Duane Burton

A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.

Aim : To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea.

A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.

Abstract  Aim:  To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome (IBS) and significant bloating.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial.

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.

BACKGROUND & AIMS Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). METHODS We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. RESULTS Subjects on the GCD had more bowel movements per day (P = .04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). CONCLUSIONS Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.govNCT01094041.

Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans

BACKGROUND Prucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. AIMS To evaluate the effects of prucalopride on gastrointestinal and colonic transit. METHODS A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0.5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours. RESULTS There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0.12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. CONCLUSION Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation.

Prospective Study of Motor, Sensory, Psychologic, and Autonomic Functions in Patients With Irritable Bowel Syndrome

BACKGROUND & AIMS The aim of this study was to assess pathophysiology in irritable bowel syndrome (IBS). METHODS A total of 122 IBS patients (3 male) and 41 healthy females underwent the following: questionnaires (symptoms, psychology), autonomic function, gut transit, gastric volumes, satiation, rectal compliance, and sensation (thresholds and pain ratings) testing. Proportions of patients with abnormal (<10th and >90th percentiles) motor or sensory functions according to bowel symptoms (constipation [C], diarrhea [D], mixed [M),) pain/bloat, and number of primary symptoms were estimated. RESULTS IBS subgroups (C, D, M) were similar in age, gastric and small-bowel transit, satiation, gastric volumes, rectal compliance, sensory thresholds, and pain ratings. IBS was associated with body mass index, somatic symptoms, and anxiety and depression scores. Significant associations were observed with colonic transit (IBS-C [P = .078] and IBS-D [P < .05] at 24 h; IBS-D [P < .01] and IBS-M [P = .056] at 48 h): 32% of IBS patients had abnormal colonic transit: 20.5% at 24 hours and 11.5% at 48 hours. Overall, 20.5% of IBS patients had increased sensation to distensions: hypersensitivity (<10th percentile thresholds) in 7.6%, and hyperalgesia (pain sensation ratings to distension >90th percentile for ratings in health) in 13%. Conversely, 16.5% of IBS patients had reduced rectal sensation. Pain greater than 6 times per year and bloating were not associated significantly with motor, satiation, or sensory functions. Endorsing 1 to 2 or 3 to 4 primary IBS symptoms were associated with abnormal transit and sensation in IBS. CONCLUSIONS In tertiary referral (predominantly female) patients with IBS, colonic transit (32%) is the most prevalent physiologic abnormality; 21% had increased and 17% had decreased rectal pain sensations. Comprehensive physiologic assessment may help optimize management in IBS.

Performance characteristics of scintigraphic transit measurements for studies of experimental therapies.

Background : The intra‐ and inter‐individual reproducibility of gastrointestinal and colonic transit tests require full characterization.

SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication

Background: Impaired gastric accommodation may lead to dyspeptic symptoms. A non-invasive method using single photon emission computed tomography (SPECT) has been developed to measure gastric volumes. Aims and methods: Our aims were: to assess the accuracy of SPECT with three dimensional image analysis to measure balloon volumes in vitro; to compare gastric barostat balloon volumes measured post-meal and post-distension with total gastric volumes measured simultaneously with SPECT; to present normal gastric volume data for healthy adults; and to compare SPECT data in health with symptomatic post-fundoplication patients. Results: In vitro balloon volumes measured by SPECT were highly accurate (R2=0.99). When measured simultaneously by gastric barostat and SPECT, postprandial/fasting volume ratios (2.2 (0.12) (mean (SEM)) v 2.3 (0.15), respectively; p=0.6) and post-distension volume ratios (1.4 (0.1) v1.3 (0.1); p=0.2) were highly comparable. In females, postprandial gastric volumes (675 (14) v 744 (20) ml for males; p=0.004) and changes in gastric volumes (464 (14) ml v 521 (20) ml for males; p=0.01) measured by SPECT were significantly lower than in males. No effects of age or body mass index were noted. The postprandial/fasting gastric volume ratio by SPECT was lower in post-fundoplication patients (2.7 (0.2)) than in healthy controls (3.4 (0.1); p=0.003). Conclusions: SPECT provides a non-invasive estimate of the effect of a meal on total gastric volume that is comparable to changes in balloon volume observed with the gastric barostat. The SPECT technique is promising for investigation of gastric volumes in health and disease and the effects of pharmacological agents.

Development of a test to measure gastric accommodation in humans

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of (99m)Tc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 +/- 11 (SE) ml and mean postprandial volume was 690 +/- 32 ml (P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.

Background The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood. Aims To compare gastric motor and sensory functions in Helicobacter pyloripositive or negative patients with non-ulcer dyspepsia. Patients Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls. Methods The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI). Results Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated toH pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent amongH pylori positive patients (4/5H pylori positive versus 4/12H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI. Conclusion Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.