PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk.

BACKGROUND AND AIMS: Habitual physical activity is understood to help prevent type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects on both metabolism and the vascular system. However, individuals do not have uniform cardiometabolic responses to physical activity. Here we explore the extent to which variation in the proliferator-activated receptor-alpha (PPARα) gene, which modulates carbohydrate and lipid metabolism, vascular function, and inflammation, predicts the overall cardiometabolic risk (CMR) profile of individuals engaging in various levels of physical activity. METHODS AND RESULTS: 917 unrelated, community volunteers (52% female, of Non-Hispanic European ancestry) aged 30-54 years, participated in the cross-sectional study. Subjects were genotyped for 5 single nucleotide polymorphisms in the PPARα gene, from which common haplotypes were defined. A continuous measure of CMR was calculated as an aggregate of 5 traditional risk factors: waist circumference, resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose. Regression models were used to examine the main and interactive effects of physical activity and genetic variation on CMR. One common PPARα haplotype (H-23) was associated with a higher CMR. This association was moderated by daily physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased physical activity was associated with a steeper reduction of CMR in persons carrying the otherwise detrimental H-23 haplotype. CONCLUSIONS: Variations in the PPARα gene appear to magnify the cardiometabolic benefits of habitual physical activity.

Efficacy and tolerability of once-daily oral therapy with telithromycin compared with trovafloxacin for the treatment of community-acquired pneumonia in adults.

A randomised, double-blind study of adults with community-acquired pneumonia (CAP) resulted in clinical cure rates of 90.0% for telithromycin and 94.2% for trovafloxacin. Bacteriological eradication rates were also comparable for both treatments. All high-risk patients (i.e. > or = 65 years old [n=25], Pneumonia Severity Index score > or = 111 [n=16], pneumococcal bacteraemia [n=4]) were clinically cured. In infections caused by Mycoplasma pneumoniae and Chlamydophila (Chlamydia) pneumoniae, clinical cure rates were 93.3% (14/15) for telithromycin and 100% (16/16) for trovafloxacin. Possibly drug-related, treatment-emergent adverse events (TEAEs) were considered mild and occurred in 47.2% of telithromycin and 33.0% of trovafloxacin patients. The most frequently reported, possibly drug-related, TEAEs were diarrhoea and nausea for telithromycin and diarrhoea and headache for trovafloxacin. Serious TEAEs occurred in 1.9% of telithromycin and 1.8% of trovafloxacin subjects and were considered not drug related. No deaths occurred during the study. Telithromycin and trovafloxacin were safe and comparable in efficacy in these patients with CAP.

Once-daily oral gatifloxacin versus oral levofloxacin in treatment of uncomplicated skin and soft tissue infections: double-blind, multicenter, randomized study.

This was a double-blind, multicenter study in which 410 adults (> or =18 years of age) with uncomplicated skin and soft tissue infections (SSTIs) were randomized to receive either 400 mg of gatifloxacin orally once daily or 500 mg of levofloxacin orally once daily for 7 to 10 days. The study protocol called for four assessments-before and during treatment, at the end of treatment, and posttreatment. Efficacy evaluations included clinical response and bacterial eradication rates. Of 407 treated patients, 202 (108 women, 94 men) received gatifloxacin and 205 (111 women, 94 men) received levofloxacin. For clinically evaluable patients, the cure rates were 91% for gatifloxacin and 84% for levofloxacin (95% confidence interval [CI] for the difference, -2.0 to 15.2%). Clinical cure rates for microbiologically evaluable patients were 93% for gatifloxacin and 88% for levofloxacin (95% CI for the difference, -6.5 to 16.8%). The bacterial eradication rate was 92% for each group, with gatifloxacin eradicating 93% of the methicillin-susceptible Staphylococcus aureus isolates and levofloxacin eradicating 91% of them. Both drugs were well tolerated. Most of the adverse events were mild to moderate, and nausea was the most common adverse event in each treatment arm. Once-daily oral gatifloxacin (400 mg) is clinically efficacious and well tolerated compared with once-daily levofloxacin (500 mg) for the treatment of patients with uncomplicated SSTIs.

Blood pressure recovery curves after submaximal exercise. A predictor of hypertension at ten-year follow-up.

The purpose of this study is to examine the usefulness of blood pressure recovery curves after submaximal exercise in apparently normotensive young adults as an early predictor for hypertension. Twenty-six college age males in 1977, with normal blood pressures at rest, were given the Harvard Step Test and postexercise blood pressures were recorded. Criteria were set that differentiated a hypertensive from a normotensive response to exercise. In 1987, these individuals were contacted regarding their blood pressure status. Nine out of ten subjects who demonstrated a hypertensive response to exercise in 1977, now have been given the diagnosis of hypertension. Eleven out of twelve subjects who demonstrated a normotensive response to exercise in 1977, now are still considered to be normotensive. A proposed hypothesis is that during the course of this disease, exercise can unmask hypertension in subjects who have the potential for developing hypertension but currently have a normal resting blood pressure.