Dataset Information

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

ABSTRACT: BACKGROUND: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 ?2 agonist on these parameters. METHODS:Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated. RESULTS:At baseline, compared to controls, rectal capacity was lower (P = .03) while the mean pressure (P = .02) and elastance (P = .01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ? .02) the heart rate in controls and FI and reduced (P = .03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P = .04) and reduced rectal capacity (P = .03) in FI. The effects of atropine and clonidine on compliance (r = .44, P = .003), capacity (r = .34, P = .02), pressures during sinusoidal oscillation (r = .3, P = .057), pressure (r = .6, P < .0001), and volume sensory thresholds (r = .48, P = .003) were correlated. CONCLUSIONS:The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.

SUBMITTER: Sharma M

PROVIDER: S-EPMC6160337 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Sharma M M Feuerhak K K Zinsmeister A R AR Bharucha A E AE

Neurogastroenterology and motility 20180601 10

<h4>Background</h4>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 α<sub>2</sub> agonist on these parameters.<h4>Methods</h4>Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. ...[more]

PMID: 29856103

Similar Datasets

Project description:Introduction and hypothesisTo evaluate change in fecal incontinence symptom severity after 8 weeks of darifenacin therapy in patients with double incontinence-urgency urinary incontinence (UUI) and fecal incontinence. Important secondary outcomes included fecal incontinence symptom distress and impact on quality of life, fecal incontinence episodes, global impression of improvement and overactive bladder symptom distress and impact.MethodsProspective open-label cohort study of women presenting primarily with UUI, diagnosed with double incontinence and electing antimuscarinic therapy for UUI. Women ≥ 18 years with moderate or greater bothersome UUI and fecal incontinence of liquid/solid stool with St. Marks (Vaizey) score ≥ 12 were included. Subjects were treated with darifenacin 15 mg daily for 8 weeks. The primary outcome was change in fecal incontinence symptom severity using the St. Marks (Vaizey) score after 8 weeks. Sample size was based on the minimally important difference of the St. Marks, -5, and standard deviation, ± 8.5; 30 subjects provided 80% power and type I error of 0.05, including a 15% attrition rate.ResultsThirty-two women were consented with mean baseline St. Marks (Vaizey) score of 18.0 ± 3.0. Mean age was 66.5 ± 10.3 years. Twenty-eight subjects (29/32, 87.5%) completed assessments. St. Marks (Vaizey) score significantly improved from 18.0 to 11.0 [mean difference - 7.0, 95% confidence interval (CI): -8.7, -5.3], and 19 subjects (19/32,67.9%) met the minimally important difference. Statistically significant improvements were also noted in fecal incontinence frequency, quality of life, and overactive bladder symptom bother and quality of life (all p < 0.01).ConclusionsDarifenacin can be considered a highly effective early intervention in women suffering from double incontinence.Clinical trial registrationBladder Antimuscarinic Medication and Accidental Bowel Leakage (BAMA), https://clinicaltrials.gov/ct2/show/NCT03543566 , NCT03543566.

Project description:PurposeUrinary incontinence and fecal incontinence are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may have a role in continence. Identification of genetic variants associated with urinary incontinence and fecal incontinence could result in a better understanding of etiologic pathways, and new interventions and treatments.Materials and methodsWe previously generated genome-wide single nucleotide polymorphism data from Nurses' Health Studies participants. The participants provided longitudinal urinary incontinence and fecal incontinence information via questionnaires. Cases of urinary incontinence (6,120) had at least weekly urinary incontinence reported on a majority of questionnaires (3 or 4 across 12 to 16 years) while controls (4,811) consistently had little to no urinary incontinence reported. We classified cases of urinary incontinence in women into stress (1,809), urgency (1,942) and mixed (2,036) subtypes. Cases of fecal incontinence (4,247) had at least monthly fecal incontinence reported on a majority of questionnaires while controls (11,634) consistently had no fecal incontinence reported. We performed a genome-wide association study for each incontinence outcome.ResultsWe identified 8 single nucleotide polymorphisms significantly associated (p <5×10-8) with urinary incontinence located in 2 loci, chromosomes 8q23.3 and 1p32.2. There were no genome-wide significant findings for the urinary incontinence subtype analyses. However, the significant associations for overall urinary incontinence were stronger for the urgency and mixed subtypes than for stress. While no single nucleotide polymorphism reached genome-wide significance for fecal incontinence, 4 single nucleotide polymorphisms had p <10-6.ConclusionsFew studies have collected genetic data and detailed urinary incontinence and fecal incontinence information. This genome-wide association study provides initial evidence of genetic associations for urinary incontinence and merits further research to replicate our findings and identify additional risk variants.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets