No abstract

Abacavir (1592U89) is a nucleoside inhibitor of human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT). Resistance to abacavir was studied with abacavir alone and with abacavir in combination with other nucleoside analogues in cell culture, in virus isolates from zidovudine/lamivudine clinical trials, and in the first dose-escalating 12-week clinical trial (CNA2001) to evaluate abacavir clinical potency. Abacavir alone in vitro selected for mutations at HIV RT codons K65R, L74V, Y115F, and M184V. However, abacavir combined with zidovudine selected against virus with the M184V mutation. Abacavir therapy in vivo resulted in large decreases in HIV load (>1 log), even in 1 subject who had the M184V mutation at baseline. A total of 51% of subjects showed new mutations at any of codons K65R, L74V, and M184V after abacavir monotherapy, compared with 11% who received zidovudine/abacavir. Small changes (2- to 4-fold) in abacavir susceptibility were detected. On stopping therapy, reselection of the pretherapy sequence occurred within 4 weeks.

Hypoxia worsens brain injury following trauma, but the mechanisms remain unclear. The purpose of this study was to determine the effect of traumatic brain injury (TBI) and secondary hypoxia (9% oxygen) on apoptosis-related protein expression, cell death, and behavior. Using a murine weight-drop model, TBI led to an early (6 h) increase followed by a later (24 h) decrease in neuronal apoptosis inhibitor protein (NAIP) expression in the olfactory and motor cortex; in contrast, TBI led to a sustained (6 h to 7 days) increase in NAIP in the striatum. The peak increase in the expression of NAIP (6-12 h) following TBI alone was delayed (1-7 days) when hypoxia was added to TBI. Hypoxia following TBI further depleted other apoptosis inhibitor proteins (IAPs) and activated caspases, as well as increased contusion size and worsened cell death. Hypoxia added to TBI also increased motor and feeding activity on days 2 and 4 compared to TBI alone. Hypoxia without TBI had no effect on the expression of IAPs or cell death. These findings show that IAPs have a potential role in the increased vulnerability of brain cells to hypoxia following TBI, and have implications for configuring future therapies for TBI.

Substance use is known to negatively impact outcomes in patients living with HIV by decreasing adherence to and effectiveness of antiretroviral therapies. Alcohol and other drug abuse and dependence are widespread among HIV-positive individuals, though reported rates vary greatly by study, suggesting the possibility of under-reporting. The extent to which patients minimize symptoms and the factors that influence reporting remain to be determined. The present study sought to gauge the degree to which substance use is under-reported in a primary care HIV clinic by evaluating the influence of anonymity versus confidentiality of self-report on endorsement rates. Patients (n=55) currently receiving medical treatment completed a confidential questionnaire assessing the presence of alcohol abuse, other drug misuse, and Generalized Anxiety Disorder (GAD). Another group of 55 patients completed a comparable survey, but did so anonymously. The two groups were similar in terms of demographic characteristics, but self-report of substance use differed depending on how symptoms were assessed, with anonymous questionnaires yielding significantly (p<.05) higher rates, compared to confidential surveys. Under-reporting appeared specific to alcohol and substance use, with no statistically significant differences between anonymous and confidential surveys in the proportion of patients endorsing symptoms of GAD. The fact that the screener specifically designed to identify patients in need of further evaluation produced lower rates of reported alcohol and drug use suggests that more work is needed to identify appropriate tools for accurately assessing substance use in HIV-positive patients so that adequate services and referrals can be offered to those in need.

Thirty‐six consecutively admitted psychiatric inpatients were orally administered the Beck and Zung depression scales. Wide Range Achievement Test reading scores also were obtained. The Beck and Zung correlated significantly (p 0.001) with Diagnostic and statistical manual of mental disorders (DSM‐III; American Psychiatric Association, 1980) depression criteria. When the patients were subdivided by diagnosis (Depression and mixed Depression vs. others), and depression scores compared, only the Zung significantly differentiated the two groups (F = 12.51, p <0.001). When subdivided by reading scores, both high (grade level M = 8.7) and low (grade level M = 3.2) groups' Beck and Zung scores correlated equally well with the DSM‐III criteria measure. This study substaintiated the common practice of orally presenting written tests to low functioning patients most convincingly in the case of the Zung Depression Scale.