D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism.

As the dopaminergic and GABAergic systems have been implicated in alcohol-related behaviors, variants of the D2 dopamine receptor (DRD2) and GABA(A) receptor beta3 subunit (GABRB3) genes were determined in a population-based association study of Caucasian non-alcoholic and alcoholic subjects. In severe alcoholics, compared to non-alcoholics, a significant increase was found in the prevalence (P = 1.7 x 10(-5)) and frequency (P = 1.6 x 10(-5)) of the DRD2 minor (A1) allele. Moreover, a significant progressive increase was observed in A1 allelic prevalence (P = 3.1 x 10(-6)) and frequency (P = 2.7 x 10(-6)) in the order of non-alcoholics, less severe and severe alcoholics. In severe alcoholics, compared to non-alcoholics, a significant decrease was found in the prevalence (P = 4.5 x 10(-3)) and frequency (P = 2.7 x 10(-2)) of the GABRB3 major (G1) allele. Furthermore, a significant progressive decrease was noted in G1 allelic prevalence (P = 2.4 x 10(-3)) and frequency (P = 1.9 x 10(-2)) in non-alcoholics, less severe and severe alcoholics, respectively. In sum, in the same population of non-alcoholics and alcoholics studied, variants of both the DRD2 and GABRB3 genes independently contribute to the risk for alcoholism, with the DRD2 variants revealing a stronger effect than the GABRB3 variants. However, when the DRD2 and the GABRB3 variants are combined, the risk for alcoholism is more robust than when these variants are considered separately.

African-American physicians and smoking cessation counseling.

While African American physicians can play a key role in encouraging black patients who smoke to quit, little is known about the views and activities of these physicians with respect to antitobacco programming. In the process of developing a protocol for encouraging physicians' smoking cessation intervention, 96 African-American physicians completed a survey indicating their knowledge, attitudes, and practices relating to stop smoking counseling. Few physicians reported patient help-seeking behavior and 47.9% cited lack of patient motivation as a key barrier to intervention. Only 46.8% believed that it is possible to accomplish a lot of cessation help in a few minutes time, and 34.4% believed that setting up and maintaining an office protocol would require a great deal of effort. Explaining health risks (71.9%) and enrolling patients in programs (66.6%) were perceived as keys to patient cessation; fewer than half of the physicians surveyed discuss specific strategies for quitting with their patients. Physicians indicated a willingness to offer more counseling in the future and were open to a range of strategies for learning more about effective approaches. Our findings support the need for dissemination of such information, particularly among specialists, to support antitobacco efforts among African-American physicians.

Pharmacokinetics in low dose extrapolation using animal cancer data.

Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.

Recruitment to a school-based adult smoking-cessation program: do gender and race/ethnicity make a difference?

BACKGROUND: Recruitment to interventional research, clinical trials, and community-based health programs remains a central public health challenge, particularly among low-income and multi-ethnic populations. Utilizing existing community institutions and "opportunistic" communication channels within these settings for recruitment seems an optimal strategy for overcoming barriers to participation. However, such institutions frequently serve heterogeneous populations, and little is known regarding intra-community variations in program uptake. METHODS: This paper reports the gender and race/ethnic differences in subject characteristics and enrollment patterns among 435 Latino and African American participants in a smoking-cessation program delivered through one such community institution, an inner-city school district in Los Angeles County. RESULTS: Enrollees were more likely to be female and Latino. Recruitment strategies tailored specifically to this program were more effective then recruitment through channels such as regular school activities, particularly among African Americans. CONCLUSIONS: Intragroup variations need to be carefully considered in the design and implementation of such programs if they are to receive acceptance and to succeed.

Stature loss following treatment for Wilms tumor.

BACKGROUND: The study was designed to estimate reduction in adult stature induced by megavoltage radiation therapy (RT) of the spine in children treated for Wilms tumor and to ascertain whether the dose reduction in successive National Wilms Tumor Study Group (NWTSG) trials has mitigated late effects of RT in these children. PROCEDURE: Effects of RT dose, age at treatment, and chemotherapy on stature of 2,778 children with Wilms or another solid tumor of the kidney were analyzed using statistical models accounting for the dependence of height on gender and advancing age. Model predictions were validated by descriptive analysis of heights measured at 17 to 18 years of age for 205 patients. RESULTS: Radiation-induced reductions below normal height depended on dose, portal size, and age at treatment and were not augmented by doxorubicin or cyclophosphamide. Younger children were more strongly affected. Predicted height deficit at age 18 years was 1.8 cm for a child treated with 10 Gy to the flank at age 4 years. Observed height deficits at age 1 7 to 18 years were 4.1 cm for 57 patients who received 15-24 Gy at a mean age of 55 months and zero for 16 children who received RT doses under 15 Gy at a mean age of 83 months. CONCLUSIONS: Reduction in stature following RT to the pediatric spine is dose- and age-dependent, persists into adulthood, and is not exacerbated by doxorubicin or cyclophosphamide. Average height deficits observed at maturity for children receiving doses currently recommended by the NWTSG are clinically nonsignificant.