Review article: metoclopramide and tardive dyskinesia.

Background: Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA issued a black box warning regarding long-term or high-dose use of this medication because of the risk of developing tardive dyskinesia.

Aims: To review the mechanism of action and pharmacokinetic properties of metoclopramide, the risk of metoclopramide-induced tardive dyskinesia, potential mechanisms that may alter and to summarize the clinical context for appropriate use of the drug.

A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.

Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans. Genes controlling adrenergic and serotonergic mechanisms (ADRA2A, GNB3, and SLC6A4) affect gastric emptying (GE), volume (GV), and satiation. Fat mass and obesity-associated gene (FTO) is linked with satiety.

Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers.

Background: The mechanism of action of bisacodyl in the unprepared human colon remains unclear.

Aim: To evaluate the effect of oral bisacodyl on the overall and regional colonic transit in humans.

Methods: In a double-blind, randomized, placebo-controlled study of 25 healthy participants, effects of oral bisacodyl (5 mg p.

Smoking, drinking and incident tuberculosis in rural India: population-based case-control study.

Background: To investigate the extent to which smoking and/or drinking can increase the incidence of pulmonary tuberculosis (TB), a population-based case-control study was conducted in rural south India.

Methods: A total of 1839 males and 870 females treated in 2000-03 by state TB clinics were interviewed at home in 2004-05 about their education, smoking and drinking habits before disease onset. As controls, 2134 men and 2119 women without TB were randomly chosen from case villages and interviewed.

Breastfeeding and breast cancer risk in India: a multicenter case-control study.

Breast cancer incidence is low in India compared with high-income countries, but it has increased in recent decades, particularly among urban women. The reasons for this pattern are not known although they are likely related to reproductive and lifestyle factors. Here, we report the results of a large case-control study on the association between breastfeeding and breast cancer risk.

Peripheral mechanisms in the control of appetite and related experimental therapies in obesity.

The function of the stomach and the gut hormonal responses to food ingestion constitute highly integrated homeostatic responses that maintain euglycemia and normal digestion. This intrinsic feedback involves vagal and hormonal mechanisms. Important signals such as GLP-1 and PYY that arise peripherally induce satiation and also delay gastric emptying or increase insulin secretion.

Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or 7alphaC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry.

Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7alpha-hydroxy-4-cholesten-3-one (7alphaHCO or 7alphaC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the (75)SeHCAT retention test. Our aim was to develop a serum 7alphaC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C).

Selected interventions in nuclear medicine: gastrointestinal motor functions.

The measurement of gastrointestinal functions by the use of scintigraphy is established in clinical practice and research. The most commonly used test is the gastric-emptying test, which is acknowledged as the gold standard to measure gastric motility and is conducted according to a consensus statement from the national nuclear medicine and motility societies. Other techniques are somewhat more esoteric (eg, measurement of gastric accommodation with single-photon emission computed tomography) or the scintigraphic approach is not the acknowledged gold standard (eg, colonic transit, rectoanal angle, and emptying, esophageal transit).

Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids.

Breath tests (BT) using 13C-substrates have been proposed for the measurement of gastric emptying (GE). The mathematical analysis of the breath 13CO2 excretion that most accurately predicts GE t(1/2) from simultaneous scintigraphy is unresolved. To compare five mathematical methods to estimate GE t(1/2) by BT with t(1/2) from simultaneous scintigraphy.

Pharmacogenetics of low dose clonidine in irritable bowel syndrome.

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (gastrointestinal, GI) sensorimotor functions. We aimed to determine whether candidate ADR-SER genes affect GI responses to low dose clonidine (CLO) in humans. Forty healthy and 120 irritable bowel syndrome (IBS) participants received CLO, 0.

Serotonin in the gastrointestinal tract.

Purpose Of Review: To assess the role of serotonin and its control in the manifestations and treatment of lower functional gastrointestinal disorders.

Recent Findings: Recent literature has explored several novel concepts in the association of serotonin and symptoms, alterations in tissue levels of serotonin and its reuptake protein, aspects of the genetic determinants of serotonergic function (particularly 5-HTTLPR) and its relationship to gastrointestinal motor and sensory functions, and novel serotonergic agents used in therapy of lower functional gastrointestinal disorders. The most consistent findings are the increase in plasma 5-hydroxytryptamine (5-HT) in diarrheal diseases and reduction in constipation.

Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects.

Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 microg lubiprostone per day in a parallel-group, placebo-controlled trial.

Relationship between clinical features and gastric emptying disturbances in diabetes mellitus.

Background And Objectives: Gastric emptying (GE) may be delayed or rapid in diabetes mellitus. We sought to ascertain differences in risk factors or associated features (i.e.

Drug development and IBS drugs: experience from the past, current challenges, and proposal for the future.

Over the past decade, the failed promise of animal models and preclinical pharmacology, and a changing landscape in the regulatory perspectives have impacted the development of drugs for the treatment of irritable bowel syndrome (IBS). In general, animal models have failed to predict efficacy of medications developed for visceral pain. On the contrary, extensive experience with different endpoints in large, randomized, and controlled trials has generated some data on psychometric validation and unprecedented information about responsiveness of binary or global endpoints.

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.

Association of the dusp6 (mkp3) gene with mouse brain weight and forebrain structure.

PYST1/MKP3 is a negative feedback modulator of fibroblast growth factor 8 (Fgf8) signaling in the mammalian isthmic organizer of the brain, which affects the development of the midbrain and the hindbrain. The Dusp6 (Mkp3) gene is also highly expressed in the mouse embryonic forebrain. However, its role in forebrain development and function remains largely unknown.

Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials.

Background & Aims: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT(3)) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS).

Methods: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT(3) antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently.

Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome.

Background & Aims: In experimental animal models of irritable bowel syndrome (IBS) and human studies, peripheral kappa opioid agonists have been shown to decrease sensation to colonic distention. The aim of this study was to compare the effects of the kappa opioid agonist, asimadoline, and placebo on episodes of abdominal pain in patients with IBS.

Methods: After a 2-week run-in period, 100 patients with IBS were randomized (3:2 ratio) to receive asimadoline, up to 1 mg 4 times daily, or placebo for 4 weeks in a double-blind study.

Appetite and obesity: a gastroenterologist's perspective.

This review focuses on the gastrointestinal tract's control of appetite and interventions directed to the gut that are effective in the treatment of obesity. It examines the evidence linking gut hormones to the control of both appetite and upper gastrointestinal motility, the evidence that stomach function is altered and contributes to satiation in obesity and outlines the principles of therapy for obesity which are directed at the gastrointestinal tract. These therapies impair fat absorption or alter stomach functions through pharmacological, device, endoscopic, or surgical approaches.

Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study.

Background: In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying.

Aim: To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms.