Distribution of colorectal adenomas: implications for bowel cancer screening.

OBJECTIVE: To determine the distribution of colorectal adenomas relative to the splenic flexure in an asymptomatic population undergoing colonoscopy, as an indicator of the number of patients with adenomas who would be missed by screening with flexible sigmoidoscopy. DESIGN: Retrospective survey of medical records. SETTING: Private endoscopy centres in Melbourne, Victoria. SUBJECTS: All 1131 asymptomatic individuals who underwent full colonoscopy between 1 January 1995 and 31 December 1997 after referral from a bowel cancer prevention program organised by the endoscopy centres. People referred were aged either 40 years or over with a first-degree relative with bowel cancer, or 50 years or over with marked anxiety about bowel cancer. MAIN OUTCOME MEASURES: Presence and distribution of colorectal adenomas. RESULTS: Polyps were found in 270 individuals (24%) and were confirmed to be adenomas in 138 (12%). These 138 comprised 106 men and 32 women, with mean age 54 years (range, 40-78 years). Most (86%) had a single adenoma. Position of adenomas in relation to the splenic flexure was: distal only in 85 of the 138 people (62%), proximal only in 34 (25%), and both distal and proximal in 19 (14%). CONCLUSIONS: In 25% of asymptomatic people found to have adenomas by this bowel cancer prevention program, the adenomas were found only in the proximal colon, well beyond the reach of the flexible sigmoidoscope. This distribution of adenomas suggests that screening programs cannot rely solely on flexible sigmoidoscopy.

Heartburn: community perceptions.

BACKGROUND AND AIMS: To determine the prevalence of heartburn in the Australian community, and document factors precipitating it and medications used in treatment. METHODS: Telephone interviews with 1200 individuals aged 18 years or more were conducted one weekend in 1996. Each respondent was asked four questions about heartburn, its severity, factors causing it and current therapy. RESULTS: Fifty-six per cent of respondents reported that they had suffered from heartburn at some time in the past and 37% had symptoms at least once every 4-6 months. The frequency of heartburn increased with age and was more common in men (40.7%) than women (32.6%). There was no difference in frequency between city and rural dwellers, or between white- and blue-collar workers. Almost half the individuals experienced mild pain or discomfort, one-third had moderate discomfort and 15% reported severe pain or discomfort. Women were more likely to report greater problems than men. Aggravating factors included spicy foods, greasy/rich foods, stress, alcohol, overeating, pregnancy, smoking, food allergy and coffee. More than half the respondents relied on antacids to control symptoms, 20% used prescription medications and a similar number did not use any medication. CONCLUSION: Heartburn is common in the Australian community and sufferers attribute symptoms to various lifestyle events, including diet and stress. Antacid usage is the commonest mode of therapy.

Reflux disease: the view of the internist.

Pathogenesis of GERD is mainly concerned with a defective antireflux barrier to gastric and duodenal contents. Transient lower oesophageal sphincter relaxation is thought to be the main mechanism by which reflux is permitted, but the mucosal exposure time to the refluxate, the nature of the refluxed material and oesophageal clearance are important mechanisms. The Internist only sees the 'tip of the iceberg' as far as GERD is concerned, and generally these are severe resistant cases of GERD. In this group, endoscopy is mandatory to assessing degree of inflammation and treatment is generally with proton-pump inhibitors, which have made the therapy of GERD relatively easy. Although treatment is effective, problems relating to safety of long-term profound gastric acid suppression, cost and effect on quality of life remain to be resolved.

Relationship of satiety to postprandial glycaemic, insulin and cholecystokinin responses.

The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin (CCK) remain unclear. The aim of this study was to test the hypothesis that the magnitude of the postprandial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety. Seven healthy, male volunteers consumed equal carbohydrate portions (0.5 g/kg body weight) of six test meals (Rice Bubbles, Sustain, Vita-Brits, All-Bran, porridge and white bread) in random order after an overnight fast. An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight. Serum CCK, plasma glucose and insulin and subjective satiety (measured by a rating scale) were assessed over 3 h and quantified using the glycaemic index (GI), insulin index (II), the peak satiety score and area under the incremental curve (AUC). The observed GIs (mean +/- SE) ranged from 42.5 +/- 2.6 for All-Bran to 116.2 +/- 11.4 for Rice Bubbles, using white bread as the reference food (GI = 100). Peak satiety scores varied eightfold from 0.21 +/- 0.4 for Sustain to 1.64 +/- 0.4 for All-Bran. Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals (r = -0.916, p less than 0.001 and r = -0.926, p less than 0.001). A direct relationship was observed between satiety (AUC) and the CCK response (AUC) (r = 0.73 p less than 0.01). The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety.

Potential regulators of feeding behavior in anorexia nervosa.

We recruited 10 patients with anorexia nervosa and 6 age- and height-matched control subjects. Basal and postprandial concentrations of glucose, insulin, cholesterol, amino acids, gastrin, and pancreatic polypeptide (PP) were measured in response to a standard mixed meal. The only satiety signal that was significantly different between the anorectic group and the control group was PP (P less than 0.001). Tryptophan-LNAA and tyrosine-LNAA ratios were not significantly different in the two groups; however, there was a trend toward a lower tryptophan-LNAA ratio in the anorectic group. Gastrin concentrations were significantly decreased in the anorectic group (P less than 0.001) as were basal insulin concentrations (P less than 0.05). Decreased gastrin concentrations may play a role in the gastric symptoms associated with anorexia nervosa. Previous findings that PP release is diminished in obesity, together with the present findings of PP increase in anorexia nervosa, suggest that this peptide may play a role in appetite control mechanisms.

Campylobacter pylori--a role in non-ulcer dyspepsia?

Non-ulcer dyspepsia (NUD) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified. The pathophysiology of NUD is probably heterogeneous. Eighty-two subjects with NUD were studied in a prospective randomized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate (CBS) chewable tablets at a dose of four tablets daily for 1 month. The role of Campylobacter pylori and associated histological gastritis was evaluated. Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25% of age-matched controls. C. pylori was associated with acute and chronic inflammation (P less than 0.001) in the antrum. C. pylori was cleared in 59% of CBS-treated subjects compared with only 4% placebo (P less than 0.05). Both acute and chronic inflammation improved in subjects cleared of bacteria. Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms. In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups. This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia.

Effect of renal failure or portacaval shunt on release of neurotensin in man.

Neurotensin-like immunoreactivity (NTLI) is released into the circulation following a meal. However, the factors influencing its degradation and metabolism are uncertain, but it is presumed that the kidneys and liver are involved. This study has determined the release of NTLI after a liquid fat meal (200 ml 20% Intralipid) in 10 healthy control subjects, five patients with stable chronic renal failure (CRF), and five patients after a portacaval shunt (PCS), to assess the possible role of the liver and kidney in NTLI metabolism. NTLI was measured by radioimmunoassay using both specific C and N terminally directed antisera. The results showed: Basal NTLI levels are similar in controls, after PCS, and in CRF. A liquid fat meal produces a single early peak of NTLI and levels are greater after PCS than in controls or CRF. Levels return much more slowly to basal in CRF and after PCS. Thus it is likely that both the liver and kidney are involved in the metabolism and clearance of NTLI.

Central and peripheral proglumide administration and cholecystokinin-induced satiety.

Peripheral (50 mg/ml) or central (50 micrograms/microliter) injections of proglumide were made into Sprague-Dawley rats which displayed satiety-like responses after the peripheral (100 micrograms/kg) or central (50 ng in 1 microliter) administration of cholecystokinin (CCK). The satiety produced by CCK injection into the lateral hypothalamus, area postraema and ventromedial hypothalamus was significantly reversed by proglumide injections into these areas during a 4 h food intake test. Peripheral injection of proglumide after central or peripheral CCK injection did not modify this type of CCK-induced satiety. Central proglumide injection produced a reliable decrease in water intake and this is compatible with previous findings which describe the stimulation of water intake after central gastrin administration. These results suggest that various central and peripheral mechanisms which are involved in the regulation of appetite may function independently as a 'failsafe' system.

The effect of atropine and vagal stimulation on the release of neurotensin-like immunoreactivity in man.

This study investigated the food stimulated release of neurotensin-like immunoreactivity (NTLI) in man with and without the administration of atropine, and the influence of vagal stimulation by modified sham feeding and insulin hypoglycaemia. NTLI was measured, after ethanol extraction, by specific C- and N-terminally directed antisera. With both a liquid fat meal and a mixed meal an early peak of NTLI occurred. The mixed meal also produced a second sustained rise in plasma NTLI. An intramuscular injection of 0.6 mg atropine sulphate abolished the early peak, but had no effect on the late peak. Modified sham feeding and insulin hypoglycaemia did not release NTLI. We conclude that it is possible that a cholinergic non-vagal mechanism is responsible for the early phase of food stimulated release of NTLI in man, and that the second sustained rise may be cholinergically independent.

Comparative effects of bombesin and porcine gastrin-releasing peptide in the dog.

Bombesin and porcine gastrin-releasing peptide (GRP) share a common C-terminal decapeptide fragment and are known to have similar bioactivity. The potencies of parenterally administered GRP and bombesin have been compared in their effects on gastric acid output, serum gastrin, and serum pancreatic polypeptide. In the dose range 0-720 pmol/kg/hr, infusions of both peptides resulted in dose-related increases of gastric acid output and corresponding elevations of serum gastrin and pancreatic polypeptide. At the dose of 1440 pmol/kg/hr, both bombesin and GRP resulted in a decrease in gastric acid output and serum gastrin. The mechanism of this inhibition is unknown. No significant difference in potency between the two peptides in changing gastric acid output, serum gastrin, and pancreatic polypeptide was observed. The demonstration of equimolar potency of porcine GRP and bombesin support the concept that GRP is mammalian bombesin.

Gastrins and gastrinomas.

The past 20 years have seen gastrin attain true hormonal status. Its structure has been characterized, it has been synthesized, radioimmunoassays for its measurement in blood and tissues have been developed and its physiology and metabolism elucidated. Of much interest to clinicians has been the association between gastrin and tumours of the pancreas (gastrinomas) and atrophic gastritis. The advent of gastrin measurement has facilitated the diagnosis of gastrinoma and the availability of powerful acid suppressants has altered the therapy of gastrinoma.

Ventricular, paraventricular and circumventricular structures involved in peptide-induced satiety.

Cholecystokinin, bombesin or gastrin (2 microliter of 50 ng/microliter) was injected stereotaxically into the paraventricular nucleus of the hypothalamus, the arcuate/ventromedial area, the subfornical organ, the area postrema and the cerebral aqueduct of Sprague-Dawley rats and the effects of these injections on food and water intake were studied. While the injection of cholecystokinin reduced food intake when it was injected into both hypothalamic loci, food and water intake were most severely affected by the injection of this peptide into the cerebral aqueduct. Bombesin reduced food intake after its injection into all areas except the subfornical organ and reliable reductions in water intake were seen after injection of this peptide into all areas except the paraventricular nucleus. Minor reductions in food intake were seen following gastrin injection into the paraventricular nucleus while increased water consumption was observed after this peptide was injected into the paraventricular nucleus and cerebral aqueduct. In a second study 6-hydroxydopamine injections (2 microliter of 8 micrograms/microliter were made into the five areas studied 10 days before animals were injected with 100 micrograms/kg of cholecystokinin (i.p.). All 6-hydroxydopamine-injected animals reduced their food and water intake in response to the cholecystokinin challenge as did intact controls. These results indicate that while the changes in food and water intake produced by the central injection of cholecystokinin, bombesin or gastrin may involve central catecholamine systems, those occurring after its systemic administration do not. Therefore, if the release of gastrointestinal peptides during natural feeding is part of a homeostatic mechanism regulating hunger and satiety, this mechanism may operate without directly involving central catecholamine systems.