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diff --git a/40505-8.txt b/40505-8.txt deleted file mode 100644 index 76ece45..0000000 --- a/40505-8.txt +++ /dev/null @@ -1,10030 +0,0 @@ -The Project Gutenberg EBook of Scurvy Past and Present, by Alfred Fabian Hess - -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: Scurvy Past and Present - -Author: Alfred Fabian Hess - -Release Date: August 14, 2012 [EBook #40505] - -Language: English - -Character set encoding: ISO-8859-1 - -*** START OF THIS PROJECT GUTENBERG EBOOK SCURVY PAST AND PRESENT *** - - - - -Produced by Bryan Ness, Thiers Halliwell and the Online -Distributed Proofreading Team at http://www.pgdp.net (This -file was produced from images generously made available -by The Internet Archive/American Libraries.) - - - - - -Transcriber's notes: - -In this plain text version, bold script is denoted by =equals signs= and -italic script by _underscores_. Underscores are also used with curly -brackets to represent subscripted characters (e.g. CO_{2}). Text that -was originally rendered in small capitals now appears in full capitals. -Footnotes are located below the relevant paragraphs. - -The book contains numerous spelling inconsistencies. No change has been -made to those representing archaic spellings (e.g. 'somethimes', 'urin', -'feavers', 'joynts') and those occurring in quotations. Spelling -variants occurring with similar frequency have been left in their -original form (e.g. Röntgen/Roentgen, rachitic/rhachitic, -albumen/albumin - the correct spellings is used for egg albumen but both -are used randomly for serum/urine albumin). Most other spelling -inconsistencies have been changed to the more-frequent or more-accurate -form (e.g. twofold-->two-fold, guinea pig-->guinea-pig, oedema-->edema, -neuroedema-->neuredema, gm.-->g., Luborsch-->Lubarsch, Bauman-->Baumann, -McCluggage-->McClugage, Eijkmann-->Eijkman). Although the spelling of -'fæces' and its adjective 'fecal' is not consistent, the two spellings -are used consistently throughout the book and therefore have not been -altered. Similarly 'hemorrhage' and 'hemoglobin' are consistently spelt -thus, while other words relating to blood consistently use the æ -ligature, e.g. 'hæmatemesis', 'hæmatoma', 'hæmaturia', 'leukæmia', -'hyperæmia'. - -Wrong or missing French accents and typos have been corrected where -necessary. German expressions in the bibliography contain various -apparent inconsistencies that have not been changed because of my -unfamiliarity with the language and what was perhaps legitimate at the -time of writing (e.g. 'Muench. med. Woch.', 'Muenchn. med. Woch.' and -'Muenschner med. Woch.'; 'Barlow'schen Krankheit' 'Moeller-Barlow'sche -Krankheit', 'Moeller-Barlow'scher Krankheit', and 'Moeller-Barlowscher -Krankheit'; 'Beiträge z.', 'Beitraege zur', 'Beitrag zur'). The term -'Gernest-mark' on p. 108 should probably be 'geruestmark' (or perhaps -gerüstmark) as used elsewhere in the book (pp. 96, 107, 108 and 128). - -The book also contains numerous hyphenation inconsistencies. Some of -these have been altered to conform with the most common usage in the -text, but most have not been changed because hyphenation is notoriously -variable and subject to fashion. - -Subheading use is somewhat inconsistent; for example, under the -subheading 'Alimentary Tract' in chapter IV, there appear various -non-alimentary items, and in the same chapter 'Microscopic Pathology' -appears as a stand-alone subheading whilst its equivalent 'Gross -Pathology' is relegated to a bold in-line paragraph introduction. - -The bibliography contains two very similar references attributed to Gee. -The second appears to be a duplicate of the first, but it is probable -that the title is incorrect because the publication details (1889, XXV, -85) relate to a different paper by Gee entitled 'Bloody Urine the Only -Sign of Infantile Scurvy', and although there are several comments in -this book about scurvy and haematuria (blood in the urine), e.g. p. 204, -none cite Gee's paper. - -The second entry for Morse, J. L. in the bibliography should be numbered -as (2) and the source should be Boston Med. and Surg. Journal, 1914, -CLXX, 504. (not Jour. Am. Med. Assn.). - -Inconsistent punctuation in the bibliography list has been corrected -(e.g. semicolon-->colon). - - * * * * * - - - - - SCURVY - - PAST AND PRESENT - - BY - - ALFRED F. HESS, M.D. - - CLINICAL PROFESSOR OF PEDIATRICS, UNIVERSITY AND BELLEVUE HOSPITAL - MEDICAL COLLEGE, NEW YORK CITY - - _ILLUSTRATED_ - - [Illustration] - - PHILADELPHIA AND LONDON - J. B. LIPPINCOTT COMPANY - - - COPYRIGHT, 1920, BY J. B. LIPPINCOTT COMPANY - - PRINTED BY J. B. LIPPINCOTT COMPANY - AT THE WASHINGTON SQUARE PRESS - PHILADELPHIA, U. S. A. - - - - -PREFACE - - -Interest in scurvy has been stimulated in the last few years as the -result of a new and broader conception of nutrition. It has come to be -realized that in addition to the substances heretofore recognized as of -essential importance in the dietary--the proteins, fats, carbohydrates -and the salts--there is still another group, termed "vitamines," -"accessory food factors" or "food hormones," which must be included in -order to render the diet complete and adequate. It has become -increasingly evident that the attention of physiologists and of -clinicians has been focussed too sharply and too narrowly on the caloric -value of foodstuffs. At the same time we have begun to appreciate the -existence of a group of nutritional disorders which depend largely on a -deficiency of these illusive vitamines or food factors, and which -evidently are of vital importance to the welfare of the individual and -of mankind. Scurvy is one of this newly-constituted group, and due to -this association has acquired a fresh and broader significance. It is in -this light that the intensive research work must be interpreted, which -has been applied within the past few years, both in this country and -abroad, to problems relating to this disorder. It is clear that the -subject is in its infancy, and is destined to participate in a -consideration of many of the nutritional and infectious diseases of the -adult and the child. - -The World War has tended also to demand a renewed consideration of -scurvy. This disorder has played a rôle in all wars--in the campaigns of -the Cæsars, the pilgrim ages of the Crusaders, and the numerous wars of -the last century. In the recent war it existed among the various -armies, particularly those in the East, to an extent greater than at -first was realized. In Mesopotamia it is stated to have been one of the -decisive factors in forcing the surrender of the British at Kut. Its -incidence, however, was not limited to the military forces. Reports from -England and the continental countries clearly indicate that scurvy -prevailed among the civilian population during the past few years to a -degree unknown in peace times. This was especially true of infants and -children. - -For the past seven years I have been engaged in an investigation of -scurvy both in the laboratory and in the clinic, and have treated -various aspects of the subject in a large number of articles published -in various medical journals. In the course of these studies there has -been ample opportunity for a comprehensive review of the -widely-scattered literature. No treatise on scurvy has been published in -English since the classical work of Lind in 1772. The time, therefore, -seemed opportune to gather into one volume the recent advances in this -field and to offer to the clinician, to the hygienist, and to the -biological chemist a presentation of the existing status of this -important nutritional disease. - -It is with pleasure that I acknowledge my obligation to Dr. Lester J. -Unger, who has assisted in carrying out much of the work described in -this volume. Thanks are due also to Dr. Charles Gottlieb for the -radiographs which are here reproduced, and to Dr. Gertrude McCann for -seeing the work through the press. To my associates in the clinic who -shared in the observations, and to friends who read various chapters in -the course of their preparation, I wish to express my appreciation. - - ALFRED F. HESS. - - New York, - August, 1920. - - - - -CONTENTS PAGE - - -PREFACE iii-iv - -CHAPTER I - -HISTORY OF SCURVY 1 - - (_a_) OUTBREAKS ON LAND; (_b_) OUTBREAKS AT SEA; (_c_) INFANTILE - SCURVY; (_d_) SCURVY IN THE WORLD WAR - - -CHAPTER II - -PATHOGENESIS AND ETIOLOGY 23 - - PATHOGENESIS: THEORIES; POTASSIUM DEFICIENCY; ACIDOSIS; TOXIC; - BACTERIAL; VITAMINE (ACCESSORY FACTOR) - -ETIOLOGY: BREAST-FED INFANTS 35 - - ARTIFICIALLY FED INFANTS: PASTEURIZED MILK; BOILED AND STERILIZED - MILK; DRIED MILK; CONDENSED MILK; PROPRIETARY FOODS (EFFECT - OF ALKALIZATION) 40 - - AGE, SEASON AND CLIMATE; ECONOMIC STATUS; PSYCHIC ELEMENT; - PREDISPOSITION; EFFECT OF OTHER FOOD CONSTITUENTS; EXCITING - FACTORS - - -CHAPTER III - -THE ANTISCORBUTIC VITAMINE 62 - - CHARACTERISTICS: RELATION TO HEAT, DRYING, AGING, ULTRA-VIOLET - RAYS, SHAKING 65 - - MODE OF ACTION--(_a_) DIRECT: AS A NUTRIMENT; ANTITOXIN; - CATALYZER; (_b_) INDIRECT: ENDOCRINE ACTION 69 - - FATE IN THE BODY: STORING; CONTENT IN BLOOD; EXCRETION; FATE IN - GASTRO-INTESTINAL TRACT; EFFECT ON DIGESTIVE PROCESSES 74 - - IRREGULARITIES OF ACTION; EFFECT ON GROWTH - - -CHAPTER IV - -PATHOLOGY 81 - - (_a_) GROSS: GENERAL APPEARANCE; HEMORRHAGES; ANASARCA; HEART; - LUNGS; ALIMENTARY TRACT AND ITS GLANDS; URINARY TRACT; LYMPH - NODES; ORGANS OF INTERNAL SECRETION; BRAIN AND SPINAL CORD; - BONES; - - (_b_) MICROSCOPIC: SKIN; MUSCLES; BLOOD-VESSELS; - LUNGS; HEART; INTESTINAL TRACT AND ITS GLANDS; KIDNEY; - ADRENALS; PANCREAS; THYMUS; CENTRAL NERVOUS SYSTEM; PERIPHERAL - NERVES; RETINA; BONES - - -CHAPTER V - -EXPERIMENTAL SCURVY 111 - - HISTORICAL REVIEW - - PATHOGENESIS 116 - - PATHOLOGY: EFFECT ON THE FOETUS; SCURVY IN THE MONKEY; - MICROSCOPIC PATHOLOGY; BONES; TEETH; NERVES; BLOOD VESSELS; - INTERPRETATION OF BACTERIA IN THE TISSUES 122 - - SYMPTOMS 135 - - -CHAPTER VI - -ANTISCORBUTIC FOODS 143 - - HISTORICAL REVIEW 143 - - MILK: RAW; PASTEURIZED; DRIED 150 - - FRUITS AND FRUIT JUICES: DRIED 153 - - VEGETABLES: CABBAGE; EFFECT OF HEATING. POTATO. SWEDE 158 - DEHYDRATED VEGETABLES: CANNED FOODS (TOMATOES) 166 - - GERMINATED CEREALS AND PULSES; MEAT AND EGGS; BEER AND ALCOHOLIC - BEVERAGES; MISCELLANEOUS - - CONCLUSIONS 173 - - -CHAPTER VII - -SYMPTOMATOLOGY AND DIAGNOSIS 176 - - IN ADULTS 176 - - IN INFANTS: (_a_) ACUTE; (b) SUBACUTE; (_c_) LATENT.--HEMORRHAGE - OF GUMS; SUBPERIOSTEAL HEMORRHAGE: SKIN; MUCOUS MEMBRANES - AND SUBCUTANEOUS TISSUES; HEMORRHAGES OF INTERNAL ORGANS; - NAILS AND HAIR; ECZEMA; EDEMA; TENDERNESS; BEADING OF RIBS; - SEPARATION OF EPIPHYSIS; "WHITE LINE"; CARDIOVASCULAR SYSTEM; - "CARDIORESPIRATORY SYNDROME"; NERVOUS SYSTEM; URINARY SYSTEM; - THE BLOOD AND BLOOD-VESSELS; NUTRITION AND GROWTH; FEVER; - COMPLICATIONS; EPIDEMIC FORM 183 - - DIFFERENTIAL DIAGNOSIS: RHEUMATISM; PURPURA; CONGENITAL SYPHILIS; - BONE TUMORS; OSTEOMYELITIS; POLIOMYELITIS, ETC. 219 - - -CHAPTER VIII - -PROGNOSIS 225 - - -CHAPTER IX - -TREATMENT 230 - - PREVENTATIVE; CURATIVE - - NON-DIETETIC - - -CHAPTER X - -METABOLISM 241 - - IN ADULTS: BODY EXCHANGES 241 - - IN INFANTS: BODY EXCHANGES; ANALYSIS OF ORGANS; CHEMISTRY OF - BLOOD 242 - - IN ANIMALS: MONKEY; GUINEA-PIG 245 - - -CHAPTER XI - -RELATION OF SCURVY TO OTHER DISEASES 248 - - BERIBERI; SHIP-BERIBERI; PELLAGRA; RICKETS; OSTEOGENESIS - IMPERFECTA; OSTEOMALACIA; HUNGER EDEMA; "MEHLNAERSCHADEN"; - EXUDATIVE DIATHESIS; DISEASES DUE TO A FOOD EXCESS - -APPENDIX: LIND'S RECIPES FOR PREPARING STABLE ANTISCORBUTICS 259 - -BIBLIOGRAPHY 261 - - - - -ILLUSTRATIONS - - -FIG. PAGE - - 1. Dependence on potato as antiscorbutic 7 - - 2. Weight curve of scorbutic baby. Effect of alkalization of milk 51 - - 3. Lumbar cord in case of scurvy 104 - - 4. Lumbar cord in case of scurvy. Focal degeneration 104 - - 5. Bone in scurvy. Microscopic pathology 105 - - 6. Subperiosteal hemorrhage and separation of epiphysis. - Roentgenogram 108 - - 7. Complete restitution of epiphysis without deformity. - Roentgenogram 109 - - 8. Curve of fecal excretion in scurvy 120 - - 9. Diagrammatic representation of guinea-pig scurvy 128 - -10. Loss of weight in guinea-pig scurvy 139 - -11. Dried milk as an antiscorbutic 140 - -12. Dehydrated vegetables as a cause of scurvy 164 - -13. Cure of scurvy by addition of canned tomato 166 - -14. Failure of yeast as prophylactic 171 - -15. Temperature, pulse, and respiration in scurvy 186 - -16. Subperiosteal hemorrhage and separation of epiphysis. - Roentgenogram 192 - -17. Periosteal "tags" and "streamers." Roentgenogram 193 - -18. Infant with marked scurvy. Characteristic position 198 - -19. Scorbutic beading of ribs. Roentgenogram 198 - -20. "White line." Roentgenogram 199 - -21. Cardiac enlargement. Roentgenogram 200 - -22. Electrocardiogram showing "cardiorespiratory syndrome" 201 - -23. Stationary weight during cure of scurvy. Oliguria followed by - polyuria 206 - -24. Development of scurvy in spite of normal gain in weight 214 - -25. Retardation of growth in length when no orange juice was given - and supergrowth when given once more 216 - - -TABLES - -TABLE PAGE - - 1. Fecal flora of scorbutic infants 29 - - 2. Necropsy reports of scurvy 82 - - 3. Relative distribution of the antiscorbutic factor in the commoner - foodstuffs 157 - - 4. Platelets and other blood cells in scurvy 209 - - 5. Data of epidemic of scurvy 218 - - 6. Duration of treatment before marked improvement was noticed 237 - - - - - SCURVY - PAST AND PRESENT - -CHAPTER I - -HISTORY OF SCURVY[1] - - -[1] The best historical review of scurvy is to be found in Hirsch's -Handbook of Geographic and Historical Pathology, from which account we -have drawn many facts. - -=Outbreaks on Land.=--Like many other diseases, the life history of -scurvy shows several distinct phases. We hear of it first as a plague, -infesting armies and besieged towns; then as a dread disease, decimating -the sailors of the navy and of the mercantile marine, and, since the end -of the last century, more often as a nutritional disturbance, -endangering the health of infants. Very recently it has acquired an -entirely new interest, as the representative of a class of disorders -which has revealed the essential importance to man of unknown dietary -factors. - -It is difficult, as may be imagined, to define with precision the -earliest description of scurvy, as the older references are so vague as -to be open to individual interpretation. The reference of Hippocrates to -a large number of men in the army who suffered from pains in the legs -and gangrene of the gums, which was accompanied by loss of teeth, seems -sufficiently definite to be identified as this disease. The Greek, Roman -and Arabian writers do not seem to have been acquainted with scurvy. -This is as we should expect, for fruits and vegetables grew in such -plenty in these southern countries that scurvy must have been a disorder -of rare occurrence. - -An interesting early description of scurvy, and one which is quite -convincing, is that of de Joinville, who accompanied the Crusaders in -their invasion of Egypt under St. Lewis, about the middle of the -thirteenth century. He refers to the lividity and spongy condition of -the gums, and describes how "the barber surgeons were forced to cut away -the dead flesh from the gums to enable the people to masticate their -food"; he describes their debility, their tendency to faint, and the -black spots on their legs. The disease broke out in Lent, during which -time the soldiers partook of no meat, but consumed a species of eel -which they believed "ate the dead people" and therefore led to this -loathsome disease. - -It is probable that scurvy existed in the northern parts of Europe and -Asia ever since they were settled by man. We should hardly expect to -have records of this condition, in view of the low educational status of -the people, their greatly restricted literature, and their lack of -intercourse with the people in the southern countries. In the sixteenth -century, with the development and spread of education, we begin to hear -of scurvy from various sources. Claus Magnus, in his "History of the -Northern Nations," published in 1555, described the disease which he -tells us flourished among the soldiers in the camps and in the prisons. -About this time Ronsseus, Echtius and Wierus wrote special treatises on -this disease, and recommended many dietary measures which we recognize -to-day as most efficacious. The number of monographs on this subject -multiplied with great rapidity in the course of the next twenty-five or -fifty years; none of them, however, added anything essential to our -knowledge. In 1645 the Faculty of Medicine at Copenhagen published a -"consilium" for the benefit of the poor, treating of the causes, -prevention and cure of this disease, which was prevalent among the Danes -and other northern nations. - -The colonists of the northern part of America were sorely afflicted with -scurvy. It is said that the French met with such high mortality during -the severe winters in Canada, that they frequently debated the wisdom of -abandoning this settlement. This was true also in regard to the English -and their settlement in Newfoundland. Indeed, it was scurvy which forced -the early settlers in Hudson Bay to discontinue their intentions of -colonizing that region. - -In an essay published in the eighteenth century (1734), Bachstrom -described an epidemic of scurvy which occurred in 1703 during the siege -of Thorn, in Prussia, by the Swedes, which caused the death of 5000 of -the garrison, in addition to a large number of the inhabitants. It is -interesting to note that this epidemic took place in the middle of the -summer, and not in the cold season. From this time on we meet with many -descriptions of scurvy in connection with the wars at various periods. -For instance, in the Russian armies, in the war between the Austrians -and the Turks in 1720; in the English troops who had taken Quebec from -the French in 1759; among the French soldiers in the army of the Alps in -the spring of 1795. It is unnecessary to review these accounts in -detail. This period is distinguished rather by the appearance of a great -classic on Scurvy, the work of the English naval hygienist, Lind (1752). -This book has intrinsic value to-day, and, at the time it appeared, -served to crystallize the conception of scurvy, which had been stretched -out of all proportions to include an ever-increasing conglomeration of -clinical conditions. Scurvy had become the Alpha and Omega of -professional routine, the catchword of the day, the asylum ignorantiæ of -the practical man. Into this chaos, as Hirsch expresses it, "the first -beams of light fell when Lind's classical work appeared." - -It will be of little value to consider the great number of epidemics of -scurvy which occurred from this time to the present day. They may be -found in tabular form in the excellent survey of scurvy by Hirsch. The -literature of this long period may likewise be found in a work of -encyclopædic character, that of Krebel, which gives the titles, with a -summary of the various articles on this subject, appearing to the year -1859. If we look over the chronological table compiled by Hirsch, we -note a remarkable similarity regarding the incidence of the recurring -epidemics. In almost all cases they broke out among troops, whether in -Russia, in India, in Africa, or in our United States. The epidemics -which are not attributable to military life or campaigns are found to -have taken place generally in prisons, insane asylums, poorhouses or -houses of refuge and correction. It would seem that no war is omitted -from this list of sickness and death. There are in all 143 land -epidemics between 1556 and 1877, two occurring in the sixteenth century, -four in the seventeenth, 33 in the eighteenth, and 104 in the nineteenth -century. The marked increase in the nineteenth century occurred in -institutions, in asylums and prisons, rather than in the armies. This -fact may be ascribed to altered social conditions which led to a great -multiplication of eleemosynary institutions. - -Coming down to more recent times, we learn that scurvy occurred -extensively during the Crimean War, and that it was prevalent also among -the troops in our own Civil War. In the "Medical and Surgical History of -the War of the Rebellion," we find the following statements: - - "A scorbutic tendency was developed at most of our military posts - during the winter season, after the troops had been confined to the - use of the ordinary ration with the desiccated vegetables. The - latter in the quantities failed to repress the disease. At posts - which could be readily supplied with potatoes only the taint was - manifested, on account of a want of liberality in the issues." And - again: "Among the white troops during the five and one-sixth years - covered by the statistics, 30,714 cases of scurvy were reported; and - 383 deaths were attributed directly to that disease." - -Munson writes: "It (scurvy) prevailed among our troops during the Civil -War and its recognition was a surprise and shock to professional ideas -preconceived from practice in civil life." - -As is well known, the besieged in Paris during the Franco-Prussian War -in the winter of 1870-71 suffered severely from scurvy. The accounts of -their pitiable condition have been portrayed for us by numerous French -writers (Delpech, Hayem, Lasèque and Legroux). The people lived mainly -on rice and bread, with an occasional addition of potatoes or horse -meat. The winter was exceptionally severe, which was supposed to have -intensified the scorbutic condition. Not only were the inmates of the -prisons on the Seine attacked, numbering about one thousand, but even -the patients in the military hospitals developed the disease. It is of -interest to remember that the siege lasted but little over four months, -from September 17th to January 27th, the date of the armistice. - -In the Russo-Japanese War, after the siege of Port Arthur, it was found -that one-half of the garrison of 17,000 men had scurvy. - -Although there are certain parts of the world where scurvy is of -frequent occurrence, no country has been entirely free from it. As might -be expected, it has been particularly prevalent in the North, where -vegetation is scanty--in Greenland, Alaska, Russia and the Baltic -States. It has likewise prevailed in the tropics when the crops have -failed. India has been conspicuous for its large number of epidemics; -some years ago scurvy occurred in Arabia among the English troops -stationed at Aden, both among the British and the native troops. A -recent communication from Aruba, a small island of Dutch Guiana, lying -north of Venezuela, illustrates how devastating scurvy still is in some -parts of the world. This account tells of 3000 cases of this disease -which occurred in 1915 among a population of less than 10,000, owing to -the fact that the crops had failed almost entirely during the years -1912, 1913 and 1914. - -It is important for us to realize that we are still dependent on the -annual crops for our protection from scurvy; in other words, the world -is leading a hand-to-mouth existence in regard to its quota of -antiscorbutic food. The truth of this condition has been realized for -Ireland, sadly illustrated by numerous epidemics, notably the great -epidemic of 1847 reported by Curran. It was demonstrated by the -outbreaks of scurvy in Norway in 1904 and 1912, and was brought to the -attention of many in the United States in the spring of 1916. In this -year our potato crop fell far below the normal, with the result that -scurvy appeared in various parts of the United States, especially in -institutions (Fig. 1). - -[Illustration: Fig. 1.--A comparison between the requisitioned quantity -(in thousand pound units) of potatoes and other vegetables, and the -quantity received per month by an institution in which more than 200 -cases of scurvy occurred at the beginning of April, 1916. The total -height of column represents the amount needed and requisitioned; the -solid black portion the amount received. The number of inmates in the -institution remained approximately the same. - -The chart illustrates our great dependence on the potato during the -winter months. This is due not only to its intrinsic antiscorbutic -potency, but, probably quite as much, to the fact that fully twice as -many pounds of potatoes are consumed during the winter as of all other -vegetables combined. Therefore, if this crop fails or is dehydrated, -scurvy will develop in the spring.] - -The fact that scurvy may occur in any land and climate, even in the -garden spots of the world, is strikingly shown by the epidemics reported -from Algiers, and the ravages of this disease among the gold seekers in -California in 1849. Nothing could be more incongruous than the -occurrence of a deficiency disease in this land of plenty. - -=Outbreaks at Sea.=--It is doubtful, however, whether attention would -have been focussed so early and so sharply on scurvy, had it not been -for the voyages of exploration undertaken in the sixteenth century. -These long trips on sailing vessels, where for many months little or no -fresh vegetable or animal food was obtainable, were almost as if -designed to make a test of the dietetic origin of scurvy. The result was -inevitable--five to six months after the ships were out of touch with -land, the majority of the crew frequently were incapacitated by this -disease, thereby wrecking many an expedition.[2] - -[2] The fact that crews of vessels which set sail in winter were more -subject to scurvy than those which set out in the summer must be -attributed to the existence of latent scurvy among the sailors at the -time of sailing, rather than to the season of the year. - -The earliest account of the outbreak of scurvy at sea is that of Vasco -de Gama, who in 1497 discovered a passage to the East Indies by way of -the Cape of Good Hope. The narratives of subsequent explorers, -especially those of Cartier and of Drake, are replete with descriptions -of the ravages of scurvy. The expedition of Lord Anson in 1740 is -always cited as a memorable example of an undertaking which foundered as -the result of scurvy. After a cruise of four years, this expedition had -lost from this disease more than four out of five of the original number -of its crews. In striking contrast to this picture, and to that -furnished by the voyages of earlier navigators, is that of Captain Cook, -who in 1772 undertook a voyage lasting over three years, sailing from -52° north to 71° south, with a loss of but one of his crew from disease, -and that not from scurvy. This remarkable feat, more than any other, -centered attention on the feasibility of preventing scurvy, and resulted -in measures tending to eradicate it from the navy. Captain Cook -attributed the absence of scurvy among his crew to "sweetwort," an -infusion of barley, which he prepared fresh and served liberally. He -also prized the antiscorbutic value of sauerkraut. - -We find accordingly in 1795, at the instance of Sir Gilbert Blaine, that -improvements were introduced in the victualling of the fleet. As the -result of a regular ration of lemon juice, the incidence of scurvy fell -precipitously. It is due largely to this provision that between the -years 1779 and 1813, according to the statistics of Sir Jay Barrow, the -morbidity and the mortality in the British Navy was decreased by 75 per -cent. - -It has been shown that it took a generation after the efficacy of -antiscorbutics had been demonstrated in various expeditions, for an -antiscorbutic to be included in the ration of the navy. The merchant -marine of England was far more conservative, and for many years after -scurvy had been eradicated from the navy we still read of its occurrence -on the vessels making voyages to India, China and Ceylon. Gradually, -however, its incidence became less and less. Its toll of death, before -preventive measures were employed, may be appreciated from the fact that -it has been estimated that scurvy destroyed more sailors than all other -causes incidental to sea life, including the great slaughter of naval -warfare. Sir R. Hawkins stated in the latter part of the sixteenth -century that he could give an account of 10,000 mariners who had been -destroyed by scurvy during the twenty years that he had been at sea. - -As is well known, scurvy has played an important rôle in Arctic and -Antarctic explorations, and has been the cause of the failure of many of -these expeditions. It is now realized that the development of scurvy is -quite preventable, that if a sufficient quantity of meat (especially raw -meat) is consumed, explorers can be entirely independent of a supply of -fresh vegetables. This fact was brought out by the Arctic Survey -Committee (British), who "were appointed to enquire into the causes of -the outbreak of scurvy in the recent Arctic expedition" (1877), and who -reported that it may result from an absence of fresh meat. That this -conclusion was sound has been proved by the experiences of Nansen and of -Johansen, who wintered safely in Franz-Josefsland on a diet of meat and -bacon. More recently Stefánsson has carried out successful Arctic -explorations, depending entirely on fresh meat as antiscorbutic -foodstuff and making no provision whatsoever for vegetable food. - -=Infantile Scurvy.=--Glisson, to whom we owe the first description of -rickets, likewise was the first to recognize scurvy in infants. In his -classic treatise on rickets, written in 1668, he writes as follows: - - "The scurvy is sometimes conjoyned with the affect. It is either - hereditary, or perhaps in so tender a constitution contracted by - infection, or lastly, it is produced from the indiscreet and - erroneous Regiment of the infant, and chiefly from the inclemency of - the air and climate where the child is educated." - - "The scurvy complicated with this affect hath these signs: 1. They - that labor under this affect do impatiently indure purgations; but - they who are only affected with the Rachites do easily tolerate the - same. 2. They are much offended with violent exercises, neither can - they at all endure them. But although in this affect alone, there be - a kind of slothfulness and aversation from exercise, yet exercise - doth not so manifestly, at least not altogether so manifestly hurt - them, as when the scurvy is conjoyned with the Rachites. 3. Upon any - concitated and vehement motion they draw not breath without much - difficulty, they are vexed with diverse pains running through their - joynts, and these they give warning of by theyr crying, the motion - of the Pulse is frequent and unequal, and somethimes they are - troubled with a Palpitation of the Heart, or threatened with a - Lypothymie, which Affects are for the most part soon mitigated, or - altogether appeased by laying them down to rest. 4. Tumours do very - commonly appear in the Gums. 5. The urin upon the absence of the - accustomed feavers is much more intense and increased." - -Glisson's description of scurvy was entirely lost sight of, overshadowed -by his description of rickets, so that for over two hundred years no -word of infantile scurvy is to be found either in the English or other -literature. There is no doubt that from time to time cases must have -occurred, but they were looked upon probably as rickets or as a -manifestation of one of the hemorrhagic diseases. - -In 1859 Moeller described some cases which evidently were scurvy, but -which he termed "acute rickets." He realized that they presented a novel -clinical picture but failed to recognize that they represented a -disorder quite distinct from rickets.[3] This article was followed -within the next few years by reports of other German writers (Bohn, -Steiner, Foerster) who, accepting Moeller's point of view, considered -these cases merely as an acute form of rickets. They were led to this -erroneous conclusion chiefly on account of the lack of marked -involvement of the gums, which they considered an essential sign, -influenced by their conception of adult scurvy. This viewpoint has -pervaded the German literature even to the present day, when it is still -considered necessary to bring further evidence that infantile scurvy in -its pathogenesis and pathology is identical with adult scurvy. - -[3] Infantile scurvy is frequently termed "Die Moellersche Krankheit." -There seems to be no occasion for giving Moeller credit for discovering -this disease, as he believed that he was dealing with rickets merely in -an acute form. He recognized the clinical similarity to scurvy, but in -one of his cases sharply differentiates it from adult scurvy by the fact -that "lemon juice and fresh vegetables" were of no avail in the -treatment. - -In 1871 Ingerslev, an assistant of Hirschsprung in Copenhagen, wrote a -paper on "A Case of Scurvy in a Child," which is quite convincing. Two -years later Jalland, an English physician, reported a similar case of -"Scurvy in a Ten-Months-Old Infant." In 1878 Cheadle reported three -cases of infantile scurvy with typical tumefaction of the gums, and -obscure tenderness of the legs, and followed this paper by two others, -which appeared in 1879 and 1882. Cheadle clearly recognized the disease -as scurvy. However, as the title of his first paper--"Three Cases of -Scurvy Supervening on Rickets in Young Children"--indicates, he -considered it a condition engrafted upon rickets. About this time (1881) -Gee presented a brief but accurate account of five cases of scurvy which -he termed "osteal or periosteal cachexia." - -In 1883, Barlow published his classical paper on this subject, the first -to furnish anatomical proof that this disorder of infants presented the -pathological changes characteristic of adult scurvy. Previous to this -publication there had been but one autopsy report, that by Moeller, -which had been incorrectly interpreted. The work of Barlow was accepted -remarkably quickly in England and in America, but less promptly on the -Continent. This was probably due to the fact that infantile scurvy was -occurring far more frequently in these two countries, and that the -subject was open therefore to more prompt investigation. This increased -prevalence of infantile scurvy in the two great English-speaking nations -has continued to the present time, and no doubt is due to the extensive -employment of artificial feeding and of proprietary foods. In 1894 not -less than 106 cases were reported to the Academy of Medicine of New York -City by various physicians, and in 1898 the comprehensive investigation -of the American Pediatric Society appeared, which was based on 379 -cases. - -It was soon evident that infantile scurvy occurred to a greater or less -degree throughout the civilized world. In France, Monfalcon had reported -a case in 1820 which is sometimes referred to as the earliest case of -infantile scurvy mentioned in the literature. It relates, however, to an -older child and was published as a case of scorbutic rickets. Netter -was one of the first in France to recognize the true nature of the -disorder, and published several papers in 1898 describing typical cases. -Infantile scurvy was, however, almost unknown in that country until what -is termed "lait maternisé" and "lait fixé" came into vogue. This is -apparent from a table prepared by Lecornu, which gives a list of all -cases in the French literature between 1894 and 1904, and of the diets -on which they came about. The former of these milk preparations is -subjected to various manipulations and then heated to a temperature -above the boiling point; the latter is shaken violently in a machine to -render the fat globules smaller, and is then sterilized by one of the -usual methods. - -Switzerland has undergone an experience similar to that of France. -Previous to 1903 only five cases of infantile scurvy had been published -from that country. In this year Stoos published an additional five. In -1907 Bernheim-Karrer reported nine cases, all of which had developed on -homogenized milk, a process very similar to that employed by the French -to break up the fat globules. The increase of infantile scurvy in -Switzerland may be judged by the fact that a commission was formed in -the following year to investigate its occurrence. - -In Germany there was for many years continued discussion as to the true -nature of scurvy. Some believed it to be a form of rickets, others a -form of scurvy; still others a combination of scurvy and rickets. Some -thought it merely hereditary syphilis, and not many years ago Naegeli -looked upon it as an entity distinct from scurvy on rickets. The subject -attained additional importance through an epidemic of infantile scurvy, -which broke out in Berlin in 1898, among infants who received milk from -one of the largest dairies. The episode led to prolonged discussion in -the Berlin Medical Society, and to several excellent papers, among -which that by Neumann deserves particular mention. - -The disorder has been reported in Holland by DeBruin, who recorded -numerous cases; in Denmark, by Hirschsprung, who refused to recognize -its scorbutic nature; in Italy, by Concetti, and by others. It was not -long before there were reports of cases from almost every part of the -world, including Australia (Money) and East India (Nichols). - -In view of the fact that scurvy is endemic among adults in Russia, we -should also expect to find infantile scurvy widespread in that country. -In point of fact, quite the contrary seems to be the case. In connection -with the great scurvy epidemic in Russia (1898-99), Tschudakoff -personally examined over 10,000 persons and found 11.11 per cent. of the -people sick with this disease. He states that in the course of this -large experience he did not meet with a single case under the age of -five years. Fuerst writes that Filatow, the great Russian children's -specialist, declared that he knew of no case of Barlow's disease -described in the Russian literature. This is not literally correct, as -Doepp described an epidemic of scurvy in the St. Petersburg Foundling -Asylum occurring in 1831. It serves to emphasize, however, the paucity -of cases among infants in this great land of endemic adult scurvy. -Lyabmow, in referring to the scurvy in Kazan, tells us that among 28,000 -cases only a few infants were affected, and Rauchfuss made the statement -at the International Congress at Copenhagen, in 1884, that although he -had seen a great many cases of scurvy, he had never seen it in children -one to two years of age. We shall not, in this place, comment on this -interesting and apparently paradoxical situation, but shall have -occasion to refer to it in considering the pathogenesis. It may be added -that in Norway and Sweden, where scurvy is to some extent also endemic -among the adult population, there is a similar lack of scurvy among -infants. - -=Scurvy in the World War.=--The greatest advance in medicine during the -past generation has been in the fields of hygiene and preventive -medicine. One might therefore have expected that the World War would -have differed from previous wars in a notable absence of scurvy among -the troops and the civilian population. This is true to a limited degree -only. Reports which have been published in the course of the war, and -especially since hostilities have ceased, show that the troops who were -incapacitated by scurvy must have numbered many thousands. As was to be -expected, scurvy occurred most often in Russia, where it is endemic. The -largest number of cases was reported by Boerich, who as director of a -Red Cross Central Station in Russia saw 1343 cases. Other German -physicians who had charge of caring for the Russian prisoners give -accounts of the occurrence of some hundreds of cases of scurvy. An -article by Much and Baumbach gains added interest from the novel -suggestion that scurvy is transmitted by means of vermin. That scurvy -must have reached large proportions is shown by the fact that in July, -1916, a medical commission was sent by the Germans to investigate the -scurvy in a Russian army corps, and that it was necessary to establish -for this disease in every division a sanatorium comprising 100 beds. -Hoerschelman, who wrote an account of this investigation, blames the bad -hygienic surroundings, the lack of sleep, the overexertion, as well as -the deficiency of food, for the occurrence of the epidemic. As usual, -very few cases occurred among officers. He describes a number of -instances where scurvy was feigned by rubbing the gums and making them -bleed, or by irritating them with the juice of tobacco. These reports on -scurvy in Russia bring us little new from a purely medical standpoint. -They emphasize the occurrence of night-blindness as an early and -frequent symptom. It is difficult to judge whether this manifestation -was due entirely to the scurvy, or was in part the result of other -deficiencies in the diet. For instance, Hift states that the -night-blindness was cured by cod liver oil, or by the water in which -beef liver had been cooked. This would point rather to a deficiency of -the fat-soluble vitamine, as these substances could have little effect -in curing scurvy. The cases reported by Wassermann, where neuritic pains -in the legs played a considerable rôle, evidently are also not simple -scurvy, but may well be the result of more than one food deficiency or a -complicating ostitis. In the same way some reports show clearly that -"hunger edema" complicated scurvy. - -Scurvy occurred next in frequency among the nations neighboring Russia. -Speyer tells us that a German sanitary commission was sent to Bulgaria -largely with the object of investigating scurvy in that country. The -excellent monograph on the pathology of scurvy just written by Aschoff -and Koch was founded on an experience in Roumania among Turkish, German -and Austrian soldiers. Added to its other woes the Servian army was -visited by scurvy. Wiltshire gives us a description of this disease -based on an observation of 3000 cases in the first half of the year -1917. In regard to scurvy in this part of the world, Morawitz writes -that when he reached Roumania he was surprised to find scurvy the most -prevalent disease in the army, and that since the spring of 1917 it was -widely disseminated among the German troops. Lobmeyer writes of scurvy -among the Turkish troops, and Disqué reports 500 cases among prisoners -captured in Turkestan. - -Along the Western front very few cases are described. There is an -account by Korbsch of 51 cases in this area in 1915. Schreiber describes -30 cases among the German prisoners of war captured in the beginning of -1917, which were diagnosed as purpuric rheumatism. Arneth recounts that -sporadic cases of scurvy occurred among the German troops, especially -among the older soldiers, and that in many cases this was combined with -the hunger edema. He attributes the scurvy to a dependence on dehydrated -vegetables in the ration. - -From all these accounts it is evident that scurvy played an important -rôle in the general nutrition of the troops on the Eastern front. -Probably it was of the latent variety, which is exceedingly difficult to -diagnose, but which increases the susceptibility to infection, and -intensifies the severity of all medical or surgical diseases. Von -Niedner takes this point of view, stating that although scurvy had been -largely prevented in this war, the obscure rudimentary type had not been -eradicated. He remarks upon a fact, noted in our Civil War and other -wars, that under these conditions eruptions assume a hemorrhagic -character in typhoid fever, cerebrospinal fever, rheumatism and other -infections. Pick made a similar observation at a medical meeting in -Vienna in reference to scurvy in the Austrian army, drawing attention to -the hemorrhagic diathesis existing among the troops and expressing the -opinion that scurvy was occurring in this war as in previous wars. - -Very little scurvy seems to have broken out among the British troops in -Europe. Thirty-two cases were reported as occurring in the middle of -1915 at a divisional rest station in France. It made marked inroads, -however, on the health of the Colonial troops in Mesopotamia. In the -report of the Mesopotamia Commission we read that 7500 men were lost to -the force in 19 weeks as a result of scurvy, and that this happened in -the summer of 1916 although additions had been made to the ration in the -previous spring. A conception of the extent of the scurvy may be formed -from the accompanying table, published by Willcox: - - Scurvy Beriberi - (Indians) (British) - - 1916 (July 1--Dec. 31) 11,445 104 - 1917 2,199 84 - 1918 825 51 - -It will be noted that thousands of cases occurred among the Indian -troops. This was due to the fact that the British ate more potatoes and -fresh meat. In his official report of the outbreak of scurvy among -Indian troops, Colonel Hehir writes: "The only vegetable now allowed is -2 ounces of potatoes and the only fresh meat 28 ounces a week. It is -very doubtful whether this authorized ration, if not supplemented by -other vegetables and more meat, is sufficient to prevent scurvy." In the -account which this officer gives of the medical conditions during the -siege of Kut-el-Amara, it is stated that there were 1050 admissions for -scurvy, fully developed, incipient and latent. It is remarked that those -Indians who ate horseflesh were decidedly less affected. From the fact -that special hospitals for scurvy were established in June, 1916, at -Bagdad, Amora and Basrah, it is evident that a large number of cases -must have been encountered. Most significant in this connection, -however, are the preventive measures which were instituted by the -British government. A body of 256 men, designated as the Madras -Gardener's Corps, were dispatched to Mesopotamia to plant gardens all -over the country and to supply packets of seeds to various units. At -Bagdad alone their output of vegetables was over 400,000 pounds. This -certainly constitutes a remarkable innovation in the hygiene of armies. - -The French army was not entirely spared from scurvy. In 1917 Harvier, an -army surgeon, was surprised to discover that 95 per cent. of the 800 -troops of which he had charge suffered from scurvy; he tells us that -other epidemic centres were recognized later outside this sector. -Elsewhere we read of the occurrence of scurvy in France, involving 40 -per cent. of the 1700 men of the South African Labor Corps, and that -this disorder was still more serious in another company owing to the -fact that it was not recognized (Dyke).[4] Benoit reported 63 cases -which he discovered in 1917 among 300 laborers. According to his -account, all these laborers received the same food, and those with -scurvy recovered quite independently of any change in the dietary. - -[4] The writer adds that he believes that the health of the natives at -home is protected by Kaffir beer, which they consume even to the amount -of 3 gallons a day, and which is made from germinated Kaffir corn. This -cereal is germinated by steeping it in water for forty-eight hours and -is then dried in the sun. Only enough is prepared for one brew. The -French prepared a similar fermented beverage for these South African -laborers; the sole difference in its mode of preparation was that the -corn had not been germinated. - -There are many accounts of scurvy among the Italian troops. Vannutelli -gives a description of an epidemic of some 200 cases of infectious -purpura with manifestations of hemorrhagic scurvy. Another writer -informs us that in June, 1916, scurvy broke out among some Italian -troops stationed at an altitude of 1500 to 2000 metres (Gingui). -Vallardi gives an account of 180 cases among Italian troops in -Macedonia, accompanied by slight jaundice and enlargement of the glands. - -The American soldiers seem to have been practically spared from scurvy. -This was due probably to their ample ration and to the fact that -they were in the field for a comparatively short period. The -Surgeon-General's report to date, which has been kindly furnished me, -showed but 5 cases in 1917 occurring in Europe and the United States, -and but 15 cases reported during the year 1918. - -_The civilian population_ of the various warring countries was by no -means spared. There are no reports from Russia to indicate the extent of -scurvy, but from what is known of the food conditions prevailing there -toward the end of the war, one can be certain that the number must have -been large. The greatest amount of scurvy has been reported from -Austria, more particularly from Vienna. Previous to the war scurvy was a -rare disease in this city, both among adults and infants. During the -war, however, as the result of a lack of fresh food and the dependence -on dehydrated vegetables, a large number of cases developed. Tobler -reports over 200 cases in children between the ages of two and fifteen -years, which occurred in 1917 in child-caring institutions where the -milk supply was markedly deficient, where fresh vegetables were lacking, -and the supply of potatoes gave out about Christmas, 1916. A conception -of the deficiency of the milk supply may be gained from the statement -that there were but sixteen quarts a day for about 1500 people. Some of -these children were undergoing fresh-air treatment and were out of doors -in the "sun stations" day and night. For the cure of these children a -simple decoction of fir-tops was used, a therapeutic procedure stated by -Lind to have been of value in the Russo-Swedish War of 1708. - -That scurvy must have occurred extensively among the infants in Vienna -may be gathered from the report of Erdheim, who records 31 autopsies on -infants under the interesting title of the "Barlow Heart." In Berlin -scurvy occurred also in the foundling asylums, as reported by Eric -Mueller and by Brandt. This was caused by a diet of pasteurized milk and -dehydrated vegetables. In an article bearing the suggestive title of "On -a Marked Increase in Barlow's Disease in the Years of the War -1917-1918," Epstein states that in Prague there had been an endemic -increase of infantile scurvy since August, 1917. The only information -regarding scurvy among the adult civilian population of Germany is that -furnished by Morawitz, who states that this disorder occurred -sporadically. Here again it is probable that there were many latent or -rudimentary cases which were not recognized. - -In Great Britain there are reports which show that scurvy manifested -itself in institutions caring for the poor. In Glasgow we learn of 50 -cases developing in the Poor Law Hospital in the course of fifteen -months, and in Newcastle of 16 cases appearing in the Poor Law Infirmary -in the course of three months. - -It is probable that when more detailed reports are available, it will be -found that there was far more scurvy than was appreciated during the -course of the war. It will be impossible, however, to gain even an -approximate knowledge of the extent to which this disorder prevailed, as -in many instances it was inextricably interwoven with other nutritional -diseases. The situation which Enright describes in Cairo among the -Turkish prisoners suffering from war edema, where there was "evidently a -scorbutic factor involved," probably held true for many other parts of -the world. War and scurvy must still be regarded as associated evils, -for war is closely linked with famine and food deprivation--the dominant -factor in the production of scurvy. - - - - -CHAPTER II - -PATHOGENESIS AND ETIOLOGY - - -At the outset it may be stated that there is no longer any reason to -doubt that adult scurvy and infantile scurvy are one and the same -disease, having an identical pathogenesis. For many years, far longer -than the facts warranted, there was discussion whether Barlow's disease -was true scurvy or merely a form or a complication of rickets, or -perhaps a distinct hemorrhagic disease. This question may be relegated -to the past, so that we may proceed to consider the pathogenesis of -scurvy in the infant and in the adult under a common heading. - -There is no need of studying all the theories which have been advanced -to account for scurvy. They have been manifold and most of them have -died a natural death. For many years the _potassium deficiency theory_, -suggested by Garrod, gained wide acceptance. That scurvy should be -attributed to a lack of this salt is readily comprehensible in view of -the abundance of potassium in the antiscorbutic foodstuffs, the fruits -and the vegetables. It was not long before it was evident that this was -not the correct solution, as the salts of potassium served neither to -prevent nor to cure scurvy. This theory was accordingly modified to -include only organic potassium. Experiment, however, failed to support -the validity of this hypothesis, and it was gradually abandoned. - -Another theory which had a short but popular career was the _citric acid -theory_, which was maintained vigorously by Netter. This explanation -seemed logical in view of the marked potency of the citrous fruits, and -particularly when it was shown that human milk contains a greater -percentage of the salts of citric acid than cow's milk, and that some of -these salts are lost in the course of heating. This hypothesis withstood -neither the practical test nor chemical investigation. It was found that -the various salts of citric acid, either singly or in combination, are -unable to cure scurvy. This treatment has been employed repeatedly on -man and on animals with little or no success; we also have resorted to -it in vain. It was shown, furthermore, that it rested on an insecure -chemical basis, as boiled milk contains but 0.1 g. per litre less citric -acid than raw milk--an amount which is negligible from a therapeutic -point of view. - -Before considering what may be termed the prevailing theories, a few -lines must be devoted to the _acidosis theory_ championed by Sir Almroth -Wright. According to this writer scurvy is due primarily to an excess of -acid compared with alkaline food.[5] A theory of this nature was open to -verification, and soon collapsed when put to the test. It was found, in -the first place, that an addition of alkali was unable to cure -experimental scurvy. It may be added that we have found it of no value -in infantile scurvy. Holst and Froelich pointed out that potatoes and -peas, two excellent antiscorbutic vegetables, have an alkaline and not -an acid ash; that adding hydrochloric acid to dandelion juice improves -rather than diminishes its potency; that 1 g. of cabbage, which suffices -to protect a guinea-pig from scurvy, does not contain sufficient alkali -to neutralize an acid state; and, finally, that scurvy is not -encountered in the well-established acidosis of diabetes. - -[5] The cases on which Wright based his theory were soldiers who -developed scurvy during the siege of Ladysmith. It is probable that the -men were suffering from starvation, purpura and dysentery. That they did -not have scurvy is proved by the fact that they were cured by giving -lactate and bicarbonate of soda. - -Let us turn to some of the current theories of the etiology of scurvy. -For years many have held to the _toxic theory_, believing that poisons -either were consumed in the food or formed in the intestine by means of -bacterial action. At present this view is held by the minority. The -situation in this respect may be compared to that of beriberi, about -which there is also no consensus of opinion, a minority attributing it -to the action of an unknown toxin. - -A consideration of the clinical course of scurvy sheds but little light -on this aspect, and can be interpreted as well for as against the action -of a toxin. The nervous system, which is well known to be particularly -vulnerable to toxins, is but slightly affected--the cardiorespiratory -phenomena (indicating an involvement of the pneumogastric nerves), the -occasional changes in the optic disks, and the abnormality of the tendon -reflexes constitute the aggregate. In a general way it may be stated -that the symptoms resemble those brought about by poisons of various -kinds--the cottonseed poisoning in swine, the toxic products of the -wheat embryo, or even mercurial poisoning in man.[6] The nervous -symptoms, especially the irritability of the heart, remind one of the -enterogenous intoxication or enterotoxic polyneuritis described by Von -Noorden. Such analogies are interesting and suggestive, but can be -accorded little weight in deciding the question at issue. - -[6] In chronic mercurial poisoning the following suggestive symptoms -occur: anemia, bleeding and spongy gums, loosening of the teeth, a -quickened pulse, ulcers of the extremities. At times mercury attacks the -nervous system, producing palsy. The resemblance is heightened by the -fact that calcium metastases have been found in the muscle in -experimental scurvy (Hart and Lessing) comparable to those -characteristic of mercurial poisoning. - -If a toxin is to be regarded as the proximate cause of infantile scurvy, -the question naturally arises as to the nature of the toxin. Is it -exogenous or endogenous? There is sound basis for believing that the -hypothetical poison is not introduced preformed in the food. In the -first place, infantile scurvy frequently develops in babies who receive -milk of the very best grade indeed, in contradistinction to rickets, -this is not preëminently a disease of the poor. Furthermore, there is no -relation between the concentration of the food mixture and its liability -to induce scurvy. For example, if among a large number of infants -receiving pasteurized milk from a common source, some are given the milk -diluted by one-half, others given it diluted by one-third, and still -others whole milk, the last group will show the least tendency to -scurvy, which we should not expect were the poison contained in the -food. Nor is it at all uncommon to encounter scurvy in an infant which -has been fed with a very dilute milk mixture. Another side of this -question should, however, be mentioned--stale pasteurized milk is more -apt to produce scurvy than the freshly pasteurized, but here again the -injury is in inverse ratio rather than in direct ratio to the amount -consumed. There are reports of adult scurvy having been occasioned by -decomposed food, such as Torup's investigation of Nansen's polar -expedition, but the diet had not been faultless in other respects. The -experiments of Jackson and Harley, who produced scurvy in monkeys by -feeding tainted tinned meat, cannot be unreservedly accepted, as they -are substantiated by no pathological examination of the bones, and the -diarrhoea and the blood and mucus in the stools do not suggest simple -scurvy. - -Of those who held to the toxic origin of scurvy the majority had in mind -an endogenous toxin, although the conception of the nature of this -poison varied greatly. The minority report of the American Pediatric -Society states that "scurvy appears to be a chronic ptomaine poisoning -due to the absorption of toxins." Neumann considered scurvy a chronic -poisoning, formed probably from the albumin of the milk, and considered -the fact that the infant refused to take the harmful food as weighty -evidence of its toxic nature. Kohlbrugge included scurvy in his group of -"fermentive diseases," due to the overgrowth of harmful bacteria in the -intestine, which are normally restrained by the acid reaction of the -chyme. McCollum and Pitz, on the basis of a study of experimental -scurvy, suggested that as the result of a break in the metabolism it -might be due to the retention of fæces and consequent absorption of -toxins. Still more recently Gerstenberger suggested that as the result -of the break in the metabolism of carbohydrates, a defunctioning -substance, possibly oxalic acid, is produced, which has a strong -affinity for calcium. - -It is of no avail to discuss these various hypotheses--the formation of -intestinal toxins--except where they are based on observations which can -be tested and controlled. This is true solely of _the relation of -constipation to scurvy_, and we shall confine ourselves therefore to a -consideration of this aspect of the question. - -There can be no question whether retention of fæces of itself can bring -about scurvy; this is excluded by the marked instances of constipation -frequently encountered among thriving babies. The majority of bottle-fed -babies and a large number of the breast-fed suffer from a greater or -less degree of constipation. On looking over our records of infantile -scurvy from this point of view, and comparing them with non-scorbutic -infants, we have not been able to note a characteristic distinction. -Some of the infants had normal stools, others suffered from -constipation, while the records of a great number showed occasional -loose stools. Furthermore, in cases of latent or subacute infantile -scurvy, it was of no moment whether a laxative was given or whether -constipation was induced by means of opium. The report of the American -Pediatric Society shows that the majority have had a similar experience; -the bowels were regular in seventy-four instances, irregular in fifteen, -constipated in one hundred and twenty-six, and diarrhoeal in -seventy-seven. In this connection, it may be pointed out that the -preparation termed "malt soup," the diet which in our experience has -been most frequently associated with scurvy, is essentially laxative, -and, on the other hand, that one of the most potent antiscorbutics is -potato, which has no definite laxative property. It may be added, as -noted elsewhere, that scurvy developed in infants in spite of their -receiving cod liver oil or olive oil for long periods. It is evident, -therefore, that the retention of fæces is not the essential factor in -the etiology of scurvy. Its secondary rôle, especially after scurvy has -developed, will be considered later in this chapter. - -In order to elucidate this question Torrey and Hess made a study of the -relation of the intestinal flora to the scurvy of guinea-pigs and of -infants. In guinea-pigs they found in the intestinal tract merely such -bacteria as are encountered on the oats and hay fed these animals. The -bacteria were few in number and hardly any were actively proteolytic. -Furthermore, there was no change in the flora on adding antiscorbutic -food, although the scorbutic symptoms disappeared. Recently Givens and -Hoffman, as the result of a similar study, have come to the same -conclusion. The investigation of infants led to similar results, and is -illustrated in Table 1. It will be seen that the infants were all on a -high carbohydrate diet, and that in two instances the flora was -compared, not only during the active scorbutic process, but after orange -juice had been given for a week or more. The bacteria were such as one -should expect on a diet rich in carbohydrates; putrefactive organisms -were present only in small numbers; and in the case in which they were -most numerous (S), they had disappeared upon the subsequent examination, -although the scurvy had become more marked. It is evident, therefore, -that in the scurvy of infants as well as of guinea-pigs there is no -overgrowth of putrefactive bacteria in the intestinal tract, and -therefore no basis for the hypothesis of ptomaine or similar -intoxication. Other poisons may, however, be absorbed from the intestine -as the result of a prolonged deprivation of an essential vitamine. - - TABLE 1 - FECAL FLORA OF SCORBUTIC INFANTS - ======================================================================= - | | | | M | | - I | | | |S a | | - n | | | |o t | | - f | Diet. | Date. |Scorbutic |u o e | Types | Remarks. - a | | |condition.|r f r | of | - n | | | |c i |bacteria.| - t | | | |e a | | - | | | | l.| | - --+-------------+-------+----------+------+---------+------------------ - M.|Malt soup and|Dec. 1|Subacute |Rectum|B. |{Normal infant's - | cereal | | | | acidoph.|{ flora. - | | | | |B. |{Gram + bac. - | | | | | bifidus |{ predominant. - | | | | |M. |{No spore-bearing - | | | | | ovalis |{ or putrefactive - | | | | | |{ types. - | | | | |B. coli |{B. acidoph. about - | | | | | |{ 40% viable bact. - | Do. |Dec. 4| Do. | Do. | Do. | Do. - |Same, also |Dec. 11|Sub- | Do. | Do. |{Relatively more - | 20 c.c. | |periosteal| | |{ B. coli. - | liquid | |hemorrhage| | |{Many B. bifidus - | petrolatum, | | | | |{No putrefactive - | one week | | | | |{ bact. - |Same diet, |Dec. 21|Markedly | Do. | Do. | Normal infants' - | oil stopped,| |improved | | | flora. - | _orange | | | | | Bacteria as - | juice_ | | | | | above. - | 10 days | | | | | - K.|Malt soup and|Dec. 11|Sub- |Rectum|Strepto- |{Gram - bacteria - | cereal | |periosteal| | cocci |{ predominant. - | | |hemorrhage| |B. coli |{B. coli gram + - | | | | |M. ovalis|{ diploc. numerous - | | | | | |{B. acidoph. few. - | | | | | |{B. bifidus few. - |Do. + |Dec. 21|Markedly | Do. |B. |{Gram + bact. - | _orange | |improved | | bifidus |{ predominant. - | juice_ | | | |B. coli |{Many B. bifidus. - | (60 c.c.), | | | |Strepto- |{Streptoc. - | 8 days | | | | cocci |{ unchanged. - | | | | | | - S.|Formula: |Dec. 21|Mild |Rectum|B. lact. |{Gram + and - - | Cream, | |scurvy | | aerog. |{ bact. about - | water, | | | |B. coli |{ equal. Many - | flour, | | | |M. ovalis|{ lact. aerog. - | sugar, | | | |B. |{Putrefactive - | also cereal | | | | bifidus |{ bact. in - | | | | |B. |{ minority. - | | | | | welchii | - |Malt soup and|Feb. 11|More | Do. |B. lact. |{Gram + bact. in - | cereal | |marked | | aerog. |{ great majority - | | | | |M. ovalis|{ (B. bifidus). - | | | | |B. |{Spore bearers - | | | | | bifidus |{ very few. - | | | | |Dipher- |{Flora not at all - | | | | | oids |{ putrefactive. - ----------------------------------------------------------------------- - -There are those who believe that scurvy is of _bacterial origin_, some -going so far as to regard it as a communicable disease. This viewpoint -was maintained by the famous Boerhaave and supported with all the weight -of his authority by Villemin in the seventeenth century. It is a view -held by many, if not by the majority, of physicians in Russia to-day, -and recently has been advanced by European army surgeons. This question -illustrates in an interesting manner how the trend of the day influences -medical thought--it has been suggested lately by Much and Baumbach that -the scurvy microörganism may be carried by means of lice. But clinical -experience points absolutely against the infectious nature of scurvy. -Indeed, the only episode which lends any support to this opinion is its -widespread and seemingly epidemic character; the fallacy of such -deductions has been well illustrated in regard to beriberi, which for -many years was regarded as an infectious and communicable disease. The -fact that whenever scurvy occurs among a body of troops the officers are -spared, constitutes convincing evidence against its communicability. -This peculiarity of incidence was noted by Hoerschelman and others in -the recent World War, and is referred to in the Report of the War of the -Rebellion. Many of the earlier writers, in discussing the occurrence of -ship scurvy, drew attention to the paucity of cases among the officers. - -When we turn to bacteriological studies we find that some years ago -Ausset claimed to have isolated "a pasteurella type of organism" from a -case of infantile scurvy, and suggested it as the causative agent of -this disorder. On the other hand, Hart, Rehn, Hirschsprung, von Starck, -Schmorl, and recently Boerich, have failed to find bacteria in the -blood, although the total number of cultures must be admitted to have -been small. Czerny and Keller report negative bacterial growth from -fluid aspirated from affected joints. - -The only articles considering this important question from the -experimental side are those of Jackson and Moody, and of Moore, who -conclude tentatively that scurvy may be a bacterial infection. Jackson -and Moody cultivated a diplococcus from the tissues of scorbutic animals -after death, reproduced hemorrhages by inoculating cultures of these -microörganisms into the circulation, and recovered the bacteria from the -tissues some weeks later. Their results are open to the criticism that -bacteria were found only after death, and that all blood cultures -during life proved negative. An article by Moore, however, which has -just appeared from this same laboratory, states that "an organism of the -streptococcus viridans type was isolated from the blood" in a case of -adult scurvy. In one instance we recovered an organism of this type from -the blood of an infant suffering from scurvy. It is highly important -that more blood cultures should be carried out in the course of human or -animal scurvy, and that particular note should be made of the stage of -the disorder when they are taken. - -There is no doubt that invasion of the blood-stream does occur readily -in the course of scurvy, but this takes place generally after the -disease has developed and must be regarded as a secondary phenomenon and -therefore unessential from an etiologic standpoint. Indeed one of the -striking and important symptoms of scurvy is the marked susceptibility -to infection (furunculosis, nasal diphtheria, "grippe," etc.), which -comes about as the result of the nutritional disturbance. An excellent -example of this interrelationship is the "epidemic" of hemorrhagic -scurvy described in the chapter on symptomatology. Hemorrhages coming -about in this way should be regarded as focal complications rather than -as truly scorbutic. It should be realized that, at the present time, it -is not possible to distinguish between local symptoms which are truly -nutritional or scorbutic in nature, and those which are bacterial and of -secondary origin. - -The newest theory, and the one at present most widely accepted, is the -_vitamine_ (_accessory factor_) _theory_. It was evident to Lind in the -seventeenth century that scurvy could be prevented and cured by means of -fruits or vegetables, a fact which became increasingly clear to -succeeding generations. Until the latter part of the nineteenth -century, however, this miraculous virtue of plants stimulated little -inquiry and no research. As far back as 1841 Budd realized that "the -explanation depended on the study of organic chemistry, and the -experiments of physiologists," but until recently it was not perceived -that the solution of the problem involved the introduction of a new -chemical factor. This view suddenly took shape after Eijkman in 1897 -showed the nature of polyneuritis in fowl, and Hopkins in 1906, going a -step farther, demonstrated the necessity of one or more unidentified -food factors for the normal nutrition of the rat. The work which -established this novel theory on a scientific basis in relation to -scurvy was the classic investigation of Holst and Froelich, referred to -so frequently in connection with experimental scurvy. These -investigators showed that the mere drying of vegetables was sufficient -to deprive them of their antiscorbutic power, although from a chemical -standpoint they seemed unaltered; that high degrees of heat had -generally the same effect; that under certain conditions these foods -withstood prolonged heating, demonstrating that the antiscorbutic factor -was not a ferment; that acids and alkalies played no essential rôle in -the etiology; that fats, proteins and carbohydrates were not significant -factors; that as little as 1.0 g. of cabbage suffices to afford -protection to a guinea-pig. In other words, by a process of exclusion -they showed that it is a disorder due to the lack of an unidentified -food factor. - -Subsequent studies, carried out within the past few years, have served -only to strengthen this viewpoint. For example, an "artificial orange -juice" composed of the various salts, citric acid, and sucrose in the -proportions in which they are found in the natural juice, failed, -in the experience of Hess and Unger, to protect or to cure -guinea-pigs--demonstrating that this preparation did not contain the -essential factor. In the same way, Harden and Zilva were able to protect -animals from scurvy with a preparation of lemon juice which had been -almost entirely deprived of its salts. It is needless to multiply these -examples. It is sufficient to state that there has been no investigation -during the last years of intensive study of scurvy, which has tended to -weaken the vitamine hypothesis. It may be stated, therefore, that -experiments have demonstrated that scurvy is due essentially to the lack -of a specific vitamine. It is unwise to proceed farther and place it in -the group of so-called "deficiency diseases," including beriberi, -pellagra, etc., unless the reservation is made that these several -diseases may present marked differences. It is quite possible that one -may be what might be termed a simple deficiency disease, whereas another -may have important additional etiologic factors. At any rate, unless it -is realized that there has been no proof that all are due to similar -deficiencies, we may, by stamping them all alike and by grouping them -together, be misled into taking their close relationship for granted. In -regard to scurvy, there may well be other etiologic factors, but they -are of a secondary character. Bacterial invasion has been referred to in -this connection, and it is possible that toxins are absorbed from the -intestine after nutrition has been disturbed. Diarrhoea and digestive -disturbances may play a rôle. Whether the total intake of food or the -correlation of its constituents--protein, carbohydrate, fat and -salts--affects the action of the vitamine, is one which has not been -well studied clinically or experimentally. In regard to beriberi, it is -claimed that there is a direct ratio between the quantity of -carbohydrate ingested and the amount of vitamine required. No such -interrelationship exists in regard to scurvy. This was evident a few -years ago (1917) when some infants receiving pasteurized milk, prepared -with the addition of 3 per cent. flour, did not tend to develop scurvy -more readily than others receiving simple pasteurized milk. A -consideration of the antiscorbutic vitamine will be postponed for a -subsequent chapter. - -=Etiology.=--In considering infantile scurvy we are concerned almost -entirely with the artificially-fed baby. It is true that in the -literature we meet with scattered reports of _scurvy in breast-fed -babies_ and that these cases seem to constitute a noteworthy group; in -point of fact, they are comparatively few. The collective investigation -of the American Pediatric Society includes ten infants who had been -given breast milk exclusively, and Concetti adds another ten in his -compilation of 682 cases.[7] In spite of their paucity these cases -require separate consideration because they represent an important -aspect from an etiologic standpoint. How are we to explain the fact that -human milk may lead to rather than protect against this disorder? On -investigating more closely it is found that these cases differ in -several important respects from the group which has been artificially -fed. They are of a different age; instead of being in the second half -year of life they are generally but a few months old. Furthermore, the -signs are not the same. The hemorrhages involve the upper extremities -fully as frequently as the lower extremities, and often appear at -unusual sites--for example, on the scalp or as large subcutaneous -effusions at various parts of the body. In many instances it has been -noted that the nursing mothers were suffering from some debilitating -disease such as tuberculosis or syphilis, or had an insufficient supply -of milk, or that there had been some other unusual factor, as Freund has -shown in an article devoted to this particular aspect. It is not -necessary, however, to fall back on these attendant circumstances to -exclude from consideration many of the cases. For example, Crandall's -case of "scurvy in an infant of six weeks" should be invalidated, not -because, as Freund suggests, the mother had rheumatism and insufficient -milk, but because of the age of the infant, and the course of the -disease; first one arm was involved, then the other, then hemorrhages -appeared on the skin, and finally it was cured by giving a teaspoonful -of fresh cream before each nursing. Had the baby really suffered from -scurvy it could not have been cured by this means. Southgate's case must -also be rejected, not because the mother was tuberculous but in view of -the symptoms--the arms and legs were pseudoparetic, "the legs, feet and -hands were double their normal size," and moderately large hemorrhages -were present on the back and chest. It seems hardly necessary to discuss -in detail the score of cases which comprise this group, as, in general, -the same criticism applies to all. Some evidently were congenital -syphilis, still more must be regarded as sepsis, and others as unknown -toxic conditions. Apart from these cases the question must be considered -whether scurvy can occur in a breast-fed infant. Personally, we have -never met with a case of this kind, and, as Finkelstein aptly remarks, -there has been "no necropsy of a breast-fed case or conclusive X-ray -picture." It seems possible only if an infant, for a period of months, -has obtained a scanty supply of milk, or when the milk has been -exceedingly deficient in the antiscorbutic vitamine. Even under such -conditions it does not seem possible for scurvy to become manifest in -six weeks (Crandall's case), or in four weeks, as in a case reported by -the American Pediatric Society, unless we believe that the infant -suffered also from a certain degree of intrapartum or congenital scurvy. -In view of the fact that an infant requires about one pint of milk to -furnish it with an adequate daily quota of the antiscorbutic factor, it -is theoretically possible, under extreme conditions, for it to become -scorbutic, in spite of being nursed at the breast. Such an occurrence -must be regarded as exceedingly rare, far more so than the current -statistics illustrate, for considerably less than a pint of milk a day -will prevent the appearance of manifest scurvy for a period of several -months. Some of the reported cases may have been latent scurvy, rendered -acute by a complicating bacterial infection. - -[7] These figures constitute an irrefutable argument against the -statement frequently made that a monotonous diet leads to scurvy. It is -only when the monotonous diet does not contain an adequate quantity of -antiscorbutic vitamine that it is to be feared. - -It might be expected that by ascertaining _the occurrence of infantile -scurvy in countries where it is endemic_, we could learn under what -conditions and how frequently breast-fed babies develop this disorder. -Approaching the question from this angle, it is found that the -available data is meagre and not entirely convincing. Peculiarly enough -infantile scurvy has rarely been reported from Russia, where scurvy is, -in many sections, endemic. For example, although Tschudakoff, who -personally examined over 10,000 persons, in connection with the great -scurvy epidemic in Russia (1898-99) found 11.11 per cent. of the people -suffering from this disease, he did not meet with a single case under -the age of five years. Fuerst writes that Filatow, the celebrated -Russian children's specialist, declared that he knew of no instance of -Barlow's disease described in the Russian literature.[8] Shortly after -the recent war scurvy broke out among the wet-nurses in an infant asylum -in Vienna. A very few of the infants nursed by these women developed the -disorder, far fewer than might have been expected (personal -communication). Hopkins recently wrote a communication to the effect -that in the island of Aruba, in the Dutch West Indies, they had been -unable to grow any crops in 1912, 1913, 1914, that 3000 cases of scurvy -had developed there during the year 1915, and that in 1917 it was again -being noted. In answer to a personal inquiry regarding the occurrence of -scurvy among the infants of Aruba, he wrote that "infantile scurvy is -very rare," although "most all of the babies are breast-fed for about a -year."[9] - -[8] This is not literally correct, as Doepp described an epidemic of -scurvy in the St. Petersburg Foundling Asylum occurring in 1831. - -[9] During 1919 in Aruba there were 293 births and 30 deaths under one -year, most of these deaths being due to intestinal diseases. The mothers -subsist mainly on maize or guinea small corn, with some goat and sheep -meat, and a little fresh fish, but no vegetables or fruit. The water is -brackish. - -On the other hand, descriptions of the coincidence of scurvy in mother -and nursling are even more fragmentary; in fact, we have been able to -find but two reports of this kind. The one most frequently cited is that -of Cheadle, which consists merely of the following bald statement: "With -the exception of one or two doubtful cases, of which the details of -breast-feeding and diet are imperfectly given, the only instances of -scurvy arising in sucklings are those when the nursing mother has been -suffering from scurvy at the time." The other report has been gleaned -from a recent editorial in the _British Medical Journal_, which refers -to the above mentioned outbreak of scurvy in Vienna, affecting in some -cases both mothers and breast-fed infants. - -It is difficult to pass judgment on this question in view of the paucity -of data. In the near future, probably, when we learn in detail about the -epidemics of scurvy which occurred during and immediately following the -war, we shall be in a better position to weigh its pros and cons. In -view of the above data it does not seem that nursing infants readily -develop scurvy, even though their mothers do not obtain a full quota of -antiscorbutic vitamine in their food. This appears to be the clinical -result, whatever its interpretation may be. It cannot be explained on -the assumption that human milk contains a particularly large quota of -this factor. In a test carried out to elucidate this question it was -found that eight ounces a day of breast milk was insufficient to -alleviate the symptoms in a case of scurvy, and that twelve ounces -barely sufficed. This milk was from a woman who was on a liberal diet -containing an adequate supply of vegetables. It had been previously -demonstrated that sixteen ounces of cow's milk is sufficient to cure -infantile scurvy, so that it is evident that human and cow's milk do not -differ essentially in this respect. There are, however, other factors to -be considered--for example, the incomparable freshness of the milk -suckled from the breast, which may endow it with additional potency, or -the possibility that the lack of vitamine may be compensated for by the -large quantity of milk consumed. It also may not be entirely immaterial -whether the vitamine is supplied in one dose, as, for example a daily -feeding of orange or tomato juice, or whether this factor is furnished -to the infant in frequent small quantities in the mother's milk -throughout the day. In this connection we cannot help contrasting the -relation of beriberi to breast feeding. As is well known, infants which -develop beriberi are almost always nursed and not bottle-fed, and show -signs of this disorder, although the mothers are in apparent health, and -give no clinical evidence of disease. - -Turning to a consideration of _the artificially-fed infant_, there -exists a somewhat similar situation in regard to the occurrence of -scurvy on a diet of raw cow's milk. In almost all reports of this kind -the quantitative viewpoint is entirely disregarded, and little or -nothing is stated to indicate how much milk the infant consumed. And yet -this factor is of essential importance in interpreting the cause of the -nutritional failure. It is clear, for example, that if a baby receives -but eight ounces daily of raw milk--one-half the requisite amount--it -may well develop scurvy, notwithstanding the fact that the milk has not -been heated. In addition to the quantity, there are other factors which -play a greater or less rôle in the relation of raw milk to the etiology -of scurvy. It is no doubt of consequence whether the fodder of the cows -was rich or very poor in the antiscorbutic factor, and, accordingly, -whether the baby received what may be termed an "antiscorbutic-rich" or -an "antiscorbutic-poor" milk. Furthermore, the age of the milk must be -borne in mind, for we have found that even raw milk loses some of its -potency on becoming stale.[10] - -[10] Moore raises the interesting question as to whether a diseased -condition of the cow may decrease the vitamines of the milk--whether a -certain outbreak of scurvy among guinea-pigs might have been due to -their having been fed on the milk of a cow suffering from experimental -streptococcus mastitis. If such proves to be the case, it would have an -important bearing on the question of scurvy and pseudo-scorbutic -conditions in nursing infants. - -One of the mooted questions relative to the etiology of scurvy is the -rôle of heated milk, and more particularly of _pasteurized milk_. In -view of the vogue which pasteurization has acquired in the large -municipalities, especially in the United States, this aspect has assumed -increasing importance, and deserves detailed investigation. -Pasteurization has achieved so much in limiting the infectious diseases, -especially the diarrhoeal disorders of infancy, that it has come to be -looked upon as heresy to deprecate its virtues in any regard. - -It has become increasingly evident that in the course of pasteurization -milk loses an important measure of antiscorbutic vitamine. The term -pasteurization, when employed in this connection, is not meant to be -synonymous merely with the heating of milk to 140° to 165° F., but -embraces the entire commercial process--the heating, handling, -subsequent cooling, aging and all other factors involved. There can be -no doubt that milk which has undergone this elaborate treatment has -suffered in its antiscorbutic property. In 1914 Hess and Fish reported -mild cases of scurvy occurring among infants who had received milk -heated to a temperature of 165° F. for thirty minutes. This degree of -heat is claimed by many physicians and hygienists, including the -National Commission on Milk Standards, not to destroy its chemical -constituents. Nevertheless typical cases of scurvy supervened after this -diet had been followed for a period of six to nine months. Subsequent -experience, published by Hess in 1917, with milk heated to only 145° F., -served to confirm the previous observations. That these cases were true -scurvy was proved by the fact that a cure resulted when raw milk was -substituted. A similar experience in Berlin reported by Neumann and -others was convincing, but was not heeded in this country. In 1901 one -of the largest dairies in that city established a pasteurizing plant -where all milk was raised to a temperature of about 60° C. After an -interval of some months infantile scurvy began to be reported from -various sources throughout the city. Neumann depicts the situation as -follows: "Whereas, Heubner, Cassel and myself had seen only thirty-two -cases of scurvy from 1896 to 1900, the number of cases suddenly rose -from the year 1901, so that the same observers--not to mention a great -many others--treated eighty-three cases in 1901 and 1902." At a spirited -meeting held by the Berlin Medical Society in 1903 to discuss this -subject, Heubner was able to report 65 cases. An investigation was made, -and the pasteurization discontinued. The result was almost immediate, -the cases decreasing just as suddenly as they had increased. These -reports and others demonstrate that unless additional antiscorbutic food -is given, a diet of pasteurized milk will lead to the development of -scurvy. As the antiscorbutic vitamine is not entirely destroyed by -pasteurization, the severity of the disorder will be in inverse ratio to -the amount of milk which is consumed. - -It has been our experience that milk pasteurized in the home or -institution did not lead to scurvy to the same extent as that which was -commercially pasteurized. Babies fed on home-pasteurized milk did not -develop manifest scurvy. The difference in the two processes consists -mainly in the amount of handling during the process of heating and the -subsequent aging which the milk undergoes. An interval of forty-eight -hours usually elapses between commercial pasteurization and the delivery -of the milk to the consumer. In New York city most of the better-grade -milk is pasteurized at the farm, so that it is subjected to a longer -period of aging than the poorer grade, which is not pasteurized until it -reaches the city. Although our results indicated the effect of freshness -or staleness on milk which had been heated, they showed also that other -factors must be involved, for home-pasteurized milk which is forty-eight -hours old is superior to the commercial product of the same age. This -difference we believe is due to the handling which the milk undergoes, -to the mechanical processes involved in commercial pasteurization. - -In considering this aspect of the development of infantile scurvy on a -diet of heated milk, it is of interest to refer to the experience of -Switzerland and of France. In 1907 Bernheim-Karrer reported nine cases -of scurvy which occurred on "homogenized" milk. This milk is forced -between rapidly-rotating surfaces at a temperature of 55° to 65° C. at a -pressure of 150 atmospheres. This process had been introduced the year -previous by a large dairy which was well known for its excellent grade -of milk. Before this innovation, milk usually had been boiled for a long -while before being fed to infants. In France a similar epidemic of -scurvy followed the introduction of the use of homogenized milk (lait -fixé). Lecornu gives an interesting account of this episode, remarking -on the large number of cases of scurvy occurring on this milk compared -with sterilized milk, which was employed so much more extensively. These -experiences furnish excellent examples of _the harmful effect of -industrial methods on milk_, especially on its antiscorbutic vitamine. -Lecornu also emphasized the scorbutic influence of "lait maternisé," -which is similar to the German Gaertner milk, and is subjected to -dilution, centrifugation, and sterilization.[11] He states that before -this preparation was introduced scurvy was practically unknown in -France. Lecornu attributes the deleterious effect of the "lait -maternisé" and the "lait fixé" to bacterial contamination, as does -Bernheim-Karrer. We believe, rather, that its loss of potency is due to -the mechanical processes to which it has been subjected. - -[11] In the case of the "lait maternisé," which is a milk of high fat -content, the dilution of the preparation also must have been a factor. -Ounce for ounce, cream is poorer in antiscorbutic vitamine than an equal -quantity of milk. It is also possible that the mere dilution of -milk--quite apart from the absolute amount consumed--is not immaterial -in affecting this highly sensitive vitamine. - -Boiled and, more particularly, sterilized milk, is regarded as a common -cause of infantile scurvy and figures prominently among the foods held -accountable for this disorder. It has been pointed out, however, that -thousands of infants, especially in Europe, receive milk of this kind, -and do not develop scurvy. Statistics such as those of Variot, who has -distributed in his out-patient department, during a period of twelve -years, 400,000 quarts of sterilized milk (heated in half-litre bottles -and hermetically sealed at the farm) without observing a case of scurvy, -must be accorded weight in this connection.[12] Escherich, some years -previously, stated that he did not meet with scurvy in Graz, although he -was accustomed to feed babies on sterilized milk. Budin, the celebrated -French children's specialist, writes: "As for the so-called infantile -scurvy which is alleged to follow the use of sterilized milk, I have -heard a very great deal about it during the last few years, but I am -still looking for my first case." Evidence from such sources cannot be -summarily cast aside, but must be given due consideration. It is evident -that the mere heating or sterilization of milk, although it reduces the -antiscorbutic vitamine, does not do so to a degree sufficient to lead to -the production of clinical scurvy. Our experience accords with that of -the above observers. Some years ago we fed infants with milk which had -been boiled for five minutes, and, at another time, made use of -home-made evaporated milk which had been heated for a period of -seventeen hours, until it had been reduced to one-eighth its volume. -This evaporated milk was well borne for months, although slightly -caramelized in the course of heating, and did not lead to any signs of -scurvy. Clearly there are other factors involved in this question -besides the mere subjection to heat. We believe that every step in the -process is important--the freshness of the milk, whether or not it is -agitated and exposed to the air, whether it is sealed carefully and used -soon after sterilization,[13] and, finally, whether the baby receives a -sufficient quantity. If this milk, which has certainly lost some of its -vitamine content, is given in small amount, it will not supply an -adequate amount of the antiscorbutic factor. - -[12] It is to be noted, however, that Variot remarks that these infants -frequently develop anemia unless additional diet is given, so that it -must be considered open to question whether some of these babies did not -have latent scurvy. Of course, unless it is certain that these infants -were receiving only sterilized milk, and absolutely no other food, for a -period of at least six months, they cannot be considered apposite to the -question. - -[13] Carel reports an interesting case which points to the importance of -staleness. A baby was taken to the country with a supply of sterilized -milk sufficient to last for some weeks. At the end of this time it did -not thrive, but regained its health when a fresh supply of milk was -used. When this second supply became stale the infant again developed -the same signs, and the condition was diagnosed as scurvy. - -Neumann, Czerny, and others state that they have even cured infantile -scurvy by giving boiled milk obtained from a different source. In the -Berlin epidemic, Neumann laid particular emphasis on the fact that the -milk which induced scurvy had been doubly heated, having been -pasteurized commercially and later boiled in the home before it was fed -to the baby. Plantenga has also laid stress on the influence of -_two-fold heating_, citing an interesting experience with scurvy in his -clinic. When the milk was pasteurized one day and boiled for five -minutes on the subsequent morning, 23 cases of infantile scurvy -developed among the 200 infants attending his dispensary. The following -year when the procedure was altered so that the milk was merely -pasteurized, no case of this disorder developed. There can be no doubt -that milk which has been heated twice must have lost more of its -antiscorbutic properties than milk which has been heated but once, and -that aging also must contribute to this loss. Whether there is what may -be termed a peculiar sensitization of milk following pasteurization, has -not been definitely shown. - -Up to the present time _dried milk_ has played an insignificant rôle in -the etiology of infantile scurvy. One of the factors which has hindered -the general acceptance of dried milk by physicians and laymen has been -the fear that its use might lead to the development of Barlow's disease. -It is therefore important to consider this aspect of the subject, -especially as dried milk seems destined to be used to an increasing -extent. A recent report to the Local Government Board by Coutts states -that "Millard and Naisch in England confirmed the testimony of Miele in -Belgium, and Gautier and Genevoix in France, that scurvy is not to be -feared" from this foodstuff. This coincides with our experience, namely, -that _dried milk not only does not lead to scurvy, but may contain -sufficient antiscorbutic vitamine to cure this disorder_. Recently a -scorbutic baby was fed with milk which had been dried by the so-called -Just-Hatmaker process--whereby it is subjected on a drum for a few -seconds to about 230° F.--with the result that the hemorrhages of the -gums began to be absorbed in about three days, and all symptoms to -disappear shortly thereafter. This infant received dried milk to the -equivalent of 24 ounces of fresh milk, and this preparation had been -dried and canned somewhat over three months before it was used. Recently -two infants, suffering from marked scurvy, were treated with milk which -had been dried six months previously. The one received only sixteen -ounces a day and the other a quart; both recovered within a few days -after this food had been substituted for malt soup. Not long ago, as -reported elsewhere in a paper by Unger and myself, after curing a baby -of scurvy by means of this milk, it was maintained in health for a -subsequent period of three months on a diet which contained no -additional source of antiscorbutic vitamine. These results are -emphasized as illustrating the peculiar relationship of drying and of -the application of heat to the antiscorbutic vitamine, and because -recently several reports have appeared, for example, that of Barnes and -Hume in England, and of Hart, Steenbock and Smith in this country, to -the effect that dried milk is devoid of antiscorbutic value. The -difference of opinion is due to the assumption that dried milk is a -uniform product and has identical antiscorbutic properties. For milk to -retain its antiscorbutic value, notwithstanding drying, it must have -been rich in vitamine before desiccation, it must have been dried -quickly, and packed within the shortest possible interval in air-tight, -preferably hermetically sealed, containers. As in relation to the -heating of milk, so in regard to its drying, it is not the degree of -heat to which it is subjected which is all important, but rather the -associated conditions. The merits of each process will have to be tested -individually and perhaps even each particular brand of milk.[14] - -[14] In making tests of dried milk particular attention should be paid -to the age of the milk before it is desiccated. Investigators should -also be certain that the milk has not undergone heating previous to the -drying process. Some well-known brands of dry milk have been not only -pasteurized, but subsequently evaporated before drying. - -In the foregoing, the dictum has been accepted without comment that -fresh milk may be either rich or poor in antiscorbutic vitamine. This -point of view has recently gained general acceptance, on the assumption -that the milk of the stall-fed cow is markedly deficient in this factor. -Recent work by Hart, Steenbock and Ellis gives evidence that "summer -pasture milk is much richer in this nutritive factor than dry feed milk -or winter produced milk, involving the use in the ration of corn silage -or sugar mangels." In some experiments (unpublished) we have found that -dried milk shows similar variations, being a much more potent -antiscorbutic when obtained from cows fed on fresh fodder than a similar -milk from the same cows on fodder containing a minimum amount of -antiscorbutic vitamine. The supposition of a direct quantitative ratio -between the antiscorbutic intake in the food and output in the milk -needs confirmation, especially as it does not quite coincide with the -experience among human beings in countries where adult scurvy is -endemic. In such countries--for example, Russia--nursing infants do not -develop scurvy to the extent that would be expected, and it is possible -that this exemption is due in part to a selective secretion of -antiscorbutic vitamine into the milk. - -As is well known, a diet of _condensed milk_ leads to scurvy. This is -not surprising, considering the prolonged heating to which this milk has -been subjected. It is probable that many cases of mild scurvy developing -on this food and characterized by beading of the ribs (rosary) and other -indefinite manifestations, have been erroneously diagnosed as rickets. - -It is hardly necessary to discuss separately the various kinds of milk -which have led to scurvy in the course of infant feeding.[15] The -principles laid down in the preceding discussion hold good for milk of -all kinds. Heat will destroy a certain amount of vitamine, and, if the -heating is followed by aging, still more will be lost. If an interval -elapses and a second heating ensues, there will be further loss of -vitamine. It should never be forgotten in considering foods in their -relation to the causation of scurvy, that _the amount of food_ given -must not be overlooked. For example, a pint of ordinary pasteurized milk -will lead to scurvy, whereas a quart in most cases will be sufficient to -tide the baby over until the period of mixed feeding. No general rule -can be laid down, however, as may be judged from the fact that dried -milk which has been subjected to almost all the influences which are -deleterious to the antiscorbutic vitamine--heating, drying, aging, all -carried out in a neutral medium--nevertheless retains its specific -potency. - -[15] Ausset reports a definite case of scurvy developing in a baby nine -months old, which had received buttermilk almost since birth. At the -time of admission to the hospital it was getting 900 c.c. a day. This -case is interesting on account of the acid nature of the food. - -Infantile scurvy has always been far more prevalent in England and in -America than in Europe, notwithstanding the fact that on the continent -practically all milk for babies is boiled or sterilized. This has been -ascribed, and probably rightly so, to the widespread usage of -_proprietary foods_ in the English-speaking countries. Among the cases -reported by the American Pediatric Society about 60 per cent. had been -given foods of this description. How is this relationship to be -explained? These preparations in general may be stated to consist of -cereals, sugar, with occasionally a small amount of dried milk; they are -mixed with varying proportions of water and milk and then cooked. It is -evident that two important causative factors of scurvy are thus -furnished, namely, a small and inadequate quota of milk and the -application of heat. In most instances not more than sixteen to twenty -ounces of milk are used to make up the day's feeding, and frequently -this has been previously pasteurized. But there is an additional factor -which comes into play in this connection, one to which we have recently -drawn attention in treating of "The Deleterious Effect of the -Alkalization of Infants' Food." It has been shown that the antiscorbutic -vitamine is peculiarly sensitive to the faintest alkaline reaction, in -which medium it rapidly undergoes deterioration, and even total -destruction if heat is applied. Proprietary foods, with but few -exceptions, are alkaline, having been rendered so by the addition of -potassium carbonate or bicarbonate, in order to prevent acid -fermentation of the fat and to counterbalance the relative poverty of -potassium in cow's milk. Little or no regard has been paid to this -reaction; the textbooks on children's diseases give this point no -consideration whatsoever, expressing the salt content merely in terms of -total ash. By this means ideal conditions are furnished for the -destruction of a large part of the vitamine, and if this factor is not -present in excess, scurvy will readily develop. It is to these various -circumstances--the deficiency of milk, the alkalinity and the -heating--that the scorbutic quality of proprietary foods is to be -ascribed. - -The most flagrant example of an infant's food leading to scurvy is "malt -soup"--an alkaline preparation of malt, which is prepared with flour and -a small amount of milk.[16] This food brings about scurvy almost -invariably unless an antiscorbutic is added to the dietary. That this -effect is due to the alkaline potassium carbonate was shown by a recent -test which is illustrated in chart. (Fig. 2). Here we see that in a case -of scurvy, when the food was altered and prepared with the same amount -of milk and alkali, the disorder did not abate (although the -carbohydrate had been discontinued), but when the potassium carbonate -was omitted a gain in weight ensued, and, we may add, the symptoms -disappeared. - -[16] Malt soup is prepared by dissolving the alkaline malt soup extract -in water, and mixing wheat flour with milk. These two mixtures are then -boiled together for about three minutes. According to some directions, -11 ounces of milk are used; in our formula 16 ounces were employed. - -[Illustration: FIG. 2.--Human scurvy: weight curve of a baby that -developed scurvy on a diet of malt soup (period 1). During period 2 the -flour and malt soup were omitted from the diet, the same amount of milk -and potassium carbonate being continued. The disorder did not abate. The -only change in period 3 was a discontinuation of the potassium -carbonate. This brought about a gain in weight and cure, showing the -destructive effect of the alkali on the vitamine.] - -A test of this kind once more raises the question whether carbohydrates -lead to the development of scurvy. As previously stated, there are many -who believe that the carbohydrates, especially starch, have this harmful -effect by requiring a large amount of the various vitamines for their -metabolism. This relationship was first brought forward by Bradden and -Cooper in regard to beriberi. It is a suggestion which cannot be -disregarded in view of the great amount of scurvy which comes about on -diets rich in carbohydrates, especially those containing malt sugar. We -do not believe, however, that the harmful effect which this foodstuff -exerts can be explained on the above hypothesis, as experience has shown -that infants may receive for many months equally large amounts of -carbohydrates--cane sugar, flour, or a combination of both--and -nevertheless not manifest a similar tendency to develop scurvy. - -=Age Incidence.=--Scurvy may occur at any age if the diet does not -furnish sufficient antiscorbutic factors. As a matter of fact, it is -encountered most often among infants and adults, not because these two -age-groups are particularly susceptible, but because there are peculiar -attendant circumstances. In the case of the infant, it is due to the -fact that for almost the entire first year of its life it is dependent -entirely upon milk, a foodstuff poor in antiscorbutic vitamine, and -containing, under favorable conditions, barely enough to meet its -requirement. If, therefore, the potency of the milk is weakened, or if -an insufficient quantity is fed, and more particularly when both of -these factors are involved, a scorbutic condition will ensue. The reason -why older children, those over one and a half or two years of age, do -not develop scurvy is largely due to their varied and liberal diet, -which is amply provided by the mother or guardian, so that even in times -of want they receive more than their due share of the available food -supply.[17] - -[17] It would seem, however, that the growing infant requires relatively -more antiscorbutic vitamine than does the adult. We know that its -caloric requirement is fully a quarter to a third greater. In regard to -vitamine, judgment cannot be based on experimental evidence, but on -comparative figures. For example, unless we take this viewpoint, we must -believe that, as an infant of six months weighing 15 pounds requires 15 -c.c. of orange juice daily to furnish its antiscorbutic quota, an adult -weighing 160 pounds requires 180 c.c. daily--the juice of three -good-sized oranges. On this basis the adult would require six quarts -(6000 c.c.) of fresh milk daily, twelve times the minimum requirement -for an infant, which is one pint (500 c.c.) a day. These figures are -manifestly too high. - -From a clinical standpoint scurvy may be said to occur in infants during -the second half year of their lives. There is general agreement on this -point; it is borne out by the investigation of the American Pediatric -Society and by the statistics of various individuals. On the basis of a -large experience, Still states that nearly eighty per cent. of the cases -appear between the ages of six and ten months, and that in no case did -the disorder occur before the age of five months. It is of importance -from both the etiologic and the therapeutic standpoint to distinguish -clearly between the age when infantile scurvy is commonly diagnosed, and -the earlier stage when it appears as a general nutritional disorder. We -must remember that scurvy generally takes from six to nine months to -become manifest, this developmental period varying mainly in proportion -to the degree of the dietary deficiency. It is evident, therefore, that -there must be a prolonged period of nutritional failure which precedes -the diagnosis. This stage consists of two early phases, the first months -where the faulty diet causes no apparent change and seems to have no -deleterious effect on the infant, and the second, of latent and subacute -scurvy. The "latent" condition is one merely of unsatisfactory nutrition -and retarded growth, which it is not possible to interpret; "subacute -scurvy," which develops subsequently, is distinguished by characteristic -signs and symptoms. We shall not review their symptomatology, as it is -given in the chapter devoted to this topic. The subject is brought -forward in this connection to emphasize the fact that the scorbutic -condition occurs far earlier than is generally realized, and -furthermore, that if the earlier and more subtle symptoms of scurvy were -comprehended, the age incidence would fall earlier than the current -figures indicate. The earliest instance of this disorder which we have -seen occurred in a baby four and a half months of age. - -Age does not seem to play a definite rôle in regard to the incidence -among adults. Scurvy frequently has been encountered among old men, and -is of common occurrence among the most vigorous of the nation, the young -soldiers and sailors. Some have stated that it takes place less often -among soldiers in the twenties than among those in the thirties, but -this has not been demonstrated. The fewest cases have been reported -among children over two years of age. It was due to the apparent -immunity of this age-group that, until very recently, German writers -doubted the identity of infantile and adult scurvy. The exclusion of -children of this age is merely fortuitous and, moreover, is by no means -absolute. One of the earliest cases of scurvy in children, reported by -Montfalcon, occurred in a child six years old. Bateman in America -described a case in a child of about this age. Barlow, in one of his -first articles, reported scurvy in a small group of older children. The -case so frequently quoted by German authors in this connection is that -of Fraenkel, who described both clinically and pathologically a case of -scurvy in a boy eight years of age. These cases by no means exhaust the -number which are reported. Recently, Tobler has given us an account of -scurvy, occurring during the war, in a Viennese foundling asylum which -harbored children between the ages of two and fourteen. - -=Season and Climate.=--Many of the older writers laid great stress on -the influence of season on the occurrence of scurvy, which they believed -broke out particularly in the cold and damp months of the fall, winter -and early spring. It is true that most of the epidemics have occurred at -these seasons of the year. This is merely what should be expected, -considering that the disease depends mainly upon the supply of fresh -fruits and vegetables. Where conditions are abnormal, as in war, there -have been notable exceptions to this seasonal incidence. In the "Report -of the War of the Rebellion" there is an instructive graph illustrating -the occurrence of scurvy in our Civil War and in the Crimean War, which -shows that this disease prevailed to the greatest extent during the -winter months in the former, whereas in Crimea, the season of greatest -frequency was the summer time. One of the severest outbreaks of scurvy -on record is that which occurred at the siege of Thorn in Germany in the -year 1703. During the months of July and August, when the weather was -excessively hot, scurvy ravaged the besieged army. There are, -furthermore, many reports of scurvy in the tropics during the dry -season. In the island of Aruba, in the Dutch West Indies, which has been -visited by scurvy year after year, and which is referred to elsewhere, -the disease is endemic during the dry, hot season. Formerly it broke out -on the men-of-war and vessels of the mercantile marine while they were -in southern waters. As regards infantile scurvy, it has always seemed to -us that season played a slight rôle; that cases which occurred in the -summer tended to be less severe and to be characterized by periods of -intermission rarely observed in the winter time. - -The effect of _climate_ has been accorded a variable place in the -etiology of scurvy. Lind believed that a damp, cold climate, such as -that of the Low Countries, was conducive to scurvy. On the other hand, -since it is realized that diet is the essential element, all other -factors have been regarded as of no moment whatsoever. It is difficult -to pass judgment on this question, since scurvy is now endemic in such a -limited area of the world. It seems quite possible that a damp, cold -climate, which depresses the various functions of the body, may exert an -influence where the quota of antiscorbutic foodstuff is not quite -adequate. Exposure to infection is also greater under such climatic -conditions. - -Economic status has to be considered in connection with infantile -scurvy. Numerous writers have drawn attention to the fact that scurvy is -seen relatively more frequently among the infants of the well-to-do and -the rich than among those of the poor. This curious and paradoxical -situation is due to the zealous care which the former receive--the -extreme precautions in sterilizing the milk, the addition to the -formulas of expensive proprietary foods, the watchfulness to avoid the -child's obtaining a chance bit of fruit or vegetable. Since the -popularization of commercially-pasteurized milk in the larger -municipalities, and the advertising propaganda for the sale of "baby -foods" which has extended their use among the masses, this distinction -in the social status has been largely obliterated. - -Sex seems to play no part in the etiology of scurvy. Several writers -have claimed, however, that there is a certain degree of racial -immunity. For example, Sheppard reports that the Zhob Kakai seldom -develops scurvy, although he naturally excludes vegetables from his -diet, and Boerich noted among the prisoners of war that the Slavs, -especially the White Russians, were more susceptible.[18] Of course a -lack of susceptibility of this nature can be merely relative. Such a -racial distinction may seem far-fetched, but if we admit that -disposition and habits of life can play a rôle, it is quite possible for -races to vary in their predisposition to this disorder. Moreover, we -shall see that individuals differ markedly in this respect. Lind and -others repeatedly emphasize the fact that the indolent and slothful -sailor was stricken with scurvy far oftener than the one who was active, -and claimed that physical exercise even tended to bring about a -cure.[19] Those who have had a large experience with scurvy in adults -are almost unanimous in believing that a _psychic element_ enters into -its etiology. In this way, in a measure, they account for the frequency -of scurvy among defeated troops, in besieged armies, and among men -depressed by homesickness, fatigue, and discouragement. This point of -view cannot be lightly disregarded, bearing in mind that depressed -mental states alter the functions of the organs and markedly affect -secretion. The many cases and epidemics in institutions for the insane -cannot, however, be attributed to this cause, but are probably almost -entirely due to a want of supervision of the dietary. Among infants, the -question of the influence of race and of the mental state needs but -little consideration.[20] For some time we have carefully observed the -course of scurvy among happy and contented infants compared with those -of an unhappy and fretful disposition; in some instances the former, -although the diet was similar, seemed to develop scurvy less readily -than the latter. - -[18] It would be of interest to know whether the negro infant is more -susceptible than the white baby, in view of its markedly heightened -susceptibility to rickets. There are, however, no reports or statistics -to enlighten us on this point. - -[19] "Where the indisposition is but beginning, and even when the gums -have been pretty much tainted, there have been numerous instances of a -perfect _recovery without having the benefit of fresh vegetables_; -provided the patient is able to use due exercise.... When it is advanced -to what I have called the second stage it is hardly to be cured without -their (fruits and vegetables) assistance." (Lind.) - -[20] Caillé has described a case of scurvy in an infant suffering from -Mongolian idiocy, and we have also seen a similar case. - -There can be no doubt that there is _predisposition_ to scurvy, as there -is, probably, to every nutritional disorder. Among soldiers and sailors -a certain number develop scurvy on the same ration which does not harm -others. Some years ago when scurvy developed among a group of infants -fed on pasteurized milk, this idiosyncrasy was noted. The distinction, -however, is rarely sharply defined. Careful clinical investigation will -generally show that the infants which seem to be spared are not -thriving quite normally; they are somewhat pale, and do not gain in -weight as they should, and their appetite is poor. The most interesting -experience of this kind is the following which is frequently cited: In a -family where the first child developed scurvy, Finkelstein took the -precaution, in the case of the second child, to have the milk boiled for -as short a time as possible, and to begin mixed feeding early. In spite -of these precautions this boy also developed scurvy. Finkelstein states -that once before he had met with a similar mishap. An experience which -he relates, regarding a foster-mother, an excellent nurse, who had three -infants in succession develop scurvy in spite of preventive measures, is -also of interest in this connection. The latter occurrence evidently -cannot be attributed to hereditary or family predisposition, and serves -to emphasize the inherent difficulties of the subject. v. Starck's -report of an instance where twins were fed on similar milk mixtures and -one developed scurvy, whereas the other thrived satisfactorily, is a -striking illustration of the rôle of idiosyncrasy. This case, as well as -many others, fails to be absolutely convincing in view of the fact that -the daily intake of milk is not recorded. - -A predisposition to scurvy cannot be ascribed to a condition of general -malnutrition. For example, among infants it has never seemed that those -suffering from marasmus or atrophy were particularly prone to develop -scurvy. Whether syphilis, tuberculosis or malaria tends to precipitate -the onset of this disorder cannot be stated.[21] In view of the fact -that prematurity is such an important factor in the pathogenesis of -rickets, it would be of interest to know whether a similar relationship -exists between infantile scurvy and prematurity. The only clinical -condition which we have found predisposing to scurvy is the "exudative -diathesis" of Czerny, a term which implies a tendency to develop -exudations of the skin or of the mucous membranes. Probably it is not -without significance that in this diathesis the blood-vessels may evince -a decided weakness, an increased permeability, as demonstrated by the -"capillary resistance test." (See Symptomatology.) - -[21] Many of the older authors believed that mercurial drugs were -especially prejudicial in cases of scurvy. - -Nothing whatsoever is known regarding the possible influence of the fat, -protein, carbohydrate and salt content of the diet on the development of -scurvy. Is it entirely immaterial whether one or another food element -largely predominates, or is the antiscorbutic factor to some extent -modified by other components of the food? Influences of this kind, which -at most are secondary, cannot be ascertained by the biologic test which -at present has to be relied on to measure the development of scurvy and -the potency of antiscorbutics. It is quite possible that the course of -scurvy may be affected by the character of gastric and intestinal -digestion, by the activity of the glands which pour their secretions -into these organs, by the destruction or elimination of the -antiscorbutic factor in the food. The frequent association of dysentery -and scurvy noted during the recent war and referred to by many previous -writers, shows the effect of intestinal disorders. These hypotheses are -tentatively advanced because it is evident that some factor exists, -apart from the mere antiscorbutic value of the diet, which at times -exerts a potent influence on the development of scurvy. Cases developing -in spite of a moderate amount of antiscorbutic food, and others not -responding to the addition of vegetables or fruit to the diet--although -not numerous--have occurred too frequently and have been reported by too -experienced observers to be brusquely disregarded. For example, Neumann, -one of the keenest clinical students of scurvy, stated that he had met -with four instances of this nature. Hess and Fish reported two similar -experiences. - -The secondary etiologic factors are mainly predisposing; a few words, -however, must be added concerning what may be termed _exciting factors_. -Infection is the most important condition which may suddenly and -precipitously induce scurvy. This fact was brought to our attention in -1912 in connection with the outbreak of scurvy among infants receiving -pasteurized milk. Its explanation was not clear at the time, but was -elucidated by subsequent experience, and was described in 1917 as -follows: "Latent scurvy was prematurely changed to florid scurvy by the -presence of a ward infection; an epidemic of 'grippe' precipitated an -epidemic of scurvy exceptional in its hemorrhagic tendency." The -association of scurvy and infection has been recently emphasized by -McCarrison and others, and seems to hold good for the other so-called -deficiency diseases. In this connection one other exciting cause of -scurvy may be mentioned, namely, trauma. The older writers noticed that -following a fall or an accident, a sailor frequently developed scurvy, -and Barlow in 1894 remarked on the influence of trauma in connection -with infantile scurvy. As might be inferred, its effect is mainly to -induce premature rupture of the weakened blood-vessels; in infants we -have seen this occasioned by pressure exerted on the lower end of the -thigh to ascertain the presence of tenderness. Viewing the situation -broadly, it must be acknowledged that except for the realization that -scurvy is due to a new food factor--a vitamine--our fundamental -understanding of its pathogenesis has advanced but little, in spite of -the employment of experimental methods and the availability of modern -technic. - -It is doubtful whether mere clinical studies will contribute in a large -measure to the solution of the pathogenesis of scurvy. Much may, -however, be learned by investigations of the metabolism in human -scurvy--an aspect of the problem which, as will be brought out in a -subsequent chapter, hardly has been explored. By this means may be -acquired a clearer understanding of the effect of an antiscorbutic -deficiency on the tissues and on cellular activity. Much may be expected -from physiologic and pharmacologic studies of the specific vitamine, -although it is not yet available in a pure state. Finally, it is -probable that the solution of similar questions relating to the -pathogenesis of cognate disorders--a study which is engaging the best -efforts of so many workers throughout the world--will shed light on this -particular disease. - - - - -CHAPTER III - -THE ANTISCORBUTIC VITAMINE[22] - - -[22] Vitamine is used throughout this monograph as synonymous with -"accessory food factor" or "food hormone" as a convenient descriptive -term, without any intention of connoting a definite chemical substance. - -We shall not discuss the subject of vitamines in general, but confine -ourselves to the more limited field of the antiscorbutic vitamine. The -recognition of the "accessory" dietary factors is of such recent date, -however, that it will be well to consider briefly how attention came to -be directed to them and how their existence was ascertained. As in the -case of so many scientific discoveries, it is difficult to point to the -exact time when the advance was made. On looking back we find that -Lunin, in 1881, noting that mice were unable to live on a diet -consisting of protein, fats, carbohydrates, salts and water, came to the -conclusion "that other substances indispensable to nutrition must be -present in milk besides caseinogen, fat, lactose and salts." This work -did not stimulate similar investigations, nor did Lunin, as might have -been expected, allude to scurvy. The work which focussed attention on -this novel aspect of dietetics was the report of Eijkman, in 1897, to -the effect that when fowl are fed decorticated rice, they develop a -disease resembling beriberi, and that the paralytic symptoms disappear -on feeding them rice polishings or its alcoholic extract. Here, for the -first time, was a positive rather than a negative experiment, and one -capable of simple verification. The subject was placed on a scientific -basis by the classic investigation of Hopkins, who experimented with -purified food substances, and demonstrated how diets which were -deficient could be rendered adequate. As early as 1906 he wrote "the -animal body is adjusted to live either upon plant tissues or other -animals, and these contain countless substances other than the proteins, -carbohydrates and fats." "In diseases such as rickets, and particularly -in scurvy, we have had for long years knowledge of a dietetic factor, -but though we know how to benefit these conditions empirically, the -real errors in the diet are to this day quite obscure." The work of -Osborne and Mendel, and McCollum and Davis in this country, of -Schaumann, Funk, Stepp and others, all led to the conclusion that -purified diets are unable to satisfy the nutritive requirements of rats -or mice, and that extracts of the natural foods suffice to render the -diet adequate. - -The same rule holds for man, who, when deprived of these vitamines, -develops the so-called deficiency diseases--typically modern disorders. -Regarded as a group, they are a consequence of our altered mode of life -and peculiar civilization. They follow naturally upon the development of -immense cities housing millions of people, who necessarily must receive -perishable foodstuffs produced at a great distance. To even a greater -extent they are the product of countless ingenious methods devised -mainly to render foods stable--drying, heating, the addition of -preservatives--most of which accomplish their object, but incidentally -rob the food of its essential vitamine. - -None of the vitamines has been isolated in a pure state. The nearest -approach to this desired end has been the work of Funk, who obtained the -water-soluble vitamine in a state of such concentration that about 3 mg. -sufficed to cure a pigeon of polyneuritis. In considering the attributes -of the antiscorbutic vitamine, it must be borne in mind that this factor -is referred to as it exists in various foods; for example, in orange -juice or in cabbage, and furthermore, that the method of ascertaining -its presence or concentration is limited to the crude biological test of -animal feeding. - -The antiscorbutic factor is distinguished by being the most sensitive of -the three vitamines, the most unstable, the least resistant to physical -or chemical processes. It may be regarded as one of the most delicate -indicators of the biological integrity of foodstuffs; however, as Falk -and his co-workers have shown, the enzyme property of living matter is -still more readily destroyed. The antiscorbutic vitamine is soluble in -water, and therefore is termed by some the "water-soluble C" factor. It -is also soluble in alcohol, as shown by the experiments of Hess and -Unger and of Harden and Zilva, and the therapeutic tests on infants of -Freise and of Freudenberg.[23] It possesses, therefore, the solubility -of the water-soluble vitamine. Some have suggested that it may be -derived from this vitamine, others that instead of one there may be a -series of antiscorbutic factors--suggestions based on pure hypothesis. -Holst and Froelich showed that this vitamine passes, without appreciable -loss, through dialyzing parchment, and Harden and Zilva (2) that it can -pass through a porcelain filter. The latter, using the method of -Seidell, demonstrated that this vitamine is not adsorbed by fine -precipitates such as fuller's earth, differing in this respect from the -water-soluble vitamine; and that in a mixture of equal volumes of -autolyzed yeast and orange juice, the antiscorbutic vitamine remained -unaffected, whereas the water-soluble A was entirely removed. - -[23] Freise cured a case of infantile scurvy by giving about 2 c.c. of -an extract obtained from turnips by means of absolute alcohol. Seven -weeks were necessary to cause a disappearance of symptoms. Freudenberg -employed an extract of carrots, prepared with 96 per cent. alcohol, and -effected a quicker cure. - -One of the most distinctive characteristics of the antiscorbutic factor -is its _sensitiveness to even moderately high degrees of heat_. In this -respect it differs markedly from the water-soluble or so-called -"antineuritic vitamine" which withstands exposure to high temperature. -The reaction of the antiscorbutic vitamine in this regard is not a -simple one, and cannot be expressed by a mere statement of the degree of -heat and the length of exposure. Numerous other factors, especially the -reaction of the medium, but also the physical environment, must be taken -into consideration--for example, cabbage is more resistant to the action -of heat than its juice. An understanding of the relation of -antiscorbutics to heat may perhaps best be obtained by considering the -subject in connection with some definite foodstuffs. The most exhaustive -study from a quantitative standpoint is that of Delf. She showed that -when cabbage is subjected for an hour to a temperature of 80° to 100° -C., 90 per cent. of its antiscorbutic vitamine is lost, and that 80 per -cent. is lost when a temperature of 90° to 100° is maintained for twenty -minutes, or a temperature of 60° for a period of sixty minutes. This -experiment shows that the destructive influence of heat is enhanced to a -comparatively slight degree by a rise of temperature, only about -threefold when it is raised from 60° C. to the boiling point. This -result points to a temperature coefficient of about 1.5 to 10° C. of -temperature. It is suggested by Delf that this low coefficient of -destruction is opposed to the enzyme or protein-like theory of the -nature of the vitamine, and suggests a simpler constitution. On the -other hand, we must bear in mind that the proteins which have been used -in experiments and found to possess a high coefficient of heat, have -been tested in the pure state, whereas the vitamine of the cabbage is -bound up in the cell. - -Experiments with this vitamine as found in milk accord with the above -investigation, demonstrating that intensity of heat is not as -destructive as prolonged heating. This agrees with the clinical -experience that milk which has been boiled for a few minutes does not -induce scurvy as readily as pasteurized milk which has been heated for -45 minutes to 140° or 165° F. (Hess and Fish). - -As demonstrated by tests with orange and with lemon juice, the -antiscorbutic vitamine is greatly protected from the destructive effect -of heat when it is associated with an acid. This was shown first by -Holst and Froelich and has been confirmed by numerous observers. An -excellent example of marked thermostability conferred on a food by its -acid reaction is furnished by the tomato, which is strongly -antiscorbutic even after it has been subjected to the canning process. -Conversely, Harden and Zilva have shown that the vitamine is destroyed -by alkali even when dilute (one-fiftieth normal sodium hydrate) and kept -in contact at room temperature; this alteration does not take place at -once, but in the course of several hours. - -It is true that the antiscorbutic factor is peculiarly sensitive to -_drying_, but there are exceptions to this rule, so that it is incorrect -to state, as does the British Report of the Medical Research Committee, -that "it may be regarded as an axiom that dry or dried foodstuffs will -not prevent scurvy." We have shown that fresh milk dried by the -Just-Hatmaker process may retain by far the greater moiety of its -virtue. In this regard rapidity of desiccation and subsequent protection -from oxidative processes are important factors. The general rule holds -true, however, that this vitamine, in contradistinction to the -"water-soluble" vitamine, is readily damaged and destroyed by drying. - -This vitamine is peculiarly sensitive to _aging_, especially when it is -present in an alkaline or neutral medium; but even in an acid medium its -potency soon diminishes. Harden and Zilva found this to be the case with -lemon juice stored for a fortnight in the cold room, and our experience -has been similar in regard to orange juice kept in the refrigerator -under a layer of liquid petrolatum. In milk the antiscorbutic factor -diminishes with age, especially following pasteurization, in the course -of which most of the acid-forming bacteria have been destroyed. Aging -has the least effect when the food with which the vitamine is associated -has been dried. This is true not only of lemon and of orange juice as -demonstrated experimentally and clinically, but even of milk, which even -after it has been dried and stored for months, may still possess marked -curative value.[24] - -[24] Reference is made to a milk dried by the Just-Hatmaker process, -containing about 3 per cent. of moisture. The clinical data on which -this conclusion is based are given in the previous chapter. - -Experiments by Harden and Zilva showed that exposure of lemon juice to -_ultra-violet rays_ for eight hours does not influence its antiscorbutic -activity, that exposure of autolyzed yeast for the same length of time -likewise does not impair its "antineuritic" potency, but that under -identical conditions the fat-soluble factor in butter becomes -inactivated. Similar tests carried out by the author with orange juice -led to the same result. It thus appears that one of the vitamines--not -the most unstable--manifests a peculiar sensitiveness to a certain form -of physical or chemical action. - -In view of the fact that _shaking_ partly destroys pepsin and rennin, as -shown by Shaklee and Meltzer, it would be of interest to ascertain -whether this process brings about any impairment of the antiscorbutic -vitamine. Particular interest is attached to this question because it is -generally recognized that milk loses some of its potency in the course -of handling--whatever may be comprised by this term. In experiments on -the fat-soluble vitamine Steenbock and his co-workers found that -"somewhere in the course of the manipulation to which the butter fat had -been subjected, factors had been introduced which were responsible for a -vitamine destruction." - -Before discussing the question of the manner in which the antiscorbutic -vitamine functionates, it may be well to state briefly the type of the -disturbance which its deficiency occasions. The chief manifestation is -damage to the integrity of the endothelium of the vessels, resulting in -hemorrhage--whether from diapedesis or from rhexis or both of these -conditions, the microscope does not inform us. Nor can it be stated -positively that the endothelium has not been injured by a secondary -toxic or bacterial factor. However this may be, the end result of the -deficiency is endothelial damage, a pathologic condition which may be -demonstrated clinically in scurvy by the "capillary resistance test" -(chapter VII). The other marked functional alteration in scurvy is -increased susceptibility to infection; but how a vitamine deficiency -induces this vulnerability cannot be explained. Clinical tests show that -the blood contains sufficient antitoxin (diphtheria) to afford -protection. Harden and Zilva found that "guinea-pigs fed on an -unrestricted mixed diet, on a quantitatively restricted mixed diet, and -a scorbutic diet showed no differentiation in amboceptor and agglutinin -titres, and in the complement activity of the blood." If this is to be -interpreted as indicating that the protective substances of the body -undergo but little alteration, we must consider whether susceptibility -to infection, as well as tendency to hemorrhage, is not due largely to -alteration in the cement substance of the endothelial and epithelial -membranes. - -=The Mode of Action of the Vitamine.=--One of the most interesting as -well as puzzling questions in regard to the antiscorbutic vitamine -concerns the manner in which it prevents or cures scurvy. It is a -subject which at present is in a state of flux, hardly having emerged -from the realm of hypothesis, so that detailed consideration will profit -little. At first the _modus operandi_ was explained and accepted as -enzyme action, but it was soon evident, in view of the thermostability -of the vitamine, that it could not be classed as a ferment or enzyme in -the generally-accepted sense of this term. In general, it may be stated -that there are two main views: one that the vitamine acts directly, and -the other that it acts indirectly through the function of the endocrine -glands. _Direct action_, furthermore, may be accomplished in at least -one of three ways. The vitamine may (1) serve as a source of nutriment -for the tissues, (2) exert an antitoxic effect on toxic products, or (3) -function as a catalyzer. The first interpretation is evidently the -simplest and conforms to the long-established knowledge of caloric food -factors. That such small amounts as 2 c.c. of orange juice daily should -suffice to protect an animal from nutritional disaster runs counter, -however, to former conceptions of food nutrition. Further than this -there is little against this viewpoint. In its favor is the fact that, -up to a certain point, antiscorbutics act in direct ratio to the amount -given; for example, 2 c.c. of canned tomato juice is insufficient to -prevent scurvy in guinea-pigs, 3 c.c. will protect some but not all of -a series, whereas when the amount is increased to 4 c.c. daily all -animals will be saved. As we are considering new food factors it is -manifestly unwise to judge them by old standards, and to decide offhand -that they cannot possess such a high degree of nutritive power. This -question must be regarded as still open. - -The antitoxic theory suffers from the fact that the toxic origin of -scurvy cannot be established. Before this is possible, it is clear that -it will be difficult to bring forward convincing evidence of a -neutralizing substance. Against this theory is the fact that elimination -therapy is of no avail in the treatment of infantile scurvy. Hess and -Unger (1919) failed to alleviate the symptoms by means of catharsis, -diuresis, sweating and repeated intravenous injections of normal salt -solution. In its favor it may be advanced, in a general way, that the -vitamine, in many characteristics, resembles an antitoxin--in its -extreme lability, its destruction by heat, aging and alkalies. On the -other hand, antitoxins also are readily destroyed by acid which, as has -been shown, exerts a protective influence on the antiscorbutic factor. -The rapidity of action of the vitamines, one of the most impressive -phenomena, calls to mind the neutralizing action of an antitoxin, and -probably has given rise to the analogy. Williams suggests that the -vitamines have "a general, non-specific, antitoxic or eliminative -action" on toxic substances resulting from the metabolic decomposition -of food. - -The theory has been advanced that the action of the vitamines is -catalytic. Although this viewpoint has been taken regarding the -water-soluble rather than the antiscorbutic vitamine, it will be well to -review briefly the work on which it is based. Among the first to suggest -this hypothesis were Vedder and Clark, who noted a relationship between -the amount of vitamine required by fowls and their carbohydrate intake. -Funk in 1913 made a similar observation in regard to beriberi, and in -the following year, with von Schoenborn, showed that a vitamine-free -diet led to hyperglycæmia, with diminished amount of hepatic glycogen, -and that the addition of water-soluble vitamine diminished the -hyperglycæmia and increased the liver glycogen. The work of Burge and -his co-workers on the catalase content of tissue led to a similar -conclusion. Their results may be summarized by the statement that the -oxidative processes are hampered and fail to balance the autolytic -changes, and, furthermore, that a relationship exists between the -catalase activity, acidosis and normal oxidative processes. This theory -would presuppose that scurvy is due to the formation of toxins which are -normally in process of continual destruction in the body. According to -some, these catalyzed toxic substances are metabolic in character, -originating from incompletely oxidized food; according to another -interpretation, they are the product of autolyzed tissue cells (tissue -toxins). The difficulty with this explanation is that scurvy cannot be -prevented or cured by a diet containing food of high catalytic power. -For example, wheat embryos which, according to recent investigations of -Crocker and Harrington, have a high catalytic activity, were found of no -therapeutic value in relation to infantile scurvy (Hess, 3). - -This problem has been approached from quite a different angle. As is -well known, certain bacteria require serum, blood, milk, etc., in order -to grow satisfactorily on artificial culture media. It has been -established recently, primarily by the work of Lloyd, that this -peculiarity in the cultivation of microörganisms is due largely to -their requirement of vitamine. She found a relationship of the inverse -order between the amount of amino acid present in the culture medium and -the amount of vitamine required to stimulate the growth of strains of -meningococcus. Reasoning from this experience, she suggests that the -action of the accessory growth factors is to increase the reaction -velocity of the proteolytic metabolism. Here we find the vitamines once -more regarded as catalyzers. This author, however, associates their -activity with proteolytic rather than with carbohydrate metabolism. -Interesting and suggestive work of similar nature has been carried out -in relation to the growth of protozoa and of yeasts (Eddy). -Investigations of this kind, dealing with unicellular organisms -propagated on a simple food, have the advantage of greatly simplifying -the problem. - -The recent work of Dutcher falls under this caption, differing merely in -the fact that he attributes to the vitamines an _indirect action_. He -has demonstrated that the tissues of polyneuritic birds show a decrease -in catalase activity to a point 56 per cent. below normal, and that this -activity is largely restored when the birds are cured with vitamine. -According to this writer the vitamine functions as a metabolic -stimulant, and its lack results in a depression of the body oxidations -with an accompanying formation of toxic metabolic products, injurious to -the nervous system. The action is regarded as coming about in an -indirect manner, being accomplished through the hormone action of the -vitamines on one or more glands of internal secretion. - -The _endocrine hypothesis_, suggested by Funk in his monograph, is not -without some corroborative evidence. In testing the pharmacologic action -of the water-soluble vitamine, Uhlmann found that it stimulated the -various glands of the digestive tract, in this respect acting like -pilocarpine. Some years ago Albert expressed the opinion that the action -of this vitamine was "vagotropic" like atropine, and recently Dutcher -has reported definite relief and cessation of polyneuritic symptoms by -means of pilocarpine (0.5 mg. subcutaneously). He claims equally good -results from thyroxin, the hormone of the thyroid gland, from desiccated -thyroid and from tethelin (pituitary). Voegtlin and Myers conclude, as -the result of experiments with brewers' yeast, that the chemical and -physical properties of secretin and vitamine are identical. - -The early work of Funk and Douglas, which showed that various _glands of -internal secretion_ diminish in size and undergo degenerative changes -when the diet is vitamine-free, the newer work of McCarrison and of -Dutcher to the same effect, clearly point to an intimate relationship -between some of the endocrine glands and the vitamines. As regards -scurvy, the only work is that of Rondoni, McCarrison and of LaMer and -Campbell on the adrenal glands, which were found by all to be enlarged -in guinea-pigs suffering from this disorder. These investigations must -be regarded as tentative rather than conclusive until confirmed by -similar necropsy reports in man. In this connection it should be noted -that thyroid, parathyroid or suprarenal extract is of no avail in the -treatment of scurvy. This failure may, however, be explained by the fact -that the normal balance of glandular activity was not established. We -must bear in mind, however, that although the vitamines may influence -the secretion of the glands of internal secretion, this explanation does -not satisfactorily account for the symptoms of the "deficiency -diseases." These disorders do not in the slightest respect resemble the -clinical pictures which we are accustomed to associate with a lack of -activity of the glands of internal secretion. If the polyneuritis of -beriberi and the hemorrhages of scurvy are attributable to a diminished -secretion of the endocrine glands, then it will be necessary to revise -present conceptions of their physiologic functions. - -=The Fate of the Vitamine in the Body.=--One of the most important -questions in relation to the antiscorbutic vitamine, quite apart from -its chemical nature, physiologic function, and its source, is its fate -in the human body after it has reached the alimentary canal or been -carried to the tissues. It can be readily appreciated that our knowledge -of this aspect is very meagre. We shall endeavor, however, to detail -what little is known of this subject, conscious of the fact that -investigations of the next few years may contradict our present -viewpoints. - -Most of the constituents necessary for the construction of tissue or for -carrying on its functions can be synthesized by the animal body from the -basal foodstuffs. It has been ascertained within the past decade that -certain constituents--for example, some amino-acids of the protein -molecule--are building-stones which cannot be primarily elaborated by -the cells, but must be supplied by the food. At present the -vitamines--including the antiscorbutic vitamine--are included in this -new and essential group of substances which the human organism cannot -manufacture. Animal experiments seem to bear out this conception of the -vitamine whether we regard them as dynamic or as indispensable tissue -elements in the structural sense. - -A closely-related but less fundamental question is that of _the ability -of man to store vitamines_--whether the tissues can hoard an excess of -these factors, or whether, in this respect, we are carrying on a -precarious hand-to-mouth existence in regard to cellular nutrition. It -is of course clear that at all times the various organs and tissues must -contain a certain amount of the vitamines. This has been shown for the -water-soluble or "antineuritic vitamine" by the fact that even the -organs of birds which have died of polyneuritis contain an appreciable -quantity of the specific vitamine, although an insufficiency of this -very factor has led to their death. That such is the case is -demonstrated for the antiscorbutic vitamine by the fact that muscle -tissue contains sufficient antiscorbutic to protect individuals -subsisting largely on a diet of which raw meat constitutes the sole -antiscorbutic agent (Stefánsson). It is very probable that some organs -contain more of the vitamines than others; this has been proved for the -"antineuritic" factor, and seems to hold good for the antiscorbutic--the -liver being particularly rich. No quantitative study has been carried -out from this point of view regarding the antiscorbutic vitamine, and it -would be well worth our while to ascertain the relative antiscorbutic -potency of the various organs of the body. Some time ago we undertook -experiments to determine whether the guinea-pig is capable of storing -this vitamine. One series of guinea-pigs was fed daily 6 c.c. of orange -juice for a period of two weeks, whereas another series, of about the -same weight, was given, in addition to the basal ration, only 3 c.c. -per capita (the minimal protective dose). After this preliminary period -both series were placed on a diet containing practically no -antiscorbutic. Both groups came down with scurvy after about the same -interval, leading to the conclusion that there could have been little if -any storing of the excess vitamine by those which received twice the -"minimal protective dose." The experiments of Harden and Zilva, who fed -a concentrated lemon juice, showed that this potent agent also was -unable to provide against a subsequent period of antiscorbutic -deficiency. It should be realized that the results of these tests on -guinea-pigs cannot be applied to man without tests on other species. - -It might be thought that _the blood_--the purveyor of the vitamines to -the tissues--would be particularly rich in these essential factors. -Such, however, was not our experience in respect to the antiscorbutic -vitamine. The blood possibly varies greatly in this respect according to -the diet of the individual, or even according to the interval elapsing -after the ingestion of antiscorbutic food. Our opinion is based on the -surprisingly poor therapeutic effect of blood transfusion in the -treatment of scurvy. To illustrate: An infant weighing about fifteen -pounds received six intravenous injections of citrated blood--one of 200 -c.c., given by the direct method, and a month later five smaller -transfusions with citrated blood, which aggregated 205 c.c.[25] In spite -of this addition of blood, the hemorrhage and congestion of the gums did -not disappear, nor the general condition improve, as would have happened -had 50 or 75 c.c. of orange juice been given by mouth. It seems probable -that small quantities of vitamine are being transmitted at all times by -the blood and supplied to the cells, but that its normal content of this -factor is not great. The antiscorbutic potency of blood may perhaps be -compared to that of milk. Animal investigation may show that various -vessels--for example, those supplying or draining certain glandular -organs--differ in the antiscorbutic quality of the blood which they -carry. It is evident, therefore, that many transitory factors may -influence the vitamine content of the blood, and that--as in the case of -milk and fruits and vegetables--we are not dealing with a constant and -unvarying agent. - -[25] The dates and quantities of the transfusions were as follows: March -26th, 200 c.c.; April 27th, 30 c.c.; April 28th, 35 c.c.; April 29th, 30 -c.c.; May 2nd, 75 c.c.; May 3rd, 35 c.c. - -Nothing whatsoever is known concerning the _excretion_ of the -antiscorbutic vitamine. No attempts have been made to recover it from -the urine, or to ascertain if, when large amounts are ingested, the -excess is thrown off by the body. This suggests the question--a -corollary of that raised in connection with the vitamine content of the -blood--whether it is immaterial if the vitamine is taken frequently in -small amounts, or is provided only occasionally and at longer intervals -in larger amounts. Is it of no moment whether the infant receive its -quota of antiscorbutic every few hours through the medium of the breast -milk, or only once a day in the form of orange juice or tomato? If we -turn to studies on the other vitamines for enlightenment as to the -possibility of excretion, we find that Muckenfuss recovered the -water-soluble factor from ox bile and from human urine.[26] In this -article he proposes the interesting question of a possible variation in -the vitamine output under pathological conditions, which may be -responsible for the development of functional disturbances in children. - -[26] This investigation was carried out by means of activating fuller's -earth with these fluids. This method is inapplicable to the -antiscorbutic vitamine, which is not adsorbed by this material. An -attempt to feed concentrated human urine to guinea-pigs resulted in -their death. - -It would be of interest to know the _fate of the antiscorbutic vitamine -in the gastro-intestinal tract_. How is it affected by a lack of the -acid gastric juice, or by the alkaline intestinal secretions, or by the -bacteria in the lumen of the gut? From which part of the intestine is it -largely absorbed? May an appreciable amount undergo destruction before -this is accomplished? None of these questions can be answered -satisfactorily in the present state of our knowledge, but they suggest -that the mere fact that an adequate quota of antiscorbutic vitamine is -provided in the food does not necessarily insure an adequate supply for -the tissues. If in addition to the question of intake we must take into -account that the vitamines may suffer various vicissitudes, it may come -to pass that pathological conditions at times destroy or render them -partially inactive. In this way we may account for irregularities in the -clinical course of disorders associated with vitamine deficiency. - -Of prime importance, however, is the effect of the vitamines _on the -glands of the alimentary tract and on the digestive processes_. A -diminution of gastric juice, or in some instances a total absence, has -been observed in adult scurvy, and noted by us in two cases of infantile -scurvy. As mentioned elsewhere, some consider the function of the -water-soluble vitamine analogous to that of secretin. In applying this -hypothesis to scurvy it must be borne in mind that the sequence may be -reversed, that the lack of vitamine may not lead to the gastric achylia, -but that the achylia may come about secondarily as the result of the -malnutrition. - -We have referred to _"irregularities" in the course of the "deficiency -diseases."_ A careful perusal of the literature leaves one with the -impression that the most experienced observers are not entirely -satisfied with the exclusively etiologic relationship of the vitamine to -its respective nutritional disorder. In regard to scurvy, more -particularly, there are numerous scattered reports where the disorder -did not yield to antiscorbutic foods as might have been expected, or -where, on the other hand, it suddenly and inexplicably retrogressed, -although there had been no alteration in the dietary.[27] These -instances are not common, but they occur from time to time, and their -occurrence must be accounted for. In relation to beriberi and avian -polyneuritis improvement of this kind has frequently been explained on -the theory of a sudden mobilization of vitamines from the tissues. There -is, however, no data on which to base such explanations, and it may be -that a lack of parallelism between vitamine intake and the clinical -course may be due at times to processes taking place in the alimentary -tract. - -[27] Neumann, for example, writes that he has seen at least four -children whose condition was not improved, although in addition to the -milk, they took asparagus, spinach, and other vegetables or apple sauce. -Some years ago we had a similar experience. It has likewise happened -that infantile scurvy did not recur, although the diet was the same as -that which originally led to the disorder. - -The fat-soluble vitamine has been termed by some the growth vitamine. -All the vitamines, however, are closely associated with the function of -growth, which their deficiency tends to inhibit. In the chapter on -symptomatology, it will be pointed out that infants suffering from -scurvy fail to grow normally both in length and in weight. To a certain -extent this may be due to a loss of appetite, which is one of the -characteristic phenomena accompanying the scorbutic condition. On the -other hand, this anorexia may be secondary and not primary to the -impairment of the growth impulse, which may lead to a dysfunction of -various body processes. - -It is of little value to look ahead and try to foresee what the next -decade will bring forth in regard to the nature of the vitamines. -Investigation has broadened remarkably during the past few years and now -embraces the chemical field--chemical and adsorption methods, the large -realm of biology, including studies in physiology and pharmacology; and -recently pathology has once more been called upon to aid in the solution -of the problem. Probably additional vitamines will be discovered. From -time to time it has been suggested that a specific growth vitamine -exists quite distinct from the three which are recognized, and recently -Mellanby has suggested still another food factor--a specific "rachitic -vitamine." When we reflect that the characteristic functions of the -various organs--the kidneys, liver, etc.--must depend on essential -differences in chemical structure, the complexity of the entire problem -of unidentified factors becomes evident.[28] - -[28] For recent and comprehensive reviews of the vitamines the reader is -referred to papers by A. B. Macallum (Trans. Royal Canadian Institute, -Toronto, 1919) and by W. H. Eddy (Abstracts of Bacteriol. 1919, Vol. -iii, 313.) - - - - -CHAPTER IV - -PATHOLOGY - - -Physicians have had a general knowledge of the pathology of scurvy for a -great many years. Lind, in his "Treatise on the Scurvy," published in -1772, included a chapter on "dissections" and a postscript on -"Appearances on Dissections of Scorbutic Bodies," based on a large, -although indefinite, number of postmortem examinations. In the century -which followed, there are to be found many reports of scurvy, especially -in connection with the frequent wars, but it is surprising how little -detailed pathologic information they furnish. Barlow's publication in -1883, establishing the identity of the scurvy of adults and of infants, -must be regarded as the modern milestone in the study of the pathology -of this disorder. This work did not contribute richly to the data of the -subject, or suggest novel interpretations, but directed attention to a -new source of material--the increasing number of cases of infantile -scurvy--at a critical moment when the opportunity for the study of -scurvy in the adult was rapidly becoming less. At the time of Barlow's -exposition of the true nature of "acute rickets," scientific medicine -was concentrating its interest on pathology. Tissues were being -carefully studied by means of the microscope, and scurvy was subjected -to this new method of investigation. As a result of intensive -application of this technic, a lesion of the bones was identified and -established as characteristic of scurvy. Study was focussed so -exclusively on the bones, that for many years, indeed until very -recently, the other organs of the body were neglected. This is true of -the gross as well as of the microscopic anatomy. Protocol after protocol -gives a hasty account of the appearance of the various organs, merely as -a routine introduction to a careful and often minute study of the bones -(Table 2). As the result of this myopic vision, enlargement of the -heart, for example, which should have been noted many years ago, was, -until recently, unobserved--indeed, the heart is but occasionally -mentioned in the protocols. - - TABLE 2 - NECROPSY REPORTS OF SCURVY - ====================================================================== - Number| | | | - of | Author |Date| Gross | Microscopic - Cases | | | | - ------+------------------+----+---------------+----------------------- - ADULTS - Many |Lind |1772|Brief summaries| - 51 |von Himmelstein |1843|Brief summaries| - 8 |Hayem |1871|Résumé |Brief résumé. - 7 |Lasèque & Legroux |1871|Fairly detailed| - 7 |Charpentier |1871|Brief summaries| - 13 |Sato & Nambu |1908|Fairly detailed|Fairly detailed. - 2 |Urizio |1917|Brief summaries|Brief summaries. - 1 |Feigenbaum |1917|Brief summary |Brief summary. - 23 |Aschoff & Koch |1919|Very complete |Very complete. - - INFANTS AND CHILDREN - 1 |Smith |1876|Brief report | - 3 |Barlow |1883|Fairly detailed|Bones, brief report. - 1 |MacKenzie |1883|Brief summary | - 1 |Northrup |1892|Brief report | - 1 |Cassel |1893|Brief report | - 2 |Sutherland |1894|Fairly detailed|Brain and liver, 1 case - 1 |Reinert |1895|Very complete |Fairly complete. - 1 |Hirschsprung |1896|Summary | - 3 |Meyer |1896|Fairly detailed| - 1 |Baginsky |1897|Fairly detailed|Brief, bones more in - | | | | detail. - 1 |Naegeli |1897|Fairly detailed|Bones only. - 1 |Manz |1899|Summary | - 5 |Schoedel & Nauwerk|1900|Very complete |Very complete. - 1 |Jacobsthal |1900|Very complete |Very complete. - 1 |Stoos |1903|Fairly complete|Bones only. - 1 |Looser |1905|Summary | - 1 |Hoffmann |1905|Summary |Bones only. - 1 |Stoeltzner |1906|Bone only |Bone only. - 22 |Fraenkel |1908|Résumé |Bones only. - 1 |Nobécourt et al |1913|Brief report |Bone only. - 3 |Ingier |1913|Brief report |Bones, very complete. - 1 |Bahrdt & Edelstein|1913|Complete |Bones, brief report. - 31 |Erdheim |1918|Brief summaries|Brief résumé. - 1 |Epstein |1918|Very detailed | - ---------------------------------------------------------------------- - -A new era in the pathology of scurvy was inaugurated by the availability -of experimental scurvy and also by the stimulation occasioned by the -recent conception of vitamines and the so-called deficiency diseases. In -endeavoring to elucidate this fascinating problem, it has gradually been -realized that pathology may be of service--for example, in relation to -the involvement of the endocrine glands. Accordingly, studies of the -minute pathology of the various organs have been undertaken in many -laboratories throughout the world (Italy, India, England, Germany and -the United States). An additional stimulus to investigation in pathology -has been furnished by the recent war, which, as shown elsewhere, led to -a great increase in scurvy among both the military and civilian -population. The excellent report of Aschoff and Koch from Roumania was -made possible by this catastrophe, and will no doubt soon be followed by -others of similar character. - -=Gross Pathology.--General Appearance.=--The skin usually is pale, -livid, and dotted with numerous petechiæ. These vary in size from the -tiniest pin-points, barely recognizable to the naked eye, to ecchymoses -of moderately large size. The most frequent site is the lower -extremities. The trunk is always less affected, hemorrhages tending to -occur along the mid-line and especially around the umbilicus. There may -be also larger superficial hemorrhages, showing great differences in -color, from the redder tone of the more recent, to the blues, browns and -greens of the older lesions. Bleeding from the nose and mouth is not -uncommon in fatal scurvy, and occasionally exophthalmos is present, -usually unilateral, and due to subperiosteal hemorrhage of the orbital -plate of the frontal bone. Rigor mortis is generally slight, and, -according to Lind and to von Opitz, decomposition takes place rapidly. - -There may be great emaciation, especially where secondary infection has -supervened. General wasting occurs, however, in uncomplicated scurvy due -to starvation--the result of lack of appetite or a deficiency of the -general food supply. Children, especially infants, are undersized, as -illustrated in treating of the symptomatology, and their bones may be -decidedly smaller than normal. Generally there is some edema about -the ankles, and in children a somewhat characteristic puffiness about -the eyes. General anasarca also occurs, in some cases associated with -renal involvement. Peculiar boggy, "tumor-like" masses of localized -edema may be present, which were considered by the earlier writers -(Lind) to be one of the typical lesions of this condition. - -=Hemorrhages.=--Hemorrhage is such a striking manifestation that it is -not surprising to find it was regarded by the older writers as the -pathognomonic sign of scurvy. The bleeding may take place into almost -any organ, and vary from small petechiæ to very extensive -extravasations. The hair follicles and sweat glands are particularly -susceptible, as Lasèque and Legroux noticed in cases occurring in the -French prisons. Aschoff and Koch, during the recent war, noted the same -peculiarity of involvement, calling attention also to the fact that -previous skin diseases such as keratosis or seborrhea seemed to -predispose to this localization. - -Trauma plays a very important rôle in determining the location of the -deeper as well as of the superficial hemorrhages. In adults, especially -in soldiers, in whom the greater number of cases have been recorded, the -lower extremity is the commonest site, between the knee and ankle, the -area most exposed to blows as well as acted upon by static congestion. -In infants, the inner aspect of the thighs is a frequent site due to the -trauma of the diaper. - -The most characteristic hemorrhage, the subperiosteal, will be fully -discussed when considering the bone lesions. The deeper hemorrhages may -be very extensive. They tend to follow the connective-tissue strata, and -in the muscles are usually limited by the muscle sheaths. The blood -surrounds the muscle fibres, which appear quite intact. The neighboring -blood-vessels are congested and may contain thrombi, both venous and -arterial. Such thrombi are found also in areas where extravasation has -not taken place, and conversely, hemorrhages occur where no thrombi are -demonstrable, so that a mutual causal relationship cannot be proved. -Further evidence in regard to the mechanism of these extravasations is -presented in the discussion of the minute anatomy. Brownish pigment, -undoubtedly derived from the blood, is frequently found in the -neighborhood of the hemorrhagic areas. New connective tissue also grows -in these areas, so that in healing cases a marked formation of scar -tissue will be found. Bizarre forms of hemorrhage at times have given -rise to confusion in diagnosis; hemorrhage involving the right lower -abdominal quadrant may simulate appendicitis; when occurring in the -region of the transverse colon it has been mistaken for an epigastric -new-growth. - -Certain parts of the body seem less predisposed to hemorrhage. The -central nervous system is often spared, notwithstanding extensive -bleeding elsewhere, the meninges being somewhat more frequently -involved. Hemorrhage of the lungs is also less common than might be -expected, and it is probably true as Lasèque and Legroux suggested, that -previous pulmonary disease, particularly tuberculosis, is an important -predisposing factor. - -=Anasarca.=--This comprises the second characteristic lesion found in -scurvy at necropsy and was referred to in the earliest records of the -disease. In the account of his dissections Lind writes: "The breast, -belly and several other parts of the body were filled with this water -or serum," mentioning also the pericardium and ventricles of the brain. -He also noted that all the tissues seemed to contain an excessive amount -of fluid, a condition which may be so striking that the muscles appear -bathed in serum. In one of his first cases with postmortem verification, -Barlow described this appearance as follows: "The muscular walls of the -thorax were pale yellow and watery, as though they had been bathed in -serum." In many cases this edema is most marked in the neighborhood of -the hemorrhages, for example, in the muscles of the thigh when -subperiosteal hemorrhage has taken place; less frequently it is produced -by venous thrombosis. - -Any or all of the serous cavities may be involved in this hydrops, the -order of frequency being pericardium, pleuræ, peritoneum, and joint -surfaces, especially the knee. The fluid is clear and straw-colored, or, -in the event of secondary infection, becomes cloudy and -fibrino-purulent. Later the exudate may become organized so that the -entire cavity is filled with a solid mass, which binds the organs -together and obliterates the cavity. The exudate may be blood-stained or -apparently consist entirely of clotted blood. - -=Heart.=--In the protocols of most necropsies, the heart is passed over -with scant mention. For example, Lind's only statement in this regard is -that "all those who died suddenly, without any visible cause of their -death, had the auricles of their heart as big as one's fist, and full of -coagulated blood." Barlow accords it no attention, nor do most of the -writers who immediately followed him. The first careful description of -the heart is to be found in the excellent work of Schoedel and Nauwerk, -which contains the following record in regard to three of the five -necropsies on infantile scurvy: (1) Pericardial fluid somewhat -increased, both ventricles moderately dilated, the right somewhat -hypertrophic. (2) The heart showed a hypertrophy of the right and left -ventricles, as well as dilatation of the right ventricle. (3) The right -ventricle is dilated and slightly hypertrophied, the muscles pale and -tough. There is no word of comment relative to these cardiac changes, -which evidently were considered fortuitous. The same observation holds -true in regard to a necropsy on an eight-year-old child reported by -Ingier, which showed a moderate hypertrophy of the left ventricle. We -look in vain, likewise, for information on the subject in the work on -guinea-pig scurvy by Holst and Froelich, and that on scurvy in the -monkey by Hart and Lessing. The first linking of cardiac enlargement -with scurvy is found in a paper by Darling, who described "right-sided -hypertrophy and degenerative changes in the vagus and all its branches." -Hess described and demonstrated by means of roentgenograms the enlarged -heart in infantile scurvy. Recently Erdheim, in an article entitled "Das -Barlowherz," reported the occurrence of enlargement of the heart, -especially of the right ventricle, in 21 out of 31 necropsies of -infantile scurvy, and concluded that a direct ratio exists between the -degree of enlargement and the intensity of the disorder. These reports -gain added interest in view of the enlargement of the right heart so -frequently encountered in beriberi, and described by Andrews in infants -dying of this condition. In addition to the definite statement of -Darling regarding adults, mention may be made of the observation of -Aschoff and Koch, that in two cases of uncomplicated scurvy there were -fatty degeneration and dilatation of the heart. Fatty degeneration of -the muscle is frequent, brown atrophy exceptional. Sato and Nambu also -found hyperæmia and atrophy with increase of connective tissue between -the muscle fibres. - -The pericardial cavity contains almost invariably an increased quantity -of fluid, which may be so great as to impede the heart's action. -Adhesive pericarditis has been described. The cardiac valves are normal, -unless previously damaged. - -=Lungs.=--The lungs are almost always congested, but apart from this are -remarkably free from abnormality. Smaller or larger hemorrhages are -described occasionally, which are usually considered truly scorbutic; -Andrews, however, found similar lesions in beriberi. In the necropsy of -Stephen Mackenzie's case, described by Barlow, these small hemorrhages -are stated to have resembled small red tubercles scattered throughout -the lung. There may be pulmonary infarcts. Edema of the lungs is not -uncommon, as we should expect, especially as a terminal condition. -Pneumonia, lobular or lobar, is one of the most frequent complications -and causes of death. Active tuberculosis is a not uncommon secondary -manifestation. - -Subserous hemorrhages are almost the rule; if infection supervenes, the -pleuræ become thickened and covered with an exudate of pus and fibrin. - -=Alimentary Tract.=--The lesions of the gums so well recognized -clinically are fully discussed under symptomatology. The remarkable fact -that these hemorrhages do not appear in edentulous gums has been the -centre of the controversy as to the identity of adult scurvy and -Barlow's disease. This same lack of involvement is noted in adults whose -teeth have been extracted. Where teeth are present, the gums are swollen -and edematous, often of a livid, reddish color; less frequently, pale -and pouting. Hemorrhage is seen at the edge of the gum adjacent to the -teeth. In advanced cases the gums are enormously swollen, fungous, -ulcerated and covered with a foul, greenish, necrotic mass, which may -extend widely over the buccal mucous membrane. The teeth become loosened -and fall out. Secondary infection undoubtedly plays the chief rôle in -producing this condition, for the most severe forms are found only where -caries and pyorrhoea preëxisted. This seat of infection may serve as the -source of dissemination throughout the body, giving rise to many of the -lesions found at postmortem, especially in the lower part of the -intestinal tract. - -The _stomach_ shows no characteristic changes. Congestion of the mucosa -is frequent, at times associated with small superficial erosions; the -latter gain added interest in view of their occurrence in guinea-pig -scurvy. Hemorrhages occur here also and may involve any of the mural -coats. - -The _duodenum_ shows often intense congestion. This occurs with -sufficient frequency to demand attention, especially as a similar -condition has been described in other disorders grouped with scurvy. -Willcox and others found congestion of the duodenum and of the lower -intestine in beriberi, and Andrews described not only congestion but -even minute hemorrhages. Small duodenal ulcers are by no means -infrequent both in human and in guinea-pig scurvy (Holst and Froelich). -The presence of such marked congestion surrounding the papilla of Vater -would lead us to expect the occurrence of catarrhal jaundice associated -with scurvy. But, on the contrary, icterus has rarely been noted in -scurvy. Urizio has described jaundice in this connection, but it is -difficult to decide whether his cases were true scurvy, as they occurred -in an epidemic of jaundice and no histologic examination of the bones -was carried out. - -The _intestine_ may present a variety of lesions.[29] The mucosa is -frequently congested and swollen, and the solitary follicles and Peyer's -patches enlarged. These changes may progress to necrosis and extensive -ulceration. In an outbreak of scurvy occurring in this country in 1917, -in a large institution for epileptics, ulceration was a frequent lesion -at necropsy.[30] Dysentery, a frequent complication of scurvy in some -epidemics, may add to this ulceration and lead to even complete -sloughing of the inner lining of the intestine. Hemorrhages are found in -the mucous, serous or muscular layers. Here, as elsewhere, the -hemorrhages vary in size from petechiæ to large infiltrations of blood. -A very striking picture is sometimes presented by the pale, edematous -intestinal wall dotted or streaked with vivid red. - -[29] For details regarding the intestinal lesions in infantile scurvy, -the reader is referred to Barlow's description of the case of Stephen -Mackenzie, to one necropsy report by Theodor Fischer, one by -Hirschsprung, one by Meyer, and five by Schoedel and Nauwerk. The -prevailing lesions are hemorrhages, pigmentation, follicular ulceration, -and enlargement of the mesenteric glands. - -[30] The potato crop largely failed this year, and there was -considerable scurvy in the spring, as described in the chapter on -antiscorbutics. - -=Liver.=--The liver is frequently congested, as would be expected in -view of the involvement of the right heart. Erdheim found congestion, -however, in only nine among thirty-one necropsies, although enlargement -of the heart was present twenty-one times. There may be hemorrhages in -the glandular tissue or under the peritoneum. "Cloudy" and fatty -degenerations occur occasionally, and in some cases an early cirrhosis. -Lind found abscess of the liver, and wrote that in a few instances "the -matter or corruption was hardened, as it were, into a stone." - -=Spleen.=--This organ is usually somewhat enlarged and congested. -Charpentier, in the Paris epidemic of 1871, found it often three to four -times the normal size and very soft, and Lind tells us that "the spleen -was three times bigger than natural, and fell to pieces, as if composed -of congealed blood." It must be remembered that the pathologic as well -as the clinical picture of the scurvy of Lind and his time was generally -complicated by infection. The enlargement is usually by no means so -great, and no doubt is due in part to intercurrent infections. On -section, it is found frequently to contain much reddish-brown pigment. -Hemorrhage may also occur. In beriberi, Andrews observed frequent -congestion of the spleen and also a loss of normal markings. - -=Pancreas.=--There is but one reference to a lesion of the pancreas in -scurvy, that of Sato and Nambu, who encountered hemorrhage of this organ -in one case among the necropsies performed in the course of the -Russo-Japanese War. - -=Kidneys.=--Here again, congestion and hemorrhage are the two lesions -most commonly found. The kidneys also may show any of the forms of -nephropathy ordinarily recognized, but these must be regarded as -complicating conditions and not a part of the true scurvy. - -Small hemorrhages may be found in the uterus, bladder or urethra. They -are especially common in the bladder, both in man and in the guinea-pig, -and in some instances may be the cause of the hæmaturia noted during -life. - -=Lymph-nodes.=--General enlargement of the lymph-nodes has been -described, but occurs probably only in advanced cases where a general -infection has been superadded. As a rule the enlargement is confined to -nodes draining areas where hemorrhage has occurred. On section these -nodes are reddish or brownish as the result of the pigment which they -contain, the "black and red spots of different sizes" mentioned by Lind. -Following infection they may become purulent, resulting in the inguinal -buboes so frequently mentioned by the older authors,[31] or in the -purulent mesenteric nodes associated with intestinal ulceration. - -[31] Lind writes: "In the months of July and August I opened near -seventy large swellings in the groin, proceeding entirely from scurvy." -... "We found the glands under their arm-pits much enlarged and -surrounded with purulent matter, as well as the muscles of their arms -and thighs." ... "The glands of the mesentery are generally obstructed -and swelled. Some of these were found partly corrupted and -imposthumated." - -=Organs of Internal Secretion.=--Until recently these organs have -received but little attention. It is probable, however, that in the near -future they will be the object of close study and that new information -will be acquired as to their condition in this disorder. Hemorrhages are -commonly seen in the adrenals, enlarging them greatly and giving them a -deep red color; the hemorrhage generally involves mainly the medullary -portion.[32] It is probable that careful scrutiny will disclose -hemorrhages in the other glands of internal secretion. The question of -the involvement of these glands will be again considered under the -microscopic anatomy, and has been taken up from a functional standpoint -in treating of the possible indirect action of the vitamines. - -[32] In view of the report of Hart and Lessing of calcium deposits in -the adrenal glands of monkeys suffering from scurvy, special attention -should be given to this point in necropsies on human beings. - -=The brain and the spinal cord= likewise have been but little studied. -It is hardly to be expected that much will be learned from an -investigation of the gross pathology of these organs, but the -microscopic anatomy offers a promising field of research. Hemorrhage may -occur into the brain substance, into the cord or the membranes -surrounding them. Pachymeningitis hemorrhagica interna has been -described frequently (Meyer, Hayem, Sutherland, Sato and Nambu) and may -give rise to the symptoms of meningitis. Sutherland reports an instance -where thrombosis of the basal artery was found postmortem. In one case, -that of Feigenbaum, hemorrhage of the cord was diagnosed during life and -confirmed at necropsy. - -The peripheral nerves may be the seat of hemorrhages, the blood lying -between the nerve trunk and its sheath. This is particularly well -illustrated in the recent work of Aschoff and Koch. - -=Bones.=--Palpation of the body will often reveal distinct lesion of the -bones, such as fractures, either ununited or healed with the formation -of large calluses; subperiosteal hemorrhages, especially of the distal -end of the femur or of the tibia, may be evident to the eye as well as -to the touch. Crepitation of the bones may serve to further establish -the break in continuity of the bones. This lesion was well known to the -older writers. Lind writes that "in some, when moved, we heard a small -grating of the bones. Upon operating those bodies the epiphyses were -found entirely separated from the bones; which, by rubbing against each -other, occasioned this noise." "All the young persons under 18 had in -some degree their epiphyses separated from the body of the bone, this -water having penetrated into the very substance of it." Poupart was also -struck by this phenomenon in young adults. - -Another bony alteration which is readily palpable is "beading" of the -ribs, the counterpart of the rhachitic rosary. This has not been -considered a sign of scurvy, and when noted clinically or at postmortem -has been passed over without comment, just as has been the case with -cardiac hypertrophy. In infants the beading has been attributed to -rickets, and this error has been largely responsible for the general -opinion that almost all infants suffering from scurvy suffer also from -rickets. If we scan the literature with this question in mind, we find -numerous casual references to beading of the ribs in scurvy. Fraenkel's -frequently cited case of a child of seven who died of acute scurvy, -showed beading of the ribs during life as well as after death. The true -scorbutic character of these enlargements was substantiated by -microscopic examination. In their pathologic studies on scurvy among -soldiers, Aschoff and Koch frequently describe beading of the ribs, -which they attribute to an infraction of the costochondral -junctions.[33] There may be fracture at this junction, or a separation -of the cartilages from the sternum, as described by Lind. - -[33] The beading may have the usual, rounded, smooth, knobby character. -There may be, however, what one might term "angular beading," the -junction taking on a step-like form, as if the abutting ends of the -cartilage and the bone were of unequal size and not well fitted to each -other. The cartilage overtops the bone, so that on palpating the joint -there is a precipitous fall as we run the finger outward from the -surface of the cartilage, or a sudden elevation on palpating the rib -from without inward toward the sternum. - -This beading of the ribs, which involves mainly the middle tier, was -described by Holst and Froelich in their classic report of guinea-pig -scurvy, and has been noted by all subsequent investigators in this -field. It has usually been called "rhachitic" or "pseudo-rhachitic" in -spite of the fact that this junction is the site of typical scorbutic -microscopic lesions. Hart and Lessing refer to the "rhachitic rosary" in -monkeys, likewise not realizing that it is the product of scurvy. - -The subperiosteal hemorrhage has long been recognized as a lesion -characteristic of scurvy.[34] It occurs exceptionally in the upper -extremities, and most commonly at the lower end of the femur; it may, -however, involve almost any of the bones, and has been described in -connection with the scapula, cranial vault, orbital plate of the frontal -bone, ribs, etc. It varies greatly in its size, being confined to a -small area or extending a long distance on the shaft of the bone. It -rarely is as large as one would expect from external appearance, as much -of the swelling is due to edema and hemorrhage into the soft parts. The -periosteum rarely becomes separated at the line of junction of the -epiphysis and diaphysis. The underlying blood coagulates rapidly, and -the periosteum begins to calcify within a few weeks, as shown by the -X-ray. - -[34] There seems to be some misconception as to the pathogenesis of the -subperiosteal hemorrhage in scurvy. In most reports this lesion is -described as if it resulted from a hemorrhage burrowing its way beneath -the periosteum and raising it from the subjacent bone. In point of fact, -such an event is impossible, as will be fully realized when one -experiences the great difficulty in separating periosteum from normal -bone. Scurvy involves a periosteum which is not normal; it is insecurely -attached to the shaft of the bone, so that it is readily stripped off by -hemorrhage. - -The most frequent site of fracture, or separation of the epiphysis, is -the lower end of the femur. This may be accompanied by local swelling, -or be discovered at necropsy, or during life by means of the X-ray in -cases in which it has not been suspected. An interesting fracture -reported by the author, and also mentioned by Kaufmann and by Schoedel, -is that of the head of the femur leading to the development of coxa -vara. In the author's case, the condition was found in a scorbutic -infant who had never stood on its feet. Schoedel suggests that scurvy -may at times be the etiologic factor in coxa vara as well as in some -cases diagnosed as congenital dislocation of the hip. - -On sectioning the bones longitudinally the cortex is noted to be -exceedingly thin, a mere shell and very brittle. The trabeculæ are so -thin and reduced in number that the bone has become a very fragile -structure. The marrow is no longer deep red at the ends of the long -bones, but yellowish, frequently presenting a patchy appearance. It has -a gelatinous consistency. This "Geruestmark" is one of the -characteristic anatomical changes of scurvy, and will be fully described -in considering the microscopic picture. Hemorrhages can be clearly -distinguished in the marrow, and are of varying shades denoting their -irregular occurrence. These hemorrhages were considered by Looser to be -the cause of the connective-tissue formation in the marrow, but do not -occur with sufficient constancy to warrant this interpretation. -Moreover, this "frame-work marrow" is found where there is no evidence -of previous hemorrhage. - - -MICROSCOPIC PATHOLOGY - -=Skin.=--As pointed out by Aschoff and Koch, examination of skin which -to gross appearance was the seat of typical small hemorrhages, showed -various lesions. In some, perhaps the most typical forms, there had -been a fresh extravasation of red blood-cells. This condition is found -usually in the subepidermal layers, especially in the papillary stratum. -These small hemorrhages occur very frequently about the hair follicles -and sweat glands, especially when they have been diseased. Where the -bleeding has been of long standing, dark brownish pigment deposits are -found and all blood-cells may have disappeared. Phagocytic cells are -almost always present and may be of the "wandering" or of the more fixed -connective-tissue type. Many round cells may be seen in these areas -lying between the connective-tissue strands or around the blood-vessels. -Rheindorf, as quoted by Tuechler, has called attention to this -round-celled reaction, which in many instances gives a picture analogous -to the granulomas, and which leads him to infer an infectious origin for -these lesions. Other areas which appeared to be the seat of hemorrhage -are shown by the microscope to be small abscesses or new connective -tissue often loaded with pigment and detritus, apparently representing -the final stage of these lesions. Aschoff and Koch have found that -suitably-stained preparations frequently show a loss of elastic fibres, -which Rheindorf states constitutes one of the earliest changes of this -disorder. The blood-vessels in the vicinity of the hemorrhages are -congested, especially the capillaries and small venules. - -=The muscles= also present a similar diverse picture of old and recent -hemorrhages, pigment deposit and round-celled infiltration. Increase of -connective tissue is usually found between the fibre bundles and in some -cases where the hemorrhages are apparently of long standing, as -evidenced by loss of contour of the red cells and pigmentation of the -surrounding areas, this scar tissue formation is very marked. Changes in -the muscle fibres themselves have not been encountered by all observers. -Hayem describes widespread fatty degeneration and a deposit of pigment -within the fibres, Leven a loss of sarcolemma, while Lasèque and Legroux -found fatty changes which were equally marked in muscles showing no -hemorrhage. On the other hand, Aschoff and Koch, in their careful -studies, did not find noteworthy fatty change of the fibres, but -observed often that the fibres within the hemorrhagic areas seemed -shrunken and were stained abnormally deep with eosin. - -In monkeys dying of experimental scurvy, Hart and Lessing describe -granules in the muscles, which, judged by their staining affinities, -evidently contained calcium and were similar to those found in the -adrenal glands. - -=Blood-vessels.=--A similar difference of opinion obtains in regard to -the changes in the walls of the blood-vessels, especially of those in -hemorrhagic areas. This question is of particular interest because of -its bearing on the problem of the mechanism involved in the escape of -the blood. Since it has been demonstrated that neither the clotting time -nor the viscosity of the blood is markedly changed in scurvy but that -weakness of the vessel walls exists, as demonstrated by "the capillary -resistance test," it is natural that we should seek an explanation in -the microscopic pathology of the vessels. So far no change has been -found. The application of some of the newer stains, such as those for -mitochondria and other cell granules, has not been resorted to for this -study, and might furnish valuable information. - -Hayem found fatty infiltration of the walls of the small veins and -capillaries, and believed this to play an important rôle in the etiology -of these bleedings. Lasèque and Legroux also found occasional fatty -changes. Other authors have failed to demonstrate similar lesions, or -have considered them due to postmortem change. Koch searched in vain for -"rents" in the vessel walls to account for the escape of blood. Hyaline -degeneration has also been described, but is believed to result from -secondary infections and not to be an intrinsic lesion of scurvy (Sato -and Nambu, Aschoff and Koch). - -Thrombosis of vessels is found both in the neighborhood of hemorrhage -and elsewhere, the thrombi at times completely occluding the vessels and -giving rise to typical wedge-shaped infarcts. The lung often shows areas -of this kind. - -=Lungs.=--Hemorrhages of various size occur in the tissue of the lung or -in the air spaces. Hemorrhagic infarcts also have been described, and -Sato and Nambu report hyaline degeneration of the blood-vessel walls. -Secondary pneumonias, usually broncho-pneumonic in type, are of common -occurrence, and in many epidemics constitute the prevailing cause of -death. Tuberculous lesions are also frequently present, and are stated -to assume fresh activity as the result of the nutritional disorder. -Edema occurs frequently, the fluid in the acini often containing red -blood-cells. Subpleural hemorrhages, thickening of the pleura, purulent -or fibrinous pleurisy are common lesions. - -=Heart.=--Although hypertrophy and dilatation of the heart have been -noted by several observers, microscopic changes have rarely been -recorded. Meyer, and also Leven, report fatty degeneration of the muscle -fibres, which, however, was found by Aschoff and Koch in only one case. -Sato and Nambu described an increase of connective tissue, and others -anemia and pigmentation. Thickening of the pericardium and subserous -hemorrhages also occur. - - -ALIMENTARY TRACT - -=Gums.=--Where it has been possible to examine the gums of early cases, -where swelling, redness or bluish discoloration are the chief symptoms -and before secondary infection has set in, the microscopic picture is -very similar to that of the skin. Small hemorrhages, round-celled -infiltration, increase of connective tissue, clumps of pigment -containing cells, or a diffuse deposit of brownish granules complete the -picture. Congestion and edema are usually evident. The changes are most -pronounced in the deeper layers of the submucosa and about the muscles, -leaving the superficial layers strikingly intact, beneath an apparently -normal epithelium. In the later stages, erosion of the mucosa occurs, -and the upper layers of submucosa become involved. Polynuclear cells -appear in great numbers, abscesses and ulcers are formed, which with -proper staining can be shown to harbor the various types of mouth -bacteria, cocci, spirillæ, etc. The pigmentation becomes intense, and a -marked increase of the newly-formed connective tissue takes place. - -The lesions of the stomach are neither characteristic nor, as a rule, -very striking. Hemorrhages occur, the larger ones generally in the -subperitoneal layers, the smaller ones in any of the coats. Thickening -of the wall follows or accompanies these hemorrhages. Superficial -erosions of the mucosa or even ulcers may be seen. - -The striking congestion of the duodenum has been fully discussed in -considering the gross pathology. At any level in the intestinal tract -hemorrhage may take place, with the resulting pigmentation and scar -tissue formation. The lymphoid structures--solitary follicles and -Peyer's patches--are usually intensely congested and often the seat of -hemorrhage. They constitute the sites of predilection for ulcerative -processes of the gut. Bacteria can be demonstrated at times in the -submucous layers; however, no type has been found to predominate, the -flora being composed of the usual intestinal forms. Aschoff and Koch -have demonstrated in these ulcers the spirilla and fusiform bacilli so -commonly found in the mouth. These follicular ulcers may be found in any -part of the intestine, and may be shallow erosions, or extend through -the follicle into the deeper tissues. Hemorrhages are commonly located -about the follicles. The epithelial layer is edematous, often showing an -increased number of cells. - -The lymph-nodes may be congested, or edematous and hemorrhagic. Pigment -is usually present and in some cases the peripheral sinus is distended -with pigment-loaded cells. Where secondary infection has occurred, -extensive necrosis of the glands is seen. This is found frequently in -mesenteric nodes where severe intestinal lesions are present. The nodes -lying in the drainage paths of hemorrhagic areas, especially the -inguinal nodes, show active resorption of blood and blood pigments, and, -as noted above, may be the seat of infection. - -=Liver.=--In this organ, likewise, no change is found with sufficient -regularity to warrant its acceptance as a distinctive lesion of scurvy. -Fatty infiltration is, however, very common in the centre as well as in -the periphery of the lobules. It is frequently associated with -congestion, which may be so great as to lead to atrophy. In one case of -Aschoff and Koch the picture resembled that of primary liver atrophy. -The organ frequently contains extravasated blood or depositions of old -blood pigment. It should be noted that Boerich described early cirrhosis -in several of his cases, and that Aschoff and Koch record that one of -their severe, acute cases showed "a recent cellular cirrhosis." An -exceptional lesion is reported by Reinert--a "leucocytic" infiltration -of the liver and spleen occurring in a three-year-old child, and -resembling that seen in pseudoleukæmia. Finally, it should be remembered -in this connection that Hart and Lessing found calcium deposits not only -in the muscles and adrenal glands of their monkeys, but also in the -liver. - -=The spleen= shares the general congestion of the internal organs. Sato -and Nambu invariably found large numbers of pigment granules in this -organ. Hirschsprung noted many Malpighian corpuscles, Reinert describes -a true hyperplasia of the splenic pulp, and others mention infarcts and -subcapsular hemorrhages. - -=The kidneys= are often normal. On the other hand, various forms of -nephritis are found, with cloudy swelling or interstitial change--a not -infrequent complication of scurvy. More typical of the primary disease -are congestion and hemorrhages, the bleedings occurring either under the -capsule, into the interstitial tissues, or into the lumina of the -tubules. Hayem found fatty infiltration of this organ and Aschoff and -Koch a slight change of this kind in one case. - -=Adrenals.=--A new interest in the study of the adrenals in diseases of -the "deficiency" group has been created by the recent work of -McCarrison. This author found the adrenals increased in size and weight -in guinea-pigs dying of scurvy, whereas the adrenalin content of these -glands was markedly decreased. On section there was hemorrhagic -infiltration, "usually circumscribed in extent and situated around the -periphery of the adrenal cortex." This was seen even in early cases -before hemorrhage had occurred elsewhere in the body. He describes also -"degenerative changes in the cellular elements of cortex and medulla" -consisting of vacuolation and disintegration of the cells with -disappearance or loss of staining reactions of their nuclei. Rondoni, -some years previously, had called attention to this increase in size and -hyperæmia of the adrenals in guinea-pigs fed exclusively cereal diets. -He, as well as McCarrison, noted an increase, though much less marked, -as the result of starvation. LaMer and Campbell recently have confirmed -McCarrison's report of an augmentation in the weight of the adrenal -glands in guinea-pigs fed on diets deficient in the antiscorbutic -factor. - -Comparable lesions have as yet not been found in human scurvy. These -glands have been found normal by Jacobsthal, Schoedel and Nauwerk, -Ingier and Epstein. In the cases of Aschoff and Koch no abnormality was -noted except an almost constant increase in lipoid content. In those of -Boerich the glands were normal in all but one case; in this instance the -medulla was somewhat increased in size. In passing, we may repeat that -Hart and Lessing found calcium deposits in the adrenals of four of their -five monkeys, a lesion which has never been recorded in man. - -It is valuable in this connection to compare the adrenal in scurvy -with that of beriberi. In this disorder, Albert found the adrenal normal -in one case, and Andrews describes only congestion in his eighteen -necropsies. Ono found an increased adrenalin content in nine fatal -cases, and states that the medulla appeared "fatter" than normal. More -data will have to be obtained before it can be determined whether -characteristic changes occur in scurvy, and how to interpret the -hypertrophy described by several authors as common to guinea-pig scurvy. - -=Pancreas.=--Sato and Nambu appear to be the only investigators who have -described lesions in the pancreas. They found hemorrhages in one case -among thirteen. - -=Thymus.=--This organ has rarely been examined. Aschoff and Koch found -no abnormalities in adults, nor did Jacobsthal in a case of infantile -scurvy. Boerich noted enlargement in one instance. - -=Other Organs of Internal Secretion.=--Very little attention has been -paid to these organs. Aschoff and Koch state that the thyroids and -hypophyses were normal in their cases. - -=Generative Organs.=--No abnormalities have been described. - -=Central Nervous System.=--The most frequent abnormality of the central -nervous system is, as would be expected, hemorrhage; this has been -discussed in the section dealing with gross pathology. No specific -changes have been found in nerve-cells or fibres of the brain. - -In a case of fatal scurvy in an infant a "focal degeneration of the -lumbar cord" has been described, extending for a distance of about a -quarter of an inch (Hess). The lesion differed from that of -poliomyelitis in the absence of round-celled infiltration and of the -characteristic changes in the anterior horn cells (Figs. 3 and 4). The -outstanding feature was a loss of cells in the lateral groups of the -left anterior horn; there were also fewer nerve fibres in this region, -but this diminution was less striking. No definite interpretation of -this case can be made as the data are insufficient to permit a -conclusion as to whether the lesion was truly scorbutic or the result of -an associated process. Schoedel and Nauwerk found no change in the -spinal cord stained by Marchi's method. - -[Illustration: FIG. 3.--High power. Section of lumbar cord showing -normal cells in lateral group of right anterior horn.] - -[Illustration: FIG. 4.--High power. Section of lumbar cord showing focal -degeneration and absence of cells in lateral group of left anterior -horn.] - -=Peripheral Nerves.=--The sheaths of the large nerves as well as those -of the vessels are very often invaded by hemorrhage. The extravasated -blood is found to lie around but rarely among the nerve fibres, which do -not show any pathological alteration. Ingier is one of the very few to -describe a degeneration of the nerve fibres. In one guinea-pig in which -scurvy was induced she found "many marked degenerated fibrillar bundles -of both sciatic and peroneal nerves, slight degeneration of the phrenic -nerves and one vagus and its cardiac branch." Another animal is referred -to as having shown "very marked and well-developed degeneration of the -nerves of the lower extremities." It is open to question whether -starvation played a rôle in the causation of these lesions. Schoedel and -Nauwerk, and Aschoff and Koch examined these nerves but failed to find -any lesions; the latter directed their attention especially to the vagus -of twenty-two cases. - -=Retinal hemorrhages= were found by Jacobsthal, and by Kitamura, who -records "decided edema of the retina, marked bleeding and circumscribed -hypertrophy of the nerve fibres" such as is found in albuminuric -retinitis. These changes are considered again under the symptomatology -of scurvy. - -=Bones.=--Our knowledge of the minute pathology of the bones is far more -complete and detailed than that of any other structure. This was to be -expected in view of the fact that this is the only tissue in which the -lesions are diagnostic. In considering the microscopic pathology it must -be remembered that all the bones are rarely affected by scurvy, and that -those that are involved show the scorbutic changes to a varying degree. -One of the peculiarities of the lesion is that it involves the end of -the diaphysis or rather the junction of the diaphysis and the cartilage. -The bones most apt to show typical changes are the ribs; we shall -therefore describe a section made through a costochondral junction. - -The costochondral junction is generally swollen, somewhat beaded, and -when cut longitudinally shows on gross examination a transverse -yellowish bar, corresponding to the area of disorganization which will -be described below. Under the microscope the line of juncture is not -sharp and straight as is normally the case, but presents a wavy or -irregular contour, the cartilage jutting into the bony end of the rib, -instead of abutting in neat apposition to it. The bone is hollowed out -and irregularly concave, whereas the cartilage presents a convex -appearance. At the site of the junction is the _Truemmerfeld area_, -where the normal tissue is splintered and fragmented. Everything in a -state of disorder--trabeculæ of bone of various shapes and sizes lie -scattered about, the cells irregularly arranged and much distorted, -signs of recent hemorrhage, unrecognizable detritus. The picture is that -of weakened bone having been crushed by the pressure of the more compact -cartilage. Higher magnification shows that there are few osteoblasts -(generally associated with the deeper fragments of bone), a varying -number of intact red cells, according to the occurrence of hemorrhage, -and occasional spindle- and star-shaped connective-tissue cells. -Covering this mass of detritus there is frequently, as Aschoff and Koch -have emphasized, more or less protective fibrin which has undergone some -hyaline or connective-tissue organization. - -The cartilage is also not normal. Its cells do not present an orderly -arrangement, the proliferating columns having disappeared in the central -convex portion, and being present to a varying extent near the -periosteal borders. If we judge from sections of early scurvy in -guinea-pigs, this disturbance of the columnar formation of the -proliferating cartilage is one of the early signs of scurvy, and is -associated with an unevenness and irregularity in shape and size of the -bone trabeculæ. In young individuals, where cartilage activity is great, -these changes are most marked and the entire zone of active cells may be -somewhat widened. - -Below the Truemmerfeld is the _Geruestmark or framework marrow_, another -distinguishing feature of scurvy. This extends for about 5 to 10 mm. -toward the lymphoid marrow, where it ends more or less abruptly. It is -composed of a loosely-constructed fibrillar tissue on a -gelatinous-appearing groundwork, of sparsely scattered cells, and bony -trabeculæ which are markedly thin and weak. Here and there are -hemorrhages and blood pigment, especially adjacent to the -"Truemmerfeld." Another feature which strikes one at first glance is -that the entire marrow area is incompletely filled by the thin and -greatly-depleted trabeculæ of the spongiosa. The question has been -raised whether this rarification is to be considered entirely of -scorbutic origin. It is due evidently to a lack of function of the -osteoblasts, which are diminished in number, and are represented by a -layer of shrivelled spindle cells along the walls of the atrophied bony -columns. They may fail almost entirely, as may its osteoid border, which -is significant of active bone tissue. The lack of bony structure and -rarification clearly is not due to an increase in the number or the -function of the osteoclasts, for these do not appear in excess. It is -mainly the result of normal bone resorption with a lack of normal bone -regeneration. Aschoff and Koch suggest that the framework marrow may be -able to manufacture bone, but cannot accomplish this because there is a -lack of material from which to make osteoid tissue. This, they believe, -constitutes the primary deficiency--a lack or faulty development of -cement substance, which in turn may depend on an alteration of colloid -material. Regarded in this light, the lesions of the bones resulting in -fracture and those of the blood-vessels resulting in rupture and -hemorrhage are dependent on a deficiency of the same basic material. - -[Illustration: FIG. 5.--Infantile scurvy. Epiphyseal junction of lower -end of femur: (a) calcified cartilage at "Truemmerfeld"; (b) hemorrhage -in the fibrous marrow (Gernest-mark). Bone cortex and trabeculae -abnormally thin. McCallums' Text Book of Pathology. W. B. Saunders Co.] - -Hemorrhage occurs in the bone as elsewhere; it is almost never lacking. -It appears either as large hemorrhages in the spongiosa, especially -where the normal marrow joins either the Geruestmark or the -Truemmerfeld, or merely as scattered cells, possibly the result of -diapedesis. The blood-vessels in these areas are narrow and extremely -thin-walled. The most typical site of hemorrhage is beneath the -periosteum, a lesion widely known on account of its clinical -significance (Fig. 16). Here the blood may extend for a considerable -distance along the shaft, but rarely beyond the epiphyseal line. The -clot forms readily, demonstrating that the nature of the hemorrhage is -not a defect in coagulation, and in its midst may be seen fibrin, -pigment, granulation tissue, and more or less firm connective -tissue--constituting the callus. The inner surface of the periosteum is -frequently lined with newly-formed bone and with a more or less dense -deposition of lime salts, which becomes heavier in the course of the -healing process, and is readily observed in radiographs. This -periostitis ossificans may result in the clot being surrounded by a -perfect shell of bone, with bony columns penetrating the deeper layers. - -As the result of the lack of bone formation and the consequent weakening -of the corticalis and the spongiosa, frequently a separation of the -diaphysis from the epiphysis results. This lesion should not be regarded -as a true separation, for, as Barlow pointed out, the line of cleavage -is not at the junction, but below it, involving the uppermost region of -the diaphysis. It is therefore correct to speak of a fracture or -infraction. This lesion is generally accompanied by a deformity of the -surface contour of the junction, due to a displacement of the cartilage, -as a result of which "angular beading" of the rib is brought about. In -some instances the cartilage is "telescoped" into the crushed end of the -bone. To a varying extent fibrin covers the end of the fractured bone; -the angles adjacent to the periosteum contain blood which becomes -organized into dense connective tissue, thus serving as a splint for -the fractured parts. In the course of healing a large number of foreign -body giant-cells appear, blood-vessels sprout from the periosteum as -well as the bony surface, and the necrosed tissue gives place to an -active formation of callus, which generally leads to complete -regeneration and restitution. It is remarkable how quickly and perfectly -an epiphysis may become reunited to its shaft (Figs. 6 and 7). -Sometimes, however, this takes place with resulting deformity, as in the -development of coxa vara of the femur. - -[Illustration: FIG. 6.--Posterior-anterior view of shoulder of infant -(R. S.) 17 months old. Severe scurvy. Subperiosteal hemorrhage of -humerus, and separation of upper epiphysis.] - -[Illustration: FIG. 7.--Anterior-posterior view of same shoulder (see -fig. 6) 22 months later. Complete restitution of epiphysis without -deformity of humerus.] - -As Czerny and Keller have stated, it is difficult to define sharply the -relation of bone fragility to scurvy. Histologically there is great -similarity between the "osteotabes infantum" described by Ziegler and -conditions sometimes found in infantile scurvy. The main distinction is -that in the latter disorder the lesion is less generally distributed -throughout the skeleton, and is particularly marked in a limited area of -the bones (epiphyses). In considering this question it should be borne -in mind that, experimentally, osteoporosis and scurvy can be brought -about by diets which are absolutely dissimilar. For example, Bartenstein -showed that young guinea-pigs develop osteoporosis and multiple -fractures on a diet of raw milk containing an adequate quota of -antiscorbutic vitamine. - -=Rickets= and infantile scurvy are commonly found associated, although -they bear no causal relationship to each other. The distinctive -characteristic of rickets is the broad area of osteoid tissue which is -formed at the epiphyseal junction, a broad band of incompletely -calcified cartilage not found in scurvy. In the latter disease -osteoblastic bone growth is greatly inhibited, but what growth does take -place occurs in a normal and orderly manner. The osteophytes, for -example, which so commonly develop at right angles to the axis of the -bone in the subperiosteal hemorrhages, are composed of apparently normal -bone. Another marked distinction between the two conditions is the -paucity of blood-vessels in the cartilaginous area and in the marrow in -scurvy, compared with the increased vascularity so generally encountered -in rickets. It is evident, therefore, that although these two -nutritional disorders bear a superficial resemblance to each other -pathologically, they are radically different and almost antithetical. - - - - -CHAPTER V - -EXPERIMENTAL SCURVY - - -There is no mention whatsoever of scurvy in animals previous to 1895, -when Theobald Smith wrote: "When guinea-pigs are fed with cereal (it has -been observed for some years in this laboratory), with bran and oats -mixed, without any grass, clover, or succulent vegetable, such as -cabbage, a peculiar disease, chiefly recognizable by subcutaneous -extravasations of blood, carries them off in from four to eight weeks." -Smith did not pursue the subject further. - -Coincident with the appreciation of the value of experimental methods, -one would have expected attempts to produce scurvy in animals. The -disorder had been recognized for a great many years, the fact that it -was occasioned by a dietary deficient in fresh food was widely known, so -that it would seem natural for clinicians or laboratory workers to have -tried to induce the disease in animals by a similar restricted diet. -There is, however, no suggestion of such an experiment in the voluminous -literature on scurvy. The explanation of the neglect of an experimental -study of scurvy appears to be that this was considered a disorder which -required little investigation--its etiology, its prevention and its cure -seemed thoroughly understood. It is strange that the mere fact that such -a severe disturbance responded, as if by magic, to the administration of -simple foodstuffs should not have awakened curiosity as well as wonder, -and stimulated inquiry into the nature and significance of the curative -agent. - -In 1903 Bolle published the results of experiments on guinea-pigs which -had been fed for various periods on raw or sterilized milk. He reported -that the animals developed a marked fragility of the bones, varying in -intensity in proportion to the degree of heat to which the milk had been -subjected. These changes Bolle interpreted as typical scurvy, but it is -difficult to decide whether the disorder was actually true scurvy, in -view of the indefinite description of the bone lesions. - -Bartenstein repeated Bolle's work and described in detail the changes in -the bones. From his work we learned that it was of little moment whether -the animals were fed raw or sterilized milk--their nutrition failed -within about the same length of time, and they died within a month. The -chief pathologic change was a marked fragility of the bones, leading to -spontaneous fractures, or to breaking of the bones in the course of -ordinary manipulation. Bartenstein described the disorder as "beginning -with the degeneration of the marrow, and secondarily leading to an -atrophy of the bone due to increased absorption and deficient new -formation of bone, especially at the endochondral lines of ossification. -As the result of the osteoporosis, spontaneous fractures occur without -noticeable hemorrhagic diathesis." He found a deficiency of calcium in -the bones of animals suffering from even a mild degree of this disorder. -Hart and Lessing are of the opinion that we cannot accept Bartenstein's -diagnosis of scurvy. They compare this disorder to that described by -Ziegler as "osteotabes infantum," in which there is a more or less -pronounced "jelly marrow" which has replaced the lymphoid cells in -scattered areas. They sum up their analysis of the question with the -statement that "the primary marrow changes in the diaphysis, the marked -lacunar absorption by osteoclasts, the absence of subperiosteal -hemorrhages, do not indicate typical scurvy." Schmorl produced -comparable lesions in dogs and came to the conclusion that the disorder -was one "very similar" to scurvy but not identical with it, the -essential difference being that in all animals there was a most marked -absorption of bone by osteoclasts. - -Similar results were obtained by others. In 1904 Peiper and Eichloff -attempted to produce scurvy in dogs by means of a diet composed -exclusively of raw or of sterilized milk. The following year we find a -report by Esser of feeding goats on sterilized milk. None of these -studies hits the mark; a condition of fragilitas ossium was produced -rather than typical scurvy. - -In 1907 the first systematic and convincing experimental study of scurvy -appeared. In this year Holst and Froelich published a preliminary -account of their classic work, undertaken in an endeavor to fathom the -nature of "ship beriberi," a disorder which disabled so many of the -sailors in the Norwegian navy. We must remember that until recently -attention has been focussed on the infectious diseases, and little -thought given to the investigation of nutritional disorders. Although -experimental investigation in this field may be stated to have been -initiated by this work, it in turn had been stimulated by a conception -of dietary diseases which had just begun to be realized. This new -viewpoint was the result of the work of Eijkman. As has been mentioned -in considering the pathogenesis of human scurvy, Eijkman demonstrated -that hens developed polyneuritis, a disease resembling beriberi, when -fed on polished rice, and that the simple change to a diet of unpolished -rice, or the addition of rice polishings to the dietary, sufficed to -protect or to cure. This work had been repeated and substantiated. It -was evident to those who considered the question that the old lines of -thought in regard to food and dietetics inadequately explained -remarkable phenomena of this kind. It was also clear that nutritional -disorders were subject to experimental investigation in a way similar to -the infectious diseases, which were absorbing the interest of the -various laboratories. It is unnecessary to review the rapid rise of -investigative work in this field. It may be stated, in general, that -during the past few years the investigations of scurvy have become so -numerous that an established research technic may be said to have -developed in connection with its study. - -Attempts have been made to produce scurvy in various animals, but it has -been brought about regularly only in the guinea-pig and in the monkey. -Experiments on the dog are as yet too few to justify our regarding this -animal as definitely available for this study. The nutrition of rats, -mice, rabbits, hogs, pigeons, fowl, receiving a diet identical with that -which regularly occasions scurvy in guinea-pigs, either progresses -normally or a state of malnutrition develops which cannot be identified -with scurvy. Recently Hart, Steenbock and Smith have reported that -cattle can be reared to maturity on a diet which will produce scurvy in -the guinea-pig in four to five weeks. We are therefore confronted with -the remarkable and inexplicable phenomenon, a fact concurred in by -almost all investigators, that a diet induces either normal nutrition or -malnutrition, according to the experimental animal employed. A diet of -polished rice, or other decorticated grain, will lead to the development -of scurvy in the guinea-pig, to polyneuritis in the pigeon or fowl, or, -according to Holst and Froelich, to a combination of these disorders in -the hog.[35] The basis of these divergent results cannot be surmised, -and is worthy of the most thorough investigation. It may well be that -the elucidation of this problem--for example, why we are able to bring -about scurvy in the guinea-pig but not in the rabbit, will shed light on -the pathogenesis of this disorder. Are we to conclude that some of these -animals have the power to synthesize the vitamine whereas others must -depend upon the food for it, or are we to presuppose an ability to -maintain normal life and function without any or with a minimal amount -of this vitamine? The difference between these two groups, the -susceptible and non-susceptible animals, probably is not as absolute as -we have been wont to regard it. Recently Harden and Zilva have shown -that although rats are able to thrive on a diet free from antiscorbutic -vitamine, they show an appreciable gain in weight when this factor is -added to the dietary. If such be proved to be the case, we must regard -the non-susceptibility of the rat, the rabbit, etc., as relative rather -than absolute. - -[35] Hogs fed on 1.5 kg. of rye bread and 0.5 kg. of meat heated to 100° -or 110° C. for a half hour showed the hemorrhages, loosening of the -teeth and affections of the gums characteristic of scurvy, as well as -the paralysis and neuritis typical of polyneuritis. - -From time to time a doubt has been raised as to whether we should accept -guinea-pig scurvy as the counterpart of human scurvy. This question can -be answered only by comparing the disorder in the one species with that -in the other--as to mode of production, pathology, symptomatology, means -of cure and all other phenomena. Viewed from these standpoints it is -found that in almost every respect the disorder is identical in man and -in the guinea-pig. The outstanding distinction is the difference in the -length of time elapsing before the development of symptoms. In the child -or in the adult it takes about six months of the deficient diet before -clinical symptoms are manifest and a diagnosis can be established; in -the guinea-pig the disorder can be recognized two weeks after -restricting the diet. In the one instance we seem to be dealing with a -nutritional disorder which is chronic or at least subacute, and in the -other with a markedly acute condition. This distinction is open, -however, to certain qualifications. In the first place, we must consider -the duration of life of the two species, the comparatively short span of -the guinea-pig compared with that of man. It must be borne in mind, -furthermore, that the guinea-pig is placed on a diet absolutely devoid -of all antiscorbutic vitamine, whereas this rarely obtains in human -beings. For example, the diet which is most markedly scorbutic for -infants is the "malt soup" previously mentioned, but even this food -contains an amount of the antiscorbutic factor which is not negligible. -But after taking these differences into consideration, it is -nevertheless evident that the guinea-pig is far more sensitive to scurvy -than man. This does not indicate that the guinea-pig is an unsuitable -experimental animal, any more than the fact that the pigeon is more -susceptible to polyneuritis than man indicates that it is unsuited to -investigations of beriberi. It merely prevents our carrying out delicate -quantitative experiments, and cautions against drawing too finely-spun -deductions. In all nutritional investigations it should never be -forgotten that conclusions drawn from experiments on animals are merely -provisional, and must await substantiation on man, and, furthermore, -that where differences in reaction are noted, the clinical data should -be accorded full consideration. - -=Pathogenesis of Guinea-pig Scurvy.=--From a pathogenetic point of view -guinea-pig scurvy and human scurvy show remarkable points in common. Any -diet that leads to the development of scurvy in man likewise brings it -about in the guinea-pig, and contrariwise, any food which cures the -disorder has the same beneficent effect on both species. This similarity -extends so far that, as will be shown in the chapter on antiscorbutics, -the relative potency of the various foods is approximately the same for -man and for the guinea-pig. The parallelism generally is striking. The -dietary which has been commonly employed in experimental scurvy has been -that first suggested by Holst and Froelich, namely, oats, hay and water. -Recently, however, this dietary has been enlarged in order to make it -more complete, so as to include adequate protein, water-soluble and -fat-soluble vitamine, and inorganic salts. To this end the group of -workers at the Lister Institute (Chick and co-workers, Harden and Zilva) -place their animals on a basal diet of one part of crushed oats and two -of wheaten bran, and a daily ration of 50 to 60 c.c. of milk autoclaved -for one hour at 120° C. This milk still retains a small amount of -antiscorbutic vitamine. Cohen and Mendel have employed, apparently with -good result, a "soy bean cracker," containing soy bean flour which has -been heated for 30 minutes at 15 pounds' pressure (120° C.), 3 per cent. -of sodium chloride, the same percentage of calcium lactate and of dried -brewers' yeast, and raw milk sufficient to supply 5 per cent. of -butter-fat. - -The use of raw milk was introduced by Jackson and Moore, and adopted by -McCollum and Pitz and again by Pitz in a series of interesting -experiments. The milk was given _ad libitum_. The results of these -investigations were puzzling at first, until it was shown by Chick, Hume -and Skelton that the dietary on which they were based contained a -fundamental error which accounted for their lack of consistence. -Although milk is not rich in the antiscorbutic factor, it possesses it -in moderate degree, so that the outcome will be quite different -according to whether a guinea-pig takes, for example, 50 c.c. or 100 -c.c. daily. It is quite evident, therefore, that a food of this kind -cannot be offered _ad libitum_, and that if this rule is not observed, -most disconcerting results will follow.[36] This basic error in framing -the dietary has made it impossible to accept the deductions of these -authors. The conclusions of McCollum and Pitz are so striking and have -led to such wide discussion, that they require consideration, in spite -of the fact that the error in the dietary is now recognized. These -authors found that the cæcum of their animals was greatly distended with -putrefying fæces. As the cæcum is extraordinarily large and delicate in -this species, they drew the deduction that the development of scurvy in -the guinea-pig was due principally to the retention of fæces. "An -impacted cæcum, the seat of putrefaction, may cause injury to the cæcal -wall, sufficient to permit the invasion of the tissues by bacteria, or -the animals may perhaps be injured primarily by the absorption of toxic -products of bacterial origin." Accessory dietary factors or vitamines, -according to this theory, are supposed to play no part in the disorder, -and antiscorbutics, such as orange juice, are considered to owe their -efficacy mainly to their laxative properties, and to be replaceable by -other laxatives such as phenolphthalein or oleum petrolatum. The -efficacy of orange juice is supposed to be due to its content of -citrates, and to be replaceable by what was termed "artificial orange -juice," a mixture composed of the various salts, citric acid and -sucrose, in the proportions in which they are found in the natural -juice. - -[36] A guinea-pig requires about 80 to 100 c.c. of fresh milk per diem -to protect it from manifest scurvy, if this constitutes its sole -antiscorbutic quota. There is, however, a great difference in the amount -of milk which individual animals consume, so that if we furnish it _ad -libitum_ our results will be irregular, one animal developing scurvy and -another remaining well, according to individual appetite. Frequently -guinea-pigs take very little milk at first, learning gradually to drink -more and more, so that it comes to pass that only after some weeks, if -at all, they take sufficient to afford protection. Under these -circumstances, if any addition is made to the dietary after the -experiment has progressed, the lack of development or cure of the scurvy -may mistakenly be attributed to this newly introduced factor, whereas, -in point of fact, it is due to an increased consumption of milk. - -These reports stimulated renewed interest in experimental scurvy, -suggesting new aspects, and therefore directing attention to points -requiring investigation. There were no data at hand on the consistency -of the contents of the bowel in guinea-pigs, so that it was necessary to -make appropriate observations in normal and in scorbutic animals. It -was soon reported by various workers, Rappleye, Cohen and Mendel, Hess -and Unger, and others, that there was no definite relationship between -the occurrence of scurvy and impaction of the cæcum. In Fig. 8 we see -portrayed the stool output of a guinea-pig during the period in which it -was developing scurvy, and during a subsequent period when it was being -cured by means of orange juice. It is clear that there was no -significant variation in the output during these divergent periods. A -similar conclusion was arrived at by those who examined the cæcums of -animals postmortem. Cohen and Mendel write: "Summarizing our experience -with nearly one hundred scorbutic animals, we conclude that actual -impaction of the fæces in the cæcum occurred in about one-quarter of the -cases, and visible damage to wall, _i.e._, congestion or hemorrhage, or -impaction, or both, was found in perhaps half of the cases. It should be -noted that this statement covers all the diets we have tried." We concur -in this conclusion. Not infrequently we found the cæcums of markedly -scorbutic pigs to contain semi-fluid fæces, the consistency of its -contents depending on the character of the diet, quite apart from its -adequacy and lack of the antiscorbutic factor. For example, a diet rich -in milk, containing 100 c.c. or more, led to the formation of rather -solid fæces; if oats were added to the milk diet the fæces in the cæcum -were found to be still more solid, and this portion of the gut more -often impacted. This condition could be detected by palpation even -during life. Just as we encountered scorbutic animals on an oat, hay and -water diet, who had semi-fluid fæces in the cæcums, so we met with -others which were on a milk diet, and showed no signs of scurvy, -although their cæcums were impacted with fæces of a putty-like -consistence. Guinea-pigs do not seem to be able to tolerate a diet -containing a large quantity of the fat of cow's milk. Such a diet leads -to impaction of the large intestine resulting in death, but does not -induce scurvy. Jackson and Moore produced a condition of this kind by -feeding pigs with cream containing 26 to 28 per cent. fat. "In every -case," they write, "the large intestine was distended with light -mustard-colored semi-solid fæces." This pathological condition is not -understood, but is quite distinct from scurvy, and remarkable in view of -the fact that the milk of the guinea-pig contains as high as 25 per -cent. of fat. It is an interesting illustration of the marked biological -difference in the butter-fat of various species. - -[Illustration: FIG. 8.--Shows a period with the development of scurvy, -and one where it was cured by giving orange juice. It will be noted that -there was no marked constipation while the animal had scurvy. During a -period of a few days the amount of stool was scanty, corresponding to -the decreased intake of oats and hay on the days preceding. Broken line -represents clinical course of scurvy.] - -Nor was it found, as McCollum and Pitz claimed, that antiscorbutics were -replaceable by laxatives in the diet. Without entering into the details -of this aspect of the subject, which will be considered in the chapter -on symptomatology, it may be stated that attempts to prevent the -occurrence of scurvy or to cure it by means of laxatives invariably -failed. Chick, Hume and Skelton, as well as Hess and Unger, gave oleum -petrolatum to a series of pigs without the slightest favorable effect. -Hart, Steenbock and Smith recently reported that they had administered 1 -c.c. of this oil on alternate days to one series of pigs, and 2 mg. of -phenolphthalein on alternate days to another series, without relieving -the scurvy. Cohen and Mendel, in order to test the adequacy of their -diet as to roughage, supplemented it with additions of considerable -filter paper and sawdust, "without averting the appearance of scurvy." -It is evident, therefore, that constipation does not play an essential -rôle in the pathogenesis of scurvy in the guinea-pig, and that -antiscorbutics are by no means synonymous or interchangeable with -laxatives. These results accord with observations on infantile scurvy. - -=The Pathology.=--The pathology of guinea-pig scurvy is essentially that -of human scurvy. Hemorrhages and separations of the epiphyses or -fractures of the long bones dominate the macroscopic picture. The -hemorrhages are found rarely in the gums, but are common about the -joints, in the muscles of the jaw or in those of the hind legs. They may -be subcutaneous and appear as bluish discolorations at various parts of -the body, especially if the disorder has resulted in death or if -infection has been superadded. On stripping the skin we often note -hemorrhages in the intercostal muscles, and beading of the ribs at the -site of the costochondral junctions, least marked in the upper and in -the floating ribs. This has been frequently described in connection with -guinea-pig scurvy; its similarity to the rosary of human rickets has -been drawn attention to recently by Jackson and Moore. It should not be -regarded as "pseudo-rhachitic," but as typically scorbutic, from a -microscopic as well as a macroscopic viewpoint. On closer examination a -yellowish-white transverse line may be seen at the epiphyseal junction -of the ribs, and frequently some subperiosteal hemorrhage. Beading of -this character has been reported by Ingier also in the "snuffles" of -hogs and as the result of trauma. A similar enlargement of the chondral -junctions of the sternum may be found on examining its posterior -surface. - -_The joints_ of the body always show some changes. The epiphyses are -enlarged to a variable degree, resembling the epiphyses typical of human -rickets. As in infants, this change is met with most commonly at the -wrist joint, involving the ulna and the radius. The knee-joint is -likewise often involved, especially the ends of the tibia; the elbow, -ankle, and the shoulder may also show an articular swelling of the -bones. About these joints hemorrhages in the subcutaneous tissues may be -seen, or edema extending along the extremities. Not infrequently a -fracture of one of the long bones is found, which may or may not have -been diagnosed during life. The common site of fracture is the lower -part of the tibia or fibula. Much more frequent than fractures are -separations of the epiphyses, which long since have been recognized as -typical of infantile scurvy. Even gentle handling in the course of -performing the necropsy may occasion a lesion of this kind--of the tibia -at the knee, of the radius or ulna at the wrist, or indeed at any of the -epiphyseal junctions. The infracted ends occasionally may be seen held -insecurely by a delicate band of periosteum. The shafts of the bones are -brittle, rarefied, and easily broken. - -On opening _the chest_, slight hemorrhages may be noted in the -pericardium and in the visceral and costal pleuræ. The heart is -frequently enlarged, and the pericardial sac contains an excess of -serum; the right ventricle, however, is not found disproportionately -hypertrophied. Pneumonia is met with very frequently and constitutes a -common terminal infection. - -On opening _the abdomen_ we may note subperitoneal hemorrhages of the -muscular wall or of the coils of intestine. The liver and spleen are -generally normal, as is the pancreas. The kidney frequently shows minute -hemorrhages beneath the capsule and on section. - -_The adrenals_ not infrequently are large. This fact was first brought -out by Rondoni and Montagnani, and is of added interest in view of its -confirmation by McCarrison as well as by LaMer and Campbell. Its -significance is discussed at length in the consideration of the adrenal -gland in human scurvy. In view of the fact that fasting leads to a -similar hypertrophy, and that guinea-pig scurvy frequently is -complicated by fasting, these observations should be extended. In all -investigations of this kind, bacterial cultures should be taken of the -adrenals, or other organs, to be certain that there is no complicating -infection. - -There have been no reports as to the effect of scurvy on the size of the -testicles, ovary, thymus, thyroid or parathyroid glands in the -guinea-pig, such as have been made by McCarrison in relation to avian -polyneuritis. - -_The alimentary tract_ occasionally shows macroscopic changes similar to -the lesions found in man. The entire canal is frequently very empty, -especially the stomach and the small intestine, due to the lack of -appetite for some days previous to death. In the stomach we may find -areas of congestion or numerous small superficial ulcers surrounded by -congestion and covered with mucus; occasionally these ulcers are -somewhat larger and deeper. The larger ulcers are more frequently -situated in the first part of the duodenum, often proximal to the -papilla of Vater. Holst and Froelich described this lesion in one of -their early communications. More common than ulceration of the duodenum -is a diffuse congestion of its upper part. This lesion is of note -because it has been described frequently in the protocols of human -necropsies, and is found in beriberi, in avian polyneuritis, and in -pellagra in man. Its significance is unknown, and has indeed never been -discussed. - -Lower down in the bowel there are occasionally areas of congestion and -ulceration, but no section seems particularly predisposed to these -lesions. The contents of the bowel, especially of the cæcum, as -mentioned above, depend more on the character of the food than on the -existence of scurvy. If the diet has consisted of milk and oats, the -cæcum will be found full and perhaps impacted, whereas if hay and oats -have been fed, the cæcum will be less full and its contents semisolid. - -In view of the fact that many of the animals have taken very little food -for some days previous to their death, it will be well to describe -briefly the macroscopic picture of _simple starvation_ in guinea-pigs. -When guinea-pigs are given only water they live about one week; if -orange juice is added to this water diet they succumb a little later to -starvation. Under all these conditions the striking pathologic -change--absent in scurvy--is edema. It is true that the limbs may show -slight edema in scurvy, and that the pericardial and the pleural sacs, -and even the peritoneal cavity, occasionally contain a small quantity of -serum, but it is comparatively an insignificant amount. Moreover it is -difficult to decide to what extent this edema is due to scurvy, and to -what extent to starvation. In typical starvation, on the other hand, -such as occurs on the limited diets enumerated above, we find marked -subcutaneous edema, sometimes a true anasarca, and frequently also -ascites. We are reminded of the "war edema" and its frequent association -with starvation. Another distinction between the two conditions is the -fact that the marrow in starvation is yellow and not red as in scurvy. -In passing, it may be mentioned that the ascites was greater when orange -juice had been given than where the animal received only water. - -In perusing the literature but one study has been noted on _the effect -of a scorbutic diet on the foetus_. This investigation was carried out -on a large series of guinea-pigs by Ingier (1915). The following -comprise her conclusions: - -"1. Pronounced cases of Barlow's disease may be produced in the foetus -as early as ten to fifteen days after the commencement of dieting -pregnant guinea-pigs with oats and water. There are wide individual -variations. The scorbutic changes in the skeleton are greatest in the -earlier embryonic stages. The foetuses of that period, with -practically no exceptions, die and show marked traces of impeded growth. - -"2. Foetuses from the later period of pregnancy are born alive, and -apparently fully developed, with comparatively slight changes in the -osseous system. - -"3. Even a short extension of the period of extra-uterine dieting on -milk from scorbutic mothers, and later on oats and water, is sufficient -to change the latent scurvy into a highly-pronounced case. - -"4. The foetus cannot be kept alive longer than the adult animal, -about twenty-eight days, either by intra-uterine dieting alone or by -combined intra- and extra-uterine dieting. - -"5. The mothers show signs of the disease at an early period and are -more severely attacked than non-pregnant animals. Death also occurs -comparatively often in the first period of gestation." - -In these experiments intra-uterine fractures, premature births and -still-born litters are frequently mentioned. This suggests naturally an -inquiry as to whether similar occurrences have been observed in human -scurvy. In considering the pathogenesis of human scurvy, we have -remarked on the meagreness of the data on this most interesting aspect -of this disorder. In view of the similarity between human and guinea-pig -scurvy, we should expect not only miscarriages and still-births to -result, but cases of congenital scurvy, especially of the latent or -rudimentary type. - -=Scurvy Has Been Induced Also in the Monkey.=--The most extensive -investigation of this kind is that of Hart and Lessing, who brought -about scurvy in several young Macaci Rhesi which had been fed for some -months on boiled condensed milk with the addition of cooked rice and -pig-nuts. Typical scurvy resulted in all but one instance, and in this -case an old animal was used and a different pathological picture -developed. These experiments require brief reviewing, as the clinical -signs and gross pathology in monkeys differ somewhat from those -encountered in guinea-pigs, and particularly as these distinctions -render scurvy in monkeys and in infants practically identical. - -Apart from general listlessness and lack of activity, the first sign is -hemorrhage of the gums, the characteristic sign of infantile scurvy. -This is stated to be constant; in the guinea-pig it is most exceptional. -Another sign characteristic of infantile scurvy is the subperiosteal -hemorrhage, which in the guinea-pig may be found as a small effusion -near one of the larger joints or the costochondral junctions, but in the -monkey consists of large effusions, similar to those described by -Barlow. Subperiosteal hemorrhages of the cranial bones were constantly -seen, and not infrequently involvement of the scapula and of the -maxilla. Hemorrhage into the orbit leading to exophthalmos and to -hemorrhagic discoloration of the upper lid--a lesion not infrequent in -human scurvy--is also described; in guinea-pigs we have met with -exophthalmos only in two instances. In all other respects scurvy in the -monkey resembles that in the guinea-pig, even to the extent of the -scorbutic rosary of the lower true ribs. Hart and Lessing describe the -presence of the "white line" of Fraenkel, which is referred to at length -in treating of the symptomatology of human scurvy. This is a shadow, -seen by means of the X-ray, traversing the long bones near their -epiphyses--a definite "shadow band" associated with a narrow light zone -lying just beneath it. This "white line" has been noted likewise by -Talbot, Dodd and Peterson in the scurvy of monkeys. - -=Microscopic Pathology.=--Turning to the microscopic pathology, we find -that the changes are similar to those described elsewhere in connection -with human scurvy. It will be unnecessary, therefore, to give more than -a general survey of the typical alterations. Little has been added to -the description of lesions so carefully depicted in the first report of -Holst and Froelich (1907). The bone marrow at the ends of the diaphyses -in proximity to the epiphyseal junction loses its normal lymphoid -character and is replaced by a reticular or fibrillated substance, the -so-called "framework" marrow (Geruestmark of Schoedel and Nauwerk) -containing a homogeneous mucoid tissue and only a few osteoblasts and -marrow cells. The number of blood-vessels is considerably reduced and -fresh hemorrhage or blood pigment is frequently seen. The osseous tissue -itself shows marked changes, corresponding to the rarification and -brittleness noted on gross examination. The osseous trabeculæ are fewer -in number and those which remain are slender and irregular, and -frequently appear as isolated islets. The cortical substance also -becomes very thin. There are marked alterations in the intermediate -cartilages, especially of the ribs.[37] Instead of the cells being -arranged in orderly rows, they are irregularly placed, and frequently -greatly reduced in size and number. The bone trabeculæ on which they -abut are not well formed or of equal length, and do not present an even -and transverse plane, but are misshapen, small, so that the line of -junction with the cartilage is zigzag. In cases of marked scurvy the -junction may be entirely disorganized and deformed, showing fractures of -the rarefied bone and hemorrhages in the neighborhood. This leads -frequently to a macroscopic deformity of bone, a bulging of the surface -at the costochondral junction--the scorbutic "beading" or "rosary" of -the ribs. Recently Delf and Tozer have described these changes, -classifying them as those occurring in "incipient," "definite," "acute," -"chronic definite," and "chronic acute" scurvy. Fig. 9 shows these types -in diagrammatic form. In this figure we see how varied may be the -manifestations of this nutritional disorder, according to whether it has -existed for a shorter or a longer time; in some instances the picture is -very puzzling. The "incipient scurvy" corresponds to what we have termed -clinically "latent scurvy" in infants, a condition which cannot be -diagnosed and is manifested merely by a faulty nutrition which responds -promptly to the addition of an antiscorbutic to the diet. There have -been no histologic examinations in man at this incipient stage, but we -may infer that they are similar to the bony changes found in the -guinea-pig. When the scurvy has become chronic in an animal which has -lived for months on a quota of antiscorbutic food sufficient to preserve -life but insufficient to prevent the development of scurvy, we find a -microscopic picture at the costochondral junction differing widely from -that seen in the acute stage. Not only are the columns of cartilage -cells represented merely by misshapen vestiges, but an ossified band -(Fig. 9) is seen at the junction. It is probable that this is -frequently the cause of the marked cessation of growth which has been -described in connection with this type of scurvy in infants. Delf and -Tozer interpret this ossified band at the junction as "an attempt to -strengthen the junction in an abnormal manner, the normal process having -broken down." If the animal is again deprived of antiscorbutic food the -ossified band breaks down, the junction becomes deformed and -disorganized, and a condition of "chronic scurvy (acute)" is stated to -have developed. - -[37] These changes are not found in every specimen, so that in order to -be able to exclude scurvy definitely, it is necessary to examine a -considerable number of ribs; several may be normal, only one or two -showing the characteristic microscopic changes. - -[Illustration: FIG. 9.--Diagrammatic representation of guinea-pig scurvy -(copied from Delf and Tozer by the courtesy of the Cambridge Press). - -1. Diagram of normal rib-junction. - -2. Diagram of rib-junction to illustrate "Incipient Scurvy." This -rib-junction is very nearly normal, but shows what may be regarded as -the first recognizable signs of the onset of the disease; these are: -(_a_) An appearance of general abnormality (when compared with the -normal). (_b_) Unevenness of the junction and slight disorganization of -the rows of cartilage cells. (_c_) Shortening of the length of the rows -of cartilage cells. (_d_) Shortening, and decrease in number of the -trabeculæ. (_e_) Increased amount of blood in the marrow cavity. - -3. Diagram of rib-junction to illustrate "Definite Scurvy." Histological -signs vary considerably in these cases (according to the severity of the -disease), and may approach in appearance those characteristic of the -"Acute" condition. The rows of cartilage cells may be almost normal, but -are more often noticeably shortened and usually somewhat disorganized or -arranged in circular groups. The trabeculæ are usually about half the -normal length and have a truncated appearance. The junction as a whole -may present an uneven, slightly disorganized appearance and there is -sometimes a certain amount of macroscopic deformity. - -4. Diagram of rib-junction to illustrate "Acute Scurvy." In these cases -the junction and rows of cartilage cells are often completely -disorganized, causing a marked macroscopic deformity of the bone. The -bone of the shaft is frequently fractured. The marrow is no longer in -contact with the edge of the junction and the space is filled with a -mass of connective tissue; this is very characteristic in cases of -fracture. A condition in which the trabeculæ have almost disappeared and -the rows are much shortened is also found in "Acute Scurvy," in those -ribs in which no fracture of the shaft has occurred; usually, however, -there is little or no ossification across the junction. There is -frequently hemorrhage into the marrow cavity. - -Diagrams 5 and 6 illustrate types of "Chronic Scurvy." - -5. May be described as "Chronic Definite Scurvy." The rows are much -shortened but not disorganized and an ossified band extends across the -junction. - -6. May be described as "Acute Chronic Scurvy." The junction is deformed, -and the rows are very disorganized; the trabeculæ have disappeared and -an ossified band extends across the junction. There is no connective -tissue to be seen and no existing, or recent, fracture.] - -It has been noted by many investigators that _changes in the teeth_ take -place in the course of scurvy. They become somewhat yellow and lose -their glistening appearance, and occasionally break off. The molars -commonly become loosened, so that they can readily be removed from their -alveolar sockets; less frequently this is true of the incisors. Until -recently, however, this subject has not been studied in detail, and no -significant histologic changes in the teeth have been described. Jackson -and Moore showed that with marked changes in the teeth there was often -"great dilatation of the veins in the pulp attended by more or less -hemorrhage into the pulp," and that "in guinea-pigs fed on oats and hay -there was almost complete necrosis of the pulp of the incisor teeth, -also more or less necrosis in the pulp of the molars." - -Recently an intensive study of this subject has been made by Zilva and -Wells, which is of special interest because it describes the first -beginnings of these lesions, and particularly because we have no -knowledge whatsoever of the dental changes which occur in human scurvy. -These investigators found a fibroid degeneration of the pulp of the -teeth, a pulpar fibrosis. "It is clear at once," they write, "and it is -an important fact that no trace of cellular organization, no trace of -cell nuclei, no trace of interstitial cement substances can be found -anywhere. Nerves, cells, blood-vessels, and odontoblasts have all shared -the process of fibrication and are no longer recognizable." These -radical changes in the teeth, brought about by a deficiency of -antiscorbutic vitamine, were demonstrated not only in guinea-pigs but -also in monkeys. In some instances they were found where a histologic -examination of the costochondral junctions showed nothing abnormal. -"Profound changes were recorded where the scorbutic changes during life -were so slight as to be almost unrecognizable," and, they continue, "the -mildest degree of scurvy which could just be discovered at the -postmortem examination produced well-defined changes in the structure of -the teeth." If this work is confirmed, we must consider the teeth as one -of the first tissues of the body to be affected by scurvy. The authors -quite rightly raise the question whether the teeth of young children may -not likewise be injured by a deficiency of antiscorbutic vitamine, -whether this may not play a rôle in the dental caries so prevalent -among civilized communities. It is evident, they state, that such -transient conditions of infantile scurvy as have been described by Hess -as "subacute" or "latent" scurvy, may occur more often than is usually -suspected, and may reasonably be expected to influence dentition. It -seems quite possible that the caries of the permanent teeth is due not -only to infantile rickets but also to infantile scurvy. - -Besides the typical histologic changes in the bones there are -alterations in _other organs_ which require mention. All investigators -have found a degeneration of the muscles, showing a loss of their -striations, swelling of the fibres, and the presence of -irregularly-distributed vacuoles and granules. The interstitial tissue -frequently is permeated with edema, as we should expect from gross -appearances. Holst and Froelich have reported a fatty degeneration of -the heart muscle, as well as of the epithelium of the mucous membrane of -the glands of the stomach and of the intestine. Hart and Lessing, in -their protocols of necropsies on monkeys, describe an interesting lesion -associated with the degenerated muscle fibres--a collection of granules -staining deep blue with hæmatoxylin and dissolving on the addition of -acid. These granules, interpreted as being composed of calcium, were -found in the muscles of the limbs, of the tongue, and in the heart. It -is reasonable to attribute their formation to an absorption of bone -throughout the body. Similar calcium deposits were seen frequently in -the adrenal glands, in their cortex, or at the border of the cortex and -medulla. This lesion gains special interest in view of the calcium -deposits described so frequently in connection with mercurial poisoning, -more particularly as the symptoms of scurvy and of this toxic condition -have marked clinical resemblances. - -There has been but little histologic investigation of the _nerves_ in -experimental scurvy. In fact, the only systematic study of the kind is -that of Holst and Froelich, whose attention was drawn to this field in -an attempt to solve the relationship between scurvy and ship beriberi. -These writers found a true Wallerian polyneuritis in only two pigs, one -of which had been fed on wheat bread made with yeast, and the other on -decorticated barley. In many instances, however, there was extensive -degeneration of the axis cylinders without degeneration of the sheaths. -They do not, however, attribute great importance to these changes, as -the same lesions were found in the nerves of animals fed on cabbage and -fresh potatoes. In view of the confusing reports on the nerves of birds -in experiments on polyneuritis, one cannot be too careful in drawing -conclusions from histologic studies of this kind. - -In the study by Jackson and Moore on experimental scurvy in guinea-pigs, -the histology of _the blood-vessels_ is carefully considered. "Marked -thinning of the wall" was found and depicted; "the wall as a whole had -partially melted away, leaving few traces." These parts of the wall -contained many small round bodies resembling cocci, which were stained a -deep blue by the Wright and the Giemsa methods. These bodies were -present also in the lumen of the vessel and in the inner layers of the -more normal portions of the wall. In addition to such changes in the -veins, "lesions having the shape, location, and characteristics of -infarcts, were found in the ends of the diaphyses of the long bones." As -a result of this pathologic picture the authors are of the opinion that -they may have been dealing with a mild infection. This is quite -possible, as scurvy tends to render the tissues less resistant to the -entrance of bacteria. We believe, however, that even if such were the -case, the phenomenon must be regarded merely as secondary in its -relation to the pathogenesis of scurvy. - -Following the study on the pathology of experimental scurvy, Jackson and -Moore undertook to determine primarily whether the small stained bodies -seen in the sections of the scurvy lesions were bacteria. This -investigation has been cited frequently as presenting cogent evidence in -favor of the _infectious nature of scurvy_, so that it will be necessary -to consider it fully; the general question of whether scurvy is a -bacterial infection is discussed under the consideration of etiology. - -As is well known, Morpurgo, a generation ago, claimed to have produced -rhachitic lesions in young rats by means of artificial infection with a -gram-positive diplococcus. Pappenheimer brought about similar lesions in -rats by the injection of a suspension of bone marrow from a rhachitic -animal. Koch injected a streptococcus longus intravenously into young -dogs, occasioning gross bony changes of the epiphyses and costochondral -junctions, and microscopic changes resembling scurvy--an irregular line -of ossification and "a framework" marrow, which, however, showed regions -of osteoid. Jackson and Moody were able to isolate from the crushed -tissue of their guinea-pigs "a diplococcus of low virulence with a -tendency to form chains and produce green (color) on blood agar." Pure -strains of these organisms inoculated into the circulation of -guinea-pigs and rabbits, living under ordinary conditions (a mixed diet -consisting of green vegetables, hay and oats), gave rise in most -instances to hemorrhagic and other lesions in the bones, joints, -muscles, lymph-glands or gums. Hemorrhages were found beneath the -periosteum in the region of the lower incisor teeth and the acetabulum -and ribs. These results are far from constituting evidence in favor of -the microbic origin of scurvy. They show merely that the tissues of -scorbutic animals frequently harbor bacteria, and that injections of -these bacteria will bring about hemorrhages which may be subperiosteal -in character. They are open to the specific criticism that scurvy was -produced readily in the rabbit, an animal which otherwise does not -develop scurvy, and, furthermore, they differ from feeding experiments -in inciting scurvy notwithstanding the fact that the animals were -receiving an antiscorbutic diet (green vegetables). Cultures of the -hearts' blood of the affected animals were sterile in every instance; a -result obtained likewise by Holst and Froelich. - -Further studies of this kind should be carried out and should include -cultures of the blood and tissues of guinea-pigs in the various stages -of scurvy, especially the early stage. In addition, a histologic study -should be made of the bones of animals injected with bacteria -(preferably streptococci), in order to ascertain whether notwithstanding -an unrestricted diet, typical lesions can be produced by this means. - -For further details of the pathology of scurvy, the reader is referred -to the chapter on human pathology. - -=Symptoms.=--Let us consider the symptomatology of guinea-pig scurvy. In -the course of an observation of many hundreds of animals we have been -struck by the striking uniformity of the signs and symptoms. The animals -made use of were almost invariably of moderate size, weighing from 200 -to 300 grams. Where heavier pigs were employed the disease progressed -less rapidly, but the signs were the same; they were, however, more -difficult to elicit, owing to the subcutaneous fat. Most of the animals -were on a diet of hay, oats and water _ad libitum_, but there was no -variation in symptoms where fat and fat-soluble vitamine were supplied -by an addition of egg yolk or of cod liver oil, or where egg albumen was -fed to render the protein adequate, or where the inorganic salts were -supplemented by additions of sodium or calcium chloride. - -There is a variability in the sign which signalizes the onset of the -disorder--sometimes it consists of a flattening of the weight curve, at -others of an inordinate excitability of the animal, or frequently of a -tender joint, generally a wrist. The joints almost invariably become -tender early in the disease, causing the animal to wince and cry when it -is examined. Accompanying this tenderness there is often slight swelling -due to edema, or perhaps some hemorrhage, which alters the sharp, -clean-cut contour of the joint. This edema may extend upward along the -tendon sheaths. Soon the animal becomes lethargic rather than nervously -active, and may look ill, as manifested by a roughness of its coat and -its unnatural posture. Frequently it sits on three legs with the tender -hind leg drawn upward and outward so as to escape pressure--a posture -termed by Chick, Hume and Skelton (1918, 2) "_the scurvy position_," and -indicative of hemorrhage into the joints or muscles. At times it lies -curled up, with the side of its face resting on the floor, as if to -support its painful or sensitive jaw; this they have termed the -"_face-ache position_." The two diagnostic signs, however, are the -hemorrhages about the joints and the loosening of the teeth. The -diagnosis frequently can be established by the twelfth to the fourteenth -day; the earliest diagnosis was made on the eighth day. Hemorrhages -appear somewhat later than tenderness, and are situated at the joints, -most frequently at the knee, which may be markedly swollen and show a -bluish or reddish discoloration, extending upward or downward for some -distance. Other joints are often involved, frequently the wrist, the -ankle or the shoulder. In other cases hemorrhages into the muscles are -noted, especially of the leg or of the thigh, and later, especially -toward the end, hemorrhages from the bowel. Fractures or separations of -the epiphyses may be found on examination or may be occasioned by the -physical examination. A frequent site of this lesion is at the wrist or -at the knee, involving the head of the tibia or the lower end of the -femur. These fractures knit rapidly when an antiscorbutic is given, but -result at times in deformity. - -_Loosening of the teeth_ is another typical sign. It is, however, one -which does not appear early and is somewhat difficult to elicit. The -molar teeth are generally involved, especially those of the upper jaw, -which may be so completely separated from their alveolar sockets that -they can readily be removed by forceps. It is, however, impossible to -examine the molar teeth satisfactorily during life. Far less frequently -an incisor tooth becomes loosened; more often it loses its glistening -appearance and looks dull and yellowish. Occasionally an incisor tooth -fractures. The gums are rarely altered sufficiently to aid diagnosis; -not infrequently they are congested or bluish, rarely hemorrhagic, and -never ulcerous or spongy. This is the chief difference between the -symptomatology of scurvy in the guinea-pig and in man, and probably is -the result of lesser susceptibility of the former to infection by -pyogenic bacteria. In general, however, the disorder in the guinea-pig -bears a closer analogy to infantile than to adult scurvy; due to the -fact, possibly, that young pigs are generally used for the experiments. - -A sign of great interest, although not of diagnostic importance, is the -_"beading" of the ribs_ noted by many observers, and emphasized by -Jackson and Moore. It has been described also in monkeys by Hart and -Lessing. This is an enlargement or swelling of the costochondral -junctions of the ribs, especially of the lower true ribs. It corresponds -clinically to the "beading" and the "rosary" so characteristic of -infantile rickets and mistakenly termed the "rhachitic rosary." As -pointed out, in discussing the symptomatology and pathology of human -scurvy, this sign must be regarded as truly scorbutic in animals as well -as in infants. The "rosary" is difficult to palpate in pigs which have -considerable subcutaneous tissue; in thin animals, however, its course -can be followed, the gradual development and subsequent disappearance. -In this connection the enlargement of the epiphyses must be mentioned, -another sign supposed to be characteristic of rickets in infants. Marked -swelling of the wrists is frequently encountered in guinea-pigs -suffering from scurvy--a bony enlargement involving the lower epiphyses -of the ulna and of the radius. This is met with far more commonly in -chronic scurvy than in the usual acute case. Where the disorder has -existed for a long period, these bony knobs may persist indefinitely, -constituting the sole residual sign of a former scorbutic condition. - -The relation of _loss of weight_ to the development of the scurvy -requires consideration. In experiments carried out on rats to test the -diets in respect to the water-soluble and the fat-soluble vitamines, the -weight curve is used as the main criterion to judge whether the -foodstuff is adequate. In guinea-pigs we cannot employ the weight curve -as a criterion. Not infrequently an animal develops scurvy, and -nevertheless does not lose in weight, but even gains slowly and -steadily. This occurs when the appetite remains good, and the dietary is -complete except for antiscorbutic vitamine. The same holds true for -human scurvy, as we have noted in connection with the symptomatology. We -have attempted to make up for this defect by adding to the charts a -curve representing the clinical course (Fig. 10). Although this curve is -computed on an empirical basis, it gives a comparatively true picture of -the disease and is far more exact than attempting to portray the disease -by means of a weight curve.[38] Indeed, when we rely on the latter -method it is impossible frequently to illustrate graphically the -reaction of guinea-pigs to various influences. Another disadvantage of -the weight curve is that it is influenced by factors having no direct -relation to scurvy, especially infections of various types which retard -the gain. - -[38] A maximum count of 35 was formulated, representing the highest -degree of clinical scurvy. This includes three grades of beading of the -ribs, four of tenderness of each knee and wrist joint, and four of -swelling of each of these joints. It is apparent from the clinical curve -(Fig. 10) that an animal may have developed a marked degree of scurvy -(20 points), and gained rather than have lost in weight. - -[Illustration: FIG. 10.--Hay, oats, and water _ad libitum_ during period -I resulted in a lack of gain in weight, and in a development of scurvy. -During period II, 1.5 c.c. of orange juice were given daily, and as will -be seen there was a marked gain in weight and disappearance of the -scorbutic signs, although, as is generally the case, they continue to -develop for a short while after an antiscorbutic is given. When the -orange juice was discontinued in the third period, the weight once more -fell and the scurvy redeveloped. The broken line represents the course -of the scurvy, and is a composite formed on the basis of the aggregate -of the scorbutic signs. Each square represents a 2-day interval.] - -Guinea-pigs generally die of scurvy after having lost about one-third of -their body weight; occasionally the loss is greater, reaching almost 50 -per cent. This loss is due partly to the scorbutic condition, but to a -greater extent to starvation occasioned by a marked lack of appetite. In -this connection it may be noted that guinea-pigs frequently lose for a -few days following the addition of an antiscorbutic to the dietary (Fig. -11). This reaction is evident from a perusal of the weight charts of -other investigators, and occurs likewise in human scurvy. This loss is -accompanied, as Gerstenberger has pointed out, by diuresis, which may be -so marked that it is evident to the casual observation of those caring -for the animals. - -[Illustration: FIG. 11.--These guinea-pigs developed scurvy in spite of -receiving a large quantity of the water in which young carrots had been -cooked for only 20 minutes. It will be noted, however, that although the -pigs developed scurvy they did not lose weight, as is usually the case. -After they had developed definite scurvy they were given in addition the -equivalent of 80 c.c. of a dried milk prepared by being heated to about -116° C. for a few seconds. The addition of this milk to the diet cured -the scurvy, showing that it had largely retained its antiscorbutic -vitamine.] - -Exophthalmos may be mentioned again in this connection as a very rare -sign of guinea-pig scurvy. Hæmaturia also occurs at times; it is not -known how frequently it is present, whether it is an early manifestation -in the guinea-pig as in the infant, or whether the source of the blood -is the kidney or the bladder. - -The superficial lymphatic glands are frequently palpable in scurvy, -especially those in the inguinal region. This sign is emphasized by some -pathologists. It has seemed to us attributable less to the nutritional -condition than to the infections which so frequently complicate the -disorder. - -According to Jackson and Moore a rise of temperature does not accompany -scurvy in the guinea-pig. As the result of an examination of nine -guinea-pigs they conclude that "experimental scurvy is a non-febrile -disease in the majority of affected animals." Nor did they find a -leucocytosis, the average leucocyte count of eight scorbutic pigs being -about 8000. - -As the data are meagre, a consideration of the chemical alterations -associated with the scurvy of guinea-pigs and monkeys will be taken up -in conjunction with the metabolism of human scurvy. The therapy of -animal scurvy will also be deferred (chapter VI), as the reaction to -dietetic measures is practically the same in man and in animals. In -concluding this chapter we would call attention to the following -interesting statement contained in the recent paper by Delf and Tozer: -"In other experiments, however, where a liberal supply of an -antiscorbutic was given and where the fat-soluble A growth factor was -known to be deficient, the resulting histological changes in the -rib-junctions of the animals examined were found to resemble closely -those of 'Definite' or of 'Definite Chronic' scurvy. In these test cases -the antiscorbutic chosen was, we believed, deficient in the fat-soluble -A growth factor (for example, orange juice). This fact is mentioned -because in the case of an animal not receiving an adequate supply of -fat-soluble A the resulting changes in the junctions are not dissimilar -from, and are likely to be confused with, those caused by scurvy alone." -If this observation is confirmed, it emphasizes the necessity in -nutritional experiments, of constructing a dietary which is complete in -every respect except the one under investigation; it also suggests the -development of new pathologic entities in relation to other nutritional -disorders resulting from a lack of the accessory food factors. - - - - -CHAPTER VI - -ANTISCORBUTIC FOODS - - -=Historical Review.=[39]--It is impossible to state when and how the -knowledge of the value of antiscorbutic foodstuffs came to be -appreciated. It is probable that the potency of herbs and fruits in -scurvy was known empirically to individuals and groups of people long -before the fact gained general recognition. A most interesting history -of antiscorbutics is given in the excellent work of Hirsch and in our -great classic on scurvy by Lind. The first realization of the value of -lemons and oranges seems to have been the result of a chance discovery. -Budd tells us that in the sixteenth century sailors of a Dutch sailing -vessel laden with these fruits were attacked with scurvy, and that, when -they partook of the lemons and oranges in the cargo, a miraculous cure -resulted. He narrates also the following striking incident, which is -mentioned likewise by Lind: - -[39] It is of interest that John Hall, the son-in-law of Shakespeare, -and a prominent physician of Warwickshire, was one of the first to urge -the use of antiscorbutics. In a quaint work entitled, "Select -Observations on English Bodies, or Cures both Empericall and Historical" -(1657 London), he describes how he cured scurvy by means of brewing a -beer or ale from "Scorbutick hearbs, _viz._: scurvy grass, water-cresses -and brook lime." This book, which ran through at least two editions, has -not achieved the popularity of the works of the father-in-law. - -In the year 1600 four sailing vessels left England for the East Indies. -The sailors on three of these ships did not receive lime juice, whereas -those on the fourth received their daily quota. The men of the first -three ships suffered severely from scurvy, but those on the fourth -escaped. - -In an excellent work on "Scorvey," published in 1685, Harvey wrote: -"Wherefore most acids, especially spirit of salt marine, juice of -sorrel, limons, citrons, etc., are so deservedly extolled in some -scorbutic distempers and seconded with good success." Thus we see that -even at this early date it was taken for granted that citrous fruits -possessed virtue in curing scurvy. Bachstrom (Observationes circa -Scorbutum, 1734) evidently was well-acquainted with the antiscorbutic -value of scurvy grass, and relates the story of a sailor severely -disabled from scurvy who was put ashore to perish on Greenland, and -crawled on the ground, grazed on scurvy grass like a beast of the field, -and was able to return home perfectly recovered. (Cited from Lind.) - -The credit for forcing a general acceptance of the antiscorbutic value -of fresh food belongs to Lind. He did not, however, have an easy task, -and in 1747, in order to convince those who still were skeptical, he -resorted to an experiment on human beings. Twelve patients in his -hospital were given the same diet, except that some received sea-water -in addition to their dietary, others vinegar, or elixir of sulphuric -acid, or a daily portion of cider, or oranges and one lemon daily. The -last two groups, as we should expect, recovered quickly; one man who -received cider improved, but in no other case was any alleviation noted. - -Lind extols the value of lemons and oranges, of berries, of sour -cabbage, of cider, and of all fresh fruits and vegetables. In spite of -the fact, however, that Lind's teaching was based on an experience with -thousands of patients suffering from scurvy in the naval hospital, his -ideas did not take root. It required an event which came directly under -the official eye to bring about radical changes in the diet of the -sailors. In 1795 the English Fleet suffered from a severe epidemic of -scurvy, which was finally controlled by giving the sailors fresh -vegetables and fruit. This therapeutic result was so convincing that -thenceforth a daily ration of lime juice was ordered for the sailors and -a regular issue provided for the navy. This marks the cessation of -scurvy as a scourge of the British navy. From this time the disease -appeared only sporadically. The sharp decrease in the incidence can be -appreciated by Budd's statement that 1457 cases of scurvy were admitted -to the Royal Naval Hospital in 1780, whereas in 1810 an English -physician reported that in the seven preceding years he had not treated -a single patient in this hospital suffering from scurvy. In another -marine hospital, between the years 1806 and 1810, only two cases of -scurvy were admitted. - -Nothing was done for the British merchant service until over half a -century later, although scurvy continued to make its appearance among -the sailors with varying severity. Smith states in the article on this -subject in Allbutt's System of Medicine: "In 1864 it was pointed out by -Doctor Barnes that during the twelve years following 1851, 1058 cases of -scurvy had been admitted into the hospital ship _Dreadnought_." In 1854 -a law was passed requiring every vessel to carry an adequate supply of -lime juice. This law, however, failed in effect, due to the fact that a -large part of the lime juice was adulterated. A new shipping-act was -passed, therefore, in 1867, with the object of preventing adulterations, -at the same time increasing the daily quota for each seaman from half an -ounce to one ounce. - -It may be of interest to add a few words concerning certain -antiscorbutics which have been under discussion or recognized for so -many years that they have acquired an historical aspect. One of these -foodstuffs is sauerkraut, which was recognized by Lind in 1772 as having -particular potency in this disease. It is interesting to note, in this -connection, that this writer appreciated the close relationship of -acidity to antiscorbutic virtue. "One quality," he writes, "entering the -most perfect antiscorbutic composition is a vegetable accescency." He -prized sauerkraut for its inherent value, and particularly, because he -found that "sour cabbage will keep for an East-India voyage." - -The famous navigator Cook, whose voyages were remarkable for the freedom -from illness which his sailors enjoyed and the absence of scurvy, always -kept a large supply of sauerkraut on hand. It was believed by many that -the immunity of the Dutch seamen to scurvy was due to their large -consumption of this vegetable. As the result of this empirical -knowledge, the English navy in 1780 introduced the use of sauerkraut -into its ration. As just noted, however, this antiscorbutic was -supplanted some few years later by an issue of lime juice. - -It is common knowledge that outbreaks of scurvy follow closely upon a -failure of the potato crop. This has been particularly the case in -Ireland, where it was especially evident in relation to the great -epidemic of scurvy in 1847. Holst and Froelich inform us that "all -scurvy epidemics in Norway in the nineteenth and beginning of this -century followed failure of the potato crop." Nor is this danger past. -In an article entitled "The Rôle of Antiscorbutics in Our Dietary," the -author recently reported that the partial failure of the potato crop in -the eastern part of the United States led to the development of scurvy -in numerous institutions, in one of which over 200 cases of definite -scurvy developed in the spring (1916). - -The occurrence of scurvy in the navy and on sailing vessels has been -associated in the minds of many with the large amounts of salted meat -which necessarily was included in the dietary. It was evident that meat -that was salted had no antiscorbutic value, but the query has been -raised whether eating a considerable amount of salted meat did not -induce scurvy. Lind mentions "flesh long salted" as leading to the -development of scurvy. The question of the value of meat as an -antiscorbutic is of importance at the present time, chiefly in -connection with Polar expeditions and army rations. As the result of an -outbreak of scurvy in the Polar expedition of 1875-6, a British Arctic -Survey Committee was appointed to make an investigation. In 1877 it -reported that "although the scurvy was due to the absence of lime juice -from the sledge dietaries, meat in large amounts is able to prevent the -disease." Stefánsson also emphasized the value of meat in preventing -scurvy in the Polar regions. In his expeditions he has found that raw -meat, if taken in sufficient quantity, is able to afford complete -protection. Jackson, who lived for some years among the Samoyeds, tells -us that this tribe, owing to the fact that they consumed considerable -reindeer meat, never suffered from scurvy in spite of the fact that they -ate no vegetables or fresh fruit during the winter. - -The following account, a personal communication from Dr. Harrison J. -Hunt, who spent four years in the Arctic regions, is of interest in this -connection: - -"For some four years I was with the Smith Sound Eskimos, on the -northwest coast of Greenland. These people get nothing but animal food -normally, and have lived that way for many generations, yet are healthy, -of good physique, and are normal in other ways. Scurvy was unknown to -them as far as I could ascertain; certainly there was none while I was -among them. Much of their meat is eaten raw, and the rest only partly -cooked; that is, 'rare done.' - -"Whalers who were accustomed to winter in Hudson Bay practically always -had scurvy in the crew. It was common knowledge among the captains that -fresh meat was curative of scurvy, and it was their practice to obtain -meat from the Eskimos whenever possible for that purpose. The last -English expeditions to the South Polar regions were afflicted with -scurvy which was entirely and quickly eradicated by the use of fresh -seal meat in the place of salt meats and canned foods. They do not state -that this meat was eaten raw or even rare cooked. On the Danish coast of -Greenland, during seasons poor in game, scurvy is quite common, but the -natives there live largely on breadstuffs (very coarse rye bread). -Personally, during my four years in the Arctic, I took no fresh -vegetables whatever, or other commonly-called antiscorbutics, relying -solely on rare or raw meat. I never was stronger or more healthy in my -life. I did have dried fruits and vegetables, and usually plenty of -fresh bread. Usually the Eskimos eat their raw meat in a frozen -condition, and I can attest that it is extremely palatable in that -condition." - -We do not wish to discuss, in this place, the value of meat as an -antiscorbutic; in passing, however, it may be said that, as in the case -of the other antiscorbutics, its efficacy will depend largely upon the -amount consumed. The British Mesopotamia Commission Report of 1917 shows -that scurvy can develop on a ration which includes 28 ounces of meat a -week. We must remember, however, that this refers to cooked meat, -whereas in the Polar expeditions meat generally was eaten in a raw -state. - -Recently an historical inquiry has appeared in an article by Chick, Hume -and Skelton as to the antiscorbutic virtue of limes and lemons. This -sketch is of exceptional interest because it treats of the oldest and -most cherished antiscorbutics, and particularly because it has unearthed -a peculiar fallacy in their connection. As they state, there would -appear to be every reason for believing "that the use of so-called lime -juice was responsible for the disappearance of scurvy from the British -navy in the first decade of the nineteenth century." It would seem, -however, that the lime juice which gained this great reputation in the -navy some 125 years ago was in reality lemon juice, and that it was not -until about 50 years ago that lime juice was really used. These authors -show--by one of those striking human experiments which, occasionally, is -available--that in a Polar exploration which was organized in 1850 lemon -juice was issued to each man, and that no case of scurvy developed, -whereas in a similar expedition which went out in 1875 lime juice was -issued and scurvy developed the following spring with great severity -among the sledge crews. This investigation, therefore, seems to prove -that lime juice, the prototype of antiscorbutics, has been accorded a -false position; that in reality the sailors of the past have been -protected by lemon juice. - -=Antiscorbutic Foods.=--As far as has been ascertained, the -antiscorbutic food factor exists in all fresh vegetable and animal -tissues, being present to a far greater degree in the former than in the -latter. It is distinguished by being associated in nature with cells -which are the seat of active metabolism, just as the water-soluble -vitamine is associated mainly with cells which are in an inactive or -dormant state. Vegetables or fruits may be mildly or highly -antiscorbutic; there is indeed a remarkable difference in their content -of antiscorbutic factor or vitamine. They vary widely also in the degree -to which their potency is affected by physical or chemical conditions. -In this chapter the most common animal and vegetable antiscorbutic -foodstuffs will be considered and the effect which processes such as -drying, canning, change of reaction, etc., exert on their specific -value. Their therapeutic application in the prevention and cure of -scurvy will be considered in a subsequent chapter. Until recently our -knowledge of this subject was empirical and inaccurate; as the result of -scientific work, however, carried out during the past few years in -different parts of the world, quantitative and comparative figures of -antiscorbutic food values have been evolved. - -=Milk.=--It is important to have as accurate an idea as possible of the -value of milk as an antiscorbutic, as the infant depends on it during -the first months of its life for a supply of this essential factor. -Considerable attention has been paid to this question in the last few -years, and recent reports tend to confirm the former estimations which -had been overlooked and forgotten. In 1847 Curran wrote that in the -Irish epidemic of this year they had admitted to the Dublin Union -Hospital 80 cases of scurvy which had been on a diet which included one -pint of milk daily, but was deficient in vegetables. From this -experience he realized that milk was not rich in the principles which -protect against scurvy. In the following year Parkes came to the same -conclusion, stating that 500 to 750 c.c. of raw milk did not always -suffice to prevent scurvy. In addition to these opinions concerning -adults, similar conclusions have been drawn from clinical experience -with infants. Barlow (1894) realized that a small amount of milk was -insufficient to protect against scurvy. Still writes: "The antiscorbutic -power of fresh, unboiled milk is evidently slight." In 1914 Hess and -Fish pointed out that "milk must not be considered as having potent -antiscorbutic properties." Nevertheless, when this question was raised -recently by the experimental work of Jackson and Moore, and that of -McCollum and Pitz, it was not appreciated that, like other -antiscorbutics, milk must be regarded from a quantitative standpoint, -and that, as it is a weak antiscorbutic, its effect must depend largely -on the quantity consumed. - -The first laboratory work on this subject was that of Froelich in 1912, -who showed that guinea-pigs could be protected by an exclusive diet of -fresh milk, and that raw milk is more effective than heated milk. In his -work, the amount of milk taken by the animals was not measured, so that -it is impossible to glean from it more than these general conclusions. -In the following year, as a result of some quantitative experiments, -Funk stated that he was able to protect guinea-pigs with 50 c.c. of -fresh milk in addition to an oat diet. This estimate, as subsequent -workers showed, is too low. Chick, Hume and Skelton were the first, -however, to investigate the antiscorbutic potency of milk in a -systematic and convincing manner. They demonstrated that if the daily -consumption of fresh milk was less than 50 c.c., a guinea-pig died -almost as quickly as if it received no milk; if the daily quota varied -from 50 to 100 c.c., a greater or less protection from scurvy was -observed, varying proportionately with the amount consumed; if 100 to -150 c.c. were taken daily, which practically amounts to a complete milk -diet, satisfactory growth and development occurred, and no symptoms of -scurvy were observed. This represents in a general way the present -conception of the antiscorbutic power of milk. In passing, it may be -remarked that it is not altogether clear why 50 c.c. of milk do not -afford partial protection, and prolong the life of the animal for a -definite length of time. The authors conclude that "milk is evidently a -food poor in the antiscurvy accessory factor, and a ration large in -comparison with that of other antiscorbutic materials is necessary to -afford satisfactory protection from scurvy." The error must be avoided, -however, of regarding milk as a standard article of diet containing a -definite and specific amount of vitamine per cubic centimetre. It will -be shown later that this point of view cannot be taken in regard to -vegetables, and it is probable that it cannot be assumed for milk. - -A general conception of the antiscorbutic potency of cow's milk may be -gleaned from the fact that it requires a minimum of about sixteen ounces -(500 c.c.) daily to protect an infant from scurvy or to cure it. Twelve -ounces have failed to effect a cure in several instances, although the -milk was raw and of the best grade. If it is pasteurized, a larger -quantity is required, depending upon various conditions connected with -the heating process and upon the age of the milk, circumstances fully -discussed in relation to etiology. Thus it becomes evident that -pasteurized milk assumes a two-fold rôle, acting as an antiscorbutic if -little of its vitamine content has been destroyed and if a large -quantity is consumed, or leading to the development of scurvy when one -or both of these conditions is unfavorable. The same holds true for milk -which has been boiled for a short period. If the milk has been heated -twice, it tends to produce scurvy; if it is condensed, the greater part -of its antiscorbutic value is destroyed. - -It seems necessary to emphasize again the important fact that _dried -milk_ may possess marked antiscorbutic potency, depending on the method -of preparation (Fig. 11). As stated, sixteen ounces of milk dried by the -Just-Hatmaker process cured scurvy promptly, in spite of the fact that -the milk had been dried six months previously. Here, therefore, is a -food of high caloric value, compact, antiscorbutic, and stable. The fact -that milk, in spite of drying, retains this labile vitamine for so long -a period, demonstrates that it is available in the most remote parts of -the world, and that the possibilities of its transportation are -unlimited. - -Little is known regarding the antiscorbutic content of the milk of the -various domestic animals. Some claim that goat's milk is notably rich in -this particular, but experiments with it are too few to warrant -conclusions. Lind writes: "Goats, of all animals, afford the richest -whey, possessed of the greatest antiscorbutic virtue ... which in a -singular manner restores the constitution when weakened and impaired by -scurvy." Human milk possesses about the same potency as cow's milk, as -mentioned in the discussion of the occurrence of infantile scurvy in -countries where the adult form is endemic. Twelve ounces of human milk, -from a woman on a liberal and varied diet, barely sufficed to alleviate -the symptoms of a case of moderate intensity. - - -FRUIT JUICES - -=Orange and Lemon Juice.=--The most thoroughly studied antiscorbutic -foods are orange and lemon juice, which have been singled out because -they contain the antiscorbutic factor in the highest concentration. It -has been ascertained through the work of various investigators that -guinea-pigs require about 3 c.c. daily of either of these juices to -protect them from scurvy, but that about half this amount is sufficient -to prevent the manifestation of clinical signs. - -Both of these juices withstand heat remarkably well. Orange juice can be -boiled for 10 minutes without noting any diminution of its antiscorbutic -value, and lemon juice heated to 110° C. without appreciably losing its -efficacy. However, orange juice undergoes some change as the result of -being heated in an autoclave for 45 minutes at a temperature of 110° -under 10 to 15 pounds pressure. Although 6 c.c. of this heated -preparation were able to prevent the development of scurvy, the -guinea-pigs did not gain nearly as well as those which received 3 c.c. -of the unheated juice. It seemed as if there was a destruction of some -factor apart from the antiscorbutic principle. - -In spite of the fact that these juices withstand heat well, they are -sensitive to some other conditions. Orange juice which had been stored -in the cold for three months was unable to protect guinea-pigs in the -dosage of 3 c.c. per animal, resembling in its action the autoclaved -juice. When this orange juice was six months old, double this quantity -failed to protect; throughout this period it was kept in the ice-box -and covered with a layer of oleum petrolatum to avoid the access of air -or possible contamination. Harden and Zilva met with a similar -experience, and state that "after storing treated (concentrated) lemon -juice for about a fortnight in a cold room, a marked loss can be -observed in its potency." - -These authors reported also that when orange juice is _rendered slightly -alkaline_ it loses its antiscorbutic potency. This question was -investigated in relation to canned tomato juice, as well as to orange -juice, and it was found that shortly after having been rendered 0.05 N -alkaline to phenolphthalein, neither of these foods had lost an -appreciable amount of its antiscorbutic factor. Five cubic centimetres -per capita daily of freshly-alkalized orange juice were able to cure a -group of pigs which had developed scurvy on another diet. If, however, -24 hours were allowed to elapse instead of only one-half to one hour, -between the alkalization and the feeding, then a considerable amount of -the antiscorbutic factor was lost. The same general rule seems to hold -for alkalization as for heating, _i.e._, the length of time the -antiscorbutic food is subjected to the deleterious influence is fully as -important as the intensity of the process. Advantage has been taken of -the fact that freshly-alkalized orange juice retains its potency, in -using it intravenously in the treatment of infantile scurvy. - -_Subcutaneous injections_ of neutralized orange juice failed to cure -scurvy in guinea-pigs; Harden and Zilva were equally unsuccessful with -large doses of their concentrated lemon juice. This is of interest in -view of the marked therapeutic result which Shiga obtained with -subcutaneous injections of the water-soluble vitamine in pigeons -suffering from polyneuritis. It should be added that Holst and Froelich -(1912) failed to cure scurvy in guinea-pigs by intraperitoneal -inoculations of orange juice. - -_Lemon juice or orange juice may be dried_ and lose little of its -antiscorbutic power. In their paper of 1912 Holst and Froelich reported -the efficacy of lemon juice evaporated in a vacuum, and recently Harden -and Zilva published experiments which proved that "by evaporating the -treated lemon juice to dryness in an acid medium an active dry residue -is obtained." Still more recently Givens has shown that orange juice -reduced to a powdered form by means of a spraying process has lost -little of the antiscorbutic factor. These results prove that under -certain conditions the antiscorbutic factor withstands drying; one of -these favorable influences is an acid reaction, and another, rapidity of -desiccation.[40] - -[40] Preserved mulberries which had been sugared and cooked for -one-quarter to one-half an hour were found by Holst and Froelich (1912) -to possess good antiscorbutic power three months later. - -=Lime Juice.=--Recently an investigation of lime juice has been carried -out by Chick, Hume and Skelton. They were "unable to detect any -significant protection in a daily ration of from 5 to 10 c.c. of -preserved lime juice which was several months or a year or more old." -Crude lime juice of various ages had slight antiscorbutic value, -affording only partial protection in a daily ration of 5 c.c. Even fresh -juice was found not to be very efficacious compared with lemon juice. -The authors conclude that "the relative value of these two fruit juices -deduced from the trials with monkeys is therefore in accord with that -obtained in the experiments with guinea-pigs, _i.e._, the value of fresh -lemon juice is approximately four times that of fresh lime juice." Holst -and Froelich in 1907 carried out a similar but less extensive -investigation. They also found that lime juice was unable to protect -guinea-pigs from scurvy. Fuerst, a co-worker of Holst, continued this -work, and in his article of 1912 stated that guinea-pigs should not be -protected by a daily addition to their ration of 25 g. of lime juice; -these guinea-pigs received a mixed diet consisting of dry vegetables, -butter, almonds and malt extract. These two reports of the Norwegian -investigators on this interesting subject should have attracted -attention. - -=Other Fruits.=--A word may be said in regard to some other fruits. The -antiscorbutic potency of _raspberries_ was tested by Holst and Froelich -(1912) and found comparable to oranges and to lemons. The juice was also -highly resistant to heat, so that 10 c.c. of freshly-pressed juice were -of protective value, even after it had been subjected to 100 or 110° C. -for one hour. Guinea-pigs which were thus treated showed no microscopic -signs of scurvy in any of the ribs, in the tibiæ or the femora. - - TABLE 3 - TABLE SHOWING THE RELATIVE DISTRIBUTION OF THE ANTISCORBUTIC FACTOR - IN THE COMMONER FOODSTUFFS[*] - ===================================================================== - Classes | Anti- | Classes | Anti- - of |scorbutic| of |scorbutic - Foodstuffs | Factor | Foodstuffs | Factor - ------------------------+---------+------------------------+--------- - _Meat, Fish, Etc.:_ | |_Vegetables and Fruits:_| - Lean meat (beef, | | Cabbage, fresh | +++ - mutton, etc.) | + | Cabbage, cooked | + - Liver | + | Cabbage, dried | Very - Tinned meats | 0 | | slight - Beef juice | + | Swede, raw expressed | - | | juice | ++ - _Milk, Cheese, Etc.:_ | | Lettuce | ++ - Milk, cow's, whole raw| + | Carrots, fresh raw | + - Milk, cow's, skim raw | + | Carrots, dried | 0 - Milk, cow's, dried | + | Beetroot, raw, | Less - Milk, cow's, | Less | expressed juice | than + - boiled | than + | Potatoes, raw | ... - Milk, cow's, | Less | Potatoes, cooked | + - pasteurized | than + | Potatoes, dried | 0 - Milk, cow's, condensed| Less | Beans, fresh, raw | ++ - (sweetened) | than + | Onions | ++ - | | Lemon juice, fresh | +++ - _Eggs:_ | | Lemon juice, preserved| ++ - Fresh | ?0 | Lime juice, fresh | ++ - Dried | ?0 | Lime juice, preserved | Very - | | | slight - _Cereals, Pulses, Etc.:_| | Orange juice | +++ - Wheat, maize, rice, | | Raspberries | ++ - whole grain | 0 | Grapes | + - Wheat germ | 0 | Apples | + - Wheat, maize, bran | 0 | Bananas | Very - White wheaten flour, | | | slight - pure corn flour, | | Tomatoes (canned) | ++ - polished rice, etc. | 0 | - Linseed, millet | 0 |_Miscellaneous:_ | - Dried peas, lentils, | | Yeast, autolyzed | 0 - etc. | 0 | Meat extract | 0 - Soy beans, haricot | | Beer | 0 - beans | 0 | Cod liver oil | 0 - Germinated pulses or | | Olive oil | 0 - cereals | ++ | Human blood | + - --------------------------------------------------------------------- - [*] This table is a modification of one prepared by the Medical - Research Committee - -These authors also reported that they found _banana_ and _apple_ poor in -antiscorbutic power, 30 g. daily being insufficient to protect a -guinea-pig (Table 3). This was our experience with banana in the -treatment of infants suffering from mild scurvy. The banana has been -shown by Sugiura and Benedict to be poor also in the water-soluble -vitamine. It would be of interest to determine the difference in -vitamine content between the fully ripe and the unripe fruit. - -In view of the fact that _grapes_ are used considerably in the treatment -of infantile scurvy, it is of importance to realize that they are poor -in the antiscorbutic principle. Chick and Rhodes found that three of -four guinea-pigs receiving 20 g. daily developed scurvy; they rated the -potency as ten times less than that of orange juice. - - -VEGETABLES - -It is everyday knowledge that fresh vegetables are of great value in the -protection from, and cure of, scurvy. The first experimental -investigation of this subject was that of Holst and Froelich, published -in 1907, and continued in a series of papers extending to 1916. These -investigators tested the potency of a large number of vegetables by -feeding them in varying quantities to guinea-pigs. They found that all -vegetables have antiscorbutic value but to a markedly varying degree. -Cabbage, sorrel leaves, endive, head salad, and dandelion leaves, were -found to be of most avail in protecting against scurvy, whereas carrots, -cooked potatoes and cooked turnips, and cauliflower proved to be of less -value. In general, it may be stated that the leafy vegetables have more -antiscorbutic power than the roots or the tubers. This generalization, -we shall see, is not without exception, _e.g._, the swede. Similar -experimental work has been recently carried on by a group of -investigators at the Lister Institute, who have added considerably to -our knowledge in this field. In all this experimental work cabbage has -been found to be the most potent of the vegetables, and therefore -experiments have centered about it just as in considering fruits the -work has centered about orange juice or lemon juice. We shall, -therefore, discuss in detail its reaction to heat and dehydration. - -=Cabbage.=--Holst and Froelich found that 1 g. daily of fresh cabbage -afforded nearly complete protection to guinea-pigs, and Delf has -corroborated this work. This amount is sufficient to prevent the -development of manifest scurvy, although it does not induce satisfactory -growth. In this respect it is comparable to giving 1.5 c.c. of orange -juice daily. If guinea-pigs take only 0.5 g. of raw cabbage, scurvy will -develop; whereas 2 g. or more will promote satisfactory growth and no -scorbutic changes will be found on microscopic examination. - -=Effect of Heating.=--Vegetables are of decidedly less antiscorbutic -value when cooked than raw; cabbage, for instance, on being boiled is -weakened about one-half. Heating to 110° C. for an hour destroys almost -all of its antiscorbutic factor. Delf's tests did not show so great a -loss. She came to the conclusion, of theoretical and practical value, -that slow cooking at a low temperature is much more deleterious than -rapid cooking at a higher temperature. Hess and Unger found that carrots -lost much of their antiscorbutic power after boiling, and that this was -the result of a true destruction, the vitamine not having been merely -dissolved in the water of boiling; for if guinea-pigs consumed 40 c.c. -per capita of this water, they were not protected against scurvy (Fig. -11). Acidulating the water with 10 per cent. vinegar did not reduce the -loss, an experience similar to that of others using citric acid or lemon -juice. - -_Vegetables cannot be considered from an antiscorbutic standpoint as a -standard and uniform foodstuff, as they vary in their content of this -factor according to their freshness and age._ This was demonstrated by -means of feeding experiments with carrots. For example, 35 g. of old -carrots, such as were used for feeding the laboratory animals, afforded -but little protection after having been cooked in an open vessel for -about 45 minutes, whereas the same amount of young carrots cooked this -way protected the guinea-pigs. It is obvious that this distinction is of -importance in evaluating the antiscorbutic content of the various foods, -and in considering whether individuals and groups of individuals are -receiving an adequate quota of antiscorbutic vitamine. It will be noted -later that it is also of importance in connection with the potency of -dehydrated vegetables. Recent experiments indicate that not only age, -but the _degree of ripeness_ must be considered in appraising the food -value of vegetables. Feeding experiments showed that tomatoes which were -fully ripe were more potent than those which were slightly green. -Probably many other factors play a rôle in determining the richness of -vegetables in vitamine. It may not be immaterial whether they are -allowed to ripen on the vine or shrub, or mature subsequently. The -nature of the soil may also affect the antiscorbutic quality of the -vegetables or fruit. So that it is evident that we must not be schematic -in considering this question, and must realize that a table of -antiscorbutic values, such as accompanies this text (Table 3), does not -furnish definite and inflexible values. - -There is a marked difference between _vegetables and vegetable juices_ -in keeping quality, and in their reaction to heat and to acid. In -general, it may be stated that the juices are much more sensitive. Holst -and Froelich brought out this point in 1912 and enlarged upon it in -their publication of 1916. The different juices vary greatly in this -respect; for example, dandelion juice is acutely sensitive to heat, -whereas sorrel leaves withstand high temperatures very well. In regard -to these differences an analogy may be drawn to the fruit juices. Lemon, -orange and raspberry juices are markedly thermostable, but lime juice is -weakened markedly by heat. Many of these juices are protected by the -addition of acid--5 per cent. of lemon juice increasing the -thermostability of cabbage juice--whereas, as we have stated, little is -gained by cooking vegetables in an acid medium. - -=Potato.=--The civilized world is dependent for its quota of -antiscorbutic foodstuff largely upon the potato. It might be thought, -therefore, that this would signify that the potato is endowed with great -antiscorbutic power. Such is not the case, however, as demonstrated both -by laboratory tests and clinical experience. Considering its importance, -there have been surprisingly few feeding experiments carried out with -potato. Holst and Froelich (1912) found that 17 g. of potatoes, steamed -at 100° C. for 30 minutes, afforded but slight protection, and that it -required 20 g. to fully protect a guinea-pig. Givens and Cohen failed to -ward off scurvy by means of cooked potatoes fed to the equivalent of 5 -g. of the raw vegetable (guinea-pigs will not eat raw potatoes). There -are no accurate figures as to the quantity of potatoes needed to protect -a human being from scurvy. The statement of Doctor Guy, however, who -after careful study of convicts' diets, concluded that 14 ounces daily -would protect them from scurvy (if the ration included one ounce of -other fresh vegetable and 4 ounces of meat), is probably close to the -mark.[41] With the experience that potatoes play such a significant rôle -in the prevention of scurvy, how are we to interpret the fact that they -are only mildly antiscorbutic? Potatoes are consumed in very large -amounts; in the Temperate Zone probably twice as many pounds of potatoes -are consumed during the winter as of all other vegetables combined (Fig. -1). It is evident, therefore, that in a practical evaluation of -antiscorbutic foodstuffs, not only the intrinsic antiscorbutic potency -must be considered, but also the quantity of the vegetable or fruit -consumed. - -[41] Dr. Guy's evidence, Report of the Lords Commissioners of the -Admiralty on the Outbreak of Scurvy in the Recent Arctic -Expedition--1877 (cited from Chick and Hume). - -=Swede.=--We cannot leave the consideration of vegetable antiscorbutics -without adding a few words as to the value of swede juice,[42] which has -been recently highly recommended by Chick and Rhodes, who found it -comparable to the cabbage and the onion, and even to orange juice. For -example, 25 c.c. of raw swede juice were equivalent to 1.5 g. of raw -cabbage. It is, therefore, more potent than the juice of raw carrot, and -far more efficacious than the juice of the beetroot (Table 3). Tests -carried out with this antiscorbutic in infant feeding seemed to show -that it is of value in this field. The authors believe that the potency -of vegetables is closely associated with certain botanical species, and -that in this way the marked virtue of the swede can be explained, as it -belongs to the natural order of Cruciferæ, which includes also the -cabbage, the scurvy grass and the cresses. If, however, this is a rule -of nature, it is difficult to explain the marked difference between the -lime and the lemon, which are both varieties of Citrus Medica. - -[42] The swede is a root vegetable of the natural order Cruciferæ. It is -grown to a large extent in England, but is practically unknown in the -United States. - -=Dehydrated Vegetables.=--For hundreds of years fresh vegetables have -been dried to serve as food during the winter months and have fulfilled -a useful purpose on account of their small bulk and great food value. -The question for us to consider, however, is whether dehydrated -vegetables still retain their antiscorbutic quality and can be counted -on to supply this factor in the dietary. At present this subject is -engaging the attention of laboratory workers as well as of practical -dietitians and food hygienists. The experience of the past is not happy -in this regard. In the Medical and Surgical History of the War of the -Rebellion we read as follows: "A scorbutic tendency was developed at -most of our military posts during the winter season, after the troops -had been confined to the use of the ordinary ration with desiccated -vegetables. The latter in quantities failed to repress the disease." In -spite of this and similar military experiences[43] the employment of -dehydrated vegetables was urged recently for rationing our soldiers, the -claim being made that "by simply soaking in water and boiling in the -same water these vegetables are brought back to the condition of fresh -vegetables." Both in this country and in England there was strong -propaganda during the war to dehydrate vegetables on an enormous scale -and to substitute them for the fresh food. - -[43] "We find the College of Physicians at Vienna sent to Hungary great -quantities of the most approved antiscorbutic herbs dried in this -manner; which were found to be of no benefit. Many of these would have -their virtues as little impaired by drying as spinage, _e.g._, marsh -trefoil. Kramer tried almost every species of dried herbs to no -purpose." (Treatise on The Scurvy. James Lind, London, 1772, p. 143.) - -[Illustration: FIG. 12.--Hay, oats, water _ad libitum_, and 7 g. of -dehydrated carrots dried at a room temperature of about 130° F. about 1 -month previously. All animals developed scurvy. The marked gain in -weight when an equivalent amount of fresh carrots was substituted for -the dehydrated vegetable corresponded to the disappearance of scorbutic -signs. Guinea-Pig B 951 did not receive fresh carrots, as it was -evidently ailing at the time the second period began.] - -Experimental investigation on this subject may be summarized as showing -that vegetables dried according to present methods lose their -antiscorbutic value as the result of dehydrating (Fig. 12), and that -they become still more impoverished as the result of aging. We should -not sweepingly condemn the principle of dehydration, as very possibly -some slight modifications in the process may be devised which will -counteract the deteriorating influence. In their paper of 1912, to which -reference has been made so often, Holst and Froelich reported that -potatoes, carrots, peas, lentils and almonds have practically no -protective value after they are thoroughly dried. In two reports--one -giving the results of feeding various brands of dehydrated carrots to -guinea-pigs, and the other of an attempt to cure scurvy in babies by -means of these carrots--we also came to the conclusion that the -antiscorbutic factor had been almost completely destroyed. Givens and -Cohen (1918) found that even cabbage dried at a low temperature retained -only a small amount of its potency after a month, and Delf and Skelton -came to practically the same conclusion, also noting that the cabbage on -being kept, steadily lost what little of the antiscorbutic factor had -survived the drying process. The same was true of the fat-soluble -factor. These authors made an observation which may prove of value in -helping to solve this problem, namely, that "the residual amount is -distinctly greater if the cabbage is plunged into boiling water before -drying." This protective action of heat they suggest may indicate that: -"Some at least of the destruction may be due to the activity of an -enzyme or other body originally present in the living tissue." - -Another observation which may prove of practical value in rendering -dehydrated vegetables the nutritional equivalent of the fresh vegetable -is that when the carrots selected for dehydration are young and fresh a -product is obtained which possesses decided antiscorbutic power. In this -connection the following statement by Falk and his co-workers in a study -of the enzyme action of vegetables and the effect of dehydration is -significant: "In considering these enzyme results, it may be pointed out -that the state of ripeness and the age of the vegetable undoubtedly -influence the activities." - -The most promising dehydration experiment has been conducted by Holst -and Froelich and was published in 1916 in a paper which has passed -unnoticed. They dried white cabbage so that it retained its -antiscorbutic properties, and, to a large extent, its color and taste, -for a period of two years. This result was accomplished by keeping out -all moisture and preventing hydrolysis,[44] a method which is employed -in preserving antitoxins, toxins and agglutinins. It is by far the most -encouraging test reported, and should be made the basis of further work -by those actively interested in perfecting dehydration. - -[44] The cabbage was subjected to a preliminary drying for 8 days at 37° -C. It was then put in an air-tight desiccator which contained a dish of -phosphorus pentoxid. (The pentoxid was replaced for several weeks until -it ceased to liquefy.) It was then placed in cylinders which had been -rendered air free by means of a suction pump and which contained -phosphorus pentoxid. This was kept at 37° C. and examined after 10, 18 -and 26 months. A similar result was not obtained when calcium chlorid -was employed, the temperature held at 37° C. and the cabbage was kept in -an air-tight cylinder rather than in a vacuum. However, under these -conditions if the cabbage was placed in the ice-box at a temperature of -4°, 10° or 12° C. the antiscorbutic property was conserved after -boiling. - -[Illustration: FIG. 13.--Cure of scurvy by the addition of canned -tomato. In this case, as frequently, the alleviation of symptoms -preceded the gain in weight.] - -=Canned Food (Tomatoes).=--In the course of canning, as in dehydrating, -most vegetables and fruits lose their antiscorbutic properties. A -general denunciation, however, of all canned foods is incorrect, as -there are exceptions to this rule. It has been shown by Hess and Unger -that canned tomatoes possess a high degree of antiscorbutic power (Fig. -13), and it is probable that most of the acid fruits and vegetables are -able to withstand the canning process. It was found, in an experiment -embracing many series of guinea-pigs, that 4 c.c. daily of strained, -canned tomato are sufficient to afford protection, even when a lot was -used which had been prepared a year previously. This is indeed -remarkable, considering that the food undergoes a two-fold heating in -the course of canning, during one of which ("processing") the -temperature is raised to fully 230° F. Tomatoes have another advantage -over most other vegetables in that they are richly endowed with the -water-soluble vitamine, as shown by our tests on pigeons suffering from -polyneuritis, and by the experiments on rats of Osborne and Mendel, who -found tomatoes far superior in this respect to turnips, onions, -beetroots or beans. They are also rich in the fat-soluble vitamine. In -view of the availability of canned tomatoes and their excellent keeping -quality they are well suited to an extended use as an antiscorbutic. In -the subsequent chapter we shall discuss their employment in infant -feeding and in the army ration. - -=Germinated Cereals and Pulses.=--In 1912 Fuerst reported that although -the resting seed--the cereal grain, the pea, bean and lentil--are poor -in antiscorbutic vitamine, they develop this principle as soon as they -germinate. They possess, in other words, latent antiscorbutic -properties, and are potentially antiscorbutic. This observation is not -only of scientific interest but of practical value, as these pulses are -well suited for transport and do not readily deteriorate. For this -reason, Chick and her co-workers at the Lister Institute, who were -searching for an antiscorbutic foodstuff for the army, directed their -attention to the utilization of the pulses. In the course of a thorough -investigation (1919) they found that although it required 30 to 40 g. -daily of dry green peas to prevent scurvy in the guinea-pig, a -consumption of 10 g. of the germinated peas afforded satisfactory -protection.[45] The soaked seeds have an antiscorbutic value comparable -to many of the fresh vegetables; by no means as great as cabbage, but -somewhat greater than that of carrots. As the result of cooking, their -potency was found to be reduced about 75 per cent. We shall have -occasion to refer to this antiscorbutic food in the chapter on treatment -in connection with the rationing of armies. - -[45] The pulses, after having been soaked in water for 24 hours, were -kept moist, with access of air, for about 48 hours at room temperature, -and during this time germinated, developing a radicle usually about 1 -cm. in length. - -=Meat and Eggs.=--As has been stated, animal tissues are distinctly -inferior to fruits and vegetables in the antiscorbutic principle. As -there has been no accurate evaluation of these foods--the only test -being one by Chick, Hume and Skelton, where 10 c.c. of raw beef juice -failed to protect guinea-pigs--we have to depend upon clinical -experience for our knowledge. Beef juice is highly rated by physicians -in the prevention of infantile scurvy, but it is probably far less -potent than vegetables or fruit juices. The Arctic explorers, and many -who have lived in the Arctic regions, agree that the inhabitants are -protected from scurvy during the winter months by their diet of fresh -meat and fish. The Admiralty Enquiry on the outbreak of scurvy in the -Arctic Expedition of 1875 reported that a large ration of meat is -necessary to afford protection. Curran (1847) described three cases -admitted to the hospital in the great Irish epidemic of that year, where -the diet previously had included three-quarters of a pound of meat on -five days of the week. From these and similar experiences the conclusion -is manifest that the divergence of opinion regarding the value of meat -is based upon quantitative differences in the rations. Evidently, if -sufficient meat is provided, the development of scurvy will be obviated. -Another factor which must be borne in mind is that those who refer to -meat in the Arctic regions refer to fresh raw meat, which is a far more -valuable antiscorbutic than the ordinary cooked meat. - -There is almost no experimental data on the antiscorbutic value of -_eggs_. Hard-boiled eggs were fed to guinea-pigs and it was found that 9 -g. per capita daily was insufficient to protect them. An attempt was -also made to cure infantile scurvy with a daily addition of one raw egg -to the dietary, but without avail. It is possible that fresh raw eggs -have an antiscorbutic value comparable to meat, but the large quantity -required makes dependence upon them impracticable. - -=Beer and Alcoholic Beverages.=--For generations beer has been highly -regarded as an antiscorbutic. Captain Cook prized it greatly and always -supplied his men with a freshly-made infusion of malt called -"sweetwort." Lind writes: "Beer and fermented liquors of any sort will -be found the best antiscorbutic remedies" (p. 76). He refers at -different times to the value of spruce beer, ale, wine and other vinous -liquors. In his excellent book on "Military Hygiene," Munson writes: -"Good beer and wine have decided value, also vinegar." On the other -hand, recent scientific experiment has shown that beer has practically -no antiscorbutic value. There is but one study on this subject, that of -Harden and Zilva, which is quite convincing. They found that guinea-pigs -and monkeys developed scurvy in spite of the fact that they received, -respectively, 50 c.c. and 180 c.c. of beer daily. They conclude, as a -result of their experiments, that "bottled ale and stout and fined beer -as brought on to the market, are lacking both in antineuritic and -antiscorbutic accessory factors, and that kilned material is also -wanting in these two principles." The apparent contradiction between -practical experience and laboratory investigation in regard to beer is -due to a difference in the process of brewing. Cook and Lind and the -older authors refer to freshly-made beer, whereas the modern beer which -was tested in the laboratory was made from "high-dried" material. The -antiscorbutic potency of beer as formerly used was due to its -preparation from freshly-germinated grain and its consumption shortly -after brewing. Dyke tells us of an interesting incident illustrating the -importance of this distinction. In the recent war an outbreak of scurvy -occurred among the Kaffir labor battalion in France. At home these -natives consume a large amount, as much as three gallons a day, of -Kaffir beer, which is made from freshly-germinated corn, and is consumed -shortly after it is made. The French prepared a similar fermented -beverage for their South African laborers, the sole difference in -preparation being that the process of germination had been omitted for -reasons of convenience. Scurvy resulted, a disorder which is practically -unknown among the natives at home. - -=Miscellaneous Foodstuffs.=--During the past few years a great many -different kinds of foods have been tested in the laboratory for their -antiscorbutic value. It will be well for completeness' sake to say a -word about them, although they have been found to possess little or no -antiscorbutic properties. The studies of Holst and Froelich showed -definitely that all the cereals--oat, barley, rye, maize, and -preparations made from the bran or from the endosperm--are devoid of -antiscorbutic vitamine. Cohen and Mendel added 3 per cent. of calcium -lactate or sodium chloride, or 5 per cent. of butter, without enhancing -the value of oats in this respect. - -[Illustration: FIG. 14.--Failure of yeast as a prophylactic; latent -scurvy promptly yielding to orange juice.] - -As is well known, yeast possesses the water-soluble vitamine in marked -concentration. It is natural, therefore, that its antiscorbutic power -was put to the test, especially as it has been accorded therapeutic -value. Hess and Unger showed that autolyzed yeast was of no value in -the cure of infantile scurvy (Fig. 14); Chick and Hume (1917) and Cohen -and Mendel (1918) came to the same conclusion in regard to guinea-pig -scurvy, making use of autolyzed yeast, yeast extract and dried brewers' -yeast. - -In view of the fact that cod liver oil is practically a specific for -human rickets, Hess and Unger tried the effect of this oil both in -infantile scurvy and in that of guinea-pigs. It proved to have no -protective or curative value. The animal experiments were confirmed by -Cohen and Mendel. The use of olive oil also proved futile. - -Pitz in 1918 reported that in animal experiments he had found that -lactose was able to protect against scurvy, and attributed this result -to its power to alter the intestinal flora. We shall not enter into a -detailed discussion of this question, as the study was carried out on a -ration embodying unlimited and uncontrolled amounts of milk, and it has -since been shown that the apparent cure was due to an increased -consumption of milk by the animals in the progress of the experiment. -Cohen and Mendel, Harden and Zilva, Hart, Steenbock and Smith (1919) all -failed to protect or to cure their animals with lactose when they were -placed on a ration which was definitely measured and limited. Hess and -Unger failed to cure infantile scurvy by means of lactose. - -It has been suggested that scurvy is due to a lack of secretion of the -endocrine glands, a question which will be referred to again in -considering the relation of scurvy to other "deficiency diseases." With -this idea Ingier added thyroid, hypophysis, thymus and parathyroid to -the food of guinea-pigs, or gave it parenterally. She was unable to -observe any beneficial results. Jackson and Moore met with the same -result on feeding desiccated thyroid gland. We may add that we gave -dried thyroid and also parathyroid glands in the treatment of infantile -scurvy without effect. - - -CONCLUSIONS - -Any consideration of the question of antiscorbutic foodstuffs brings -into sharp relief the difference between empiricism and scientific -investigation. For well over a hundred years it was generally known that -scurvy could be cured by fruits or vegetables, and yet no further -progress was made toward a more complete understanding of the value of -these foodstuffs. As far back as 1847 Budd ascribed the action of -antiscorbutic foods "to an essential element, which, it is hardly too -sanguine to state, will be discovered by organic chemistry or the -experiments of physiologists in a not far distant future." Busk, in -giving his testimony in 1877 before the British Scurvy Commission, said -that it was his belief "that scurvy was due to the fact that the diet -was lacking in a peculiar and as yet little-understood factor." The -question remained in this hypothetical and inactive state until it was -attacked recently by experimental methods. Decided advance has been made -only in the past few years, since these foodstuffs have been studied -from a quantitative viewpoint. - -The antiscorbutic factor is abundant in fresh foods, especially in -vegetables and fruits, and to a considerably less extent in animal -foods, such as milk, meat and fish. Among the vegetables there is a -marked distinction in potency. A beginning has been made in -standardizing these various foodstuffs, in grading them approximately -according to their antiscorbutic efficacy (Table 3). It should be -remembered, however, that the importance of an antiscorbutic food -depends not only on its intrinsic content of the antiscorbutic factor, -but quite as much on the amount of the food which is eaten. For example, -although potatoes possess only moderate virtue compared with orange -juice, they are of greater practical value in view of the large -quantities which are consumed and their availability when green -vegetables are lacking. Furthermore, the fact recently brought out that -the various vegetables, and perhaps the fruits as well, have -considerably more value when they are fresh and young than when they are -old, warns us not to carry our quantitative standardization too far. - -Fruits and vegetables which are dehydrated have been found to have lost -their antiscorbutic properties. This generalization is not without its -exception, for it has been found that cabbage and tomato withstand -drying well, and that if milk is dried under favorable conditions it -retains a very large part of its antiscorbutic value. It may be stated -that the outlook is bright in regard to dehydration, as the problem has -not yet been thoroughly studied, and the process may be so improved that -there will be little difference in the nutritional value between the -fresh and the dehydrated food. - -The study of antiscorbutic values points a lesson in regard to the -methods of cooking vegetables. It has demonstrated that short cooking, -associated with a high degree of temperature, is less deleterious than -longer cooking at a low degree. In other words, that less damage is -brought about by boiling or by steaming vegetables than by stewing them. -Here age and freshness again play a rôle; in fact, a double rôle, as the -older and tougher vegetables contain not only less antiscorbutic, but -require more prolonged cooking. - -In general, the belief is correct that canning destroys the -antiscorbutic value of foods, but once more an exception must be made, -for it has been found that acid foods, such as the tomato, withstand the -canning process with but little loss of potency. - -The field of antiscorbutic foodstuffs is one which is fertile for future -investigation. The antiscorbutic status of milk heated to various -heights of temperature and subjected to various degrees of aging -furnishes problems of great practical importance. A lack of growth has -been noted when antiscorbutics are given which have been subjected to a -high degree of heat (_e.g._, autoclaved orange juice). Whether this is -due to the destruction of some other growth factor is a question which -has been raised by several experimental studies and requires an answer. - -It is quite possible that we shall find useful antiscorbutic foods which -at present are unknown or unappreciated. The recent introduction of the -swede, of the canned tomato and of germinated pulses suggests and even -renders this probable. On the other hand, the recognition of the -comparative poverty of the antiscorbutic factor in lime juice shows the -importance of putting each foodstuff to the experimental test. - - - - -CHAPTER VII - -SYMPTOMATOLOGY AND DIAGNOSIS - - -The identity of scurvy in the infant, in the young child and in the -adult is thoroughly established and requires no further substantiation. -There are, however, sufficient differences between the symptoms of adult -scurvy and those of Barlow's disease to render it advisable to consider -them separately. These distinctions are due largely to the fact that the -former disorder affects mature tissues, whereas the latter is engrafted -upon tissues which are in the process of rapid growth and development. -The symptomatology is influenced also by the striking differences in -environment--the passive, shielded existence of the infant, contrasted -with the active and exposed life of the adult. Although we shall, -therefore, treat adult and infantile scurvy separately, it should be -borne in mind that, from an etiologic and pathologic viewpoint, such a -division is artificial and is resorted to merely for purposes of -clarity. - -=Adult Scurvy.=--The earliest sign of scurvy is usually a change in the -complexion of the individual. His color becomes sallow or muddy, an -aspect difficult to describe, but one which is characteristic, and -constitutes an important danger signal to the eye of the experienced -physician. About the same time the patient loses his accustomed vigor, -seemingly becomes indolent and complains of tiring quickly, and of -breathlessness. He may experience fleeting pains in the joints and -limbs, especially in the legs, symptoms which are frequently attributed -to rheumatism. At this early stage the appetite may still be normal, -there is usually no loss in weight, but merely a general malaise which -is significant, although in no way distinctive. Very soon the gums -become sore, bleed readily, and are found to be congested, spongy, and -somewhat hemorrhagic at their edges. Absolute reliance must not, -however, be placed on this sign for early diagnosis, as at times it does -not appear until later. Careful examination at this stage will disclose -petechial spots on the body, more especially on the legs, at the site of -the hair follicles, or even larger ecchymoses, depending upon the -hemorrhagic tendency of the individual, his exposure to bruising, the -adequacy of his diet, and secondary infection. Less frequently bleeding -from the nose occurs early, or the eyelid suddenly becomes swollen and -purple, or the urine shows the presence of blood. - -These signs progress steadily with a varying degree of rapidity. The -complexion becomes more dingy and somewhat brownish, the weakness -increases so that the slightest exertion causes breathlessness and -palpitation, and the gums become spongy and even fungous. If there is -infection of the gums and the teeth are carious, the breath is extremely -foul--a sign long associated with scurvy. Later the teeth become loose -and may fall out, and the alveolar process undergoes necrosis. The -surface hemorrhages increase in severity, large effusions appearing on -the trunk, on the extremities, and less often beneath the mucous -membrane of the mouth. A bloody diarrhoea may take the place of the -constipation which is generally noted earlier in the disease. There are -at this time hemorrhages into the muscles and deeper tissues, especially -into the calves of the legs, giving rise to hard, brawny, tender -swellings which have been termed "scurvy sclerosis." This is sometimes -the earliest sign noted by the patient and may puzzle the physician who -has not met with it before. The swelling may be found in the popliteal -space or at the site of the tendo Achilles, and result in lameness and -contracture of the neighboring joint. Frequently there is slight edema -of the ankles associated with a glossiness of the extensor surfaces of -the legs. This infiltration differs from ordinary edema in being firm -and not pitting on pressure. The skin is dry and rough, the follicles -being unusually elevated;[46] the hair likewise is dry and loses its -lustre. Not infrequently subperiosteal hemorrhages occur, giving rise to -exquisitely tender swellings, especially of the tibia or of the femur, -or of the ramus of the lower jaw, as has been noted in connection with -guinea-pig scurvy. If there are wounds or ulcers they assume a -hemorrhagic aspect, the edges becoming bluish or livid and showing no -tendency to heal; even scars which have existed for many years change in -color and show an altered state of nutrition, and ulcers long healed -break out afresh. - -[46] As the result of an experience with thousands of cases of scurvy in -the Serbian army, Wiltshire has recently laid great emphasis on this -follicular hyperkeratosis. He states that the earliest recognizable sign -of scurvy is an enlargement of the hair follicles of the inner and -anterior aspects of the thigh and upper leg, which show numerous conical -elevations about the size of a pin's head. A hair, broken or unbroken, -frequently pierces the follicle. - -Nowadays, the disease usually does not reach this stage, and rarely -progresses further. If, however, the patient remains untreated, he -becomes progressively weaker and more lethargic; there is frequent -palpitation, shortness of breath, and increasing loss of weight. The -pains in the limbs render him helpless and an object of pity. Marked -edema may be added to the picture as the result of starvation, so that -the legs become swollen, and even the face becomes bloated. Hemorrhages -into the skin as large as the palm of the hand appear on different parts -of the body. The gums swell to such an extent that they overlap and may -even hide the teeth and protrude from the mouth as foul fungoid growth. -Death comes about in various ways. Frequently sudden and fatal syncope -occurs, due to heart weakness or to the pouring out of fluid into the -pleural or the pericardial cavities. Another frequent cause of death is -secondary infection, resulting in pneumonia, which finally ends the -suffering of the patient. The fatal outcome is thus described in the -narrative of Lord Anson's voyage: - - "Many of our people, though confined to their hammocks, ate and - drank heartily, were cheerful, and talked with much seeming vigor, - and in a loud, strong tone of voice; and yet, on their being the - least moved, though it was only from one part of the ship to - another, and that in their hammocks, they have immediately expired; - and others, who have confided in their seeming strength, and have - resolved to get out of their hammocks, have died before they could - well reach the deck. And it was no uncommon thing for those who - could do some kind of duty, and walk the deck, to drop down dead in - an instant, on any endeavor to act with their utmost vigor; many of - our people having perished in this manner during the course of this - voyage." - -The disease may develop and progress in various ways. It may remain -latent for a long period and be cured by some accidental change of -diet, or, as more frequently occurs, it runs a moderately acute course, -and is promptly cured by means of antiscorbutics. In the days when -scurvy was common and widespread it sometimes became chronic, developing -into the "inveterate scurvy" of the older authors, which was notably -resistant to treatment. Harvey, in his treatise published in 1685, -states that "a mild scurvy may continue or be protracted to ten, twenty, -or thirty years." - -In addition to the general picture of the disease which we have -presented, mention should be made of other less common symptoms. As is -well known, one of the characteristic signs of scurvy is _hemorrhage_. -Indeed, in many of the systematic treatises of medicine it is classified -as a hemorrhagic disease. Besides the bleeding into the gums, skin and -bones, hemorrhage into the stomach may take place, giving rise to -hæmatemesis, or there may be hemorrhage into the eye, under the -conjunctiva or into the anterior chamber, leading to the destruction of -the eyeball. A very unusual form is meningeal bleeding, giving rise to -symptoms of apoplexy. It may be stated in general that hemorrhage -dominates the picture of scurvy. Eruptions which in normal individuals -are simply macular or papular, assume a hemorrhagic character when -occurring in a scorbutic individual. This phenomenon was noted in the -recent war in connection with the eruption of typhus fever, and has been -observed by military and naval surgeons in numerous expeditions. - -Scurvy reduces the nutritional state of probably all the cells and -tissues of the body. If the resistance is still further lowered by -exposure, nutritional disturbances will result more readily than where -the tissues are normal and well nourished. For this reason we believe -that scurvy may predispose to _frostbite_. Reports of congelations -occurring in the trenches in the course of the World War tend to confirm -our opinion that scurvy was a predisposing factor in many of these -cases. This has been true in other wars. For example, Munson writes that -"during the Crimean War the temperature was never very low and a report -of the times suggests that the large number of congelations observed -among the soldiers might well be regarded as gangrene owing to a -scorbutic tendency exaggerated by the cold." - -In connection with the involvement of the gums, another typical symptom -of scurvy, it should be remembered that this sign may appear late and -therefore fail to be of value for early diagnosis, and that it occurs -also in purpura and thus may lead to error. This is especially the case -if there is pyorrhoea. As is well known, hemorrhages of the gums -appear only where teeth are present, and are absent in the edentulous -gums of old people as well as in babies who have no teeth. Immerman is -probably correct in believing that an injury is always necessary to -produce a hemorrhagic lesion in scurvy, and that this explains the early -involvement of the gums and also their non-implication in the absence of -teeth. - -It is a common belief that separation of the epiphyses occurs only in -infants and young children, and not in the scurvy of adults. This, -however, is not correct, as in severe adult scurvy there is frequently a -separation of the epiphyses of the long bones of the lower extremities -or of the ribs, the latter resulting in a sinking of the sternum. - -The pulse is sometimes slow and feeble, having been recorded as low as -40 beats per minute, but more frequently is rapid, in the neighborhood -of 140. It is, however, almost invariably unduly excited by emotion or -by mild physical activity. Frequently there is a low type of fever, -which has been termed "scorbutic fever," but which probably should be -regarded as a complication of the disease rather than as an intrinsic -symptom. - -There is little tendency to the formation of pus. Although the lymphatic -glands are frequently enlarged and effusions into the tissues and into -cavities of the body are by no means uncommon, they show little tendency -to become purulent. In the severe cases described by the older authors, -the breaking down of the glands in the inguinal region--buboes--is -frequently noted. The urine is apt to be scanty, becoming much more -profuse following treatment. Perspiration is also retarded. - -A peculiar symptom reported in connection with numerous epidemics of -scurvy, both on sea and on land, is _nyctalopia or night-blindness_. The -patients can see fairly well during the day, but have very little vision -as soon as darkness develops. This phenomenon has puzzled many -observers, as nothing abnormal has been found on examination of the -eyes. Recently O'Shea, who met with many cases of this nature among -soldiers, has reported that in an ophthalmic examination of 22 cases the -only abnormality was pallor of the optic disc in 3 cases. This weakness -of sight is due to the general nutritional weakness and has been -reported in connection with other exhausting and nutritional -diseases--for example, hunger edema. More rarely there is day-blindness. - -As a complication, dysentery may be mentioned. This has been described -by Schreiber and others in scurvy epidemics occurring in the course of -the World War. Jaundice may appear, and might be expected to occur more -often in view of the marked congestion of the upper duodenum found so -frequently at necropsy. - -Pericarditis, hydrothorax, pleurisy with effusion, pneumonia, are common -complications of severe forms of scurvy. Lind reports that the dominant -complication varies in different epidemics; that on one cruise many -cases of diarrhoea would occur and on another many pulmonary -infections. - -O'Shea reports the exceptional case of a man who was operated upon for -acute appendicitis. A large hemorrhage in the wall of the cæcum was -found, as well as some other hemorrhages in the peritoneal cavity. This -report is interesting, not so much from a diagnostic standpoint as -because "contrary to what might have been expected, scorbutic cases when -operated upon showed no particular tendency to hemorrhage." - -=Infantile Scurvy.=--The stereotyped picture of infantile scurvy and the -one which this term commonly suggests, is that of the acute form of the -disease. In _acute infantile scurvy_ we have to do generally with a -poorly-nourished, pale infant with a peculiarly alert and worried -expression. As we approach its bed it whimpers or cries out in terror. -Frequently its posture is characteristic, as it lies quietly on its back -with one thigh everted and flexed on the abdomen. Examination shows that -one or even both thighs are swollen and exquisitely tender, or that -there is merely tenderness, the baby shrieking at the slightest pressure -upon the lower end of the femur. If teeth are present, the adjacent gums -are red, swollen and bleed readily. This is the syndrome which the -medical student is taught to carry away to guide him in his everyday -practice. It is the acute, florid type, and presents a striking picture, -but must not be regarded as the common form of the disorder. If we are -to diagnose infantile scurvy early and not overlook its more subtle -manifestations, the classic textbook description must be augmented by -portrayals of types of the disorder which are less crude and more -difficult to recognize--of "subacute" and of "latent" scurvy. - -The commoner form, which we have termed "_subacute infantile scurvy_," -comprises a large number of symptoms which are inconclusive -individually, and frequently escape correct interpretation. The affected -baby is usually in the second half of the first year of life, and does -not gain in weight or gains but slightly for weeks. It may be fairly -well nourished, but is pale or sallow, with perhaps slight edema of the -upper eyelids. The mother or nurse complains that the child is irritable -and peevish, and that the appetite is poor or capricious. The gums show -a lividity or slight peridental hemorrhage, which on subsequent -examination may be no longer visible, and may have consisted merely of a -rim of crimson edging the borders of the upper gum, perhaps behind an -upper incisor, as Still pointed out. On closer examination it may be -observed that the papillæ of the tip of the tongue are markedly -congested, and that a petechial spot is to be seen on its frenum, on the -palpebral conjunctiva, or here and there on the surface of the body, -more especially where there are erosions, eczema or other skin lesions. -Attention may be called to tenderness of the lower thighs, which in some -instances is definite, in others so ill-defined and fleeting that it is -impossible to convince oneself of its significance or even reality. -There may be slight edema over the crests of the tibia, of a kind which -does not pit on pressure. The knee-jerks are almost always markedly -exaggerated. The urine is diminished in volume but is generally normal -or contains a trace of albumen and red and white blood-cells. The pulse -is frequently rapid, and becomes markedly rapid and irregular on the -slightest excitement. The respirations are also rapid (Fig. 15). - -These symptoms do not constitute a rigid entity, but are subject to -manifold variations. The syndrome may be rendered less typical and clear -by the fact that the infant has gained steadily rather than lost in -weight, as is sometimes the case if the food has been insufficient -during the first few months of life. Roentgenograms of the bones may -show the "white line" at the epiphyses first described by Fraenkel (Fig. -20) or a thickening of the periosteum. However, too great reliance -should not be placed on these signs in making an early diagnosis of -this disorder, as neither is invariably present. - -An instance of subacute scurvy, which in many respects is typical, is -the following: - - I. F., girl, was seen when 3 months old, weighing somewhat over 8 - pounds. She was given Schloss milk, 4 ounces, and then 5 ounces - every three hours, and did well, weighing 11¼ pounds two months - later. As she failed to gain for some weeks, although getting 6 - ounces of food, it was thought that this might be due to the fact - that she was getting pasteurized milk and had never received an - antiscorbutic. Autolyzed yeast had been tried as a prophylactic - antiscorbutic, but failed to bring about a gain. When, however, - orange juice was substituted for the yeast, a prompt growth-reaction - resulted, a gain of 1¼ pounds in four weeks. Accompanying this - lack of gain in weight there were many of the other symptoms - enumerated above; irritability, pallor, slight tenderness of the - lower ends of the femora, albumin and a few red and white cells in - the urine. The pulse- or heart-beat was frequently over 150, and the - respiration 60 (Fig. 15). The diagnosis of subacute scurvy was - substantiated by the prompt subsidence of all symptoms when orange - juice was administered. - -[Illustration: FIG. 15.--Chart of I. F., aged 7 months, showing a prompt -effect on pulse, respiration and temperature of substitution of orange -juice (30 c.c.) for autolyzed yeast (30 c.c.) and a further response -when the former was replaced by potato (15 g.).] - -Infantile scurvy may be dormant for a long time. The diagnosis of -_latent scurvy_ is based mainly on the reaction to specific therapy, on -the marked improvement when orange juice, tomato, potato or other -antiscorbutic food is given. The symptoms themselves are suggestive, and -do not enable an absolute diagnosis to be made. In our experience with -many cases of this kind the usual course has been as follows: The infant -has been generally from 6 to 9 months of age, and fed for a considerable -period on pasteurized milk, which may or may not have been prepared with -cereal decoction. Nor has it been material whether gruels also had been -given. When about 6 months of age the baby ceased to thrive, to gain -satisfactorily, to look healthy, and to feed as it should. The most -careful investigation or physical examination has failed to solve the -difficulty. On the other hand, the history of a diet of heated milk, -especially if the quantity was not large, considered in conjunction with -the pallor and poor appetite, the increased knee-jerks, and perhaps a -rapid pulse and respiration (the cardiorespiratory syndrome), has -awakened suspicion. Orange juice or canned tomato, prescribed in such -cases with a view to diagnosis as well as to treatment, frequently -brings about a magic result. The following case, the weight chart of -which is reproduced (Fig. 14), is fairly typical of this abnormal -nutritional state: - - H. S., boy, born December 15, 1915, was artificially fed until - January 4, 1916, when he weighed 6½ pounds. He was given 28 - ounces of Schloss milk a day. (This was prepared from pasteurized - milk which was not heated a second time. It contains per litre - (quart) 140 c.c. of whole milk, 140 c.c. of 20 per cent. cream, 50 - g. of dextrimaltose, 5 g. of plasmon, 0.2 g. of potassium chlorate, - and 700 c.c. of water.) By March 1 he weighed 9 pounds, and gained - three-quarters of a pound more in the course of this month. During - April he gained only 4 ounces. As will be seen from the chart, - there was almost a cessation of gain from April 10 to May 3, - although yeast was added to the diet. May 2, orange juice was given. - The weight advanced at once, the color and the general appearance - improved, and an eczematous condition of the face rapidly healed. It - will be noted from the chart that the gain occurred, although the - food intake remained the same. - - Epicrisis: A baby 4 months old with latent scurvy, which existed - since he was at least 3 months of age. - -_This condition of latent scurvy is probably the commonest type of the -disorder, especially in the larger cities where almost the entire milk -supply for infants is pasteurized._ It usually passes unrecognized. Most -infants fortunately are given orange juice by the time they are 6 months -of age, and may receive a small amount of vegetable or potato before -they are much older, so that they are protected from serious harm in -this way. But there is no doubt a considerable number, especially those -peculiarly susceptible, who quite unbeknown to anyone pass through the -state of latent scurvy. - -If this large group of cases were included in the incidence of infantile -scurvy, we should not look upon it as a disorder which occurs rarely -during the first six months of life. - -When scurvy goes unrecognized or untreated for a long time, or the -antiscorbutic content of the food is exceptionally small, or the patient -unusually susceptible, the disorder may progress and resemble the -advanced cases described in connection with the adult type of this -disease. Happily such instances are rare. One of the most typical and -vivid descriptions of _an extreme case_ of infantile scurvy is that -reported by Vincent: - - The infant lay in its bed extremely apathetic and barely conscious. - Its face was ashy gray in color, the respirations were extremely - frequent, the pulse-rate was 144 per minute, and the temperature - 103.2°. When touched it moaned feebly, and made no attempt at - movement. The mouth was kept open, the lower jaw hanging away from - the face. There was a complete absence of muscular tone, so that the - infant appeared to be quite incapable of voluntary movement. - - The mouth presented a horrible appearance. No sign of the teeth - could be discovered, though it was stated that several had appeared. - All that could be seen was a purple mass, which was so extensive - that on superficial inspection it was difficult to distinguish - between the upper and lower jaws, despite their wide separation. - Scattered over this purple mass were areas of necrosing tissue, the - odor of which was extremely unpleasant. - - Petechial hemorrhages were distributed over the back and limbs, and - a large patch of extravasated blood was found in the region of the - left hip. - - Tenderness was present in all the limbs, as manifested by moaning - and by the facial expression. There was a general enlargement over - both humeri throughout their length; the ulna and radius did not - appear to be thus affected, but the index-finger of the right hand - was enlarged, especially at the junction of the metacarpal bone with - the first phalanx, the enlargement being at each side of the joint. - In the legs the signs were extreme. At both knee-joints the skin was - tightly stretched over the swollen epiphyses; the tenderness also - was greater than at any other part. - - Bleeding from the gums and nose had occurred; no history of - hæmaturia could be obtained. The motions were semisolid, green, and - offensive. During the last twenty-four hours the infant had refused - food. - - The baby was given large amounts of lemon juice and subcutaneous - injections of salt solution and the necrosing surfaces of the gums - were scraped and swabbed with boracic solution. By the third day the - pulse was 100, the temperature 99.8°, the odor from the mouth - scarcely noticeable, and the general condition distinctly improved. - It continued to improve and to gain in weight and when seen at the - end of the sixth week of treatment it was doing well and was quite - happy. - -It will be well to consider in detail the signs and symptoms which may -develop in the course of scurvy. - -=Hemorrhage.=--_Hemorrhage of the gums_ is one of the characteristic -signs of scurvy. For a reason not clearly understood it involves first -and foremost the tissues about the upper incisors. If, however, we fix -our attention too narrowly to this region we may be led into error; in -several instances we have first encountered hemorrhages about the molar -or the canine teeth, which had been overlooked because the anterior part -of the gums had been found normal. Where teeth are absent or not in the -course of eruption hemorrhages do not appear. At the onset the gums may -be merely deep red or bluish red, especially if they overlie upper -incisors which are close to the surface. Hemorrhage is particularly apt -to occur where the edges of the teeth have just broken through the -mucous membrane. In this connection the question arises as to whether -every hemorrhage of the gums in infants is to be considered a sign of -scurvy. This is a matter of some diagnostic importance. We have seen -hemorrhages of the gums at the site of erupting molar teeth where, as -prolonged observation proved, not even latent scurvy existed. This sign -should not, therefore, be regarded as pathognomonic. In two infants -entirely free from scurvy we have noted slight hemorrhage of the gums -overlying incisor teeth. It should be well understood that such an -occurrence is most exceptional; it is to be attributed probably to -bacterial invasion or to a constitutional hemorrhagic condition. One of -these cases was the following: - - The infant was 8½ months old. It had been nursed by the mother up - to this time and was well nourished, but when first seen had some - fever, probably due to a grippe infection. About ten days later - distinct linear hemorrhages of the gums were noted over the two - upper incisor teeth. No treatment was instituted for this condition, - and it healed within a week. There was no subsequent sign of similar - hemorrhage or of other scorbutic manifestation in the months that - the baby was under observation. - -The localization of the hemorrhage in the gums is due largely to trauma, -occasioned by the sharp contact of the jaws or of the nursing-bottle. -Local infection plays almost no rôle in infants, although in the adult -where there is caries of the teeth it frequently incites hemorrhage. -Dental caries and gingival infection may lead to local hemorrhage, even -where the nutritional conditions are normal. - -Subperiosteal hemorrhage is a sign distinctive of infantile scurvy, -although it must be borne in mind that it may take place in the scurvy -of adults. It involves most frequently the lower end of the femur and -the tibia, but occurs in connection with the humerus, the mandible, the -scapula and other bones.[47] The hemorrhage usually manifests itself as -a swelling which appears suddenly at the lower end of the femur or -femora. It is brought about by trauma, at times in the course of -diapering, or by manipulation in testing for local tenderness. The -swelling is very tender, and varies in size from an enlargement which is -difficult to appreciate, to one which renders the leg fully twice its -normal circumference (Fig. 18). It may involve merely a small part of -the long bone or extend up or down the shaft for a long distance. As -might be supposed from the nature of this lesion, the enlargement -persists for weeks, frequently long after the gums and the general -symptoms have disappeared. During this period it becomes harder and less -tender, and may develop the consistency of bone; it is in this stage -that such swellings have been diagnosed as new growths, and that -incision or even amputation of the leg has been resorted to. In -subacute cases the swelling--which must be regarded as hemorrhagic -rather than scorbutic--may be absorbed gradually in spite of the fact -that no antiscorbutic food has been given. This has led to the mistaken -conclusion that the scurvy has been cured without dietetic treatment. - -[47] There seems to be some misconception as to the pathogenesis of the -subperiosteal hemorrhage in scurvy. In most reports this lesion is -described as if it resulted from a hemorrhage burrowing its way beneath -the periosteum and raising it from the subjacent bone. In point of fact, -such an event is impossible, as will be fully realized when one -experiences the great difficulty in separating periosteum from normal -bone. The scorbutic process involves the periosteum so that it is no -longer normal but becomes insecurely attached to the shaft of the bone, -and is readily stripped off by hemorrhage. - -Subperiosteal hemorrhage may be clearly seen by means of the fluoroscope -or in X-ray photographs (Figs. 16 and 17). The shaft of the bone appears -surmounted by an elongated blood-clot, which is more or less distinct -according to its age and density. It may become calcified, as clearly -seen in figures. More often the periosteum undergoes calcification or -ossification, especially near the site of the separation of the -epiphysis. This gives rise to a bizarre radiographic picture which may -be difficult to interpret--the opaque strip or streamer being almost -unrecognizable as periosteum (Fig. 17). - -[Illustration: FIG. 16.--Infant 11 months old. Separation of lower -epiphysis of femur. Fraying of end of femur and head of tibia. -Subperiosteal hemorrhage surrounding lower part of shaft of femur, with -calcification of periosteum and of clot.] - -[Illustration: FIG. 17.--Infant 11½ months old. Separation of lower -epiphysis of femur with marked subperiosteal hemorrhage. Typical -periosteal "tags" or "streamers." The connection of these "streamers" -with the periosteal layer is evident.] - -Hess and Unger observed that in several instances where subperiosteal -hemorrhage had been diagnosed, X-ray examination disclosed that the -swelling of the thigh was due mainly to infiltration of the muscles and -subcutaneous tissue. It is surprising how an infiltration of serum gives -rise to a swelling which resembles in appearance and consistency the -classical subperiosteal tumor. - -The skin, mucous membranes and subcutaneous tissues are frequently the -sites of hemorrhage. There is a difference of opinion as to how -frequently petechial hemorrhages occur in scurvy, particularly as to -whether they are encountered early in this disorder. Great variation in -this regard may be noted in individuals and in groups of cases occurring -at different times. In the cases reported in 1914 by Hess and Fish, -petechial hemorrhages were frequently an early sign, to such an extent -that they led to a study of the blood and blood-vessels in this -disorder. The hemorrhages in this "scurvy epidemic" were the result of a -complication of scurvy with an infectious disease. It is not necessary, -however, for infection to exist to bring about a rupture of the small -vessels. The idiosyncrasy of the individual has to be considered as well -as the fact that infants have a tendency to develop minute skin -hemorrhages, especially such as have an exudative diathesis. In the -course of scurvy, petechiæ may be found not only in the skin, but in -the mucosa of the mouth, especially overlying the hard palate, and also -in the palpebral conjunctiva, identical with the minute petechiæ so -significant of general sepsis. In addition to these minute hemorrhages -larger ones are not infrequently found in various parts of the body, -especially in the neighborhood of the joints. They appear as -discolorations of various intensities and shades, and are often -interpreted as being merely the result of bruises. These have been -encountered most often about the knee-joint, on the forehead, or in the -concha of the external ear, where they may best be seen by means of -transmitted light. - -A form of hemorrhage which must be especially mentioned, although it is -very infrequent, is that taking place into the orbit, leading to a -_proptosis of the eyeball_, usually the left (Still). This sign should -be borne in mind, as it occurs occasionally before other symptoms have -rendered the diagnosis clear, and may lead to a diagnosis of tumor. - -As mentioned above, hemorrhages into the muscles or between the muscle -planes are very common in adults, leading to hard swellings, the typical -"scurvy sclerosis." Such effusions occur much less frequently in -infants, due probably to their lack of activity. In addition to these -hemorrhages there are serous effusions of the muscles similar to those -which are found in the pleural and pericardial cavities. These effusions -are very striking at necropsy, when one incises the muscles--for -example, the muscles of the thigh. During life they are frequently -mistaken for subperiosteal hemorrhages. - -Less frequently there are _hemorrhages into the internal organs_. These, -however, play a comparatively insignificant rôle in the symptomatology -of this disease. At postmortem examination we find numerous hemorrhages -of the pleura, pericardium and peritoneum, which rarely produce -symptoms during life. Still records a case with marked abdominal pain -and swelling, which he believed to have been due to hemorrhage into the -wall of the intestine. As previously mentioned, O'Shea met with a case -of hemorrhage into the cæcum which was mistakenly operated upon for -appendicitis. Hæmothorax and hæemopericardium occur, especially -associated with local inflammatory processes of tuberculous nature. The -clinical aspect of hemorrhage of the gastro-intestinal and the -genito-urinary tracts will be considered elsewhere. - -In the scurvy of adults as well as that of infants, _the nails and the -hair_ are altered by the nutritional condition. Mention has been made of -the hyperkeratosis recently emphasized by Wiltshire as an early sign, -occurring especially on the thighs and legs. The skin is frequently dry, -the so-called "goose skin" that is seen in some poor nutritional states. -The nails are thin, brittle and lined; at times small hemorrhages will -be noted beneath them. The hair also becomes thin and dry, and there is -a tendency for petechial hemorrhages to develop at the roots. - -In a paper on the therapeutic value of yeast and of wheat embryo the -author called attention to the fact that _eczema_ may occur in -connection with infantile scurvy, and be cured by means of orange juice. -We have met with eight cases of eczema in infantile scurvy, which, in -almost every instance, have yielded promptly to an antiscorbutic, thus -proving their scorbutic nature. A case of this kind is the following: - - M. L., seven months old, was getting "Molkenadaptierte" milk, and in - addition autolyzed yeast. On May 25th it developed nasal diphtheria, - but soon afterward did well. On June 9th it was gaining, but its - pulse was 160 and respirations 80. A few days later it developed - marked eczema about the neck and to a less extent on the back and - buttocks. The "capillary resistance test" was negative. - Cardiographic tracings showed merely a simple tachycardia. A few - days later petechial spots appeared at the site of the eczema. On - June 17th orange juice was given. The appetite improved, the - cardiorespiratory syndrome disappeared, and the child began to gain. - The eczema also cleared up rapidly without any local treatment. - -We wish to draw particular attention to this skin condition, as it is -generally not mentioned, or has been regarded merely as a chance -occurrence. The report of the American Pediatric Society includes two -cases of eczema as a complicating condition. This symptom is of special -interest in view of the fact that a similar skin lesion constitutes one -of the typical signs of pellagra. In a case of infantile scurvy we have -seen an eruption at the nape of the neck which was symmetrical and -greatly resembled that of pellagra. Andrews refers to the occurrence of -eczema in his description of infantile beriberi. - -In a paper published a few years ago attention was drawn by Hess and -Fish to the fact that infantile scurvy frequently is associated with the -exudative diathesis of Czerny, a pathological condition which -predisposes to the development of exudations of the skin and the mucous -membranes. Infants suffering from this condition--intertrigo, eczema, -recurrent bronchitis--seem to be particularly susceptible to scurvy and -to develop it more quickly than others. - -As is well known, _edema_ constitutes a not infrequent symptom of adult -scurvy. It has not, however, been accorded any place in the -symptomatology of infantile scurvy. We do not refer to the edema in -connection with subperiosteal hemorrhage or separation of the epiphyses -of the long bones, but a mild and peculiar form which is seen early in -the disease. It involves most regularly the upper eyelids, and the -legs--especially the skin covering the lower part of the tibiæ. In the -latter site it differs from edema as usually encountered, in that it -does not pit on pressure; it is firm, tense, causing some glossiness of -the overlying skin, which is rendered difficult to wrinkle or to pinch -between the fingers. Not infrequently the skin is slightly reddened, a -sign of interest, in view of a similar, although much more intense, -hyperæmia seen in pellegra. - -In addition to this very mild edema there may be marked swelling, -resulting in what might be called, following the terminology of -beriberi, "wet scurvy." The legs, body and even the face may be swollen. -This has been frequently described in adult scurvy, and occasionally in -infantile scurvy. The first case of infantile scurvy described in -America, that of Northrup, had marked edema of the scrotum. Edema is -frequently met with in "ship beriberi," a disorder considered by some -writers to be a combination of beriberi and scurvy. - -The symptom leading to the diagnosis of scurvy most often is -_tenderness_ or swelling of one of the extremities, as the antecedent -clinical signs, comprising latent scurvy, are generally overlooked. -These manifestations involve usually the distal end of the thigh or -thighs. The tenderness is elicited most readily by pressure just above -the knee, which causes the baby to wince, and to quickly flex the thigh, -a reaction termed by Heubner "the jumping-jack phenomenon." As a result -of pain and tenderness, the leg lies often immobile in a state of -pseudo-paralysis (Fig. 18). There may be tenderness elsewhere than in -the long bones. Kerley refers to two cases showing tenderness of the -spine, and we have seen a similar case. Not infrequently there is -tenderness of the chest wall, the earliest symptom noted by nurse or -mother being unaccountable crying whenever the baby is lifted by the -thorax. This is largely due to the sensitiveness of the ends of the -cartilage and bone which are pressed together at their junction. - -[Illustration: FIG. 18.--Infant with marked scurvy. Characteristic -posture and swelling of right thigh.] - -An early sign of infantile scurvy is _beading of the ribs_--the -development of a "rosary" similar to that characteristic of rickets -(Fig. 19). This has recently been described by Hess and Unger in an -article devoted to this subject. That this rosary is truly scorbutic and -not rhachitic is proved by the fact that it recedes rapidly when -antiscorbutic foodstuff is given, and that it remains uninfluenced by -treatment with cod liver oil. A similar scorbutic rosary occurs in -guinea-pig scurvy, but has been termed "pseudo-rhachitic." It is -important that this sign should be recognized, as it is probable that -much of the confusion regarding the relationship and frequent -association of these two diseases is due to considering the beading -rhachitic. The interpretation of infantile scurvy as "acute rickets," -the view held previous to the writings of Barlow, was based largely on -the development of the rosary. To-day the error is made of regarding -early scurvy as chronic rickets; the rickets supposed to be occasioned -by a diet of condensed milk is probably more often scurvy. This beading -differs generally from the round knobby "rosary" usually encountered. It -is more angular, the junction taking on a step-like form, as if the -abutting ends of the cartilage and the bone were of unequal size, and -not well fitted to each other. In the accompanying radiograph (Fig. 19) -it will be noted that the "beads" present an irregular appearance. - -[Illustration: FIG. 19.--Same infant as in figure 17. Scorbutic beading -of the ribs (rosary). This developed on a diet which included cod liver -oil, and decreased when an antiscorbutic was given. Note peculiar ragged -appearance of "beads."] - -In Figs. 6, 16 and 17 will be seen illustrations of a _separation of the -epiphyses_ of the head of the humerus, and of partial and of complete -separation of the lower ends of the femora. This is a frequent lesion of -fully developed scurvy in infants, children, and even in young adults. -It is most frequent at the lower end of the femur, the upper end of the -tibia, the head of the humerus, and the costochondral junctions. It is -to these epiphyseal separations that the term fracture or infraction -usually refers. Union is remarkably perfect even where no splint has -been employed, and nature has effected the cure (Fig. 7). Occasionally -there is some deformity, as when coxa vara develops. The callus is often -remarkably large; an old callus sometimes undergoes destruction in the -course of scurvy. - -We have referred to use of röntgenograms in connection with separation -of the epiphyses, subperiosteal hemorrhage, cardiac enlargement and -beading of the ribs. In addition to its application in these -connections, the X-ray may be of service to show a peculiar alteration -of the ends of the long bones--_the white line of Fraenkel_. This is -portrayed in Fig. 20. It is best seen at the lower ends of the radius -and femur, and appears as a white, transverse, somewhat irregular band. -Its diagnostic value has been greatly exaggerated, as it is frequently -not present when the disease is advanced (observe radiographs -illustrating separation of the epiphyses). This sign should therefore -not be relied on for establishing the diagnosis. Furthermore, changes -may be seen in connection with rickets (cases receiving antiscorbutic -diet) which are very difficult to differentiate from the "white line." -It cannot be employed as a criterion of the progress of the case, as it -may persist for months after all other signs and symptoms have -disappeared. - -[Illustration: FIG. 20.--Radiograph. Infant 14 months of age, showing -"_white line_" at wrist some months after cure of scurvy.] - -The joints may be involved in scurvy. In most instances, however, where -swelling of the joints is diagnosed, the lesion is periarticular. An -effusion of serum or of blood does occur occasionally into the joints -and has been found at operation, at necropsy, and by puncture. If these -effusions are allowed to go undisturbed, to be absorbed as a result of -antiscorbutic treatment, they rarely suppurate. Czerny and Keller -report the articular fluid as invariably sterile. - -The cardiovascular system has been given but scant attention in -connection with scurvy. Adults complain not infrequently of palpitation -and pain over the pericardium, or rather of a tightness or oppression in -the chest. Little information is given regarding the size of the heart. -Darling described enlargement of the heart, especially a right-sided -hypertrophy, which he thought was pathognomonic of the Rand type of -scurvy. The pulse is described in some cases as slow, and in others as -rapid. In descriptions of infantile scurvy the entire subject is -generally passed over without mention--for example, in the excellent -report of the American Pediatric Society nothing whatsoever is stated -regarding the heart's action or the pulse. Barlow wrote: "There is -nothing to note regarding the heart and lungs." - -In a paper written a few years ago, it was pointed out by the author -that there is frequently enlargement of the heart, and more especially -of the right heart. This can be elicited at the bedside and has been -substantiated in numerous cases by means of the Röntgen-ray, which -demonstrates not only enlargement of the heart, but also a marked -broadening at its base, at the site of the large vessels (Fig. 21). -These phenomena resemble closely the description of Reinhard in cases of -beriberi. - -[Illustration: FIG. 21.--Radiograph. Scorbutic infant 14 months of age, -showing cardiac enlargement and broadening of shadow at base of heart.] - -Necropsy protocols usually are incomplete and unsatisfactory in their -descriptions of the heart. The excellent monograph of Schoedel and -Nauwerk, however, which reports five careful necropsies, contains the -following data regarding three: - -1. Pericardial fluid somewhat increased, both ventricles moderately -dilated, the right somewhat hypertrophic. - -2. The heart showed a hypertrophy of the right and left ventricles, as -well as dilatation of the right ventricle. - -3. The right ventricle dilated and slightly hypertrophied, the muscles -pale and tough. - -In addition to this enlargement of the heart, or perhaps associated with -it, there is a combination of signs which has been termed "_the -cardiorespiratory syndrome_" (Hess). It will be noted in the above -description of a case of subacute scurvy, that the pulse- or heart-beat -was frequently over 150, and the respiration 60. These phenomena were -noted in several instances before their significance and intimate -relationship to scurvy were realized. The heart-beat not infrequently is -found to be 200 per minute, and to be characterized by marked -lability--increasing to an astonishing degree as the result of slight -exertion or excitement. A mild febrile disturbance causing a rise of -temperature to little more than 100° F. will send the pulse-rate up 30 -beats. It must not be thought that this refers to severe cases; the -babies we have in mind are similar to the one cited as an instance of -subacute scurvy. Apparently they are not ill, but show merely some -tenderness of the thighs, pallor, and the other minor signs described. -The cardiographic tracings showed a simple tachycardia with an -exceptionally tall T-wave in some tracings, such as is commonly seen in -exophthalmic goitre (Fig. 22). - -[Illustration: FIG. 22.--Electrocardiogram in case showing -cardiorespiratory syndrome. Tachycardia with exceptionally tall T-wave.] - -The rapidity of respirations is perhaps a more delicate indicator of -this disturbance than the pulse and has been found to be markedly -affected when the latter was merely slightly increased in rate. For -example, in one instance the respirations were 64, 60 and 64 on three -successive days, while the pulse was 124, 141 and 136; in other words, -there was a 2:1 instead of the normal 4:1 pulse-respiration ratio. The -accompanying chart (Fig. 15) illustrates the phenomenon in all its -details better than a verbal description. There is one point in -connection with it, to which especial attention should be called. This -is a reaction evident at a glance at the chart--the sharp drop in the -pulse and in the respiratory rate when orange juice was given. It is the -essence of the phenomenon; a therapeutic response which proves that the -rapidity is scorbutic in nature. - -The main involvement of the _respiratory system_ in scurvy is the -polypnoea just described in connection with the cardiorespiratory -syndrome. There is no aphonia, a sign so typical of adult and of -infantile beriberi, although at times the voice is abnormal and whining. -The lungs frequently show some dullness posteriorly, which may be due to -engorgement or to the pressure of the enlarged heart. Pneumonia is a -frequent complication and edema a terminal event. Hydrothorax associated -with hydropericardium is of frequent occurrence, and was noted in the -early description of this disease in adults and in the first account of -Barlow. These effusions rarely progress to what may be termed the -clinical degree and under antiscorbutic treatment are rapidly absorbed. - -It is commonly thought that scurvy does not involve _the nervous -system_; that this is a feature which distinguishes it sharply from -beriberi, another "deficiency disease." This view is incorrect, for the -nervous system is probably affected in many cases of scurvy. The -rapidity and lability of the pulse, combined with the rapid -respirations, would seem to be due to a disturbance of the vagus -mechanism. It is true that in beriberi the vagus is involved to a still -greater extent, especially its recurrent laryngeal branch which brings -about the characteristic aphonia. In scurvy the knee-reflexes are -generally increased. Very rarely they are absent in infantile scurvy, as -described in adults. It is impossible to judge whether the pain and -tenderness in infants are due in part to a sensitiveness of the nerve -trunks as well as of the periosteum. Careful studies in adult scurvy -should furnish an answer to this question. No methodical examination -for areas of anæsthesia or paræsthesia, signs which occur so frequently -in connection with beriberi, has been carried out in scurvy. In certain -epidemics, however, pains in the limbs have been prominent symptoms. - -The optic discs are generally pale in both infants and in adults, with -occasional signs of neuredema. Nyctalopia, so frequently encountered, -must be regarded as a circulatory symptom rather than as one of nervous -origin. - -In a recent paper the author described a focal degeneration of the -lumbar cord in a case of infantile scurvy, the lesion involving mainly -the anterior horn cells (Figs. 3 and 4). In view of this report it would -be well to watch for corresponding clinical signs of involvement of the -spinal cord. Herpes has been described in connection with both adult and -infantile scurvy. In one of the early cases in the American literature -Fruitnight reported a case with herpes in a girl five years of age. In -considering the rôle of the nervous system, mention should be made of -cases where sweating constituted an important symptom. Finkelstein lays -particular stress on this symptom in infantile scurvy. We have not met -with it frequently; possibly it is due in part to complicating rickets. - -As would be expected, the nervous system is at times the site of -hemorrhage. Such lesions cannot, however, be considered essentially -nervous. For instance, hemorrhage into the meninges may occur, as in the -case of Sammis, where there was "a general clonic convulsion" before -death, and a blood-clot 2½ inches long by ½ inch wide was found at -necropsy between the dura and arachnoid. Fife reported a similar case. -Finkelstein also has drawn attention to the occurrence of meningeal -hemorrhage, and Hess and Fish reported obtaining bloody cerebrospinal -fluid from a case with meningeal symptoms. Recently Aschoff and Koch -have depicted hemorrhages in the sheath of the sciatic nerve, which -undoubtedly must have given rise to symptoms during life. - -In view of many of these symptoms, especially those involving the vagus, -scurvy must be looked upon as a disorder which may seriously affect the -nervous system. Furthermore, when we note the marked reaction brought -about by the antiscorbutic vitamine--for example, the sharp fall in the -rate of respirations and of pulse, as shown in Fig. 15, after giving -orange juice, we must conclude that the antiscorbutic vitamine -functions, at least indirectly as an antineuritic vitamine--that it must -possess this character to allay the various nervous signs of this -disorder. - -The urinary system is frequently involved in the course of scurvy. Among -38 cases Still reports that 89 per cent. gave evidence of urinary -changes and that 60 per cent. showed hæmaturia. Finkelstein found -urinary signs in at least a third of his cases. Our figures, the result -of a study of subacute and mildly acute cases, correspond more nearly -with those of Finkelstein. - -The occurrence of pronounced renal hemorrhage as a first symptom of -scurvy is emphasized in many descriptions of this disease, and has -impressed itself in the minds of physicians. It is true that this occurs -sometimes at the onset, as does hemorrhage into or about the joints, or -hemorrhage behind the eyeball. It is well to bear these possibilities in -mind, but they must be regarded as very exceptional early signs of this -disorder. We have encountered frank hæmaturia but once in the early -stage of infantile scurvy. The blood emanates generally from the -kidneys, although the submucous hemorrhages of the bladder as well as in -the urethra, described both in man and in guinea-pigs, indicate that the -blood in the urine may have its origin lower down in the tract. This -bleeding should be regarded not as a sign of nephritis, but rather as a -hemorrhagic manifestation. It is less frequent in adults than in -infants. O'Shea reports some degree of hemorrhage in 15 per cent. of his -cases (adults). - -A true nephritis, however, may occur in connection with scurvy. There -may be albumen and many casts, or a urine loaded with casts and -cylindroids. These peculiar casts may appear suddenly, as in the -alimentary intoxication of infants, and disappear just as rapidly when -antiscorbutic treatment is given. The urine may contain a large number -of pus cells as in pyelitis. This condition may be accompanied by -irregular fever, but in two instances we have encountered it where the -temperature was normal. It is to be regarded, probably, merely as one of -the manifestations of secondary infection so commonly associated with -scurvy. Some pus cells may continue to be present in the urine for a -period of months. This is likewise true of the red cells. We have under -observation at present an infant which had subacute scurvy almost three -years ago and still has red blood-cells in the urine. - -Oliguria is a common symptom of both adult and infantile scurvy. Lind -mentioned this symptom, and in this connection remarks on the beneficent -effect of antiscorbutic treatment. Charpentier called attention to the -fact that in a case of scurvy the urine decreased from 1250 g. to 800 g. -The report of the American Pediatric Society mentions scanty urine in 9 -cases and suppression of urine in one. This sign, however, was not -emphasized until recently, when Gerstenberger, and Hess and Unger drew -attention to its frequent occurrence in infants. It has some diagnostic -significance and should be borne in mind where a decreased excretion of -urine is reported. A counterpart of this symptom is the sudden -outpouring of urine frequently noted after antiscorbutic treatment has -been instituted. This polyuria accounts for the loss of weight or lack -of gain which sometimes accompanies unmistakable general improvement, -and which is difficult otherwise to understand (Fig. 23). It is -interesting to learn that oliguria occurs commonly in both adult and -infantile beriberi. - -[Illustration: FIG. 23.--Joseph G., aged 9 months. Chart showing -stationary weight (due to oliguria followed by diuresis) in spite of -marked variation of fluid intake. A=Schloss milk; B=cod liver oil; C=egg -yolk; D=1 ounce of orange juice; E=potato (orange juice stopped).] - -One of the earliest, as well as one of the most constant symptoms of -scurvy, is a _lack of appetite_. It is a typical sign of latent scurvy, -although occasionally we have met with cases where the appetite remained -unimpaired until the hemorrhagic stage was reached. In adults there is -sometimes bulimia and a marked capriciousness of the appetite. Anorexia -is a true scorbutic symptom, disappearing with remarkable rapidity when -antiscorbutic food is given, and not capable of alleviation by tincture -of gentian or other vegetable bitters. Whether it depends upon a lack of -secretions in the gastro-intestinal tract is not known, as there has -been no thorough study of this aspect of the disorder. The hydrochloric -acid generally is deficient in cases of scurvy. Recently McCarrison has -laid emphasis on the importance of the impairment of the digestion and -assimilative function in scurvy. This subject gains added interest in -view of the recent reports of Uhlmann as well as of Voegtlin, showing -that water-soluble vitamine acts as a stimulant for the various -secretions of the gastro-intestinal tract. - -As a result of McCollum's statement that scurvy is due mainly to -_constipation_, marked attention has been directed recently to the -action of the bowels in this disorder. This question has been discussed -in the chapter on etiology, and, therefore, will be referred to in this -place merely from the clinical viewpoint. In our experience the activity -of the bowel varies greatly in cases of latent or subacute scurvy. In a -great many instances it has been normal; more often there has been -slight constipation, and exceptionally there has been irregular -diarrhoea. In other words, no causative relationship or parallelism -could be observed between the emptying of the intestinal tract and the -development of scurvy. This in general has been the experience of -others. In the report of the American Pediatric Society the bowels are -stated as having been regular in 74 cases, irregular in 15, constipated -in 126, and diarrhoeal in 65. It may be added that we were unable to -cure scurvy by means of liquid petrolatum or phenolphthalein, either in -infants or in guinea-pigs, and likewise unable to protect guinea-pigs -from scurvy by means of various laxatives. On the other hand, opium -given in the form of the camphorated tincture did not lead to an -intensification of the symptoms, although, in one case, the bowels did -not move for over three days. - -As complications involving the gastro-intestinal tract may be mentioned -the vomiting of blood, which is stated in the above report as occurring -in 2 of the 361 cases, as well as bleeding from the bowel, which was -noted in 37 cases, in 12 of which there was bloody diarrhoea. However, -these are late symptoms, and correspond to the mycotic ulcers which are -so frequently found, especially in the large intestine, in cases of -scurvy. Mention may again be made of the fact that hemorrhages may occur -under the peritoneum and give rise to symptoms simulating appendicitis -or general peritonitis. - -Jaundice has been described in connection with certain epidemics of -scurvy. To our knowledge it has not been reported in infants. - -The presence of worms has been frequently reported in the bowel or in -the stool of patients suffering from beriberi. There have been no -similar investigations in relation to scurvy. It would be interesting to -inquire into this question, as it is quite possible that a lack of -antiscorbutic foodstuff may favor the presence of parasites in the -intestinal canal. - -Before closing this consideration of the involvement of the alimentary -tract, we would call attention to the relation of stomatitis to scurvy. -Among adults this is a common complication. In infants it is uncommon, -due to the absence of carious teeth and secondary infection; we have -encountered it in but two instances. Stomatitis is of importance in this -connection, as it frequently develops on the basis of malnutrition, -scurvy being one of the disorders which may constitute the substratum. -Such may be the case where stomatitis occurs in epidemic form--for -example, among large bodies of troops. It may be remarked that -stomatitis at times was a very common disease among the soldiers in the -recent war. - - TABLE 4 - THE PLATELETS AND OTHER BLOOD-CELLS IN SCURVY - ====================================================================== - Name | Date | Platelets | Leuko- | Erythro- | Hmgl. % | Remarks - | | | cytes | cytes | (Sahli) | - -----+------+-----------+--------+-----------+---------+-------------- - M. H.| 5/ 3 | 280,000 | ...... | ......... | .. | - | 5/ 4 | 248,000 | 10,000 | ......... | .. | - | 5/ 5 | ....... | ...... | ......... | .. |Boiled orange - | | | | | | juice given. - | 5/ 8 | ....... | ...... | 4,300,000 | 35 | - | 5/16 | ....... | 15,900 | ......... | .. | - | 7/ 2 | ....... | 6,800 | 5,456,000 | 40 |Well but pale. - A. L.| 5/ 3 | 300,000 | ...... | ......... | .. | - | 5/ 5 | ....... | 21,000 | ......... | .. | - | 5/ 9 | ....... | ...... | 5,480,000 | .. | - | 5/11 | 382,000 | ...... | ......... | .. | - | 5/13 | ....... | ...... | ......... | 65 | - | 5/16 | ....... | 11,500 | ......... | .. | - H. C.| 5/ 8 | 320,000 | 20,000 | ......... | .. | - | 5/ 9 | ....... | ...... | 5,340,000 | .. | - | 5/13 | ....... | ...... | ......... | 70 | - | 5/16 | 362,000 | ...... | ......... | .. | - B. B.| 5/ 4 | 496,000 | 21,000 | ......... | .. |A severe case. - | 5/13 | 585,000 | 14,000 | 3,200,000 | 70 | - | 5/18 | ....... | 17,600 | ......... | .. | - | 7/13 | ....... | 40,000 |=7,672,000=| 82 |Has gained well - | | | | | | lately. - | 7/15 | ....... | ...... |=7,640,000=| 88 | - H. Y.| 5/15 | 560,000 | ...... | ......... | .. | - | 5/16 | 424,000 | ...... | ......... | .. | - | 7/ 9 | ....... | ...... | 5,750,000 | 45 | - ----------------------------------------------------------------------- - -Scurvy is associated with an alteration of both _the blood and the -blood-vessels_. The characteristic pallor, which is one of the most -common as well as earliest symptoms, is due in a large measure to the -anemia. This anemia is of the secondary type, but has definite -peculiarities, and does not resemble that encountered in the course of -tuberculosis, rickets or marasmus. The hemoglobin is greatly diminished, -far out of proportion to the decrease in the number of the red cells. -Not infrequently we will find a hemoglobin index of 0.5. Table 4, above -taken from the article on this subject by Hess and Fish (1914), brings -out the details of the blood-picture. It shows that there may be a -polycythemica, which may persist after the other signs of the disorder -have disappeared. Brandt has recently made similar observations, -reporting in one instance over ten million red cells two months after -treatment. In soldiers suffering from scurvy Wassermann has encountered -cases where, during convalescence, the red-cell count has risen to over -six or seven millions and the hemoglobin to 110 or 120 per cent. Under -the microscope the red cells show poikilocytosis, anisocytosis and a -lack of hemoglobin; they are slightly enlarged, with the occasional -occurrence of exceptionally large cells resembling the "dropsical cells" -described in connection with chlorosis. Sometimes a few nucleated red -cells and myeloblasts are seen; megaloblasts are also reported.[48] The -blood-picture bears a remarkable similarity to that of chlorosis, a -point of interest, in view of the fact that both scurvy and chlorosis -have been attributed to a disordered function of the endocrine glands. -The "dropsical cells" suggest a disturbance of the salt balance in the -plasma. In some cases we have found a decreased fragility of the red -cells, which also has been described in chlorosis. - -[48] Senator regarded the marrow in scurvy as being aplastic. Nobécourt, -Tixier and Maillet report postmortem examinations where the marrow -showed an increased number of myelocytes and nucleated red cells of -various kinds. They consider the typical blood change an intense myeloid -reaction of the blood. - -The total number of leucocytes is slightly increased. In our cases the -mononuclear cells have averaged 66 per cent., which is somewhat high -even for infants. This has been the experience of Labor, who, however, -also describes an eosinophilia during convalescence, a phenomenon which -we have not encountered. Some describe a marked increase in the -polynuclear cells, which, probably, is to be regarded as the reaction to -secondary infections. There is indeed a marked difference of opinion in -regard to the morphology of the blood in scurvy in adults as well as in -infants. Some found a large number of one type of cell--for example, -nucleated red cells, myelocytes, eosinophiles--whereas others have -failed to observe an increase of these cells. The divergent reports -probably should be attributed to the fact that the investigators are -describing scurvy of various grades of severity, of different stages of -development, or complicated by intercurrent disease. - -Nobécourt, Tixier, and Maillet have questioned whether there is always -complete recovery from this anemia, which is severe from the standpoint -of hemoglobin and iron. The older authors reported instances where men -have been weakly and ailing for the remainder of their lives after an -attack of scurvy. In some infants pallor and anemia may persist for -months after apparent cure; however, this is the exception rather than -the rule. - -In view of the fact that scurvy frequently is classed as a hemorrhagic -disease, and that hemorrhages play such an important rôle in its -symptomatology, a consideration of the factors concerned in the -_coagulability of the blood_ is of interest. In an investigation (Hess -and Fish) it was found that the oxalated plasma (of blood taken directly -from a vein) showed a slightly delayed coagulation time--eight to -fourteen minutes. The "bleeding time" carried out according to the -simple method of Duke was slightly increased. Holt reports a case where -a child bled to death following incision into an epiphyseal swelling at -the lower end of the femur. The number of blood platelets is increased, -running parallel, as is usually the case, with the number of red cells -(Table 4). This increase in the blood-platelets, recently confirmed by -Tobler and by Brandt, is a very exceptional phenomenon, and was not -anticipated in connection with a disorder characterized by hemorrhage. -The antithrombin content of the plasma is normal. - -The investigation was directed to a study of the integrity of the -blood-vessels in order to account for the hemorrhages. To this end the -"capillary resistance test" was devised.[49] In the majority of cases -this was found to be "positive" (the blood-vessels showing an increased -permeability) and to become negative when antiscorbutics were given and -the symptoms disappeared. This shows that the cellular structure of the -vessels is altered in the course of scurvy, and indicates probably that -this is an important cause of the hemorrhages. The edema of the face and -ankles, the outflow of serum into the body cavities and into the muscles -(Barlow) must be regarded as other evidences of the inadequacy of the -vessel walls. The tendency of children with exudative diathesis to -develop scurvy is perhaps still another manifestation of vascular -weakness. This point of view has been strengthened recently by the -pathological studies of Aschoff and Koch, who regard scurvy as a -nutritional disorder in which there is a lack of some colloidal -substance needed for the normal structure of the vessels. - -[49] A blood-pressure band, or tourniquet, is placed about the arm, and -the pressure increased until the forearm becomes cyanosed and the radial -pulse is almost obliterated. The pressure is then maintained at this -level for 3 minutes. The principle of this test consists in subjecting -the capillaries and venules to increased intra-vascular pressure to -observe whether this strain results in the escape of blood. In infants -the pressure was usually raised to 90 mm.; in some cases it had to be -raised higher in order to entirely obstruct the return flow of the -blood. - -The test is considered to be "positive" when the forearm shows many -petechial spots. In normal infants petechiæ were almost always absent, -or there were few to be seen. This is not a specific test for scurvy, -but demonstrates a weakness of the vessel walls, whatsoever may be the -cause. It is found to be positive in the majority of cases of scurvy. - -When one makes a subcutaneous puncture in infants suffering from scurvy, -a small hemorrhage very often develops at the site of the puncture -wound. This is not the case when one makes a hypodermic puncture in a -normal person or in a hemophiliac, although it does occur in cases of -purpura. This "stick test" is not a constant sign of scurvy, but, like -the capillary resistance test, was found in many cases and disappeared -with the subsidence of the disorder. It shows that the cells of the skin -and subcutaneous tissues are affected, and possibly that their -thromboplastic power is diminished. - -=Nutrition and Growth.=--The general nutrition suffers in scurvy as the -disease progresses. It is a mistake, however, to picture the scorbutic -individual, either adult or infant, as in a state of malnutrition. Not -infrequently he appears well nourished, an appearance which is -heightened by the slight edema of the face. Infants generally for a -period of weeks or months preceding the onset maintain a stationary -weight. This may be the only sign of the scorbutic condition. For -example: - - An infant seen in 1915 gained about one-half a pound during the - months of February, March, April and May. At this time it was - somewhat over 9 months of age and had never received raw milk or - other antiscorbutic food. In June it was given orange-peel juice, - and gained 2 pounds within a month. There were no other scorbutic - signs or symptoms, and no loss of appetite during the months of - February and March, although the baby was suffering from a - progressive scurvy. - -The growth impulse of the body throughout an attack of scurvy remains -unimpaired, being merely in an inactive or quiescent state. Fig. 14 -shows this very well, demonstrating that when an antiscorbutic food is -added to the dietary the gain may be abnormally great--there may be -supergrowth. Generally such marked increases are due to an increase in -the consumption of food, following the stimulation of the appetite. -However, decided gain in weight may follow the giving of orange juice or -other antiscorbutic despite the fact that the intake of food is -maintained at the same level. - -[Illustration: FIG. 24.--Development of scurvy in spite of normal gain -in weight in a baby who had been underfed since birth.] - -Although it may be stated as a principle that the development of scurvy -is accompanied by a failure to gain in weight, there are exceptions to -this rule. Under certain conditions the weight may follow a perfectly -normal course during the entire period. Fig. 24 illustrates this -clinical paradox: - - A baby was seen in January, when it was 7½ months of age. Toward - the end of February, in spite of constant and normal gain in weight, - he manifested unmistakable signs of scurvy--peridental hemorrhage - over the upper incisor teeth, which were erupting, and tenderness of - the lower ends of the femora. The scorbutic nature of these signs - were substantiated by their prompt subsidence on the administration - of orange juice. We explain the phenomenon as follows: This baby had - been starved in a two-fold sense throughout the first months of its - life--it had received a diet lacking in caloric value as well as - deficient in antiscorbutic vitamine. Its growth impulse had been - held in abeyance for months by both of these factors. When - sufficient calories were supplied in the dietary, growth was no - longer repressed, and a steady gain resulted in spite of the - continued inadequacy of the antiscorbutic factor. - -It has been shown that during the period of infancy undernourishment -must be extreme to occasion stunting of growth in length. In animals -Aron demonstrated that lack of nutrition led to a decrease of the fat -and of the muscle of the body, but that the skeleton nevertheless -continued to grow, and the ash content of the body to increase. In -marasmus, or infantile atrophy, the baby usually grows in length, -although its weight remains stationary or decreases. In scurvy we have -shown that there is frequently a definite retardation of growth in -length, an observation which has been recently confirmed by Epstein in -babies which developed this disorder in the foundling asylum of Prague -during the war. This fact shows how profoundly the metabolism must be -disturbed by this disorder. Figure 25 portrays this retardation in -growth and the sharp reaction when orange juice was added to the -dietary. It also demonstrates that the growth impulse remains unimpaired -and capable of quick response when the essential food factor is -furnished. - -[Illustration: FIG. 25.--Showing retardation of growth in length during -the period when no orange juice was given and supergrowth when it was -given once more, O. J.=orange juice. O. P. J.= orange-peel juice. Lower -curve represents the normal.] - -=Fever.=--Fever frequently accompanies scurvy. It is generally of a low -grade, ranging between 100° and 101°, as may be seen in Fig. 15. There -is a difference of opinion as to whether the rise of temperature should -be considered as truly scorbutic in nature, as "scorbutic fever," or -regarded merely as a condition grafted upon the nutritional disturbance. -A phenomenon which might seem to argue for its essential scorbutic -character is the sharp subsidence on giving antiscorbutic food. On the -other hand, this may quite as well be interpreted as due to a secondary -reaction, checking the absorption of toxins or bacteria. High -temperatures--for example, fever of 103° or over--are attributable to a -complicating infection and should lead to careful examination for the -source of the trouble; pyelitis should particularly be borne in mind. In -a recent case fever of uncertain origin disappeared following the -transfusion of blood. - -We have already considered numerous _complications_ of scurvy, and shall -therefore not go over this ground again. Many of them are due to -hemorrhages or to serous effusions in various parts of the body. Another -large group in adults as well as in infants are the result of infection. -The respiratory tract is particularly susceptible, pneumonia -constituting the most common cause of death. In infants we meet with -frequent attacks of "grippe," widespread occurrence of _nasal -diphtheria_, furunculosis and torpid ulcers of the skin, pyelitis, -otitis, adenitis, etc. We have encountered nasal diphtheria--with -typical bloody mucous discharge--so frequently in connection with -scurvy, that where this local infection occurs among a group of infants -they should be carefully examined for latent or mild scurvy. Aschoff and -Koch recently have laid emphasis on the frequency with which diphtheria -complicated scurvy among adults (soldiers). Dysentery is another -complication resulting from an invasion of bacteria. Local infections -occur more often in adults than in infants--cervical adenitis following -gingival pyorrhoea, "bubo" of the groin following infection of the -lower extremity, abscess of the calf of the leg following hemorrhage -into this region. - -Scurvy sometimes occurs in _epidemic form_, especially in the army, but -also, as in Russia, among the civilian population. This results when a -large group of individuals have been maintained on a limited and -inadequate ration, and especially where this nutritional condition is -complicated by intercurrent infection. It should not be interpreted as -evidence of the bacterial origin of scurvy. A few years ago the author -reported an epidemic of scurvy in connection with an outbreak of grippe -in an infant asylum. Twelve infants in one ward were affected. The signs -were atypical--an undue degree of hemorrhage occurring at atypical sites -(Table 5). It will be noted from the table that the ages of the infants, -the distribution of the hemorrhages, the development of signs (in some -instances) in spite of antiscorbutic treatment, the sharply defined -epidemic character, distinguish these cases from the scurvy commonly -seen. This is an instance where latent scurvy was prematurely changed to -acute scurvy by an intercurrent ward infection; an epidemic of grippe -precipitated a pseudo-epidemic of scurvy. It is important, especially -for army surgeons, to bear in mind that where latent scurvy exists a -bacterial invasion will lend the disorder a hemorrhagic character. This -has been noted during the recent war in connection with typhus fever on -the Eastern front, and was remarked upon during the Crimean War and our -War of the Rebellion. Some years ago Wherry made a similar observation -in the course of experiments with the plague bacillus--guinea-pigs fed -on a cereal diet developed far more hemorrhages subsequent to infection -than those which received cabbage in addition. - - TABLE 5 - DATA OF EPIDEMIC OF SCURVY - ==================================================================== - |Age|Weight| Site of | | | - Case| , |_lbs._| Hemor- | Date | Diet | Remarks - |Mos| _oz._| rhages | | | - -----+---+------+----------+-------+--------------+----------------- - 1. | 6½| 9 6|Humerus, |Apr. 19|Breast milk |Grippe since end - J. H.| | | tibia, | | (1 week); | of February; - | | | face. | | pasteurized | nephritis; - | | 10 4|Upper |May 9| milk | v. Pirquet - | | | eyelid | | previously. | negative. - 2. | 5| 12 14|External |May 4|Pasteurized |Twitchings and - L. S.| | | ear, | | milk formula;| convulsions; - | | | parietal | | orange juice | signs of intoxi- - | | | bones, | | 1 oz. daily | cation; red - | | | vertebral| | since April | cells in urine - | | | column, | | 22. | blood fever to - | | | abdominal| | | 101° F.; v. Pir- - | | | wall | | | quet negative. - 3. | 10| 12 8|Femur |Apr. 19|Pasteurized |Grippe end of - A. R.| | | | | milk formula;| January; again - | | | | | vegetables | in April; fever - | | |Femur |June 4| for a month; | until April 17; - | | | again | | orange juice | v. Pirquet - | | | swollen | | longer; get- | positive; - | | | and | | ting orange | gums negative. - | | | tender. | | juice and | - | | | | | vegetables. | - 4. | 5| 7 |Both ears;|Apr. 29|Breast milk |Grippe through- - D. E.| | | parietal | | since April | out March; in- - | | | bones. | | 19; May 30, | toxication; - | | | | | changed to | nephritis; no - | | | | | pasteurized | relapse although - | | | | | milk. | no orange juice - | | | | | | given. - 5. | 10| 15 13|Ear and |Apr. 27|Pasteurized |Two teeth; - T. K.| | | face | | milk, cereal,| gums negative; - | | | | | vegetable, | v. Pirquet - | | | | | soup; orange | negative. - | | | | | juice since | - | | | | | April 15. | - 6. | 4| 8 4|Tibia |May 8|Pasteurized |Grippe end of - P. G.| | | | | milk | February and - | | | | | formula. | first half of - | | | | | | March gained 20 - | | | | | | oz. during last - | | | | | | month; v. Pir- - | | | | | | quet negative. - 7. | 2| 6 4|Abdomen |Mar. 7|Breast milk |Grippe; probable - I. P.| | | | | for past | source of - | | | | | week; past- | epidemic. - | | | | | eurized milk | - | | | | | previously. | - -------------------------------------------------------------------- - - -DIAGNOSIS - -A correct and early _diagnosis_ of scurvy is the more important in view -of the fact that we possess a specific remedy, and that the disorder is -not self-limited. Recognition generally presents little difficulties for -those who have seen cases, but is a stumbling block where the -symptomatology has been gleaned merely from the textbooks. It has been -our experience that medical students who were conversant with scurvy -from a theoretical standpoint failed to diagnose a case presented to -them in the clinic. Where diagnosis is uncertain, the most important aid -is an exact knowledge of the previous diet, and observation of the -reaction of the patient to antiscorbutic treatment. These diagnostic -points should be constantly remembered in relation to the discussion -which follows, and will not be reiterated in the differentiation of -scurvy from the various other diseases. - -The scurvy of adults and of infants are very similar. The main -difference is the subjective symptoms in the adult--pains in various -parts of the body--and the fact that the gums are frequently the site of -infection and ulceration, as well as of hemorrhage. It might be thought -that when scurvy occurs in epidemic form it would be readily -recognized, but experience shows that for months it may permeate the -ranks of troops or the inmates of almshouses, and pass as rheumatism. -This is the cardinal diagnostic error in adult as well as in infantile -scurvy--time and again, and in spite of urgent and repeated warnings, -patients continue to be treated for _rheumatism_. Holt writes: "In fully -four-fifths of the cases which have come to my own notice this -(rheumatism) has been the previous diagnosis." Such has been our -experience. The diagnosis should not be difficult. In sporadic cases, -the individual has limited his diet usually on account of indigestion, -or diarrhoea, or following some dietetic whim or medical advice given -months previously. Where scurvy occurs _en masse_ it may follow an -inability to obtain fresh food--as during war, on shipboard, in the -Tropics or in the Arctic regions--or be the result of a misplaced -reliance on some article of food--for example, dehydrated vegetables. -More careful investigation will disclose that the "rheumatic" pains and -tenderness are not in the joints but in the muscles and tendons. The -calf muscles are frequently painful and excessively tender and somewhat -swollen or infiltrated; the hamstring tendons or the tendo Achilles may -be sore and slightly swollen and the site of slight subcutaneous -hemorrhages. In some cases there is bone tenderness, pain on percussion -of the shins or of the sternum. These signs may be accompanied by, or -even precede, hemorrhages in the gums. The diagnosis of rheumatism in -infants indicates a lack of knowledge of pediatrics, as this disease is -hardly ever encountered in babies under a year and a half of age. - -It is not always easy to differentiate scurvy from _purpura_. In either -disease the gums may be hemorrhagic and swollen, there may be scattered -subcutaneous hemorrhages and pains in the limbs. Occasionally, as in a -case seen a few years ago, we may be forced to resort to the dietetic -test. A close inquiry into the previous diet, however, a history of -previous attacks of purpura, the number, and especially the large size, -of the subcutaneous hemorrhages, and above all, the diminished number of -blood-platelets, should make diagnosis possible. In scurvy the platelets -are almost always over 300,000 per cubic millimetre, whereas in purpura -they are reduced to less than 200,000. - -In the army it may be difficult to distinguish scurvy from _beriberi_, -especially if they occur side by side as in the recent English campaign -in Mesopotamia. There may be a combination of the two diseases, a -picture similar to ship-beriberi, regarded by Nocht as a hybrid of these -diseases. The diagnosis is rendered more difficult, as at times scurvy -is associated with signs of neuritis. We shall have to depend on the -involvement of the gums and the hemorrhages in scurvy, and on the -hyperæsthesia, paræsthesia, and anæsthesia in beriberi; marked edema -points to the latter disease. - -We have thus far had in mind frank and outspoken cases of scurvy. When -we come to consider latent or early cases, the diagnosis is more -difficult and may have to be merely tentative. All that need be added, -in view of the clinical picture sketched above, is that this condition -should not be forgotten in treating adults who have malaise and -indefinite "rheumatic" pains and, more particularly, in relation to -infants who fail to gain, whose appetite is capricious, whose -disposition has become fretful and who have developed the sallow -scorbutic complexion. This warning is particularly opportune at present -in the United States, where pasteurized milk is fed so extensively to -infants, and an antiscorbutic food is not always given. - -In addition to the symptoms just enumerated, tenderness of the bones, -especially of the distal ends of the femora, should be sought for, the -urine should be examined carefully for red blood-cells, and perhaps the -ends of the long bones radiographed for "the white line" of Fraenkel. - -The experience of Comby with infantile scurvy is illuminating. Among the -fifty-five cases which he has seen, the diagnosis was erroneous in -forty-five, and among thirteen cases recently met with, the physician -failed to recognize the disorder in all but two. The infants had been -given sodium salicylate, had been treated with electricity and massage -for the supposed acute poliomyelitis, or given mercury for syphilis, or -incisions or trephining had been carried out for acute osteomyelitis. -Some had been put into plaster casts for coxalgia or for Potts' disease. -This experience requires little comment. It should be added, however, -that in the course of an epidemic of poliomyelitis, such mistakes are -apt to happen, and, to our knowledge, did occur in the recent epidemic. - -In regard to "_the pseudo-paralysis" of congenital syphilis_ diagnosed -as scurvy, it should be remembered that this lesion occurs almost always -before the fifth month of life. A history of previous papular eruption, -the bilateral enlargement of the epitrochlear glands, and the Wassermann -test should suffice to establish the correct diagnosis. - -Besides the clinical conditions enumerated above, we may add the -following, which have been confused with scurvy: Neuritis, hemorrhagic -nephritis, calculus of the urinary tract, renal tumor, orbital tumor, -appendicitis, peritonitis, pleurisy and pneumonia. Holt writes as -follows: "I have known two cases to be operated upon by eminent -surgeons, once with a diagnosis of sarcoma and once of ostitis of both -tibiæ. Not until the subperiosteal hemorrhages and epiphyseal -separations were discovered was the nature of the trouble suspected." -Recently we saw a case of fracture of the distal end of the femur -diagnosed as infantile scurvy; the baby had caught its thigh between the -bars of the crib and snapped the bone in trying to extricate itself. -Finkelstein adds acute endocarditis, hemorrhagic septicæmia with -multiple bone swellings, and leukæmia as having been confused with -scurvy. - -In an interesting account of scurvy in the Russian army during the -recent war, Hoerschelmann states that tired soldiers at times feign -scurvy. They produce a "pseudo-scurvy" by means of scratching the gums -with their nails or rubbing them with tobacco, and at the same time -bring about hemorrhages of the skin by means of trauma. - -Scurvy in the breast-fed infant has been fully considered under -etiology. We wish merely to state again that one cannot be too cautious -in venturing this diagnosis in a nursing baby. The great majority of -reported cases are not scurvy, but bacterial infections, syphilis, or -various forms of intoxication. In establishing a diagnosis the same -principles hold as in the case of bottle-fed infants. - -The most important consideration in the diagnosis of scurvy is to keep -in mind the heterogeneous character of its symptoms, and the manifold -diseases with which it may be confused. Surgeons should be alert to this -danger when about to perform operations for osteomyelitis or bone -tumor. The mistakes occur because cases are infrequently seen and -because the signs, being dependent largely upon hemorrhage, occur in -such varied locations of the body. Where diagnosis cannot be made from -the signs or symptoms, the most important aid is a thorough acquaintance -with the previous diet of the individual and observation of his reaction -to antiscorbutic treatment. - - - - -CHAPTER VIII - -PROGNOSIS - - -The outcome of scurvy, as we encounter it in peace time in the Temperate -Zone, is generally favorable, so that it plays but an insignificant -rôle in our mortality statistics. This results from the fact that we are -abundantly provided with a specific remedy, so that if the diagnosis is -made early and treatment is prompt and thorough, the patient will -rapidly recover and suffer no physical disability. Where antiscorbutic -foodstuffs are not procurable, however, this disease constitutes a -terrible scourge, causing many deaths and spreading among an army, a -ship's crew, or among the civil population with the rapidity of an -epidemic. For example, the ships of the East India Company in their -voyages round the Cape often lost nearly one-half of their crews, and in -Lord Anson's famous voyage round the world 380 out of 510 seamen -perished from the disease. Moreover, if the antiscorbutic treatment is -inadequate or the patient goes untreated for a long period, the cure may -be incomplete, a condition of malnutrition and weakness developing, -which may persist for years. To appreciate this clinical condition we -must refer to the account of physicians who saw thousands of cases of -severe and untreated scurvy among the sailors, who were of necessity -deprived of aid until they reached land. Lind laid stress on a type of -this disease which developed under these circumstances and which he -termed "obstinate scurvy." He writes: "I have met with numerous -instances not only among the common seamen, but of officers, with whom -it had taken such deep root in the constitution as to prove a lasting -affliction to them during a great part of their lives.... Persons are -likewise subject in different periods of their life afterwards to -habitual rheumatism, pains and stiffness in their joints; and sometimes -eruptions on the skin." In his treatise on scurvy, published in 1685, -Harvey refers to this chronic nutritional disorder as "inveterate -scurvy." He pictures patients who had gone untreated for a long time as -"molested with vagrant, ambulative, distending, creeping, vellicating or -lancinating pains of several parts of the body.... They are often loose -and subject to falling into violent fluxes of the belly, diarrhoea and -lienteries." - -Infants as well as adults usually recover rapidly and completely from -scurvy, the result depending largely upon the early recognition of the -disease. We must always bear in mind, however, that from a histologic -standpoint the cure is not simultaneous with the magic disappearance of -the clinical symptoms, but that months probably elapse before the -tissues return to their normal state. It is difficult to give reliable -mortality statistics for infantile scurvy, for so many cases are of the -rudimentary form that percentages are necessarily misleading. Still -writes that in 5 out of 64 cases the disease proved fatal by diarrhoea -and exhaustion. The American Pediatric Society reports 29 deaths out of -397 cases, which gives a similar mortality percentage. When infantile -scurvy was not so generally recognized by physicians the mortality was -much higher, and we find that Barlow encountered 7 deaths in his first -series of 31 cases. - -Even when the child recovers it may not regain its normal health if it -has continued for a prolonged period in a state of chronic scurvy. It -may remain pale and fail to gain in weight in spite of a liberal and -well-balanced diet. Cases of this kind are not infrequent. In this -connection it is worthy of note that 4 of the 41 cases of "coeliac -disease," an interesting intestinal condition described by Still, had -scurvy just before or during the onset of the disease. This observation -conforms to the experience that chronic bowel disorders often follow in -the wake of adult scurvy. - -In adults the heart may be weakened by scurvy, and death may result from -cardiac failure. Cardiac disturbances occur also in infantile scurvy. -This involvement might be expected, in view of the tachycardia -(cardiorespiratory phenomenon) which is so frequent a symptom of -infantile scurvy. The heart may be rapid for months or even for years -after the disorder, and tachycardia may develop on the occasion of even -a mild infectious disease. For example, a fever of 101°, due to a common -coryza, may cause the heart-beat to rise to perhaps 180 a minute. -Children so affected succumb readily to infection, especially to -pneumonia, which may lead to sudden collapse followed by death. - -An important factor in the prognosis of scurvy, as in that of other -disorders due to a lack of vitamines, is the marked susceptibility to -infection. Even latent or subacute scurvy causes a peculiar -susceptibility to diphtheria (especially the nasal type), to coryza, -bronchitis, and pneumonia. A perusal of the literature shows that this -susceptibility was noted by the older authors in relation to adults. - -The local signs usually disappear quickly without leaving any trace. The -hemorrhages are absorbed and the eczema heals within a few days. The -fractures unite promptly with the formation of an unusually large -callus. The urine, which may have contained red blood-cells or have been -markedly hemorrhagic, quickly becomes normal and, in our experience, -gives no further evidence of renal damage. Still reports, however, the -case of a frail child who had a trace of albumen in the urine two years -after an attack of scurvy. A rare local injury, which may lead to death, -is cerebral hemorrhage. Recently Sammis reported a case of this kind, -which was characterized by convulsions during life, and in which -subdural hemorrhage was found at necropsy. - -If we acknowledge an individual idiosyncrasy to scurvy we should expect -a tendency to a recurrence of the disease. Lind was of this opinion, -stating that "by observations made on this disease, it appears that -those who are once afflicted with it, especially in so high a degree as -that squadron was, are more subject to it afterwards than others." It is -difficult at the present day to express a personal opinion on this -matter, as clinical experience is meagre and the scurvy of guinea-pigs -is so acute that it cannot be used for comparison. Some of the -recurrences have been due probably to the fact that the patient had not -been completely cured of his first attack. We have met with two cases of -recurrences in infants, one of which is of particular interest as it -happened in spite of giving lemon juice in the intervening period. The -history was as follows: - - In September, 1914, one month after the baby was admitted to the - institution, it developed scurvy of a moderate grade. It was then - six months of age and weighed 10¼ pounds. It was put on a simple - mixture containing from 24 to 30 ounces of pasteurized milk and was - given in addition ½ ounce of lemon juice a day. It improved, but - during the winter had bronchitis, otitis, enteritis, and later - furunculosis. In spite of the fact that it had been receiving an - antiscorbutic for almost this entire period, it developed scurvy - once more in February, at the age of 11 months, and when it weighed - 14½ pounds. It was evident that this baby was peculiarly - susceptible to scurvy. It may be added that the second attack was - complicated by nasal diphtheria. - -In this connection attention should be drawn to a peculiar and puzzling -clinical phenomenon, which we have noted several times. Even if the -antiscorbutic treatment is carried out incompletely and only for a short -period, recrudescences may not take place. We have seen cases where -orange juice was given for merely ten days or two weeks--that is, only -until all scorbutic signs had disappeared,--and yet the scurvy did not -return, the infants thrived for months thereafter, but were merely -somewhat pale and undernourished. In the case of two babies which we -have in mind, the diet remained absolutely unchanged, with the exception -of the short period of antiscorbutic treatment, but this seemed -sufficient to bring about a diminished susceptibility. - - - - -CHAPTER IX - -TREATMENT - - -"Seek the cure of scurvy neither in the armamentarium of the physician -nor in the apothecary shops. The druggist will be of as little aid to -you as the art of the surgeon. On the other hand, employ fresh -vegetables, the juice of fresh antiscorbutic plants, oranges and lemons -or the juice of those fruits preserved with sugar; in this way without -other means you will be able to overcome this terrible disease." This -reads like the advice of some modern therapeutist; it is, however, the -conclusion of a physician (Kramer) who wrote on scurvy almost two -hundred years ago, and shows that the treatment of scurvy has undergone -no fundamental change in the intervening years. Our resources, however, -have been amplified by an increased knowledge of the relative value of -antiscorbutic foodstuffs and by the introduction of some new ones. - -=Prevention.=--In the Temperate Zone, under ordinary conditions, the -adult population consumes sufficient antiscorbutic foodstuff to protect -it from scurvy. Under exceptional circumstances, however--for example, -when the potato crop fails, or, in the case of individuals, when the -diet has been unduly restricted, scurvy will be encountered. This -disorder is still an important problem, however, in relation to the -health of adults in the Tropics, in military expeditions and in Polar -explorations. From what has been stated in the preceding chapter, it is -evident that, at the present time, no reliance can be placed on -dehydrated vegetables as a protective agent. The recent suggestion of -using germinated dried pulses and seeds, under circumstances where fresh -food is not available, is practical and probably will be resorted to in -the future. To this end the pulses (beans, peas, lentils) are soaked in -water for 24 hours, and then kept moist with access of air for about 48 -hours at room temperature. During this period they sprout and develop -small radicles. They are cooked in the usual way and have been found to -possess an antiscorbutic value comparable to that of most vegetables. An -individual should receive about four ounces a day of these sprouted -seeds. In the treatment of some Serbian soldiers suffering from scurvy, -Wiltshire found that this amount of germinated beans brought about a -cure. There are, however, two drawbacks to their general use. The -prolonged cooking necessary for their preparation reduces their -antiscorbutic potency, and they have been found indigestible when -consumed in sufficient quantity. - -Under similar conditions canned tomatoes can be employed; they have the -disadvantage of greater bulk, but are a more potent antiscorbutic, -require no preparation whatsoever, and are readily digested. They form -part of the present ration of the United States Army, in which they can -be given "in lieu of an equal quantity of potatoes not exceeding twenty -per cent. of the total issue."[50] The necessity of including an -antiscorbutic in the army ration has been recognized only in recent -years; during our Civil War and for thirty years thereafter there was no -such provision. It was stated at that time that a general scorbutic -taint pervaded the troops--a mere euphemism for the widespread existence -of subacute or latent scurvy. Even to-day the ration of the French and -of the Italian armies makes no definite provision in this regard and the -Russians provide merely for a variable quantity of vegetables. - -[50] We have been unable to ascertain through inquiries from the -Surgeon-General's Office the nature of the experience which led to their -incorporation in the ration, and whether they were added specifically as -an antiscorbutic. They appear for the first time in the revision of the -Army Regulations of 1895. The only reference to the antiscorbutic -property of canned tomatoes which we have been able to find in the -literature is in the excellent treatise by Munson on Military Hygiene. - -Recently it has been shown that lemon and orange juices (Givens and -McClugage) can be dried and still preserve their antiscorbutic value. It -is quite possible that concentrated preparations of this kind will be -serviceable for army use and in regions where fresh fruit or vegetables -cannot be obtained.[51] - -[51] Since the above was written, an article has appeared by P. W. -Bassett-Smith (Scurvy: With Special Reference to Prophylaxis in the -Royal Navy. Lancet, London, 1920, I, 1102) showing that _lemon juice can -be prepared in tablet form_ and preserve its efficacy for at least three -months. Each tablet contained the equivalent of 24 c.c. of lemon juice, -and less than one-fifth of a tablet was sufficient to protect a -guinea-pig from scurvy. This therapeutic procedure seems of great -promise in providing an antiscorbutic ration for the navy or the army. - -Lind makes numerous ingenious suggestions for preparing antiscorbutic -remedies (Lind, pp. 7, 8 and 9) which have a practical as well as -historic interest. (Appendix 1.) One of these includes a formula for the -preparation of orange and lemon juice which may be preserved for years; -another gives a method for the preservation of berries and other fruits -which are to be picked when partly ripe and put up in earthen pots; -still another gives the recipe for preparing a simple decoction of fir -tops, which was found by the Swedes efficacious in preventing the -development of scurvy among their soldiers. It is interesting that a -similar practice was resorted to in Vienna during the recent war and -recommended as a prophylactic for scurvy in children (Tobler). - -_The prevention of infantile scurvy_, especially in its rudimentary -form, is of great practical importance, because of its frequent -occurrence. There is no question but that breast milk and raw cow's milk -furnish sufficient antiscorbutic vitamine, but there is a difference of -opinion as to whether pasteurized milk, or milk that has been brought -just to the boiling-point, or even sterilized milk, is adequate in this -respect. Much of this divergence of opinion is due to the fact that the -various clinicians have not considered or stated the quantity of milk -which they have found sufficient to protect, and also because milk -itself differs in its antiscorbutic value according to its freshness and -probably also according to the fodder of the cows.[52] Without entering -once more into a discussion of this question, it may be stated that -unless the cow's milk is raw, the infant should receive additional -antiscorbutic foodstuff. Moreover, this supplement to the dietary should -be made as soon as possible, so as not to allow the vitamine deficiency -and inadequate diet to exist for even a short period. In our experience -there is no contra-indication to the giving of orange juice or of -strained canned tomato, the two antiscorbutics with which we have had a -large experience, to babies one month of age or even younger. The common -practice, however, is to wait until the infant is five or six months of -age, which certainly must allow a rudimentary scorbutic condition to -develop. At the age of a month one teaspoonful of orange juice may be -given; it should be diluted with water and sugar added if it is tart. -This may be administered notwithstanding the fact that a baby has a -tendency to looseness of the bowels, as orange juice, as recently -pointed out by Gerstenberger, has practically no laxative action. -Occasionally babies regurgitate orange juice, but the reaction usually -ceases after a day or two. If it does not, a small amount of an -alkali--for example, limewater or sodium bicarbonate--may be added just -previous to feeding; in this state the juice will be better -tolerated.[53] The amount of orange juice should be increased so that -when the baby is three months of age it receives one tablespoonful. - -[52] It is not possible to say exactly how much raw milk a baby needs to -protect it against the development of scurvy. We may, however, reach an -approximate estimation of this figure. We know that it takes about 2 -c.c. of orange juice to protect a guinea-pig against manifest scurvy, -and about 10 c.c. to protect a baby. The ratio, therefore, between the -guinea-pig and the infant in this regard would seem to be about 5 to 1. -We also know that it takes about 80 to 100 c.c. daily of fresh cow's -milk to protect a guinea-pig for long periods. If we assume the ratio of -5 to 1, it would therefore seem that it would require about 500 c.c. or -a pint, of fresh raw milk daily as a minimum to protect the baby. (It is -quite possible that a slight negative balance of the vitamine may exist -unless a still greater amount is given.) - -[53] Orange juice undergoes a decided color change as soon as it has -become neutral or very slightly alkaline, assuming a more translucent -and far deeper yellow or amber color. This change may be utilized by the -attendant in determining the reaction, thus rendering titration or other -time-consuming methods unnecessary. - -A few years ago Hess and Fish recommended the use of an infusion of -orange peel in infant feeding. The peel was finely grated, soaked -overnight in water (1 ounce of the peel to 2 ounces of water), and a -small amount of sugar added to this liquid. Animal experiments showed -that this preparation possessed decided antiscorbutic value. This -decoction may well be used for the sake of economy, and even when the -orange juice is employed the infusion of the peel may be added. - -An antiscorbutic which vies with orange or with lemon juice in -adaptability for infant feeding is _canned tomatoes_, as recently -suggested by Hess and Unger. Tomatoes are not in good repute among food -experts in view of the small amount of calories which they contain--only -about 100 to the pound--and are regarded with suspicion amounting almost -to superstition by mothers and nurses as a food for children. In spite -of this fact, it may be stated without hesitation that they are fully as -well borne by infants a few weeks or months of age as orange or lemon -juice. In considering antiscorbutics, it has been shown that -notwithstanding the canning process and subsequent aging, they preserve -their potency. The dose is two tablespoonfuls for babies over three -months of age. The tomatoes are merely strained through a colander and -warmed (not cooked). To illustrate their innocuous character, it may be -added that as much as 6 and 8 ounces a day of this juice have been given -to a baby under one year of age without producing untoward symptoms. -This antiscorbutic should have wide applicability, especially in the -United States.[54] - -[54] There is no relation whatever between the acidity of canned -vegetables and their possible contamination with tin. Experiments -carried out to determine this question demonstrated, for example, that a -"sample of red kidney beans showing the highest acidity contained the -least tin," and that those samples containing the most tin were all -relatively low in acidity. (Report of Conn. Agric. Station Bull. 200, -1917, J. P. Street.) - -Another antiscorbutic which can be used in a routine way to prevent -infantile scurvy is _swede juice_, prepared by grating the raw vegetable -and squeezing the pulp in muslin. Chick and Rhodes report that this -juice has been adopted for use in some of the English infant-welfare -centres. It should be given in about the same dosage as the tomatoes, -and seems applicable where the swede can be readily obtained. - -For babies over six months of age, reliance may be placed on the -ordinary household vegetables--potatoes, spinach, carrots, squash, etc. -Attention should be paid to the amount which is taken, as one or two -teaspoonfuls of a vegetable which is poor in antiscorbutic power, such -as carrots or beets, will be insufficient to protect against scurvy. -Especially is this true if the vegetables are old and stale and are -cooked for a long period;[55] some years ago two infants under our care -developed scurvy in spite of a small daily ration of vegetables. - -[55] Salant, in experiments on rabbits, found that old or winter carrots -did not have the same protective action against tartrates as young -carrots, although their diuretic action is the same. - -Potato in the amounts usually consumed is a valuable antiscorbutic. It -is not an exaggeration to state that it is the main antiscorbutic -bulwark of man. In giving baked potato to children it is commonly -advised to use the floury part just beneath the peel; this should be put -through a sieve and mixed thoroughly with boiled milk so as to -constitute a cream; for younger babies it can be prepared with water to -form a diluent similar to the barley water so commonly employed to -dilute cow's milk (1 tablespoonful of potato to a pint of milk, cooked -for 15 minutes). Little reliance should be placed on beef juice in the -usual dosage and none on eggs. - -=Cure.=--There is almost nothing in the realm of therapy which is so -striking as a scorbutic patient's prompt reaction to antiscorbutic -treatment. It is all the more marvelous as the cure is effected by means -of foodstuffs with which we are accustomed to associate no specific -virtue. A magic result is seen frequently within 24 or 48 hours. A baby -which has had a poor appetite, has been irritable and exquisitely -tender, suddenly regains its appetite, is no longer fretful, and can be -handled without occasioning crying. Within a week, if the case is mild, -all definite symptoms of scurvy may have disappeared, and soon -thereafter the infant is thriving and apparently cured. A table is here -reproduced (Table 6) from the report of the American Pediatric Society -showing the duration of treatment before marked improvement was noticed: - - TABLE 6 - DURATION OF TREATMENT BEFORE MARKED IMPROVEMENT WAS NOTICED - ========================================================== - | Days Cases | Weeks Cases | Months Cases | - |------------------+------------------+------------------| - | 1 19 | 1 47 | 1 6 | - | 2 58 | 2 27 | 2 4 | - | 3 46 | 3 8 | 3 4 | - | 4 26 | 4 1 | | - | 5 19 | 5 1 | | - | 6 1 | 6 1 | | - | 7 2 | | | - | 8 2 | | | - | 9 1 | | | - | 10 7 | | | - | 12 2 | | | - | | | | - ---------------------------------------------------------- - -In most instances a gain of weight accompanies improvement. In not a few -instances, however, there is a temporary loss or cessation of weight, -due in part to an increased excretion of urine. Occasionally there is -observed a short exacerbation of the symptoms following the giving of an -antiscorbutic--a swelling of the thigh or hemorrhage of the gums. A -similar phenomenon has been noted in relation to the treatment of -polyneuritis in birds and of beriberi in man. - -In the cure of scurvy the same dietetic remedies are employed as in its -prevention. Orange juice is the sovereign remedy, and should be given in -a dosage of about 2 ounces a day.[56] Canned tomato is also most -efficacious. If these changes in the dietary are carried out, it is not -absolutely necessary to alter the food, although it is advisable to do -so. Some writers, for example Neumann and Czerny, treat the disorder by -giving milk which has been scalded or brought to the boiling-point. -Others lay particular stress on changing the source of the milk supply, -believing that the sameness of the diet leads to the occurrence of -scurvy. Such, however, cannot be the case, as otherwise breast-fed -babies would be highly subject to this disease. In the report of the -American Pediatric Society one case developed on condensed milk and was -cured by sterilized milk, and another developed on pasteurized milk and -was cured by sterilized milk and broths. These results are explicable; -large amounts of milk were given to effect the cure. It may be said in -general that in addition to giving fruit or vegetable juices the milk -should be either raw or heated to as low a degree as possible (duration -of heating as well as height of temperature). Furthermore, the -antiscorbutic treatment should be continued for a period of months, as -the clinical improvement far outstrips the restoration of the bones and -other tissues. It seems necessary again to call attention to the fact -that too great reliance has been placed on the use of beef juice, which -has been shown, both in experiment and in the clinic, to possess -comparatively weak antiscorbutic properties. - -[56] It is difficult to state the exact dosage of orange juice which is -necessary. One teaspoonful daily has failed to cure, and rapid cures -have been accomplished by giving one tablespoonful. It is well, however, -to give a larger amount if it is tolerated. - -Orange juice may be given intravenously. This method may be resorted to -where the patient is in an advanced stage of the disease or where food -cannot be tolerated by mouth; for example, in cases such as that -mentioned by Cheadle, where death took place owing to the fact that the -antiscorbutic could be taken only sparingly, on account of the extreme -prostration of the patient. For this purpose the orange juice is -obtained in as sterile a manner as possible, boiled for about five -minutes and is rendered neutral or slightly alkaline just previous to -its injection by the addition of normal sodium hydroxide. Hess and Unger -report three cases where this procedure was carried out without the -slightest untoward reaction. In one instance, improvement was noted 16 -hours after the injection. In view of the novelty of this treatment it -may be of interest to cite a case: - - A baby 16 months old had hemorrhage of the gums and tenderness of - the legs, which were held in the characteristic flexed and everted - position. Eliminative treatment was tried without avail; Dover's - powder and warmth to promote perspiration; caffeine to promote - diuresis; and 2 tablespoonfuls of liquid petrolatum three times a - day to increase elimination from the bowels. Intravenous injections - of salt solution also proved of no value. - - Four intravenous injections of orange juice were given--6 c.c., 12 - c.c., 6 c.c., and 35 c.c. As was stated, improvement was noted 16 - hours after the first injection. The infant was less irritable, the - gums no longer hemorrhagic, and the "capillary resistance test" - (that is to say, the development of petechial spots on the forearm - when a tourniquet was applied for 3 minutes to the upper arm) - changed from positive to negative. - -Harden, Zilva and Still have recommended the use of a concentrated lemon -juice for the cure of scurvy, constituting a form of "intensive" -treatment. In four cases this proved to be of clinical value. Freise has -made use of an alcoholic extract of turnips, and Freudenberg of a -similar extract of carrots. These preparations did not seem to be -markedly potent, and therefore possess no particular therapeutic -advantages. - -=Non-dietetic Therapy.=--There is little to be done for the patient in -addition to the giving of sufficient antiscorbutic. No one has reported -success with any drug. We have tried the use of atropin, adrenalin, -thyroid and parathyroid extracts, cod liver oil, autolyzed yeast, -lactose, sodium chloride, calcium chloride, etc., without noting any -improvement. Mercurials are stated to be positively harmful, especially -when ulcers are present. The patient should be kept in bed, and exertion -not allowed on account of the involvement of the heart, which has led to -sudden collapse and death. The gums may be treated with nitrate of -silver stick or tincture of myrrh. If there is fracture of the long -bones with displacement, splints should be applied. Under no -circumstances should hemorrhagic effusions in or about the joints be -incised. The patient should be placed in a room which is well aired and -lighted, and should be handled and dressed as infrequently as possible, -so as to avoid discomfort and pain. It is particularly important that -intercurrent infections should be avoided by shielding patients from -contact with those who have infectious diseases, especially respiratory -infections. - - - - -CHAPTER X - -METABOLISM - - -Studies of the chemical exchanges in scurvy have been surprisingly few. -It is a field that should repay investigation, promising to afford a -clearer insight into the intermediary metabolism in this disorder. One -of the first to touch upon this question was Garrod, who in 1848 -reported that there was a diminution of potassium salts in the urine and -in the blood of scurvy patients. In 1877 Ralfe confirmed the potassium -deficiency in the urine, but denied its importance from an etiologic -standpoint, as he was unable to benefit scurvy patients by administering -potassium nitrate. He reported an increase of uric acid in the urine, a -diminution of the total acidity, and a reduction of the alkaline -phosphates. Litten found the analyses of the urine very contradictory in -respect to potassium, but stated that beyond a doubt its uric acid -content is increased at the height of the disease, although this -diminishes rapidly with convalescence. These few and scattered articles -comprise the sum of metabolic studies up to the last decade, and even -during the succeeding period they have been very few--so few, indeed, -that they furnish insufficient data from which to draw conclusions. - -The first careful study of the mineral metabolism in a case of scurvy is -that of Baumann and Howard, published in 1912. Its conclusions are not -very definite. They may be summed up by their statement that "chlorin -and sodium were retained during the fruit-juice period, but excreted in -excess of the intake during the preliminary period," and that "more -potassium, calcium and magnesium were retained during the fruit-juice -period." - -This same year Lust and Klocman published the first metabolism study of -a case of infantile scurvy. The baby was 18 months old and the metabolic -changes were investigated during the active, convalescent, and "the -healing stage" of the disorder. This study seems to have been carefully -carried out. The fact, however, that the infant received 800 c.c. daily -of slightly-boiled milk during the active stage, and was improving at -this time, may also have had a beneficial effect on the metabolism in -respect to scurvy. The results of these writers are surprising--quite -different from what they expected or what we should have expected. They -write: "The balance of the mineral metabolism, including the total ash, -the calcium, phosphorus and chlorin during the florid stage of the -disease must be regarded not only as not damaged, compared to that of -the healthy child, but indeed as somewhat increased." "All the more -striking, on the contrary, are the results found during the stage of -convalescence. Here the balances were all markedly negative, and only -after a lapse of weeks was the tendency manifested to a return to normal -conditions." The authors regard these results as indicating a sort of -washing out of "dead material" during convalescence--of material which -had gathered during the florid stage of the disease. According to their -interpretation the disease is due, not to a primary or secondary salt -deficiency, but to a disturbance in salt elimination, and in the first -place, of a calcium excretion. This is shown by the fact that even in -the "stage of healing," when the total ash and the phosphorus balance -once more had become positive, the calcium balance nevertheless remained -somewhat negative. The metabolism of infantile scurvy, they believe, far -from showing a resemblance to rickets, manifests quite the contrary -tendency. The study of this case of infantile scurvy and that of Baumann -and Howard of a case of adult scurvy, comprise the total investigation -of the metabolism in human scurvy. - -In the course of a recent discussion on rickets before the Medical -Society of Vienna, Moll states briefly that in a case of infantile -scurvy, at the height of the disease, he found a positive calcium -balance, which became poor and later negative on giving fruit juice; in -other words, a partial confirmation of the work which has just been -cited. - -In 1913 Bahrdt and Edelstein reported the analyses of the organs of an -infant almost nine months old who died of scurvy; an examination of the -tissues, especially of the bones, should be most valuable in checking up -determinations of the metabolism during life. This investigation runs -absolutely contrary to that of Lust and Klocman. The bones showed a -decrease of ash, especially of calcium and of phosphorus, and also a -lack of calcium in the muscles, but normal amounts in the liver and in -the kidneys. These conditions resemble the deficiency of ash and of lime -commonly associated with rickets, and it seems quite possible that this -infant had rickets as well as scurvy, and that in this way the -discrepancy between the two reports is to be explained. The fact that -the water content of the bones was two to three times the normal, also -lends emphasis to this interpretation. _In any metabolism study of -infantile scurvy, great care will have to be exercised that the disorder -is not complicated by rickets_, and the issue thereby confused. It will -be very difficult to avoid this pitfall, for there is no test by which -early rickets can be diagnosed. The danger of this complication may be -realized when we bear in mind that the majority of infants have rickets -to some degree. An investigation of the chemistry of adult scurvy has an -advantage from this point of view. - -Chemical examination of the blood has yielded such valuable information -regarding metabolic diseases, that it might be expected to shed light on -the disturbances of scurvy. The only investigation from this standpoint -is that of Hess and Killian, who have reported estimations of the urea, -creatinine, sugar, CO_{2} combining power, diastase, cholesterol, -chlorine and calcium.[57] The urea content was normal, varying between -12 and 14 mg. per 100 c.c. of blood; this is the average of twenty-one -tests on ten cases of infantile scurvy. (In severe cases of beriberi -Yano and Nemoti have recently reported that the blood contains an -increase of urea, and that its excretion is frequently disturbed.) The -creatinine was estimated in two cases and was found to be 2.0 mg. and -1.7 mg. per cent., respectively,--also normal figures. The blood sugar -varied from 0.12 to 0.14 per cent. and was examined in almost all the -cases in which urea was estimated; these figures are at the upper level -of normality (no attention was paid to the interval elapsing between the -feeding and the withdrawal of the blood). The diastatic activity was -likewise normal. The CO_{2} combining power showed figures under 40 to -45, according to the Van Slyke method, and indicated therefore a mild -degree of acidosis. In six cases the chlorides were estimated, the -figures being remarkably constant at about 0.42 or 0.43. Cholesterol was -a little below normal in the four cases examined. Contradictory results -were obtained in regard to calcium. Earlier tests showed a definite -deficiency of this salt, but those carried out more recently have -generally yielded normal results. Further studies of the blood calcium -are highly desirable to ascertain whether it varies in amount in the -circulation, and especially in different stages of the disease. This -aspect is worthy of particular attention in view of the positive calcium -balance noted by Lust and Klocman during the active stage of scurvy, and -the negative balance during the period of convalescence. - -[57] Almost all of these cases were receiving liberal daily amounts of -cod liver oil, which should exclude the possibility of complicating -rickets. - -It is evident from the limited data concerning the blood chemistry of -scurvy that it is a field which has been inadequately explored and will -repay more intensive study. Investigations of this kind have recently -been made possible by the introduction of accurate methods requiring -only small quantities of blood. - -Studies of the metabolism of animals suffering from scurvy are almost as -few as those on man. The work of Morgan and Beger, which is frequently -quoted in this connection, is not applicable, as it concerns rabbits, -which do not develop scurvy. They found that rabbits fed solely on oats -and water suffered in their nutrition (loss of appetite, emaciation, -paralysis of hind legs), and could be cured by the addition of sodium -bicarbonate to the dietary. In 1916 Lewis and Karr published a paper on -the constituents of the blood and the tissues of guinea-pigs fed on an -exclusive oat diet. They found the urea content several times greater -than normal, but that it fell to normal once more if cabbage or orange -juice was given. From the standpoint of scurvy, this investigation is -open to the criticism that the diet was too incomplete, and also, as the -authors suggest, that the animals suffered from partial starvation and a -lack of water. - -In the following year Karr and Lewis published a paper on a different -phase of this subject, and came to the following conclusions: "No -changes in urinary elimination of phenols, nor in the degree of -conjugation of the phenols, were observed, provided the factor of -partial starvation was ruled out. This is believed to indicate that no -increased bacterial action occurs in the intestine of scorbutic -guinea-pigs despite the difficulty of evacuation of the fæces." These -results are in harmony with the bacteriological study of Torrey and -Hess, who found that there was no increase in the proteolytic flora of -the intestine in infants or in guinea-pigs suffering from scurvy. - -In 1917 Baumann and Howard published the only metabolism study which has -been carried out on guinea-pigs suffering from scurvy, and they are of -the opinion that this disorder has a profound effect on the mineral -metabolism of this animal. The calcium was excreted in notably large -amount; potassium was also lost, and to a greater extent than sodium; -the only element which was consistently retained during the active stage -as well as during the period of recovery, was magnesium. This study was -followed shortly by one from the same laboratory, by Howard and -Ingvaldsen, carried out on a monkey suffering from scurvy. It was -inconclusive, not conforming to the experiments on the guinea-pigs; the -authors state that the "changes in the mineral excretion of the monkey -during the scorbutic period were not sufficiently significant to admit -of easy interpretation." "The marked loss of the various mineral -substances encountered in experiments with man and guinea-pig was not -observed in the present series." It should be remembered, however, that -the diets of the guinea-pigs and the monkeys were quite different, the -former consisting mainly of oats, and the latter of condensed milk. It -is quite possible that the basic diet may play a rôle in the metabolism -of this disease, although, as stated elsewhere, its effect cannot be -noted clinically. Special attention should be paid to this factor in -metabolic studies, in view of the widely-held opinion that the -carbohydrates exert a potent influence in the development of beriberi. - -The investigations of the nitrogen metabolism in man and in animals have -been most unsatisfactory. The two on human beings--an infant and an -adult--were negative; that on guinea-pig scurvy cannot be utilized on -account of the restricted diet of oats, which contained insufficient -nitrogen, whereas the one on the monkey showed some loss of nitrogen, -which led the authors to suggest an increased nitrogenous catabolism in -scurvy. This comprises the total data on this subject. - -Summarizing the results of these few metabolic studies, it may be stated -that they harmonize on one point only--the positive balance of calcium -during the active stage of the disease. The investigation of Baumann -and Howard on adult scurvy, of Lust and Klocman and of Moll on infantile -scurvy, and of Howard and Ingvaldsen on the monkey, are all in agreement -in this important conclusion. - - - - -CHAPTER XI - -RELATION OF SCURVY TO OTHER DISEASES - - -In the foregoing there has been frequent reference to the close -relationship between scurvy and the incidence of the infectious -diseases--to the fact that a scorbutic condition increases the -susceptibility to infection. This is indeed one of the most -characteristic, as well as one of the most important phenomena -associated with scurvy and other disorders resulting from vitamine -deficiency. Mention has been made of the special susceptibility to the -diphtheria bacillus, and to the organisms leading to coryza and the -respiratory diseases, but no doubt this applies also to invasion by -other bacteria. We wish, however, to confine ourselves to the -nutritional disorders, first in their relationship one to the other, and -second, as a group of deficiency diseases, due to a lack of vitamines of -various kinds. As is well known, in addition to scurvy, this group -generally includes beriberi, a disease attributed to a lack of the -water-soluble vitamine, and xerophthalmia, an eye condition which -recently has been brought about in rats by placing them on a diet free -from fat-soluble vitamine. These, however, form only the nucleus of the -disorders which commonly are included in this category. Schaumann, the -first to formulate this classification, illustrated his conception of -the interrelationship by depicting the various members as spokes of a -wheel surrounding a central hub. He included scurvy, rickets, -osteomalacia, typical beriberi, ship-beriberi, pellagra and -mehlnaerschaden. Funk made a similar classification of disorders which -he termed the "avitaminosen." There is a tendency to enlarge rather than -to decrease the membership of this class, and recently war or hunger -edema, infantile atrophy and diarrhoea, sprue, coeliac disease, -leprosy and others have been proposed as suitable candidates. At the -present time it is impossible to determine which and how many of this -motley company should be associated with scurvy. Some, possibly, are the -result of a lack of vitamine, but for the present it will be well to -bear in mind that three vitamines only have stood the test of -experiment, and only these three therefore can be definitely connected -in a causal relationship with pathologic conditions. In addition to this -consideration of the interrelationship of the "deficiency diseases," the -kinship of allied disorders--more particularly of rickets--must be -discussed. - -Although at first thought _beriberi_ and scurvy would seem far apart -from a clinical point of view, they have some important features in -common. In both there is a tendency to a rapidity of the heart's action -and a marked lability of the pulse, to an enlargement of the cardiac -ventricles, to an involvement of the vagus, and to an exaggeration of -the deep reflexes. It is unnecessary to describe these signs and -symptoms in detail, as they have been fully considered under -symptomatology. It has been recorded from time to time that under -certain circumstances scurvy has developed in man where one should have -expected beriberi, and _vice versa_. Darling, who has had a large -experience in this field, writes: "A deficient dietary in a tropical -African negro mine laborer causes severe scurvy, in a Cape Colony -African mine laborer, mild scurvy, and in some African negroes a diet -that causes scurvy in one set of men causes neuritis in others." -Possibly some minor differences in the dietary can explain this -difference in reaction--for we do not know all the sources of the -water-soluble vitamine, but such an experience deserves to be cited as -it is not an isolated instance. It is all the more worthy of attention -because it harmonizes to a certain extent with the everyday experience -of animal investigation. As has been stated elsewhere, a diet of -decorticated grain will lead to scurvy in the guinea-pig, to -polyneuritis in the pigeon, and to a combination of these diseases in -the hog! Results of this kind show that there must be a relationship -between the etiologic factors of scurvy and of beriberi. It is unwise at -present to attempt to define the relationship more precisely. The -remarkable observation, first made by Fuerst, and since confirmed by -numerous investigators, that seeds and legumes are devoid of -antiscorbutic potency but acquire this power on sprouting, constitutes -another link in the evidence of their kinship. Funk has suggested that -the antiscorbutic vitamine can be formed from the "antineuritic" -vitamine, a theory which is very attractive but needs confirmation and -experimental proof. It is quite evident that this change does not -usually occur in animals, in view of the specificity of the vitamines -for their respective diseases--of the antiscorbutic for scurvy and the -water-soluble for beriberi. - -It will be noted that "_ship-beriberi_" is included in this group of -diseases. Very little is known about this condition, except what is -contained in the investigation of Nocht (1903) and that of Holst and -Froelich. It is a very rare condition but of interest because it is -characterized by spongy, hemorrhagic gums and other signs encountered in -scurvy. The feature which differentiates it sharply from scurvy, -however, is an anæsthesia of the extremities. Ship-beriberi is generally -regarded as a combination of beriberi and scurvy. Where these two -disorders occur concomitantly, the beriberi manifests itself some months -before the scurvy, as the latter takes much longer to develop. - -In considering the vitamines in connection with diseases of the nervous -system, mention may be made of "central neuritis" and the "peripheral -neuritis" which has been reported from the West Indies. This bears only -a partial resemblance to beriberi, as there is no edema, nor dyspnoea, -and its course is more chronic. Judging from the report of Edwards from -Jamaica, the cases more closely resemble pellagra, terminating after -many years. A degeneration of the cells of the spinal cord was found and -"in some isolated patches of the cerebellum and in the roots of the -optic and auditory nerves." The disease occurs among the poor classes -whose diet is inadequate chiefly in nitrogen. - -Eijkman was the first to draw an analogy between beriberi and -_pellagra_, and thus to suggest that the latter might be a disease due -to an unidentified factor; he compared the pernicious effect of a diet -of polished rice with that of decorticated corn. Of recent years, -largely as the result of the investigations of Goldberger and his -co-workers, pellagra has come to be regarded as a dietetic disorder -primarily due to a lack of adequate protein, rather than to a lack of a -specific vitamine. Its relationship to scurvy cannot, therefore, at the -present time, be discussed from an etiologic viewpoint. Apart, however, -from the question of etiology, the two diseases have certain clinical -symptoms in common. Weston states that "distinguished physicians, who -were really astute observers, have mistaken pellagra for scurvy, eczema, -various kinds of intestinal troubles, syphilis, and many other -diseases." In the chapter on symptomatology, attention has been directed -to the fact that an eczema which yields to antiscorbutic treatment may -occur in scurvy; at times it presents the symmetrical arrangement so -typical of pellagra. In other cases a fleeting erythema may be observed, -another sign noted frequently in pellagrins. In some instances -congestion of the gums has been recorded. In describing a little girl of -three who had pellagra, Weston writes: "The gums are also red and -swollen, suggesting scurvy." This child had eaten large amounts of -turnips, so that there could have been no question of complicating -scurvy. Lombroso and some of the earlier authors drew attention to the -fact that fragility of the bones, of the ribs and of the long bones, was -often associated with pellagra. These various clinical similarities -should not be construed as evidence in favor of the "avitamine" nature -of pellagra. They indicate, rather, that in nutritional disorders, -whatever may be their underlying cause, the vessels, the bones, -and other tissues may suffer and lead to similar--but not -identical--clinical pictures.[58] - -[58] There is no adequate reason for placing in this group "coeliac -disease," a nutritional disorder of children recently described by -Still, and suggested by McCarrison as belonging to the category of the -vitamine deficiency diseases. A case of this kind has come to our -attention which resembled pellagra in many respects. It showed the -bright red, denuded tongue, the intestinal symptoms, the occasional -edema, marked loss in weight, and evanescent erythema--all symptoms of -markedly disturbed nutrition but not distinctive of a lack of vitamines. - -The relation between scurvy and rickets is a subject which was discussed -by Glisson. With the renewed interest in infantile scurvy which followed -Barlow's work toward the end of the last century, children's specialists -ranged themselves into opposing camps on the question of the -interrelationship and interdependency of these two diseases. Some -accepted Barlow's dictum that infantile scurvy is an absolutely distinct -and separate entity; others, for example, Hirschsprung, declared that -the so-called scurvy was merely a form of rickets; whereas a third group -considered it a combination of rickets and scurvy. This last viewpoint -was actively maintained by Cheadle on the clinical side, and later by -Schoedel and Nauwerk on the pathologic side--the latter declaring that -rickets is "an inseparable component of infantile scurvy," and that the -entire disease should be regarded merely as "an episode in the course of -rickets." Even Barlow, in a paper published in 1894, wrote: "Rhachitic -changes already present may act as a physiological determinant of the -sites in which scurvy becomes manifest" and "rickets as a basis plus -inadequate food gives the simplest explanation of the typical case" (of -scurvy). - -We had an exceptional opportunity to test this thesis in 1914, in an -institution where scurvy broke out among infants who were on a diet of -pasteurized milk. All these infants were receiving cod liver oil daily, -as prophylactic treatment against rickets. Many infants have been seen -since that time, who in spite of receiving cod liver oil developed -scurvy, and others in whom large doses of this oil failed to mitigate -the scurvy, although it prevented rickets. The same failure has been -encountered in the treatment of scurvy in guinea-pigs. This experience -has been without exception, both from a prophylactic and a curative -standpoint. - -Confusion between the two diseases has resulted from the fact that the -majority of infants in the Temperate Zone have some degree of rickets. -Thus the two diseases have been found very frequently associated in -pathologic examination of the bones, leading some to infer that they are -in some way interdependent. They have been also confused clinically, as -mentioned in another connection, owing to the fact that beading of the -ribs--the rhachitic rosary--has been mistakenly regarded as a -pathognomonic sign of rickets, whereas it is also a sign common to -scurvy. It is important to bear in mind that from the pathologic -viewpoint scurvy and rickets present strikingly dissimilar pictures--the -former is characterized by an almost complete cessation of activity of -bone-forming elements, whereas the latter is distinguished by a -hyperplastic condition leading to a marked overgrowth of cartilage and -of abnormal bone. Viewed from the pathologic, etiologic and clinical -standpoint, we believe that there is no basis for assuming an -interrelationship between the two disorders, and that scurvy will -develop as readily and as rapidly where rickets is absent as where it is -present.[59] - -[59] The only evidence in favor of a true interrelationship is furnished -by a necropsy report of Hart and Lessing on one of five monkeys fed on a -scorbutic diet. This animal died of disseminated tuberculosis, and the -bones showed "the classic picture of severe rickets." This occurrence -cannot be explained, although illness and lack of exercise no doubt -played a rôle. Until similar cases are reported, the incident must be -regarded merely as interesting and suggestive. - -It is premature to discuss the relationship of these two disorders from -the vitamine standpoint. In 1910 Schaumann suggested that rickets was -due to a lack of a specific food factor, and somewhat later Funk -included it among the "avitaminosen." Recently Mellanby, as the result -of experiments on dogs, has affirmed that the fault lies in a lack of -the fat-soluble or a closely-related vitamine. Investigations of the -near future will probably decide the merits of this contention; our -experience is that rickets develops in infants even where the diet -contains adequate fat-soluble vitamine. If rickets is proved to be a -disorder depending on a vitamine, it belongs, naturally, in the same -group as scurvy. This would indicate relationship, but not -interrelationship. Just as the mere fact that a lack of vitamines leads -to scurvy and to beriberi does not signify, in theory or in practice, -the existence of pathogenetic interrelationship. However, as stated, -this is a subject which does not as yet rest on a secure foundation. - -_Osteogenesis imperfecta and osteomalacia_ are disorders of dietetic or -metabolic origin characterized by fragility of the bones. The latter -has developed new significance and importance due to its increased -occurrence in almost epidemic form in the Central Empires at the close -of the World War. The etiology of both disorders is most obscure. In the -future in considering their pathogenesis it will be well to draw a sharp -distinction between them. Osteogenesis imperfecta is a disease in which -an injury occurs to the foetus without any manifest illness in the -mother, which seems to indicate a primary lesion of the foetus -(perhaps metabolic); osteomalacia, on the other hand, attacks the mother -who gives birth to an apparently healthy foetus. The latter gains -added interest because it is a disease of the bones which is attributed -to dysfunction of the endocrine glands, to a disturbance especially of -the parathyroid. If this observation is confirmed, it furnishes another -anatomical basis for associating the glands of internal secretion with -pathologic conditions of the bones. - -One cannot survey the various diseases of the bones--scurvy, rickets, -osteoporosis, osteogenesis imperfecta, osteomalacia, etc.,--without -realizing that this group is at present in a state of great confusion -and will have to be rearranged and winnowed. The differentiation -between some of these diseases is not in every instance clear -morphologically--for instance, early cases of scurvy and -osteoporosis--so that it is difficult to consider them satisfactorily -from the standpoint of pathogenesis. Clinical differentiation is still -more difficult and uncertain. It seems probable that new entities will -be established, as has happened in the past. It is not so long since -rickets included almost all the bone diseases of infants. Gradually -congenital syphilis, scurvy, and achondroplasia were segregated as -distinct diseases. Probably a similar separation of other pathologic -conditions, now so entangled as to be indistinguishable, will be -evolved. - -Among the diseases which have been attributed to a vitamine deficiency -are "war or hunger edema," sprue, the "mehlnaerschaden" of infants, and -the "exudative diathesis" described by Czerny and Keller. Future -investigation will disclose whether any of these disorders belong in the -group with scurvy. The _hunger edema_, noted in the late war and in -previous wars, seems to be a complex condition, quite dissociated from -scurvy, as many of the sufferers consumed comparatively large quantities -of potatoes or other vegetables. The "_mehlnaerschaden_" resembles -scurvy and the other vitamine disorders in its tendency to produce -hydremia and susceptibility to infection. It also develops in spite of a -liberal supply of antiscorbutic foodstuff in the dietary. As its name -implies, it comes about on a diet containing large quantities of -carbohydrate, of the cereal paps so commonly fed to infants. It is -conceivable that an unbalanced diet of this kind may not provide a -sufficiency of all the vitamines. - -It does not seem probable that _exudative diathesis_, a term which -implies a predisposition to develop exudations or denudations of the -skin and mucous membranes, is the result of a lack of vitamine. This -condition does, however, predispose to scurvy. The association was very -evident in the group of cases reported by Hess and Fish in 1914. It is -not without significance that the blood-vessels in exudative diathesis -also show a decided weakness, an increased permeability, as judged by -the "capillary resistance test." In both scurvy and in exudative -diathesis eczema and petechial hemorrhages are encountered. - -There may be _nutritional diseases due to an excess of food_ rather than -to a deficiency. A superfluity may be harmful by hindering the proper -utilization of the food, or may possibly lead to the formation of -deleterious products. Disturbances of this kind do occur. For example, -it is by no means uncommon for an infant which has been overfed with -milk to show the typical signs of rickets. Young guinea-pigs which are -fed liberal amounts of cow's milk develop a disease characterized by -fragility of the bones. The experience of Lubarsch, who produced -osteogenesis imperfecta in rabbits by means of a diet consisting mainly -of liver, or adrenal gland, is of interest, especially as this condition -did not come about when they were fed muscle tissue. - -From what has been stated, it must be evident that this subject not only -is in a state of flux but that it is in a state of great confusion. This -applies not only to the relationship of vitamines to these disorders, -but to their identification and demarcation pathologically as well as -clinically. During the past few years we have begun to regard these -diseases from a new viewpoint, which no doubt will be helpful, but it is -probable that they will not be sharply defined and their relationships -determined until it is possible to bring about each disease definitely -and regularly in an experimental animal. Until this time we should -proceed slowly, and not bring about "confusion worse confounded" by -yielding to the vogue, and grouping together heterogeneous and -little-understood clinical conditions under the caption of deficiency -diseases. There is a growing danger of attributing every unexplained -nutritional disorder to the new, overworked, but ill-defined -vitamines--of their sharing with the secretions of the endocrine glands -the fate of becoming the dumping-ground for every unidentified disorder. - - - - -APPENDIX - - -Extract from "Treatise on Scurvy," by James Lind, London, 1772. - -(a) _Recipe for preparing a stable orange or lemon juice._ Let the -squeezed juice of these fruits be well cleared from the pulp and -purified by standing for some time; then poured off from the gross -sediment; or, to have it still purer, it may be filtrated. Let it then -be put into any clean open vessel of china or stone-ware, which should -be wider at the top than bottom, so that there may be the largest -surface above to favor the evaporation. For this purpose a china basin -or punch-bowl is proper, and generally made in the form required; all -earthen glazed vessels are unfit, as their glazing will be dissolved by -the acid. Into this pour the purified juice, and put it into a pan of -water, upon a clear fire. Let the water come almost to a boil, and -continue nearly in that state (with the basin containing the juice in -the middle of it) until the juice is found to be of the consistence of a -thick syrup when cold. The slower the evaporation of the juice the -better; and it will require at least twelve or fourteen hours -continuance in the bath heat before it is reduced to a proper -consistence. - -It is then, when cold, to be corked up in a bottle for use. Two dozen -good oranges, weighing five pounds four ounces, will yield one pound -nine ounces and a half of pure juice; and when evaporated, there will -remain about five ounces of rob, or extract; which in bulk will be equal -to less than three ounces of water. So that thus the acid, and the -virtues of twelve dozen lemons or oranges, may be put into a quart -bottle, and preserved for several years. - -I have now some extract of lemons which was made four years ago. - -Those who intend this extract for making punch may infuse some of the -fresh peel of the oranges or lemons into the spirit before it is used. - -But for this purpose I find it is sufficient to add a very small -quantity of the outer peel to the extract a little before it is taken -off the fire, and there will be all that is requisite to make it -entirely equal to the freshest fruit. - -(b) _How to preserve berries and other fruits for long periods._ And it -may be proper to acquaint them that most berries, and several fruits, -when gathered two-thirds ripe on a dry day, while the sun shines, if put -into earthen pots, or rather in dry bottles, well corked, and sealed up, -so that no air or moisture can enter, will keep a long time, and at the -end of a year, be as fresh as when new pulled. - -(c) _Method of preparing an antiscorbutic decoction from fir-tops, -leaves, bark, etc._ When the Swedes carried on a war against the -Muscovites, almost all the soldiers of their army were destroyed by the -scurvy, having putrid gums, rigid tendons, etc. But a stop was put to -the progress of this disease by the advice of Erbenius, the King's -physician, with a simple decoction of fir-tops, by which the most -deplorable cases were perfectly recovered, and the rest of the soldiers -prevented from falling into it. - -I am inclined to believe by the description given by Cartier of the -ameda tree, with a decoction of the bark and leaves of which his men -were so speedily recovered, that it was the large swampy American spruce -tree. - -A simple decoction of the tops, cones, leaves or even green bark and -wood of these trees is an excellent antiscorbutic medicine; but it will, -I am apt to think, become much more so when fermented, as in making -spruce beer. By carrying a few bags of spruce or its extract to sea, -this wholesome drink may be prepared at any time. But where it cannot be -had the common fir-tops used for fuel in the ship should be first boiled -in water, and the decoction afterwards fermented with molasses in the -common method of making spruce beer; to which a small quantity of -wormwood and horse-radish root (which it is easy to preserve fresh at -sea) may be added. The juice of the cocoanut tree was experienced to be -of very great benefit to several persons afflicted with the scurvy. - - - - -BIBLIOGRAPHY - - -ALBERT, J.: A Case of Infantile Beriberi with Autopsy Report, Phillip. -Jour. of Sci., Sec. B, 1908, III, 345. - -AMERICAN PEDIATRIC SOCIETY: Collective Investigation on Infantile Scurvy -in North America, Arch. of Ped., 1898, XV, 481. - -ANDREWS, V. L.: Infantile Beriberi, Phillip. 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XC, -505. - - - - -INDEX - - - A - - Acid, effect on keeping qualities of antiscorbutics, 66, 161 - - Acidosis, 244 theory, 24 - - Adrenals, 102 - in guinea-pig scurvy, 122 - - Adult, scurvy in, history of, 1 - - Age incidence, 51 - - Aging, effect on antiscorbutics of, 67 - - Agglutinins, effect of scurvy on, 68 - - Alimentary tract, gross pathology, 89 - microscopic pathology, 100 - - Alkalization, effect on milk of, 50 - on orange juice of, 66, 154 - - Amboceptor, effect of scurvy on, 68 - - Anasarca, 86, 196 - - Animals, scurvy in, 114 - - Anorexia, 206 - - Antiscorbutics, and antiscorbutic foods, 143, =149=, 157 - history of use of, 9, 143 - - Antitoxin, effect of scurvy on, 68 - - Appendicitis, confused diagnosis, 183 - - Appetite, 206 - - Apple, antiscorbutic value of, 158 - - Armies, scurvy in, 3, 15 - - Army, use of canned tomatoes in ration of U. S., 231 - - - B - - Bacteria, fecal, in scurvy, 28 - as etiological factor in scurvy, 134 - in tissues, 133 - - Bacterial theory of scurvy, 30 - - Banana, antiscorbutic value of, 158 - - Beading of ribs, 197 - in guinea-pig, 129, 137 - pathology of, 94 - - Beans, germinated, 167, 231 - - Beef juice, 236 - - Beer, antiscorbutic value of, 20, =169= - - Beriberi, differential diagnosis, 221 - relation to scurvy, =249= - - Berries, antiscorbutic value of, 156 - - Blindness, 182 - - Blood cells, changes in, 209-211 - - Blood cells, chemistry of, 244, 245 - coagulability of, 211 - - Blood vessels, changes in, 68, =98=, 209 - in guinea-pigs, 133 - - Blood, vitamine content of, 76 - - Bones, gross pathology, 93 - microscopic pathology, 105 - - Brain, pathology, 93 - - Breast fed, scurvy in, 35 - - - C - - Cabbage, antiscorbutic value of, 159 - dehydrated, 165 - effect of heat on, 159 - - Calcium, deposits of, 98, 102, 103 - metabolism, 241-247 - - "Capillary resistance test," =212=, 257 - - Carbohydrates, 34, 59 - - "Cardiorespiratory syndrome," 200 - - Cardiovascular system, 199 - - Carrots, antiscorbutic value of, 159, 160 - - Central nervous system, gross pathology, 93 - microscopic pathology, =104= - - Cereals, antiscorbutic value of, 170 - germinated, 167 - - Cerebrospinal fluid, 203 - - Chlorides, 242-247 - - Citric acid theory, 23 - - Climate, 55 - - Complement, effect of scurvy on, 69 - - Complexion, characteristic change in, 176, 184 - - Complications of scurvy, 182, 202, 205, 217 - - Constipation, 27, =118-122=, 207 - - Cord, spinal, pathology, 93, 104 - - Creatinine, 244 - - Cure, 236 - - - D - - Death, causes of, 179, 227 - - Deficiency diseases, general discussion, 63, 248 - - Diagnosis, 176, 219 - - Diastase, blood content of, 244 - - Diet, general, 59 - - Digestive disturbances, 78 - - Diphtheria, antitoxin in blood, 68 - as complication of scurvy, 217 - - Drying, effect on vitamines of, 66 - - Duodenum, pathology, 89 - - Dysentery, 59, 182 - - - E - - Economic status, 55 - - Eczema, 195 - - Edema, 178, 184, =196= - hunger, 256 - war, 256 - - Eggs, antiscorbutic value of, 168 - - Endocrine organs, gross pathology, 92 - microscopic pathology, 104 - extracts of, as preventive, 172 - theory of vitamine action, 72 - - Epidemics, 2, 217 - - Epiphyses, separation of, 96, 181, =198= - - Etiology, =35= - exciting factors in, 60 - - Excretion of vitamine, 77 - - Expeditions, scurvy in Arctic, 10 - - Experimental scurvy, 111 - pathogenesis, 116 - pathology, 122 - symptoms, 135 - - Exudative diathesis, 59, 256 - - Eyeball, proptosis, 193 - - - F - - Familial tendency, 58 - - Fats, in diet, effect on scurvy, 59 - - Fever, 181, =216= - - Foetus, effect of scorbutic diet on, 125 - - Food, excess of, 257 - - Foods, antiscorbutic, 143, =149= - proprietary, 49 - - Fractures, 95 - - Frost-bite, 180 - - Fruit juices, 153 - - Fruits, fresh, 144 - - - G - - Generative organs, pathology, 104 - - Glands, endocrine, 72 - changes in, 73, 92, 104 - - Glucose, blood content of, 244 - - Grapes, antiscorbutic value of, 158 - - Growth in scurvy, 213 - - Guinea-pig scurvy, 112, 114 - - Guinea-pig pathogenesis, 116 - pathology, 122 - relation to human, 115 - symptoms, 135 - - Gums, 177, 181, 184 - in infantile scurvy, =189= - pathology of, 89, 100 - - - H - - Hair, changes in, 194 - - Heart, =200= - gross pathology, 87 - microscopic pathology, 99 - - Heat, effect on vitamine of, 65 - - Hemorrhages, 180, 189 - as early symptoms, 178 - distribution of, 84 - gastric, 208 - orbital, 193 - subperiosteal, 95, =191= - urinary, 204 - - History of scurvy, 1 - - Hog, effect of scorbutic diet on, 115 - - Hypophysis, 104 - - - I - - Infantile scurvy, history, 10 - in artificially fed, 40 - in breast-fed, 35 - increase during World War, 21-22 - relation to epidemic scurvy of adults, 15, 37 - relation to rickets, 11, =110=, =252= - symptomatology, =183= - - Infection, as exciting factor, 60, 218 - increased liability to, 68 - effect on prognosis, 227 - - Intestines, gross pathology, 90 - microscopic pathology, 100 - - Intravenous use of orange juice, 238 - - Irregularities in course of deficiency diseases, 78 - - - J - - Jaundice, 208 - - Joints, lesions of, 199 - - - K - - Kidneys, gross pathology, 91 - microscopic pathology, 102 - - - L - - Latent scurvy, 179, 183, =187= - - Laxatives, failure to cure with, 28, =207= - - Lemon juice, antiscorbutic value of, 153, 234 - dried, 155, 232 - ration in British Navy, 9, 144 - - Lentils, value as antiscorbutic, 167, 231 - - Lice, theory of transmission of scurvy by, 30 - - Lime juice, antiscorbutic value of, 156 - fallacy in regard to, 149 - use in British Navy, 144 - - Liver, gross pathology, 91 - microscopic pathology, 101 - - Lungs, gross pathology, 88 - microscopic pathology, 99 - - Lymph-nodes, gross pathology, 92 - microscopic pathology, 101 - - - M - - Malnutrition, general, 58 - - Malt soup, 50 - - Marrow, changes in, 107 - - Meat, fresh, 147, =168= - salt, 146 - - "Mehlnaerschaden" of Czerny, 256 - - Metabolism in scurvy, 241-247 - - Milk, alkalized, 50 - amount necessary to prevent scurvy, 49, 117, =150= - boiled, 44, 65 - condensed, 48 - dried, 46, 66, =152= - effect of industrial methods on, 43 - evaporated, 45 - pasteurized, 40, 65 - home vs. commercial, 42 - sterilized, 44 - breast, amount necessary to prevent scurvy, 36, 39, 153 - as cause of beriberi, 39 - cows, antiscorbutic value of, 40, 152 - goats, antiscorbutic value of, 153 - - Mineral metabolism in scurvy, 241-247 - - Monkey, scurvy in, 114, =127= - pathology, 128 - - Muscles, pathology, 97 - - - N - - Nails, changes in, 194 - - Necropsy reports, 82 - - Nephritis, 205 - - Nerves, peripheral, in guinea-pig - scurvy, 132 - pathology, 105 - - Nervous system, effect of scurvy on, 202 - - Nutrition, general, in scurvy, 58, 59, 213 - - Nyctalopia, 182 - - - O - - Orange juice, antiscorbutic value of, =153=, 234 - "artificial," 33 - dried, 155 - effect of alkalization of, 154 - intravenous use of, 238 - subcutaneous use of, 155 - peel, antiscorbutic value of, 234 - - Osteogenesis imperfecta, 255 - - Osteomalacia, differentiation of, from scurvy, 255 - - Osteomyelitis, differentiation of, from scurvy, 222 - - Osteoporosis, differentiation of, from scurvy, 255 - - Osteotabes infantum, 109 - - - P - - Pains, as early symptom, 176 - - Pancreas, gross pathology, 91 - microscopic pathology, 104 - - Pasteurized milk, 40 - - Pathogenesis of scurvy, theories of, 23 - - Pathology of scurvy in guinea-pig, 122 - in man, gross, 83 - microscopic, 96 - in monkey, 128 - - Peas, antiscorbutic value of, 167, 231 - - Pellagra, 251 - - Phenols, excretion of, 245 - - Phosphate metabolism, 241-247 - - Pigeon, effect of scorbutic diet on, 114 - - Pneumonia, 202 - - Posture, characteristic, in guinea-pig, 136 - - Posture, characteristic, infant, 183 - - Potassium deficiency theory, 23 - metabolism, =241-247= - - Potatoes, antiscorbutic value of, 6, 7, 146, =161=, 235 - - Prevention of scurvy, 230 - - Prognosis, 225 - - Protein in diet, effect on scurvy, 59 - - Psychic element in scurvy, 57 - - Pulse, 181, =201= - - Pulses, germinated, 167, 231 - - Purpura, differential diagnosis, 221 - - Pyorrhoea, relation to lesion of gums, 181 - - - R - - Racial immunity, 56 - - Rats, effect of scorbutic diet on, 114, 115 - - Recurrent scurvy, 228 - - Respirations, 201 - - Retina, hemorrhages in, 105 - - Rheumatism, confusion with scurvy, 176, 220 - - Ribs, beading of, 197 - pathology, 94 - in guinea-pig, 129, 137 - - Rickets, relation of, to scurvy, =11=, =110=, =252= - - Rosary, 94, 197 - - - S - - Sauerkraut, antiscorbutic value of, 145 - - Season, effect on incidence, 54 - - Sex, effect on incidence, 56 - - Shaking, effect on antiscorbutic factor, 68 - - Ship beriberi, 250 - - Skin, pathology, 96 - - Spleen, gross pathology, 91 - microscopic pathology, 102 - - Sprue, 256 - - Starvation, pathology of, 125 - - Stomach, gross pathology, 89 - microscopic pathology, 100 - - Storage of vitamine in body, 74 - - Streptococcus in blood in scurvy, 134 - - Subacute form of scurvy, 184 - - Subcutaneous use of antiscorbutics, 155 - - Swede, antiscorbutic value of, =162=, 235 - - Symptomatology, in adult, 176 - in infant, 183 - - Syphilis, congenital, differential diagnosis, 222, 223 - - - T - - Teeth, in guinea-pig scurvy, 130, 137 - in human scurvy, 177 - - Temperature, in guinea-pig scurvy, 141 - in human scurvy, 181, =216= - - Thymus, pathology of, 104 - use of gland in treatment, 172 - - Thyroid, pathology of, 104 - use of gland in treatment, 172 - - Tomatoes, canned, antiscorbutic value of, =166=, 231, 234 - in U. S. Army ration, 231 - - Toxic theory of pathogenesis of scurvy, 25 - - Treatment of scurvy, 230 - duration of, 237 - non-dietetic, 239 - - - U - - Ultra-violet rays, effect on antiscorbutics, 67 - - Urea content of blood, 244 - of tissues, 245 - - Urine in scurvy, =204-206= - - - V - - Vegetable juices, keeping qualities of, 161 - - Vegetables, antiscorbutic value of 144, =158= - canned, 166 - dehydrated, 163 - effect of heat on, 159 - fresh, 144, =158= - ripeness of, effect on antiscorbutic value, 160 - - Vitamine, antiscorbutic, general discussion of, 62 - action of, 68, 69 - as antitoxin, 69 - as catalytic agent, 70 - as nutriment, 69 - blood content of, 76 - effect of heat on, 65 - of ultra-violet ray on, 67 - excretion of, 77 - - Vitamine, experimental evidence for, 62 - fate in body, 74, 77 - relation to water-soluble factor, 65, 67 - relation to antineuritic vitamine, 67 - resistance to chemical and physical processes, 64 - storage in body of, =74= - theory of scurvy, 32 - - - W - - Weight, loss of, 138, 213 - - "White line" of Fraenkel, =128=, =198= - - World War, scurvy in, 15 - - - X - - X-ray in diagnosis of scurvy, 128, 192, 198 - - - Y - - Yeast, antiscorbutic value of, 171 - - - - - -End of Project Gutenberg's Scurvy Past and Present, by Alfred Fabian Hess - -*** END OF THIS PROJECT GUTENBERG EBOOK SCURVY PAST AND PRESENT *** - -***** This file should be named 40505-8.txt or 40505-8.zip ***** -This and all associated files of various formats will be found in: - http://www.gutenberg.org/4/0/5/0/40505/ - -Produced by Bryan Ness, Thiers Halliwell and the Online -Distributed Proofreading Team at http://www.pgdp.net (This -file was produced from images generously made available -by The Internet Archive/American Libraries.) - - -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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