对发展中国家改善用药的10点建议

WHO建议改善药品管理的工作要在国家药物政策保障之下.在许多国家,执行国家药物政策的机制是实施国家基本药物计划,其要点是强调公共领域的药品选择、采购、流通与使用的合理性.不适当的处方使医疗质量降低并导致资源浪费.本文以探讨在国家药物政策范畴内鼓励更合理地使用药品的问题为重点,在已有证据的基础上,详细阐明基本药物计划内容中的合理用药问题.本文评述了在发展中国家改善用药状况的有效策略及最新知识,并为决策者与管理者提出达到改善用药目标的建议.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Prophylactic control of post‐operative nausea and vomiting using ondansetron and ramosetron after cardiac surgery

Background: The aim of this study was to evaluate the efficacy of ondansetron and ramosetron in the reduction of post‐operative nausea and vomiting (PONV) associated with patient‐controlled analgesia (PCA) after cardiac surgery. Methods: A total of 320 patients scheduled for elective cardiac surgery were enrolled. Patients were randomly assigned to one of four treatment regimens (n=80 in each group): no prophylactic antiemetics (group P); intravenous (i.v.) ondansetron 4 mg at the end of surgery and 12 mg added to PCA (group O); i.v. ramosetron 0.3 mg at the end of surgery and no antiemetics added to PCA (group R1); and i.v. ramosetron 0.3 mg at the end of surgery and 0.6 mg added to PCA (group R2). Results: The incidence of PONV during the 48‐h post‐operative period was lower in groups O (46%), R1 (54%), and R2 (35%) compared with group P (71%, P<0.001). The incidence and severity of nausea were lower in groups O, R1, and R2 than in group P during the 24‐h post‐operative period, whereas the incidence and severity of nausea during 24–48 h after surgery were lower in groups O and R2, but not in group R1, than in group P. Compared with group P (53%), the frequency of rescue antiemetic usage was significantly lower in groups O (34%) and R2 (29%), but not in group R1 (43%). Conclusion: The addition of either ondansetron or ramosetron to PCA can reduce the incidence of PONV during 48 h after cardiac surgery.     

Linkage of human chorionic gonadotrophin and placental lactogen biosynthesis to trophoblast differentiation and tumorigenesis

Normal trophoblast of the human placenta elaborates at least two major protein hormones, chorionic gonadotrophin (hCG) and placental lactogen (hPL). Molar and choriocarcinoma tissues characteristically synthesize large amounts of hCG and hPL. To examine the role of trophoblast differentiation in the expression of the hCG and hPL genes, we studied the cytological distribution of their mRNAs in tissue sections of human hydatidiform mole and choriocarcinoma by in situ hybridization. Histologically, these tissues are in different stages of cellular differentiation. In normal placenta, hCG alpha/beta mRNA can be localized to some cytotrophoblasts and primarily to the syncytium, whereas hPL mRNA appears only in the syncytial layer. In hydatidiform mole, which still retains placental villous morphology, the hPL gene and hCG alpha and beta genes are expressed but are poorly localized because of the admixture of cyto- and syncytiotrophoblasts. By contrast, choriocarcinoma, which is devoid of placental villous pattern but in which the cyto- and syncytiotrophoblast-like components are distinguishable, expresses hCG alpha and beta in the syncytial-like areas but little, if any, hPL. These results suggest that a certain level of trophoblast differentiation, such as villous formation, is associated with hPL expression, while the hCG alpha gene and the hCG beta gene can be expressed in more disorganized tissues which contain cytotrophoblastic elements.     

Characterization of human chorionic gonadotropin in urine of patients with trophoblastic diseases by Western blotting using specific antibodies

Human chorionic gonadotropin (hCG) from urine of patients with trophoblastic diseases was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blotting using specific antibodies. Western blotting using anti-hCG beta carboxy-terminal peptide (CTP) revealed that the molecular weights of the beta subunits of the three molar hCG samples were identical to that of standard hCG beta, but those of choriocarcinoma hCG samples were individually different. In the five choriocarcinoma hCG samples, the beta subunits of three samples were apparently larger than standard hCG beta, while those of two samples were smaller than standard hCG beta but larger than desialylated standard hCG beta. These results suggest that structural changes of carbohydrates of hCG, which may be induced by malignant transformation of the trophoblast, can be observed as differences in molecular weight. In SDS-PAGE under nonreducing conditions. Western blotting using anti-hCG beta-CTP revealed a single band corresponding to hCG beta. Under reducing conditions with dithiothreitol (DTT), however, a second low-molecular-weight material (called here CTP') could be observed with anti-hCG beta-CTP. All five choriocarcinoma hCG samples were much more susceptible than standard hCG to cleavage of CTP' by DTT. We conclude that estimations of molecular weight and susceptibility to DTT reduction of urinary hCG by Western blotting using specific antibodies are useful in the diagnosis of choriocarcinoma.