RESUMEN
The dose of docetaxel is currently calculated based on body surface area and does not reflect the pharmacokinetic, metabolic potential or genetic background of the patients. The influence of genetic variation on the clearance of docetaxel was analysed in a two-stage analysis. In step one, 583 single-nucleotide polymorphisms (SNPs) in 203 genes were genotyped on samples from 24 patients with locally advanced non-small cell lung cancer. We found that many of the genes harbour several SNPs associated with clearance of docetaxel. Most notably these were four SNPs in EGF, three SNPs in PRDX4 and XPC, and two SNPs in GSTA4, TGFBR2, TNFAIP2, BCL2, DPYD and EGFR. The multiple SNPs per gene suggested the existence of common haplotypes associated with clearance. These were confirmed with detailed haplotype analysis. On the basis of analysis of variance (ANOVA), quantitative mutual information score (QMIS) and Kruskal-Wallis (KW) analysis SNPs significantly associated with clearance of docetaxel were confirmed for GSTA4, PRDX4, TGFBR2 and XPC and additional putative markers were found in CYP2C8, EPHX1, IGF2, IL1R2, MAPK7, NDUFB4, TGFBR3, TPMT (2 SNPs), (P<0.05 or borderline significant for all three methods, 14 SNPs in total). In step two, these 14 SNPs were genotyped in additional 9 samples and the results combined with the genotyping results from the first step. For 7 of the 14 SNPs, the results are still significant/borderline significant by all three methods: ANOVA, QMIS and KW analysis strengthening our hypothesis that they are associated with the clearance of docetaxel.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Especies Reactivas de Oxígeno/metabolismo , Taxoides/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel , Haplotipos , Humanos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Taxoides/metabolismoRESUMEN
A project called Better cancer care in Buskerud was started in 1991 in the county of Buskerud, in Norway. The main objective was to improve the out-patient services for cancer patients at the central hospital. In this article we describe the activities at the out-patient clinic during the period 1991-1993. The clinic was staffed by two oncologists and two cancer nurses. A total of 8060 consultations were held with patients during the period. Breast cancer patients comprised the largest group (30%), followed by patients with gastrointestinal cancer (24%) or malignant lymphoma (13%). The hospital's Department of Surgery was particularly relieved to hand over the administration of chemotherapy. The number of patients who received radiotherapy at the nearest cancer centre did not increase, however, during the period. We conclude that the project in Buskerud was a success, and that most of the objectives were achieved.
Asunto(s)
Oncología Médica/normas , Neoplasias/terapia , Servicio Ambulatorio en Hospital/normas , Adulto , Anciano , Femenino , Humanos , Masculino , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias/diagnóstico , Noruega , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricosRESUMEN
In patients admitted to a general medical ward, the incidence of hyponatremia on admission was 3.6%. Mortality was more than three times higher among patients with hyponatremia than among the patients as a whole. The triad hyponatremia, hypoalbuminemia and hypervolemia indicated a poor prognosis. A diversity of medical illnesses was associated with hyponatremia, and the use of diuretics was a major contributor to the electrolyte disturbance. Treatment of asymptomatic hyponatremia is discussed, with special emphasis on restriction of fluids.