Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7-15.5)). Conclusions: In patients with reflux disease, the GABA B agonist baclofen significantly inhibits gastrooesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA B agonists may be useful as therapeutic agents for the management of reflux disease.

Protein-rich supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69-80 yr) compared with eight young male controls (18-34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control (P = 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2%; P = 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls (P = 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min; P = 0.007). Appetite decreased in young, while it increased in older (P < 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men.

Background and aims: Radiofrequency energy (RFe) treatment to the lower oesophageal sphincter (LOS) and gastric cardia is a new luminally delivered therapy proposed as an alternative treatment for gastro-oesophageal reflux disease (GORD). However, it is unclear how RFe achieves its antireflux effect. This study investigated the effects of RFe on mechanisms of spontaneous reflux in patients with GORD. Methods: Twenty patients with GORD underwent endoscopy, symptom evaluation, and combined postprandial oesophageal manometry and pH monitoring before and six months after RFe, and 24 hour ambulatory pH monitoring before and at six and 12 months after treatment. Results: RFe reduced the rate of postprandial transient LOS relaxations from 6.8 (5.7-8.1) (median (interquartile range) per hour to 5.2 (4.2-5.8) per hour (p<0.01), and increased mean basal LOS pressure from 5.2 (SEM 0.3) mm Hg to 8.0 (SEM 0.4) mm Hg (p<0.01). The number of reflux events was reduced from 10 (2-15.3)/3 hours to 5 (3.5-8.5)/3 hours (p<0.05) and there was an associated significant reduction in acid exposure time from 5.4% (0.4-14.7) to 3.9% (0.4-6.6) (p<0.05). RFe significantly reduced ambulatory oesophageal acid exposure from 10.6% (7.8-13.0) to 6.8% (3.1-9.1) (p<0.01) at six months and 6.3% (4.7-10.9) (p<0.05) at 12 months. All patients required acid suppressant medication for symptom control before RFe. Six months after treatment, 15 patients (75%) were in symptomatic remission and 13 (65%) at 12 months. Conclusions: RFe has significant effects on LOS function that are associated with improvement in the antireflux barrier. Uncontrolled clinical data also suggest a beneficial effect in the control of reflux symptoms in these patients.

The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 mg) or saline (230 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq 99m Tc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia.Therapies specifically targeting postprandial glycemia are important in the management of type 2 diabetes, especially in patients with relatively good overall glycemic control (HbA 1c #7.5%; 58 mmol/mol) (1). The rate of gastric emptying is an established determinant of postprandial blood glucose (2), a principle illustrated by "short-acting" glucagonlike peptide 1 (GLP-1) receptor agonists, such as exenatide, where the capacity to slow gastric emptying predominates over the insulinotropic effect in the postprandial setting (3).Small intestinal glucose absorption, predominantly via sodium-glucose cotransporter 1 and GLUT2 transporters, is limited to ;0.5 g/min per 30 cm (2). Interventions that increase the exposure of luminal glucose to the mucosal surface can therefore augment glucose absorption. We previously reported that the anticholinergic agent hyoscine delays the absorption of intraduodenally infused glucose in humans by decreasing small intestinal flow (4), indicating PHARMACOLOGY AND THERAPEUTICSthat modulation of small intestinal motor function can impact substantially on postprandial glycemia. Exogenous GLP-1 has been reported to inhibit both fasting and postprandial duodenal motility in humans (5,6), but its impact on the flow of chyme and on small intestinal transit and glucose absorption have not previously been explored. We therefore examined the effects of the short-acting form of exenatide on small intestinal motor function and glucose absorption in response to an intraduodenal glucose infusion in both healthy subjects and patients with type 2 diabetes. RESEARCH DESIGN AND METHODS SubjectsWe studied 10 healthy subjects and 10 patients with type 2 diabetes managed by diet alone, after obtaining written informed consent (Table 1). None ...