Nicholas S. Coleman

Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome

BACKGROUND & AIMS 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. METHODS Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. RESULTS Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002). CONCLUSIONS C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.

Antral motility measurements by magnetic resonance imaging

Magnetic resonance imaging has been recently proposed as a promising, noninvasive technique to assess the motility of the gastric antrum. However, so far the reproducibility and dependence on test meal composition has not been evaluated. In this study, snapshot echo‐planar magnetic resonance imaging was used to measure the frequency, propagation speed and percentage occlusion of antral contractions in 28 healthy volunteers. They were fed either liquid (n=12), mixed liquid/solid (n=8) or mixed viscous/solid (n=8) nutrient (1350 kJ) test meals, and a total of 208 motility measurements were performed. No effect of meal type on antral motility parameters was observed. Antral contraction frequency was 3.0 ± 0.2 min−1 (mean ± SD, n=164), propagation speed was 1.6 ± 0.2 mm s−1 (n=164) and the percentage occlusion was 58 ± 14% (n=76). Overall, 21% of measurements did not provide useful antral motility data, because, in the supine position, the antrum was not filled by the test meal. Simple methods to overcome this and reduce scanning time to a minimum are proposed. The results show that the noninvasive magnetic resonance imaging evaluation of antral motility is accurate and reproducible and has potential to become a standard tool for such investigations.

Effect of a novel 5-HT3 receptor agonist MKC-733 on upper gastrointestinal motility in humans.

Background : Although 5‐HT3 antagonists have been used to treat chemotherapy‐induced emesis and diarrhoea‐predominant irritable bowel syndrome, the effects of 5‐HT3 agonists in humans are unknown.

Echo-planar magnetic resonance imaging of Gaviscon alginate rafts in-vivo

Liquid Gaviscon and Gaviscon Advance are established reflux suppressant formulations. This study describes the use of echo‐planar magnetic resonance imaging (EPI) to visualise non‐invasively intragastric alginate rafts of Liquid Gaviscon and Gaviscon Advance in healthy subjects. Secondly, the feasibility of using relaxation rate (T2−1) measurements to monitor changes in the physicochemical properties of the rafts in‐vivo is evaluated. Six subjects ingested 500 mL of a liquid meal and received a single dose of 20 mL Liquid Gaviscon or 10 mL Gaviscon Advance on 2 separate visits each and were imaged every 15 min. An alginate raft was observed in the stomach for all subjects and both treatments. The raft was observed to consist of a few large fragments on the majority of the scans for both products. At t = 60 min a raft was still present in all cases. Three‐dimensional volume reconstructions showed, for the first time, the spatial distribution of the rafts within the gastric lumen. The T2−1 data showed potential for assessment of dynamic changes in the physicochemical properties of the alginate rafts in‐vivo. We conclude that EPI shows great potential in assessing alginate rafts formation in‐vivo.