Publications

We evaluated the association between kidney dysfunction and sudden cardiac death risk among ambulatory women with coronary heart disease. The Heart and Estrogen Replacement Study evaluated the effects of hormone treatment on cardiovascular events among 2763 postmenopausal women with coronary heart disease. Kidney dysfunction was categorized by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation. Multivariate proportional hazards models were used to adjust for cardiovascular risk factors, congestive heart failure, and myocardial infarction. At baseline, 37% (n=1027) had an eGFR of >60 mL/min, 54% (n=1503) had an eGFR of 40 to 60 mL/min, and 8% (n=230) had an eGFR of <40 mL/min. During the 6.8-year follow-up period, there were 136 adjudicated sudden cardiac deaths. The rate of sudden cardiac death was higher in those with lower kidney function (0.5% per year among those with an eGFR >60; 0.6% per year with an eGFR between 40 and 60; and 1.7% per year with an eGFR <40 mL/min; P for trend <0.001). After multivariate analysis with baseline risk factors, eGFR at 40 to 60 mL/min was not a significant predictor, but eGFR at <40 mL/min remained strongly associated with sudden cardiac death (hazard ratio: 3.2; 95% CI: 1.9 to 5.3); adjustment for incident congestive heart failure and myocardial infarction during follow-up diminished this association (hazard ratio: 2.3; 95% CI: 1.3 to 3.9), suggesting that congestive heart failure and myocardial infarction mediated only part of the association between kidney dysfunction and sudden cardiac death. Advanced kidney dysfunction is an independent predictor of sudden cardiac death among women with coronary heart disease.

Macrophage recognition of Salmonella enterica serovar Typhimurium leads to a cascade of signaling events, including the activation of Src family and Syk kinases and the production of reactive oxygen species (ROS), which are critical for host innate defense during early stages of bacterial infection. ROS production depends on the NADPH oxidase, but little is known about the innate immune receptors and proximal adapters that regulate Salmonella-induced ROS. Herein, we demonstrate that serovar Typhimurium induces ROS through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12. This pathway is highly analogous to the pathways utilized by Fc receptors and integrins to regulate ROS production. Oral infection of mice with serovar Typhimurium demonstrates that the DAP12-dependent pathway regulates cecal colonization during early stages of Salmonella infection. Thus, DAP12 is an important regulator of Salmonella-induced ROS production in macrophages, and TREM2 is essential for linking DAP12 to the innate response to serovar Typhimurium.

There are few studies of HIV risk behavior among men who have sex with men (MSM) in sub-Saharan Africa. We conducted a behavioral survey of MSM in peri-urban "township" communities in Gauteng province, South Africa. Between October 2004 and March 2005, 199 MSM completed an interviewer administered pen-and-paper standardized questionnaire. The sample was 94% black, 83% identified as gay, and 12% as bisexual. Among those reporting sex with other men in the prior six months (n = 147), 59% reported unprotected anal intercourse (UAI). Increased risk of UAI was associated with both regular drinking (adjusted odds ratio (OR) 4.1, 95% confidence interval (CI) 1.4, 12.6) regular drinking to intoxication (OR 2.6, 95% CI 1.0, 6.8), and reporting symptoms of rectal trauma resulting from anal intercourse (AI; OR 4.3, 95% CI 1.8, 10.4). Decreased risk of UAI was associated with the exclusive use of lubricants that are latex-compatible for AI (OR 0.3, 95% CI 0.1, 0.7). Township MSM in South Africa are at high risk of HIV infection. Targeted sexual health and risk reduction interventions that address the link between alcohol use and HIV risk are urgently needed.