P-selectin Expression Tracks Cerebral Atrophy in Mexican-Americans.

BACKGROUND AND PURPOSE: We hypothesized that the P-selectin (SELP) gene, localized to a region on chromosome 1q24, pleiotropically contributes to increased blood pressure and cerebral atrophy. We tested this hypothesis by performing genetic correlation analyses for 13 mRNA gene expression measures from P-selectin and 11 other genes located in 1q24 region and three magnetic resonance imaging derived indices of cerebral integrity. METHODS: The subject pool consisted of 369 (219F; aged 28-85, average = 47.1 ± 12.7 years) normally aging, community-dwelling members of large extended Mexican-American families. Genetic correlation analysis decomposed phenotypic correlation coefficients into genetic and environmental components among 13 leukocyte-based mRNA gene expressions and three whole-brain and regional measurements of cerebral integrity: cortical gray matter thickness, fractional anisotropy of cerebral white matter, and the volume of hyperintensive WM lesions. RESULTS: From the 13 gene expressions, significant phenotypic correlations were only found for the P- and L-selectin expression levels. Increases in P-selectin expression levels tracked with decline in cerebral integrity while the opposite trend was observed for L-selectin expression. The correlations for the P-selectin expression were driven by shared genetic factors, while the correlations with L-selectin expression were due to shared environmental effects. CONCLUSION: This study demonstrated that P-selectin expression shared a significant variance with measurements of cerebral integrity and posits elevated P-selectin expression levels as a potential risk factor of hypertension-related cerebral atrophy.

Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.

Widespread HIV counseling and testing linked to a community-based tuberculosis control program in a high-risk population.

The aim of the work reported here was to evaluate community-wide screening for HIV infection that was linked to a tuberculosis control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cité Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and tuberculosis. All of the screened subjects were offered post-test HIV counseling. Those with active tuberculosis received treatment, while those with latent tuberculosis and HIV infection were offered an opportunity to participate in a trial of antituberculosis chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cité Soleil. HIV infection was detected in 1,629 (15.4%) and active tuberculosis in 242 (2.3%). Latent M. tuberculosis infection was found in 4,800 (67.5%) of 7,309 community residents who completed tuberculosis screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection found in this screened population, as compared to other groups undergoing HIV screening in the same community, suggests that people at high risk for HIV infection selectively sought or accepted tuberculosis clinic screening. Also, many people with active tuberculosis were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, the results indicate that community-based screening for HIV infection within a tuberculosis control program can result in effective targeting of screening for both infections.

PIP: Findings are reported from an evaluation of community-wide screening for HIV infection linked to a tuberculosis (TB) control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cite Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and TB. All screened subjects were offered post-test HIV counseling. Those with active TB received treatment, while those with latent TB and HIV infection were offered an opportunity to participate in a trial of anti-TB chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cite Soleil. HIV infection was detected among 1629 (15.4%) and active TB in 242 (2.3%). Latent M. tuberculosis infection was found in 4800 (67.5%) of 7309 community residents who completed TB screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection in this screened population, compared to other groups screened in the same community, suggests that people at high risk for HIV infection selectively sought or accepted TB clinic screening. Also, many people with active TB were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, these results indicate that community-based screening for HIV infection within a TB control program can result in the effective targeting of screening for both infections.

School achievement and absence in children with chronic health conditions.

Families of 270 children with chronic health conditions observed in 11 subspecialty clinics at a tertiary care center were surveyed to assess the relation of demographic and health variables to school achievement and absenteeism. National achievement test scores and school days absent were compared with North Carolina state results. The mean days absent for children with chronic health conditions was 16 days, compared with the state average of less than 7 days, during the 1981-1982 academic year. The mean national achievement score for the chronically ill children was at the 51st percentile, compared with the 63rd percentile for the state's sixth graders. Log of school days absent was correlated with the number of clinic visits, physician rating of activity limitations, sex, and specific health conditions (R2 = 0.17, P = 0.001). National achievement scores were mainly related to socioeconomic factors and specific health conditions (R2 = 0.44, P = 0.001), but were unrelated to school absence. Children with spina bifida, sickle cell disease, or epilepsy, and children with the added burden of low socioeconomic status, were at particular risk for poor school achievement.