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Title: Scurvy Past and Present
Author: Hess, Alfred Fabian
Language: English
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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





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