Therapeutic use of diets

Critical Review T H E R A P E U T I C U S E OF D I E T S J U L I A N D . BOYD, 1V[.D.

I o w a C~Tu IOWA H E custom of the p a s t in p r e s c r i b i n g diets f o r those who were ill

w a s to specify the exclusion of certain types of foods which were T considered undesirable because of the n a t u r e of the p a t i e n t ' s illness. 1 A m o r e positive a p p r o a c h to the p r o b l e m is to prescribe certain specified foods which are needed b y the b o d y f o r the m a i n t e n a n c e of normal n u t r i t i o n in health or in illness, then to a d a p t the n a t u r e of the prescribed foodstuffs to meet the r e q u i r e m e n t s peculiar to the pat i e n t ' s condition. The growing recognition 2 of disease states b r o u g h t a b o u t by deficiency of the diet in certain essentials f o r n o r m a l nutrition has led to the adoption of this second a p p r o a c h to diet control as being m u c h safer f o r the p a t i e n t and m u c h more effective t h e r a p e u t i cally. Evidence is r a p i d l y a c c u m u l a t i n g to show t h a t a t t e n t i o n should be p a i d to the completeness of the diet of the individual who is not ill so t h a t disease m a y be avoided and t h a t o p t i m u m levels of health m a y be approached. The needs of the p a t i e n t with ally t y p e of illness are qualitatively similar to, those during health, and equal attentio,n should be directed t o w a r d meeting them. The weakness, anorexia, or inc a p a c i t y of the p a t i e n t m a k e s it i m p e r a t i v e t h a t the a t t e n d a n t s maintain the initiative in supplying, food of a t h o r o u g h l y suitable nature for the patient. The first consideration in designing a d i e t a r y prog r a m f o r a p a t i e n t with a n y t y p e of illness should be the completeness of the diet in all recognized essentials of nutrition, with liberal r a t h e r t h a n m i n i m a l amounts of the protective d i e t a r y substances. The l~ature and amount of the foodstuffs m a y be d e t e r m i n e d to meet the peculiar conditions imposed b y the n a t u r e and degree of the p a t i e n t ' s illness, but valueless restrictions should not be imposed. I n other words, the diet p r e s c r i p t i o n should be one of inclusion r a t h e r t h a n exclusion, restrictions always being a c c o m p a n i e d b y advice as to the inclusion in the diet of substitutes which n u t r i t i o n a l l y are equivalent to the p r o h i b i t e d foods. Unless such a policy is pursued, a prescribed diet of limitation m a y be a source of d a n g e r and of d a m a g e r a t h e r t h a n of benefit 3 to the patient, and the induced d i s t u r b a n c e of nutrition m a y m o r e t h a n offset the t h e r a p e u t i c value of the restriction.- In all instances, the p a t i e n t r a t h e r t h a n his disease should be treated. F o r convenience in discussion, therapeutic dietetics m a y be eo.nsidered u n d e r the following categories: 1. Diet in acute or chronic illness in which the n a t u r e of the disease does not of itself p r e d i c a t e the types of foods which m a y be used. 2. Diet in conditions in which the p a t i e n t ' s ability to digest or assimilate foodstuffs is impaired. F r o m the ]Department of Pediatrics, College of Medicine, State U n i v e r s i t y of Iowa. 234

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3. 4. 5. 6.

Diets f o r those with allergic states. Diets designed to correct specific or nonspecifie deficiency states. Diets designed to alter the acid-base balance of the tissues. Diets f o r the control of diabetes mellitus and other d i s t u r b a n c e s of metabolism. 7. Diets designed to conserve the excreto~ T functions. P r e l i m i n a r y to the discussion of t y p e s of diet m a n a g e m e n t best a d a p t e d to each of the above conditions, it is well to r e v i e w the char~ acteristics of a desirable diet f o r the h e a l t h y individual since the t h e r a p e u t i c diet will be based on a similar r e g i m e n so f a r as possible. Clinical and metabolic studies h a v e indicated t h a t diets of a high p r o t e c t i v e content offer the individual definite a d v a n t a g e s over the t y p e of diets c u s t o m a r i l y offered in homes and commercial eating establishments. As a guide in designing the diet of a h e a l t h y child of school age, the following ingredients have been specified 4 as a desirable basic daily intake, these foods to be s u p p l e m e n t e d b u t not replaced by foodstuffs whic:h m a y h a v e a l o w e r p r o t e c t i v e power, but which offer a t t r a c t i v e or economically desirable sources of e n e r g y : 1 1 I 1 I 1 2 I

q u a r t of m i l k or 2 eggs ounce of b u t t e r teaspoonful cod liver oil orange, or tomato, or apple additional serving o~ f r u i t servings o~f vegetables, o.ne o.f a fibro.us nature serving of meat, fowl, fish, or liver

While some of the essentials of the diet m a y be supplied equally well in the f o r m of other foods, those listed are of a t y p e r e a d i l y available and of p r o v e d efficacy. Omissions are not to be made, unless the omitted foodstuff is replaced b y a n o t h e r of c o m p a r a b l e p r o t e c t i v e efficacy. I n designing t h e r a p e u t i c diets, this list m a y be used as a guide, a l t e r i n g t h r o u g h suitable substitution in such a m a n n e r as the p a t i e n t ' s age, physical condition, or disease m a y require. As an aid in m a k i n g such an a d a p t a t i o n , it is well to consider each of the foods listed as to the reason for its inclusion in the list of requisites and as to the n a t u r e of permissible substitutions2 Milk is the only p r a c t i c a l food source of calcium. The n o r m a l child needs 11/2 pints of m i l k daily in o r d e r to meet a d e q u a t e l y the calcium d e m a n d s of his g r o w i n g body. E q u a l amounts of s k i m m e d milk or of b u t t e r m i l k will s u p p l y similar a m o u n t s of' calcium, as will 4 ounces of cheese. Oranges s t a n d n e x t in p r a c t i c a b i l i t y as a source of calcium, b u t in this r e g a r d ten a v e r a g e sized oranges will be required as a substitute for a pint and a h a l f of milk. The calcium content of other n a t u r a l food p r o d u c t s need not be ignored, but its concentration is so low t h a t t h e y do not r e p r e s e n t suitable sources of importance. Calcium salts m a y be employed w h e n milk cannot be t a k e n in sufficient a m o u n t s ; t h e i r utilization is less certain t h a n t h a t in milk, especially d u r i n g illness and in the y o u n g child. Dicalcium p h o s p h a t e seems to offer a d v a n t a g e s o v e r o t h e r calcium salts, p a r t i c u l a r l y those which do not contain phosphate. A suitable daily dosage to meet the entire calcium r e q u i r e m e n t is 90 grains, or 6 grams. Because of its bulk, this is best i n c o r p o r a t e d in some semisolid food.

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Milk is an important source of protein and when taken in the amount indicated will supply a good share of the body% needs in a desir'ab]e form. Suitable substitutes for this protein can be obtained from other sources of animal protein, such as meat products, in amounts greater than would be needed if milk were included in the diet. I n the discussion of allergy, other milk substitutes will be named. The vitamin B and G content of milk is notewoIChy when the prescribed amount is ingested. W h e n necessary to eliminate milk from the diet, increased servings of vegetables and of meat, especially liver, will help to complete the requirements for these vitamins. Foods made f r o m seeds, such as whole grain products, peas and beans, also are valuable sources of vitamin B. The root vegetables are p r e f e r r e d to the leafy types as sources of vitamin G. l\~any of the so-called concentrates of these two vitamins are not appreciably richer in their content than are some of the common foods. Crystalline vitamin B has bee~ produced and when commercially available m a y find a place of value in supplying that principle to those whose assimilative ability is so lowered that ordinary foodstuffs cannot be employed for the purpose. ~ While whole milk, cream, and butter may constitute valuable sources of vitamin A, this property need not be stressed if the child is receiving cod liver oil in the amounts prescribed. Liberal servings of the pigmented vegetables also will forestall deficiency of vitamin A, if ingested and well utilized. Concentrates of vitamin A are available in the form of pro-vitamin carotene or the oil of halibut liver, and these may be employed if necessary to insure completeness of supply. Cod liver o.il offers a recognizedly adequate source of vitamin D; without the continuous use of it or of some equally potent source of the vitamin, there is the utmost likelihood of deficiency of vitamin D except in the individuals receiving considerable solar or other ultr~violet irradiation; the lack of clinical evidence of that deficiency does not negate its existence or its significance in the maintenance of the general level of health. W i t h suitable amounts of vitamin D, as viosterol or as certain suitable concentrates of cod liver oil, the vitamin D requirement may be met as well as with cod liver oil. Unless p r o p e r l y fortified, however, these products m a y fail to insure adequacy of vitamin A intake. Moreover, they fail to supply significant amounts of iodine and of valuable f a t t y acids as contained in cod liver oil. Fruits and vegetables supplement the m i n e r a l intake, provide bulk necessary for the regulation of intestinal elimination, and constitute important sources of vitamins A, B, C, and G. Because of the instability of vitamin C, it is well to include one raw vegetable or f r u i t in each d a y ' s food allowance; although orange or tomato is popularly specified for this purpose, most raw fruits or vegetables offer vitamin C in amounts sufficient for the body's needs, if suitable quantities are ingested. Acid fruits such as tomatoes retain much of the vitamin even after cooking. When therapeutic conditions make it necessary, vitamin C may be supplied as cevitamie acid. 7 W h e n roughage is contraindicated, juices from vegetables and fruits may be employed. A wide variety of fruits and vegetables usually is desirable, with emphasis being placed on the succulent types r a t h e r t h a n those which are essentially of a starchy or seedy nature.

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E g g s offer a deMrable t y p e of protein, t o g e t h e r with other organic and inorganic substances of value to the r a p i d l y g r o w i n g animal organism. T h e y do not seem to be essential foodstuffs b u t are v a l u a b l e in their content of p r o t e c t i v e substances. Meat p r o d u c t s and m i l k can be used to replace the p r o t e i n t h e y would s u p p l y ; if cod liver oil is being t a k e n as prescribed, the v i t a m i n content of the egg will not be needed. W i t h a liberal i n t a k e of iron-containing foods, such as liver and other m e a t products, l e a f y vegetables, or inorganic iron p r e p a r a tions, egg will not be needed f o r t h a t purpose. The chief defense f o r including egg in the list of foods o r d i n a r i l y prescribed lies in the f a c t t h a t it is the foodstuff designed by N a t u r e for the r a p i d l y g r o w i n g chicken f r o m the earliest e m b r y o n i c s t a g e ; it obviously is rich in the principles necessary for tissue growth, and possibly it furnishes imp o r t a n t substances of a n a t u r e not yet recognized. Meats are specified because of their content of proteins which are similar in t h e i r n a t u r e to those o f the h u m a n body. D u r i n g i n f a n c y the p r o t e i n need can be met b y s u ~ c i e n i amounts of milk, but therea f t e r the inclusion of m e a t is desirable. M e a t also is a valuable source of iro~t and o.f vitamins B and G; the iron, however, is less available f o r h u m a n use tlhan t h a t f r o m n o n a n i m a l sources, s L i v e r is superior to lean m e a t in several respects and can b e used a d v a n t a g e o u s l y at least once or twice weekly. Gelatin is not a s a t i s f a c t o r y source of tissuebuilding p r o t e i n ; proteins f r o m vegetable sources are less valuable for the b o d y t h a n those of animal origin. DIET SUPERVISION DURING ILLNESS

The n u t r i t i v e r e q u i r e m e n t s of the b o d y are not lessened by illness; on the c o n t r a r y , certain food r e q u i r e m e n t s are definitely increased when an individual is ill. The p a t i e n t ' s n u t r i t i o n a l state at the onset of illness will d e t e r m i n e the u r g e n c y of his nutritional needs d u r i n g a b r i e f illness; if p r o p e r a t t e n t i o n has been paid to his diet, a f a i r store of vitamins, minerals and possibly of protein will serve to tide him over a period of a few clays of reduced intake. However, it is not safe to depend on such a m a r g i n of s a f e t y ; it can be depleted rapidly, and insufficient food ingestion m a y p r e c i p i t a t e the child into a condition m u c h more serious t h a n the original illness. During. acute illness, p a r t i c u l a r attention must be directed to the intake of a readily absorbed and utilized source of energT, together with fluids in amounts sufficient to replace those lost t h r o u g h excretion. I f this is not assured, the d e v e l o p m e n t of ketosis and d e h y d r a t i o n m a y be expected, either of which in itself m a y lead to an u n f a v o r a b l e outcome. F e v e r increases the calorie needs of the b o d y b y about 10 p e r cent f o r each degree of elevation of t e m p e r a t u r e . E v e n in cbronic conditions which are not associated with m a r k e d elevations of temp e r a t u r e , the e n e r g y r e q u i r e m e n t s are considerably h i g h e r t h a n would be expected for a child confined to his bed. 9 F u e l consumption will not be lessened if food is not i n g e s t e d ; the b o d y ' s stored foodstuffs or its own tissues will be sacrificed f o r the purpose. I f the p a t i e n t ' s condition permits, a diet composed of milk (skimmed, if whole milk is not t o l e r a t e d ) , f r u i t juices reinforced with dextrose, and simple ices will do m u c h to m a i n t a i n adequate n u t r i t i o n and to combat the illness. Milk soups m a y f o r m vehicles for pur~ed vegetables. C o n c e n t r a t e d f o r m s of vitamins A and D m a y be used at such times w i t h value since

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the reduced intake of f a t m a y offer less h a z a r d to gastrointestinal upsets. Foods should be chosen w i t h a view to t h e i r value to the child, the completeness of the combination offered, t h e i r readiness of ingestion and digestibility, and their p a l a t a b i l i t y a n d attractiveness. While the child'~s distaste f o r food m a y t a x the i n g e n u i t y of attendants to the utmost, the problem is not m e t b y offering foods merely because t h e y will be eaten; the diet should meet the n u t r i t i o n a l needs as completely as the situation will permit. I t is u n n e c e s s a r y f o r a p a t i e n t to lose a considerable a m o u n t of weight d u r i n g a short illness if his a t t e n d a n t s are actively concerned w i t h the a m o u n t s and n a t u r e of the food he receives. W h e n the n a t u r e of the illness or the p a t i e n t ' s inability to eat makes it necessary, it is o b l i g a t o r y t h a t n u t r i e n t fluids be given p a r e n t e r a l l y . R i n g e r ' s solution is a vehicle of choice since it supplies not only fluid, but also the mineral constituents needed b y the body. I t can be given by a n y p a r e n t e r a l route as an isotonic solution; aqueous solutions of dextrose up to a 6 p e r cent concentration m a y be a d d e d if it is to be given subcutaneously, or in g r e a t e r concentration if given intravenously. I n some situations an aqueous isotonic solution of dextrose (6 p e r cent) m a y be fed by g a r a g e to g r e a t a d v a n t a g e . W h e n hypertonic solutions are given, t h e y will dilute themselves b y imbibition f r o m available b o d y fluids before they are a b s o r b e d ; f o r this reason the use of hypertonic solutions of dextrose b y g a r a g e , or subcutaneously, is contraindicated. The rate of continuous administration of fluids intravenously should be within the limits of handling by the c i r c u l a t o r y system; 3 c.c. p e r k i l o g r a m of b o d y weight p e r h o u r is the rate suggested b y Marriott, I-Iartmann, and Senn. 1~ Diarrhea introduces a serious hazard in the m a n a g e m e n t o.f acute or chronic illness; it m a y result in dehydration and m a y greatly reduce the absorption of ingested foods. Before co.nsidering the dietary factors in the m a n a g e m e n t of diarrhea, it is i m p o r t a n t to emphasize t h a t diarrhea usually must be considered only as a symptom, and m a y be caused b y widely d i v e r g e n t conditions. D u r i n g acute infectious diseases of a n y type, the motility of the gastrointestinal t r a c t m a y be dist u r b e d in such a m a n n e r t h a t nausea, vomiting, and d i a r r h e a result. The gastrointestinal s y m p t o m s in such p a t i e n t s are not d e p e n d e n t on the diet p r e v i o u s l y ingested, nor on infection within the digestive canal. P r o p e r t h e r a p y will s t a r t with a search for the n a t u r e and source o f the p a r e n t e r a l infection. In the i n f a n t and y o u n g child this will be f o u n d in the u p p e r r e s p i r a t o r y tract, throat, or ears in the g r e a t m a j o r i t y of instances. W h e n such infection has subsided, either s p o n t a n e o u s l y or as the result of local t r e a t m e n t , the digestive dist u r b a n c e s will disappear. The d i e t a r y m a n a g e m e n t of such patients will not differ f r o m t h a t described in the foregoing. I n the case of the infant, acidified feedings m a y be t o l e r a t e d b e t t e r t h a n m i l k dilutions, and d e x t r o s e m a y be substituted f o r other f o r m s of c a r b o h y d r a t e with a d v a n t a g e . ~ I t m a y be desirable to s k i m the milk m o r e or less comp l e t e l y or to employ a dilution of e v a p o r a t e d milk. F o o d refusal, vomiting, and d i a r r h e a f r e q u e n t l y result in severe d e h y d r a t i o n in inf a n t s with severe p a r e n t e r a l infection; to p r e v e n t a f a t a l outcome the use of fluids b y some p a r e n t e r a l route f r e q u e n t l y is i m p e r a t i v e . 1V[arriott and his associates ~~ advise t h a t in severe d i a r r h e a of a n y causation the following p r o c e d u r e s be e m p l o y e d : restrict all food b y mouth ;

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give by vein an isotonic solution of sodium lactate (Hartmann's solution), reinforced by l~inger% solution and dextrose; slow continuous intravenous administration is preferable, but if the concentrations described above are used, the subcutaneous route may be employed. Transfusions should be used to supplement this form of treatment. When the acute diarrhea has been checked and tissue turgor has been restored, a dietary regimen may be instituted. ~iVfilk products, fruit juices and vegetable pur~es, and an easily assimilable source of vitamins A and D may be Used initially, coarser and less easily digestible foods being restored to the diet as convalescence progresses. In diarrheas dependent on bacillary enteI~itis, as in typhoid fever or bacillary dysentery; the diarrhea is largely independent of the type of diet; adequacy of intake must be maintained in Spite of the diarrhea. Readily absorbable foods of low roughage content are called for, well fortified with dextrose or other simple sugar. Because of impaired absorption and the increased energy requirement imposed by the disease, a high calorie intake is demanded. In severe fulminating, diarrhea associated with bacillary dysentery, the chief need is for fluids; these patients often die from dehydration, and in spite of vigorous parenteral administration, fluid needs may not be met in sufficient degree to prevent death. Continuous intravenous administration of 5 per cent dextrose solution in Ringer's solution is called for, injected at a rate of 3 to 5 c.c. per minute. In the treatment of diarrhea in childhood, the use of an apple diet has been popularized during the past few years. In the presence of considerable dehydration, that condition should receive first consideration in the manner outlined previously. In the absence of toxic symptoms, the enteral condition may be treated by feeding nothing other than scraped raw apple, using fruit which is completely ripe and mellow. One to four tablespoonfuls are given eve~. hour or two for a period of forty-eight hours. Aside from water, nothing else is offered by mouth. At the conclusion of the period, the patient is placed on a routine of three meals daily, these consisting of farina, toast, and cocoa made with water, soup with rice, scraped beef with toast, cottage cheese, and ripe banana. After another forty-eight hours has elapsed, boiled milk m a y be added, t h e n v e g e t a b l e pur~e and finally f r u i t in small amounts. Birnberg, ~ in describing this regimen, states t h a t it should not be used for y o u n g infants. ~[inor v a r i a n t s of this p r o c e d u r e are described b y various authors. Possibly substances other t h a n apple would be equally effective ; Grodecki ~a rep o r t s t h a t he has used r a w ripe t o m a t o f o r the t r e a t m e n t of d i a r r h e a for thirty-five years, a t t r i b u t i n g its beneficial effect to its content of vitamins and acids. Fasold has s u b s t i t u t e d suspensions of cellulose f o r s c r a p e d apple and has obtained s a t i s f a c t o r y results; he feels t h a t the action of apple is mechanical and adsorptive. The r e v i e w e r has had no experience w i t h the apple cure and does not feel qualified to comment critically concerning it. Chronic colitis has been attributed by numerous autho,rities to deficiency of diet. ~ I n chronic d i a r r h e a of a n y origin, i m p a i r e d absorption predisposes to the d e v e l o p m e n t of ctietary deficiency. Because of these two interrelated facts, much attention must be devoted to the diet of the patient with chronic diarrhea. The nature of the food residue m u s t be such t h a t it will not lead to additional i r r i t a t i o n of

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the intestinal mucosa; nutritional essentials of all types must be ineluded in the dietary; and because ef the likelihood of wastage through imperfect absorption, the intake of the protective substances must be g r e a t e r than would be necessary if the intestinal function were normal. Such patients should receive, then, a low residue diet rich in all recognized vitamins and essential minerals, with a liberal protein allowance. The p r e p o n d e r a n t use of milk and other d a i r y products, vegetable purses, ripe mellow fruits, f r u i t juices, meat, liver, eggs, cod ]iver oil, simple sugars, and limited amounts of t h o r o u g h l y cooked cereal products should meet the nutritional needs of the patient in a m a n n e r compatible with his intestinal condition. In allergic colitis, food sensitivity must be properly treated. Equal attention must be directed to tile correction of anemia t h r o u g h transfusions, and possibly the use of vaccines in baeterial forms of the disease. In childhood, such a regimen has led to a p p a r e n t cure even in p r o v e d eases of severe ulcerative colitis. As a cause or a sequel of chronic inanition, patients may present evidence of inability to absorb ingested foodstuffs in any degree comparable to the normal state. Such a condition sometimes is seen following prolonged misfeeding with foods which are not a d a p t e d to the individual's digestive capacity, o r following severe debilitating' illness. In other patients, the intestinal dysfunction has developed insidiously, without apparent etiology. Chr'on~c intestinal indigestion may vary markedly in degree, and to some extent as to the type o.f impairment of absorption. Usually these patients fail to absoi% fats and complex carbohydrates efficiently, as in so• celia.c disease; sometimes the abso.rptio.n of fat is less affected than that of starches. The retardation of growth, p r o t u b e r a n t abdomen, extreme emaciation, precocious and extreme tooth decay, and the f r e q u e n t development of rickets and s c u r v y which these patients manifest offer evidence of the severe nutritional problem that t h e y present. W h e n the usual diet is ingested by such a child, voluminous stools are passed, and m a r k e d loss of weight m a y occur within a few hours. M a n y clinicians feel satisfied if t h r o u g h their d i e t a r y corrections they are able to keep such a child alive and avoid loss of weight, even though normal g r o w t h progress is not attained. Yet, t h r o u g h suitable d i e t a r y measures, such children have bem~. observed to assimilate an adequate diet, and to resume norreal rates of growth. All patients with absorptive difficulties will utilize protein foods, as a class, b e t t e r than e i t h e r fats or carbohydrates. This fact is the basis for the three-phase high protein diet as recommended by Itowland, Sauer, Parsons, ~ and others in the d i e t a r y m a n a g e m e n t of celiac disease. Sauer states that such d i e t a r y t r e a t m e n t has led to rapid and p e r m a n e n t improvement in the m a j o r i t y of twenty-five patients with celiac disease during a period of seven years. The first stage in the diet used b y him consisted exclusively of powdered p r o t e i n milk dissolved in l~inger's solution and given in increasing s t r e n g t h and amount; when the p a t i e n t ' s frees gave evidence of good utilization of this food, it was supplemented by the addition of other foods pred o m i n a n t l y of protein nature, such as meat serum or scraped lean meat, egg white, or cottage cheese. P o w d e r e d skimmed milk may be substituted for the protein milk as food tolerance permits. Under this regimen the body weight should increase, and abdon'tinal disten-

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tion should subside. Cod liver oil, orange juice, and iron should also be added to the diet by installments. This phase of the diet control may require continuance for months or years before the paticnt"s food tolerance finally will permit the adoption of the third and most difficult phase of the di e t - - t he introduction of complex carbohydrates in the form of thoroughly cooked starches, and other foods not difficult of digestion. Sauer warns against the introduction of bread, potato, sugar, ice cream, candy, cake, and fresh milk until late in the course of treatment ; with recurrence of symptoms, the earlier form of the diet should be resumed. The disease is not cured by this or by the procedures to be described subsequently; dietary control of celiac disease is directed toward the maintenance of nutrition until the lapse of months or years leads to the gradual acquisition of normal digestive tolerance. While clinical experience has shown that patients with celiac disease can usually tolerate well diets consisting almost exclusively of protein, as described in the foregoing, evidence as to normality of growth and development under such a regimen is not convincing, nor has the necessity for such rigorous limitation been demonstrated. Haas 16 reported the successful maintenance treatment of young children with celiac disease by the rise of large amounts of ripe banana; his observations were confirmed by others. Tbe impression was gained that the banana possesses unique properties which account for its tolerance by children with impaired absorptive capacity. Nelson, 17 however, has reported the progress of children with celiac disease under a plan of diet control which provided a liberal allowance of protein in the form of boiled skimmed milk, cottage cheese, egg white, and sieved liver, but which supplied the majority of the calories, as dextrose, orange juice, and tomato juice in larg e amounts, leading to rapid and permanent gain in weight and subsequently in height. Cod liver oil (1 dram) was given daily. Bananas were used as an acceptable alternative for other types of simple sugars; the sugar of the thoroughly ripe banana is invert sugar, which apparently is well utilized and readily absorbed, whereas more complex sugars may remain in the bowel and undergo fermentation. 1V[etabolic studies indicated excellent retentions of nitrogen, calcium, and phosphorus, and successive clinical studies pointed to good utilization of all the foods mentioned as indicated by the character of the stools and the physical progress of the children. As in all forms of diet t herapy in this disease, rigid and continuous adherence to the prescribed regimen was required throughout early childhood; dietary indiscretions always result in copious stools of the type which characterize celiac disease. However, the superior physical progress of these patients and their apparent tolerance for simple sugars indicate that something other than the strictly protein diet is called for in celiac disease. Boca.use of its case of assimilability, dextrose is a very valuable adjunct in the feeding of the sick. Stearns and Moore ~s have reported the exceptionally rapid growth and recovery of a three-year-old child with severe malnutrition, which dated from infancy and which was associated with intolerance for complex carbohydrates, tie was placed on a dietary regimen similar to that described by Nelson; his food utilization was excellent, as evidenced by his retentions of nitrogen, calcium, and phosphorus, and he gained 1] kg. and grew 14.5 cm. during a period of nine months.

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Chronic malnutrition, in older children has respomnded favorably te the same regimen. Stearns, Catherwood, and K a n t r o w 19 have reported comparative diet studies on five malnourished children, each from 10 to 20 per cent below the average weight for his height. The best and most consistent gain was obtained with a diet of high dextrose content (from 220 to 445 grams a. day), high in its content of protein, minerals and vitamins, low in fat and in c a r b o h y d r a t e s other t h a n dextrose. More t h a n 45 calories per pound per day were r e q u i r e d ; good gains were obtained when the value exceeded 50. To achieve similar gains with a diet high in fat and low in dextrose, from 250 to 500 calories more per child per day were required. The protein allowance was about 2 gin. per pound per day. Metabolic studies showed good retentions. The diets just described are rational; t h e y are composed of foods most readily assimilated, which tax the p a t i e n t ' s energies to the least e x t e n t ; t h e y contain ample amounts of body-building proteins and minerals, and large supplies of vitamins. T h e y can be used successfully f o r the nutrition of patients with greatly diminished absorptive capacity or of children with normal digestive function. Under the l a t t e r circumstances, constipation p r o b a b l y would be troublesome, because of the unnecessary restriction of foods with unabsorbable residue. The inclusion of coarse fruits and vegetables and the substitution of other sugars and starches for dextrose would make the diet suitable for the healthy normal child. Constipation in children and infants is preponderantly dependent on faults in the diet; correction of the diet will result in relief in all except the small group with organic or functional disturbances which i n t e r f e r e with normal intestinal motility. 2~ In v e r y y o u n g infants, the commonest cause is insufficiency of food; the constipation is only a symptom of the more serious u n d e r l y i n g deficiency. T h r o u g h the use of s u p p l e m e n t a r y or increased amounts of any well-designed milk feeding, normal bowel function may be expected. With the infant of three months or older, who is gaining weight regularly and at a good rate, constipation f r e q u e n t l y depends on the absence of sufficient unabsorbed residue in the bowel. R a t h e r t h a n e m p l o ~ n g even the mildest of laxatives, it is b e t t e r to add sieved fruits to the daily diet, offering g r a d u a l l y increasing amounts up to an ounce or two daily. The fibrous h'uits (prunes, apples, peaches, pears, apricots) are best for this p u r p o s e ; the sieved pulp is the effective agent, r a t h e r t h a n the juice. T h e dried f r u i t is stewed and sieved and fed f r o m a spoon. Constipation in the older child m a y be p a r t l y due to habit, but usually it is augmented by the habitual use of diets containing inadequate amounts of the coarser fruits and vegetables. The d i e t a r y regimen for a normal child, described in the first p a r t of this presentation, usually will prove anti-constipating; if it is not, it can be supplemented b E additional or l a r g e r servings of fruits and vegetables. Constipation per se should not be considered as an evidence of illness; it seems to have little or no deleterious effect on the general healthy ~ I t is evidence, however, Of the existence of causative conditions, and in the great m a j o r i t y of instances these are p u r e l y of d i e t a r y origin. Tt:IERAPEUTIC DI]~TE,TICSIN ALLERGIC DISTURBANCES Students of al]ergy have demonstrated the responsible rSle played by tissne hypersensitivity in the causation and modification of many

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diseases and m i n o r disturbances of physiologic function. 22' 2~ The ubiquity of hypersensitizatio~, the appeal of the new to p o p u l a r fancy, and the difficulties associated w i t h the establishment or disestablishment of allergy as the principal a g e n t of disease, have led to the attributing of m a n y diverse disease stages to allergy. L e t it be recognized t h a t certain conditions obviously depend p r i m a r i l y on tissue sensitization; t h a t in other conditions a l l e r g y is one of the i m p o r t a n t factors in the causation of disease; that in some other conditions the coexistence of allergy may modify the manifestations of a disease dependent on other primary etiologic factors. This recognition makes it necessary to consider the rhle which allergy plays in any given condition, but it should not blind the physician to the need for treating with equal vigor the nonallergic factors contributing to the disease. According' to Vaughan, 2a allergy must be recognized as a pathologic exaggeration of a normal physiologic response, rather than a pathologic condition p e r se. Sehick 2~ distinguishes between physiologic degrees of sensitization and the m o r e m a r k e d states of h y p e r s e n s i t i v i t y ; he would reserve the t e r m allergy f o r the f o r m e r and s p e a k of the clinically a p p a r e n t states of a l l e r g y as h y p e r e r g y . One m u s t recognize t h a t allergy is responsible f o r the changes which occur in the b o d y fluids and tissues following specific infections, a l t e r i n g the response of the individual to subsequent exposures to these infections. 24 Sensitizations m a k e their a p p e a r a n c e following the i n t r o d u c t i o n of m a n y complex substances into the b o d y ; t h e y persist f o r indeterminate periods of time but in general tend to d i s a p p e a r if contact with the sensitizing allergen is avoided. 2~ While in the m a j o r i t y of instances there is little or no clinical evidence of the allergic reaction in the individual, it m a y become sufficiently m a r k e d to i n t e r f e r e with certain b o d y functions, sometimes to such a degree t h a t the condition is recognized as a state of disease. An individual m a y be clinically sensitive to n u m e r o u s allergens in n o t e w o r t h y degree or m a y respond only to a few. Because of the p r e v a l e n c e of sensitization ~ and the occurrence of m a r k e d allergic s y m p t o m s in the m i n o r i t y of the population, it is suggested t h a t clinical allergy is dependent on intrinsic as well as extrinsic f a c t o r s ; the individual with p r o n o u n c e d allergy is predisposed t h r o u g h his h e r e d i t a r y m a k e - u p to a t t a c k s of an allergic nature, and sensitization which will occur as a m a t t e r of course in his contacts w i t h his e n v i r o n m e n t will serve to arouse this l a t e n t inherent p a t t e r n of response. V a u g h a n 28 states t h a t f r o m 7 to ]O per cent of the p o p u l a t i o n show some o u t s p o k e n manifestations of a l l e r g y ; an additional 50 p e r cent show m i n o r or t r a n s i t o r y forms. F r o m a f o u r t h to a h a l f of all individuals will show positive skin tests to various allergens. The list of disease conditions a t t r i b u t e d to allergy is long and seems limitless; those w i t h p r o v e d relationship are f e w e r b u t are of significant n u m b e r and variety. E v i d e n t l y certain conditions m a y have a l l e r g y as a c o n t r i b u t o r y cause, yet m a y exist i n d e p e n d e n t l y in the absence of d e m o n s t r a b l e significant sensitization. Foods m a y act as allergens; this is commonest d u r i n g the first two y e a r s of life, and following the fifth y e a r foods are p r o g r e s s i v e t y less i m p o r t a n t as a cause of allergic disease. 25 While the m e c h a n i s m of sensitization to foods is not clear, it is g e n e r a l l y considered to follow the enteral or p a r e n t e r a l i n t r o d u c t i o n of the offending f o o d s t u f f or ~ts i n c o m p l e t e l y digested components. As an e x p l a n a t i o n for those in-

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stances of sensitization o f the infant to foodstuffs which he n e v e r has been given in his diet, Hill 2G believes that they m a y have reached the f e t u s following t h e i r ingestion by the mother. The usual presence of clinical al]ergy in some other members of t h e family is emphasized b y most writers on the subject. The foodstuffs most often incriminated in allergy are eggs, milk, and w h e a t ? 2 While evidence is not conclusive, there is much to ]end support to the opinion that sensitizat~0n is d e p e n d e n t solely upon the protein constituents of food and t h a t p r o d u c t s which are completely devoid of nitrogenous compounds cannot act directly as allergens, z7 An individual m a y be sensitive to one of the protein constituents of a food b u t not to others ; t h r o u g h certain processing, s o m e proteins m a y lose in v a r y i n g degree their p r o p e r t y of causing allergy. R a t n e r and Gruehl ~s h a v e reported studies on the a n a p h y l a c t o g e n i c properties of milk in which they have c o m p a r e d the response of animals to whole r a w milk, m i l k boiled four hours, canned u n e v a p o r a t e d milk, e v a p o r a t e d milk, and dried milk. T h e y state t h a t milk sensitivity is most common to the lactalbumin and lactoglobulin fractions, less so to the casein fraction. L o n g boiling alters the first two, rendering t h e m less anaphylactogenic, I n the u n e v a p o r a t e d products, however, the action seems to reverse itself a f t e r the m i l k cools, the p r o d u c t s again assuming allergenic qualities. H e a t incident to e v a p o r a t i o n seems quite effective as a p a r t i a l l y den a t u r i z i n g medium, and individuals sensitive to the w h e y proteins (milk albumin and globulin) but insensitive to casein m a y tolerate e v a p o r a t e d milk well, whereas milk in other forms would incite a reaction. It'ill 2s states t h a t he has observed sensitivity to egg on n u m e r o u s occasions where it was certain t h a t the i n f a n t had not been exposed to egg since his b i r t h ; he a t t r i b u t e s the sensitization to p r e n a t a l influences and considers the positive skin test as an index of the existence of clinical allergy. The sensitization to cereal p r o d u c t s is a function of their p r o t e i n content, not of the s t a r c h ; R a t n e r and Grueh] 27 believe t h a t while various g r a i n p r o d u c t s m a y serve as allergens, they lose this p r o p e r t y if they can be purified sufficiently to eliminate the protein fractions. Thus, p u r e sugars are ~ot allergens and may be used safely in diets of patients with allergy of any nature. Various methods are employed to determine the foods responsible for allergic reactions in a given patient. Skin tests may be of value, but t h e i r evidence is not at all conclusive. The p e r c e n t a g e incidence of p o s i t i v e reactors is much g r e a t e r t h a n those showing clinical evidence of sensitivity2a; an allergic individual m a y give positive tests to substances which p r o v e innocuous when t r i e d clinically and fail to react b y skin tests to o t h e r foods whose allergenic p r o p e r t y is readily demonstrable. An i n d i v i d u a l ' s food dislikes are not r e l a t e d to his food sensitivities, and no weight should be p u t on such observations. On the other hand, the p a t i e n t who is old enough to observe his symptoms in relation to the t y p e of food he has eaten m a y be able to tell quite a c c u r a t e ] y t h a t eertah~ foods agree with him while o t h e r foods lead to illness. Often allergy to the suspected foods can be demonstrated, according to V a u g h a n . 2a I f an a c c u r a t e d i a r y is made of all foods eaten, the offending foods m a y be deteeted t h r o u g h a correlation of the occurrence of allergic m a n i f e s t a t i o n s w i t h the previous dietary. W h e n such measures are insufficient, a special diet m a y be prescribed

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f o r diagnostic purposes. Such diets, t e r m e d elimination diets, h a v e been described b y V a u g h a n , 2a Cobb, 25 and l~owe. 29' ao T h e y are m a d e up of a m i n i m u m n u m b e r of foods, these chosen f r o m those least frequently concerned with the p r o d u c t i o n of allergy, a n d with the exclusion of those causing positive skin tests or clinical s y m p t o m s in the patient. The r e s u l t a n t diet m u s t be one which at least a p p r o x i m a t e s all the requisites of n o r m a l nutrition, since it m a y be necessary to e m p l o y it exclusively for a period of two or three weeks or even longer before f o r m i n g a n y conclusion as to the state of allergy. P r e l i m i n a r y to the institution of such a t r i a l diet, Rowe 3~ emphasizes the importanee of ruling out causes other t h a n a l l e r g y f o r the p a t i e n t ' s s y m p toms. t t i l F G does not a t t e m p t to eliminate all foods causing reactions w h e n multiple sensitizations exist, eliminating only those offering g r e a t e s t evidence of reaction. Because of the u n c e r t a i n t y of eomposition of commercially p r e p a r e d foods, none of these can be included in the test diet. W e i g h t m a i n t e n a n c e is assured t h r o u g h sufficient ingestion of the sugars, starches, and oils which are specified in the trial diet. t~owe ~~ designs his group of elimination diets in such a w a y t h a t he feels t h e i r content of v i t a m i n s A, B, C, and G is assuredly sufficient f r o m the a m o u n t s of fruits and v e g e t a b l e s included; v i t a m i n D should be included in the f o r m of cod liver oil, halibut liver oil, or viosterol, m a k i n g sure t h a t the oily vehicle of the l a t t e r is one acceptable to the allergic state of the patient. U l t r a v i o l e t light m a y be s u b s t i t u t e d if circumstances require. He emphasizes t h a t w h e n milk is not offered, the protein content of the diet will be ina d e q u a t e unless meat, eggs, or ]egumes are offered two or three times daily; in addition, 4 to 6 gin. of dicalcium phosphate should be given daily w h e n milk is excluded f r o s t the diet, in order to m a i n t a i n sufficient i n t a k e of these minerals. I n the s t u d y of u n d e r n o u r i s h e d individuals or children, Rowe 3~ offers first a test diet including milk, unless circumstances definitely f o r b i d ; suitable milk substitutes such as sobee or eemae m a y be used u n d e r such conditions, or m i l k m a y be r e i n t r o d u c e d into the diet at the earliest possible moment. As a basic diet f o r p a t i e n t s with multiple or u n d e t e r m i n e d sensitivity, he suggests the following test r e g i m e n : one or more servings of rice, corn, tapioca, sago, sweet or white p o t a t o ; one or more servings of lamb, beef, chicken, soy bean, lima beau, dried p e a s ; one or more servings of spinach, carrot, beet, artichoke, asparagus, pea, t o m a t o ; one or more servings of lemon, g r a p e f r u i t , pear, peach, apricot, pineapple. I n the p r e p a r a t i o n of the foregoing, use sufficient a m o u n t s of the fol. lowing: mazola, wesson, olive, or sesame oils; white v i n e g a r if lemon is excluded; salt, cane or beet sugar, and glucose. Quantities of these sufficient to m a i n t a i n weight should be used. While a whole g r o u p of the foregoing m a y be omitted if necessary, this is not desirable; the test diet m u s t be m a d e metabolically adequate. Rowe29, ao and Cobb 2s have pub]ished e l a b o r a t e l y complete menus a n d recipes, offering series of elimination diets designed to avoid the ingestion of eertain individual or groups of foods most c o m m o n l y f o u n d to be allergenie. V a u g h a n =a suggests t h a t in eliminating certain foodstuffs, the biochemical or the phylogenetic n a t u r e of the suspected foodstuff be k e p t in mind and related foods be r e m o v e d as we]l. Once conclusions have been reached as to the n a t u r e a n d significance of food sensitivity, it is necessary to determine w h a t d i e t a r y measures

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should be taken. Diets prescribed for continuous use must be constructed with greater care than those used t e m p o r a r i l y ; since they are diets of exclusion, t h e y also should include enough protective foods and of such a v a r i e t y t h a t avoidance of any degree of nutritional deficiency is assured. The various published diets for patients with allergy offer v a r y i n g degrees of nutritional safety; some have been p r e p a r e d with creditable care f r o m the nutritional standpoint, whereas others appear to have been designed with the allergy in mind more than the welfare of the patient as an individual. It is well to remember t h a t three decades ago, experimental animals were being offered synthetic diets thought complete in essential nutritive factors and that they failed to prosper equally with littermates receiving diets consisting of unrefined foods. While our recognition of nutritional essentials is b r o a d e r now t h a n then, there is no assurance that it is complete. Growing evidence indicates t h a t b e t t e r health is assured those receiving diets with generous amounts of protective foodstuffs than those with maintenance allowances. The diet of the allergic individual may easily be restricted to such a degree, t h r o u g h the substitution of biologically sterile energy sources for c r u d e r foodstuffs t h a t likelihood of deficiency disease of greater or lesser magnitude is not improbable. Some controversy exists between students of allergy diseases as to the relative desirability of desensitization to offending foodstuffs as compared with their continued elimination from the diet. Vaughan 2:~ states t h a t desensitization is unsatisfactory, t h a t avoidance of offenders is better, and that such procedure will lead to a loss of sensitivity to them sooner than will be accomplished by desensitizatii)n. W i t h avoidanee, sensitivity m a y be lost within a few months, or a few years, or possibly n e v e r ; he states that on the average about f o u r and one-half years is required for specific sensitivity to be lost. R atner, a~ in discussing the t r e a t m e n t of milk allergy, advises first the elimination of all w h e y proteins, rare beef, and beef serum. I f the p a t i e n t has no sensitivity to casein, e v a p o r a t e d milk m a y be employed d u r i n g this period if well tolerated. Then a tolerance for u n e v a p o r a t e d milk is developed g r a d u a l l y by giving graded amounts daily b y mouth, starting out with one drop or even less, and building the daily intake up slowly until in the course of several months the customary amount is being ingested. Once tolerance has been attained, he states that milk must be ingested daily t h r o u g h o u t life, to maintain desensitization. Since specific food sensitivities come and go, it is wise to recheck the p a t i e n t ' s state of food sensitivity f r o m time to time, to adapt his diet to his progressive condition, or to restore him to a nonrestricted diet so far as possible. Dietary Manc~geme~,t of Infa.ntile Eczema..--It is easy to eliminate egg and wheat p r o d u c t s f r o m the diet of the i n f a n t w i t h o u t incurring the risk of qualitative or quantitative nutritional deficiency. Many allergic infants will tolerate e v a p o r a t e d milk when milk ingestion 2s in any other f o r m will result in an exacerbation of the eczema. R a t n e r 28 found t h a t dried milk preparations, those t r e a t e d by prolonged boiling, and a commercial milk p r o d u c t advertised as being hypoallergic still r e t a i n e d w h e y proteins in a form capable of producing allergic reactions in animals sensitized to those types of proteins. W h e n milk of animals of other species is easily available, it may be

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t r i e d as a food f o r the milk-sensitive infant. Hill states, however, t h a t infants sensitive to c o w ' s m i l k usually r e a c t to g o a t ' s milk as well. H e states t h a t m i l k sensitivity of infants usually will d i s a p p e a r spont a n e o u s l y within a few months. The p r o d u c t s sobee a n d c e m a c - - p r e p a r e d f r o m soy b e a n and beef, respectively, t o g e t h e r w i t h m i n e r a l salt mixtures, oils, and other p r o t e c t i v e s u b s t a n c e s ~ h a v e p r o v e d of value as milk replacements. E a c h requires the use of additional foods as sources of energy. R a t n e r ' s w o r k 27 indicates t h a t p u r e crystalline sugars, dextrimaltose, or corn s y r u p m a y be used f o r this purpose, none of these s e r v i n g as allergens. The use of c o n c e n t r a t e d sources of u n s a t u r a t e d f a t t y acids has been r e c o m m e n d e d r e c e n t l y as a r e m e d y f o r infantile eczema, on the premise t h a t there is a deficiency of these acids in such infants. TM 83, ~ While f a v o r a b l e results h a v e been r e p o r t e d by some investigators, others r e p o r t t h a t no benefit has resulted f r o m t h e i r use. 3~ Linseed oil a n d corn oil are a m o n g the p r o d u c t s r e c o m m e n d e d f o r this purpose. Sensitization to the p r o t e i n of linseed oil has been r e p o r t e d following its use.

A correlation has been m a d e f r e q u e n t l y between the occurrence of eczema in i n f a n t s and a t e n d e n c y to obesity. Such i n f a n t s seem to i m p r o v e if their w e i g h t gain is checked moderately. U r b a e h 36 states t h a t a reduction in caloric i n t a k e t o g e t h e r with suitable local t r e a t m e n t f r e q u e n t l y will result in healing of the lesions. H e r e c o m m e n d s feeding the a t r o p h i c eezematous i n f a n t in a m a n n e r to b r i n g the w e i g h t up to normal. I n the e x u d a t i v e f o r m of the disease, he reduces the intake of f a t and of salt. A review of the l i t e r a t u r e on allergy and diseases a t t r i b u t e d to t h a t condition reveals m a n y c o n t r a d i c t o r y statements, and leads to the impression t h a t m u c h basic physiologic s t u d y will be necessary before dogmatic s t a t e m e n t s can be m a d e concerning the causation, mechanism, and r a t i o n a l t r e a t m e n t of clinical h y p e r s e n s i t i v i t y to protein. I n the m e a n t i m e it seems a p p a r e n t t h a t a n y t h e r a p e u t i c approae:h to these conditions m u s t include ~ttention to nonal]ergic as we~l as allergic f a c t o r s in the etiology a n d t h a t t h e r a p e u t i c measures which c a r r y the p r o b a b i l i t y of p r o d u c i n g a s u b o p t i m a l state of n u t r i t i o n should be avoided. Careful p l a n n i n g of the p r e s c r i b e d diet should p e r m i t adequate n u t r i t i o n a n d yet avoid the use of foodstuffs to which the patient is clinically allergic. I n a subsequent review the discussion of t h e r a p e u t i c dietetics will be continued. I%EFEI%ENCES 1. 2. 3. 4. 5. 6.

1Yewburgh, L . H . : J . A . 1~. A. 105: 1034~ 1935. Orr, J . B . : Scot. J. Agric. 14: 383, 1931. Wilder, I~. M.: J . A . iV[. A. 97: 435, 1931. Boyd, J . D . : J. PEDIAT. 6: 249, 1935. Idem: Ibid. 2: 226, 1933. Vorhaus, M. G., Williams~ R. 1% and Waterman, 1%. E. : J . A . 1VL A. 105: 1580, 1935. 7. Abt, A. 1% and Epstein, I. M. : J . A . M . A . 104: 634, 1935. Wright, I. S.: Proc. Soc. Exper. Biol. & Med. 32: 475, 1934. Dalldorf, G., and Russell, It. : J . A . M . A . 104: 1701, 1935. 8. Elvehjem, C . A . : J . A . !XI. A. 98: 1047, 1932. Josephs, t I : Bull. Johns Hopkins Hosp. 49: 246, 1931. 9. Peterman, M. G., Hug, I., and Clausen, N. C. : Arch. Pediat. 49: 67, 1932.

248

THE JOuR~NAL 0F PEDIATRICS

10. /YIarriott, W. Mc:K.~ Hartmann~ A. :F., and Senn, M. J . E . : J. PEDIAT. 3: 181, 1933. 11. Boyd, J . D . : J. PEDIAT. 4: 263~ 1934. 12. Birnberg, T . L . : Am. J. Dis. Child. 54: 18, 1933. 13. Grodecki, ]~'.: Pediatria polska 13: 35, 1933. (Abst. Am. J. Dis. Child. 49: 753, 1935.) 14. :Fletcher, A . A . : J. Am. Dietet. A. 7: 1, 1931. Hare, D. C.: Brit. M. J. 2: 162, 1934. Maekie, T. T., and Pound, R. E.: J-. A. M. A. 104: 613, 1935. Mackie, T . T . : J.A.M.A. 104: 175, 1935. 15. I-Iowland: Tr. Am. Pediat. Soe. 33: 11, 1921. Sauer, L . W . : Am. J. Dis. Child. 34: 934, 1927. Parsons, L . G . : Am. J. Dis. Child. 43: 1293, 1932. 16. I-Iaas, S . V . : Am. J. Dis. Child. 28: 421, 1925. 17. Nelson, ~ . u Am. J. Dis. Child. 39: 76, 1930. 18. Stea~'ns, G., and Moore, D. L . R . : Am. J. Dis. Child. 42: 774, 1931. ]9. Stearns, G., Catherwood, R., and Kantl~ow, A.: Proc. Soc. E x p e l Biol. & Me d. 32: 1463~ 1935. 20. Eech%, A . F . : Wien. klin. Wchnschr. 43: 534, 1930. 21. ~'risch, L A.: J. PEDIAT. 6: 784~ 1935. 22. Rowe, A. /-I.: J. A. M. A. 91: 1623~ 1928. 23. Yaughan, W. T.: Am. J. Digest. Dis. & Nutrition 1: 384, 1934. 24. Schiek, B , and Peshkin, M. M.: J. PEDI~.T. 5: 698~ 1934. 25. Cobb, C. B . P . : Am. J. Dis. Chi]d. 50: 187, 1935. 36. Urbach, E.: Wien. klin. Wchnsehr. 45: 496, 1932. 27. Rutner, B , and Gl'uehl, H . L . : Am. Y. Dis. Child. 49: 307~ 1935. 28. /~atner, B , and Gruehl, 1~. L.: Am. J. Dis. Child. 49: 287, 1935. 29. ~owe, A. H.: J. A]lergy 2: 92, 1931. 30. t~owe, A. H.: Am. J. Digest. Dis. & Nutrition 1: 387, 1934. 31. ~ t n e r ~ B.: J. A. M. A. 105: 934, 1935. 32. Hill, L. W.: J. I~ 2: ]33, 1933. 33. ttansen, P . E . : Prec. Soc. Exper. Biol. & Med. 30: 1198, 1933 34. Cornbleet, T.: Arch. Dermat. & Syph. 31: 224, 1935. 35. Taub, S. J , and Zakon, S . J . : J . A . ~V[.A. 105: 1675, 1935. 36. ~rbach, E.: Wien. klin. Wehnschr, 45: 496, 1932.