Biomedical subjects

T Wolfson

Publications and source records attributed to T Wolfson.

11 recordsLinked to original sources

PubMed2004

A multimodal assessment of driving performance in HIV infection.

OBJECTIVE: To examine if HIV-seropositive (HIV+) individuals are at risk for impaired driving. METHODS: Sixty licensed drivers (40 HIV+, 20 HIV-) completed a neuropsychological (NP) test battery and driving assessments. Eleven HIV+ subjects were NP-impaired. Driving-related skills were assessed using 1) two driving simulations (examining accident avoidance and navigational abilities), 2) the Useful Field of View (UFOV) test, and 3) an on-road evaluation. RESULTS: HIV+ NP-impaired subjects had greater difficulty than cognitively intact subjects on all driving measures, whereas the HIV- and HIV+ NP-normal groups performed similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on Visual Processing and Divided Attention tasks but not in overall risk classification. They also had a higher number of simulator accidents (1.3 vs 2.0; p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2 blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs 36%; p = 0.02). Impairment in Executive Functioning was the strongest NP predictor of failing the on-road drive test. NP performance and both simulations independently contributed to a model predicting 48% of the variance in on-road performance. CONCLUSION: HIV+ NP-impaired individuals are at increased risk for on-road driving impairments, whereas HIV+ individuals with normal cognition are not at a significantly higher risk than HIV- subjects. Executive Functioning is most strongly associated with impaired on-road performance. Cognitive and simulator testing may each provide data in identifying driving-impaired individuals.

AIDS Dementia Complex↗

PubMed2004

Rate and correlates of weight change in Huntington's disease.

OBJECTIVE: To determine the rate and correlates of weight change in a large, well characterised sample of patients with Huntington's disease followed at 44 sites by the Huntington Study Group. PARTICIPANTS AND METHODS: Weight change was assessed in 927 adults with a definite diagnosis of Huntington's disease who were followed prospectively for (mean (SD)) 3.4 (1.4) years. The unified Huntington's disease rating scale was used to assess weight, motor dysfunction (including chorea and dystonia), depressive symptoms, and functional decline. RESULTS: Random effects modelling determined that patients gained an average of 0.11 (1.7) kg/year and their chorea scores increased by 0.36 (0.78) points/year. There were significant but weak relations between weight loss and increasingly severe chorea (r = -0.13), worse baseline motor performance (r = -0.12), less severe baseline depressed mood (r = 0.14), and poorer baseline independence ratings (r = 0.07). Patients who were within 0 to 2 years of symptom onset at the time of the baseline visit gained more weight than those with longer disease duration. CONCLUSIONS: Weight loss following symptom onset is not a consistent feature of Huntington's disease. The mechanisms contributing to weight change in this condition are unclear and probably multifactorial. Future studies examining asymptomatic carriers of the mutation could be helpful in identifying incipience of low body weight and may be better suited for identifying clinical correlates of weight loss than studies in symptomatic patients.

Chorea↗

PubMed2001

Circuit party attendance, club drug use, and unsafe sex in gay men.

PURPOSE: We examined the population demographics and club drugs used in gay circuit parties and estimated the reported unsafe sexual behavior associated with each drug, the reasons for attending circuit parties, and the unsafe sex associated with different reasons. METHODS: A brief questionnaire was provided to a nonrandom sample of party attendees covering demographics, drugs used, sexual activity, and reasons for attending gay circuit parties at three major North American parties in 1998-1999. A total of 1169 usable questionnaires were obtained. Odds ratios for unsafe sex for the drugs surveyed [alcohol, marijuana, methylenedioxymethamphetamine (Ecstasy), ketamine (Special K), crystal methamphetamine (crystal meth), cocaine, volatile nitrites (poppers), and gamma-hydroxybutyrate (GHB)] were calculated, as was significance of unsafe sex for the 10 major reasons for attending parties. RESULTS: 12-month party drug use was high: > 50% reported using alcohol, Ecstasy, and Special K. Frequent (rather than occasional) use of Ecstasy, Special K, and poppers had an association with unsafe sex at parties. Poppers also showed a statistically significant association with unsafe sex in 12 months (not necessarily at parties) while crystal meth and GHB showed a trend. Attending circuit parties "to look and feel good," "to have sex," and "to be uninhibited and wild" were associated with higher levels of unsafe sex in 12 months. IMPLICATIONS: In this sample, circuit party attendees are well educated and financially secure. Party drug use is high. It appears that use of poppers, Ecstasy, Special K, crystal meth, and GHB are associated with various measures of unsafe sex. More comprehensive research on club drug use in gay men is required.

Adult↗

PubMed2001

Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection.

Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.

Adult↗

PubMed2001

Symptomatic HIV seroconverting illness is associated with more rapid neurological impairment.

OBJECTIVES: To establish whether symptomatic seroconverting illness in HIV infected people is associated with more rapid development of neurological impairment. METHODS: 166 HIV infected subjects with a known date of HIV infection enrolled in a longitudinal study of neurocognitive function were stratified by whether or not they had experienced a symptomatic serconverting illness. RESULTS: 29 of 166 (17.5%) dated HIV seroconverters had a history of symptomatic seroconverting illness. Though baseline neurocognitive function was similar, subjects with a symptomatic seroconverting illness developed clinical neurocognitive impairment significantly more rapidly than their asymptomatic counterparts in a survival analysis model (636 v 1075 days till impaired). CONCLUSION: Symptomatic seroconverting illness predisposes to more rapid neurocognitive impairment.

AIDS Dementia Complex↗

PubMed2000

Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources.

OBJECTIVE: To identify the sources of HIV virions in CSF by modeling treatment-associated HIV dynamics. BACKGROUND: We postulated a model in which cell-free CSF virions originate from two major sources, namely, systemic non-CNS and CNS tissues, the latter including brain parenchyma and meninges. The model predicted that with initiation of antiretroviral therapy, the acute-phase decline in CSF HIV RNA levels would be controlled by the kinetics of the dominant virion source (systemic versus CNS). Based on prior observations, we hypothesized that the dominant source of CSF virions would shift from systemic to CNS in more advanced disease. METHODS: Three patient groups were studied: Group 1 (n = 5): nondemented, with early HIV disease (CD4+ lymphocytes > or = 400/microL) or pleocytosis (CSF leukocytes > or = 4/microL); Group 2 (n = 5): nondemented, with advanced HIV disease (CD4+ < 400/microL) and no pleocytosis; Group 3 (n = 2): patients with HIV-associated dementia (HAD). All patients began a new, highly active antiretroviral treatment regimen and underwent serial lumbar punctures and phlebotomies. RESULTS: For patients in Group 2, the rate of decline in CSF HIV RNA was slower than in plasma (p < 0.00001). For Group 1, the rate of decline in CSF was not different from plasma (p > 0.25). Patients with HAD showed high CSF HIV RNA after 5 to 6 weeks of treatment despite a 100-fold decrease in plasma HIV RNA. CONCLUSIONS: CSF and plasma HIV dynamics became increasingly independent in advanced HIV disease, and the compartmental discrepancy was largest in HAD. Our findings suggest that viral replication in CNS tissues may constitute a major, independent source of CSF HIV RNA. In patients with HAD, brain parenchyma itself may be the principal CNS tissue source, and CNS-targeted treatment strategies may be required to eradicate this infection.

Anti-HIV Agents↗

PubMed1999

Extending the p-plot: heuristics for multiple testing. HNRC group.

In the problem of large-scale multiple testing the p-plot is a graphically based competitor to the notoriously weak Bonferroni method. The p-plot is less stringent and more revealing in that it gives a gauge of how many hypotheses are decidedly false. The method is elucidated and extended here: the bootstrap reveals bias and sampling error in the usual point estimates, a bootstrap-based confidence interval for the gauge is given, as well as two acceptably powerful blanket tests of significance. Guidelines for use are given, and interpretational pitfalls pointed out, in the discussion of a case study linking premortem neuropsychological and postmortem neuropathologic data in an HIV cohort study.

Humans↗

PubMed1999

The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

AIDS Dementia Complex↗

PubMed1999

Neuropsychological impairment-associated visual field deficits in HIV infection. HNRC Group. HIV Neurobehavioral Research Center.

PURPOSE: To examine the relationship between loss in peripheral visual sensitivity and neuropsychological functioning in seropositive patients with human immunodeficiency virus (HIV) without infectious retinopathy. METHODS: Subjects carefully screened for retinal disease and well-matched across demographic and medical variables were grouped according to normal (perimetry-nl) versus abnormal (perimetry-abnl) performance on achromatic automated perimetry and short-wavelength automated perimetry, standard clinical ophthalmologic measures of visual function. All subjects completed a detailed neuropsychological test battery and were classified as impaired or unimpaired, globally and across eight neurocognitive domains. Subjects were also classified according to whether they met diagnostic criteria for minor cognitive/motor disorder (MCMD) or HIV-associated dementia (HAD). RESULTS: Visual field loss was associated with lower performance in the abstraction, perceptual-motor, learning, and motor domains. Significant group differences were also found on numerous individual neuropsychological tests. Based on clinical ratings, we found deficits in learning and motor functioning. No perimetry-nl subjects met criteria for MCMD or HAD, whereas 32% of perimetry-abnl subjects met diagnostic criteria for syndromic cognitive disorders (five MCMD and one HAD). In a subset of subjects who underwent a lumbar puncture, there was a trend for the perimetry-abnl group to have a higher concentration of beta2 microglobulin, a marker for central nervous system immune activation. CONCLUSIONS: These results suggest that in some HIV-infected people reduced visual function may be caused by nonretinal disease, and perimetry may present a sensitive measure of HIV-related brain dysfunction.

Adult↗

PubMed1998

Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group.

OBJECTIVE: To compare rates and anatomical patterns of brain atrophy during 3 stages of human immunodeficiency virus (HIV) disease. DESIGN: Comparisons of multiple serial brain magnetic resonance images in men without HIV infection and HIV-infected men in Centers for Disease Control and Prevention (CDC, Atlanta, Ga) stages A, B, and C. SETTING: Longitudinal cohort study of the San Diego HIV Neurobehavioral Research Center, San Diego, Calif. PARTICIPANTS: Eighty-six HIV-1-positive (HIV-positive) and 23 HIV-negative men who were similar in age and risk group. The number of HIV-positive men in each CDC stage was as follows: A, 33; B, 19; C, 34. All HIV-positive men were free of clinically detectable opportunistic neurologic illness. MAIN OUTCOME MEASURES: Regional volumes of serial magnetic resonance images converted to standardized slope estimates of change in regional volumes of interest. RESULTS: Medically asymptomatic men (CDC stage A) and medically symptomatic men (CDC stage C) had more rapid loss of cortical tissues than did HIV-negative men as manifested by higher slopes (Tukey honestly significant difference test, P=.02 and P=.001, respectively) for cortical fluid volume. Accelerated ventricular volume enlargement occurred only in men with CDC stage C disease. Reduction in the volume of white matter was accelerated in participants with CDC stage C disease compared with participants with CDC stage A disease. Of the gray matter regions, only the caudate nucleus sustained accelerated volume loss during CDC stage C disease. Participants whose systemic disease progressed to a higher CDC stage had significantly accelerated ventricular volume increases and caudate atrophy. Rates of cortical and subcortical fluid volume increases and reductions in the volumes of white matter and the caudate nucleus were significantly related to the rate of decline in the CD4+ lymphocyte count. CONCLUSIONS: In the absence of cerebral opportunistic disease, HIV infection causes progressive atrophy within the gray and white matter in the brain. These changes were most severe in the most advanced stage of disease but were evident even in medically asymptomatic HIV-positive persons. Within the gray matter, the caudate nucleus exhibited progressive volume loss linked to disease stage and the rate of decline of the CD4+ cell count. Structural brain changes can begin in the early stages of HIV infection and accelerate during advanced illness.

Adult↗

PubMed1987

Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography.

Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization.

Adolescent↗