Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging.

BACKGROUND: 5-HT(3) antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility. AIM: To assess the effects of ondansetron compared with placebo in healthy volunteers on SBWC and motility in two different groups of subjects, one studied using MRI and another using manometry. METHODS: Healthy volunteers were given either a placebo or ondansetron on the day prior to and on the study day. Sixteen volunteers underwent baseline fasting and postprandial MRI scans for 270 min. In a second study, a separate group of n = 18 volunteers were intubated and overnight migrating motor complex (MMC) recorded. Baseline MRI scans were carried out after the tube was removed. RESULTS: Fasting SBWC was markedly increased by ondansetron (P < 0.0007). Ondansetron reduced the overall antroduodenal Motility Index (P < 0.04). The subjects who were intubated had significantly lower fasting SBWC (P < 0.0002) compared with the group of subjects who were not intubated. CONCLUSIONS: The 5-HT(3) receptor antagonism increased fasting small bowel water. This was associated with reduced fasting antroduodenal Motility Index which may explain the clinical benefit of such drugs.

Effect of bran, ispaghula, and inert plastic particles on gastric emptying and small bowel transit in humans: the role of physical factors.

BACKGROUND: Coarse bran is known to accelerate transit through the whole gut and to increase stool weight. This effect is much reduced by grinding the bran, suggesting that particle size influences gut motor patterns. AIMS: To compare the effect of 15 g coarse bran with 15 g inert plastic particles and 7 g of ispaghula on the gastric emptying and small bowel transit of a rice pudding test meal. SUBJECTS: 13 healthy volunteers. METHODS: Transit of 99mTc labelled rice studied by gamma-scintigraphy measuring gastric emptying and colonic arrival over 10 hours. Small bowel transit was estimated from the difference between time to 50% gastric emptying and 50% colonic arrival. RESULTS: Bran delayed gastric emptying by 22 (SEM 8) minutes compared with control values of 88 (SEM 6) minutes p < 0.05. Ispaghula and plastic particles had no significant effect. Small bowel transit was accelerated compared with control values of 322 (SEM 29) minutes, decreasing by 95 (29) minutes and 62 (22) minutes after bran and plastic particles respectively. Ispaghula again showed no significant effect. CONCLUSION: Coarse bran delays gastric emptying and accelerates small bowel transit. The marked acceleration of small bowel transit also seen with inert plastic particles may be due to increased upper gut secretions after stimulation of enteric nerves.

Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.

A prospective placebo-controlled, randomized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed. After detoxification, each of the 538 patients included was randomly assigned to one of three groups: 177 patients received placebo, 188 received Acamprosate at 1.3 g/day (low dose group) and 173 received 2.0 g/day (high dose group) for 12 months. This was followed by a single blind 6 month period on placebo. The patients' mean age was 43.2 +/- 8.6 years. Their mean daily alcohol intake was high (nearly 200 g/day) and of long duration (9.5 +/- 7.1 years). Abstinence figures followed the order high dose > low dose > placebo. The difference was significant at 6 months (P < or = 0.02) but not at 12 months (P = 0.096). The number of days of continuous abstinence after detoxification was 153 +/- 197 for the high-dose group versus 102 +/- 165 for the placebo group (P = 0.005), with the lose-dose group reporting 135 +/- 189 days. Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months (P = 0.002) and 12 months (P = 0.005). During the 6-month post-treatment period, no increased relapse rate or residual drug effect was observed. The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently (P < 0.01). This study confirms the pharmacological efficacy of Acamprosate and its good acceptability. As an adjunct to psychotherapy, this study supports the inclusion of Acamprosate in a strategy for treating alcoholism.

Monoclonal antigranulocyte antibody imaging in inflammatory bowel disease: a preliminary report.

The 99Tcm-labelled antigranulocyte antibody BW250/183 has been used in the detection of intestinal inflammation in patients with active ulcerative colitis and Crohn's disease. Planar images were obtained up to 24 h after intravenous injection of the antibody. Eight out of nine patients with ulcerative colitis and six out of seven patients with Crohn's disease gave positive images. In 11 patients distribution of the inflammation was confirmed by barium studies, colonoscopy or surgery, whilst in two the antibody scan suggested more extensive disease than barium enema. None of the patients had any adverse reactions. Imaging with BW250/183 appears to give an accurate indication of the extent of inflammation in inflammatory bowel disease.