腹腔镜手术病人咪达唑仑-芬太尼-异丙酚麻醉诱导的优化配伍方案

目的 采用权重配方法探讨腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导的优化配伍方案。方法选择ASAⅠ或Ⅱ级择期腹腔镜手术病人60例，男34例，女26例，年龄31～55岁。诱导药物的低效量和足量分别确定为咪达唑仑0．02、0．06mg／kg，芬太尼2、6μg／kg，异丙酚0．5、1．5mg／kg。根据权重配方法，将病人随机分配至3种药物不同剂量组合的6个配伍组（n=10）。连续监测脑电双频谱指数（BIS）、心率（HR）、平均动脉压（MAP）、脉搏血氧饱和度（SpO2）。各组依次静脉注射相应剂量咪达唑仑、芬太尼、异丙酚和罗库溴铵0．6mg／kg行麻醉诱导和气管插管。记录诱导前即刻、异丙酚注入后1、2min、插管即刻、插管后1、3、5、7min的BIS、MAP及HR。按权重配方法的剂量优化原则评判复合药效，分析各组份药的重要程度及相互作用的性质。结果以BIS为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／ks、异丙酚1．0mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑和芬太。尼具有相加性作用；以MAP为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg，kg、异丙酚1．5mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑具有协同性作用，异丙酚与芬太尼具有相加性作用；以HR为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．0mg／kg配伍时，芬太尼为主药，异丙酚与咪达唑仑和芬太尼具有协同性作用。结论腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导在维持镇静方面为相加作用，在维持血液动力学稳定方面为协同作用；优化配伍方案为咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．5mg／kg。     

四类抗感染药物不良反应相关因素的探讨与分析

目的：使输液疗法中药物不良反应降到最低限度，使患者获得安全、有效的治疗，同时，也是对有限药物资源的维护。方法：对用四类抗感染药物出现不良反应91例患者行减慢输液速度、平卧、松解领扣、按合谷穴、心理护理、保暖、进饮食等处置。结果：91例药物不良反应，有89例顺利完成输液治疗，2例无效，更换药物。结论：有责任感，加强观察护理及时发现患者反应前驱症状，迅速采取有效措施，会取得满意效果。     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

应用3H-TdR掺入法对SMMC-7721细胞株药敏试验条件的探讨与应用

目的探讨3H-TdR掺入法在进行SMMC-7721系细胞肿瘤药敏试验实验时的最佳实验条件.方法确定出3H-TdR掺入法药敏实验时的最适细胞浓度、最适实验药物浓度、3H-TdR掺入最适时间;在最适条件下采用3H-TdR掺入法测定肝癌SMMC-7721细胞株对临床常用的9种抗癌药物的敏感性.结果应用3H-TdR掺入法检测肝癌SMMC-7721细胞株药敏试验的最适实验细胞浓度为1×104个/孔,最适试验药物浓度为1×PPC,3H-TdR最适掺入时间为收集细胞前8 h;肝癌SMMC-7721细胞株对DDP、ADM、5-FU、CPT高度敏感,对MTX、VP-16、MMC、NVB低度敏感,对PYM不敏感.结论 3H-TdR掺入法可用于肿瘤药物敏感性测定并确定出它的最适实验条件.     

泌尿系感染病原菌的变迁及耐药性分析

目的了解近年来泌尿系感染病原菌的变迁及耐药现状. 方法应用回顾性调查分析方法,对我院1997至2000年间泌尿系感染检测的1 026株病原菌的分布及耐药性进行统计分析. 结果在泌尿系感染的病原菌中,G+球菌上升,G-杆菌下降,真菌上升,其中粪肠球菌上升和变形菌属下降差异有显著性(P<0.05),药敏实验结果对以往常用的抗菌药物青霉素类、复方新诺明、红霉素、诺氟沙星及一代头孢显示较高的耐药性,2000年耐药率>81.6%,对三代头孢、环丙沙星、庆大霉素呈中度耐药,耐药率在42.9%～78.3%,对阿米卡星及头孢哌酮/舒巴坦呈轻度耐药,耐药率<36.7%. 结论随着抗生素的更新换代、人口老龄化及医院感染等因素的变化,泌尿系感染病原菌的分布及耐药性均发生了变迁.     

Cough and converting enzyme inhibitors

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.     

Olfactory Absorption of Insulin to the Brain

A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of ¹²⁵I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain.     

Preparation and evaluation of temperature sensitive liposomes containing adriamycin and cytarabine

Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature (T_c) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, T_c of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near T_c and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine) only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below T_c. However, ADM release from TSL was increased at the near and above T_c. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near T_c. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed, the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.     

P-glycoprotein (P-gp) function in T cells: implications for organ transplantation

P-glycoprotein (P-gp), a member of the adenosine triphosphate (ATP)-binding cassette (ABC) family of transporter molecules, is responsible for maintaining low intracellular concentrations of a variety of extracellular compounds and xenobiotics, and for transport of various intracellular molecules. Many drugs are P-gp substrates and intracellular concentrations of these agents may be critical for drug action. Experience in oncology indicates that repeated exposure to P-gp substrate cytotoxic drugs leads to the selection of drug-resistant tumor cells that overexpress P-gp. Since immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus and corticosteroids are substrates for P-gp and since T-cells also express P-gp, it is conceivable that an analogous mechanism exits for therapy-resistant graft rejection. As will be discussed in this article, P-gp may interfere with the response to immunosuppressive therapy through several distinct mechanisms, and as such may represent an attractive therapeutic target.     

天冬胶作为血管栓塞剂毒性实验的初步报告

目的:从其毒性和相关特性方面研究天冬胶作为血管栓塞剂的可行性。方法:昆明小鼠腹腔注射天冬胶后观察外貌行为、食物消耗、体重情况。最后检测WBC、血小板、RBC和Hb浓度;测定血清ALT、肌酐和尿素氮浓度。病理检查心、肝、肾、脾、脑、腹膜、生精组织及腹壁肌肉。大腿肌肉注射天冬胶的小鼠1、3、7 d后各处死,取局部肌肉标本送病理检查。结果:1.仅实验组给药后第1天反应稍差及食量显著低于对照组(P<0.001)外,第2天起各组外貌行为无异常、食量无显著差异(均P>0.05)。2.各组小鼠的体重随时间而增加,除实验组2于实验1周后增长速度显著低于实验组1(P<0.02)和对照组(P<0.001)外,其他无显著差异。3.各组血WBC、血小板、RBC、Hb及血清ALT、肌酐和尿素氮浓度无显著差别。4.仅1个实验组小鼠肝脏内可见多灶性淋巴细胞和其他炎症细胞浸润区,其他组肝脏表现正常。实验组腹膜出现少许慢性炎症细胞的浸润和间皮细胞的增生。其他均无病理改变。大腿肌肉内仅见少许残留异物,无病理改变。结论:天冬胶使用安全、生物相容性较好,作为血管栓塞剂有较好的前景。