Montri Gururatsakul

Small Bowel Homing T Cells Are Associated With Symptoms and Delayed Gastric Emptying in Functional Dyspepsia

OBJECTIVES:Immune activation may have an important pathogenic role in the irritable bowel syndrome (IBS). While little is known about immunologic function in functional dyspepsia (FD), we have observed an association between cytokine secretion by peripheral blood mononuclear cells (PBMCs) and symptoms in IBS. Upper gastrointestinal inflammatory diseases are characterized by enhanced small bowel homing α4-, β7-integrin, chemokine receptor 9 (CCR9) positive T lymphocytes. We hypothesized that increased cytokine release and elevated circulating small bowel homing T cells are linked to the severity of symptoms in patients with FD. Thus, we aimed to (i) compare cytokine release in FD and healthy controls (HCs), (ii) quantify “gut homing” T cells in FD compared with HC and patients with IBS, and (iii) correlate the findings to symptom severity and gastric emptying.METHODS:PBMC from 45 (Helicobacter pylori negative) patients with FD (Rome II) and 35 matched HC were isolated by density gradient centrifugation and cultured for 24 h. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) was measured by enzyme-linked immunosorbent assay. CD4+ α4β7+CCR9+ T cells were quantified by flow cytometry in FD, HC and 23 patients with IBS. Gastric emptying was measured by scintigraphy. Symptom severity was assessed utilizing the standardized Gastrointestinal Symptom Score.RESULTS:FD patients had significantly higher TNF-α (107.2±42.8 vs. 58.7±7.4 pg/ml), IL-1β (204.8±71.5 vs. 80.2±17.4 pg/ml), and IL-10 (218±63.3 vs. 110.9±18.5 pg/ml) levels compared with HC, and enhanced gut homing lymphocytes compared with HC or IBS. Cytokine release and CD4+α4β7+CCR9+ lymphocytes were correlated with the symptom intensity of pain, cramps, nausea, and vomiting. Delayed gastric emptying was significantly associated (r=0.78, P=0.021) with CD4+α4β7+CCR9+ lymphocytes and IL-1β, TNF-α, and IL-10 secretion.CONCLUSIONS:Cellular immune activation with increased small bowel homing T cells may be key factors in the clinical manifestations of H. pylori-negative FD.

The ageing gut: diminished symptom response to a standardized nutrient stimulus

Background  The prevalence of dyspepsia and the severity of reflux symptoms decreases with advancing age. We postulate that advancing age influences sensory function and this will be associated with a diminished symptom response to a standardized meal stimulus.Our aim was to assess the influence of age on visceral sensory function.

Association between clinical manifestations of complicated and uncomplicated peptic ulcer and visceral sensory dysfunction

Background and Aims:  Peptic ulcer disease (PUD) usually manifests as either dyspepsia or less commonly with complications such as bleeding. Patients with bleeding ulcers are often asymptomatic until the bleeding occurs. A lack of dyspeptic symptoms might be explained by impaired visceral sensory function. The aim of this study was to assess symptom profiles and compare visceral sensory thresholds in patients with bleeding peptic ulcer (BPU) and uncomplicated PUD.

Complicated and uncomplicated peptic ulcer disease: altered symptom response to a nutrient challenge linked to gastric motor dysfunction.

Background: Bleeding peptic ulcer (BPU) frequently occurs in the absence of preceding dyspeptic symptoms. We have observed that patients with BPU had a diminished symptom response to nutrient challenge test compared to uncomplicated peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in patients with uPUD than BPU because there are greater derangements in gastric motor function. Aim: To assess gastric emptying in patients with BPU, uPUD and healthy controls (HC). Methods: We studied 17 patients with BPU, 10 with uPUD, and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding solution, containing 5 MBq 99mTc-rhenium sulphide colloid, every 5 min up to a cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for the total, proximal and distal stomach. Results: Patients with uPUD had significantly higher gastric retention in the proximal and total stomach at 100 min than HC and BPU, while BPU had similar percent retention to HC. Patients with uPUD had significantly higher cumulative symptom response to the nutrient challenge than did HC and BPU, while BPU had similar symptom responses to HC. Conclusions: Patients with uPUD have significantly delayed gastric emptying compared to HC and BPU. Data suggest that in addition to alterations of visceral sensory function, altered gastric motor function occurs during a nutrient challenge in uPUD but not BPU. Gastric motor function may contribute to the manifestation of dyspeptic symptoms in PUD.

Influence of Simethicone Added to the Rinse Water during Colonoscopies on Polyp Detection Rates: Results of an Unintended Cohort Study

Background and Aims: Simethicone is a common antifoaming agent that is added to endoscopic rinse solutions, but data regarding its effect on polyp detection rates is lacking. In this study, we report the effect of discontinuation of this practice on polyp detection rates. Methods: Procedure data of 4,254 consecutive colonoscopies were used. Patients underwent standard bowel preparation with polyethyleneglycol (Glycoprep®). Colonoscopies were performed utilising Olympus EVIS EXERA III, CV-190 equipment, while quality data (withdraw times, polyp detection rates, quality of bowel preparation) was assessed utilising an endoscopy reporting system (Provation®). Following an educational event that highlighted that simethicone may form deposits in the channels of endoscopes, the practice to add simethicone (InfacolR, Nice Pak) to the auxiliary channel water pump was abandoned, but endoscopists were not notified about this change. After 5 days and performing 75 colonoscopies, the change of practice was identified and addition of simethicone recommenced. Results: The discontinuation of simethicone use reduced the polyp detection rate from 55% (95% CI 53–56) to 45% (95% CI 34–56, 1-sided, p = 0.028); the polyp detection rate returned to the pre-intervention levels of 55% (95% CI 52–58) upon resumption of normal practice. Conclusion: The addition of simethicone to the auxiliary water pump during colonoscopy results in a 10% increase in polyp detection rates.

S1318 STW5 Leads to Changes in Immunologic Response, as Assessed by Cytokine Secretion, in Healthy Controls, but Not Subjects With Irritable Bowel Syndrome (IBS)

STW5 Leads to Changes in Immunologic Response, as Assessed by Cytokine Secretion, in Healthy Controls, but Not Subjects With Irritable Bowel Syndrome (IBS) Jenny Persson, Gerald Holtmann, Amelia N. Pilichiewicz, Montri Gururatsakul, MingXian Yan, Edmund C. Khoo, Judith Gapasin, Charlotte Goess, Nora B. Zschau, Lee-Anne Faraguna, Birgit Adam, Tobias Liebregts, Richard H. Holloway, Jane M. Andrews