Antianginal effect of isosorbide dinitrate spray in patients with exercise-induced stable angina.

Ten patients with stable exercise-induced angina took part in this study. Isosorbide dinitrate and placebo sprays were administered in a double-blind, randomized crossover study. The dose of isosorbide dinitrate given was two squirts (= 2.5 mg) 2 min before testing. When taken before exercise it significantly improved (p less than 0.014) exercise tolerance. Significant (p less than 0.0005) ischaemic changes in the electrocardiogram also occurred. These effects occurred later than with placebo. Exercise time was prolonged with the active drug. The results of this study show that isosorbide dinitrate spray improves the exercise tolerance of patients with ischaemic heart disease.

Piroxicam capsules versus suppositories: a pharmacokinetic and clinical trial.

15 patients with rheumatoid arthritis or osteoarthritis received a single dose (20 mg) piroxicam (Felden) as suppository. Serum piroxicam concentrations were assayed by fluorometry 1, 2, 4, and 8 h after the installation of the suppository, the mean values being 1.3, 1.9, 1.8, and 1.8 mg/l, respectively. Then the patients continued on oral piroxicam 20 mg daily for maximum 3 weeks, and serum piroxicam levels (mean 6.3 mg/l) were checked at the end of this period. Nine patients then continued on piroxicam suppositories 20 mg daily for one week, and serum piroxicam levels (mean 4.5 mg/l) were again assayed at the end of this maintenance. Pain at rest, pain on motion, and joint movement restriction were scored on day 1, after oral maintenance, and after rectal maintenance. Reduced scores were found with time, but the only statistically significant effect was in the overall subjective pain relief measured after oral maintenance. Rectal irritation was recorded in one patient. It is concluded that a) absorption of piroxicam from suppository was adequate, b) it was possible to maintain adequate serum piroxicam levels by repeated administration of suppository for one week, and c) the gastrointestinal toleration was acceptable in these patients selected for showing poor tolerance towards other nonsteroidal antiinflammatories.

Prazosin enhances the antihypertensive effects of beta-blockers during isometric and dynamic exercise.

Eighteen hypertensive (WHO I-II) outpatients volunteering for an open comparative cross-over trial were treated with the non-selective beta-blocker sotalol (80 mg b.i.d.) the beta-selective atenolol (50 mg b.i.d.) alone and each in combination with prazosin (3-5 mg b.i.d.) for 4 to 8 weeks each in balanced order. The blood pressure (BP) and heart rate (HR) were measured sitting and standing as well as during relatively heavy dynamic (ergometer) and isometric (sustained handgrip) exercises. The four-week treatment with sotalol lowered the HR without much influence on the BP. Atenolol similarly lowered the HR but was somewhat more active on the BP. Both beta-blockers failed to modify the pressor responses to exercise significantly. The addition of prazosin to beta-blockers improved their efficacy. Lowered BP values were recorded during dynamic and even isometric work, partly due to lowered baseline BP levels. The side effects were generally mild, and no excessive hypotension was encountered. The results suggest that the antihypertensive combination of the vasodilator, prazosin, with moderate doses of beta-blockers may be valuable in helping patients to maintain lower blood pressures during daily physical stress.

Chronic antral gastritis, Lewis(a+) phenotype, and male sex as factors in predicting coexisting duodenal ulcer.

Chronic antral gastritis, Lewis(a+) phenotype (Le(a+)), and male sex are common in patients with peptic ulcer. To approximate the relative risks (RR) and possible interactions of these factors in predicting coexisting active duodenal (DU) or gastric ulcer (GU), a consecutive endoscopic series of 140 ulcer patients and 215 non-ulcer controls was examined. The Lea phenotype (Le(a+) versus Le(a-)) was determined immunohistochemically as binding of Le(a)+-specific monoclonal antibody to surface epithelial secretory mucosubstances in gastric biopsy specimens. The presence versus absence of the gastritis was determined histologically from antral specimens. The RRs of the factors in the prediction of ulcer were approximated as age-adjusted RRs when the risk of ulcer in the absence of the factors--that is, in the absence of gastritis, in female sex and in Le(a-) phenotype--was applied as a base line (RR = 1). A case-control design, logistic linear modelling, and the maximal likelihood method were used in estimation of the risks. The RR of coexisting distal ulcer (DU or pyloric or prepyloric GU) was increased in the presence of gastritis (RR = 10.2), in male sex (RR = 3.0), and in Le(a+) phenotype (RR = 1.8). The RR of proximal ulcer (angular or corpus GU) was increased in the presence of gastritis (RR = 35) but decreased in the presence of male sex (RR = 0.5) and Le(a+) phenotype (RR = 0.7). As predictors of both distal and proximal ulcer, gastritis, sex, and Le(a) phenotype were independent of each other; that is, their joint value in prediction of ulcer is a multiplicand of the marginal risks. Thus, a 50-fold difference in the joint RR could be approximated between the extreme risk groups for distal ulcer--that is, between Le(a+) males with gastritis and Le(-a) females with normal antrum. In a consecutive series of outpatient endoscopies, 45% of females and 8% of males could be categorized to these extreme 'low'- and 'high'-risk groups, respectively. We conclude that sex, Le(a) phenotype, and gastritis are factors that, at least in ordinary outpatient endoscopy material, divide subjects to subgroups with very different risks and probabilities for having coexisting peptic ulcer.

Chronic gastritis and gastroduodenal ulcer: a case control study on risk of coexisting duodenal or gastric ulcer in patients with gastritis.

Chronic (atrophic) gastritis (AG) is common in active duodenal (DU) and gastric ulcer (GU) disease. In this case control study in consecutive prospective outpatients (571 cases and 1074 controls) who had undergone diagnostic upper gastrointestinal endoscopy and routine biopsies from both antral and body mucosa, we calculated the risk of coexisting active DU and/or GU in different gastritis of the antrum or body and according to grade (superficial gastritis, mild, moderate or severe atrophic gastritis). The risk of coexisting active gastroduodenal ulcer (ulcer in duodenum and/or stomach), as well as the risk of DU or GU, was dependent upon the presence and grade of gastritis in antrum and body mucosa. The risk of coexisting ulcer, as expressed as an age adjusted relative risk (RR) and calculated as odds ratio of gastritis in cases and controls, was significantly increased in the presence of superficial antral and body gastritis (RR = 8.5 (7.0-20.0) in men; RR = 5.8 (3.3-10.2) in women), as compared with the risk of ulcer in subjects with histologically normal mucosa (RR = 1). The risk of ulcer, and the risk of GU in particular, increased further with increasing severity of antral gastritis. In such patients with moderate or severe atrophic antral gastritis the RR of coexisting ulcer even exceeded 20 in men and 10 in women (RR = 25.6 (9.0-72.7) in men; RR = 11.7 (5.9-23.0) in women). On the other hand, the RR of ulcer, and the RR of DU in particular, was below 1 in the presence of atrophic gastritis in the gastric body, irrespective of the grade of gastritis in the antrum. We conclude that the type and grade of gastritis strongly predicts the risk of coexisting peptic ulcer, and that the risk of coexisting DU or GU increases with an increase in grade of AG of the antrum but decreases with an increase in grade of AG of the gastric body.

Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients.

The new angiotensin-converting enzyme (ACE) inhibitor fosinopril was compared with the ACE inhibitor enalapril in a multicenter (n = 11), multinational (Denmark, Finland, Iceland, Norway, and Sweden), double-blind, randomized, parallel-group 24-week study in 195 patients with mild to moderate essential hypertension [supine diastolic blood pressure, (SDBP) > or = 95 to < or = 110 mm Hg]. After discontinuing all previous antihypertensive medication, patients were entered into a placebo lead-in period of 4-6 weeks, followed by 24 weeks of randomized treatment with the active compounds administered with a double-dummy technique. The dose of fosinopril was 20 mg, which could be increased to 40 mg after 8 weeks (average 25.6 mg); that of enalapril was 10 mg, which could be increased to 20 mg after 8 weeks (average 12.9 mg). Hydrochlorothiazide 12.5 mg could be added after 16 weeks and was administered to 27% of the patients in the fosinopril group and to 30% in the enalapril group. All drugs were administered once daily. Supine systolic BP (SSBP) decreased from 157 to 143 mm Hg in the fosinopril group (p < 0.01), and from 159 to 147 mm Hg in the enalapril group (p < 0.01). SSDP decreased from 100 to 89 mm Hg in the fosinopril group (p < 0.01) and from 100 to 92 mm Hg in the enalapril group (p < 0.01). Throughout the study period, fosinopril reduced SSBP and SDBP numerically more than did enalapril, by 0-3 mm Hg. Adverse events (AE) caused withdrawal of study medication in 8 patients in the fosinopril group and in 14 patients in the enalapril group (NS). The number of reported AE was not statistically different in the two groups. Inhibition of the ACE was assessed in a subgroup of patients (n = 26, 13 in each group). Fosinopril caused a greater inhibition of ACE at the doses used in the present study, which was statistically significant. Both fosinopril and enalapril caused statistically significant reductions in BP of a similar magnitude, and both agents were well tolerated. However, fosinopril was consistently numerically slightly more effective than enalapril in reducing BP. There were fewer withdrawals due to AE (NS) in the fosinopril group, and the overall recorded AE were fewer in the fosinopril group (NS).