Efficacy of optimised thiopurine therapy in patients with moderate-to-severe ulcerative colitis: retrospective long-term follow-up from two randomised trials.

Objective: The long-term outcome of thiopurine therapy in patients with ulcerative colitis (UC) enrolled in prospective trials have not been evaluated. We aimed to assess the effects of optimised thiopurine maintenance therapy for UC.

Methods: Long-term data were obtained from patients from our center enrolled in two randomised, prospective, open-label, controlled studies comprising 66 thiopurine-naïve moderate-to-severe patients with UC consisting of a low dose azathioprine (AZA)/allopurinol combination or AZA monotherapy.

The Use and Efficacy of Biological Therapies for Inflammatory Bowel Disease in a Danish Tertiary Centre 2010-2020.

Background: Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center.

Methods: We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre.

Optimized thiopurine therapy before withdrawal of anti-tumour necrosis factor-α in patients with Crohn's disease.

Objective: Two meta-analyses have found that the risk of relapse in Crohn's disease (CD) was ~40 and 50% 1 and 2 years, respectively, after withdrawal of anti-tumour necrosis factor-α (anti-TNFα). The aim of this study was to evaluate relapse rates in CD when thiopurine therapy was optimized before anti-TNFα withdrawal.

Patients And Methods: An observational study was conducted including patients with CD in remission with optimized thiopurine therapy before anti-TNFα withdrawal.

Randomized clinical trial: a pilot study comparing efficacy of low-dose azathioprine and allopurinol to azathioprine on clinical outcomes in inflammatory bowel disease.

Background: Treating inflammatory bowel diseases (IBD) using thiopurines is effective; however, a high rate of adverse effects and lack of efficacy limit its use. Retrospective studies have suggested that treatment with low-dose thiopurines in combination with allopurinol is associated with higher remission rates and lower incidence of adverse events.

Aim: To compare the rates of clinical remission and the rates of adverse events in IBD patients treated with either standard treatment with azathioprine or low-dose azathioprine in combination with allopurinol.

The Impact of Endoscopic Inflammation and Mucosal Healing on Health-related Quality of Life in Ulcerative Colitis Patients.

Background: Health-related quality of life [HRQoL] is impaired in ulcerative colitis and is correlated to clinical disease activity. The recent shift towards more objective treatment goals like mucosal healing generates a need for evaluating the association between endoscopic disease activity, mucosal healing and HRQoL.

Methods: In this cross-sectional study, patients with either active or inactive ulcerative colitis underwent sigmoidoscopy.

Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-la in moderately active ulcerative colitis.

Background: Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment.

Aim: To extend pilot data and identify a suitable dose of IFN-beta-1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety.

Functional characterization of muscarinic receptor subtypes in human duodenal secretion.

Aim: Acetylcholine (ACh) stimulates ion secretion in the small intestine and colon. The purpose of the present study was to characterize the ACh-induced electrogenic ion transport in human duodenum and determine the muscarinic receptor subtypes functionally involved.

Methods: Biopsies from the second part of duodenum were obtained from 28 patients during endoscopy.

Novel modified Ussing chamber for the study of absorption and secretion in human endoscopic biopsies.

The aim of this study was to design and evaluate a modified Ussing chamber, that makes use of constant air suction (modified Ussing air suction chamber, MUAS) for fixation of biopsy specimens. Standard size forceps biopsies were taken from the descending part of duodenum from patients undergoing endoscopy. Short circuit current (SCC) and conductance (G) were measured during basal conditions and after addition of different sugars and secretagogues.

Reappraisal of bicarbonate secretion by the human oesophagus.

Background And Aims: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion and thus contribute to the therapeutic efficacy of the drug in gastro-oesophageal reflux disease.

Subjects And Methods: In nine healthy volunteers, oesophageal "steady state" perfusion of a 10 cm open segment of distal oesophagus was performed twice in random order.

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects.

Background: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was present also in the stomach of DU patients.

Methods: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H.

Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function.

The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from the luminal acid to near neutrality at the surface of the epithelial cells, thereby acting as an important mucosal defence mechanism.

Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements.

Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans.

Background: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal release of prostaglandin (PG) E2 by means of a method that enables simultaneous measurements in the stomach and the duodenum.

Methods: Gastric and duodenal perfusions were performed twice in random order during control conditions or after pretreatment with indomethacin (100 mg intravenously) in eight healthy volunteers.

Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis.

5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations of leukotriene B4 and prostaglanding E2 in rectal dialysis fluid from 23 males with clinically and sigmoidoscopically active, distally located ulcerative colitis were measured by radioimmunoassays in a double-blind, placebo-controlled, parallel design study before and after rectal administration of an enema containing 0.

Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers.

The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion and luminal output of PGE2 into the stomach and the duodenum of nine healthy volunteers using a new technique permitting simultaneous measurements. In the stomach modified sham feeding increased bicarbonate secretion from 382 (62) mumol/h (mean (SEM)) to 959 (224) mumol/h (p < 0.

Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers.

Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects.

Colloidal bismuth subcitrate causes sustained release of gastric mucosal prostaglandin E2.

Gastric application of high doses of colloidal bismuth subcitrate (CBS) stimulates mucosal prostaglandin E2 (PGE2) production, which is considered part of the mechanism by which the drug accelerates peptic ulcer healing. Whether therapeutic, orally administered, doses of CBS cause a sustained stimulation of prostaglandin production is not known. We have, therefore, determined gastric luminal release of PGE2 during 'steady-state' perfusion of the stomach with CBS (10 mg/ml; isotonic mannitol 5 ml/min) and 4 h after the last oral dose of the drug (240 mg b.

A natural flavonoid, IdB 1027, increases gastric luminal release of prostaglandin E2 in healthy subjects.

IdB 1027 is an anthocyanidin pigment occurring in bilberries. In laboratory animals this compound shows gastric protective effects without influencing acid secretion. To study how IdB 1027 would affect gastric luminal release of prostaglandin (PG) E2 and basal fluid and acid secretion, we have carried out 'steady state' perfusions of the stomach in 10 healthy males before and after oral administration of IdB 1027 (600 mg b.

Prostaglandin E2 is a mediator of 5-hydroxytryptamine induced water and electrolyte secretion in the human jejunum.

Studies in the rat jejunum in vivo have shown that 5-hydroxytryptamine (5-HT) causes secretion of fluid and luminal release of prostaglandin (PG) E2. These effects can be blocked by indomethacin and ketanserin, which suggests that PGE2 may be an important intermediate in the transduction mechanism leading to 5-HT induced fluid secretion. To test this hypothesis in man 'steady state' perfusions (9 ml/min) were done in eight healthy volunteers using the triple lumen technique.

Fasting and postprandial serum concentrations of glycine- and taurine-conjugated bile acids in Crohn's disease.

Fasting and postprandial serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a high-pressure liquid chromatographic-enzymatic assay in 17 patients with ileal Crohn's disease and in 17 controls. The postprandial concentrations of the taurine-conjugated bile acids in the patients were significantly lower than in the controls, whereas the concentrations of the glycine conjugates were not significantly different. The total glycine to taurine ratios of serum bile acids were significantly higher in the patients (means, 2.