Effect of bepridil in patients with chronic stable angina: results of a multicenter trial

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.     

Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables

A multivariate Cox regression analysis with time-dependent variables has been performed on the data of 415 patients with cirrhosis included in a controlled clinical trial of 10-15 mg prednisone daily versus placebo. The analysis showed that a poor prognosis was associated with a low prothrombin index, marked ascites, GI bleeding, high age, high daily alcohol consumption, high bilirubin and alkaline phosphatase and low albumin values, little liver connective tissue inflammation, and poor nutritional status. Prothrombin index and ascites showed significant interaction with the treatment in such a manner that high prothrombin index and absence of ascites were associated with a beneficial effect of prednisone, whereas low prothrombin index and presence of ascites were associated with a harmful effect of prednisone treatment. The final model was validated in independent patients by comparing their actual survival with that predicted from the model, using a split-sample testing technique. The prognostic factors were combined with an index that can be used to update prognosis whenever changes occur in the clinical status of a patient during the course of the disease. The probability of surviving the next 3 or 6 months can be estimated from the prognostic index at any time during the course. The index may be of value for the correct timing of special therapeutic procedures such as liver transplantation.     

Cardiovascular effects of coffee and caffeine

This study evaluated the cardiovascular effects and elimination kinetics of coffee and caffeine in 54 volunteers selected according to 3 gradations of daily caffeine consumption, cigarette smoking status and the presence of caffeine intolerance. After 24 hours of caffeine abstinence, subjects received coffee and 2.2 mg/kg of caffeine (equivalent to 2 cups of coffee). Blood pressure, heart rate, systolic time intervals and plasma concentrations of caffeine were measured before and at timed intervals after coffee and caffeine. There were no differences in response to coffee and caffeine. The average systolic/diastolic blood pressure increased 9/10 mm Hg. The maximal decrease in heart rate averaged 10 beats/min, and there were small increases in the systolic time intervals. There were no cardiovascular differences among the various groups. Caffeine in the smokers and heavy caffeine users had a shorter half-life (3.2 and 4.1 hours) than that in nonsmokers and nonusers (5.1 and 5.3 hours). In the caffeine-intolerant group it had a longer half-life, while the cardiovascular effects were similar to those of the other groups. Thus, irrespective of the amount of daily caffeine consumption, smoking status or caffeine intolerance, the cardiovascular responses were similar and tolerance, if present, was gone by 24 hours.     

Intravenous insulin decreases urinary albumin excretion in long-term diabetics with nephropathy

Summary The effect of intravenous injection of insulin on heart rate, plasma noradrenaline and urinary excretion rates of albumin and beta-2-microglobulin was examined in 10 long-term diabetics, 5 of whom had albuminuria. — In patients without albuminuria intravenous injection of insulin resulted in changes similar to but less pronounced than those previously observed in short-term diabetics: albumin excretion, plasma noradrenaline and heart rate increased, creatinine excretion decreased significantly. —Intravenous injection of insulin increased heart rate but not plasma noradrenaline in long-term diabetics with albuminuria. Arterial blood pressure did not change after insulin. Contrary to expectation insulin decreased urinary albumin excretion (from 418 to 312 g/min, 27 per cent) in these patients. There was a marked decrease in urinary excretion rates of beta-2-microglobulin and creatinine (55 and 17 per cent, respectively) after insulin. — The decrease in albumin excretion after insulin in diabetics with albuminuria is most likely due to renal vasoconstriction. The absence of a rise in albumin excretion after insulin may be due to severe morphological changes in glomeruli in these patients.     

Cellular and humoral immune responses in a population from the Baringo District, Kenya to Leishmania promastigote lipophosphoglycan.

In a cross-sectional house-to-house study in a leishmaniasis-endemic area in Kenya, the cellular and humoral immune response to Leishmania lipophosphoglycan (LPG) was determined. Clinical data, peripheral blood mononuclear cells, and plasma were obtained from 50 individuals over the age of eight years. Lymphoproliferation and interferon-gamma (IFN-gamma) production by these cells were examined. It was shown that cells from all six individuals in the population with a history of kala-azar responded to LPG in the lymphocyte proliferation assay, and four of these six responded in the IFN-gamma assay. In contrast, cells from 12 of 44 individuals from the study area with no history of kala-azar and none of the five Danish control samples responded to LPG. Antibodies against LPG were detected by enzyme-linked immunosorbent assay in 45 of 50 plasma samples. Our findings clearly show that mononuclear cells from kala-azar patients cured of infection were able to respond to the LPG preparation. The finding of a specific cellular immune response to LPG in 12 of 44 individuals with no history of kala-azar is consistent with previous epidemiologic studies, in which it has been shown that a proportion of L. donovani infections run a subclinical course. The high frequency of individuals with antibodies against LPG might indicate that a majority of the population had been exposed to the parasite.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Danish 1905 cohort: a genetic-epidemiological nationwide survey

OBJECTIVES. The authors studied nonagenarians, a rapidly growing age group whose cognitive and physical abilities have yet to be investigated systematically. METHODS. All Danes born in 1905 were invited to participate in a home-based 2-hour multidimensional interview, including cognitive and physical performance tests and collection of DNA, carried out by lay interviewers. Population-based registers were used to evaluate representativeness. RESULTS. There were 2,262 participants. A total of 1,632 (72%) gave a DNA sample. Participants and nonparticipants were highly comparable with regard to marital status, institutionalization, and hospitalization patterns, but men and rural area residents were more likely to participate. Six months after the survey began, 7.2% of the participants and 11.8% of the nonparticipants had died. DISCUSSION. Despite the known difficulties of conducting surveys among the extremely old, it was possible to conduct a nationwide survey, including collection of DNA, among more than 2,000 fairly nonselected nonagenarians using lay interviewers.     

Leishmania mexicana complex: human infections in the Republic of Panama

Parasites of the genus Leishmania responsible for human cutaneous leishmaniasis in the New World form 2 major taxonomic divisions: the Leishmania braziliensis and the L. mexicana complexes. We report the isolation and characterization of the L. mexicana complex among humans in the Republic of Panama. Characterization was based on parasite morphology, pathogenesis in infected golden hamsters, cellulose acetate isoenzyme electrophoretic mobilities, and membrane-specific monoclonal antibodies using the radioimmune binding assay technique.