Peritonitis is the cause of death of 92 per cent of those patients who die after being admitted to a hospital with the diagnosis of acute appendicitis, according to the results of a survey made in Philadelphia by Bower and his associates.1Peritonitis is also a frequent cause of death in ruptured "peptic" ulcer and penetrating wounds of the abdomen. Whether the administration of penicillin may provide any hope for a favorable outcome in fulminating, diffuse peritonitis may be readily ascertained by a controlled study in animals. For example, Bower and his associates1have described a method for the production of peritonitis in the dog by occlusion of the blood supply of the appendix and the subsequent oral administration of castor oil. The bacteriologic flora of this experimental peritonitis is quite similar to that of peritonitis in man.2In addition, it has been found that the mortality from

Our use of an aluminum phosphate gel in the therapy of peptic ulcer resulted from observations on the effect of aluminum hydroxide gel on the absorption of phosphates from the intestine. In a publication1on the effect of aluminum hydroxide gel on the well-being and longevity of Mann-Williamson dogs, Fauley, Ivy, Terry and Bradley suggested that the unfavorable effects of this chemical in such animals might be due to an interference with the absorption of phosphates. The present report (a) includes data which demonstrate that aluminum hydroxide gel interferes with phosphate absorption and (b) presents the results of the use of aluminum phosphate gel in the treatment of experimental and clinical peptic ulcer. Experimental ulcers were produced in Mann-Williamson dogs. The preparation of such an animal includes performing a gastrojejunostomy and diverting the pancreatic juice and bile into the terminal portion of the ileum (last 20 to 25 cm.).

Two preparations of aluminum hydroxide (an aluminum hydroxide cream and colloidal aluminum hydroxide) were given to two groups of Mann-Williamson dogs on a special diet (87 dogs were used) to determine the prophylactic value against the jejunal ulcer that results post-operatively in such dogs. The first group received relatively large doses of the Al preparations four times daily. No prophylactic value was obtained. The second group received sufficient doses of the Al preparations at hourly intervals from 8 A. M. to 8 P. M. and another dose at midnight, to control free acidity continuously during the day. No prophylactic value was obtained. In fact, the therapy proved to be deleterious. The most striking effect of the Al was to cause a decrease in appetite, a decrease in dietary intake, and a more rapid loss of weight. The cause of this is discussed and the explanation is advanced, principally as an hypothesis for future experimental testing, that the aluminum, in the presence of a relative deficiency of pancreatic juice and bile for digestive activities which these Mann-Williamson dogs suffer, combined excessively with phosphates and produced a sufficient degree of phosphorus deficiency to reduce appetite. (The most conspicuous early symptom of a phosphorus deficiency is anorexia). These experimental results would indicate that aluminum hydroxide therapy should not be employed for treating a “peptic” ulcer complicated by the presence of a relative pancreatic and biliary insufficiency, as might occur with fibrous pancreatitis or a gastro-enterostomy.

Local muscular spasm in the jejunum is not an essential factor for the development of jejunal ulcer after gastrojejunostomy.

The irritating action of gastric juice, the nutritional state of the animal and the greater susceptibility of jejunal mucosa to irritation by acid (as compared to duodenal mucosa) are the principal factors concerned in the development of jejunal ulcers in dogs prepared by the Exalto-Mann-Williamson technique. To study the relative rôles played by gastric juice and nutrition the following experiments were performed: Control Series with “Stock Diet.” A group of 42 control dogs were operated by the Mann-Williamson technique and fed a diet consisting of ground meat (parboiled), milk, bread, and cod liver oil. All dogs died with a jejunal ulcer within a period of 17 weeks. Fundusectomy with “Stock Diet.” Eleven dogs were fundusectomized (three-fourths of fundus removed) and then three weeks later the Mann-Williamson operation was performed. The maximum survival time after the second operation was only 15 weeks, but the incidence of ulcer was only 27 per cent. The dogs lost weight rapidly, having been deprived of the greater part of both gastric and pancreatic digestion. It thus became obviously necessary to feed a diet more easily digested and absorbed. A Series in which Nutrition was Improved: (Special diet). Twenty dogs were similarly operated and fed a more easily assimilated diet consisting of finely ground cooked meat, wheat and barley flour, dried milk, tomato juice, bonemeal, cod liver oil, fresh whole milk, raw ground pancreas (200 gm. daily), fresh ground liver (200 gm. daily), corn syrup (100 gm. daily) and banana flour. This diet was fed three or four times a (day, some dogs eating as much as from 4 to 6 lbs. daily. Ten of the dogs lost weight from the start; but only three died with ulcer within 17 weeks, the others dying from other causes than ulcer. Nine of the remaining ten survived from 20 to 58 weeks, but died with ulcer. The other dog was anesthetized at 82 weeks and no ulcer was found. Only two of these dogs lost weight appreciably, most of which resulted after the ulcer started to bleed.

Resection of at least 66 per cent of the stomach in 10 out of 12 dogs resulted in varying degrees of compensatory hypertrophy of the gastric remnant. It is believed that the hypertrophy was due to rapid eating of large quantities of food due to the polyphagia incident to inadequate digestion. The jejunum at the stoma was also hypertrophied. The emptying time of the stomach was permanently decreased in spite of the hypertrophy. The acidity of the gastric contents returned practically to normal in from three to five months. Jejunal ulcers developed in 3 of the 12 dogs.

The following factors as determinants of chronicity of ulcer of the stomach and upper intestines have been discussed: (1) infection, (2) mechanical effect of food and motility, (3) blood flow and fibroblastic reaction, (4) allergy, (5) nutrition or digestive disturbance, (6) corrosive or irritating action of gastric contents, and (7) mucosal susceptibility. Experimental evidence is cited which shows that the roughage in or consistency of the diet in the presence of a factor conducive to connective tissue proliferation is conducive to the formation of a chronic gastric ulcer in rabbits. Experiments have been devised in an attempt to evaluate the mechanical, nutritional, chemical and mucosal susceptibility factors in the etiology of intestinal ulcers following gastroenterostomy. The evidence shows that all these factors operate and that the mechanical, chemical and mucosal susceptibility factors are the most important. On keeping the mechanical factor constant and varying the chemical factor (the change in the chemical factor leads to some change in nutrition, which could not be avoided in all animals), it is shown that the chemical factor is the most important. On keeping the nutritional factor constant and by analyzing the chemical, mechanical and mucosal susceptibility factors, it is shown that the jeJunaI mucosa is more sensitive to the irritating action of gastric contents than duodenal mucosa.

The following factors as determinants of chronicity of ulcer of the stomach and upper intestines have been discussed: (1) infection, (2) mechanical effect of food and motility, (3) blood flow and fibroblastic reaction, (4) allergy, (5) nutrition or digestive disturbance, (6) corrosive or irritating action of gastric contents, and (7) mucosal susceptibility.

Clinical experience and experimental observations indicate that the consistency of the diet may have a bearing on the healing of gastric ulcers. That the physician believes the consistency of the diet is an important therapeutic item in the management of patients with ulcers is shown by the fact that a liquid or soft diet, with or without a preceding period of starvation, is used in all the generally accepted therapeutic procedures. Bolton, 1 in his book on Ulcer of the Stomach, stated that in his opinion there is no doubt that diet influences the production and propagation of ulcer of the stomach. He stated that excessive amounts of imperfectly masticated, and hurriedly swallowed food of `indigestible' quality, although alone being unable to produce the initial lesion, yet are able to assist in so doing, and in promoting the extension and delaying the healing of an ulcer of the stomach. The fact

Ferguson was able to produce uniformly in rabbits gastric ulcers which persisted from 2 to 8 months or longer. He incised the anterior wall of the stomach and at the point of incision removed a piece of mucosa and then closed the stomach by a silk suture, the rabbits being kept on a diet of hay, oats and carrots. It occurred to us that this observation provided a method of studying the effect of diet on the healing of this experimental gastric ulcer. In our first series of rabbits we found that if a lesion was made in the posterior wall of the stomach in which no silk suture was present and one in the anterior wall in which a silk suture was present and the rabbits placed on the stock diet of hay, oats and carrots, that the posterior lesion healed in 30 days, but the anterior lesion did not. This showed that the silk suture was a factor in delaying healing and that in the absence of the silk, diet played no rôle in delaying healing. Anterior lesions of the Ferguson type were made in 29 rabbits. Twelve were placed on the stock diet and 17 on a diet of milk, bread and mashed boiled carrots. The rabbits were sacrificed on the 30th day. All of the 12 rabbits on the “rough diet” had ulcers at the 30th day. Only 3 of the 17 on the “soft diet” had ulcers. The results show that the silk suture per se is not sufficient to prevent the ulcer from healing and that a “rough diet” plus the silk suture factor are sufficient to produce a chronic gastric ulcer, grossly and histologically, and that a “soft diet” favors the healing of gastric lesions.

In the experimental study of the cause of jejunal ulcer following gastro-enterostomy, 3 factors have become quite evident as playing an etiological rôle; first, the irritating and digestive properties of the gastric contents; second, the motor drive of the stomach, and third, the possible greater susceptibility of the jejunal mucosa as compared to the duodenal mucosa to the first 2 factors. We have devised an operation in the dog for the purpose of analysing the relative rôle played by these 3 factors. The operation consists in (1) dividing the duodenum about one inch below the pyloric sphincter and the jejunum about 12 inches below the ligament of Treitz; (2) then the distal end of the jejunum is anastomosed to the proximal end of the duodenum; (3) the distal end of the duodenum is closed and the proximal end of the jejunum is anastomosed (end-to-side) to the distal ileum about 15 inches from the ileocecal valve. The gastric chyme on being ejected strikes the first inch of the duodenum and then passes into the jejunum. There is no pancreatic juice or bile to play a rôle in neutralization, since these secretions are diverted to the lower ileum. The principle of the operation is that the acid factor is constant for both the duodenal and jejunal mucosa, and the motor drive of the stomach affects chiefly the duodenal mucosa. If an ulcer occurs only in the duodenal mucosa, it would mean that it was caused by the acid plus the motor drive factor. If an ulcer occurs in both the duodenal and jejunal mucosa, it would mean that the acid factor was the chief cause. If an ulcer occurs in the jejunal mucosa only, it would mean that its mucosa is more susceptible to the action of the gastric contents than the duodenal mucosa.

ArticleTHE EFFECT OF EXCLUSION OF PANCREATIC JUICE ON GASTRIC DIGESTIONGordon B. Fauley, and A. C. IvyGordon B. FauleyFrom the Department of Physiology and Pharmacology, Northwestern University Medical School, and A. C. IvyFrom the Department of Physiology and Pharmacology, Northwestern University Medical SchoolPublished Online:01 Jul 1929https://doi.org/10.1152/ajplegacy.1929.89.2.428MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 89Issue 2July 1929Pages 428-437 Copyright & PermissionsCopyright © 1929 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1929.89.2.428History Received 29 April 1929 Published online 1 July 1929 Published in print 1 July 1929 Metrics

ArticleTHE EFFECT OF HUNGER ON THE EMPTYING TIME OF THE STOMACHA. C. Ivy, and Gordon B. FauleyA. C. IvyFrom the Department of Physiology and Pharmacology, Northwestern University Medical School, and Gordon B. FauleyFrom the Department of Physiology and Pharmacology, Northwestern University Medical SchoolPublished Online:01 Dec 1929https://doi.org/10.1152/ajplegacy.1929.91.1.206MoreSectionsPDF (449 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 91Issue 1December 1929Pages 206-209 Copyright & PermissionsCopyright © 1929 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1929.91.1.206History Received 10 July 1929 Published online 1 December 1929 Published in print 1 December 1929 Metrics