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The psyche and the stomach
GASTROENTEROLOGY
HISTORICAL
1981;66:665-14
SERIES
The Psyche and the Stomach A Historical STEWART
Vignette
WOLF
St. Luke’s Hospital, Bethlehem, Pennsylvania, Laboratories, Inc., Bangor, Pennsylvania
The association of emotional problems with disturbances in the behavior of the stomach-behavior that causes discomfort and disability-has been a part of conventional wisdom for many centuries. References to stomach troubles brought on by the stresses of life are found in the works of painters, poets, and philosophers extending back as far as the beginning of the Christian era. The first description of actual changes in the stomach during emotional upsets, however, appears in Beaumont’s classic monograph published in 1833, wherein he describes his studies of Alexis St. Martin, a man who had sustained a gunshot wound in the abdomen that left him with a permanent gastric fistula (1). Although Beaumont provided the first objective confirmatory evidence of the linkage between gastric function and emotionally significant experiences, he accorded relatively little attention either to the gastric findings he observed or to the associated emotional states of his “cantankerous” subject. Beaumont described what he saw as follows: “In febrile diathesis, or predisposition, from whatever cause-obstructed perspiration, undue excitement by stimulating liquors, overloading the stomach with food-fear, anger, or whatever depresses or disturbs the nervous system-the villous coat becomes sometimes red and dry, and at other times pale and moist, . .” and loses its smooth and healthy appearance.. He goes on to describe “deep red pimples,” “irregular circumscribed red patches,” and “aphthous crusts-like the rolling up of the mucous coat into small shreds. . . .” Such changes were accompanied by suppression of secretions and marked delay in gastric digestion and emptying of the stomach. Beaumont and St. Martin are pictured in Figures 1 and 2. Beaumont’s work stimulated several investigators Received August 11, 1989. Accepted October 16, 1989. Address requests for reprints to: Stewart Wolf, M.D., Vice President for Medical Affairs, St. Luke’s Hospital, Bethlehem, Pa. 18015. 0 1981 by the American Gastroenterological Association 0016-5085/81/030605-10602.50
and
Totts
Gap
Medical
Research
to study animals, chiefly dogs, with surgically induced gastric fistulas. The earliest reports were those of Bassow from Russia (Z), Blondlot (3) and Claude Bernard (4) from France, and Pavlov’s teacher, Heidenhain (5) and Bidder and Schmidt (6) from Germany. From these studies of surgically induced gastric fistulas a ground work of understanding of normal gastric physiology was laid and the dependence of gastric secretion and motor activity on the intactness of the vagus nerve was established. The stage was set for the monumental studies of Ivan Pavlov (Figure 3) who, near the turn of the century elicited a flow of gastric juice from his dogs in sham feeding experiments in which the esophagus was interrupted and exteriorized so that swallowed food, instead of reaching the stomach, simply fell to the floor (7). The evoked secretory response occurring in anticipation of feeding became known as the psychic phase of gastric secretion. Pavlov’s important discovery had actually been preceded by an observation made independently on a fistulous human subject in 1878 by a young French medical student, Charles Richet (Figure 4). Richet’s subject was a 15yr-old youth named Marcellin who had acquired an esophageal stricture from the accidental ingestion of potassium hydroxide. Verneuil, a surgeon on the faculty of the University of Paris had operated on the boy in 18’76,providing him with an opening into his stomach through his abdominal wall (8). Successful surgical gastrostomies had been performed for only 1 or 2 yr at that time. Verneuil called young Richet’s attention to the unusual opportunity for the study of stomach function. Richet’s investigation of the fistulous young man provided the basis for his theses for both the M.D. (9) and Docteur es Science (lo), the French equivalent of a Ph.D. in Science. The former dealt with the sensibility of the gastric mucosa and the latter with the chemistry of the gastric juice. During the course of his experiments Richet noted increased gastric se-
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Figure 1. Colonel William Beaumont.
cretion when he allowed Marcellin to chew some candies, which, of course, could not traverse the esophagus to the stomach. Richet failed, however, to realize the importance of his observation and to explore it further. Later he wrote in his memoirs (11) “Too often-we can only see what we are looking for; absurd in the extreme . . . because one must observe whatever happens, even what one does not expect, especially what one does not expect.” Pavlov built his revolutionary hypothesis of central neural integrative function on his demonstration of visceral conditional or anticipatory responses (12). He showed that habitual responses to conditional stimuli (symbols) could be acquired through repetition and, furthermore, that an established pattern of response could be disrupted or even lost as a consequence of emotionally disturbing events. On one occasion Pavlov was preparing to demonstrate the conditional salivary response to a representative of the Tsar. Pavlov selected his most reliable performer and placed the dog on a table close to the podium. All eyes were turned toward the royal emissary, including those of Pavlov’s canine subject who appeared transfixed by the drama. Pavlov sounded his bell, but not a drop of saliva emerged from the cannula in the dog’s salivary duct! The experience was, of course, a great embarrassment for the professor, but from it he learned that conditional reflexes could be inhibited during emotionally charged
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situations. At another time, several of Pavlov’s dogs lost their formerly reliable conditional reflexes following what must have been a terrifying experience, a sudden flood in the kennels. This catastrophe led Pavlov to recognize degrees of vulnerability in the animals to emotionally engendered inhibition depending upon contrasting temperaments associated with different breeds (13). Pavlov’s studies of “psychic secretion” soon found confirmation in observations on human subjects when in 1905 Cade and Latarjet published their observations of a patient who had acquired in infancy an epigastric hernia in which a portion of the stom(14). Eventually the mucosal ach was incarcerated surfaces of the trapped pouch ulcerated through to the outside, leaving the patient with a spontaneously produced “Pavlov pouch.” These investigators confirmed Pavlov’s work on animals with regard to secretion in the pouch in response to food taken into the stomach, and in response to “psychic” stimuli in the form of discussion of appetizing dishes. Cade and Latarjet, however, made no notes of changes in vascularity or color changes in the exposed mucous membrane. In 1907, Kaznelson provided further confirmation of Pavlov’s sham feeding experiments in studies on a human subject who had an esophageal as well as a gastric fistula (15).
Figure 2. Alexis St. Martin.
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Figure 3. Ivan Pavlov.
Gastric Accompaniments stress
of Emotional
Gastric fistulas, occurring accidentally or produced surgically, made possible the linking of emotionally charged experiences to the behavior of the stomach. Such data are difficult to gather in intact subjects owing to the stomach’s relative inaccessibility to direct observation. Gastric fistulas in human subjects had been available for study long before Beaumont’s perceptive and original observations on Alexis St. Martin. Reports in the literature of gastric fistulas in human subjects go back at least to 1564 when Matthew Cornax, a Viennese professor of medicine and physician to Emperor Ferdinand, published an account of a man, who, while hunting, was
wounded in the abdomen by a stake (16). It penetrated his stomach and left him with a permanent gastric fistula. Neither Cornax’s paper nor dozens of others describing fistulous human subjects in the intervening years before Beaumont’s work made any mention of alterations in the stomach accompanying emotional changes in their subjects. In the early years of the present century, Anton Carlson (Figure 5) carried out extensive studies of a human subject, Mr. Vlcek, who had a gastric fistula one-half inch in diameter. In the course of his investigations of the contractile activities of the stomach, Carlson noted inhibition of gastric contractions during fear (17). When, on the other hand, strong gastric contractions were present, he observed that accompanying each one was a deepening of the red color of the mucous
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Figure 4. Charles Richet as a medical student.
membrane. With respect to secretion, he noted that the resting, fasting stomach secretes acid gastric juice, an observation contrary to the findings of Beaumont and Pavlov, who had held that in the absence of stimuli, mechanical or chemical, the stomach remained empty and failed to secrete. Carlson’s patient lived for years, serving alternately as experimental subject and diener in the laboratory, feeding himself through his stoma and enjoying good health, free from gastrointestinal complaints. It is striking that, while enhanced gastric secretory and motor activity had been recognized in association with sham feeding and the presumably pleasant emotion, appetite, “negative” emotions, fear, anxiety, and anger had been shown by Beaumont and Carlson to be accompanied by diminished gastric secretory and motor activity. Such inhibitory effects on the stomach provided the basis for classical contributions by Walter Cannon (Figure 6), a contemporary of Carlson who, although he had no chance to study a fistulous human being, nevertheless, made extensive observations on gastric motor and secretory functions in animals in response to threats and hazards of various sorts (18). Enhanced gastric activity in humans under emotionally stressful circumstances was probably first noted by Gordon and Chernya who in 1940 reported a patient with a gastric fistula, whose gastric secretion of acid had been consistently in the low normal range until,
during a period of restlessness, homesickness, and resentment toward their experimental demands, he displayed a marked hyperacidity (19). A further documentation of increased gastric activity during certain types of emotional stress was provided by Bela Mittlemann’s studies of patients with duodenal ulcer carried out in collaboration with Harold Wolff (20). By studying the gastric juice of their subjects obtained through a swallowed Levine tube and by recording gastric contractions from an indwelling balloon, Mittlemann and Wolff were able to observe increases in gastric secretion and motility during stressful interviews. The following year the author’s studies of Tom were begun in collaboration with Wolf and Wolff (21). The year was 1941 when Tom was 56 years old (Figure 7). The research continued until Tom’s death in 1958 at age 73 (22). Tom’s gastric fistula was the result of a surgical operation performed at the old New York Hospital in 1895. At the age of 9, Tom had accidentally burned his esophagus by swallowing scalding hot clam chowder. A complete esophageal occlusion ultimately developed, necessitating his gastrostomy. The work with Tom contributed several new items to our body of knowledge about the stomach. The exposed gastric mucosa of Tom made it possible to observe the vascularity of the stomach as reflected by the color of the mucosa and the degree of engorgement as well as secretion and motor activity.
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Figure 5. Anton Carlson. Tom’s gastrostomy also afforded the opportunity to make prolonged or frequently repeated measurements of gastric function. In Tom and in other fistulous subjects whom we were privileged to study, we found that fright, depression, and attitudes of being overwhelmed were associated with pallor of the mucosa, diminished acid secretion, and reduced gastric motor activity. The reaction was similar to that described by Cannon in his cats when they were required to face a barking dog (18). What we were able to add was evidence of hyperactivity in the stomach that accompanied more aggressive attitudes and feelings of anger and resentment. Under circumstances characterized by hostility and resentment, we observed in Tom, and in other subjects, hyperemia and engorgement of the gastric mucosa, together with accelerated secretion of HCl and enhanced contractile activity in the stomach. Dr. Cannon, who had been a member of the Committee that had awarded a National Research Council Fellowship to the author, was so interested in the projected studies of Tom that he visited the laboratory in New York and spent several days observing the experiments, talking at length with Tom and watching his stomach. Dr. Cannon then wrote in the Foreword of Human Gastric Function that: “He (Tom) had an
emotional range and responsiveness that permitted nice discriminations which the authors have fully utilized. The interesting fact that frustration and repressed conflict were associated with hyperemia and with increase of motility and secretion will come as a surprise to many. Likewise highly significant is evidence that engorgement of the mucosa, whatever its cause, is associated with lessened resistance to trauma, for, as the authors point out, this condition has importance in explaining the incidence of gastric ulcer. Obviously the extent and variety of testimony here accumulated provides interest not only for clinicians but for physiologists, pharmacologists, psychiatrists and pathologists as well” (21). The “bipolar” nature of changes in gastric function that we observed to be characteristic of what appeared to be quite different and distinguishable emotional configurations found confirmation in the studies of Reichsman et al. whose subject was a 6yr-old girl with a gastric fistula (23). Using motion pictures they provided elegant documentation of the child’s contrasting behaviors. Her aggressive behavior was associated with gastric hyperfunction while her withdrawal or “giving up” behavior was accompanied by inhibition of gastric secretory and motor
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Figure 6. Walter Cannon.
Figure 7. The author with Tom.
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1981
activity. It was therefore of interest that in an earlier study Farr and Lueders (24) found high levels of gastric secretion in hypomanic patients but low levels in those with mental depression. Margolin et al. (25) had an opportunity to study a woman psychiatric patient with a surgically induced gastric fistula. They observed deviations in their subject’s gastric function that accompanied the probing of unconscious conflicts identified through psychoanalytic techniques. They concluded that their subject had made an unconscious association of her gastric fistula with a vagina and the investigator’s instrumentation with sexual assault. An important series of observations on intact human subjects was made by Weiner et al. (26). They gathered indirect evidence on gastric acid secretion through the measurement of pepsinogen concentration in the blood. They were able not only to show elevated values of pepsinogen in patients with duodenal ulcer, but also temporary elevations of the enzyme in military recruits and other healthy subjects during emotionally stressful events. Epigastric
Pain and Ulceration
In further studies of Tom we were able to show that during gastric hyperfunction, characterized by mucosal hyperemia and engorgement, not only was there increased acid secretion and motor activity but a lowering of pain threshold and, as Dr. Cannon pointed out, increased fragility of the gastric mucous membrane. Indeed, sustained hyperactivity of the stomach was accompanied by epigastric pain that could be relieved by milk or alkali. Further, it was shown that native gastric juice was capable of digesting the mucosa if the protective mucous coating were removed or otherwise deficient. In fact, a peptic ulcer was induced in the mucosa of Tom when a portion of the membrane, deficient in mucous production, was kept in contact with his own gastric juice for a period of 3 days. Appetite,
Hunger, and Satiety
Appetite, an emotional state characterized by the pleasurable anticipation of eating, was shown in Tom, as it had been in other human subjects and in animals, to be associated with enhanced gastric activity. Hunger is not necessarily a pleasant experience. Indeed, hunger is perhaps more commonly _ unpleasant, even painful. As distinct from appetite, an aspect of the feeling of hunger has a peripheral sensory component. Cannon and Washburn, in 1912 (27) associated the pangs of hunger with contraction of the gastric antrum. Later, Patterson and Sand-
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Weiss (28) showed that duodenal contractions could give rise to hunger sensations as well. Satiety has been the subject of extensive study in the past few years. Smith et al. have shown that afferent impulses from the mucosal surface of the gut from mouth to jejunum play a major role in the interruption of eating. Even sham feeding was sufficient to induce temporary satiety if reinforced by the peripheral effects of cholecystokinin (29). Nausea Studies of Tom and of other fistulous and intact humans have shown that reduced gastric activity associated with attitudes of withdrawal are often accompanied by sensations of nausea. Indeed, nausea, whether induced by emotionally stressful circumstances, by vestibular stimulation or by emetic drugs, was shown to be associated with a striking gastric hypoactivity, marked dilatation of the organ and lack of motility (30). At the same time, as previously shown by Ingelfinger (3l), contractile activity in the first portion of the duodenum was enhanced, creating thereby a reversal of the usual gastroduodenal gradient. With an accompanying relaxation of the pyloric sphincter, the contents of the duodenum were regurgitated into the stomach. Subsequent vomiting was accompanied by a relaxation of the cardiac sphincter so that Tom’s gastric content was forced into the distal blind end of his esophagus. These gastric and duodenal changes, characteristic of nausea, were subsequently confirmed by other investigators in animal experiments (32).
Placebo Effects A placebo effect is, of course, an aspect of the psychologic communication between patient and physician. The power of the placebo has been recognized since antiquity, but evidence that placebos produced changes in the end organ was lacking until the studies of Tom provided quantitative evidence in the form of measurable changes in Tom’s gastric function after administration of placebos, changes as marked as those induced by potent pharmacodynamic agents (33). Gastric Ulcer Accompanying Emotional Crisis
Intense
Tom underwent an intense emotional crisis which afforded the investigator an opportunity to observe a spontaneous ulceration of the gastric mucosa during an episode of continuous high level acid secretion.
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The set of circumstances followed the discovery of a carcinoma on the exposed portion of Tom’s gastric mucosa. The microscopic picture was that of an adenocarcinoma of very malignant appearance. Tom refused to consider any surgical operation except a local removal. He particularly refused to countenance a procedure directed at closing the stoma with which he had lived for so many years. His wishes were respected, and only a narrow margin of skin and uninvolved gastric mucosa around the lesion were resected. Before the operation and since the initial discovery of the carcinoma, Tom’s gastric juice was found to be consistently achlorhydric. Biopsy of the uninvolved portion of the exposed mucosa, made at the time of the removal of the carcinoma, showed typical atrophic gastritis, very similar to that induced experimentally in dogs by injections of a preparation of human gastric juice containing a property of powerfully inhibiting hydrochloric acid secretion (3436). A striking finding was that after surgical removal of the carcinoma, HCl secretion reappeared as before in Tom’s stomach. Tom survived 2 yr after the operation. During that time he was continuously dehydrated because of uncontrollable leakage through his enlarged gastric fistula. It was literally impossible for him to keep enough fluid inside him to maintain adequate water and electrolyte balance. Tom consistently resisted the most vigorous entreaties to undergo a revision of the stoma. To those who were looking after him, the importance of persuading him to submit to an operation was so great that it can be said that Tom was under intense pressure which he vigorously resented. Throughout this period his gastric acidity remained persistently high. Eventually one, then a second, and then a third ulcer appeared on the mucosa near the stoma. It was presumed at the time that the ulcers represented recurrent carcinoma, so efforts to persuade Tom to submit to an operation were intensified but still futile. He therefore returned home with ulcers still present.
Tom’s Final Days Within a day or two, Tom began to bleed profusely from one of the ulcers. Admitted as an emergency patient to New York Hospital, he underwent biopsy of the ulcer. No neoplastic tissue was found. At length, but too late, he agreed to an operation to revise the stoma. An old pyelonephritis had flared up and, in addition, Tom developed bronchopneumonia. He soon died in uremia in his 74th year, 65 years after his esophageal occlusion. At autopsy no evidence of cancer was found. The ultimate tribute to Tom was paid by the brilliant Dutch investigator J.J. Groen, former professor of medicine at Hadassah Medical School in Jeru-
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salem and now professor of psychobiology at the University of Leiden. He wrote, “The real stimulus, the spark that ignited the chain reaction of investigational energy, came from the encounter with a seemingly unimpressive small man, named Tom. The researches carried out on this gastric fistulous subject, Tom, and other subjects that offered comparable opportunities for study, were not only just another set of good experiments. They showed to everybody who could see, that the problems of so-called psychosomatic relationships could be studied with straightforward methods of clinical investigation.“(37).
Perspective The Relationship
of Subject and Investigator
Over a span of 400 years, studies of patients with gastric fistulas have contributed in different ways to our understanding of the stomach and its functions. What can be learned from a human subject with a gastric fistula is determined in part by the relationship between investigator and subject. Beaumont’s association with Alexis St. Martin was sometimes turbulent and was interrupted for months or years at a time. His more than 200 recorded observations were made in segments spread over 8 years. St. Martin was exasperatingly unreliable, improvident, and stubborn. He complained a great deal of dizziness and weakness during experimentation, and he was overimbibing much of the time between experimental sessions. Richet’s patient, Marcellin, on the other hand, was cooperative and dependable, appearing at the laboratory for study each morning at the appointed time. Carlson’s papers reveal little of the personality of Mr. V., although he must have been conscientious since he worked for years as a helper in the laboratory and was apparently reliable as an experimental subject. Tom was a warm, sensitive, short tempered and impatient, but very loyal person who applied himself to his duties with intensity. He also took a great interest in the studies of his stomach. He was fully aware and thoroughly proud of his position as a contributor to medical science. Tom enjoyed the respect and affection of the hospital family and especially the expressed interest and often deference of distinguished visitors. He grew to look upon the author (more than 25 years his junior) almost as a father and depended upon him in myriad ways for guidance and support with personal and family matters. The Influence of the Times One hundred years ago Beaumont wrote, “I have availed myself of the opportunity afforded by a
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concurrence of circumstances which probably never can again occur. .." (1).It may be that the precise series of events which resulted in a permanent opening into the stomach of Alexis St. Martin has not been repeated, but Beaumont’s opportunity to study the physiology of the stomach at close range through a gastric fistula has not remained unique. By virtue of new approaches to the study from one generation to the next, additional facts have been learned and various aspects of the problem of gastric function have been clarified. The problem could never be disposed of by a single worker, however ideal his opportunities, for the questions put to nature vary from one generation to the next. An investigator’s horizon is limited by the height of the vantage point on which he stands. These vantage points are the prevailing concepts of the day. Few men have been able to look beyond the horizon of their generation. Beaumont’s work was influenced by the widespread interest in inorganic chemistry which prevailed in his day. Therefore, in his studies on Alexis St. Martin he was principally concerned with discerning the process involved in converting a bolus of food into an amorphous, semifluid thyme. He interested himself primarily in the properties of gastric juice, as he emphasized in the title of his treatise: Experiments and Observations on The Gastric Juice and the Physiology of Digestion. The critics of Beaumont’s day, too, were preoccupied with the same considerations, and they were disappointed by his failure to show whether or not there was a “vital force” in the stomach which enabled food to be chymified more readily in vivo than when incubated with gastric juice in vitro. Richet’s observations on an early gastrostomy patient were made 50 years after Beaumont’s publication. His interest in the nervous system led him to explore the sensibility of the gastric mucosa. Also, he showed that gastric acidity increased during the process of digestion and, noting the relative homogeneity of the material delivered to the duodenum, despite the wide diversity of food ingested, Richet speculated that the duodenum exercises control over gastric emptying. Richet further concerned himself with the chemistry and physiologic properties of gastric juice. He was the first to observe the capability of the gastric juice to coagulate milk, discovered later to be attributable to the presence of renin (38). He was able to confirm the demonstrations by William Prout (39) and by Beaumont that hydrochloric acid was present in the stomach. Moreover, he showed that the concentration of HCl was greater in carnivorous than in herbivorous animals and that to some extent HCl was linked to nitrogen-containing organic substances. Carlson, 25 years after Richet, was subject to dif-
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ferent prevailing influences in physiology. The passage of time had offered him a new approach to the investigation of his patient with a gastric fistula. The star of “vitalism” had faded, and “mechanism” had taken its place. A great school of physiologists had appeared whose interests lay in the behavior of organs and in the mechanics of their interrelationships. Carlson’s work was primarily concerned with kinetics. The majority of his experiments on the stomach were directed towards a study of gastric motility and of “hunger contractions” in particular. Beaumont, Richet, and Carlson had each detected changes in gastric function in association with varying emotional states, but they made no systematic observations upon them. Neither did they seem to appreciate the magnitude of the changes and their possible relation to epigastric distress and disease. Richet, who had made the original observation of the psychic secretion of gastric juice, had discussed it only in his memoirs. His concern with the stomach was but a transient passion during his student days. As a professor he assigned the topic to his student, Carvalho, who soon abandoned physiology to participate in the restoration of past glories of France.” Carvalho did write a thorough going review of studies in gastric physiology with an extensive bibliography for the remarkable Dictionaire De Physiologie edited for 18 years by Charles Richet (40). The work was interrupted by World War I and never resumed. Pavlov’s investigations were stimulated by his mentor, Sechenov, whose monograph, Reflexes of the Brain appeared during the dawn of neurophysiology when investigators in Western Europe had begun to attempt to unravel the complex circuitry of the brain and to identify some of the pathways and mechanisms involved in visceral and general behavior (41). Pavlov developed a theory of communication within the brain in which the ultimate response was dependent upon the interplay of facilitatory and inhibitory influences. The studies of Tom were undertaken a few years after the publication of Walter Cannon’s classic monograph, Bodily Changes in Pain, Hunger, Fear and Rage (18) and a year after Flanders Dunbar’s Emotions and Bodily Changes (42). The time was propitious for a systematic investigation into “the physiology of emotion.” Within a few years the author had an opportunity to study, in addition to
*Carvalho, an impecunious Basque, had married another of Richet’s students, a wealthy American, Anna Coleman. The couple purchased the Chateau Viilandrie and devoted the rest of their lives to restoring and promoting it. Indeed, the survival of the magnificent French chateaux and their accessibility to visitors is due to legislation originally proposed by Dr. and Mrs. Carvalho.
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Tom, 4 other patients with gastric fistulas including a man with a gastrostomy required because a head injury had rendered him effectively decorticate (43). Among the others, one had an associated duodenal ulcer, and another underwent bilateral vagotomy during the period of study. The clearest lesson from these studies was that to understand a man’s stomach one must understand the man.
References 1. Beaumont W. In: Experiments and observations on the gastric juice and the physiology of digestion. Plattsburg: F.P. Allen, 1633. 2. Bassow DR. Voie artificielle dans l’estomac des animaux. Bull Sot Natur Moscou 1643;16:315. (Cited by Richet: Du sue gastrique chez l’homme et les animaux: Ses proprietes chimiques et physiologiques. Paris, Librarie Germer Baillere et Cie). 3. Blondlot N. Trait analytique de la digestion considered particulierement dan l’homme et dans les animaux vertebres, 1843. (Cited by Richet: Du sue gastrique chez I’homme et les animaux: ses proprietes chimiques et physiologiques. Paris, Librarie Germer Baillere et Cie). 4. Bernard C. Leqons sur les proprietes physiologiques et les alterations pathologiques des liquides de l’organisme. Paris, Bailleurs, 1659. und trophische Dru5. Heidenhain RPH. Ueber secretor&he sennerven. Pflug Arch Ges Physiolamte 1676;17:1. und der Stoff6. Bidder F, Schmidt C. Die Verdauungssaefte wechsel. Mitau % Leipzig, 1652. 7. Pavlov I. In: The work of the digestive glands. English translation from the russian by WH Thompson. London: C. Griffin and Co., 1910. 6. Verneuil H. Observation de gastro-stomie pratiquee avec success pour un retrecissement cicatriciel infranchissable de l’oesophage. Bull Acad Med 1676;5:1023. et cliniques sur la 9. Richet C. In: Recherches experimentales sensibilite. Paris: Masson, 1677. 10. Richet C. Des proprietes chimiques et physiologiques du sue gastrigue chez l’homme et les animaux. Appendix A. J Anat Physiol 1678;14:170. 11. Richet C. Souvenirs d’un physiologist. Paris: J. Peyronnet & Cie, 1944. 12. Pavlov I. In: Conditioned reflexes. An investigation of the physiological activity of the cerebral cortex. (Translated by GV Anrep. New York: Oxford University Press, 1927; also New York: Doyer Publications, 1966). 13. Pavlov I. In: Lectures on Conditional Reflexes (Translated by WH Gantt New York International Publishers, 1926). 14. Cade A, Latarjet A. Realisation pathologique du petit estomac de Pavlov. Etude Physiol. Path Gen 1995;7:221. am Erwachsenen 15. Kaznelson H. Scheinfutterungsversuche Menschen Pfluegers Archiv Ges Physiol 1997;118:327. 16. Cornax M. Medical consultations apud aegnoteos secundum artem et experientiam salubriter instituendae enchiridion, Bale, 1564. (Cited by CG Cumston) Med J Ret 1926;124:229. 17. Carlson AJ. Contributions to the physiology of the stomach. Articles l-23. Am J Physiol 1912;31:151. 16. Cannon WB. In: Bodily changes in pain, hunger, fear and rage. New York: D. Appleton, 1929. 19. Gordon OL, Chernya YM. Physiology of the gastric secretion in man; studies on patients with gastric fistula and artificial esophagus. Klin Med (No. 12) 194@18:63.
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20. Mittlemann B, Wolff HG. Emotions and gastroduodenal function: experimental studies on patients with gastritis, duodenitis and peptic ulcer. Psychosom Med 1942;4:5-61. 21. Wolf S, Wolff HG. In: Human gastric function. 1st ed. New York: Oxford University Press, 1943. 22. Wolf S. In: The stomach. New York: Oxford University Press, 1965. 23. Reichsman F, Engle GL, Segal HL. Behavior and gastric secretion: the study of an infant with a gastric fistula. Psychosom Med 1955;17:461. 24. Farr CB, Lueders CW. Gastric secretory functions in the psychosis. Arch Neural Psychiatr 1923;10:546. 25. Margolin SG, et al. Variations of gastric functions during conscious and unconscious conflict states. Life stress and bodily disease, ARNMD Proceedings. Baltimore: Williams & Wilkins co., 1950. 26. Weiner H, Thalen M, Reiser MF, Mirsky IA. Etiology of duodenal ulcer. 1. Relation of specific psychological characteristics to rate of gastric secretion (serum pepsinogen) Psychosom Med 1957;19:1. 27. Cannon WB, Washburn AL. An explanation of hunger. Am J Physiol 1912;29:441-5. 26. Patterson TL, Sandweiss DJ. Relationship between gastroduodenal motility phases and symptoms associated with duodenal ulcer in the human. Am J Dig Dis 1942;9:375-361. 29. Smith GP, Gibbs J. Postprandial satiety. In: Progress in psychobiology and physiological psychology. Sprague JM, Epstein AN, eds. Vol. 6, 179-242, New York: Academic Press, 1979. 30. Wolf S. The relation of gastric function to nausea in man. J Clin Invest 1943;22:677-62. 31. Ingelfinger FJ. Behavior of the duodenum during nausea. Bull N Engl Med Center 1942;4:120. 32. Gregory RA. Changes in intestinal tone and motility associated with nausea and vomiting. J Physiol 1948;105:56-65. 33. Wolf S. Effect of suggestion and conditioning of the action of chemical agents in human subjects. The pharmacology of placebos. J Clin Invest 1950;20:199. 34. Wolf S, Smith WO, Joel W. Experimental atrophic gastritis associated with inhibition of parietal cells. Trans Assoc Am Phys 1958;71:396. 35. Smith WO, Du Val MK, Joel W, et al. Further studies on experimentally induced atrophic gastritis in dogs. Trans Assoc of Am Phys 1966;73:346-55. 36. Hennes AR, Sevelius H, Llewellyn T, et al. Atrophic gastritis in dogs: production by intradermal injection of gastric juice in Freund’s adjuvant. Arch Path01 1962;73:261-7. 37. Groen JJ. Introduction. In: Life stress and bodily disease. Association for Research in Nervous and Mental Disease. Vol. XXIX. Wolff HG, Wolf SG, Hare CC, eds., Baltimore: Williams & Wilkins, Co., 1950. 36. Richet C. De quelques faits relatifs a la digestion chez les poissons. Arch Physiol Norm Path01 Paris (2nd ser.) 1662; l&536-58. 39. Prout W. On the nature of the acid and saline matters usually existing in the stomachs of animals. Philos Trans 1624;114:45. 46. Richet C. Dictionnaire de Physiologie, Ancienne Librairie Germer Bailliere, Paris, Vol. l-9, 1695-1913. 41. Sechenov I. In: Reflexes of the brain. (Reprinted by Idz-Vo Academy of Medicine, Nauk., USSR, 1952). 42. Dunbar F. In: Emotions and bodily changes. 2nd ed. A survey of literature on psychosomatic interrelationships, 1916-1933. New York: Columbia University Press, 1938. 43. Doig RK, Wolf S, Wolff HG. Study of gastric function in a “decorticate” 23:1-40.
man with gastric fistula. Gastroenterology
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The Psyche and the Stomach A Historical STEWART
Vignette
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St. Luke’s Hospital, Bethlehem, Pennsylvania, Laboratories, Inc., Bangor, Pennsylvania
The association of emotional problems with disturbances in the behavior of the stomach-behavior that causes discomfort and disability-has been a part of conventional wisdom for many centuries. References to stomach troubles brought on by the stresses of life are found in the works of painters, poets, and philosophers extending back as far as the beginning of the Christian era. The first description of actual changes in the stomach during emotional upsets, however, appears in Beaumont’s classic monograph published in 1833, wherein he describes his studies of Alexis St. Martin, a man who had sustained a gunshot wound in the abdomen that left him with a permanent gastric fistula (1). Although Beaumont provided the first objective confirmatory evidence of the linkage between gastric function and emotionally significant experiences, he accorded relatively little attention either to the gastric findings he observed or to the associated emotional states of his “cantankerous” subject. Beaumont described what he saw as follows: “In febrile diathesis, or predisposition, from whatever cause-obstructed perspiration, undue excitement by stimulating liquors, overloading the stomach with food-fear, anger, or whatever depresses or disturbs the nervous system-the villous coat becomes sometimes red and dry, and at other times pale and moist, . .” and loses its smooth and healthy appearance.. He goes on to describe “deep red pimples,” “irregular circumscribed red patches,” and “aphthous crusts-like the rolling up of the mucous coat into small shreds. . . .” Such changes were accompanied by suppression of secretions and marked delay in gastric digestion and emptying of the stomach. Beaumont and St. Martin are pictured in Figures 1 and 2. Beaumont’s work stimulated several investigators Received August 11, 1989. Accepted October 16, 1989. Address requests for reprints to: Stewart Wolf, M.D., Vice President for Medical Affairs, St. Luke’s Hospital, Bethlehem, Pa. 18015. 0 1981 by the American Gastroenterological Association 0016-5085/81/030605-10602.50
and
Totts
Gap
Medical
Research
to study animals, chiefly dogs, with surgically induced gastric fistulas. The earliest reports were those of Bassow from Russia (Z), Blondlot (3) and Claude Bernard (4) from France, and Pavlov’s teacher, Heidenhain (5) and Bidder and Schmidt (6) from Germany. From these studies of surgically induced gastric fistulas a ground work of understanding of normal gastric physiology was laid and the dependence of gastric secretion and motor activity on the intactness of the vagus nerve was established. The stage was set for the monumental studies of Ivan Pavlov (Figure 3) who, near the turn of the century elicited a flow of gastric juice from his dogs in sham feeding experiments in which the esophagus was interrupted and exteriorized so that swallowed food, instead of reaching the stomach, simply fell to the floor (7). The evoked secretory response occurring in anticipation of feeding became known as the psychic phase of gastric secretion. Pavlov’s important discovery had actually been preceded by an observation made independently on a fistulous human subject in 1878 by a young French medical student, Charles Richet (Figure 4). Richet’s subject was a 15yr-old youth named Marcellin who had acquired an esophageal stricture from the accidental ingestion of potassium hydroxide. Verneuil, a surgeon on the faculty of the University of Paris had operated on the boy in 18’76,providing him with an opening into his stomach through his abdominal wall (8). Successful surgical gastrostomies had been performed for only 1 or 2 yr at that time. Verneuil called young Richet’s attention to the unusual opportunity for the study of stomach function. Richet’s investigation of the fistulous young man provided the basis for his theses for both the M.D. (9) and Docteur es Science (lo), the French equivalent of a Ph.D. in Science. The former dealt with the sensibility of the gastric mucosa and the latter with the chemistry of the gastric juice. During the course of his experiments Richet noted increased gastric se-
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Figure 1. Colonel William Beaumont.
cretion when he allowed Marcellin to chew some candies, which, of course, could not traverse the esophagus to the stomach. Richet failed, however, to realize the importance of his observation and to explore it further. Later he wrote in his memoirs (11) “Too often-we can only see what we are looking for; absurd in the extreme . . . because one must observe whatever happens, even what one does not expect, especially what one does not expect.” Pavlov built his revolutionary hypothesis of central neural integrative function on his demonstration of visceral conditional or anticipatory responses (12). He showed that habitual responses to conditional stimuli (symbols) could be acquired through repetition and, furthermore, that an established pattern of response could be disrupted or even lost as a consequence of emotionally disturbing events. On one occasion Pavlov was preparing to demonstrate the conditional salivary response to a representative of the Tsar. Pavlov selected his most reliable performer and placed the dog on a table close to the podium. All eyes were turned toward the royal emissary, including those of Pavlov’s canine subject who appeared transfixed by the drama. Pavlov sounded his bell, but not a drop of saliva emerged from the cannula in the dog’s salivary duct! The experience was, of course, a great embarrassment for the professor, but from it he learned that conditional reflexes could be inhibited during emotionally charged
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situations. At another time, several of Pavlov’s dogs lost their formerly reliable conditional reflexes following what must have been a terrifying experience, a sudden flood in the kennels. This catastrophe led Pavlov to recognize degrees of vulnerability in the animals to emotionally engendered inhibition depending upon contrasting temperaments associated with different breeds (13). Pavlov’s studies of “psychic secretion” soon found confirmation in observations on human subjects when in 1905 Cade and Latarjet published their observations of a patient who had acquired in infancy an epigastric hernia in which a portion of the stom(14). Eventually the mucosal ach was incarcerated surfaces of the trapped pouch ulcerated through to the outside, leaving the patient with a spontaneously produced “Pavlov pouch.” These investigators confirmed Pavlov’s work on animals with regard to secretion in the pouch in response to food taken into the stomach, and in response to “psychic” stimuli in the form of discussion of appetizing dishes. Cade and Latarjet, however, made no notes of changes in vascularity or color changes in the exposed mucous membrane. In 1907, Kaznelson provided further confirmation of Pavlov’s sham feeding experiments in studies on a human subject who had an esophageal as well as a gastric fistula (15).
Figure 2. Alexis St. Martin.
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Figure 3. Ivan Pavlov.
Gastric Accompaniments stress
of Emotional
Gastric fistulas, occurring accidentally or produced surgically, made possible the linking of emotionally charged experiences to the behavior of the stomach. Such data are difficult to gather in intact subjects owing to the stomach’s relative inaccessibility to direct observation. Gastric fistulas in human subjects had been available for study long before Beaumont’s perceptive and original observations on Alexis St. Martin. Reports in the literature of gastric fistulas in human subjects go back at least to 1564 when Matthew Cornax, a Viennese professor of medicine and physician to Emperor Ferdinand, published an account of a man, who, while hunting, was
wounded in the abdomen by a stake (16). It penetrated his stomach and left him with a permanent gastric fistula. Neither Cornax’s paper nor dozens of others describing fistulous human subjects in the intervening years before Beaumont’s work made any mention of alterations in the stomach accompanying emotional changes in their subjects. In the early years of the present century, Anton Carlson (Figure 5) carried out extensive studies of a human subject, Mr. Vlcek, who had a gastric fistula one-half inch in diameter. In the course of his investigations of the contractile activities of the stomach, Carlson noted inhibition of gastric contractions during fear (17). When, on the other hand, strong gastric contractions were present, he observed that accompanying each one was a deepening of the red color of the mucous
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Figure 4. Charles Richet as a medical student.
membrane. With respect to secretion, he noted that the resting, fasting stomach secretes acid gastric juice, an observation contrary to the findings of Beaumont and Pavlov, who had held that in the absence of stimuli, mechanical or chemical, the stomach remained empty and failed to secrete. Carlson’s patient lived for years, serving alternately as experimental subject and diener in the laboratory, feeding himself through his stoma and enjoying good health, free from gastrointestinal complaints. It is striking that, while enhanced gastric secretory and motor activity had been recognized in association with sham feeding and the presumably pleasant emotion, appetite, “negative” emotions, fear, anxiety, and anger had been shown by Beaumont and Carlson to be accompanied by diminished gastric secretory and motor activity. Such inhibitory effects on the stomach provided the basis for classical contributions by Walter Cannon (Figure 6), a contemporary of Carlson who, although he had no chance to study a fistulous human being, nevertheless, made extensive observations on gastric motor and secretory functions in animals in response to threats and hazards of various sorts (18). Enhanced gastric activity in humans under emotionally stressful circumstances was probably first noted by Gordon and Chernya who in 1940 reported a patient with a gastric fistula, whose gastric secretion of acid had been consistently in the low normal range until,
during a period of restlessness, homesickness, and resentment toward their experimental demands, he displayed a marked hyperacidity (19). A further documentation of increased gastric activity during certain types of emotional stress was provided by Bela Mittlemann’s studies of patients with duodenal ulcer carried out in collaboration with Harold Wolff (20). By studying the gastric juice of their subjects obtained through a swallowed Levine tube and by recording gastric contractions from an indwelling balloon, Mittlemann and Wolff were able to observe increases in gastric secretion and motility during stressful interviews. The following year the author’s studies of Tom were begun in collaboration with Wolf and Wolff (21). The year was 1941 when Tom was 56 years old (Figure 7). The research continued until Tom’s death in 1958 at age 73 (22). Tom’s gastric fistula was the result of a surgical operation performed at the old New York Hospital in 1895. At the age of 9, Tom had accidentally burned his esophagus by swallowing scalding hot clam chowder. A complete esophageal occlusion ultimately developed, necessitating his gastrostomy. The work with Tom contributed several new items to our body of knowledge about the stomach. The exposed gastric mucosa of Tom made it possible to observe the vascularity of the stomach as reflected by the color of the mucosa and the degree of engorgement as well as secretion and motor activity.
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Figure 5. Anton Carlson. Tom’s gastrostomy also afforded the opportunity to make prolonged or frequently repeated measurements of gastric function. In Tom and in other fistulous subjects whom we were privileged to study, we found that fright, depression, and attitudes of being overwhelmed were associated with pallor of the mucosa, diminished acid secretion, and reduced gastric motor activity. The reaction was similar to that described by Cannon in his cats when they were required to face a barking dog (18). What we were able to add was evidence of hyperactivity in the stomach that accompanied more aggressive attitudes and feelings of anger and resentment. Under circumstances characterized by hostility and resentment, we observed in Tom, and in other subjects, hyperemia and engorgement of the gastric mucosa, together with accelerated secretion of HCl and enhanced contractile activity in the stomach. Dr. Cannon, who had been a member of the Committee that had awarded a National Research Council Fellowship to the author, was so interested in the projected studies of Tom that he visited the laboratory in New York and spent several days observing the experiments, talking at length with Tom and watching his stomach. Dr. Cannon then wrote in the Foreword of Human Gastric Function that: “He (Tom) had an
emotional range and responsiveness that permitted nice discriminations which the authors have fully utilized. The interesting fact that frustration and repressed conflict were associated with hyperemia and with increase of motility and secretion will come as a surprise to many. Likewise highly significant is evidence that engorgement of the mucosa, whatever its cause, is associated with lessened resistance to trauma, for, as the authors point out, this condition has importance in explaining the incidence of gastric ulcer. Obviously the extent and variety of testimony here accumulated provides interest not only for clinicians but for physiologists, pharmacologists, psychiatrists and pathologists as well” (21). The “bipolar” nature of changes in gastric function that we observed to be characteristic of what appeared to be quite different and distinguishable emotional configurations found confirmation in the studies of Reichsman et al. whose subject was a 6yr-old girl with a gastric fistula (23). Using motion pictures they provided elegant documentation of the child’s contrasting behaviors. Her aggressive behavior was associated with gastric hyperfunction while her withdrawal or “giving up” behavior was accompanied by inhibition of gastric secretory and motor
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Figure 6. Walter Cannon.
Figure 7. The author with Tom.
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activity. It was therefore of interest that in an earlier study Farr and Lueders (24) found high levels of gastric secretion in hypomanic patients but low levels in those with mental depression. Margolin et al. (25) had an opportunity to study a woman psychiatric patient with a surgically induced gastric fistula. They observed deviations in their subject’s gastric function that accompanied the probing of unconscious conflicts identified through psychoanalytic techniques. They concluded that their subject had made an unconscious association of her gastric fistula with a vagina and the investigator’s instrumentation with sexual assault. An important series of observations on intact human subjects was made by Weiner et al. (26). They gathered indirect evidence on gastric acid secretion through the measurement of pepsinogen concentration in the blood. They were able not only to show elevated values of pepsinogen in patients with duodenal ulcer, but also temporary elevations of the enzyme in military recruits and other healthy subjects during emotionally stressful events. Epigastric
Pain and Ulceration
In further studies of Tom we were able to show that during gastric hyperfunction, characterized by mucosal hyperemia and engorgement, not only was there increased acid secretion and motor activity but a lowering of pain threshold and, as Dr. Cannon pointed out, increased fragility of the gastric mucous membrane. Indeed, sustained hyperactivity of the stomach was accompanied by epigastric pain that could be relieved by milk or alkali. Further, it was shown that native gastric juice was capable of digesting the mucosa if the protective mucous coating were removed or otherwise deficient. In fact, a peptic ulcer was induced in the mucosa of Tom when a portion of the membrane, deficient in mucous production, was kept in contact with his own gastric juice for a period of 3 days. Appetite,
Hunger, and Satiety
Appetite, an emotional state characterized by the pleasurable anticipation of eating, was shown in Tom, as it had been in other human subjects and in animals, to be associated with enhanced gastric activity. Hunger is not necessarily a pleasant experience. Indeed, hunger is perhaps more commonly _ unpleasant, even painful. As distinct from appetite, an aspect of the feeling of hunger has a peripheral sensory component. Cannon and Washburn, in 1912 (27) associated the pangs of hunger with contraction of the gastric antrum. Later, Patterson and Sand-
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Weiss (28) showed that duodenal contractions could give rise to hunger sensations as well. Satiety has been the subject of extensive study in the past few years. Smith et al. have shown that afferent impulses from the mucosal surface of the gut from mouth to jejunum play a major role in the interruption of eating. Even sham feeding was sufficient to induce temporary satiety if reinforced by the peripheral effects of cholecystokinin (29). Nausea Studies of Tom and of other fistulous and intact humans have shown that reduced gastric activity associated with attitudes of withdrawal are often accompanied by sensations of nausea. Indeed, nausea, whether induced by emotionally stressful circumstances, by vestibular stimulation or by emetic drugs, was shown to be associated with a striking gastric hypoactivity, marked dilatation of the organ and lack of motility (30). At the same time, as previously shown by Ingelfinger (3l), contractile activity in the first portion of the duodenum was enhanced, creating thereby a reversal of the usual gastroduodenal gradient. With an accompanying relaxation of the pyloric sphincter, the contents of the duodenum were regurgitated into the stomach. Subsequent vomiting was accompanied by a relaxation of the cardiac sphincter so that Tom’s gastric content was forced into the distal blind end of his esophagus. These gastric and duodenal changes, characteristic of nausea, were subsequently confirmed by other investigators in animal experiments (32).
Placebo Effects A placebo effect is, of course, an aspect of the psychologic communication between patient and physician. The power of the placebo has been recognized since antiquity, but evidence that placebos produced changes in the end organ was lacking until the studies of Tom provided quantitative evidence in the form of measurable changes in Tom’s gastric function after administration of placebos, changes as marked as those induced by potent pharmacodynamic agents (33). Gastric Ulcer Accompanying Emotional Crisis
Intense
Tom underwent an intense emotional crisis which afforded the investigator an opportunity to observe a spontaneous ulceration of the gastric mucosa during an episode of continuous high level acid secretion.
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The set of circumstances followed the discovery of a carcinoma on the exposed portion of Tom’s gastric mucosa. The microscopic picture was that of an adenocarcinoma of very malignant appearance. Tom refused to consider any surgical operation except a local removal. He particularly refused to countenance a procedure directed at closing the stoma with which he had lived for so many years. His wishes were respected, and only a narrow margin of skin and uninvolved gastric mucosa around the lesion were resected. Before the operation and since the initial discovery of the carcinoma, Tom’s gastric juice was found to be consistently achlorhydric. Biopsy of the uninvolved portion of the exposed mucosa, made at the time of the removal of the carcinoma, showed typical atrophic gastritis, very similar to that induced experimentally in dogs by injections of a preparation of human gastric juice containing a property of powerfully inhibiting hydrochloric acid secretion (3436). A striking finding was that after surgical removal of the carcinoma, HCl secretion reappeared as before in Tom’s stomach. Tom survived 2 yr after the operation. During that time he was continuously dehydrated because of uncontrollable leakage through his enlarged gastric fistula. It was literally impossible for him to keep enough fluid inside him to maintain adequate water and electrolyte balance. Tom consistently resisted the most vigorous entreaties to undergo a revision of the stoma. To those who were looking after him, the importance of persuading him to submit to an operation was so great that it can be said that Tom was under intense pressure which he vigorously resented. Throughout this period his gastric acidity remained persistently high. Eventually one, then a second, and then a third ulcer appeared on the mucosa near the stoma. It was presumed at the time that the ulcers represented recurrent carcinoma, so efforts to persuade Tom to submit to an operation were intensified but still futile. He therefore returned home with ulcers still present.
Tom’s Final Days Within a day or two, Tom began to bleed profusely from one of the ulcers. Admitted as an emergency patient to New York Hospital, he underwent biopsy of the ulcer. No neoplastic tissue was found. At length, but too late, he agreed to an operation to revise the stoma. An old pyelonephritis had flared up and, in addition, Tom developed bronchopneumonia. He soon died in uremia in his 74th year, 65 years after his esophageal occlusion. At autopsy no evidence of cancer was found. The ultimate tribute to Tom was paid by the brilliant Dutch investigator J.J. Groen, former professor of medicine at Hadassah Medical School in Jeru-
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salem and now professor of psychobiology at the University of Leiden. He wrote, “The real stimulus, the spark that ignited the chain reaction of investigational energy, came from the encounter with a seemingly unimpressive small man, named Tom. The researches carried out on this gastric fistulous subject, Tom, and other subjects that offered comparable opportunities for study, were not only just another set of good experiments. They showed to everybody who could see, that the problems of so-called psychosomatic relationships could be studied with straightforward methods of clinical investigation.“(37).
Perspective The Relationship
of Subject and Investigator
Over a span of 400 years, studies of patients with gastric fistulas have contributed in different ways to our understanding of the stomach and its functions. What can be learned from a human subject with a gastric fistula is determined in part by the relationship between investigator and subject. Beaumont’s association with Alexis St. Martin was sometimes turbulent and was interrupted for months or years at a time. His more than 200 recorded observations were made in segments spread over 8 years. St. Martin was exasperatingly unreliable, improvident, and stubborn. He complained a great deal of dizziness and weakness during experimentation, and he was overimbibing much of the time between experimental sessions. Richet’s patient, Marcellin, on the other hand, was cooperative and dependable, appearing at the laboratory for study each morning at the appointed time. Carlson’s papers reveal little of the personality of Mr. V., although he must have been conscientious since he worked for years as a helper in the laboratory and was apparently reliable as an experimental subject. Tom was a warm, sensitive, short tempered and impatient, but very loyal person who applied himself to his duties with intensity. He also took a great interest in the studies of his stomach. He was fully aware and thoroughly proud of his position as a contributor to medical science. Tom enjoyed the respect and affection of the hospital family and especially the expressed interest and often deference of distinguished visitors. He grew to look upon the author (more than 25 years his junior) almost as a father and depended upon him in myriad ways for guidance and support with personal and family matters. The Influence of the Times One hundred years ago Beaumont wrote, “I have availed myself of the opportunity afforded by a
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concurrence of circumstances which probably never can again occur. .." (1).It may be that the precise series of events which resulted in a permanent opening into the stomach of Alexis St. Martin has not been repeated, but Beaumont’s opportunity to study the physiology of the stomach at close range through a gastric fistula has not remained unique. By virtue of new approaches to the study from one generation to the next, additional facts have been learned and various aspects of the problem of gastric function have been clarified. The problem could never be disposed of by a single worker, however ideal his opportunities, for the questions put to nature vary from one generation to the next. An investigator’s horizon is limited by the height of the vantage point on which he stands. These vantage points are the prevailing concepts of the day. Few men have been able to look beyond the horizon of their generation. Beaumont’s work was influenced by the widespread interest in inorganic chemistry which prevailed in his day. Therefore, in his studies on Alexis St. Martin he was principally concerned with discerning the process involved in converting a bolus of food into an amorphous, semifluid thyme. He interested himself primarily in the properties of gastric juice, as he emphasized in the title of his treatise: Experiments and Observations on The Gastric Juice and the Physiology of Digestion. The critics of Beaumont’s day, too, were preoccupied with the same considerations, and they were disappointed by his failure to show whether or not there was a “vital force” in the stomach which enabled food to be chymified more readily in vivo than when incubated with gastric juice in vitro. Richet’s observations on an early gastrostomy patient were made 50 years after Beaumont’s publication. His interest in the nervous system led him to explore the sensibility of the gastric mucosa. Also, he showed that gastric acidity increased during the process of digestion and, noting the relative homogeneity of the material delivered to the duodenum, despite the wide diversity of food ingested, Richet speculated that the duodenum exercises control over gastric emptying. Richet further concerned himself with the chemistry and physiologic properties of gastric juice. He was the first to observe the capability of the gastric juice to coagulate milk, discovered later to be attributable to the presence of renin (38). He was able to confirm the demonstrations by William Prout (39) and by Beaumont that hydrochloric acid was present in the stomach. Moreover, he showed that the concentration of HCl was greater in carnivorous than in herbivorous animals and that to some extent HCl was linked to nitrogen-containing organic substances. Carlson, 25 years after Richet, was subject to dif-
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ferent prevailing influences in physiology. The passage of time had offered him a new approach to the investigation of his patient with a gastric fistula. The star of “vitalism” had faded, and “mechanism” had taken its place. A great school of physiologists had appeared whose interests lay in the behavior of organs and in the mechanics of their interrelationships. Carlson’s work was primarily concerned with kinetics. The majority of his experiments on the stomach were directed towards a study of gastric motility and of “hunger contractions” in particular. Beaumont, Richet, and Carlson had each detected changes in gastric function in association with varying emotional states, but they made no systematic observations upon them. Neither did they seem to appreciate the magnitude of the changes and their possible relation to epigastric distress and disease. Richet, who had made the original observation of the psychic secretion of gastric juice, had discussed it only in his memoirs. His concern with the stomach was but a transient passion during his student days. As a professor he assigned the topic to his student, Carvalho, who soon abandoned physiology to participate in the restoration of past glories of France.” Carvalho did write a thorough going review of studies in gastric physiology with an extensive bibliography for the remarkable Dictionaire De Physiologie edited for 18 years by Charles Richet (40). The work was interrupted by World War I and never resumed. Pavlov’s investigations were stimulated by his mentor, Sechenov, whose monograph, Reflexes of the Brain appeared during the dawn of neurophysiology when investigators in Western Europe had begun to attempt to unravel the complex circuitry of the brain and to identify some of the pathways and mechanisms involved in visceral and general behavior (41). Pavlov developed a theory of communication within the brain in which the ultimate response was dependent upon the interplay of facilitatory and inhibitory influences. The studies of Tom were undertaken a few years after the publication of Walter Cannon’s classic monograph, Bodily Changes in Pain, Hunger, Fear and Rage (18) and a year after Flanders Dunbar’s Emotions and Bodily Changes (42). The time was propitious for a systematic investigation into “the physiology of emotion.” Within a few years the author had an opportunity to study, in addition to
*Carvalho, an impecunious Basque, had married another of Richet’s students, a wealthy American, Anna Coleman. The couple purchased the Chateau Viilandrie and devoted the rest of their lives to restoring and promoting it. Indeed, the survival of the magnificent French chateaux and their accessibility to visitors is due to legislation originally proposed by Dr. and Mrs. Carvalho.
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Tom, 4 other patients with gastric fistulas including a man with a gastrostomy required because a head injury had rendered him effectively decorticate (43). Among the others, one had an associated duodenal ulcer, and another underwent bilateral vagotomy during the period of study. The clearest lesson from these studies was that to understand a man’s stomach one must understand the man.
References 1. Beaumont W. In: Experiments and observations on the gastric juice and the physiology of digestion. Plattsburg: F.P. Allen, 1633. 2. Bassow DR. Voie artificielle dans l’estomac des animaux. Bull Sot Natur Moscou 1643;16:315. (Cited by Richet: Du sue gastrique chez l’homme et les animaux: Ses proprietes chimiques et physiologiques. Paris, Librarie Germer Baillere et Cie). 3. Blondlot N. Trait analytique de la digestion considered particulierement dan l’homme et dans les animaux vertebres, 1843. (Cited by Richet: Du sue gastrique chez I’homme et les animaux: ses proprietes chimiques et physiologiques. Paris, Librarie Germer Baillere et Cie). 4. Bernard C. Leqons sur les proprietes physiologiques et les alterations pathologiques des liquides de l’organisme. Paris, Bailleurs, 1659. und trophische Dru5. Heidenhain RPH. Ueber secretor&he sennerven. Pflug Arch Ges Physiolamte 1676;17:1. und der Stoff6. Bidder F, Schmidt C. Die Verdauungssaefte wechsel. Mitau % Leipzig, 1652. 7. Pavlov I. In: The work of the digestive glands. English translation from the russian by WH Thompson. London: C. Griffin and Co., 1910. 6. Verneuil H. Observation de gastro-stomie pratiquee avec success pour un retrecissement cicatriciel infranchissable de l’oesophage. Bull Acad Med 1676;5:1023. et cliniques sur la 9. Richet C. In: Recherches experimentales sensibilite. Paris: Masson, 1677. 10. Richet C. Des proprietes chimiques et physiologiques du sue gastrigue chez l’homme et les animaux. Appendix A. J Anat Physiol 1678;14:170. 11. Richet C. Souvenirs d’un physiologist. Paris: J. Peyronnet & Cie, 1944. 12. Pavlov I. In: Conditioned reflexes. An investigation of the physiological activity of the cerebral cortex. (Translated by GV Anrep. New York: Oxford University Press, 1927; also New York: Doyer Publications, 1966). 13. Pavlov I. In: Lectures on Conditional Reflexes (Translated by WH Gantt New York International Publishers, 1926). 14. Cade A, Latarjet A. Realisation pathologique du petit estomac de Pavlov. Etude Physiol. Path Gen 1995;7:221. am Erwachsenen 15. Kaznelson H. Scheinfutterungsversuche Menschen Pfluegers Archiv Ges Physiol 1997;118:327. 16. Cornax M. Medical consultations apud aegnoteos secundum artem et experientiam salubriter instituendae enchiridion, Bale, 1564. (Cited by CG Cumston) Med J Ret 1926;124:229. 17. Carlson AJ. Contributions to the physiology of the stomach. Articles l-23. Am J Physiol 1912;31:151. 16. Cannon WB. In: Bodily changes in pain, hunger, fear and rage. New York: D. Appleton, 1929. 19. Gordon OL, Chernya YM. Physiology of the gastric secretion in man; studies on patients with gastric fistula and artificial esophagus. Klin Med (No. 12) 194@18:63.
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20. Mittlemann B, Wolff HG. Emotions and gastroduodenal function: experimental studies on patients with gastritis, duodenitis and peptic ulcer. Psychosom Med 1942;4:5-61. 21. Wolf S, Wolff HG. In: Human gastric function. 1st ed. New York: Oxford University Press, 1943. 22. Wolf S. In: The stomach. New York: Oxford University Press, 1965. 23. Reichsman F, Engle GL, Segal HL. Behavior and gastric secretion: the study of an infant with a gastric fistula. Psychosom Med 1955;17:461. 24. Farr CB, Lueders CW. Gastric secretory functions in the psychosis. Arch Neural Psychiatr 1923;10:546. 25. Margolin SG, et al. Variations of gastric functions during conscious and unconscious conflict states. Life stress and bodily disease, ARNMD Proceedings. Baltimore: Williams & Wilkins co., 1950. 26. Weiner H, Thalen M, Reiser MF, Mirsky IA. Etiology of duodenal ulcer. 1. Relation of specific psychological characteristics to rate of gastric secretion (serum pepsinogen) Psychosom Med 1957;19:1. 27. Cannon WB, Washburn AL. An explanation of hunger. Am J Physiol 1912;29:441-5. 26. Patterson TL, Sandweiss DJ. Relationship between gastroduodenal motility phases and symptoms associated with duodenal ulcer in the human. Am J Dig Dis 1942;9:375-361. 29. Smith GP, Gibbs J. Postprandial satiety. In: Progress in psychobiology and physiological psychology. Sprague JM, Epstein AN, eds. Vol. 6, 179-242, New York: Academic Press, 1979. 30. Wolf S. The relation of gastric function to nausea in man. J Clin Invest 1943;22:677-62. 31. Ingelfinger FJ. Behavior of the duodenum during nausea. Bull N Engl Med Center 1942;4:120. 32. Gregory RA. Changes in intestinal tone and motility associated with nausea and vomiting. J Physiol 1948;105:56-65. 33. Wolf S. Effect of suggestion and conditioning of the action of chemical agents in human subjects. The pharmacology of placebos. J Clin Invest 1950;20:199. 34. Wolf S, Smith WO, Joel W. Experimental atrophic gastritis associated with inhibition of parietal cells. Trans Assoc Am Phys 1958;71:396. 35. Smith WO, Du Val MK, Joel W, et al. Further studies on experimentally induced atrophic gastritis in dogs. Trans Assoc of Am Phys 1966;73:346-55. 36. Hennes AR, Sevelius H, Llewellyn T, et al. Atrophic gastritis in dogs: production by intradermal injection of gastric juice in Freund’s adjuvant. Arch Path01 1962;73:261-7. 37. Groen JJ. Introduction. In: Life stress and bodily disease. Association for Research in Nervous and Mental Disease. Vol. XXIX. Wolff HG, Wolf SG, Hare CC, eds., Baltimore: Williams & Wilkins, Co., 1950. 36. Richet C. De quelques faits relatifs a la digestion chez les poissons. Arch Physiol Norm Path01 Paris (2nd ser.) 1662; l&536-58. 39. Prout W. On the nature of the acid and saline matters usually existing in the stomachs of animals. Philos Trans 1624;114:45. 46. Richet C. Dictionnaire de Physiologie, Ancienne Librairie Germer Bailliere, Paris, Vol. l-9, 1695-1913. 41. Sechenov I. In: Reflexes of the brain. (Reprinted by Idz-Vo Academy of Medicine, Nauk., USSR, 1952). 42. Dunbar F. In: Emotions and bodily changes. 2nd ed. A survey of literature on psychosomatic interrelationships, 1916-1933. New York: Columbia University Press, 1938. 43. Doig RK, Wolf S, Wolff HG. Study of gastric function in a “decorticate” 23:1-40.
man with gastric fistula. Gastroenterology
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