RESUMEN
the early and med-term follow-up results and technical points of new re-dilated stent in the treatment of pulmonary artery bifurcation opening stenosis, and explore its feasibility and advantages. From March 2019 to October 2020, 10 children [5 males, mean age (7±3) years], mean weight 18.75(13.35,23.05) kg with pulmonary artery bifurcation opening stenosis were treated with new re-dilated stents in the Central China Fuwai Hospital. Including 5 cases of tetralogy of Fallot, 4 cases of pulmonary atresia, 1 case of anomalous origin of coronary artery, all children were given new re-dilated stent implantation. Echocardiography, chest X-ray and electrocardiogram were performed 1 day, 3, 6, 12 months after intervention. Pulmonary artery CTA was performed after 6 or 12 months to evaluate the results, including restenosis, malposition and rupture. A total of 16 stents were implanted in 10 children, 5 cases had simultaneous stenosis of bifurcation openings of pulmonary arteries, and 1 stent was implanted in each of the left and right pulmonary artery openings. The pressure of right ventricular and gradient was significantly decreased immediately after intervention, from preoperative (38-80) mmHg(1 mmHg=0.133 kPa) to postoperative (0-22) mmHg, only one patient's pressure gradient is over 20 mmHg (22 mmHg), and all cases discharged successfully. Stent restenosis, malposition, fracture and other abnormalities were not observed in follow-up. Stents implantation for patients with pulmonary artery bifurcation opening stenosis is very more difficult. A good strategy can ensure that the intervention is safe and effective. It not only avoids the risk of repeated surgery, but also achieves good med-term follow-up results.
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Cardiopatías Congénitas , Arteria Pulmonar , Niño , Preescolar , Constricción Patológica , Femenino , Cardiopatías Congénitas/cirugía , Humanos , Masculino , Pronóstico , Stents , Resultado del TratamientoRESUMEN
In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Etiquetado de Medicamentos , Control de Medicamentos y Narcóticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Vigilancia de Productos Comercializados , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , Aprobación de Drogas , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
OBJECTIVE: To study the mechanism of early chemosensitivity and later chemoresistance of Cytarabine (Cyt) to HL-60 cells to regulate ERK/Slug signal pathway. MATERIALS AND METHODS: HL-60 cells were stably transfected with NF-κBp65 siRNAï¼P53 up-regulated modulator of apoptosis (PUMA) siRNA (PUMA siRNA) and Slug siRNA respectively or exposed to 25 nM U0126 for 24h, then the cells were exposed to Cyt (250 nM) respectively. In different time point after Cyt treatment, the activity of NF-κB and the expression of Erk1/2, NF-κBp65, Slug and PUMA protein were detected. The cells survival rate and apoptotic index were detected by MTT and TUNEL methods. RESULTS: After the HL-60 cells were exposed to Cyt (250 nM) for 24 h, the activity of NF-κB reached maximum value, and reached minimum value for 48 h. The expressions of NF-κBp65 and PUMA reached maximum value after exporser to Cyt (250 nM) for 24 h, and reached minimum value after 48 h. Erk1/2 phosphorylation and Slug expression began to increase after exporser to Cyt (250 nM) for 24 h, and reached maximum value for 48 h. The cells survival rate was decreased, and arrived to minimum value (29.5 ± 4.6, F = 12.74, p < 0.01). The cells apotosis rate was increased, and arrived to maximum value (14.2 ± 2.8, F = 15.02, p < 0.01). By inhibiting NF-κBp65 or PUMA by siRNA transfection, the cells survival rate was enhanced and the apotosis rate was significantly declined after exporsed to Cyt (250 nM). When NF-κBp65 was inhibited, the expression of PUMA was decreased. By inhibiting Erk1/2 phosphorylation and Slug expression, the cells survival rate began to decrease for 24 h, and reached the fewest at 48 h after exporsed to Cyt (250 nM) (19.8 ± 2.7, F = 11.4, p < 0.01 and 17.4 ± 0.6, F = 15.3, p < 0.01). The cells apotosis rate began to increase from 24 h, and reach a head at 48 h after exporser to Cyt (250 nM) (28.6 ± 4.7, F = 9.84, p < 0.01 and 27.6 ± 6.4, F = 10.31, p < 0.01. After Erk1/2 phosphorylation inhibited, Slug expression was lowered and PUMA expression was significantly increased. The changes are most distinct after the cells were exporser to Cyt (250 nM) for 48 h. By Slug inhibition had no effect on Erk1/2 phosphorylation, but increase the expression of PUMA. CONCLUSIONS: The chemosensitiveness of HL-60 cells to Cyt were relation to the up-regulation of PUMA induced by NF-κB. The chemoresistance to Cyt was related to the up-regulation of Slug induced by Erk1/2, which inhibited the expression of PUMA.
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Proteínas Reguladoras de la Apoptosis/biosíntesis , Citarabina/farmacología , Técnicas de Silenciamiento del Gen/métodos , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Proto-Oncogénicas/biosíntesis , Factores de Transcripción/biosíntesis , Regulación hacia Arriba/fisiología , Antimetabolitos Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis/genética , Células HL-60 , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción de la Familia Snail , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Off-label use of medicines is common. Because many off-label uses have not been carefully studied, it is important that postmarketing drug safety systems be able to identify, assess, and monitor adverse events that occur in the off-label setting. The full range of postmarketing surveillance and analysis tools can be utilized to study the adverse effects of medicines used off-label.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Uso Fuera de lo Indicado , Sistemas de Registro de Reacción Adversa a Medicamentos , HumanosRESUMEN
The contemporary science of drug safety seeks not only to identify the risks associated with the use of medicines but also to quantify these risks, identify their risk factors, and assess strategies to minimize them. It monitors the use of medicines in actual practice to understand how the medical care system interacts with the intrinsic pharmacologic properties of medicines to produce the observed effects. To the extent possible, these analyses use a population-based approach that at times requires creativity and innovation. The key to effective safety management of drugs in the postmarketing setting is the ability to access sufficient good-quality data, interpret the data appropriately, challenge old assumptions, and define best practices in contemporary drug safety approaches.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vigilancia de Productos Comercializados/métodos , Monitoreo de Drogas , Humanos , Vigilancia de Productos Comercializados/normas , Medición de Riesgo , Factores de Riesgo , Gestión de Riesgos , Estadística como Asunto , Trastornos Relacionados con Sustancias , Estados Unidos , United States Food and Drug AdministrationRESUMEN
INTRODUCTION: Human immunodeficiency virus (HIV) infection is associated with several central nervous system (CNS) infections and neoplasms. These opportunistic processes generally occur with advanced immunosuppression, but if an accurate diagnosis is made, effective treatment can frequently be initiated. METHODS: In an attempt to assess the safety, diagnostic yield, and utility of stereotactic brain biopsy in the clinical management of suspected HIV-associated primary CNS lymphoma, we retrospectively studied the performance of biopsy in HIV-seropositive patients presenting with focal intracranial lesions. This analysis included 435 patients undergoing brain biopsy, identified through a local case series (n=47) combined with all published cases (n=388). The years of analysis for this study were 1984 and 1997. We also assessed the survival of HIV-associated intracranial mass lesions and of PCNSL patients treated at JHU. RESULTS: Definitive histopathological diagnoses were established in eighty-eight percent of biopsied cases: primary CNS lymphoma (PCNSL) (30%), CNS toxoplasmosis (CNS TOXO) (16%), progressive multifocal leukoencephalopathy (PML) (25%), and other specific diagnoses (17%). Post-biopsy morbidity within thirty days was 8.4% and mortality was 2.9%. PCNSL was the most common diagnosis among cases biopsied after failure of anti-toxoplasmosis therapy, 134/205 (65%). In the local case series, biopsy-related morbidity was associated with poor functional status, decreased platelet count, and number of lesions at presentation. The median survival of irradiated PCNSL cases was 29 days longer than untreated cases (median survival 50 days versus 21 days, respectively, Chi-square=6.73, P<0.01). DISCUSSION: Stereotactic brain biopsy had a high diagnostic yield for HIV-associated focal intracranial lesions, however, the biopsy complication rate in this patient population was relatively high. PCNSL was diagnosed in the majority of patients failing anti-toxoplasmosis therapy. Survival after irradiation for PCNSL remains very poor.
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Complejo SIDA Demencia/complicaciones , Complejo SIDA Demencia/patología , Encéfalo/patología , Seropositividad para VIH/patología , Linfoma Relacionado con SIDA/patología , Complejo SIDA Demencia/mortalidad , Estudios de Seguimiento , Seropositividad para VIH/complicaciones , Humanos , Linfoma Relacionado con SIDA/complicaciones , Linfoma Relacionado con SIDA/mortalidad , Linfoma Relacionado con SIDA/radioterapia , Morbilidad , Estudios Retrospectivos , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.
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Inhibidores de Captación Adrenérgica/administración & dosificación , Amitriptilina/administración & dosificación , Antiarrítmicos/administración & dosificación , Infecciones por VIH/complicaciones , Mexiletine/administración & dosificación , Dolor/tratamiento farmacológico , Adulto , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neuritis/complicaciones , Neuritis/virología , Dolor/virología , Nervios Periféricos/virologíaRESUMEN
UNLABELLED: A retrospective chart review was conducted to determine the effect of alpha-Interferon (alpha-IFN) on disease progression, symptom palliation, and survival in HIV-associated Progressive Multifocal Leukoencephalopathy (PML). METHODS: Subjects were HIV seropositive patients diagnosed with PML at the Johns Hopkins Hospital between 1985 and July of 1986. Diagnostic criteria for PML included both clinical symptomatology and histologic or radiographic confirmation. All patients with concomitant CNS infections were excluded. Patients receiving a minimum treatment of 3 weeks of 3 million units of alpha-IFN daily were compared to untreated historical controls. From 104 PML cases reviewed, 77 met the defined criteria for PML. Twenty-one patients had received open-label alpha-IFN treatment in a non-randomized manner for at least 3 weeks, and 32 met criteria for inclusion in the untreated group as historical controls. Deceased treated patients were comparable to deceased untreated patients with respect to age, gender, race, HIV risk factors, AIDS-defining illnesses, and CD4+ counts. CD4+ counts and use of anti-retroviral medications within 6 months of PML onset were higher among those who were living at the time of the study. RESULTS: Among deceased patients, median survival of treated patients was 127.5 days longer than that of untreated patients (Chi-square=4.21, P=0.04). When living and deceased treated patients were combined, the median survival was 325 days (range 35 - 1634) versus 121 days (range 46 - 176) in untreated patients (Chi-square=13.47, P < 0.001). When survival times in untreated patients were left-censored to account for possible survivorship bias in treated patients, survival in treated patients remained significantly prolonged (325 days versus 175.5 days, Chi-square=4.65, P=0.03). In addition, use of alpha-IFN was associated with a significant delay in the onset of memory loss (Chi-square=8.59, P < 0.01). Seven alpha-IFN treated patients showed sustained remissions of several months to over a year, with documented improvements in mental status, aphasia, dysarthria, dysphagia, paresis, and dyscoordination. Moreover, four IFN-treated patients had evidence of MRI lesion regression, although this was not always correlated with clinical remission. Four of 32 untreated patients also reported transient symptomatic improvements. CONCLUSION: This open-label study suggests that alpha-IFN may delay progression, palliate symptoms, and significantly prolong survival in HIV-associated PML, and we therefore suggest that a controlled clinical trial is warranted.
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Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Interferón-alfa/uso terapéutico , Leucoencefalopatía Multifocal Progresiva , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/terapia , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Leucoencefalopatía Multifocal Progresiva/mortalidad , Leucoencefalopatía Multifocal Progresiva/terapia , Leucoencefalopatía Multifocal Progresiva/virología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
A consecutive series of 71 patients diagnosed with HIV-associated dementia (HAD) (1984-1994) were studied to characterize the clinical course of HAD, and to identify predictive markers of rapid neurologic progression. Neurologic progression rate was determined from the change in the Memorial Sloan Kettering (MSK) dementia severity score from diagnosis to death. Those with the most rapid progression in neurologic disability were compared with those with slow or no progression. Autopsy material was immunostained for macrophage activation markers and gp41 in 30 individuals. Median survival was 3.3 months and 6.1 months for rapid-progression and no-progression patients, respectively. Rapid progression was associated with injection drug use but not with race, gender, or age. CD4+ cell counts were lower at diagnosis among rapid-progression than no-progression patients but no differences in AIDS-defining illnesses or patterns of antiretroviral therapy were found. At presentation, rapid-progression patients had more prominent symptoms of mental slowing than those with no progression; however, no other clinical features, CSF, or imaging features distinguished the groups. Less abundant macrophage activation in both basal ganglia and midfrontal gyrus regions, as judged by HAM56 immunostaining, was noted in 9 no-progression patients, compared with 12 rapid-progression patients. Neurologic progression and survival with HAD is highly variable. A significant proportion of individuals with dementia have prolonged survival of more than 12 months and remain cognitively stable. A history of injection drug use and presentation with prominent psychomotor slowing is associated with more rapid neurologic progression, and these patients tend to show more abundant macrophage activation within the CNS.
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Complejo SIDA Demencia/psicología , Complejo SIDA Demencia/clasificación , Complejo SIDA Demencia/fisiopatología , Adulto , Cognición/fisiología , Progresión de la Enfermedad , Femenino , Infecciones por VIH/etiología , Humanos , Masculino , Persona de Mediana Edad , Desempeño Psicomotor/fisiología , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Análisis de SupervivenciaRESUMEN
To determine the clinical and virological correlates of neuropsychological test performance decline in HIV infection, we measured viral burden in blood in 272 HIV-seropositive men without dementia in the Baltimore arm of the Multicenter AIDS Cohort Study (MACS). These measures were then related to neuropsychological (NP) decline, defined as a decline relative to prior best performance of 2.0 standard deviations or more on one or more neuropsychological tests. A short battery of NP tests (Mini-Screen Battery) was administered to all 272 men. NP test performance decline was identified in 53/272 (19.5%) of participants on the Mini-Screen Battery. Follow-up NP data were available for 204 participants who had undergone the Mini-Screen. The frequency of sustained NP test performance decline was 7.8% for the Mini-Screen Battery. A lower CD4+ cell count was weakly associated with sustained NP test performance decline. After adjustment for CD4+ cell count, hemoglobin, body mass index, and presence of AIDS, none of the viral burden measures (p24 antigenemia, plasma viremia, quantitative culture) correlated with sustained NP test performance decline. We conclude that these measures of blood HIV viral burden are not markers for NP decline, but that a lower CD4+ cell count is.
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Complejo SIDA Demencia/inmunología , Complejo SIDA Demencia/virología , Proteína p24 del Núcleo del VIH/sangre , Viremia/inmunología , Viremia/virología , Complejo SIDA Demencia/tratamiento farmacológico , Adulto , Antivirales/administración & dosificación , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , Proteína p24 del Núcleo del VIH/aislamiento & purificación , VIH-1 , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Viremia/tratamiento farmacológico , Zidovudina/administración & dosificaciónRESUMEN
OBJECTIVES: To determine the impact of neurologic disease on length of stay and total hospital charges for hospitalizations related to human immunodeficiency virus (HIV) infection. DESIGN: Review of all HIV-related hospitalizations from all acute nonfederal hospitals in Maryland in 1991 and 1992. Neurologic status and HIV disease status were determined by codes from the International Classification of Diseases, Ninth Revision Clinical Modification, in an administrative database. Total hospital charges and length of stay were also included in this database. RESULTS: Of 12 128 HIV-related hospitalizations (6013 patients with the acquired immunodeficiency syndrome [AIDS], 308 HIV-seropositive patients with symptoms without AIDS, and 5807 HIV-seropositive patients without symptoms), neurologic disease occurred in 1013 (8.4%), predominantly in patients with AIDS. In all HIV-seropositive patients, those with primary neurologic disease had a long mean (+/- SD) length of stay (16.4 +/- 16.5 days vs 9.3 +/- 11.3 days; P < .001) and higher mean (+/- SD) total charges ($12,733 +/- $12,009 vs $8069 +/- $11,247; P < .001) than those without neurologic disease. In patients with AIDS, those with primary neurologic disease also had a longer mean (+/- SD) length of stay (17.2 +/- 17.2 days vs 11.7 +/- 12.7 days; P < .001) and higher mean (+/- SD) total charges ($13,430 +/- $12,470 vs $10,794 +/- $13,537; P < .001) than those without neurologic disease. After adjustment for age, sex, race, and stage of HIV infection in all HIV-seropositive patients, our results indicated that neurologic disease increased the length of stay by 3.3 days (95% confidence interval [CI], 2.9-3.8) and total charges by $2552 (95% CI, $2111-$2993). After adjustment for age, sex, and race in discharged patients with AIDS, the results showed that neurologic disease increased length of stay by 2.24 days (95% CI, 0.73-3.77) and total charges by $1512 (95% CI, $40-$2894). CONCLUSION: Neurologic disease increases the length of stay and total hospital charges of HIV-infected patients.
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Infecciones por VIH/complicaciones , Hospitalización/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Enfermedades del Sistema Nervioso/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/economía , Adulto , Femenino , Infecciones por VIH/economía , Seropositividad para VIH/economía , Encuestas de Atención de la Salud , Precios de Hospital/estadística & datos numéricos , Hospitalización/economía , Humanos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Maryland/epidemiología , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/economía , Enfermedades del Sistema Nervioso/etiología , Revisión de Utilización de RecursosRESUMEN
A masked-threshold and a loudness-balance method have been developed to estimate the attenuation of communication headsets and hearing protectors with built-in active noise reduction (ANR) systems. Both methods are used to estimate the attenuation of the ANR systems and the masked-threshold method is also used to estimate the total attenuation (active plus passive) of the device. The procedures are designed to be used in the presence of environmental noise, and to minimize the noise exposure of subjects during the measurements. For comparison, physical measurements of insertion loss have also been performed using a miniature microphone in the concha. Experiments showed that the masked-threshold methods tends to give increased estimates of the attenuation if the noise reduction of the left and right earcup ANR systems differs, as commonly occurs in practice. In contrast, the loudness-balance method reduces the estimates of the active attenuation. Insertion loss measurements may be influenced by the position of the microphone, owing to the spatial variability of the sound field under an earmuff when the ANR system is operating. Differences between physical and subjective measurements of up to 20 dB have been obtained in this study at frequencies of 250 Hz and below for a device in which the sound pressure varied substantially near, and within, the ear canal.
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Dispositivos de Protección de los Oídos , Espectrografía del Sonido , Percepción del Habla , Adulto , Umbral Auditivo , Comunicación , Diseño de Equipo , Humanos , Percepción Sonora , Ruido , Enmascaramiento Perceptual , PsicoacústicaRESUMEN
The objective of this study was to determine if sustained decline in psychomotor speed tests is associated with an increased risk of progression to dementia, acquired immunodeficiency syndrome (AIDS), or mortality in human immunodeficiency virus (HIV)-1-infected homosexual men in the Baltimore site of the Multicenter AIDS Cohort-Study (MACS). Clinical and neuropsychological data were obtained on 291 HIV+ homosexual men seen semi-annually over a nine year period (1986-1994). A proportional hazards model was used to assess the predictive value of sustained psychomotor slowing (defined as a 2.0 standard deviation (s.d.) decline in performance on either the Symbol Digit Modalities test or Trailmaking test at two consecutive evaluations). Time-dependent co-variates included in the model were sustained psychomotor slowing, number of attended visits, CD4+ lymphocyte count, hemoglobin and antiretroviral medication use. HIV+ participants with and without sustained psychomotor slowing were compared. Outcome variables were the development of dementia, AIDS and death. HIV+ subjects with sustained psychomotor slowing had an increased hazard of dementia (Risk ratio (RR) = 5.0, P = 0.008), AIDS (RR = 2.4, P = 0.02), and death (RR = 2.0, P = 0.04). A similar analysis using sustained cognitive decline in one domain from a more extensive neuropsychological test battery failed to show any predictive value. Sustained decline in psychomotor performance in HIV infection was predictive of dementia, AIDS and death. This brief neuropsychological test battery may be useful for early detection of HIV+ individuals with a poorer prognosis who may benefit from more aggressive treatment to prevent HIV dementia.
Asunto(s)
Complejo SIDA Demencia/mortalidad , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Infecciones por VIH/complicaciones , Trastornos Psicomotores/virología , Síndrome de Inmunodeficiencia Adquirida/psicología , Síndrome de Inmunodeficiencia Adquirida/terapia , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/virología , Estudios de Cohortes , Demografía , Infecciones por VIH/psicología , Infecciones por VIH/terapia , Humanos , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Pronóstico , Trastornos Psicomotores/diagnóstico , Factores de Riesgo , Resultado del TratamientoRESUMEN
There are a variety of HIV-related neurologic complications that have numerous causes. HIV-related neurologic illnesses are specific to the stage of HIV infection, although the greatest burden of neurologic disease and the most disabling syndromes occur in the more advanced stages. As the number of HIV-infected persons continues to increase worldwide and as antiretroviral and other anti-infective therapies improve patient survival in the advanced stages of HIV infection, the burden of neurologic disease will continue to increase.
Asunto(s)
Infecciones por VIH/epidemiología , Enfermedades del Sistema Nervioso/epidemiología , Complejo SIDA Demencia/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adolescente , Adulto , Distribución por Edad , Antivirales/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Salud Global , Infecciones por VIH/complicaciones , Infecciones por VIH/transmisión , Humanos , Incidencia , Recién Nacido , Linfoma Relacionado con SIDA/epidemiología , Linfoma Relacionado con SIDA/etiología , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades Neuromusculares/complicaciones , Enfermedades Neuromusculares/epidemiología , Enfermedades Neuromusculares/etiología , Paraparesia Espástica Tropical/complicaciones , Paraparesia Espástica Tropical/epidemiología , Paraparesia Espástica Tropical/etiología , Prevalencia , Factores de Riesgo , Distribución por SexoRESUMEN
We studied the features and frequency of sensory neuropathy among 79 HIV-1-infected individuals participating in a multicenter clinical trial of zalcitabine (2'3'-dideoxycytidine, or ddC) antiretroviral therapy. The trial compared zalcitabine monotherapy (2.25 mg/day) versus combination therapy (2.25 mg/day ddC) with zidovudine (ZDV, formerly AZT) versus monotherapy with ZDV alone. Neuropathy developed in 34% of ddC recipients but in only 4% of comparable patients treated with ZDV alone--a 7.9-fold increase in the attack rate of neuropathy. Using risk factor analysis, we found that diabetes mellitus was significantly associated with the development of toxic neuropathy (p = 0.02), and weight loss may contribute to its appearance. Like HIV-associated sensory neuropathy, ddC-related toxic neuropathy is a predominantly sensory, length-dependent, symmetric, painful neuropathy. Dose reduction lessened the severity of symptoms, although objective signs of neuropathy persisted. Patients with subclinical neuropathies or significant neuropathy risks such as diabetes may be poor candidates for ddC therapy.
Asunto(s)
Enfermedades del Sistema Nervioso/inducido químicamente , Trastornos de la Sensación/inducido químicamente , Zalcitabina/administración & dosificación , Zalcitabina/efectos adversos , Adulto , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Seropositividad para VIH/tratamiento farmacológico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/fisiopatología , Factores de Riesgo , Trastornos de la Sensación/epidemiología , Trastornos de la Sensación/fisiopatología , Análisis de Supervivencia , Zalcitabina/uso terapéuticoRESUMEN
To determine the clinical correlates of HIV-1-associated vacuolar myelopathy (VM), we designed a case-control study based on 215 AIDS autopsies in which we examined the spinal cord. We defined a case as an individual dying with AIDS and with VM present at autopsy; we defined a control as an individual dying with AIDS without VM. VM was found in 100 of 215 (46.5%) autopsies, with no apparent temporal trends. A higher number of AIDS-defining illnesses was strongly associated with the likelihood of VM (trend chi-square = 26.52, p < 0.001). Systemic infection with Mycobacterium avium-intracellulare and Pneumocystis carinii pneumonia were each associated with the pathologic findings of VM in both univariate and multivariate models. In the brain, multinucleated giant cells were detected in more cases than in controls (odds ratio = 3.68, 95% CI = 1.73 to 7.47, p < 0.001). The clinical features of HIV-1 dementia were not associated with VM; in contrast, predominantly sensory neuropathy was more common in VM cases than in controls (odds ratio = 5.00, 95% CI = 1.35 to 18.5, p < 0.05). Fifty-six cases with VM had detailed neurologic evaluations, but only 15 (26.8%) had signs and symptoms of myelopathy. The presence of symptomatic myelopathy was related to the pathologic severity: none of 17 cases with grade 1, five of 26 with grade 2, and 10 of 13 with grade 3 had clinical features of myelopathy (trend chi-square = 21.16, p < 0.005). VM is a common neuropathologic finding that is frequently unrecognized during life. The association with the number of systemic illnesses, M avium-intracellulare infection, and P carinii pneumonia suggests that the development of VM is related to the severity of immunosuppression.
Asunto(s)
Infecciones por VIH/etiología , Infecciones por VIH/patología , VIH-1 , Enfermedades de la Médula Espinal/etiología , Enfermedades de la Médula Espinal/patología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/etiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Estudios de Casos y Controles , Intervalos de Confianza , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedades de la Médula Espinal/epidemiología , Vacuolas/patologíaRESUMEN
Quantified magnetic resonance imaging (MRI) was related to neuropsychological (NP) test scores in an asymptomatic HIV-1 seropositive group, a non-demented AIDS/ARC group, a group of subjects with HIV-1 dementia, and a seronegative control group. The MRIs were quantified using three planimetric measures of brain structure: the bicaudate ratio (a measure of caudate region atrophy), the bifrontal ratio (a measure of frontal region atrophy), and the ventricle to brain ratio (a measure of overall cerebral atrophy). Cognitive performance was assessed with standard NP tests. Significant correlations between the MRI ratios and many of the NP tests were observed. Of the tests grooved pegboard, part B of the trail making test, the verbal fluency test, and the digit span forward were associated with MRI abnormalities. The bicaudate ratio was most closely associated with the NP tests. These findings indicate that ventricular enlargement, especially in the region of the caudate, is closely related to poor NP test performance in HIV-1 infection.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Encefalopatías/fisiopatología , Encéfalo/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Encéfalo/diagnóstico por imagen , Encefalopatías/diagnóstico , Encefalopatías/etiología , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/fisiopatología , Ventrículos Cerebrales/fisiopatología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Seropositividad para VIH , VIH-1 , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , RadiografíaRESUMEN
Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1-seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1-seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia.