RESUMEN
Reactive astrocytosis is a well-documented feature of HIV encephalitis (HIVE), but it is unclear whether restricted infection of astrocytes contributes to this phenomenon. In addition, the part played by reactive and/or infected astrocytes in AIDS-related dementia is not fully understood. In this study of patients at different stages of the human immunodeficiency virus (HIV) infection, who had been treated at most with one antiretroviral drug, reactive astrocytes were identified by immunopositivity for glial fibrillary acidic protein (GFAP) and infected astrocytes by positivity for HIV Nef protein. Results were compared for drug-using AIDS patients with (n=9) and without (n=7) HIVE, for presymptomatic HIV-positive drug users (n=12) and for control HIV-negative subjects (n=20), including a group who used drugs (n=10). GFAP-reactive astrocytes in both grey and white matter were significantly more numerous in HIVE subjects than in each of the other groups but did not correlate with viral load. Nef-positive astrocytes were confined to HIVE cases and to white matter, but were numerous in only one subject who was treatment-naive. Nef-positive microglia were identified in all HIVE cases and in occasional AIDS and presymptomatic subjects who did not have HIVE. The results suggest that astrocytes may form an additional viral reservoir in late HIV infection and may contribute to HIVE. However, the number of GFAP-positive astrocytes was neither increased in pre-AIDS nor in drug abuse, in contrast with microglia which we have shown previously to be up-regulated in both states.
Asunto(s)
Complejo SIDA Demencia/patología , Astrocitos/química , Astrocitos/virología , Productos del Gen nef/análisis , Proteína Ácida Fibrilar de la Glía/análisis , Complejo SIDA Demencia/complicaciones , Complejo SIDA Demencia/metabolismo , Adulto , Astrocitos/patología , Recuento de Células , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/virología , Femenino , Gliosis/metabolismo , Gliosis/patología , Gliosis/virología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Provirus , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/patología , Carga Viral , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
It is generally thought that infection of the central nervous system (CNS) by HIV-1 can occur early, even around the time of seroconversion, and evidence from animal studies supports this. However, the mode and timing of viral entry remain poorly understood since there have been comparatively few studies of the early neuropathology of HIV infection. In this study, samples of frontal and temporal lobes, and basal ganglia, were selected from 12 HIV-positive drug users who had been infected for 4-130 months before death, 10 HIV-negative drug users and 10 non-drug using controls, all age and sex matched. Routine and immunocytochemical staining showed that leptomeningeal and perivascular lymphocytic infiltrate was upregulated in HIV-infected cases compared with the two control groups, and choroid plexitis was confined to the HIV-positive subjects, suggesting an association with viral infection. In contrast, CD68-positive microglia were enhanced in both HIV- positive and HIV-negative drug users, considerably above the baseline seen in normal controls. However, there was no statistical difference between the three groups in relation to astrocytes. Screening and competitive polymerase chain reaction (PCR) undertaken on multiple samples including brain tissue, choroid plexus and leptomeninges from four of the HIV-positive subjects and one control case showed that the pro-viral burden was never more than 13 copies/microg DNA and was negative in multiple samples from one HIV-positive case and one control case. All the basal ganglia samples were PCR-negative. This study has not revealed any t spots' of viral load in brain tissue, choroid plexus or meninges, either early or late in the course of pre-symptomatic HIV infection. Drug use alone is associated with significant upregulation of microglia and this may predispose to HIV infection of the nervous system in drug users.
Asunto(s)
Infecciones por VIH/etiología , Infecciones por VIH/patología , Microglía/patología , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/patología , Adulto , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Aracnoides/patología , Encéfalo/virología , Cadáver , Plexo Coroideo/patología , Femenino , VIH/aislamiento & purificación , Seronegatividad para VIH , Humanos , Inmunohistoquímica , Inflamación/patología , Linfocitos/patología , Masculino , Microglía/inmunología , Piamadre/patología , Valores de Referencia , Trastornos Relacionados con Sustancias/virología , Regulación hacia ArribaRESUMEN
INTRODUCTION: Immersion in cold water is compatible with long-term survival, even when the period of immersion is relatively long. Guidelines for resuscitation after immersion stress the importance of prolonged resuscitation using advanced life support techniques. METHODS: Deaths due to drowning in south-east Scotland between 1991 and 1997 were reviewed, using a variety of data sources. RESULTS: 95 deaths (69 males, 26 females) from drowning occurred in the following sites: sea, 35; bath, 15; flowing freshwater, 26; still freshwater, 19; 22 (23%) of the drowning incidents were witnessed, 73 (77%) were unwitnessed. 28 individuals were recovered within 1 h of being seen alive, 13 having had witnessed accidents, 15 having had unwitnessed accidents. Six individuals were not resuscitated at the scene by the emergency services, despite being last seen alive within the previous hour. A further five individuals were initially resuscitated, but declared dead at the scene within 1 h of being known to be alive. CONCLUSIONS: Members of the emergency services, are failing to both initiate prehospital resuscitation and to continue this to hospital for victims of near drowning. There appears to be potential to reduce the drowning death rate by improving resuscitation. The emergency services and the public should be educated about the need to resuscitate those found in water.
Asunto(s)
Ahogamiento/mortalidad , Ahogamiento Inminente/terapia , Resucitación/métodos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Servicios Médicos de Urgencia/métodos , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Escocia/epidemiología , Distribución por Sexo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Bilateral Wilms' tumor occurs at a younger age than unilateral disease. While it generally has a good prognosis, it presents a therapeutic dilemma to balance curative surgical resection with preservation of renal tissue. A 15 year review of bilateral Wilms' tumors diagnosed at Princess Margaret Hospital was undertaken. Of 46 Wilms' tumor cases, eight were designated bilateral by diagnostic imaging (median age 1.1 years compared with 3.5 years for unilateral tumors). The surgical management entailed primary nephrectomy with contralateral biopsy in two patients, and bilateral biopsy and delayed resection in all remaining surviving patients (one patient died of perioperative complications). Seven patients had localized disease (stage I/II) and the six surviving patients received chemotherapy with vincristine and actinomycin; no patient received radiotherapy. All are alive and well (median follow-up 5.1 years). The remaining patient presented with pulmonary metastases and died of disease progression. Pathologic review revealed that four patients had truly bilateral disease demonstrable by histology, three had unilateral Wilms' tumor with contralateral nephrogenic rests, and in one patient the biopsies of the contralateral kidney showed neither tumor nor nephrogenic rests. In most cases pathological material was subject to external review. Follow-up demonstrates excellent renal function with compensatory hypertrophy in the remaining renal tissue. Conservative surgery and simple out-patient based, low toxicity chemotherapy is curative in most patients.