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B J Brew

Publications and source records attributed to B J Brew.

At least 55 records · Page 3Linked to original sources
PubMed1996

Predictive markers of AIDS dementia complex: CD4 cell count and cerebrospinal fluid concentrations of beta 2-microglobulin and neopterin.

A predictive marker for AIDS dementia complex (ADC) in a cohort of neurologically asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected patients with < 200 CD4 cells/microL was sought. Patients were assessed neurologically and neuropsychologically at entry. Blood and cerebrospinal fluid (CSF) were taken for assay of beta 2-microglobulin (beta 2M), and neopterin and T cell subsets were assessed from blood. Patients were evaluated every 4 months. Of 37 patients recruited, 35 had sufficient follow-up data. Seventeen patients progressed to ADC stage > or = 1. In univariate analyses, concentrations of CSF beta 2M and neopterin and CD4 cell count were each significantly associated with ADC development. In a multivariate analysis, concentrations of CSF beta 2M remained significant, with levels > 5 mg/L carrying approximately 17 times the risk of ADC. CSF beta 2M and neopterin levels and CD4 cell count are useful in identifying patients at risk of ADC and as such can be used to target high-risk patients so therapy can be optimized.

AIDS Dementia Complex↗
PubMed1996

Pilot study of the efficacy of atevirdine in the treatment of AIDS dementia complex.

OBJECTIVES: To determine the efficacy of the non-nucleoside reverse transcriptase inhibitor atevirdine in the treatment of AIDS dementia complex (ADC). DESIGN: Open label pilot study. METHODS: Ten patients with ADC (stage 1 or 2) who were intolerant to zidovudine or dideoxyinosine, or in whom the antiretrovirals had failed to prevent further decline in CD4 cell levels, were entered into the study. Atevirdine, 1800 mg daily in three divided doses, was given over a 12-week period. Patients were assessed neurologically and neuropsychologically every 4 weeks. Cerebrospinal fluid analysis was performed at entry and at weeks 4 and 12. Technetium-99 exametazine single photon emission computed tomographic cerebral perfusion scans and magnetic resonance imaging brain scans were performed at weeks 0 and 12. RESULTS: Five patients completed the 12 week protocol. Four of these five responded to atevirdine, as judged by quantified neurological and neuropsychological assessments. Atevirdine was well tolerated apart from the development of rash, anxiety, intermittent diarrhoea and fatigue. CONCLUSIONS: These preliminary results suggest that atevirdine is efficacious in the treatment of ADC. Larger blinded studies of this class of drug in the treatment of ADC are required.

AIDS Dementia Complex↗
PubMed1996

Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patient with AIDS.

Microsporidia are zoonotic protozoa which were rare human pathogens prior to 1985, when Enterocytozoon bieneusi was described in human immunodeficiency virus-infected patients with chronic diarrhea. Another species, Encephalitozoon (Septata) intestinalis, is associated with diarrhea and chronic sinusitis, and approximately 25 cases have been reported in the literature. However, other microsporidial infections in human immunodeficiency virus-infected patients remain extremely rare. We report the first case of a Pleistophora sp.-like microsporidian infection presenting as a progressive severe myosotis associated with fever and weight loss. The organism was demonstrated by light microscopy and electron microscopy in corneal scrapings, skeletal muscle, and nasal discharge. Electron microscopy showed an electron-dense surface coat with "sunflare"-like projections surrounding all stages of development of meronts (two to four nuclei, dividing by binary fission), sporonts, and sporoblasts. Division of sporonts, in which sporonts separate from the thick outer coat, creating a sporophorous vesicle, is by binary fission, differentiating this organism from Pleistophora sp. The spore measures 4.0 by 2.5 microns and has a rugose exospore. A new genus and species, Trachipleistophora hominis, has been established for this parasite. The patient was treated with albendazole, sulfadiazine, and pyrimethamine, and the clinical symptoms resolved.

AIDS-Related Opportunistic Infections↗
PubMed1996

Association between HIV distal symmetric polyneuropathy and Mycobacterium avium complex infection.

OBJECTIVES: Pronounced infiltration of activated macrophages occurs in the peripheral nerves of patients with HIV distal symmetric polyneuropathy (DSPN). Mycobacterium avium complex (MAC) is a common facultative intracellular parasite of the macrophage in advanced HIV disease and may induce macrophage activation. Whether MAC disease is associated with DSPN was examined prospectively. METHODS: One hundred and fifty consecutive patients with HIV infection were assessed for the probability of DSPN. Blood cultures for MAC were performed, independently of neurological assessment, as part of the investigation of unexplained fever, anaemia, weight loss, or, less commonly, diarrhoea. RESULTS: There were 20 patients with possible, 14 with probable, and 22 with definite HIV DSPN. Blood cultures for MAC were performed on 80 patients, of whom 39 were positive and 41 negative. The test for trend, when corrected for CD4 count, disclosed a significant association (P = 0.01). There was no statistically significant association between DSPN and cytomegalovirus (CMV) disease. CONCLUSION: Coinfection of the macrophage by MAC may further activate the HIV infected macrophage thereby accelerating the elaboration of neural toxins or MAC infection of the macrophage itself may lead to the production of neural toxins.

Adult↗
PubMed1996

Clinical Markers of the Presence of Dementia and Neuropsychological Impairment in HIV Infection.

OBJECTIVE: To identify clinical, laboratory and demographic markers which are associated with the presence of dementia and neuropsychological impairment in severely immunodeficient patients. METHOD: Fifty-nine HIV+ patients participated in the study. Patients were assessed neurologically and neuropsychologically, and a subset of patients underwent lumbar punctures. Logistic regression was used to determine which variables from a set including age, education, IQ, depression, anxiety, CD4 cell counts, haemoglobin, serum and CSF â2 microglobulin and neopterin, constitutional symptoms, past opportunistic infections and use of antiretroviral therapy was associated with the occurrence of dementia and neuropsychological impairment. RESULTS: An increased likelihood of neurological and neuropsychological dysfunction was associated with diarrhoea at some time in the recent past, elevated serum neopterin at the time of assessment, and increased age. A decreased likelihood of impairment was associated with a higher estimated IQ, more years of education, and the presence of an AIDS-defining illness at the time of assessment. CONCLUSION: Recent diarrhoea, elevated serum neopterin, advanced age and low education and IQ can serve as ''signals'' for the presence of neurological and neuropsychological dysfunction.

AIDS Dementia Complex↗
PubMed1996

Prospective analysis of seizures occurring in human immunodeficiency virus type-1 infection.

A prospective, case-control study was undertaken to characterise seizures occurring in the context of human immunodeficiency type-1 (HIV-1) infection. Fifty consecutive patients with a documented seizure were enrolled along with fifty control patients. Among cases the median CD4 cell count was 8/mm3 and 84% had a prior AIDS defining illness; 14/mm3 and 80% among the control group. Generalised seizures were seen in 84%, partial with secondary generalisation in 10% and partial in 6%. Associated conditions included cerebral toxoplasmosis (22%), cryptococcal meningitis (8%), progressive multifocal leukoencephalopathy (6%), cytomegalovirus encephalitis (6%), central nervous system (CNS) lymphoma (2%), and other causes (14%) including pre-HIV epilepsy. No associated condition was identified in 42% of patients of whom 18% were receiving foscarnet therapy at the time of seizure, compared with 4% of control patients (p < 0.001). Concentrations of cerebrospinal fluid â2-microglobulin and neopterin, markers that have been associated with HIV-1 involvement of the CNS, were elevated in 12/12 and 13/13 patients, respectively, of the group with no identifiable cause for their seizure. We conclude that seizures occur principally in patients with advanced HIV-1 disease, with opportunistic infections of the CNS the predominant underlying condition. In the group with no identifiable cause foscarnet therapy and subclinical HIV-1 involvement of the CNS may be factors responsible for seizure activity.

AIDS-Related Opportunistic Infections↗
PubMed1996

The relationship between AIDS dementia complex and the presence of macrophage tropic and non-syncytium inducing isolates of human immunodeficiency virus type 1 in the cerebrospinal fluid.

We sought to determine the clinical significance of macrophage tropic and non-syncytium inducing isolates of human immunodeficiency virus type 1 (HIV-1) in the cerebrospinal fluid (CSF) of patients with and without AIDS dementia complex (ADC). HIV-1 was isolated from the CSF of 31 patients with and without ADC. The isolates were then characterised as to the degree of macrophage tropism by quantitation of p24 production and the presence of syncytium inducing (SI) or non-syncytium inducing (NSI) isolates by MT2 assay and SupT1 coculture. The degree of macrophage tropism varied according to the donor macrophage that was used except in strongly macrophage tropic isolates. Moderate and severe ADC (stage > or = 2) was associated with the presence of highly macrophage tropic isolates in the CSF (P = 0.01). The sensitivity and specificity values of a highly macrophage tropic isolate in the CSF for ADC stage > or = 2 were 82% and 66% respectively while the predictive value was 64%. Three of four asymptomatic patients with such highly macrophage tropic isolates in the CSF subsequently developed ADC after an average of 4 months. Twenty-eight isolates from the CSF and 23 from the blood were NSI regardless of the presence or absence of ADC. The predictive value of an SI isolate in the blood reflecting an SI isolate in the CSF was 37.5% while the predictive value of an NSI isolate in the blood reflecting an NSI in the CSF was 100%. These data suggest that host factors are essential in determining the degree of macrophage tropism in HIV-1 and that such tropism is important for the presence and possibly subsequent development of ADC. The CSF usually has NSI isolates regardless of the presence of ADC and irrespective of the presence of such isolates in the blood thereby suggesting that the CSF is behaving virologically as a separate compartment to the blood.

AIDS Dementia Complex↗
PubMed1995

AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations.

To evaluate the presence and distribution of central nervous system infection by human immunodeficiency virus type 1 (HIV-1), we used immunohistochemical methods to map the HIV-1 p24 core protein in the brains of 55 autopsied patients with acquired immunodeficiency syndrome (AIDS). In a subset of 40 of these patients who had undergone antemortem neurological evaluation of the AIDS dementia complex (ADC), we analyzed the relation between the severities of the viral infection and clinical dysfunction. Viral antigen was detected in macrophages and cells with morphological and immunohistochemical characteristics of microglia as well as multinucleated cells. The distribution of antigen-positive cells preferentially involved certain deep brain structures, especially the globus pallidus, other basal ganglia nuclei, and the central white matter. Overall, the presence and frequency of infected cells were highly correlated with the histological findings of multinucleated-cell encephalitis and in general with the clinical ADC stage. However, infection was often more limited than might be "anticipated" from the severity of patients' clinical dysfunction: Only 61% of patients with at least ADC stage 1 had detectable antigen and of these only approximately 30% of the brain sections were antigen positive. These results suggest a pathogenetic model of ADC where virus- or cell-coded toxins amplify the effect of limited brain infection.

AIDS Dementia Complex↗
PubMed1995

Quinolinic acid production is related to macrophage tropic isolates of HIV-1.

We sought to determine whether the neurotoxin quinolinic acid (QUIN) was produced by macrophages or lymphocytes infected with isolates of HIV-1 with varying degrees of macrophage tropism derived from patients with varying stages of AIDS dementia complex (ADC). Highly macrophage tropic isolates and minimally macrophage tropic isolates were used to inoculate macrophages and QUIN production was measured. Similarly, QUIN production from macrophages was monitored using a purified cell free highly macrophage tropic isolate and laboratory isolates SF33 and SF2. Each of these experiments was also performed with lymphocytes. We found that macrophages infected with macrophage tropic isolates of HIV-1 led to QUIN production while lymphocytes did not produce QUIN. The ability of the HIV-1 infected macrophages to produce QUIN was related to the viral inoculum and the degree of macrophage tropism of the isolate. The severity of ADC in the patient from whom a particular isolate was derived was not per se a determining factor for QUIN production. Purified cell free ADC isolates also led to QUIN production by macrophages thereby suggesting that HIV-1 infection alone is capable of inducing QUIN production.

AIDS Dementia Complex↗
PubMed1995

Neurocytotoxity of quinolinic acid in human brain cultures.

Quinolinic acid (QUIN) is a tryptophan metabolite which has been found to be an excitotoxin in rats, although its toxicity in humans is unknown. QUIN has been implicated in the pathogenesis of AIDS dementia complex. This study examined the effect of QUIN on human fetal brain tissue in vitro. After at least 14 days in vitro, QUIN was added to the cultures in the feeding medium, and lactate dehydrogenase (LDH) efflux at 20 h and neuronal morphology were used as a measure of neuronal injury. LDH levels in media from cultures exposed to QUIN concentrations of 5 and 10 mM were consistently elevated compared to controls. Overall, LDH levels in media from cultures exposed to lower QUIN concentrations did not differ significantly from controls. These data are comparable to animal in vitro studies, and support the hypothesis that QUIN is toxic to human central nervous system neurons and further strengthen its potential role in the pathogenesis of AIDS dementia complex.

AIDS Dementia Complex↗
PubMed1994

Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases.

Nitric oxide has been proposed to mediate cytotoxic effects in inflammatory diseases. To investigate the possibility that overproduction of nitric oxide might play a role in the neuropathology of inflammatory and noninflammatory neurological diseases, we compared levels of the markers of nitric oxide, nitrite plus nitrate, in the CSF of controls with those in patients with various neurologic diseases, including Huntington's and Alzheimer's disease, amyotrophic lateral sclerosis, and HIV infection. We found that there were no significant increases in the CSF levels of these nitric oxide metabolites, even in patients infected with HIV or in monkeys infected with poliovirus, both of which have significantly elevated levels of the neurotoxin quinolinic acid and the marker of macrophage activation, neopterin. However, CSF quinolinic acid, neopterin, and nitrite/nitrate levels were significantly increased in a small group of patients with bacterial and viral meningitis.

Alzheimer Disease↗
PubMed1994

The clinical spectrum and pathogenesis of HIV encephalopathy, myelopathy, and peripheral neuropathy.

Human immunodeficiency virus infection commonly affects the nervous system, with the most important features being a dementing illness, a myelopathy, and a neuropathy. In the past year, important advances have been made in the epidemiology and treatment of these conditions. Moreover, a better understanding of the pathogenetic mechanisms has emerged, with particular emphasis being placed upon gp120, tumor necrosis factor, and quinolinic acid and other partly characterized neurotoxins. This review highlights these advances in the context of the clinical syndromes.

AIDS Dementia Complex↗
PubMed1994

Cerebrospinal fluid HIV-1 p24 antigen and culture: sensitivity and specificity for AIDS-dementia complex.

We prospectively evaluated 94 patients with AIDS-dementia complex (ADC) and a smaller group of 27 patients with other HIV-1 related neurological conditions to determine the usefulness of cerebrospinal fluid (CSF) p24 antigen and HIV-1 culture in the diagnosis of ADC. The presence of ADC correlated with detectable CSF p24, but not with a positive culture. However, only 54% of the patients with severe or end stage (stages 3 and 4) ADC had detectable CSF p24 and only 25% had a positive culture. Among those with detectable CSF p24, there was no discernible relationship between the severity of ADC and the amount of CSF p24. The diagnostic sensitivity of CSF p24 in ADC was 21% whereas the specificity was 98%. CSF HIV-1 culture had a sensitivity of 30% and a specificity of 80%. To address the possibility of binding of p24 in immune complexes, thereby escaping detection, an acid hydrolysis procedure was performed on the CSF and serum samples. This did not, however, make an appreciable difference in the detection rate of p24. To delineate whether the finding of cell free virus in the CSF was associated with ADC, CSF culture for HIV-1 was performed on both cell depleted and cell associated fractions. It was uncommon for CSF to be culture positive in only the cell free fraction and there was no relationship to the presence or severity of ADC.

AIDS Dementia Complex↗
PubMed1994

HIV dementia.

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AIDS Dementia Complex↗
PubMed1993

HIV-related neurological disease.

Early neurological complications present an opportunity to make an early diagnosis of HIV infection. Patients may present with subtle symptoms and signs of neurological disease, but many HIV-related complications are readily treated if they are correctly diagnosed. As there are also neurological side effects of anti-HIV drugs, the management of patients with neurological complications and HIV disease requires accurate diagnosis.

AIDS Dementia Complex↗
PubMed1993

Human immunodeficiency virus-related headache.

We retrospectively assessed the frequency and clinical characteristics of headache occurring in human immunodeficiency virus (HIV)-infected patients in whom we had excluded all other causes, and determined the frequency of a similar headache in an HIV-negative group. Over a 1-year period, the HIV-related headache occurred in 2.8% of total admissions to the HIV service as opposed to 0.2% of admissions to the neurology service. The affected patients had advanced HIV infection (CD4+ cell count = 58.9 +/- 80.3; normal, > 500 x 10(-6)/l). The headache had features similar to those ascribed to HIV aseptic meningitis and was not related to the presence of AIDS dementia complex or its subsequent development over a 6-month follow-up. We propose that this is a distinct clinical entity related to HIV infection that is similar, if not identical, to HIV aseptic meningitis except for the lack of a CSF pleocytosis, probably reflecting the lymphocyte depletion that is characteristic of the more advanced state of HIV infection.

AIDS Dementia Complex↗