summaryrefslogtreecommitdiff
path: root/40505-0.txt
diff options
context:
space:
mode:
Diffstat (limited to '40505-0.txt')
-rw-r--r--40505-0.txt9642
1 files changed, 9642 insertions, 0 deletions
diff --git a/40505-0.txt b/40505-0.txt
new file mode 100644
index 0000000..87d5bc3
--- /dev/null
+++ b/40505-0.txt
@@ -0,0 +1,9642 @@
+*** START OF THE PROJECT GUTENBERG EBOOK 40505 ***
+
+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. Jour. of Sci., 1912, VII,
+67.
+
+ANSON, Lord: Walter and Robins, Voyage Round the World, London, 1848.
+
+ARNETH: Ueber Skorbut im Felde, Deutsch med. Woch., 1918, XLIV, 509.
+
+ARON, H.: Biochemie des Wachstums des Menschen and die hoeheren Tiere,
+Jena, 1913, Gustav Fischer, 58.
+
+ASCHOFF, L., and KOCH, W.: Der Skorbut, Jena, 1919, Gustav Fischer.
+
+AUSSET, E.: (1) La Maladie de Barlow, Annal. de med. et chir. Inf.,
+1904, VIII, 289.
+
+AUSSET, E.: (2) Un cas de maladie de Barlow chez un enfant nourri
+exclusivement avec du babeurre frais, Bull. Méd., 1910, XXIV, 675.
+
+BACHSTROM: Observationes circa Scorbutum, 1734.
+
+BAGINSKY, A.: Demonstration von anatomischen Praeparaten eines Falles
+von Barlowscher Krankheit, Berl. klin. Woch., 1897, XXXIV, 324.
+
+BAHRDT, H., and EDELSTEIN, F.: Organanalysen bei Barlowscher Krankheit,
+Zeitschr. f. Kinderheilk., 1913, IX, 415.
+
+BARLOW, T.: (1) On Cases described as Acute Rickets, Med. Chir. Trans.,
+1883, LXVI, 159.
+
+BARLOW, T.: (2) Infantile Scurvy and Its Relation to Rickets, Lancet,
+London, 1894, II, 1075.
+
+BARNES, K. E., and HUME, E. M.: Relative Antiscorbutic Value of Fresh,
+Dried and Heated Cow's Milk, Biochem. Jour., 1919, XIII, 306.
+
+BARROW, SIR JAY: Supplement to Encyclopedia Britannica, article "Navy,"
+cited by Budd.
+
+BARTENSTEIN, L.: Beitraege z. Frage des kuenstlichen Morbus Barlow bei
+Tieren, Jahrb. f. Kinderheilk., 1905, LXI, 6.
+
+BATEMAN: Scurvy in a Child, Birmingham Med. Review, 1886, Abstr. Arch.
+Ped., 1886, III, 304.
+
+BAUMANN, L., and HOWARD, C. P.: (1) Metabolism of Scurvy in an Adult,
+Arch. Int. Med., 1912, IX, 665.
+
+BAUMANN, L. and HOWARD, C. P.: (2) Mineral Metabolism of Experimental
+Scurvy of the Guinea-pig, Am. Jour. Med. Sci., 1917, CLIII, 650.
+
+BENOIT, A.: Une Épidémie de Scorbut, Paris Méd., 1919, IX, 469.
+
+BERNHEIM-KARRER: Saeuglingskorbut bei Ernaehrung mit Homogenisierter
+Berner Alpenmilch, Korrespondenzbl. f. Schweizer Aerzte, 1907, XXXVII,
+593.
+
+BLANE, SIR GILBERT: Observations on the Diseases Incident to Seamen,
+1789, London, J. Murray.
+
+BOERHAAVE: Cited by Lind.
+
+BOERICH, R.: Ueber Skorbut, Archiv. f. Klin. Med., 1919, CXXX, 151.
+
+BOHN: Acute Rachitis, Jahrb. f. Kinderheilk., 1868, II, 201.
+
+BOLDYREFF, W. N.: Quelques Considerations sur les Causes étiologiques du
+Scorbut, Comp. rend. soc. de biol., 1917, LXXX, 911.
+
+BOLLE, C.: Zur Therapie der Barlowschen Krankheit, Ztschr. f. diaetet.
+u. physik. Therap., 1902-03, VI, 354.
+
+BRADDEN, W. L., and COOPER, E. A.: The Influence of the Total Fuel Value
+of a Dietary upon the Quantity of Vitamine Required to Prevent Beriberi,
+Brit. Med. Jour., 1914, I, 1348.
+
+BRANDT, H.: Blutuntersuchungen bei Barlow'scher Krankheit, Archiv. f.
+Kinderheilk., 1919, LXVII, 395.
+
+BUDD, G.: Tweedies' System of Pract. Med., Phila., 1841, Lea and
+Blanchard, 99.
+
+BUDIN, P.: The Nursling, London, 1907, Caxton Pub. Co.
+
+BURGE, W. E., and NEILL, A. J.: (1) The Effect of Starvation on the
+Catalase Content of the Tissues, Am. Jour. Phys, 1917, XLIII, 58.
+
+BURGE, W. E., and NEILL, A. J.: (2) The Normal Mechanism for the Control
+of Oxidation in the Body, Am. Jour. Phys., 1918, XLVI, 117.
+
+BUSK, G.: Report of Committee on Scurvy, etc., London, 1877.
+
+CAILLÉ, A.: Minority Report, Amer. Ped. Soc. Collective Investigation
+(see above).
+
+CAREL: Un Cas de Scorbut imputable au Lait Stérilisé, Bull. de la Soc.
+de Pédiat. de Paris, 1910, XII, 79.
+
+CASSEL: Ein Fall von Skorbut, Arch. f. Kinderheilk., 1893, XV, 350.
+
+CHARPENTIER, P.: Étude sur le Scorbut, Paris, 1871, A. Delahaye.
+
+CHEADLE, W. B.: Infantile Scurvy, Allbutt's System of Med., 1901, V, 64.
+
+CHICK, H., and DELF, E. M.: The Antiscorbutic Value of Dry and
+Germinated Seeds, Biochem. Jour., 1919, XIII, 199.
+
+CHICK, H., and HUME, M.: The Distribution Among Foodstuffs (especially
+those suitable for the rationing of armies) of the Substances required
+for the Prevention of (a) Beriberi and (b) Scurvy, Trans. Soc. Trop.
+Med. and Hyg., 1917, X, 141.
+
+CHICK, H., and SKELTON, R. F.: (1) An Estimate of the Antiscorbutic
+Value of Milk in Infant Feeding, Lancet, London, I, 1918, 1.
+
+CHICK, H., and SKELTON, R. F.: (2) The Relative Content of Antiscorbutic
+Principle in Limes and Lemons, Lancet, London, 1918, II, 735.
+
+CHICK, H., and RHODES, M.: An Investigation of the Antiscorbutic Value
+of the Raw Juices of Root Vegetables, Lancet, London, 1918, II, 774.
+
+COHEN, B., and MENDEL, L. B.: (1) Diet and Roughage in Relation to the
+Experimental Scurvy of Guinea-pigs, Proc. Soc. Exp. Biol. and Med.,
+1918, XV, 122.
+
+COHEN, B., and MENDEL, L. B.: (2) Experimental Scurvy of the Guinea-pig
+in Relation to the Diet, Jour. Biol. Chem., 1918, XXXV, 427.
+
+COMBY, J.: (1) Twelve New Cases of Infantile Scurvy, Arch. de Méd. des
+Enfants, 1917, XX, 337.
+
+COMBY, J.: (2) Infantile Scurvy, Presse Médicale, 1918, XXVI, 480.
+
+CONCETTI, L.: Sopra due casi di morbo di Barlow, Rev. di clin. pediat.,
+Firenze, 1909, VII, 225.
+
+COPLANS, M.: (1) On the Etiology of Scurvy, Lancet, London, 1904, I,
+1714.
+
+COPLANS, M.: (2) On the Etiology of Scurvy, Jour. Trop. Med., London,
+1904, VII, 99.
+
+COUTTS, F. J. H.: Upon an Inquiry as to Dried Milks, etc. Report to the
+Local Govt. Board, 1918, New Series No. 116, 31.
+
+COUVY: Une Épidémie de Beriberi et de Scorbut, Annales d'Hygiène de Méd.
+Coloniales, 1911, XIV, 97.
+
+CRANDALL, F. M.: Scurvy in an Infant of Six Weeks, Arch. of Pediat.,
+1899, XVI, 851.
+
+CROCKER, W., and HARRINGTON, G. F.: Catalase and Oxidase Content of
+Seeds, Jour. Agricult. Research, Wash., D. C., 1918, XV, 137.
+
+CURRAN, J. O.: Observations on Scurvy, etc., The Dublin Quart. Jour.
+Med. Sciences, 1847, IV, 107.
+
+CZERNY A., and KELLER, A.: Handbuch des Kindes Ernaerung, etc., Leipzig,
+1907, II, 93.
+
+DARLING, S. T.: The Pathologic Affinities of Beriberi and Scurvy, Jour.
+Am. Med. Assn., 1914, LXIII, 1290.
+
+DELF, E. M., and SKELTON, R. F.: The Effect of Drying on the
+Antiscorbutic and Growth-Promoting Properties of Cabbage, Biochem.
+Jour., 1918, XII, 448.
+
+DELF, E. M., and TOZER, F. M.: The Antiscorbutic and Growth-Promoting
+Properties of Raw and Heated Cabbage, Biochem. Jour., 1918, XII, 416.
+
+DELPECH, M. A.: Le Scorbut pendant le Siège de Paris, Annales d'Hyg.,
+1871, XXXV, 2nd S.
+
+DISQUÉ, L.: Enstehung and Verlauf des Skorbuts im Jahre, 1916, Med.
+Klinik, 1918, XIV, 10.
+
+DUKE, W. W.: Pathogenesis of Purpura Hemorrhagica, Arch. Int. Med.,
+1912, X, 445.
+
+DUTCHER, R. A.: Nature and Function of the Antineuritic Vitamine, Proc.
+Nat. Acad. of Sci., 1920, VI, 10.
+
+DYKE, H. W.: An Outbreak of Scurvy in the South African Native Labour
+Corps, Lancet, London, 1918, II, 513.
+
+EDDY, W. H.: Further Observations on Pancreatic Vitamine, Proc. Soc.
+Exper. Biol. and Med., 1917, XIV, 164.
+
+EDITORIAL: Deficiency Diseases in Vienna, Brit. Med. Jour., 1920, I,
+477.
+
+EDWARDS, C. R.: Peripheral Neuritis in Jamaica, Jour. Trop. Med. and
+Hyg., 1916, XIX, 53.
+
+EIJKMAN, C.: Eine beriberiaehnliche Krankheit der Huehner, Virchow's
+Archiv., 1897, CXLVIII, 523.
+
+ENRIGHT, J. I.: War Edema in Turkish Prisoners, Lancet, London, 1920, I,
+314.
+
+EPSTEIN, A.: Ueber eine Auffaellige Haeufung der Barlow'schen Krankheit
+im den Kriegsjahren, 1917-1918, Jahrb. f. Kinderheilk, 1918, LXXXVIII,
+237.
+
+ERDHEIM, J.: Ueber das Barlowherz, Wien. klin. Woch., 1918, 1293.
+
+ESCHERICH, T.: (1) Skorbut. Verhandl. d. Gesellsch. f. Kinderheilk.,
+1898, XV, 77.
+
+ESCHERICH, T.: (2) Zur Kenntnis der Unterschiede zwischen den
+natuerlichen und kuenstlichen Ernaehrung des Saeuglings, Wien klin.
+Woch., 1900, XIII, 1185.
+
+ESSER: Blut-und Knochenmarksveraenderungen bei Ernaehrungsschaden,
+Verhandl. deutschen Naturforsch. u. Aerzte, Abt. f. Innere Med., 1908,
+86.
+
+FALK, K. G., MCGUIRE, G., and BLOUNT, E.: The Oxidase, Peroxidase,
+Catalase and Amylase of fresh and dehydrated vegetables, Jour. Biol.
+Chem., 1919, XXXVIII, 229.
+
+FEIGENBAUM, D.: Ein Beitrag zur Kenntnis der Rückenmarkblutungen beim
+Skorbut, Wien. klin. Woch., 1917, XXX, 1455.
+
+FIFE, C. A.: Pathology of Infantile Scurvy, N. Y. Med Jour., 1910, XCI,
+1322.
+
+FILATOW: Cited by M. Schubert, Beriberi und Skorbut, Deutsch. Arch. f.
+klin. Med., 1905, LXXXVI, 79.
+
+FINKELSTEIN, H.: Lehrbuch der Saeuglingsk., II, Berlin, 1912.
+
+FISCHER, Th.: Zur Kenntnis der hereditaeren Syphilis, Muenchn. med.
+Woch., 1890, XXXVII, 621.
+
+FOERSTER, R.: Ein Fall von acute Rachitis, Jahrb. f. Kinderheilk, 1868,
+I, 444.
+
+FRAENKEL, E.: Fortschritte a. d. Gebiete der Roentgenstrahlen, 1904,
+VII, Nos. 5 and 6; 1906, X, No. 1; 1908, Ergaensungsbd., XVIII.
+
+FREISE, E.: Der Alkoholextract aus Vegetabilien als Traeger.
+Barlowheilende Stoffe, Monatschr. f. Kinderheilk, 1914, XII, 687.
+
+FREUDENBERG, E.: Beitrag zur Frage des Barlow-Schutzstoffes. Monatschr.
+f. Kinderheilk, 1914, XIII, 141.
+
+FREUND, G.: Zur Kenntnis der Barlow'schen Krankheit (Brust Kind) Arch.
+f. Klin. Med., 1905, LXXXVI, 129.
+
+FROELICH, T.: Experimentelle Untersuchungen ueber den infantilen
+Skorbut, Ztschr. f. Hyg. u. Infektionskrankh., 1912, LXXII, 155.
+
+FRUITNIGHT, J. H.: Infantile Scurvy, Especially its Differential
+Diagnosis, Arch. of Pediat., 1894, XI, 486, 573.
+
+FUERST, L.: Infantiler Scorbut oder Haemorrhagische Rhachitis, Berl.
+klin. Woch., 1895, XXXII, 389.
+
+FUERST, V.: Weitere Beitraege zur Aetiologie des experimentellen
+Skorbuts des Meerschweinchens, Ztschr. f. Hyg. u. Infektionskrankh.
+1912, LXXII, 121.
+
+FUNK, C.: (1) On the Chemical Nature of the Substance which Cures
+Polyneuritis in Birds, Jour. Physiol., 1911, XLIII, 395.
+
+FUNK, C.: (2) Die Vitamine, Wiesbaden, 1914, J. F. Bergman.
+
+FUNK, C., and DOUGLAS, M.: Studies on Beriberi, VIII, Jour. Physiol,
+1914, XLVII, 475.
+
+FUNK, C., and VON SCHOENBORN, E.: The Influence of a Vitamine Free Diet
+on the Carbohydrate Metabolism, Jour. Physiol., 1914, XLVIII, 328.
+
+GARROD, A. B.: On the Nature, Cause and Prevention of Scurvy, Month.
+Jour. Med. Sci., 1848, Vol. VIII, 457.
+
+GEE: (1) On Osteal or Periosteal Cachexia, St. Bart. Hosp. Rep., 1881,
+XVII, 9.
+
+GEE: (1) On Osteal or Periosteal Cachexia, St. Bart. Hosp. Rep., 1881,
+Rep., 1889, XXV, 85.
+
+GERSTENBERGER, H. J.: Pathogenesis of Infantile Scurvy, an Hypothesis,
+Am. Jour. Med. Sci., 1918, CLV, 253.
+
+GINGUI, F.: Riforma Med., 1918, XXXIV, 22.
+
+GIVENS, M. H., and HOFFMAN, G. L.: Preliminary Observations on the
+Relation of Bacteria to Experimental Scurvy in Guinea-pigs, Jour. Biol.
+Chem., 1920, XLI, 33.
+
+GIVENS, M. H., and MCCLUGAGE, H. B.: The Antiscorbutic Property of
+Fruits, Am. Jour. Dis. Child., 1919, XVIII, 30.
+
+GLISSON: Treatise on the Rickets, London, 1651.
+
+GOLDBERGER, J.: Studies on Pellagra, Hyg. Lab. Bull's., 1914-1920.
+
+GUERRERO and QUINTO: Cited by Vedder, Beriberi, p. 259.
+
+HARDEN, A., and ZILVA, S. S.: (1) Note on the Etiology of Scurvy in
+Guinea-pigs, Biochem. Jour., 1918, XII, 270.
+
+HARDEN, A., and ZILVA, S. S.: (2) The Differential Behavior of the
+Antineuritic and Antiscorbutic Factors Towards Adsorbents, Biochem.
+Jour., 1918, XII, 93.
+
+HARDEN, A., and ZILVA, S. S.: (3) The Antiscorbutic Factor in Lemon
+Juice, Biochem. Jour., 1918, XII, 259.
+
+HARDEN, A., and ZILVA, S. S.: (4) Accessory Factors in the Nutrition of
+the Rat, Biochem. Jour., 1918, XII, 408.
+
+HARDEN, A., and ZILVA, S. S.: (5) An Investigation of Beer for
+Antineuritic and Antiscorbutic Potency, Jour. of the Institute of
+Brewing, 1918, XXIV, 197.
+
+HARDEN, A., and ZILVA, S. S.: (6) The Susceptibility of the
+Antiscorbutic Principle to Alkalinity, Lancet, London, 1918, II, 320.
+
+HARDEN, A., ZILVA, S. S., and STILL, G. F.: Infantile Scurvy,
+Antiscorbutic Factor of Lemon Juice in Treatment, Lancet, London, 1919,
+I, 17.
+
+HARLAN, G. P.: Land Scurvy in England, Brit. Med. Jour., 1917, II, 46.
+
+HART, C.: Der Skorbut der kleinen Kinder (Moeller-Barlow'sche Krankheit)
+Nach Experimentellen Untersuchungen, Jahrb. f. Kinderheilk, 1912, LXXVI,
+507.
+
+HART, C., and LESSING, O.: Der Skorbut der Kleinen Kinder, Stuttgart,
+1913, Ferdinand Enke.
+
+HART, E. B., STEENBOCK, H., and ELLIS, N. R.: Influence of Diet on the
+Antiscorbutic Potency of Milk, Jour. Biol. Chem., 1920, XLII, 383.
+
+HART, E. B., STEENBOCK, H., and SMITH, D. W.: Effect of Heat on the
+Antiscorbutic Properties of Some Milk Products, Jour. Biol. Chem., 1919,
+XXXVIII, 305.
+
+HARVEY, G.: A New Discourse of the Smallpox and Malignant Fevers with an
+Exact Discovery of the Scurvy, London, 1685.
+
+HARVIER, P.: Épidémie de Scorbut, Paris Méd., 1917, VII, 394.
+
+HAWKINS, SIR R.: Voyage to the South Sea, A. D. 1593, in Purchas's
+"Pilgrim," Vol. IV.
+
+HAYEM, M. G.: Note sur l'Anatomie Pathologique du Scorbut, Gazette Méd.
+de Paris, 1871, XXVI, 126.
+
+HESS, A. F.: (1) Infantile Scurvy: II. A New Aspect of the
+Symptomatology, Pathology and Diet, Jour. Am. Med. Assn., 1915, LXV,
+1003.
+
+HESS, A. F.: (2) Infantile Scurvy: III. Its Influence on Growth (Length
+and Weight), Am. Jour. Dis. Child., 1916, XII, 152.
+
+HESS, A. F.: (3) Infantile Scurvy: IV. The Therapeutic Value of Yeast
+and of Wheat Embryo, Am. Jour. Dis. Child., 1917, XIII, 98.
+
+HESS, A. F.: (4) Subacute and Latent Infantile Scurvy, The
+Cardiorespiratory Syndrome (a New Sign), Jour. Am. Med. Assn., 1917,
+LXVIII, 235.
+
+HESS, A. F.: (5) Infantile Scurvy: V. A Study of Its Pathogenesis, Am.
+Jour. Dis. Child., 1917, XIV, 337.
+
+HESS, A. F.: (6) The Rôle of Antiscorbutics in Our Dietary, Jour. Am.
+Med. Assn., 1918, LXXI, 941.
+
+HESS, A. F.: (7) Focal Degeneration of the Lumbar Cord in a Case of
+Infantile Scurvy, Jour. Infect. Dis., 1918, XXIII, 438.
+
+HESS, A. F., and FISH, M.: Infantile Scurvy: The Blood, the
+Blood-Vessels, and the Diet, Am. Jour. Dis. Child., 1914, VIII, 386.
+
+HESS, A. F., and KILLIAN, J. A.: Chemistry of the Blood in Scurvy, Proc.
+Soc. Exp. Biol. and Med., 1918, XVI, 43.
+
+HESS, A. F., and UNGER, L. J.: (1) Experiments on the Scurvy of
+Guinea-pigs, Proc. Soc. Exp. Biol. and Med., 1918, XV, 82.
+
+HESS, A. F., and UNGER, L. J.: (2) The Scurvy of Guinea-pigs: I. The
+Experimental Dietary, Jour. Biol. Chem., 1918, XXXV, 479.
+
+HESS, A. F., and UNGER, L. J.: (3) The Scurvy of Guinea-pigs, II,
+Experiments on the Effect of the Addition of Fruits and Vegetables to
+the Dietary, Jour. Biol. Chem., 1918, XXXV, 487.
+
+HESS, A. F., and UNGER, L. J.: (4) Experiments on Antiscorbutics, Report
+of an Antiscorbutic for Intravenous Use, Proc. Soc. Exp. Biol. and Med.,
+1918, XV, 141.
+
+HESS, A. F., and UNGER, L. J.: (5) Canned Tomatoes as an Antiscorbutic,
+Proc. Soc. Exp. Biol. and Med., 1918, XV, 96.
+
+HESS, A. F., and UNGER, L. J.: (6) Scurvy: VIII, Factors Affecting the
+Antiscorbutic Value of Foods, Am. Jour. Dis. Child., 1919, XVII, 221.
+
+HESS, A. F., and UNGER, L. J.: (7) The Scurvy of Guinea-pigs: III. The
+Effect of Age, Heat and Reaction on Antiscorbutic Foods, Jour. Biol.
+Chem., 1919, XXXVIII, 293.
+
+HESS, A. F., and UNGER, L. J.: (8) The Deleterious Effect of the
+Alkalization of Infants' Food, Jour. Am. Med. Assn., 1919, LXXIII, 1353.
+
+HESS, A. F., and UNGER, L. J.: (9) Scorbutic Beading of the Ribs, Am.
+Jour. Dis. Child., 1920, XIX, 331.
+
+HEUBNER, O.: Ueber die Barlowsche Krankheit, Berl. klin. Woch., 1903,
+XL, 285.
+
+HIFT, R.: Beobachtungen ueber Skorbut and Hemeralopie, Abstract,
+Deutsch. med. Woch., 1918, XLIV, 100.
+
+HIMMELSTEIN, von S.: Beobachtungen ueber den Skorbut, Arch. f. d.
+gesammte Med., 1843, V, 490.
+
+HIRSCH, A.: Handbook of Geographical and Historical Pathology, London,
+1885, New Sydenham Society.
+
+HIRSCHSPRUNG, H.: Die Moellersche Krankheit. Jahrb. f. Kinderheilk,
+1896, XLI, 1.
+
+HOERSCHELMAN, E.: Zur Klinik der Skorbuts in der russischen Armee,
+Deutsch. med. Woch., 1917, XLIII, 1617.
+
+HOFFMANN: Untersuchungen eines Falles von Barlow'scher Krankheit,
+Beitraege z. path. Anat., 1905, Suppl. VII, (Festschrift fer Arnold).
+
+HOLST, H., and FROELICH, T.: (1) Experimental Studies Relating to Ship
+Berberi and Scurvy, Jour. of Hyg., 1907, VII, 634.
+
+HOLST, H., and FROELICH, T.: (2) Ueber experimentellen Skorbut, Ztschr.
+f. Hyg. u. Infektionskrankh., 1912, LXXII, 1.
+
+HOLST, H., and FROELICH, T.: (3) Scorbutus and its Prophylaxis, Norsk.
+Mag. f. Laegevidensk., 1916, LXXVII, 989.
+
+HOLT, L. E.: Diseases of Infancy and Childhood, New York and London,
+1919, Appleton.
+
+HOPKINS, F. G.: (1) The Analyst and the Medical Man, Analyst, 1906,
+XXXI, 395.
+
+HOPKINS, F. G.: (2) Feeding Experiments Illustrating the Importance of
+Accessory Factors in Normal Dietaries, Jour. of Physiol., 1912, XLIV,
+425.
+
+HOPKINS, G. R.: The Etiology of Scurvy, Jour. Am. Med. Assn., 1917,
+LXIX, 1641.
+
+HOWARD, C. P., and INGVALDSEN, T.: The Mineral Metabolism of
+Experimental Scurvy of the Monkey, Johns Hopkins Hosp. Bull., 1917,
+XXVIII, 221.
+
+HUTCHISON, R.: Some Disorders of the Blood and Blood-Forming Organs in
+Early Life, Lancet, London, 1904, I, 1253.
+
+INGIER, A.: (1) Beitraege zur Kenntnis der Barlowschen Krankheit,
+Frankfurt. Ztschr. f. Path., 1913, XIV, 1.
+
+INGIER, A.: (2) A Study of Barlow's Disease Experimentally Produced in
+Fetal and Newborn Guinea-pigs, Jour. Exper. Med., 1915, XXI, 525.
+
+JACOBSTHAL, H.: Zur Pathologie der Knochenerkrankungen bei Barlowscher
+Krankheit, Beitraege z. path. Anat., 1900, XXVII, 173.
+
+JACKSON, F., and HARLEY, V.: An Experimental Inquiry into Scurvy,
+Lancet, London, 1900, I, 1184.
+
+JACKSON, L., and MOODY, A. M.: Bacteriologic Studies on Experimental
+Scurvy in Guinea-pigs, Jour. Infect. Dis., 1916, XIX, 511.
+
+JACKSON, L., and MOORE, J. J.: Studies of Experimental Scurvy in
+Guinea-pigs, Jour. Infect. Dis., 1916, XIX, 478.
+
+JALLAND, W. H.: Med. Times and Gazette, London, 1873, I, 248.
+
+JOHANNESON, A.: Ueber die Sterilization der Milch. Jahrb. f.
+Kinderheilk, 1901, LIII, 251.
+
+KARR, W. G., and LEWIS, H. B.: Phenol Excretion of Guinea-Pigs
+Maintained on an Exclusive Oat Diet, Am. Jour. Physiol., 1917, XLIV,
+586.
+
+KAUFMANN, E.: Lehrbuch der Speziellen Pathologischen Anatomie, Berlin,
+1911, Georg Reimer.
+
+KERLEY, C. G.: Practice of Pediatrics, Phila., 1918, Saunders & Co.
+
+KITAMURA, S.: Ein Beitrag zur Kenntnis der Netzhautveraenderungen beim
+Skorbut, Deutsch. med. Woch., 1910, XXXVI, 403.
+
+KOCH, J.: Untersuch. uber die Lokalisation d. Bakterien, etc., Zeitschr.
+f. Hyg., 1911, LXIX.
+
+KOHLBRUGGE, J. H.: Die Gaerungskrankheiten, Centralbl. f. Bakt. etc.,
+Orig. 1911, LX, 223.
+
+KORBSCH, R.: Ueber Skorbut im Felde, Deutsch. med. Woch., 1919, XLV,
+185.
+
+KRAMER: Medicina Castrensis, 1721, Cited by Charpentier (see above).
+
+LABOR, M.: Eine Beobachtung ueber das Blutbild des Skorbuts, Wien. klin.
+Woch., 1916, XXIX, 912.
+
+LAMER, V. K., and CAMPBELL, H. L.: Changes in Organ Weight Produced by
+Diet Deficient in Antiscorbutic Vitamine, Proc. Soc. Exper. Biol. and
+Med., 1920.
+
+LASÈQUE, Ch., and Legroux, A.: L'Épidémie de Scorbut dans les Prisons de
+la Seine et a l'Hôpital de la Pitié, Arch. Gén., 1871, II, 5, 680.
+
+LECORNU, P.: Les Laits Industriels, Thèse de Paris, 1904.
+
+LEVEN, M.: Une Épidémie de Scorbut observée a l'Hôpital Militaire d'Ivry
+pendant le Siège de Paris, 1871.
+
+LEWIS, A. B., and KARR, W. G.: Changes in the Urea Content of the Blood
+and Tissues of Guinea-pigs Maintained on an Exclusive Oat Diet, J. Biol.
+Chem., 1916, XXVIII, 17.
+
+LIND, J.: Treatise on Scurvy, London, 1772.
+
+LITTEN, M.: Nothnagel's Handbuch der Spec. Path. u. Therap., 1901, VIII,
+3, 277.
+
+LLOYD, D. J.: On Vitamines, Amino Acids, and Other Chemical Factors
+Involved in the Growth of the Meningococcus, Jour. of Path., 1916-17,
+XXI, 118.
+
+LOBMEYER, G.: Kriegschirurgische Bedeutung des Skorbuts, Abstracted in
+Deutsch. med. Woch., 1918, XLIV, 557.
+
+LOOSER, E.: Ueber die Knochenveraenderungen beim Skorbut, Jahrb. f.
+Kinderheilk., 1905, LXII, 743.
+
+LUBARSCH, O.: Ueber alimentaere Schlagaderverkalkung, Muench. med.
+Woch., 1910, Nr. 30, 1577.
+
+LUNIN, N.: Ueber die Bedeutung der Anorganischen Salze fuer die
+Ernaehrung des Thiers, Ztschr. f. physiol. Chem., 1881, V, 31.
+
+LUST, F., and KLOCMAN, L.: Stoffwechselversuche bei Barlow'sche
+Krankheit, Jahrb. f. Kinderheilk., 1912, LXXV, 663.
+
+LYABMOW: Aerztl. Gesellschaft zu Kasan, 1900, Cited from M. Schubert,
+Beriberi und Skorbut, Arch. f. klin. Med., 1905, LXXXVI, 79.
+
+MCCARRISON, R.: (1) The Pathogenesis of Deficiency Disease, Indian Jour.
+Med. Research, 1919, VI, 275.
+
+MCCARRISON, R.: (2) The Influence of the Scorbutic Diet on Adrenal
+Gland, Indian Jour. Med. Research, 1919, VII, 188.
+
+MCCOLLUM, E. V., and DAVIS, M.: The Necessity of Certain Lipins in the
+Diet during Growth, Jour. Biol. Chem., 1913, XV, 167.
+
+MCCOLLUM, E. V., and PITZ, W.: The Vitamine Hypothesis and Deficiency
+Diseases, A Study of Experimental Scurvy, Jour. Biol. Chem., 1917, XXXI,
+229.
+
+MACKENZIE: Reported by Barlow, 1883.
+
+MARFAN, A. B.: Maladies des Os, Paris, 1912.
+
+MANZ, R.: Beitraege zur Kenntnis der Moeller-Barlow'scher Krankheit.
+Inaug. Addr., Heidelberg, 1899.
+
+MEDICAL AND SURGICAL HISTORY OF THE WAR OF THE REBELLION, 1888,
+Washington, I, Part 3, Chap. 8.
+
+MELLANBY, E.: An Experimental Investigation of Rickets, Lancet, London,
+1919, I, 407.
+
+MEYER, E.: Ueber Barlow'sche Krankheit, Arch. f. Kinderheilk, 1896, XX,
+202.
+
+MOELLER: (1) Acute Rachitis, Koenigsberg. med. Jahrb, 1859, I.
+
+MOELLER: (2) 2 Faelle von acuter Rachitis, Koenigsberg. med. Jahrb.
+1862, III.
+
+MOLL, L.: Stoffwechsel in Barlow'sche Krankheit, Mitteil. d. Gesellsch.
+f. innere Med. u. Kinderheilk. in Wien, 1919, XVIII.
+
+MONFALCON: Rachitis, Dictionnaire des Sciences, 1820, XLVI.
+
+MONEY: Three Cases of Infantile Scurvy, Intercolon. Med. Jour. of
+Australia, 1897.
+
+MOORE, J. J.: Experimental Studies in Diet Deficiency Diseases, Proc.
+Inst. of Med. of Chicago, 1918, 254.
+
+MORAWITZ, P.: (1) Echter und Falscher sporadischer Skorbut, Muench. med.
+Woch., 1918, LXV, 339.
+
+MORAWITZ, P.: (2) Der Skorbut und verwandte Krankheiten, Jahresb. f.
+aerztl. Fortbildung, March, 1919, 15.
+
+MORGAN, A., and BEGER, C.: Zeitschr. Physiol. Chem., 1915, XCIV, 324.
+
+MORPURGO, B.: Ueber eine Infectioese Form der Knochenbruchigkeit bei
+weissen Ratten, Verhandl. d. deutsch. patholog. Gesellsch., 1900, III,
+40.
+
+MORSE, J. L.: (1) Infantile Scorbutus (50 cases), Jour. Am. Med. Assn.,
+1906, XLVI, 1073.
+
+MORSE, J. L.: (1) Infantile Scorbutus (50 cases), Jour. Am. Med. Assn.,
+CLXX, 504.
+
+MUCH, H.: Skorbut, Muench. med. Woch., 1917, LXIV, 854.
+
+MUELLER, E.: Ueber ein gehaeuftes Auftreten von Skorbut bei Kindern,
+Berlin klin. Woch., 1918, LV, 1024.
+
+MUCKENFUSS, A. M.: The Excretion of Vitamines, Arch. of Pediat., 1919,
+XXXVI, 80.
+
+MUNSON, E. L.: Military Hygiene, New York, 1901.
+
+MURLIN, J. R.: Some Problems of Nutrition in the Army, Boston Med. and
+Surg. Jour., 1918, CLXXIX, 396.
+
+NAEGELI, O.: Zur pathologischen Anatomie und zum Wesen des Morbus
+Barlow, Centralbl. f. allg. Path. u. path. Anat., 1897, VIII, 687.
+
+NANSEN and JOHANSEN: Cited by Holst and Froelich (see above).
+
+NETTER: Le Scorbut Infantile, La Semaine Médicale, 1899, No. 8.
+
+NEUMANN, H.: Bemerken ueber Barlow'sche Krankheit, Deutsch. med. Woch.,
+1902, XXVIII, 628.
+
+NICHOLS: Infantile Scurvy, Brit. Med. Jour., 1896, I, 25.
+
+VON NIEDNER: Hæmorrhagische Exantheme, Med. Klinik, 1918, XIV, 333.
+
+NOBÉCOURT, P., TIXIER, L., and MAILLET: Hematologie et Altérations
+osteo-médullaires dans la Maladie de Barlow, Compt. Rend. de l'Assoc. de
+Pédiatrie, 1913-15, 123.
+
+NOCHT, B.: Festschrift zum 60 Geburtstage v. R. Koch, 1903, 203.
+
+VAN NOORDEN, C.: Ueber enterogene Intoxicationen, Berl. klin. Woch.,
+1913, L, 51.
+
+NORTHRUP, W. P.: Scorbutus in Infants, Arch. of Pediat., 1892, IX, 1.
+
+ONO, S.: Adrenalin Content of Suprarenal, Taiwan Igakuku Zasshi, Tokio,
+1916, CLXX, 1014.
+
+OSBORNE, T. B., and MENDEL, L. B.: (1) The Relations of Growth to the
+Chemical Constituents of the Diet, Jour. Biol. Chem., 1913, XV, 311.
+
+OSBORNE, T. B., and MENDEL, L. B.: (2) The Distribution of Water Soluble
+Vitamine, Jour. Biol. Chem., 1919, XXXIX, 29.
+
+O'SHEA, H. V.: Scurvy, The Practitioner, 1918, Oct.-Nov.
+
+PAPPENHEIMER, A.: Further Experiments upon the Extirpation of the Thymus
+in Rats, Jour. Exper. Med., 1914, XX, 477.
+
+PARKES: Med.-Chir. Rev., 1848, Art. VIII.
+
+PEIPER and EICHLOFF: Korrespondenzbl. d. Verein d. Aerzte, Stralsund,
+1904.
+
+PICK, F.: Skorbut, Deutsch. med. Woch., 1916, XLII, 1402.
+
+PICKENS, R. M.: A Death from Scurvy, Lancet, London, 1917, II, 21.
+
+PITZ, W.: Studies of Experimental Scurvy, Jour. Biol. Chem., 1918,
+XXXIII, 471.
+
+PLANTENGA, B. P.: Rohe Milch als Saeuglingsnahrung, Arch. f.
+Kinderheilk., 1912, VIII, 155.
+
+POUPART: Étranges Effets du scorbut arrivés à Paris en 1699, Hist. de
+l'Acad. Royale des Sci., 1699.
+
+RALFE, C. H.: Inquiry into the General Pathology of Scurvy, Lancet,
+London, 1877, I, 868; II, 81.
+
+RAPPLEYE, W. C.: A Note on Experimental Scurvy in the Guinea-pig, Boston
+Med. and Surg. Jour., 1918, CLXXIX, 98.
+
+RAUCHFUSS: Cited from Heubner, O., Lehrbuch f. Kinderheilk., Leipzig,
+1903, I, 698.
+
+REHN, H.: Ein Fall von Skorbut, Berl. klin. Woch., 1889, XXVI, 11.
+
+REINERT, E.: Ein Fall von Barlow'scher Krankheit, Muenschner med. Woch.,
+1895, XLII, 370.
+
+REINHARD, P.: Roentgenbefunde bei beriberiartigen Erkrankungen, Arch. f.
+Schiffs-u. Tropenhyg., 1916, 20.
+
+REPORT OF MESOPOTAMIA COMMISSION: London, 1917.
+
+RICHARD, R., and LLOYD, G. W.: Early Signs of Scurvy, Brit. Med. Jour.,
+1920, I, 329.
+
+RONDONI, P.: Remarks on the Pathogenesis of Deficiency Diseases and on
+Pellagra, Brit. Med. Jour., 1919, I, 542.
+
+SALANT, W.: The Importance of Diet as a Factor in the Production of
+Pathological Changes, Jour. Am. Med. Assn., 1917, LXIX, 603.
+
+SAMMIS, J. F.: A Case of Scurvy with Cerebral Hemorrhage, Arch. of
+Pediat., 1919, XXXVI, 274.
+
+SATO, T., and NAMBU, K.: Zur Pathologie und Anatomie des Skorbuts,
+Virchow's Arch., 1908, CXCIV, 151.
+
+SCHAUMANN: Die Aetiologie der Beriberi unter Beruchsichtigung des
+gesammten Phosphorstoffwechsels, Beihefte z. Arch. f. Schiffs-u.
+Tropenhygiene, 1910, XIV, 325.
+
+SCHMORL, G.: (1) Ueber Stoerung des Knochenwachstums bei Barlow'scher
+Krankheit, Centralbl. f. allg. Path. u. path. Anat., 1899.
+
+SCHMORL, G.: (2) Zur Path. Anatomie der Barlowschen Krankheit Beiträge
+z. path. Anat., 1901, XXX.
+
+SCHMORL, G.: (3) Ueber die Pathogenese der bei Moeller-Barlowscher
+Krankheit auftretenden Knochenveraenderungen, Jahrb. f. Kinderheilk,
+1907, LXVI, 50.
+
+SCHOEDEL, J., and NAUWERK, C.: Untersuchungen ueber die
+Moeller-Barlow'sche, Krankheit, Jena, 1900.
+
+SCHREIBER, G.: Scorbute et Dysenterie, Paris Médical, 1918, VII, 508.
+
+SCHREIBER, G., and FRANÇOIS, M.: Scorbut Infantile chez un enfant de
+quatre ans nourri au lait homogénéisé, Arch. de Méd. des Enfants, 1914,
+XVII, 610.
+
+SEIDELL, A.: Vitamines and Nutritional Diseases, U. S. Public Health
+Reports, 1916, XXXI, 364.
+
+SENATOR, H.: Ueber lymphadenoide und aplastische Veraenderungen des
+Knochenmarks, Zeitschr. f. klin. Med., 1904, LIV, 1.
+
+SHAKLEE, A. O., and MELTZER, S. J.: (1) The Mechanical Destruction of
+Pepsin, Am. Jour. Physiol., 1908, XXIII, 29.
+
+SHAKLEE, A. O., and MELTZER, S. J.: (2) The Influence of Shaking upon
+Trypsin and Rennin, etc., Proceed. Soc. Exp. Biol. and Med., 1908, VI,
+103.
+
+SHEPPARD, A. L.: Scurvy in Zhob, Baluchistan, Indian Jour. Med.
+Research, 1916, IV, 340.
+
+SMITH, T.: Hemorrhagic Periostitis of the Shafts of Several Long Bones
+with Separation of the Epiphyses, Trans. Path. Soc., London, 1876,
+XXVII, 219.
+
+SMITH, TH.: Bacilli in Swine Disease, U. S. Dept. Agric., Bureau Animal
+Industry, Ann. Rep. 1895-96, 172.
+
+SMITH, W. J.: Scurvy, Allbutt's System of Med., 1901, V, 586.
+
+SOUTHGATE, F. H.: A Case of Scurvy in a Breast-Fed Infant, Arch. of
+Pediat., 1893, X, 505.
+
+SPEYER: Waden-Abszesse bei Skorbut, Deutsch med. Woch., 1918, XLIV, 626.
+
+VON STARCK: Quoted from Czerny and Keller (see above).
+
+STEENBOCK, H., BOUTWELL, P. W., and KENT, H. E.: Fat-Soluble Vitamine,
+J. Biol. Chem., 1918, XXXV, 517.
+
+STEFÁNSSON, V.: Observations on Three Cases of Scurvy, Jour. Am. Med.
+Assn., 1918, LXXI, 1715.
+
+STEINER: Kompendium der Kinderkrankheiten, Leipzig, 1878, F. C. W.
+Vogel.
+
+STEPP, W.: (1) Experimentelle Untersuchungen ueber die Bedeutung der
+lipoide fur die Ernaehrung, Zeitschr. f. Biol., 1911, LVII, 135.
+
+STEPP, W.: (2) Weitere Untersuch. ueber d. Unentbehrlichkeit d. Lipoide,
+etc., Zeitschr. f. Biol., 1912, LIX, 366.
+
+STILL, G.: (1) Common Disorders and Diseases of Childhood, 1915, London,
+3rd Ed.
+
+STILL, G.: (2) Coeliac Disease, Lancet, London, 1918, II, 163.
+
+STOELTZNER, W.: Ein Anatomisch untersuchter Fall von Barlow'scher
+Krankheit, Jahrb. f. Kinderheilk., 1906, LXIII, 36.
+
+STOOS, M.: Barlowsche Krankheit, Correspondenzbl. f. Schw. Aerzte, 1903,
+XXXIII, 497.
+
+SUGIURA, K., and BENEDICT, S. R.: The Nutritive Value of the Banana,
+Jour. Biol. Chem., 1918, XXXVI, 171.
+
+SUTHERLAND, G. A.: On Hæmatoma of the Dura Mater Associated with Scurvy
+in Children, Brain, 1894, XVII, 27.
+
+TALBOT, F. B., DODD, W. J., and PETERSON, H. O.: Experimental Scorbutus
+and the Röntgen Ray Diagnosis of Scorbutus, Boston Med. and Surg. Jour.,
+1913, CLXIX, 232.
+
+TOBLER, W.: Der Skorbut in Kindesalter, Zeitschr. f. Kinderheilk., 1918,
+XVIII, 63.
+
+TORREY, J. C., and HESS, A. F.; The Relation of the Intestinal Flora to
+the Scurvy of Guinea-pigs and of Infants, Proc. Soc. Exp. Biol. and
+Med., 1918, XV, 74.
+
+TORUP: Report of the Committee Appointed to Inquire into the Causes of
+the Outbreak of Scurvy in the Recent Arctic Expedition, London, 1877.
+
+TROP. DIS. BULL.: 1918, XII, 257.
+
+TSCHUDAKOFF: Cited from Heubner, O.; Lehrbuch. f. Kinderheilk., Leipzig,
+1903, I, 698.
+
+TUECHLER: (Quotes Rheindorf) Ueber Skorbut, Med. Klin., 1918, XIV, 112.
+
+UHLMANN, F.: Beitraege zur Pharmakologie die Vitamine, Zeitschr. f.
+Biol. 1918, XLVIII, 419, 457.
+
+URIZIO, L.: Skorbut und nicht-spirochaetogener Icterus epidemicus, Wien.
+klin. Wochenschr., 1917, XXX, 1449.
+
+VALLARDI, C.: Riforma Med., 1918, XXXIV, 793.
+
+VANNUTELLI, F.: Un Epidemia di Porpora Infettiva con Manifestazione
+Emorragico-scorbutiche tra le Truppe Combattenti, Il Policlinico, Sez.
+Pratica, 1917, XXIV, 873.
+
+VARIOT, G.: Du Lait Stérilisé, Compt. rend. de l'Acad. d. Sci., 1905,
+CXXV, 1002.
+
+VEDDER, E. B.: Beriberi, New York, 1913, Wm. Wood & Co.
+
+VEDDER, E. B., and Clark: A Study of Polyneuritis Gallinarum, Phillip.
+Jour. Sci., 1912, VII.
+
+VILLEMIN: Cause et Nature de Scorbut, Bull. d. l'Acad. de Med., 1874,
+680, 739.
+
+VINCENT, R.: The Nutrition of the Infant, New York, 1904, Wm. Wood & Co.
+
+VOEGTLIN, C.: The Effect of Alkali on Vitamines, Proc. Amer. Soc. Biol.
+Chem., 1916, 24.
+
+VOEGTLIN, C., and MYERS, C. N.: A Comparison of the Influence of
+Secretin and the Antineuritic Vitamine on Pancreatic Secretion and Bile
+Flow, Jour. Pharm. and Exp. Therap., 1919, XIII, 301.
+
+WASSERMANN, S.: (1) Ueber Hochwertige Erythrozyten and Hemoglobinbefunde
+bei Kriegern, Muench. med. Woch., 1918, LXV, 927.
+
+WASSERMANN, S.: (2) Ueber eine mit Schwellung und Roetung der Beine
+verbundene Knochenschmerzhaftigkeit bei Kriegern, Wien klin. Woch.,
+1918, LXVIII, 968.
+
+WESTON, W.: Pellagra in Early Childhood, Am. Jour. Dis. Child., 1914,
+VII, 124.
+
+WHERRY, W. B.: The Influence of Scurvy on Hemorrhages in Plague. Jour.
+Infect. Dis., 1909, VI, 564.
+
+WILLCOX, W. H.: Treatment and Management of Diseases Due to a Deficiency
+of Diet, Scurvy and Beriberi, Brit. Med. Jour., 1920, I, 73.
+
+WILLIAMS, R. R.: Some General Aspects of the "Vitamine" Problem, Amer.
+Med., 1916, N. S. XI, 756.
+
+WILTSHIRE, H.: Hyperkeratosis of the Hair Follicles in Scurvy, Lancet,
+London, 1919, II, 564.
+
+WRIGHT, A. E.: The Causation and Treatment of Scurvy, Lancet, London,
+1908, II, 725.
+
+YANO, K., and NEMOTI, T.: Studies of the Blood in Beriberi, Arch. Int.
+Med., 1917, XX, 103.
+
+ZIEGLER, E.: Ueber Osteotabes infantum u. Rachitis, Centralb. f. allgem.
+Path. u. patholog. Anat., 1901, XII, 865.
+
+ZILVA, S. S.: (1) Action of Ultra Violet Rays on the Accessory Food
+Factors, Biochem. Jour., 1919, XIII, 164.
+
+ZILVA, S. S.: (2) Influence of Deficient Nutrition on the Production of
+Agglutinins, Complement and Amboceptor, Biochem. Jour, 1919, XIII, 172.
+
+ZILVA, S. S., and WELLS, F. M.: Change in the Teeth of the Guinea-pig
+Produced by a Scorbutic Diet, Proceed. of the Royal Soc., 1919, B. 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 THE PROJECT GUTENBERG EBOOK 40505 ***
generated by cgit v1.2.3 (git 2.25.1) at 2026-08-10 09:17:36 +0000