Publications

Immune responses to Mycobacterium tuberculosis are only partially effective; they drive the bacteria into a latent state, but rarely eliminate them. Unfortunately, the latent state of M. tuberculosis is reversible, and reactivation tuberculosis is the source of most transmission. Studies in animal models and in humans have not yet yielded a comprehensive picture of the mechanisms or correlates of immunity to M. tuberculosis infection, or of why immunity fails to eradicate the pathogen. This Review proposes that there are distinct stages in the immune response to M. tuberculosis that form an 'immunological life cycle'. It is hoped that this thesis will provide a framework for investigation to understand immunity to M. tuberculosis and to guide tuberculosis vaccine discovery and development.

CONTEXT

PTH therapy improves bone mineral density (BMD) and decreases fractures in postmenopausal osteoporosis, but cost and the burden of daily injections limit its use.

OBJECTIVE

We evaluated two novel approaches to the use of 6 months of PTH therapy over 2 yr.

DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS

We conducted a randomized, double-blinded trial of two combinations of daily PTH(1-84) and monthly ibandronate in 44 postmenopausal women with low bone mass. Participants received either 6 months of concurrent PTH and ibandronate, followed by 18 months of ibandronate (concurrent) or two sequential courses of 3 months of PTH followed by 9 months of ibandronate (sequential) over 2 yr.

MAIN OUTCOME MEASURES

Bone turnover markers were measured. Areal and volumetric BMD were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography, respectively.

RESULTS

Over 2 yr, areal BMD at the spine and hip increased similarly in both groups, with 7.5 and 8.2% increases in spine BMD in the concurrent and sequential arms, respectively (difference -0.6%, 95% confidence interval=-3.4-2.1%). Volumetric BMD also increased similarly between groups. With concurrent therapy, mean N-propeptide of type I collagen increased 75% between baseline and month 1 and then declined. With sequential therapy, the second 3-month PTH course increased N-propeptide of type I collagen markedly (209%), although to a lesser absolute degree than the first.

CONCLUSIONS

Six months of PTH(1-84), used over 2 yr with a bisphosphonate in either of our dosing regimens increased BMD substantially. Short PTH courses may provide the benefits of anabolic osteoporosis therapy with reduced burden for patients.

RATIONALE

Contamination by bacterial or fungal organisms reduces the effectiveness of mycobacterial culture for diagnosis of pulmonary tuberculosis (TB). We evaluated the effect of an anti-microbial and an anti-fungal oral rinse prior to expectoration on culture-contamination rates.

METHODS

We enrolled a consecutive random sample of adults with cough for ≥ 2 weeks and suspected TB admitted to Mulago Hospital (Kampala, Uganda) between October 2008 and June 2009. We randomly assigned patients to oral rinse (60 seconds with chlorhexidine followed by 60 seconds with nystatin) vs. no oral rinse prior to initial sputum collection. Uganda National Tuberculosis Reference Laboratory technicians blinded to the method of sputum collection (with or without oral rinse) processed all sputum specimens for smear microscopy (direct Ziehl-Neelsen) and mycobacterial culture (Lowenstein-Jensen media).

RESULTS

Of 220 patients enrolled, 177 (80%) were HIV-seropositive (median CD4-count 37 cells/uL, IQR 13-171 cells/uL). Baseline characteristics were similar between patients in the oral-rinse (N = 110) and no oral-rinse (N = 110) groups. The proportion of contaminated cultures was significantly lower in the oral-rinse group compared to the no oral-rinse group (4% vs. 15%, risk difference -11%, 95% CI -18 to -3%, p = 0.005). Oral rinse significantly reduced the proportion of contaminated cultures among HIV-infected patients (3% vs. 18%, risk difference -14%, 95% CI -23 to -6%, p = 0.002) but not HIV-uninfected (6% vs. 4%, risk difference 2%, 95% CI -12 to +15%, p = 0.81) patients. However, the proportion of smear-positive specimens (25% vs. 35%, p = 0.10) and culture-positive specimens (48% vs. 56%, p = 0.24) were lower in the oral-rinse compared to the no oral-rinse group, although the differences were not statistically significant.

CONCLUSIONS

Oral rinse prior to sputum expectoration is a promising strategy to reduce mycobacterial culture contamination in areas with high HIV prevalence, if strategies can be devised to reduce the adverse impact of oral rinse on smear- and culture-positivity.

It is now presumed that youth do not move directly from adolescence to adulthood, but rather pass through a transitional period, "emerging adulthood." The Revised Inventory of the Dimensions of Emerging Adulthood (IDEA-R) is a self-report instrument developed to examine the attributes of this period. "At-risk" youth appear to enter emerging adulthood developmental tasks at a slightly earlier age than general population youth. In the present study, a 21-item version of the IDEA was administered to a sample of 1676 "at-risk" continuation (alternative) high school students in Southern California. Principal component factor analysis with orthogonal rotation revealed three factors the authors labeled "Identity Exploration," "Experimentation/Possibilities," and "Independence." Overall, the measure demonstrated high internal consistency. Construct validity analyses indicated that the measure was correlated with demographics, risk behaviors, and psychological measures. The authors conclude that the IDEA-R is a useful instrument for measuring emerging adulthood in at-risk populations.