SECTION VIII--Editorial T h e editorial

contributions published in this J o u r n a l represent only the opinions of their u'rftcrs. S u c h being the case, this J o u r n a l or the A m e r i c a n Association is in n o w a y respottsible for editorial expressions.

G E N E R A L P R I N C I P L E S I N V O L V E D IN T H E D I A G N O S I S OF G A S T R O - I N T E S T I N A L D I S E A S E diagnosis in the field of gastro-intesA CCURATE tinal disease is still a very difficult m a t t e r notw i t h s t a n d i n g the tremendous amount of work of high c h a r a c t e r which has long been devoted to this field. G a s t r o - i n t e s t i n a l disease is one of the oldest recognized and best defined of the medical specialties. The subject of the physiology of the g a s t r o - i n t e s t i n a l t r a c t has been also one of the earliest and most intensively studied of the special systems. The field of gastrointestinal disease always has been and still is one of the most a t t r a c t i v e and i m p o r t a n t of the whole subject of internal medicine. The subject has never been relatively a neglected one nor has it ever failed to comprise among its workers many of the g r e a t e s t of reedical minds of the period for many generations past. D i e t a r y laws and rules have characterized almost every p r i m i t i v e as well as all civilized peoples, and yet we must honestly class as but little b e t t e r than taboos and prejudices many of the d i e t a r y customs of the present day. Religion and racial custom still determine the so-called laws of dietetics f a r more certainly than do the results of scientific research and study. The fact of the difficulty still existing in the diagnosis of g a s t r o - i n t e r s t i n a l disease is not the result of lack of facilities and o p p o r t u n i t y offered by scientific progress and study. Mechanics and physics early cont r i b u t e d their methods to the study of the gastro-intestinal t r a c t and a relatively correct i n t e r p r e t a t i o n of the p r i m i t i v e functions of the tube very promptly was recognized by all of the early anatomists. The Zapotecs and the Mayas among others, of our own hemisphere probably understood the a n a t o m y of the t r a c t very early, certainly long before the brake-like incubus of religion p e r m i t t e d adequate anatomical studies of the human body in Europe and perhaps even in Asia. Long before c h e m i s t r y had risen to the d i g n i t y of a science its methods of study were being applied also to the elucidation of g a s t r o - i n t e s t i n a l problems, and this science in p a r t i c u l a r still remains one of the most fertile fields of study in connection with the subject. E x p e r i m e n t a l physiology almost may be said to have had its conception in studies of this field and it remains even to this day one of the most valuable methods of study, present and future. The discovery of the microscope almost immediately contributed its help in direct application to the study of the physiology and pathology of the digestive tract, and at least in diagnosis we but stand on the threshold of its possible c o n t r i b u t i o n s to the subject. O p e n i n g address. * R e a d b e f o r e t h e F o r t n i g h t , Session of 1934, N e w Y o r k A c a d e m y Medicine, Oct. 21, 1934. t A t t e n d i n g P h y M c i a ~ tq Bell~vue Hos~)itaI, F c u r t h S z r v L : . S u b m i t t e d October 24, 1934.

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Radiology, as you shall hear later, has become one of our most effective arms in the conquest of gastrointestinal disease, and yet our e r r o r s in the diagnosis of disturbances of the g a s t r o - i n t e s t i n a l t r a c t are of shocking frequency, and our knowledge of selective dietetics still rates below t h a t of the instinct of the lower animals. As a m a t t e r of fact our dietetic h a b i t s are still more dictated by instinct, custom and ancestry, sometimes even by religion, than by scientific fact. I am fully aware t h a t my statements must seem to many of you who have considered the matter, as very broad and rash. Especially must they seem so to those of our cloth who have devoted t h e i r chief interests to this field t h r o u g h o u t long and rich professional lives. I believe however t h a t a dispassionate weighing of the facts of diagnostic e r r o r in this field as shown in the dead house of any large general hospital will serve to s u b s t a n t i a t e my statements in general. The timeliness of such a period of intensive study as we are i n a u g u r a t i n g tonight will no doubt be a p p a r e n t to us all before the days of the period of this serious consideration are over. There are of course reasons f o r our p a r t i c u l a r f r a i l i t i e s and inadequacies in this field of diagnosis. I think it will be helpful, if not flattering, for us to consider a few of them. Many, if not most, of our failures are due to the extreme complexity of the subject and to the delicate i n t e g r a t i o n which the gastro-intestinal t r a c t bears to all the other functions of the human body both in health and in disease. We may almost correctly state t h a t there are no general or special disturbances of the body which do not manifest themselves in some degree at least by symptoms or signs of g a s t r o - i n t e s t i n a l disorder. Consider for example the very f a m i l i a r symptom of nausea. It appears as an evidence of fright, of worry, and of many if not most other forms of mental and nervous disease. It is developed by v e r t i g o ; it is a sign of p r e g n a n c y ; it is one of the initial symptoms of most of the infections; it is intimately associated with visual disturbances, with trauma, shock, malnutrition, and with most of the surgical as well as medical diseases of the abdomen. It is frequent in pneumonia and in t r a u m a of the thorax, even with those of the extremities. I believe that one m a y almost say t h a t it is the most frequent symptom of all diseases of the body and of many physiological variations. It is even occasioned by political ccnditions, p a r t i c u l a r l y at the present time. This is but an example. The welfare of the entire body is essentially dependent on the i n t e g r i t y of the g a s t r o - i n t e s t i n a l tract. Most disease conditions of any of the systems, cause not only symptoms but abnormal signs also of the g a s t r o - i n t e s t i n a l tract. W o r r y and f r i g h t check or limit g a s t r o - i n t e s t i n a l secretion, favor abnormal putrefection and fermentation, delay or paralyze the all

EDITORIAL essential peristalsis, manifested by chemical and radiographic signs familiar to us all. Innumerable other states and diseases far remote anatomically from the gastro-intestinal tube also wreck changes of the same character. Gastro-intestinal symptoms, signs and pathology are among the most constant evidences of cardio-vascular disease and even the properly trained cardiologist must know how to distinguish these symptoms; he also must be a gastro-enterologist. The student of renal disease constantly is called upon to differentiate gastro-intestinal signs and symptoms due to kidney defects from those produced by integral pathology of the gastro-intestinal tract or perhaps from identical findings and symptoms primarily caused by widely distant and entirely foreign pathology to that of the organs in which he is primarily most concerned. Genital and endocrine diseases cause marked vagaries of the functions and signs of the digestive tube. Even the endocrinologist and the obstetrician must be serious students of gastro-enterology. This is equally true of every speciality of medicine. The student of dietetics in particular must familiarize himself with the ethnology, the history and the sociology of gastroenterology. Woe betide the patient of the specialist in pulmonary disease whose attendant never explores below the costal margins. I think that I have presented sufficient excuse for the tremendous difficulties of accurate diagnosis in gastro-intestinal disease, and incidentally I trust I have pointed out the great need which every practitioner and every research worker has for a broad general knowledge at least of the general principles concerned in the diagnosis of gastro-intestinal disturbances. It is of course axiomatic, for the same reasons that the specialist in the diagnosis as well as the therapeusis of the gastro-intestinal tract must be most broadly~ informed on general diseases and especially concerning those conditions such for example as pernicious anemia, sprue and the like which are strikingly evidenced by gastro-intestinal signs and symptoms. The gastroenterologist who is not an earnest student of internal medicine in particular is a very poor gastroenterologist. I say this in no disparagement of the gastroenterological specialist or for that matter of any other specialist, for true specialization in this day and stage of medical evolution is indispensible, and especially so in the tremendous field of gastroenterological diagnosis which demands not only broad learning but also very high technical training and ability in the very difficult and highly intricate methods of this speciality. Concerning this you will hear very much from f a r greater authority within the next few days. My purpose is to point out as convincingly as possible the absolute need for breadth of vision on the part of every one of us and at the same for as high a degree of technical perfection in the methods of diagnosis as is possible for any of us to attain. Even with such equipment, error in this difficult field is certain to occur all too frequently with the very best of us, and it is our hope that the frank discussion, earnest study and broad demonstrations which we are to receive within the next few days will return all of us to our offices and clinics better prepared to recognize and to treat the patient suffering from gastro-intestinal symptoms and pathology.

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It is not my function this evening to enter into the technical details of the diagnosis of gastro-intestinal diseases but rather to point out the general principles which apply to them. In extension of the ideas presented above, I would then first state that in every case of suspected gastro-intestinal disease a preliminary general examination should be made so that gastro-intestinal disorders of extra visceral origin may be first detected. This should eliminate from confusion such conditions as reflex vomiting, pernicious anemia, sprue, cerebral disease and many other conditions in which treatment should be directed primarily to pathology outside the gastro-intestmal tract. I feel also that second consideration should be accorded to the possibility of gastro-intestinal signs and symptoms developing as a result of disease factors introduced entirely from without. Such infections as uncinariasis for example, and other similar conditions may be readily enough confused with instances of gastric carcinoma or ulcer as they are m no small number of cases. Inadequate, superabundant, unbalanced or unaccustomed diet must be also considered as responsible for many signs and symptoms of gastro-intestmal disease and one must recall these possibilities before assuming primary pathology of the tract itself. In relation to these dietetic problems as a cause of gastro-intestinal disease it must be recognized that racial and ancestral customs play a very important part particularly when radical changes in physical habits, in climate, altitude and in sun and light conditions exist. Roughly stated, it will be found as a general rule that the most desirable diet and dietary customs in any locality will be those which the natives in that area habitually select. As has already been stated, it is not the function of this paper to consider in and detail the special technic of diagnostic examinations since all these are to be taken up in detail both in lecture and in demonstration. There are however certain general points in the diagnosis which properly fall to my function for presentation. The first of these is to point out that in diagnosis as in treatment, the gastro-intestinal tract can not be considered as separated from the general organism. On the contrary it is only when the general condition of the body as a whole is fully appraised that we are able properly to evaluate the data which lead up to adequate diagnosis; hence I feel that final diagnosis can only be arrived at properly after a general examination of the entire body has been conducted and weighed in relation to the evidence of history and environmental conditions. This must be then supplemented by a careful special examination of the gastrointestinal tract by whatever special technic may be indicated by the evidence elicited. In the course of this seminar you will be appraised fully of all of the newer methods of examination and of the invaluable data which they are able to present to the diagnostician. You will in particular be authoritatively informed of the tremendous contributions of radiography to this special field of medicine. In regard to the radiographic findings in particular I wish however to sound a warning note. So accurate, so valuable has the roentgenographic measures for the diagnosis of gastro-intestinal pathology become that many clinicians, especially some of the younger school

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AMERICAN JOURNAL OF DIGESTIVE DISEASES AND NUTRITION

have, I feel, come to r e l y too exclusively e i t h e r in a p o s i t i v e or in a n e g a t i v e w a y on X - r a y findings in d i a g n o s i s . Too o f t e n in t h e w o r k - u p of a v e r a g e hosp i t a l cases of g a s t r o - i n t e s t i n a l d i s e a s e I find t h a t the X - r a y findings only a r e sought, w i t h an a l m o s t complete i g n o r i n g of t h e t r e m e n d o u s l y v a l u a b l e lessons which chemical e x a m i n a t i o n s of t h e s e c r e t i o n s a r e still c a p a b l e of f u r n i s h i n g us. Too o f t e n the i n t e r n r e s o r t s to t h e use of t h e fluoroscope and X - r a y p l a t e before, r a t h e r t h a n a f t e r , a p r o p e r h i s t o r y h a s been taken. Chemical and m i c r o s c o p i c e x a m i n a t i o n s a r e neglected or u n d e r v a l u e d in the face of p o s i t i v e or n e g a t i v e r a d i o g r a p h i c facts, a n d by. no m e a n s i n f r e quently, g r a v e e r r o r s in d i a g n o s i s a n d in t r e a t m e n t t h e r e f o r e ensue. N e w m e t h o d s have much supplem e n t e d , b u t r a r e l y d i s p l a c e d t h e old. Quite as o f t e n also do we find t h a t the p h y s i c a l exa m i n a t i o n h a s been s l i g h t e d or even o m i t t e d . Too f r e q u e n t l y b e c a u s e of n e g a t i v e X - r a y findings, the rectoscope a n d s i g m o i d o s c o p e and t h e i r g r e a t possib i l i t i e s in t h e w a y of a c c u r a t e d i a g n o s i s a r e f o r g o t t e n . Too often, f a r too f r e q u e n t l y , even is t h e simple p r o c e d u r e of a d i g i t a l e x a m i n a t i o n a n d i n s p e c t i o n of the a n u s and r e c t u m o m i t t e d u n d e r t h e excuse t h a t the X - r a y findings a r e r e p o r t e d as n e g a t i v e . These e r r o r s of neglect a r e not t h e f a u l t of t h e r a d i o g r a p h e r ; t h e y a r e even v e r y commonly t h e r e s u l t of his too g r e a t efficienty in t h e d i a g n o s i s of g a s t r o i n t e s t i n a l p a t h o l o g y so t h a t t h e o t h e r m e t h o d s of exa m i n a t i o n a r e neglected. I also feel t h a t r e c o g n i z i n g as we m u s t t h e h i g h t e c h n i c a l skill of t h e a v e r a g e m o d e r n r a d i o g r a p h e r , t h a t the clinical d i a g n o s t i c i a n neglects to view h i m s e l f t h e films a s s e m b l e d by t h e e x p e r t , as it were, t h r o u g h t h e eyes of t h e clinician, a n d too o f t e n also does t h e c l i n i c i a n f o r g e t t h e t r e m e n d o u s value w h i c h m a y be afforded h i m by his own use of t h e fluoroscope, a g a i n viewed t h r u t h e eyes of the clinician, f a m i l i a r as he should be w i t h t h e chemical, m i c r o s c o p i c a n d p h y s i c a l a s p e c t s of t h e case, all t h r o w n as i t were, on t h e screen of t h a t m o s t v a l u a b l e of all d i a g n o s t i c m e t h o d s , a well and p e r s o n a l l y t a k e n history. F i n a l l y I would a g a i n i m p r e s s upon all of you t h e v e r y g r e a t v a r i a t i o n s w h i c h occur in t h e g a s t r o - i n t e s t i n a l t r a c t still w i t h i n t h e wide r a n g e of p h y s i o logical i d i o s y n c r a s y - - v e r y f r e q u e n t l y t h e s e a l m o s t imperceptibly, v e r g e over t h e line into real m o r p h o l o g i c a l o r chemical p a t h o l o g y , while y e t still capable of corr e c t i o n a l o n g p h y s i o l o g i c a l m e t h o d s of t r e a t m e n t . T h e g a s t r o - e n t e r o l o g i s t m u s t be a v e r y b r o a d man, one f a m i l i a r w i t h m a n y fields w i t h i n t h e r e a l m of m e d i c i n e and y e t s u p e r f i c i a l l y viewed as f a r f r o m t h e definite s u b j e c t of g a s t r o - i n t e s t i n a l disease. N o t f o r one m o m e n t m a y he be allowed to f o r g e t t h a t g a s t r o intestinal physiology and pathology are inextricably blended w i t h t h e f u n c t i o n s of t h e body as a whole and as a r e s u l t of its r e a c t i o n s to e n v i r o n m e n t . H a r l o w Brooks, N e w Y o r k City, N e w York. ENTEROGASTRONE H E o r i g i n a l o b s e r v a t i o n of E w a l d and Boas (1886) t h a t t h e p r e s e n c e of u n d i g e s t e d f a t in t h e u p p e r i n t e s t i n e causes an i n h i b i t i o n of g a s t r i c m o t o r act i v i t y has been r e p e a t e d l y confirmed. T h a t f a t h a s a s i m i l a r i n h i b i t o r y effect on g a s t r i c s e c r e t i o n w a s demo n s t r a t e d by P a v l o v and h i s s t u d e n t s ( L a b a s s o v ) . The n a t u r e of t h e i n h i b i t o r y m e c h a n i s m concerned h a s

T

been c o n s i d e r e d to be e n t i r e l y n e r v o u s u n t i l recently. In 1926 F a r r e l l and I v y (1) i n t r o d u c e d a new concept c o n c e r n i n g t h e m e c h a n i s m of t h e i n h i b i t i o n w h e n t h e y observed i n h i b i t i o n of an a u t o - t r a n s p l a n t e d g a s t r i c pouch following the i n t r o d u c t i o n of f a t into t h e m a i n stomach. This demonstrated that a humoral a g e n c y m u s t be considered as p l a y i n g a rSle in t h e g a s t r i c i n h i b i t i o n caused by fat. T h i s was soon conn r m e d by L l m and his colleagues (2). L a t e r , F e n g , l-Ion and L l m (~) ~ound t h a t f a t also i n h i b i t e d t h e s e c r e t m n of a t r a n s p l a n t e d g a s t r i c pouch, a n d t h a t t n e m m m t o r y h u m o r a l a g e n t w a s not some p o s t - a b sorp61ve c i r c u l a t i n g s u b s t a n c e o r i g i n a t i n g I r o m dig e s t e d 1at. ~tmgmy, Z e t t e i m a n and i v y (4) s i m i l a r l y I o u n d t h e m m m t m n o~ m o t n t t y c a u s e d by f a t was not uue to p o s t - a o s o r p t t v e c i r c u l a t i n g I a t t y suDstances. ~tu~gley anu Ynelps (5) nave r e c e n t l y subm~tteu evidence s n o w i n g O~at glucose a c t i n g m t h e u p p e r l n t e s u n e lnnlul~s g a s t r m inO~lllty by some n u m o r a l a g e n c y a n d tna~ the a g e n t was not tne a b s o r b e d c l r c u l a u n g glucose. These o b s e r v a t m n s , of course, s u g g e s t e d t h e possib m t y tna~ when u n d i g e s t e d I a t (~acty d~gests s u m u la~e secre~mn a n d m o t m t y ) c o n t a c t s the u p p e r ~ntest l n a l mucosa a cnalone ( l n m m t o r y a u t a c o m ) ;s elabora~eu a n d c a r r m u by ~he blood i I a t t y l y m p h is m a c ~lve) 1,o t n e s t o m a c h w h e r e it causes l n I l l b l t l o n oI m o t ] h t y anu s e c r e u o n , t I t i n s hypothes~s w e r e t r u e such an i n h i b i t o r y s u b s t a n c e should be e x ~ r a c t a m e xrom t n e u p p e r i n t e s t i n a l mucosa. I n Iac~, r~osal~a and L l m ((i) have f o u n d t h a t w h e n r e l a t i v e l y l a r g e doses o~ a c n o l e c y s t o k m m p r e p a r a t m n , ~upplmd by the a u t h o r , were r e j e c t e d i n t r a v e n o u s l y g a s t r i c s e c r e u o n was i n h i b i t e d . 'l'hls s t i m u l a t e d L l m a n d m s colleagues (7) to d e t e r m i n e w h e t h e r a specific s u b s t a n c e m~ght be i s o l a t e d f r o m i n t e s t i n a l mucosa, w m c n would m n i b l t g a s t r i c a c t i v i t y w i t h o u t h a v i n g an er~ecc on p a n c r e a t m and b ] l i a r y flow. T h e y w e r e successful m p r e p a r i n g such an e x t r a c t , a l t h o u g h t h e y f o u n d t h a t s i m i l a r l y p r e p a r e d e x t r a c t s of muscle a n d g a s t r i c m u c o s a also caused i n h i b i t i o n , b u t to a less e x t e n t t h a n e x t r a c t s of i n t e s t i n a l mucosa. B e c a u s e of t h e s t r o n g p r e s u m p t i v e evidence, t h e y c o n s i d e r e d t h e h u m o r a l i n h i b i t o r y , or chalonic, s u b s t a n c e and t h e inh i b i t o r y s u b s t a n c e in t h e i r e x t r a c t to be identical. So, t h e y n a m e d t h i s g a s t r i c i n h i b i t o r y p r i n c i p l e of i n t e s tinal extracts "enterogastrone." More recently, Lira, L i n g a n d L i u (8) have r e p o r t e d t h a t t h e y have been able to remove all t h e vaso-dep r e s s o r and toxic s u b s t a n c e s f r o m t h e active e x t r a c t . I n d e p e n d e n t l y , G r e e n g a r d , M a i s o n a n d I v y (9) have also been able to p r e p a r e an e x t r a c t w h i c h is f r e e f r o m o b j e c t i v e l y detectible toxic s u b s t a n c e s , a n d w h i c h inh i b i t s both s e c r e t i o n a n d m o t i l i t y in t h e dog. However, it is believed t h a t the p r e p a r a t i o n is not y e t sufficiently p u r e to w a r r a n t i n j e c t i o n s into man. I t would a p p e a r t h a t e n t e r o g a s t r o n e is a s u b s t a n c e w h i c h m a y prove to be of p r a c t i c a l value. A n y subs t a n c e which possesses t h e g a s t r i c i n h i b i t o r y a t t r i b utes of a t r o p i n e w i t h o u t its u n d e s i r a b l e side effects would be of p r a c t i c a l value in c e r t a i n cases of " p e p t i c " ulcer. I t is not k n o w n w h e t h e r e n t e r o g a s t r o n e is active h y p o d e r m a t i c a l l y , which will depend l a r g e l y on