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Armstrong D.,McMaster University | Sifrim D.,Wingate Institute of Neurogastroenterology
Gastroenterology Clinics of North America | Year: 2010

This article highlights current and emerging pharmacological treatments for gastroesophageal reflux disease (GERD), opportunities for improving medical treatment, the extent to which improvements may be achieved with current therapy, and where new therapies may be required. These issues are discussed in the context of current thinking on the pathogenesis of GERD and its various manifestations and on the pharmacologic basis of current treatments. © 2010 Elsevier Inc.

Mertens V.,Catholic University of Leuven | Dupont L.,University Hospital Gasthuisberg | Dupont L.,Catholic University of Leuven | Sifrim D.,Wingate Institute of Neurogastroenterology | Sifrim D.,Catholic University of Leuven
Current Gastroenterology Reports | Year: 2010

Lung transplantation has become a valuable treatment for end-stage pulmonary disorders in an attempt to improve quality of life and extend survival. Development of chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is responsible for the vast majority of deaths after lung transplantation. Up to 50% of lung transplant patients develop BOS within the first 5 years after transplantation. A high prevalence of gastroesophageal reflux and aspiration of gastric components has been described after lung transplantation. Reflux and aspiration have been implicated in the development of BOS and antireflux surgery has been proposed; however, the causal relationship with BOS and the impact of reflux in lung transplantation survival needs to be further elucidated. © Springer Science+Business Media, LLC 2010.

Palit S.,Queen Mary, University of London | Palit S.,Wingate Institute of Neurogastroenterology | Lunniss P.J.,Queen Mary, University of London | Scott S.M.,Queen Mary, University of London
Digestive Diseases and Sciences | Year: 2012

Human defecation involves integrated and coordinated sensorimotor functions, orchestrated by central, spinal, peripheral (somatic and visceral), and enteric neural activities, acting on a morphologically intact gastrointestinal tract (including the final common path, the pelvic floor, and anal sphincters). The multiple factors that ultimately result in defecation are best appreciated by describing four temporally and physiologically fairly distinct phases. This article details our current understanding of normal defecation, including recent advances, but importantly identifies those areas where knowledge or consensus is still lacking. Appreciation of normal physiology is central to directed treatment of constipation and also of fecal incontinence, which are prevalent in the general population and cause significant morbidity. © Springer Science+Business Media, LLC 2012.

Amarasinghe G.,Queen Mary, University of London | Sifrim D.,Queen Mary, University of London | Sifrim D.,Wingate Institute of Neurogastroenterology
Drugs | Year: 2014

Functional esophageal disorders are a group of disorders that cause esophageal symptoms, although with negative results on investigation with standard esophageal tests. Therefore, structural disorders, motility disorders with a histopathological basis and gastroesophageal reflux disease (GERD) are excluded. They are frequently encountered by clinicians, and so a systematic and evidence-based approach to investigation, diagnosis and treatment are crucial. There are four functional esophageal disorders defined by the ROME III consensus, namely functional heartburn, functional chest pain, functional dysphagia and globus. Since the advent of ROME, the specification of diagnostic criteria for functional esophageal disorders has allowed more comparable studies and clinical trials. Despite this, the evidence base for many therapies in use at present is not as robust as would be desired. In this paper, we discuss the four categories of functional esophageal disorders. We then propose diagnostic algorithms based on current evidence. Finally, we discuss current therapies for each of the four functional esophageal disorders based on current evidence. © 2014 Springer International Publishing Switzerland.

Sanger G.J.,Wingate Institute of Neurogastroenterology | Sanger G.J.,Queen Mary, University of London | Quigley E.M.M.,Alimentary Pharmabiotic Center
Clinical Medicine Insights: Gastroenterology | Year: 2010

After the problems associated with the non-selective 5-HT4 receptor agonists cisapride and tegaserod, the 5-HT4 receptor is now beginning to come in from the cold. Thus, prucalopride is now the first of a new class of drug defined by selectivity and high intrinsic activity at the 5-HT4 receptor. Prucalopride has been developed for treatment of chronic constipation rather than constipation-predominant irritable bowel syndrome (IBS). This follows the trend of first evaluating new gastrointestinal (GI) prokinetic drugs in disorders where disrupted GI motility is known to exist, rather than in a functional bowel disorder where changes in motility are uncertain. If prucalopride is not progressed towards the IBS indication, it has at least shown the way for other selective 5-HT4 receptor agonists. Most notable among these is TD-5108 (velusetrag), also characterized by good selectivity at the 5-HT4 receptor, high intrinsic activity and efficacy in patients with chronic constipation.

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