等位基因特异PCR技术检测结核分支杆菌rpoB基因突变研究

目的 建立并评价等位特异多聚酶链反应检测结核分支杆菌耐利福平基因rpoB突变的方法。方法 设计与rpoB基因突变后的碱基配对的引物用于扩增突变基因，建立AS－PCR检测rpoB基因突变的方法，并对58株结核菌进行了检测。结果 AS－PCR检测结核菌耐利福平相关基因rpoB的敏感性为77.3%，特异性达91.7%。AS－PCR检测rpoB基因，有1628A→T、1657C→T，G和1673C→T突变分别占耐利福平结核菌株的18.2%，22.7%和36.4%。检测rpoB突变与MIC测定RFP耐药率和PCR－SSCP检测的总符合率分别为86.2%和74.1%。检测试验可在3－4h内完成。结论 AS－PCR方法是检测结核菌耐利福平基因突变的敏感和快速方法，可在临床实验室使用并为临床医师提供治疗依据。     

Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine

The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D₂ against LY-171555 (0.05–0.25 mg/kg); but not to the D₁ agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D₁ antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D₂ antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D₁ or D₂ receptor activation; for example, the stimulus properties of this substance might involve both D₁ and D₂ receptor activation.Some of these results were presented at the meeting of the Society for Neuroscience, Toronto, 1988     

The discriminative stimulus and subjective effects of d-amphetamine,phenmetrazine and fenfluramine in humans

The discriminative stimulus (DS) and subjective effects of d-amphetamine (AMP), phenmetrazine (PMT) and fenfluramine (FFL) were studied in a group of normal healthy adults. Subjects (N=27) were trained to discriminate between placebo and 10 mg AMP (PO). Fourteen of the subjects (discriminators) reliably learned the discrimination, whereas the other 13 did not. Nearly all discriminators labelled AMP as a stimulant, and AMP, relative to placebo, increased ratings of drug liking and general activity level, and produced typical stimulant-like subjective effects, as measured by the Profile of Mood States, the Addiction Research Center Inventory, and a series of visual analog scales. The discrimination accuracy of discriminators increased as a function of hour after drug ingestion, as did analog ratings of how certain subjects were that their discrimination responses were correct. Discriminators were tested with doses of PMT (25 and 50 mg) and FFL (20 and 40 mg) to determine whether the DS properties of these drugs would substitute for those of AMP. Both doses of PMT consistently substituted for AMP, and PMT produced subjective effects very similar to those of AMP. Conversely, neither dose of FFL consistently substituted for AMP, and FFL produced essentially no subjective effects. These findings are consistent with results from discrimination studies with other species, and provide further evidence of the validity of this procedure for studying the DS properties of drugs in humans. Offprint requests to: L.D. Chait     

败血症98例临床分析

目的：探讨近年来败血症病原菌变迁和对常用抗菌药物的敏感状况以及影响败血症预后的因素。方法：回顾性分析1998～2004年的98例经血培养和临床资料证实的败血症。结果：98例败血症患者血培养共分离出致病菌102株，属社区获得性败血症81例（82．7％），医院获得性17例（17．3％）。革兰阳性菌、革兰阴性菌和真菌感染分别占34．3％、60．8％、4．9％。社区获得性败血症以大肠埃希菌为主，其次是金黄色葡萄球菌和肺炎克雷伯菌。医院获得性败血症以大肠埃希菌、真菌和不动杆菌为主。23抹金葡菌中苯唑西林耐药率39．1％，未发现对万古霉素耐药的菌株；31株大肠埃希菌对氨苄西林、阿米卡星和左氧氟沙星耐药率分别占90．3％、61．3％和45．2％，但对头孢三代、四代及酶抑制剂耐药率较低（12．9％～19．1％），未发现对亚胺培南-西司他丁耐药菌株。院内感染、血小板下降、血糖升高及休克增加了败血症患者病死率。结论：院内感染败血症病原菌中真菌和不动杆菌呈上升趋势，大肠埃希菌和金葡菌感染首选亚胺培南-西司他丁和万古霉素，大肠埃希菌院外败血症可首选头孢三代或亚胺培南-西司他丁。     

Graves甲亢多种治疗方法对Graves眼病影响的系统评价

目的 通过榆索、分析文献系统评价131I、手术、抗甲状腺药物(ATD)治疗Graves病(GD)对Graves眼病(GO)的影响.方法 检索了MEDIJNE(1966年-2006年3月)、EMBASE(1984-2005年)、The Cochrane Library(2006年第1期)、中国生物医学文献光盘数据库(EBMdisc,1978年1月-2006年4月)和中国学术期刊全文数据库(CNKI,1994-2006年)所收录的有关不同GD治疗方法对GO影响的文献,同时从参考文献中追溯文献.对纳入研究的方法学质量进行评价,根据是否采取预防甲状腺功能低下(简称甲低)发生的措施对纳入研究进行亚组分析,结果采用RevMan4.2软件进行统计学分析.结果 最终纳入随机对照研究5项,非随机对照研究2项,病例对照研究1项,共1625例患者.Meta分析显示:如GD治疗后早期未采取措施预防甲低,131I与手术治疗、131I与ATD治疗GD在诱发或加重GO以及减轻GO症状方面莘异有统计学意义[检验值分别为2.31,5.97,3.70,5.55;P均＜0.05];如GD治疗后早期采取措施预防甲低,手术与ATD治疗GD在诱发或加重GO以及减轻GO症状方面差异无统计学意义(检验值分别为0.27,0.99;P均＞0.05),尚无研究涉及131I治疗GD后早期采取甲低预防措施时131I对GO的影响.结论 若未及时采取甲低预防措施,131I较ATD、手术治疗GD更容易诱发或加重GO,减轻GO的症状却不如后两者,对于治疗前已有活动性GO的患者,应慎用131I.     

低剂量奥沙利铂并氟脲嘧啶对晚期复发直肠癌放疗增敏作用的临床观察

目的：观察奥沙利铂（L-OHP）并5-氟脲嘧啶、甲酰四氢叶酸钙（5-Fu／LV）配合放疗治疗晚期复发直肠癌患者的增效作用与毒性反应。方法：23例无法手术的晚期复发直肠癌患者进行盆腔放疗，在放疗的第1、5同前一天开始给予L-OHP30mg／m。静滴0．5h，LV100mg／m^2和5-Fu375mg／m^2静滴4h，连用4d。25例单纯放疗者为对照组。结果：放疗结束时，观察组局部症状缓解率较对照组高，尤其对会阴区下坠疼的改善明显（P〈0．05），且转移症状亦有所缓解。两组有效率分别为78．3％、48％（P〈0．05），完全缓解分别为8．7％、4．0％。主要毒副反应是消化道反应、神经毒性、静脉炎，骨髓抑制。结论：利用低剂量L-OHP并5-Fu／LV的增敏作用配合放疗治疗晚期、复发直肠癌可提高近期疗效，改善症状，尤其对于伴远外转移者，为理想、安全的治疗手段。     

RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed.     

乳腺癌新辅助化疗后动态增强MRI表现与病理反应性相关性研究

目的探讨乳腺癌新辅助化疗后动态增强MRI（DCE—MRI）表现的形态学和时间信号强度曲线（TIC）类型与病理学反应性的关系。方法45例乳腺癌患者经新辅助化疗结束后行乳腺DCE—MR检查及手术治疗。应用AW4．2图像工作站观察残余肿瘤强化的形态和TIC类型（共3型）。由病理科医师对乳腺癌化疗后手术标本的病理反应性进行评估，分为1～5级，5级为病理完全缓解，4级和5级为组织学显著反应。分析病理反应性级别与DCE—MRI残余强化的TIC类型、形态的关系，统计方法采用精确概率法。结果45例中病理反应性5级7例，4级16例，3级16例，1和2级共6例。20例I型曲线中组织学显著反应者占70．0％（14／20），而6例Ⅲ型曲线均为组织学反应不显著者。TIC类型在不同的病理反应级别分布差异有统计学意义（P=0．001）。组织学显著反应且有残余强化者共18例，其中非肿块性强化11例。残余强化的肿块（非肿块）形态表现在不同病理反应性分级中分布差异有统计学意义（P=0．012）。结论乳腺癌新辅助化疗后DCE—MRI的形态及血液动力学表现特点与化疗后病理反应性相关。非肿块性强化和I型TIC与组织学显著反应有关。     

Effect of Kang''''ai Injection(康艾注射液) on Serum Level of Soluble Interleukin-2 Receptor and Vascular Endothelial Growth Factor in Patients with Esophageal Carcinoma during Radiotherapy

Radiotherapy(RT)is an important ap-proach for treatment of esophageal carcinoma(EC),especially for patients who have missedthe chance of surgical section.The efficacy ofRTis not satisfactory for its1-year,3-year and5-year survival rates being merely50%,20%,and10%respectively(1).Researches in recent years showed thatbetter efficacy can be obtained by combiningRTwith Chinese herbal medicines for EC thatincapable to be resected.Kang ai Injection(康艾注射液,KAI)is a Chinese herbal prep-arati…