In-vitro activity of dapsone and two potentiators against Mycobacterium avium complex

The efficacy of dapsone against Mycobacterium avium, M. intracellulare, M. kansasii, M. fortuitum and M. tuberculosis was determined by disc elution in agar. The minimal inhibitory concentration at which 90% of the colony forming units were inhibited (90MIC) by dapsone was 8 mg/l for M. avium, M. intracellulare and M. kansasii and greater than or equal to 32 mg/l for M. tuberculosis and M. fortuitum. The 90MICs were confirmed by culturing these test organisms with dapsone in the BACTEC 460 system. Reduction of the 90MIC from 8 mg/l to 2 mg/l was observed by combining dapsone with either or both of the potentiators tested. The dapsone-potentiator combinations had no effect on the bacteria with 90MICs of greater than or equal to 32 mg/l. The clinical relevance of this drug combination against M. avium complex infections remains to be evaluated.     

Cigarette yield and the risk of myocardial infarction in smokers

BACKGROUND: Although cigarette smoking is a major risk factor for acute myocardial infarction (MI), cigarette tar yield has not been clearly demonstrated to affect MI risk. METHODS: A case-control study of first MI in smokers aged 30 through 65 years was conducted among 68 hospitals in an 8-county area during a 28-month period. Case subjects were smokers hospitalized at any of the area hospitals with a first MI. Approximately 4 community control smokers per case subject were randomly selected from the same geographic area using random digit dialing. Detailed data on smoking history and cigarette brand were collected. RESULTS: We identified 587 case subjects and 2685 controls who smoked cigarettes with known tar yields. After adjustment using multivariable logistic regression, the odds ratios (ORs) for subjects smoking medium- and high compared with low-tar-yield cigarettes were 1.86 (95% confidence interval [CI], 1.21-2.87) and 2.21 (95% CI, 1.47-3.34), respectively. The adjusted OR increased as tar per day intake increased (P<.001 for the trend); compared with the lowest category of tar per day, the ORs (95% CIs) for increasing tar per day were 1.16 (0.83-1.62), 1.85 (1.35-2.52), 2.42 (1.54-3.78), and 2.50 (1.78-3.52). There was a similar trend of increasing ORs as tar per day increased in smokers of lower-yield cigarettes (P<.001 for the trend) and when low-yield cigarette smokers were excluded (P<.001 for the trend). CONCLUSIONS: Smoking higher-yield cigarettes is associated with an increased risk of MI, and there is a dose-response relationship between total tar consumption per day and MI.     

Surface and cytoskeletal events regulating leukocyte membrane topography

The experiments reviewed here establish that surface components and surface functions can assume predictable, asymmetric patterns within the continuous plasma membranes of mammalian leukocytes. Recent biophysical and morphological studies show that receptor redistribution can occur very rapidly and that a unique geometric association is maintained between moving receptors and surface geometry. Based on these experimental data, a new working model for surface topographical control has been proposed. Its essence is the entrainment of certain receptors and receptor complexes on membrane waves that are generated by microfilament-membrane interaction. Several pathological conditions associated directly or indirectly with cytoskeleton and membrane abnormalities have been described. The continued application of modern biochemical, immunologic, and biophysical techniques to probe the underlying defects should provide new insight into the mechanisms of leukocyte response to surface stimulation.     

Physicians’ preferences for active-controlled versus placebo-controlled trials of new antihypertensive drugs

OBJECTIVE: To evaluate physicians' preferences for referring patients to, and using information from, active-controlled trials (ACTs) versus placebo-controlled trials (PCTs) of new antihypertensive drugs. DESIGN AND SETTING: Nationwide mailed survey, with telephone contact of nonresponders to assess nonresponse bias. PARTICIPANTS: One thousand two hundred primary care physicians randomly selected from the American Medical Association's Master File. Of 1,154 physicians eligible to respond, 651 (56.4%) returned completed questionnaires. MEASUREMENTS AND MAIN RESULTS: We measured physicians' stated willingness to encourage hypertensive patients to enroll in ACTs and PCTs of new antihypertensive drugs, their views of the relative merits of ACTs versus PCTs, their stated willingness to prescribe new drugs tested in ACTs or PCTs, and their views regarding the overall justifiability of the 2 designs. Physicians were significantly more likely to indicate they would encourage their patients to enroll in ACTs than in PCTs (P <.0001). Physicians thought ACTs provided more valuable information for their practices, were more likely to lead to a public health benefit, offered enrolled patients greater opportunity for personal benefit, and were less likely to expose enrolled patients to unnecessary risks (all P <.0001). Physicians were more likely to prescribe new drugs that had been compared in ACTs (P <.0001), and viewed ACTs as a more justifiable method for testing new antihypertensive drugs (P <.0001). There was no evidence of nonresponse bias for these main results. CONCLUSIONS: Although PCTs remain the standard method for testing new antihypertensive drugs, physicians strongly prefer ACTs. Using ACTs to test new antihypertensive drugs may enhance the efficiency of patient recruitment and more strongly influence physicians' prescribing practices.