bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mebeverine decreases mass movements and stool frequency in lactulose‐induced diarrhoea
Authors: Washington  , Ridley  , Thomas  , Spiller  , Watts  , Wilson  
Published: March 2003

Background:In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine’s mode of action in man.Aim:To examine mebeverine’s effect on transit though the gut during lactulose‐induced diarrhoea.Methods:Nine healthy volunteers undertook a two‐way randomized crossover study. Diarrhoea was induced using lactulose pre‐treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric‐coated capsules containing radiolabelled 8.4 mm tablets and 180–250 μM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards.Results:Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75–2.75) to 1.5 (IQR 1.25–2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2–2) to 1 (1–2), and the number of retrograde movements from 1 (0–2) to 0 (0–0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9–3.2) to 2.8 (2.6–4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8–2.0) h to 1.0 (0.52–1.32) h, P = 0.02).Conclusion:Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.
Development of a digestive health status instrument: tests of scaling assumptions, structure and reliability in a primary care population
Authors: Shaw  , Talley  , Adlis  , Beebe  , Tomshine  , Healey  
Published: March 2003

Background:The absence of valid and reliable health status measures for functional gastrointestinal illness has limited research and patient care for this common group of disorders. A self‐report survey has been developed.Methods:Initial development focused on extensive pre‐testing of patients, primary care physicians and gastroenterologists. The disease‐specific portion included the Rome criteria for dyspepsia subgroups and the Manning and Rome criteria for irritable bowel syndrome. The Short Form‐36 was added. Psychometric analyses included techniques of multitrait scaling, scale internal consistency and criterion validation.Results:Six hundred and ninety patients presenting to their primary care physician for treatment of heartburn, abdominal pain or discomfort completed the 98 question survey. The disease‐specific portion revealed five components including reflux, dysmotility, a two‐domain bowel dysfunction complex, and a pain index. Internal consistency measures demonstrated good to excellent reliability. Scaling successes were observed on multitrait scaling. The disease‐specific portion was reduced to 34 questions. Criterion validity was demonstrated with the correlation of the disease‐specific questions to the SF‐36.Conclusions:The psychometric analyses lend credence to the concept of stomach and bowel symptom subgrouping as proposed by expert consensus. The psychometric properties of the five summated disease‐specific scales compare favourably with standardized health status measures.
Effects of tablet and effervescent formulations of ranitidine 75 mg and cimetidine 200 mg on gastric acidity and oesophageal acid exposure in healthy humans
Authors: Varannes S. Bruley Des , Duquesnoy  , Mamet  , Slama  , Galmiche  , Scarpignato  
Published: March 2003

Background:Because of their tolerance and safety, low doses of H2‐receptor antagonists are now increasingly used in some countries for self‐care medication of gastro‐oesophageal reflux symptoms.Aim:The purpose of this randomized, double‐blind, placebo‐controlled, five‐way crossover study was to determine and to compare the effects of low doses of ranitidine and cimetidine both on gastric pH and on oesophageal acid exposure.Methods:Gastric and oesophageal pH were simultaneously monitored in 20 healthy subjects using two glass pH electrodes, after placebo and single doses of ranitidine 75 mg and cimetidine 200 mg (effervescent and tablet forms), for 4 h before and after a meal.Results:During the fasting period, median gastric pH rose significantly with both drugs, but more rapidly with the effervescent forms; the oesophageal acid exposure was significantly decreased by all drug regimens. After the meal, although there was no significant difference in gastric pH values, oesophageal acid exposure was significantly decreased in comparison with placebo with both forms of ranitidine (P < 0.05), and also for ranitidine tablets in comparison with cimetidine tablets (P < 0.05).Conclusions:Low doses of ranitidine and cimetidine increase gastric pH, with a more pronounced effect for ranitidine. Effervescent formulations of both drugs induce a slightly more rapid initial increase in pH than tablets. Ranitidine demonstrates a more prolonged effect than cimetidine and decreases oesophageal acid exposure monitored after a meal ingested 4 h after the drug intake.
Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study
Authors: Dekkers  , Beker  , Thjodleifsson  , Gabryelewicz  , Bell  , Humphries  ,   THE EUROPEAN RABEPRAZOLE STUDY GROUP
Published: March 2003

Background:Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer.Method:This randomized, double‐blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy.Results:After 2 weeks, complete ulcer healing was documented in 69% of patients given rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole‐treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4‐week treatment period. Mean changes from baseline to end‐point in fasting serum gastrin were significantly greater in the rabeprazole group, but at end‐point mean values were well within normal limits for both groups. No clinically meaningful changes or other between‐group differences were observed in laboratory parameters.Conclusion:In this study, rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.
The DU‐MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy
Authors: ZANTEN S. J. O.VELDHUYZEN VAN , BRADETTE  , FARLEY  , LEDDIN  , LIND  , UNGE  , BAYERDÖRFFER  , SPILLER  , O'MORAIN  , SIPPONEN  , WRANGSTADH  , ZEIJLON  , SINCLAIR  
Published: March 2003

Aim: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6‐month treatment‐free period in patients with active duodenal ulcer.Methods: This was a double‐blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1‐week b.d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C‐urea breath test and histology, performed at pre‐entry, at 4 weeks after the end of all therapy and at 6 months.Results: The intention‐to‐treat (intention‐to‐treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention‐to‐treat/per protocol): OMC—85% and 92%, OAC—78% and 87% and O—0% (O). Ulcer healing (intention‐to‐treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high.Conclusion: The OMC and OAC 1‐week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.
Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies
Authors: SIMMONDS  , MILLAR  , BLAKE  , RAMPTON  
Published: March 2003

Background: The therapeutic efficacy of 5‐aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties.Aim: To compare in vitro the antioxidant effects of conventional drugs (5‐aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4‐aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N‐acetylcysteine, glutathione, verapamil).Methods: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell‐free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol‐amplified chemiluminescence.Results: 5‐aminosalicylic acid and balsalazide were more potent antioxidants than 4‐aminosalicylic acid or N‐acetyl‐5‐aminosalicylic acid in cell‐free systems. 5‐aminosalicylic acid (20 m M) and balsalazide (20 m
M) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4‐aminosalicylic acid (20 m
M). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 m
M) inhibited chemiluminescence by 100% in cell‐free systems and by 60% in rectal biopsies. N‐acetyl cysteine (10 m
M), and both oxidized and reduced glutathione (10 m
M), completely inhibited chemiluminescence in cell‐free systems, but not with rectal biopsies.Conclusions: The antioxidant effects of compounds varies between cell‐free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy.
Treatment options for Helicobacter pylori infection when proton pump inhibitor‐based triple therapy fails in clinical practice
Authors: LEE  , BRESLIN  , HYDE  , BUCKLEY  , O'MORAIN  
Published: March 2003

Background: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined.Aims: To evaluate proton pump inhibitor‐based triple therapies as first‐line eradication regimens in clinical practice, and to establish the efficacy of second‐line regimens in the context of an initial failed eradication attempt.Methods: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first‐line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2‐week proton pump inhibitor‐based triple therapy regimen as described, and 12 patients received a further 1‐week proton pump inhibitor‐based triple therapy regimen.Results: Including 308 patients, the intention‐to‐treat (ITT) eradication rates for OAC and OMC as first‐line regimens were 72% (95% CI: 63–80%) and 73% (95% CI: 67–79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow‐up gives an initial eradication rate of 78% (95% CI: 69–86%) for OAC and 79% (95% CI: 73–85%) for OMC. There were 60 patients (21%; 95% CI: 17–26%) in whom the initial eradication attempt was unsuccessful. With second‐line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58–73%) patients. The eradication rates with the quadruple regimen and 2‐week triple therapy regimens were 75% (95% CI: 56–94%) and 80% (95% CI: 63–98%) respectively (P = 0.71). The eradication rate with a repeat 1‐week regimen was 33% (95% CI: 7–60%).Conclusions: The eradication rates achieved in this `in practice' study with recommended first‐line 1‐week proton pump inhibitor‐based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1‐week proton pump inhibitor‐based triple therapy regimen was not successful as a salvage therapy. Both the 2‐week proton pump inhibitor‐based triple therapy regimen and the 1‐week quadruple therapy regimen were successful second‐line treatments in  ≥75% of patients.
Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole
Authors: OLAFSSON  , BERSTAD  , BANG  , NYSÆTER  , COLL  , TEFERA  , HATLEBAKK  , HAUSKEN  , OLAFSSON  
Published: March 2003

Background: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline.Aim: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin.Methods: One hundred and eighty‐three patients were randomized to one of four 10‐day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C‐urea breath test was performed at 8 weeks.Results: Intention‐to‐treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex‐smokers (93%) and smokers (89%) (P = 0.06). Fifty‐three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002).Conclusions: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.
Dexamethasone inhibits IFNγ‐induced MHC class II expression of intestinal epithelial cells independently of the TGF‐β1 regulatory pathway
Authors: RUEMMELE  , DIONNE  , LEVY  , SEIDMAN  
Published: March 2003

Background: In the presence of inflammation, an increased expression of enterocyte MHC class II is observed, leading to altered mucosal antigen handling. Corticosteroids are potent anti‐inflammatory drugs, widely used in treating inflammatory bowel disorders. However, their diverse mechanisms of action are only partially understood.Aim: To evaluate effect and mechanisms of corticosteroids on intestinal crypt epithelial cell MHC class II.Methods: The effect of dexamethasone treatment on cytokine‐induced MHC class II expression was measured in IEC‐6 cells by immunofluorescence and flow cytometry. To determine the role of the TGF‐β1 regulatory pathway in mediating the effects of dexamethasone, neutralizing anti‐TGF‐β antibodies were used. Additionally, endogenous and dexamethasone‐stimulated IEC‐6 cell TGF‐β1 production was measured by ELISA.Results: Dexamethasone potently down‐regulated IFNγ‐induced class II expression on IEC‐6 cells, in a dose‐dependent manner. TGF‐β1 had a similar inhibitory effect on class II expression. However, neutralizing anti‐TGF‐β antibodies did not alter the effect of dexamethasone. Furthermore, dexamethasone reduced endogenous TGF‐β1 synthesis.Conclusions: Corticosteroids inhibit cytokine‐induced MHC class II expression on IEC‐6 cells in a TGF‐β1 independent way. This effect may markedly alter enterocytic antigen presentation, reducing the aberrant state of activation of mucosal immune cells.
Post‐prandial intragastric and duodenal acidity are increased in patients with chronic pancreatitis
Authors: Geus  , Eddes  , Gielkens  , Gan  , Lamers  , Masclee  
Published: March 2003

Objectives: Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum.Methods: We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions. Postprandial gastrin and cholecystokinin release were also determined.Results: Median 24‐h intraduodenal pH (5.90 vs. 6.00) and intragastric pH (1.60 vs. 1.70) were not significantly different between patients and controls. However, in the 2‐h postprandial periods intraduodenal pH was below five for a significantly higher percentage of time in chronic pancreatitis patients compared to controls (lunch: 14.5% vs. 0.17%, P=0.011; dinner: 24.1% vs. 5.75%, P=0.05). The post‐dinner intragastric pH was below three for a significantly higher percentage of time in chronic pancreatitis patients vs. controls (72.2 vs. 48.9%, P=0.04). Postprandial gastrin release was not significantly different between the two groups. Postprandial secretion of cholecystokinin (CCK), as enterogastrone, was significantly (P < 0.01) reduced in chronic pancreatitis patients (78 ± 13 pmol/L, 120 min) compared to controls (155 ± 14 pmol/L, 120 min).Conclusions: Median intraduodenal and intragastric pH are not significantly decreased in patients with chronic pancreatitis and exocrine insufficiency but the postprandial time with an acidic pH in the duodenum (pH < 5) and in the stomach (pH < 3) is significantly (P ≤ 0.05) increased.
Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies
Authors: Danesh  
Published: March 2003

Background: The published epidemiological studies of chronic Helicobacter pylori infection and gastric cancer yield conflicting results, so there is uncertainty as to whether any material association exists and, if so, how strong it is.Aim: To review these studies quantitatively.Methods: A systematic review of sero‐epidemiological studies published before 1998 of H. pylori and gastric cancer, as identified by computer‐assisted literature searches of relevant journals, reference lists and discussions with authors. All relevant studies identified were included, subdivided by study design. The following was abstracted from published reports: adjusted odds ratio (or, in prospective studies, the risk ratio) and confidence interval, study design, type of controls, mean age, mean duration of follow‐up, assay methods, location of study, and degree of adjustment for confounders.Results: The 34 retrospective studies included in total 3300 gastric cancers, but their controls were of uncertain validity. The 10 ‘nested’ case–control comparisons in prospective studies included in total only 800 gastric cancers, and combined analysis of them yielded a risk ratio of 2.5 (95% CI: 1.9–3.4; 2P < 0.00001) for gastric cancer in people seropositive for H. pylori antibodies.Conclusions: The prospective studies suggest that gastric cancer is 2 or 3 times as common in those chronically infected by H. pylori, but to help investigate causality, further observational studies are still needed, as are large‐scale randomized trials of whether antibacterial regimens reduce the eventual incidence of gastric cancer.
On demand therapy with omeprazole for the long‐term management of patients with heartburn without oesophagitis—a placebo‐controlled randomized trial
Authors: Lind  , Havelund  , Lundell  , Glise  , Lauritsen  , Pedersen  , Anker‐Hansen  , StubberÖD  , Eriksson  , Carlsson  , Junghard  
Published: March 2003

Aim: To observe the natural course of gastro‐oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long‐term management of these patients.Methods: We investigated the efficacy of on‐demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double‐blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short‐term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6‐month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue.Results: According to life‐table analysis, after 6 months the remission rates were 83% (95% CI: 77–89%) with omeprazole 20 mg, 69% (61–77%) with omeprazole 10 mg, and 56% (46–64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life.Conclusions: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On‐demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.