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Biomedical subjects

B J Brew

Publications and source records attributed to B J Brew.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS.

OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: Tertiary referral teaching hospital. PATIENTS: During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis. RESULTS: No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group. CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome.

We describe two cases of serologically confirmed human T-lymphotropic virus type I (HTLV-I)-associated myelopathy involving North American men coinfected by the human immunodeficiency virus type 1. Our first patient suffered from a gradually progressive spastic paraparesis for 10 years prior to presenting with Kaposi's sarcoma, while our second patient developed subacutely progressive spastic paraparesis in the setting of full-blown acquired immunodeficiency syndrome. Autopsy examination of the spinal cords from these two cases revealed widespread axonal loss and demyelination principally involving the lateral columns of case no. 1 and the lateral and anterior columns of case no. 2. Vascular sclerosis and hyalinization were prominent in both cases, but in neither was there a conspicuous inflammatory component. In case no. 2, HTLV-I mRNA was not detected by in situ hybridization, but HTLV-I proviral DNA sequences were detected in this case by polymerase chain reaction. Neither case exhibited multinucleated cell (human immunodeficiency virus type 1) myelitis, vacuolar myelopathy, or evidence of HTLV-II infection by polymerase chain reaction assay.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients.

Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both beta 2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, L-kynurenine or kynurenic acid with the ratio of serum:CSF albumin concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1-infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1-infected patients secondary to activation of indoleamine-2,3-dioxygenase.

AIDS Dementia Complex↗
PubMed1992

Medical management of AIDS patients. Central and peripheral nervous system abnormalities.

This article discusses the wide range of neurologic complications of HIV infection according to degree of advancement of systemic HIV disease. The focus is principally on those disorders that appear at least in part to be directly related to HIV: AIDS dementia complex, peripheral neuropathy, and myopathy. Unusual disturbances such as seizures and transient neurologic disorders are also discussed.

AIDS Dementia Complex↗
PubMed1992

Increased neopterin levels in brains of patients with human immunodeficiency virus type 1 infection.

Postmortem levels of native neopterin (D-erythro-neopterin) were measured in cerebral cortical samples from 44 human immunodeficiency virus type 1-infected and eight uninfected, nonneurological control patients. Cerebral cortical gray and white matter neopterin levels for the controls ranged from 0.5 to 7.2 pmol/mg of protein in contrast to neopterin levels in brains of the virus-infected patients, which frequently were more than threefold and occasionally more than 30-fold higher than mean control levels. Cortical neopterin levels did not correlate with severity of the acquired immunodeficiency syndrome dementia complex, but subcortical levels correlated with the presence of active human immunodeficiency virus type 1 infection, as reflected by pathological evidence of multinucleated giant cell encephalitis. Evidence of opportunistic cytomegalovirus infections in approximately 25% of the human immunodeficiency virus type 1-infected patients was associated with enhanced levels of neopterin in frontal cortex.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV nomenclature.

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Acquired Immunodeficiency Syndrome↗
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

Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status.

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.

AIDS Dementia Complex↗
PubMed1991

AIDS dementia complex and HIV-1 infection: a view from the clinic.

The AIDS dementia complex (ADC) is a clinical syndrome which characteristically presents as a "subcortical dementia" with cognitive, motor and behavioral changes. While the pathogenesis remains puzzling in a number of critical aspects, ADC likely relates in a fundamental way to HIV-1, itself, rather than to a secondary, opportunistic condition. This review focuses on some of the clinical information which bears on the pathogenesis of this syndrome and its relation to HIV-1 infection. This information derives from studies of the clinical character of ADC, its epidemiology and natural history, cerebrospinal fluid analysis, neuroimaging results, clinical correlates of pathological findings and its response to antiviral therapy.

AIDS Dementia Complex↗
PubMed1991

HTLV-I-associated myelopathy associated with blood transfusion in the United States: epidemiologic and molecular evidence linking donor and recipient.

Six months after receiving 58 units of blood components, a 65-year-old white man from New York City, with no other risk factors for human T-lymphotropic virus type I (HTLV-I) infection, developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Investigation of blood donors identified a 25-year-old white Hispanic woman from Florida whose platelets had been given to the patient and who was seropositive for the virus on a serum specimen obtained 2 years after the donation. She was born in Cuba and had had 2 sexual relationships with men who either had been born in or had resided in the Caribbean. Polymerase chain reaction (PCR) studies of peripheral blood mononuclear cells indicated that both donor and recipient were infected with HTLV-I. Molecular studies of a 595-nucleotide sequence in the 5' envelope region of HTLV-I indicated that the viruses from donor and recipient were identical in each of 32 positions in which published HTLV-I sequences demonstrate molecular heterogeneity; the donor and recipient viruses were also identical in 2 additional positions in which they differed from all published sequences. Transfusion-associated HAM/TSP has occurred in the United States, but additional cases should be prevented by screening blood donations for HTLV-I. Molecular studies of HTLV-I may prove useful in defining the genetic heterogeneity of HTLV-I isolates in the United States and in studying transmission of this virus.

Adult↗
PubMed1991

Pursuit eye movement dysfunction in HIV-1 seropositive individuals.

Studies of smooth pursuit eye movements were conducted in 30 ambulatory drug-free HIV-1 seropositive patients who did not yet manifest marked clinical signs of the AIDS Dementia Complex. Seropositive patients demonstrated disturbances in pursuit eye movements that were correlated with extent of immunosuppression, with impairments on neuropsychological tests of fine motor control/speed, and with independent clinical staging of the AIDS Dementia Complex. The results provide quantitative evidence that oculomotor disturbances are present in HIV-1 seropositive individuals before the manifestation of marked AIDS Dementia Complex. For this reason, and because more severe eye movement impairments have been observed in patients with AIDS, quantitative eye movement studies may provide a useful neurobehavioral procedure for characterizing and monitoring progression of CNS involvement associated with HIV-1 infection from early in its course.

Adult↗
PubMed1990

Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS)

OBJECTIVE: To evaluate safety, tolerance, and potential efficacy of interferon-alpha and zidovudine combination therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). DESIGN: Open, phase-I study with randomization between two preparations of interferon-alpha. SETTING: Outpatient clinic of a cancer research center. PATIENTS: Forty-three patients with Kaposi sarcoma associated with AIDS. INTERVENTIONS: Patients were treated with interferon-alpha, 4.5, 9, or 18 million U/d, and zidovudine, 100 or 200 mg orally every 4 hours. MEASUREMENTS AND MAIN RESULTS: Neutropenia was the major dose-limiting toxicity. Fatigue, liver enzyme elevation, anemia, and thrombocytopenia were dose-limiting in some patients. Maximum tolerated dosages for interferon-alpha 2a with zidovudine, respectively, were 4.5 million U/d with 200 mg every 4 hours or 18 million U/d with 100 mg every 4 hours. An interferon-alpha n1 [corrected] dosage of 9 million U/d with zidovudine dosages of either 100 or 200 mg every 4 hours induced dose-limiting toxicity in most patients. Of 37 evaluable patients, 17 (46%; 95% CI, 30% to 62%) showed complete or partial tumor regression. Antitumor effects occurred more frequently in patients with baseline CD4 counts above 200 x 10(6) cells/L (65%) than in patients with lower baseline counts (30%, P = 0.05). Effects on CD4 cells were related to both initial CD4 count and interferon dose. Increased skin test reactivity and decreased serum human immunodeficiency virus (HIV) p24 antigen and virus recovery from blood cells were seen. CONCLUSIONS: Combined therapy with interferon-alpha and zidovudine can be safely administered to patients with AIDS and Kaposi sarcoma. The observed effects on tumor growth, HIV replication, and immune function support further studies of the combination in patients at various stages of HIV infection.

Acquired Immunodeficiency Syndrome↗
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↗