Mice were implanted subcutaneously with a pellet containing 0.5 mg estradiol or with a placebo. Eight to 12 days later platelet aggregation was produced in pial arterioles by injuring their endothelium in vivo with a noxious light/dye stimulus. The time between the onset of the noxious stimulus and the appearance of platelet aggregates was significantly shortened (p less than .02) by estradiol treatment in young (2 month old) mice. The same treatment had the opposite effect in 4-6 month old mice and significantly delayed the onset of aggregation (p = .01). When platelet rich plasma (PRP) was prepared, aggregation by sodium arachidonate was always inhibited in PRP from estradiol treated mice, irrespective of age. Estradiol treatment had no effect on aggregation induced ex vivo by ADP. Thus the enhanced aggregation observed in pial arterioles of young estradiol treated mice may not reflect direct effects of estradiol on the platelet itself. The data are discussed in light of the literature suggesting enhancement of ischemic vascular disease, including strokes, in patients receiving estrogens, and especially high doses of estrogens.

Adenosine Diphosphate↗

PubMedDate not supplied

Design and statistical issues in multicenter trials of severe head injury.

Multicenter clinical trials are the most powerful agent to evaluate new therapies in medicine, but have failed to impact traumatic brain injury, in which at least 20 such trials have been performed, without a positive result. Such trials need to be carefully planned, with a run-in period to ensure center compliance. Stratification, careful monitoring, adequate sample size, interim analysis and adequate numbers of patients per center are all vital requirements for a useful outcome in such trials.

Craniocerebral Trauma↗