The control-of-consumption approach to alcohol abuse prevention. I. A reconceptualization

The single-distribution theory of alcohol consumption and the derived prevention strategy, the control-of-consumption approach, are conceptualized as three probabilistic relationships between four variables, collectively called "the Ledermann string": availability, average consumption, proportion of heavy drinkers, and prevalence of damage. This conceptualization suggests four different intervention strategies, only one of which is seriously considered by advocates of the single-distribution theory: restrictions on availability. A companion article reviews the scientific literature on the relationships of the Ledermann string.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery

BACKGROUND: Our aim was to study the pharmacokinetics and pain scores following administration of single oral doses of either diclofenac or high-dose acetaminophen (paracetamol). METHODS: In the morning, the day after tonsillectomy, children 5-15 years of age were randomized in a double-blind manner to receive either diclofenac 1-2 mg.kg-1 (n=11) or acetaminophen 22.5 mg.kg-1 (n=10). Postoperative pain was assessed by self-report and blood samples were drawn every 30 min for 4 h after medication. RESULTS: Large interindividual differences in maximum plasma diclofenac concentrations (Cmax) were found. Mean Cmax was 2.4+/-1.3 microg.ml-1 and mean tmax was 2+/-0.5 h. No significant reduction in pain score with diclofenac was seen at any of the assessments during the study period. Eight of 10 children achieved Cmax of acetaminophen within the 10-20 microg.ml-1 antipyretic range. Mean tabs was 0.7+/-0.3 h and mean Cmax and tmax were 12.7+/-3.8 microg ml-1 and 1.4+/-0.5 h, respectively. No significant reduction in pain score with acetaminophen was seen at any of the assessments during the study period. CONCLUSIONS: The achieved concentrations of diclofenac and acetaminophen were not able to significantly reduce the children's pain score during the 5 h postingestion study period. Analgesic plasma acetaminophen concentrations may be higher than those required for antipyresis.     

Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

Objectives. We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. Design. Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. Results. Eight pigs died and seven were excluded due to mediastinal infection (n = 2) or failure to produce MR (n = 5). Thus, 28 pigs were included and were divided into three groups: controls (n = 12), mild MR (mMR; n = 10), and moderate to severe MR (sMR; n = 6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. Conclusions. A new model for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.