SEVENTY-TWO HOUR COMPARISON OF METHYLPREDNISOLONE SULEPTANATE AND METHYLPREDNISOLONE SODIUM SUCCINATE IN PATIENTS WITH ACUTE ASTHMA

SUMMARY The efficacy and safety of the methylprednisolone prodrugs methylprednisolone suleptanate and methylprednisolone sodium succinate were evaluated in a multicentre, randomised, double-blind, double-dummy parallel study of 88 patients hospitalised with acute asthma. Each study drug was administered as a bolus intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48 hours. Methylprednisolone 32mg was administered orally 6 hours after the last dose. Pulmonary function, medical events, and clinical laboratory values were assessed at predefined intervals before and during the 72-hour study. The primary response measure of pulmonary function was per cent predicted forced expiratory volume in one second (FEV₁) at 48 hours. Secondary response measures were peak expiratory flow rate (PEFR) and FEV₁/forced vital capacity (FVC) ratio. Although both drugs demonstrated within-group mean changes from baseline (starting at 6 hours) that were statistically significant for each response, there were no statistically significant differences between the two groups. The mean percent predicted FEV₁ at 48 hours and mean per cent change from baseline were 64% and 13% (p<0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p<0.0001) for the methylprednisolone sodium succinate group, respectively. The mean PEFR and FEV₁/FVC ratio at 48 hours were 5.77 l/s and 73% for the methylprednisolone suleptanate group and 5.78 l/s and 76% for the methylprednisolone sodium succinate group, respectively. There were no clinically or statistically significant between-group differences in any of the safety parameters. In this study, methylprednisolone suleptanate and methylprednisolone sodium succinate have been shown to be therapeutically equivalent in the treatment of patients hospitalized with acute asthma.     

携带LacZ的腺病毒载体在牵引骨痂局部转染成纤维细胞和成骨细胞的表达

目的:利用小鼠胫骨牵引成骨动物模型,在牵引成骨过程中局部给予携带了LacZ的腺病毒载体后观察其表达情况,以探讨基因治疗促进骨折愈合的可行性。方法:实验于2004-10/2006-01在中南大学湘雅三医院完成。①实验分组:取雄性8周龄CD-1小鼠20只,随机数字表法分为实验组和对照组,每组各10只。②实验方法:所有小鼠接受左胫骨中上段骨干横行截骨安置特制延长外固定架,胫骨牵引过程包括5d静止期,10d牵引期,牵引速率为0.1mm/次,2次/d,共0.2mm/d。牵引期第7天实验组牵引骨痂局部注射5μL携带了LacZ的腺病毒载体,对照组局部注入等量未含LacZ腺病毒液。③实验评估:注射后第3天麻醉后杀取动物,采集左胫骨标本,分别作组织学检查和组织化学分析。结果:纳入小鼠20只,均进入结果分析。在牵引第10天,牵引骨痂中纤维间区形成,两端的新生骨由骨折两端中心生长延伸。骨髓腔内外可见大量新生骨形成。X-Gal底物染色显示,在实验组新生骨组织内可见大量细胞呈阳性染色;而对照组未发现阳性染色细胞。结论:在牵引成骨过程中,骨痂局部注射携带LacZ的腺病毒,能成功转染局部的成纤维细胞及成骨细胞,并表达LacZ基因,为临床应用基因治疗促进骨牵引延长或骨折愈合提供可行性。     

脑功能磁共振成像在针刺合谷、足三里与内关、三阴交穴位后的影像学特征变化比较

目的:利用功能磁共振技术观察针刺不同经脉的两组穴位后,人脑运动功能区的活动情况。方法:试验于2004-10/2006-06在中山大学附属第二医院进行。选取健康右利手志愿者11名,均为医学院学生。试验采用多组块设计,包括静息期和针刺期。每个受试者接受4次针刺,针刺穴位依次取右侧合谷、内关、三阴交、足三里穴,针刺同时采用荷兰飞利浦公司生产的Philips Intera1.5T超导型MR扫描仪进行功能磁共振扫描,两穴位刺激成像的间隔时间为15min。采用统计参数图进行数据统计学分析,用t检验分析,P<0.01的象素构成针刺激活的特异性脑区图。结果:11名受试者均进入结果分析。①针刺合谷穴引起平均信号强度升高脑区主要为双侧额中回,中央前后回、颞中上回,同侧楔前叶、岛盖以及对侧舌回、脑岛、顶下小叶。②针刺内关穴引起平均信号强度升高脑区主要为双侧额中回、尾状核、中央前后回、扣带回、颞中上回及对侧岛盖、缘上回、下丘脑、顶下小叶。③针刺足三里穴引起平均信号强度升高脑区主要为双侧颞中回、额中上回,同侧岛叶、枕上回以及对侧中央前后回、岛盖、角回。④针刺三阴交穴引起平均信号强度升高脑区主要为双侧颞中回、额下回、中央后回,同侧顶上小叶、岛叶及对侧中央前后回、顶下小叶。结论:在同一受试者,针刺不同穴位可引起相同部位脑功能区激活,不同人针刺相同穴位激活的脑功能区有一定差异,针刺效果可能并非通过单一脑功能区,而是通过有功能联系的多个脑功能区所形成的一个复杂的流动性网络的相互作用而实现的。     

低血糖指数膳食改善超重老年糖尿病患者氧化应激水平

目的:观察低血糖指数的膳食对2型糖尿病患者氧化应激状态的影响。方法:2004-10/11在上海市静安区二个社区卫生服务中心招募受试者,经医生明确诊断为2型糖尿病、病程超过6个月,体质量指数≥24kg/m2的老年糖尿病志愿者43名,受试者对试验知情同意。采用随机交叉试验随机分配至低血糖指数饮食组和高血糖指数饮食组,每种膳食分别连续使用4周,间隔洗脱期4周,比较试验前后患者超氧化物歧化酶、脂质过氧化产物丙二醛和谷胱甘肽过氧化物酶含量的变化。结果:受试者依从性好,除1人因试验期间发现肿瘤而退出试验,42名志愿者按设计要求完成试验。膳食干预后低血糖指数饮食组和高血糖指数饮食组的超氧化物歧化酶活力分别升高了15.68%和21.33%,丙二醛水平分别下降23.94%和21.55%,谷胱甘肽过氧化物酶活力分别升高了15.74%和17.09%;干预后低血糖指数饮食组丙二醛下降水平与高血糖指数饮食组比较差异有显著性意义(P<0.05),而超氧化物歧化酶和谷胱甘肽过氧化物酶活性两组间差异无显著性意义(P>0.05)。结论:在控制总能量的基础上给予平衡膳食能够改善其氧化应激水平,采用低血糖指数食物有助于氧化应激水平的改善。     

大鼠苍白球炎症反应后黑质铁代谢的改变

目的:观察苍白球炎症对黑质铁代谢的影响及其对黑质多巴胺能神经元的毒性作用,探讨帕金森病与炎症反应的关系。方法:实验于2004-12/2006-05在首都医科大学北京神经科学研究所完成。选择健康SD雄性大鼠20只,随机数字表法分为生理盐水组和脂多糖组,每组10只。①脑立体定位注射生理盐水或脂多糖入大鼠双侧苍白球,分别于术前、术后7,14,21,28d观察大鼠行为学改变,采用动物行为轨迹分析软件计算平均运动速度及30min内运动距离。②用药4周后麻醉后处死大鼠(n=10,每组各5只),用免疫组织化学染色、Perl’s铁染色观察黑质游离铁及铁蛋白表达以及酪氨酸羟化酶阳性神经元、小胶质细胞变化。③另10只大鼠于用药后4周断头提取蛋白,采用高效液相色谱法定量统计分析纹状体多巴胺含量变化。结果:纳入动物20只,均进入结果分析。①两组大鼠行为学观察:脂多糖组大鼠术后7,14,21,28d的平均运动速度、30min内运动距离较术前呈进行性减少,生理盐水组大鼠运动指标无明显变化。脂多糖组动物术后14,21,28d平均运动速度和30min内运动距离低于生理盐水组,差异均有显著性意义[分别为(0.95±0.1),(1.65±0.10)cm/min;(0.75±0.08),(1.60±0.09)cm/min;(0.45±0.07),(1.73±0.07)cm/min;(1710±180),(2970±180)cm;(1350±144),(2880±156)cm;(1170±126),(3314±140)cm,P<0.05,0.01]。②脂多糖组大鼠苍白球、黑质小胶质细胞增生且呈现异常激活状态。黑质酪氨酸羟化酶阳性神经元低于生理盐水组[分别为(3002.0±362.1),(6079.0±510.2)个,P<0.01]。③脂多糖组大鼠黑质内铁蛋白及游离铁水平较生理盐水组明显增加。④大鼠纹状体多巴胺含量:脂多糖组纹状体多巴胺含量低于生理盐水组,差异有显著性意义[分别为(16.49±1.79),(22.79±1.56)nmol/g,P<0.05]。结论:苍白球的炎症导致黑质多巴胺能神经元的变性,黑质中游离铁和铁代谢相关蛋白的改变可能在这一过程中发挥重要作用。     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Application of biosafety principles in blood establishments

In light of increasing public and employee concern over potential infectious hazards associated with blood and other body fluids, several government agencies (the Food and Drug Administration, the Centers for Disease Control, the Occupational Safety and Health Administration, the Environmental Protection Agency, the Health Care Financing Administration and the National Heart, Lung and Blood Institute) cosponsored a Biosafety Workshop in April 1988. The objective of the workshop was to identify appropriate biosafety practices and standard control procedures to protect workers involved in the collection, storage, and transportation of human blood donations with the least possible disruption of the nation's blood supply. Speakers focused on human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the safety principles discussed were considered equally applicable to other known (e.g., non-A, non-B hepatitis and human T-lymphotropic virus type I (HTLV-1) blood-transmitted infections. The resulting consensus included the need for blood establishments to develop and apply thoughtful biosafety programs to address staff training, accident prevention, HBV vaccination, handling spills, managing contaminated waste and transporting blood specimens. There was lack of agreement, however, on the usefulness of gloves during the phlebotomy of healthy blood donors.     

Establishing a phase I unit: organisation

Summary— The organisation of a phase I unit must take into account the safety, quality and scientific requirements of such studies. The clinical pharmacology unit demands a highly qualified staff, as well as intensive care equipment. The investigator, generally a clinical pharmacologist who coordinates the different tasks as a project leader, has often to initiate a fruitful collaboration with a specialised consultant staff in order to implement the studies.     

Fluoxetine in orthostatic hypotension of Parkinson's disease: A clinical and experimental pilot study

Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension.