卡培他滨单药治疗老年晚期乳腺癌的疗效分析与评价

目的观察老年晚期乳腺癌应用卡培他滨单药方案化疗的疗效与毒性。方法 65岁以上晚期老年乳腺癌患者30例,给予卡培他滨2000mg/(m2·d),服2周停1周为1个疗程。所有患者均评估毒性,至少用过2个周期的患者评估疗效。结果 30例患者共完成105个疗程,中位化疗疗程数为3.5个。总有效率为36.7%,临床受益率为66.7%,中位疾病进展时间(TTP)7.9个月,中位生存期14个月。Ⅲ、Ⅳ度不良反应有:Ⅲ度白细胞下降6例(20%),Ⅲ度手足综合征5例(17%),Ⅲ度腹泻2例(7%),Ⅳ度恶心、呕吐2例(7%)。结论初步研究结果显示卡培他滨单药治疗老年晚期乳腺癌疗效较好,毒性可耐受。     

卡培他滨联合顺铂治疗晚期三阴性乳腺癌的疗效观察

目的:观察卡培他滨联合顺铂治疗雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)均阴性(三阴性)晚期乳腺癌的疗效与毒副反应。方法:48例经免疫组化证实ER、PR、HER-2阴性的晚期转移性乳腺癌患者,其中24例患者单用卡培他滨2500mg·m-2,分早晚两次口服,连服14d,21d为1个周期;24例患者接受卡培他滨+顺铂方案:顺铂30mg·m-2静脉滴注,d1～d3,卡培他滨1250mg·m-2,分两次口服,连续服用14d,21d为1个周期。观察2组疗效及毒副反应。结果:卡培他滨单药组与联合化疗组完成疗程数分别为(4.2±0.9)和(4.0±0.7)个疗程。卡培他滨单药组与联合化疗组有效率分别为29.2%和33.4%。其中,卡培他滨单药组24例患者中位疾病进展时间(TTP)为5个月,1年生存率为65.7%;联合化疗组24例患者中位TTP为6个月,1年生存率为67.7%。卡培他滨单药组Ⅲ度手足综合征多于联合化疗组,联合化疗组毒副反应主要为胃肠道反应、白细胞降低、乏力等,经对症处理后均好转。结论:卡培他滨联合顺铂治疗晚期三阴性乳腺癌疗效好,毒副反应可以耐受。     

多西紫杉醇联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的临床观察

目的观察多西紫杉醇联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的疗效和不良反应。方法蒽环类药物治疗失败的晚期乳腺癌患者32例,接受卡培他滨和多西紫杉醇联合方案化疗。卡培他滨2000mg/(m2.d),第1～14天;多西紫杉醇25～30mg/m2,第1、8、15天,21d为1个疗程,至少治疗2个疗程。结果完全缓解4例,部分缓解11例,稳定12例,进展5例,总有效率46.9%,平均TTP5.5个月。主要不良反应为骨髓抑制,胃肠道反应和手足综合征,Ⅲ Ⅳ度白细胞下降15.6%,其余多为Ⅰ～Ⅱ毒性反应。结论多西紫杉醇联合卡培他滨治疗蒽环类药物耐药的晚期乳腺癌,有较好的疗效,毒性可以耐受,为有效的解救方案。     

多西紫杉醇联合卡培他滨新辅助化疗13例局部晚期乳腺癌的观察

目的探讨多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌的疗效及安全性。方法 13例局部晚期乳腺癌初治患者,卡培他滨药2500 mg/(m2?d),分早晚2次,餐后30 min口服。连续服用2周,休息1周为1个周期。多西紫杉醇75 mg/m2,静脉输注1 h滴完。21 d为1个周期,2周期后评价疗效。结果 13例局部晚期乳腺癌中治疗后完全缓解4例,部分缓解6例,稳定2例,进展1例,有效率76.92%(10/13),主要不良反应为白细胞减少,发生率为82.33%,其中Ⅲ度占29.61%,没有发现有Ⅳ度。结论多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌疗效确切,不良反应可耐受。     

62例卡培他滨联合长春瑞滨治疗晚期乳腺癌的疗效观察

目的 观察卡培他滨联合长春瑞滨治疗晚期乳腺癌的疗效.方法 62例晚期乳腺癌患者均接受卡培他滨1日1000mg/m2,分两次餐后30min口服,连用14d,间隔7d;长春瑞滨25mg/m2,于第1、8天快速静脉滴注,21d为1个疗程,化疗大于2个疗程.结果 62例患者中CR1例(1.6%),PR29例(46.8%),SD 24例(33.9%),PD 8例(16.1%),有效率为48.4%.结论 卡培他滨联合长春瑞滨治疗晚期乳腺癌有较好的疗效,不良反应轻,患者可耐受.     

多西紫杉醇卡培他滨治疗蒽环类耐药的乳腺癌研究

目的 观察多西紫杉醇(docetaxel,DTX)联合卡培他滨(capicitabine)治疗蒽环类耐药的晚期乳腺癌的疗效及安全性.方法 60例确诊蒽环类耐药的转移性乳腺癌分为两组,联合组30例给予卡培他滨950mg/m2,每日两次,口服,第1～14 d;DTX 37.5mg/(m2·d),静脉滴入,第1、8d.对照组30例DTX 50mg/(m2·d),静脉滴入,第1、8d.两组每3周为1个周期,连用2个周期,治疗结束2周后评价疗效.结果 60例均可评价疗效,联合组有效率(CR PR)为53.3%(16/30),中位生存时间为15.3个月,Ⅰ～Ⅱ度反应占70.0%(21/30),Ⅲ～Ⅳ度反应占30.0%(9/30),主要为手足综合征、骨髓抑制、脱发和消化道毒性.对照组有效率(CR PR)为26.7%(8/30),中位生存时间为11.9个月.对照组Ⅰ～Ⅱ度反应占50.0%(15/30),Ⅲ～Ⅳ度反应占33.3%(10/30),主要为发热、肌痛、关节痛等.有效率和生存期比较差异均有统计学意义(P＜0.05).结论 多西紫杉醇联合卡培他滨是治疗蒽环类化疗失败复发转移性乳腺癌的有效方案,且较DTX单药有优势,不良反应可以耐受.     

卡培他滨单药化疗对老年晚期胃癌的近期疗效观察

目的 讨论卡培他滨单药化疗对老年晚期胃癌的近期疗效.方法 16例晚期胃癌患者采用卡培他滨单药化疗方案共38周期.结果 完全缓解3例,部分缓解8例,无变化4例,病情进展1例,总有效率为68.75％;中位缓解期6个月,中位生存期8个月,1年生存期占45.00％,临床受益共15例(93.75％);不良反应轻,对症治疗后均好转,无死亡病例发生,无患者因不良反应中止治疗.结论 卡培他滨单药化疗对老年晚期胃癌的近期疗效较好,使用方便,不良反应轻,老年患者能够接受,可作为经济状况良好的老年晚期胃癌患者的一线治疗方案,可在更多的患者中应用,以进一步探讨其疗效.     

多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌的临床观察

目的观察多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌的疗效、影响因素和不良反应。方法采用多西紫杉醇联合卡培他滨治疗24例蒽环类耐药晚期三阴性乳腺癌患者。多西他赛3周给药剂量为75 mg/m2,静脉滴注,第1天,卡培他滨2000 mg/m2,分早、晚2次口服,d1~14。化疗以21 d为1个周期,至少应用2个周期。结果本组患者治疗有效率为50.0%,中位疾病进展时问为7.9个月,无化疗相关死亡病例,主要不良反应为骨髓抑制、手足综合征及胃肠道反应,Ⅲ~Ⅳ级白细胞下降为16.6%。结论多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌仍有较好的近期疗效,不良反应可耐受,是有效的治疗方案。     

卡培他滨间断用药治疗合并有多种慢性疾病的老年性晚期乳腺癌临床疗效分析

目的：观察卡培他滨间断用药治疗合并有多种慢性疾病的老年性乳腺癌患者的疗效及副作用。方法：26例晚期老年性乳腺癌患者,应用单药卡培他滨间断化疗。卡培他滨每日2500mg/m2,d1～14。中位化疗间隔时间为2.5个月,中位化疗周期为5个周期。结果：CR0例（0）,PR3例（11.6%）,SD18例（69.2%）,PD5例（19.2%）,1年存活率为92.3%,2年存活率为88.5%,3年存活率达76.9%。不良反应轻,主要为白细胞减少和胃肠道反应。对血糖、血压、心功能无明显影响。结论：对于合并有多种慢性疾病的老年性晚期乳腺癌,单药卡培他滨间断治疗是值得选择和进一步研究的治疗方案。     

卡培他滨沙利度胺治疗晚期乳腺癌对比研究

目的观察沙利度胺联合卡培他滨对晚期乳腺癌的疗效及毒性。方法46例Ⅲ～Ⅳ晚期乳腺癌随机分为卡培他滨联合沙利度胺组（A组）和卡培他滨组（B组）,A组23例接受卡培他滨2500mg/m2,分早晚两次餐后30min温开水送服,第1～14天,间隔7天,沙利度胺100mg,口服,第1～14天,21天为1周期,化疗4个周期;B组23例不服用沙利度胺。结果A组：CR3例,PR9例,SD8例,PD3例,有效率52.2%,疾病控制率为87%;B组：CR1例,PR4例,SD13例,PD5例,有效率21.7%,疾病控制率为73.9%。结论卡培他滨联合沙利度胺治疗晚期乳腺癌疗效较好,不良反应轻,患者可耐受。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.