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Elyse J. Singer

Bio: Elyse J. Singer is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Neurocognitive & Viral load. The author has an hindex of 48, co-authored 137 publications receiving 7345 citations. Previous affiliations of Elyse J. Singer include United States Department of Veterans Affairs & University of California, San Diego.


Papers
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Journal ArticleDOI
25 Jun 2008-PLOS ONE
TL;DR: A role for elevated LPS levels in driving monocyte activation in AIDS is suggested, thereby contributing to the pathogenesis of HAD, and evidence that cofactors linked to substance abuse and HCV co-infection influence these processes is provided.
Abstract: Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.

461 citations

Journal ArticleDOI
13 Mar 2011-AIDS
TL;DR: Findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.
Abstract: Objective: To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART. Design: This study is an observational cohort study. Methods: MRS was performed in 268 patients: HIV-negative controls (N ¼28), HIVpositiveneuroasymptomaticindividuals(N ¼124),andindividualswithAIDSdementia complex (ADC; N ¼50) on stable antiretroviral therapy (ART) with a mean duration of infection of 12 years and CD4 cell count of 309cells/ml. Four metabolites were measuredover creatine:N-acetylaspartate (NAA), markerof neuronal integrity;choline (Cho), myoinositol, markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia, frontal white matter (FWM), and mid-frontal cortex. Analyses included analysis of variance, analysis of covariance, linear, and nonparametric regression models. Results: Cognitive impairment was found in 48% of HIV-infected individuals. Both HIV-positive groups showed significant increases in myoinositol/creatine or Cho/ creatine in all brain regions when compared to controls; a significant decrease in Glx/creatine in the FWM was observed in the neuroasymptomatic group; and only individuals with ADC showed a significant reduction in NAA/creatine, although a significant trend for decreasing NAA/creatine in the basal ganglia was found across the groups. Effects related to aging and duration of infection, but not central nervous system penetration effectiveness were observed. Conclusion: Brain inflammatory changes remain ubiquitous among HIV-infected individuals, whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease. 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2011, 25:625‐633

314 citations

Journal ArticleDOI
TL;DR: Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses in HIV.
Abstract: We examined the interrater (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV.

287 citations

Journal ArticleDOI
TL;DR: Previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex are extended.
Abstract: The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.

263 citations

Journal ArticleDOI
TL;DR: A positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy was found and rhNGF was safe and well tolerated, but injection site pain was frequent.
Abstract: Objective: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HIV-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291). Background: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. Methods: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 μg/kg rhNGF, or 0.3 μg/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. Results: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments ( p = 0.001) and for pin sensitivity ( p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HIV RNA levels or other laboratory indices. Conclusions: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy. rhNGF was safe and well tolerated, but injection site pain was frequent.

252 citations


Cited by
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01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
01 Dec 2003-Pain
TL;DR: In this article, the authors provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain, and develop a core set of outcome domains would facilitate comparison and pooling of d
Abstract: Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d

3,476 citations

Journal ArticleDOI
TL;DR: This report reviews the collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neuroc cognitive impairment to categorize individuals with subclinical impairment.
Abstract: In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.

2,292 citations