Objective-To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients.Design-Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks.Setting-Multicentre outpatient study at secondary referral centres in five European countries.Patients-297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal antiinflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial.Interventions-Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal antiinflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion.End point-Frequency of gastric and duodenal ulceration or lesions, or both.Measurements and main results-The cumulative incidence of peptic ulceration by eight weeks was 10-3% (27/263); 2 out of 135 (1-5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency ofgastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by four weeks, this difference was not evident by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection.Conclusions-Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.

In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.

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.

To assess the effect of 4 weeks' therapy with ranitidine 150 mg twice daily on the healing of symptomatic NSAID-associated gastric and duodenal ulcers, 149 arthritic patients were randomly allocated to one of three treatment groups: ranitidine with NSAID continued, ranitidine with NSAID discontinued, and placebo with NSAID discontinued. The healing frequency in patients with gastric ulceration was 67, 68 and 47%, and in those with duodenal ulceration 61, 81 and 42%, respectively. Only the difference between the duodenal ulcer healing rates for ranitidine with NSAID discontinued and placebo was statistically significant (P = 0.02). Healing rates were uninfluenced by gender, age, smoking habits, alcohol consumption, ulcer frequency or size, arthritic disease, or participating country.

Tandamine hydrochloride, a thiopyranoindole, was more active than desmethylimipramine in inhibiting the tyramine pressor response after single oral doses in human volunteers. When compared with a placebo, tandamine was found to possess significant anticholinergic activity, to reduce appetite and to produce sedation. Compared with clomipramine, it caused a smaller inhibition of 5-HT but a more marked inhibition of dopamine uptake into human platelets. Further clinical and pharmacological studies with tandamine may help to elucidate the respective roles of different monoamines in depression, sedation and appetite.