Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program

An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis.     

Youth characteristics and contextual variables influencing physical activity in young adolescents of parents with premature coronary heart disease

This study examined influences on physical activity of young adolescents whose parents have premature coronary heart disease (CHD). Consistent with Bronfenbrenner's theory, the influences examined were personal characteristics of the subjects and selected contextual variables (peers, family, and community). Subjects were 113 youths, aged 11 to 14, 53% boys, 73% Caucasian, all with parents with premature CHD. Children were most likely to be active if their fathers were active, and those living in the coastal region were less likely to be active than other children. Peer influence interacted with both pubertal status and geographic region in its effect on children's activity. Children were more active when they had active peers only when the youth were midpubertal or when they were in the coastal region. Results emphasize the importance of nursing interventions to influence behaviors of these vulnerable children.     

Cost-effectiveness of Chlamydia Vaccination Programs for Young Women

We explored potential cost-effectiveness of a chlamydia vaccine for young women in the United States by using a compartmental heterosexual transmission model. We tracked health outcomes (acute infections and sequelae measured in quality-adjusted life-years [QALYs]) and determined incremental cost-effectiveness ratios (ICERs) over a 50-year analytic horizon. We assessed vaccination of 14-year-old girls and catch-up vaccination for 15–24-year-old women in the context of an existing chlamydia screening program and assumed 2 prevaccination prevalences of 3.2% by main analysis and 3.7% by additional analysis. Estimated ICERs of vaccinating 14-year-old girls were $35,300/QALY by main analysis and $16,200/QALY by additional analysis compared with only screening. Catch-up vaccination for 15–24-year-old women resulted in estimated ICERs of $53,200/QALY by main analysis and $26,300/QALY by additional analysis. The ICER was most sensitive to prevaccination prevalence for women, followed by cost of vaccination, duration of vaccine-conferred immunity, and vaccine efficacy. Our results suggest that a successful chlamydia vaccine could be cost-effective.     

False-positive transcarinal needle aspirate in the evaluation of bronchogenic carcinoma

Advances in the staging of regional mediastinal lymph node metastases from lung carcinoma include transcarinal needle aspiration. However, since most clinicians feel that documented tumor involvement of subcarinal nodes is a strong contraindication to aggressive surgical resection, a falsely positive carinal aspirate could deny a patient potentially curative resectional surgery. Herein, we present a case of a falsely positive transcarinal needle aspirate in which resectional surgery was carried out with a subsequent 34-month disease-free state.