RESUMEN
OBJECTIVE: To address the need for brief, reliable, valid, and standardized quality of life (QOL) assessment applicable across neurologic conditions. METHODS: Drawing from larger calibrated item banks, we developed short measures (8-9 items each) of 13 different QOL domains across physical, mental, and social health and evaluated their validity and reliability. Three samples were utilized during short form development: general population (Internet-based, n = 2,113); clinical panel (Internet-based, n = 553); and clinical outpatient (clinic-based, n = 581). All short forms are expressed as T scores with a mean of 50 and SD of 10. RESULTS: Internal consistency (Cronbach α) of the 13 short forms ranged from 0.85 to 0.97. Correlations between short form and full-length item bank scores ranged from 0.88 to 0.99 (0.82-0.96 after removing common items from banks). Online respondents were asked whether they had any of 19 different chronic health conditions, and whether or not those reported conditions interfered with ability to function normally. All short forms, across physical, mental, and social health, were able to separate people who reported no health condition from those who reported 1-2 or 3 or more. In addition, scores on all 13 domains were worse for people who acknowledged being limited by the health conditions they reported, compared to those who reported conditions but were not limited by them. CONCLUSION: These 13 brief measures of self-reported QOL are reliable and show preliminary evidence of concurrent validity inasmuch as they differentiate people based upon number of reported health conditions and whether those reported conditions impede normal function.
Asunto(s)
Estado de Salud , Enfermedades del Sistema Nervioso/psicología , Neurología/instrumentación , Calidad de Vida , Encuestas y Cuestionarios/normas , Anciano , Femenino , Humanos , Internet/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neurología/métodos , Pacientes Ambulatorios/psicología , Reproducibilidad de los Resultados , AutoinformeRESUMEN
The signature for human immunodeficiency virus type 1 (HIV-1) neurovirulence remains a subject of intense debate. Macrophage viral tropism is one prerequisite but others, including virus-induced alterations in innate and adaptive immunity, remain under investigation. HIV-1-infected mononuclear phagocytes (MPs; perivascular macrophages and microglia) secrete toxins that affect neurons. The authors hypothesize that neurovirulent HIV-1 variants affect the MP proteome by inducing a signature of neurotoxic proteins and thus affect cognitive function. To test this hypothesis, HIV-1 isolates obtained from peripheral blood of women with normal cognition (NC) were compared to isolates obtained from women with cognitive impairment (CI) and to the laboratory adapted SF162, a spinal fluid R5 isolate from a patient with HIV-1-associated dementia. HIV-1 isolates were used to infect monocyte-derived macrophages (MDMs) and infection monitored by secreted HIV-1 p24 by enzyme-linked immunosorbent assay (ELISA). Cell lysates of uninfected and HIV-1-infected MDMs at 14 days post infection were fractionated by cationic exchange chromatography and analyzed by surface enhanced laser desorption ionization time of flight (SELDI-TOF) using generalized estimating equations statistics. Proteins were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE) and identified by tandem mass spectrometry. Levels of viral replication were similar amongst the HIV-1 isolates, although higher levels were obtained from one viral strain obtained from a patient with CI. Significant differences were found in protein profiles between virus-infected MDMs with NC, CI, and SF162 isolates (adjusted P value after multiple testing corrections, or q value <.10). The authors identified 6 unique proteins in NC, 7 in SF162, and 20 in CI. Three proteins were common to SF162 and CI strains. The MDM proteins linked to infection with CI strains were related to apoptosis, chemotaxis, inflammation, and redox metabolism. These findings support the hypothesis that the macrophage proteome differ when infected with viral isolates of women with and without CI.
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Trastornos del Conocimiento/metabolismo , Infecciones por VIH/metabolismo , VIH-1/patogenicidad , Macrófagos/metabolismo , Macrófagos/virología , Proteoma , Complejo SIDA Demencia/sangre , Complejo SIDA Demencia/metabolismo , Células Cultivadas , Cognición , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/virología , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , VIH-1/fisiología , Hispánicos o Latinos , Humanos , Proteómica , Espectrometría de Masas en Tándem , Virulencia , Replicación ViralRESUMEN
HIV infection is increasing in minority groups, particularly in African American and Hispanic women. Although the incidence of HIV dementia has decreased since the advent of highly active antiretroviral treatment, prevalence of neurocognitive complications has increased as patients are now living longer. This study's purpose was to determine the psychometric properties of the Spanish-language HIV Dementia Scale (HDS) in a group of HIV-infected women. We recruited 96 women: 60 HIV-seropositive and 36 HIV-seronegative. Modification of the HDS into a Spanish-language version consisted of translating the instructions, substituting four words in Spanish (gato, media, azul, piña), increasing 1 second in the psychomotor speed because the Spanish alphabet has more letters than the English alphabet, and not offering clues for memory recall. Cognitive impairment (CI) was defined according to the modified American Academy of Neurology HIV-dementia criteria including an asymptomatic CI group. Statistical analysis consisted of analysis of variance to determine group differences and receiver operator characteristics (ROC) to determine the optimal cutoff point for the screening of CI. HDS-Spanish total score and subscores for psychomotor speed and memory recall showed significant differences between HIV-seronegative and women with HIV-dementia (p < 0.001) and between HIV-seropositive women with normal cognition and those with HIV-dementia (p < 0.001). The optimal cutoff point of 13 or less had performance characteristics of 87% sensitivity and 46% specificity for HIV-associated CI (50.0% positive predictive value, 85.0% negative predictive value). The HDS-Spanish translation offers a useful screening tool with value for the identification of Hispanic women at risk of developing HIV-associated symptomatic neurocognitive disturbances.
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Complejo SIDA Demencia/clasificación , Complejo SIDA Demencia/diagnóstico , Complejo SIDA Demencia/epidemiología , Adulto , Depresión/clasificación , Femenino , Seronegatividad para VIH , Seropositividad para VIH , Humanos , Pruebas de Inteligencia , Memoria , Persona de Mediana Edad , Estudios Prospectivos , Psicometría , Desempeño Psicomotor , Puerto Rico/epidemiología , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
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.
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Complejo SIDA Demencia/diagnóstico , Complejo SIDA Demencia/fisiopatología , Investigación , Complejo SIDA Demencia/patología , Complejo SIDA Demencia/terapia , Academias e Institutos , Algoritmos , Terapia Antirretroviral Altamente Activa , Trastornos del Conocimiento/clasificación , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/virología , Progresión de la Enfermedad , VIH-1 , Humanos , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Specific proteins produced from monocytes may be linked to the pathogenesis and aid in the diagnosis of HIV-1-associated dementia (HAD). OBJECTIVE: The authors assessed whether a diagnostic phenomic protein profile could be obtained from monocyte-derived macrophages (MDM) from HIV-1-infected patients with cognitive impairment. METHODS: Twenty-one HIV-1-infected Hispanic women and 10 seronegative controls matched by age and sex were followed at the University of Puerto Rico Medical Sciences Campus, where neuropsychological, immune, and viral parameters were tested. Monocytes were recovered by Percoll gradient centrifugation from peripheral blood mononuclear cells. MDM lysates were prepared after 7 days of cultivation and protein profiles analyzed by surface enhanced laser desorption/ionization (SELDI)-time of flight (TOF) ProteinChip tests. Classification trees were prepared for statistical analyses. RESULTS: A total of 177 protein peaks from 2 to 80 kDa were evaluated in 31 patient MDM lysates by SELDI-TOF ProteinChip assays. Select protein peaks, at 5028 and 4320 Da, separated HIV-1-infected from HIV-1-seronegative subjects with a sensitivity of 100% and a specificity of 80%. Thirty-eight peaks were used to differentiate HIV-1-infected subjects with and without cognitive impairment. A 4348 Da protein separated the two groups with a sensitivity of 100% and a specificity of 75%. CONCLUSIONS: The identification of unique phenomic MDM profiles from cognitively impaired HIV-1-infected patients supports the hypothesis that changes in monocyte function parallel the development of HAD.
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Complejo SIDA Demencia/patología , VIH-1 , Macrófagos/fisiología , Proteómica , Complejo SIDA Demencia/virología , Adulto , Recuento de Linfocito CD4 , Diferenciación Celular , Cognición , Estudios de Cohortes , Femenino , Humanos , Macrófagos/química , Persona de Mediana Edad , Monocitos/patología , Pruebas Neuropsicológicas , Análisis por Matrices de Proteínas , Puerto Rico , Sensibilidad y Especificidad , Técnica de Sustracción , Carga ViralRESUMEN
BACKGROUND: Flumazenil is a competitive benzodiazepine receptor antagonist, reverts the sedation effects of benzodiazepines and its effect on electroencephalographic (EEG) patterns is controversial. The purpose of this study was to describe flumazenil's effect on EEG patterns of patients undergoing conscious sedation. METHODS: Ten voluntary patients, aged 16-23, at elective oral surgery had conscious sedation with midazolam and local anesthesia. After the procedure, sedation was reversed with flumazenil. Each patient had 4 EEGs of 4 minutes each: baseline, 5 minutes after midazolam, prior to flumazenil, and 8 minutes after flumazenil. A clinical neurophysiologist interpreted EEGs blinded to time. RESULTS: Eight patients had an awake and 2 had an awake and drowsy normal EEG. After midazolam all developed a diffuse beta wave and alpha wave attenuation or dropout. Prior to flumazenil 7 presented diffuse beta and scattered theta waves, and 3 an awake pattern (procedure required > 30 minutes). After flumazenil, reversal of beta and theta waves and appearance of alpha waves was noted; no changes occurred when procedure lasted more than 30 minutes. One patient presented with diffuse theta waves, 6 Hz. CONCLUSIONS: Flumazenil reverts midazolam EEG changes if administered < 30 minutes after midazolam administration, midazolam-induced EEG changes revert spontaneously after 30 minutes, and flumazenil may precipitate theta activity.