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.     

Crowns cemented on crown preparations lacking geometric resistance form. Part II: effect of cement.

PURPOSE: This study evaluated the effect of different cements on resistance to dislodgment of crowns cemented on preparations lacking geometric resistance form. MATERIALS AND METHODS: A preparation that offered no geometric resistance form, with 20 degrees total occlusal convergence (TOC), 0.9 mm wide shoulder finish line, and a 2.5 mm axial wall height was created on an ivorine tooth using a milling machine. Ten metal test specimen die replicas and 10 standardized metal crowns with recipient sites for the application of external forces through a universal testing machine were fabricated. The crowns were cemented on the dies under 5 and 10 kg external loads, the marginal openings measured, loaded to dislodgment, and cleaned of cement. The process was repeated using zinc oxide and eugenol (ZOE), zinc phosphate (ZPh), resin modified glass ionomer (RMGI), and composite resin (CR) cements. RESULTS: Marginal openings under 5 kg cementation loads were 74.63 (+/-15.04) for ZOE, 75.98 (+/-18.20) microm for ZPh, 98.58 (+/-22.62) microm for RMGI, and 105.82 (+/-20.07) microm for CR cements respectively; under 10 kg cementation loads they were 57.62 (+/-15.86) microm, 59.55 (+/-15.41) microm, 95.00 (+/-19.52) microm, 101.30 (+/-12.52) microm respectively. Oblique dislodgment forces, measured with a Universal testing machine, were 40.18 (+/- 6.76) N for ZOE, 215.65 (+/-45.79) N for ZPh, 165.43 (+/-19.53) N for RMGI, and 181.54 (+/-30.75) N for CR respectively when crowns were cemented under 5 kg loads. The corresponding values for 10 kg loads were 38.62 (+/-4.19), 274.86 (+/-54.22), 139.70 (+/-21.71), and 160.40 (+/-21.21) respectively. Only zinc phosphate cement produced statistically enhanced resistance when crowns were cemented under 10 kg force (p value = 0.035). CONCLUSIONS: Under the conditions of the present study only crowns cemented with zinc phosphate displayed increased resistance to dislodgment on preparations lacking resistance form.     

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.     

Characterization of an immunologic polymorphism (D79H) in the heavy chain of factor V.

BACKGROUND: During the study of a family with hereditary factor (F)V deficiency (FV Amersfoort, 1102 A > T in exon 7) we identified an individual with 5% FV heavy chain antigen (FV(HC)) and 50% FV light chain antigen (FV(LC)). Further testing revealed that apart from the FV Amersfoort allele a second variant FV allele was segregating in this family, which encodes for a FV molecule with a reduced affinity for mAb V-23 used in the FV heavy chain ELISA (ELISA(HC)). OBJECTIVE: Identification and characterization of the molecular basis responsible for the reduced affinity of the variant FV for mAb V-23. METHODS: Family members of the proband were screened for mutations in the exons coding for the heavy chain of FV, after which the recombinant variant FV could be generated and characterized. Next, the cases and controls of the Leiden Thrombophilia Study (LETS) were genotyped for carriership of the variant FV. RESULTS: In the variant FV allele a polymorphism in exon 3 (409G > C) was identified, which predicts the replacement of aspartic acid 79 by histidin (D79H). Introduction of this mutation in recombinant FV confirmed that it reduces the affinity for binding to mAb V-23. The substitution has no effect on FV(a) stability and Xa-cofactor activity. In Caucasians the frequency of the FV-79H allele is approximately 5%. Analysis of the LETS revealed that the FV-79H allele is not associated with FV levels (FV(LC)), activated protein C sensitivity (using an activated partial thromboplastin time-based test) or risk of venous thrombosis (OR 1.07, CI 95: 0.7-1.7). CONCLUSION: The D79H substitution in FV should be considered as a neutral polymorphism. The monoclonal antibody V-23, which has a strongly reduced affinity for FV-79H, is not suitable for application in diagnostic tests.     

Insulin resistance Type A and short 5th metacarpals.

BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes and a variety of defects of insulin action. METHODS: We describe three members of an extended family spanning two generations with insulin resistance Type A and short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic ovaries, diabetes, features of acromegaly, raised creatine kinase and triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal steroid and testosterone levels were normal. The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene. The proband's son had a muscular build, raised creatine kinase, hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and genetic syndromes associated with insulin resistance. This family was diagnosed as having insulin resistance Type A. This family does not conform entirely to any of the previously described syndromes and a number of family members have the phenotype of short 5th metacarpals, which appears to be associated with the features of insulin resistance Type A.     

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。     

高果糖诱导IR大鼠模型血清脂质代谢的改变及意义

目的: 评估高果糖膳食对机体胰岛素敏感性及血清脂质代谢的影响及意义.方法:以高果糖膳食(果糖占总热量34.5%)诱导并经钳夹技术证实建立胰岛素抵抗(IR)大鼠模型,生化比色法测定血清游离脂肪酸(FFA),生化酶法测定血清甘油三酯(TG)及总胆固醇(TC).结果:高果糖膳食喂养4周后,实验组大鼠葡萄糖输注率由(11.5±0.6)mg/kg·min-1下降至(6.6±0.4)mg/kg·min-1(P<0.01);血清FFA由(0.45±0.09)mmol/L增至(0.78±0.19)mmol/L(P<0.01);TG由(0.54±0.10)mmol/L增至(0.96±0.22)mmol/L(P<0.01);TC由(1.96±0.32)mmol/L增至(2.42±0.21)mmol/L(P<0.01).结论:高果糖膳食可导致机体严重IR,是建立IR大鼠模型的有效手段;该模型同时伴有血清脂代谢各相关指标的明显异常,血脂的变化既是IR的结果,也是IR向纵深发展的原因和必要条件.     

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。     

Increasing prevalence of penicillinase‐producing Neisseria gonorrhoeae and the emergence of high‐level, plasmid‐mediated tetracycline resistance among gonococcal isolates in The Gambia

Summary One hundred and three strains of Neisseria gonorrhoeae isolated from a periurban STD clinic in The Gambia were studied for antimicrobial susceptibility, plasmid profile, and serogroup using standard procedures. Seventy-nine (77%) were penicillinase producers (PPNG) and fully resistant to penicillin (MIC ≥8 mg/l). One isolate showed chromosomally induced resistance to penicillin (MIC 2 mg/l). None of the isolates was sensitive to tetracycline; 16 (16%) showed intermediate resistance (MICs 1–8 mg/l) and 87 (84%) showed high-level plasmid-mediated resistance (TRNG) (MICs >10 mg/l). This is the first report of TRNG in The Gambia. Only 6 (6%) strains were fully sensitive to trimethoprim-sulphamethoxazole (MIC <8 mg/l); 78 (76%) showed intermediate level resistance (MICs 8–16 mg/l) and 19 (18%) were fully resistant (MIC >32 mg/l). Indications of an increase in MIC to ciprofloxacin and ceftriaxone were found in 6 (6%) and 1 (1%) strains, respectively, although all remained fully sensitive (MICs 0.004–0.03 mg/1 and 0.001–0.015 mg/l). All PPNG and TRNG strains carried the 3.2 MDa and 25.2 MDa plasmids, respectively. All isolates carried the 2.6 MDa cryptic plasmid and 9 (3 PPNG and 6 non-PPNG) carried the 24.5 MDa conjugative plasmid. Forty-four (43%) strains were typed group W1, 58 (56%) W11/111 and 1 had cross-reacting antigens. Because PPNG are frequently encountered and high-level TRNG is now prevalent, the newer cephalosporins and quinolones must now be considered as first-line drugs for the treatment of gonorrhoea in The Gambia.