RESUMEN
Neuropsychologic function was assessed in 13 children with symptomatic human immunodeficiency virus disease (Centers for Disease Control Class P2), ranging in age from 14 months to 12 years. Before the initiation of treatment, eight patients were classified as having encephalopathy. Psychologic tests were administered both before and after 6 and 12 months of continuous-infusion azidothymidine (AZT; zidovudine) treatment. After 6 months of treatment a significant increase of 15.5 (+/- 3.3) IQ points was demonstrated in general cognitive functioning (p less than 0.001). Follow-up for 10 of these patients indicated that after 12 months of AZT therapy, they had maintained their gains in IQ points. Improvements in adaptive behavior after 6 months of therapy, assessed with a standardized interview, paralleled the findings on the IQ data. No significant differences in the amount of change was observed for the different subgroups. The magnitude of these improvements could not be explained by practice effects, environmental changes, or general improvement in physical state. We conclude that neuropsychologic function was significantly improved with continuous infusion AZT treatment.
Asunto(s)
Complejo SIDA Demencia/tratamiento farmacológico , Pruebas Neuropsicológicas , Zidovudina/uso terapéutico , Complejo SIDA Demencia/fisiopatología , Complejo SIDA Demencia/psicología , Adaptación Psicológica , Niño , Preescolar , Evaluación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Infusiones Intravenosas , Inteligencia , Pruebas de Inteligencia , Masculino , Zidovudina/administración & dosificaciónRESUMEN
Zidovudine pharmacokinetics were determined in 16 children with human immunodeficiency virus infection who were being treated intravenously and orally on an intermittent schedule (every 6 hours). The intravenous doses studied were 80 (n = 3), 120 (n = 4), and 160 (n = 5) mg/m2/dose, infused over 1 hour. Fourteen patients were monitored after an oral dose of zidovudine at 120 (n = 2), 180 (n = 7), or 240 (n = 5) mg/m2/dose. Zidovudine was assayed with a reverse-phase high-pressure liquid chromatography method. Zidovudine disappearance after intravenous administration was rapid and biexponential, with half-lives of 14 and 90 minutes and a total clearance of 641 +/- 161 ml/min/m2. The volume of distribution at steady state was 45 +/- 28 L/m2. These pharmacokinetics parameters are very similar to those reported in adults. When administered orally, zidovudine was rapidly absorbed. The fraction of the oral dose that was bioavailable was 0.68 +/- 0.25, so that a 50% increment in the dose, in the conversion from intravenous to oral administration, resulted in plasma zidovudine concentrations after oral dosing that were nearly identical to those achieved with the 1-hour intravenous infusion. However, a dose of 180 mg/m2 given orally every 6 hours maintained plasma zidovudine concentrations in the target range of 1 mumol/L for less than half of the dosing interval. Other schedules, routes of administration, or oral drug formulations may have to be considered if sustained continuous exposure to micromolar zidovudine concentrations is desired.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , Zidovudina/farmacocinética , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Administración Oral , Disponibilidad Biológica , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Femenino , Semivida , Humanos , Lactante , Infusiones Intravenosas , Absorción Intestinal , Masculino , Tasa de Depuración Metabólica , Zidovudina/administración & dosificación , Zidovudina/sangreAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Linfoide/tratamiento farmacológico , Fenitoína/farmacocinética , Niño , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Humanos , Leucemia Linfoide/complicaciones , Masculino , Mercaptopurina/farmacología , Tasa de Depuración Metabólica/efectos de los fármacos , Metotrexato/farmacología , Prednisona/farmacología , Vincristina/farmacologíaRESUMEN
Previous studies have failed to establish a direct relationship between behavioral disorders and organic pathology in long-term survivors of childhood acute lymphoblastic leukemia. We evaluated 23 long-term survivors who received central nervous system preventive therapy with cranial irradiation and intrathecal chemotherapy, using neuropsychologic tests and computed tomographic brain scans. The patients were in continuous first remission for 7 to 11 years, and none were receiving chemotherapy. On the basis of their CT scan findings, they were divided into three groups: 10 with normal CT findings, five with intracerebral calcifications, and eight with cortical atrophy. Neuropsychologic test results allowed prediction of CT scan findings with an 87% accuracy (P less than 0.001), indicating a strong correlation between the presence and type of CT scan abnormality and neuropsychologic functioning. Tests that measured verbal memory, attention, and functions correlated with frontal lobe integrity were most powerful in discriminating between groups.
Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos de la Comunicación/diagnóstico , Leucemia Linfoide/complicaciones , Tomografía Computarizada por Rayos X , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/prevención & control , Trastornos de la Comunicación/etiología , Trastornos de la Comunicación/prevención & control , Citarabina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfoide/tratamiento farmacológico , Masculino , Mercaptopurina/administración & dosificación , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Pruebas Neuropsicológicas , Prednisona/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encéfalo/efectos de la radiación , Hormona del Crecimiento/metabolismo , Leucemia Linfoide/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Ritmo Circadiano , Femenino , Humanos , Inyecciones Espinales , Leucemia Linfoide/fisiopatología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversosAsunto(s)
Traumatismos Faciales , Leucemia Linfoide , Neoplasias de los Tejidos Blandos , Enfermedad Aguda , Adulto , Antineoplásicos/uso terapéutico , Femenino , Humanos , Leucemia Linfoide/tratamiento farmacológico , Leucemia Linfoide/patología , Recurrencia , Remisión Espontánea , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/patologíaAsunto(s)
Antineoplásicos/efectos adversos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Neoplasias Orbitales/tratamiento farmacológico , Rabdomiosarcoma/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Preescolar , Ciclofosfamida/efectos adversos , Dactinomicina/efectos adversos , Humanos , Masculino , Vincristina/efectos adversosRESUMEN
Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state.
Asunto(s)
Hepatitis B/complicaciones , Síndrome de Wiskott-Aldrich/complicaciones , Anticuerpos Antivirales/análisis , Antígenos Virales/análisis , Enfermedad Crónica , Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Síndrome de Wiskott-Aldrich/inmunologíaRESUMEN
During maintenance therapy with intraventricular methotrexate, progressive dementia developed in a child with meningeal leukemia. Cerebrospinal fluid levels of MTX were in the nontoxic range and neurologic evaluation failed to demonstrate anatomic obstruction, infection, or folate depletion. The patient's symptoms gradually resolved when the methotrexate was discontinued, suggesting that methotrexate neurotoxicity may occur in the absence of an elevated CSF concentration of MTX.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Metotrexato/efectos adversos , Psicosis Inducidas por Sustancias/etiología , Preescolar , Femenino , Humanos , Inyecciones Intraventriculares , Metotrexato/administración & dosificación , Metotrexato/uso terapéuticoRESUMEN
This report describes a patient with acute lymphoblastic leukemia who developed arthritis of the knee caused by Candida tropicalis. Systemic therapy with amphotericin B apparently suppressed but did not eliminate the infection. Resolution of the arthritis occurred only after three intra-articular injections of amphotericin B. Intra-articular administration of amphotericin B may be a useful adjunct to systemic antifungal therapy in the treatment of these infections.