Publications

Allogeneic HSCT is the most reliable, robust, and effective cell-based biotherapy currently available to pediatric and adult patients with hematologic malignancies. The central role of donor-derived lymphocytes in mediating an effective antitumor effect, preventing and controlling opportunistic infections, and causing GVHD is well documented in animal experiments and human trials. The profound lymphopenia after conditioning regimens coupled with molecular tools to distinguish host versus donor cells provides investigators a window into immune recovery after allogeneic HSCT. Serial analyses of T cell subsets linking immunophenotype with function have revealed the kinetics of donor-derived T cell recovery after allografting and provided insights into ways the immune system can be manipulated to augment the graft-versus-tumor (GVT) effect without inducing GVHD. As this review demonstrates, investigators are not limited to being passive observers of this immune reconstitution; rather, we have an opportunity to shape the allografted T cells repertoire to selectively augment immune function.

OBJECTIVE

To examine the independent effects of race or ethnicity and insurance status on use of tubal sterilization rates.

METHODS

This study used cross-sectional data collected by the 2002 National Survey of Family Growth. The survey is designed to represent women and men aged 15-44 years in the household population of the United States. Our main outcome measure was tubal sterilization at any time before interview. A multivariable logistic regression model was used to estimate the effects of race or ethnicity and insurance status on rates of tubal sterilization after adjusting for important confounders.

RESULTS

The sample consisted of 7,643 women: 66% were white, 15% were Hispanic, and 14% were African American; 68% had private insurance and 32% had public or no insurance. After adjusting for age, insurance status, parity, income, education, marital status, and religion, African-American women were more likely than white women to undergo tubal sterilization (adjusted odds ratio 1.43, 95% confidence interval 1.08-1.88). After adjusting for age, race or ethnicity, parity, income, education, marital status, and religion, women with public or no insurance were more likely to undergo sterilization compared with women with private insurance (adjusted odds ratio 1.38, 95% confidence interval 1.09-1.74).

CONCLUSION

African-American women and women with no or public insurance were more likely to have undergone tubal sterilization compared with white women and women with private insurance, respectively. Additional research to identify factors that influence women's decision to undergo sterilization is warranted.

LEVEL OF EVIDENCE

II.

OBJECTIVE

This study was undertaken to assess the acceptability of levonorgestrel emergency contraception (EC).

STUDY DESIGN

We examined attitudes and use patterns among 1950 women in a randomized trial evaluating access to EC through advance provision, pharmacies, or clinics.

RESULTS

Most women considered EC to be safe (92%) and effective (98%). Compared with women with clinic access, women with direct pharmacy access were no more likely to use EC within 24 hours (odds ratio [OR] = 1.65, 95% CI = 0.82-3.30) or to report it very convenient (OR = 1.41, 95% CI = 0.77-2.56). However, women with advance provisions were more likely to use EC promptly (OR = 2.43, 95% CI = 1.24-4.80) and report high convenience (OR = 4.25, 95% CI = 2.32-7.76). Advance provision increased use by all women, whereas pharmacy access increased use only among condom users. Inconvenience and fear of side effects were common reasons for nonuse.

CONCLUSION

Women viewed EC favorably. Advance provision improved promptness and convenience of use overall, while pharmacy access benefited specific populations.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death, seems to be increasing in worldwide prevalence, and carries with it a significant health and economic burden. Smoking cessation is the only available intervention proven to halt disease progression. The authors discuss the role of the newly approved agent, varenicline, in promotion of smoking cessation. The remainder of presently available therapies treat the symptoms of COPD, but do not impact progression of disease. As the understanding of the pathogenesis of COPD improves, new targets for therapies are emerging. Given the large number of potential targets and the results of recent studies, it seems unlikely that a single new agent will result in a cure. Rather, management of COPD should involve a multi-pronged approach including smoking cessation, bronchodilators, treatment of infection, and eventual targeting of inflammatory pathways and genetic predispositions. In this article, the authors discuss presently available therapies as well as agents under development.

Fractionation of cytosolic sphingosine kinase (SKase) activity by gel filtration chromatography gave rise to a 96-kDa peak that contained only the SK2 form of SKase (by Western analysis) and a broad ca. 46 kDa peak that contained only SK1 forms. SK2 appeared to have a bound accessory protein. When tested with the classic SKase inhibitor dimethylsphingosine (DMS), SK1 was extensively inhibited; however, SK2 was not inhibited but unexpectedly was activated. Activation of SK2 was the result of DMS enhancing the affinity of the enzyme for sphingosine, and, at low concentrations of ATP and sphingosine, activated by more than 100%. Activation of SK2 could be demonstrated in the cytosolic fraction indicating it was unrelated to the purification step. The immunomodulator FTY720 also activated SK2 (although to a lesser extent), but was a potent inhibitor of SK1. SK2 from rat liver and spleen was also not inhibited by DMS. L-Sphingosine and to a lesser extent dihydrosphingosine and phytosphingosine were effective inhibitors of both forms.