Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers

INTRODUCTION: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE: In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS: Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS: Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION: Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.     

立体定向放射外科治疗鼻咽癌的初步应用

目的探讨立体定向放射外科（ＳＲＳ）在鼻咽癌治疗中应用的可行性及价值。方法１９９６年８月至１９９７年１２月用Ｘ－刀治疗鼻咽癌１３例,其中初治者６例,复发者７例。初治者结合外照射７０～７５Ｇｙ,Ｘ－刀靶区周边剂量为１７～２２．５Ｇｙ（中位剂量１８Ｇｙ）。复发者中行外照射加Ｘ－刀３例,Ｘ－刀多次治疗４例,其中行２次者３例,４次者１例。靶区周边剂量为１８～３０Ｇｙ（中位剂量２４Ｇｙ）。结果初治者局控率为８３．３％（５／６）。复发者局控率为７１．４％（５／７）。初治者全部存活,中位生存期１１个月。复发者存活２例,死亡５例,中位生存期７个月。结论ＳＲＳ为提高鼻咽癌治疗的局控率,降低后期并发症发生率提供了安全有效的途径。确切评价ＳＲＳ在鼻咽癌治疗中的作用尚需累积更多的病例资料,进行较长期的观察研究。     

CLINICOP ATHOLOGICAL ANALYSIS OF CAUSES OF PERINATAL DEATH

The perinatal mortality rates and causes of deaths in our hospital within the three 5-year periods (1955-1959, 1976-1980, 1981-1985) were reported as well as the total number of births (16,846), deaths (457), and autopsies (393, autopsy rate 85.9%). The perinatal mortality for the three 5-year periods was 44.5%, 23.8%, and 17.2% respectively; it declined more significantly in 1981-1985 than in 1976-1980. Anoxia was the first cause of death for the three 5-year periods. Other causes in sequence in 1955-1959 were traumatic intracranial hemorrhage and pulmonary diseases, in 1976-1980 malformation and pulmonary diseases, and in 1981-1985 anoxia, pulmonary diseases and hyaline membrane disease. Results suggest that accurate analysis of causes of deaths depends on meticulous systematic fetal and neonatal autopsy, including macerated fetuses, extensive discussion by pathologists, obstetricians and neonatalogists, and indispensable placental examination.     

几种超短肽的抗抑郁作用

超短肽(overshort peptides,简称OSP)是一类由2～4个氨基酸组成的活性肽,存在于体内,参与多方面的生理、生化或病理过程,其中有些OSP分布于CNS,可能参与情感等高级神经活动的调节。为了探讨OSP可能的药用前景,我们对其中5个OSP进行了抗抑郁作用研究。     

三维超声诊断胎儿泌尿系统结构异常的临床价值

目的：探讨三维超声诊断胎儿泌尿系统结构异常的临床价值。方法：对2100例胎儿行二维超声检查，再行三维超声检查，排除其他系统的结构异常。重点检查胎儿肾脏、输尿管、膀胱及羊水，与引产或出生后的结果对照分析。结果：胎儿泌尿系统异常37例，发病率为1．67％；其中肾脏异常28例，输尿管异常8例，膀胱异常1例。误诊1例，漏诊1例。羊水减少20例，多种畸形并发3例。出生29例，引产8例。结论：该方法能明确诊断胎儿泌尿系统结构异常，是减少漏诊、误诊，降低医疗风险的重要方法。     

甲基强的松龙对嗅鞘细胞移植治疗受损视网膜神经节细胞的早期保护效应

目的:观察注射甲基强的松龙对嗅鞘细胞移植治疗受损视网膜节细胞的早期保护作用。方法:实验于2005-09/2006-09在北京大学医学部神经解剖实验室完成。实验动物分组:成年雄性SD大白鼠55只随机取出7只为正常对照组,不进行任何实验处理;其余48只为实验组,在手术显微镜下经动物的左侧眶上缘暴露视神经,然后将视神经鞘顺向划开,在距眼球后壁2mm处将视神经剪断。将实验组动物随机分成4组,每组12只:①损伤组。②静脉注射甲基强的松龙组,动物实施术后30min给予一次性尾静脉注射甲基强的松龙注射液(90mg/kg)。③嗅鞘细胞移植组,动物术后移植嗅鞘细胞组织层。④给药后嗅鞘细胞移植组,动物术后30min给予一次性尾静脉注射甲基强的松龙注射液(90mg/kg),然后移植嗅鞘细胞组织层。术后21d麻醉下处死各组大鼠。实验评估:通过视神经逆行荧光标记和蛋白免疫印迹方法观察视网膜神经节细胞存活状况以及热休克蛋白27表达情况。结果:55只SD大鼠均进入结果分析。①视网膜神经节细胞的存活数量:甲基强的松龙静脉注射组高于损伤组[(16.525±9.557),(9.889±5.585)个/视野,P<0.1],给药后嗅鞘细胞移植组明显高于甲基强的松龙静脉注射组和嗅鞘细胞移植组[(28.881±13.660),(16.525±9.557),(13.513±6.840)个/视野,P<0.1,<0.01]。②各组视网膜神经节细胞热休克蛋白27的表达:甲基强的松龙静脉注射组高于损伤组,给药后嗅鞘细胞移植组明显高于甲基强的松龙静脉注射组和嗅鞘细胞移植组。结论:早期注射甲基强的松龙使受损视网膜神经节细胞存活率升高,并使热休克蛋白27表达上调,同时亦表现出了对移植嗅鞘细胞移植治疗受损视网膜神经节细胞的显著保护效应。     

健康教育路径在择期剖宫产术产妇中的应用

[目的]探讨健康教育路径在择期剖宫产术产妇中的应用效果。[方法]将180例行择期剖宫产术分娩的产妇随机分为实验组和对照组各90例,对照组采用传统健康教育方式,实验组按照健康教育路径进行健康教育。[结果]两组住院时间、住院费用、产妇满意度和健康知识评分比较差异有统计学意义。[结论]健康教育路径的实施,使产妇接受系统、科学的医疗护理照护,可缩短住院时间,降低住院费用,提高产妇满意度和护理工作质量。     

Tei指数与有创心功能参数的相关性研究

目的探讨Tei指数与评价心功能的其它超声学指标及有创心功能参数的相关性。方法30只新西兰白兔随机分为手术组及假手术组,每组15只,手术组采用开胸结扎冠状动脉前降支的方法制作心肌梗死模型,假手术组只行开胸术。手术后4周,行超声心动图检查,测定左心室射血分数(LVEF),二尖瓣口血流图舒张早期和舒张晚期血流峰值之比(E/A)以及Tei指数,同期行血流动力学测定,获得左室舒张末压(LVEDP)、 dp/dtmax、-dp/dtmax参数。比较手术组与假手术组间各项指标的差别,并以Tei指数为因变量,LVEF、E/A、LVEDP、 dp/dtmax、-dp/dtmax为自变量行多元线性相关及回归分析。结果手术组与假手术组比较,除E/A无统计学差异外,Tei指数、LVEF、LVEDP、 dp/dtmax、-dp/dtmax均有显著差别。多元线性回归分析结果显示,Tei指数除与E/A无相关性外,与LVEF、LVEDP、 dp/dtmax、-dp/dtmax均有不同程度的相关。结论Tei指数能综合评价左心室的收缩及舒张功能。     

拓扑替康对人子宫内膜癌细胞株AN3CN抑制作用的研究

目的观察拓扑替康(TPT)对人子宫内膜癌细胞株AN3CN生长的抑制作用及TPT对诱导肿瘤细胞调亡的作用。方法共分为5组,对照组不加TPT,治疗组根据所加TPT浓度的不同分为20μgL组、40μgL组、80μgL组及160μgL组。MTT法检测各组在不同时间经TPT处理后的肿瘤细胞抑制率,流式细胞术检测各组细胞经TPT处理24小时后的细胞周期变化,电子显微镜观察各组肿瘤细胞形态学改变。结果治疗组不同浓度的TPT对AN3CN细胞的生长均有抑制作用,其中40μgL组和80μgL组随药物作用的延长,肿瘤抑制率也显著增大,各治疗组G0G1期的细胞比例数增加,S期和G2M期细胞减少,其中40μgL组、80μgL组和160μgL组与对照组差异显著(P<005),各治疗组的细胞在形态学上呈细胞调亡的表现。结论TPT对子宫内膜癌细胞株AN3CN的生长具有抑制作用,并且诱导肿瘤细胞调亡是TPT抗肿瘤作用的机理之一。