bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double‐blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis
Authors: KRUIS W. , SCHÜTZ E. , FRIC P. , FIXA B. , JUDMAIER G. , STOLTE M. 
Published: October 2003

BackgroundAminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non‐pathogenic E. coli.MethodsA total of 120 patients with inactive ulcerative colitis were included in a double‐blind, double‐dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse‐free times and global assessment.ResultsThe start and end scores of the CAI demonstrated no significant difference (P=0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse‐free time of 103±4 days for mesalazine and 106±5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported.ConclusionsFrom the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.
The management of failed dual or triple therapy for Helicobacter pylori eradication
Authors: RINALDI V. , ZULLO A. , PUGLIANO F. , VALENTE C. , DIANA F. , ATTILI A. F. 
Published: October 2003

Background:After each treatment for Helicobacter pylori infection there is an eradication failure rate ranging from 5 to 50%. Thus, the best therapy schedule and treatment regimen sequence have still to be identified.Methods:Patients with H. pylori infection were randomized to receive either a 1‐week triple therapy of omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tetracycline 500 mg b.d. (OCT; 78 patients) or a 2‐week dual therapy of omeprazole 20 mg b.d. and amoxycillin 1 g b.d. (OA; 75 patients). H. pylori infection at entry and eradication 4–6 weeks after therapy had ended were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur with either the OCT or OA regimens, patients were switched over to the OA or OCT therapy, respectively. Eradication in these patients was assessed 4–6 weeks after conclusion of treatment by a further endoscopy.Results: H. pylori eradication was achieved in 67.9% (95% CI = 57.6–78.3%) of patients treated with the OCT regimen and in 75.7% (95% CI = 65.9–85.5%) of patients treated with the OA therapy (χ2 = 1.11; P = 0.29). Moreover, H. pylori eradication was achieved in 39.1% (95% CI = 19.2–59.1%) of patients re‐treated with the OA regimen and in 88.9% (95% CI = 74.4–100%) of patients re‐treated with the OCT therapy (χ2 = 8.52; P = 0.003). Thus, the overall success rate `per protocol' analysis in our study was 81.6% (95% CI = 72.9–90.3%) for the triple and dual therapy sequence and 97.3% (95% CI = 93.6–100%) for dual followed by triple therapy (χ2 = 8.14; P = 0.004).Conclusions:Our data found that H. pylori eradication with OA therapy after OCT therapy failure was poor, while that obtained with OCT after OA therapy was good.
Effects of oral cisapride on small bowel motility in irritable bowel syndrome
Authors: EVANS P. R. , BAK Y.‐T. , KELLOW J. E. 
Published: October 2003

Background:Cisapride has been reported to improve symptoms in patients with constipation‐predominant irritable bowel syndrome.Aim:To compare the effects of a 24‐h oral dose regimen of cisapride on interdigestive and post‐prandial small bowel motor activity in irritable bowel syndrome patients with predominant constipation, irritable bowel syndrome patients with predominant diarrhoea and healthy subjects.Methods:In 12 irritable bowel syndrome patients (11 females, aged 44 ± 12 years)—constipation‐predominant (irritable bowel syndrome‐C, n=5) and diarrhoea‐predominant (irritable bowel syndrome‐D, n=7)—and six healthy subjects, small bowel motor activity was continuously recorded using an ambulatory technique over a 48‐h period. Subjects received, in single‐blind fashion, placebo tablets q.d.s. in the first 24 h then cisapride 10 mg q.d.s. in the second 24 h. Additional control groups were 13 healthy subjects (eight females, aged 39 ± 13 years) and 10 irritable bowel syndrome patients (10 females, aged 49 ± 14 years) who were studied in identical fashion but who did not receive cisapride.Results:Cisapride increased migrating motor complex phase 2 motility index in both irritable bowel syndrome‐D (P < 0.01) and irritable bowel syndrome‐C (P < 0.05) patients, as well as in healthy subjects (P < 0.01). An increase in fasting discrete clustered contractions occurred in irritable bowel syndrome‐D patients (P < 0.001) and in healthy subjects (P < 0.01), but not in irritable bowel syndrome‐C patients; the proportion of discrete clustered contractions that were propagated, however, increased only in irritable bowel syndrome‐D patients (P < 0.001). In addition, cisapride resulted in an increase in post‐prandial motility index in irritable bowel syndrome patients (P < 0.05). Such motor alterations were not observed during the 48‐h recording period in the healthy or irritable bowel syndrome patient control groups who did not receive cisapride.Conclusions:Oral cisapride influences interdigestive and post‐prandial small bowel motor activity in both irritable bowel syndrome patients and healthy subjects; the effects of cisapride may be more marked in patients with predominant diarrhoea than in patients with predominant constipation.
Effects of 3‐days' intake of a sustained‐release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility
Authors: STACHER G. , SCHNEIDER C. , STEINRINGER H. , HOLZÄPFEL A. , GAUPMANN G. , STACHER‐JANOTTA G. 
Published: October 2003

Background:Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained‐release preparation of the nitric oxide donor isosorbide dinitrate on swallow‐initiated oesophageal contractions and the lower oesophageal sphincter.Methods:Twelve healthy men, aged 23–32 years, received, at 1‐week intervals and under random double‐blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side‐hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5‐mL water swallows were evaluated.Results:Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg ± 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 ± 1.0 mmHg) than after placebo (17.9 ± 1.7 mmHg; P<0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo.Conclusions:Twenty and 40 mg sustained‐release isosorbide dinitrate twice daily had no effect on swallow‐initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.
Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro‐oesophageal reflux disease
Authors: ROBINSON M. , MATON P. N. , RODRIGUEZ S. , GREENWOOD B. , HUMPHRIES T. J. 
Published: October 2003

BackgroundThis study examined the dose–response effects of the new proton‐pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro‐oesophageal reflux disease.MethodsThis study had a single‐centre, double‐blind, randomized, two‐way crossover design. Twenty patients were treated for two 7‐day periods separated by a 7–10‐day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24‐hour ambulatory pH monitoring. Acid‐reflux time was defined as the percentage of time over 24 h that oesophageal pH was <4. A dosage was considered effective if reflux time was reduced to <6%, a number which has been our internal laboratory reference.ResultsBoth rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting> 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side‐effects for either dosage.ConclusionsPathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well‐tolerated in this short‐term study.
Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats
Authors: DAVIES N. M. , SHARKEY K. A. , ASFAHA S. , MACNAUGHTON W. K. , WALLACE J. L. 
Published: October 2003

Background:Cyclo‐oxygenase‐1 (COX‐1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo‐oxygenase‐2 (COX‐2) is induced at sites of inflammation. Little is known about the regulation of COX‐2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX‐1 and COX‐2 expression shortly after administration of NSAIDs or ethanol.Methods:Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT‐PCR of COX‐1 and COX‐2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.Results:Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX‐2 mRNA expression and a marked increase in COX‐2 immunoreactivity, particularly in the superficial mucosa. Expression of COX‐1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre‐treatment with prostaglandin E2 prevented the induction of COX‐2 by aspirin. Salicylate and indomethacin caused modest increases in COX‐2 immunoreactivity but no change in COX‐2 mRNA. Neither concentration of ethanol affected COX‐2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.Conclusions:These results demonstrate a rapid up‐regulation of COX‐2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.
Absence of gaseous symptoms during ingestion of commercial fibre preparations
Authors: ZUMARRAGA L. , LEVITT M. D. , SUAREZ F. 
Published: October 2003

Background:While fibre is believed to cause gaseous symptoms, a study in healthy volunteers showed no increase in flatulence when the diet was supplemented with fermentable (psyllium) or non‐fermentable (methylcellulose) fibre. However, extrapolation of this observation to subjects who use fibre is arguable since these individuals may have a propensity to gaseousness. In the present study, gaseous complaints during fibre ingestion were assessed in subjects who believed that a previous exposure to fibre induced gas.Methods:In a double‐blind protocol, subjects were randomized to one of four treatment periods, during which the regular diet was supplemented for 1‐week periods with two daily doses of: placebo 10 g, psyllium 3.4 g, methylcellulose 2 g or lactulose 5 g. A symptom diary was maintained for 1‐week periods on or off treatment.Results:During treatment, the lactulose group passed gas significantly more often than did the psyllium or the methylcellulose group (P=0.01). No other symptom was significantly different among the treatment groups.Conclusions:(1) psyllium and methylcellulose did not cause greater gaseous symptomatology than did placebo in subjects who believed that these preparations caused gas; and (2) subjects commonly misidentify dietary components that cause gaseous symptoms.
Use of a novel electronic data collection system in multicenter studies of irritable bowel syndrome
Authors: HARDING J. P. , HAMM L. R. , EHSANULLAH R. S. B. , HEATH A. T. , SORRELLS S. C. , HAW J. , DUKES G. E. , WOLFE S. G. , MANGEL A. W. , NORTHCUTT A. R. 
Published: October 2003

Background:The reliability of symptom data collected during efficacy studies in irritable bowel syndrome (IBS) is paramount to the proper assessment of potential therapeutic agents. Historically, data have been collected on paper diary cards, which patients were requested to fill out at a specified interval. However, with paper diary cards it is not possible to determine whether the cards are filled out as required, or at random times. To circumvent this problem, a novel electronic data collection system that ensures the reliability and security of data entry was used.Methods:Data were collected from 640 patients during the 2‐week screening and 12‐week treatment phases of two multicentre trials of IBS. The electronic data collection system used was based upon a touchtone telephone system.Results:The electronic data collection system had a potential 8135 up‐time hours during the study. An up‐time of 8040 h and down‐time of 95 h was observed. This corresponds to an up‐time of approximately 99%. Patient compliance for data entry in the two studies was 81% and 83%, respectively. On a single random day during their daily telephone call, patients were asked questions to assess satisfaction with the system. On aggregate, 79% of patients were satisfied or very satisfied with the system, only 10% were dissatisfied or very dissatisfied.Conclusion:A unique electronic data collection system was tested for use in clinical studies in IBS. This system provided 100% reliability as to the date of data entry, and data were not subject to modification once entered. This methodology represents a marked advancement in clinical studies of IBS.
Oral budesonide therapy for steroid‐dependent ulcerative colitis: a pilot trial
Authors: KELLER R. , STOLL R. , FOERSTER E. C. , GUTSCHE N. , DOMSCHKE W. 
Published: October 2003

Background:Budesonide, a corticosteroid with high topical anti‐inflammatory activity and low systemic activity, has been shown to prolong time to relapse in Crohn's disease. In the present study, the efficacy of budesonide in an oral pH‐modified‐release formulation was evaluated for maintenance treatment in patients with steroid‐dependent ulcerative colitis.Methods:Fourteen patients with steroid‐dependent ulcerative colitis in the reduction phase of conventional glucocorticosteroids (c‐GCS) following a severe attack, were treated with budesonide 3 mg t.d.s. for 6 months. The primary investigation parameters were changes in the clinical activity index (CAI) and in the daily dose of c‐GCS.Results:In 11 cases the CAI improved significantly and treatment with c‐GCS could be terminated. Three patients experienced relapse and needed further c‐GCS treatment. The average daily dose of c‐GCS and the average value of the CAI before treatment with budesonide were significantly higher in the relapse group than in the remission group.Conclusions:In patients with c‐GCS‐dependent ulcerative colitis, a dose of 9 mg budesonide daily in an oral pH‐modified‐release formulation was well tolerated, significantly decreased the CAI, and rendered c‐GCS unnecessary in the majority of cases.
Intragastric pH after oral administration of single doses of ranitidine effervescent tablets, omeprazole capsules and famotidine fast‐dissolving tablets to fasting healthy volunteers
Authors: HEDENSTRÖM H. , ALM C. , KRAFT M. , GRAHNÉN A. 
Published: October 2003

Background:The therapeutic effect of drugs inhibiting acid production on acid‐related discomforts is related to both the onset and duration of action of the drug. The effects on gastric pH by single oral doses of some acid‐inhibiting drugs were investigated by measuring daytime (morning to lunch) intragastric pH in healthy volunteers.Methods:This randomized, single‐dose, 4‐way crossover study included 15 healthy fasting subjects. Effervescent ranitidine tablets 150 and 300 mg, fast‐dissolving famotidine tablets 20 mg and capsules of omeprazole 20 mg were administered. Measurements of intragastric pH were performed every 4 s for 10 min prior to drug administration and during the following 4 h.Results:The effervescent ranitidine tablets (150 or 300 mg) produced similar changes in intragastric pH: following an immediate increase to about pH 5, intragastric pH decreased slightly over the next 10–20 min. Thereafter pH increased steadily, reaching pH 4 after 20–40 min and pH 6 after about 70 min. After famotidine, pH 4 was reached after 80 min, significantly slower than ranitidine. After omeprazole, pH 3 was never reached. Ranitidine 150 and 300 mg showed significantly larger integrated pH responses over the 4‐h observation period, compared to famotidine (P=0.0288 and 0.0074) or omeprazole (P < 0.001).Conclusions:After single‐dose administration to healthy fasting volunteers), ranitidine effervescent tablets showed a significantly more rapid onset of action and a significantly larger integrated pH response compared to either famotidine 20 mg fast‐dissolving tablets or omeprazole 20 mg capsules.
Interaction of an aluminium–magnesium containing antacid and gastric mucus: possible contribution to the cytoprotective function of antacids
Authors: GRÜBEL P. , BHASKAR K. R. , CAVE D. R. , GARIK P. , STANLEY H. E. , LAMONT J. T. 
Published: October 2003

Background: Antacids are generally thought to protect the gastric mucosa from damage primarily by their ability to neutralize hydrochloric acid, but recently other mechanisms of antacid cytoprotection have been suggested. The aim of our study was to determine if the antacid hydrotalcit (Mg6Al2(OH)16CO3×4H2O) and its clinical formulations Talcid (suspension and tablet) can influence the acid barrier properties of pig gastric mucus (PGM). Methods: Viscosities, flow patterns of injected HCl, and permeability to HCl were assayed in solutions of PGM with and without added antacid. Results: Talcid‐suspension markedly increased mucin viscosity between pH 2 and 7. In contrast, powdered Talcid‐tablet and hydrotalcit noticeably reduced mucin viscosity at pH 5 and below. HCl barely diffused through PGM‐Talcid‐suspension, whereas the acid was able to quickly penetrate a PGM‐Talcid‐tablet powder or PGM‐hydrotalcit mixture. When injected into a mixture of PGM‐Talcid‐suspension, HCl travelled in a single distinct channel whereas in both PGM‐Talcid‐tablet powder or PGM‐hydrotalcit mixtures, the acid mixed irregularly throughout. Experiments with antacids alone revealed that Talcid‐suspension, but not Talcid‐tablet nor hydrotalcit, had barrier properties similar to PGM. Conclusion: Talcid‐suspension has viscoelastic features similar to gastric mucin and may afford mucosal protection by its ability to maintain or mimic the barrier properties of gastric mucus gel. In contrast, powdered Talcid‐tablets and hydrotalcit reduce the barrier function of gastric mucus.
Prevention of heartburn relapse by low‐dose famotidine: a test meal model for duration of symptom control
Authors: MANN S. G. , COTTRELL J. , MURAKAMI A. , STAUFFER L. , RAO A. N. 
Published: October 2003

Aim: To establish whether patients taking famotidine 10 mg to treat an episode of heartburn were protected from a recurrence of symptoms after a subsequent test meal. Methods: Frequent heartburn sufferers (n=366) were randomized to receive double blind treatment with famotidine 10 mg or 2×250 mg chewable alginate tablets within 30 min of a spontaneous episode of heartburn. After 4 h, patients with no or slight residual symptoms consumed a meal likely to induce heartburn. Over the next 4 h patients recorded the severity of heartburn and any consumption of ‘rescue’ antacids. At the end of this time they rated the global efficacy of their treatment in controlling meal‐induced symptoms. Results: Study groups were well matched for all baseline characteristics. Of the 366 randomized patients, 276 took study medication and data from 269 patients (132 famotidine, 137 alginate) were analysed for efficacy. Compared to the alginate control group famotidine treated patients reported better global efficacy following the test meal (P<0.001; relative odds for a more favourable response: 2.26 [95% CI: 1.45–3.53]). Fewer patients receiving famotidine resorted to antacid rescue (P = 0.038; relative odds for a more favourable response: 2.24 [95% CI: 1.04–4.79]) and peak heartburn was significantly less severe with famotidine treatment (P<0.001; relative odds for a more favourable response: 2.90 [95% CI: 1.85–4.53]). Eleven famotidine‐treated patients (8%) and 13 alginate patients (9%) reported adverse events. Conclusion: Compared to patients receiving an alginate preparation, patients self medicating with famotidine 10 mg for heartburn are better protected against a recurrence of their symptoms when they next eat. This suggests that the duration of acid control (9 h) previously demonstrated with this dose translates into a similar duration of measurable symptom control during the day.