Roy G. Shorter

Crohn's Disease and Cancer

Abstract A follow-up study of 449 patients with Crohns enteritis, enterocolitis or colitis showed the incidence of colonorectal cancer to be 20 times greater in these cases than in a control population. Life-table methods were used for analysis, and complete follow-up observation was achieved in 442 (98.4 per cent) of the patients. (N Engl J Med 289:1099–1103, 1973)

Whipple's Disease: Clinical, Biochemical, and Histopathologic Features and Assessment of Treatment in 29 Patients

Whipples disease is a chronic systemic illness, the optimal treatment of which remains poorly defined. In our analysis of a 30-year, 29-patient experience with Whipples disease at the Mayo Clinic, the frequent initial manifestations of diarrhea, weight loss, arthritis, and lymphadenopathy correlated with findings reported previously by other investigators. Antibiotic therapy yielded rapid symptomatic and biochemical improvement, and histologic changes in the small bowel occurred subsequently. Despite antimicrobial therapy, relapses in patients with Whipples disease are common, and the central nervous system is considered the most serious site of involvement for recurrence. Administration of an antibiotic agent that is able to cross the blood-brain barrier may be more important in preventing relapse than prolonged duration of initial antimicrobial therapy.

A working hypothesis for the etiology and pathogenesis of nonspecific inflammatory bowel disease.

From our studies (1-6) and a review of the literature, we have developed a working hypothesis for the etiology and pathogenesis of nonspeci f ic i n f l a m m a t o r y bowel disease (chronic ulcerative colitis and Crohn s enterocolitis). This speculation is, first, that inflammatory bowel disease (IBD) results from the establishment of a state of hypersensitivity to antigen(s) of bacteria normally present in the individuals gastrointestinal tract and that the pathologic and clinical features of IBD then result from a predominantly cell-mediated hypersensitivity reaction in the bowel wall, and second, that the gut is the principal immune organ involved. The latter point is important to the concept and is supported by the conclusions of Fichtelius (7), who characterized the gut lymphoid tissue as a first-order central lymphoid organ, and by the work of Clarke (8), among others. How does the state of hypersensitivity become established when, normally (9), there is a mucosal block to the confrontation of the gut lymphoid tissues by bacterial antigen(s) from the lumen? We suggest that it could develop as a result of increased permeability of the gut mucosa, allowing the passage into the bowel wall of macromolecules and nonenteropathic gram-negative bacteria, and their resulting recognition by the gut-associated lymphoid tis-

Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies

BACKGROUND/AIMS Previous studies have shown that secretory losses in patients with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be suppressed by the somatostatin analogue, octreotide, thus facilitating fluid balance. However, the hormone also has antianabolic actions that may interfere with the use of infused amino acids. METHODS Amino acid metabolism, pancreatic enzyme synthesis and secretion, and mucosal protein turnover were measured by primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation with pentagastrin and cholecystokinin 8. RESULTS In comparison with normal healthy controls, baseline measurements of amino acid metabolism were normal in patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were elevated. Octreotide therapy improved fluid balance but suppressed gut hormone (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses. CONCLUSIONS Octreotide improves fluid balance in patients who have undergone jejunostomy but reduces the use of amino acids for splanchnic protein synthesis. This may interfere with the physiological process of adaptation to intestinal resection.

Primary Sclerosing Cholangitis and Celiac Disease: A Novel Association

The association of primary sclerosing cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with chronic cholestatic liver disease at ages 32, 46, and 62 years, respectively. In each patient, endoscopic retrograde cholangiography showed the typical findings of primary sclerosing cholangitis. Histologic features of liver biopsy were compatible with the diagnosis. Two patients had associated chronic ulcerative colitis. All three patients complained of frequent loose stools and weight loss; subsequent testing showed severe steatorrhea (204 to 323 mmol/d of fecal fat on a 100 g fat diet). Total villous atrophy was found in all three patients on histologic examination of the small bowel. Celiac disease was diagnosed at the time of presentation in two patients who had primary sclerosing cholangitis and was diagnosed three years after the onset of primary sclerosing cholangitis in the third patient. The celiac disease responded to a gluten-free diet in each patient whereas the primary sclerosing cholangitis was not affected by dietary treatment. The possibility of a chance association of primary sclerosing cholangitis and celiac disease cannot be accurately assessed but seems unlikely given the rarity of both diseases. The relationship between the two diseases remains unknown, although an immunologic connection is suspected. Celiac disease should be considered in the differential diagnosis of severe steatorrhea in patients with primary sclerosing cholangitis.

Renal Function in Donors and Recipients of Renal Allotransplantation: Radioisotopic Measurements

Excerpt In patients with renal allografts, serial determinations of renal function are of prognostic significance. Trends in renal function may be considered as reflecting a balance between effecti...

Further Studies of in Vitro Cytotoxicity of Lymphocytes from Patients with Ulcerative and Granulomatous Colitis for Allogeneic Colonic Epithelial Cells, Including the Effects of Colectomy

Further studies have been made of the cytotoxicity in vitro of lymphocytes from the peripheral blood of patients with ulcerative colitis, granulomatous colitis, or regional enteritis for allogeneic colonic epithelial cells when incubated at 37 C for 4 hr in the presence of complement. It has been shown that this cytotoxic effect was eliminated by total colectomy or, in one instance, by hemicolectomy with removal of the diseased segment, and the possible significance of these observations is discussed. In 2 patients, despite the cytotoxic effects of the lymphocytes for colonic epithelial cells, no cytotoxicity was found for gastric or ileal epithelial cells. Lymphocytes from healthy subjects and patients with diseases other than ulcerative colitis or granulomatous enterocolitis also were tested for cytotoxic effects in vitro on allogeneic colonic epithelial cells. So far this cytotoxic property has been found to be specific to lymphocytes from patients with ulcerative colitis or granulomatous enterocolitis.

Inhibition of in vitro cytotoxicity of lymphocytes from patients with ulcerative colitis and granulomatous colitis for allogeneic colonic epithelial cells using horse anti-human thymus serum.

Summary This study reports the cytotoxic effects in vitro of lymphocytes from the peripheral blood of patients with granulomatous or ulcerative colitis on suspensions of allogeneic colonic epithelial cells after 4 hr of incubation at 37 C. It has shown also that this effect can be inhibited by preliminary incubation of the lymphocytes in the presence of 10% horse anti-human thymus serum but not normal horse serum. Preliminary incubation of the colonic epithelial cells with either serum did not produce any similar inhibitory effect. If the hypothesis is accepted that the cytotoxic effects of lymphocytes on colonic epithelial cells may have a role in the pathogenesis of granulomatous or ulcerative colitis, then it is suggested that a clinical trial of horse anti-human thymus serum, possibly in association with other immunosuppressives, might prove valuable.

Relationships between pancreaticobiliary ductal anatomy and pancreatic ductal and parenchymal histology

To determine whether ductal or parenchymal histologic abnormalities were related to the type of openings of the pancreatic duct and common bile duct into the duodenum, 390 unfixed human postmortem en bloc pancreaticoduodenal specimens were examined anatomically, radiographically, and histologically. In 353 specimens, ductal openings were classifiable: 25% had a well‐defined ampulla, 18% a long common channel, 31% a short common channel, 7% an interposed septum, and 19% had separate openings for the pancreatic and bile ducts. Ductal histologic abnormalities were present in 25% of the specimens and most (77%) were found in the pancreatic head. When ductal openings were grouped according to the presence or lack of a prominent common channel, ductal epithelial abnormalities were more common in the absence of a prominent common channel (30% vs. 19%, p < 0.04). Papillary epithelial hyperplasia was associated only with the absence of a prominent common channel (P = 0.02). Histologic abnormalities were more common in the elderly (P < 0.005) but were not associated with cause of death or the presence of the minor pancreatic duct. Lack of a common channel is associated with abnormal ductal epithelium. This anatomic arrangement may be a factor in pancreatic carcinogenesis.

Effects of Preliminary Incubation of Lymphocytes with Serum on their Cytotoxicity for Colonic Epithelial Cells

Experiments were carried out to assess the effect of preliminary incubation of normal lymphocytes or lymphocytes from subjects with active chronic ulcerative colitis (CUC) or granulomatous colitis (GC) with their own sera, pooled normal human serum, or sera from other patients with CUC or GC, including sera obtained 10 days following colectomy, on their cytotoxicity for human colonic epithelial cells in vitro, Sera from a small number of patients with some gastrointestinal diseases other than inflammatory bowel diseases also were included in the study. It was shown that preliminary treatment for 4 days of lymphocytes from normal individuals with CUC or GC sera led to their demonstration of cytotoxic properties for colonic epithelium, but that this was not found if 10-day postoperative CUC sera, fetal calf serum, pooled normal human serum, or sera from patients with other diseases were used. The cytotoxicity of lymphocytes from patients with CUC or GC for colonic cells in vitro was decreased markedly by pretreatment with CUC or GC sera from other patients with these diseases, but not by similar treatment with their own serum or with 10-day postoperative CUC sera, fetal calf serum, pooled normal human serum, or sera from patients with diseases ther than CUC or GC.