Kelly Feuerhak

Increased Nutrient Sensitivity and Plasma Concentrations of Enteral Hormones During Duodenal Nutrient Infusion in Functional Dyspepsia

OBJECTIVES:Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in patients with functional dyspepsia vs. healthy controls.METHODS:Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 min each, with a 120-min washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagon-like peptide 1 (GLP1), and peptide YY were measured during infusions.RESULTS:Moderate or more severe symptoms during lipid (4 controls vs. 14 patients) and dextrose (1 control vs. 12 patients) infusions were more prevalent in patients than controls (P≤0.01), associated with higher dyspepsia symptom score (P=0.01), worse QOL (P=0.01), and greater plasma hormone concentrations (e.g., GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively.CONCLUSIONS:Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia.

Reproducibility of high-definition (3D) manometry and its agreement with high-resolution (2D) manometry in women with fecal incontinence.

While widely used in clinical practice, the reproducibility of high‐definition anorectal manometry (HD‐ARM) remains unclear. We evaluated the intra‐individual reproducibility of HD‐ARM and compared pressures measured with HD‐ARM and high‐resolution anorectal manometry (HR‐ARM).

Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system.

Pressure drift (PD), resulting from differences between room and body temperature, reduces the accuracy of pressure measurements with the Manoscan high resolution manometry (HRM) system. Our aims were to assess PD during anorectal HRM.

A novel technique for bedside anorectal manometry in humans

Currently, anorectal manometry (ARM), which is used to diagnose defecatory disorders and identify anal weakness in fecal incontinence (FI) is generally conducted in specialized laboratories. Our aims were to compare anorectal functions measured with high‐resolution manometry (HRM) and a novel portable manometry device.

A pharmacological challenge predicts reversible rectal sensorimotor dysfunctions in women with fecal incontinence

In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α2 agonist on these parameters.

Effects of Alfuzosin, an Alpha-1 Αdrenergic Antagonist on Anal Pressures and Bowel Habits, in Women With and Without Defecatory Disorders

BACKGROUND & AIMS Some patients with defecatory disorders (DD) have high anal pressures that may impede rectal evacuation. Alpha‐1 adrenoreceptors mediate as much as 50% of anal resting pressure in humans. We performed a randomized, placebo‐controlled study of the effects of alfuzosin, an alpha1‐adrenergic receptor antagonist, on anal pressures alone in healthy women and also on bowel symptoms in women with DD. METHODS In a double‐blind study performed from March 2013 through March 2017, anal pressures were evaluated before and after 36 women with DD (constipation for at least 1 year) and 36 healthy women (controls) were randomly assigned (1:1) to groups given oral alfuzosin (2.5 mg immediate release) or placebo. Thereafter, patients were randomly assigned (1:1) to groups given oral alfuzosin (10 mg extended release) or placebo each day for 2 weeks. Participants kept daily diaries of bowel symptoms for 2 weeks before (baseline) and during administration of the test articles (treatment). Weekly questionnaires recorded the overall severity of constipation symptoms, bloating, abdominal pain, nausea, and vomiting; overall satisfaction with treatment of constipation was evaluated at weeks 2 and 4. The primary endpoint was the change in the number of spontaneous (SBMs) and complete SBMs (CSBMs) between the treatment and baseline periods. We evaluated relationships between stool form, passage, and complete evacuation. RESULTS Alfuzosin reduced anal resting pressure by 32 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo (P = .0001) and anal pressure during evacuation by 26 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo, (P = .03). However, alfuzosin did not significantly increase the rectoanal gradient, SBMs or CSBMs compared with placebo. Both formulations of alfuzosin were well tolerated. Hard stools and the ease of passage during defecation accounted for 72% and 76% of the variance in the satisfaction after defecation, respectively, during baseline and treatment periods. CONCLUSIONS In a randomized trial, alfuzosin reduced anal pressure at rest and during simulated evacuation in healthy and constipated women, compared with placebo, but did not improve bowel symptoms in constipated women. This could be because the drug does not improve stool form or dyssynergia, which also contribute to DD. ClinicalTrials.gov number, NCT 01834729.

466 A Novel Portable Device to Measure Anorectal Pressures: Comparison With High Resolution Manometry

Abnormalities in rectal compliance have been identified in irritable bowel syndrome (IBS), wherein patients exhibit decreased rectal compliance in response to experimental distention (Kwan CL, et al. Neurogastroenterol Motil 2004; Shroff S, et al. DDW 2012). However, these differences in rectal physiology are not uniformly present in all IBS subjects. We sought to examine whether psychiatric comorbidity (e.g., depression, anxiety) in IBS has mechanistic relevance to rectal compliance. We hypothesized that dysregulation of autonomic tone inherent in mood disorders leads to decreased rectal compliance in IBS patients. Methods: 38 female subjects (43.6 ±11.1 yrs; 22 Rome III IBS/16 healthy controls) were recruited. Measures of mood (Beck Depression and Anxiety Inventories, [BDI, BAI]) and somatization (Patient Health Questionnaire [PHQ-15]) were collected. Both groups underwent 4 series of 6 pseudo-randomized, barostat-controlled rectal distentions using either high pressure (HPD, 50 mmHg) or low pressure (LPD, 25 mmHg) delivery. Dynamic rectal compliances (ΔV/ΔP) were derived from the ascending phase of the distention. Multivariate linear regression was employed to determine whether psychiatric comorbidity independently influenced rectal compliance. Results: Dynamic rectal compliance was significantly lower in IBS vs. controls for both LPD (8.1±1.8 vs. 9.4±1.6 ml/mmHg; p=0.03) and HPD (6.0±1.1 vs. 7.0±1.1 ml/mmHg; p =0.01). High ratings in anxiety (BAI≥16), depression (BDI≥14) and somatization (PHQ-15≥15) were identified in 31.8%, 40.9%, and 50.0% of IBS subjects, respectively. In high anxiety subjects, rectal compliance was significantly diminished with HPD (5.6±0.8 vs. 6.7±1.1 ml/mmHg; p =0.008), and trended lower during LPD (7.9±1.5 vs. 8.8±1.8 ml/ mmHg, P=0.18). High depression scores were also associated with decreased rectal compliance with HPD (5.6±1.0 vs. 6.8±1.2, p=0.02) and trended toward lower compliance during LPD (8.1±1.5 vs. 8.8±1.8 ml/mmHg, P=0.2). In contrast, degree of somatization did not influence rectal compliance with either distention stimulus (P.0.20 for each). Multivariate analyses suggested the effects of anxiety on rectal compliance were independent of IBS during HPD (B=-0.04, p=0.06), but not LPD (B=-0.008, p=0.8). Depression and somatization had no effect on rectal compliance independent of IBS at either pressure level (p .0.15 for each).Conclusions: Decreased dynamic rectal compliance is observed in IBS with both low pressure and high pressure rectal distensions. Mood symptoms common to IBS also are associated with diminished rectal compliance, particularly withmore noxious stimuli. Anxiety appears to influence rectal compliance independent of the functional GI diagnosis itself, an effect potentially mediated by sympathetic autonomic regulation of intestinal motor function.