Publications

Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite, Brugia malayi. Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS-/- mice or in eosinophil recruitment. We also found that ICOS was not required for the differentiation of alternatively activated macrophages (AAMPhi) that express Ym1 and Fizz1. Although the production of IgE was slightly reduced in ICOS-/- mice, this was not as significant as in CD28-/- mice. In contrast to live infection, the primary response of ICOS-/- mice immunized with soluble B. malayi antigen and complete Freund's adjuvant resulted in significantly fewer IL-4-producing cells in the lymph nodes. As previously reported, we observed a defect in antibody isotype switching toward the IgG1 isotype in ICOS-/- mice during live infection. Interestingly, there was a significant enhancement of parasite-specific IgG3 isotype antibodies. CD28-/- and MHC class II-/- mice also had enhanced parasite-specific IgG3 isotype antibodies. Our results suggest that ICOS is not required to maintain a chronic cellular Th2 response. The primary role of ICOS in a chronic helminth infection could be to drive antibodies toward type 2 isotypes. T-independent antibody response to the parasite could be enhanced in the absence of costimulation and T cell help.

BACKGROUND

Physical inactivity, poor diet, excessive alcohol consumption, and smoking are modifiable risk factors associated with development of chronic diseases. Although the prevalence of diseases associated with these detrimental lifestyle behaviors is high among women in the United States, they may not receive adequate counseling from physicians.

METHODS

To predict physicians' lifestyle counseling practices, we assessed personal, professional, and health behavior characteristics from responses to a self-administered survey of breast cancer risk reduction practices. Subjects were California physicians identified through AMA Masterfile, in family practice, internal medicine, or obstetrics/gynecology, who were asked to report the percentages of women patients they counseled on physical activity, diet, alcohol, and smoking.

RESULTS

Of 1647 eligible physicians, 822 (50.0%) responded. Fifty-six percent reported counseling at least 75% of patients about physical activity, 54.6% about diet, and 44.8% about alcohol. More than three quarters (78.7%) counseled at least 75% of patients about smoking. In logistic regression analyses, woman gender, family practice, and internal medicine specialties emerged as significant predictors of counseling for all lifestyle behaviors. Older age was associated with dietary and alcohol counseling. Race/ethnicity was associated only with smoking counseling, and country of medical school was associated with counseling for physical activity and smoking. Sources of new medical knowledge emerged as predictors for all types of counseling, whereas physicians' own level of physical activity only predicted counseling about physical activity.

CONCLUSIONS

Physicians' personal, professional, practice, and health behavior characteristics were associated with reported lifestyle counseling of women patients. Results reveal important directions for future physician-based interventions to improve counseling.

Despite their huge health toll, substance abuse disorders remain underappreciated and underfunded. Reasons include stigma, tolerance of personal choices, acceptance of youthful experimentation, pessimism about treatment efficacy, fragmented and weak leadership, powerful tobacco and alcohol industries, underinvestment in research, and difficult patients. Positive signs include declining prevalence rates, successful counter-marketing campaigns, changing public attitudes, new scientific discoveries that could yield new treatments, and effective new organizations. Further progress will require better treatment, more research, better education of health professionals, more nongovernmental support, and stronger leadership. Policy changes regarding each of the three substance groups are indicated, as are reforms in the criminal justice and educational systems.