Watery diarrhoea in medullary carcinoma of the thyroid occurs in up to 30% of cases and may respond to removal of tumour tissue (Williams, 1966; Bernier et al., 1969). Previous clinical studies have shown abnormalities of small bowel motility and fluid and electrolyte absorption (Bernier et al., 1969; Isaacs et at., 1974). Among the substances elaborated by the tumour which could cause diarrhoea, prostaglandins and calcitonin are suggested causative agents. Raised blood and tumour prostaglandins have been found in some patients, and prostaglandins can produce diarrhoea in man and experimental animals (Williams et al., 1968; Cummings et al., 1973). Prostaglandins activate the adenyl cyclase/cAMP mechanism, leading to net intestinal fluid secretion. In contrast, calcitonin is invariably raised in medullary carcinoma (Melvin et al., 1972). It is also a potent secretagogue in both human and rabbit small intestine (Kisloff and Moore, 1977; Gray et al., 1975), but its mechanism of action is unknown. In order to determine the mechanism of diarrhoea in a patient suffering from this tumour, we first measured plasma levels of hormones known to alter intestinal fluid transport. Secondly, distal ileal flow was monitored, as an index of net fluid absorption in the small intestine. The cyclic AMP levels in the patients' small bowel mucosa were also measured. Finally, the diarrhoeagenic factor in the patient's plasma was studied by bioassay in the dog small intestine.

Aims: To determine carriage rates and densities of methanogens and sulfate-reducing bacteria in adults and children using molecular methods, and to also determine if a reciprocal relationship exists between these organisms.Methods and Results: Real-time PCR was used to detect and quantify methanogens and sulfate-reducing bacteria. Real-time PCR was more sensitive than breath methane measurements. Real-time PCR assays were applied to faecal DNA samples collected from 40 children and 12 adults. Methanogens were present in 25% of the children and 42% of the adults studied, and sulfate-reducing bacteria were detected in 15% of the children and 58% of the adults. High levels of sulfate-reducing bacteria were found in two methanogenic adults.Conclusions: Carriage rates and densities of methanogens and sulfate-reducing bacteria are greater in adults than in children. Competition does not necessarily lead to the predominance of one group in the faecal microflora.Significance and Impact of the Study: This study describes sensitive, molecular assays that could be used to monitor these organisms in gastrointestinal disease. Therapeutic exclusion of one group from the bowel would not necessarily lead to the expansion of the other, as there does not appear to be a reciprocal relationship between these groups.

The eubacterial population was studied in faecal samples of related and unrelated children. Temporal temperature gradient gel electrophoresis (TTGE) provided a snapshot of the bacterial population and allowed calculation of the degree of similarity in the predominant faecal microflora of identical twin pairs, fraternal twin pairs and unrelated paired controls. The highest levels of similarity were found in genetically identical twins. Significant differences were observed between the identical and fraternal twins (P = 0.037), strongly suggesting a genetic influence over the composition of the faecal microflora. The unrelated control group had the lowest similarity and was significantly different from the twins (P = 0.001). The results of this study indicate that host genetics influence the composition of the dominant eubacterial population in children.

In a randomized clinical trail to assess acceptability, yields, costs, and unwanted effects of screening procedures, 232 subjects (137 with family history of colorectal carcinoma or adenoma, 95 without) were offered either flexible sigmoidoscopy or colonoscopy. Subjects with polyps found on sigmoidoscopy were followed up by colonoscopy. The two procedures were similar in compliance (65%) and yield (19% adenoma, 15% hyperplastic polyps). Polyps of either type were more common in those with a family history (prevalence: 41% compared with 24% without family history, p = 0.04). Costs per procedure were 60% lower for sigmoidoscopy, but follow-up colonoscopy reduced this cost advantage to 20% per subject. The subjects found the preparation for sigmoidoscopy easier, but the procedure more uncomfortable and embarrassing, as colonoscopy was performed under sedation. In this hospital-based study, colonoscopy was as acceptable to subjects, and only slightly more costly than sigmoidoscopy. Advantages of sigmoidoscopy would be greater for use outside hospitals and with less intensive follow up.

Bacterial products fmet-leu-phe (FMLP), muramyl dipeptide (MDP) and lipopolysaccharide (LPS) were assayed for their ability to alter the inflammatory response to lambda carrageenan-induced pleurisy in Hooded Surgery rats. Continuously infused FMLP, or one initial i.v. dose of FMLP, MDP or LPS either ablated or partially suppressed the pleurisy. Total circulating leucocytes and neutrophils were suppressed by 55-65% when compared to the normal circulating leucocyte response to carrageenan pleurisy, excepting the protocol incorporating a single i.v. dose of FMLP where suppression was intermediate at 30%. There were also significant changes in the expression of FMLP receptors on circulating neutrophils. MDP and LPS induced a receptor number increase of 2 and 1.7 times initial value respectively, whilst a continuous FMLP infusion caused a receptor decrease to 0.3 times the initial value. The introduction of bacterial products at an alternative site to that of the pleurisy had an anti-inflammatory effect and the pleurisy was reduced.

The rapid expansion of knowledge in gut endocrinology can be attributed, in part, to the development of laboratory techniques for isolation, purification, characterization and synthesis of gastrointestinal peptides and for their sensitive and specific assay in body fluids permitting physiological studies.

Keshavarziam, A. M.D.; Anagnostides, A. M.D.; Chadwick, V. S. M.D.; Fitzpatrick, M. L. Ph.D. Author Information

Thirty eight patients with Crohn's disease and 30 patients with ulcerative colitis have been assessed using the technique of faecal excretion of 111Indium granulocytes to quantify precisely acute inflammatory activity. At the time of each faecal granulocyte measurement the serum concentration of the acute phase protein C-reactive protein and the erythrocyte sedimentation rate were estimated. C-reactive protein concentration was significantly higher in Crohn's disease than ulcerative colitis both overall and particularly in relation to given levels of granulocyte excretion. No such distinction was observed between the erythrocyte sedimentation rates in the two diseases. The present findings show that the acute phase response differs significantly between Crohn's disease and ulcerative colitis. Patients with ulcerative colitis may be constitutionally different from those with Crohn's disease and unable to mount a major acute phase response to their own disease.

An asymptomatic woman with Crohn's colitis developed an ESR of 92 and was found by 111Indium leucocyte scanning to have two hepatic abscesses. Their early detection led to successful treatment.

A patient with a 10-year history of episodes of venous thrombosis, a high ESR, an elevated plasma polyclonal 1gG concentration, and bleeding from esophageal varices had obstruction of both superior and inferior vena cavas with "downhill" esophageal varices and a normal portal vein with normal portal pressure. Extensive investigations revealed no predisposing factor for the venous thromboses, but the patient made a good clinical response to steroids and dapsone, with no further episodes of bleeding nor evidence of major venous thrombosis. The causes and outcome of "downhill" varices are discussed.

Normal volunteers (n = 6), patients with untreated celiac disease and subtotal villous atrophy (n = 6), patients with nonresponsive celiac disease (n = 2), and patients with celiac disease on a gluten-free diet with a virtually normal biopsy specimen (n = 6) drank a liquid fat meal after an overnight fast. Gallbladder emptying was monitored by using 99mTc-eHIDA, and blood samples were taken for cholecystokinin estimation by radioimmunoassay after high-performance liquid chromatography. The half-times of gallbladder emptying were 20.4 +/- 2.9 min (mean +/- SEM) for normals and 22.1 +/- 2.8 min in treated patients with celiac disease (NS). In patients with untreated celiac disease half-times were 154.3 +/- 10.3 min (p less than 0.02 vs. normals and treated patients with celiac disease), and in 2 nonresponsive patients, half-times were 40.7 and 37.3 min. Integrated plasma cholecystokinin responses were 473 +/- 87 and 436 +/- 137 pmol X L-1 X 30 min-1 in normals and treated patients with celiac disease (NS). In untreated patients with celiac disease values were 16 +/- 9 pmol X L-1 X 30 min-1 (p less than 0.001 vs. normals and treated patients with celiac disease), and in nonresponsive patients values were 442 and 322 pmol X L-1 X 30 min-1. In 2 patients studied before and during gluten-free diet half-times for gallbladder emptying changed from 168.9 and 302.4 min to 20.1 and 23.4 min, and cholecystokinin responses changed from 0 and 45 to 623 and 298 pmol X L-1 X 30 min-1. Cholecystokinin immunoreactivity cochromatographing with cholecystokinin-octapeptide was responsible for 50%-60% of circulating cholecystokinin in normals and in treated patients but the small amount of cholecystokinin that was released in untreated patients with celiac disease cochromatographed with cholecystokinin-33/39. We conclude that there is a reversible defect of gallbladder emptying and cholecystokinin release in celiac disease.

Two siblings with eosinophilic gastroenteritis who presented with severe iron deficiency anemia and hypoalbuminemia associated with varying degrees of mucosal damage are described. Using a monoclonal antibody to the secreted form of eosinophil cationic protein, we demonstrated activated degranulating eosinophils in the gastrointestinal mucosa that correlated with the degree of histologic damage. This finding suggests that eosinophils may have a primary role in the tissue damage in this condition. Oral disodium cromoglycate (Nalcrom) failed to alter the clinical, radiologic, and histologic abnormalities. Prednisolone, however, was beneficial in 1 case but did not completely reverse the abnormalities.

To examine the effect of atropine on cholecystokinin (CCK) release, we studied CCK concentrations after a liquid fat meal in five volunteers both with and without pretreatment with atropine. In control studies peak plasma CCK 8 concentrations were 15.0 +/- 6.2 pmol l-1, and the integrated plasma CCK 8 response was 415 +/- 216 pmol l-1(2)h-1. Peak plasma CCK 33/39 concentrations were 16.5 +/- 4.6 pmol l-1, and integrated CCK 33/9 response was 469 +/- 200 pmol l-1(2)h-1. After pretreatment with atropine postprandial CCKs were undetectable (p less than 0.05 versus control studies). The abolition of measurable CCK release by atropine may entirely account for its inhibitory effects on biliary secretion and in part for its effect on the pancreas.

Hemorrhagic colitis is a rare but well-recognized complication with ampicillin or penicillin derivative treatment. Early colonoscopy has been advocated in establishing the diagnosis by demonstrating the characteristic pattern of only right-sided involvement and so distinguishing it from other colitides. We report a patient who developed colitis after amoxycillin therapy in whom 111Indium leucocyte scan demonstrated right-sided colitis which alerted us to the diagnosis. Discontinuation of the antibiotic resulting in rapid improvement, and return of the 111Indium leucocyte scan to normal in this patient suggests that ampicillin-associated colitis should not be considered purely as a hemorrhagic disease but may in some cases have an inflammatory component.

The cephalic phase of pancreatic secretion in humans was investigated using modified sham feeding and a duodenal perfusion system. Studies performed in 5 normal volunteers were designed so that trypsin and bicarbonate outputs during sham feeding, with or without pretreatment with atropine, were compared to “maximal” pancreatic secretory response to exogenous stimulation with caerulein and secretin. The role of gastric acid entry to the duodenum in mediating cephalic responses was assessed by a comparison between outputs observed when gastric aspiration (∼-80% efficient) was used alone and when acid entry was completely abolished by combining gastric aspiration with cimetidine pretreatment. To evaluate the role, if any, of gut hormone release in the pancreatic secretory response to sham feeding, plasma gastrin and cholecystokinin concentrations were monitored throughout. Trypsin outputs during sham feeding were 31.9 ± 10.45 kallikrein inactivator units per 30 min, equivalent to four times basal output and 92% of maximal, but were only 54% maximal in subjects pretreated with cimetidine. Atropine suppressed basal trypsin output and abolished the response to sham feeding (4.98 ± 3.89 kallikrein inactivator units per 30 min). A modest increase in bicarbonate secretion during sham feeding (3.30 ± 1.97 mmol/30 min versus basal of 0.68 ± 0.74 mmol/30 min, p = 0.5) was not influenced by atropine but was abolished by cimetidine pretreatment. No significant changes in plasma gastrins were observed in these studies and plasma cholecystokinins remained undetectable throughout. We conclude that there is tonic vagal stimulation of trypsin secretion, and that sham feeding markedly increases trypsin output, which is augmented further by acid entry into the duodenum. There is no direct effect of cephalic stimulation on bicarbonate secretion or on gastrin or cholecystokinin release.