Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association.

OBJECTIVE: To establish, in a single resource, up-to-date recommendations for primary care physicians regarding prevention strategies for a first stroke. PARTICIPANTS: Members of the National Stroke Association's (NSA's) Stroke Prevention Advisory Board and Cedars-Sinai Health System Department of Health Services Research convened on April 9, 1998, in an open meeting. The conference attendees, selected to participate by the NSA, were recognized experts in neurology (9), cardiology (2), family practice (1), nursing (1), physician assistant practices (1), and health services research (2). EVIDENCE: A literature review was carried out by the Department of Health Services Research, Cedars-Sinai Health System, Los Angeles, Calif, using the MEDLINE database search for 1990 through April 1998 and updated in November 1998. English-language guidelines, statements, meta-analyses, and overviews on prevention of a first stroke were reviewed. CONSENSUS PROCESS: At the meeting, members of the advisory board identified 6 important stroke risk factors (hypertension, myocardial infarction [MI], atrial fibrillation, diabetes mellitus, blood lipids, asymptomatic carotid artery stenosis), and 4 lifestyle factors (cigarette smoking, alcohol use, physical activity, diet). CONCLUSIONS: Several interventions that modify well-documented and treatable cardiovascular and cerebrovascular risk factors can reduce the risk of a first stroke. Good evidence for direct stroke reduction exists for hypertension treatment; using warfarin for patients after MI who have atrial fibrillation, decreased left ventricular ejection fraction, or left ventricular thrombus; using 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for patients after MI; using warfarin for patients with atrial fibrillation and specific risk factors; and performing carotid endarterectomy for patients with stenosis of at least 60%. Observational studies support the role of modifying lifestyle-related risk factors (eg, smoking, alcohol use, physical activity, diet) in stroke prevention. Measures to help patients improve adherence are an important component of a stroke prevention plan.

A randomized community trial to increase mammography utilization among low-income women living in public housing.

BACKGROUND: A randomized trial was conducted to evaluate the impact of a community-based intervention on mammography use among low-income women living in public housing. METHODS: All 41 public housing high-rise buildings were randomized to treatment and delayed treatment (control) conditions. After a cross-sectional baseline survey, an intervention called Friend to Friend was conducted in the treatment buildings by American Cancer Society and building resident volunteers. The intervention consisted of a health professional talk, small group discussions, and an opportunity to request assistance in obtaining a mammogram or mammogram reminder. A second cross-sectional survey was conducted to measure differences in screening rates between the study groups. RESULTS: Participation in the intervention averaged 27%. The study groups were equivalent at baseline. At follow-up, the proportion of women age 50-79 years who reported mammography screening in the previous 15 months was significantly higher in the treatment group (64%) than in the control group (52%). Breast cancer knowledge, attitudes, and beliefs did not differ between groups. CONCLUSIONS: These findings suggest that a multidimensional intervention which reaches women within their social environment and uses community volunteers can increase mammography utilization among women in public housing.

Peroxidase activation of 4-hydroxytamoxifen to free radicals detected by EPR spectroscopy.

4-Hydroxytamoxifen is a major metabolite of the antiestrogenic drug tamoxifen used in the treatment of women with breast cancer. 4-Hydroxytamoxifen is broken down by a horseradish peroxidase/H2O2 system very much more rapidly than tamoxifen and causes much greater DNA damage determined by 32P-postlabelling. EPR spin trapping of 4-hydroxytamoxifen reaction products in the presence of the free radical trap 5,5-dimethyl-1-pyrroline N-oxide, together with glutathione as a hydrogen donor, resulted in the generation of a species with the characteristics of the glutathione thiyl radical (aN approximately 15.3 G, aH approximately 16.2 G). Support for the creation of thiyl radicals comes from the close to stoichiometric time dependent formation of glutathione disulfide concomitant with the loss of glutathione. Similar results were obtained using 4-hydroxytoremifene but no radical formation or glutathione loss could be detected using 3-hydroxytamoxifen (droloxifene). On-line LC-ESI MS analysis of the incubation products from 4-hydroxytamoxifen has identified three products with a protonated molecular mass of 773, consistent with the formation of dimers of 4-hydroxytamoxifen. The role that radical mechanisms have in the carcinogenic effects of tamoxifen in the endometrium or other target organs of women taking this drug remains to be established.

Formation of C1' located sugar radicals from X-irradiated cytosine nucleosides and -tides in BeF2 glasses and frozen aqueous solutions.

Free radical formation in nucleosides and nucleotides containing cytosine as base was studied after X-irradiation at 77 K of samples prepared in frozen aqueous BeF2 glasses and in frozen aqueous solutions by means of electron spin resonance (ESR) spectroscopy. By comparison with radical patterns from the cytosine base and from 1-CH3-cytosine, by using specifically base-deuterated nucleosides and by comparison between the 2'-deoxy- and the ribonucleotide it could be demonstrated that a radical at the C1'-position of the sugar was formed in nucleosides and nucleotides in both matrices. Quantitative analysis showed that in the BeF2 glass an initial population of about 10% of substrate located species due to this radical was present at 77 K and developed to about 25% after decay of the .OH (.OD) radicals at about 140 K. This was taken as proof that at least part of these radicals were formed from .OH radicals. In frozen aqueous solutions about 20% of C1' located sugar radicals were found to be present at 77 K, the population remaining roughly constant with increasing temperature to 140 K. The mechanistic findings of these unexpected results are discussed in terms of mobile .OH radicals and/or hole transfer in the glass and in the glassy regions of the frozen aqueous solutions.

DNA in glasses at 77 K: high energy ionizing radiation versus UV electron ejection.

Most in the field of ionizing radiation damage to DNA in frozen aqueous solutions agree that two major types of radical ions are formed, i.e. G+/A+ and T-/C-. The main evidence stems from EPR and strand break studies. Fluid solutions exposed to laser light are known to give G+ and esolv- with low yields of single strand breaks. We have explored this contrast by photoionizing DNA solutions at 77 K, in the expectation that this would prevent the formation of esolv- and hence that the results might be similar to those for high energy radiation. They are not: the results show only the formation of G+ (or) (A+), the fate of the ejected electrons is unclear except for sodium perchlorate glasses when they react to give O-.