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Biomedical subjects

J C McArthur

Publications and source records attributed to J C McArthur.

At least 19 recordsLinked to original sources
PubMed1992

Effect of chronic substance abuse on the neuropsychological performance of intravenous drug users with a high prevalence of HIV-1 seropositivity.

Limited data are available on cognitive performance in populations of intravenous drug users during the early, asymptomatic stages of human immunodeficiency virus type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were evaluated neuropsychologically on a semiannual basis. This analysis focused on whether history of substance abuse influenced neuropsychological test performance. At baseline, 102 participants were HIV-1-seropositives who were free of acquired immunodeficiency syndrome and 49 participants were seronegative. Multivariate analyses, adjusting for correlation of repeated outcome measures, were conducted to determine predictors of neuropsychological functioning. Effects of the frequency of reported past use of marijuana, heroin, cocaine, barbiturates, and alcohol were not statistically associated with performance on the tests. Age and education were the most important predictors of test performance, and a significant practice effect was observed for most measures. After adjustment for age, education, the practice effect, and frequency of drug use, neuropsychological performance over time did not vary by HIV-1 serostatus. Overall, after acutely intoxicated individuals were excluded, neither frequency of drug and alcohol use nor HIV-1 seropositivity significantly influenced neuropsychological test performance over a 1-year period.

Adult↗
PubMed1992

Cytokine expression in the brain during the acquired immunodeficiency syndrome.

The pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin-1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV-seropositive and -seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin-1 and -6, tumor necrosis factor-alpha and -beta, and interferon gamma. Levels of soluble CD4, CD8, and interleukin-2 receptor, as well as interferon gamma, tumor necrosis factor-alpha, beta 2-microglobulin, neopterin, and interleukin-6 and -1 beta were assayed in the cerebrospinal fluid and plasma of many of these individuals during life. The HIV-seropositive group included individuals without neurological disease, those with CNS opportunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present on microglial cells, which were frequently positive for tumor necrosis factor-alpha. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin-1 and interferon gamma and less frequently for tumor necrosis factor and interleukin-6. There were gliosis and significant increases in MHC class II antigen, interleukin-1, and tumor necrosis factor-alpha in HIV-positive patients compared to HIV-negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, beta 2-microglobulin, and neopterin. There was no correlation in HIV-positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of "immune activation" in the brains of HIV-positive compared to HIV-negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 infection and intravenous drug use: longitudinal neuropsychological evaluation of asymptomatic subjects.

A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus.

Adult↗
PubMed1992

Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis.

Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1-seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1-seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia.

AIDS Dementia Complex↗
PubMed1992

Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS)

We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The diagnostic utility of elevation in cerebrospinal fluid beta 2-microglobulin in HIV-1 dementia. Multicenter AIDS Cohort Study.

We measured serum and CSF beta 2-microglobulin (beta 2M) levels in HIV-1 seropositive individuals with and without dementia to determine the frequency and diagnostic utility of elevation of CSF beta 2M. We compared 34 samples from 27 patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive participants in the Multicenter AIDS Cohort Study, none of whom had progressive dementia. Neurosyphilis and CNS opportunistic processes were excluded in all subjects. We stratified the nondemented subjects by duration of HIV seropositivity and peripheral blood CD4 count. Compared with the nondemented group, demented subjects had significantly higher CSF total protein, IgG%, and CSF albumin/serum albumin ratios. A highly significant association was found between elevated CSF beta 2M and reduced CD4 count (p less than 0.0001). No significant differences were noted between the demented and nondemented groups in CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF beta 2M was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with dementia (p less than 0.0001). We derived a cutoff of 3.8 mg/l from the distribution of CSF beta 2M in the nondemented group. The determination of CSF beta 2M had a sensitivity of 44%, specificity of 90%, and a positive predictive value of 88% for diagnosis of HIV dementia when compared with nondemented subjects with CD4 counts less than 200. In those without dementia, there was a strong correlation between serum and CSF beta 2M (r = 0.50, p less than 0.0001), but in demented subjects CSF beta 2M was elevated independently of serum levels, suggesting that CSF beta 2M is produced within the brain in HIV dementia. In the absence of CNS opportunistic processes, elevated CSF beta 2M greater than 3.8 mg/l is a clinically useful marker for HIV dementia.

AIDS Dementia Complex↗
PubMed1992

Cerebrospinal fluid beta 2-microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment.

OBJECTIVE: To determine the relationship between cerebrospinal fluid (CSF) beta 2-microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine. DESIGN: A prospective study. SETTING: Tertiary referral hospital. PATIENTS, PARTICIPANTS: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study. INTERVENTIONS: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed. MAIN OUTCOME MEASURES: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments. RESULTS: There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy. CONCLUSIONS: CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy.

AIDS Dementia Complex↗
PubMed1991

Epstein-Barr virus in AIDS-related primary central nervous system lymphoma.

Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of AIDS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.

Central Nervous System Neoplasms↗
PubMed1991

Stereotactic brain biopsy in the diagnosis of malignant lymphoma.

Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically.

Adolescent↗
PubMed1991

Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease.

We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.

Biopterins↗
PubMed1991

HIV-1 infection and nervous system abnormalities among a cohort of intravenous drug users.

A group of 109 HIV seropositive and 51 seronegative intravenous drug users was evaluated for the presence of HIV-1-related neurologic disease using clinical, neurologic, neuropsychological, and electrophysiologic evaluations. About 80% of HIV seropositive subjects had less than two constitutional symptoms. CD4 cell counts were less than 500/mm3 among 56% of seropositive participants; three individuals were receiving zidovudine. Neurologic abnormalities were found frequently among the cohort, independently of HIV-1 serostatus; electrophysiologic abnormalities were uncommon. Participants from both serologic groups scored significantly lower on neuropsychological tests as compared with norms established for a cohort of homosexual men, and there was no clear association between HIV-1 serostatus and performance on these tests. This study suggests that HIV infection was not the dominant cause of neurologic abnormalities among the study cohort.

Adult↗
PubMed1991

Normative data for a brief neuropsychological screening battery. Multicenter AIDS Cohort Study.

This study reports normative data for a group of 733 homosexual/bisexual men stratified by age (range 25 to 54 years) and by education on the following six neuropsychological tests: (1) Digit Span (WAIS-R), (2) Rey Auditory Verbal Learning Test, (3) Symbol Digit Modalities Test, (4) Controlled Oral Word Association Test, (5) Grooved Pegboard, and (6) The Trail Making Test. Analysis demonstrates that both age and education are important determinants of performance for several of these measures.

AIDS Dementia Complex↗
PubMed1990

Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.

We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.

AIDS Dementia Complex↗
PubMed1990

Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease.

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV+ than in HIV- individuals. HIV+ individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV+ categories compared to HIV- individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV+ individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV+ than in HIV- individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1-2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 remained elevated with a gradual decrease over the subsequent years of follow-up.

Antigens, CD↗