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ON INFANTILISM FROM CHRONIC 
 INTESTINAL INFECTION 
 
THE MACMILLAN COMPANY 
 
 NEW YORK • BOSTON • CHICAGO 
 ATLANTA • SAN FRANCISCO 
 
 MACMILLAN & CO., Limited 
 
 LONDON • BOMBAY • CALCUTTA 
 MELBOURNE 
 
 THE MACMILLAN CO. OF CANADA, Ltd. 
 
 TORONTO 
 
On Infantilism from 
 
 Chronic Intestinal 
 
 Infection 
 
 CHARACTERIZED BY THE OVER- 
 GROWTH AND PERSISTENCE OF 
 FLORA OF THE NURSLING PERIOD 
 
 A Study of the Clinical Course, Bacteriology, Chemistry and 
 Therapeutics of Arrested Development in Infancy 
 
 BY 
 C. A. HERTER, M.D. 
 
 Professor of Pharmacology and Therapeutics 
 Columbia University 
 
 THE MACMILLAN COMPANY 
 
 1908 
 
 All rights reserved 
 
Copyright, 1908 
 By THE MACMILLAN COMPANY 
 
 Set up and electrotyped. Published November, 1908 
 
 <PHE MASON-HENRY PRSSS 
 8YRACUSK, N. Y. 
 
CONTENTS 
 
 INFANTILISM 1 
 
 The Symptoms and Signs of Intestinal Infantilism.. 7 
 
 (1) Arrest in Development of the Body 8 
 
 (2) Mental Powers and Development of the Brain 10 
 
 (3) Abdominal Distension 11 
 
 (4) Anaemia 12 
 
 (5) Fatigue 13 
 
 (6) Disturbances of Intestinal Function 14 
 
 The Bacterial Flora of the Intestinal Tract 18 
 
 (1) Organisms of the Bacillus Bifidus Type 23 
 
 (2) Organisms of the Bacillus Infantilis Type 26 
 
 (3) Coccal Forms 29 
 
 The Urinary Expressions of Infection Underlying In- 
 fantilism 33 
 
 Features Eelating to the Intestinal Contents 39 
 
 The Calcium and Magnesium Balances 45 
 
 The Fat Loss by the Feces 48 
 
 Pathology , 53 
 
 Eetardation in Development 54 
 
 The Acute and Subacute Infections Leading to Infan- 
 tilism 75 
 
 Mild Types of Intestinal Infantilism 77 
 
 The Sequelae and Prognosis of Intestinal Infantilism 78 
 
 The Therapeutic Modification of Bacterial Conditions 81 
 
 General Hygienic Measures 83 
 
 Dietetic Measures 86 
 
 The Carbohydrates 87 
 
 The Fats 91 
 
 The Proteins 94 
 
 The Use of Gelatin 96 
 
 Pharmacological Measures 106 
 
 conclubions 112 
 
 V 
 
 430565 
 
 V. 
 
INFANTILISM 
 
 I PKOPOSE in this publication to describe some 
 of the leading features of an obscure affection of 
 childhood with the study of which I have been for 
 several years engaged but of whose nature I have 
 only recently been able to form a reasonably satis- 
 factory conception. This pathological state is 
 marked by a striking general retardation in the 
 growth of the body implicating the skeleton, the 
 muscles and. the organs, while permitting a rela- 
 tively fair development of the brain. The mate- 
 rial on which the present description is based 
 consists of five cases of intestinal infantilism 
 which I regard as typical and fully developed 
 examples of this distinctive state. And in addi- 
 tion to these cases I have studied ^ve others of 
 shorter duration and subacute course, which I am 
 disposed to consider as instances of intestinal 
 infection capable of giving rise to pronounced 
 infantilism when the former condition has per- 
 sisted through many months. With the exception 
 of two of the cases comprising these two groups, 
 I owe to Dr. L. E. Holt the opportunity to study 
 these patients. He has helped me by freely plac- 
 ing at my disposal his full clinical notes and by 
 
 1 1 
 
2 INFANTILISM 
 
 giving me access to his patients. In several 
 instances the patients have been observed by Dr. 
 Holt and myself conjointly during a period of 
 years under varying dietetic conditions. The 
 definite character of the symptom-complex about 
 to be described has long been recognized by 
 Dr. Holt, who has interested me in the present 
 investigation. 
 
 I am also under obligations to the Eockefeller 
 Institute for Medical Eesearch, especially during 
 the past year, for aiding me with facilities for 
 engaging in the extremely complex bacteriologi- 
 cal problems with which this study was beset. 
 I am especially indebted to Mr. A. I. Kendall, 
 Fellow of the Eockefeller Institute, for technical 
 help. 
 
 It has not been possible to investigate with 
 equal thoroughness all the cases of intestinal in- 
 fantilism that constitute the basis of this publica- 
 tion. In some instances attention has been given 
 especially to certain limited aspects of the patho- 
 logical i)roblem, while in other cases study has 
 been especially focused on other features; but in 
 three instances the investigations have had a wider 
 and more representative aim. In two of these three 
 instances the patients have been under my per- 
 sonal observation during periods of many months, 
 and through close attention it has been possible 
 to detect and to follow with unusual detail numer- 
 ous manifestations of the morbid process. I shall 
 
INFANTILISM 3 
 
 not undertake in the present publication to give 
 full individual histories of the cases observed, but 
 shall merely give very brief outlines embodying 
 the chief clinical data, and to these outlines such 
 references will be made from time to time as may 
 serve to illustrate the various points under dis- 
 cussion. 
 
 Case I. Male, aet. 8 years. Older sister in good health. ISTor- 
 mal infancy with average growth. During third year reached 
 weight of 31 lbs. At this time irregularities of digestion, especi- 
 ally periods of diarrhoea with mucus. Gradual loss of weight, 
 increasing abdominal distension, carbohydrate intolerance and 
 fat diarrhoea. Between third and seventh years weight did not 
 exceed 31 lbs. Usually losses in summer, gains in winter, weight 
 usually between 25 and 28 lbs. Moderate anaemia. Increasing 
 lassitude. Drowsiness during day. Walking dif&cult. Eapid 
 onset of fatigue. Peevishness, emotional instability, slight signs 
 of rickets. Appetite nearly always keen. Many dietetic experi- 
 ments tried between third and seventh years with little success. 
 Movements several daily, soft, voluminous, gray, fatty, gaseous, 
 odor indolic, reaction usually slightly acid or neutral. Mucus 
 variable, at times very abundant, in masses on surface or mixed 
 with feces. Urine rich in indican and phenol. Aromatic oxyacids 
 not markedly excessive. During last year gradual decrease in 
 indican. Eeactions for indolacetic acid very marked. November, 
 1907, weight, 25 lbs. ; height, 36 ins. Careful dietetic and hygienic 
 measures instituted. Next four months slight gains and losses in 
 weight but no material improvement in weight though decided 
 improvement in character and frequency of stools and diminution 
 in signs of intoxication. From March, 1907, to July, 1908, unin- 
 terrupted somewhat uneven gain in weight to 31 lbs. Also gain in 
 height (about li/g inch). Movements became entirely normal in 
 color, consistence and frequency. Urine shows striking reduction 
 in putrefactive products. Mental and emotional condition greatly 
 improved. Expression animated. Physical activity greatly 
 increased, walking fair for considerable distances. Abdominal 
 distension much diminished. During past six months there has 
 been a radical alteration in the bacterial flora of the large intes- 
 
4 INFANTILISM 
 
 tine, marked by the establishment of B. lactis aerogenes and B. 
 coll. Still remains very sensitive to carbohydrates, even a slight 
 increase being quickly followed by large fermentative movements. 
 Under such conditions the child ceases to gain weight and there 
 is a return of coccal forms in the feces, but B. Mfidus cannot be 
 detected. Such a temporary interruption in growth occurred dur- 
 ing August, 1908. 
 
 Case II. Female, aet. 9 years. Two older children, always 
 well. Normal infancy, nursed during early months. At end of 
 second year irritant medication followed by gastritis lasting 
 several days and only slowly subsiding. Present illness dates 
 from this. Slight signs of rickets somewhat antecedent to the 
 gastritis. By third year nutrition was impaired and development 
 became much retarded. Child markedly undersized, head slightly 
 rachitic, digestive tract irritable, carbohydrates very badly 
 tolerated, fat absorption much impaired, abdomen much distended. 
 By fourth year walking still very imperfect and child much 
 undersized. Weight at this time not recorded, but nutrition 
 much impaired and remained so during fourth, fifth, and sixth 
 years. Throughout this time there were moderate anaemia, fat 
 diarrhoea, grayish, voluminous, gas-holding, indolic stools. Urine 
 regularly gave intense indican reactions. Ethereal sulphates, 
 phenols and aromatic oxyacids regularly much increased, micturi- 
 tion often extremely frequent. During this entire period emo- 
 tional instability, peevishness, great physical langour, walking 
 quickly followed by fatigue. In sixth year, after more than a 
 year of careful regulation of diet, gradual improvement in nutri- 
 tion, and gain in physical strength with slow disappearance of 
 neuromuscular disorders. Simultaneously gradual diminution of 
 putrefactive products in urine and pronounced improvement in 
 feces, which became formed, colored, of normal fat content and 
 nearly free from indol and phenol. Gradual appearance of 
 B. lactis aerogenes and B. coli in large numbers in the feces. 
 At six and one-half years weight rose to 45 lbs. During next 
 year gained 2 lbs. During following year gained 10 lbs., to 
 58 lbs. During last six months gained 7 lbs. with rapid gain in 
 stature. Onset of epileptiform seizures during this period with 
 return of putrefactive products in urine. 
 
 Case III. Female, aet. about 7 years. Under observation 
 together with Dr. L. E. Holt for past 3 years. When first seen, 
 greatly emaciated. Abdomen much distended, superficial veins 
 distended markedly. Skin white and wrinkled. Anaemia mod- 
 
INFANTILISM 5 
 
 erate. Head slightly rachitic, well developed. Extremely emo- 
 tional and peevish, but intelligent. Movements voluminous, 
 acholic in appearance, usually two or three daily; odor putre- 
 factive (indolic), reaction usually neutral or acid. Fatty acid 
 crystals very abundant, mucus variable, indol regularly present, 
 phenol sometimes. Diarrhoea easily provoked by use of carbohy- 
 drates. Urine frequently voided, indican abundant, phenol and 
 aromatic oxyacids excessive. Eecord of weight lost, but child 
 much beneath average weight for about one year before observa- 
 tion. Loss in weight dates from middle of third year, when 
 irregular diarrhoea and large movements became chronic. During 
 first two years under observation only slight gain in weight, but 
 some improvement in movements, which became seldom diarrhoeal 
 but remained voluminous. During past year more rapid gam in 
 weight, but still markedly under weight. Case closely resembles 
 Case I, but infantilism is somewhat less pronounced in degree. 
 Conditions for dietetic treatment much less favorable than in 
 Case I. Outlook is now for decided permanent retardation m 
 growth. Child was normal at birth and for first two years. 
 
 Case IV. Male, aet. 3 years. Normal weight at birth, nursed 
 6 weeks. Modified milk. Did well first year. Then irregular 
 intestinal troubles, diarrhoea with mucus. Marked anaemia 
 gradually developed (Hb 35%) vnth great abdominal distension. 
 Appetite poor. Peevishness. Slow loss in weight from 16th 
 month. Movements gray, voluminous, pasty. Fatty acid crystals 
 extremely abundant, indol, but no skatol; phenol at times. Urme, 
 much indican usually, also excess phenols and aromatic oxyacids. 
 Many experiments with diet; peptonized milk; kumyss, egg white, 
 rare scraped meat. Nestle 's Food, etc. Appetite capricious. 
 Weight at 20 mos., 16 lbs.; height, 3034 inches; at 27 mos., lo lbs. 
 Gradually gained to 17 lbs. then acute slight enterocolitis for 4 or 
 5 days. Gradually lost weight to less than 15 lbs. At 33 mos., 
 weight, 16% lbs.; height, 31 inches. Hb. 34%. Very slow 
 improvement in weight and movements. Now (3 years) 18 lbs. 
 and Hb. 61%. Appetite never satisfied, tongue clean and red. 
 Abdominal distension persists. Spirits improved. Tendency to 
 diarrhoea from carbohydrates continues. Milk remains basis of 
 diet. Improvement probably delayed by impracticability of fol- 
 lowing patient closely. x^ tt u 
 Case V. Female, aet. 9i/o years. Patient of Dr. L. E. Holt. 
 Third of four children; others healthy. Partly nursed 3 mos., 
 did poorly, was weaned. Fed on sterilized milk, cream, lime- 
 
6 INFANTILISM 
 
 water rest of first year. Did only fairly well; fat but pale. 
 Measles at 18 mos.; mild. Vaccinated at 2 years; sore healed 
 normally. With vaccination, vomiting and fever. Troubles of 
 digestion rather marked ever since. Vomiting and fever rarely, 
 but tendency to soft movements and diarrhoea with occasional 
 constipation. During fifth and sixth years marked irregularities 
 of bowels associated with efforts to increase diet. Seizures of 
 loss of appetite, headache and loss in weight, light-colored stools, 
 lasting several weeks. Marked abdominal distension, tongue 
 coated, breath not good. Food, milk, a little bread, beef juice. 
 With every effort to give carbohydrates child shows digestive 
 derangements after a few days. At 51/2 years, weight, 21% lbs.; 
 height, 35 inches. Very pale, spleen, liver, glands palpate normal, 
 tongue slightly coated, abdomen smaller than formerly; a small, 
 pathetic, delicate little child with no animation. Sometimes does 
 not walk for 2 or 3 months. Eemained very much under weight 
 until nearly 9 years old, with periods of great abdominal dis- 
 tension and continued intolerance for carbohydrates and fats. 
 Constipation at times, owing probably to milk diet. Facial 
 neuralgia frequent, anaemia marked. Great listlessness. Walks 
 only a few steps about the house. Appetite always excellent now, 
 could take much more but cannot tolerate increased food. Milk 
 agrees best. Diet somewhat enlarged with barley broth, baked potato, 
 butter, tapioca pudding. On this diet good gain in weight lately. 
 Gain to 33 lbs. at 914 years and rather rapid gain in height to 
 38iy4 inches. Head 20 inches, somewhat rachitic, flat type and 
 large parietal bones. Morbid appetite for chalk, dirt, cigar 
 ashes, pencils, etc. Urinary indications of intestinal putrefaction 
 but slight. Anaemia still marked. This case of intestinal infan- 
 tilism is of somewhat different type from the others in this group. 
 Less indication of ordinary indolic putrefaction, more tendency 
 to anaemia. Uncertainty as to pathology from standpoint of 
 bacterial flora. 
 
 The symptom-complex which I wish to de- 
 scribe is so clearly definable that few physicians 
 with a practice among children will fail to 
 recognize a few instances of this unmistakable 
 and extreme manifestation of a morbid nutri- 
 tional process. I shall group under the follow- 
 
INFANTILISM 7 
 
 ing heads the facts and views which I desire 
 to present. 
 
 1. The Symptoms and Signs of Intestinal 
 
 Infantilism. 
 
 2. The Bacterial Flora of the Intestinal 
 
 Tract in Cases of Infantilism. 
 
 3. The Urinary Expressions of the Infection 
 
 underlying Infantilism. 
 
 4. The Pathology of Intestinal Infantilism. 
 
 5. The Acute and Subacute Infections lead- 
 
 ing to the Establishment of Intestinal 
 Infantilism. 
 
 6. Mild Types of Intestinal Infantilism. 
 
 7. The Sequelae and Prognosis of Intestinal 
 
 Infantilism. 
 
 8. The Therapeutic Modification of the Bac- 
 
 terial Conditions in Intestinal Infantilism. 
 
 The Symptoms and Signs of Intestinal 
 Infantilism 
 
 The patients comprising the group of the 
 type of fully developed infantilism which I 
 desire to describe varied from four to six years 
 of age at the time when they first came under 
 observation. In each case the child had been 
 ill for one year or longer at the time of its 
 first observation by Dr. Holt or by myself, and 
 had suffered from pronounced irregularities 
 referable to the digestive tract. In each case 
 there was a history of periods of disturbed 
 
8 INFANTILISM 
 
 nutrition with loss of weight alternating with 
 periods of improvement in nutrition and gain 
 in weight. But these variations ultimately cul- 
 minated in each case in a state in which there 
 was apparently a complete arrest of develop- 
 ment, and although obvious symptoms of di- 
 gestive disturbance, such as diarrhoea, were 
 checked by suitable treatment, there remained 
 an arrest in growth and the utmost difficulty 
 was experienced in securing any noteworthy 
 increase in weight. 
 
 The clinical features characteristic of pro- 
 nounced infantilism may be divided into two 
 groups, the chief or essential clinical features 
 and the minor or accessory features. 
 
 The chief or essential clinical features are 
 the following: (1) an arrest in the development 
 of the body; (2) the maintenance of mental 
 powers and fair development of the brain; 
 (3) marked abdominal distension; (4) moderate 
 grade of anaemia; (5) rapid onset of physical 
 and mental fatigue; (6) various obtrusive irregu- 
 larities referable to the intestinal tract. These 
 features may be considered in turn. 
 
 (1) Arrest in Development of the Body. The 
 arrest in development is the most striking 
 feature of these cases. In Case I the patient 
 at the age of seven years weighed only 25 pounds^ 
 
 ^ Holt gives the weight for a boy of two years as 26.5 pounds. 
 The weight at seven years should not be far from 50 pounds, 
 
INFANTILISM 9 
 
 and had a height of only 36 inches.^ In 
 Case V the patient at the age of nine years 
 weighed only 29 pounds. In this case the child 
 was first observed at a time when some im- 
 provement had set in, a gain of two pounds 
 having been made in the course of the past 
 year, but previous to this time the patient had 
 for some time remained in a stationary con- 
 dition as regards weight and development. In 
 Case II there was a period of about two years 
 (from the third to the fifth year) in which 
 there was a striking arrest of development, 
 and the maintenance of a nearly stationary 
 weight despite the fact that the utmost care 
 was taken to insure dietetic conditions favor- 
 able to an improvement in growth. In the two 
 remaining cases exact data are lacking, but in 
 both instances retardation of growth was a 
 striking feature during a long period of time. 
 In several instances it was noticed that there 
 was a slight tendency to improvement in weight 
 during the winter months, this tendency to 
 improve being more than overbalanced by losses 
 made during the summer. These losses in 
 weight were always attributable to an increase 
 in disturbances referable to the intestinal func- 
 tions and were commonly associated with 
 diarrhoea. This diarrhoea was, however, not 
 necessarily very pronounced or of long dura- 
 
 * Thirty-five inches is the height given for three years. 
 
10 INFANTILISM 
 
 tion, and often consisted rather in an excessive 
 softening of the intestinal contents and increase 
 in mncns than in an acnte watery diarrhoeal 
 condition 
 
 (2) The Maintenance of Mental Potvers and 
 Fair Development of the Brain. It is note- 
 worthy that despite the retardation in the 
 general development of the organism, the brain 
 is fairly well developed in all of the cases of 
 infantilism nnder observation. Thns in Case I, 
 although the height was only 36 inches and 
 the weight 25 ponnds, the circumference of the 
 head was 20 inches.^ Entirely comparable con- 
 ditions were noted in the other cases. The 
 intelligence of these patients was in every 
 instance good, and contrasts very strikingly 
 with the bad physical development. Of course 
 these children are all defectively educated owing 
 in part, at least, to the physical retardation 
 which makes it inadvisable or impossible to 
 secure even the ordinary educational oppor- 
 tunities. It is noteworthy that in all of these 
 children there was a certain slowness of mental 
 action and perhaps a somewhat greater thought- 
 fulness than is usual in children of their age. 
 In replying to questions these children have 
 often shown some irritability and peevishness, 
 and in several instances I think there is no 
 
 *Holt gives 19.7 inches for the circumference of the male head 
 at four years; 20.5 inches at five years. 
 
INFANTILISM 11 
 
 doubt that the mental processes subserving 
 self-preservation were more than usually acute 
 for children of their ages. It is possible that 
 this was the result of the isolation to which 
 all of these patients had been subjected and 
 of an inability to enter into the play of chil- 
 dren of the same age. The necessity for living 
 very carefully and obeying the directions of 
 the physician and nurse has tended to make 
 these children somewhat introspective as regards 
 their own ailments and to form the basis of 
 what might, with increasing consciousness, 
 develop in after life into a hypochrondriacal 
 condition. In all of the patients periods of 
 langour have been very noteworthy during the 
 time of arrested physical development. Fre- 
 quently for hours at a time they show little 
 or no desire to play or to speak and their 
 faces at these times look pinched and distressed. 
 There has been no difficulty in any of these 
 cases in teaching the children to be cleanly, 
 and there is no doubt that what they have 
 lost in the direction of spontaneity and play- 
 fulness, as the result of disease, has been in 
 a measure compensated by an improved self- 
 control, which, in the case of diet, has come to 
 amount almost to automatism. 
 
 (3) Marked Abdominal Distension, Marked 
 abdominal distension, due in part to a dis- 
 tension of the colon with gas and probably 
 
12 INFANTILISM 
 
 also to distension of the small intestine, has 
 been a feature of these cases. The distension 
 has varied somewhat from time to time, but 
 there have been long periods in each case in 
 which the distension showed little variation and 
 a return to normal abdominal conditions was 
 never witnessed. As these patients gradually 
 improved in physical condition under suitable 
 dietetic treatment, the distension gradually 
 became less. This condition of distension, when 
 once established, is not necessarily accompanied 
 by any intestinal or gastric flatulence in the 
 sense of actual passing of considerable quanti- 
 ties of gas. It appears that the abdominal 
 distension was preceded in each case by a period 
 in which gas formation had been active and 
 flatulence pronounced, but that after a time 
 partial paralysis of the gut sets in, which per- 
 mits the accumulation of gas even though the 
 latter be not necessarily formed in great excess. 
 The abdominal veins are frequently markedly 
 dilated, especially over the upper part of the 
 abdomen. 
 
 (4) Moderate Anaemia. In all of the ^yq 
 cases of infantilism which were studied, mod- 
 erate anaemia was a feature. The haemoglobin 
 was diminished to 75-60 per cent, in Cases I, 
 II and III without a corresponding diminution 
 in the number of red blood cells. In two 
 instances, however (Cases IV and V), the 
 
INFANTILISM 13 
 
 anaemia was considerably more pronounced, and 
 in Case V was a long persistent feature of the 
 disease. In the latter instance the haemoglobin 
 was at one time only 22 per cent., and there 
 was a moderate diminution in the number of 
 red blood cells. In all of these cases there is 
 reason to think that the volume of blood is at 
 least moderately below what it should be for 
 a child of the same weight. This suspicion is 
 based on the pallor of the body and the 
 extremities, which may be much out of propor- 
 tion to the fall in haemoglobin. The white 
 blood cells were examined in Case I. No note- 
 worthy departures from the normal were noted.^ 
 
 Leucocytes 5000 
 
 Small mononuclears 33% 
 
 Large mononuclears 1% 
 
 Eosinophiles 1% 
 
 Polymorphonuclears 62% 
 
 Transitionals 3% 
 
 An examination made on April 22, 1908, gave the foUowirig: 
 Leucocytes 6000 
 
 Small mononuclears 35% Polymorphonuclears 51% 
 
 Large mononuclears 2% Myelocytes 6% 
 
 Eosinophiles 3% Transitionals 3% 
 
 (5) Rapid Onset of Fatigue. A character- 
 istic feature of these cases of infantilism is 
 the rapid onset of muscular fatigue. Indeed, 
 it would probably be more accurate to say 
 that the muscles are never thoroughly rested 
 
 * An examination made Dec. 30, 1907, by Dr. Baldwin gave 
 the following results: 
 
14 INFANTILISM 
 
 and that a state of fatigue is cliroiiic. The 
 older children, at the height of the develop- 
 mental arrest, are unable to walk more than a 
 few blocks without being thoroughly tired. 
 They are also unable to walk up and down 
 stairs. Learning to walk is a slow and dis- 
 couraging process. In Case II the child did 
 not learn to stand until it was more than four 
 years old, up to which time it crept languidly 
 on the floor. During the fifth year it learned 
 to walk with great difficulty. Essentially the 
 same condition existed in Cases III, IV and 
 V. It is to be noted that the muscles are soft 
 and flabby in these cases of infantilism. The 
 readiness with which mental fatigue comes on 
 has already been commented upon. As will be 
 seen later in a discussion of the pathology of 
 this condition, there is good evidence for believ- 
 ing that both the muscular and mental fatigue 
 are the result of a chronic intoxication. 
 
 (6) Disturbances of Intestinal Function. One 
 of the most striking and characteristic features 
 of infantilism has to do with the disturbance 
 incidental to intestinal function. Although such 
 disturbances may be reduced to a minimum 
 through very careful feeding, the dietaries of 
 these children are usually such when they come 
 under the observation of physicians that they 
 show very obvious disorders of function. Diar- 
 rhoea was a feature of all of the cases with 
 
INFANTILISM 15 
 
 whicli this report deals. Pronounced watery 
 diarrhoeal attacks are, however, comparatively 
 rare. Much more frequent are the disturbances 
 manifesting themselves by the appearance of 
 soft stools containing an abundance of neutral 
 fat, soap and fatty acid crystals. The excess 
 of fat is often sufficiently great to constitute 
 a condition of true steatorrhoea, if thereby we 
 imply a loss of fat serious to nutrition. Dur- 
 ing a part of the time the stools are not of 
 abnormal frequency. Nevertheless they contain 
 an excess of fat unless the diet is especially 
 regulated with a view to reducing its fat con- 
 tent. During exacerbations of the diarrhoeal 
 disturbance the patients are in especially poor 
 condition, losing weight and suffering from 
 cold hands and feet and showing a pinched 
 appearance. These diarrhoeal disorders, though 
 often of short duration, may also cause marked 
 prostration, and on many days patients are so 
 much enfeebled as to get about with greatly in- 
 creased difficulty. With the cessation of the 
 diarrhoea there is a tendency to rapid recovery, 
 although a loss in weight of half a pound or 
 a pound may not be regained for several weeks. 
 The details relating to the morphological and 
 chemical characters of the intestinal contents 
 will be discussed in another section of this 
 paper. 
 
16 INFANTILISM 
 
 Among the minor or accessory clinical fea- 
 tures observed in our cases of infantilism are 
 to be included sweating about the head during 
 sleep, excessive appetite, somewhat excessive 
 thirst and consequent increase in the urine, 
 various indications of nervous instability and 
 an habitually subnormal temperature with cold 
 and pale hands and feet. In three of the cases 
 (Cases I, II and V) the sweating, especially 
 of the skin of the head, was for a time well 
 marked, but this symptom very soon disappeared 
 with return of strength. An excessive appe- 
 tite, at least at certain times, was a feature 
 in all the cases. Occasionally, especially dur- 
 ing the diarrhoeal periods, there is loss of 
 appetite. But the maintenance of a large appe- 
 tite is a feature in these cases. A similar 
 readiness to take food has been noticed in the 
 subacute affections which, beginning in early 
 infancy, lead to the state of infantilism. The 
 abnormal, sometimes even voracious, appetite 
 is probably due to the condition of chronic 
 enteritis which exists in these patients and is 
 probably similar in its origin to an increase 
 in appetite observed in some neurasthenic 
 adults. The nervous instability is shown in 
 some of these patients by rapid variations in 
 temper from insignificant causes. In one in- 
 stance (Case I) there was also a tendency to 
 urticarial outbreaks, which occurred from time 
 
INFANTILISM 17 
 
 to time without definitely assignable cause. 
 In another case (Case II) there developed 
 attacks of petit mat which, as will afterwards 
 be more fully stated, gave way to epileptiform 
 seizures of grand mal. 
 
 In four of the ^yq cases of infantilism there 
 were very slight indications of rickets, but it 
 may be said in general that the signs of 
 rickets, if present at all, do not form part of 
 the symptom-complex at present under discus- 
 sion. Outside the present group I have seen 
 well-marked instances which showed no signs 
 of rickets. There are no striking pulmonary 
 or circulatory peculiarities in these cases. The 
 pulse is usually regular when the patients are 
 quiet, of low tension and small in volume. 
 The pulse is unduly accelerated by slight acti\dty 
 or slight exterior nervous stimuli. Abnormalities 
 of the spleen, liver or thyroid have not been 
 detected. In one case (Case I) there was slight 
 enlargement of the posterior cervical glands. 
 A status of blood occurs readily in artificially 
 congested areas of the skin — an effect like that 
 of the so-called meningeal streak being readily 
 produced. The tongue is apt to be somewhat 
 more red than normal, and the papillae swollen, 
 but in none of our cases was there any denu- 
 dation of epithelium or any indication of the 
 occurrence of geographical tongue. The tongue 
 
 2 
 
18 INFANTILISM 
 
 is at times slightly swollen and on its edges 
 marked by impressions of the teeth. 
 
 The Bacterial Floea of the Intestiitai. Tract 
 IN Cases op Infantilism 
 
 The difficnlties that lie in the way of the 
 adequate understanding of the bacterial con- 
 ditions of the digestive tract have been in gen- 
 eral so numerous as to discourage attempts to 
 investigate the nature of the flora in chronic 
 diseases of the intestine. Of these difficulties 
 there are three which are specially obvious, — 
 first the multiplicity of the floral types; sec- 
 ondly, the imcertainty of cultivating the really 
 dominant organisms; third, the difficulty of 
 obtaining for study those products of symbiotic 
 bacterial action which are truly representative 
 of the decompositions which occur in the intes- 
 tine. Although efforts have been made in the 
 present study to overcome these obstacles, these 
 efforts have been only in part successful. Still 
 it is fair to say that the methods of investi- 
 gation employed have yielded a helpful if not 
 satisfying conception of the processes that hold 
 sway in the digestive tract in the state of 
 infantilism. It is not intended to discuss in 
 detail in the present communication the methods 
 of investigation employed, nor to describe fully 
 the characters of the organisms which have 
 been found to dominate the intestinal flora. In 
 
INFANTILISM 19 
 
 many directions the details concerning the 
 nature of the organisms which have been found 
 to be dominant in these cases have not been 
 established with sufficient precision. Knowl- 
 edge is especially scanty at the present time in 
 regard to the biochemical activities of certain 
 of the organisms that have been found to 
 dominate the intestinal tract in these cases. 
 Especially is knowledge lacking in regard to 
 the products of symbiotic growth of the chief 
 organisms observed. For the present purpose 
 it will suffice to state that the methods of bac- 
 terial study which have proved most service- 
 able in this investigation have been (a) the 
 study of the Gram-stained fecal fields; (h) the 
 study of the sediments of the sugar-bouillon 
 and plain bouillon tubes after inoculation with 
 the mixed fecal flora; (c) a variety of aerobic 
 and anaerobic cultural procedures involving the 
 use of many kinds of media made necessary 
 by the difficulty of growing certain species of 
 bacteria in pure culture.^ In these studies bac- 
 teria were obtained not only from the feces, 
 but from material derived by the use of calomel 
 catharsis from the upper levels of the intes- 
 tine. Such catharsis failed, however, in general, 
 to show radical differences between the bacterial 
 
 * In the case of one of the microorganisms to be described 
 (B. infantilis) careful studies were made of the products of 
 growth. The results will be separately published in conjunction 
 with Mr. Kendall. 
 
20 INFANTILISM 
 
 types so obtained and those obtained from the 
 feces, despite the fact that coccal and Gram- 
 negative forms were usually obtained in greater 
 abundance from these upper regions. A dis- 
 tinction of greater significance was found to 
 relate to differences noted between the bacteria 
 derived from the fecal masses and those derived 
 from the mucous membrane of the intestine. 
 To these differences further reference will be 
 made. About three years ago, while studying 
 a patient with intestinal infantilism, I observed 
 that the Gram-stained fecal fields were regu- 
 larly made up of almost exclusively Gram- 
 positive microorganisms. These positive bac- 
 teria were almost exclusively slightly curved 
 rods from two to three microns in length and 
 about one-half micron in diameter. The ends 
 of these rods were sometimes rounded and 
 sometimes pointed. Morphologically similar 
 fields are sometimes observed in normal breast- 
 fed children as has been noted by Tissier, 
 Moro and others. But while it may be re- 
 garded as entirely normal to find organisms 
 of this character in a certain proportion of 
 healthy, breast-fed children, it was surprising 
 to find organisms of this nature as the domi- 
 nant bacteria in children five or six or even 
 eight years of age. The study of normal chil- 
 dren at these ages has failed to give any such 
 pictures as those which I have noticed in the 
 
INFANTILISM ' 21 
 
 group of cases of infantilism now under con- 
 sideration. Similar organisms have, however, 
 been observed in the Gram-stained fields in a 
 group of young children fed on cow's milk 
 and suffering from pronounced acute or sub- 
 acute gastro-enteritis. As I shall point out 
 later, it appears highly probable that the cases 
 of chronic infantilism have their origin in 
 intestinal disorders of very early life charac- 
 terized by the presence of dominant Gram- 
 positive flora of the kinds above described. 
 
 The nature of these Gram-positive organisms, 
 which constitute so persistent and dominant a 
 feature in our cases of infantilism when at the 
 height of their development, has been involved 
 in much obscurity. In 1900 Escherich described 
 a fatal hospital epidemic among young children 
 in which he observed that the stools in certain 
 instances consisted almost wholly of Gram- 
 positive rods, morphologically of the type just 
 mentioned. He gave to this condition the name 
 of blue bacillosis {Blaue Bacillose) to signalize 
 the fact of the Gram-positive nature of the 
 bacilli in question. Escherich also observed 
 that when the bacterial stools of the children 
 in question were transferred to ordinary culture 
 media, there was no growth of Gram-positive 
 organisms, but only of the Gram-negative 
 colon-like bacteria which were an insig- 
 nificant feature in the field. This latter observa- 
 
22 INFANTILISM 
 
 tion I can confirm, and it is only by tlie use 
 of very careful cnltnral methods that it has 
 been possible to obtain some insight into the 
 nature of the Gram-positive organisms seen in 
 these fields. As will be pointed out in what 
 follows, there are three kinds of organisms 
 which may give rise to appearances in the 
 Gram-stained field similar to those occasioned 
 by the presence of the Gram-positive, slightly 
 curved or straight rods which have been men- 
 tioned. These organisms are the Bacillus hi- 
 fidus of Tissier, the Bacillus acidophilus of 
 Moro and a hitherto apparently undescribed 
 organism which will be called here Bacillus 
 infantilis. 
 
 That the B. hifidus of Tissier, or an organ- 
 ism bearing an extremely close resemblance to 
 it, is present in large numbers in the intes- 
 tinal contents of our cases of infantilism is 
 indicated in part by the study of the sedi- 
 ments of the sugar-bouillon fermentation tubes 
 and in part by other cultural procedures. I 
 observed several years ago that when the mixed 
 fecal flora from a case of infantilism or from 
 certain instances of acute or subacute enteritis 
 in infants were inoculated into sugar-bouillon 
 fermentation tubes (lactose, dextrose and saccha- 
 rose) there was a very abundant growth in 
 the tubes of bifid organisms, either growing 
 separately or in groups in which individual 
 
INFANTILISM 23 
 
 bifurcating organisms are fused together so as 
 to give rise to varied pictures. A study of 
 the fermentation tube sediments not merely 
 served to attract attention to the occurrence 
 of bifid types of bacteria in the intestinal con- 
 tents, but also drew attention to certain other 
 forms of bifid microorganisms that may occur 
 under the same cultural conditions and to the 
 importance of certain coccal forms of bacteria. 
 It will be convenient to discuss the dominant 
 types of organisms in our cases under the 
 following heads: (1) organisms of the B. hifidus 
 type; (2) organisms of the B, infantilis type; 
 (3) coccal forms. 
 
 (1) Organisms of the Bacillus hifidus Type. 
 Although it has been easy to obtain from the 
 fermentation tubes very abundant and domi- 
 nant growths of bifid, lactic acid-producing 
 microorganisms corresponding to the morphology 
 of B. hifidus of Tissier, considerable difficulty 
 was encountered in obtaining these organisms 
 in pure culture. Mr. Kendall has now succeeded 
 in growing the organisms in question on various 
 media under anaerobic conditions. The organ- 
 isms were derived not merely from the stools 
 of patients with infantilism, but also from the 
 stools of certain cases of subacute enteritis in 
 infants which have already been alluded to as 
 presenting fields made up almost exclusively of 
 Gram-positive bacilli. The organisms in ques- 
 
24 INFANTILISM 
 
 tion grow on dextrose-agar plates as lenticular 
 or helmet- shaped colonies and on anaerobic 
 agar slants present beaded, grey, shining 
 colonies slightly opaque or translucent. Mor- 
 phologically, the organisms present the typical 
 Y-shaped or bifid form. They are Gram-posi- 
 tive and vary in size from two to four microns 
 in length and from six tenths of a micron to 
 one micron in width. They are sometimes 
 apparently slightly motile. In fermentation 
 tubes and associated with other bacteria they 
 grow well in dextrose, lactose and saccahrose 
 bouillon, but especially well in the two former. 
 They produce lactic acid and are capable of 
 maintaining themselves at a considerable grade 
 of acidity. For this reason they have been 
 classed as acidophile bacteria. The justice of 
 regarding them as strict acidophile organisms 
 may, however, perhaps be questioned, since in 
 the absence of interfering organisms they may 
 grow well in sugar-bouillon in which the acidity 
 is in large degree neutralized by the presence 
 of calcium carbonate. It appears rather that 
 they are capable of withstanding a higher degree 
 of acidity than some other intestinal micro- 
 organisms, as, for example, colon bacilli, and 
 are therefore able to thrive when the colon 
 bacilli are no longer able to reproduce them- 
 selves in consequence of the excess of acid. 
 These organisms coaggulate milk, but do not 
 
INFANTILISM 25 
 
 peptonize it. They do not grow on gelatin. 
 Although they may be regarded as anaerobic 
 organisms, it is true that after a time they 
 grow to the surface in agar stick cultures and 
 may even cause a slight elevation of the sur- 
 face of the agar. These organisms do not 
 always show bifurcation, and under certain 
 cultural conditions tend to develop rarefication 
 of their protoplasm in spots, so that the Gram- 
 stain is retained irregularly, giving rise to 
 punctate forms of bifidus. This punctate form 
 of bifidus may be plain or may undergo 
 branching. 
 
 Successful plate cultures indicate that the 
 bifidus type of organisms is very abundantly 
 represented in the feces of certain cases of 
 intestinal disorder, including not only cases of 
 infantilism, but the subacute conditions already 
 mentioned. They have been studied by Mr. 
 Kendall with especial care in Case I of the 
 infantilism group and in some instances of 
 subacute intestinal infection characterized by 
 Esche rich's blue bacillosis. I have found them 
 also in Cases II, III and IV. It is impossible 
 at present to say just how large a proportion 
 of the organisms in the cases mentioned belong 
 to the B. bifidus type, but the plate cultures 
 indicate that they are prominent all the time, 
 though sometimes more largely dominant than 
 at others. With the exception of Case I of 
 
26 INFANTILISM 
 
 our group of infantilism patients, the presence 
 of B, hifidus in large numbers in the stools 
 has been commonly inferred from the bifid 
 forms found in the fermentation tube sedi- 
 ments and from the morphological characters 
 of the organisms in the smears from the stools, 
 rather than from cultures on plates. 
 
 It seems worth noting that in the studies 
 made from mucus obtained from the stools in 
 Case I, Case II and in one of our patients 
 with subacute blue bacillosis, sugar-bouillon 
 fermentation tubes inoculated with carefully 
 washed mucus have shown the development of 
 a great abundance of bifid forms, apparently 
 in almost pure culture, whereas inoculations 
 made from the fecal material from the same 
 cases showed a far less rich growth as well 
 as the presence of other varieties of micro- 
 organisms. 
 
 (2) Organisms of the Bacillus Infantilis Type, 
 The organism to which the name Bacillus 
 infantilis has been applied was first noticed by 
 Mr. Kendall while working on the cases of 
 infantilism described in this paper. This 
 organism, or type of organism — for there are 
 several variants — occurs not rarely in the stools 
 of breast-fed and bottle-fed infants. It has 
 been isolated also from a number of children 
 ranging from two to seven years of age, and 
 has been obtained from one adult. Under 
 
INFANTILISM 27 
 
 normal conditions the number of organisms of 
 this type growing upon nutrient sugar-agar 
 plates is not great. In fact it is frequently- 
 difficult to obtain cultures. In certain cases, 
 however, especially in those showing the Gram- 
 positive fields of the blue bacillo sis type, the 
 number is greatly increased, judging from their 
 abundance in plate cultures. 
 
 In stained stools, the organisms appear as 
 rather thin. Gram-positive rods, agreeing in 
 size with Tissier's B, hifidus communis. The 
 B. infantilis has not been observed to occur 
 with pointed ends, as is the case with at least 
 some varieties of the B, hifidus. The organism 
 forms spores which are central (but occasion- 
 ally terminal), causing a slight swelling of the 
 rod. In the vegetative state B. infantilis as 
 studied by Mr. Kendall is actively motile. It 
 usually occurs singly or in pairs, but under 
 certain conditions, particularly in fluid media, 
 may form chains of several elements. (In length 
 it varies from 2.5 — 3 microns, in width from 
 0.5 — 0.75 microns.) Occasionally one sees dis- 
 tinct branches in anaerobic dextrose agar. B. 
 infantilis is ordinarily isolated from anaerobic 
 plates, although it has been obtained without 
 difficulty in some instances when grown under 
 aerobic conditions. After the first generation 
 upon artificial media, it grows readily in the 
 incubator at body temperature and much less 
 
28 INFANTILISM 
 
 readily at 20° C. The submerged colonies are 
 of two types, one lenticular and yellowish, the 
 other rather irregular in outline and woolly 
 in appearance. The surface colonies are usually 
 dull and have a tendency to spread. The sur- 
 face growths are gray. There are two types 
 of growth upon agar. The first is almost 
 invisible and is limited largely to the conden- 
 sation water. The second is more vigorous 
 and spreading. Spores are readily formed upon 
 the surface of slants, usually within 48 hours. 
 The bacilli in the spore stage are slightly 
 spindle-shaped, frequently with a deeply stain- 
 ing Gram-positive granule at either end of the 
 rod, more usually at one end only. Many cul- 
 tures produce a mucin-like substance. In fluid 
 media spore-formation is delayed and is fre- 
 quently absent. In sugar-bouillon (dextrose, 
 lactose) there are two types of growth. The 
 first corresponds to the form that grows poorly 
 on agar, showing a slight sediment with usually 
 a transient turbidity and no pellicle; the sec- 
 ond type of growth is indicated by a moderate 
 turbidity and the development of a sediment 
 and usually a pellicle. Upon plain broth there 
 is no turbidity and in many strains a pellicle 
 is formed. The bacilli from the sediment are 
 usually elongated, show irregular or punctate 
 staining and may occur singly, in pairs or 
 less commonly in chains. Milk is not coagu- 
 
INFANTILISM 29 
 
 lated by B. infantilis, nor is there any evi- 
 dence of peptonization. The reaction is usually 
 slightly alkaline after four to seven days, 
 although this alkalescence is not marked and 
 may be absent. In fermentation tubes the 
 organisms produce acid, but no gas in dextrose 
 or lactose or saccharose. The acid production 
 in lactose is relatively slight. On gelatin there 
 is a very slight growth and frequently none 
 at all. There is no liquefaction. B, infantilis 
 inhibits the gas production of the colon bacillus 
 when the two organisms are grown in dex- 
 trose or lactose bouillon, the gas production of 
 the colon bacillus being sometimes restricted 
 to the extent of 80 per cent. The colon bacilli 
 grow at first more rapidly, but soon the advan- 
 tage thus obtained is permanently lost and 
 B. infantilis distinctly checks the further growth 
 of B, coli, B, infantilis forms neither indol 
 nor skatoL It forms volatile bases in great 
 abundance, chiefly ammonia. We have found 
 methylamin among the products. 
 
 It is impossible to state at present to what 
 extent the Gram-positive rods observed in the 
 fields obtained from children with infantilism 
 consist of B. infantilis. 
 
 (3) Coccal Forms, The third group of organ- 
 isms consists of coccal forms, the relation of 
 which to one another is still obscure. In our 
 cases of infantilism, Griam-positive coccal forms 
 
30 INFANTILISM 
 
 have at times been abundant, and even when 
 not prominent in the fecal fields may grow freely 
 in the sngar-bonillon fermentation tubes. They 
 consist chiefly of larger and smaller diplococci 
 or coccobacilli corresponding closely in mor- 
 phology and cultural characters to the entero- 
 coccus of Thiercelin or the Micrococcus ovalis 
 described by Hirsch-Libmann. The enterococcus 
 forms acid on dextrose, lactose and saccharose 
 and coagulates milk. 
 
 In one of our cases of infantilism associated 
 with profound anaemia (Case V) the fecal 
 fields showed very large numbers of small. 
 Gram-positive cocci. These were found espe- 
 cially in certain parts of the stools where they 
 were seen to the exclusion of other organisms. 
 It was especially in the mucus and about the 
 epithelial elements that these organisms were 
 noted in such abundance and concentration. 
 In respect to these organisms Case V presents 
 an exception to the remaining four cases in 
 the infantilism group. The character of the 
 coccal forms occuring in this case have not as 
 yet been thoroughly studied. 
 
 It is worthy of mention that neither the 
 B. hifidus forms nor the B. infantilis forms 
 that have been isolated from our cases of 
 infantilism have exhibited pathogenicity when 
 injected into guinea-pigs. In Case I it was 
 observed that the relative proportion of organ- 
 
INFANTILISM 31 
 
 isms of these three types which appeared upon 
 anaerobic plates varied a good deal from day 
 to day without apparent cause. 
 
 As regards the presence of organisms of the 
 B, coll and B. lactis aerogenes groups, it may 
 be stated that such organisms are infrequent 
 in the feces in our cases of infantilism, when 
 they are in their most pronounced stage. This 
 is true also of the subacute cases of intestinal 
 infection already mentioned. Indeed in this 
 latter group of cases it is the rule to see Gram- 
 positive fields, wholly free from organisms, 
 suggesting either B. lactis aerogenes or B. coli. 
 It is probably owing to the almost entire or 
 the complete absence of these normal intes- 
 tinal inhabitants that the gas production in 
 the fermentation tubes inoculated with the 
 mixed fecal flora from the cases of infantilism 
 at their height, has been slight or lacking. 
 These conditions, however, hold true only for 
 our cases in their most highly developed form. 
 As recovery has set in it has been observed in 
 Cases I, II, III and IV that with improvement 
 in nutrition there has been a relative decrease 
 in the number of Gram-positive bacterial ele- 
 ments in the feces and a corresponding develop- 
 ment of Gram-negative forms corresponding to 
 B. lactis aerogenes and B. coli. In the case 
 of infantilism (Case II) in which the greatest 
 improvement in nutrition has been observed, 
 
32 INFANTILISM 
 
 B. lactis aerogenes lias lately been isolated 
 from the plates in great numbers. In this 
 case an increase in gas production has gone 
 hand in hand with the establishment of the 
 normal flora in the feces. It may also be 
 remarked that in this case the improvement in 
 nutrition and the gradual restoration of the 
 normal flora occurred with comparative rapidity 
 during a period of eighteen months, and not 
 until after the child had reached the age of 
 eight years; previous to this recovery had 
 been extremely slow during three years. It 
 should also be stated that in this same case 
 (Case II) the disappearance of Gram-positive 
 organisms of the B, hifidus type was associated 
 with the great falling off in the growth of 
 B. hifidus in the fermentation tubes. B. hifidus 
 was represented in the fermentation tubes not 
 by well-staining bifid forms, but by small 
 punctate rod forms apparently atrophic in 
 character, though still capable of cultivation. 
 Finally it should be stated in reference to 
 Case II that with the disappearance of organ- 
 isms of the B, hifidus type and the reestab- 
 lishment of B, lactis aerogenes and B. coli, the 
 intestinal tract began to show excessively large 
 numbers of B, aerogenes capsulatus. This 
 organism had not before been noted as a 
 prominent inhabitant of the intestinal tract, 
 and was indeed probably present in only small 
 
INFANTILISM 33 
 
 numbers, if at all, previous to the eighth year 
 of life. 
 
 The Ueinaky Expressions of the Ineection 
 underlying infantilism 
 
 Considerable attention was devoted to the 
 characters of the urine in our cases of infan- 
 tilism, especially in Cases I, II and III. In 
 Case I the specific gravity of the urine ranged 
 from 1010 to 1015, and the volume of urine 
 was habitually large — 800 c.c. to 1100 c.c. In 
 Case II, during the time between the fifth and 
 ninth years of life, the specific gravity of the 
 urine ranged usually from 1010 to 1018. The 
 volume of urine varied from 600 c.c. to 1000 
 c.c. daily. In Case III the volume was mod- 
 erate and the specific gravity ranged from 
 1020 to 1030. In the remaining cases there 
 were not enough observations to enable any 
 general statements to be made as to the vol- 
 ume and specific gravity of the urine. 
 
 The nitrogen excretion was recorded in three 
 instances, and it may be stated that it tends 
 to be high in proportion to the weight of the 
 child. For example, in Case II, with a weight 
 of 32 pounds, the nitrogen excretion ranged 
 from 5.7 grams to 6.5 grams daily. In Case I 
 the nitrogen excretion ran uncommonly high, 
 namely from 7 to 9 grams daily at a time 
 when the weight was only 25 pounds. These 
 
34 INFANTILISM 
 
 results are clearly attributable to the high 
 protein feeding which was incidental to efforts 
 to reduce the carbohydrates, which had proved 
 very liable to cause diarrhoea. The excessive 
 appetite was doubtless a factor in rendering 
 it easy to consume so large an amount of 
 protein food. The same statement may be 
 made, though less strongly, in regard to Case 
 II. In Case III the nitrogen excretion cannot 
 be said to have run abnormally high in pro- 
 portion to the weight of the child, though full 
 data relating to this point are not available. 
 
 In regard to the nitrogen of ammonia in our 
 cases, there is nothing noteworthy. In Case III 
 the nitrogen of ammonia formed from 2.4 to 
 3.3 per cent, of the total nitrogen excreted. 
 In Case II the nitrogen excretion was likewise 
 normal, seldom going above 4 per cent, of the 
 total nitrogen. In Case I also the nitrogen of 
 ammonia usually varied within normal limits. 
 A very large number of observations in this 
 case show that the percentage of nitrogen of 
 ammonia varied habitually between 3.25 and 
 4.50 per cent. At one time, while the patient 
 had a cold in the head, the nitrogen of ammonia 
 rose on two successive days to 4.78 and 5.96 
 per cent, of the total nitrogen. The urine at 
 this time gave a strong Legal reaction for 
 acetone in the distillate. On a few other occa- 
 sions, however, the nitrogen of ammonia reached 
 
INFANTILISM 35 
 
 or exceeded these figures without being asso- 
 ciated with acetone. 
 
 As regards the excretion of uric acid in this 
 case, it may be stated to have been so variable, 
 as measured by the ratio between uric acid 
 and the urea output, that no definite con- 
 clusions can be reached in the case of patients 
 Nos. II and III. This is true also of Case I 
 during the early period of observation, but 
 during recent months (March and April, 1908), 
 under conditions of great uniformity of diet 
 and habits, the uric acid excretion (like that 
 of total nitrogen) varied but little from day 
 to day With a few exceptions the uric acid 
 bore a proportion to the urea very close to 
 1:30. Taking into account the nature of the 
 diet^ this must be regarded as indicating an 
 excessive excretion of uric acid, both absolute 
 and relative.^ It is worthy of notice that there 
 should have occurred a rise both in the abso- 
 lute and the relative amount of uric acid 
 excreted just at the time when the nutritional 
 conditions of the patient began to undergo a 
 distinct improvement. 
 
 * Given in section on therapeutic measures. 
 
 'For example the actual quantities excreted during successive 
 days is expressed in grams by the following figures: 0.383, 0,388, 
 0.413, 0.454, 0.397, 0.387, 0.439, 0.406, 0.421, 0.427, 0.399, 0.488, 
 0.458, 0.486, 0.452, 0.449, 0.477, 0.433, 0.443, 0.517, 0.463, 0.427, 
 0.432, 0.449, 0.459, 0.480, 0.471, 0.545, 0.452, 0.473, 0.461, 0.468, 
 0.466, 0.456, 0.406, 0.415, 0.467, 0.422, 0.420, 0.397, 0.437. 
 
36 INFANTILISM 
 
 Special attention was devoted to a study of 
 the urinary indications of putrefactive decom- 
 position in the intestine. Such indications are 
 known to have been very pronounced in Cases 
 I, II, III and IV, and very similar indications 
 of putrefaction have been found in the sub- 
 acute infections of early infancy already alluded 
 to as being associated with the Gram-positive 
 fecal fields. The urinary signs of excessive 
 decomposition in the intestine are shown mainly 
 in four different ways: First, there is a rise 
 in the ethereal sulphates. It is no uncommon 
 thing in cases of infantilism for the ratio of 
 the ethereal to the preformed sulphates to 
 reach 1:4 or 1:6, whereas the normal ratio in 
 childhood is 1:12 to 1:18. Even higher pro- 
 portions are observed in the subacute stage 
 which the writer regards as leading into the 
 chronic state of infantilism. Secondly, pro- 
 nounced indicanuria is a very prominent fea- 
 ture, as shown in all the cases examined except 
 Case V, which did not come under close 
 observation until the nutritional state had begun 
 to improve. Quantitative determinations of the 
 indican have not been made, but the qualitative 
 results leave little doubt that the indican is 
 habitually highly excessive when the disease is 
 at its height. This is true also of the sub- 
 acute fore-period of the disease. It is true, 
 however, that with the improved intestinal con- 
 
INFANTILISM 37 
 
 ditions which precede a change for the better 
 in nutrition, the indican may begin to decline. 
 There may thus be a time in the history of 
 the disease when despite the fact that the 
 child still remains nearly stationary in weight 
 from week to week, and even from month to 
 month, the indican is much lower than was 
 previously the case. Another apparently regu- 
 lar feature of the putrefactive decompositions 
 in infantilism is the occurrence of an excess of 
 phenol in the distillate of the urine (the dis- 
 tillates include phenols and cresols). The ob- 
 servations made in our cases are partly quan- 
 titative by the method of Kossel and Penny 
 and partly qualitative (with Millon's reagent). 
 In Case II the repeated examinations of the 
 distillate made at short intervals during a 
 period of five years showed an excess of phenol 
 to be a regular feature. The phenol for 24 
 hours varied from 38-90 milligrams (in the 
 quantitative observations). Case III likewise 
 gave very strong MUon reactions with the dis- 
 tillate. In Case I the distillate also regularly 
 contained excessive amounts of phenolic sub- 
 stances as indicated by the following figures 
 (representing milligrams) for the twenty-four 
 hours: 75, 71, 84, 79, 87, 93, 62, 78, 90, 100, 
 74, 62, 87, 90, 73, 90, 45, 81, 91, 63, 74. Once 
 without assignable cause the phenol in the dis- 
 tillate fell to 19 milligrams. Another feature 
 
38 INFANTILISM 
 
 of tlie urine referable to putrefactive decom- 
 position in tlie intestine is the presence of 
 aromatic oxyacids in the urine. It is probable 
 that both paraoxyphenylacetic acid and para- 
 oxyphenylpropionic acid are frequently present 
 in excess in these cases.^ The acids in solu- 
 tion in the urine are capable of reacting with 
 Millon's reagent even in the cold, and it is 
 a noteworthy feature of our cases that in many 
 instances the urine gives the characteristic 
 behavior of the aromatic oxyacids when treated 
 with Millon's reagent in the cold. Urines con- 
 taining these aromatic oxyacids also give a 
 marked diazo-reaction after distillation of the 
 phenols. It may be mentioned further that 
 the urines from the subacute infections, which 
 are regarded as constituting the early stage of 
 chronic infantilism, are liable to give a very 
 pronounced reaction with Millon's reagent in 
 the cold in the absence of volatile phenols. 
 Finally it should not be overlooked that a 
 marked degree of indolaceturia occurred in 
 Case I and was a continuous feature in this 
 patient. The presence of indolacetic acid was 
 detectable also in the urine of Case 11 where, 
 however, it was not pronounced. In Case III 
 
 'Paraoxyphenylacetic acid is not readily burned in the body 
 and hence appears in the urine when absorbed from the intestine. 
 The homologous higher acid undergoes combustion and hence is 
 less likely to reach the urine, even if formed in equal or greater 
 amount as the result of putrefaction. 
 
INFANTILISM 39 
 
 it gave rise to a moderate reaction with strong 
 hydrochloric acid and potassium nitrite. From 
 experience gained with the urines of the sub- 
 acute infections leading to chronic infantilism, 
 I am disposed to think that indolaceturia is 
 not a regular feature in this type of disease, 
 although it is sometimes very prominent. 
 
 It may be further stated that the urines 
 from the cases of infantilism showed slight or 
 negative reactions with paradimethylamidoben- 
 zaldehyde, that skatol red was regularly absent 
 and that in Cases I, II and III the urines 
 were sometimes observed to show a slight 
 reducing action when boiled with Fehling's 
 solution. 
 
 Features Relating to the Intestinal Contents. 
 There are several features relating to the 
 gross and microscopical appearances of the 
 intestinal contents and to their chemical nature 
 which require at least brief consideration. The 
 character of the movements is influenced to a 
 considerable extent by the nature of the food, 
 and in general it may be stated that on an 
 ordinary mixed diet containing a fair propor- 
 tion of fat, carbohydrates and proteins and in 
 which milk forms part of the regimen, the 
 movements are voluminous, gray or light-brown 
 in color and of sufficiently low specific gravity 
 to float on the surface of water. If the quan- 
 tity of food be considerable the movements may 
 
40 INFANTILISM 
 
 be very large indeed. If the carboliydrates be 
 abundant, tbe fresh movements are apt to be 
 filled with bubbles of gas. The stools are 
 usualy formed, though so soft that any increase 
 in the watery constituents gives the stool a 
 diarrhoeal character. The movements usually 
 have a sour odor which is clearly recognizable 
 despite the fecal odor due to the presence of 
 indol. The odor of butyric acid is seldom 
 more than slight and is frequently absent. 
 Mucus is very abundant at times both in, 
 masses on the surface of the feces and inti- 
 mately mingled with them in small bits. In 
 loose movements after the use of calomel large 
 flakes of mucus are usually brought away. 
 Large numbers of well-preserved individual 
 epithelial elements are habitually carried away 
 in the feces. Their number may be very large 
 in some parts of the stool. Preparations of 
 the feces show moderately dense bacterial 
 fields almost always containing numerous epi- 
 thelial elements, with nuclei usually well pre- 
 served and with a small area of cytoplasm 
 about them. These epithelial elements may 
 occur separated or closely aggregated in con- 
 siderable numbers. In some cases it is com- 
 mon to find on the surface of the feces and 
 mingled with the mucus, numbers of small, 
 spheroidal cells, from three to four microns in 
 diameter, containing spherical nuclei and pos- 
 
INFANTILISM 41 
 
 sessing homogeneous, highly refractile cell 
 bodies. They are often bile-stained, and if 
 present in large numbers give a pink or red- 
 dish color to the mucus with which they are 
 mixed. These cell elements stain readily with 
 carbol-fuchsin and are acid-fast. When I first 
 saw them I thought they might be epithelial 
 elements^ but now believe them to have an 
 origin extraneous to the digestive tract. They 
 may possibly be some form of yeast, but the 
 fact that we have not been able to grow them 
 in sugar media appears against this view. 
 
 The microscopical fields show the presence 
 of an abundance of fatty acid crystals, and it 
 is owing to the presence of these that watery 
 suspensions of feces (say one gram feces to 
 ten grams water) in a test tube show the 
 optical peculiarities due to the presence of 
 large nujnbers of small crystals. The reaction 
 of the feces is usually slightly acid, but often 
 it is neutral. If, however, meat be an abun- 
 dant constituent of the diet the reaction may 
 be sliglitly alkaline. In some instances it has 
 been noticed that the drying of the feces is 
 associated with the separation of large num- 
 bers of crystals which have the characteristic 
 appearance of triple phosphates (ammonio- 
 magnesian phosphate). 
 
 There are also several chemical characters 
 in the feces of infantilism which deserve men- 
 
42 INFANTILISM 
 
 tion. Even when the feces are acholic in 
 appearance, extraction with alcohol shows the 
 presence of moderate quantities of bilirubin. 
 It is thus erroneous to draw the conclusion 
 from the appearance of the stools that bile 
 fails to enter the intestinal tract. It is also 
 noteworthy that the reaction for hydrobilirubin 
 with concentrated bichloride of mercury is 
 extremely slight and sometimes negative. This 
 points to the absence of a strong reducing action 
 on the part of the bacteria present in the 
 intestinal tract. I think it probable that the 
 failure to detect marked evidence of reducing 
 action by the bacteria in the digestive tract 
 is to be explained in these cases by the com- 
 paratively small number of microorganisms of 
 the butyric acid type — a type conspicuously 
 active in causing reductions. Indol is a nearly 
 constant constituent of the freshly voided feces 
 in children suffering from intestinal infanti- 
 lism. It may easily be demonstrated in the 
 distillate either by the paradimethylamidoben- 
 zaldehyde reaction of Ehrlich, or better still, 
 by means of the /8-naphthaquinone sodium 
 monosulphonate reaction. The quantity is usually 
 not large, but rarely may run up to 20-30 
 milligrams in 100 grams of the moist feces. 
 The presence of indol in the feces may be 
 correlated with the occurrence of strong indi- 
 canuria, but sometimes the indicanuria may be 
 
INFANTILISM , 43 
 
 pronounced even though only a trace of indol 
 is detectable in the feces. This is owing to 
 the fact that there is not any fixed relation 
 between the quantity of indol produced in the 
 intestine and the quantity absorbed. As the 
 patients improve in digestion and nutrition, 
 the quantity of indol in the feces grows less, 
 and may in time become very slight. In 
 diarrhoeal movements also the proportion of 
 indol is apt to be slight. I have never 
 observed skatol in the movements from any 
 patients of the type now under consideration. 
 Phenolic substances can almost always be 
 detected in slight amounts in the distillate 
 from the feces. Sometimes the reaction for 
 them is strong. In Case I the feces contained 
 a substance which gave reactions correspond- 
 ing to indolacetic acid. I have not, however, 
 had the opportunity to separate this substance 
 in purity and in sufficient quantity from the 
 feces to actually settle its identity. The hy- 
 drogen sulphide contents of the feces in cases 
 of intestinal infantilism is commonly small.^ 
 
 ^ The following determinations of hydrogen sulphide in the 
 feces are indicative of the range in percentage: 
 
 Case I Per cent. Per cent. 
 
 Date solids H2S 
 
 Nov. 27, '07 25.89 .0144 
 
 Nov. 29, '07 9.97 .0144 
 
 Dec. 3, '07 29.85 .0113 
 
 Dee. 5, '07 25.41 .0127 
 
44 INFANTILISM 
 
 The hydrogen sulphide exists in bound form, 
 and I have never been able to detect the free 
 gas in the fresh movements. Methyl mercap- 
 tan is also absent although the bacteria from 
 the feces may produce a small amount of 
 methyl mercaptan when grown in plain broth. 
 It appears true in general, however, that the 
 bacteria present in these cases do not form 
 mercaptan abundantly, and commonly they do 
 not make it at all under the conditions just 
 mentioned. The volatile fatty acids derivable 
 from the feces in cases of infantilism are 
 moderate in amount and appear to be rather 
 low in butyric acid. Acetic acid may be 
 detectable. Aldehydes have not been detected. 
 The gas production of the mixed fecal flora 
 when grown in dextrose, saccharose and lactose 
 bouillon, is variable. Commonly it is smaller 
 than normal. The fecal flora may, indeed, fail 
 to form gas under these conditions. With 
 
 Per cent. Per cent, 
 
 solids HsS 
 
 '07 17.37 .041 
 
 '07 32.60 .031 
 
 '07 27.67 
 
 '07 28.82 .0111 
 
 '07 28.04 
 
 '07 27.00 .0190 
 
 '07 20.88 .0170 
 
 '07 26.15 .0201 
 
 '08 21.00 .009 
 
 These low percentages of hydrogen sulphide are the more note- 
 worthy in view of the excess of other putrefactive products. 
 
 Date 
 
 Dec. 
 
 7, ' 
 
 Dec. 
 
 7, ' 
 
 Dec. 
 
 10, ' 
 
 Dec. 
 
 11, ' 
 
 Dec. 
 
 14, ' 
 
 Dec. 
 
 16, ' 
 
 Dec. 
 
 20, '( 
 
 Dee. 
 
 24, '( 
 
 Jan 
 
 18, '( 
 
INFANTILISM 45 
 
 improvement attended by a return of B. coli 
 and B. lactis aerogenes the gas production 
 increases to normal. 
 
 The Calcium and Magnesium Balances, In 
 the state of arrested development which con- 
 stitutes the striking feature of the cases of 
 infantilism here reported, it is of especial 
 interest to seek for information regarding the 
 calcium and magnesium intake and output. It 
 is obvious that the failure of skeletal growth 
 calls for explanation and that this explanation 
 is to be sought either in the inability of the 
 skeleton to utilize calcium and magnesium com- 
 ing to it in the blood, or the inability of the 
 blood and lymph streams to obtain from the 
 digestive tract sufficient quantities of the alkali 
 earths to supply the necessary materials for 
 skeletal growth. In order to determine the 
 relations between the intake and the outgo of 
 the alkali earths from the body in a state of 
 infantilism, two observations were made by 
 Dr. Wakeman upon Case I, each observation 
 covering a period of ten days. The second of 
 these observations serves as the basis for the 
 data to be referred to here, the observation 
 having been made under thoroughly satisfac- 
 tory conditions from every point of view. The 
 period of ten days in question extended from 
 noon, March 10, 1908, to noon, March 20, 1908 
 — a period during which the subject remained 
 
46 INFANTILISM 
 
 essentially stationary in weight. The calcium, 
 magnesium and phosphoric acids taken in the 
 food were accurately determined. The calcium, 
 magnesium and phosphoric acids were also 
 determined in the urine and feces correspond- 
 ing to this period, the feces being carefully 
 marked off from the fore and after periods by 
 means of charcoal. 
 
 During the period of ten days the calcium 
 (calculated as calcium oxide) found in the 
 urine was 0.1151 grams, giving a daily average 
 of 0.0115 grams. In the feces during the same 
 period, the calcium oxide amounted to 9.59 grams, 
 giving a daily average of 0.959 grams. The 
 calcium oxide present in the feces and urine 
 together during the ten days amounted to 
 9.71 grams, with a daily average of 0.971 
 grams. The calcium oxide of the food during 
 the same period amounted to 9.81 grams with 
 a daily average of 0.982 grams. There was 
 thus a positive balance of calcium during the 
 ten-day period amounting to 100 milligrams, in- 
 dicating a daily retention of calcium oxide of 
 only 10 milligrams. It is roughly estimated 
 that in the normal growth of a child between 
 the second and the sixteenth years, the daily 
 retention of calcium oxide by the body should 
 be more than ten times the amount retained in 
 this case. The amount indicated as retained 
 is, in fact, so small in this instance as to fall 
 
INFANTILISM 47 
 
 almost within the limit of experimental error. 
 There was thus no appreciable retention of 
 calcium oxide during the period in question. 
 During another ten-day period in which the 
 calcium oxide was studied by Dr. Wakeman 
 under somewhat less favorable experimental 
 conditions, there was shown an actual loss of 
 calcium oxide in the feces and urine as com- 
 pared with the calcium oxide taken in with 
 the food. The very small quantities of calcium 
 found in the urine in the experimental periods 
 relating to this case point to defective absorp- 
 tion of calcium from the intestinal tract. 
 
 Precisely similar results were obtained from 
 the study of the magnesium balance. During 
 the ten -day period corresponding to the one 
 for which the figures for calcium oxide have 
 just been given, the urine contained one gram 
 of magnesium (calculated as magnesium oxide), 
 giving an average of 0.10 grams daily. Dur- 
 ing the same period the magnesium in the 
 feces was equivalent to 1.35 grams of mag- 
 nesium oxide, giving an average of 0.135 grams 
 daily. The magnesium oxide of the urine and 
 the feces in this ten-day period was equivalent 
 to 2.35 grams. On the other hand, the mag- 
 nesium of the food (calculated as magnesium 
 oxide) was 2.19 grams. It is thus evident 
 that for the entire period of ten days there 
 was a loss of magnesium oxide equivalent to 
 
48 INFANTILISM 
 
 0.16 grams. This amoimt may possibly fall 
 within the limits of experimental error. The 
 result indicates that during the period in ques- 
 tion the body was retaining no magnesium. 
 The cause of this failure of the organism to 
 retain magnesium and calcium will be discussed 
 in considering the pathology of infantilism. 
 
 The study of the phosphoric acid of the 
 urine and feces on the one hand, and of the 
 food on the other, gives results comparable with 
 those just given for calcium and magnesium. 
 During the ten-day period the urine contained 
 10.46 grams of phosphoric acid, or an average 
 of 1.05 grams of phosphoric acid daily. The 
 feces during the same period contained 10.70 
 grams of phos]ohoric acid, an average of 1.07 
 grams daily. During the ten-day period the 
 urine and feces together contained 21.16 grams 
 of phosphoric acid with a daily average of 
 2.12 grams. During this same time the food 
 contained 20.29 grams of phosphoric acid with 
 a daily average of 2.03 grams. These results 
 thus indicate a slight loss of phosphoric acid 
 during the ten-day period in question, but the 
 loss is so small as to fall nearly within the 
 limits of experimental error, and hence is to 
 be disregarded. 
 
 The Fat Loss by the Feces, In all of the 
 cases of infantilism it has been noteworthy 
 that the stools have been excessively fatty, 
 
INFANTILISM] 49 
 
 even where only moderate quantities of fat 
 have been taken with the food. The presence 
 of large amounts of fatty acids has already 
 been referred to in speaking of the appear- 
 ances of the feces in these cases. Another 
 characteristic is the presence of soaps, the 
 white masses of which, looking like small 
 granular coagula of casein, sometimes give a 
 very noteworthy appearance to the stools. 
 These masses of white soaps (probably calcium 
 soaps) have often been mistaken for casein. 
 
 In Case I the fats of the feces were sub- 
 jected to careful study. It was found that the 
 total percentage of fats in the solids was 
 uniformly high even on a diet containing only 
 moderate amounts of fat. Thus at different 
 periods, lasting from two to ten days, the per- 
 centages of fats of the solids of the feces 
 amounted to 29.80, 31.93, 32.78, 44.60, 39.21, 
 41.96, 47.26, 40.90, 25.01, 39.66, 36.16. These 
 figures include not merely the ethereal ex- 
 tracts, but also the fatty acids in the form of 
 soaps. They therefore represent the total fats 
 lost. It will be seen that these figures repre- 
 sent a large loss of fat of the food. The 
 actual loss of fat for various periods is shown 
 by the following table, which shows also the 
 losses of soaps and the losses of calcium com- 
 bined as soaps (assuming the soaps to con- 
 sist wholly of soaps of calcium) : 
 
50 
 
 INFANTILISM 
 
 Table I 
 Showing actual loss of fat with feces during various periods: 
 Case I 
 
 Total fats Soaps Calcium Oxide 
 
 per per from soaps 
 
 period period per period 
 
 Date of Period Grams Grams Grams 
 
 Dec. 2, 6, 8, '07 21.6 1.46 0.145 
 
 Dec. 13, 14, 19, 20, '07.. 23.8 0.93 0.092 
 
 Dec. 20, 21, '07 22.2 3.16 0.313 
 
 Dec. 25, 29, 31, '07 20.9 2.69 0.266 
 
 Jan. 19, 20, '08 13.0 2.61 0.258 
 
 Jan. 26, 27, '08 17.0 4.20 0.416 
 
 Feb. 8, 9, 10, '08 29.2 4.67 0.463 
 
 Feb. 14, 15, 16, 17, '08.. 32.1 4.74 0.469 
 
 March 10 to 20, '08 55.6 10.80 1.070 
 
 Comparing these figures, representing tlie loss 
 of fat, with the figures representing the intake 
 of fat during one of the periods studied 
 (March 10-20, 1908) it was found that the per- 
 centage of fat absorbed was 85.5, while the 
 percentage of fat lost was 14.5. These figures 
 indicate the considerable extent to which the 
 fat is lost in these cases on a diet containing 
 only a moderate amount of fat, since in a 
 normal individual one would look for a fat 
 absorption of from 92 to 98 per cent. But 
 these figures relate to a period of improve- 
 ment and by no means show the worst fat 
 absorption noted in Case I. At an earlier 
 period, with the same daily intake of fat 
 (38.28 grams), the losses were frequently from 
 20 to 25 per cent., and once reached 40 per 
 cent, of the ingested fat. 
 
INFANTILISM 51 
 
 Observations have been made in Case I rela- 
 tive to the proportions existing between the 
 neutral fats, the fatty acids and the soaps. 
 They show that fat splitting and saponifica- 
 tion have occurred in high degree in the intes- 
 tinal tract, since the fatty acids range from 
 40.75 per cent, to 80.25 per cent., while the 
 soaps vary from 3.89 per cent, to 20.08 per 
 cent. The neutral fats, on the other hand, 
 range from 6.88 to 39.85 per cent. It is 
 thus evident that the greater part of the fats 
 lost are in the form of fatty acids and that 
 the sum of the fatty acids and the soaps make 
 up on the average about three quarters of the 
 total fat lost. These losses cannot, of course, 
 be attributed to any failure of fat splitting 
 in the intestine, but are clearly referable to a 
 diminished power of absorption. It is note- 
 worthy that so considerable a percentage of 
 the total fats lost is in the form of soaps of 
 the fatty acids. The importance of this fact 
 lies in the consideration that these soaps are 
 for the most part calcium and magnesium 
 soaps (chiefly the former), and that they 
 represent a loss of calcium and magnesium 
 to the organism dependent on non-absorption 
 of the soaps of these alkaline earths. It is 
 true that only a relatively small percentage 
 (say 10 per cent.) of the calcium lost in the 
 feces is present in the form of soaps, but it 
 
52 INFANTILISM 
 
 is obvious that the non-absorption of the quan- 
 tity of calcium represented by this proportion 
 is enough to determine whether the organism 
 shall or shall not gain calcium for the pur- 
 pose of building up the skeleton. The same 
 considerations hold true also of magnesium. 
 
 Let us take a specific example relating to 
 calcium. Between March 10 and 20 there 
 was a loss of 10.8 grams of soaps. These 
 soaps consist almost entirely of soaps of cal- 
 cium and have been calculated as such in the 
 foregoing table. On this assumption the cal- 
 cium oxide representing these soaps would 
 amount to 1.07 grams. For a period of one 
 year the calcium oxide thus lost as soaps 
 would amount to more than 36 grams. The 
 gain of so much calcium by the skeleton, or 
 its loss through the feces, is clearly an im- 
 portant element in the skeletal growth.^ 
 
 * I have calculated that the average yearly accretion of calcium 
 oxide by the skeleton between the third and sixteenth year is 51.6 
 grams. If we deduct 36 grams of calcium oxide as representing 
 the loss through soaps, we see that there will be left but little 
 calcium for the purpose of skeleton building. 
 
 The above result was reached by the following data: 
 Estimate of the average yearly addition of calcium (as calcium 
 oxide) to the human skeleton between the third and sixteenth 
 year. 
 
 Weight of body at 3 years 16 kilos 
 
 Weight of body at 16 years 50 kilos 
 
 Estimated weight of skeleton in % of total at 3 years. . . 15% 
 Estimated weight of skeleton in % of total at 16 years. . 17% 
 
 Weight of skeleton at 3 years 2.4 kilos 
 
 Weight of skeleton at 16 years 8.5 kilos 
 
INFANTILISM 53 
 
 PATHOIiOGY 
 
 It is desirable to consider the data that 
 have been presented in the foregoing pages 
 with a view to their bearing on the pathology 
 of intestinal infantilism. It is believed that 
 the data now available suffice to form a con- 
 ception of the nature of the processes that 
 underlie this serious disorder of nutrition, even 
 if they do not serve to satisfactorily clear up 
 all questions relating to the etiology of the 
 affection. There are two large and distinct 
 but related features of intestinal infantilism 
 which must be taken into account in any 
 endeavor to understand the morbid processes 
 on which the clinical manifestations depend. 
 These are, first, the extreme retardation in 
 general bodily development, secondly, the state 
 
 Undried bone contains 22% of bone earth 
 
 Skeleton of 2.4 kilos contains 0.53 kilo bone earth 
 
 Skeleton of 8.5 kilos contains 1.87 kilos bone earth 
 
 Accretion of bone earth by skeleton between the age of 3 and 
 
 16 years equals 1.34 kilos 
 Bone earth contains approximately 84% calcium phosphate 
 Bone earth contains approximately 13% calcium carbonate 
 1.34 kilos bone earth contain 1.125 kilos calcium phosphate 
 1.34 kilos bone earth contain 0.175 kilos calcium carbonate 
 1.125 kilos calcium phosphate contain 0.60 kilos calcium oxide 
 0.175 kilo calcium carbonate contains 0.07 kilos calcium oxide 
 Total calcium oxide in 1.34 kilos 
 
 of bone earth = 0.67 kilos calcium oxide 
 
 This represents the accretion of calcium oxide during thirteen 
 jears of skeletal growth. The yearly average accretion of calcium 
 oxide in skeletal growth between these years therefore equals 
 0.0516 kilos or 51.6 grams. 
 
54 INFANTILISM 
 
 of intoxication which manifests itself in promi- 
 nent derangements of the neuromuscular system. 
 
 The Retardation in Development, The re- 
 tardation in the development of the body 
 implicates, as already stated, the skeleton, 
 muscles, fat and viscera generally, while 
 slowing the growth of the brain in relatively 
 slight degree. Where are we to seek for an 
 explanation of the actual check to the general 
 growth and the disparity in state of bodily 
 nutrition as compared with that of the brain? 
 
 The retardation in growth undoubtedly de- 
 pends in the main on a simple cause — insuffi- 
 ciency of the foodstuffs absorbed from the 
 digestive tract. Such insufficiency of absorp- 
 tion may be referable to an inadequate food 
 supply or to imperfect absorption of food- 
 stuffs from the tract. The dietetic conditions 
 in our cases were of such a nature as not to 
 exclude the former factor, although making 
 impaired absorption largely responsible for the 
 diminished supply of food materials available 
 for the growth of the body. In thus stating 
 the case no allowance is made for the pos- 
 sibility that there may be disturbances of 
 metabolism wliich make for the impaired util- 
 ization of foodstuffs after their absorption. 
 It will be pointed out in the course of this 
 discussion that metabolic derangements do to 
 some extent exist, but that they are to be con- 
 
INFANTILISM 55 
 
 sidered as secondary to the absorption of 
 mildly toxic but continually formed products. 
 The following considerations will, I believe, 
 serve to show that the leading cause of the 
 arrest of growth is neither deficient food^ nor 
 specific disorders of metabolism, but serious 
 defects in digestion and absorption which find 
 expression in a failure of the organism to get 
 its proper share of nutritious materials from 
 the digestive tube. These defects may be con- 
 sidered from the standpoint of the carbo- 
 hydrates, the fats, the proteins and the salts 
 respectively. 
 
 It has been pointed out that a prominent 
 feature in the nutritional history of intestinal 
 infantilism is the intolerance for carbohydrates, 
 which even in moderate amounts lead quickly 
 to soft or diarrhoeal movements, often with 
 an increase in mucus and sometimes with a 
 markedly excessive formation of intestinal gases. 
 Even if the disturbances incidental to the 
 moderate use of carbohydrates are for a time 
 at least less obtrusive than those just men- 
 tioned, the physician is ultimately convinced 
 that his patient is freest from intestinal symp- 
 toms when this class of foodstuffs is much 
 
 ^ It is true that in each of the five cases there were times when 
 the food was deficient in amount, but in all instances repeated 
 efforts were made (sometimes unsuccessfully) to increase the food 
 supply sufficiently to make it enough for the needs of normal chil- 
 dren of corresponding weight, or even in excess of their needs. 
 
56 INFANTILISM 
 
 restricted. This conviction lias the practical 
 result that the child is in considerable degree 
 deprived of that class of foodstuffs on which 
 the organism mainly depends for its caloric 
 needs. The formation of adipose deposits de- 
 pends in childhood, in at least a measure, on 
 the ability of the organism to appropriate 
 carbohydrates in greater quantity than is 
 necessary to maintain the body weight, this 
 surplus being clearly convertible into fat by 
 obscure synthetic processes. Under normal 
 conditions it is further probable that the sugars 
 and starches furnish a portion of the material 
 used in the upbuild of the living protoplasm 
 generally, especially that of the muscles and 
 parenchymatous organs. But from experience 
 with diabetic persons and from various physio- 
 logical facts we know that these functions of 
 the carbohydrates may be in large degree sub- 
 stituted by the fats and proteins of the food. 
 The development of a diabetic child is possible 
 if the carbohydrates are replaceable by these 
 other foodstuffs, but only in this case. The 
 same statement probably holds equally true 
 of many children suffering from digestive 
 derangements. It being necessary to deprive 
 our patients with infantilism to a considerable 
 extent of their carbohydrates, we turn with 
 especial interest to learn how these children 
 dispose of their fats and proteins. 
 
INFANTILISM 57 
 
 The fats are on the whole better tolerated 
 than the carbohydrates by our patients with 
 intestinal infantilism. That is to say, if we 
 give to a child whose caloric needs are 1000 
 calories per diem, 100 grams of carbohydrates 
 or its approximate caloric equivalent in fats 
 (say 50 grams of fat), the latter may cause 
 less obvious disturbances of function than the 
 former. But from this we are not justified 
 in concluding that the fats are in reality well 
 utilized. They may be tolerated in the sense 
 that they do not promptly bring on obtrusive 
 symptoms, but examination of the movements 
 shows that the absorption of fats is far below 
 the standard for health, as regards neutral 
 fats, fatty acids and soaps. Thus in Case I 
 there was during a period of two days of fat 
 diarrhoea a loss of 22.2 grams of fat (neutral 
 fat, fatty acids and soaps) or 11.1 grams 
 daily. This large loss in fat represents nearly 
 40 per cent, of the fat intake at the time and 
 is equivalent to a waste of about 100 calories 
 daily. Losses of from seven to eight grams 
 of fat daily were common, representing 25 per 
 cent, of the fat ingested. In this great loss 
 of fat we have the key to the understanding 
 of the failure in nutrition which constitutes 
 the most prominent feature of intestinal in- 
 fantilism. 
 
58 INFANTILISM 
 
 It is obvious that such a fat loss (and the 
 exam]Dle is representative of the cases which 
 have up to the present come to my notice, 
 having been also marked in Cases II, III and 
 IV), when added to an intolerance for carbo- 
 hydrates, can lead to nothing less than a state 
 of well-defined under-nutrition. We can imitate 
 this condition by withholding fats in large 
 degree from young animals. In making this 
 experiment with young puppies and with young 
 pigs I found it easy to prevent any increase 
 in weight notwithstanding milk proteins were 
 given much in excess of ordinary requirements, 
 together with the milk sugar naturally present 
 in milk. I therefore believe that the incapacity 
 to absorb fats and carbohydrates is in itself 
 sufficient to explain a state of infantilism in 
 the human subject despite the free use of 
 proteins. It will be seen, however, that the 
 failure to absorb fats entails two other con- 
 sequences which lend their influence to hinder 
 development — a loss in calcium and magnesium 
 salts and an increase in intestinal jDutrefac- 
 tion. Before discussing these factors in the 
 pathology of infantilism, it is desirable to con- 
 sider the fate of the ingested proteins. 
 
 A study of the nitrogen balances (for three 
 separate periods) derived from a comparison 
 of the nitrogen ingested with the nitrogen lost 
 with the urine and feces (in Case I) shows 
 
INFANTILISM 59 
 
 that only an insignificant amount of nitrogen 
 (0.65 gm. in 10 days) was retained. This is, of 
 course, a not surprising result if we consider 
 the very small gain of the patient in weight; 
 and there is no reason to doubt that this 
 result, derived from a study of Case I, could 
 have been paralleled by studies of the nitrogen 
 balances in any of the other cases of infan- 
 tilism during the period of almost total arrest 
 in growth. 
 
 Table II 
 Showing the intake of nitrogen with the food and loss of nitro- 
 gen with the feces, according to periods. 
 Case I 
 
 N of Food N of Feces Loss of N 
 
 Grams Grams Per cent. 
 
 Period I (3 days) 22.89 2.34 10.2 
 
 Period II (4 days) 29.03 4.39 14.7 
 
 Period III (10 days) 66.46 8.44 12.5 
 
 Total N in Total N in Gain or loss Average daily 
 
 Urine Urine + in N per gain or loss 
 
 Grams Feces period in N 
 
 Grams Grams Grams 
 
 Period I (3 days) . . . 19.07 21.41 -|-1.48 -f 0.49 
 
 Period II (4 days) . . 24.66 29.05 —0.02 —0.005 
 
 Period III (10 days) 56.36 64.80 +1.66 -[-0.166 
 
 If we look at the figures in Table II which 
 relate to the absorption of nitrogen from the 
 digestive tract, for the periods in question in 
 Case I, we note that the absorption of protein 
 (as measured by its nitrogen content) is not 
 so complete as it should be. In period I, cov- 
 ering three days, the nitrogen of the food was 
 22.89 grams and that of the feces 2.34 grams. 
 The loss of nitrogen by the feces in this period 
 
60 INFANTILISM 
 
 was 10.2 per cent. In period II, covering four 
 days, the nitrogen of the food was 29.03 grams, 
 the nitrogen of the feces, 4.39 grams. The 
 nitrogen lost by the feces in this period was 
 14.7 per cent. In period III the food con- 
 tained 66.46 grams of nitrogen and the feces 
 8.44 grams. Here the loss in nitrogen equaled 
 12.5 per cent.^ In health the loss of nitrogen 
 by the feces under comparable conditions of 
 protein feeding is not greater than 7 or 8 per 
 cent, of the nitrogen ingested. So we may 
 say that the protein absorption in Case I was 
 somewhat under 90 per cent, instead of 92 per 
 cent, or over. Protein absorption is therefore 
 relatively much better than the absorption of 
 fat, despite the fact that it is somewhat 
 impaired. 
 
 Our interest in the fate of the inorganic 
 salts centers about the alkali earths. It has 
 been made out that in Case I, where a careful 
 balance was made of the calcium and mag- 
 nesium, the organism failed to gain either of 
 these elements. Under these conditions it is 
 not surprising that the skeleton should remain 
 stationary in weight. In a healthy, growing 
 child, weighing 25 pounds, there should be 
 definite evidence of the absorption of calcium 
 
 * Some portion of the nitrogen of the feces is attributable to 
 the epithelial detritus present here in excess, but it is difficult to 
 make a fair allowance for this. 
 
INFANTILISM 61 
 
 and magnesium in quantitievS sufficient to account 
 for the uninterrupted and rapid growth of the 
 skeleton during infancy and childhood. 
 
 Even under wholly normal conditions the 
 quantity of calcium daily absorbed from the in- 
 testine of a young child is small, while the 
 loss of calcium by the feces is large. Thus in 
 a normal child of nine months the feces con- 
 tained 2.122 grams of calcium (estimated as 
 oxide), while the food contained only a little 
 more than this — 2.194 grams.^ It is perfectly 
 obvious that any influence which tends to 
 diminish the absorption of this small propor- 
 tion of the ingested calcium must jeopardize 
 the small daily supply of this element which 
 is required for the growth of the skeleton. 
 And it is important to note that in some 
 apparently healthy children the maintenance of 
 a positive or negative calcium balance is 
 determined by apparently so slight a factor 
 as the variation in the percentage of fat in 
 the milk. Thus Eothberg^ found that the use 
 of skimmed milk insured a positive calcium 
 balance (even in some children with definite 
 signs of rickets), whereas in a certain number 
 of children the use of full-fat milk caused a 
 
 * See O. Eothberg. ' ' TJeber den Einfluss der organischen 
 Nahrungskomponenten auf den Kalkumsaltz kunstlich genahrten 
 Saulinge. " Jahri. f. Einderheillc.j 66, der dritten Folge, 
 16 Band, Heft 1, 1907. 
 
 'Log. cit. 
 
62 INFANTILISM 
 
 marked negative balance. Quite similar results 
 were obtained by Birk^ in his study of tbe 
 magnesium metabolism in nurslings. And it 
 may be further noted that both in the case of 
 calcium and magnesium a negative balance 
 may be induced in some children by the free 
 use of carbohydrates, for reasons at present 
 not clear. 
 
 It has been several times mentioned that a 
 leading feature in the pathology of infantilism 
 is the large loss in fat by the feces. A portion of 
 this fat (varying in Case I from 14 to 20 per 
 cent, of the total fat lost) is present as soaps 
 and especially as soaps of calcium. If we as- 
 sume that the soaps of the feces exist as soaps 
 of calcium (an assumption not far from the 
 truth, since magnesium soaps are present in 
 only small proportion) it is clear that the loss 
 of saponified fat entails a significant loss of 
 calcium. Thus in Case I the loss in soaps during 
 a ten-day period amounted to 19.8 grams, cor- 
 responding to a withdrawal of 1.07 grams of cal- 
 cium oxide during the same time. This is a 
 quantity of calcium sufficiently large to be of 
 the first importance to the skeleton, for in a 
 case where there is practically no gain and no 
 loss in skeletal calcium, a positive balance would 
 be established by the absorption and appropriation 
 
 "^TJeber den Magnesimnsaltz des Saulings." Jahrh. f. Kin- 
 derheiXk., 66 der dritten Folge, 16 Band, Heft 3, 1907. 
 
INFANTILISM 63 
 
 of any portion of the calcium habitually lost 
 as soap. The utilization of the entire amount 
 of calcium present as soap would make possible 
 a fair skeletal growth; and I have calculated 
 that the full absorption of this calcium (through 
 improved soap absorption) would in itself be 
 almost enough to account for a wholly normal 
 skeletal development. It is possible, however, 
 that in order to secure normal skeletal growth 
 we should have to obtain a somewhat improved 
 absorption of calcium not present as soap. I 
 cannot further discuss this point for I do not 
 know enough of the conditions attending physio- 
 logical fat absorption. 
 
 Sufficient evidence has now been brought for- 
 ward to support the contention that the arrested 
 growth of infantilism can be explained by the 
 inability of the organism to secure an adequate 
 supply of nutrient materials from the lumen of 
 the digestive tract. The failure to absorb suf- 
 ficient calcium and magnesium accounts for the 
 arrest of skeletal growth ; the restricted absorp- 
 tion of carbohydrates and fats explains the 
 failure to lay up fat, and at least partially ac- 
 counts for the cessation in the growth of muscle. 
 The proportionate retardation in the growth of 
 the viscera doubtless has a similar origin although 
 possibly here the physiological adaptation of vis- 
 ceral structures to the needs of the rest of the 
 body may have an influence. The relatively large 
 
64 INFANTILISM 
 
 size of the head and brain may be in part due 
 to the large size of the brain at birth, but it 
 appears that the growth of the brain in infan- 
 tilism is somewhat out of proportion to the very 
 slow development or entire arrest of the body 
 in general. This is perhaps attributable to the 
 protected position of the central nervous sys- 
 tem, in the sense that it not merely exercises 
 a kind of first call on the nutritive materials 
 which it requires but is also in large measure 
 screened from the action of certain poisonous 
 substances by the action of the liver, muscles, 
 etc. 
 
 The leading feature of infantilism — the pro- 
 longed arrest of development in early childhood — 
 is thus seen to be due to an impaired power 
 of absorption of nutrient materials in so far as it 
 depends on a lack of available fats, salts and 
 proteins. The relation between insufficient car- 
 bohydrates and defective absorption is less simple, 
 for the restriction in this class of foodstuffs is 
 often one encouraged by the physician on ac- 
 count of the evil consequences following even 
 the moderate use of sugars and starches. Prob- 
 ably a failure on the part of the intestine to 
 promptly absorb the dextrose formed during 
 the digestion of starches is a factor in depriv- 
 ing the organism of its proper share of car- 
 bohydrates, but this would perhaps not suffice 
 to make this deprivation significant but for the 
 
INFANTILISM 65 
 
 intervention of a second factor, namely the 
 excessively rapid decomposition of dextrose by 
 bacteria. 
 
 The impaired power of absorbing foodstuffs 
 from the intestinal tract I believe to be refer- 
 able to a chronic inflammatory process impli- 
 cating especially the lower lengths of the small 
 intestine and perhaps the contiguous portion of 
 the colon. This inference is based in part on 
 the occurrence of mucus and epithelial cells 
 intimately mingled with the intestinal contents 
 and partly on certain resemblances between the 
 signs of chronic saccharo-butyric putrefaction 
 in adults, a condition in which there is direct 
 evidence of congestion and inflammation of the 
 mucous membrane of the ileum and colon. The 
 inflammation of the digestive tract in infantil- 
 ism can be confidently attributed to the pres- 
 ence and dominance of an unsuitable bacterial 
 flora. 
 
 It is likewise to this unsuitable bacterial flora 
 that we have to attribute the excessive putre- 
 factive decompositions in the intestinal tract on 
 which depends the second leading group of 
 symptoms of intestinal infantilism — namely the 
 chronic intoxication of the neuromuscular sys- 
 tem which is in every case discernible. Among 
 the products of putrefaction in the intestine 
 are indol, indolacetic acid, phenol and the aro- 
 matic oxyacids. We know that indol exerts 
 
66 INFANTILISM 
 
 an irritant action on the central nervous sys- 
 tem, an action which if long continued leads 
 to depression of function. Likewise the de- 
 pressant action of indol on the muscles is well 
 marked.^ Of the action of the other aromatic 
 putrefactive substances on the neuromuscular 
 system little is positively known. Clinical ob- 
 servation makes me think that indolacetic acid 
 may exert an action similar to that of indol, 
 but milder in intensity. The fact that the 
 signs of intoxication (emotional irritability and 
 depression, rapid muscle fatigue) undergo strik- 
 ing amelioration coincidentally with a marked 
 fall in the quantity of the aromatic putre- 
 factive substances in the urine seems a reliable 
 indication that the neuromuscular intoxication 
 is related to the excessive absorption of such 
 putrefactive substances from the digestive tract. 
 There is another aspect of this excessive putre- 
 faction which must not be overlooked in any 
 discussion of the pathology of infantilism, 
 namely the loss of food material which it 
 entails. As an instance we may take the case 
 of tryptophan and indolacetic acid. The latter 
 is sometimes formed in such large quantities 
 from the former, in the course of putrefaction, 
 as to rob the organism of a not insignificant 
 quantity of tryptophan — an amino-acid which 
 
 ^ See experiments cf F. S. Lee, mentioned in my volxmie, Com- 
 mon Bacterial Infections of the Digestive Tract, p. 255. 
 
INFANTILISM 67 
 
 there is every reason to regard as essential to 
 nutrition. There may be a similar loss of 
 tyrosin owing to the putrefactive conversion of 
 this amino-acid into aromatic oxyacids in the 
 intestinal tract. Finally it must be regarded 
 as an open question whether the products of 
 putrefaction, after absorption, may not have 
 some damaging influence on the processes of 
 metabolism themselves through their action on 
 cells entrusted with important assimilative 
 powers. 
 
 The two cardinal features of infantilism, 
 arrest of bodily growth and the group of 
 symptoms based on chronic intoxication, thus 
 have their origin in an abnormal intestinal 
 flora possessed of a high degree of parasitism 
 owing to a long period of adaptation. The 
 nature of the pathological flora has been already 
 described in so far as it has been studied in 
 a small number of typical examples of intes- 
 tinal infantilism. The interpretation of these 
 findings can, however, be undertaken only with 
 much caution, owing to the scantiness of our 
 real knowledge of the biological characters of 
 the microorganisms which we have found to 
 be so regularly and persistently associated with 
 intestinal infantilism. The evidence on which 
 we must base a judgment is circumstantial 
 rather than direct. It is unlikely that the 
 pathological state can be experimentally repro- 
 
68 INFANTILISM 
 
 duced in animals by means of the organisms 
 which we have fonnd to be characteristic of 
 the chronic human infection. The ordinary 
 tests of pathogenicity have given negative 
 results with the three types of organisms 
 which appear most intimately related to the 
 infection, namely B, hifidus, B. infantilis and 
 the cocco-bacillary forms.^ In other words, we 
 cannot here apply the criteria that have served 
 so well in studying acute infectious diseases. 
 There are, nevertheless, certain obtrusive phe- 
 nomena which cannot be overlooked and which 
 call for some comment. The great abundance 
 of B, hifidus in the formed and diarrhoeal 
 stools of infantilism, and in the mucus con- 
 tiguous to the mucosa, suggests a relationship 
 of a causative nature to the inflammatory 
 process within the gut. This suggestion is 
 made the more reasonable by the fact that 
 periods of improvement in absorption (due 
 presumably to amelioration in the intensity of 
 the inflammation) have been associated in 
 numerous instances with a partial disappear- 
 ance of B. hifidus from the stools or through 
 a modification in the morphology of the organ- 
 ism pointing plainly to a decline in vigor. It 
 is perhaps true that the same argument might 
 
 *It should be stated that a dog was fed on milk inoceulated 
 with B. infantilis after sterilization. The animal developed a 
 persistent diarrhoea which ceased only with the discontinuation of 
 the infantilis milk. A second trial gave a similar result. 
 
INFANTILISM 69 
 
 be applied with equally good reason to the 
 relation of B, infantilis to infantilism, except 
 that we have not found this organism in the 
 mucus. Finally the fact must be mentioned 
 that the disappearance of B. hifidus and B, 
 infantilis has been noticed to be concomitant, 
 not only with clinical improvement, but with 
 an increase in the numbers of the cocco-bacillary 
 forms which are apparently always present. 
 This fact seems to indicate that this group of 
 organisms is less objectionable than the micro- 
 organisms which it replaces. A fact which 
 calls for especial comment is the occurrence 
 of B. hifidus and B. infantilis in the stools of 
 normal infants and in small numbers in some 
 healthy adults. Tissier and other French ob- 
 servers have insisted on the presence of B. 
 hifidus in the stools of nurslings, even main- 
 taining that this microorganism is the charac- 
 teristic and dominant one. It is necessary to 
 reconcile this contention with the suspicion just 
 expressed that B, hifidus is actually an inju- 
 rious agent in our cases of infantilism. In 
 this connection it is important to state at the 
 outset that the study of many Gram- stained 
 smears from normal nurslings indicates that 
 in the United States there are numerous 
 normal nurslings from whom one can obtain 
 no evidence of the presence of B. hifidus in 
 the stools; and this assertion is supported by 
 
70 INFANTILISM 
 
 the results of careful cultural procedures car- 
 ried on by experienced persons. On the other 
 hand, B, hifidus did appear in the cultures 
 from some of the normal nurslings' stools 
 examined by us; and in some instances the 
 Gram-stained fecal fields showed a great abun- 
 dance of positive forms possessing a mor- 
 phology indistinguishable from the plain form 
 of B, hifidus. But there are two comments to 
 be made on these findings. First, we have 
 never been able to obtain in plate cultures so 
 many bifidus organisms from normal nurslings 
 as from cases of infantilism, and it seems a 
 safe inference that these bacteria are in reality 
 more abundantly present (in at least some 
 cases of infantilism) than in healthy nurslings. 
 Secondly, it must be plainly stated that there 
 is no sound evidence that the greater number 
 of the Gram- stained positive bifidus-like bac- 
 teria in the nurslings' stools are in reality 
 examples of B. hifidus. The French writers 
 have assumed that the organisms seen in the 
 fecal fields are bifidus, but the contention has 
 never, I believe, been successfully sustained by 
 adequate cultural methods. We know that B. 
 infantilis and some acidophile bacteria (other 
 than B, hifidus, which is to be ranked as an 
 acidophile microorganism in the sense of 
 being able to grow in a strongly acid medium, 
 though not in the sense of being restricted in 
 
INFANTILISM 71 
 
 growth in a neutral medium) may exist in 
 fecal fields side by side with the plain form 
 of B, hifidiis and indistinguishable from it. 
 
 Thus such evidence as is now available indi- 
 cates that B. hifidus is considerably more abun- 
 dant in the stools of infantilism than in the 
 stools of normal nurslings. It may be that 
 any detrimental action exerted by these bac- 
 teria is due to their relative predominance in 
 the intestinal tract of infantilism, perhaps also 
 to a failure in a normally existing balance or 
 symbiosis with bacteria of the B, coli or B. 
 lactis aerogenes types. It will require con- 
 siderable further study to determine this ques- 
 tion. Likewise the relation of B. infantilis to 
 the genesis of infantilism must be left open. 
 It may, however, be stated with much con- 
 fidence that intestinal infantilism is associated 
 (at least in some of the most extreme cases) 
 with the persitence and dominance of types of 
 flora which belong especially to the period of 
 infancy and the persistent dominance of which 
 in the third, fourth, fifth, sixth and even 
 eighth year of life (as I have observed it) 
 must be regarded as distinctly pathological. 
 
 There are some features in the pathology 
 of infantilism that remain obscure despite a 
 somewhat close study of the subject. For 
 example, I cannot yet offer a satisfactory 
 explanation of the extreme abdominal disten- 
 
72 INFANTILISM 
 
 sion met with in most of our cases. Neither 
 B, hifidus nor B, infantilis are gas-formers. 
 The same is true of the various coccal and 
 cocco-bacillary forms. It is unlikely that any 
 of them are primarily concerned with the 
 intestinal gas-production. Possibly owing to 
 slow absorption from the small intestine the 
 carbohydrates there are decomposed by B, 
 lactis aerogenes, which is probably present in 
 the upper part of the small intestine. We 
 know, for example, that when acting on potato 
 this organism forms gas abundantly. But the 
 study of the diarrhoeal fecal fields gives no 
 suggestion that there is any excessive multi- 
 plication of B. lactis aerogenes in the small 
 intestine.^ 
 
 I find it impossible at present to offer a 
 well-supported explanation of the putrefactive 
 cleavages which are so active in the intestine. 
 Which bacteria or groups of bacteria are 
 responsible in this disease for the production 
 of indol, indolacetic acid, phenol and para- 
 oxyphenylacetic acid is still far from clear. 
 Until we meet with more success in getting 
 B. infantilis and B, hifidus to grow outside 
 the body as they grow in the intestinal tract, 
 we cannot hope to clear up this feature of 
 
 ^ It must be remembered that we have not had the opportunity 
 to study bacteriologically any of our infantilism patients in the 
 stage characterized by active gas-formation and distension of the 
 small intestine. 
 
INFANTILISM 73 
 
 the pathology of the affection, and it seems 
 best at present not to attempt its discussion. 
 
 It has been shown that the persistence and 
 overgrowth of bacterial flora of the nursling 
 period is a characteristic of the infantilism 
 patients reported in this publication. Of the 
 conditions leading to this persistence and over- 
 growth nothing positive is known, and this 
 necessary knowledge can be gained only by very 
 careful and extended bacteriological studies of 
 the intestinal bacteria in the earliest stages of 
 the disease. 
 
 The condition of infantilism which has been 
 described is one possessing clearly defined 
 clinical characters. "Whether the bacterial causes 
 of the affection, or, more properly, its bac- 
 terial associations, are always of the same 
 nature as those here described must be left 
 an open question. The studies which have 
 been made point to a definite relation between 
 the clinical phenomena and the peculiar bac- 
 terial flora, but the thoroughly studied cases 
 have been few, and wider experience may 
 possibly teach us that our definite clinical type 
 may be associated with more than one group 
 or symbiotic association of bacteria. 
 
 Other etiological factors than intestinal in- 
 fection in the cases of intestinal infantilism 
 seem improbable, although they cannot be posi- 
 tively excluded. The recovery which has taken 
 
74 INFANTILISM 
 
 place in Case I, and in a still more striking 
 degree in Case II, as a result of carefully 
 planned dietetic and hygienic measures, seems 
 to speak against the specific influence of non- 
 intestinal elements of causation, as for exam- 
 ple disorders in the functions of glandular 
 organs, such as the thyroid gland or the an- 
 terior lobe of the pituitary body. It is note- 
 worthy that in all our cases of infantilism 
 there have been at least some indications of 
 rickets. Since the retardation in the growth 
 of the skeleton seems clearly referable to the 
 inadequate absorption of calcium and mag- 
 nesium, it is likely that such indications of 
 rickets as have been observed are also related 
 to this defect in assimilation of the alkali 
 earths. Our cases point, however, to the cor- 
 rectness of the view that something more than 
 mere failure to adequately absorb calcium and 
 magnesium must enter into the pathology of 
 rickets, since in cases of such marked skeletal 
 retardation as we have in our examples of 
 infantilism there should have been the fullest 
 opportunity for the development of rickets, 
 were this disease dependent merely on the 
 non-assimilation of the bone-forming elements. 
 Under the circumstances the relative slight- 
 ness of the rachitic manifestations is a feature 
 of considerable interest. 
 
INFANTILISM 75 
 
 The Acute and Subacute Infections Leading 
 TO Infantilism 
 
 Although unable to give an adequate account 
 of the bacteriology of the acute and subacute 
 cases of enterocolitis which in my judgment 
 are the antecedents of chronic infantilism, I 
 wish to mention here the existence of a type 
 of intestinal inflammation which stands in this 
 causative relation to the chronic affection. 
 These cases usually begin between the end of 
 the first year and the middle of the third. 
 They are characterized by diarrhoea (usually 
 without tenesmus) with an abundance of mucus, 
 but no blood. The diarrhoeal discharges are 
 usually not very frequent. The loss in weight 
 is not rapid (1-2 ounces daily), but may 
 progress until the child is much emaciated. 
 There is usually considerable flatulence. There 
 is a moderate or marked fall in haemoglobin. 
 The temperature is normal or subnormal. The 
 appetite may be unimpaired. The disease lasts 
 from three to six weeks and recurrences are 
 very apt to occur. The carbohydrates are very 
 badly tolerated and many relapses are cer- 
 tainly due to their incautious use. 
 
 The urine in the course of this disease gives 
 intense reactions for indican and for aromatic 
 oxyacids. 
 
 An examination of the Gram-stained fields 
 from the stool of a typical example of this 
 
76 INFANTILISM 
 
 infection shows it to consist almost wholly of 
 Gram-positive bacilli (often lying parallel to 
 each other in groups) presenting the morpho- 
 logical characters of the simple form of B. hifidus. 
 From the stools B, hifidus can be readily cul- 
 tivated and the same microorganism grows 
 very freely in its bifid forms in dextrose bouil- 
 lon fermentation tubes. B, infantilis is obtain- 
 able from the stools of some cases, perhaps of 
 all. From the mucus B, hifidus grows freely, 
 sometimes almost alone, in fermentation tubes. 
 It appears probable that B, hifidus is very 
 abundant in the stools of these cases, but it is 
 not possible at present to say to what extent 
 it makes up the fecal fields. A noteworthy 
 feature is the very small number of Gram- 
 negative bacteria seen in the fields. 
 
 The close similarity between the intestinal 
 flora in this acute or subacute affection and in 
 infantilism makes a causal relation between the 
 former and the latter highly probable. Up to 
 the present time I have had no opportunity to 
 observe an indubitable transition of the acute 
 disease into the chronic one with the help of 
 methods adequate to establish the proof of 
 such a relation as that just suggested. The 
 methods now employed were not known to us 
 when the cases of infantilism here described 
 were in their subacute stage. On the other 
 hand, the acute or subacute cases presenting 
 
INFANTILISM 77 
 
 the flora above mentioned have not been long 
 enough under observation to determine whether 
 any of them are developing the extreme and 
 persistent retardation to which the word infan- 
 tilism may properly be applied. 
 
 Mild Types of Intestinal. Infantilism 
 
 It seems to me desirable to restrict the use 
 of the word infantilism to those cases of 
 intestinal origin in which the subjects are 
 strikingly undeveloped for years and in which 
 the absolute arrest of growth has persisted for 
 at least one year. The atrophic conditions of 
 infancy which are grouped under the term 
 marasmus belong in a different clinical cate- 
 gory and have, I believe, a different genesis. 
 There are, however, instances of a moderate 
 retardation in growth (not necessarily with 
 actual arrest in development) which appear to 
 be mild types of the condition which has been 
 described in this study only in its extreme 
 examples. B. hifidus appears to be less abun- 
 dantly present in these milder cases, in which 
 various coccal forms may be prominent and in 
 which Gram-negative forms (representing B. coli) 
 are probably seldom lacking. No serious attempt 
 has yet been made to study these mild forms 
 of arrested growth of intestinal origin, but 
 there is reason to think that at least some of 
 
78 INFANTILISM 
 
 these cases are allied to the severer type both 
 in etiology and pathology. 
 
 The Sequelae ai!Td Peognosis of Intestinal 
 
 Infantilism 
 I have not at command the data from a 
 sufficient number of instances of infantilism to 
 permit even an approach to generalization as 
 to the outcome of the disease. Only the patient 
 study of many cases through extended periods 
 of time and under well understood conditions 
 will yield the facts necessary for safe general- 
 ization. Nevertheless there are some obvious 
 commentaries which are justified by limited 
 experience. Of these by far the most impor- 
 tant is that in general the outlook is very 
 largely determined by the nature of the care 
 which the patient can obtain. Neglect means 
 deterioration into a state of extreme involution, 
 ending either in death (from intercurrent 
 disease or exhaustion) or in a relatively fixed 
 state of under-development little ameliorated by 
 any course of treatment at present known to 
 us. Intelligent and careful treatment, on the 
 other hand, leads to at least some degree of 
 improvement and perhaps to a very striking 
 betterment in nutrition and growth. Whether 
 a child whose arrest of growth has lasted for 
 five years, leaving him at the end of that time 
 50 per cent, below the average weight for this 
 
INFANTILISM 79 
 
 age, can under any conditions be expected to 
 develop into a man of average size, I am 
 unable to say. That our methods of treating 
 such cases fall short of the ideal is not im- 
 probable, and it may be that in children with 
 extreme but uncomplicated infantilism the out- 
 look for progress toward normal development 
 would be considerably better than we can at 
 present assert it to be, assuming that further 
 improved methods should come into use. 
 
 From the cases observed by Dr. Holt and 
 myself we have been instructed in several 
 particulars relating to sequelae and complica- 
 tions. Case V of our group developed a high 
 grade of simple anaemia which lasted several 
 years; yet after so lasting the child began to 
 grow in a promising manner despite the fact 
 that the anaemia still persists. The fact is 
 instructive as pointing to a dissociation of the 
 causes of the anaemia and the causes of the 
 retarded growth. No opinion can be ventured 
 as to the ultimate influence of the anaemic 
 state on the prognosis. In Case IV there was 
 an early and marked anaemia, but this did 
 not persist for more than a year, and as the 
 nutritional conditions improved the haemoglobin 
 rose from 35 to 61 per cent. In Case III 
 anaemia was only moderate, and during the 
 past two years there has been a gradual and 
 fairly satisfactory growth of the body. In 
 
80 INFANTILISM 
 
 Case II the improvement was very slow 
 through many years, but recently has become 
 remarkably rapid. With this rapid improve- 
 ment in growth some errors were made in 
 diet owing to a desire to push the gain by 
 full feeding. This experiment resulted disas- 
 trously in that it was soon followed by grand 
 mal epileptiform seizures, coming at short 
 intervals. Two years previous to this out- 
 break the child had had a few short seizures 
 of loss of consciousness without motor symp- 
 toms, and it now appears that these were 
 probably examples of petit mal. The onset of 
 grand mal seizures was attended here by a 
 very considerable rise in the indications of 
 intestinal putrefaction. I believe this case to 
 be a clearly defined and unimpeachable instance 
 of epilepsy developing as the result of cerebral 
 irritative intoxication from putrefactive prod- 
 ucts absorbed from the intestine. I have long 
 maintained that such cases occasionally arise, 
 but it is seldom that the antecedent conditions 
 are so well known to the physician as in this 
 case. This case is thus in my judgment a 
 singularly definite example of epilepsy arising 
 from intestinal intoxication in a child with a 
 nervous system rendered unstable by long intox- 
 ication of milder intensity than that needed to 
 induce grand mal seizures. In this instance a 
 rapid improvement set in with the institution 
 
INFANTILISM 81 
 
 of very careful regulation of diet and environ- 
 ment, but the ultimate outcome of the epilepti- 
 form state cannot be predicted. 
 
 The Theeapeutic Modification of the Bac- 
 TEKiAL. Conditions in Intestinal Infantilism 
 
 The central aim in the treatment of in- 
 fantilism is the modification of the bacterial 
 flora of the intestine. There is no evidence 
 that any therapeutic measures which do not 
 exert some direct or indirect influence in this 
 direction can be truly effective. To bring 
 about an amelioration of the bacterial condi- 
 tions in the intestine is a task of the utmost 
 difficulty, calling for an understanding of 
 principles, close attention to details, and pains- 
 taking care during a long period of time. In 
 some important aspects there is a close similarity 
 between the therapeutic requirements of intes- 
 tinal infantilism and those of the extreme 
 forms of chronic saccharo-butyric putrefaction 
 associated with an infection by bacteria of the 
 B. perfringens and streptococcus types. In 
 both we have to deal with a chronic entero- 
 colitis leading to failure in nutrition; in both 
 the element of intoxication is prominent, and 
 in both apparently trivial errors in diet are 
 followed by temporary setbacks. There are, 
 however, two highly significant differences be- 
 tween these types of infection, and both of 
 
 6 
 
82 INFANTILISM 
 
 these differences make for a more favorable 
 outlook in the case of the disease of childhood 
 — at least so far as the prospect of life is 
 concerned. One of these differences lies in 
 the nature of the pathological process, the 
 other in the circumstances attendant on child- 
 hood. The process in extreme saccharo-butyric 
 putrefaction is one of very long standing, and 
 probably leads to an impairment in the ability 
 of the mucosa to regenerate adequately the 
 excessively desquamated epithelium; it is ques- 
 tionable whether in infantilism the damage to 
 the mucosa is ever so profound as this. And 
 as regards the attendant circumstances of 
 childhood there is the essential fact that the 
 patient's age makes it possible to control with 
 precision the conditions of his life, whereas in 
 the extreme saccharo-butyric infections of adults 
 the freedom of action possessed by the indi- 
 vidual sooner or later leads him to make mis- 
 takes in his habits of life which lead to dangerous 
 relapses and ultimately to death. 
 
 What I shall here write about the treatment 
 of infantilism is based on the study of only 
 a small number of patients, and for this 
 reason, if for no other, will be incomplete. 
 This, however, does not deter me from offer- 
 ing some definite advice in regard to treat- 
 ment, for I believe that the experience gained 
 from the highly detailed study of a few patients 
 
INFANTILISM 83 
 
 will prove useful in the handling of this not 
 very uncommon condition, by those whose 
 opportunities for study have been less good 
 than mine. I shall arrange what I have to 
 say under the following headings: 
 
 General Hygienic Measures. 
 
 Dietetic Measures. 
 
 Pharmacological Measures. 
 
 Genekal Hygienic Measures 
 In the care of the subjects of infantilism the 
 hygiene of environment is of much importance 
 in reinforcing the effects of more specific 
 therapeutic measures. Two environmental re- 
 quirements stand out sharply and require the 
 consideration of the physician; first, a tem- 
 perate, equable and fairly sunny climate, and, 
 secondly, soothing human surroundings and 
 limited companionship. In all marked states 
 of infantilism the circulation is impaired and 
 the loss of animal heat is a severe tax to the 
 organism if there be prolonged exposure to 
 cold. In Case II the cold months of winter 
 were spent in a mild climate, which made it 
 possible to be out of doors a large part of 
 the day without excessive radiation of heat, 
 and there is good reason to think this pre- 
 caution was a material help in paving the way 
 for the subsequent improvement in nutrition. 
 In Case I it was impracticable to send the 
 
84 INFANTILISM 
 
 child to a warm climate in winter, and the 
 exposure to the winter's cold in New York 
 seemed clearly an obstacle to quick improve- 
 ment in nutrition. Except on the most in- 
 clement days the child should be out of doors 
 for a time despite the drain on animal heat, 
 for the alternative of remaining indoors is 
 still more objectionable. It is especially in the 
 sununer months that these children tend to do 
 badly. This is probably attributable mainly to 
 the difficulty in securing food sufficiently free 
 from objectionable bacteria during the hot 
 months, but is doubtless due in part to the 
 prostrating effects of prolonged exposure to a 
 high temperature. By taking great care it is 
 possible to avoid these common summer dis- 
 turbances of digestion connected with hot 
 weather, and this is in itself a very important 
 advantage. Even in selecting a mild winter 
 climate it is necessary to balance the advan- 
 tages of mild weather against the dangers that 
 arise from the inability to secure clean food. 
 
 It is essential that the attendant should be 
 a person of more than ordinary tact, gentle- 
 ness, good sense, patience and cheerfulness, 
 for the subject of infantilism is often irritable, 
 peevish and emotionally depressed and depress- 
 ing. The patient should see visitors only 
 seldom and only for a few minutes at a time. 
 If permitted to play with other children he 
 
INFANTILISM 85 
 
 should be with only one child at a time. The 
 intoxication leads to so much physical and 
 mental languor that it is inadvisable to attempt 
 to teach these children in the ordinary ways. 
 They can only be coaxed, very tactfully and 
 cautiously, into an interest in numbers, letters 
 and objects of various colors and shapes. 
 Prolonged attention is undesirable and leads 
 to extreme fatigue. These children are des- 
 tined to be much retarded in the acquirement 
 of knowledge, but as their natural intelligence 
 is not distinctly impaired they can develop 
 satisfactorily in a few directions. The illness 
 of these unfortunate children is not without 
 the compensation that they cannot be forced 
 into the stupid conventional pleasures so com- 
 monly provided for children. To this and to 
 the opportunity for quiet reflection I am dis- 
 posed to attribute the noticeable thoughtfulness 
 of most of the subjects of infantilism. When 
 the stage has been reached in which there is 
 a steady gain in weight, the periods of teach- 
 ing can be increased. I believe that the ulti- 
 mate mental growth of these children will be 
 good in cases that are carefully managed. 
 One patient of extreme type whom I have 
 had under observation from time to time for 
 ten years is now married and in good health. 
 She is a well educated and cultivated person, 
 but undersized. 
 
86 INFANTILISM 
 
 The patients must be encouraged to take 
 exercise daily, even if it causes fatigue. In 
 experiments which I made on healthy young 
 men who were intoxicated experimentally with 
 indol, it was found that active exercise dis- 
 tinctly aided the subjects in overcoming the 
 sense of great fatigue from which they suf- 
 fered. This is probably to be attributed to 
 the improved opportunity for oxidation which 
 exercise affords. I have noticed the same 
 effect of exercise on several adults with pre- 
 sumably indolic intoxication. But it is easy 
 to overdo in exercise for these retarded chil- 
 dren, and it is important to avoid excessive 
 fatigue as it apparently acts unfavorably on 
 the digestive processes. 
 
 Dietetic Measuees 
 Dietetic measures are the keystone of the 
 therapeutic arch in infantilism. Without the 
 closest attention to them there is little chance 
 of beneficially modifying the intestinal pro- 
 cesses which underlie the affection. Cautious 
 and prolonged experimentation is necessary to 
 obtain the best dietetic conditions for each 
 patient. The problem varies somewhat in dif- 
 ferent individuals and may vary for the same 
 patient from time to time. It may be stated 
 in the following general terms: to secure the 
 absorption of foodstuffs adequate in quality 
 
INFANTILISM 87 
 
 and quantity for the reasonably rapid growth 
 of skeleton, muscles, blood and nervous sys- 
 tem, with as little waste as possible from non- 
 absorption and as little opportunity as possible 
 for excessive putrefaction. If the absorption 
 of foodstuffs be indeed adequate for the growth 
 of bones, muscles and nervous system it is 
 probable that it will suffice also for the growth 
 of viscera and the production of sufficient fat. 
 It is necessary to discuss separately the dif- 
 ferent types of foodstuffs in their relation to 
 infantilism before considering any special diet- 
 ary as a whole. 
 
 The Carbohydrates, It has been already 
 mentioned that the carbohydrates are the 
 obvious and fruitful cause of derangements of 
 digestion that are clinically determinable, espe- 
 cially diarrhoea and flatulence. Probably by 
 far the greater number of acute disturbances 
 of digestion in the course of infantilism are 
 referable to errors relating to the carbohy- 
 drates. I deem it impossible at present to 
 speak with precision and fulness regarding the 
 relative merits and demerits of the various 
 carbohydrate foods with respect to infantilism. 
 From a considerable, but by no means ex- 
 haustive, experience with various carbohydrate 
 foods I have reached the conclusion that such 
 carbohydrate food as can be taken by these 
 patients is best given in the form of starch- 
 
88 INFANTILISM 
 
 holding preparations, and not in any ordinary 
 form of sugar. I have seen the best results 
 from the use of well-boiled rice or arrow- 
 root or cream of wheat, supplemented with a 
 partly dextrinized preparation such as the 
 Huntley and Palmer breakfast biscuits. Milk 
 sugar, in the proportions in which it occurs in 
 milk, may also be well taken, especially when 
 a distinct improvement in nutrition is already 
 in progress. I suspect that milk sugar is 
 better tolerated than an isodynamic quantity 
 of glucose or saccharose, but have no proof 
 that this is so. Foods which contain an abun- 
 dance of soluble carbohydrates, as Mellin's 
 food or malted milk, cannot be recommended. 
 Perhaps the most objectionable of all ordinary 
 natural carbohydrate foods is potato, which 
 can generally be counted on to occasion flatu- 
 lence. The reason for this is not at present 
 clear. In the severest forms of infantilism 
 the total quantity of carbohydrates which can 
 be tolerated may be very small, and it may 
 be possible to supply less than one fifth of 
 the calories required by the organism (instead 
 of nearly one half as in health) in this way. 
 An especial sensitiveness to carbohydrates may 
 be developed during febrile attacks (as those 
 due to taking cold), and it is then best to 
 withdraw them entirely for a few days. 
 
INFANTILISM 89 
 
 In every case of infantilism one of the most 
 important and difficult tasks for the physician 
 is to determine how much carbohydrate food 
 his patient can utilize at a given time. The 
 amount which is appropriate at one time may 
 be less or more than can be tolerated at 
 another. Where the patient can take a small 
 quantity of carbohydrates it seems best to 
 give it divided in the several kinds. Thus at 
 one time in the day the child receives a 
 Huntley and Palmer breakfast biscuit with 
 minced beef or chicken or with beef juice; at 
 another time he receives a portion of boiled 
 rice with one or two ounces of milk, and at 
 still another time he receives a larger portion 
 of milk alone. It is unwise to concentrate the 
 carbohydrates at one period; thus milk, rice 
 and biscuit should not be given at one meal. 
 If the allotted carbohydrates appear to be well 
 tolerated (i.e, cause little or no flatulence, no 
 marked softening of the stools, no increase of 
 mucus and no increase of indican in the urine) 
 it may be cautiously increased in amount. If 
 the child has been receiving twenty grams of 
 boiled rice at a feeding, the amount should be 
 increased by five grams rather than by ten 
 grams until a point is reached at which it 
 appears, after a trial of several days, that the 
 increased amount is not well tolerated (i.e. 
 causes flatulence or abdominal discomfort or 
 
90 INFANTILISM 
 
 slight diarrhoea or increase of indican). It 
 may then be necessary to fall back to the 
 original amount of rice, or it may be that a 
 portion of the attempted increase can be main- 
 tained with advantage.^ 
 
 In every experiment made with a view to 
 establishing a diet the following cardinal rnle 
 should be observed: the physician should vary 
 only one article of diet at a time. If more 
 than one article of diet be varied at once the 
 experiment will lack scientific precision and 
 the best results cannot be attained. When a 
 tentative diet is tried it should be so made 
 up as to permit a definite gain in knowledge 
 from intelligent successive variations in the 
 amounts of the various foodstuffs employed. 
 This careful and painstaking experimentation 
 calls for much patience, but is rewarded by 
 the fact that it leads to a gain in definite 
 information. Haphazard, quick variations of 
 
 ^I have made a fe-w observations on the use of diastatic fer- 
 ments as an aid in the digestion of carbohydrates, but such 
 experience as I have had has been too unsystematic to permit any 
 definite inferences as to the value of such enzymes. I doubt very 
 much if their use materially influences the course of the affection 
 or makes it possible to increase the carbohydrate food more rapidly 
 than would otherwise be the case. This latter point, which is one 
 of considerable practical importance, must be settled by well- 
 planned experimental methods. In the meantime I think it well 
 to give the patient the benefit of the doubt by employing small 
 quantities of an active diastatic ferment, prepared in the dry 
 form, as, for example, taka- diastase. The powder should be well 
 mixed with the food at body temperature. 
 
INFANTILISM 91 
 
 several factors simultaneously may accidentally 
 give good results at times; yet in the long 
 run there is a saving of time, for all con- 
 cerned, if the physician takes the trouble to 
 proceed more deliberately with the establish- 
 ment of the dietetic treatment. 
 
 The Fats, The intestinal infections asso- 
 ciated with infantilism call for the most care- 
 ful regulation of the fat intake. This intake 
 cannot be prescribed in any fixed and special 
 terms, but only on the basis of a general 
 principle. The principle to be obeyed is the 
 following: give only so much fat as will in 
 large measure be resorbed. The stools should 
 not be permitted to continue voluminous and 
 excessively fatty. The objections to this con- 
 tinual fat loss are mainly two — the unnecessary 
 and harmful loss of calcium and magnesium 
 soaps and the interference with digestion and 
 absorption which is occasioned by the presence 
 of fatty material, the latter tending to favor 
 intestinal putrefaction. From the fact that cal- 
 cium and magnesium are constantly lost as 
 soaps it does not necessarily follow that if we 
 prevent the alkali earth metals from being 
 saponified we shall prevent them from being 
 lost in the feces. We are still too ignorant 
 of the conditions under which these elements 
 are absorbed to form a judgment on this point. 
 If we may judge from the case of healthy 
 
92 INFANTILISM 
 
 children already cited, it is not unfair to 
 assume that positive balances in calcium and 
 magnesium are more likely to be attained by 
 the reduction of the milk fat than through 
 permitting the free use of milk fat. While I 
 am not sure that we are justified in trans- 
 ferring these results on nearly healthy infants 
 to the absorption in our cases of infantilism, 
 it is obvious that at least there is a possibility 
 of securing improved absorption if we check 
 the persistent loss of soaps with the stools. 
 Much more study is necessary to show us 
 whether the alkali earth metals are normally 
 absorbed in an important degree as soaps of 
 these elements. Probably this is one of the 
 most important ways of absorption for these 
 metals and we should strive not to prevent 
 saponification but to secure good soap absorption. 
 In any case of infantilism in which there is 
 a continuous excessive loss of fat, the intake 
 of fatty food should be gradually lowered 
 until the feces no longer show the indications 
 of such loss. When the level has been reached 
 at which the movements are no longer homo- 
 geneous, but are made up of a conglomerate 
 of small individual masses, the fat loss will 
 not be excessive. From time to time the fat 
 may be somewhat increased, for if the progress 
 of the affection is favorable there will be a 
 
INFANTILISM 93 
 
 gradual increase in the power of absorbing 
 fat. 
 
 In Case I the relation between the intake 
 of fat and the loss of fat in the feces was 
 carefully determined by Dr. Wakeman for a 
 period of eleven days, during which there 
 existed an insignificant positive calcium bal- 
 ance, a very small retention of nitrogen and 
 an essentially stationary weight. The daily 
 intake of fat (neutral fats, fatty acids and 
 soaps) amounted to 38.28 grams, the intake 
 for the period having been 382.8 grams.^ Dur- 
 ing the same period there was a daily loss of 
 fats equal to 5.56 grams, or 55.6 grams for 
 the period. The fat loss is here equivalent to 
 14.5 per cent, of the ingested fat. This is dis- 
 tinctly in excess of the normal fat loss, but 
 does not represent extremely low fat absorp- 
 tion. The fat excess was sufficient to prevent 
 the conglomeration of the feces. Two months 
 before this period the absorption of fat was 
 much less good with the same fat intake, for 
 it reached at this time as high as 22 per cent., 
 and even 25 per cent., of the ingested fat. 
 
 * These fats were distributed as follows : 
 
 Neutral fats 66.55 per cent. 
 
 Fatty acids 16.49 per cent. 
 
 Soaps 16.96 per cent. 
 
 The figure here given for soaps is doubtless too high, as other 
 substances than fat must have found their way into the ether 
 extract. 
 
94 INFANTILISM 
 
 The fat loss was even larger tlian this at the 
 time when the patient first came nnder ob- 
 servation, and on several subsequent occasions. 
 On these occasions the fat intake was decreased 
 to meet the poor absorption. Although the 
 fat loss was as great as 14.2 per cent, so 
 recently as three months ago, in Case I, I did 
 not at this time make any further reduction 
 in fat, as there was evidence of a slowly in- 
 creasing power of absorption. Eecently (June 1, 
 1908) I deemed it best to reduce the fat to 
 25 grams daily, and on this basis an entirely 
 satisfactory absorption was secured. It should 
 be noted that the relatively good fat absorp- 
 tion of recent periods in this patient does not 
 represent the actual state of absorption until 
 a period of general symptomatic improvement 
 (without considerable gain in weight, though 
 a forerunner to such gain) had set in. 
 
 The Proteins. On the use of the proteins 
 in infantilism I have not as yet been able to 
 obtain much specific information, as oppor- 
 tunities for thorough investigation of the effects 
 of different types of proteins have been in- 
 adequate. In children under three years of 
 age it is probably good practice to give the 
 greater part if not all the proteins of the 
 food as milk proteins. The conditions of 
 digestion are apt to be such in infantilism 
 that eggs are not well tolerated, but there is 
 
INFANTILISM 95 
 
 no evidence that this is due to an intolerance 
 of egg albumin, but rather that it is due to 
 an intolerance for the constituents of the yolk. 
 The question of the use of meat is one that 
 comes up in every case in children over three 
 years of age. In Cases I and II small quan- 
 tities of meat were permitted during long 
 periods of time as part of the protein food. 
 There was no evidence of any detrimental 
 effects from the cautious use of meat. On the 
 other hand, there is also no positive evidence 
 that the use of meat might not have been 
 dispensed with, through the substitution of 
 milk proteins. I have not been able to satisfy 
 myself either in Case I or Case II that the 
 cautious use of minced beef or minced chicken 
 once daily has tended to cause greater putre- 
 factive decomposition than was the case where 
 milk proteins alone were used. But in both 
 these cases there were periods when meat 
 was allowed in excessive amounts, as indicated 
 by symptoms of intoxication and unnecessarily 
 abundant putrefactive products in the urine. 
 A consideration which has had some influence 
 in determining the use of meat has been the 
 presence of iron in such food. The dietary 
 in cases of infantilism tends to be low in iron 
 and it has seemed desirable to make use of 
 some meat rather than to use milk as the 
 exclusive source of protein, but whether this 
 
96 INFANTILISM 
 
 has really been effective in helping to over- 
 come the anaemia nearly always present, it is 
 impossible to say. 
 
 It has already been mentioned that the 
 physician tends in the treatment of infantilism 
 to give an excess of protein owing mainly to 
 the difficulty in giving an adequate quantity of 
 carbohydrates and fats. I have myself tended 
 to make use of a greater quantity of protein 
 food than has perhaps been wise. The tend- 
 ency to give protein in relative excess was 
 constantly noted in both Case I and Case II. 
 It is only latterly that I have learned to re- 
 place in a measure the typical protein foods 
 by the least objectionable form of protein — 
 namely gelatin. 
 
 The Use of Gelatin, The use of gelatin as 
 a foodstuff in bacterial infections of the intes- 
 tinal tract has never received the attention it 
 deserves. The physician is not infrequently 
 confronted with a dietetic problem which con- 
 sists in endeavoring to maintain nutrition under 
 conditions where no combination of the ordi- 
 nary proteins with fats and carbohydrates 
 suffices to maintain a fair state of nutrition. 
 The difficulty which most frequently arises is 
 that every attempt to use carbohydrate food 
 is followed by fermentative disturbances of an 
 acute or subacute nature which delay recovery 
 or even favor an existing infection to the 
 
INFANTILISM 97 
 
 point of threatening life. The attempt to 
 replace the carbohydrates in large degree by 
 proteins is blocked by the serious difficulty 
 that all the ordinary proteins, when given in 
 amounts distinctly in excess of the habitual 
 quantities, afford material for putrefactive de- 
 compositions which it is necessary to restrict. 
 A great desideratum, therefore, is a food 
 which, while readily undergoing absorption, 
 shall furnish a supply of caloric energy and 
 which at the same time shall be exempt from 
 ordinary fermentative decomposition. Such a 
 food exists in gelatin. 
 
 The exact nature of all the cleavage prod- 
 ucts of gelatin is not at present known.^ Cer- 
 tain facts, however, stand out significantly. 
 One is that gelatin contains no tryptophan 
 nucleus and that it can hence yield neither 
 
 * The following figures (representing percentages) have been 
 obtained for the composition of gelatin: 
 
 Glycocoll 16.5 Glutaminic acid 0.88 
 
 Alanin 0.8 Aspartic acid 0.56 
 
 Aminovaleric acid 1.0 Serin 0.4 
 
 Leucin 2.1 Lysin 2.75 
 
 Prolin 5.2 Arginin 7.62 
 
 Phenylalanin 0.4 Histidin 0.40 
 
 These figures have been obtained by Emil Fischer, P. A. Levene 
 and E. H. Aders: Ueber die Hydrolyse des Leims. Zeitschr. f. 
 physiol. Chemie, XXXV, p. 70, 1902. See also Emil Fischer and 
 E. Abderhalden: Notizen iiber die Hydrolyse von Proteinstoffen, 
 Zeitschr. f. physiol. Chemie, XLII, p. 540, 1904. 
 
 The absence of cystin from gelatin is noteworthy, though it is 
 doubtful if it Dossesses any bearing on its use in the present 
 connection. 
 7 
 
98 INFANTILISM 
 
 indol nor skatol nor indolacetic acid nor indol- 
 propionic acid. This fact makes it evident that 
 no decomposition of gelatin that can occur 
 within the intestinal tract can directly con- 
 tribute to an intoxication in which the fore- 
 going substances are concerned. A second 
 peculiarity of almost equal importance is the 
 fact that gelatin contains no tyro sin nucleus, 
 even the relatively impure gelatin which is 
 sold for cooking purposes giving only a slight 
 and questionable reaction with Millon's reagent. 
 The absence of the tyro sin nucleus in gelatin 
 renders it impossible for paraoxyphenylacetic 
 acid or paraoxyphenylpropionic acid to be formed 
 in the course of bacterial decomposition of 
 gelatin. In many chronic bacterial infections 
 of the digestive tract paraoxyphenylacetic acid 
 finds its way into the urine in excessive amounts. 
 Similarly phenol arises in large part, perhaps 
 exclusively, from the decomposition of tyro sin 
 in the intestinal tract. It is thus evident that 
 in any case of infantilism in which there is 
 the usual evidence of excessive putrefaction, 
 gelatin may be employed as a food without 
 incurring any risk of increasing intestinal 
 putrefaction in the directions just mentioned. 
 
 While gelatin does not contain either the 
 tryptophan nucleus or the tyro sin nucleus, it 
 gives a considerable yield of phenylalanin. It 
 is possible that through oxidation of phenyl- 
 
INFANTILISM 99 
 
 alanin in the body phenolic derivatives may- 
 be produced in slight amount (through hydrox- 
 ilation of the aromatic nucleus), but the facts 
 at the present time known relating to this 
 point are opposed to this view. 
 
 Among the most important cleavage products 
 of gelatin is glycocoll or amidoacetic acid. It 
 has been recovered to the extent of 16% per 
 cent, of the original gelatin. Alanin is present 
 in considerably smaller quantities. Leucin is 
 also a not unimj^ortant cleavage product. 
 These monamino acids, together with the 
 diamino acids, go to furnish a large part of 
 the caloric value of gelatin. In this respect 
 gelatin resembles other proteids. I do not 
 know whether entirely satisfactory studies have 
 been made of the caloric potential of gelatin 
 furnished to the human body, but it may 
 probably be regarded as not very different 
 from that of protein in general, namely about 
 4.3 calories for one gram of gelatin. Assum- 
 ing that the caloric value of gelatin is about 
 four calories per gram, it is seen that 30 
 grams of gelatin (about 1 ounce) will yield 
 the organism in the neighborhood of 120 
 calories. An ounce of gelatin can be taken 
 without difficulty in 24 hours in the food of 
 any child weighing not less than 28 to 30 
 pounds. This quantity of gelatin cannot, of 
 course, be given at one meal, but may be so 
 
100 INFANTILISM 
 
 scattered through the feedings for the day as 
 to be easily introduced. It is obvious, how- 
 ever, that if owing to the practically complete 
 resorption of this quantity of gelatin, a child 
 receives 120 calories, this is an extremely im- 
 portant contribution to the entire caloric energy 
 of the organism, since it may amount to from 
 10 to 12 or even 15 per cent, of the total re- 
 quirements of the organism. It requires no 
 argument to show that the difference between 
 a child's being able to avail itself of 30 grams 
 of gelatin daily and not being able to avail 
 itself of it may make extremely important 
 differences in its nutritional record. In younger 
 children — children one or two years of age — 
 smaller quantities of gelatin may advantageously 
 be employed. It is not difficult to introduce 
 from 10 to 15 grams daily of Cox's gelatin^ 
 into the milk or fermented milk of a child 
 suffering from an acute intestinal infection. 
 
 On the theoretical basis which has just been 
 brought out, we should expect to obtain cer- 
 tain results in practice. We may stop for a 
 moment to inquire to what extent the results 
 of practice have justified the use of gelatin in 
 the food. Unfortunately I have no studies so 
 conducted as to enable me to make an un- 
 
 * This is the form of gelatin which I have commonly employed. 
 It may be mentioned that Dr. Wakeman found it to contain 0.74 
 per cent, of calcium oxide and a trace of magnesium. 
 
INFANTILISM 101 
 
 equivocal inference that a gain in weight has 
 been exclusively attributable to the addition 
 of gelatin to the dietary, but I have observa- 
 tions on several carefully studied cases which 
 make me think this probable. The case in 
 which the evidence for this is most satisfac- 
 tory is that of a child of two years with 
 chronic infection with B. hifidus and B. in- 
 fantilis. Here for a time the food consisted 
 exclusively of kumyss, as all effort to give 
 carbohydrate food caused exacerbations of 
 diarrhoea. On this diet it was impossible to 
 secure a gain in weight. The addition of 
 15 grams of gelatin daily was followed by a 
 gain in weight, which ceased when the gelatin 
 was stopped and again recurred when it was 
 once more added to the kumyss. And it may 
 be remarked in passing that such a combina- 
 tion of a fermented milk (thus largely ridding 
 it from sugar) with gelatin seems to constitute 
 the most appropriate treatment in some acute 
 and subacute ileo-colic infections of childhood 
 in which the intolerance for carbohydrates 
 occasions a serious loss in weight and blocks 
 the path to recovery. It is perhaps worth 
 mentioning in this connection that both B. 
 hifidus and B, infantilis may be regarded as 
 practically uncultivable on ordinary gelatin 
 media. We may reasonably ask ourselves if 
 one of the advantages of gelatin as a food 
 
102 INFANTILISM 
 
 may not be due in part to the failure of these 
 and some other acidophile bacteria to grow on 
 this type of protein. 
 
 It is somewhat helpful in formulating our 
 indications for the use of gelatin to think of 
 this food in its various substituent relations 
 to the different types of foodstuffs. Given a 
 full protein ration, it is probably true that 
 either the carbohydrates alone or the fats 
 alone may be substituted wholly by gelatin, 
 perhaps not indefinitely, but for a considerable 
 time. On the other hand, given average normal 
 rations of fats and carbohydrates, the typical 
 proteins may be replaced by gelatin, not 
 wholly, be it noted, but only in part. To what 
 extent these proteins can be substituted by 
 gelatin has been much discussed and is still 
 the subject of experimental inquiry. Any re- 
 liable general statement on this important point 
 is at present impossible. Murlin^ made an 
 experiment on a man of 70 kilograms net 
 weight and receiving a diet holding ten per 
 cent, more than the fasting requirement of 
 nitrogen and 51 calories per kilogram of 
 potential energy, of which fully two thirds were 
 supplied by carbohydrates. Under these con- 
 ditions it was possible to supply 63 per cent, 
 of the total nitrogen as gelatin for a period 
 
 ***The Nutritive Value of Gelatin/* I. Amer. Jour, of 
 Fhysiol., XIX, No. ill, p. 285 
 
INFANTILISM 103 
 
 of two days and still to maintain a small 
 retention of nitrogen.^ I do not know any 
 pathological condition in which I would recom- 
 mend the therapeutic use of gelatin in quan- 
 tities and proportions even approximating those 
 used in the experiment just mentioned. A 
 certain disgust arises from the taking of large 
 quantities of gelatin, and this in itself limits 
 its use. It is doubtful if most adults can 
 tolerate more than 50 grams of gelatin daily 
 for a considerable period, and many cannot 
 take more than 30 or 40 grams without de- 
 veloping a dislike. Thus we are in general 
 limited in using gelatin to about 10 or 15 per 
 cent, of the total caloric requirements. In 
 using this proportion of gelatin as part of the 
 dietary of a patient with infantilism it is always 
 desirable to formulate a clear conception as 
 to the reason for which it is given in the 
 individual case — whether mainly to replace fats, 
 
 ^ It appears that the high percentage of glycocoll in gelatin 
 may be an important factor in this retention of nitrogen, which 
 is however only temporary. This temporary character of the 
 glycocoll nitrogen retention may help to explain the inadequacy 
 of gelatin as a substitute for typical protein food. See Murlin, 
 * ' The Nutritive Value of Gelatin, ' ' II. Amer. Jour. Physiol., XX, 
 No. i, p. 234. 
 
 If one represents the protein metabolism in starvation by one 
 the use of about the same quantity of gelatin reduces the protein 
 waste of the body 23 per cent. (Kirchmann: Zeitschr. f. Biol., 
 XL, p. 54, 1900.) 
 
 In sparing protein small quantities of gelatin appear to have 
 about as much effect as larger amounts. 
 
104 INFANTILISM 
 
 carbohydrates or proteins. In a case where 
 carbohydrates and fats are tolerated in fair 
 amount without disturbance the use of gelatin 
 should be regarded as a means of reducing 
 the requirements of ordinary protein food with 
 a view to limiting intestinal putrefaction based 
 on the breakdown of tryptophan and tyro sin. 
 On the other hand, where carbohydrates must 
 be used sparingly or fats are badly resorbed, 
 or where both these conditions prevail, gelatin 
 should be utilized with a view to replacing in 
 part either or both these foodstuffs, but with- 
 out reducing the ordinary protein nitrogen 
 below a fair average requirement. 
 
 Thus we may summarize as follows the 
 qualities for which gelatin can be recommended 
 as a foodstuff in cases of infantilism: (1) a 
 considerable degree of caloric value, (2) as a 
 partial substitute for carbohydrates, fats or 
 common proteins, (3) as incapable of under- 
 going putrefaction based on the presence of 
 the tryptophan or tyro sin molecules, (4) on 
 account of prompt absorption, and (5) owing 
 to its inability to support certain specific 
 forms of bacterial life associated with this 
 disease. 
 
 Finally, in reference to diet, the following 
 example may be given. The following dietary 
 was successfully employed in Case I during 
 several critical months, that is, while the 
 
INFANTILISM 105 
 
 transition was being made frona a condition 
 of stationary weight to one of uninterrupted 
 gains in weight. This dietary was subsequently 
 modified by reducing its content of fat by the 
 addition of small quantities of whiskey and 
 by some minor changes. 
 
 Brealcfast, 6:30 — 7:00 A. M. 6 ounces milk with gelatin 
 
 1 Huntley & Palmer biscuit 
 Lunch, 9:30 A. M. 6 ounces milk with gelatin 
 
 2 Huntley & Palmer biscuits 
 Dinner, 1:30 p. m. Scraped beef and juice (one 
 
 tablespoonful of each) 
 1 tablespoonful vegetable* 
 1 tablespoonful rice 
 
 1 Huntley & Palmer biscuit 
 Afternoon Lunch, 4:30 P. m. 6 ounces broth with gelatin 
 Supper, 6:30 p. M. 1 tablespoonful rice 
 
 6 ounces milk with gelatin 
 
 2 Huntley & Palmer biscuits 
 Total quantity milk daily, 18 ounces 
 
 Total broth daily (beef tea, chicken or mutton broth), 6 ounces 
 
 Total rice daily, 2 tablespoonfuls 
 
 Total Huntley & Palmer biscuits daily, 6 
 
 Total gelatin daily (Cox's), 1 box (about 1 ounce) 
 
 Beef juice from 1 lb. round of beef, daily 
 
 I have calculated that the caloric value of this dietary la 
 
 approximately as follows: 
 
 Fat 342 calories 
 
 Proteins 205 calories 
 
 Gelatin 120 calories 
 
 Carbohydrates 480 calories 
 
 1147 calories 
 *The vegetables used were spinach, string beans, carrots and 
 peas. It was necessary at times to eliminate these vegetables 
 entirely from the dietary for short periods of time, as they act in 
 an irritative way. 
 
 These figures are based on the assumption 
 that the patient got in this dietary 38 grams 
 
106 INFANTILISM 
 
 of fat, 8 grams nitrogen in the form of pro- 
 teins, other than gelatin, 30 grams gelatin, 27 
 grams milk sugar, and from 90 to 100 grams 
 of starch and dextrine, in the form of Huntley 
 & Palmer biscuits, rice, vegetables, broths, etc. 
 The assumption that the caloric value of this 
 diet is about 1150 calories cannot be far from 
 the truth. By changes subsequently made and 
 mentioned above, this caloric value was re- 
 duced to about 1100 calories. 
 
 I am inclined to think the above dietary 
 might be criticized as containing an excess of 
 proteins. The excess is, however, much less 
 now than when the patient first came under 
 observation, for it is obvious that an excess 
 of proteins for a child weighing 25 pounds is 
 considerably less excessive for a child weighing 
 31 pounds. I am, however, disposed to think 
 that the protein is still from 20 to 25 per 
 cent, in excess of an ideal diet, but I have 
 not reduced it simply because the patient is 
 doing so well that I am disposed to let well 
 enough alone. I shall, however, consider it 
 proper to make a slow reduction in the pro- 
 teins if I cannot otherwise satisfactorily reduce 
 the quantity of putrefactive products in the 
 urine. 
 
 Pharmacological Measures 
 
 Although pharmacological measures do not 
 have a large share in the treatment of intes- 
 
INFANTILISM 107 
 
 tinal infantilism there are a few topics which 
 require at least a mention in this connection. 
 These are the use of iron, the use of alcohol, 
 the employment of cathartic and antiseptic 
 medicaments and the administration of calcium 
 and magnesium salts and of phosphoric acid. 
 I believe that in general iron preparations are 
 not well tolerated by the stomachs of these 
 patients and that it is better to avoid their 
 use. It is also to be questioned whether iron 
 is helpful for the amelioration of the asso- 
 ciated anaemia. It is certain that the anaemia 
 may greatly improve as the result of the insti- 
 tution of a suitable diet, without the aid of 
 drugs. The objection to the use of iron appears 
 to me extremely well defined during the period 
 of absolute arrest of growth. When growth 
 has begun anew and is progressing in a satis- 
 factory way iron preparations may be em- 
 ployed with benefit to a persistent anaemia, and 
 even without noticeable detrimental effect on 
 digestion. It is desirable to employ the least 
 irritant preparations and to desist promptly 
 when increased digestive disturbances occur. 
 
 The administration of from 5 c.c. to 10 c.c. 
 of whiskey with the milk, kumyss or broth 
 may prove a helpful measure where the hands 
 and feet are persistently cold and the peri- 
 pheral circulation is feeble. In warm weather 
 the alcohol should be omitted except, perhaps, 
 
108 INFANTILISM 
 
 in the morning. The doses just mentioned may 
 be repeated three or four times daily in some 
 instances. 
 
 As to the use of cathartics it is certain that 
 they should always be sparingly employed and 
 not frequently. It is not clear that they 
 accomplish any unmixed good. Small doses of 
 calomel may be used from time to time to 
 bring away the considerable quantities of 
 mucus which accumulate in the upper colon or 
 to bring away putrefactive products which have 
 been suspected to accumulate. The good that 
 is accomplished by such evacuations is com- 
 monly balanced in part by some prostrating 
 effect of the cathartic and the disturbance of 
 regular intestinal habits. I am disposed to 
 believe that the chief legitimate use of cathartics 
 arises when there has been an error of diet, 
 but as such errors are very largely avoidable, 
 the resort to cathartic medicaments should be 
 rare. Where the rapid diminution of putre- 
 faction is required, a quickly acting cathartic, 
 such as castor oil, is probably the most effective 
 remedy. I have little faith in the use of 
 intestinal antiseptics in the management of in- 
 fantilism and think we should avoid experi- 
 menting with them, at least until we get a 
 more rational basis for their use than at 
 present exists, and can feel assured that those 
 we try are harmless. Yet it is possible the 
 
INFANTILISM 109 
 
 future will teach us something about the rational 
 use of suitable antiseptics. 
 
 Where defective absorption of calcium and 
 magnesium is so conspicuous a feature as in 
 the processes underlying infantilism, it becomes 
 essential for us to inform ourselves fully as 
 to the conditions that promote the absorption 
 of salts of the alkali earths. At present our 
 knowledge on this important point is far from 
 satisfactory. What can we do to secure better 
 absorption of lime and magnesium salts? I 
 have already indicated my belief that those 
 conditions which mitigate the inflammatory state 
 of the small intestine are those that lead to 
 spontaneous improved absorption. But we may 
 not be able to wait patiently for this improve- 
 ment; we may feel obliged to do something 
 to secure a larger absorption of salts by offer- 
 ing the mucous membrane of the intestine a 
 larger or wider choice of alkali earth com- 
 pounds. Physicians frequently do in fact at- 
 tempt this. One way of so doing is by giving 
 the patient those salts which occur in the 
 bones, especially the phosphates and carbonates 
 of calcium and magnesium. As to the efficacy 
 of such attempts we know nothing definite, but 
 are warranted in suspecting that they are 
 largely futile. Since the feces contain an excess 
 of phosphates of the alkali earths in infantilism, 
 it is clear that the intestine must have chances 
 
110 INFANTILISM 
 
 to take up these salts, but fails to use them. 
 In healthy young dogs (and presumably in 
 children) the normal mucous membrane appar- 
 ently takes up inorganic tricalcium phosphate 
 as well as the calcium salts of milk.^ But 
 under the pathological conditions of infantilism 
 there is no reason to suppose that calcium 
 phosphate would have any different fate from 
 the calcium salts of the milk, which we know 
 to be imperfectly absorbed. Possibly one factor 
 in the defect of absorption is the failure of 
 the gastric juice to secrete hydrochloric acid 
 in adequate quantity, — a function which must 
 facilitate the absorption of calcium and mag- 
 nesium through the gradual formation of the 
 chlorides. However this may be in fact, we 
 shall do well to give our alkali earth salts in 
 soluble form. For this purpose the lactates of 
 calcium and magnesium may be used. From 
 20 to 40 milligrams of calcium lactate may be 
 given in aqueous solution in the food three 
 times daily without any detrimental effects. I 
 do not think we are justified in stating posi- 
 tively that this is a truly efficacious method of 
 securing an improved absorption in marked 
 cases of chronic enteritis, but it probably is 
 the best method at our disposal. It deserves 
 
 "Hans Aron and Karl Frese. Biochem. Zeitschr., IX, pp. 185- 
 207, 1908. 
 
INFANTILISM 111 
 
 to be experimentally worked out with the 
 utmost care. 
 
 Finally a word should be said on the admin- 
 istration of phosphoric acid. It is as important 
 to give phosphoric acid as to give calcium and 
 magnesium where the skeleton is retarded, but 
 the acid should be given separately from the 
 alkali earths in order to avoid the precipita- 
 tion of insoluble phosphates in the lumen of 
 the gut. Where the stomach is not sensitive 
 the acid sodium phosphate may be given, but 
 where this difficulty does exist the dilute phos- 
 phoric acid may be given before meals. 
 
 I shall not attempt to discuss here the use 
 of fermented milks because I do not at present 
 possess the necessary data. I am, however, 
 making experimental observations on this sub- 
 ject and hope before long to consider it 
 systematically. 
 
 It is believed that the foregoing considera- 
 tions regarding the pathology and management 
 of intestinal infantilism justify the conclusion 
 that the outlook for the amelioration of extreme 
 cases of this affection is in reality much better 
 than might be supposed from the results com- 
 monly obtained. The task of management is 
 at best a tedious one, but it is one which 
 repays deliberate effort, both in the variety of 
 scientific interest it affords and in the satis- 
 faction it yields through its practical successes. 
 
112 INFANTILISM 
 
 It is essential to realize clearly that rapid 
 recoveries are not to be expected under any 
 circumstances, after a state of true infantilism 
 has been developed. Moreover it will be a 
 help to recognize that the process of recovery 
 may very properly be regarded as made up of 
 two distinct stages. The first stage is one of 
 improved nervous and digestive conditions, with 
 signs of diminishing intoxication. In this stage 
 there is little or no gain in weight although 
 there may be a slight improvement in strength. 
 This stage may last from three months to a 
 year. At the end of this time the patient 
 begins to gain distinctly in weight as well as 
 to continue growing in strength, and when 
 this occurs an uninterrupted improvement may 
 be reasonably looked for. The important thing 
 is to understand that improved bacterial con- 
 ditions must precede by a considerable time a 
 significant gain in weight. 
 
 Conclusions 
 
 In view of the many details which it has 
 been necessary to incorporate in this study of 
 infantilism, it seems to me desirable to sum- 
 marize the chief conclusions which may be 
 drawn. 
 
 The following are the facts which I would 
 especially emphasize : 
 
INFANTILISM 113 
 
 1. There is a pathological state of child- 
 hood marked by a striking retardation in 
 growth of the skeleton, the muscles and the 
 various organs and associated with a chronic 
 intestinal infection characterized by the over- 
 growth and persistence of bacterial flora belong- 
 ing normally to the nursling period. To this 
 condition may be applied the term Intestinal 
 Infantilism. 
 
 2. The chief manifestations of intestinal 
 infantilism are arrest in the development of 
 the body; maintenance of good mental powers 
 and a fair development of the brain; marked 
 abdominal distension; a slight or moderate or 
 considerable degree of simple anaemia; the 
 rapid onset of physical and mental fatigue; 
 irregularities of intestinal digestion resulting 
 in frequent diarrhoeal seizures. Clinical fea- 
 tures of secondary importance are excessive 
 appetite, various minor signs of nervous in- 
 stability, a subnormal temperature, cold hands 
 and feet, and slight signs of rickets. 
 
 3. A study of the bacterial flora of the 
 intestinal tract in cases of infantilism shows 
 that the dominant bacteria of the upper and 
 lower colon and probably of the ileum are 
 largely Gram-positive organisms belonging to 
 the groups of organisms which may be desig- 
 nated as the Bacillus hifidus type, the Bacillus 
 infantilis type and the coccal type. It is 
 
114 INFANTILISM 
 
 impossible to say to what extent B, hifidus 
 and B, infantilis constitute the dominant types, 
 partly because of the difficulty in forming 
 reliable estimates of the quantitative relations 
 between these organisms, partly because they 
 vary in the same individual under different 
 conditions of diet and at different stages of 
 the disease. Noteworthy is the absence of 
 organisms of the B, coli and B, lactis aero- 
 genes type, not only from the feces but from 
 material collected through the use of a cathartic. 
 The dominance of these Gram-positive organ- 
 isms relates, however, only to infantilism in 
 its incipiency and at its height. 
 
 4. Among the urinary expressions of the 
 bacterial state associated with intestinal in- 
 fantilism is to be constantly found an excess 
 of putrefactive products of intestinal origin. 
 Prominent among these are indican and phenol 
 compounds. At times indolacetic acid is a 
 prominent putrefactive product. Sometimes the 
 aromatic oxyacids are much in excess. 
 
 5. Among the characteristic features relat- 
 ing to the intestinal contents are the presence 
 of neutral fat, fatty acids and soaps in marked 
 excess, pointing to impaired fat absorption. 
 With this condition is associated usually an 
 increase of mucus and other evidence of excessive 
 desquamation of epithelial elements. 
 
INFANTILISM 115 
 
 6. A careful study of the calcium and 
 magnesium balances in one of our cases (Case I) 
 showed failure of normal resorption of calcium 
 and magnesium, thus accounting for the failure 
 of skeletal growth. The amount of calcium 
 lost by the feces as soaps of calcium was 
 sufficient to have furnished a fair skeletal 
 growth had these calcium soaps been absorbed 
 instead of lost. It is a practical certainty that 
 the loss of calcium and magnesium through 
 the feces is the explanation of the impaired 
 skeletal growth in intestinal infantilism. 
 
 7. In the pathology of intestinal infantilism 
 two leading features call for explanation — 
 first, the retardation of growth; second, the 
 chronic intoxication. The retardation in growth 
 can apparently be explained on the basis of 
 the imperfect absorption of nutritive material 
 which can be demonstrated in these cases. 
 This impaired absorption of foodstuffs is 
 probably to be ascribed to a chronic inflamma- 
 tion located in the ileum and colon and asso- 
 ciated with the presence of abnormal forms of 
 bacteria. The intoxication which is so promi- 
 nent a feature of intestinal infantilism at its 
 height may confidently be ascribed to the action 
 of putrefactive products of intestinal origin 
 upon the central nervous system and muscles. 
 The exact relation of the abnormal bacterial 
 flora to the pathological conditions in the in- 
 
116 INFANTILISM 
 
 testine is not yet clear. The chief evidence in 
 favor of the causal relationship between the 
 phenomena of infantilism and the overgrowth 
 and persistence of flora of the nursling period, 
 especially B, hifidus, is fonnd in the changes 
 that occur during convalescence when these 
 organisms are gradually replaced by those of 
 the type appropriate to childhood. A further 
 evidence in the same direction is seen in the 
 great increase in the infantile types of bac- 
 teria during periods of relapse. There is no 
 evidence at present that intestinal infantilism 
 has any other origin than a purely intestinal 
 one. 
 
 8. There is a condition of acute or subacute 
 infection of the intestinal tract in early infancy 
 which leads to great losses in weight and 
 strength, the persistence of which is a probable 
 cause of chronic infantilism. This condition, 
 like chronic infantilism, is associated with the 
 dominance of Gram-positive microorganisms in 
 the intestinal tract, mainly those belonging to 
 the groups of B. hifidus and B, infantilis, or 
 certain other acidophile bacteria which are 
 closely related. The bacterial conditions of this 
 acute or subacute infection, if not identical 
 with those of chronic infantilism, are never- 
 theless very similar, and this is a further 
 reason for regarding the chronic condition as 
 
INFANTILISM 117 
 
 the outcome of the more acute state just 
 mentioned. 
 
 9. The state of intestinal infantilism is a 
 very persistent one and not likely to be fol- 
 lowed by normal growth except as the result 
 of careful therapeutic interference. A certain 
 proportion of such infantilism children die from 
 acute infections of the intestine; others are per- 
 manently retarded in growth, which leads to 
 pronounced dwarfism. 
 
 10. Eational therapeutic interference in cases 
 of chronic intestinal infantilism offers hope of 
 the reestablishment of the processes of growth 
 even in cases in which the bodily arrest has 
 been extreme and of long duration. If it is 
 too much to say that the most satisfactory 
 methods of treatment are now known, it may 
 be claimed, at least, that we are in possession 
 of certain principles of treatment which, when 
 carefully applied, are likely to yield better 
 results than any that have heretofore been 
 employed. 
 
 11. Temporary relapses are very common 
 in the course of this disease, even when great 
 care is being taken to prevent them. The 
 most frequent cause of such relapses is the 
 attempt to encourage growth by the use of 
 increased amounts of carbohydrates. When a 
 relapse occurs the feces become voluminous, 
 lose their conglomerate appearance and become 
 
118 INFANTILISM 
 
 of lighter color. They show the presence of 
 coccal forms in excessive numbers and there 
 is in persistent relapses a return of B, in- 
 fantilis and B. hifidus. Any disturbance of 
 digestion which checks growth or causes loss 
 in weight is to be accounted a relapse. 
 
 12. A permanently undersized individual is 
 the outcome, even in the most favorably pro- 
 gressing instances, of the severe form of 
 infantilism. This condition is not incompatible 
 with a high degree of mental development. 
 
The Common Bacterial Infections of the 
 
 Digestive Tract 
 
 And the Intoxications arising from them 
 
 By C. A. HERTER, M.D. 
 
 Professor in Pharmacology and Therapeutics in 
 Columbia University 
 
 Clothe 360 pages, l2mo, $l.SO net 
 
 "Now that it has been clearly shown how large is the part 
 played by the intestinal flora in many apparently remote morbid 
 processes, the'appearance of the present volume is to be regarded as 
 a boon to the profession. It is especially valuable, however, not 
 alone from the fact that it ofifers a summary of what has been learned 
 from and is suggested by the work of others in this field, but in that 
 it comprises the results of the enormous amount of original work 
 relating to the subject carried out in the author's laboratory, and 
 contains a wealth of new information that seems destmed to form 
 what may almost be termed a new point of departure in diagnosis 
 and treatment." — Medical Record. 
 
 "The methods of investigating the digestive tract outlined in 
 this volume will prove valuable to the practitioner who would de- 
 termine the presence of abnormal bacterial processes before the 
 onset of the clinical signs of incurable or highly refractory states of 
 intoxication— and this is the all-sufficient raison d'etre for the book. 
 Considerable stress has been laid by the author on methods developed 
 in his laboratory, in the belief that their painstaking application will 
 furnish practitioners with reliable indications as to the progress of 
 many cases of infection oi\.\iQ^\z^%\:\vt\x^zty —Merck' s Archives. 
 
 "Those to whom the terminology of the bacteriologist is not 
 unfamihar will find here not only a well written but also an inter- 
 esting and suggestive study of a rich fauna and a discussion of 
 questions of much import, for they are fundamental in relation to 
 a great human woe, indigestion. Particularly alluring is the an- 
 tagonism existing between different bacteria, the opposition of the 
 native to the immigrant forms."— 7%^ Nation. 
 
 "Dr. Herter's book is bound to have the effect of broadening 
 our conception of the subject of infectious diseases of the digestive 
 tract, and deserves a wide reading."— 6^^^?/'^^ C. Whipple. 
 
 Published by 
 
 THE MACMILLAN COMPANY 
 
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A SYSTEM OF MEDICINE 
 
 By Many Writers, edited by Thomas Clifford Allbutt, 
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 SECOND EDITION. Thoroughly revised and in the case 
 of many articles entirely re-written. NOW READY: — 
 
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 Alimentary Canal ; and Diseases of the 
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