Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It remains essential to document the neuropsychological profile of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and minor forms human immunodeficiency virus (HIV)-associated neurocognitive impairment by quantifying the magnitude of impairment across eras of treatment. Indeed, with the introduction of the highly active antiretroviral therapy (HAART), there is evidence of changes in aspects of ADC. To allow quantitative and qualitative comparisons with the HAART era studies, we developed a summary of neuropsychological performance acquired in pre-HAART era studies in advanced HIV infection and ADC. Using a meta-analytical procedure and a test nomenclature that accounts for task complexity, we found that individuals with symptomatic infection (but no AIDS) demonstrated a global mild level of cognitive impairment, except for the domains complex attention/psychomotor speed, motor coordination, and learning, which showed moderate impairment. Individuals with AIDS demonstrated a global moderate level of cognitive impairment with a predominance of deficits in attention, complex attention/psychomotor speed, learning, motor coordination, with additional deficits in verbal memory and reasoning. Individuals with ADC demonstrated the most severe cognitive disturbances in domains of learning, motor coordination, with additional deficits in veibal fluency and verbal memory. Moderate impairment was evidenced in domains of complex attention/psychomotor speed, whereas naming and visuospatial functions were relatively preserved. The profile of deficits in ADC suggests that it may not be only interpreted as a worsening form of the impairment that is seen in the AIDS and symptomatic stages of HIV disease but that there are also additional deficits suggestive of an alternate pathogenetic process(es).
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PMID:The neuropsychological profile of symptomatic AIDS and ADC patients in the pre-HAART era: a meta-analysis. 1690 29

Human immunodeficiency virus (HIV) infection is often complicated by the development of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC). Implications of kynurenine pathway (KP) are suggested in ADC and other inflammatories brain diseases. The first and regulatory enzyme of the KP is the indoleamine-2,3-dioxygenase (IDO). IDO activation is known to contribute to the modulation of the immune response during various infectious diseases particularly in AIDS. HIV and viral proteins can activate IDO in immune cells leading to an increase catabolism of tryptophan through the KP; the consequence being the production of immuno-modulative and neuroactive metabolites. This mechanism is likely to favour HIV persistence. The present study analysed concomitantly several parameters involved in IDO regulation and activity associated with HIV-1-infection. We investigated relevant intracellular and extracellular mechanisms involved in the regulation of IDO expression and activity during the HIV infection and replication in human monocyte-derived macrophages (MdM). Using a complementary set of in vitro experiments, we found that HIV-1/Ba-L infection induces IDO expression and increases its activity in MdM. We also showed that IDO activation by HIV-1 is likely to be a direct effect of the infection and seems to be independent of IFN-gamma production.
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PMID:Modulation of indoleamine-2,3-dioxygenase expression and activity by HIV-1 in human macrophages. 1965 12

Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.
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PMID:Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. 2011 83

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.
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PMID:Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. 2096 Dec 12

Recent reports suggest that a growing number of human immunodeficiency virus (HIV)-infected persons show signs of persistent cognitive impairment even in the context of combination antiretroviral therapies (cART). The basis for this finding remains poorly understood as there are only a limited number of studies examining the relationship between CNS injury, measures of disease severity, and cognitive function in the setting of stable disease. This study examined the effects of HIV infection on cerebral white matter using quantitative morphometry of the midsagittal corpus callosum (CC) in 216 chronically infected participants from the multisite HIV Neuroimaging Consortium study currently receiving cART and 139 controls. All participants underwent MRI assessment, and HIV-infected subjects also underwent measures of cognitive function and disease severity. The midsagittal slice of the CC was quantified using two semi-automated procedures. Group comparisons were accomplished using ANOVA, and the relationship between CC morphometry and clinical covariates (current CD4, nadir CD4, plasma and CSF HIV RNA, duration of HIV infection, age, and ADC stage) was assessed using linear regression models. HIV-infected patients showed significant reductions in both the area and linear widths for several regions of the CC. Significant relationships were found with ADC stage and nadir CD4 cell count, but no other clinical variables. Despite effective treatment, significant and possibly irreversible structural loss of the white matter persists in the setting of chronic HIV disease. A history of advanced immune suppression is a strong predictor of this complication and suggests that antiretroviral intervention at earlier stages of infection may be warranted.
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PMID:Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies. 2155 60

We report a case of a patient with highly active anti-retroviral therapy-resistant human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML). The patient showed an improvement in imaging findings and clinical symptoms after mefloquine was introduced as an additional treatment. Serial assessment of white matter lesions was conducted by proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion-weighted imaging (DWI). As the clinical symptoms improved, the N-acetylaspartate/creatine ratio increased, the choline/creatine ratio decreased, and the elevated ADC value decreased. These concomitant changes suggested that (1)H-MRS and DWI were useful for the assessment of the therapeutic effect on PML.
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PMID:Akinetic mutism caused by HIV-associated progressive multifocal leukoencephalopathy was successfully treated with mefloquine: a serial multimodal MRI Study. 2289 19

The human immunodeficiency virus (HIV) adult day care ADC) center is an important component in the continuum of care for the HIV ill client, providing therapeutic advantages to the client and administrative advantages to the community as it copes with the growing HIV epidemic. The HIV ADC center was designed using several models of adult day programs for developmental, psychosocial, geriatric and neuropsychiatric treatment. The HIV ADC client is typically in a non-acute phase of a chronic disability resulting from some combination of primary HIV pathology and secondary illnesses associated with the Acquired Immune Deficiency Syndrome (AIDS) and is in need of some level of rehabilitation. The HIV ADC client is. typicall a gay or bisexual male, a man or woman who is or has been adbicted to intravenously injected drugs, or the sexual partner of someone in these groups. Programming addresses the psychosocial needs and daily reallties of these populations. This article describes occupational therapy intervention focused on maintaining, restoring, or adapting functional skills, with special attention to the daily activities most affected by cognitive/ perceptual dysfunction.
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PMID:Adult day care for people with human immunodeficiency virus. 2393 Nov 79


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