Lubiprostone: chronic constipation and irritable bowel syndrome with constipation.

Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. The FDA has approved lubiprostone for the treatment of chronic constipation in men and women and the treatment of women with irritable bowel syndrome with constipation (IBS-C). Lubiprostone specifically activates type-2-chloride channels on the apical membrane of epithelial cells.

Endoscopy of the esophagus in gastroesophageal reflux disease: are we losing sight of symptoms? Another perspective.

Gastroesophageal reflux disease (GERD) is an extremely common chronic disorder associated with impaired quality of life and huge economic burden. Recently, an International Consensus Group developed a global definition of GERD (The Montreal Definition): a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The traditional endoscopy-based classification of GERD patients into one of three groups - non-erosive reflux disease, erosive esophagitis, and Barrett's esophagus - is fraught with several limitations.

Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors?

Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS.

Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation.

Lubiprostone, a locally acting highly selective type-2 chloride channel activator, has been US FDA approved since January 2006 for the treatment of adults with chronic idiopathic constipation and FDA approved since April 2008 for the treatment of woman aged 18 years or older suffering from irritable bowel syndrome (IBS) with constipation. Through activation of the type-2 chloride channels located on the luminal side of intestinal epithelial cells, it promotes fluid secretion, increasing the liquid content of stool and accelerating small bowel as well as colonic transit. Lubiprostone has demonstrated efficacy with respect to increasing weekly spontaneous bowel movements and improving stool consistency, straining and constipation severity, both in short- and long-term studies.

Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials.

Objectives: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD.

Methods: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women >/=18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating.

Successful physical therapy for constipation related to puborectalis dyssynergia improves symptom severity and quality of life.

Purpose: This study evaluated symptom severity and quality of life in patients with puborectalis dyssynergia before and after physical therapy.

Methods: Twenty-two patients with puborectalis dyssynergia were prospectively enrolled into a multidisciplinary program for the treatment of pelvic floor and bowel disorders in this case series. All patients had functional constipation and evidence of puborectalis dyssynergia.

Tegaserod for female patients suffering from IBS with mixed bowel habits or constipation: a randomized controlled trial.

Objectives: Though the greatest proportion of irritable bowel syndrome (IBS) patients report a mixed bowel pattern (IBS-Mixed), no available therapies have been rigorously evaluated in this subgroup. This study aimed to evaluate the efficacy and safety of the 5-HT(4) agonist tegaserod in women with IBS-Mixed and IBS with constipation (IBS-C).

Methods: This prospective, double-blind, randomized, placebo-controlled, multicenter study was conducted in 100 centers in North America, South America, and Europe.

Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention.

Evidence suggests that distinct mechanisms underlie diabetic and idiopathic gastroparesis. Differences in gastric acid in gastroparesis of different etiologies and varying degrees of gastric stasis are uninvestigated. We tested the hypotheses that 1) gastric pH profiles show differential alteration in diabetic vs.

Recent developments in the therapy of irritable bowel syndrome.

There is tremendous activity and excitement in the arena of drug development for the treatment of the irritable bowel syndrome (IBS). Pharmacologic therapy has been largely limited to gut acting therapeutic agents including antidiarrheals, laxatives and antispasmodics that primarily target individual symptoms. Various antidepressants have gained popularity although their efficacy in clinical trials has been modest and their clinical utility is limited by untoward side effects.

American College of Gastroenterology guideline on the management of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H.

Successful treatment of common variable immunodeficiency disorder-associated diarrhea with budesonide: a case report.

Purpose: Common variable immunodeficiency disorder (CVID) is an immunological disease that can present with gastrointestinal (GI) symptoms including chronic diarrhea and abdominal pain. We report a patient with CVID and chronic diarrhea who significantly improved with budesonide.

Methods: A 47-yr-old woman with CVID-associated diarrhea, steatorrhea, abdominal pain, and bloating for several years had an exhaustive evaluation for secondary causes of her symptoms, which was unrevealing.

A randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn's disease.

Background & Aims: The aim of this study was to compare the safety and efficacy of alicaforsen, a first-generation antisense inhibitor of intercellular adhesion molecule 1, with placebo in subjects with active Crohn's disease, a disorder in which intercellular adhesion molecule 1 is overexpressed.

Methods: In 2 identical double-masked, placebo-controlled studies, 331 subjects with active Crohn's disease were treated with either alicaforsen (221 subjects) or placebo (110 subjects) administered via 2-hour intravenous infusion 3 times a week for 4 weeks. Patients then returned for follow-up every 2 weeks.

Irritable bowel syndrome: update on colonic neuromuscular dysfunction and treatment.

Recent discoveries regarding the relatively autonomous workings of the enteric nervous system have expanded our understanding of the pathophysiology of irritable bowel syndrome (IBS). However, the heterogeneity of the pathogenesis of IBS continues to create unique challenges for clinicians who care for these patients. Advances in our understanding of the structure and functions of the brain-gut axis and its interplay with other potentially important factors, such as genetic predisposition, inflammation, and psychological unrest, have led to new developments in the field of targeted pharmacotherapy for IBS sufferers.

A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.

Background: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease.

Materials And Methods: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive).

Design of treatment trials for functional gastrointestinal disorders.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice.

Functional bowel disorders.

Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD.

Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data.

Background: Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance.

Methods: A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation.