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。     

儿童呼吸道苛养菌分离培养及药敏分析

目的：分析儿童呼吸道苛养菌的感染率及常用抗生素的耐药状况。方法：采用儿童呼吸道2050份咽拭子及痰标本进行苛养菌分离培养与鉴定，并对其中617株苛养菌做了药敏试验，结果：显示275株肺炎链球菌，耐药率较高的有红霉素81.1%，苯唑西林76.9%，复方磺胺甲恶唑76.9%，四环素65.4%；104株流感嗜血杆菌、184株副流感嗜血杆菌、54株卡他莫拉菌对氨苄西林耐药率分别为17.6%,28.9%,64.9%，对亚胺培南/西司他丁耐药率分别为16.4%，16.5%，0，同时复方磺胺甲恶唑的耐药率也分别高达56.7%，56.7%，64.9%。结论：提示苛养菌在儿童呼吸道感染中占有重要的地位，及时掌握这类细菌的耐药动态，对合理使用抗生素，延缓耐药株的产生有极其重要的临床意义。     

全雄激素阻断治疗晚期前列腺癌

为了评价全雄激素阻断治疗晚期前列腺癌的疗效，采用双侧睾丸切除、Ｆｌｕｔａｍｉｄｅ和Ｆｉｎａｓｔｅｒｉｄ联合治疗Ｄ２期前列腺癌病人５例。随访１５～２０个月，结果ＰＳＡ均正常，前列腺体积缩小６１．２％～６９．３％，有显著性差异（Ｐ＜０．０１），骨转移灶缩小、部分消失，积水肾脏完全恢复正常，所有病人治疗后全部有效。表明全雄激素阻断对晚期前列腺癌有良好的治疗效果。提出在三个层次上阻断雄激素治疗晚期前列腺癌的策略。     

Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone

Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received ICV infusions with 100 μg corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene, glycol) did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (≈0.5 g/kg per day), also showed a robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (≈3.0 g/kg per day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol consumption by acting in the brain, probably by way of neuronal membrane mechanisms.     

呋苄青霉素药代动力学及组织分布的研究

呋苄青霉素是由我国开发成功的一个酰脲类青霉素。本项研究采用微生物法,以狗和正常人为受试对象,以氧哌嗪青霉素和羧苄青霉素为对照进行药代动力学研究,结果表明,3个药的药—时曲线符合二室开放式模型,呋苄青霉素较其它对照药具较高的即刻血浓度和较低的肾清除率。用微生物法和放射自显影法测定的呋苄青霉素在小鼠体内组织分布汪明,呋苄青霉素广泛分布于体内各组织,尤其在肺、肝、肠中的浓度明显高于羧苄青霉素。     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

泌尿生殖道患者沙眼衣原体和支原体检测及支原体药敏分析

目的　检测皮肤性病门诊泌尿生殖道患者沙眼衣原体 (CT)和支原体感染情况及支原体培养加药敏分析。方法　对5 0 95例泌尿生殖道感染者用金标法检测沙眼衣原体抗原 ,用微量肉汤稀释法检测解脲支原体 (Uu)和人型支原体 (Mh)并进行 8种抗生素的药敏试验。结果　 5 0 95例泌尿生殖道感染者中衣原体阳性 417例 ,总阳性率为 8 2 % ,女性患者阳性率 ( 11 2 % )明显高于男性患者阳性率 ( 6 2 % ) ,有显著性差异 ( χ2 =40 1,P <0 0 1) ;检出支原体 172 8例 ,总阳性率为 3 3 9% ,女性患者阳性率 ( 4 3 0 % )明显高于男性患者阳性率 ( 2 8 0 % ) ,有显著性差异 ( χ2 =114 8,P <0 0 1) ;其中Uu感染 ( 12 5 1例 ,2 4 6% )明显高于Mh感染 ( 71例 ,1 4% )和Uu +Mh混合感染 ( 4 0 6例 ,8 0 % )。Uu对红霉素、罗红霉素、交沙霉素、阿奇霉素、强力霉素、美满霉素、氧氟沙星、环丙沙星的高度敏感率分别为 60 3 %、67 5 %、73 2 %、85 3 %、5 5 7%、40 1%、2 5 6%、2 7%。Uu +Mh混合感染对 8种抗生素均出现不同程度的耐药菌株。结论　湖南地区泌尿生殖道感染患者中 ,衣原体、支原体感染处于国内较高水平。支原体对不同种类抗生素有较高的耐药性 ,特别是Uu +Mh混合感染 ;临床上做支原体培养加药敏试验 ,对指导