Familial adenomatous polyposis: from bedside to bench and vice versa. A tribute to the somatic cell geneticist P. Meera Khan.

Familial adenomatous polyposis (FAP) is characterized by the presence of numerous adenomatous polyps in the colorectum, as well as an autosomal dominant mode of inheritance. This syndrome will inevitably lead to colorectal cancer when left untreated, and it is estimated that 1% of all colorectal cancer cases are due to it. Over the past 20 years molecular genetic studies on FAP patients have laid down the basis for the elucidation of the genetic phenomena that ultimately result in the development of colorectal cancer.

Treatment of mesenteric desmoid tumours with the anti-oestrogenic agent toremifene: case histories and an overview of the literature.

Desmoid tumours are histologically benign but due to their infiltration and compression of surrounding structures potentially life-threatening fibromatous lesions of unknown aetiology. The annual incidence rate is 2-4 per million people. The mesenteric variant constitutes about 10% of all desmoid tumours, although in familial adenomatous polyposis (FAP) patients this may be up to 70%.

Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease.

Background: The approval of azathioprine (AZA) for the long-term therapy of patients with Crohn's disease in The Netherlands.

Methods: Review and update of the literature on clinical efficacy and safety of AZA in inflammatory bowel disease.

Results: AZA and its metabolite 6-mercaptopurine (6-MP) are effective in the treatment of active Crohn's disease.

Faecal parameters in the assessment of activity in inflammatory bowel disease.

Background: Determination of inflammatory activity is helpful when assessing the efficacy of drugs in therapeutic trials and in facilitating management of individual patients with inflammatory bowel disease (IBD). Faecal parameters have been hypothesized to be more specific than non-faecal measurements in the assessment of intestinal inflammation.

Methods: Review of the literature on faecal measurements in IBD.

The role of the barostat in human research and clinical practice.

The barostat is a recently developed device used to study the physiology and pathophysiology of the motor and sensory functions of the gastrointestinal tract. It can monitor volume changes while maintaining a set constant pressure and deliver controlled distensions of gastrointestinal organs. Simultaneously, motility and visceral perception may be assessed.

Endoscopic regression of Barrett's oesophagus during omeprazole treatment; a randomised double blind study.

Background: Barrett's oesophagus, columnar metaplasia of the epithelium, is a premalignant condition with a 50-100-fold increased risk of cancer. The condition is caused by chronic gastro-oesophageal reflux. Regression of metaplasia may decrease the cancer risk.

Functional dyspepsia has a good prognosis irrespective of H. pylori status. Long-term follow-up of symptoms after anti H. pylori treatment.

Aim: A prospective study with anti H. pylori therapy was done in patients with functional dyspepsia.

Methods: Inclusion criterion was the absence of any macroscopic abnormality in oesophagus, stomach, and duodenum, irrespective whether H.

Cholecystokinin secretion in patients with chronic pancreatitis and after different types of pancreatic surgery.

Unlabelled: Cholecystokinin (CCK) secretion may be affected in patients with chronic pancreatitis (CP), but little is known on the effect of pancreatic surgery on CCK secretion. We measured CCK secretion (radioimmunoassay, RIA) in response to bombesin infusion (100 ng/kg/20 min) for 120 min to test CCK secretory capacity, to ingestion of a liquid diet (400 kcal) for 120 min, and in response to a solid fat-rich meal (500 kcal) for 120 min. These studies were performed in 45 patients with CP (25 with exocrine insufficiency), 15 patients after duodenum-preserving pancreatic head resection (DPRHP), 18 patients after the Whipple operation, 12 patients after distal pancreatectomy (DP), and 35 control subjects.

Differences in cholecystokinin release and gallbladder contraction between emulsified and nonemulsified long-chain triglycerides.

Background: Fat is a potent stimulus of cholecystokinin (CCK) release. Apart from lipolysis, fatty acid chain length, and saturation, emulsification may also determine the magnitude of CCK release.

Methods: We have studied the effect of emulsification of soybean oil on CCK and pancreatic polypeptide (PP) release (radioimmunoassay [RIA]) and gallbladder motility (ultrasonography).

Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition.

Background: Gastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern.

Design: The effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h-1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects.

Large-scale production of natural cytokines during activation and expansion of human T lymphocytes in hollow fiber bioreactor cultures.

We studied the large-scale production of a variety of natural cytokines during the activation and expansion of human T lymphocytes in a hollow fiber bioreactor culture system. Peripheral blood mononuclear cells (PBMC) were activated using phytohemagglutinin plus recombinant interleukin-2 (IL-2). Phytohemagglutinin was either present in the hollow fiber bioreactor during the entire 15-16-day culture period or only during the 20-h preactivation of the PBMC in culture bags.

Gall bladder emptying in severe idiopathic constipation.

Background: It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder.

Aim: To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls.

Methods: Gall bladder emptying (ultrasonography) was studied in response to neural, cephalic-vagal stimulation with modified sham feeding (MSF) for 90 minutes and in response to hormonal stimulation with cholecystokinin (CCK, 0.

Duodenal meal stimulation leads to coeliac artery vasoconstriction and superior mesenteric artery vasodilatation: an intra-abdominal ultrasound study.

To evaluate the influence of duodenal feeding on splanchnic blood flow, 14 patients with normal coeliac and superior mesenteric arteries underwent intra-abdominal duplex scanning of the systemic and splanchnic circulation under standardised basal and meal-stimulated conditions. Doppler samples and diameter measurements were taken of the aorta, coeliac artery, common hepatic artery, splenic artery, superior mesenteric artery, and inferior mesenteric artery. Duodenal meal stimulation has no systemic effects (p > 0.

Post-prandial intragastric and duodenal acidity are increased in patients with chronic pancreatitis.

Objectives: Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum.

Methods: We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions.

The influence of Helicobacter pylori on oesophageal acid exposure in GERD during acid suppressive therapy.

Background: Helicobacter pylori exaggerates the effect of acid suppressive drugs on intragastric pH. It is unknown whether this is relevant for the treatment of GERD.

Aim: To compare oesophageal acid exposure and symptoms in H.

Expression of T cell activation antigen CD134 (OX40) has no predictive value for the occurrence or response to therapy of acute graft-versus-host disease in partial T cell-depleted bone marrow transplantation.

CD134 (OX40) is a member of the tumor necrosis factor family which is expressed by activated T lymphocytes. CD134 expression on T cells was monitored during the first 35 days post-transplant in 14 patients, receiving either an HLA-identical sibling bone marrow transplant (BMT), a matched unrelated transplant (MUD-BMT) or an autologous peripheral blood progenitor cell transplant (PBPCT). The sibling and unrelated grafts were partially depleted of T cells.

Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication.

Objective: After Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function.

Methods: We have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months).

Superoxide dismutases in the human colorectal cancer sequence.

Purpose: The oxidant-antioxidant balance within tissues is thought to contribute to the development and progression of cancer. Previous investigations have indicated changes in this balance during the colorectal oncogenic process that merit further investigation. The aim of the present study was to evaluate whether the human colorectal cancer sequence is accompanied by changes in the protein and activity levels of the antioxidant enzymes manganese- and copper/zinc-superoxide dismutase (Mn-SOD and Cu/Zn-SOD).

Effect of insulin and glucose on basal and cholecystokinin-stimulated exocrine pancreatic secretion in humans.

Pancreaticobiliary secretion is reduced during acute hyperglycemia. In nondiabetics, this inhibitory effect also may result from hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary secretion.

Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study.

Background: Serum chromogranin A (CgA) is regarded as a reliable marker of neuroendocrine proliferation. We previously described increased serum CgA levels during short-term profound gastric acid inhibition.

Aim: To investigate serum gastrin and CgA levels in dyspeptic patients during continuous medium- (6 weeks to 1 year), or long-term (1-8 years) gastric acid suppressive therapy.

Hyperglycemia reduces pancreaticobiliary secretion in response to modified sham feeding in humans.

Background/aims: We have investigated the effect of acute hyperglycemia on pancreaticobiliary secretion and pancreatic polypeptide (PP) release.

Methods: Duodenal outputs of bilirubin, trypsin, lipase, amylase and bicarbonate were measured using a recovery marker under basal conditions and in response to modified sham feeding (MSF) in 6 healthy subjects on two separate occasions: during normoglycemia and during acute hyperglycemia (15 mmol/l).

Results: During hyperglycemia the basal pancreaticobiliary output was significantly (p < 0.

Effect of i.v. amino acids on satiety in humans.

Background: Parenteral nutrients suppress oral food intake. Separate i.v.

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans.

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l).

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

Background: Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying.

Aims: To investigate whether intravenous amino acids also influence antroduodenal motility.