To preliminarily determine the appropriate dosage of carboplatin （CBP） at AUC of 5 mg-M1^-1·min^-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer （NSCLC）. Thirty-f...To preliminarily determine the appropriate dosage of carboplatin （CBP） at AUC of 5 mg-M1^-1·min^-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer （NSCLC）. Thirty-five Chinese senile patients with NSCLC in advanced stage （Ⅲ/Ⅳ） were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol＋CBP, Gemzar＋CBP and NVB＋CBE The dose of CBP was at 5 mg.mL^-1·min^-1 of area under the concentration-time curve （AUC）. Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% （46/96） of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% （27/96） of the subjects. However, other side effects were slight. The mean score of quality of life （QOL）, according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL^-1·min^-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL^-1·min^-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.展开更多
Background: Pyrazinamide (PZA) is one of the most important drugs for tuberculosis (TB) treatment, however, its susceptibility is not routinely tested. High-resolution melting (HRM) curve analysis has been widely used...Background: Pyrazinamide (PZA) is one of the most important drugs for tuberculosis (TB) treatment, however, its susceptibility is not routinely tested. High-resolution melting (HRM) curve analysis has been widely used for many applications. In this study, HRM assay was developed and evaluated for the detection of PZA resistance in Mycobacterium tuberculosis clinical isolates. Methods: Ninety five M. tuberculosis clinical isolates with different susceptibility patterns to anti-TB drugs were used to evaluate this assay. Isolates were phenotypically (Bactec MGIT 960) and genotypically (HRM and pncA gene sequencing) analysed for PZA resistance. Results: Bactec MGIT 960 analysis revealed that 29 of the 95 M. tuberculosis isolates were PZA resistant. In comparison to the Bactec MGIT 960, HRM showed a sensitivity of 47.7% and specificity of 74.6%, and the overall agreement between the two methods was 68.4%. Based on DNA sequencing, a correlation of 0.67 (significant at p-value pncA mutations was observed. PZA resistance was strongly associated with multi-drug resistant (MDR)-TB as it was shown in 79.3% of the MDR isolates included in the study. Conclusion: HRM is simple and useful for screening clinical M. tuberculosis isolates for PZA resistance, however, further modifications to improve its performance are required.展开更多
基金a grant from a key research program of the Education Bureau of Hubei Province (D2006-02-002).
文摘To preliminarily determine the appropriate dosage of carboplatin （CBP） at AUC of 5 mg-M1^-1·min^-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer （NSCLC）. Thirty-five Chinese senile patients with NSCLC in advanced stage （Ⅲ/Ⅳ） were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol＋CBP, Gemzar＋CBP and NVB＋CBE The dose of CBP was at 5 mg.mL^-1·min^-1 of area under the concentration-time curve （AUC）. Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% （46/96） of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% （27/96） of the subjects. However, other side effects were slight. The mean score of quality of life （QOL）, according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL^-1·min^-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL^-1·min^-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.
文摘Background: Pyrazinamide (PZA) is one of the most important drugs for tuberculosis (TB) treatment, however, its susceptibility is not routinely tested. High-resolution melting (HRM) curve analysis has been widely used for many applications. In this study, HRM assay was developed and evaluated for the detection of PZA resistance in Mycobacterium tuberculosis clinical isolates. Methods: Ninety five M. tuberculosis clinical isolates with different susceptibility patterns to anti-TB drugs were used to evaluate this assay. Isolates were phenotypically (Bactec MGIT 960) and genotypically (HRM and pncA gene sequencing) analysed for PZA resistance. Results: Bactec MGIT 960 analysis revealed that 29 of the 95 M. tuberculosis isolates were PZA resistant. In comparison to the Bactec MGIT 960, HRM showed a sensitivity of 47.7% and specificity of 74.6%, and the overall agreement between the two methods was 68.4%. Based on DNA sequencing, a correlation of 0.67 (significant at p-value pncA mutations was observed. PZA resistance was strongly associated with multi-drug resistant (MDR)-TB as it was shown in 79.3% of the MDR isolates included in the study. Conclusion: HRM is simple and useful for screening clinical M. tuberculosis isolates for PZA resistance, however, further modifications to improve its performance are required.
文摘目的:探讨“冬病夏治”全方配伍和无白芥子配伍延胡索乙素在模型家兔“肺俞”穴皮下药代动力学特征及药代动力学-药效动力学(PK-PD)模型的相关性。方法:支气管哮喘模型家兔随机分成延胡索单方组、缺白芥子组、全方组,微透析技术收集14 h穴位皮下透析液,液相色谱-质谱法(Liquid Chromatography Mass Spectrometry,LCMS)法检测方中君药延胡索主要成分延胡索乙素浓度,获得药代动力学参数;酶联免疫吸附试验(ELISA)法检测对应时间点模型动物血清中IgE水平,获得药效学参数;对药动学、药效学参数进行PK-PD模型拟合。结果:白芥子配伍后的药峰浓度(C_(max))、药时曲线下面积(AUC_(0-t))、平均滞留时间(MRT_(0-t))均显著增加(P<0.01,P<0.01,P<0.05),达峰时间(T_(max))提前(P<0.01);“浓度-时间-效应”三维曲线表明,方中有白芥子配伍时,药效出现更快、消退更慢,起效时间晚于峰浓度,具有一定滞后性。结论:动力学参数、PK-PD模型结果表明,白芥子配伍能够改变“方中君药”——延胡索的主要成分延胡索乙素穴位局部的皮下分布,促进方中君药有效成分快速吸收,延长滞留时间,在方剂中起到主药、改善其他药物分布的“双重”作用。
