680 Elevated Chemokine mRNA in Rectal Mucosa Following Gastrointestinal Infection and in Irritable Bowel Syndrome

Spiller, Robin; Garsed, Klara; Cox, Joanne; Kelly, F. M.; Zaitoun, Abed M.; Dukes, George E.; Hastings, Margaret; Mahida, Yashwant R.; Richards, Marguerite G.; Hall, Ian; Whorwell, Peter J.; Wilde, Jonathan I.

doi:10.1016/s0016-5085(09)60475-3

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“…In this subgroup of IBS we have demonstrated activated circulating peripheral blood mononuclear cells with increased cytokine production and an associated increase in inflammatory gene expression. 26 We have also demonstrated the importance of anxiety and depression, 27 which, along with adverse life events, increase the risk of PI-IBS. 28 The changes observed in PI-IBS are similar to those in IBS-D, the predominant bowel disturbance being diarrhoea with a similar prognosis.…”

Section: Risk and Benefitsmentioning

confidence: 86%

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

et al. 2015

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BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2 g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53);p = 0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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Section: Risk and Benefitsmentioning

confidence: 86%