A new ileostomy produces diarrhea which then gradually decreases in volume over the next three to four months. The role of the ileum in this apparent adaptation to loss of colonic water absorptive capacity was determined directly by measuring water absorptive capacity in ileal test segments in vivo . The results suggest that the initial diarrhea is caused at least in part by loss of normal absorptive capacity in the distal ileum and that the adaptation over the next several months actually is caused primarily by a return of ileal absorptive capacity to normal. The test segments also showed mucosal hyperplasia and hyperabsorption four months after ileostomy, suggesting that part of the adaptation may involve an increase in ileal absorptive capacity above normal.

The effects of an oral neomycin and penicillin regimen on intestinal bacteriology and on morphology and function of the small intestine of mice were investigated. Quantitative and qualitative stool cultures on selective media of the treated animals revealed only growth of yeast organisms. The treated animals developed enlargement of the ceca with fluid contents and watery stools, resembling characteristics of germfree animals. Radioautography with tritiated thymidine revealed an increased epithelial cell migration rate in the mice treated with the antibiotics for 3 to 5 wk. A slight increase in villus height was also noted. The treated male mice showed greater variance than the treated females in epithelial cell migration rates. Histochemical staining reactions showed a decrease in nonspecific esterase and in NADH dehydrogenase activity in the proximal gut of the antibiotic animals. Stains of distal gut and those for acid and alkaline phosphatase, NADPH dehydrogenase, lactic dehydrogenase, and succinic dehydrogenase were similar to the controls. A slight increase in sucrase activity and a slight decrease in lactase activity in the antibiotic animals was observed in contrast to control animals. Germfree mice, however, had greater sucrase and lactase activity. Transport of L-methionine was slightly reduced in the distal segment of the treated animals. Since the direction of these changes is away from the intestinal state observed in germfree animals, they are probably the result of the direct action of the antibiotics on the gut.

From the Departments of Pediatrics and Internal Medicine, Yale University School of Medicine and the Yale-New Haven Hospital, New Haven, Conn. * Reprints: Department of Pediatrics, 333 Cedar Street, New Haven, Connecticut 06510. Supported in part by grants from the Public Health Service (1-R01-02700) and the Mead Johnson Company. The patients described were studied in the Yale Children’s General Clinical Research Center with USPHS grant (FR-00125-03). Dr. Katz is a USPHS fellow in Gastroenterology, USPHS AM-5156-09. A and ~-ague gasiroiniestiiial i~’fll~..~:‘~i.-~ vag stromtestma complaints may be manifestations of granulomatous bowel disease as well as of pure psychiatric disorders. Indeed, the intense psychologic problems of the pubertai or adolescent child may at times impede the detection of

Precipitins to the peptic-tryptic digest of gluten, fraction III, were found in the intestinal secretions (stool or small bowel fluid) of 12 patients with celiac disease but not in control specimens. The intestinal precipitins were demonstrable when the patients were ingesting gluten and were detected in three patients 6 months after the elimination of dietary gluten. Precipitins were more likely to be detected in the small bowel fluid than in the stool, indicating perhaps that the precipitating substance was originating in the upper intestine where the effect of gluten is maximal. Elevated serum IgA levels as well as high titers of hemagglutinating antibodies to gluten were usually present in the blood of patients with active celiac disease. It is proposed that the precipitins represent antibodies that are produced and secreted by the gut. The demonstration of precipitins to gluten fractions in patients with celiac disease may be a specific test for this disorder as well as a clue to the cause of gluten sensitivity.

Coproantibodies to the peptic-tryptic digest of wheat (fraction III) were demonstrated in three patients with celiac disease but were not demonstrated in 14 control subjects with various diarrheal diseases nor in six normal subjects. This preliminary report suggests that the polypeptides of gluten may elicit the production of antibodies within the gut and that the intestine continues to secrete these antibodies for extended periods even in the apparent absence of ingested wheat proteins. These copro-antibody studies are being further evaluated as to their specificity in the diagnosis of celiac disease.

A 13-year-old boy with chronic diarrhea and abdominal pain since 6 months of age, and recurrent fevers since 12% years of age, was found to have deficiency of IgA and nodular lymphoid hyperplasia of the small intestine. This disorder was similar to that of "dysgammaglobulinemia and intestinal lymphoid hyperplasia" described in adults in 1966. An associated giardiasis was eliminated by atabrine therapy and a malabsorption syndrome, cleared after treatment with tetracycline. Diarrhea and abdominal pain were not alleviated until he was treated with monthly fresh frozen plasma infusions. It is to be emphasized that other forms of chronic diarrhea not related to immunoglobuun deficiencies do not respond to this type of therapy.

An association between the presence in the stool of precipitating substances to cow's milk and the occurrence of milk-induced gastrointestinal bleeding, protein loss and diarrhea was demonstrated in four children. This precipitating substance was not found in the stools of patients with a variety of diarrheal and other disorders. It is suggested that an antigen-antibody reaction is involved in the precipitation of milk protein by the fecal substance and that this substance is a coproantibody. No precipitins to milk proteins were detected in their serums, but titers to alpha lactalbumin were high in three of the four children. Immunologic mechanisms may be involved in gastrointestinal milk sensitivity, although the role of antibodies in the pathogenesis of the disorder might only be a secondary one.

The effect of removal of major portions of proximal and distal small intestine on albumin degradation was studied in 3 patients, 2 to 12 years after resection.

A 15-year-old boy with congenital lymphedema, ascites, hypoproteinemia, and a jejunal biopsy diagnostic of intestinal lymphangiectasia was studied. I131 albumin survival was evaluated by differential counting of the radioactivity in the lymphedematous and in the normal arm. When a diet containing 150 gm of fat was fed daily, the I131 albumin half-life was 3.7 days in the normal arm and 22 days in the lymphedematous arm. Substitution of 75 gm MCT for 75 gm dietary fat increased the half-life in the normal arm to 5.1 days. Reduction of dietary fat to 25 gm per day further increased the half-life to 6.5 days in the normal arm. The I131 albumin half-life in the lymphedematous arm was not significantly affected by these dietary changes. Although approximately 50% of the injected dose of labeled albumin had disappeared from the normal arm within 4 days, fecal and urinary losses accounted for only 15% of the injected dose. The high level of radioactivity remaining in the lymphedematous arm suggested significant "trapping" of the radioactive albumin. Albumin, cleared more slowly from the lymphedema because of inadequate lymphatic drainage, becomes unavailable to the metabolic pool. The observed rapid albumin half-life in intestinal lymphangiectasia is, thus, partly due to this "trapping" in addition to the known enteric losses of plasma proteins.

Case Studies1 October 1967Mechanisms of Steatorrhea in the Zollinger-Ellison SyndromeROBERT M. VOGEL, M.D., L. DONALD WEINSTEIN, M.D., TEODORO HERSKOVIC, M.D., HOWARD M. SPIRO, M.D., F.A.C.P.ROBERT M. VOGEL, M.D.Search for more papers by this author, L. DONALD WEINSTEIN, M.D.Search for more papers by this author, TEODORO HERSKOVIC, M.D.Search for more papers by this author, HOWARD M. SPIRO, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-4-816 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDiarrhea is a prominent clinical feature of the Zollinger-Ellison syndrome (1). In approximately one half of the well-studied cases of non-beta islet cell adenomas diarrhea is associated with marked gastric hypersecretion and intractable peptic ulcer disease; it is within this group that steatorrhea and malabsorption occur (1-13). Although the gastric hypersecretion may be responsible for the diarrhea, the precise etiologic mechanism has not been fully elucidated. Theoretically, hyperacidity must lead to steatorrhea by two possible mechanisms: [1] inactivation of pancreatic enzymes, particularly lipase, by acid duodenal contents or [2] production of jejunal abnormalities. If this hypothesis is correct, drastic reduction...References1. SINGLETONKERNWADDELL JWFWR: Diarrhea and pancreatic islet cell tumor: report of a case with a severe jejunal mucosal lesion. Gastroenterology 49: 197, 1965. CrossrefMedlineGoogle Scholar2. MAYNARDPOINT EPWW: Steatorrhea associated with ulcerogenic tumor of pancreas. Amer. J. Med. 25: 456, 1958. CrossrefMedlineGoogle Scholar3. SANCHEZSOMMERS GCSC: Peptic ulcer diathesis with a mixed adenocarcinoma of pancreas: case report. Gastroenterology 38: 467, 1960. CrossrefMedlineGoogle Scholar4. SUMMERSKILL WH: Malabsorption and jejunal ulceration due to gastric hypersecretion with pancreatic islet cell hyperplasia. Lancet 1: 120, 1959. CrossrefMedlineGoogle Scholar5. RAWSONENGLANDGILLAMFRENCHSTAMMERS ABMTGGJMFA: Zollinger-Ellison syndrome with diarrhoea and malabsorption. Observations on a patient before and after pancreatic islet-cell tumor removal without resort to gastric surgery. Lancet 2: 131, 1960. CrossrefMedlineGoogle Scholar6. KABLER JD: Rare malabsorption syndromes. Ann. Intern. Med. 52: 1221, 1960. LinkGoogle Scholar7. HAUBRICHO'NEILBLOCK WSFSMA: Observations on steatorrhea associated with gastric hypersecretion and pancreatic islet cell neoplasm. Ann. Intern. Med. 56: 302, 1962. LinkGoogle Scholar8. SHAYCHEYKOIDEBURNETT HWYSMWE: Mechanism of the disordered physiology involved in Zollinger-Ellison syndrome. Report of a case. Amer. J. Dig. Dis. 7: 401, 1962. CrossrefMedlineGoogle Scholar9. JONES R: The Zollinger-Ellison syndrome: report of a case presenting with steatorrhea. Aust. New Zeal. J. Surg. 32: 274, 1963. CrossrefMedlineGoogle Scholar10. PARRISHRAWLINS JADC: Intestinal mucosa in the Zollinger-Ellison syndrome. Gut 6: 286, 1965. CrossrefMedlineGoogle Scholar11. JACKSONBLAIRDAWSONREEDWATTS RHELPJJDWP: Gastrin activity of tumour tissue in a child with Zollinger-Ellison syndrome. Lancet 2: 908, 1963. CrossrefMedlineGoogle Scholar12. DELEUTYTGATVAN GOIDSENHOVEN JHGE: Diarrhea associated with pancreatic islet-cell tumors. Amer. J. Dig. Dis. 9: 97, 1964. CrossrefMedlineGoogle Scholar13. MELNYKKRIPPAEHNEBENSONDUNPHY CSWWJAJE: Spontaneous remission of Zollinger-Ellison syndrome. Arch. Intern. Med. (Chicago) 115: 42, 1965. CrossrefMedlineGoogle Scholar14. DONALDSONVONELGENDWIGHT RMPRRW: Gastric hypersecretion, peptic ulceration and islet cell tumor of pancreas. (The Zollinger-Ellison syndrome.) New Eng. J. Med. 257: 965, 1957. CrossrefMedlineGoogle Scholar15. GREGORYTRACY RAHJ: The constitution and properties of two gastrins extracted from hog antral mucosa. Gut 5: 103, 1964. CrossrefMedlineGoogle Scholar16. GREGORYTRACY RAHJ: A note on the nature of the gastrin-like stimulant present in Zollinger-Ellison tumours. Ibid., p. 115. Google Scholar17. CREAMER B: Small-intestinal mucosal dynamics and the environment. Brit. Med. J. 2: 1373, 1964. CrossrefMedlineGoogle Scholar18. JAMES AH: Gastric epithelium in the duodenum. Gut 5: 285, 1964. CrossrefMedlineGoogle Scholar19. COOKNASSIMCOLLINS PBJRJ: The effects of thyrotoxicosis upon the metabolism of calcium, phosphorus, and nitrogen. Quart. J. Med. 28: 505, 1959. MedlineGoogle Scholar20. CRANEEVANS CWDW: Thyrotoxic steatorrhea. Brit. Med. J. 2: 1575, 1966. CrossrefMedlineGoogle Scholar21. COOKLENNARD-JONES HBJE: Effect of antisecretory drugs on gastric hypersecretion in endocrine adenoma syndromes. Lancet 2: 247, 1966. CrossrefMedlineGoogle Scholar22. CLARKEGLENILLINGWORTH AMAIC: Zollinger-Ellison syndrome treated without gastric surgery. Lancet 1: 1360, 1964. CrossrefMedlineGoogle Scholar23. WADDELLLEONSINSZUIDEMA WRAJGD: Gastric secretory and other laboratory studies on two patients with Zollinger-Ellison syndrome. New Eng. J. Med. 260: 56, 1959. CrossrefMedlineGoogle Scholar24. ANGERVALLDOTEVALLLEHMANNORBERG LGKEPB: Zollinger-Ellison syndrome. Report of a case. Gastroenterology 44: 512, 1963. CrossrefMedlineGoogle Scholar25. POTHCLEVELANDNASH EJBRJB: Pancreatic secretion and peptic ulcer formation. Amer. J. Surg. 101: 154, 1961. CrossrefMedlineGoogle Scholar26. BANKMARKSSEALYLOUWSILBER SINRJHW: Malignant Zollinger-Ellison syndrome in a Bantu woman with prolonged remission after gastric radiotherapy. Gut 6: 279, 1965. CrossrefMedlineGoogle Scholar27. LAWRIEWILLIAMSONHUNT RSAWJN: Zollinger-Ellison syndrome treated with poldine methyl methosulphate. Lancet 1: 1002, 1962. CrossrefMedlineGoogle Scholar28. GREGORYTRACY RAHJ: The preparation and properties of gastrin. J. Physiol. (London) 156: 523, 1961. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT M. VOGEL, M.D.; L. DONALD WEINSTEIN, M.D.; TEODORO HERSKOVIC, M.D.; HOWARD M. SPIRO, M.D., F.A.C.P.Affiliations: New Haven, ConnecticutFrom the Division of Gastroenterology, Department of Medicine, Yale-New Haven Hospital and Yale University School of Medicine, New Haven, Conn.This study was supported in part by grant FR-0038 to the Yale Clinical Research Center from the U. S. Public Health Service, Washington, D. C.Dr. Spiro was aided in this work by grant AM-5156-09 9070-41-48574, U. S. Public Health Service, Washington, D. C.Requests for reprints should be addressed to Robert M. Vogel, M.D., Department of Medicine, Yale University School of Medicine, 333 Cedar St., New Haven, Conn. 06510. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGastric Secretion in Zollinger-Ellison SyndromeZollinger-Ellison Syndrome: Clinical Presentation in 261 PatientsPathophysiology of the Exocrine PancreasPathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome)The Malabsorption SyndromeDiarrhoea: mechanisms and treatment.A case of the Zollinger-Ellison syndrome associated with hyperplasia of salivary and Brunner's glandsEffects of brocresine on zollinger-ellison syndrome report of 2 casesDisturbances in Fat Digestion Induced by Acidic Jejunal pH Due to Gastric Hypersecretion in ManClinical Observations on MalabsorptionMalabsorptionDas Zollinger-Ellison-SyndromThe Zollinger-Ellison Syndrome with SteatorrheaPhysiologic responses to gastric acid hypersecretion in Zollinger-Ellison syndrome 1 October 1967Volume 67, Issue 4Page: 816-822KeywordsAdenomasDiarrheaEnzymesHospital medicineLipasesMedical servicesPeptic ulcersZollinger Ellison syndrome ePublished: 1 December 2008 Issue Published: 1 October 1967 PDF downloadLoading ...

A 15-year-old boy with congenital lymphedema, ascites, hypoproteinemia, and a jejunal biopsy diagnostic of intestinal lymphangiectasia was studied. I131 albumin survival was evaluated by differential counting of the radioactivity in the lymphedematous and in the normal arm. When a diet containing 150 gm of fat was fed daily, the I131 albumin half-life was 3.7 days in the normal arm and 22 days in the lymphedematous arm. Substitution of 75 gm MCT for 75 gm dietary fat increased the half-life in the normal arm to 5.1 days. Reduction of dietary fat to 25 gm per day further increased the half-life to 6.5 days in the normal arm. The I131 albumin half-life in the lymphedematous arm was not significantly affected by these dietary changes. Although approximately 50% of the injected dose of labeled albumin had disappeared from the normal arm within 4 days, fecal and urinary losses accounted for only 15% of the injected dose. The high level of radioactivity remaining in the lymphedematous arm suggested significant trapping of the radioactive albumin. Albumin, cleared more slowly from the lymphedema because of inadequate lymphatic drainage, becomes unavailable to the metabolic pool. The observed rapid albumin half-life in intestinal lymphangiectasia is, thus, partly due to this trapping in addition to the known enteric losses of plasma proteins.