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Sauter M.,University of Zurich | Heinrich H.,University of Zurich | Fox M.,University of Zurich | Fox M.,NIHR Nottingham Digestive Diseases Biomedical Research Unit | And 5 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: Measurements of anorectal function using high-resolution anorectal manometry (HR-ARM) and rectal barostat technology provide more reliable results than standard ARM with an elastic balloon; however, HR-ARM results have not been compared to ARM and standard barostat protocols are impractical in routine clinical practice. The aim of this study was to validate HR-ARM against standard ARM and standard barostat against a novel Rapid Barostat Bag (RBB) measurement and elastic balloon measurements of rectal function. Methods: Twenty-six healthy volunteers (15 female, 11 male, 19-52 years) were studied. Measurements of anal function and simulated defecation were compared for 12-sensor HR-ARM and 6-sensor standard ARM using line plots from the same recording. Rectal capacity, compliance, and sensation (volume threshold) were measured by elastic balloon, standard barostat, and RBB methods using stepwise inflation of a 700-mL polyethylene bag to 40 mmHg distension by electronic barostat and handheld syringe monitored by sphygmo-manometer, respectively. Results are reported as mean ± SD. Bland-Altman plots and correlation coefficients (r) for measurements were calculated. Key Results: There was excellent agreement between HR- and standard ARM measurements (r > 0.86, <25 mmHg difference) and between standard barostat and RBB measurements of rectal capacity (r = 0.97, <25 mL difference). Correlation coefficients of threshold volumes for initial perception, urgency and discomfort were 0.37, 0.71, and 0.95, respectively. No significant correlation was present with elastic balloon measurements. Time to complete studies was shorter for HR-ARM than standard ARM and for RBB than standard barostat in historical controls. Conclusions & Inferences: HR-ARM with RBB measurements of anorectal function provides quick and reasonably accurate measurements of continence function suitable for use in routine clinical practice (ClinicalTrial.gov NCT01456442). © 2014 John Wiley & Sons Ltd. Source


Arends J.E.,University Utrecht | Arends J.E.,Members of the European Study Group on Viral Hepatitis ESGVH | Ghisetti V.,Microbiology and Virology Laboratory | Ghisetti V.,Members of the European Study Group on Viral Hepatitis ESGVH | And 6 more authors.
Journal of Clinical Virology | Year: 2014

Hepatitis E virus (HEV) genotype 3 is the most recently characterized hepatotropic virus and is increasingly being recognized as the cause of unexplained liver disease in many western countries. Although asymptomatic in most cases, HEV GT3 may be responsible for a wide range of illnesses, from mild to fulminant acute hepatitis, and also chronic hepatitis in immunocompromised patients. Extrahepatic manifestations have been occasionally described. Anti-HEV antibody detection by immunoassays is hampered by moderate test accuracy particularly in immunocompromised hosts while a WHO international standard for molecular detection of HEV RNA by RT-PCR has recently been introduced. This review describes the basic virology, epidemiology, clinical virology and treatment of HEV GT3 infections in high income countries. © 2013 Elsevier B.V. Source


Yang J.-F.,Zhejiang University of Science and Technology | Yang J.-F.,Zhejiang University | Fox M.,University of Zurich | Fox M.,NIHR Nottingham Digestive Diseases Biomedical Research Unit | And 6 more authors.
World Journal of Gastroenterology | Year: 2015

AIM: To validate 4-sample lactose hydrogen breath testing (4SLHBT) compared to standard 13-sample LHBT in the clinical setting. METHODS: Irritable bowel syndrome patients with diarrhea (IBS-D) and healthy volunteers (HVs) were enrolled and received a 10 g, 20 g, or 40 g dose lactose hydrogen breath test (LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h (13 measurements). The detection rates of lactose malabsorption (LM) and lactose intolerance (LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT. RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups (P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT (97%-100%, Kappa 0.815-0.942) with high sensitivity (90%-100%) and specificity (100%) at all three lactose doses in both groups. CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. Source


Negm O.H.,University of Nottingham | Negm O.H.,Mansoura University | Hamed M.R.,University of Nottingham | Hamed M.R.,Mansoura University | And 9 more authors.
Clinical and Vaccine Immunology | Year: 2015

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzymelinked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotypespecific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. Copyright © 2015, American Society for Microbiology. All Rights Reserved. Source


Yang J.,Zhejiang University | Fox M.,University of Zurich | Fox M.,NIHR Nottingham Digestive Diseases Biomedical Research Unit | Cong Y.,Zhejiang University | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Irritable bowel syndrome patients with diarrhoea (IBS-D) often report intolerance to milk; however, the mechanism underlying these symptoms is unknown. Aim To assess the role of psychological factors, immune activation and visceral sensitivity on the development of lactose intolerance (LI) in IBS-D patients. Methods Fifty-five IBS-D patients and 18 healthy controls (HCs) with lactase deficiency underwent a 20-g lactose hydrogen breath test (LHBT). Patients were categorised as lactose malabsorption (LM; malabsorption only) or LI [malabsorption plus increase in total symptom score (TSS). Measurements included (i) psychological status; (ii) enteric biopsies with quantification of mast cells (MCs), T-lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv) rectal sensitivity before and after lactose ingestion. Results LI was more prevalent in IBS-D patients than HCs [25/55 (46%) vs. 3/18 (17%), P = 0.029]. IBS-D patients with LI had (i) higher levels of anxiety than those with LM (P = 0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P = 0.006) and HCs (P < 0.001); (iii) raised serum TNF-α compared with LM (P = 0.034) and HCs (P < 0.001) and (iv) increased rectal sensitivity after lactose ingestion compared with LM (P < 0.001) or HCs (P < 0.001). Severity of abdominal symptoms after lactose ingestion was associated with the increase in visceral sensitivity after lactose intake (r = 0.629, P < 0.001), MCs (r = 0.650, P < 0.001) and anxiety (r = 0.519, P < 0.001). Conclusions IBS-D patients with lactose intolerence are characterised by anxiety, mucosal immune activation and increased visceral sensitivity after lactose ingestion. The presence of these biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or mast cell stabilisers (ClinicalTrials.gov Identifier: NCT01286597). © 2013 John Wiley & Sons Ltd. Source

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