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Biomedical subjects

Raul Gonzalez

Publications and source records attributed to Raul Gonzalez.

At least 19 recordsLinked to original sources

Mastoid fontanelle approach for sonographic imaging of the neonatal brain.

This pictorial review describes in detail the examination technique used to study the neonatal brain via the mastoid fontanelle and offers a panoramic view of the anatomical structures that can be identified in each US slice. The brain lesions are grouped as congenital malformations, haemorrhage, cerebellar lesions and sinus venous thrombosis. In each section, the additional information obtained through the mastoid fontanelle is provided.

Brain↗

Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.

OBJECTIVE: To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. DESIGN: In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. METHODS: Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. CONCLUSIONS: As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.

Adult↗

Additive deleterious effects of methamphetamine dependence and immunosuppression on neuropsychological functioning in HIV infection.

Methamphetamine (MA) dependence and HIV infection are independently associated with cerebral dysfunction, especially within frontal-basal ganglia circuits. Recent evidence indicates that MA dependence has an additive effect on neuropsychological (NP) deficits associated with HIV infection. This study extends prior findings by examining the combined effects of MA dependence (MA+) and immunosuppression (i.e., CD4 lymphocyte count <200) on NP functioning in 284 HIV+ individuals. Prevalence of NP impairment was examined in four demographically comparable groups: (1) MA+/CD4 < 200; (2) MA+/CD4 > or = 200; (3) MA-/CD4 < 200; and (4) MA-/CD4 > or = 200. Results revealed that both MA dependence and immunosuppression were significant predictors of NP impairment. More importantly, additive effects were evident whereby the MA+/CD4 < 200 group exhibited the highest rate of NP impairment. Findings indicate that MA dependence conveys an additive deleterious impact on NP status in immunosuppressed persons with HIV infection, perhaps reflecting the combined effects of neuropathophysiological mechanisms in fronto-striatal circuits.

Adult↗

Buttocks lifting: how and when to use medial, lateral, lower, and upper lifting techniques.

New buttocks-lifting techniques are evolving rapidly, with some so recent that very few surgeons have performed them. However, a few new principles may be drawn from the various techniques in an attempt to produce better results and minimize scars. The indications for use of a medial, lateral, lower, or upper buttocks lift are presented in this article. There is no technique for all seasons and a surgeon who intends to perform a buttocks lift must evaluate the four techniques and the indications for each. An intramuscular implant helps to improve results even further and should be used when appropriate.

Buttocks↗

Demographically adjusted normative standards for new indices of performance on the Paced Auditory Serial Addition Task (PASAT).

The Paced Auditory Serial Addition Task (PASAT) is a complex cognitive test sensitive to neuropsychological disorders. Its traditional Total Correct score seemingly reflects multiple cognitive abilities, including attention, working memory, and processing speed. Snyder, Aniskiewicz, and Snyder (1993) modified scoring guidelines for the PASAT to give credit only for "dyads." This method emphasizes working memory operations and has been found superior to Total Correct scores at detecting cognitive impairments in several investigations. To date, normative standards are not available for the "dyad" scoring method, thus limiting its utility in clinical and research settings. The current investigation provides demographically adjusted normative data based on a sample of 500 healthy adults of varied age, education, sex, and race (African American and Caucasian) for various indices of performance on the PASAT, including "Total Dyads" obtained across the four PASAT trials. In addition, we describe and present normative data on four other indices designed to quantify various aspects of performance on the PASAT: invalid responding, effects of varied information processing speed demands, and tendency to omit responses and to make arithmetic errors.

Abstracting and Indexing↗

Neuropsychological functioning in a cohort of HIV- and hepatitis C virus-infected women.

OBJECTIVE: To evaluate the neurocognitive function in 220 women enrolled in the Women's Interagency HIV Study (WIHS), a study of disease progression in women living with HIV/AIDS and in HIV-negative controls. METHODS: We evaluated the prevalence of abnormal neuropsychological (NP) results in hepatitis C virus (HCV)-positive compared with HCV-negative women in combination with HIV serostatus. RESULTS: NP impairment was significantly higher for HCV-positive women in comparison with HCV-negative women [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.17-3.51]. Women co-infected with HCV and HIV demonstrated greater abnormal NP performance than those not infected with either, particularly if there was evidence of CD4 T-lymphocyte immunosuppression [> 200 x 10(6) CD4 cells/l (OR, 3.48; 95% CI, 1.49-8.15) and < or = 200 x 10(6) CD4 cells/l (OR, 5.38; 95% CI, 1.46-19.84)]. Women who were HCV-positive/HIV-positive and not taking antiretroviral therapy (ART) were more likely (OR, 7.03; 95% CI, 2.63-18.82) to demonstrate NP impairment than those who were HCV-negative/HIV-negative. In analyses controlling separately for education, intelligence quotient, depression, sedating drug use, head injury, ethnicity, and history of substance use, HCV continued to significantly predict NP impairment. The HCV effect did not reach significance when controlling for age in bivariate or multivariate analyses although the odds ratio for NP abnormalities in HCV-infected patients was only slightly reduced (ORs above 1.9). After testing for an interaction between age and infection status, we conducted age-stratified analysis and showed a significant effect of infection status for those aged under 40 years. CONCLUSIONS: The effect of aging on co-infected populations will require further study. This study has demonstrated the association of HCV with the risk of neurocognitive impairment in women living with HIV/AIDS and suggests that co-infection has an additive effect.

Adult↗

Investigating neurocognitive features of hepatitis C virus infection in drug users: potential challenges and lessons learned from the HIV literature.

Studies of neurocognition in drug users with hepatitis C virus (HCV) infection are urgently needed but face many challenges. We review similarities between human immunodeficiency virus (HIV) and HCV infection in their neurocognitive features, discuss challenges associated with research among drug users, advocate that the HIV literature can usefully inform studies of HCV, and review findings by our group on neurocognition among substance users with HIV and/or HCV infection.

Adult↗

Temperament and risky behaviors: a pathway to HIV?

BACKGROUND: Certain sexual behaviors and abuse of substances contribute to the risk of becoming HIV-infected. Because dispositional characteristics are likely to influence this process, we examined the association between temperament and HIV serostatus in subjects with heavy use of drugs and various sexual risk behaviors. METHODS: Two hundred and thirty individuals (81% of whom were HIV-infected) were assessed for underlying temperamental characteristics, substance use, and risky sexual behaviors. Toward this goal, a factor analysis was conducted on a new self-rated Temperament Autoquestionnaire (Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A)). MANOVA was used to examine overall associations between risky behaviors and temperament. Additionally, directed MANOVAs were conducted for each of six drugs of abuse (alcohol, marijuana, cocaine, opioids, other stimulants, and sedative hypnotics). RESULTS: Factor analysis confirmed the hypothesized temperament structure of five distinct factors: Cyclothymic, hyperthymic, anxious, irritable-explosive, and depressive. Heavy users of cocaine, other stimulants, and alcohol were more likely to have an irritable-explosive temperament. Interestingly, heavy users of opioids were more likely to show depressive and hyperthymic traits. The inclusion of HIV status as a predictor of temperament did not alter the results. Unlike a previous study, no direct significant relationships were found between risky sexual behaviors and specific temperaments. LIMITATIONS: Relatively small sample size for a factor analytic study, and cross-sectional design, which cannot determine a cause and effect relationship. CONCLUSIONS: We succeeded in studying and validating five distinct affective temperaments in a substance abuse population. Irritable-explosive, and to a lesser extent, depressive and hyperthymic traits, were associated with substance use, and may place individuals at risk for HIV infection via that mechanism. That current risky sexual practices were not directly linked to temperament may reflect modification in sexual behavior following the acquisition of HIV disease.

Acquired Immunodeficiency Syndrome↗

The influence of executive functions, sensation seeking, and HIV serostatus on the risky sexual practices of substance-dependent individuals.

From a public health standpoint, identifying factors that contribute to risky sexual practices among substance-dependent individuals is critical, particularly in the context of HIV infection. This study examines the respective contributions of executive neurocognitive functions, sensation seeking, and HIV serostatus in predicting risky sexual practices among poly-substance users (with a history of dependence primarily for cocaine or cocaine/heroin). HIV+ (n=109) and HIV- (n=154) substance-dependent individuals were assessed using three neurocognitive tasks of executive functions: Stroop reaction time, delayed non-matching to sample, and the Iowa Gambling Task. Sensation seeking was assessed using the Sensation Seeking Scale-V. Greater sensation seeking was associated with more risky sexual practices among HIV+ participants, particularly among those who performed best on the Iowa Gambling Task. Our findings indicate that continued risk behavior among HIV+ drug users may be driven by sensation seeking (a personality trait common among drug users); however, the impact of executive functions is less clear.

Adult↗

Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence.

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

Adult↗

Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors.

Nucleoside reverse transcriptase inhibitors (NRTIs) suppress human immunodeficiency virus (HIV) replication, but are often associated with mitochondrial toxicity. Although well studied outside of the central nervous system, no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV. The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria. N-acetylaspartate (NAA; sensitive to alterations in mitochondrial integrity) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and/or stavudine (two NRTIs likely to cause mitochondrial toxicity), 14 HIV+ individuals taking zidovudine and lamivudine, 16 HIV+ individuals not currently taking antiretrovirals, and 17 HIV- controls. The HIV+ groups were comparable on demographic measures, estimates of illness severity, and estimated length of HIV infection. Those taking didanosine and/or stavudine had a significant 11.4% decrease in concentrations of frontal white matter NAA compared to HIV- controls, whereas NAA levels of the other HIV+ groups were intermediate. Group differences in metabolites were not found in frontal gray matter. Lower levels of frontal white matter NAA were associated with longer periods of didanosine and/or stavudine treatment (r = -.41, P = .06). Levels of NAA were not related to length of zidovudine/lamivudine treatment (r = -.04, P = .44). Furthermore, taking more than one of stavudine, didanosine, and abacavir increased the likelihood of having reduced NAA. The results are consistent with previous studies finding HIV-related changes in neuronal integrity. However, because NRTIs can injure mitochondria, we propose that the observed reductions in NAA in individuals taking didanosine and/or stavudine may be the result of depleted brain mitochondria and/or alterations in cellular respiration. Measurement of brain metabolites sensitive to impairments in energy metabolism, including NAA, may aid in early detection of subclinical NRTI-mediated mitochondrial toxicity.

Adult↗

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

Adult↗

Qualitative aspects of verbal fluency in HIV-associated dementia: a deficit in rule-guided lexical-semantic search processes?

HIV-associated dementia (HAD) is widely considered a "subcortical" dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals with HAD, 51 nondemented persons with HIV infection (HIV+), and 30 healthy controls (HC) who were comparable for age, education, sex, ethnicity, and estimated premorbid verbal intelligence. The verbal fluency protocols were scored to obtain the total number of correct words, average phonemic cluster size, total number of switches between phonemic clusters, and the proportion of error responses (i.e., intrusions, perseverations, and variants). Consistent with prior research, HAD participants produced significantly fewer total correct words relative to the HC and nondemented HIV+ groups. The HAD group also demonstrated fewer switches and a higher proportion of response errors (especially intrusion errors), but no differences were observed in average cluster size. Findings are interpreted as reflecting a disruption of rule-guided lexical-semantic search strategies in HAD, perhaps mediated by prefrontal-striatal circuit dysfunction, rather than depleted lexical-semantic memory stores.

AIDS Dementia Complex↗

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.

Adult↗

Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection.

The current study explored the predictive validity of the Global Deficit Score (GDS) approach in summarizing neuropsychological (NP) test results, and specifically in detecting HIV-associated cognitive impairment. A comprehensive NP test battery was administered to 88 HIV+ subjects and 61 healthy HIV- controls comparable for age, education, and ethnicity. Demographically corrected test data were converted to a GDS, which simulates clinicians' ratings by quantifying the number and degree of impaired performances throughout the test battery while attaching relatively less significance to superior performances and/or those within normal limits. Our results indicated that the GDS approach effectively discriminated HIV+ and normal control groups, and accurately classified HIV+ individuals with NP impairment based on the "gold standard" clinical rating approach. Consistent with previous studies using different subject samples and different NP test batteries, the GDS cutpoint of >or=0.50 yielded optimal balance between sensitivity and specificity in classifying NP impairment, thus supporting the generalizability of the method. Moreover, the ability of the GDS to predict NP impairment across several cutpoints was quite strong, with positive predictive power values ranging from 0.71 to 1.00. These findings support the validity of the GDS as a clinically useful way of summarizing results on NP testing.

Adult↗

Initial validation of a screening battery for the detection of HIV-associated cognitive impairment.

This study sought to develop and validate a screening battery for detecting HIV-related neuropsychological (NP) impairment. Six NP measures representing the ability areas most likely affected by HIV infection were paired in 14 combinations and their diagnostic accuracy rates compared. The measures were selected from a larger NP battery administered to 190 HIV-seropositive (HIV+) participants. Screening battery performance was classified as NP impaired if demographically corrected T-scores fell below 40 on both tests, or below 35 on one test. Using blind clinical ratings of NP test results from the larger battery as the "gold standard" for global NP status (impaired or unimpaired), we found that several test combinations demonstrated adequate diagnostic accuracy in detecting NP impairment. The most sensitive test combinations were the Hopkins Verbal Learning Test-Revised (HVLT-R; Total Recall) and the Grooved Pegboard Test nondominant hand (PND) pair and the HVLT-R and WAIS-III Digit Symbol (DS) subtest pair (sensitivity = 78% and 75%, respectively). Both test combinations (HVLT-R/PND, HVLT-R/DS) were more accurate than the HIV Dementia Scale (HDS) in classifying HIV+ participants as NP impaired or unimpaired. Results suggest that demographically corrected T-scores from pairs of common NP measures may serve as valid screening instruments to identify subjects with HIV-related neurocognitive impairment who could benefit from more extensive NP examination.

Adult↗

Computerized reaction time battery versus a traditional neuropsychological battery: detecting HIV-related impairments.

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the "gold standard," impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments.

AIDS Dementia Complex↗