动脉调转术治疗合并肺动脉高压的室间隔缺损型心室大动脉连接异常患儿的手术适应证探讨

目的总结动脉调转术(ASO)治疗年龄6~84个月、合并中~重度肺动脉高压(PH)的室间隔缺损(VSD)型心室大动脉连接异常复杂先天性心脏病患儿的手术疗效,探讨适当的手术适应证。方法2000年1月至2004年12月,对23例年龄6~84个月、中~重度PH合并VSD的大动脉转位(TGA)和右室双出口(肺动脉瓣下室间隔缺损,Taussig-B ing畸形)患儿行ASO,其中男15例,女8例,年龄7~84(22±21)个月,肺动脉压力24~80(44±14)mm Hg(1 mm Hg=0.133 kPa),肺血管阻力(PRA)49.2~1261.9 dyn.s.cm-5。合并主要畸形:左室流出道狭窄3例,肺动脉瓣下隔膜1例,主动脉瓣下隔膜1例。手术在全麻、低温(18℃~22℃)、低流量(50 m l.kg-1.m in-1)体外循环下完成ASO,合并畸形同期矫治。对合并中~重度肺动脉高压的患儿,围手术期给予α受体阻滞剂或持续吸入低流量一氧化氮(NO)等治疗,改善肺血管压力;连续监测并控制肺动脉压、左房压、右房压。结果23例患儿病死率13%,3例死亡患儿死亡原因均与术前肺血管压力和阻力增高无明显关系。余患儿虽然术后呼吸机辅助时间及重症监护时间明显延长,但术后肺动脉压力均明显下降(23 mm Hg±9 mm Hg,t=13.28,P=0.000),痊愈出院。结论对年龄6~84个月,合并VSD并发中~重度PH的VSD型TGA和Taussig-B ing畸形患儿,如一般状况良好,紫绀不严重(经皮血氧饱和度>60%),X线胸片示两肺血较多,心导管检查显示肺血管阻力仍在可接受的范围(PRA<1000dyn.s.cm-5),采用ASO仍可取得满意的效果,扩大了ASO的手术适应证。     

医用机器人辅助股骨带锁髓内针远端锁钉瞄准系统的实验研究

目的研制在骨折治疗中精确定位的机器人辅助远端锁钉瞄准系统。方法在以股骨髓内针远端锁钉植入手术中,采用模块化、小型化的并联机器人结构设计,应用机械臂空间定位技术,双目视觉、6自由度的机器人辅助髓内针远端锁钉瞄准系统。结合C型臂定位并实施导航控制进行远端锁钉植入。髓内针被分别置入塑料股骨(Swiss Sybone,5根,35孔)、人类干股骨标本(2根,12孔)、新鲜人尸体大腿(1具,6孔)。非扩髓型髓内针的尺寸范围从9/310到12/340。应用机器人辅助瞄准系统对上述髓内针进行远端锁钉植入,术中C型臂透视确认螺钉准确置入,记录锁钉植入过程的X线透视时间。结果所有远端锁孔被成功地锁定。在53个锁孔中,6例(11.1%)钻头触到锁定孔道,仍顺利穿过锁孔,没有对髓内针造成损伤。螺钉植入过程中需要的术中X线透视时间为1.8s±0.3s。结论医用机器人使仅应用两幅计算机校准的X线图像,不需要额外的术中X线透视来导航器械,手术过程中总的X线透射时间显著减少。人机交互功能操作易于掌握,可作为机器人辅助长骨治疗中精确定位和稳定操作的技术平台。     

Taurine inhibition of metal-stimulated catecholamine oxidation

Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cyto-protective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessedin vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50–500 μM)- and manganese (10 μM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO₄-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1–20 mM). Protein carbonyl formation induced by ferric iron (500 μM) and L-dopa (500 μM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 μM) and ferric chloride (75 μM) to LLC-PK₁ cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK₁ cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.     

KNT009安全性药理学研究

目的:观察KNT009对小鼠神经系统、犬心血管系统及呼吸系统的影响。方法:实验均分高、中、低剂量组及空白对照和阳性对照共5个组,小鼠实验给药组分别单次慢速静脉注射(iv)KNT009 160、80和40 mg/kg,加替沙星80 mg/kg,观察动物的自发活动和爬杆能力;犬实验给药组分别单次慢速iv KNT009 40、20 和10 mg/kg,加替沙星20 mg/kg,观察药物对犬血压、ECG、呼吸频率及节律的影响。结果:单次慢速iv KNT009对小鼠自发活动和爬杆能力无明显影响。单次慢速iv KNT009可降低犬收缩压、舒张压、平均动脉压,减慢心率,延长QT间期,使犬呼吸频率减慢,呼吸幅度加大,且均存在量效关系,3 h后上述指标基本恢复正常,加替沙星也有类似变化。结论:KNT009对心血管和呼吸系统有一定的影响,可使血压下降,心率减慢,QT间期延长,呼吸频率减慢,呼吸幅度加大。     

拉呋替丁鼠伤寒沙门氏菌基因回复突变试验

目的　体外观察拉呋替丁能否诱发鼠伤寒沙门氏菌组氨酸营养缺陷型突变株的回复突变。方法　Ames试验用TA97、TA98、TA10 0、TA10 2菌株并分加与不加肝微粒体酶活化系统( +/ -S9)试验。结果　拉呋替丁对四个菌株各剂量组的回复菌落数都未超过自然回复菌落数,Ames试验结果为阴性。结论　未见拉呋替丁致突变性。     

西洛他唑降低链脲佐菌素诱发糖尿病大鼠肾脏VCAM-1表达

目的　探讨西洛他唑对高糖大鼠肾组织VCAM - 1的影响及对肾脏的可能保护作用。方法　雄性SD大鼠,链脲佐菌素(STZ)制备糖尿病大鼠模型。观察西洛他唑12周后对血糖、糖化血红蛋白、肾重/体重比值、肾脏VCAM - 1mRNA及蛋白表达的影响。结果　糖尿病对照组及各治疗组肾重/体重比值均明显增加(P <0 . 0 1);VCAM - 1mRNA表达在糖尿病组明显升高,药物治疗后有显著改善( P <0. 0 1);Westernblot各组均有VCAM - 1表达,糖尿病组较正常组表达增强,药物治疗后呈下降趋势。结论　STZ诱发的糖尿病大鼠肾脏VCAM - 1表达增加,西洛他唑降可低糖尿病大鼠肾组织VCAM - 1mRNA和蛋白表达,对糖尿病肾脏具有保护作用。     

国产盐酸舍曲林胶囊和片剂的人体药物动力学及生物等效性

目的研究国产盐酸舍曲林胶囊及片剂的相对生物利用度、药物动力学特征及生物等效性.方法采用随机、开放、3×3拉丁方设计实验,18名男性健康受试者分别单剂量口服含舍曲林50 mg的试验片剂、胶囊及参比制剂.采用HPLC-MS/MS/MS法测定给药后不同时间的血药浓度,计算3者的药物动力学参数及评价其生物等效性.结果 18例健康志愿者口服参比制剂和试验制剂舍曲林胶囊及片剂后,参比制剂中舍曲林的主要药物动力学参数cmax为(10.14±3.43)μg·L-1;tmax为(4.44±1.10)h;AUC0～96为(262.82±100.66)μg·h·L-1;t1/2为(29.19±4.91)h.试验制剂片剂中舍曲林的主要药物动力学参数cmax为(10.16±3.22)μg·L-1;tmax为(4.33±1.85)h;AUC0～96为(269.71±107.47)μg·h·L-1;t1/2为(30.99±6.49)h.试验制剂胶囊中舍曲林的主要药物动力学参数cmax为(10.39±3.59)μg·L-1;tmax为(4.94±1.30)h;AUC0～96为(264.45±112.57)μg·h·L-1;t1/2为(29.68±5.25)h.试验制剂片剂和胶囊分别对参比制剂的相对生物利用度F为(103.4%±18.2%)、(99.8%±13.6%).结论经统计学分析,国产试验制剂胶囊剂和片剂与参比制剂具有生物等效性.     

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.     

带锁滑动鹅头钉治疗粉碎性股骨转子间骨折的临床研究

为了总结分析运用自行研制的带锁滑动鹅头钉治疗粉碎性股骨转子间骨折的疗效,随机将69例Evan'sⅢ型、Ⅳ型的患者分为两组,一组采用自制带锁滑动鹅头钉治疗(观察组);一组采用DHS治疗(对照组).分别对两组患者的一般资料、手术资料及术后功能恢复情况进行评估比较.结果骨折平均愈合时间观察组为3.65±0.97个月,对照组为4.32±1.38个月,两组比较,术后9个月观察组患侧较健侧平均缩短0.82±0.36cm,对照组平均缩短1.08±0.51cm,两组比较差异有显著性意义(P＜0.05).观察组显效率91.1%,对照组显效率71.1%,两组比较,具有非常显著性差异(P＜0.01).提示带锁滑动鹅头钉治疗粉碎性股骨转子间骨折具有防止骨不连及各种畸形愈合.     

非骨水泥型假体周围早期骨密度变化临床观察

为观察非骨水泥型假体置换术后周围骨密度的变化,对25例非骨水泥型人工假体置换患者分别于术后1周、3个月及6个月应用双能X线骨密度仪,按Grune[1]分7个测量兴趣区测量假体周围骨密度.结果显示假体周围骨密度术后3个月平均丢失11.7%,6个月平均丢失17.77%.其中以1和7区明显,1区术后3、6个月分别减少21.25%、25.55%(P＜0.01),7区术手3、6个月分别减少22.80%、32.14%(P＜0.01).说明假体置换术后早期周围骨密度均有不同程度的减少,其中以假体近端(1、7区)明显,且骨量丢失以术后前3个月最为显著.