Effect of mibefradil, a T-type calcium channel blocker, on morbidity and mortality in moderate to severe congestive heart failure: the MACH-1 study. Mortality Assessment in Congestive Heart Failure Trial.

BACKGROUND: Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. METHODS AND RESULTS: This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction <35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (alpha=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients (P=0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant (P=0.093). Treatment groups had similar cardiovascular mortality (P=0.246), cardiovascular morbidity/mortality (P=0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. CONCLUSIONS: When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.

Long-term antianginal and antiischemic effects of mibefradil, the novel T-type calcium channel blocker: a multicenter, double-blind, placebo-controlled, randomized comparison with sustained-release diltiazem.

This study compared the efficacy, safety, and tolerability of mibefradil to sustained-release diltiazem in patients with chronic stable angina pectoris. At week 12, statistically equivalent mean increases in exercise tolerance test (ETT) duration of > 1 minute were observed in both groups. Similar improvements in time to onset of angina and time to persistent 1 mm ST-segment depression were also observed with both drugs. Large reductions in heart rate, blood pressure, and rate-pressure product were observed at each stage of the ETT among patients treated with mibefradil. Each drug was associated with at least a 70% reduction from baseline in anginal frequency and nitroglycerin consumption. Patients maintained on mibefradil during the withdrawal period had significant increases in all three ETT variables at week 16 compared with placebo. The effectiveness of mibefradil is comparable with sustained-release diltiazem in treating chronic stable angina pectoris, although mibefradil provides greater reductions in heart rate and cardiac workload.

Corneal melting in a chronic alcoholic contact lens wearer.

PURPOSE: We report a case of bilateral keratitis in a 43-year-old alcoholic patient who wore soft daily wear contact lenses. METHODS: After consecutive negative cultures of corneal and conjunctival scrapings and after observing no improvement following antibiotic therapy, the patient was clinically diagnosed with vitamin A deficiency. RESULTS: After 20 days of treatment with vitamin A, the patient's cornea completely healed. Laboratory results confirmed the clinical diagnosis. CONCLUSIONS: When the ophthalmologist is confronted with corneal melting in a known alcoholic or drug-user, it is imperative to consider the possibility of vitamin A deficiency as a possible cause, especially in the contact lens wearer.

Infected right atrial thrombus: serious complication of intravenous fluid replacement catheter. A case report.

The authors report a case of infected right atrial thrombus as a complication of an IV fluid replacement catheter, the first case of its kind in the English literature. Previously, this entity has been reported as a complication of parenteral nutrition catheters.

Thrombolytic therapy for acute myocardial infarction after oral surgery.

Two cases of mild-to-moderate bleeding after thrombolytic streptokinase therapy are presented, and the treatment modalities are discussed. To the best of our knowledge, these are the first two cases reported in the medical and dental literature.

Prevalence of diabetes mellitus in Ethiopian immigrants.

The prevalence of diabetes mellitus among 445 new immigrant Ethiopian Jews was studied immediately after their arrival to Israel, and found to be 0.4%. This low prevalence could be attributed to their long trek accompanied by severe malnutrition which caused death to the old, weak and sick, leaving a selectively young and healthy population group.

Fatty acid composition of adipose tissue in Ethiopian immigrants: a prospective study during their first year in Israel.

We measured the subcutaneous adipose tissue fatty acid composition in 22 male Ethiopian Jews, aged 17-65, shortly after their immigration to Israel. These subjects showed a concentration of linoleic acid (17.8%), which was relatively low compared with Israeli levels, and a high concentration of palmitic acid (28.5%). The linoleic/saturated (P/S) ratio was 0.52. After 5 months, a repeat measurement indicated increases of the linoleic acid content and of the P/S ratio to 20.1% and 0.62, respectively (P less than 0.05). In another sample from the same immigrant group, levels after 1 year in Israel were 20.9% and 25.1% for linoleic and palmitic acid, respectively, and the P/S ratio was 0.67. These results differed significantly (P less than 0.02) from those obtained in the first sample after immigration. Apart from decreasing plasma triglyceride levels, no pattern of lipid changes was discernible in our limited samples. Changes in subcutaneous fatty acid composition reflect changes in diet over months, suggesting a decreased carbohydrate intake and in increased fat intake. It remains to be seen whether changing fatty acid composition in conjunction with changes in blood lipids or other factors, over a prolonged period of time, will affect the cardiovascular risk in the immigrants.

Blood pressure in Ethiopian immigrants: relationship to age and anthropometric factors, and changes during their first year in Israel.

Blood pressure was measured in 483 Ethiopian immigrants during the first week following their arrival in Israel. Mean levels of diastolic (DBP) and systolic blood pressures (SBP) were very low compared with known levels in the Israeli population. BPs were elevated in men greater than 20 years old and in women greater than 40 years old. Quetelet index averaged below 2.00 g/cm2. Considerable weight gains were observed in 265 individuals examined after 1 year. Simultaneously, DBP increased by 4 mm Hg on average, whereas the changes in SBP were small. At the end of 1 year, the mean SBP ranged from 107 (age 5-9 and 10-14) to 124 mm Hg (age greater than or equal to 60) and mean DBP from 69 (age 10-14 and 15-19) to 78 mm Hg (age greater than or equal to 60), remaining nevertheless considerably lower than levels observed in diverse Israeli population groups. Covariance analysis revealed that initial BPs, gender, age, and weight gain significantly affected SBP and DBP at the end of the year.

Central retinal-artery occlusion in a patient with circulating lupus anticoagulant.

The circulating lupus anticoagulant is a spontaneously acquired immunoglobulin that has been associated in vivo with an increased risk of thrombotic episodes. We describe the case of a young woman with central retinal-artery occlusion associated with circulating lupus anticoagulant in the absence of systemic lupus erythematosus or any other autoimmune or collagen vascular disease. In cases of central retinal-artery occlusion without apparent cause, the presence of the lupus anticoagulant should be excluded especially in cases that have been exposed to the human immunodeficiency virus.

Lipids and lipoproteins in new immigrant Ethiopian Jews in Israel.

In an investigation of lipid levels following a period of deprivation and prolonged travel, 206 male and 272 female Ethiopian Jewish immigrants to Israel were evaluated at the end of 1984. This ethnic group, most of whom are lean persons who had apparently consumed a high simple carbohydrate diet, revealed distinct (cross-sectionally evaluated) age and sex patterns of lipid distribution. Total cholesterol in the Ethiopians resembled that in Israeli-born adolescents or adult resident Israelis at ages 8 years through 20-29 years, but mean levels were considerably lower in Ethiopians at ages 30-39 years through 60 years, where they do not exceed 175 mg/dl for males and 190 mg/dl for females. Mean triglyceride levels were higher for Ethiopian females than in Israeli females up to age range 40-49 years. While the levels in Israelis increase steadily with age, no clear age pattern was discernible in the levels in the Ethiopians (at least cross-sectionally). Among the Ethiopian males, levels were considerably higher than those among Israeli males in childhood and adolescence. In Ethiopian adults, the triglyceride levels appeared to be slightly lower than those in resident Israelis. The Ethiopian immigrants displayed markedly reduced high density cholesterol (38 mg/dl for males, 39 mg/dl for females) compared with levels of between 50 and 53 mg/dl for Israelis at age 8-9 years. These differences diminished with age, until, at around age 20-29 years, mean levels became comparable (around 42 mg/dl for males and 50 mg/dl for females) and remained so at older ages. The distinct lipid patterns in the Ethiopian Jewish immigrants to Israel are subject to ongoing follow-up to investigate the effect of a quasi-western diet and a western lifestyle on this ethnic group.

More rapid relief of pain with isosorbide dinitrate oral spray than with sublingual tablets in elderly patients with angina pectoris.

To evaluate the possibility of improving clinical practice in the treatment of angina pectoris, the duration of relief of pain with isosorbide dinitrate (ISDN) oral spray and sublingual tablets were compared in elderly patients with chronic stable angina pectoris. Nine patients (mean age 67 years) were studied in a randomized crossover trial. The patients underwent bicycle ergometry, which resulted in typical chest pain associated with electrocardiographic ST-segment depression in all 9. The patients received ISDN oral spray or sublingual tablets immediately on termination of exercise. At least 6 hours later another ergometry test was performed and the patients were crossed over to the other drug. ISDN spray relieved pain in all patients at a mean duration of 61.6 +/- 24.4 seconds after administration, whereas the duration of relief of pain by ISDN sublingual tablets was 112.4 +/- 70 seconds. The difference was highly significant (p less than 0.0005). It is concluded that clinical practice of treatment of angina pectoris in the elderly can be improved by using ISDN oral spray rather than sublingual tablets. The spray is effective at twice the rapidity of the sublingual tablet.