Biomedical subjects

Richard Clark

Publications and source records attributed to Richard Clark.

22 records · Page 2Linked to original sources

PubMed2002

The secretory synapse: the secrets of a serial killer.

Cytotoxic T lymphocytes (CTLs) destroy their targets by a process involving secretion of specialized granules. The interactions between CTLs and target can be very brief; nevertheless, adhesion and signaling proteins segregate into an immunological synapse. Secretion occurs in a specialized secretory domain. Use of live and fixed cell microscopy allows this secretory synapse to be visualized both temporally and spatially. The combined use of confocal and electron microscopy has produced some surprising findings, which suggest that the secretory synapse may be important both in delivering the lethal hit and in facilitating membrane transfer from target to CTL. Studies on the secretory synapse in wild-type and mutant CTLs have been used to identify proteins involved in secretion. Further clues as to the signals required for secretion are emerging from comparisons of inhibitory and activating synapses formed by natural killer cells.

Animals↗

PubMed2002

Emergency department use among the homeless and marginally housed: results from a community-based study.

OBJECTIVES: This study examined factors associated with emergency department use among homeless and marginally housed persons. METHODS: Interviews were conducted with 2578 homeless and marginally housed persons, and factors associated with different patterns of emergency department use were assessed in multivariate models. RESULTS: Findings showed that 40.4% of respondents had 1 or more emergency department encounters in the previous year; 7.9% exhibited high rates of use (more than 3 visits) and accounted for 54.5% of all visits. Factors associated with high use rates included less stable housing, victimization, arrests, physical and mental illness, and substance abuse. Predisposing and need factors appeared to drive emergency department use. CONCLUSIONS: Efforts to reduce emergency department use among the homeless should be targeted toward addressing underlying risk factors among those exhibiting high rates of use.

Adult↗

PubMedDate not supplied

Measuring adherence to antiretroviral therapy in a diverse population using a visual analogue scale.

PURPOSE: To examine the performance of an instrument to assess adherence based on a visual analogue scale, compared to an instrument based on 3-day recall, using unannounced pill counts in the place of residence as the gold standard. METHOD: We prospectively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco, California, with three adherence assessments over no more than 4 months. RESULTS: Mean adherence using the visual analogue scale, 3-day recall, and unannounced pill count methods were 82.5%, 84.2%, and 75.9%, respectively. The correlation between visual analogue scale and unannounced pill count was high (r = 0.76) and was not statistically different from that between 3-day recall and unannounced pill count (r = 0.71; p =.52). Both methods were also similarly inversely correlated with HIV viral load (r = -0.49 and -0.34, respectively; p =.22 for the difference in the correlations). The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all subpopulations examined. CONCLUSION: A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population. Given its simplicity, the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care.

Anti-HIV Agents↗

PubMedDate not supplied

Higher rates of viral suppression with nonnucleoside reverse transcriptase inhibitors compared to single protease inhibitors are not explained by better adherence.

BACKGROUND: Although evidence suggests that antiretroviral (ARV) regimens containing nonnucleoside reverse transcriptase inhibitors (NNRTIs) are superior to single-protease inhibitor (PI)-based regimens at suppressing viral load, it is unclear how much of the improved viral suppression is due to intrinsic drug potency versus higher levels of adherence to simpler regimens. We therefore examined adherence and viral suppression in NNRTI and single-PI regimens in a cohort of largely ARV-experienced participants by using objective measures of adherence. METHOD: Participants were recruited from the Research on Access to Care in the Homeless (REACH) Cohort and were included in the study if they were on single-PI-based or NNRTI-based highly active antiretroviral therapy (HAART) regimens for at least 3 months prior to study entry. Adherence was measured by unannounced pill counts at the participant's usual place of residence. The primary outcome was suppression of HIV viral RNA to <50 copies/mL. RESULTS: Among 109 individuals who were followed for a median of 8.7 months, the odds of virologic suppression were approximately 8 times higher (p < .01) for participants on NNRTI-based regimens (n = 53) compared with those using single-PI-based regimens (n = 56) when controlling for adherence, as well as other potential confounders in a multivariable analysis. The only other independent predictors of viral suppression in multivariable modeling were ARV adherence (p < .01), CD4 nadir (p = .02), and continuous months on current regimen prior to the start of adherence monitoring (p < .01). There was no significant difference in adherence by unannounced pill counts in participants receiving NNRTI- versus single-PI-containing regimens. CONCLUSION: A higher proportion of individuals using NNRTI-based regimens had viral suppression when compared to those taking single-PI-containing regimens, and this association was not confounded by higher levels of adherence. These results suggest that improved viral suppression on NNRTI regimens compared to single-PI regimens is more closely associated with regimen potency than higher levels of adherence.

Adult↗