Ramu, Shivabalan Kathavarayan

AbstractBackgroundThis study compared the effects of ondansetron and placebo in patients with diabetes mellitus and symptoms of dyspepsia (diabetic gastroenteropathy [DGE]).MethodsWe performed a randomized, double‐blinded, placebo‐controlled study of ondansetron tablets (8 mg) three times daily for 4 weeks in DGE patients. Symptoms were assessed with the Gastroparesis Cardinal Symptom Index daily diaries. Gastric emptying (GE) of solids (scintigraphy) and duodenal lipid infusions (300 kcal over 2 h) were each assessed twice, with placebo and ondansetron. Drug effects on GE, symptoms during the GE study and during lipid infusion, and daily symptoms were analyzed.Key ResultsOf 41 patients, 37 completed both GE studies and one completed 1; 31 completed both lipid infusions and four only placebo; and all 35 randomized patients completed 4 weeks of treatment. Compared to placebo, ondansetron reduced the severity of fullness (p = 0.02) and belching (p = 0.049) during lipid infusion but did not affect GE T1/2. Both ondansetron and placebo improved daily symptoms versus the baseline period (p < 0.05), but the differences were not significant. In the analysis of covariance of daily symptoms during the treatment period, the interaction term between treatment and the acute effect of ondansetron on symptoms during lipid challenge was significant (p = .024).Conclusions & InferencesOndansetron significantly reduced fullness during enteral lipid infusion in patients with DGE. Overall, ondansetron did not improve daily symptoms versus placebo. But patients in whom ondansetron improved symptoms during enteral lipid challenge were perhaps more likely to experience symptom relief during daily treatment.

AbstractBackground and AimsUp to 50% of patients with Parkinson disease have constipation (PD‐C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD‐C is unknown. We aimed to compare anorectal function of patients with PD‐C versus idiopathic chronic constipation (CC).MethodsAnorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high‐resolution anorectal manometry (HR‐ARM) in patients with PD‐C and control patients with CC, matched for age and sex.ResultsWe identified 97 patients with PD‐C and 173 control patients. Eighty‐six patients with PD‐C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD‐C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET.In the multivariate model comparing CC and PD‐C (AUROC = 0.76), PD‐C was associated with a lower anal squeeze increment (odds ratio [OR] for PD‐C, 0.93 [95% CI, 0.91–0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03–1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66–0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08–1.26]).ConclusionsCompared with CC, PD‐C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

AbstractBackground and objectivesChronic constipation (CC) may be caused by defecatory disorders (DDs) and associated with reduced rectal sensation. Among patients with type 1 diabetes (T1D) and CC (T1DCC patients), the prevalence of DDs and reduced rectal sensation is unknown. We sought to compare complications of T1D, anorectal dysfunction, and CC symptoms, among T1DCC patients with versus without a DD.MethodsAnorectal pressures at rest and during squeeze and evacuation, as well as rectal sensation and rectal balloon expulsion time (BET) were measured with high‐resolution anorectal manometry in 114 consecutive T1DCC patients.ResultsThirty‐seven patients (32%) had prolonged BET, suggestive of a DD. Complications of T1D included peripheral neuropathy (n = 67, 59%), retinopathy (n = 42, 37%), and nephropathy (n = 26, 23%). Among these complications, only retinopathy was associated with, that is, more prevalent in patients with normal (45%) than prolonged BET (19%). Compared with patients with normal BET, patients with prolonged BET had a lower rectal pressure (mean [SD], 32 [23] mm Hg vs. 23 [19] mm Hg,p = 0.03), greater anal pressure (91 [23] mm Hg vs. 68 [36] mm Hg,p < 0.001), and lower rectoanal gradient (−67 [30] mm Hg vs. −36 [32] mm Hg,p < 0.0001) during evacuation. Anal resting pressure and anal squeeze increment were below normal in 14 (13%) and 32 (29%) of patients and one or more rectal sensory thresholds were above normal in 34 (30%) patients; these abnormalities affected similar proportions in the normal and prolonged BET cohorts.ConclusionsAmong T1DCC patients, 37 (32%) had prolonged BET, which was associated with anorectal pressures indicative of a DD but was not associated with reduced rectal sensation, suggesting that DDs are more likely explained by abdomino‐anal dyscoordination than visceral disturbance.

AbstractBackgroundThe optimal methods for measuring and analyzing anal resting and squeeze pressure with high‐resolution manometry (HRM) are unclear.MethodsAnal resting and squeeze pressures were measured with HRM in 90 healthy women, 35 women with defecatory disorders (DD), and 85 with fecal incontinence (FI). Pressures were analyzed with Manoview™ software and a customized approach. Resting pressures measured for 20, 60, and 300 s were compared. During the squeeze period, (3 maneuvers, 20 s each), the squeeze increment, which was averaged over 5, 10, 15, and 20 s, and squeeze duration were evaluated.ResultsCompared to healthy women, the anal resting pressure, squeeze pressure increment, and squeeze duration were lower in FI (p ≤ 0.04) but not in DD. The 20, 60, and 300 s resting pressures were strongly correlated (concordance correlation coefficients = 0.96–0.99) in healthy and DD women. The 5 s squeeze increment was the greatest; 10, 15, and 20 s values were progressively lower (p < 0.001). The squeeze pressure increment and duration differed (p < 0.01) among the three maneuvers in healthy and DD women but not in FI women. The upper 95th percentile limit for squeeze duration was 19.5 s in controls, 19.9 s in DD, and 19.3 s in FI. Adjusted for age, resting pressure, and squeeze duration, a greater squeeze increment was associated with a lower risk of FI versus health (OR, 0.96; 95% CI, 0.94–0.97).ConclusionsThese findings suggest that anal resting and squeeze pressures can be accurately measured over 20 s. In most patients, one squeeze maneuver is probably sufficient.