficult, and sometimes there is -well-marked dilatation of the vessels of the ears and _fundi oculi_. -Convulsions close the scene. - -Sec. 871. =Circulation.=--The effect of the salt on the frog's heart was -also studied in detail. It seems that, under the influence of a soluble -salt of nickel, the heart beats more and more slowly, it becomes smaller -and paler, and does not contract evenly throughout the whole extent of -the ventricle; but the rhythm of the ventricular and auricular -contractions is never lost. - -It is probable that there is a vaso-motor paralysis of the abdominal -vessels; the blood-pressure falls, and the heart is not stimulated by -the blood itself as in its normal state. In support of this view, it is -found that, by either pressing on the abdomen or simply inverting the -frog, the heart swells up, fills with blood, and for a time beats well. - -=Nervous System.=--The toxic action is referable to the central nervous -system, and not to that of peripheral motor nerve-endings or motor -nerve-fibres. It is probable that both nickel and cobalt paralyse to -some extent the cerebrum. The action on the nerve-centres is similar to -that of platinum or barium, and quite different from that of iron. - -Sec. 872. =Action on Striped Muscle.=--Neither nickel nor cobalt has any -effect on striped muscle. In this they both differ from arsenic, -antimony, mercury, lead, and iron--all of which, in large doses, -diminish the work which healthy muscle is capable of performing. - -Sec. 873. =Separation of Nickel or Cobalt from the Organic Matters or -Tissues.=--It is very necessary, if any case of poisoning should occur -by either or both of these metals, to destroy completely the organic -matters by the process already detailed on p. 51. Both nickel and cobalt -are thrown down, if in the form of acetate, from a neutral solution by -sulphuretted hydrogen; but the precipitation does not take place in the -presence of free mineral acid; hence, in the routine process of -analysis, sulphuretted hydrogen is passed into the acid liquid, and any -precipitate filtered off. The liquid is now made almost neutral by -potassic carbonate, and then potassic acetate added, and a current of -sulphuretted hydrogen passed through it. The sulphides of cobalt and -nickel, if both are present, will be thrown down; under the same -circumstances zinc, if present, would also be precipitated. Cobalt is -separated from zinc by dissolving the mixed sulphides in nitric acid, -precipitating the carbonates of zinc and cobalt by potassic carbonate, -collecting the carbonates, and, after washing, igniting them gently in a -bulb tube, in a current of dry hydrochloric acid; volatile zinc chloride -is formed and distils over, leaving cobalt chloride. - -Sec. 874. To estimate cobalt, sulphide of cobalt may be dissolved in nitric -acid, and then precipitated by pure potash; the precipitate washed, -dried, ignited, and weighed; 100 parts of cobaltous oxide (Co_{3}O_{4}) -equals 73.44 of metallic cobalt. Cobalt is separated from nickel by a -method essentially founded on one proposed by Liebig. The nitric acid -solution of nickel and cobalt (which must be free from all other metals, -save potassium or sodium) is nearly neutralised by potassic carbonate, -and mixed with an excess of hydrocyanic acid, and then with pure caustic -potash. The mixture is left exposed to the air in a shallow dish for -some hours, a tripotassic cobalticyanide (K_{3}CoCy_{6}) and a -nickelo-potassic cyanide (2KCy, NiCy_{4}) are in this way produced. If -this solution is now boiled with a slight excess of mercuric nitrate, -hydrated nickelous oxide is precipitated, but potassic cobalticyanide -remains in solution, and may be filtered off. On carefully neutralising -the alkaline filtrate with nitric acid, and adding a solution of -mercurous nitrate, the cobalt may then be precipitated as a mercurous -cobalticyanide, which may be collected, washed, dried, decomposed by -ignition, and weighed as cobaltous oxide. After obtaining both nickel -and cobalt oxides, or either of them, they may be easily identified by -the blowpipe. The oxide of nickel gives, in the oxidising flame with -borax, a yellowish-red glass, becoming paler as it cools; the addition -of a potassium salt colours the bead blue. In the reducing flame the -metal is reduced, and can be seen as little greyish particles -disseminated through the bead. Cobalt gives an intense blue colour to a -bead of borax in the oxidising flame. - - -IV.--PRECIPITATED BY AMMONIUM SULPHIDE. - -Iron--Chromium--Thallium--Aluminium--Uranium. - - -1. IRON. - -Sec. 875. It was Orfila's opinion that all the salts of iron were -poisonous, if given in sufficient doses; but such salts as the -carbonate, the phosphate, and a few others, possessing no local action, -may be given in such very large doses, without causing disturbance to -the health, that the statement must only be taken as applying to the -more soluble iron compounds. The two preparations of iron which have any -forensic importance are the perchloride and the sulphate. - -Sec. 876. =Ferric Chloride= (Fe_{2}Cl_{6} = 325).--Anhydrous ferric -chloride will only be met with in the laboratory. As a product of -passing dry chlorine over red-hot iron, it sublimes in brown scales, is -very deliquescent, and hisses when thrown into water. There are two very -definite hydrates--one with 6 atoms of water, forming large, red, -deliquescent crystals; and another with 12 of water, less deliquescent, -and crystallising in orange stellate groups. - -The pharmaceutical preparations in common use are:-- - -=Stronger Solution of Perchloride of Iron= (=Liquor Ferri Perchloridi -Fortior=).--An orange-brown liquid of specific gravity 1.42, and -containing about 58 per cent. of ferric chloride. - -=Tincture of Perchloride of Iron= (=Tinctura Ferri Perchloridi=), made -by diluting 1 part of the strong solution with 1 volume of rectified -spirit, and adding distilled water to measure 4. - -=Solution of Perchloride of Iron= (=Liquor Ferri Perchloridi=).--Simply -5 volumes of the strong solution made up to 20 by the addition of water; -hence, of the same strength as the tincture. - -Sec. 877. =Effects of Ferric Chloride on Animals.=--A very elaborate series -of researches on rabbits, dogs, and cats was undertaken a few years ago -by MM. Berenger-Feraud and Porte[956] to elucidate the general symptoms -and effects produced by ferric chloride under varying conditions. First, -a series of experiments showed that, when ferric chloride solution was -enclosed in gelatine capsules and given with the food of the animal, it -produced either no symptoms or but trifling inconvenience, even when the -dose exceeded 1 grm. per kilogrm.; anhydrous ferric chloride and the -ferric chloride solution were directly injected into the stomach, yet, -when food was present, death did not occur, and the effects soon -subsided. In animals which were fasting, quantities of the solution -equal to .5 grm. per kilogrm. and above caused death in from one hour to -sixteen hours, the action being much accelerated by the addition of -alcohol--as, for example, in the case of the tincture: the symptoms were -mainly vomiting and diarrh[oe]a, sometimes the vomiting was absent. In a -few cases the posterior extremities were paralysed, and the pupils -dilated: the urine was scanty or quite suppressed; death was preceded by -convulsions. - -[956] "Etude sur l'empoisonnement par le perchlorure de fer," par MM. -Berenger-Feraud et Porte, _Annales d'Hygiene Publique_, 1879. - -Sec. 878. =Effects on Man.=--Perchloride of iron in the form of tincture -has been popularly used in England, from its supposed abortive property, -and is sold under the name of "steel drops." It has been frequently -taken by mistake for other dark liquids; and there is at least one case -on record in which it was proved to have been used for the purpose of -murder. The latter case[957] is peculiarly interesting from its great -rarity; it occurred in Martinique in 1874-1876, no less than four -persons being poisoned at different dates. All four were presumed to -have had immoral relations with a certain widow X----, and to have been -poisoned by her son. In three of the four cases, viz., Char----, -Duf----, and Lab----, the cause of death seems pretty clear; but the -fourth, Ab----, a case of strong suspicion, was not sufficiently -investigated. All three took the fatal dose in the evening, between -eight and nine o'clock--Lab---- the 27th of December 1874, Duf---- the -22nd of February 1876, and Char---- on the 14th of May 1876. They had -all passed the day in tippling, and they all had eaten nothing from -mid-day, so that the stomach would, in none of the three, contain any -solid matters. The chloride was given to them in a glass of "punch," and -there was strong evidence to show that the son of the widow X---- -administered it. Char---- died after about thirteen hours' illness, -Duf---- and Lab---- after sixty-five hours' illness; Ab---- lived from -three to four days. With Char---- the symptoms were very pronounced in -an hour, and consisted essentially of violent colicky pain in the -abdomen and diarrh[oe]a, but there was no vomiting; Duf---- had also -great pain in the abdomen and suppression of the urine. Lab---- had most -violent abdominal pains; he was constipated, and the urinary secretion -was arrested; there was besides painful tenesmus. According to the -experiments of Berenger-Feraud and Porte,[958] the perchloride in the -above cases was taken under conditions peculiarly favourable for the -development of its toxic action, viz., on an empty stomach and mixed -with alcohol. - -[957] Fully reported in Berenger-Feraud's paper, _loc. cit._ - -[958] _Dub. Med. Press_, February 21, 1849. - -There have been several cases of recovery from large doses of the -tincture, _e.g._, that of an old man, aged 72, who had swallowed 85 c.c. -(3 ozs.) of the tincture; the tongue swelled, there were croupy -respiration and feeble pulse, but he made a good recovery. In other -cases,[959] 28.3 c.c. (an ounce) and more have caused vomiting and -irritation of the urinary organs. The perchloride is not unfrequently -used to arrest haemorrhage as a topical application to the uterine -cavity--a practice not free from danger, for it has before now induced -violent inflammation and death from peritonitis. - -[959] _Provincial Journal_, April 7 and 21, 1847, p. 180; see also -Taylor's _Principles and Practice of Medical Jurisprudence_, vol. i. p. -320, 2nd Edition. - -Sec. 879. =Elimination of Iron Chloride.=--Most of the iron is excreted in -the form of sulphide by the faeces, and colours them of a black hue; a -smaller portion is excreted by the urine. - -Sec. 880. =Post-mortem Appearances.=--In the experiments on animals already -referred to, the general changes noted were dryness, pallor, and -parchment-like appearance of the cavity of the mouth, the mucous -membrane being blackened by the contact of the liquid. The gullet was -pale and dry, not unfrequently covered with a blackish layer. The mucous -membrane of the stomach was generally healthy throughout; but, if the -dose was large and very concentrated, there might be one or more -hyperaemic spots; otherwise, this did not occur. The internal surface of -the intestines, similarly, showed no inflammation, but was covered with -brownish coating which darkened on exposure to the air. The liver, in -all the experiments, was large and gorged with black and fluid blood; -there were ecchymoses in the lungs and venous congestion. The kidneys -were usually hyperaemic, and contained little haemorrhages. There was also -general encephalic engorgement, and in one experiment intense congestion -of the meninges was observed. Few opportunities have presented -themselves for pathological observations relative to the effects -produced by ferric chloride on man. In a case related by Christison, in -which a man swallowed 42.4 c.c. (1-1/2 oz.) of the tincture, and died in -five weeks, there was found thickening and inflammation of the pyloric -end of the stomach. - -The case of Char----, already alluded to, is that in which the most -complete details of the autopsy are recorded, and they coincide very -fairly with those observed in animals; the tongue was covered with a -greenish fur, bordered at the edges with a black substance, described as -being like "mud"; the lining membrane of the gullet was pale, but also -covered with this dark "mud." The stomach contained a greenish-black -liquid; the liver was large and congested; the kidneys were swollen, -congested, and ecchymosed; the cerebral membranes were gorged with -blood, and the whole brain hyperaemic. - -Sec. 881. =Ferrous Sulphate, Copperas, or Green Vitriol=, FeSO_{4}7H_{2}O = -152 + 126; specific gravity, anhydrous, 3.138; crystals, 1.857; -composition in 100 parts, FeO, 25.92; SO_{3}, 28.77; H_{2}O, -45.32.--This salt is in beautiful, transparent, bluish-green, rhomboidal -prisms. The crystals have an astringent, styptic taste, are insoluble in -alcohol, but dissolve in about 1.5 times their weight of water; the -commercial article nearly always responds to the tests, both for ferrous -and ferric salts, containing a little persalt. The medicinal dose of -this salt is usually given as from .0648 to .324 grm. (1 to 5 grains), -but it has been prescribed in cases requiring it in gramme (15.4 grains) -doses without injury. Sulphate of iron has many technical applications; -is employed by all shoemakers, and is in common use as a disinfectant. -The salt has been employed for criminal purposes in France, and in this -country it is a popular abortive. In recorded cases, the symptoms, as -well as the pathological appearances, have a striking resemblance to -those produced by the chloride. There are usually colic, vomiting, and -purging; but in one case (reported by Chevallier), in which a man gave a -large dose of sulphate of iron to his wife, there was neither vomiting -nor colic; the woman lost her appetite, but slowly recovered. Probably -the action of ferrous sulphate, like that of the chloride, is profoundly -modified by the presence or absence of food in the stomach. Anything -like 28.3 grms. (an ounce) of sulphate of iron must be considered a -dangerous dose, for, though recovery has taken place from this quantity, -the symptoms have been of a violent kind. - -Sec. 882. =Search for Iron Salts in the Contents of the Stomach, -&c.=--Iron, being a natural component of the body, care must be taken -not to confound the iron of the blood or tissues with the "iron" of a -soluble salt. Orfila attempted to distinguish between the two kinds of -iron by treating the contents of the stomach, the intestines, and even -the tissues, with cold acetic acid, and allowing them to digest in it -for many hours before filtering and testing for iron in the filtrate, -and this is generally the process which has been adopted. The acid -filtrate is first treated with sulphuretted hydrogen, which gives no -precipitate with iron, and then with sulphide of ammonium, which -precipitates iron black. The iron sulphide may be dissolved by a little -hydrochloric acid and a drop of nitric acid, and farther identified by -its forming Prussian blue when tested by ferrocyanide of potash, or by -the bulky precipitate of oxide, when the acid liquid is alkalised by -ammonia. In the case of Duf----, the experts attempted to prove the -existence of foreign iron in the liver by taking 100 grms. of Duf----'s -liver and 100 grms. of the liver of a non-poisoned person, and -destroying each by nitro-muriatic acid, and estimating in each acid -solution the ferric oxide. Duf----'s liver yielded in 100 parts .08 -mgrm. of ferric oxide, the normal liver .022--nearly three times less -than Duf----'s. - -To obtain iron from the urine, the fluid must be evaporated down to a -syrup in a platinum dish, a little nitric acid added, heated, and -finally completely carbonised. The residue is dissolved in hydrochloric -acid. Normal urine always contains an unweighable trace of iron; and, -therefore, any quantity, such as a mgrm. of ferric oxide, obtained by -careful precipitation of the hydrochloric acid solution out of 200 to -300 c.c. of urine, would be good evidence that a soluble salt of iron -had been taken. The hydrochloric acid solution is first precipitated by -ammonia and ammonic sulphide. The precipitate thus obtained will not be -pure iron sulphide, but mixed with the earth phosphates. It should be -redissolved in HCl, precipitated by sodic carbonate, then acidified by -acetic acid and sodic acetate added, and the solution well boiled; the -iron will then be precipitated for the most part as oxide mixed with a -little phosphate of iron. - -Since, as before mentioned, a great portion of the iron swallowed as a -soluble salt is converted into insoluble compounds and excreted by the -faeces, it is, in any case where poisoning by iron is suspected, of more -importance to examine chemically the faeces and the whole length of the -alimentary canal, than even the contents of the stomach. In particular, -any black material lying on the mucous membrane may be sulphide of iron -mixed with mucus, &c., and should be detached, dissolved in a little -hydrochloric acid, and the usual tests applied. - -In the criminal cases alluded to, there were iron stains on certain -linen garments which acquired an importance, for, on dissolving by the -aid of nitric acid, they gave the reactions of chlorine and iron. Any -stains found should be cut out, steeped in water, and boiled. If no iron -is dissolved the stain should then be treated with dilute nitric acid, -and the liquid tested with ferrocyanide of potash, &c. It need scarcely -be observed that iron-mould is so common on shirts and any fabric -capable of being washed, that great care must be exercised in drawing -conclusions from insoluble deposits of the oxide. - - -2. CHROMIUM. - -Sec. 883. The only salts of chromium of toxicological importance are the -neutral chromate of potash, the bichromate of potash, and the chromate -of lead. - -=Neutral Chromate of Potash=, CrO_{3}K_{2}O = 194.7, containing 56.7 per -cent. of its weight of chromic anhydride, CrO_{3}.--This salt is in the -form of citron-yellow rhombic crystals, easily soluble in water, but -insoluble in alcohol. Its aqueous solution is precipitated yellow by -lead acetate or basic acetate; the precipitate being insoluble in acetic -acid. If chromate of potash in solution is tested with silver nitrate, -the red chromate of silver is thrown down; the precipitate is with -difficulty soluble in dilute nitric acid. - -Sec. 884. =Potassic Bichromate=, CrO_{3}K_{2}O = 295.2, containing 68.07 -per cent. of its weight of chromic anhydride, CrO_{3}.--This salt is in -beautiful large, red, transparent, four-sided tables; it is anhydrous -and fuses below redness. At a high temperature it is decomposed into -green oxide of chromium and yellow chromate of potash. It is insoluble -in alcohol, but readily soluble in water. The solution gives the same -precipitates with silver, lead, and barium as the neutral chromate. On -digesting a solution of the bichromate with sulphuric acid and alcohol, -the solution becomes green from the formation of chromic oxide. - -Sec. 885. =Neutral Lead Chromate=, PbCrO_{4} = 323.5, composition in 100 -parts, PbO, 68.94, CrO_{3}, 31.06.--This is technically known as -"_Chrome Yellow_," and is obtained as a yellow precipitate whenever a -solution of plumbic acetate is added, either to the solutions of -potassic chromate or bichromate; by adding chrome yellow to fused -potassic nitrate, "chrome red" is formed; it has the composition -CrO_{3}2PbO. Neutral lead chromate is insoluble in acids, but may be -dissolved by potassic or sodic hydrates. - -Sec. 886. =Use in the Arts.=--Potassic bichromate is extensively used in -the arts--in dyeing, calico-printing, the manufacture of porcelain, and -in photography; the neutral chromate has been employed to a small extent -as a medicine, and is a common laboratory reagent; lead chromate is a -valuable pigment. - -Sec. 887. =Effects of some of the Chromium Compounds on Animal Life.=--In -the chromates of potash there is a combination of two poisonous metals, -so that it is not surprising that Gmelin found the chloride of chromium, -CrCl_{3}, less active than the neutral chromate of potash; 1.9 grm. of -the last, administered to a rabbit by the stomach, caused death within -two hours, while 3 grms. of chromous chloride had no action. -Subcutaneous doses of .2 to .4 grm. of neutral chromate (according to -the experiments of E. Gergens[960] and Carl Posner[961]) act with great -intensity on rabbits. Immediately after the injection the animals are -restless, and show marked dyspn[oe]a; death often takes place within a -few hours. - -[960] _Arch. f. experiment. Pathol. u. Pharmakol._, Bd. 6, Hft. 1 and 2, -Sec. 148, 1875. - -[961] Virchow's _Archiv f. path. Anat._, Bd. 79, Hft. 2, Sec. 333, 1880. - -Diarrh[oe]a does not seem, as a rule, to follow when the salt is -administered by subcutaneous injection to animals; but Gmelin's rabbits -had considerable diarrh[oe]a when 1.9 grm. was introduced into the -stomach. The same quantity, injected beneath the skin of a dog, caused -loss of appetite, and, after six days, there was a dry exanthem on the -back, and the hair fell off in patches; there was, however, neither -diarrh[oe]a nor vomiting. Bichromate of potash causes (according to the -researches of Pelikan)[962] symptoms similar to those produced by -arsenic or corrosive sublimate; it acts as a powerful irritant of the -stomach and intestinal canal, and may even cause inflammation; on its -absorption a series of symptoms are produced, of which the most -prominent are albuminuria, bloody urine, and emaciation. From .06 to .36 -grm. (1-5-1/2 grains) is fatal to rabbits and dogs. - -[962] _Beitraege zur gerichtl. Medicin, Toxikol. u. Pharmakodynamik_, -Wuerzburg, 1858. - -Sec. 888. =Effects of some of the Chromium Salts on Man--Bichromate -Disease.=--In manufacturing potassic bichromate, the workmen exposed to -the dust have suffered from a very peculiar train of symptoms, known -under the name of "bichromate disease." It was first described in -England by Sir B. W. Richardson.[963] It appears that if the workmen -inspire the particles chiefly through the mouth, a bitter and -disagreeable taste is experienced, with an increase of saliva. This -increase of the buccal secretion gets rid of most of the poison, and in -that case but little ill effect is experienced; but those who keep the -mouth closed and inspire by the nose, suffer from an inflammation of the -septum, which gradually gets thin, and ultimately ulcerated; finally the -whole of the septum is in this way destroyed. It is stated that when a -workman has lost his nasal septum, he no longer suffers from nasal -irritation, and has a remarkable immunity from catarrh. The Chemical -Works Committee of Inquiry report (1893) that the manufacture of -bichromate of potash or soda is practically in the hands of three firms -at Glasgow, Rutherglen, and Falkirk, and that they visited all of them, -and found "that almost all the men working where dust was prevalent, -more especially between the furnaces and the dissolving tanks, had -either perforation of the septum of the nose, or had lost the -septum altogether." The bichromate also causes painful skin -affections--eruptions akin to eczema or psoriasis; also very deep and -intractable ulcerations. These the workers call "chrome holes." These -cutaneous maladies start from an excoriation; so long as the skin is not -broken, there seems to be little local effect, if any. The effects of -the bichromate are also seen in horses employed at the factories; the -salt getting into a wound or crack in the leg, produces ulceration: -horses may even lose their hoofs. - -[963] _Brit. and For. Med. Chirurg. Review_, Oct. 1863. See also a paper -by the same writer, read before the Medical Society, reported in the -_Lancet_, March 11, 1882. - -Sec. 889. Acute poisoning by the chromates is rare. In the ten years ending -1892, in England and Wales, 4 accidental deaths are ascribed to potassic -bichromate and 1 to chromic acid. Falck has, however, been able to find -in medical literature 17 cases, 6 of which were suicidal, 10 accidental, -and in 1 the bichromate was used as an abortive. In a case of poisoning -by the chromate of potash (related by Maschka),[964] in which a woman, -aged 25, took for a suicidal purpose a piece of potassic chromate, which -she described as the size of a hazel-nut (it would probably be at least -6 grms. in weight), the chief symptoms were vomiting, diarrh[oe]a, pain -in the stomach, and rapid collapse; death took place fourteen hours -after swallowing the poison. - -[964] _Prager Vierteljahrsschr. f. d. prakt. Heilk._, Bd. 131, Sec. 37, -1877; Schmidt's _Jahrb._ 1878, Bd. 178, Sec. 237. See also Schuchardt in -Maschka's _Handbuch_, Bd. ii. p. 3. - -In poisoning by potassic bichromate, there may be much variety in the -symptoms, the more usual being those common to all irritant poisons, -_i.e._, vomiting, diarrh[oe]a, and collapse, with cramps in the limbs -and excessive thirst; and the rarer affecting more especially the -nervous system, such as narcosis, paralysis of the lower limbs, and -dilatation of the pupils; occasionally there is slight jaundice. - -In a case recorded by Dr. Macniven,[965] a man took a lump of bichromate -of potash, estimated to be over 2 drachms (7.7 grms.). The symptoms -commenced in fifteen minutes, and consisted of lightness in the head, -and a sensation of great heat in the body, which was followed by a cold -sweat; in twenty minutes he vomited; he then suffered from great pain in -the stomach, giddiness, specks before the eyes, a devouring thirst, and -there was loss of power over the legs. These symptoms, again, were -followed by severe rigors and great coldness of the extremities. On the -patient's admission to hospital, two hours after taking the poison, it -was noted that the pupils were dilated, the face pale and cold, and the -pulse feeble. He complained of intense epigastric pain, and a feeling of -depression; there was some stupor; the stomach was emptied by emetics -and by the stomach-pump, and the patient treated with tepid emollient -drinks, whilst subcutaneous doses of sulphuric ether were administered. -He made a good recovery. - -[965] "On a Case of Poisoning with Bichromate of Potash," by Ed. O. -Macniven, M.B., _Lancet_, Sept. 22, 1883. - -In a case recorded by Mr. Wilson,[966] a man, aged 64, was found dead in -his bed twelve hours after he had gone to rest. During the night he was -heard to snore loudly; there were no signs of vomiting or purging, and -bichromate of potash was found in the stomach.[967] - -[966] _Med. Gazette_, vol. 33, 734. - -[967] See also cases recorded by Dr. M'Lachlan, _Glasgow Med. Journ._, -July 1881; Dr. M'Crorie, _ibid._, May 1881; Dr. R. A. Warwick, _Lancet_, -Jan. 31, 1880; and Dr. Dunbar Walker, _ibid._, Sept. 27, 1879--a summary -of all of which may be found in Dr. Macniven's paper, _loc. cit._ - -Sec. 890. Chromate of lead has also caused death. In one case[968] the -breathing of chromate of lead dust seems to have been fatal; and there -is also a double poisoning recorded by Dr. Linstow,[969] of two -children, aged three and a half and one and three-quarter years -respectively, who ate some yellow ornaments,[970] which were used to -adorn a cake, and which contained chrome yellow (chromate of lead). The -younger died in two and the elder in five days. The symptoms were -redness of the face, dulness, and an inclination to sleep; neither -complained of pain; the younger one had a little diarrh[oe]a, but the -elder neither sickness nor purging. - -[968] _Ueber toedtliche Vergiftung durch Einathmen des Staubes von mit -Chromsaeuren Blei-Oxyde gefaerbten Garne.--Vierteljahrsschr. f. ger. -Med._, 1877, Bd. xxvii. Hft. i. p. 29. - -[969] _Ibid._, Bd. xx. s. 60, 1874. - -[970] The ornaments were imitations of bees; each contained .27 grm. gum -tragacanth, .0042 grm. neutral lead chromate. - -Sec. 891. =Post-mortem Appearances.=--We possess some very exact -researches[971] upon the pathological changes induced by subcutaneous -injections of solutions of potassic bichromate on animals, and -especially on the changes which the kidneys undergo. If the animal is -killed, or dies a few hours after the injection, there are apparently no -striking appearances, but a closer microscopical examination shows -considerable changes. The epithelium of the tubuli contorti exhibits a -yellow cloudiness, and the outline of the cells is irregular and jagged. -The glomeruli are moderately injected, and their capsules contain an -albuminous exudation; the canaliculi are filled with round cells -imbedded in a fluid which, on heating, coagulates, and is therefore -albuminous or fibrinous; probably this is the first stage of the -formation of fibrinous casts. - -[971] C. Posner, _op. cit._ - -In the case quoted of the woman who poisoned herself with potassic -chromate, very striking changes were found in the stomach and -intestines. The stomach contained above a litre of dark chocolate fluid -of alkaline reaction; the mucous membrane, in the neighbourhood of the -cardiac and pyloric extremities, was swollen and red in sharply defined -patches; portions of the epithelial layer were detached, the rest of the -mucous membrane was of a yellow-brown colour, and the whole intestine, -from the duodenum to the sigmoid flexure, was filled with a partly -bloody, partly treacly-looking fluid; the mucous membrane, throughout -its entire extent, was swollen, with numerous extravasations, and in -places there were losses of substance. Similar appearances to these have -been found in other instances; the anomalous case recorded by Mr. Wilson -(_ante_) is an exception. In this instance a pint of inky, turbid -liquid, which yielded to analysis potassic bichromate, was found in the -stomach; but there were no marked changes anywhere, save a slight -redness of the cardiac end of the gullet. In Linstow's two cases of -poisoning by lead chromate, there were found in both fatty degeneration -of the liver cells, and red points or patches of redness in the stomach -and intestines. In the elder boy the changes in the duodenum were very -intense, the mucous membrane was swollen and easily detached, in the -upper part strongly injected with blood; in one place there was a -perforation, and in several places the membrane was extremely thin. In -the younger boy the kidneys seem to have been normal, in the elder -congested and containing pus. Although it was clear that the two -children died from lead chromate, a chemical analysis gave no result. - -Sec. 892. =Detection of the Chromates and Separation of the Salts of -Chromium from the Contents of the Stomach, &c.=--If in the methodical -examination of an acid liquid, which has been already filtered from any -precipitate that may have been obtained by sulphuretted hydrogen, this -liquid is made alkaline (the alkali only being added in slight excess), -and hydrated chromic oxide is thrown down mixed, it may be with other -metals of the second class, the precipitate may then be fused with nitre -and potassic carbonate, and will yield potassic chromate, soluble in -water, and recognised by the red precipitate which it gives with silver -nitrate, the yellow with lead acetate, and the green colour produced by -boiling with dilute sulphuric acid and a little alcohol or sugar. If by -treating a complex liquid with ammonium hydrosulphide, sulphides of -zinc, manganese, and iron are thrown down mixed with chromic oxide, the -same principles apply. If a chromate is present in the contents of the -stomach, and the organic fluid is treated with hydrochloric acid and -potassic chlorate, chromic chloride is formed, and dissolving imparts a -green colour to the liquid--this in itself will be strong evidence of -the presence of a chromate, but it should be supplemented by throwing -down the oxide, and transforming it in the way detailed into potassic -chromate. - -A general method of detecting and estimating both chromium and barium in -organic matters has been worked out by L. de Koningh.[972] The -substances are burnt to an ash in a platinum dish. The ash is weighed; -to the ash is added four times its weight of potassium sodium carbonate -and the same amount of potassium nitrate; and the whole is fused for -fifteen minutes. The fused mass is boiled with water and filtered; if -chromium is present, the filtrate is of a more or less pronounced yellow -colour, but manganese may produce a green colour and mask the yellow; -this colour is removed by boiling with a little alcohol. The liquid is -concentrated down to 20 c.c., filtered into a test-tube, and a -colorimetric estimation made of the chromium present by imitating the -colour by a solution of potassium chromate of known strength. To prove -that the colour is really due to chromium, acetic acid and lead acetate -are added, when the yellow chromate of lead is at once thrown down. (If -lead was in the ash, a yellow precipitate may appear on the addition of -acetic acid.) To the portion of ash insoluble in water strong -hydrochloric acid is added, and to the acid solution a large excess of -calcium sulphate is added; this precipitates barium as sulphate free -from lead sulphate, for, if the latter should be present, it does not, -under the circumstances, come down, being soluble in strong hydrochloric -acid. - -[972] _Arch. Pharm._ (3), xxvii. 944. - - -3. THALLIUM. - - Sec. 893. Thallium was discovered by Crookes in 1861. Its atomic weight - is 204; specific gravity, 11.81 to 11.91; melting-point, 290 deg. It is - a heavy diamagnetic metal, very similar to lead in its physical - properties. The nitrate and sulphate of thallium are both soluble in - water, the carbonate less so, requiring about 25 parts of water for - solution, while the chloride is sparingly soluble, especially in - hydrochloric acid. - - Sec. 894. =Effects.=--All the salts of thallium are poisonous. One of - the earlier experimenters on the physiological action, Paulet, found - 1 grm. (15.4 grains) of thallium carbonate sufficient to kill a - rabbit in a few hours; there were loss of muscular power, trembling - of the limbs, and death apparently from asphyxia. Lamy[973] used - thallium sulphate, and found that dogs were salivated, and suffered - from trembling of the limbs, followed by paralysis. The most - definite results were obtained by Marme,[974] who found that .04 to - .06 grm. of a soluble thallium salt, injected subcutaneously or - directly into the veins, and .5 grm. administered through the - stomach of rabbits, caused death. The action is cumulative, and - something like that of mercury: there are redness and swelling of - the mucous membrane of the stomach, with mucous bloody discharges; - haemorrhage may also occur from the lungs. Thallium is eliminated - through the urine, and is also found in the faeces; it passes into - the urine from three to five minutes after injection: the - elimination is slow, often taking as long as three weeks. It has - been found in the milk, in the tears, in the mucous membrane of the - mouth, of the trachea, in the secretion of the gastric mucous - membrane, and in the pericardial fluid; and in these places, whether - the poison has been introduced by subcutaneous injection, or by any - other channel. It seems probable that the reason of its being - detected so readily in all the secretions is the minute quantity - which can be discovered by spectroscopic analysis. - -[973] _Chem. News_, 1863. - -[974] _Goettinger Gelehrt. Nachrichten_, Aug. 14, No. 20. - - Sec. 895. =Separation of Thallium from Organic Fluids or Tissues.=--The - salts of thallium, if absorbed, would only be extracted in traces - from the tissues by hydrochloric acid, so that, in any special - search, the tissues are best destroyed by either sulphuric or nitric - acid, or both. In the ordinary method of analysis, when an acid - liquid is first treated with sulphuretted hydrogen, and then made - alkaline by ammonia and ammonic sulphide, thallium would be thrown - down with the manganese and iron of the blood. From the mixed - sulphides, thallium may be separated by oxidising and dissolving the - sulphides with nitric acid, evaporating off the excess of acid, - dissolving in a very little hot water, and precipitating thallous - chloride by solution of common salt. The ease, however, with which - thallium may be separated from solutions of its salts by galvanism - is so great as to render all other processes unnecessary: the best - way, therefore, is to obtain a deposit of the metal on platinum by a - current from one or more cells, and then to examine the deposit - spectroscopically. Thallium gives, when heated in a Bunsen flame, a - magnificent green line, the centre of which corresponds with wave - length 534.9; a second green line, the centre of which coincides - with W.L. 568, may also be distinguished. - - -4. ALUMINIUM. - -Sec. 896. =Aluminium and its Salts.=--A strong solution of acetate of -alumina has irritant properties, and has given rise to accidents. The -term alum, in a chemical sense, is given to a class of bodies of the -type of AlKSO_{4}. Common alum is at the present time ammonia alum, -NH_{4}Al(SO_{4})_{2} + 12H_{2}O; when made anhydrous by heat it is known -by the name of burnt alum, and possesses caustic properties. - -Sec. 897. =Action of Alum Salts.=--Death or illness has hitherto only taken -place from the ingestion of large doses of alum or the acetate, and the -symptoms in these cases have been those of an irritant poison; we are, -however, indebted to Paul Siem[975] for a research on the absorbed -substance, in which the local effects as far as possible have been -reduced. - -[975] _Ueber die Wirkungen des Aluminiums u. Berylliums, Inaug. Diss._, -Dorpat, 1886; Schmidt's _Jahrbuch_, vol. ccxi. 128. - -Siem's research was made on frogs, cats, and dogs. For frogs he employed -a double salt, consisting of sodic and aluminic lactate, to which he -ascribed the formula Al_{2}(C_{3}H_{5}O_{3})_{3}(C_{3}H_{4}NaO_{3})_{3}, -equal to 15.2 per cent. of Al_{2}O_{3}. Twenty to thirty mgrms., -administered by subcutaneous injection to frogs, caused death in from -ten to twenty-four hours. After the injection there was restlessness, -and, ultimately, general paralysis of the central nervous system. The -circulation was not affected; the heart was the last to die. - -For warm-blooded animals he used the double tartrate of sodium and -aluminium. Beginning with a small dose subcutaneously administered, he -gradually increased it, and found, under these circumstances, that the -lethal dose for rabbits was 0.3 grm. per kilo. of body weight; for dogs -0.25 grm., and for cats 0.25 to 0.28 grm.; if, however, a single dose -was administered, then cats could be killed by 0.15 grm. per kilo. The -symptoms commenced ten to twelve hours after the injection of a large -dose, but with a medium dose the symptoms might be delayed for from -three to four days, then there was loss of appetite, constipation, -emaciation, languor, and a disinclination to move. Vomiting and loss of -sensation to pain followed, the power of swallowing even saliva was -lost, and a condition supervened similar to bulbar paralysis. However -true this picture may be when large doses are given subcutaneously, it -does not follow that hydrate of alumina in small doses, given by the -mouth, mixed with food, produces any symptoms whatever. - -Alum baking-powders, containing from 30 to 40 per cent. of alum mixed -with carbonate of soda, are in commerce, and have been for a long time, -many tons being sold yearly. When water is added to such powders -decomposition takes place, the result being sodic sulphate and aluminic -hydrate, carbonic acid being given off. Were the hydrate, in small -doses, capable of producing indigestion or disease of the central -nervous system, it seems astonishing that, considering the enormous -number of persons who use alum baking-powders, there should not be some -definite evidence of its effect. The author and his family for months -together have used alum baking-powders without any apparent injury, and -there is little doubt that alumina hydrate passes out of the system -mainly by the bowel, without being absorbed to any great extent. In a -trial with regard to an alum baking-powder at Pontypridd (1893), the -prosecution advanced the theory, and supported it by eminent scientific -opinion, that aluminium hydrate was dissolved by the hydrochloric acid -of the gastric juice, forming chloride of aluminium, some of which might -be absorbed and enter the circulation; that which was not absorbed in -the stomach passed on, and, meeting the alkaline fluids of the -intestines, was again separated as aluminium hydrate, and as such -absorbed. - -If this does occur, still there is no direct evidence of its toxic -influence in the small quantities used in baking-powder. It may be -pointed out, also, that with regard to the possible lethal effect of a -non-corrosive salt of alum, presuming that the lethal dose for man is -the same as that for a cat, the amount of alumina to kill a -68-kilogramme man would have to be equal to 17 grms., or about 3 ozs. of -ammonia alum. This important question can only be settled by careful -feeding of animals carried on for a long period of time. - -Sec. 898. =Post-mortem Appearances.=--In the few cases in which persons -have been killed by large doses of alum or its salts there have been -found corrosion of the mouth, throat, and stomach, and hyperaemia of the -kidneys and intestine. In the animals experimented upon by Paul Siem, -hyperaemia of the intestine, fatty degeneration of the liver and hyaline -degeneration of the kidneys were the chief changes noted. - -Sec. 899. =Detection of Alumina.=--In all operations for the detection of -alumina, glass and porcelain vessels are to be avoided. The substances -should be burned to an ash in a platinum dish, the ash treated with -hydrochloric acid, the acid driven off by heat, and a few drops of -nitric acid added, and dissolved in hydrochloric acid, and the solution -boiled and filtered. If organs of the body are operated upon, iron and -phosphoric acid will be present in the ash; this will, indeed, be the -case with most organic substances. The filtered solution is boiled, and, -while boiling, poured into a strong solution of sodic hydrate contained -in a silver or platinum dish; the iron will now separate as oxide, and -can be filtered off. To the filtrate is added a little sodic phosphate; -it is then feebly acidified with hydrochloric acid, and ammonia added -just sufficient to render it alkaline; a light whitish cloud of alumina -phosphate, should alumina be present, is thrown down, and can be -collected, thoroughly washed, dried, ignited, and weighed as alumina -phosphate.[976] The alumina phosphate is then fused with sodic sulphate -in a platinum dish or crucible, and the fused mass treated with hot -water; the sodic phosphate dissolves, and the alumina oxide may be -filtered off and dissolved in a little hydrochloric acid or sulphuric -acid. - -[976] One part of al. phosphate is equal to 0.42 Al_{2}O_{3}, 3.733 -ammonia alum, and 4.481 potash alum. - -A solution thus prepared has the following properties:-- - -Ammonium sulphide; white precipitate of hydroxide. - -Potash or soda; white precipitate, soluble in excess. - -Ammonia; white precipitate, only slightly soluble in excess. - -There is also a blowpipe-test: if a little of the hydroxide be -collected, moistened with cobalt nitrate, and heated on charcoal by the -oxidising flame, alumina, under these circumstances, becomes of a blue -colour. - - -5. URANIUM. - - Sec. 900. =Uranium.=--The salts of uranium are intensely poisonous. The - nitrate of uranium is used in photography and the arts, and is a - common reagent in chemical laboratories. - - According to Kowalewsky,[977] the acetate of uranium possesses an - unusual power of uniting with albumin; the other soluble uranium - salts act also in a similar way. Hence concentrated solutions of - uranium salts corrode the mucous membranes, transforming, for - example, the walls of the stomach into a dead uranic albuminate. If - a non-corrosive salt of uranium is injected subcutaneously, - glycosuria is produced, with fatty degeneration of the walls of the - blood-vessels, and fatty changes in the kidneys, liver, &c. The - animal wastes and ultimately dies; 0.5 to 2.0 mgrms. of UO_{3} per - kilogrm. will kill a cat, dog, or rabbit, if injected - subcutaneously. The nitrate or acetate, when given by the mouth, - produces gastro-enteritis and nephritis, with haemorrhages in the - substance of the kidney. Uranium is not used in medicine. - -[977] _Ztschr. f. Anal. Chemie_, xxiv., 1885, p. 551. - - Sec. 901. =Detection and Estimation of Uranium.=--Uranium forms uranous - and uranic salts. Both classes of salts are not precipitated by - SH_{2}, but are precipitable by ammonium sulphide, and, therefore, - in toxicological analyses are likely to be met with in conjunction - with iron. - - The sulphides of iron and uranium may be dissolved in strong - hydrochloric acid, boiled to expel SH_{2}, and the solution then - oxidised with a little nitric acid; the solution is now alkalised - with ammonium carbonate, which precipitates the iron as oxide and - leaves the uranium in solution. On now acidifying with nitric acid - in slight excess, a solution of sodic phosphate will precipitate - uranium phosphate as a white precipitate, alkalies will give a - yellow precipitate, alkaline carbonates a yellow precipitate soluble - in excess. Barium carbonate also gives a precipitate, and is useful - in separations. Uranium oxide gives a green glass in the oxidising - flame with borax or with sodic metaphosphate. - - -V.--ALKALINE EARTHS. - -Barium. - -Sec. 902. The soluble salts of barium are undoubtedly poisonous, and are of -frequent occurrence in the arts. The chloride of barium is used in the -staining of wool, the nitrate and the chlorate in the green fires of the -pyrotechnist, the oxide and the carbonate in the manufacture of glass. -The chromate is used by artists under the name of "yellow ultramarine," -while the sulphate, technically known as "permanent white," is, on -account of its weight and cheapness, occasionally used as an adulterant -of white powders and other substances. Barium sulphide, under various -names, such as Bottcher's depilatory, Thompson's hair destroyer, _Poudre -epilatoire_, and other names, is in commerce, and has caused poisonous -symptoms.[978] - -[978] Barium carbonate and sulphate are usually enumerated as occasional -adulterants of bread, but there is no modern authentic instance of this. - -Sec. 903. =Chloride of Barium=, BaCl_{2}2H_{2}O 208 + 36; anhydrous, Ba, -65.86 per cent., Cl, 34.14; specific gravity, 3.75, is in commerce in -the form of white, four-sided, tabular crystals; water dissolves about -half its weight at ordinary temperatures, three-fourths at 100 deg. Its -solution gives a white precipitate with sulphuric acid, quite insoluble -in water and nitric acid. - -The salt imparts a green hue to an otherwise colourless flame; viewed by -the spectroscope, green bands will be visible. We may note that chloride -of barium gives two different spectra--the one at the moment of the -introduction of the salt, the other when the substance has been exposed -for some time to a high temperature. This is caused by a rapid loss of -chlorine, so that the first spectrum is due to BaCl_{2}, with a variable -mixture of BaCl, the second to BaCl alone. - -Sec. 904. =Baric Carbonate=, BaCO_{3} = 197; specific gravity, 4.3; BaO, -77.69 per cent., CO_{2}, 22.31, in its native form termed _Witherite_, -is a dense, heavy powder, insoluble in pure water, but dissolving in -acetic, nitric, and hydrochloric acids, the solution giving the -reactions of barium. - -A rat-poison may be met with composed of baric carbonate, sugar, and -oatmeal, flavoured with a little oil of aniseed and caraway. - -Sec. 905. =Sulphate of Barium=, BaSO_{4}; specific gravity, 4.59; BaO, -65.66 per cent., SO_{3}, 34.34 per cent., is a pure white powder when -recently precipitated, absolutely insoluble in water, and practically -insoluble in cold dilute acids. It is quite unalterable in the air at a -red heat; on ignition with charcoal, it may be converted almost entirely -into sulphide of barium; and by ignition with CaCl_{2} into chloride. - -Sec. 906. =Effects of the Soluble Salts of Barium on Animals.=--One of the -early notices of the poisonous characters of barium compounds was by -James Watt,[979] who found that _witherite_, given to dogs, produced -vomiting, diarrh[oe]a, and death in a few hours. Sir Benj. Brodie[980] -administered barium chloride, and noticed its paralysing effect on the -heart. Orfila[981] made several experiments, and observed that 4 grms. -of the carbonate produced death in dogs in periods varying from one to -five hours; but in these experiments the gullet was tied. The later -investigators have been Gmelin, Onsum, Cyon, and Boehm.[982] Gmelin -found barium carbonate and barium chloride act in a very similar manner; -and, indeed, it is improbable that barium carbonate, _as_ carbonate, has -any action, but, when swallowed, the hydrochloric and other acids of the -stomach form with it soluble compounds. J. Onsum made eight experiments -with both barium carbonate and chloride on animals. The respiration was -quickened and, at the same time, made weak and shallow; the heart's -action was accelerated; the animals became restless: and there was great -muscular prostration, with paralytic symptoms; convulsions did not occur -in any one of the eight animals. He found, on _post-mortem_ examination, -the right side of the heart full of blood from backward engorgement; he -describes a plugging of the small arteries with little fibrinous -coagula, having an inorganic nucleus, with constant haemorrhagic -extravasations. Onsum seems to have held the theory that the baryta -salts circulated in the blood, and then formed insoluble compounds, -which were arrested in the lungs, causing minute emboli, just in the -same way as if a finely-divided solid were introduced directly into the -circulation by the jugular vein. - -[979] _Memoirs of the Literary and Philosophical Society of Manchester_, -1790, vol. iii. p. 609. - -[980] _Phil. Trans._, 1812. - -[981] _Traite des Poisons_, 3rd ed., t. i., Paris, 1826. - -[982] Gmelin, C. G., _Versuche ueber die Wirkungen des Baryts, -Strontians, Chroms, Molybdaens, Wolframs, Tellurs, u. s. w. auf den -thierischen Organismus_, Tuebingen, 1824; Onsum, J., Virchow's _Archiv_, -Bd. 2, 1863; Cyon, M., _Archiv f. Anatomie, Physiologie, &c._, 1866; -Boehm, _Archiv f. experiment. Pathol._, Bd. 3, 1874. - -Onsum stands alone in this view. Cyon found no emboli in the lungs, and -refers the toxic effect to a paralysing influence on the heart and -voluntary muscles, and also on the spinal cord. Cyon, to settle the -embolic theory, injected into the one jugular vein of a rabbit barium -chloride, and into the other sodic sulphate, but the small arteries and -capillaries of the lungs remained clear. Boehm, operating on frogs, found -a great similarity between the action of small doses of barium salts and -that of certain organic poisons; as, for example, cicutoxin, .012 to .02 -grm. subcutaneously injected into frogs, acted as a heart-poison. So -also Blake[983] found the heart slowed, and concluded that barium -chloride had a direct action on the cardiac muscle, and also a toxic -influence on the nervous system. F. A. Falck, in experiments on rabbits, -found a great reduction of temperature after poisoning with barium -chloride (3 deg. to 12.6 deg.). - -[983] _Journ. of Anat. and Physiol._ 2nd series, 1874. - -Sec. 907. =Effects of the Salts of Barium on Man.=--There were about -fifteen cases of poisoning by barium salts on record by the end of -1883--three of which were suicidal, but most of them were due to -accident or mistake. In three cases, barium chloride was taken instead -of Glauber's salts; in one, instead of Carlsbad salts; in another, a -mixture of barium nitrate and sulphur, instead of pure sulphur; in a -sixth case, a mixture of barium acetate and raspberry syrup, instead of -sodic ethylsulphate; in a seventh, a chemist put a larger dose than was -ordered by the prescription; and in four cases barium carbonate had been -mixed with flour, and this flour used in the making of pastry. Of the -fifteen cases, nine, or 60 per cent., proved fatal; the fifteen cases -have now (1894) been increased to twenty-six. - -=Fatal Dose.=--The recorded cases of poisoning have not satisfactorily -settled the question as to the least fatal dose of the barium salts. 6.5 -grms. (about 100 grains) of the chloride have destroyed the life of an -adult woman in fifteen hours; 14 grms. (-1/2 oz.) of the nitrate of -baryta have killed a man in six and a half hours; and the carbonate of -baryta has destroyed a person in the relatively small dose of 3.8 grms. -(60 grains). On the other hand, certain Continental physicians have -prescribed barium chloride in large medicinal doses; for example, -Pirondi[984] and Lisfranc[985] have gradually raised the dose of barium -chloride from 4 decigrams up to 3 grms. (48 grains) daily, given, of -course, in divided doses. Pirondi himself took in a day 7.7 grms. (119 -grains) without bad effect. - -[984] _De la Tumeur Blanche de Genou_, ed. 2, Paris, 1836. - -[985] _Gaz. Med. de Paris_, 1835, No. 14. - -Sec. 908. =Symptoms.=--The local action of barium salts must be sharply -distinguished from the action of the absorbed salts. Kobert divides the -symptoms into seven groups:-- - -(1) Local, consisting in _malaise_, nausea, salivation, vomiting, and -pain in the stomach. This group merges so much into the next as hardly -to admit of precise separation. - -(2) Excitation of the alimentary canal, both of the nervous and muscular -apparatus. Hence vomiting, painful colic, and acute diarrh[oe]a. All -these phenomena may be produced in animals by subcutaneous injection, -and, therefore, do not depend alone upon local action. - -(3) Excitation of the brain motor centres, which leads to convulsions, -or may result in paralysis. About half the recorded cases of barium -poisoning in the human subject have been convulsed; the other half -paralysed. In one case mania resulted. - -(4) Weakness or destruction of the power of muscular contraction; this -produces in frogs, when the muscular test movements are recorded -graphically, a veratrin-like convulsion curve. In the human subject the -effect is that of great muscular weakness. - -(5) Digitalin-like influence on the heart and blood-vessels, showing -itself in great slowing of the pulse, praecordial anxiety, and strong -beating of the heart (not only sensible to the patient, but which can be -heard and felt by the bystanders). The arteries are incompressible and -rigid, the blood-pressure strikingly raised. The blood-vessels of old -people do not stand the pressure, hence haemorrhages in the lungs, -stomach, and other organs. Frogs die with the heart in systole. - -(6) Catarrhal affection of the conjunctiva, the mucous membrane of the -respiratory tract, and the nose. - -(7) Formation of insoluble baryta salts in the blood-vessels, according -to Onsum. This has not been observed in man, and the fact is disputed -(see _ante_). - -In Dr. Tidy's case,[986] in which a man, suffering from rheumatism, but -otherwise healthy, took a mixture of barium nitrate, flowers of sulphur, -and potassic chlorate, instead of sulphur, the symptoms were blisters on -the tongue, a burning pain in the gullet and stomach, with vomiting, -diarrh[oe]a, convulsions, aphonia, and coldness of the extremities. A -case, copiously detailed by Seidel,[987] in which a pregnant woman, -twenty-eight years old, took carbonate of baryta for the purpose of -self-destruction, is interesting. She probably took the poison some -little time before six in the evening; she vomited and had great pain in -the stomach, but slept during the night without further sickness. The -next morning, after drinking some coffee, the sickness was renewed; -nevertheless, at 7 A.M., she repaired to her employment, which was -distant an hour's walk; she probably suffered much on the way, for she -did not arrive until 9 A.M. The vomiting, accompanied by diarrh[oe]a, -continuing, she was sent to bed at 2 P.M. She was very cold, and -complained of great weakness; the vomiting now ceased. At 8 P.M. she -shivered violently, could scarcely swallow, and the respiration was -oppressed. At 11 she seemed a little improved; but at 3 A.M. she was -found much worse, breathing rapidly, but fully conscious; at 4 A.M. she -was again seen, but found dead; she thus lived about thirty-four hours -after taking the fatal dose. - -[986] _Pharm. Journ._, June 1868. - -[987] Eulenberg's _Vierteljahrsschrift f. ger. Med._, Bd. 27, Sec. 213. - -Sec. 909. =Distribution of Barium in the Body.=--Neumann has shown that, -after repeated injection of insoluble barium sulphate into the veins of -rabbits, barium is to be found in the liver, kidneys, spleen, and spinal -cord, but not in the muscles, thymus, or brain. G. Linossier[988] has -made a similar series of experiments, but with the more soluble -carbonate, and this salt was injected into animals for a period of -thirty days. All the organs contained some barium; lungs, muscles, and -the heart only contained traces, the liver rather more, the kidneys, -brain, and spinal cord still more, and, lastly, the bones a considerable -quantity, as much as 0.056 per cent. - -[988] _Compt. rend. Soc. Biol._ (8), iv. 122-123. - -Sec. 910. =Post-mortem Appearances.=--The _post-mortem_ appearances are -usually changes in the stomach and intestinal tract, but there are only -rarely traces of great inflammation. It is true, that in a case recorded -by Wach,[989] perforation of the stomach was found; but, since there was -old-standing disease of both liver and stomach, it is not clear that -this is to be attributed entirely to poison. In the case of suicide just -detailed, the mucous membrane of the stomach was much ecchymosed; over -the whole were strewn little white grains, sticking to the mucous -membrane, and there were also ecchymoses in the duodenum. - -[989] Henke's _Zeitschrift f. Staatsarzneik._, 1835, Bd. 30, Hft. 1, Sec. -1. - -Sec. 911. =The Separation of Barium Salts from Organic Solids or Fluids, -and their Identification.=--In the usual course of examination of an -unknown substance, the matter will already have been extracted by -hydrochloric acid, and the solution successively treated with hydric and -ammonic sulphides. The filtrate from any precipitate, after being -boiled, would in such a case give a precipitate if treated with -sulphuric acid, should a salt of barium soluble in hydrochloric acid be -present. - -If there, however, should be _special_ grounds to search for baryta in -particular, it is best to extract the substances with pure boiling -water, to concentrate the solution, and then add sulphuric acid, -collecting any precipitate which may form. If the latter is found to be -sulphate of baryta, it must be derived from some soluble salt, such as -the nitrate or the chloride. The substances which have been exhausted -with water are now treated with hydrochloric acid, and to the acid -filtrate sulphuric acid is added. If sulphate of baryta is thrown down, -the baryta present must have been a salt, insoluble in water, soluble in -acids--probably the carbonate. Lastly, the organic substances may be -burnt to an ash, the ash fused with carbonate of soda, the mass, when -cool, dissolved in HCl, and the solution precipitated with sulphuric -acid. Any baryta now obtained was present, probably in the form of -sulphate; nevertheless, if obtained from the tissues, it would prove -that a soluble salt had been administered, for (so far as is known) -sulphate of barium is not taken up by the animal fluids, and is -innocuous. - -The sulphate of barium is identified as follows:-- - -(1) A part of the well-washed precipitate is boiled with distilled -water, filtered, and to the filtrate a solution of chloride of barium -added. If there is no precipitate, the sulphate can be none other than -baric sulphate, for all the rest, without exception, are soluble enough -to give a slight cloud with baric chloride. - -(2) The sulphate may be changed into sulphide by ignition on charcoal, -the sulphide treated with HCl, the solution evaporated to dryness, and -the resulting chloride examined spectroscopically; or, the sulphide may -be mixed with chloride of calcium, taken up on a loop of platinum wire, -heated strongly in the flame of a Bunsen burner, and the flame examined -by the spectroscope. - -(3) A solution of the chloride of barium obtained from (2) gives a -yellow precipitate with neutral chromate of potash, insoluble in water, -but soluble in nitric acid. - - - - -APPENDIX. - - -Treatment by Antidotes or otherwise of Cases of Poisoning. - -Sec. 912. All medical men in practice are liable to be summoned hastily to -cases of poisoning. In such emergencies not a moment is to be lost, for -valuable lives have ere this been sacrificed simply from the delay -caused by searching for medicines and instruments, and visiting the -patient unprovided with suitable remedies. Hence it is far the safest -plan for every medical man to provide himself with an "_antidote bag_," -which, to be complete, should be furnished with the following -requisites:-- - - -I. INSTRUMENTS:-- - -(1.) A =stomach-pump= or =tube=,[990] with proper mouth gags. - -[990] The stomach-tube is simply a tube of india-rubber, from 6 to 8 -feet in length, one end of which should be a little stiff, and -have a solid rounded extremity pierced with two lateral oval -holes--catheter-like; but, on an emergency, any india-rubber tube of a -suitable length will do. It is used by passing the proper end gently -down the throat into the stomach; if the patient is insensible, or, as -in some determined suicides, obstinate, the jaws must be forcibly opened -by the handle of a spoon, and some solid substance placed between the -teeth so as to give sufficient room for the entry of the tube. If the -tube is now passed in the median line well into the grasp of the -pharynx, it is actually drawn down into the stomach by the pharyngeal -muscles, so that the operator has, as it were, only to "pay out" a -sufficient quantity of the tubing. Holding the tube in a perpendicular -position, it may then be filled with water by means of a small funnel. -When full, the end must be pinched and brought down to the ground to -deliver in a basin; it will then act as a syphon and the contents of the -stomach will be syphoned off. The tube is elevated again above the body, -and the stomach filled with water; this syphoned off, and the process -repeated. Coffee, also, or antidotes may be conveniently introduced. If -the recumbent position is necessary, the patient must, of course, be -placed on a bed or table, in order that there should be sufficient fall -for the syphon. - -(2.) A =hypodermic syringe=. - -(3.) An ordinary bleeding =lancet=. - -(4.) A =glass-syringe= with suitable canula, which may, in case of -necessity, be used for transfusion. - -(5.) =Bistoury=, =forceps= and =tubes= suitable for performing -=tracheotomy=. - -A small =battery= (interrupted current). - - -II. EMETICS:-- - -(1.) _Sulphate of zinc._ - -(2.) _Apomorphine._ - -(3.) _Mustard._ - -(4.) _Ipecacuanha._ - -The _sulphate of zinc_ may either be carried in 30-grain powders or in -the ordinary solid crystalline state, together with a little measure -made out of a small pill-box which, when exactly full, is found to -contain from 25 to 30 grains. - -A still more convenient form is that of the compressed tablets, sold as -a speciality by one or more firms. The same remarks apply to -_ipecacuanha._ - -The _apomorphine hydrochlorate_ should be in solution, a suitable -strength is 2 per cent.; a few drops of this substance, injected -hypodermically, will cause vomiting in a few minutes. - -Besides the above list, the bag should be furnished with a selection of -the so-called antidotes. - - -III. ANTIDOTES:-- - -(_a._) _Chemicals neutralising the poison._ - -=Acetic acid= and =calcined magnesia=. - -(_b._) _Precipitants of alkaloids._ - -=Tannin=--A solution of =iodine in potassic iodide=. - -(_c._) _Narcotics, or anaesthetics,_ for the treatment of the tetanic -class. - -=Chloral=--chloroform. - -(_d._) _Substances which act physiologically._ - -=French oil of turpentine.=--A solution of =atropine sulphate= for -hypodermic use (strength .8 per cent.); hypodermic dose from 5 to 6 -drops. - -Solution of =nitrate of pilocarpine= (strength 5 per cent.); dose, 10 -drops or more. - -=Muscarine=--a solution in water (strength 5 per cent.); dose, 10 drops. - -=Morphine meconate= in solution (strength 10 per cent.); dose, from 5 -drops. - -A solution of =nitrate of strychnine= (strength 2 per cent.); hypodermic -dose, from 2 to 3 drops. - -=Potassium Permanganate= in crystals. - -To these may be added a bottle of =Wyeth's dialysed iron= for use in -arsenic poisoning, a flask of =brandy=, some =chloric ether=, =aromatic -spirits of ammonia=, and some really good =extract of coffee=. - - -TREATMENT. - -Sec. 913. ACID CARBOLIC. - -Use the =stomach-tube= or =pump=, unless there is great destruction of -the mucous membrane. In the latter case, excite vomiting by injecting -subcutaneously from 5 to 6 drops of the =apomorphine= solution; or give -an emetic of =zinc sulphate=, =ipecacuanha=, or =mustard=. - -The stomach may, by the aid of the tube, be washed out with a weak -alkaline solution of =soda=; =albumen= may also be given, and such -stimulants as =brandy= and =water=, =chloric ether=, and =aromatic -spirits of ammonia=. - -It is important to apply warmth to the extremities. - -Inject subcutaneously from 2 to 3 drops of the =atropine hypodermic= -solution. - -=Nitrite of amyl= by inhalation is said to have been useful. - -In desperate cases =bleeding=, followed by =transfusion=, is to be -considered. - - -ACIDS--MINERAL, including SULPHURIC, NITRIC, HYDROCHLORIC, GLACIAL -ACETIC ACIDS. - -=Stomach-tube= or =pump=, inadmissible. - -Neutralise by calcined =magnesia=, =lime=, =chalk=, or =soda,= but not -with potash, if there is choice. - -If no neutralising agent can be immediately procured, then dilute with -plenty of water. - -Other remedies are--=oil=, =milk=, =white of eggs=, =gruel=. - -It is often recommended in such cases to administer hypodermically a -little =morphine=. - - -ACONITE--ACONITINE. - -Use at once the =stomach-tube= or =pump=, or give emetics of =sulphate -of zinc=, or hypodermic solution of =apomorphine=. - -Keep the patient in the recumbent posture. - -After the stomach has been emptied, give =atropine=, either by -hypodermic injection or by the mouth, say 4 drops of the P.B. solution; -failing atropine, 20 drops of the tincture of =belladonna=. The dose may -be repeated more or less frequently according to the condition of the -patient. - -If there is great tendency to heart-syncope, tincture of =digitalis= in -1/2-drachm doses by the mouth, or in hypodermic doses of from 10 drops -upwards. - -Apply a mustard poultice to the pericardium; aid vomiting and -elimination of the poison by plenty of water, to which may be added -brandy or any form of alcohol. - -Inhalations of =nitrite of amyl= are said to have been useful. If the -breathing stops, try =artificial respiration=. - - -ALCOHOL. - -Empty the stomach by the =tube= or =pump=, and then wash it out with -warm coffee; if the stomach-tube is not at hand, then empty the stomach -by hypodermic injection of 5 drops of =apomorphine=, or by a =mustard= -emetic, or =sulphate of zinc=. Keep the body very warm, but the cold -=douche= may be applied to the head. - -Endeavours should be made to rouse the patient, if insensible, by -shaking, shouting at him, &c. - -Inhalations of =amyl nitrite= are said to be useful. - - -ALKALIES--AMMONIA--POTASH--SODA.--=Stomach-pump= or =tube= not to be -used. - -Vomiting nearly always present, or may be produced by administering -plenty of lukewarm water; after which give =dilute vinegar=, or the -juice of =lemons= or =oranges=; =olive oil=, the =white of eggs=, -=barley water=, =arrowroot=,= and always plenty of =water= may be -administered. - -There may be [oe]dema of the glottis, especially if ammonia has been -taken. In such a case, and death threatening from suffocation, perform -=tracheotomy=. In poisoning by ammonia, with croupous respiration, keep -the room warm, and fill it with steam by means of a bronchitis kettle. - -Relieve pain by small doses of =morphine= injected subcutaneously. - - -AMMONIA.--See ALKALIES. - - -ANTIARIN.--See DIGITALIS. - - -ANTIMONY--TARTAR-EMETIC--ANTIMONIAL WINE, &C. - -The stomach will generally have been emptied by vomiting. In those rare -cases in which this does not take place, use the =stomach-pump= or -=tube=, or give hypodermic injection of =apomorphine=. - -Follow this with doses of =strong tea=, or give half-a-drachm of -=tannin= or =gallic acid= in warm water. - -Give also demulcent drinks, and stimulants in small doses, frequently -repeated. - -Keep the patient very warm by hot blankets and wraps. - -The interrupted galvanic current to the heart may be useful. - - -APOCYNIN.--See DIGITALIS. - - -ARSENIC. - -Use the =stomach-pump= or =tube=, or empty stomach by emetics, such as -hypodermic solution of =apomorphine=, or give =mustard= or =sulphate of -zinc=. The stomach should then be washed out by large quantities of -water, most conveniently administered by the pump or tube. - -If the tube or pump is not at hand, then administer at once either -=dialysed iron=, or the freshly-precipitated =hydrated oxide of iron=, -obtained by precipitating the ordinary perchloride by means of carbonate -of soda or ammonia, avoiding excess of the latter. If the operator has -sufficient chemical knowledge to precipitate the iron with fair -exactness, so that there is no great excess of ammonia, or of sodic -carbonate, then filtration is unnecessary. In other cases, filter -through a handkerchief. - -=Oil=, =mucilaginous drinks=, the =white of eggs=, and, if faintness -exists, small doses of =stimulants= may all be given. - -If the skin is cold, warmth must be applied to the body by means of hot -blankets, &c. - -Pain may be relieved by =morphine=. - - -ATROPINE--BELLADONNA--TINCTURE OF BELLADONNA. - -Empty the stomach by means of the =stomach-pump= or =tube=. - -Give an enema of =coffee=. - -Administer half a grain of =pilocarpine nitrate=; or, if that is not at -hand, =morphine= or =opium= in suitable doses will act to a certain -extent antagonistic to the poison. - -A subcutaneous dose of =muscarine= may be administered instead of -pilocarpine, but is not quite so good. - -Hot water to the feet, alternate =douches= of cold and hot water are -found useful. - -If the respiration seems likely to stop, =artificial respiration= must -be practised. - - -BELLADONNA.--See ATROPINE. - - -BENZENE. - -If swallowed, then empty the stomach by =pump= or =tube=, or by the -hypodermic injection of =apomorphine=; or give emetics, such as =zinc -sulphate=, =mustard=, or =ipecacuanha=. - -If the vapour has been _inhaled_, this is unnecessary. - -Plenty of =fresh air=. - -A subcutaneous dose of =atropine=, say 1-60th of a grain, or from 30 to -40 drops of =belladonna= tincture. - -Alternate =douches= of hot and cold water to the chest, =artificial -respiration=, if necessary. The heart to be maintained by mild -interrupted shocks of the =battery= over the region of the heart. - - -BICHROMATE OF POTASH.--See CHROMIUM. - - -BRUCINE.--See STRYCHNINE. - - -CALABAR BEAN--PHYSOSTIGMINE. - -Use =stomach-pump= or =tube=, or emetics, such as =sulphate of zinc=, -=mustard=, or =ipecacuanha=; or, better still, hypodermic solution of -=apomorphine=. - -Give hypodermic doses of 1-60th grain =atropine= until the pupils -dilate. This treatment seeming to fail, =chloral= in 10-grain doses, -every quarter of an hour, has been recommended. - -In certain cases =strychnine= has been used in hypodermic doses of -1-12th of a grain. - -=Stimulants= and =artificial respiration= will probably be necessary in -some cases. - - -CAMPHOR. - -Use =stomach-pump= or =tube=, or empty the stomach by emetics. - -Hypodermic injections of =brandy=, inhalations of =ether=, the alternate -hot and cold =douche=, warmth to the extremities by hot blankets, &c., -seem to be the best methods of treatment. - - -CANTHARIDES--CANTHARIDINE. - -Use =stomach-pump= or =tube=, if the mucous membrane of the throat is -not inflamed; or, administer hypodermic dose of =apomorphine=, or give -emetics--=sulphate of zinc, mustard,= or =ipecacuanha=. - -Allay pain with =morphine=. Give plenty of water and =demulcent drinks=. - - -CHLORAL. - -Use =stomach-pump= or =tube=, and, when the stomach is emptied, -introduce by the same means =warm coffee=, or give a hypodermic -injection of =apomorphine=, or administer emetics of =sulphate of zinc=, -or =mustard=, or =ipecacuanha.= - -An =enema of coffee= will be useful. - -Keep the limbs warm. - -Administer hypodermically 2 or 3 drops of the solution of =strychnine= -at intervals of from fifteen to twenty minutes. - -Rouse the patient by various means, such as shouting, shaking, flapping -the skin with a wet towel, &c. - -Inhalations of =amyl nitrite= are recommended. - -=Artificial respiration= may be necessary. - - -CHLORATE OF POTASH. - -Use the same treatment as for =nitrate of potash= (_which see_, p. -696). - - -CHLORIDE OF ZINC.--See ZINC. - - -CHLOROFORM--(_Inhaled_). - -Give plenty of =fresh air=, pull the tongue forward, and commence at -once =artificial respiration=. If the heart has stopped, strike the -chest two or three times very hard, over the region of the heart; this -has been found occasionally to restore its beat. Apply the =battery=, -but with a weak current only; one pole may be placed on the larynx, the -other at the pit of the stomach. - -Inhalations of =nitrite of amyl= are useful. The hot and cold =douche= -may also be used. - - -CHLOROFORM--(_Swallowed_). - -Empty the stomach by =pump= or =tube=, or by emetics, such as 5 drops of -the hypodermic solution of =apomorphine=, or =sulphate of zinc=, or -=mustard=. - -Give an enema of =hot coffee=. - -Administer large draughts of =water=, which may advantageously contain a -little =sodic carbonate= in solution. - -Attempt to rouse the patient. =Nitrite of amyl= inhalations, and, if -necessary, =artificial respiration= may be used. - - -CHROMATE OF POTASH.--See CHROMIUM. - - -CHROMIC ACID.--See CHROMIUM. - - -CHROMIUM--BICHROMATE OF POTASH--CHROMATE OF POTASH--CHROMIC ACID. - -Empty the stomach by =pump= or =tube=; administer a subcutaneous -injection of =apomorphine=, or give =sulphate of zinc=, =mustard=, or -=ipecacuanha= as emetics. Follow up by administering, suspended in -water, calcined magnesia, or carbonate of magnesia, or chalk. - -=Demulcent drinks=, such as =barley-water=, &c. - - -COCCULUS INDICUS.--See PICROTOXIN. - - -COLCHICUM--MEADOW SAFFRON--COLCHICUM WINE, TINCTURE, &C. - -Use =stomach-pump= or =tube=, or empty the stomach by emetics, such as -=sulphate of zinc=, or =mustard=, or =ipecacuanha=; or, better than all, -give a hypodermic injection of 4 or 5 drops of the solution of -=apomorphine=. - -Give =tannin= or =gallic acid= in 1/2-drachm doses, or strong tea or -coffee. - -Allay the pain in the bowels and purging by small doses of =opium= or -=morphine=. - -Keep the extremities warm, apply hot fomentations to the abdomen; -=stimulants= may be used, give plenty of =water= and =demulcent -drinks=. - - -COLOCYNTH. - -Treatment on the same lines as that for COLCHICUM. - - -CONIUM--HEMLOCK. - -Empty the =stomach= by the =pump= or =tube=, or give a hypodermic -injection of 4 or 5 drops of the solution of =apomorphine=, or emetics -of =sulphate of zinc=, or =mustard=. - -Keep up the temperature of the body by hot wraps. - -Administer, as a drink, strong =tea=, =tannin=, =gallic acids=, or any -harmless vegetable decoction containing tannin. - -=Stimulants= may be administered. - -If necessary, use =artificial respiration=. - - -COPPER--SALTS OF. - -Empty stomach by =pump= or =tube=, and either inject by the same means -or administer =white of egg= in solution in water; if no white of eggs -can be had, substitute milk; give plenty of =water= and =emollient -drinks=. - -Pain may be allayed by =opium= or =morphine=. - - -CORROSIVE SUBLIMATE--PERCHLORIDE OF MERCURY--NITRATE OF MERCURY. - -Empty the stomach by the =tube= or =pump=, and wash the organ out with -plenty of white of egg, dissolved in water or milk. If the stomach-pump -is not at hand, then give emetics, such as the solution of -=apomorphine=, hypodermically, in from 4 to 5-drop doses, or a =zinc -sulphate= emetic, or =mustard=, or =ipecacuanha=. Probably violent -vomiting is already present, then stomach-tube or emetics are -unnecessary: but, in any case, give plenty of albuminous fluids, such as -=white of egg= in water or =milk=. If neither of these is at hand, chop -any =fresh meat= up as finely as can be done in a short space of time, -diffuse in water, and administer. Follow up with =demulcent drinks=, -such as =barley-water=, =flour= and =water=, &c. - -Pain may be allayed with a little =opium= or =morphine=. - -=Stimulants= are admissible, if necessary. - - -CROTON OIL. - -Empty stomach by means of =tube= or =pump=, or give emetics of =mustard= -or =sulphate of zinc=, or administer hypodermic injection of -apomorphine. - -Give 10 drops of =laudanum= every twenty minutes or half hour, until the -pain and purging are somewhat abated, or else inject subcutaneously -small doses of =morphine= at intervals. - -Give plenty of =demulcent drinks=. - -Two or three drops of =essence of camphor= in milk are useful. - -Stimulants, such as =brandy=, =ammonia=, or =chloric ether=, are -admissible. - - -CYTISINE.--See LABURNUM. - - -CURARINE--WOORARI--URARI. - -The poison is of course introduced by a wound; if any is likely to be -still in the wound apply a =ligature=, =suck the wound=, and then wash -it with a slightly alkaline solution of =potassic permanganate=. - -Keep up the =respiration artificially=, give plenty of =water= and a -dose of spirits of nitre, apply warmth to the loins. By these means the -poison will be rapidly separated by the urine; and, if the patient can -only be kept alive by artificial respiration for a little time, he may -recover, for elimination is very rapid. - - -CYANIDE OF POTASSIUM.--See PRUSSIC ACID. - - -DIGITALIS GROUP OF HEART POISONS, _including_, besides the DIGITALINS, -ANTIARIN, APOCYNIN, NERIIN, OLEANDRIN, EVONYMIN, THEVETIN, SCILLAIN, -STROPHANTIN, and ERYTHROPHLEIN. - -Empty the stomach by the =tube= or =pump=, or administer a subcutaneous -dose (4 drops) of =apomorphine=, or give a tablespoonful of =mustard= in -water, or =sulphate of zinc=. - -Follow up with strong =tea=, or half a drachm of =tannin=, or =gallic -acid= in aqueous solution. - -A very small dose of =aconitine nitrate= in solution (say 1-200th of a -grain) may be injected subcutaneously and the effect watched; if in a -little time it seems to do good, repeat the dose. On no account let the -patient rise from the recumbent posture, or he may faint to death. - -=Stimulants= in small doses may be given frequently by the mouth, or, if -there is vomiting, by the bowel. - - -ERGOT. - -Use =stomach-pump= or =tube=, or empty the stomach by a =mustard= or -=sulphate of zinc emetic=, or give a subcutaneous injection of -=apomorphine=. - -Give a purgative, such as a drop of =croton oil=, and assist its action -by plenty of warm drinks. - -=Tannin= and =gallic acid= have also been recommended, but are probably -of but little use. - -After the bowels have well acted, and the stomach has been emptied, give -small doses of =opium= at intervals. - -Dr. Murrell recommends 1-50th of a grain of =nitro-glycerin= every -fifteen minutes. - -The recumbent position is necessary, and the circulation should be -maintained by warmth, and, if necessary, by friction. - - -ERYTHROPHLEIN.--See DIGITALIS. - - -ETHER.--The same treatment as with CHLOROFORM. - - -EVONYMIN.--See DIGITALIS. - - -FUNGI.--See MUSHROOMS. - - -GELSEMININE. - -If seen soon after taking the dose, use the =stomach-pump= or =tube=, or -give a tablespoonful of =mustard=. - -Administer a small dose of =atropine= subcutaneously, or give by the -mouth tincture of belladonna in 20-drop doses. - -=Stimulants= are admissible. - -If necessary, use =artificial respiration=. - -Rouse the patient by hot and cold =douches=. - - -HEMLOCK.--See CONIINE--CONIUM. - - -HENBANE--HYOSCYAMINE.--The same treatment as for ATROPINE. - - -HYDROCHLORIC ACID.--See ACIDS, MINERAL. - - -HYDROCYANIC ACID.--See PRUSSIC ACID. - - -HYOSCYAMINE.--The same treatment as for ATROPINE. - - -IODINE. - -Empty the stomach by =pump= or =tube=, or administer emetics, such as -the hypodermic solution of =apomorphine=, or give by the mouth =mustard= -or =sulphate of zinc=. - -Give plenty of =starch= diffused in warm water, or in the form of a -dilute paste; or give any =farinaceous substance= whatever, such as -=arrowroot=, =boiled rice=, or =flour=, or thin =gruel=. - -Inhalations of =amyl nitrite= have been recommended. - -Pain may be relieved by =morphine= or =opium=. - - -JABORANDI.--Treatment the same as PILOCARPINE. - - -LABURNUM SEEDS--CYTISINE. - -Empty stomach by =tube= or =pump=, and wash it out with =tea= or -=coffee=, or give (as an emetic) a hypodermic dose of =apomorphine=, or -(by the mouth) =mustard= or =zinc sulphate=; follow up this treatment by -an enema, or a brisk =purgative=. - -=Stimulants= may be administered, the patient may be roused by the hot -or cold =douche=. - - -LAUDANUM.--See MORPHINE. - - -LAUREL WATER.--See PRUSSIC ACID. - - -LEAD--SALTS OF. - -Empty stomach by =pump= or =tube=, or administer subcutaneously a dose -of =apomorphine=, 4 to 5 drops; or give by the mouth a =sulphate of -zinc= or =mustard= emetic. Follow up with half a drachm of =dilute -sulphuric acid=, or half an ounce of =magnesic= or =sodic sulphate=. - -=Milk= and =albuminous fluids= may be given. - -Allay pain with =opium= or =morphine=. Treat colic with hot -fomentations. - - -MEADOW SAFFRON.--See COLCHICUM. - - -MERCURY, SALTS OF.--See CORROSIVE SUBLIMATE. - - -MONKSHOOD.--See ACONITE. - - -MORPHINE--OPIUM--_Laudanum and preparations in which the OPIUM ALKALOIDS -predominate._ - -If taken by the mouth, give at once a solution of potassium permanganate -and then empty the stomach, but, if taken by hypodermic injection, both -these would be useless. The stomach in opium-poisoning is best relieved -by the =pump= or =tube,= and should then be well washed out with hot -=coffee=, leaving in the organ a pint or more. If the stomach-pump or -tube is not at hand, a large subcutaneous dose of =apomorphine= (say 10 -minims) may be given, or =mustard= or =zinc sulphate=, but there may be -difficulty in obtaining vomiting from any emetic. - -Attempt to rouse the patient by the =battery=, if at hand; by flips with -a towel, and by shaking. In all books will be found the usual direction -that you are to keep walking the patient about; but this treatment is -questionable, and likely to favour the toxic action of morphine on the -heart. - -=Ammonia= may be applied to the nostrils. - -Hot =coffee= may also be introduced into the bowels by an =enema= -apparatus, or by a simple tube. - -The alternate =cold and hot douche= to the head is good, but the body -should be kept warm with hot wraps. - -Small subcutaneous doses of =atropine= (say 1-20th of a grain) may be -administered, repeating the close every twenty minutes, and watching the -effect. - -If necessary, apply =artificial respiration=. - -Inhalations of =nitrite of amyl= have been used. - - -MUSCARINE.--See MUSHROOMS. - - -MUSHROOMS--MUSCARINE--POISONOUS FUNGI GENERALLY. - -Empty stomach by =stomach-pump= or =tube=, or give a subcutaneous dose -of =apomorphine=, or administer by the mouth either =mustard= or =zinc -sulphate=. - -Inject as soon as possible a subcutaneous dose of 2 to 4 drops of the -solution of atropine; or, after the stomach has been emptied, give -=tincture of belladonna= every half hour, in from 20 to 30-min. doses. - -It is equally important to remove the remains of the fungi from the -intestines, and for this purpose it is well to give a dose of =castor -oil=, and to use an enema. - -=Stimulants= may be given. The body should be kept warm. - - -NERIIN.--See DIGITALIS. - - -NICOTINE--TOBACCO. - -Unless the stomach has been already emptied by vomiting, use -=stomach-pump= or =tube=, or give an emetic of =mustard= and plenty of -water. - -Inject subcutaneously a small dose of =strychnine= (say 1-25th of a -grain of the nitrate), or give half a drachm of tincture of =nux -vomica=. - -=Stimulants=, such as =brandy=, =chloric ether=, &c., may be given. - -Keep the body warm, but the =cold douche= may be applied to the head. - -=Tannin= and vegetable infusions containing =tannin= may also be given, -but it is questionable if they are of much use, unless any remnants -remain in the stomach. - -Keep the patient lying down for fear of fatal syncope. - - -NITRE--NITRATE OF POTASH. - -Empty the stomach immediately by the =pump= or =tube=, or give a -subcutaneous dose of =apomorphine= (from 2 to 3 drops), or administer by -the mouth a tablespoonful of =mustard=, or a scruple of =sulphate of -zinc=. - -Dilute the poison, and attempt to wash it out of the system by giving -plenty of =water= or =mucilaginous drinks=. - -Apply hot fomentations to the loins, and keep the patient as warm as -possible. - -Stimulants that are likely to increase the kidney congestion are to be -avoided. - -Inhalations of =nitrite of amyl= have been recommended. - - -NITRIC ACID.--See ACIDS, MINERAL. - - -NITRO-BENZENE. - -Empty the stomach at once by the= stomach-pump= or =tube=, and wash the -organ out with plenty of warm water, to which advantageously a little -spirit may be added; or give emetics, such as =zinc sulphate= or -=mustard=. - -Administer stimulants, either by the stomach-tube, as an enema, or by -subcutaneous injection. - -Keep up the respiration artificially, if necessary, and maintain the -heart's action by application of weak, interrupted shocks to the -chest-wall, by means of the =battery=. - -Rouse the patient by the =douche=. - -=Atropine= subcutaneously has been recommended. - - -NITROUS OXIDE GAS. - -The treatment is the same essentially as for chloroform (_which see_). - -Inhalations of =oxygen= may do good, but oxygen is very rarely at hand. - - -NUX VOMICA.--See STRYCHNINE. - - -OLEANDRIN.--See DIGITALIS. - - -OPIUM.--See MORPHINE. - - -OXALIC ACID--BINOXALATE OF POTASH--SODIC OXALATE. - -Unless the patient has already vomited freely, empty the stomach at once -by emetics of =zinc sulphate= or =mustard=; or the =stomach-pump= or -=tube= may, in most cases, be used. If the acid has been taken, -neutralise by =chalk=, =lime water=, or, better, by =saccharated lime -water=; but on =no= account neutralise by carbonate of soda or any -alkali, for the alkaline oxalates are extremely poisonous. - -Assist elimination by the kidneys by giving plenty of water; apply hot -fomentations to the loins. - -An enema may be given, if necessary, to empty the bowels well. - - -PHOSPHORUS. - -Empty the stomach by =tube= or =pump=, and, at the same time, wash the -organ out with water to which has been added a drachm of =French -turpentine=, or give emetics. The best emetic for phosphorus is said to -be =sulphate of copper=, 4 or 5 grains dissolved in water, and given -every ten minutes until vomiting is produced. - -In default of sulphate of copper, then =sulphate of zinc= or =mustard=. - -Give 1/2-drachm doses of =turpentine=, floating on water or on mucilage, -every half hour. Inhalations of turpentine vapour, much diluted, are -also of service. The American and German turpentines are said to be of -no avail. Probably the turpentine will freely purge the patient; but, if -not, the bowels should be opened by a suitable purgative, such, for -instance, as =magnesic sulphate=. - - -PHYSOSTIGMINE.--See CALABAR BEAN. - - -PICROTOXIN--COCCULUS INDICUS. - -Use =stomach-pump= or =tube=, or empty stomach by usual emetics, _e.g._, -=mustard=, =zinc sulphate=, or =apomorphine=, subcutaneously. - -=Chloral=, in doses of from 10 to 20 grains, may be given every half -hour to allay or prevent tetanus, the effects being, of course, watched. -For the same purpose =bromide of potassium= has been recommended. In -severe cases, it may be combined with choral, 1 drachm of the bromide -with 20 grains of chloral. - - -PILOCARPINE. - -The best treatment is a subcutaneous dose of =atropine= (say 1-60th of a -grain) or tincture of =belladonna= by the mouth in 20-minim doses, to be -repeated every twenty minutes until the pupils dilate. - - -POTASH.--See ALKALIES - - -PRUSSIC ACID.[991] - -[991] J. Kossa, considering that potassium permanganate ought, -theoretically, to act as a chemical antidote to potassium cyanide, by -checking the paralysis of the respiratory centres, has performed some -experiments. Rabbits were shown to be fatally affected in a few minutes -by 0.01 grm. of the poison, but if, at the time of administration, 0.5 -grm. of permanganate dissolved in 50 c.c. of water was also introduced -into the stomach, doses of cyanide up to 0.1 grm. failed to cause death. -Larger quantities (0.2 grm.) proved fatal under similar conditions, but -the action of the poison was much delayed. Successful experiments were -also performed with aqueous solutions of hydrocyanic acid containing 0.1 -per cent. It is suggested, therefore, that, in cases of cyanide -poisoning, 1/2 to 1/3 litre of a 3 to 5 per cent. solution of -permanganate should be administered immediately (_Vratch_, through -_Nouv. rem._, ix. 567). - -Use =stomach-pump= or =tube=, or, if not at hand, an emetic of =mustard= -or =sulphate of zinc=. - -If the breathing has stopped, try =artificial respiration= and weak -shocks to the heart. - -1-60th of a grain of =atropine= subcutaneously is recommended to assist -the heart's action. - -A =brandy enema= may be given, or brandy injected under the skin. - -The body must be kept warm, but the cold =douche= may be advantageously -applied to the head. - - -SALTS OF SORREL.--See OXALIC ACID. - - -SAVIN. - -If the patient has not already emptied the stomach by repeated vomiting, -and the throat is not inflamed, use the =stomach-pump= or =tube=, and -wash the organ out with water, or give any one of the usual -emetics--such as =mustard=, =sulphate of zinc=, or =ipecacuanha=. - -If the bowels have not acted well, give a dose of =castor oil=; allay -pain with small doses of morphine. - - -SCILLAIN.--See DIGITALIS. - - -SNAKES, BITE OF. - -Suck the wound, and apply an alkaline solution of =permanganate of -potash=. - -In severe cases of cobra poisoning and other extremely venomous snakes, -death threatening, the only likely means of saving life would be -bleeding at one arm and =transfusing= blood by the other. - -=Ammonia= may be given by the mouth, and also smelt. - -In cobra poisoning and venoms which kill mainly through the respiration, -the breathing must be kept up artificially; and, should there be signs -of the heart failing, weak, interrupted =galvanic= shocks may be applied -to the walls of the chest. - -Lacerda's plan of injecting permanganate of potash under the skin is not -alone useless but mischievous, for it takes up time which might be more -valuably employed. - - -SODA CAUSTIC.--See ALKALIES. - - -SOLANINE--SOLANUM DULCAMARA--BITTER SWEET--WOODY NIGHTSHADE.--The same -treatment as for ATROPINE (_which see_). - - -STRAMONIUM.--The same treatment as for ATROPINE. - - -STROPHANTIN.--See DIGITALIS. - - -STRYCHNINE--BRUCINE--NUX VOMICA. - -Empty the stomach as quickly as possible by an emetic of =mustard=, or -=zinc sulphate=, or by a hypodermic solution of =apomorphine= (4 drops). - -The =stomach-pump= or =tube= inadmissible; for, if tetanus is present, -it cannot be applied; or, if absent, it is likely to excite a spasm. - -Place patient at once under =chloroform= or =ether=, and keep up a -gentle narcosis for several hours, if necessary. - -Darken the room, stifle all noise; if in a town, and opportunity permit, -have straw or peat placed at once before the house to deaden noise. - -If the spasms threaten the respiration, =artificial respiration= is -absolutely necessary; and, to facilitate this, it would be justifiable, -in a dangerous case, to perform =tracheotomy=, of course under -chloroform. - -=Chloral= may be given in place of chloroform, but the latter is best; -the dose of =chloral= should be, at least, half a drachm, and if no -effect is produced in half an hour, then doses of 20 grains should be -given at intervals of a quarter of an hour. - -If neither chloroform nor chloral is at hand, the juice from a -recently-smoked pipe may be diffused in a little water and a few drops -injected subcutaneously, and the effect watched. If there is a marked -improvement the treatment may be persevered in. - -=Bromide of potassium= in combination with chloral has been recommended. - -=Nitrite of amyl= inhalations are said to be of use. - -=Curarine= in a subcutaneous dose of one-third of a grain is -antagonistic so far that it paralyses the voluntary muscles. - - -SULPHURIC ACID.--See ACIDS, MINERAL. - - -TARTAR EMETIC.--See ANTIMONY. - - -TARTARIC ACID.--The same treatment as for OXALIC ACID (_which see_). - - -THEVETIN.--See DIGITALIS. - - -TOBACCO.--See NICOTINE. - - -TURPENTINE. - -Empty stomach by =tube= or =pump=, or administer the usual emetics, such -as =mustard=, or =sulphate of zinc=, or =ipecacuanha=, or give -hypodermically 3 or 4 drops of the solution of apomorphine. - -If purging is not already present, empty the bowel by enema; give plenty -of water and demulcent drinks to aid elimination by kidneys. - -Apply hot fomentations to the loins. - -Allay pain with =opium= or =morphine.= - - -VERATRINE. - -Empty the stomach by the =tube= or =pump=, or give any one of the usual -emetics--such as =mustard=, or =zinc sulphate=, or =ipecacuanha=. - -Keep the patient lying down. - -=Stimulants= may be administered. - -An enema of =hot coffee= has been recommended. - -Keep the body warm with wraps, hot blankets, &c. - - -WHITE PRECIPITATE.--The same treatment as for CORROSIVE SUBLIMATE. - - -WASPS, BEES, HORNETS--STING OF. - -An =onion= immediately applied to the part stung is a favourite popular -remedy; but =ammonia= is better. - -=Extract the sting=, if it remains in the wound. - -Give =stimulants=, if necessary. - - -ZINC. - -The only salt likely to cause poisonous symptoms is the chloride, which -is used in the arts, and is the active principle of Burnett's -disinfecting fluid. - -=Stomach-pump= or =tube= inadmissible. Give plenty of =water=, in which -=carbonate of soda= is dissolved; or, if that is not at hand, =carbonate -of potash=. - -=Eggs= and =milk= should also be given. - -Solutions of =tannin=, strong =tea=, and the like, also, to some extent, -neutralise the poison. - -The pain in the abdomen is to be allayed in the usual way--by hot -fomentations and small frequent doses of =morphine= or =opium=. - - -DOMESTIC READY REMEDIES FOR POISONING. - -Sec. 914. Large households, more especially those in which no one possesses -any special medical knowledge, would do well to furnish an ANTIDOTE -CUPBOARD, for use in cases of emergency. This cupboard may contain:-- - -(1.) _The Multiple Antidote_, which consists of saturated solution of -sulphate of iron 100 parts, water 800, magnesia 88, animal charcoal 44 -parts. It is best to have the animal charcoal and magnesia mixed -together in the dry state and kept in a well-corked bottle; when -required for use, the saturated solution of sulphate of iron is mixed -with eight times its bulk of water, and the mixture of charcoal and -magnesia added with constant stirring. The multiple antidote may be -given in wine-glassful doses, frequently repeated, in poisoning by -arsenic, zinc, opium, digitalis, mercury, or strychnine; it is of no use -in phosphorus poisoning, or in poisoning by the caustic alkalies or -antimony. - -(2.) _Calcined Magnesia_, for use in poisoning by acids. - -(3.) _French Turpentine_, for poisoning by phosphorus. - -(4.) Powdered ipecacuanha in a well-corked bottle; the bottle containing -a small pill-box which is cut down, so that when full it contains 30 -grains--the proper dose as an emetic. A similar small supply of sulphate -of zinc may also be provided. - -(5.) A tin of mustard. - -(6.) A bottle of vinegar. - -If, then, provided with such a supply, any member is known to have taken -poison, and yet the precise poison is not known, give a =sulphate of -zinc= or =ipecacuanha emetic=, and follow it up by the =multiple -antidote=, which is in itself not poisonous. - -If PHOSPHORUS has been taken, then give the =French turpentine= as -directed under Phosphorus (p. 697). - -If ACIDS, neutralise by the =calcined magnesia= (see Acids, mineral, p. -687). - -If ALKALIES, neutralise with =vinegar= (see Alkalies, p. 688). - - - - -INDEX. - - - Abel and Field's test for bismuth, 627. - Abrin, 462. - Abrus, 462. - Absynthin, 244. - Acetaldehyde, 154. - Acetanilide, 40. - Aceta-trimethyl-colchicin-amide, 409. - Acetic acid, 110. - " Deaths from, 29. - Acetum digitalis, 422. - Acetyl phenyl hydrazine, 40. - Acid, carbolic. See _Carbolic acid_. - Acid haematin, Spectrum of, 58. - Acids, mineral. See _Hydrochloric_, _Nitric_, _Sulphuric acid_, &c. - Acolyctin, 252. - Aconine, 351, 354. - Aconite alkaloids, 351. - Aconite, Bibliography of papers relating to physiological action of, - 360, 361. - " Deaths from, 30. - " extract, 351. - " liniment, 351. - " ointment, 351. - " treatment of poisoning by (App.), 687. - " Old knowledge of, 3. - " Pharmaceutical preparations of, 351. - " poisoning, Statistics of, 361. - " _Post-mortem_ appearances after poisoning by, 366. - " root, Poisoning by, 361. - " seeds, 350. - " tincture, 351. - Aconitine, 243, 252, 253, 351. - " acetate, 245 (footnote). - " action on fish, 359. - " " frogs, 359. - " " insects, 358. - " " mammals, 359, 360. - " Carbon and nitrogen percentage in, 262. - " Colour reactions of, 240. - " Commercial, 355. - " gold salt, 264, 352. - " Phospho-molybdate of, 238. - " Physiological action of, 366. - " Poisoning by, 362. - " Properties of, 351, 352. - " Separation of, from tissues, &c., 367. - " Sublimation of, 259. - " Tests for, 352, 353. - " Value of Mayer's precipitate of, 263. - Acquetta di Perugia, 11. - Acqua Toffana, 10, 11. - Adder, Thuringian, 484. - Adonidin, 434. - Aerated waters, Detection of lead in, 609. - AEsculin, 345 (footnote). - AEthusa cynapium, 457. - Agaricus pantherinus, 418. - " phalloides, Poisoning by, 417. - " ruber, 418. - Agrostemma sapotoxin, 436. - Ague drops, 532. - Alchid Becher, 5. - Alcohol, Deaths from, 29. - " Detection of, in chloroform, 144. - " Excretion of, 139. - " Fatal dose of, 137. - " _Post-mortem_ appearances after poisoning by, 138. - " Separation of, 51. - " Statistics of poisoning by, 136. - " Symptoms of poisoning by, 137. - " Toxicological detection of, 140. - " Treatment of poisoning by (App.), 688. - Alcoholic poisoning, criminal or accidental, 137. - Aldehyde, 154. - " groups, 39. - " in chloroform, 145. - Alexander VI., Death of, by poisoning, 7. - Ali Ahmed's treasures of the desert, 593. - Alkalies, Fixed caustic, 116-122. - " Chronic poisoning by, 120. - " Effects on animal and vegetable life, 118. - " Estimation of, 121. - " Local effects of, 119. - " _Post-mortem_ appearances of poisoning by, 119. - " Statistics of poisoning by, 118. - " Symptoms of poisoning by, 119. - " Toxicological detection of, 127. - " Treatment of poisoning by (App.), 688. - Alkaloids, Discovery of, 15. - " General properties of, 236. - " of the veratrums, 390. - " Quantitative estimation of, 262. - Alkyls replacing hydrogen, 36. - Allantoin, 39. - Alloxantin, 39. - Almonds, bitter, Case of poisoning by, 209. - Aloetin, 244. - Alum, 676, 677. - " Action of, 676, 677. - " _Post-mortem_ appearances after poisoning by, 678. - Aluminium, 676-679. - Aluminic and sodic lactate, 677. - " " tartrate, 677. - Alumina, Detection of, 678, 679. - " Test for, 678, 679. - Amanita muscaria, 413. - Amanitine, Carbon and nitrogen percentage in, 262. - " gold salt, 264. - Amarin, 40. - Amines, 488-490. - Ammonia, 111-116. - " action on animal life, 113. - " action on plants, 113. - " -alum, 676. - Ammoniac and mercury plaster, 635. - Ammonia, Deaths from, 29. - " Effects of, 113. - " Estimation of, 116. - " liniment, 111. - " and hypochlorite test for carbolic acid, 177. - " _Post-mortem_ appearances after poisoning by, 115. - " Properties of, 111. - " salts, Detection of, 128. - " Separation of, 115. - " Statistics of poisoning by, 112. - " Solution of, 111. - " Symptoms of poisoning by, 112. - " Tests for, 116. - " Uses of, 111. - " vapours, Poisoning by, 112. - Ammoniated mercury, Effects of, 648. - " ointment, 637. - Ammonic cyanide, 210. - Amygdalin, 194. - Amyl nitrite poisoning, 141. - Amylic alcohol, 141. - Anderseck's case of corrosive sublimate poisoning, 647. - Androctonus bicolor, 468. - " occitanus, 468. - Angelic acid, 392. - Aniline, 250. - " Characters of phospho-molybdate precipitate, 237. - " Detection of, 281. - " Fatal dose of, 281. - " Production of, from nitro-benzene, 133, 188. - " Properties of, 280. - " Separation of, 51. - " Spectrum of colour reaction, 55. - " Symptoms of poisoning by, 280. - Animal bases, 3. - Antiarin, 432. - Antidote bag, 685. - Antimonial compounds used in pyrotechny, 581. - " powder, 579. - Antimonious sulphide, 577. - Antimony, black, 580. - " chloride, 580. - " Deaths from, 29. - " Detection of, 587. - " Effects of, 582. - " Elimination of, 586. - " Flowers of, 581. - " Glass of, 581. - " in alloys, 582. - " metal, 577. - " Mirror of, 537. - " oxide, 579. - " " vapour, 585. - " pentasulphide, 578. - " Pharmaceutical preparations of, 79, 80. - " pills, 580. - " _Post-mortem_ appearances from poisoning by, 585, 586. - " poisoning (chronic), 585. - " Quantitative estimation of, 589. - " salts, Doses of, 582. - " Separation of, 50. - " sulphide, Separation of, 52. - " sulphurated, 580. - " tartarated, Antidotes for, 586. - " " Effects of, 583. - " " Estimation of, 578. - " treatment of poisoning by (App.), 688. - Antimony wine, 579. - " yellow, 582. - Antipater, Trial of, 2. - Antipyrine, Deaths from, 30. - Antiseptic action of hydric cyanide, 203 (footnote). - Ants, Poisonous properties of, 471. - Aplysia, 3. - Apocynin, 434. - Apollodorus, 3. - Apomorphine, 317. - " Separation of, 51. - Aqua Orientalis, 630. - Aromatic spirits of ammonia, 112. - Aromatic sulphuric acid, 76. - Arsen-dimethyl chloride, 38. - Arseniate of iron, 530. - " of soda, 530. - Arsenic chloride, 529, 575, 576. - Arsenic, Deaths from, 29. - " Detection of, 555. - " " in antimony sulphide, 578. - " Doses of, 535. - " eaters, 538. - " Effects of, on animals, 536, 537. - " " man, 538. - " " plants, 535. - " Elimination of, 553. - " Estimation of, 566-568. - " " as trisulphide, 571. - " Imbibition of, after death, 563. - " in the arts, 529. - " in glycerin, 560. - " in organic matters, 560. - " Introduction of, 539. - " Hydrochloric acid solution of, 530. - " (arsenious anhydride), Properties of, 524, 525. - " Law relating to, 535. - " Localisation of, in the body, 561, 562. - " Metallic properties of, 524. - " Mirrors of, 557. - " Pharmaceutical preparations of, 530. - " Physiological action of, 552. - " poisoning, Absence of symptoms in, 545. - " " Antidotes for, 553, 554. - " " Microscopical appearances of liver in, 552. - " " Museum preparations illustrative of, 550, 551. - " " _Post-mortem_ appearances of, 548-552. - " Separation of, 49, 50. - " " by Chittenden's method, 568, 569. - " Slow poisoning by, 546. - " Solubility of, 525. - " Statistics of poisoning by, 534. - " sulphide, 52, 528, 529, 573, 575. - " treatment of poisoning by (App.), 689. - Arsenious acid. See _Arsenic_. - Arsenites and Arseniates, Tests for, 555. - Arsen-methyl-chloride, 38. - Arseniuretted hydrogen. See _Arsine_. - Arsine, Development of, in Fleitmann's process, 571. - " effects on man, 527. - " uses in the arts, 527. - " Properties of, 525, 526. - Arum maculatum, 465. - " seeds, Death from, 30. - Aselline, 506. - Asiatic knowledge of poisons, 4. - Asparagin, Percentage of carbon and nitrogen in, 262. - Aspidospermine, 344. - Atkinson's infant preserver, 288. - Atropine, 251, 368, 369. - " Action of, on animals, 377. - " " infusoria, 42. - " " man, 377, 378. - " and strychnine, Tests for, 374. - " antagonistic to muscarine, 416. - " Accidental and criminal poisoning by, 375, 376. - " Carbon and nitrogen content of, 262. - " Chronic poisoning by, 379. - " Colour reactions of, 240. - " Deaths from, 30. - " effects on the iris, 374. - " effects on the heart in digitalis poisoning, 429. - " Fatal dose of, 376, 377. - " Gold salt of, 264. - " Melting point of, 259. - " Pharmaceutical preparations of, 371. - " Physiological action of, 380. - " Phospho-molybdate of, 238. - " poisoning, Diagnosis of, 380. - " " _Post-mortem_ signs after poisoning by, 380. - " " Statistics of, 375. - " " Treatment of, 380. - " Properties of, 371, 372. - " Separation of, from organic matters, 381. - " Separation of, from the urine, 381. - " Tests for, 372, 373. - " Treatment of poisoning by (App.), 689. - " Value of Mayer's precipitate, 263. - Attalus Phylometer, 2. - Autenrieth's general process of analysis for poisons, 50-54. - - Bain de Tessier, 533. - Baking-powder, 677. - Bamberger's views as to hydrogenised bases, 36. - Barium, 679. - " carbonate, 680. - " Characters of, 680. - " chloride, Deaths from, 29. - " Koningh's method of detection, 675. - Barium salts, Effect of, on man, 681, 682. - " " Fatal dose of, 682. - " " Localisation of, 683. - " " Separation and detection of, 684. - " " Symptoms of poisoning by, 682. - " sulphate, 680. - " " Identification of, 684. - " sulphide, 680. - Barley, Content of copper in, 612. - Battle's vermin-killer, 328. - Becoeur's soap, 533. - Belladonna, Alkaloids of, 369. - " Deaths from, 30. - " Pharmaceutical preparations of, 370, 371. - Benzene, 131-133. - " Purification of, 132. - " Treatment of poisoning by (App.), 689. - Benzoic acid, Tests for, 354. - Benzoline, 129. - Benzoyl-aconine, 351-353. - Benzoyl chloride method of isolating diamines, 487. - Berberine, 245. - " Carbon and nitrogen content of, 262. - " Gold salt of, 264. - " Phospho-molybdate of, 238. - Bergeron and L'Hote's researches on copper, 613. - Bernatzic's views on copper poisoning, 617. - Bernhardt's case of poisoning by carbon disulphide, 164. - Berzelius' test for arsenic, 554. - Besnou on specific gravity of alcohol and chloroform, 145. - Betaine, 501, 502. - " Carbon and nitrogen percentage of, 262. - Bibliography of chief works on toxicology, 16. - Bicarbonate of soda lozenges, 118. - Bichromate of potash. See _Chromium_. - Bichromate disease, 671, 672. - Binoxalate of potash, 572. - Binz's theory of the action of arsenic, 553. - Bishop Stortford cases of food poisoning, 507. - Bismuth citrate solution, 625. - " Extraction and detection of, 626. - " Estimation of, 627, 628. - " in the arts, 625. - " lozenges, 624. - " Medicinal doses of, 625. - " nitrate, 625. - " oxide, 625. - " oleate, 625. - " peroxide, 624. - " potassium iodide, 237. - " Properties of, 624. - " Separation of, 50. - " subgallate, 625. - " subiodide, 625. - " sulphide, 624. - " Tests for, 626, 627. - " Toxic effects of, 625. - Bitter aloes, Deaths from poisoning by, 30. - Black drop, 287. - " bryony, 465. - Blair's gout pills, 412. - Bleaching-powder, 71. - Blondlot's apparatus for production of phosphine, 231. - " modification of Marsh's test, 56. - Blood, Action of ammonia on, 114. - " Characters of, in arsine poisoning, 527. - " " carbon oxide poisoning, 59, 66. - " " dinitrobenzol poisoning, 191. - " " hydric sulphide poisoning, 58. - " " nitrobenzol poisoning, 187, 191. - " " phosphine poisoning, 224. - " " phosphorus poisoning, 222. - " " sulphuric acid poisoning, 90. - " Examination of, 56-63. - " Guaiacum test for, 61. - " corpuscles of man and animals, 62. - " Spectroscopic examination of, 57. - " spots, Treatment of, 60, 61. - Blowfly, Action of digitalins on, 429. - " Action of poisons on, 43. - Blue pill, 634. - Bluestone, 616. - Bocarme, Count, 274. - Bocklisch's flask, 486. - Boehm's experiments on barium, 681. - Boletus satanas, 418. - Bottcher's depilatory, 680. - Bottger's observations on copper, 611. - Boyle, Hon. Robert, 13. - Braun's method of estimating HCl, 101. - Bread, Content of copper in, 612. - Brieger's process for ptomaines, 485. - Brighton Green, 616. - Brinvilliers, Mad. de, 11. - Britannia metal, 582. - Britannicus, Death of, by poison, 6. - Bromine as a test for carbolic acid, 178. - Bromo-picrotoxin, 452. - Brown's lozenges, 639. - Brucine, 248, 251, 340. - " Colour reactions of, 240. - " Melting-point of, 260. - " picrate, 340. - " Phospho-molybdate of, 238. - " Physiological action of, 341. - " Platinum salt of, 264. - " Separation of, from organic matters, 343. - " Separation of, from strychnine 323. - " Spectrum of colour reactions, 55. - " sulphate, 341. - " Tests for, 342, 343. - " Value of Mayer's reagent, 263. - Brugnatelli's method of detecting mercury, 653. - Brunswick green, 616. - Buchner on solubility of arsenic, 525. - Burnett's fluid, 657. - " Symptoms of poisoning by, 660. - Busscher's case of aconitine poisoning, 363. - Butter of antimony, 587. - Butylamine, 506. - Bynssen's observations on the elimination of mercury, 650. - - Cadaverine, 494, 495. - Cadmium, 590. - " Fatal dose of, 590. - " in the arts, 590, 591. - " oxide, 590. - " Separation and detection of, 50, 52, 590. - " sulphide, 590. - Caffein, 40. - " Spectrum of murexide test for, 55. - Calabar bean. See _Physostigmine_. - Calomel, 634, 636. - Calvert's Carbolic acid powder, 167. - Camphor, 135, 243. - " Compound liniment of, 111. - " " tincture of, 285. - " Deaths from, 30. - " Effects of, 135. - " _Post-mortem_ appearances after poisoning by, 136. - " Separation of, 136. - " Spirits of, 135. - " Treatment of poisoning by (App.), 690. - " water, 135. - Camphorated oil, 30. - Camphoric acid, 135. - Cantharides, 471. - " Deaths from poisoning by, 30. - " Effects of, on animals, 472. - " " man, 473. - " Fatal dose of, 472. - " Pharmaceutical preparations of, 472. - " _Post-mortem_ appearances after poisoning by, 474. - " Tincture of, 472. - " Treatment of poisoning by (App.), 690. - Cantharidin, 244, 260, 471, 472. - " Tests for, 475. - Capsicin, 243. - Capsicum alkaloids, 248. - " seeds, as distinguished from Datura, 248. - Carbolic acid, 242. - " Changes in urine after taking, 174. - " Colorimetric method of estimating, 183. - " Deaths from, 29. - " Effects of, on animals, 169, 170. - " effects on man, 173. - " Examination of urine for, 181. - " Fatal dose of, 169. - " in organic fluids, 180. - " Museum preparations illustrative of poisoning by, 176. - " _Post-mortem_ appearances in cases of poisoning by, - 166. - " powder, 167, 183. - " " Assay of, 181, 183. - " Properties of, 166, - " Separation of, 51, 176, 180. - " soap, 167, 183. - " Statistics relating to poisoning by, 167. - " Symptoms produced by, 170. - " Tests for, 177, 178. - " Uses of, 167. - Carbon bisulphide, 163-165. - " " Deaths from, 29. - " " Chronic poisoning by, 164. - " " Poisoning by, 163. - " " Properties of, 165. - Carbon monoxide, 64-71. - " " blood, Characters of, 58, 59. - " " Detection of, 70. - " " Mass poisoning by, 67. - " " Properties of, 64. - " " Symptoms of poisoning by, 64. - " " _Post-mortem_ appearances after poisoning by, 67. - Carbylamine, 490. - Carnelley's observations on the solubility of copper, 610, 611. - Carlisle, A case of food poisoning, 508. - Cascarillin, 245. - Cassava root, Prussic acid in, 195. - Cassella, Yellow, 582. - Castor seeds, 462. - " Deaths from, 30. - Cattle poisoning by meadow saffron, 411. - Cayenne pepper, 30. - Cedrenes, 133. - Cephalopods, Action of poisons on, 43. - Cerbera odallam, 434. - Cevadine, 392. - "Chandoo," 305. - Charles IX. as a poisoner, 8. - Chelidonine, Carbon and nitrogen content of, 262. - " Spectrum of colour reaction of, 55. - Chenot's death by carbon monoxide, 65. - Ching's Worm lozenges, 639. - Chittenden's method of estimating arsenic, 568. - " on the local distribution of arsenic, 562. - Chloral, 154. - " Chronic poisoning by, 160. - " Deaths from, 30. - " Detection of poisoning by, 155. - " Effects of, on animals, 156. - " " man, 157. - " Excretion of, 161. - " Fatal dose of, 158. - " Statistics of poisoning by, 155. - " Treatment of poisoning by, 160, (App.) 690. - " Properties of, 154. - " Separation of, 51, 162. - " Symptoms of poisoning by, 159. - Chlorcodeine, 299. - Chlorine, 72. - " Detection of, 72. - " Effects of, 72. - " _Post-mortem_ appearances in cases of poisoning by, 72. - Chlorodyne, 288. - " Deaths from, 30. - Chloroform, 143. - " Chronic poisoning by, 151. - " Detection and estimation of, 152, 153. - " Effects of liquid, 148. - " " vapours of, 148-152. - " Fatal dose of liquid, 147. - " Impurities in, 144. - " Local action of, 146. - " Manufacture of, 145, 146. - " Physiological effects of, 150. - " Properties of, 144. - " _Post-mortem_ appearances after poisoning by, 148, 152. - " Separation of, 51. - " Statistics of poisoning by, 146, 148. - " Suicidal and criminal poisoning by, 149. - " Treatment of poisoning by (App.), 691. - Chloroxalmethyline, 522. - Chodomisky on the solubility of arsenic, 525. - Choline, 41, 415, 500. - Chromate of lead, Poisoning by, 673. - " potash, 670. - Chrome red, 594, 671. - " yellow, 594, 671. - Chromic acid, Deaths from, 29. - Chromium, 670-675. - " compounds, Effects of, 671. - " Detection of, 674, 675. - " Separation of, 53. - " Statistics of poisoning by, 672. - " Treatment of poisoning by (App.), 691. - Chrysammic acid, 244. - Chrysophyllum glycyphleum, 437. - Cicutoxin, 456, 457. - " Effects of, on animals, 456. - " " man, 456, 457. - " Separation of, 457. - Cinchonidine colour reaction with potash, 240. - " Platinum salt of, 264. - Cinchonine, 246, 252, 253. - " colour reaction with potash, 240. - " Phospho-molybdate of, 238. - " Platinum salt of, 264. - " Value of Mayer's precipitate of, 263. - Cinnabar, 638. - Cleator Moor case of mass poisoning by hydric sulphide, 74. - Clemen's solution of arsenic, 530. - Cleopatra's asp, 484. - Cloth, Action of hydrochloric acid on, 95. - Clupea thrissa, 469. - Coal gas, Content of carbon monoxide in, 64. - " creasote, 165. - " tar naphtha, 130-133. - Cobalt nitrate as an antidote to prussic acid, 203 (footnote). - Cobalt. See _Nickel and Cobalt_. - Cobra poison, 478-480. - " " Antidotes to, 480. - " " Detection of, 482. - " " Effects of, on animals and man, 479. - " " Fatal dose, 479. - " " Treatment of poisoning by (App.), 698, 699. - Cocaine, Action of, on pilocarpine, 403. - " Carbon and nitrogen percentage of, 262. - " Chronic poisoning by, 349. - " Deaths from, 30. - " Effects of, 349. - " Fatal dose of, 350. - " hydrochlorate, 348. - " Pharmaceutical preparations of, 348. - " _Post-mortem_ appearances in cases of poisoning by, 349. - " Properties of, 347, 348. - " Separation of, and Tests for, 348, 349. - " Sublimation of, 259. - Cocculus Indicus, Deaths from, 30. See _Picrotoxin_. - Cochineal, Spectrum of, 59. - Codamine, Reactions of, 317. - Codeine, 252. - " Carbon and nitrogen of, 262. - " Colour reactions of, 240. - " Effects of, 311. - " nitrate, 342. - " phospho-molybdate, 238. - " platinum salt, 264. - " Properties of, 310. - " Spectrum of colour reaction of, 55. - Colchiceine, 409. - " Carbon and nitrogen content of, 262. - Colchicine, 244, 408-413. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, on animals and man, 411. - " Pharmaceutical preparations of, 410. - " Phospho-molybdate of, 238. - " _Post-mortem_ appearances in cases of poisoning by, 412. - " Quack and patent medicines containing, 410. - " Separation of, 413. - " Tests for, 409. - Colchicum, Ancient knowledge of, 4. - " Deaths from, 30. - " Treatment of poisoning by (App.), 691. - " seeds, Amount of colchicine in, 408. - Collidine, 39. - Colocynth, Deaths from, 30. - " Treatment of poisoning by (App.), 692. - Colocynthin, 244. - Colophene hydrocarbons, 133. - Come's cancer paste, 532. - Conhydrine, 262. - Coniine, 39, 248, 249. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, on animals, 267. - " " blowflies, 267. - " " cats, 267. - " " frogs, 267. - " " man, 268. - " Fatal dose of, 268. - " Pharmaceutical preparations of, 266, 267. - " Phospho-molybdate of, 238. - " Physiological action of, 268. - " Platinum salt of, 264. - " _Post-mortem_ appearances in cases of poisoning by, 264. - " Properties of, 264. - " Separation of, from organic matters, 269. - " Statistics of poisoning by, 267. - " Tests for, 265. - " Value of Mayer's precipitate of, 263. - Conium, Botanical characters of, 264. - " Treatment of poisoning by, 266. - Convallamarin, 246, 254. - Copper, Chronic poisoning by, 621. - " carbonate, 620. - " Deaths from, 29. - " Detection of, 625. - " Estimation of, 622. - " leguminate, 617. - " Medicinal dose of, 616. - " nitrate, 616. - " oxide, 610. - " poisoning, Statistics of, 619. - " _Post-mortem_ appearances in cases of poisoning by, 620. - " Properties of metallic, 610. - " salts, Toxic dose of, 619. - " Separation of, 52. - " Solubility of, in various fluids, 610-612. - " subacetate, 620. - " subchloride, 620. - " sulphate, 615, 616. - " sulphide, 610. - " tartrate, 617. - " Treatment of poisoning by, 692. - " Volumetric processes for estimation of, 624. - Copperas, 668. - Coppering of vegetables, 614. - Cornutin, 445, 450. - Corrosive sublimate, Dose of, 640. - " " Effects of, 646. - " " Treatment of poisoning by (App.), 692. - Corydaline, 350. - Cotton seeds, 464. - Cream, Neill, Murders by, 325. - Creasote, 179. - " Deaths from, 30. - Cresol, 166, 178, 179. - " Examination of urine for, 181. - Cresylic acid. See _Cresol_. - Cresyl-sulphate of potash, 181. - Criminal poisoning, 33. - Croton oil, Deaths from, 30. - " Treatment of poisoning by (App.), 692. - Crowfoot, Deaths from, 30. - Crum's method of estimating nitrates, 110. - Cryptopine, Properties of, 315, 316. - Cubebin, 244. - Cuckoo-pint, 465. - Curarine, 254, 405-408. - " Action of, on cephalopods, 43. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Physiological effects of, 407. - " Platinum salt of, 264. - " Separation of, 407. - " Treatment of poisoning by (App.), 693. - Cushman's method of separating strychnine, 334, 335. - Cuttle fish, 502. - Cyanmethaemoglobin, 203. - Cyanogen chloride, 211. - Cyanuric acid, 211. - Cyclamen, 436. - Cymene, 135. - Cymogene, 129. - Cyon's experiments on barium, 681. - Cystinuria, Amides in, 494. - Cytisine, 387-390. - " Carbon and nitrogen content of, 262. - " Effects of, on animals and man, 389. - " Properties of, 388. - " Reactions of, 388. - " Treatment of poisoning by (App.), 694. - - Dalby's carminative, 287. - Darlaston case of poisoning by carbon monoxide, 68. - Da Silva's test for eserine, 399. - Datura plant, 370. - " seeds, 370. - " poisoning in India, 376. - Davidson's cancer remedy, 532. - Davie, Margaret, Execution of, 9. - Davy's method of generating arsine, 571. - Delirium from Datura poisoning, 379. - Delphinine, 252. - " Carbon and nitrogen content, 262. - " Colour reactions of, 240. - " Gold salt of, 264. - " Melting-point, 260. - " Phospho-molybdate of, 238. - Delphinoidine, Gold and platinum salts of, 264. - De Pauw's case of poisoning by digitalis, 430. - Dermatol, 625. - Desquamation after chloral poisoning, 161. - Diamines, Rate of formation of, 492. - " Separation of, 487. - Dichlorethyl sulphide, 35. - Diethylamine, 491. - Diethylenediamine, 497. - Digitalacrin, 421. - Digitalein, 419, 420. - Digitaleretin, 419, 421. - Digitaletin, 419, 420. - Digitalin, 245, 246, 419, 420, 422. - " Action of, on intestinal tract, 429. - " Case of poisoning by, 426. - " Fatal dose of, 423. - " Local action of, 427. - " Physiological action of, 427. - " Reactions of, 422. - " Spectrum of colour reactions of, 55. - Digitalis, Doses of, 424. - " Effects of, on man, 424-427. - " group of poisons, 419, 431. - " leaf, 422. - " Pharmaceutical preparations of, 422. - " _Post-mortem_ appearances after poisoning by, 430. - " Separation of, from the tissues, &c., 430, 431. - " Statistics of poisoning by, 424. - " Treatment of poisoning by (App.), 693. - Digitonin, 419. - Digitoxin, 419, 420, 426. - Dihydrolutidine, 506. - Dimethylamine, 491. - Dimethyl resorcin, 38. - Dinitrobenzene, 189-192. - " Detection of, 192. - " Effects of, 189. - Dinitrobrucine, 341. - Diodon, Poisonous properties of, 470. - Dioscorides, 3. - Disinfectants, Assay of, 188. - Disinfecting fluids, 166. - Dixon's pills, 581. - Dolbeau's experiments on anaesthetising sleeping persons with - chloroform, 149. - Domeyko's method of mercury assay, 654. - Donovan's solution of arsenic, 530. - Dott's, Dr., process for assay of opium, 283, 284. - " tests for purity of chloroform, 145. - Dover's powder, 286. - Dragendorff's method for detecting cantharidine, 476. - " method for detecting curarine, 407. - " process for separating alkaloids, 241-254. - " shorter process, 254, 255. - " reagent, 239. - Duboia Russellii, 483. - Duc de Praslin, Suicide of, 544. - Duflos' hydric cyanide, 193. - Dulcamara, 437. - Dunstan's researches on aconite, 351. - Dutch pink, 594. - Dupre's observations on copper, 613. - Dworzak and Heinrich's auto-experiments on nicotine, 277. - - Ecboline, 443, 444. - Ecgonin methyl ester, 347. - Eczema due to chromium salts, 672. - Eel, Poisonous properties of the blood of, 469. - Egyptian knowledge of poisons, 2. - Elaterin, 243. - Electrolytic method of separating lead, 609. - Emetics as antidotes (App.), 586. - Emetine, 249, 253. - " Platinum salt of, 264. - " Phospho-molybdate of, 238. - Emplastrum calefaciens, 472. - " cantharides, 472. - " plumbi, 593. - Ergot, 442-450. - " Chemical characters of, 443. - " Dose of, 446. - " Liquid extract of, 445. - " oil, 443. - " Pharmaceutical preparations of, 446. - " Physiological action of, 448, 449. - " Separation of active principles of, 450. - " Symptoms of poisoning by, 448. - Ergotin, 446. - Ergotinine, 443. - Ergotism, 446-448. - Erythrophlein, 436. - Eserine. See _Physostigmine_. - Essential oils, 133. - Ether, 141. - " as an anaesthetic, 142. - " as a poison, 142. - " Deaths from, 29. - " Fatal dose of, 142. - " recovery apparatus, 48. - " Separation of, from organic matters, 143. - Ethylamine, 41, 491. - Ethyl chloride in chloroform, 145. - Ethylidene-diamine, 492. - Ethiops mineral, 637. - " of antimony, 581. - Ethyl-mustard oil, 490. - " sulphide as a poison, 35. - Euchlorine test for carbolic acid, 178. - Eulenberg's experiments on effects of benzene vapour, 132. - " experiments on effects of creasote vapour, 180. - " experiments on effects of hydrochloric acid gas, 95. - " experiments on effects of mercury vapour, 641. - " experiments on effects of oxalic acid vapour, 514. - " experiments on effects of petroleum vapour, 130. - Euonymin, 433. - Eyesight, Affection of, from dinitrobenzene, 190. - - Falck's observations on brucine poisoning, 341, 342. - " " on phosphorus poisoning, 216. - " " on silver nitrate poisoning, 631. - " " on strychnine poisoning, 325. - Ferric chloride, 666. - " " Effects of, on animals and man, 666, 667. - " " test for carbolic acid, 177. - Ferrous sulphide, 668. - Ferrocyanide, Poisonous action of, 210. - Filehne's observations on nitrobenzene poisoning, 187. - Filicic acid, 466. - Fish, Effects of carbolic acid on, 170. - " Effects of picrotoxin on, 452. - " Poisonous, 468-470. - Fitzwalter, Maud, Poisoning of, 8. - Fleitmann's method of detecting arsenic, 571. - Fleming's tincture of aconite, 351. - " " " Poisoning by, 357. - Fleury's method of opium assay, 284, 285 (footnote). - Flour, Detection of ergot in, 445. - Flowers of antimony, 581. - Flueckiger's test for brucine, 343. - " " carbolic acid in creasote, 180. - " " coniine, 266. - " " strychnine, 338. - Fly poison, 531. - " water, 532. - Food poisoning, 506-508. - Fool's parsley, 457. - Fougnies, Case of, 274. - Foxglove. See _Digitalis_. - Fraenkel's observations on the effect of sulphuric acid on the kidney, - 85. - Fraser's observations on the effect of strophantin, 434. - French law as to poison, 22. - Fresenius and Hintz's method of detecting arsenic in wall paper, 566. - Friedlaender's aconitine nitrate, Fatal dose of, 356. - Frog's heart, Action of digitalis on, 429-431. - Froehde's reagent, 239. - Fuchsine as a test for alcohol in chloroform, 145. - Fungi, Poisonous, 413-418. - " " Deaths from, 30. - - Galmette's experiments on cobra poison, 481. - Gasoline, 129. - Gastric juice, Hydrochloric acid in, 93. - Gautier's method of isolating ptomaines, 485. - Gehlen's death from breathing arsine, 527. - Gelsemic acid, 345. - Gelsemine, Carbon and nitrogen content of, 262. - " Effects of, on animals and man, 345, 346. - " Fatal dose of, 345. - " Separation of, 347. - " Treatment of poisoning by, 694. - Gelsemium sempervirens, Botanical characters of, 345. - Gergen and Posner's observations on chromium, 671. - Gerger and Baumann's method of separating guanidine, 499. - German law as to poison, 21. - Gipsies, Knowledge of poisons possessed by, 5. - Goby, Poisonous properties of, 470. - Godfrey's cordial, 237. - Gold chloride as an antidote to cobra poisoning, 481. - " as a test for alkaloids, 287. - Goulard balsam, 593. - " water, 593. - Grandeau's test for digitalin, 422. - Grandval and Lajoux's method of separating alkaloids, 255. - Grasset and Amblard's observations on the action of morphine, 297. - Gratiolin, 244. - Green vitriol, 668. - Greek knowledge of poisons, 2. - Grehant's observations on carbon monoxide poisoning, 66. - Grehant and Martin's experiments on opium smoke, 305. - Grinrod's remedy for spasms, 287. - Group reagents, 236. - Grypsophila-sapotoxin, 436. - Guaiacol, 179. - Guaiacum test for blood, 61. - Guanidine, 498. - Gunn's method of detecting oxalic acid, 520. - Guenzburg's test for hydrochloric acid, 99. - Gusserno's experiments on lead, 597. - - Haematin crystals, 58, 59. - " Spectrum of, 60. - Hahnemann's soluble mercury, 638. - Hair-dyes, 630. - Halogens, Influence of, in compounds, 35. - Ham (American), poisoning by, 507. - Harley's experiments on aconitine, 356. - Harnack's experiments on copper, 617. - " lead, 596. - Heart, Action of digitalis on, 428. - " " poisons on, 44. - Hebrew knowledge of poisons, 5. - Heinrich's auto-experiments on cantharides, 473. - Hellebore, 242, 246, 432, 433. - Helleborein, 433. - Helleboretin, 433. - Hellebore infusion, Death from, 433. - " Poisoning by, 396. - " root, Poisoning by, 433. - Helleborin, 247, 432, 433. - Helleborus f[oe]tidus, Odorous principle in, 433. - Hemlock. See _Coniine_, _Conium_. - Hempel's method of detecting carbon monoxide, 71. - Henbane. See _Hyoscyamus_, _Hyoscyamine_. - Henry VIII.'s apprehensions as to poison, 12 (footnote). - Herniari-saponin, 436. - Hexamethylene diamine, 497. - Hilger's experiments on the solubility of copper, 611. - " test for sulphuric acid, 88. - Hind's sweating ball, 581. - Hofmann's tests for amines, 490. - " " carbon disulphide, 165. - Hog cholera, Toxines of, 505. - Homolle's digitalin, 421. - Horse chestnut, Deaths from, 30. - Hottot's aconitine, Case of poisoning by, 365 (footnote). - Hubers observations on dinitrobenzol poisoning, 189-191. - Hunter's solution of chloral, 160. - Hydric sulphide, 72-74. - " Chronic poisoning by, 74. - " Detection of, 74. - " Effects of, 73. - " _Post-mortem_ appearances in cases of poisoning by, - 74. - Hydric sulphocyanide, 211. - Hydrobenzamide, 40. - Hydrochloric acid, 29, 91-102. - " Detection of, 98. - " Effects of, 96. - " Estimation of, 100. - Hydrochloric acid, Fatal dose of, 93. - " Influence of, on vegetation, 94. - " in gastric juice, 93. - " Museum preparations of effects of poisoning by, 97, 98. - " _Post-mortem_ appearances in cases of poisoning by, 97. - " Properties of, 91. - " Statistics of poisoning by, 92. - " Treatment of poisoning by, (App.), 687. - Hydrocollidine, 506. - Hydrocotarnine nitrate, 342. - " " Reactions of, 317. - Hydrocyanic acid (Prussic acid), 192. - " Accidental and criminal poisoning by, 197. - " Action of, on living organisms, 198. - " Chronic poisoning by, 203. - " Deaths from, 30. - " Distribution of, in vegetable kingdom, 194. - " Estimation of, 209. - " Fatal dose of, 198. - " Length of time after death detectable, 208. - " Medicinal preparations of, 192. - " Poisoning by, 193. - " _Post-mortem_ appearances in cases of poisoning by, - 203. - " Properties of, 192. - " Separation of, from organic matter, 51, 206. - " Statistics of poisoning by, 196. - " Symptoms observed in animals poisoned by, 199. - " Symptoms observed in man poisoned by, 201. - " Tests for, 204. - " Treatment of poisoning by, 698. - " Use of, in the arts, 193. - Hydrofluoric acid, Deaths from, 29. - Hydropotassic Oxalate. See _Oxalic acid_. - " tartrate, 122. - Hyoscine, 385. - Hyoscyamine, 251. - Hyoscyamine, Association of, with atropine, 369. - " Carbon and nitrogen content of, 262. - " distinguished from atropine, 373. - " gold salt, 264. - " Melting-point of, 259. - " Phospho-molybdate of, 238. - " Properties of, 383. - " Separation of, from organic matters, 385. - " Tests for, 384. - " Treatment of cases of poisoning by, 694. - Hyoscyamus, Alkaloids of, 382. - " Extract of, 384. - " Juice of, 384. - " Oil of, 384. - " Ointment of, 384. - " Pharmaceutical preparations of, 383, 384. - " Tincture of, 384. - Hypaphorine, 339. - Hypochlorite and Ammonia as a test for carbolic acid, 177. - - Ibsen's experiments on strychnine, 337. - Icthyismus gastricus, 469. - Ictrogen, 463. - Igasurine, 344. - Illicium religiosum, 484. - Imide groups, 39. - Indian knowledge of poisons, 4. - Indican, Carbon and nitrogen content of, 262. - Infusoria, Action of poisons on, 42. - " Effects of carbolic acid on, 169. - Insects, Action of poisons on, 43. - Iodic acid test for morphine, 294. - Iodine, Deaths from, 29. - " with hydriodic acid as a test for alkaloids, 236. - " with potassic iodide as a test for alkaloids, 237. - " Treatment of poisoning by (App.), 694. - Iodoform test for alcohol in chloroform, 145. - Ipecacuanha and morphine lozenges, 286. - " Compound powder of, 286. - Iris, Action of poisons on, 45. - Iron chloride, Elimination of, 667. - " " Deaths from, 29. - " " Cases of murder by, 667. - " " Poisonous properties of, 665-670. - " salts, Separation of, from contents of stomach, 669. - " stains, 676. - Isatropic acid, 372. - Iso-amyl-amine, 492-506. - " nitrite, 141. - Iso-cicutine, 266. - Iso-nitrite, 490. - Iso-santonin, 442. - - Jaborandi, 402. - " Treatment of poisoning by (App.), 694. - Jaksch's test for hydrochloric acid, 99. - Javelle water, 118. - Jequirity, 462. - Jervine, 246, 393. - " Carbon and nitrogen content of, 262. - " Phospho-molybdate of, 238. - " Spectrum of furfurol reaction of, 55. - John of Ragubo, 9. - Johnson's pills, 580. - - Kamschatkan custom of taking Amanita muscaria, 414. - Katipo, 470, 471. - Keighley, Cases of lead poisoning in, 604. - Keyser's pills, 640. - Kidneys, Appearance of, in oxalic acid poisoning, 517. - " Appearance of, in phosphorus poisoning, 517. - King's yellow, 532. - Kino, Compound powder of, 285. - Kobert and Kuessner's experiments on sodic oxalate, 513. - Kobert's classification of poisons, 24, 25. - " observations on barium as a poison, 682. - " " " sphacelic acid and cornutin, 450. - " on the influence of carbon monoxide on the nervous system, - 66. - " test for prussic acid, 206. - Koller's prussic acid, 193. - Koningh's, L. de, process for detecting chromium, 675. - Koppeschaar's method of assaying carbolic acid, 182. - Kreozote. See _Creasote_. - K[)u]sa-[=u]s[=u] (Japanese Aconite root), 368 (footnote). - Kuester's observations on carbonic acid, 173. - - Laburnum seeds, Deaths from, 30. - Laburnum. See _Cytisine_. - Langaard's observations on Illicium religiosum, 454. - Langley's observations on pilocarpine, 403. - Lanthopine, Reactions of, 317. - Lassar's researches on nitric acid vapour, 104. - Lathyrus sativus, 464. - Latrodectus malmignatus, 470. - Laudanum. See _Opium_. - Laudamine nitrate, Lethal dose of, 342. - " Reactions of, 317 - Laudamosine, 317. - Lauro-cerasin, 195. - " Carbon and nitrogen content of, 262. - Lead, 591-607. - " acetate, 592, 593. - " Acute poisoning by, 597. - " as a poison, 595. - " basic acetate, 607. - " carbonate, 592, 593. - " " Dose of, 607. - " chromate, 599, 670, 671. - " " Case of poisoning by, 173. - " Chronic poisoning by, 603, 604. - " Deaths from, 29. - " Detection and estimation of, 608. - " Effects of, on animals, 596. - " " man, 597. - " " nervous system, 600. - " Elimination of, 606. - " Encephalopathy, 600. - " Fatal dose of, 606, 607. - " in American overland cloth, 596. - " in foods, 596. - " in glass, 596. - " iodide, 593. - " Localisation of, 607. - " " " in the brain, 602, 603. - " nitrate, 594. - " oxides, 591, 592. - " Physiological action of, 605. - " pigments, 594. - " plaster, 593. - " poisoning among white lead employes, 601-603. - " " from water, 604. - " " Influence of, on pregnancy, 603. - " " _Post-mortem_ appearances in, 605. - " " Statistics relative to, 594. - " " Treatment of, 607, 694. - " pyrolignite, 594. - " Separation of, 50, 52. - " sulphate, 592, 594. - " sulphide, 592, 609. - Ledoyen's disinfecting fluid, 593. - Lehmann's experiments on amount of copper soluble in fats, 611. - " experiments on the effect of copper, 618. - " observations on sulphuric acid, 89. - Lemaurier's odontalgic essence, 287. - L'Emery, Nicholas, 14. - Lemonade, Detection of lead in, 609, 610. - Lemy's experiments on thallium, 676. - Lettuce, Content of hyoscyamine in, 381. - Lewis' silver cream, 593. - Lieberman's nitroso reaction, 489. - Liebert's _Cosmetique Infaillible_, 593. - Life tests, 42-46. - Lime, Deaths from, 29. - " Oxalate identification, 520, 521. - Linstow's case of poisoning by lead chromate, 673. - Lipowitz's sulphur test for phosphorus, 232. - Liquor Ammoniae Arsenitis, 530. - " Arsenicalis, 530. - " Arsenii et Hyd. Iod., 530. - " Bellostii, 651. - " Epispasticus, 472. - " potassae, 117. - " sodae, 118. - " " effervescens, 118. - Litharge, 591. - Liver, Fatty degeneration of, in poisoning by phosphorus, 225. - " Microscopy of, in phosphorus poisoning, 227. - " of antimony, 581. - " Yellow atrophy of, 228. - Lobelia, Deaths from, 30. - Lobeliin, 249. - Locusta, 6. - Locust tree, 465. - Loew's theory as to poisons, 39. - Lowe's method of assaying disinfectants, 181. - Ludwig's experiments on the localisation of arsenic, 561, 562. - " method for the detection of mercury, 650. - Lungs, Changes of, in phosphorus poisoning, 228. - Lupinine, 463. - Lupins, 463. - Lutidine as an antidote for strychnine, 334 (footnote). - " in tobacco smoke, 276. - Lycosa tarantula, 470. - - Macdonnell's disinfecting powder, 167. - Macphail's case of poisoning by carbolic acid, 171. - MacMunn's observations on the blood in nitrobenzol poisoning, 191. - Macniven's case of poisoning by potassic bichromate, 673. - Madagascar ordeal bean, 436. - Male fern, 465, 466. - Malpurgo's test for nitrobenzene, 188. - Mandelin's reagent, 239. - Mann's reagent, 239. - Marking inks, 620. - Marsh's test for arsenic, 14, 556. - Maschka's case of acute poisoning by copper sulphate, 620. - Maschka's case of acute poisoning by oleandrin, 435. - Mason's case of arsenical poisoning, 564, 565. - Matches and Vienna paste, 213. - Maybrick case, 546-548. - Mayer's reagent, 263. - Meadow crowfoot, Deaths from, 30. - Meconic acid, 318, 319. - Meconin, Chemical composition of, 90. - " Properties of, 317, 318. - Melanthin, 437. - Meletta venenosa, 469. - Melting-point, 261. - Menispermine, 451. - Merck's aconitine, Fatal dose of, 356. - " veratrine, 392. - Mercurial lotion, 636. - " ointment, 635. - " tremor, 644. - Mercuric cyanide, 210, 648. - " ethyl chloride, 635. - " methide, 645. - " potass-iodide, 237. - " salts, Tests for, 652. - " " Volumetric estimation of, 655. - " sulphide, 638. - Mercurous acetate, 635. - " salts, 634. - " " Tests for, 652. - " " Volumetric estimation of, 655. - Mercury, 633. - " Absorption of, by the skin, 643. - " and chalk, 634. - " and quinine, 638. - " cyanide, 638. - " " Tests for, 652. - " Deaths from, 29. - " Detection of, in organic substances, 652. - " Elimination of, 650. - " Estimation of, 654. - " Green iodide of, 637. - " in the arts, 639. - " in veterinary medicine, 640. - " liniment, 635. - " Localisation of, 650. - " Medicinal preparations of, 634-639. - " Museum preparations of, illustrative of cases of poisoning - by, 649. - " nitrate, Pathological changes in cases of poisoning by, 650. - " " poisonous action of, 647, 648. - " oleate, 636. - " perchloride of, 636. - " plaster, 635. - " poisoning, statistics of, 641. - " _Post-mortem_ appearances in cases of poisoning by, 648, 649. - " Red iodide of, 637. - " " oxide of, 637. - " Separation of, 50, 52. - " subchloride, Ointment of, 636. - " " Pill of, 636. - " sulphide, 637. - " " Identification of, 653. - " sulpho-cyanide, 639. - " Tests for, 651. - " Treatment of poisoning by, 648, 692. - " vapour, Effects of, 641-643. - Metacresol, 179. - Meta-dinitrobenzol, 189. - Metaldehyde, 154. - Metantimonic acid, 579. - Metaphenylenediamine, 497. - Methaemoglobin, Spectrum of, 58. - Methene dichloride, 154. - Metho-codeine, 299. - Methylamine, 491. - " Carbon and nitrogen content of, 262. - Methylated chloroform, 144. - " spirits, Deaths from, 29. - Methyl brucine, 339 (footnote). - " " iodide, 342. - " coniine, 248. - " cresol, 179. - " cyanide, 211. - " guanidine, 499, 500. - " salicylic acid, 38. - " strychnine, 37, 339 (footnote). - Mezereic acid, 442. - Mezereon, 442. - Michet's experiments on the relative toxicity of metals, 41. - Micro-spectroscope, 54. - Milk, Contamination of, by zinc, 657. - Mineral acids, Treatment of poisoning by, 83. - " blue, 532. - " green, 616. - Mitchell and Reichert's experiments on snake poison, 477. - Mitchell's pills, 580, 640. - Mithradetes Eupator, 2. - Mitscherlich's process for the detection of phosphorus, 229. - Monkshood. See _Aconite_. - Monobromated camphor, 135. - Monochlor-ethyl sulphide, 35. - Mordant's Norton's drops, 639. - Morgagni's case of poisoning by hellebore, 433. - Morphine, 253. - " acetate, 292, 293. - " and strychnine, Detection of, 338. - " bimeconate, 287. - " Carbon and nitrogen content of, 262. - " Chemical constitution of, 293. - " Deaths from, 30. - " derivatives, 299. - " Effects of, 298. - " Extraction of, 308, 309. - " hydrate, 293. - " hydrochlorate, 292. - " lozenges, 287. - " meconate, 292. - " phospho-molybdate, 237. - " Physiological action of, 298. - " Platinum salt of, 264. - " Properties of, 291, 292. - " Separation of, 51, 307. - " Solutions of, 286, 287. - " Spectra of colour reactions of, 55. - " sulphate, 293. - " Suppository of, 286. - " tartrate, 292. - " Tests for, 294. - " Treatment of poisoning by (App.), 695. - " Value of Mayer's precipitate of, 263. - Morelle, Poisonous properties of, 418. - Morson's English creasote, 179. - Moulds, Effects of, on arsenical wallpapers, 542. - Mountain green, 616. - Mucor phymocetes, 5. - Multiple antidote (App.), 701. - Muscarine, 413-417. - " Action of, on heart in poisoning by digitalin, 429, - " Carbon and nitrogen content of, 262. - " Detection of, 416, 417. - " Gold salt of, 264. - " Poisoning by, 414-417. - " Solution of (App.), 686. - " Treatment of poisoning by (App.), 695. - Mussels, Poisoning by, 504. - Mydaleine, 498. - Mydatoxine, 504. - Mytilotoxine, 504. - - Nagelvoort's test for physostigmine, 399. - Naja Haje, Poison of, 484. - Naples yellow, 582. - Naphtha, Deaths from, 29. - Naphthal-amine (acyclic and aromatic), 36. - Narceine, 247, 253, 254. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, 313. - " Melting point of, 259. - " Platinum salts of, 264. - " Properties of, 312. - Narcotine, 252. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, 310. - " Gold and platinum salts of, 264. - " Melting-point of, 259. - " Spectrum of colour reactions, 55. - " Tests for, 309, 310. - " Value of Mayer's precipitate of, 263. - Neill, Thomas, Murders by, 325. - Nepaline, 252, 253. - " Carbon and nitrogen content of, 287. - Neriin, 435. - Neuridine, 493, 494. - Neurine, 501. - Neuwieder green, 616. - Nevin's experiments on chronic antimony poisoning, 583, 586. - Newcastle white, 594. - Nicander of Colophon, 3. - Nickel and cobalt, 662-665. - " Effects of, on animals, 663, 664. - " Identification of, 665. - " Separation of, 664. - Nickelo-potassic cyanide, 665. - Nicotine, 249. - " and coniine, Distinguishing marks between, 272, 273. - " Carbon and nitrogen in, 262. - " Colour reactions of, 240. - " Effects of, on animals and man, 273, 274. - " Estimation of, in tobacco, 270. - " Fatal dose of, 278. - " in various species of tobacco, 270. - " Phospho-molybdate of, 238. - " Physiological action of, 277. - " Platinum salt of, 264. - " _Post-mortem_ appearances in cases of poisoning, 278. - " Properties of, 271, 272. - " Separation of, from organic matters, 278. - " Treatment of poisoning by (App.), 696. - Nikitin's researches on sclerotic acid, 449. - Nitrate of mercury, 638. - Nitre, 123. - Nitric acid, 102-110. - " " Action of, on vegetation, 104. - " " Deaths from, 29. - " " Detection and estimation of, 109. - " " Effects of liquid, 105. - " " Fatal dose of, 104. - " " Local action of, 106. - " " Museum preparations of, 107. - " " _Post-mortem_ appearances in cases of poisoning by, 107. - " " Properties of, 102. - " " Symptoms of poisoning by, 103. - " " Uses in the arts of, 103. - " " vapours, 104. - Nitrobenzene, 132, 183-188. - " Action of, 187. - " Detection and separation of, 188. - " Effects of liquid, 185, 186. - " Effects of, on the blood, 191. - " Fatal dose, 186. - " Pathological appearances after poisoning by, 187. - " Poisoning by liquid, 185. - " " vapour, 184. - " Separation of, 51. - " Symptoms of poisoning by, 184. - " Treatment of poisoning by (App.), 696. - Nitro-glycerin, Deaths from, 30. - Nitro-picrotoxin, 452. - Nottingham, Cases of food poisoning in, 507. - " white, 594. - Nurse's drops, 287. - Nux Vomica, 319. - " " Aqueous extract of, 322. - " " Deaths from, 30. - " " Pharmaceutical preparations of, 322-324. - " " powder, Analysis of, 323. - " " Spirituous extract of, 322. - " " Tincture of, 323. - - Oats, Content of copper in, 612. - Obolouski's process for separating colchicine, 413. - [OE]nanthe crocata, Poisoning by, 458, 459. - Ogston's test for chloral, 162. - Oil of almonds, Deaths from, 30. - " bitter almonds, 188, 193, 209. - " juniper, Deaths from, 29. - Oils, power of dissolving copper, 611. - Ointment of subacetate of lead, 593. - Oldham, Cases of food poisoning in, 507. - Oleandrin, 435. - Onsum's experiments on barium, 681. - Opianine, 316. - Opium, Action of solvents on, 282. - " Analysis of, 282. - " Assay of, 283, 284. - " Composition of, 281-284. - " Compound powder of, 285. - " " tincture of, 285. - " Confection of, 286. - " Deaths from, 30. - " Detection of, 290. - " Diagnosis of poisoning by, 303. - " eating, 304, 305. - " Extract of, 286. - " Fatal dose of, 290. - " Liniment of, 286. - " Pharmaceutical preparations of, 285-287. - " Poisoning of children by, 289. - " _Post-Mortem_ appearances in cases of poisoning by, 306, 307. - " smoking, 305. - " Statistics of, 288. - " Tincture of, 285. - " Treatment of poisoning by (App.), 695. - " wine, 286. - " and chalk, Compound powder of, 286. - " and galls, Ointment of, 286. - " and lead pills, 285. - " and morphine, Absorption by the skin of, 303. - " " Action of, on dogs, 297. - " " Action of, on frogs, 296. - " " Action of, on man, 299-302. - " " Dose of, 289, 290. - " " Poisoning by, 296. - " " Treatment of poisoning by, 306, 695 (App.). - Orfila as a toxicologist, 15. - Organic analysis, Identification by, 261. - Organic matter, Destruction of, by hydrochloric acid, 49. - Orpiment, 529. - Ortho-cresol, 179. - Ortho-dinitrobenzene, 189. - Ortho, para, and meta derivatives as poisons, 36, 37. - Oxalate of lime, 511, 512. - Oxalic acid, Deaths from, 29. - " " Effects of, on animals, 513. - " " " leeches, 514. - " " " man, 515. - " " Estimation of, 521, 522. - " " Fatal dose of, 513. - " " in the form of vapour, 514. - " " Pathological changes produced by, 516, 518. - " " Physiological action of, 516. - " " Properties of, 510, 511. - " " Separation of, 512. - " " Statistics of poisoning by, 512. - " " Treatment of poisoning by (App.), 697. - " " Uses in the arts of, 512. - Oxal-methyline, 522. - Oxal-propyline, 522. - Oxyacanthine, Carbon and nitrogen content of, 262. - Oxycresol, 179. - Oxymandelic acid, 229. - - Pagenstecher and Schoenbein's test for prussic acid, 205. - Papaverine, 246, 253. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, 314. - " Melting-point of, 259. - " Platinum salt of, 264. - " Spectrum of colour reactions of, 55. - Papier moure, 531. - Paraceto-amido-phenol, 37. - Para-coniine, 266. - Para-cresol, 179. - Para-digitaletin, 419, 421. - Para-dinitrobenzol, 189. - Paraffin, Deaths from, 29. - " oil, 130. - Paraldehyde, 154. - Paralysis from lead, 600. - Paramenispermine, 451. - Para-phenylene-diamine, 497. - Paregoric. See _Opium_. - Parillin, 437. - Pattison's white, 594. - Payne and Chevallier's experiments on zinc, 657. - Peach, Prussic acid in, 195. - Pedler's experiments on cobra poison, 478. - Pelikan's observations on the poisonous properties of potassic - dichromate, 671. - Pellagra's test for morphine, 295. - Pennyroyal, Deaths from, 30. - Pental, 154. - Pentamethylene-diamine, 494-496. - Pentane, 154. - Peptotoxine, 502. - Perchloride of iron solution, 666. - Pereirine, 344, 345. - Personnes' method of volumetrically estimating mercury, 655. - Petroleum, 129-131. - " Effects of, 130. - " naphtha, 130. - Petit's aconitine nitrate, 355. - Petromyzon fluviatilis, 469. - Pfaff's prussic acid, 193. - Pharaoh's serpent, 639. - Phenic acid. See _Carbolic acid_. - Phenol. See _Carbolic acid_. - Phenylene-diamine, 40. - Phenylsulphate of potassium, 181. - Phloro-glucin, 37, 466. - Phlorol, 179. - Pierre divine, 616. - Phosphine, 213. - " Production of, as a test for phosphorus, 230. - " Spectrum of, 232. - Phospho-molybdic acid as a test, 237. - Phosphorated oil, 213. - Phospho-tungstic acid, 238. - Phosphorus, 5, 212-235. - " Antidotes to poisoning by, 223; (App.), 697. - " Criminal poisoning by, 221. - " Deaths from, 29. - " Detection of, 229. - " Effects of, 217. - " Fatal dose of, 216. - " paste, 214. - " Period of death by, 220. - " period after which it may be detected, 234. - " period of commencement of symptoms, 220. - " Poisoning effects of, 291. - " _Post-mortem_ appearances in cases of poisoning by, 224. - " Properties of, 212. - " Quantitative estimation of, 234. - " Separation of, 51. - " Statistics of poisoning by, 215. - " Treatment of poisoning (App.), 697. - " vapour, Effects of, 220, 221. - Phosphuretted hydrogen. See _Phosphine_. - Physostigmine, 251, 397-401. - " Carbon and nitrogen content of, 262. - " Effects of, on animals and man, 400. - " Extract of, 398. - " Fatal dose of, 402. - " Pharmaceutical preparations of, 399. - " Physiological action of, 401. - " _Post-mortem_ appearances in cases of poisoning by, - 401. - " Separation of, 401, 402. - " Spectra of colour reactions, 55. - " Tests for, 399. - " Treatment of poisoning by (App.), 690. - Picoline in tobacco smoke, 276. - Picraminic acid, 455. - Picric acid, 243, 244. - " and picrates, 454, 455. - " " Effects of, 455. - " " Tests for, 455. - Picrotoxin, 247, 451. - " Effects of, on man and animals, 452, 453. - " Fatal dose of, 452. - " Physiological action of, 453. - " Separation from organic matters of, 453, 454. - " Sublimate of, 260. - " Treatment of poisoning by (App.), 697. - Pilocarpine, 402-404. - " Chemical characters of, 402, 403. - " Effects of, 403. - " Gold and platinum salts of, 264. - " nitrate, Solution of (App.), 686. - " Sublimate of, 260. - " Tests for, 403. - " Treatment of poisoning by (App.), 698. - Pimento, 244. - " Volatile alkaloid of, 250. - Pinewood test for carbolic acid, 177. - Piperidine, 39. - Piperine, 242, 244. - " Carbon and nitrogen content of, 262. - " Phospho-molybdate of, 238. - " Platinum salt of, 264. - Piturie, 279. - Platinum chloride as a test for alkaloids, 237. - Plugge's researches on fatality of aconite, 355. - Pocula emetica, 582. - Poisons, Author's classification of, 25. - " Classification of, 23. - " General method of search for, 46-54. - " Husemann's definition of, 22. - " Kobert's classification of, 24. - " " definition of, 23. - " Legal definition of, 20. - " Lore of, 1-13. - " Scientific definition of, 22, 23. - " Statistics relative to, 28-34. - Polygalic acid, 436. - Pommerais, Case of, 430, 431. - Poor man's friend, 639. - Poppy syrup, 287. - " tea, 289. - Populin, 243. - Pork, poisoning by, 507, 508. - Porta, J. Baptista, 10. - Portsmouth-case of food poisoning, 508. - Potash binoxalate, Deaths from, 29. - " " Fatal dose of, 513. - " " Pathological changes produced by, 518. - " carbonates, 117. - " caustic, Deaths from, 29. - " Colour reactions with the alkaloids, 240 (footnote). - " Pharmaceutical preparations of, 117. - " Properties of, 116, 117. - " Statistics of poisoning by, 118. - " Treatment of poisoning by (App.), 688. - Potassic and sodic nitrate, Action of, 123. - Potassic bichromate, 470. - " " Deaths from, 29. - " " Use in the arts of, 671 - " bromide, Deaths from, 29. - " chlorate, 124. - " " Deaths from, 29. - " " Detection and estimation of, 126. - " " Effects of, 125, 126. - " " Elimination of, 126. - " " Experiments on animals with, 124. - " " Poisonous properties of, 124. - " " Uses of, 124. - " cyanide, Deaths from, 30. - " " Effects on animals and men of, 198. - " " Length of time detectable, 208. - " " _Post-mortem_ appearance in cases of poisoning by, - 204. - " " Separation of, 206. - " " Tests for, 204. - " " Treatment of cases of poisoning by (App.), 698. - " nitrate, 123. - " " Statistics of poisoning by, 123. - " " Treatment of poisoning by (App.), 696. - " phenyl-sulphate, 181. - " sulphate, 122. - " sulpho-cyanide, 211. - " xanthate, 165. - " xantho-genate, 165. - " xanthylamate, 165. - " zinc-iodide, 239. - Potassium salts, Elimination of, 123. - " Tests for, 121. - Poudre epilatoire, 680. - Powell's balsam of aniseed, 287. - Preyer's separation of curarine, 406. - Prince of Wales, precaution against poison, 12. - Pritchard, Mrs., Poisoning of, 585. - Propylamine, 491. - Protapine, Reactions of, 317. - Protoveratridine, 393. - Protoveratrine, 391. - Prussic acid. See _Hydrocyanic acid_. - Pseudo-jervine, 293. - " -morphine, 316. - Ptomaine analogous to coniine, 269. - " " nicotine, 278. - " " veratrine, 397. - " Definition of, 485. - Putrescine, 496, 497. - Pyraconine, 351, 354. - Pyraconitine, 351, 354. - Pyridine, 39, 276. - " alkaloid in the cuttle fish, 502. - Pyro-catechin, 175. - Pyro-gallol, 37. - - Quebrachine, 344. - " Spectra of colour reactions of, 55. - Quillaja-sapotoxin, 436. - Quillajic acid, 436. - Quinidine colour reaction with potash, 240 (footnote). - " Value of Mayer's precipitate of, 263. - Quinine, 248, 252. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Gold and platinum salts of, 264. - " Phospho-molybdate of, 238. - " Spectrum of colour reaction, 55. - " Value of Mayer's precipitate of, 263. - - Rat poison, 531, 680. - Rayner, Dr. Henry, on connection between insanity and lead poisoning, - 600, 601. - Realgar, 528. - Red lead, 594. - Redwood's ink, 630. - _R._ v. _Lamson_, 364, 365. - _R._ v. _M'Conkey_, 361. - _R._ v. _Moore_, 648. - _R._ v. _Smith_, 648. - _R._ v. _Taylor_, 604. - _R._ v. _Wilson_, 411. - _R._ v. _Wren_, 324. - Reid, Dr., on Darlaston case of poisoning by carbon monoxide, 68. - Reinsch's test for arsenic, 558, 559. - Resorcin, 38. - Retford case of food poisoning, 508. - Rettgers's observations on arsenical mirror, 558. - Reynold's gout specific, 410. - Rhigolene, 129. - Rh[oe]adine, Carbon and nitrogen content of, 262. - " Properties of, 316. - Rhubarb syrup, Death from, 30. - Rice, Content of copper in, 612. - Richardson's liquor bismuthi, 330 (footnote). - Richet's observations on strychnine poisoning, 329, 332. - Rinman's green, 657. - " " Production of, 662. - Ringer and Murrell's observations on gelseminine, 346. - River's prussic acid, 193. - Robinia pseudo-acacia, 465. - Robiquet's prussic acid, 193. - Roburite in connection with dinitrobenzol poisoning, 190. - Rogers' experiments on copper, 617. - Roman knowledge of poisons, 2. - Rowalewsky's experiments on uranium, 679. - Rubi-jervine, 394. - Russell's viper, 483. - Rye, Content of copper in, 612. - - Sabadilline, 249, 252. - " Carbon and nitrogen content of, 262. - " Spectra of colour reactions of, 55. - Sabatrin, 252. - Sabina communis, 459. - Saikowsky on antimony poisoning, 586. - St. Croix as a poisoner, 11. - St. Ignatius' bean, Extract of, 323. - Salamandrine, 467. - Salicin, 254. - " Melting-point of, 260. - Salicylic acid, 38, 179. - Salmon, Poisoning by tinned, 507. - Sanarelli's observations on the poison of the scorpion, 468. - Sanger's method of estimating arsenic, 570. - Sanguinarine, carbon and nitrogen content of, 262. - " Spectra of colour reactions of, 55. - Santonin, 244, 439-442. - " Effects of, on animals and man, 440. - " Fatal dose of, 440. - " Poisoning by, 440. - " _Post-mortem_ appearances in cases of poisoning by, 441. - " Separation of, 441, 442. - Sapindus sapotoxin, 436. - Sapogenin, 437. - Saponin, 246, 254, 436-439. - " Detection of, 439. - " Effects of, 437, 438. - " Melting-point of, 260. - " Properties of, 437. - " Separation of, 438. - Saprine, 500. - Sarracinin, 249. - Sarsaparilla saponin, 436. - Sarsa-saponin, 436. - Sausage, Poisoning from, 507, 509, 510. - Savin oil, 459, 460. - Savin, Treatment of poisoning by (App.), 698. - Schacht's method of assaying opium, 284 (footnote). - Schauffele's observations on the solubility of zinc, 657, 658. - Scheele, 14. - Scheele's green, 616. - " prussic acid, 193. - Scheibler's process for alkaloids, 238, 255. - Schleppe's salt, 578. - Schmiedeberg's process for estimating chloroform, 153. - Schneider and Fyfe's method of developing arsenic chloride, 576. - Schoenbein's test for prussic acid, 206. - Schraeder's prussic acid, 193. - Schroff's case of poisoning by colchicum corms, 411. - Schulze's reagent, 239. - Schweinfurt green, 532, 616. - Scillain, 434. - Scillitin, 434. - Sclererythrin, 444, 445. - Sclerocrystallin, 445. - Scleroidin, 445. - Scleromucin, 444. - Sclerotic acid, 444. - Scolosuboff's experiments on the localisation of arsenic, 561. - Scorpion poison, 468. - "Sea Hare" as a poison, 3. - Seidel's case of barium poisoning, 683. - " mercury poisoning, 643. - Senegin, 246, 254, 436. - Senier's analysis of blue pill, 634. - Shale naphtha, 150. - Sheep dipping arsenical compounds, 553. - Siebold's test for morphine, 295. - Siem's researches on alumina, 677. - Silico-tungstic acid, 238. - Silver, 628. - " Chronic poisoning by salts of, 631. - " chloride, 629. - " cyanide, 205, 211. - " Detection of, 632. - " Doses of salts of, 630. - " Use of, in the arts, 630. - " nitrate, 629. - " " Deaths from, 29. - " " Effects of, on man and animals, 630, 631. - " " Tests for, 632. - " oxide, 629. - " _Post-mortem_ appearances in case of poisoning by the salts - of, 652. - " Separation of, 50, 52. - " sulphide, 629. - Sjokvist's method of estimating free hydrochloric acid, 100. - Smelling salts, 112. - Snell's case of dinitrobenzol poisoning, 190. - Soap pill (compound), 286. - Soda bicarbonate, 118. - " Deaths from caustic, 29. - " oxalate, 513. - " Properties of, 117. - " Statistics of poisoning by, 118. - Sodic chloride, 122. - " cyanide, 210. - " nitrate, 124. - Sodium salts, 122-128. - " Tests for, 121. - Sokoloff's method of separating prussic acid, 207. - Solanidine, 386. - Solanine, 385. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Spectra of colour reactions, 55. - " Phospho-molybdate of, 238. - " Poisoning by, 387. - " Properties of, 386. - " Separation of, 387. - " Treatment of poisoning by (App.), 699. - Solomon's anti-impetigines, 639. - Soothing syrup, Deaths from, 30. - Soubeiran's ink, 630. - Spanish fly, 471. - Sparteine, 249, 279, 280. - Spectroscope as an aid to identification of poisons, 54-56. - Spectrum of aniline, 281. - " blood in nitrobenzol poisoning, 191. - " " phosphine poisoning, 232. - Sphacelic acid, 445, 450. - Spiders, Poisonous, 470, 471. - Spiritus Etheris Nitrosi, Deaths from, 29. - Staphisagrine, Carbon and nitrogen content of, 262. - Stas, Process of, for alkaloids, 239. - Statira, Poisoning of, 6. - Statistics of poisoning, 32, 33. - Steel drops, 667. - Stibine, 588. - Stillbazoline, 266. - Stockman and Dott's observations on morphine poisoning, 299. - Stomach, Redness of, 551. - Storey's worm cakes, 640. - Stourbridge case of lead poisoning, 598. - Stramonium extract, 371. - " tincture, 371. - Strophantin, 434. - Struve's experiments on the detection of potassic cyanide, 209. - Strychnic acid, 344. - Strychnine, 248. - " and atropine, Tests for, 373. - " Action of, on cephalopods, 43, 328. - " " frogs, 328. - " " infusoria, 42. - " " man, 329. - " Carbon and nitrogen content of, 262. - " chromate, 321. - " Colour reactions of, 240. - " Deaths from, 30. - " Double salts of, 322. - " Estimation of, 339. - " ethyl and methyl, 251. - " Fatal dose of, 325-328. - " Gold and platinum salts of, 264. - " Identification of, 337, 338. - " Iodide of, 322. - " nitrate, 321. - " " Fatal dose of, 342. - " phospho-molybdate, 238. - " Physiological action of, 332. - " " test for, 338, 339. - " picrate, 325, 340. - " Poisoning by, 331. - " _Post-mortem_ appearances in cases of poisoning by, 333. - " Properties of, 319-321. - " Separation of, from brucine, 323. - " Separation of, from organic matters, 334. - " Spectra of colour tests, 55. - " Statistics of poisoning by, 324. - " Sublimate of, 260. - " sulphate, 321. - " Sulpho-cyanide of, 322. - " Treatment of poisoning by (App.), 333, 699. - " trichloride, 322. - " Value of Mayer's precipitate of, 263. - Sublimation of the alkaloids, 256-261. - Sugar of lead, 593. - " Fatal dose of, 606, 607. - Suicide by poison, 2. - Suicidal poisoning, 32. - Sulphuretted hydrogen. See _Hydric sulphide_. - Sulphuric acid, 75. - " " Accidental, criminal, and suicidal poisoning by, 77, - 78. - " " Character of blood in cases of poisoning by, 90. - " " Chronic poisoning by, 86. - " " Deaths from, 29. - " " Detection and estimation of, 87. - " " External effects of, 81. - " " Fatal dose of, 78. - " " Internal effects of, 82. - " " Local action of, 79. - " " _Post-mortem_ appearances in cases of poisoning by, - 83, 85. - " " Properties of, 75. - " " spots on clothing, &c., 81. - " " Statistics as to poisoning by, 76, 77. - " " Symptoms produced by, 81. - " " Urine in cases of poisoning by, 88. - " anhydride, 76. - Sulphur in bile, 90. - Suppositoria plumbi composita, 593. - Susotoxine, 505. - Syringin, 247, 437. - - Tamus Communis, 465. - Tanqueril's observations on lead poisoning, 600. - Tarantula, 470. - Tar oil, Deaths from, 30. - Tartar emetic. See _Antimony_. - Tartaric acid, Deaths from, 29. - " Detection of lead in, 609, 610. - Tartas' case of poisoning by nitric acid, 107. - Taxine, 404, 405. - Terebenthene hydrochloride, 134. - Terpenes, 133. - Teschemacher and Smith's method for assaying opium, 283. - Tetanine, 503. - Tetanotoxine, 503, 504. - Tetramethylenediamine, 496, 497. - Tetrodon, 469. - Thallium, 675, 676. - Thebaine, 253. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Effects of, 315. - " Gold and platinum salts of, 264. - " nitrate, Lethal dose of, 342. - " Properties of, 314, 315. - " Sublimate of, 259. - Theine, 243. - " Carbon and nitrogen content of, 262. - " Gold and platinum salts of, 264. - " Phospho-molybdate of, 238. - " Sublimate of, 257-260. - Theobromine, 40, 246. - " Carbon and nitrogen content of, 262. - " Phospho-molybdate of, 238. - " Platinum, salt of, 264. - " Sublimate of, 260. - Theveresin, 434. - Thevetin, 434. - Thompson's hair destroyer, 680. - " W., observation on solubility of copper in oils, 611. - Thorn Apple, Deaths from (see _Datura_), 30. - Thudichum's method of separating potass-phenyl sulphate from urine, - 181. - Tiglic acid, 392. - Tin, separation of, 50-52. - Tincture of digitalis, 422. - " iron, 666. - Tione, Mass poisoning by lead in, 599. - Tobacco, Deaths from, 30. - " Effects of, 274. - " juice, Effects of, 273, 275. - " smoke, Chemical composition of, 275, 276 (footnote). - " Species of, 269, 270. - Toffana, 10. - Toluylenediamine, 40. - Tongue, Poisoning by tinned, 507. - Toxalbumins of Castor and Abrus, 462, 463. - Toxic action and chemical composition, 35-42. - " mydriasis and myosis, 46. - Toxines of Hog cholera, 505. - Toxiresin, 421. - Traube's observations on the action of digitalis, 428. - Tri-bromo-phenol, 178. - Tri-chlor-morphine, 299. - Tri-ethyl-amine, 491. - Tri-ethyl-phosphine, 165. - Trimethylamine, 250, 443, 491. - " Carbon and nitrogen content of, 262. - Trimethylenediamine, 493. - Trimethyl-hydroxy-amine, 501. - Trimethyl-vinyl-ammonium hydrate, 501. - Triton cristatus, 467. - Tritopine, Properties of, 317. - Triumph (H.M.S.), Mass poisoning by mercury on, 642. - Tropic acid, 371. - Tropidonotus natrix, 483. - " viperinus, 484. - Tropine, 371. - Tschirch's observations and experiments on copper poisoning, 611, 619, - 622. - Turacin, 613. - Turbith mineral, 637. - Turner's yellow, 594. - Turpentine, 133, 134. - " Deaths from, 29. - " Treatment of poisoning by (App.), 700. - Type metal, 582. - Typho-toxine, 506. - Tyrotoxicon, 504, 505. - - Udransky and Baumann's process for isolating diamines, 488. - Ullmann on the localisation of mercury, 650. - Upas tree of Singapore, 436. - Uppmann's experiments on oxalic acid, 514. - Uranium, 679. - Uric acid in cases of lead poisoning, 603. - Urine, examination of, for poison, 233. - " " in poisoning by carbolic acid, 181. - " " in poisoning by chloral, 161. - " " in poisoning by phosphorus, 222. - " " in poisoning by sulphuric acid, 88. - Urobutylchloral acid, 161. - Urochloral acid, 161. - - Valanguis' solutio solventes mineralis, 531. - Valentine's experiments on scorpion poison, 468. - Van Kobell's test for bismuth, 627. - Vauquelin's prussic acid, 193. - Vas' observations on tobacco juice, 273. - Veal, poisoning by, 507. - Vegetation, Action of hydrochloric acid on, 94. - " " nitric acid, 104. - Venetian poisoners, 9. - Venturoli's process for the separation of prussic acid, 208. - Veratralbine, 394. - Veratric acid, 392. - Veratrine, 248, 252, 390-392. - " Action of, on infusoria, 42. - " Carbon and nitrogen content of, 262. - " Colour reactions of, 240. - " Commercial, 394, 395. - " Effects of, on animals and man, 395, 396. - " Fatal dose, 395. - " Gold salt of, 264. - " Phospho-molybdate of, 238. - " Separation of, from organic matters, 397. - " Spectra of colour reactions, 55. - " Treatment of poisoning by (App.), 700. - " Value of Mayer's precipitate of, 263. - Veratroidine, 394. - Veratroidine, Carbon and nitrogen content of, 262. - Veratrum, Old knowledge of, 4. - Verdigris, 616. - Vermicelli, Content of copper in, 612. - Vermilion, 638. - Vermin killers, Composition of, 324. - " Deaths from, 30. - Vetchlings, 464. - Veterinary arsenical medicines, 531. - Vidali's method of estimating chloroform, 153 (footnote). - " " testing for atropine, 373. - " " testing for mercury cyanide, 652. - " " testing for morphine, 295. - Villiers and Favolle's test for hydrochloric acid, 99. - Vinylamine, 41. - Viper, 477. - Vis' constitutional formula for atropine, 294. - Vohl and Eulenberg's observations on tobacco smoke, 276 (footnote). - Voisin and Liouville's experiments on curare, 407. - - Wagner's method of obtaining sulphates of the alkaloids, 263. - Wall on the effects of cobra poison, 479. - Waller's, E., method of assaying carbolic acid powders, 182. - Waltisham cases of ergot poisoning, 447, 448. - Walz's method of preparing digitalin, 421. - Ward's red pill, 581. - Wasps, Poison of, 471. - Water gas, Leeds case of poisoning by, 67. - " hemlock, Deaths from. See _[OE]nanthe crocata_, 30. - " salamander, 467. - " snake, blood of, 485. - Welbeck cases of food poisoning, 507. - Wheat, Content of copper in, 612. - Whin flower, Death from, 30. - Whitchurch case of food poisoning, 507. - White lead, 594, 595. - Whitelock's case of carbolic acid poisoning, 171. - White precipitate, 636, 648. - Williams' apparatus, 44. - Witherite, 680. - Wittstock's process for colchicine, 413. - Wolverhampton case of poisoning by tinned salmon, 507. - Wormwood, 244. - Woudreton, Confession of, 8. - Wright's pearl ointment, 640. - Wunderlich's case of poisoning by nitric acid, 106. - Wyeth's dialysed iron (App.), 686. - Wyss (Oscar) case of poisoning by sulphuric acid, 84. - - Xanthin, 39, 40. - Xanthogenic acid, 165. - - Yellow atrophy of the liver, distinguished from phosphorus poisoning, - 226. - Yew, Poisoning by, 404. - - Zinc ammonia chloride, 657. - " carbonate, 656. - " chloride, 656. - " " Deaths from poisoning by, 29. - " " Poisonous effects of, 659, 660. - " " _Post-mortem_ appearances after poisoning by, 660, 661. - " Detection of, 661. - " Effects of, 658. - " green, 657. - " in the arts, 657. - " oxide, 656. - " " Effects of, on man, 658. - " Separation of, 53. - " sulphate, 656. - " " Poisonous effects of, 659. - " " _Post-mortem_ appearances after poisoning by 660. - " sulphide, 656, 657. - " " Properties of, 661. - " Tests for, 662. - " " poisoning by soluble salts of (App.), 700. - " white, 657. - " yellow, 657. - - NEILL AND COMPANY, PRINTERS, EDINBURGH. - - - - - A CATALOGUE OF - MEDICAL WORKS - PUBLISHED BY - CHARLES GRIFFIN & COMPANY, LIMITED. - - -[Illustration] - -MESSRS. 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E., M.D.), Diseases of the Heart, 12 - SEXTON (Prof.), Quantitative Analysis, 32 - ---- Qualitative Analysis, 32 - SMITH (Johnson, F.R.C.S.), Sea-Captain's Medical Guide, 35 - SQUIRE, (Ed. J, M.D.), Consumption, Hygienic Prevention of, 34 - STIRLING (Prof.), Practical Physiology, 28 - ---- Practical Histology, 29 - THORBURN (W.), Surgery of Spine, 20 - THORNTON (J.), Surgery of Kidneys, 20 - WESTLAND (A., M.D.), The Wife and Mother, 35 - SCIENTIFIC SOCIETIES (Year-book of), 36 - - -INDEX TO SUBJECTS. - - PAGE - AMBULANCE, 35 - ANAESTHETICS, 26 - ANATOMY, Human, 4 - _Anatomy and Physiology_ (_Journal of_), 22 - ASYLUM MANAGEMENT, 17 - BIOLOGY, 30 - BLOOD, Diseases of, 9 - BOTANY, 30 - BRAIN, The, 15, 16, 17, 18, 19 - CHEMISTRY, Inorganic, 32 - ---- Analysis, Qualitative and Quantitative, 32 - CHILDHOOD, Diseases of, 9 - CLINICAL Diagnosis, 8 - CLINICAL Medicine, 6, 7 - CONSUMPTION, 6, 34 - DIETARIES for the Sick, 33 - DISINFECTION and DISINFECTANTS, 33 - EMBRYOLOGY, 22 - EYE, Diseases of the, 14 - FOODS, Analysis of, 31 - FOODS and Dietaries, 33 - FORENSIC MEDICINE, 19 - GOUT, 10 - HEART, Diseases of the, 12 - HISTOLOGY, 29 - HYGIENE and Public Health, 24, 31, 33, 34 - INFANTS, Rearing of, 35 - INSANITY, Medico-legal Evidence of, 19 - KIDNEYS, Surgery of the, 20 - LABORATORY Hand-books-- - Chemistry, 32 - Histology, 29 - Pharmacy, 32 - Physiology, 28 - MEDICAL SOCIETIES, Papers read annually before, 36 - MEDICINE, Science and Practice of, 26 - MENTAL DISEASES, 16, 17 - NERVOUS ORGANS, Central, 18 - NURSING, Medical and Surgical, 33 - OBSTETRICS, 25 - PHARMACY, 32 - PHTHISIS, Fibroid, 6 - PHYSIOLOGIST'S Note-book, 27 - PHYSIOLOGY, 5, 28 - POCKET-BOOK of Hygiene, 24 - ---- Medical, 23 - ---- of Sanitary Rules, 24 - ---- Surgical, 23, 24 - ---- Zoological, 30 - POISONS, Detection of, 31 - RAILWAY INJURIES, 20 - RHEUMATISM, 11 - RUPTURES, 19 - SANITATION, 34 - SEA-CAPTAINS, Medical Guide for, 35 - SEWAGE Disposal Works, 21 - SKIN, Diseases of the, 13 - SPINAL Cord, 20 - SURGERY of Brain, 15 - ---- Civil, 23 - ---- of Kidneys, 20 - ---- Military, 24 - ---- of Spinal Cord, 20 - WOMEN, Diseases of, 25, 35 - ZOOLOGY, 30 - - -Charles Griffin & Co.'s Medical Series. - -_Standard Works of Reference for Practitioners and Students._ - -Issued in LIBRARY STYLE, large 8vo, Handsome Cloth, very fully -Illustrated. - - -1. ANATOMY AND PHYSIOLOGY. - - PAGE - =Human Anatomy=, PROF. MACALISTER, M.D., 4 - =Human Physiology=, PROFS. LANDOIS AND STIRLING, 5 - =Embryology=, PROF. HADDON, 22 - - -2. THE BRAIN, NERVOUS SYSTEM, AND LEGAL MEDICINE. - - =The Brain and Spinal Cord=, VICTOR HORSLEY, F.R.C.S., 15 - =Central Nervous Organs=, DRS. OBERSTEINER AND HILL, 18 - =Peripheral Neuritis=, DRS. ROSS AND BURY, 15 - =Mental Diseases=, BEVAN LEWIS, M.R.C.S., 16 - =Asylum Management=, CHAS. MERCIER, M.D., 17 - =Forensic Medicine and Toxicology=, PROF. DIXON MANN, 19 - - -3. DIAGNOSIS AND TREATMENT OF DISEASE. - - =Clinical Diagnosis=, DRS. V. JAKSCH AND CAGNEY, 8 - =Clinical Medicine=, JUDSON BURY, M.D., 6-7 - =Fibroid Phthisis=, SIR AND. CLARK, M.D., 6 - =Gout=, SIR DYCE DUCKWORTH, M.D., 10 - =Rheumatism=, ARCH. GARROD, M.D., 11 - =Diseases of the Blood=, WM. HUNTER, M.D., 9 - = " Childhood=, BRYAN DONKIN, M.D., 9 - = " the Eye=, DRS. MEYER AND FERGUS, 14 - = " the Heart=, A. E. SANSOM, M.D., 12 - = " the Skin=, PROF. M'CALL ANDERSON, 13 - - -4. SURGERY. - - =Brain Surgery=, VICTOR HORSLEY, F.R.C.S., 15 - =Surgery of the Kidneys=, KNOWSLEY THORNTON, F.R.C.S., 20 - = " Spinal Cord=, WM. THORBURN, F.R.C.S., 20 - =Surg. Diseases of Childhood=, BILTON POLLARD, F.R.C.S., 9 - =Railway Injuries=, H. W. PAGE, F.R.C.S., 20 - =Ruptures=, J. F. C. MACREADY, F.R.C.S., 19 - - -[***] Other Volumes in active Preparation. - - -~By Prof. MACALISTER, M.P., F.R.S.~ - - HUMAN ANATOMY - (SYSTEMATIC AND TOPOGRAPHICAL), - A TEXT-BOOK OF: - - INCLUDING THE EMBRYOLOGY, HISTOLOGY, AND MORPHOLOGY OF - MAN, WITH SPECIAL REFERENCE TO THE REQUIREMENTS - OF PRACTICAL SURGERY AND MEDICINE. - -BY - -ALEXANDER MACALISTER, M.A., M.D., F.R.S., F.S.A., - - Professor of Anatomy in the University of Cambridge, and Fellow of - St. John's College; Examiner in Human Anatomy, University of London. - -_In Large 8vo. With 816 Illustrations. Handsome Cloth, 36s._ - - -OPINIONS OF THE PRESS. - - "By far THE MOST IMPORTANT WORK ON THIS SUBJECT that has appeared in - recent years, . . . treating its subject THOROUGHLY AND - COMPREHENSIVELY. . . . The histology of the tissues is most ably and - lucidly described."--_The Lancet._ - - "THIS SPLENDID VOLUME fills up what was a great want in works on - human anatomy.... We get morphology as a basis, and thread our way - upwards."--_Saturday Review._ - - "Contains an enormous amount of valuable matter. . . . A work which - we feel sure will be a _main factor_ in the _advancement_ of - _scientific anatomy_. In addition, we must mention the FINE - COLLECTION OF ILLUSTRATIONS."--_Dublin Medical Journal._ - - "Many of the figures are of great beauty. . . . The chapters on the - brain and spinal cord, the ear, and the eye, contain _all that is - really valuable in the most recent researches_."--_Glasgow Medical - Journal._ - - "The book bears an unmistakable stamp of erudition and labour, and - will be VALUED both by teachers and pupils AS A WORK OF - REFERENCE."--_British Medical Journal._ - - "Dr. Macalister's extensive knowledge of comparative anatomy enables - him to speak with authority on many interesting but difficult - morphological problems. . . . A VERY ABLE and SCIENTIFIC - treatise."--_Edinburgh Medical Journal._ - - -~Professors LANDOIS and STIRLING.~ - - HUMAN PHYSIOLOGY - (A TEXT-BOOK OF). - WITH SPECIAL REFERENCE TO PRACTICAL MEDICINE. - -By DR. L. LANDOIS, - - PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF GREIFSWALD. - -_Translated from the Seventh German Edition, with Annotations and -Additions_, - -By WM. STIRLING, M.D., Sc.D., - - BRACKENBURY PROFESSOR OF PHYSIOLOGY IN OWENS COLLEGE, AND VICTORIA - UNIVERSITY, MANCHESTER; EXAMINER IN THE UNIVERSITIES of OXFORD, - EDINBURGH, AND LONDON: AND FOR THE FELLOWSHIP OF THE ROYAL COLLEGE - OF SURGEONS, ENGLAND. - -In Two Large 8vo Volumes, Handsome Cloth, 42s. - -With 845 Illustrations (some in Colours). - -FOURTH ENGLISH EDITION. - - -GENERAL CONTENTS. - - Part I.--Physiology of the Blood, Circulation, Respiration, - Digestion, Absorption, Animal Heat, Metabolic Phenomena of the Body; - Secretion of Urine; Structure of the Skin. - - Part II.--Physiology of the Motor Apparatus; the Voice and Speech; - General Physiology of the Nerves: Electro-Physiology; the Brain; - Organs of Sight, Hearing, Smell, Taste, Touch; Physiology of - Development. - -[***] Since its first appearance in 1880, Prof. LANDOIS' TEXT-BOOK OF -PHYSIOLOGY has been translated into three Foreign languages, and passed -through SEVEN LARGE EDITIONS. - -The Fourth English Edition has again been thoroughly revised, and a new -feature introduced--that of printing some of the Illustrations in -Colours. The number of figures has also been largely increased, from 494 -in the First, to 845 in the present Edition. In order to do full justice -to the coloured illustrations, and to admit of more of the text being -printed in large type, it has been found necessary to put the work once -again in two volumes. - - -Opinions of the Press. - - "So great are the advantages offered by Prof. LANDOIS' TEXT-BOOK, - from the EXHAUSTIVE and EMINENTLY PRACTICAL manner in which the - subject is treated, that it has passed through FOUR large editions - in the same number of years. . . . Dr. STIRLING's annotations have - materially added to the value of the work. Admirably adapted for the - PRACTITIONER. . . . With this Text-book at command, NO STUDENT COULD - FAIL IN HIS EXAMINATION."--_The Lancet._ - - "One of the MOST PRACTICAL WORKS on Physiology ever written, forming - a 'bridge' between Physiology and Practical Medicine. . . . Its - chief merits are its completeness and conciseness. . . . The - additions by the Editor are able and judicious. EXCELLENTLY CLEAR, - ATTRACTIVE, AND SUCCINCT."--_Brit. Med. Journal._ - - "The great subjects dealt with are treated in an admirably clear, - terse, and happily-illustrated manner. At every turn the doctrines - laid down are illuminated by reference to facts of Clinical Medicine - or Pathology."--_Practitioner._ - - "We have no hesitation in saying that THIS IS THE WORK to which the - PRACTITIONER will turn whenever he desires light thrown upon, or - information as to how he can best investigate, the phenomena of a - COMPLICATED OR IMPORTANT CASE. To the STUDENT it will be EQUALLY - VALUABLE."--_Edinburgh Medical Journal._ - - "LANDOIS AND STIRLING'S work cannot fail to establish itself as one - of the most useful and popular works known to English - readers."--_Manchester Medical Chronicle._ - - "As a work of reference, LANDOIS and STIRLING's Treatise OUGHT TO - TAKE THE FOREMOST PLACE among the text books in the English - language. The woodcuts are noticeable for their number and - beauty."--_Glasgow Medical Journal._ - - "Unquestionably the most admirable exposition of the relations of - Human Physiology to Practical Medicine that has ever been laid - before English readers."--_Students' Journal._ - - -IN HANDSOME CLOTH. PRICE ONE GUINEA NET. - -_~New Work by Sir ANDREW CLARK, Bart., M.D., LL.D., F.R.S.~_ - -With Tables and Eight Plates in Colours. - - FIBROID DISEASES OF THE LUNG, INCLUDING - FIBROID PHTHISIS. - -BY - -Sir ANDREW CLARK, Bart., M.D., LL.D., F.R.S., - - _Late Consulting Physician and Lecturer on Clinical Medicine to the - London Hospital_, - -AND - -W. J. HADLEY, M.D., and ARNOLD CHAPLIN, M.D., - - _Assistant Physicians to the City of London Hospital for Diseases of - the Chest_. - - - "It was due to Sir Andrew Clark that a PERMANENT RECORD of his MOST - IMPORTANT PIECE OF PATHOLOGICAL and CLINICAL WORK should be - published . . . the subject had been in his mind for many years, and - the present volume, COMPLETELY written and twice revised before his - lamented death, embodies his LATEST VIEWS upon it. . . . A volume - which will be HIGHLY VALUED BY EVERY CLINICAL PHYSICIAN."--_British - Medical Journal._ - - -From Dr. JUDSON BURY'S NEW WORK on "CLINICAL MEDICINE" - -(_See opposite page._) - -[Illustration: FIG. 221.--Showing wasting of Pectorales, and the drawing -up of the Upper Angles of the Scapulae. From the Section on Examination -of the Nervous System (Disorders of Muscular Action).] - - -_In Large 8vo, Handsome Cloth, With numerous Illustrations and Coloured -Plate. 21s._ - - CLINICAL MEDICINE. - A PRACTICAL HANDBOOK FOR PRACTITIONERS - AND STUDENTS. - -BY JUDSON BURY, M.D., F.R.C.P., - - Senior Assist. Phys., Manchester Royal Infirmary. - - - "We may say at once that Dr. Judson Bury has SUCCEEDED WELL. His - book is planned upon RATIONAL LINES, . . . intended for PRACTICAL - SERVICE. . . . His work will take a PROMINENT PLACE amongst books of - its class, and is one, too, to which the clinical student can TRUST, - as being reliable. . . . The illustrations are numerous and - TELLING."--_The Lancet._ - - "This Manual is sure AT ONCE to take a FOREMOST PLACE as a guide in - clinical work. . . . Seeks to utilise at the bedside the most recent - researches of the Physiologist, the Chemist, and the Bacteriologist. - . . . Belongs to the same series of Manuals which has given us the - issue of LANDOIS' 'Physiology,' wherein Prof. STIRLING sought to - bring the most advanced Physiology into relationship with clinical - work; and the very valuable treatise of V. JAKSCH on 'Clinical - Diagnosis."--_British Medical Journal._ - - "This is the latest of the splendid Series of Text-books which - Messrs. Charles Griffin & Company have been the means of placing in - the hands of the profession. The volume will maintain the reputation - of its predecessors, and we HEARTILY CONGRATULATE Dr. Judson Bury on - the EXCELLENCE of his book and the STERLING CONTRIBUTION to medical - literature which, in its publication, he has made."--_Dublin Medical - Journal._ - - -GENERAL CONTENTS. - -=Introductory.=--Symptoms and Physical Signs--Importance of -Inspection--Method of Examining a Patient--Case-taking. =Symptoms for -the most part Subjective in Character.=--Symptoms indicating Disturbance -of the Functions of the Nervous System--Indicating Disturbance of the -Functions of the Respiratory and Circulatory Organs--Indicating -Disturbance of the Functions of the Digestive Organs--Indicating -Disturbance of the Urinary Organs. =Examination of the Surface -of the Body.=--Changes in Size and Shape--Expression of -Face--Attitude--Walking. =Temperature.=--Temperature in Health--in -Disease. =Examination of the Skin and its Appendages.=--Changes in the -Colour of the Skin--The Moisture of the Skin--Cutaneous Eruptions:--I. -General Diseases with Cutaneous Lesions; II. Diseases of the Skin due to -Parasites; III. Local Diseases of the Skin not due to Cutaneous -Parasites--Abnormal Conditions of the Nails. =Examination -of the Respiratory System.=--Artificial Divisions of the -Chest--Inspection--Palpation--Percussion--Auscultation--The Sputum--The -Examination of the Larynx. =Examination of the Circulatory -System.=--Anatomical Relations of the Heart--Inspection and -Palpation--Percussion-Auscultation--The Pulse. =Examination of the -Blood.= =Examination of the Digestive System and of the Abdominal -Organs.=--The Tongue--The Teeth--The Gums--The Mucous Membrane of the -Mouth--Saliva--The Soft Palate, Fauces and Pharynx--The -[OE]sophagus--The Abdomen---The Stomach--Examination of Vomited -Matters--Investigation of the Contents of the Stomach and of its -Activity during Digestion--The Intestines--Examination of the -Faeces---The Liver and Gall Bladder--The Spleen--The Pancreas--The -Omentum--The Mesentery and Retroperitoneal Glands--The Kidneys. -=Examination of the Urine.=--Variations in the Quantity of the Urine--In -the Colour--Odour--Consistence--Translucency--Specific Gravity and -Reaction of the Urine--Chemical Examination of the Urine--Sediments -and Microscopical Examination of the Urine:--(_a_) Unorganised -Sediments; (_b_) Organic Deposits. =Examination of Puncture -Fluids.=--Exudations--Transudations--Contents of Cysts. -=Examination of the Nervous System.=--Anatomical and Physiological -Introduction--Investigation of the Symptoms Produced by Diseases of the -Nervous System:--Disorders of Muscular Action; of Sensation; of Reflex -Action; of Language; of Vision; of Hearing; of Taste; of Smell. - - -~By Prof. von JAKSCH.~ - -[Illustration: Fig. 86.--_a_, _b._ Cylindroids from the urine in -congested kidney.] - - CLINICAL DIAGNOSIS: - THE - Bacteriological, Chemical, and Microscopical - Evidence of Disease. - -BY PROF. R. V. JAKSCH, - - Of the University of Prague. - -TRANSLATED FROM THE THIRD GERMAN EDITION AND ENLARGED - -BY JAMES CAGNEY, M.A., M.D., - - Phys. to the Hosp. for Epilepsy and Paralysis, Regent's Park. - -With ADDITIONAL ILLUSTRATIONS, many Coloured. - -_In large 8vo. Handsome Cloth. 25s._ - -SECOND ENGLISH EDITION. - - -GENERAL CONTENTS. - -The Blood--The Buccal Secretion--The Nasal Secretion--The -Sputum--The Gastric Juice and Vomit--The Faeces--Examination of the -Urine--Investigation of Exudations, Transudations, and Cystic -Fluids--The Secretions of the Genital Organs--Methods of Bacteriological -Research--Bibliography. - - -OPINIONS OF THE PRESS. - - "A striking example of the application of the Methods of Science to - Medicine. . . . STANDS ALMOST ALONE amongst books of this class in - the width of its range, the THOROUGHNESS of its exposition, and the - clearness of its style. Its value has been recognised in many - countries. . . . The translator has done his share of the work in an - admirable manner. . . . A _standard work_ . . . as TRUSTWORTHY as it - is SCIENTIFIC. . . . The numerous and artistic illustrations form a - great feature of the work, and have been _admirably - reproduced_."--_Lancet._ - - "Supplies a real want. . . . Rich in information, accurate in - detail, lucid in style."--_Brit. Med. Journal._ - - "Possesses a HIGH VALUE. . . . There is a most admirable - bibliography."--_Edinburgh Med. Review._ - - "A new and valuable work . . . worthy of a FIRST PLACE AS A - TEXT-BOOK. . . . Of great value both to medical practitioners and - medical students."--_Journal of American Med. Association, Chicago._ - - -_In Large 8vo, Handsome Cloth._ 16_s._ - - THE DISEASES OF CHILDHOOD - (MEDICAL). - -BY - -H. BRYAN DONKIN, M.A., M.D., F.R.C.P., - - PHYSICIAN TO THE WESTMINSTER HOSPITAL AND THE EAST LONDON HOSPITAL - FOR CHILDREN: JOINT LECTURER ON MEDICINE AND CLINICAL MEDICINE AT - THE WESTMINSTER HOSPITAL MEDICAL SCHOOL. - - -OPINIONS OF THE PRESS. - - _The Lancet._--"DR. DONKIN's book is in every sense of the word a - piece of ORIGINAL WORK, REMARKABLY WELL WRITTEN, and founded on his - own LARGE EXPERIENCE." - - _British Medical Journal._--"DR. DONKIN's work possesses characters - which will earn for it a DISTINCT PLACE in the estimation of the - profession. . . . May be confidently recommended to the study of - every practitioner who takes an interest in the subjects with which - it deals." - - _Practitioner._--"Unquestionably a VERY VALUABLE contribution to the - list of works on the diseases of childhood." - - _Edinburgh Medical Journal._--"A thoughtful, accurate, and - compendious treatise, written in a charming style, and with much - vigour." - - _Medical Magazine._--"A TRULY PRACTICAL work, the record of the - personal experience and observation of an independent mind." - - - THE DISEASES OF CHILDHOOD - (SURGICAL). - -BY - -BILTON POLLARD, M.B., B.S., F.R.C.S, - - Surgeon, N.E. Hospital for Children; Assist.-Surgeon, University - College Hospital; Assist. Prof. of Clinical Surgery and Teacher of - Practical Surgery, University College. - -_EACH VOLUME PUBLISHED SEPARATELY._ - - - DISEASES OF THE BLOOD. - -BY - -WILLIAM HUNTER, M.D., F.R.S.E. - - _Assist.-Phys. London Fever Hospital; Arris and Gale Lect. R.C.S. - Eng., &c., &c._ - - -~By SIR DYCE DUCKWORTH, M.D., F.R.C.P.~ - -[Illustration: Fig. 1.--Human Articular Cartilage from head of a -metatarsal bone (Normal).] - - GOUT - (A TREATISE ON). - -BY - -SIR DYCE DUCKWORTH, - - M.D. Edin., LL.D., Hon. Physician to H.R.H. the Prince of Wales, - Physician to, and Lecturer on Clinical Medicine in, St. - Bartholomew's Hospital. - -_In Large 8vo. With Chromo-Lithograph, Folding Plate, and Illustrations -in the Text. Handsome Cloth, 25s._ - -[***] This work is the result of the special opportunities which London -Practice affords as, probably, the largest field of observation for the -study of Gout. It is based on the experience derived from both Hospital -and Private Practice, each of which furnishes distinctive phases of the -disease. - - -OPINIONS OF THE PRESS. - - "Thoroughly practical and highly philosophical. The practitioner - will find in its pages an ENORMOUS AMOUNT OF INFORMATION. . . . A - monument of clinical observation, of extensive reading, and of close - and careful reasoning."--_Practitioner._ - - "All the known facts of Gout are carefully passed in review. . . . - We have chapters upon the clinical varieties of Gout, and the - affections of special organs and textures. . . . A very VALUABLE - STOREHOUSE of material on the nature, varieties, and treatment of - Gout."--_Lancet._ - - "A very well written, clear, and THOROUGHLY SATISFACTORY EPITOME of - our present knowledge upon the subject of Gout."--_Philadelphia - Therapeutic Gazette._ - - "Impartial in its discussion of theories, full and accurate in its - description of clinical facts, and a TRUSTWORTHY GUIDE TO - TREATMENT."--_British Medical Journal._ - - -[Illustration: Fig. 1.--Gangliform Swelling on the Dorsum of the Hand of -a Child aged Eight.] - -~By A. E. GARROD, M.D., F.R.C.P.~ - - Rheumatism - AND - Rheumatoid Arthritis - (A TREATISE ON). - -BY - -ARCHIBALD E. GARROD, - - M.A., M.D. Oxon., F.R.C.P., Assistant-Physician to the West London - Hospital, &c. - -_In Large 8vo, with Charts and Illustrations. Handsome Cloth, 21s._ - - -[***] The author's aim is to give a consistent picture of Rheumatism as -a systemic disease presenting one definite set of phenomena, the result, -it is believed, of one single and specific morbid process. - - -OPINIONS OF THE PRESS. - - "The wide subject of the etiology of rheumatism is _carefully - treated_. . . . The discussion of etiology is completed by a _full - analysis_ of the conditions which determine individual attacks. - . . . Dr. Garrod is to be congratulated on having put before the - profession SO CLEAR AND COHERENT an account of the rheumatic - diseases. The style of his work is eminently readable."--_Lancet._ - - "Well written and reliable. . . . We have little doubt that this - monograph _will take rank with the best treatises_ on special - medical subjects in the English language."--_Dublin Medical - Journal._ - - "An EXCELLENT ACCOUNT of the clinical features of the diseases in - question. The chapters on treatment are THOROUGHLY - PRACTICAL."--_Manchester Medical Chronicle._ - - -_In Large 8vo, with Illustrations in the Text and 13 Folding-Plates, -28s._ - - DISEASES OF THE HEART - AND THORACIC AORTA - (THE DIAGNOSIS OF). - -by - -A. ERNEST SANSOM, M.D, F.R.C.P., - - Physician to the London Hospital; Consulting Physician, - North-Eastern Hospital for Children; Examiner in Medicine, Royal - College of Physicians (Conjoint Board for England), and University - of Durham; Lecturer on Medical Jurisprudence and Public Health, - London Hospital Medical College, &c. - -(From Chap. ix.--"The Observed Signs of Neuro-Cardiac Disease.") - -[Illustration: FIG. 6.--Case of Grave's disease with well-marked -retraction of upper eyelid (Stellway's sign). There was very little -projection of the eyeball, though prominence appeared to be extreme. -Patient aged twenty-four. (_From a photograph._)] - - - "Dr. Sansom has opened to us a TREASURE-HOUSE OF KNOWLEDGE. . . . - The originality of the work is shown on every page, an originality - so complete as to mark it out from every other on the subject with - which we are acquainted."--_Practitioner._ - - "A book which does credit to British Scientific Medicine. We warmly - commend it to all engaged in clinical work."--_The Lancet._ - - -~By PROFESSOR T. M'CALL ANDERSON, M.D.~ - -_SECOND EDITION. Now Ready, with Four Chromo-Lithographs, Steel Plate, -and numerous Woodcuts. 25s._ - - DISEASES OF THE SKIN - (A TREATISE ON), - - With Special Reference to Diagnosis and Treatment, Including - an Analysis of 12,000 Consecutive Cases. - -By T. M'CALL ANDERSON, M.D., - - _Professor of Clinical Medicine, University if Glasgow._ - -PROFESSOR M'CALL ANDERSON's Treatise, affording, as it does, a complete -_resume_ of the best modern practice, is written--not from the -standpoint of the University Professor--but from that of one who, during -upwards of a quarter of a century, has been actively engaged both in -private and in hospital practice, with unusual opportunities for -studying this class of disease, hence the PRACTICAL and CLINICAL -directions given are of great value. - -Speaking of the practical aspects of Dr. ANDERSON's work, the _British -Medical Journal_ says:--"Skin diseases are, as is well known, obstinate -and troublesome, and the knowledge that there are ADDITIONAL RESOURCES -besides those in ordinary use will give confidence to many a puzzled -medical man, and enable him to encourage a doubting patient. ALMOST ANY -PAGE MIGHT BE USED TO ILLUSTRATE THE FULNESS OF THE WORK IN THIS -RESPECT. . . . The chapter on Eczema, that universal and most -troublesome ailment, describes in a comprehensive spirit, and with the -greatest accuracy of detail, the various methods of treatment. Dr. -Anderson writes with the authority of a man who has tried the remedies -which he discusses, and the information and advice which he gives cannot -fail to prove extremely valuable." - - -OPINIONS OF THE PRESS. - - "Professor M'Call Anderson has produced a work likely to prove VERY - ACCEPTABLE to the busy practitioner. The sections on treatment are - very full. For example, ECZEMA has 110 pages given to it, and 73 of - these pages are devoted to treatment."--_Lancet._ - - "Beyond doubt, the MOST IMPORTANT WORK on Skin Diseases that has - appeared in England for many years. . . . Conspicuous for the AMOUNT - AND EXCELLENCE of the CLINICAL AND PRACTICAL information which it - contains."--_British Medical Journal._ - - "The work may be regarded as a storehouse of FACTS gathered and - sifted by one whose opinion is entitled to the highest respect, and - we have no hesitation in stating our belief that it has NO EQUAL in - this country."--_Edinburgh Medical Journal._ - - "ESSENTIALLY a useful book, clear and graphic in description, - dogmatic and hopeful on questions of treatment."--_Birmingham - Medical Review._ - - -~By Drs. MEYER and FERGUS.~ - -_Now Ready, with Three Coloured Plates and numerous Illustrations. Royal -8vo, Handsome Cloth, 25s._ - - DISEASES OF THE EYE - (A PRACTICAL TREATISE ON), - -BY EDOUARD MEYER, - - _Prof. a l'Ecole Pratique de la Faculte de Medecine de Paris, - Chev. of the Leg. of Honour, &c._ - -Translated from the Third French Edition, with Additions as contained in -the Fourth German Edition, - -By F. FERGUS, M.B., Ophthalmic Surgeon, Glasgow Infirmary. - - -The particular features that will most commend Dr. Meyer's work to -English readers are--its CONCISENESS, its HELPFULNESS in explanation, -and the PRACTICALITY of its directions. The best proof of its worth may, -perhaps, be seen in the fact that it has now gone through _three_ French -and _four_ German editions, and has been translated into most European -languages--Italian, Spanish, Russian, and Polish--and even into -Japanese. - - -Opinions of the Press. - - "A GOOD TRANSLATION OF A GOOD BOOK. . . . A SOUND GUIDE in the - diagnosis and treatment of the various diseases of the eye that are - likely to fall under the notice of the general Practitioner. The - Paper, Type, and Chromo-Lithographs are all that could be desired. - . . . We know of no work in which the DISEASES and DEFORMITIES of - the LIDS are more fully treated. Numerous figures illustrate almost - every defect remediable by operation."--_Practitioner._ - - "A VERY TRUSTWORTHY GUIDE in all respects. . . . THOROUGHLY - PRACTICAL. Excellently translated, and very well got up. Type, - Woodcuts, and Chromo-Lithographs are alike excellent."--_Lancet._ - - "Any Student will find this work of GREAT VALUE. . . . The chapter - on Cataract is excellent. . . . The Illustrations describing the - various plastic operations are specially helpful."--_Brit. Med. - Journal._ - - "An EXCELLENT TRANSLATION of a standard French Text-Book. . . . We - can cordially recommend Dr. Meyer's work. It is essentially a - PRACTICAL WORK. The Publishers have done their part in the TASTEFUL - and SUBSTANTIAL MANNER CHARACTERISTIC OF THEIR MEDICAL PUBLICATIONS. - The Type and the Illustrations are in marked contrast to most - medical works."--_Ophthalmic Review._ #/ - - - _In Large 8vo, with Numerous Illustrations, Handsome Cloth, 10s. - 6d._ - - THE BRAIN AND SPINAL CORD - - (The Structure and Functions of). - - BY - - VICTOR HORSLEY, B.S., F.R.C.S., F.R.S., - - Professor of Pathology, University College; Assistant-Surgeon, - University College Hospital, &c. - - - "The portion treating of the development of the Nervous System from - the simplest animals up to man, everywhere replete with interest. - . . . In the last four Lectures we have most clearly stated the - results of modern work. . . . WELL WORTH the study of all who wish - to apply the lessons of recent physiological research."--_Edinburgh - Medical Journal._ - - "We HEARTILY COMMEND the book to all readers and to ALL CLASSES OF - STUDENTS ALIKE, as being almost the only lucid account extant, - embodying the LATEST RESEARCHES and their conclusions."--_British - Medical Journal._ - - -_IN PREPARATION--BY THE SAME AUTHOR._ - - SURGERY OF THE BRAIN. - -BY VICTOR HORSLEY, F.R.S, &c., - - Assistant Surgeon, University College Hospital; Professor of - Pathology, University College, &c., &c. - - -_In Large 8vo. With Illustrations. 21s._ - -ON PERIPHERAL NEURITIS. - -BY JAS. ROSS, M.D., LL.D., - - Late Physician to the Manchester Royal Infirmary, and Joint - Professor of Medicine at the Owens College; - -AND JUDSON BURY, M.D., M.R.C.P., - - Senior Assistant Physician to the Manchester Royal Infirmary. - - "It will for many years remain the AUTHORITATIVE TEXT-BOOK on - peripheral neuritis."--_British Medical Journal._ - - "A monument of industry--should be carefully read by - all."--_Edinburgh Medical Journal._ - - "A MOST COMPLETE and masterly treatise."--_Sheffield Med. Journal._ - - -~By W. BEVAN LEWIS.~ - - MENTAL DISEASES - (A TEXT-BOOK OF): - - Having Special Reference to the Pathological - Aspects of Insanity. - -BY - -W. BEVAN LEWIS, L.R.C.P. Lond., M.R.C.S. Eng., - - Medical Director of the West Riding Asylum, Wakefield. - -_In Large 8vo, with Eighteen Lithographic Plates and Illustrations in -the Text. Handsome Cloth, 28s._ - - -OPINIONS OF THE PRESS. - - "Will take the HIGHEST RANK as a Text-Book of Mental - Diseases."--_British Medical Journal._ - - "Without doubt the BEST BOOK in English of its kind. . . . The - chapter on Epileptic Insanity and that on the Pathology of Insanity - are perfect, and show a power of work and originality of thought - which are admirable."--_Journal of Mental Science._ - - "The work, all through, is the outcome of original observation and - research."--_Mind._ - - "A SPLENDID ADDITION to the literature of mental diseases. . . . The - anatomical and histological section is ADMIRABLY DONE. . . . The - clinical section is concise and tersely written. It is, however, to - the pathological section that the work owes its chief merit. As a - STANDARD WORK on the pathology of mental diseases this work should - occupy a prominent place in the library of every alienist - physician."--_Dublin Medical Journal._ - - "Affords a fulness of information which it would be difficult to - find in any other treatise in the English language."--_Edin. Medical - Journal._ - - "We record our conviction that the book is the best and most - complete treatise upon the pathological aspect of the subject with - which we are familiar. . . . An ABSOLUTELY INDISPENSABLE addition to - every alienist's and neurologist's library."--_The Alienist and - Neurologist._ - - "It would be quite impossible to say too much in praise of the - ILLUSTRATIONS."--_American Journal of Insanity._ - - "The Section on Pathological Anatomy is UNRIVALLED in English - literature."--_Bulletin de la Soc. Med. Mentale de Belgique._ - - -_Large 8vo, Handsome Cloth, 16s._ - - LUNATIC ASYLUMS: - THEIR ORGANISATION AND MANAGEMENT. - -BY CHARLES MERCIER, M.B., - - _Late Senior Assistant-Medical Officer at Leavesden Asylum, and at - the City of London Asylum._ - - - =PART I. HOUSING.=--=General Principles=: Sanitary - Conditions--Supervision--Treatment and Grouping--Precautions--Size; - Cost; Equipment; Accessibility. =General Arrangements=: General - Construction; Walls; Floors; Windows; Blinds; Locks--Heating; Open - Fires; Hot Coils in the Wards; Hot Coils outside the Ward; The - Fire-places; Fire-guards--Lighting; Gas Meters--Water; The Softening - of Water; Water Meters. =Wards and Ward Offices=: (_a_) The Day - Rooms--Furniture; Floor Covering; Curtains; Tables; Seats; Screens; - Bookcase; Newspaper Stand; Letter-Box; Piano; Decorations; Flowers - and Plants; Medicine and other Cupboards--(_b_) Dormitories--Beds; - Woven Wire Mattresses; Bed Feet; Special Forms of Bedstead; - Mattresses; Pillows; Blankets; Quilts; Chamber Utensils; Mirrors; - Brushes and Combs; Lockers; Screens--Supervision Dormitories--Single - Rooms; Shutters; Ventilation and Lighting--Padded Rooms--Bath Rooms - and Baths--Urinals--Water-Closets; Position; Floor and Walls; Forms; - Water Waste Preventers--Lavatories; Basins; Towels--Sculleries--Slop - and Brush Closets--Boot Rooms--Soiled Linen Closets--Coal - Stores--Ward Stores. =The Dining and Recreation Halls, Chapel, &c.=: - Recreation Hall; Heating; Ventilation--The Chapel--Receiving - Room--Visiting Room. =Communication=: Passages; Staircases. - =Administrative Portion=: The Kitchen--Scullery--Laundry--Wash - House; Drying Room; Ironing Room; Foul Laundry; Boiler - House--Stores--Workshops--Offices; Superintendent's; Assistant - Medical Officer's; Other Officers'; Library; Dispensary; Mortuary; - Photographic Studio. =Accommodation for the Staff=: For the Medical - Superintendent--For Attendants--For Assistant Medical Officers. - =Airing Courts=: Plants--Flower Beds--Paths--Seats--Birds and Games. - - =PART II. FOOD AND CLOTHING.=--=Food=: Character of - Food--Beverages--Dietaries. =Testing=: Meat; Salt Meat; Flour; - Bread; Butter; Milk; Cheese; Sugar; Tea; Coffee; Cocoa; Vinegar; - Pepper; Mustard; Salt; Beer; Tinned Provisions; Rice; Peas and - Beans; Potatoes. =Storing and Keeping=: Meat; Tea; Coffee; Cocoa; - Mustard; Pepper; and Spices; Tinned Goods; Milk; Butter; Cheese; - Potatoes. =Serving=: Mode of--Table Furniture--Extra Diets. - =Clothing=: Women's Clothing; Dresses; Petticoats; Stays; Undermost - Garment; Stockings; Boots; Hats and Bonnets; Shawls; Men's Clothing; - Trousers; Coats; Waistcoats; Shirts and Undershirts; Drawers; - Neckties; Boots; Overcoats; Hats and Caps. - - =PART III. OCCUPATION AND AMUSEMENT.=--=Occupation=: Inducement to - Work--Difficulty from want of Intelligence--Dangers--From Use of - Tools; From Relaxation of Supervision; To Security; To Health; From - Mingling of the Sexes. =Amusements=: in the Wards--in the Airing - Courts; Quoits; Bowls; Lawn-Tennis; Skittles; Badminton; Rackets; - Fives; Croquet; Golf; Cricket; Football; Grounds; Other Open-Air - Amusements; Races, &c.--Recreations in the Recreation Hall; Dances; - Theatricals; Concerts. - - =PART IV. DETENTION AND CARE.=--=Detention=: Meaning of Term; - Limitation of Restraint. =Care=: Suicide; Suicidal Tendency in the - First Degree--Suicides in the Second Degree--Suicides in the Third - Degree--Treatment of the First Degree--Treatment of the Third - Degree--Supervision--Precautions; Razors; Knives and Scissors; - Broken Glass and Crockery; Home-Made Knives; Points of Suspension; - Means of Suspension; Fire; Water. =Violence=: Provocations and - Inducements--Aggressive Restraint--Closeness of Aggregation--Insane - Peculiarities--Treatment of Violent Patients--Dispersion--Removal of - Causes--Change of Surroundings--Forewarnings of Violence--Mode of - Assault--Assaults with Weapons--Precautions as to - Weapons--Management of Patients when Violent--Pretended Violence. - =Accident=: Causes of Accidents--Falls--Epileptic Fits--Warnings of - Fits--Amplitude of Warning--Direction of Fall--Labour of - Epileptics--Various Precautions for Epileptics--Falls from Defective - Footgear--from Feebleness--from Jostling--from Obstacles--from - Defects in Flooring--Suffocation; Impaction of Food in the - Throat--Precautions--Inhalation of Food into the - Windpipe--Epileptics at Night--Scalding--Fire--Precautions in - Construction--Precautions in Management--Provisions for the Safety - of Patients--Locks of Single Rooms--Removal of Patients should be - Practised--Fire-Extinguishing Apparatus. =Cleanliness=: - Bathing--Dirty Habits--Causes; Treatment; Neatness of Apparel. - - =PART V. THE STAFF.=--Responsibility--Treatment according to - Deserts; Awards to Merit; Awards to Faulty Conduct; Amount of - Punishment; Punishment should be Prompt; Punishment should fit the - Crime; Who should Punish; Reward and Punishment both - necessary--Supervision; Inspection; Surprise Visits--Reports. =The - Chaplain=: The Library--Repairing Books--Torn Pages: Loose Pages; - Back half off; Back wholly gone; Covers Torn; Re-sewing--Other - Duties. =The Superintendent=: Supremacy--Character--Duties--Medical - Duties. =Statutory Duties=: Duties attending the Reception of - Patients--Original Reception--Private Patient--Reception on Judicial - Order on Petition; The Order; The Certificates. - - -~By Drs. OBERSTEINER and HILL.~ - - THE - CENTRAL NERVOUS ORGANS: - _A GUIDE TO THE STUDY OF THEIR STRUCTURE IN - HEALTH AND DISEASE._ - -BY - -PROFESSOR H. OBERSTEINER, - - University of Vienna. - -_TRANSLATED, WITH ANNOTATIONS AND ADDITIONS_, - -BY - -ALEX HILL, M.A., M.D., - - Master of Downing College, Cambridge. - -_With all the Original Illustrations. Large 8vo, Handsome Cloth, 25s._ - - -[***] The Publishers have the pleasure to announce that to the English -version of this important Treatise, numerous original ADDITIONS and a -GLOSSARY of the subject have been contributed by the EDITOR, whose -admirable work in this department of research is so well known. These -Additions greatly increase the value of the book to students. - -Special attention is also directed to the ILLUSTRATIONS. Many of these -are on a plan peculiarly helpful to the student--the one-half being in -outline, the other filled in. - - -OPINIONS OF THE PRESS. - - "Dr. Hill has enriched the work with many notes of his own. . . . - Dr. Hill's translation is most accurate, the English is excellent, - and the book is very readable. . . . Dr. Obersteiner's work is - admirable. He has a marvellous power of marshalling together a large - number of facts, all bearing on an extremely intricate subject, into - a harmonious, clear, consecutive whole. . . . INVALUABLE as a - text-book."--_British Medical Journal._ - - "A MOST VALUABLE CONTRIBUTION to the Study of the Anatomy and - Pathology of the Nervous System. We cannot speak too highly of the - ability and skill which Prof. Obersteiner has brought to bear on - this most difficult subject, and of the way in which the whole work - is illustrated."--_Brain._ - - "The FULLEST and MOST ACCURATE EXPOSITION now attainable of the - results of anatomical inquiry. The Translation is done by one who is - himself a Master of Anatomy, able not only to follow his author, but - also to supplement him with the results of independent research. Dr. - Hill's additions add materially to the value of the original. The - work is specially commended to all students of mental science. . . . - The illustrative figures are of particular excellence and admirably - instructive."--_Mind._ - - -_In Large 8vo, Handsome Cloth. 21s._ - - FORENSIC MEDICINE - AND - TOXICOLOGY. - - for the Use of Practitioners and Students. - -BY - -J. DIXON MANN, M.D., F.R.C.P., - - Professor of Medical Jurisprudence and Toxicology in Owens College, - Manchester; Examiner in Forensic Medicine in the University of - London, and in the Victoria University; Physician to the Salford - Royal Hospital. - - -PART I.--Forensic Medicine. PART II.--Insanity in its Medico-legal -Bearings. PART III.--Toxicology. - - _Dublin Medical Journal._--"By far the MOST RELIABLE, MOST - SCIENTIFIC, and MOST MODERN book on Medical Jurisprudence with which - we are acquainted." - - _The Law Journal._--"This new work will be of value to all those who - as medical men or lawyers are engaged in cases where the testimony - of medical experts forms a part of the evidence. . . . A MOST USEFUL - work of reference." - - _Medical Press._--"This EXCELLENT TEXT-BOOK cannot fail to be a - success; it gives all a student requires for examination, and all - that is necessary for the practitioner." - - -_In Large 8vo, Handsome Cloth. 25s._ - - A TREATISE ON RUPTURES. - -BY - -JONATHAN F. C. H. MACREADY, F.R.C.S., - - Surgeon to the Great Northern Central Hospital; to the City of - London Hospital for Diseases of the Chest, Victoria Park; to the - Cheyne Hospital for Sick and Incurable Children; and to the City of - London Truss Society. - -_With Twenty-four Lithographed Plates and Illustrations in the Text._ - - - _Lancet._--"A MINE OF WEALTH to those who will study it--a great - storehouse of FACTS." - - _Edinburgh Medical Journal._--"Certainly by far the MOST COMPLETE - and AUTHORITATIVE WORK on the subject with which we are acquainted. - The text is clear and concise, the numerous illustrations are - REPRODUCTIONS FROM PHOTOGRAPHS from nature; the author's statements - are founded on an UNIQUE EXPERIENCE, watch is freely drawn upon." - - _Dublin Journal of Medical Science._--"This really is a COMPLETE - MONOGRAPH on the subject." - - -~By W. THORBURN, F.R.C.S. Eng.~ - - THE SURGERY OF THE SPINAL CORD - - (A Contribution to the Study of): - -By WILLIAM THORBURN, B.S., B.Sc., M.D. Lond., F.R.C.S. Eng., - - Assistant Surgeon to the Manchester Royal Infirmary. - -_In Large 8vo, with Illustrations and Tables. Handsome Cloth, 12s. 6d._ - - - "We congratulate Dr. Thorburn on his MASTERLY MONOGRAPH."--_Saturday - Review._ - - "A MOST VALUABLE CONTRIBUTION to the literature of a field of - surgery which, although but recently brought under cultivation, is - already yielding such brilliant results."--_Birmingham Medical - Review._ - - "Really the FULLEST RECORD we have of Spinal Surgery. . . . The work - marks an important advance in modern Surgery." - - "A most THOROUGH and EXHAUSTIVE work on Spinal Surgery."--_Bristol - Medical Journal._ - - "A MOST VALUABLE contribution both to Physiology and - Surgery."--_Ophthalmic Review._ - - "A VERY VALUABLE contribution to practical neurology. . . . This - book is an excellent, clear, concise monograph."--_Philadelphia - Therapeutic Gazette._ - - -~By H. W. PAGE, F.R.C.S.~ - - RAILWAY INJURIES: - - _With Special Reference to those of the Back and Nervous System, in - their Medico-Legal and Clinical Aspects._ - -By HERBERT W. PAGE, M.A., M.C. (Cantab), F.R.C.S. (Eng.), - - Surgeon to St. Mary's Hospital, Dean, St. Mary's Hospital Medical - School, &c. - -_In Large 8vo. Handsome Cloth, 6s._ - - - "A work INVALUABLE to those who have many railway cases under their - care pending litigation. . . . A book which every lawyer as well as - doctor should have on his shelves."--_British Medical Journal._ - - "Deserves the most careful study. . . . A book which every medical - man would do well to read before he presents himself for examination - and cross-examination in the witness-box on a railway - case."--_Dublin Med. Journal._ - - "This book will undoubtedly be of great use to Lawyers."--_Law - Times._ - - -~By J. KNOWSLEY THORNTON, M.B., M.C.~ - - THE SURGERY OF THE KIDNEYS, - - Being the Harveian Lectures, 1889. - -By J. KNOWSLEY THORNTON, M.B., M.C., - - Surgeon to the Samaritan Free Hospital, &c. - -_In Demy 8vo, with Illustrations. Handsome Cloth, 5s._ - - - "The name and experience of the author confer on the Lectures the - stamp of authority."--_British Medical Journal._ - - "These Lectures are an exposition by the hand of an EXPERT of what - is known and has been done, up to the present, in the Surgery of the - Kidneys."--_Edinburgh Medical Journal._ - - "The book will necessarily be widely read, and will have an - important influence on the progress of this domain of - Surgery."--_University Medical Magazine._ - - -SECOND REVISED AND ENLARGED EDITION. _With Illustrations in the Text, -and Thirty-Seven Plates. Large 8vo. Handsome Cloth, 30s._ - - SEWAGE DISPOSAL WORKS: - - A GUIDE TO THE - - _Construction of Works for the Prevention of the Pollution by Sewage - of Rivers and Estuaries._ - -BY - -W. SANTO CRIMP, MEM. INST. C.E., F.G.S., - - Late Assistant-Engineer to the London County Council. - -SECOND EDITION. REVISED AND ENLARGED. - - -PART I.--INTRODUCTORY. - - Introduction. - Details of River Pollutions and Recommendations of Various Commissions. - Hourly and Daily Flow of Sewage. - The Pail System as Affecting Sewage. - The Separation of Rain-water from the Sewage Proper. - Settling Tanks. - Chemical Processes. - The Disposal of Sewage-sludge. - The Preparation of Land for Sewage Disposal. - Table of Sewage Farm Management. - - -PART II.--SEWAGE DISPOSAL WORKS IN OPERATION--THEIR CONSTRUCTION, -MAINTENANCE, AND COST. - -_Illustrated by Plates showing the General Plan and Arrangement adopted -in each District._ - - LONDON. - Doncaster Irrigation Farm. - Beddington Irrigation Farm, Borough of Croydon. - Bedford Sewage Farm Irrigation. - Dewsbury and Hitchin Intermittent Filtration. - Merton, Croydon Rural Sanitary Authority. - Rochester, Kent, and Swanwick, Derbyshire. - The Ealing Sewage Works. - Chiswick. - Kingston-on-Thames, A.B.C. Process. - Salford Sewage Works. - Bradford, Precipitation. - New Malden, Chemical Treatment and Small Filters. - Friern Barnet. - Acton, Ferozone and Polarite Process. - Ilford, Chadwell, and Dagenham Sewage Disposal Works. - Coventry. - Wimbledon. - Birmingham. - Margate. - Portsmouth. - BERLIN. - Sewage Precipitation Works, Dortmund (Germany). - Treatment of Sewage by Electrolysis. - - "All persons interested in Sanitary Science owe a debt of gratitude - to Mr. Crimp. . . . His work will be especially useful to SANITARY - AUTHORITIES and their advisers . . . EMINENTLY PRACTICAL AND USEFUL - . . . gives plans and descriptions of MANY OF THE MOST IMPORTANT - SEWAGE WORKS of England . . . with very valuable information as to - the cost of construction and working of each. . . . The - carefully-prepared drawings permit of an easy comparison between the - different systems."--_Lancet._ - - "Probably the BEST AND MOST COMPLETE TREATISE on the subject which - has appeared in our language. . . . Will prove of the greatest use - to all who have the problem of Sewage Disposal to face. . . . The - general construction, drawings, and type are all - excellent."--_Edinburgh Medical Journal._ - - -~By Prof. A. C. HADDON.~ - - EMBRYOLOGY - - (AN INTRODUCTION TO THE STUDY OF). - -BY - -ALFRED C. HADDON, M.A., M.R.I.A., - - Professor of Zoology, Royal College of Science, Dublin. - -_In Large 8vo, with 190 Illustrations. Handsome Cloth, 18s._ - - -OPINIONS OF THE PRESS. - - "WELL and CLEARLY WRITTEN. . . . Many important discoveries or - theories are described, which are necessarily absent from Balfour's - work."--_Nature._ - - "Dr. Haddon has written the BEST of the three modern English works - on the subject."--_Dublin Medical Journal._ - - "The later chapters of Prof. Haddon's work ably demonstrate the - development of organs from the mesoblast and epiblast."--_Brit. Med. - Journal._ - - "The zoological student, to whom as a text-book it is invaluable, - will find it THOROUGH, TRUSTWORTHY, AND SOUND in all its teachings, - and well up to date. . . . We specially commend the book to our - readers."--_Nat. Monthly._ - - - THE JOURNAL - OF - ANATOMY & PHYSIOLOGY: - NORMAL AND PATHOLOGICAL. - -Conducted by - -SIR GEORGE MURRAY HUMPHRY, M.D., LL.D., F.R.S., - - Professor of Surgery, Late Professor of Anatomy in the University of - Cambridge; - -SIR WILLIAM TURNER, M.B., LL.D., D.C.L., F.R.S., - - Prof. of Anatomy in the University of Edinburgh; - -AND - -J. G. M'KENDRICK, M.D., F.R.S., - - Prof. of the Institutes of Medicine in the University of Glasgow. - -_Published Quarterly, Price 6s. Annual Subscription, 20s.; Post Free, -21s. Subscriptions payable in advance._ - - -~By R. S. AITCHISON.~ - -_SECOND EDITION. Pocket-Size, Elegantly bound in Leather, Rounded edges, -8s. 6d._ - - A MEDICAL HANDBOOK - For the use of Practitioners and Students. - -BY - -R. S. AITCHISON, M.B. (EDIN.), F.R.C.P.E., - - Physician, New Town Dispensary, Edinburgh; Visiting Physician, St. - Cuthbert's Hospital, Edinburgh, &c., &c. - -_WITH NUMEROUS ILLUSTRATIONS._ - - -=General Contents.=--Introduction--Diagnosis, Case-Taking, &c.--Diseases -of the Circulatory System--Diseases of the Respiratory System--The -Urine--Diseases of the Urinary System--Diseases of the Digestive -System--Diseases of the Nervous System--Diseases of the Haemopoietic -System--Constitutional and General Diseases--Fevers and -Miasmatic Diseases--General Data, Rules, and Tables useful -for Reference--_Post-mortem_ Examination--Rules for -Prescribing--Prescriptions. - - "Such a work as this is really NECESSARY for the busy practitioner. - The field of medicine is so wide that even the best informed may at - the moment miss the salient points in diagnosis . . . he needs to - refresh and revise his knowledge, and to focus his mind on those - things which are ESSENTIAL. We can speak HIGHLY of Dr. Aitchison's - Handbook. . . . HONESTLY EXECUTED. No mere compilation, the - scientific spirit and standard maintained throughout put it on a - higher plane. . . . EXCELLENTLY got up, handy and portable, and well - adapted for READY REFERENCE."--_The Lancet._ - - "As a means of ready reference, MOST COMPLETE. The busy practitioner - will often turn to its pages."--_Journ. of the American Med. - Association._ - - -~By MM. CAIRD and CATHCART.~ - -_FIFTH EDITION, Revised. Pocket-Size, Elegantly bound in Leather, -Rounded edges, 8s. 6d. With very Numerous Illustrations._ - - A SURGICAL HANDBOOK, - - For Practitioners, Students, House-Surgeons, and Dressers. - -BY - -F. M. CAIRD, M.B., F.R.C.S., & C. W. CATHCART, M.B., F.R.C.S., - - Assistant-Surgeons, Royal Infirmary, Edinburgh. - - -=General Contents.=--Case-Taking--Treatment of Patients before and -after Operation--Anaesthetics: General and Local--Antiseptics -and Wound-Treatment--Arrest of Haemorrhage--Shock and -Wound-Fever--Emergency Cases--Tracheotomy: Minor Surgical -Operations--Bandaging--Fractures--Dislocations, Sprains, and -Bruises--Extemporary Appliances and Civil Ambulance -Work--Massage--Surgical Applications of Electricity--Joint-Fixation and -Fixed Apparatus--The Urine--The Syphon and its Uses--Trusses and -Artificial Limbs--Plaster-Casting--Post-Mortem Examination--Appendix: -Various Useful Hints, Suggestions, and Recipes. - - "THOROUGHLY PRACTICAL AND TRUSTWORTHY, well up to date, CLEAR, - ACCURATE, AND SUCCINCT. The book is handy, and very well got - up."--_Lancet._ - - "ADMIRABLY ARRANGED. The best practical little work we have seen. - The matter is as good as the manner."--_Edinburgh Medical Journal._ - - "Will prove of real service to the Practitioner who wants a useful - _vade mecum_."--_British Medical Journal._ - - "Fulfils admirably the objects with which it has been - written."--_Glasgow Medical Journal._ - - "THIS EXCELLENT LITTLE WORK. Clear, concise, and very readable. - Gives attention to important details often omitted, but ABSOLUTELY - NECESSARY TO SUCCESS."--_Athenaeum._ - - "A dainty volume."--_Manchester Medical Chronicle._ - - -Griffin's Pocket-Book Series. - -~By Drs. PORTER and GODWIN.~ - -_FOURTH EDITION. Revised and Enlarged. Leather, Rounded Edges, with 128 -Illustrations and Folding-plate. 8s. 6d._ - - THE SURGEON'S POCKET-BOOK. - Specially adapted to the Public Medical Services. - -BY SURGEON-MAJOR J. H. PORTER. - -_REVISED AND IN GREAT PART REWRITTEN_ - -BY BRIGADE-SURGEON C. H. Y. GODWIN, - - Late Professor of Military Surgery in the Army Medical School. - - - "Every Medical Officer is recommended to have the 'Surgeon's - Pocket-Book,' by Surgeon-Major Porter, accessible to refresh his - memory and fortify his judgment."--_Precis of Field-Service Medical - Arrangements for Afghan War._ - - "The present editor--Brigade-Surgeon Godwin--has introduced so much - that is new and practical, that we can recommend this 'Surgeon's - Pocket-Book' as an INVALUABLE GUIDE to all engaged, or likely to be - engaged, in Field Medical Service."--_Lancet._ - - "A complete _vade mecum_ to guide the military surgeon in the - field."--_British Medical Journal._ - - -_Pocket Size. Leather. With Illustrations. At Press._ - - PRACTICAL HYGIENE: - INCLUDING - Air and Ventilation; Water, Supply and Purity; Food and the - Detection of Adulterations; Sewage Removal, Disposal, - and Treatment; Epidemics, &c., &c. - -BY - -SURGEON-MAJOR A. M. DAVIES, D.P.H.Camb., - - _Late Assistant-Professor of Hygiene, Army Medical School._ - - -_POCKET SIZE. LEATHER. SHORTLY._ - - SANITARY RULES AND TABLES: - A Pocket-Book of Data and General Information - -Useful to Medical Men, Medical Officers of Health, Sanitary Authorities, -Municipal Engineers, Surveyors, and Sanitary Inspectors. - -BY - -W. SANTO CRIMP, M.INST.C.E., F.G.S, - -AND - -CHARLES HAMLET COOPER, A.M.I.C.E. - - -_With Numerous Illustrations and Plate in Colours. 5s._ - - MIDWIFERY - (_AN INTRODUCTION TO THE STUDY OF._) - For the Use of Young Practitioners, Students, and Midwives. - -BY ARCHIBALD DONALD, M.A., M.D., C.M.EDIN., - - Surgeon to St. Mary's Hospital for Women and Children, Manchester; - and the Manchester and Salford Lying-in Institution. - - - _British Gynaecological Journal._--"HIGHLY CREDITABLE to the author, - and should prove of GREAT VALUE to Midwifery Students and Junior - Practitioners." - - _Sheffield, Medical Journal._--"As an introduction to the study of - Midwifery, NO BETTER BOOK could be placed in the hands of the - Student." - - -_In Crown 8vo, with Illustrations. 7s. 6d._ - - THE DISEASES OF WOMEN - (OUTLINES OF). - A CONCISE HANDBOOK FOR STUDENTS. - -BY JOHN PHILLIPS, M.A., M.D., F.R.C.P., - - Physician, British Lying-in Hospital; Assist. Obst. Physician, - King's College Hospital; Fell. and Mem. Bd. for Exam. of Midwives, - Obstet. Society; Examiner in Midwifery, University of Glasgow, &c., - &c. - - -[***] Dr. Phillips' work is ESSENTIALLY PRACTICAL in its nature, and -will be found invaluable to the student and young practitioner. - - - "Contains a GREAT DEAL OF INFORMATION in a VERY CONDENSED form. - . . . The value of the work is increased by the number of sketch - diagrams, some of which are HIGHLY INGENIOUS."--_Edin. Med. - Journal._ - - "Dr. PHILLIPS' MANUAL is written in a SUCCINCT style. He rightly - lays stress on Anatomy. The passages on CASE-TAKING are EXCELLENT. - Dr. Phillips is very trustworthy throughout in his views on - THERAPEUTICS. He supplies an excellent series of SIMPLE but VALUABLE - PRESCRIPTIONS, an INDISPENSABLE REQUIREMENT for students."--_Brit. - Med. Journal._ - - "This EXCELLENT TEXT-BOOK . . . gives just what the student - requires. . . . The prescriptions cannot but be helpful."--_Medical - Press._ - - -_In 8vo, with Illustrations. Cloth, 7s. 6d._ - - The Management of Labour and of the Lying-in Period. - -BY PROF. H. G. LANDIS, M.D., - - Starling Medical College. - - - "Fully accomplishes the object kept in view by its author. . . . - Will be found of GREAT VALUE by the young practitioner."--_Glasgow - Medical Journal._ - - -BY SIR WILLIAM AITKEN, M.D. Edin., F.R.S, - - Late Professor of Pathology in the Army Medical School; Examiner in - Medicine for the Military Medical Services of the Queen; Fellow of - the Sanitary Institute of Great Britain; Corresponding Member of the - Royal Imperial Society of Physicians of Vienna, and of the Society - of Medicine and Natural History of Dresden. - - -SEVENTH EDITION. - - THE SCIENCE AND PRACTICE OF MEDICINE. - -_In Two Volumes, Royal 8vo, Cloth, 42s._ - - "The STANDARD TEXT-BOOK in the English Language. . . . There is, - perhaps, no work more indispensable for the Practitioner and - Student."--_Edin. Medical Journal._ - - - OUTLINES OF THE SCIENCE AND PRACTICE OF MEDICINE. - A TEXT-BOOK FOR STUDENTS. - -Second Edition. Crown 8vo, 12s. 6d. - - "Students preparing for examinations will hail it as a perfect - godsend for its conciseness."--_Athenaeum._ - - -_In Large Crown 8vo. With numerous Illustrations. 10s. 6d._ - - ANAESTHETICS AND THEIR ADMINISTRATION: - A PRACTICAL HAND-BOOK FOR MEDICAL AND DENTAL - PRACTITIONERS AND STUDENTS. - -BY FREDERIC HEWITT, M.A., M.D., - - _Anaesthetist and Instructor in Anaesthetics, London Hospital; - Chloroformist and Lecturer on Anaesthetics, Charing Cross Hospital; - Anaesthetist, Dental Hospital, London; and National Orthopaedic - Hospital, &c., &c._ - - "The MOST TRUSTWORTHY book for reference on the subject with which - we are acquainted."--_Edinburgh Med. Journal._ - - "Should be on EVERY medical bookshelf."--_Practitioner._ - - "May truly be described as a valuable addition to medical - literature. . . . ABSOLUTELY ESSENTIAL to junior - practitioners."--_Practitioner._ - - "The BEST TREATISE on the subject we have yet read."--_Dublin Journ. - Med. Science._ - - -_In Large 8vo. Cloth, 12s. 6d._ - - THE - PHYSIOLOGIST'S NOTE-BOOK: - A SUMMARY OF THE - Present State of Physiological Science for Students. - -BY - -ALEX HILL, M.A., M.D., - - Master of Downing College, Cambridge. - -_With Numerous Illustrations and Blank Pages for MS. Notes._ - -General Contents.--The Blood--The Vascular System--The -Nerves--Muscle--Digestion--The Skin--The Kidneys--Respiration--The -Senses--Voice and Speech--Central Nervous -System--Reproduction--Chemistry of the Body. - - -CHIEF FEATURES OF DR. HILL'S NOTE-BOOK. - - 1. It helps the Student to CODIFY HIS KNOWLEDGE. - 2. Gives a grasp of BOTH SIDES of an argument. - 3. Is INDISPENSABLE for RAPID RECAPITULATION. - - _The Lancet_ says of it:--"The work which the Master of Downing - College modestly compares to a Note-book is an ADMIRABLE COMPENDIUM - of our present information . . . will be a REAL ACQUISITION to - Students . . . gives all ESSENTIAL POINTS. . . . The TYPOGRAPHICAL - ARRANGEMENT is a chief feature of the book. . . . Secures at a - glance the EVIDENCE on both sides of a theory." - - _The Hospital_ says:--"The Physiologist's Note-book bears the - hall-mark of the Cambridge School, and is the work of one of the - most successful of her teachers. . . . Will be INVALUABLE to - students." - - _The British Medical Journal_ commends in the volume--"Its admirable - diagrams, its running bibliography, its clear Tables, and its - concise statement of the anatomical aspects of the subject." - - "If a Student could rely on remembering every word which he had ever - heard or read, such a book as this would be unnecessary; but - experience teaches that he constantly needs to recall the form of an - argument and to make sure of the proper =classification of his - facts=, although he does not need a second time to follow the author - up all the short steps by which the ascent was first made. With a - view to rendering the book useful for rapid recapitulation, I have - endeavoured to strike out every word which was not essential to - clearness, and thus, without I hope falling into 'telegram' English, - to give the text the form which it may be supposed to take in a - well-kept Note-book; at the same time, space has been left for the - =introduction in MS.= of such additional facts and arguments as seem - to the reader to bear upon the subject-matter. For the same reason - the drawings are reduced to =diagrams=. All details which are not - necessary to the comprehension of the principles of construction of - the apparatus or organ, as the case may be, are omitted, and it is - hoped that the drawings will, therefore, be easy to grasp, remember, - and reproduce. - - "As it is intended that the 'Note-book' should be essentially a - Student's book, no references are given to foreign literature or to - recondite papers in English; but, on the other hand, references are - given to a number of =classical English memoirs=, as well as to - descriptions in text-books which appear to me to be particularly - lucid, and the Student is strongly recommended to study the passages - and Papers referred to."--_Extract from Author's Preface._ - - -By WILLIAM STIRLING, M.D., Sc.D., - - Professor in the Victoria University, Brackenbury Professor of - Physiology and Histology in the Owens College, Manchester; and - Examiner in the Universities of Oxford, Edinburgh, and London; and - for the Fellowship of the Royal College of Surgeons, England. - - -_SECOND EDITION. In Extra Crown 8vo, with 234 Illustrations. Cloth, 9s._ - - PRACTICAL PHYSIOLOGY (Outlines of): - A Manual for the Physiological Laboratory, - - INCLUDING - - CHEMICAL AND EXPERIMENTAL PHYSIOLOGY, WITH REFERENCE TO PRACTICAL - MEDICINE. - - Part I.--Chemical Physiology. - Part II.--Experimental Physiology. - -[***] _In the Second Edition, revised and enlarged, the number of -Illustrations has been increased from 142 to 234._ - -[Illustration: Fig. 118.--Horizontal Myograph of Fredericq. _M_, Glass -plate, moving on the guides _f_, _f_; _l_, Lever; _m_, Muscle; _p_, _e_, -_e_, Electrodes; _T_, Cork plate; _a_, Counterpoise to lever; _R_, Key -in primary circuit.] - - -OPINIONS OF THE PRESS. - - "This valuable little manual. . . . The GENERAL CONCEPTION of the - book is EXCELLENT; the arrangement of the exercises is all that can - be desired; the descriptions of experiments are CLEAR, CONCISE, and - to the point."--_British Medical Journal._ - - "The Second Edition has been thoroughly worked up to date, and a - large number of well-executed woodcuts added. It may be recommended - to the student as one of the BEST MANUALS he can possess as a guide - and companion in his Physiological Work, and as one that will - usefully supplement the course given by a Physiological - Teacher."--_Lancet._ - - "The student is enabled to perform for himself most of the - experiments usually shown in a systematic course of lectures on - physiology, and the practice thus obtained must prove INVALUABLE. - . . . May be confidently recommended as a guide to the student of - physiology, and, we doubt not, will also find its way into the hands - of many of our scientific and medical practitioners."--_Glasgow - Medical Journal._ - - "An exceedingly convenient Handbook of Experimental - Physiology."--_Birmingham Medical Review._ - - -~Companion Volume by Prof. Stirling.~ - -_SECOND EDITION. In Extra Crown 8vo, with 368 Illustrations. Cloth, 12s. -6d._ - - PRACTICAL HISTOLOGY (Outlines of): - A MANUAL FOR STUDENTS. - -[***] Dr. Stirling's "Outlines of Practical Histology" is a compact -Handbook for students, providing a COMPLETE LABORATORY COURSE, in which -almost every exercise is accompanied by a drawing. Very many of the -Illustrations have been prepared expressly for the work. - -[Illustration: Fig. 200.--L.S., Cervical Ganglion of Dog. _c_, Capsule; -_s_, Lymph sinus; _F_, Follicle; _a_, Medullary cord; _b_, Lymph paths -of the medulla; _V_, Section of a blood-vessel; _HF_, Fibrous part of -the hilum. x 10.] - - -OPINIONS OF THE PRESS. - - "The general plan of the work is ADMIRABLE. . . . It is very evident - that the suggestions given are the outcome of a PROLONGED EXPERIENCE - in teaching Practical Histology, combined with a REMARKABLE JUDGMENT - in the selection of METHODS. . . . Merits the highest praise for the - ILLUSTRATIONS, which are at once clear and faithful."--_British - Medical Journal._ - - "We can confidently recommend this small but CONCISELY-WRITTEN and - ADMIRABLY ILLUSTRATED work to students. They will find it to be a - VERY USEFUL and RELIABLE GUIDE in the laboratory, or in their own - room. All the principal METHODS of preparing tissues for section are - given, with such precise directions that little or no difficulty can - be felt in following them in their most minute details. . . . The - volume proceeds from a MASTER in his craft."--_Lancet._ - - "We have no doubt the OUTLINES will meet with most favourable - acceptance among workers in Histology."--_Glasgow Medical Journal._ - - -WORKS - -By J. R. AINSWORTH DAVIS, B. A., - - PROFESSOR OF BIOLOGY, UNIVERSITY COLLEGE, ABERYSTWYTH. - - BIOLOGY - (AN ELEMENTARY TEXT-BOOK OF). - -SECOND EDITION. In Two Parts. - - PART I. VEGETABLE MORPHOLOGY AND PHYSIOLOGY. With Complete - Index-Glossary and 128 Illustrations. Price 8s. 6d. - - PART II. ANIMAL MORPHOLOGY AND PHYSIOLOGY. With Complete - Index-Glossary and 108 Illustrations. Price 10s. 6d. - -_EACH PART SOLD SEPARATELY._ - - [***] NOTE.--The SECOND EDITION has been thoroughly Revised and - Enlarged, and includes all the leading selected TYPES in the various - Organic Groups. - - Of the SECOND EDITION, the _British Medical Journal_ - says:--"Certainly THE BEST 'BIOLOGY' with which we are acquainted, - and it owes its pre-eminence to the fact that it is an EXCELLENT - attempt to present Biology to the Student as a CORRELATED and - COMPLETE SCIENCE. The glossarial Index is a MOST USEFUL addition." - - "Furnishes a CLEAR and COMPREHENSIVE exposition of the subject in a - SYSTEMATIC form."--_Saturday Review._ - - "Literally PACKED with information."--_Glasgow Medical Journal._ - - - THE FLOWERING PLANT, - AS ILLUSTRATING THE FIRST PRINCIPLES OF BOTANY. - - Specially adapted for London Matriculation, S. Kensington, and - University Local Examinations in Botany. SECOND EDITION. With - numerous Illustrations. 3s. 6d. - - "It would be hard to find a Text-book which would better guide the - student to an accurate knowledge of modern discoveries in Botany. - . . . The SCIENTIFIC ACCURACY of statement, and the concise - exposition of FIRST PRINCIPLES make it valuable for educational - purposes. In the chapter on the Physiology of Flowers, an _admirable - resume_ is given, drawn from Darwin, Hermann Mueller, Kerner, and - Lubbock, of what is known of the Fertilization of - Flowers."--_Journal of the Linnean Society._ - - [***] Recommended by the National Home-Reading Union; and also for - use in the University Correspondence Classes. - - - A ZOOLOGICAL POCKET-BOOK: - or, Synopsis of Animal Classification. - -_Comprising Definitions of the Phyla, Classes, and Orders, with -explanatory Remarks and Tables._ - -By Dr. EMIL SELENKA, - - Professor in the University of Erlangen. - -Authorised English translation from the Third German Edition. - -In Small Post 8vo, Interleaved for the use of Students. Limp Covers, 4s. - - - "Dr. Selenka's Manual will be found useful by all Students of - Zoology. It is a COMPREHENSIVE and SUCCESSFUL attempt to present us - with a scheme of the natural arrangement of the animal - world."--_Edin. Med. Journal._ - - "Will prove very serviceable to those who are attending Biology - Lectures. . . . The translation is accurate and clear."--_Lancet._ - - -WORKS by A. WYNTER BLYTH, M.R.C.S., F.C.S., - - Public Analyst for the County of Devon, and Medical Officer of - Health for St. Marylebone. - -_NEW EDITION. Revised and partly Rewritten._ - - - FOODS: THEIR COMPOSITION AND ANALYSIS. - -_In Crown 8vo, Cloth, with Elaborate Tables, Folding Litho-Plate, and -Photographic Frontispiece._ - -_THIRD EDITION. Price 16s._ - - -GENERAL CONTENTS. - - History of Adulteration--Legislation, Past and Present--Apparatus - useful to the Food-Analyst--"Ash"--Sugar--Confectionery--Honey-- - Treacle--Jams and Preserved Fruits--Starches--Wheaten-Flour--Bread-- - Oats--Barley--Rye--Rice--Maize--Millet--Potato--Peas--Chinese Peas-- - Lentils--Beans--MILK--Cream--Butter--Cheese--Tea--Coffee--Cocoa and - Chocolate--Alcohol--Brandy--Rum--Whisky--Gin--Arrack--Liqueurs--Beer-- - Wine--Vinegar--Lemon and Lime Juice--Mustard--Pepper--Sweet and Bitter - Almond--Annatto--Olive Oil--Water. _Appendix_: Text of English and - American Adulteration Acts. - - "Thoroughly practical. . . . Should be in the hands of every medical - practitioner."--_Lancet._ - - "An admirable digest of the most recent state of knowledge. . . . - Interesting even to lay readers."--_Chemical News._ - - "STANDS UNRIVALLED for completeness of information."--_Sanitary - Record._ - - [***] =The THIRD Edition contains many Notable Additions, especially - on the subject of MILK and its relation to FEVER EPIDEMICS, the - PURITY of WATER-SUPPLY, the MARGARINE ACT, &c., &c.= - - - POISONS: THEIR EFFECTS AND DETECTION. - -_With Tables and Illustrations. Price 16s._ - - -GENERAL CONTENTS. - -Historical Introduction--Statistics--General Methods of Procedure--Life -Tests--Special Apparatus--Classification: I.--ORGANIC POISONS: (_a._) -Sulphuric, Hydrochloric, and Nitric Acids, Potash, Soda, Ammonia, &c.; -(_b._) Petroleum, Benzene, Camphor, Alcohols, Chloroform, Carbolic Acid, -Prussic Acid, Phosphorus, &c.; (_c._) Hemlock, Nicotine, Opium, -Strychnine, Aconite, Atropine, Digitalis, &c.; (_d._) Poisons derived -from Animal Substances; (_e._) The Oxalic Acid Group. II.--INORGANIC -POISONS: Arsenic, Antimony, Lead, Copper, Bismuth, Silver, Mercury, -Zinc, Nickel, Iron, Chromium, Alkaline Earths, &c. _Appendix_: (A.) -Examination of Blood and Blood-Spots; (B.) Hints for Emergencies. - - "One of the best and most comprehensive works on the - subject."--_Saturday Review._ - - "A sound and Practical Manual of Toxicology, which cannot be too - warmly recommended. . . . One of its chief merits is that it - discusses substances which have been overlooked."--_Chemical News._ - - - HYGIENE AND PUBLIC HEALTH (A Dictionary of): - Embracing the following subjects:-- - - I.--SANITARY CHEMISTRY: the Composition and Dietetic Value of Foods, - with the Detection of Adulterations. - - II.--SANITARY ENGINEERING: Sewage, Drainage, Storage of Water, - Ventilation, Warming, &c. - - III.--SANITARY LEGISLATION: the whole of the PUBLIC HEALTH ACT, - together with portions of other Sanitary Statutes, in a form - admitting of easy and rapid Reference. - - IV.--EPIDEMIC AND EPIZOOTIC DISEASES: their History and Propagation - with the Measures for Disinfection. - - V.--HYGIENE--MILITARY, NAVAL, PRIVATE, PUBLIC, SCHOOL. - -_Royal 8vo, 672 pp., Cloth, with Map and 140 Illustrations, 28s._ - - "A work that must have entailed a vast amount of labour and - research. . . . Will become a STANDARD WORK IN PUBLIC - HEALTH."--_Medical Times and Gazette._ - - "Contains a great mass of information of easy reference."--_Sanitary - Record._ - - -~By W. ELBORNE, F.L.S.~ - -_In Extra Crown 8vo, with Litho-plates and Numerous Illustrations. -Cloth, 8s. 6d._ - - - ELEMENTS OF - PRACTICAL PHARMACY AND DISPENSING. - -BY WILLIAM ELBORNE, B.A.CANTAB., - - Demonstrator of Materia Medica and Teacher of Pharmacy at University - College, London; Pharmacist to University College Hospital; Member - of the Pharmaceutical Society of Great Britain; Fellow of the - Chemical and Linnean Societies of London; formerly - Assistant-Lecturer in Pharmacy and Materia Medica at the Owens - College, Manchester. - - - "A work which we can very highly recommend to the perusal of all - Students of Medicine. . . . ADMIRABLY ADAPTED to their - requirements."--_Edinburgh Medical Journal._ - - "Mr. Elborne evidently appreciates the Requirements of Medical - Students, and there can be no doubt that any one who works through - this Course will obtain an excellent insight into Chemical - Pharmacy."--_British Medical Journal._ - - "The system . . . which Mr. Elborne here sketches is thoroughly - sound."--_Chemist and Druggist._ - - [***] _Formerly Published under the Title of "PHARMACY AND MATERIA - MEDICA._" - - -~By DRS. DUPRE AND HAKE.~ - -_SECOND EDITION. Crown 8vo. Cloth, 7s. 6d._ - - INORGANIC CHEMISTRY (A Short Manual of). - -BY A. DUPRE, Ph.D., F.R.S., AND WILSON HAKE, - - Ph.D., F.I.C., F.C.S., of the Westminster Hospital Medical School. - - "A well-written, clear, and accurate Elementary Manual of Inorganic - Chemistry. . . . We agree heartily in the system adopted by Drs. - Dupre and Hake. WILL MAKE EXPERIMENTAL WORK TREBLY INTERESTING - BECAUSE INTELLIGIBLE."--_Saturday Review._ - - -WORKS by Prof. HUMBOLDT SEXTON, F.I.C., F.C.S., F.R.S.E., - - Glasgow and West of Scotland Technical College. - - - OUTLINES OF QUANTITATIVE ANALYSIS. - -_With Illustrations. FOURTH EDITION. Crown 8vo, Cloth, 3s._ - - - "A practical work by a practical man . . . will further the - attainment of accuracy and method."--_Journal of Education._ - - "An ADMIRABLE little volume . . . well fulfils its - purpose."--_Schoolmaster._ - - "A COMPACT LABORATORY GUIDE for beginners was wanted, and the want - has been WELL SUPPLIED. . . . A good and useful book."--_Lancet._ - - -BY THE SAME AUTHOR. - - OUTLINES OF QUALITATIVE ANALYSIS. - -_With Illustrations. THIRD EDITION. Crown 8vo, Cloth, 3s. 6d._ - - - "The work of a thoroughly practical chemist . . . and one which may - be unhesitatingly recommended."--_British Medical Journal._ - - "Compiled with great care, and will supply a want."--_Journal of - Education._ - - -TWELFTH EDITION. _With Numerous Illustrations, 3s. 6d._ - - NURSING (A Manual of): - MEDICAL AND SURGICAL. - -BY LAURENCE HUMPHRY, M.A., M.D., M.R.C.S., - - _Assistant-Physician to, late Lecturer to Probationers at, - Addenbrooke's Hospital, Cambridge._ - - - GENERAL CONTENTS.--The General Management of the Sick Room in - Private Houses--General Plan of the Human Body--Diseases of the - Nervous System--Respiratory System--Heart and - Blood-Vessels--Digestive System--Skin and Kidneys--Fevers--Diseases - of Children--Wounds and Fractures--Management of - Child-Bed--Sick-Room Cookery, &c., &c. - - "In the fullest sense Mr. Humphry's book is a DISTINCT ADVANCE on - all previous Manuals. . . . Its value is greatly enhanced by copious - woodcuts and diagrams of the bones and internal organs, by many - Illustrations of the art of BANDAGING, by Temperature charts - indicative of the course of some of the most characteristic - diseases, and by a goodly array of SICK-ROOM APPLIANCES with which - EVERY NURSE should endeavour to become acquainted."--_British - Medical Journal._ - - "We should advise ALL NURSES to possess a copy of the work. We can - confidently recommend it as an EXCELLENT GUIDE and - companion."--_Hospital._ - - -SECOND EDITION. _Handsome Cloth, 4s._ - - FOODS AND DIETARIES: - HOW AND WHEN TO FEED THE SICK. - -BY R. W. BURNET, M.D., M.R.C.P., - - _Physician to the Great Northern Central Hospital, &c._ - - - GENERAL CONTENTS.--DIET in Diseases of the Stomach, Intestinal - Tract, Liver, Lungs, Heart, Kidneys, &c.; in Diabetes, Scurvy, - Anaemia, Scrofula, Gout, Obesity, Rheumatism, Influenza, Alcoholism, - Nervous Disorders, Diathetic Diseases, Diseases of Children, with - Sections on Prepared and Predigested Foods, and on Invalid Cookery. - - "The directions given are UNIFORMLY JUDICIOUS. . . . May be - confidently taken as a RELIABLE GUIDE in the art of feeding the - sick."--_Brit. Med. Journal._ - - "To all who have much to do with Invalids, Dr. Burnet's book will be - of great use. . . . The subject is TREATED with ADMIRABLE SENSE and - JUDGMENT by Dr. Burnet. The careful study of such books as this will - very much help the Practitioner in the Treatment of cases, and - powerfully aid the action of remedies."--_Lancet._ - - -_Shortly. In Crown 8vo extra. Handsome Cloth._ - - DISINFECTION & DISINFECTANTS: - A PRACTICAL GUIDE - - To the various Disinfectants now in Use--their Nature and Properties, - with the Methods of Analysis and of Application. - -BY - -SAMUEL RIDEAL, D.SC. LOND. - - -_In Crown 8vo. With Frontispiece. Handsome Cloth. 6s._ - - CONSUMPTION - (THE HYGIENIC PREVENTION OF). - -BY J. EDWARD SQUIRE, M.D., D.P.H. CAMB., - - Physician to the North London Hospital for Consumption and Diseases - of the Chest; Fellow of the Royal Med.-Chirurg. Society, and of the - British Institute of Public Health, &c., &c. - - -GENERAL CONTENTS.--THE NATURE OF CONSUMPTION--PREVENTIVE MEASURES: In -Infancy, Childhood, School Life, Adult Life; Exercise, Clothing, -Diet; the Household, Choice of Occupation, Residence--STATE -HYGIENE--MANAGEMENT OF EARLY CONSUMPTION:--Question of Curability, -Climatic Conditions, Travelling, &c. - - - "We can safely say that Dr. SQUIRE's work WILL REPAY STUDY even by - the most cultivated physician. . . . Although the book is not a - large one, it is FULL OF INSTRUCTIVE MATTER, and is written in a - judicious spirit, besides being VERY READABLE."--_The Lancet._ - - - PRACTICAL SANITATION: - _A HANDBOOK FOR SANITARY INSPECTORS AND OTHERS_ - _INTERESTED IN SANITATION._ - -BY GEORGE REID, M.D., D.P.H., - - Fellow of the Sanitary Institute of Great Britain, and Medical - Officer, Staffordshire County Council. - -_WITH AN APPENDIX ON SANITARY LAW_ - -BY HERBERT MANLEY, M.A., M.B., D.P.H., - -Medical Officer of Health for the County Borough of West Bromwich. - -SECOND EDITION. _Revised. With Illustrations. Price 6s._ - - -GENERAL CONTENTS. - -Introduction--Water Supply: Drinking Water, Pollution of -Water--Ventilation and Warming--Principles of Sewage Removal--Details of -Drainage; Refuse Removal and Disposal--Sanitary and Insanitary Work and -Appliances--Details of Plumbers' Work--House Construction--Infection and -Disinfection--Food, Inspection of; Characteristics of Good Meat; Meat, -Milk, Fish, &c., unfit for Human Food--Appendix; Sanitary Law; Model -Bye-Laws, &c. - - - "A VERY USEFUL HANDBOOK, with a very useful Appendix. We recommend - it not only to Sanitary Inspectors, but to ALL interested in - Sanitary matters."--_Sanitary Record._ - - -_Shortly. With Numerous Illustrations. Crown 8vo extra. Handsome Cloth._ - - THE - SEA-CAPTAIN'S MEDICAL GUIDE. - -BY - -WM. JOHNSON SMITH, F.R.C.S., L.S.A., - - Of the Seamen's Hospital, Greenwich; Surgeon, Seamen's Hospital, - Royal Albert Docks; Surgeon, Seamen's Hospital Society, &c., &c. - - - - - Transcriber's Notes - - This text follows the original work. Inconsistencies in spelling, - hyphenation, capitalisation, etc. have been retained, except as - mentioned below. This applies to chemical compound names as well. - - Textual remarks: - Page 13, Footnote [18], Jerome Cardan: also known as Jerome Cardan, - Girolamo Cardano, Hieronymus Cardanus. - Page 18, Praag van, Leonides: should be Leonides van Praag, - Isidorus. This is the (enlarged) Dutch translation of Werber's book. - Page 52: reference to the separate article on (the detection of) - Tin: there is no such article in the book. - Page 62, footnote [55]: micro-millimetre should be micro-metre. - Page 175, structural formulas: the original work gives two identical - structural formulas; both are correct, but they do not show the - difference between the two compounds. - Page 192, that of Borussica: possibly a typographical error for - Borussia (Borussica is the adjective). - Page 399, 18.1 mgrms. (.18 grain): at least one of the numbers is - wrong (possibly the second number should be .28). - Page 507: 6.4 mgmrs. (1 grain): this should probably be either 64 - mgrms. or .1 grain. In the context, the latter seems more probable. - Buchner/Buechner are different persons, both are spelled correctly. - Hofman/Hoffman/Hofmann/Hoffmann, Koehler/Koehler, Line/Linne, - Pellagra/Pellagri, Schuchardt/Schuchart: possibly these are spelling - variants or typographical errors referring to the same persons. - Kapferschlaeger: should possibly be Kupferschlaeger. - Schauffele should possibly be Schauffele or Schaeuffele. - The index has been left as in the original work, even though it is - not always alphabetic. - Advertisements: there are some references to pages 35 and 36 of the - advertisements. These pages were not present in the original. - - Changes made to the text - Some minor obvious punctuation and typographical errors have been - corrected silently. French accents and German umlauts have been - added or corrected where needed. - Multi-page tables have been combined into single tables; many tables - have been re-arranged. - Structural formulas have been moved to separate lines. - Some sections starting with Sec. were printed as section headers in the - original work; they have been treated as regular numbered sections - here. - Footnotes have been moved to under the paragraph, table, etc. they - refer to. - - Various pages: - Chever/Chever's changed to Chevers/Chevers's - Ein natuerliches System der Gift-wirkungen/Giftwirkungen standardised - to Gift-Wirkungen as in Loew's original - Aertzt (also in compound words) changed to Aerzt - Berenger-Ferraud changed to Berenger-Feraud - L. L. Hote and similar spellings changed to L. L'Hote - Grehaut changed to Grehant - - Page xxv: Duboia Ruselli changed to Duboia Rusellii - Page xxix: Aerated changed to Aerated as in text - Page xxx: (3) Silver in the Arts changed to (2) Silver in the Arts - Page xxxii: 90-392 changed to 390-392 - Page 14: Medicine changed to Medecine - Page 16: Veneneuse changed to Veneneuses - Page 17: Dagendorff changed to Dragendorff - Page 18: Webber changed to Werber; In Zwee Theilen changed to In - Zwei Theilen - Page 25: list under A. numbered (as following lists) - Page 27: Mezerein changed to Mezereon - Page 31: Section number Sec. 21. added - Page 39: alloxanthin changed to alloxantin as elsewhere - Page 44: V' changed to V^{1} as in illustration - Page 51: chloralhydrate changed to chloral hydrate as elsewhere - Page 60, table: June changed to Jan. (as described in text below - table) - Page 64: Ni(CO)^{4} changed to Ni(CO)_{4} - Page 82: Salkowski changed to Salkowsky as elsewhere - Page 94, footnote [92]: Schwefelsaeure changed to Schwefelsaeure- - Page 96: bood changed to blood - Page 124: of the legs; changed to of the legs); - Page 129: PART IV changed to PART V - Page 134: tape-worn changed to tape-worm - Page 141: IV. Ether. changed to IV.--Ether. for consistency with - other headings - Page 143: Soubeyran changed to Soubeiran - Page 164, footnote [194]: 1865 changed to 1856 - Page 214: to contains changed to to contain; Afol. changed to Afl. - Page 222: that normal changed to than normal - Page 232: Boisbeaudran changed to Boisbaudran - Page 232: see Index changed to See Sec. 314 - Page 246: Jervin changed to Jervine - Page 249: [gamma] inserted in table - Page 257: Mikroscop changed to Mikroskop - Page 270: table and paragraph "It is therefore obvious ..." moved to - before description of analysis - Page 277: [beta]. lutidine changed to [beta]-lutidine - Page 280, Sec. 340, platinum compound: C_{6}H_{5} etc. changed to - (C_{6}H_{5} etc. - Page 299, Sec. 359: of the French; changed to of the French); - Page 302: menbrane changed to membrane - Page 313: [alpha][r] changed to [[alpha]]r as elsewhere - Page 318, Sec. 384: (C_{5}H_{4}O_{3}-- changed to (C_{5}H_{4}O_{3})-- - Page 320: Pettenkoffer changed to Pettenkofer - Page 328: cephalapoda changed to cephalopoda - Page 329: under goes changed to undergoes - Page 371, footnotes [487a] and [487b]: the original work has one - footnote with two footnote anchors; the footnote has been copied for - clarity - Page 373: homotatropine changed to homatropine - Page 398: Harnach changed to Harnack - Page 409: skaken changed to shaken - Page 423: .15 to .13 grain changed to .15 to .18 grain - Page 448: They eat changed to They ate - Page 449: Wenzeln's changed to Wenzel's - Page 451: [[alpha]]D changed to [[alpha]]_{D} as elsewhere - Page 458: oenanthe changed to [oe]nanthe as elsewhere - Page 465: toxalumin changed to toxalbumin - Page 469: Petromyzon fluviatalis changed to Petromyzon fluviatilis - Page 491: bot hare changed to both are - Page 492: Heading DIAMINES. changed to Diamines. for consistency - Page 514: Uppmain changed to Uppmann - Page 533: bain de tersier changed to bain de Tessier - Page 534, table: 25-35 changed to 25-65 - Page 588: pp. 558 and 555 changed to pp. 558 and 559 - Page 591, Heading II. PRECIPITATE changed to PRECIPITATED as - elsewehere - Page 614: lamellae changed to lamellae as elsewhere - Page 617: (20 to 40 grains; changed to (20 to 40 grains); - Page 637, Ointment of Red Iodide of Mercury: closing ) added after - rubri - Page 638: Hahneman's changed to Hahnemann's - Page 656: from to time changed to from time to time - Page 662: deat changed to death - Page 679: mgrs. changed to mgrms. as elsewhere - Page 686: ANTIDOTES:-- changed to III. ANTIDOTES:-- - Page 698: zine changed to zinc - Page 702: Acolycoctin changed to Acolyctin - Page 704: Fleetman's changed to Fleitmann's - Page 705: Bec[oe]ur changed to Becoeur; - Page 706: Bynsen's changed to Bynssen's - Page 710: Duboia Ruselii changed to Duboia Rusellii - Page 711: Guenzburgh changed to Guenzburg - Page 713: Jecquirity changed to Jequirity; Kreosote changed to - Kreozote; Lanthropine changed to Lanthopine - Page 715: Mithridates changed to Mithradetes - Page 717: Pharoah's serpent changed to Pharaoh's serpent - Page 719: Rettger's changed to Rettgers's - Page 720: Sanarelle's changed to Sanarelli's; Scheppe's changed to - Schleppe's; Schraeder changed to Schraeder - Page 721: antimpetigines changed to anti-impetigines - Page 722: Teschmacher changed to Teschemacher - Page 723: Vidale's changed to Vidali's - Page 739: Bain de Tersier changed to Bain de Tessier - - - - - -End of the Project Gutenberg EBook of Poisons: Their Effects and Detection, by -Alexander Wynter Blyth - -*** END OF THIS PROJECT GUTENBERG EBOOK POISONS: EFFECTS AND DETECTION *** - -***** This file should be named 42709.txt or 42709.zip ***** -This and all associated files of various formats will be found in: - http://www.gutenberg.org/4/2/7/0/42709/ - -Produced by Chris Curnow, Harry Lame and the Online -Distributed Proofreading Team at http://www.pgdp.net (This -file was produced from images generously made available -by The Internet Archive) - - -Updated editions will replace the previous one--the old editions -will be renamed. - -Creating the works from public domain print editions means that no -one owns a United States copyright in these works, so the Foundation -(and you!) can copy and distribute it in the United States without -permission and without paying copyright royalties. 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