Effect of atropine on gastro-oesophageal reflux and transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease

Background—Atropine reduces the rate of reflux episodes in normal subjects by inhibition of transient lower oesophageal sphincter (LOS) relaxations. The aim of this study was to investigate the effect of atropine on the rate and mechanisms of reflux in patients with reflux disease.Methods—Oesophageal motility and pH were recorded for one hour after a meal in 15 patients with reflux disease. On separate days, atropine (15 μg/kg bolus intravenously, 4 μg/kg/h infusion) or saline were given and maintained for the recording period.Results—Atropine significantly reduced basal LOS pressure from 7.1 (2.2) to 2.9 (1.3) mm Hg (mean (SEM)). Atropine also reduced the rate of reflux episodes from 5.0 (2.0–8.75) to 1.0 (0–6.25) per hour (median (interquartile range)) largely because of a decrease in the rate of transient LOS relaxations from 2.0 (0–4.75) to 0 (0–0) per hour and abolition of reflux during swallow induced LOS relaxation. There was no change in the rate of reflux episodes because of absent basal LOS pressure.Conclusions—Atropine inhibits reflux in patients with reflux disease largely by inhibition of transient LOS relaxations and swallow induced LOS relaxation. These findings suggest that pharmacological control of reflux through control of transient LOS relaxations is possible in patients with reflux disease.</jats:p

Is esophageal dysphagia in the extreme elderly (>/-80 years) different to dysphagia younger adults? A clinical motility service audit

The definitive version may be found at www.wiley.comDysphagia in elderly patients has major effects on nutrition and quality of life. Although aging itself is associated with changes in esophageal motility, the impact of this on symptoms such as dysphagia is unclear. Data in the extreme elderly are also limited. Symptoms and manometric diagnoses from 23 consecutive older patients (older dysphagia [OD]) >or=80 reporting esophageal dysphagia (12 female, mean age 83 (range 80-93) were compared with those from 23 gender matched younger patients (young dysphagia [YD]) also with dysphagia (mean age 35, range [17-46]). More older patients reported dysphagia as their primary symptom (OD 22/23 vs YD 14/23, P = 0.005). Overall, dysphagia was most common for solids only (OD 16/23 vs YD 15/23) and rare for liquids only (OD 1/23 vs YD 3/23). Dysphagia for both liquids and solids was more frequent in older patients (OD 6/23 vs YD 1/23, P < 0.05). Fewer older patients reported heartburn (OD 3/23 vs YD 14/23, P = 0.001). Manometric diagnoses were generally similar between OD and YD patients with the most common diagnoses being 'nonspecific esophageal motility disorder' (nine each) and 'ineffective peristalsis' (OD = 6, YD = 7). There was a trend for diagnoses related to lower esophageal sphincter failure to be more frequent in younger subjects (OD 1 vs YD 7, P = 0.053). Despite differences in symptom patterns, broad manometric diagnoses in the extreme elderly with dysphagia are similar to younger dysphagia patients. Further studies are required to determine whether this relates to insensitivity in recording or reporting of esophageal manometry (or perceptual differences associated with aging).J. M. Andrews, R. J. Fraser, R. Heddle, G. Hebbard and H. Checkli

A comparison of micromanometric and standard manometric techniques for recording of oesophageal motility

Perfused micromanometric assemblies with an outer diameter of 2 mm or less have been developed for use in premature infants and small laboratory animals. Such assemblies offer advantages with regard to subject comfort and low perfusion rates that make them attractive for use in adults. The aim of this study was to investigate the recording fidelity of micromanometric assemblies in the measurement of oesophageal peristalsis in adults. Two micromanometric assemblies with an outer diameter of 1.8-2.0 mm and a length suitable for use in adults (165 cm), and containing micromanometric lumina of 0.28-0.35 mm i.d. and a standard lumen of 0.6-0.75 mm i.d. were evaluated. Each assembly was tested by measurement of pressure rise rate in response to sudden occlusion, and in vivo during oesophageal peristalsis by simultaneous comparison with an intraluminal strain gauge. At perfusion rates of 0.01-0.15 mL min-1 microlumina achieved pressure rise rates of 21-430 mmHg sec-1 that were comparable to 37-390 mmHg sec-1 for the standard lumina perfused at 0.15-0.6 mL min-1. During oesophageal peristalsis, micromanometric lumina recorded the occurrence and timing of all pressure waves accurately when compared with standard lumina and the microtransducer. However, microlumina under-recorded pressure wave amplitude to varying degrees dependent upon perfusion rate although the performance of microlumina could be improved to that of the standard lumen by shortening their length to 70 cm. Micromanometric assemblies are suitable for recording oesophageal peristalsis in adults although there is some impairment of absolute manometric fidelity. Fidelity can be improved by minimizing total assembly length

How does age affect manometric diagnosis in patients with dysphagia?

Abstract #180Dysphagia is commonly reported by older patients and is a major cause of nutritional inadequacy. It often occurs in the absence of structural lesions, implying a high frequency of motility disorders with advancing age. The nature of these motility changes and diagnostic patterns associated with dysphagia in older people, however, are not well defined. Methods: We reviewed the manometric findings for all patients over 80 years reporting dysphagia referred to our motility service between December 2003 and July 2005. Each older patient was gender matched to the youngest available patient with dysphagia studied during the same interval. All studies were performed using a 16 channel pneumohydraulic manometry system. Oesophageal pressures were displayed using a colour plot against length and time. Motility was classified as normal, ineffective peristalsis, hypotensive lower oesophageal sphincter, spastic, achalasia or non-specific motor abnormality. Differences between groups we reassessed with contingency tables using Fishers exact test. Results: Older patients (N =23, 12 female) had a mean age of 83 years compared to 35 years in the younger group. A greater proportion of older patients gave dysphagia as their primary symptom (22 vs 14 patients, p =0.005). Fewer older patients described heartburn as a relevant symptom (3 vs 14 patients, p =0.001). In both groups dysphagia was reported commonly for solids only (16 vs 15 patients) rarely for liquids only (1 vs 3patients) but dysphagia for both was more common in older patients (6 vs1 patient, p <0.05). Manometric diagnoses were similar for both groups:9 patients in each group had non specific oesophageal motility disorder, 6older and 7 younger patients failure of or ineffective peristalsis, and 2patients in each group achalasia. High amplitude contractions, spasm and synchronous contractions were seen in 3 older and 2 younger subjects. Three older and 4 younger patients had normal motility. Reflux related dysmotility was seen in 7 younger but no older patients. Conclusion: Although older patients report more prominent dysphagia and less heartburn than their younger counterparts, neither age nor symptomatology predict manometric diagnosis. The observation that older patients more commonly have dysphagia to both solids and liquids has important nutritional implications. The large proportion diagnosed with ‘non-specific’ oesophageal dysmotility requires more detailed manometric analysis to define localised motility differences with aging.RE Mountifield, JM Andrews, RJ Fraser, R Heddle, GS Hebbard, H Checkli

Effects of intraduodenal hydroxycitrate on glucose absorption, incretin release, and glycemia in response to intraduodenal glucose infusion in health and type 2 diabetes: a randomised controlled trial

Abstract not available.Sony S. Thazhath, Tongzhi Wu, Michelle J. Bound, Helen L. Checklin, Scott Standfield, Karen L. Jones, Michael Horowitz, Christopher K. Rayne

Effect of duodenal glucose load on blood pressure in type 2 diabetes

Abstract not available.Chinmay S. Marathe, Michael Horowitz, Laurence G. Trahair, Michelle Bound, Helen Checklin, Kylie Lange, Christopher K. Rayner, Karen L. Jone

Effects of sitagliptin on glycemia, incretin hormones, and antropyloroduodenal motility in response to intraduodenal glucose infusion in healthy lean and obese humans and patients with type 2 diabetes treated with or without metformin

The impact of variations in gastric emptying, which influence the magnitude of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) secretion, on glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60 g over 120 min [i.e., 2 kcal/min], a rate that predominantly stimulates GIP but not GLP-1) after sitagliptin versus control in 12 healthy lean, 12 obese, and 12 type 2 diabetic subjects taking metformin 850 mg b.i.d. versus placebo. As expected, sitagliptin augmented plasma-intact GIP substantially and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese but not type 2 diabetic subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired; 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying >2 kcal/min; and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.Tongzhi Wu, Jing Ma, Michelle J. Bound, Helen Checklin, Carolyn F. Deacon, Karen L. Jones, Michael Horowitz and Christopher K. Rayne

Changes in meal composition and duration affect postprandial endothelial function in healthy humans

Background: Endothelial function, measured by flow-mediated dilatation (FMD), predicts cardiovascular events, and is impaired postprandially. Objective: To evaluate the effects of changes in composition or duration of ingestion of a meal, which slows gastric emptying and/or small intestinal nutrient exposure, on postprandial endothelial function. Design: 12 healthy subjects (6 male, 6 female; 33 ± 6 years) were each studied on 3 occasions, in a randomised, crossover design. After an overnight fast, subjects consumed a (13)C-octanoic acid labeled mashed potato meal ('meal 1'), or 'meal 1' mixed with 9 g guar ('meal 2') within 10 min, or 'meal 1' divided into 12 equal portions over 60 min ('meal 3'). Brachial artery FMD was measured every 30 min for 120 min. Blood glucose, serum insulin, and gastric emptying (breath test), were evaluated for 240 min. Data are means ± SEM. Results: Compared to 'meal 1', 'meal 2' was associated with slower gastric emptying (half-emptying time 285 ± 27 vs. 208 ± 15 min, P < 0.05), lower postprandial blood glucose and insulin (P < 0.001 for both), and a delayed, but more sustained, suppression of FMD (P < 0.001). After 'meal 3', both glycemic increment and reduction in FMD were less than after 'meal 2' (P < 0.05 for both). The decrement in FMD was directly related to the increment in blood glucose (r = 0.46, P = 0.02). Conclusions: In health, postprandial FMD is influenced by perturbation of gastric emptying and the duration of meal consumption, which also impact on glycemia.Sony S. Thazhath, Tongzhi Wu, Michelle J. Bound, Helen L. Checklin, Karen L. Jones, Scott Willoughby, Michael Horowitz, and Christopher K. Rayne

Differentiating the effects of whey protein and guar gum preloads on postprandial glycemia in type 2 diabetes

Abstract not available.Linda E. Watson, Liza K. Phillips, Tongzhi Wu, Michelle J. Bound, Helen Checklin, Jacqueline Grivell, Karen L. Jones, Michael Horowitz, Christopher K. Rayne