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.
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.
PubMed | Wingate Institute of Neurogastroenterology, University of Medicine and Pharmacy, Cluj-Napoca, University of Sarajevo, University of Zürich and 9 more.
Type: Journal Article | Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society | Year: 2016
Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a large pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients.The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).
Hayat J.O.,Wingate Institute of Neurogastroenterology |
Hayat J.O.,St George's, University of London |
Gabieta-Somnez S.,Wingate Institute of Neurogastroenterology |
Yazaki E.,Wingate Institute of Neurogastroenterology |
And 6 more authors.
Gut | Year: 2015
Objective: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). Design: 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). Results: 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD +HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. Conclusion: In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.
Hobson A.R.,Addenbrookes Hospital |
Hobson A.R.,Wingate Institute of Neurogastroenterology |
Chizh B.,Addenbrookes Hospital |
Hicks K.,Addenbrookes Hospital |
And 6 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2010
Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference ± 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38°C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Aδ fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans. Copyright © 2010 the American Physiological Society.
Farmer A.D.,Wingate Institute of Neurogastroenterology |
Douthwaite H.,Queen Mary, University of London |
Gardiner S.,Queen Mary, University of London |
Aziz Q.,Wingate Institute of Neurogastroenterology |
Grahame R.,University College London
Journal of Rheumatology | Year: 2010
Objective. The stress/strain curve derived from stretching skin is not linear, but follows a J-shaped curve. An initial generous yield is followed by a steep linear phase where considerable additional force is required to achieve modest increases in deformation. The former represents the taking up of slack resulting from the alignment of dermal collagen bundles in the line of force, while the gradient of the latter represents Young's modulus for skin. Skin hyperextensibility in Ehlers-Danlos syndrome (EDS) is limited to the initial phase of taking up slack. Skin hyperextensibility and joint hypermobility (JHM) form part of the Revised 1998 Brighton diagnostic criteria for the benign joint hypermobility syndrome (BJHS), considered by many to be akin to EDS-hypermobility type. JHM may be screened for using the Beighton Score or a 5-point questionnaire. Our aim was to validate a novel method of measuring skin extensibility based on these observations in addition to revalidating the 5-point questionnaire. Methods. 250 volunteers (131 female), median age 39 years (range 18-89 yrs), without BJHS, had their joint mobility evaluated using the Beighton Score, compared to the 5-point questionnaire. A Beighton score ≥ 4/9 was considered to represent JHM. Skin extensibility was determined by placing 2 dots on the dorsum of the right hand between the second and third metacarpals, approximately 10 mm apart, and was measured using an electronic caliper. Perpendicular to the metacarpals, a force was applied until the skin was fully taut and the increment was measured. Skin-fold thickness was measured using a Harpenden caliper. A corrected skin extensibility score (CSES) was calculated by dividing the percentage increment by skin thickness. Interobserver variability was measured in a further 50 healthy volunteers. Results. The prevalence of JHM was 17.6%. Revalidation of the 5-point questionnaire returned a sensitivity of 0.85 and specificity of 0.85. The mean CSES was 23.84%/mm in the hypermobile group versus 13.55%/mm in the normal mobility group (p < 0.0001). CSES sensitivity was 0.72, specificity 0.75. The κ value for interobserver variability was 0.83. Conclusion. The CSES is a useful and reproducible measure of skin extensibility in health. Further work is warranted to validate this test in patients with BJHS. The Journal of Rheumatology Copyright © 2010. All rights reserved.
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.
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.
Pandolfino J.E.,Northwestern University |
Sifrim D.,Wingate Institute of Neurogastroenterology
Neurogastroenterology and Motility | Year: 2012
Background High-resolution manometry and esophageal pressure topography have enhanced our ability to analyze esophageal motor disturbances by improving the detail and accuracy of measurements of peristaltic activity.This has been extremely helpful in the evaluation of disorders of rapid propagation as the technique is able to define important time points and physiologic landmarks that are crucial in defining peristaltic velocity and latency intervals. Purpose The goal of the current review will be to assess how esophageal pressure topography has impacted our ability to define important phenotypes of rapid propagation. Additionally, this review will also be utilized to complement the description of the Chicago Classification of Esophageal Motor Disorders, which is presented in this supplement issue. © 2012 Blackwell Publishing Ltd.
PubMed | Wingate Institute of Neurogastroenterology
Type: Journal Article | Journal: Rheumatic diseases clinics of North America | Year: 2013
Although perceived as a rare condition, joint hypermobility syndrome is common. Its prevalence in rheumatology clinics is extremely high. Early estimates suggest that it may be the most common of all rheumatologic conditions. The problem lies in the general lack of awareness of the syndrome, its means of recognition, and the resultant failure to diagnose it correctly when present. It is a worldwide problem. This article provides an overview of hypermobility and hypermobility syndrome, stressing its multisystemic nature and the negative impact that it may have on quality of life, with particular reference to gastrointestinal involvement.