红细胞生成素大剂量冲击维持疗法治疗血液肿瘤贫血的临床研究

目的研究红细胞生成素(EPO)大剂量冲击维持疗法治疗血液肿瘤贫血患者的临床疗效和安全性.方法采用开放性非随机的临床研究方法,恶性血液肿瘤患者在化疗同时,于第1周采用EPO 120,000 U冲击用药(40,000 U皮下d1、d3、d5),随后EPO每周40,000 U皮下(d8、d15、d22)维持用药,共4周.比较治疗前后每周的血红蛋白(Hb)和红细胞压积(Hct)水平,并评价EPO治疗的不良反应.结果 2003年10月～2005年12月共入组42例同期化疗的血液肿瘤贫血患者.所有患者给予EPO治疗后Hb水平呈持续上升趋势,在治疗后第2、4周Hb比治疗前上升≥2.0g/d1的患者分别占26.8%和52.6%.在治疗后第2、4周Hb的平均值分别为85.6g/d1和92.8 g/d1,与治疗前相比均具有显著性差异(P＜0.05).治疗前后平均Hct值亦有显著性差异(P＜0.05).所有使用EPO大剂量冲击维持疗法治疗的患者均耐受良好.结论血液肿瘤贫血患者使用EPO大剂量冲击维持疗法,可有效改善患者的贫血状况,且使用安全,耐受良好.     

同步应用促红细胞生成素提高晚期胃癌化疗疗效及依从性的临床研究

目的观察促红细胞生成素（EPO）与胃癌患者化疗疗效及依从性的相关性。方法将40例局部晚期胃癌并轻度贫血患者均分为2组,每组20例,治疗组化疗同时给予EPO,开始剂量为150U／kg,每周3次,持续观察3周期化疗。对照组单纯化疗。结果整个治疗过程中,治疗组血红蛋白（Hb）、红细胞（RBC）、网织红细胞（Ref）、红细胞压积（HCrI）水平高于对照组,治疗组近期疗效明显高于对照组（P〈0．05）。结论EPO能明显改善胃癌贫血患者的血液学指标,提高化疗近期疗效及化疗依从性。     

促红细胞生成素治疗晚期非小细胞肺癌化疗相关贫血的临床观察

目的了解促红细胞生成素(EPO)对晚期非小细胞肺癌(NSCLC)化疗相关贫血的疗效。方法48例晚期NSCLC化疗后贫血患者,治疗组 25例予皮下注射EPO,剂量为150u/kg,每周三次,持续使用4周或当血红蛋白(Hb)值>120g/L时停用。结果4周后治疗组患者血红蛋白(Hb)值明显上升,与对照组相比,差异有显著性。结论EPO对晚期NSCLC化疗相关贫血的疗效显著。     

促红细胞生成素对慢性肾衰竭贫血患者骨髓超微结构的影响

目的 探讨促红细胞生成素(EPO)对慢性肾衰竭(CRF)贫血患者骨髓超微结构的影响.方法 对23例CRF贫血患者给予重组人红细胞生成素(rhEPO)100 U/kg,每周3次,并进行常规血液透析,于治疗前及治疗12周后检测血常规,观察骨髓超微结构改变情况.结果 治疗后血红蛋白、血细胞比容、网织红细胞和血小板较治疗前均升高(P＜0.05,P＜0.01);骨髓造血微环境恢复,三系各阶段血细胞超微结构恢复正常.结论 EPO是治疗CRF贫血的决定性生长因子.     

国产与进口红细胞生成素治疗慢性肾功能衰竭性贫血比较

目的:比较国产与进口红细胞生成素(EPO)治疗慢性肾功能衰竭性贫血的疗效.方法:对40例患者随机分成治疗组和对照组,每组20例,治疗组用国产EPO,对照组用进口EPO,均行皮下注射EPO 3 000 U,每周2次,比较治疗前后血红蛋白(Hb)、红细胞计数(RBC)、网织红细胞(Ret)、血细胞比容(HCT)值.结果:Hb、RBC、Ret、HCT值治疗前后比较差异有极显著性(P＜0.01),两组疗效差异无显著性(P＞0.05).结论:国产红细胞生成素疗效确定、可靠,具有药物经济学价值.     

促红细胞生成素（EPO）联合化疗治疗癌症相关性贫血

目的 :恶性肿瘤化疗的同时联合应用促红细胞生成素 (EPO) ,观察对癌症相关性贫血 (MTA)临床症状的改善效果。方法 :观察组在化疗前 1周开始给予EPO ,对照组只进行化疗不用EPO ,其他辅助治疗两组相同 (包括营养支持、粒细胞刺激因子应用、出血者止血药物的应用、重要脏器的保护等 )。结果与结论 :化疗联合用EPO能预防和治疗MTA。对靠输血提升血红蛋白后化疗的患者可明显减少输血量 ,甚至可停止输血。EPO对MTA的治疗和与化疗所致贫血的预防有肯定的疗效     

益比奥治疗NSCLC化疗致贫血的临床观察

目的 观察益比奥(rhEPO)对非小细胞肺癌(NSCLC)化疗所致贫血的疗效.方法 58例NSCLC因化疗所致贫血患者随机分组,益比奥组30例应用rhEPO 150 U/kg皮下注射每周3次;复方阿胶浆组28例给予复方阿胶浆20 ml/次,3次/d.结论 治疗4周后应用rhEPO组与复方阿胶浆组比较RBC、Hb、HCT值均上升(P＜0.05)差异有显著性;有效率治疗组74.8%与对照组24.3%比较,P＜0.05,有统计学意义.结论 应用益比奥治疗NSCLC化疗所致贫血疗效好,不良反应少,可减少对输血的需求,同时能提高患者的生活质量.     

左卡尼汀对促红细胞生成素治疗血液透析患者贫血的疗效影响

目的观察左卡尼汀对促红细胞生成素(EPO)治疗维持性血液透析(MHD)患者贫血疗效的影响。方法随机选取我院血液净化中心行MHD的慢性肾衰合并贫血患者共50例,分为对照组及试验组。对照组25例,单用EPO治疗,试验组25例,在EPO治疗的同时加用左卡尼汀,试验周期为12周。治疗期末观察各组贫血指标的变化。结果①与治疗前相比,两组的贫血状况均明显改善。②两组之间对比,试验组的血红蛋白(Hb)及红细胞压积(Hct)水平明显高于对照组(P<0.01)。结论 EPO治疗可以改善MHD患者的贫血状况,左卡尼汀可明显提高EPO治疗MHD患者贫血的疗效。     

重组人促红细胞生成素倍他依泊汀在治疗癌症贫血中的应用

重组人促红细胞生成素倍他依泊汀可增加网织红细胞数、血红蛋白水平和红细胞容积。倍他依泊汀在实体瘤化疗和血癌引起的贫血治疗中已显示疗效。每周1次给药方式既便利病人．又较经济。癌症病人对此药耐受良好，皮下给药注射部位疼痛轻微。为确保疗效，用该药预防化疗引起的贫血是重要选择。这对癌症或化疗引起的贫血的输血治疗是有效而有价值的替代。     

重组人红细胞生成素注射液治疗肾性贫血80例

我们使用国产重组人红细胞生成素注射液(宁红欣,rhuEPO,南京军区军事医学研究所研制)治疗肾性贫血,取得较好疗效。现报告如下:1　对象与方法1.1　病例选择　慢性肾功能衰竭(CRF)伴有贫血病例。血红蛋白(Hb)<90g/L,红细胞压积(HCT)<27%,共80例。1.2　给药方案　给药剂量:透析病例给rhuEPO每周100～150U/kg,非透析治疗病例每周75～100U/kg,分2或3次,治疗过程中以每4周为1个观察单位。若无明显不良反应,每周增加15～30U/kg继续治疗,直至出现治疗反应。治疗过程中,当HTC大于30%及Hb超过100g/L,EPO可减量1/4～1/3继续维持用药,给药途径…     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.