Publications

Certain ritonavir resistance mutations impair HIV infectivity through incomplete Gag processing by the mutant viral protease. Analysis of the mutant virus phenotype indicates that accumulation of capsid-spacer peptide 1 precursor protein in virus particles impairs HIV infectivity and that the protease mutant virus is arrested during the early postentry stage of HIV infection before proviral DNA synthesis. However, activation of the target cell can rescue this defect, implying that specific host factors expressed in activated cells can compensate for the defect in ritonavir-resistant HIV. This ability to rescue impaired HIV replication presented a unique opportunity to identify host factors involved in postentry HIV replication, and we designed a functional genetic screen so that expression of a given host factor extracted from activated T cells would lead directly to its discovery by rescuing mutant virus replication in nonactivated T cells. We identified the cellular heat shock protein 90 kDa α (cytosolic), class B member 1 (HSP90AB1) as a host factor that can rescue impaired replication of ritonavir-resistant HIV. Moreover, we show that pharmacologic inhibition of HSP90AB1 with 17-(allylamino)-17-demethoxygeldanamycin (tanespimycin) has potent in vitro anti-HIV activity and that ritonavir-resistant HIV is hypersensitive to the drug. These results suggest a possible role for HSP90AB1 in postentry HIV replication and may provide an attractive target for therapeutic intervention.

BACKGROUND

Enteral nutritional support is used in care for patients with head and neck cancer. This study describes the frequency and timing of gastrostomy tube placement and corresponding Medicare nutritional support claims in patients with head and neck cancer.

METHODS

Surveillance, Epidemiology, and End Results (SEER)-Medicare data for patients with head and neck cancer diagnosed from 2000 to 2005 were used in this descriptive study (N = 16,458).

RESULTS

In all, 35.1% of patients undergoing treatment had gastrostomy tubes placed; 16.9% had tubes placed before treatment, whereas 83.1% had them placed after treatment. Of those having tubes placed prior to treatment 23.7% had Medicare claims for nutritional support before treatment and 40.9% had claims after treatment began. A total of 35.4% of patients who had tubes placed before treatment and 35.5% who had tubes placed after treatment had no claims for nutritional support.

CONCLUSIONS

Future work is warranted to identify predictors and outcomes associated with provision and timing of enteral nutrition support for patients with head and neck cancer.

STUDY OBJECTIVE

To examine the effect of policies regarding access to emergency contraception (EC) on teens' promptness of EC use and satisfaction with EC access experience.

SETTING

Online survey.

PARTICIPANTS

Females, ages 14 to 19, who had engaged in unprotected intercourse at a time when they were aware of EC.

MAIN OUTCOME MEASURES

Outcomes included promptness of EC use and satisfaction with EC access experience. Outcomes were compared according to method of obtaining EC and state policies regarding EC access.

RESULTS

Surveys were completed by 531 teens from 49 states; 58% were Caucasian and 14% were African American. Only 48% of participants reported ever using EC. Teens who obtained EC without a prescription were more likely to use EC within 24 hours of unprotected intercourse (odds ratio = 2.17; 95% confidence interval: 1.06-4.44). Minors who obtained EC in pharmacist-access states were more likely to be satisfied with their EC access experience (odds ratio = 3.05; 95% confidence interval: 1.11-8.35).

CONCLUSION

Fewer than half of participants had used EC, despite being aware of EC at the time of unprotected intercourse. Policies allowing minors to access EC without a prescription may increase timely use of EC.

OBJECTIVE

Shortened telomere length has been associated with mortality in patients with coronary heart disease (CHD) and is considered as an emerging marker of biologic age. Whether depression is associated with telomere length or trajectory has not been evaluated in patients with CHD.

METHODS

In a prospective cohort study, we measured leukocyte telomere length in 952 participants with stable CHD at baseline and in 608 of these participants after 5 years of follow-up. The presence of major depressive disorder in the past month was assessed using the computerized diagnostic interview schedule at baseline. We used linear and logistic regression models to evaluate the association of depression with baseline and 5-year change in leukocyte telomere length.

RESULTS

Of the 952 participants, 206 (22%) had major depression at baseline. After the adjustment for age and sex, the patients with current major depressive disorder had shorter baseline telomere length than those without depression (mean [standard error] = 0.86 [0.02] versus 0.90 [0.01]; p = .02). This association was similar (but no longer statistically significant) after adjustment for body mass index, smoking, diabetes, left ventricular ejection fraction, statin use, antidepressant use, physical inactivity, and anxiety (0.85 [0.02] versus 0.89 [0.01], p = .06). Depression was not predictive of 5-year change in telomere length after adjustment for the mentioned covariates and baseline telomere length.

CONCLUSIONS

Depression is associated with reduced leukocyte telomere length in patients with CHD but does not predict 5-year change in telomere length. Future research is necessary to elucidate the potential mechanisms underlying the association between depression and telomere length.