RESUMEN
The development of Wilms tumor in a patient with Prader-Willi syndrome prompted us to determine the parental origin of the genes implicated in both disorders because of the sex-specific parent-of-origin effects previously demonstrated for both conditions. A paternal chromosome 15q11-q13 deletion was demonstrated, but no changes were demonstrated in a limited analysis of chromosome 11p, which harbors two Wilms tumor suppressor genes, WT1 and WT2.
Asunto(s)
Neoplasias Renales/genética , Síndrome de Prader-Willi/genética , Tumor de Wilms/genética , Deleción Cromosómica , Cromosomas Humanos Par 11 , Humanos , Lactante , Neoplasias Renales/complicaciones , Masculino , Síndrome de Prader-Willi/complicaciones , Tumor de Wilms/complicacionesRESUMEN
Survival has been shown to improve when maintenance therapy for acute lymphocytic leukemia in children is given at night rather during the day. We examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In a crossover study, we determined the pharmacokinetics of intravenous methotrexate at 10:00 and 21:00 h in six children with standard or high-risk leukemia. During the study, children refrained from concomitant drugs (6-mercaptopurine and trimethoprim sulfamethoxazole). There was a significant fall in methotrexate plasma clearance at night (from 5.6 +/- 3 ml/min/kg to 4.7 +/- 2.3 ml/min/kg p < 0.05). Renal clearance of methotrexate tended to decrease at night and unbound renal clearance decreased significantly (from 17.5 +/- 1.7 ml/min/kg to 8.5 +/- 3.6 ml/min/kg p < 0.05). Creatinine clearance did not exhibit diurnal variation, when comparing two 12-h collections, but there was a significant decrease in the nonglomerular clearance of methotrexate (from 14.8 +/- 5.2 to 6 +/- 4 ml/min/kg). Because it is a weak organic acid, the tubular secretion of methotrexate depends on urinary pH. At night urinary pH is more acidic. This may result in more reabsorption and hence reduced renal clearance.
Asunto(s)
Ritmo Circadiano , Metotrexato/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Niño , Preescolar , Esquema de Medicación , Femenino , Humanos , Riñón/metabolismo , Masculino , Tasa de Depuración Metabólica , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Five years ago, the use of preoperative chemotherapy for Wilms' tumor was adopted at this institution. Thirty children ranging in age from 5 months to 9 years had histologically confirmed Wilms' tumor (needle biopsy, n = 26; open biopsy, n = 4). Stage was determined by chest and abdominal computed tomography (CT) scan. Bilateral tumors were present in 6 children. All children received actinomycin D and vincristine from 3 weeks to 6 months before surgery. Seven children with bilateral tumors or stage IV disease also received adriamycin. CT-measured tumor masses shrunk in most cases. Subsequently, nephrectomy was performed in 23 patients and partial nephrectomy in 4, 2 of whom had bilateral disease. In 2 patients, residual bilateral well-differentiated epithelial tumor was not surgically resected. One child died before surgery. Reevaluation at delayed total or partial nephrectomy resulted in a downstaging of disease in 12 (41%). Further chemotherapy and radiation was based on the surgical stage. Postoperative chemotherapy (4 months to 2 years) was administered to all patients. The chest and/or abdomen were radiated in 12. Four patients (13%) died, 1 of radiation pneumonitis and 3 of the disease progression (2 with unfavorable histology, 1 of whom had bilateral disease). Two of 4 with unfavorable histology and 4 of 6 with stage IV disease have survived. It is concluded that this preoperative chemotherapy protocol is as effective as the National Wilms' Tumor Study (NWTS) protocol. The treated tumor is smaller, less friable, and easier to remove. Furthermore, because of downstaging, less radiation is necessary for cure.
Asunto(s)
Dactinomicina/administración & dosificación , Neoplasias Renales/tratamiento farmacológico , Vincristina/administración & dosificación , Tumor de Wilms/tratamiento farmacológico , Biopsia con Aguja , Quimioterapia Adyuvante , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Lactante , Neoplasias Renales/patología , Neoplasias Renales/radioterapia , Neoplasias Renales/cirugía , Masculino , Tumor de Wilms/patología , Tumor de Wilms/radioterapia , Tumor de Wilms/cirugíaRESUMEN
There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml.kg-1.min-1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml.min-1.kg-1 P less than 0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml.min-1.kg-1). Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance.