缺血性脑卒中后下肢深静脉血栓形成的临床分析

目的　分析缺血性脑卒中后下肢深静脉血栓形成(LDVT)的主要发病原因,为临床采用合理的预防和治疗措施提供客观理论依据。方法　分析50例缺血性脑卒中并发LDVT患者的临床特点及血液凝血、抗凝和纤溶系统分子标志物指标的变化。结果　50例脑梗塞(CI)并发LDVT患者中, 65岁以上的占60%;卧床2~4周的发病率最高;伴发疾病中以高血压、高血脂最常见;与正常对照组相比,CI并发LDVT患者的vWF、GMP 140、F1+2含量,PAI 1活性均明显升高,而AT活性、总PS含量、PC活性、PLg活性均明显降低,差异均有非常显著性意义(P<0. 01~0. 001)。结论　高龄、卧床及血液的高凝状态是CI并发LDVT的主要因素。临床上应对高龄、长期卧床及存在高凝状态的CI病人,给予必要的抗凝、溶栓药物及早期康复锻炼等预防性措施,以防止LDVT的发生。     

下肢深静脉血栓形成患者凝血、抗凝和纤溶功能的检测

目的 :通过检测下肢深静脉血栓形成 (LDVT)患者凝血、抗凝和纤溶系统各项指标 ,探讨高凝状态在LDVT发病机制中的重要作用 ,指导临床采用合理的预防及治疗措施。方法 :以 74例健康查体者作为对照组 ,测定 74例LDVT患者的血小板数量 (BPC)、血小板聚集率 (PAgT)、血小板表面α颗粒膜蛋白 (GMP - 14 0 )分子数 ;血浆凝血酶原时间 (PT)、凝血酶时间 (TT)、部分凝血活酶时间 (APTT)、纤维蛋白原 (Fg)及血管性血友病因子 (VWF)含量 ;抗凝血酶III活性 (AT -IIIA)、蛋白C活性 (PC)、总蛋白S含量 (PS) ;纤溶酶原 (PIg)活性、组织型纤溶酶原激活物活性 (tPA -A)及纤溶酶原激活物抑制物— 1(PAI- 1)的含量。结果 :与正常对照组相比 ,LDVT患者的PAgT、GMP - 14 0分子数明显升高 (P <0 .0 5 ) ;PT、TT、APTT、AT -IIIA、PC、PS、PIg活性、tPA -A水平均明显降低 ;而Fg、VWF及PAI- 1含量均明显增高 ,与正常对照组有极显著差异 (均P <0 .0 0 1)。结论 :血液凝血、抗凝和纤溶活性异常所致的高凝状态在LDVT发病机制中占有重要地位 ,临床应采用凝血、抗凝和纤溶指标联合指导LD VT的防治 ,以取得最佳疗效     

下肢深静脉血栓形成患者溶栓前后凝血、抗凝和纤溶活性改变的研究

目的观察下肢深静脉血栓（LDVT）患者溶栓前后凝血、抗凝和纤溶指标的变化，以探讨出凝血、纤溶活性改变与LDVT患者溶栓后高血栓发生率的相关性。方法测定50例LDVT患者溶栓前后抗凝血浆标本的抗凝血酶活性（AT：A）、纤维蛋白原（FIB）、纤溶酶原活性（PLG：A）、组织型纤溶酶原激活物抗原性（t—PA：Ag）、纤溶酶原活性抑制剂-1抗原性（PAI：Ag）、血浆D-二聚体（D-D）、血管性血友病因子（VWF）、Ⅷ促凝活性（Ⅷ：C）、凝血因子Ⅻ活性（Ⅻ：C）；并取32例健康体检者作对照。结果AT：A、PLG：A、t—PA：Ag、Ⅻ：C在溶栓前明显低于对照组（P〈0．01），溶栓后升高（P〈0．05或P〈0．01），其中AT：A、PIG：A、Ⅻ：C仍低于对照组（P〈0．05或P〈0．01），而t-PA：Ag无显著性差异（P〉0．05）；FIB、PAI：A、D-D、Ⅷ：C、VWF在溶栓前显著高于对照组（P〈0．01），溶栓后下降（P〈0．05或P〈0．01），其中PAI：A、D-D、Ⅷ：C、VWF下仍明显高于对照组（P〈0．05或P〈0．01），而FIB无显著性差异（P〉0．05）。结论出凝血系统机能紊乱、纤溶-抗纤溶系统失衡与LDVT患者溶栓后血栓的发生可能有密切的关系。     

老年人院内重症感染时凝血及纤溶指标的变化

目的了解老年人院内重症感染患者凝血和纤溶指标的变化,从而为临床预防性应用抗凝药物提供理论依据。方法对46例老年院内重症感染患者进行血管性血友病因子(vWF),P选择素(GMP-140),抗凝血酶(AT)活性,D-二聚体, 组织纤溶酶原激活物(t-PA),纤溶酶原激活抑制物-1(PAI-1)等多项指标进行检测,并与老年非感染患者比较。结果老年院内重症感染患者vWF、GMP-140、D-二聚体、PAI-1明显高于非感染患者,而AT、t-PA低于非感染患者。结论老年院内重症感染患者血液处于高凝状态,易于形成DIC或血栓,使病情恶化。因此,对其预防应用抗凝药物将有利于疾病的恢复。     

血栓前状态与原发性高血压关系的临床研究

目的通过观察原发性高血压患者血栓前状态（PTS）分子标志物的变化，探讨其易并发血栓性疾病的机制，为临床早期诊治提供客观依据。方法检测1000例原发性高血压患者及100例健康对照者血浆PTS分子标志物[血管性血友病因子（vWF）、血浆α-颗粒膜蛋白（GMP-140）、11-去氢血栓烷B2（11-DH-TXB：）、纤维蛋白原（FiB）、抗凝血酶（AT）]的含量，组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制物-1（PAI-1）的活性水平及血流动力学指标，并进行分析与评价。结果与正常对照组相比，高血压组患者的血浆vWF、GMP-140、11-DH-TXB，、nB含量及PAI-1活性和血粘度均明显升高，而AT含量、t-PA活性均明显下降（均为P〈0．01）。随着血压水平升高，PTS标志物水平变化越显著（P〈0．05）。结论原发性高血压燕者存在PTS，PTS与其病情进展及血栓性疾病的发生密切相关。     

糖尿病患者凝血、抗凝血及纤溶功能的变化

目的 探讨糖尿病患者凝血、抗凝血、纤溶系统的变化及意义。方法 纤维蛋白原（Fg)采用Clauss法，纤维蛋白A肽（FPA）、血管性血友病因子（vWF)、D－二聚体（D－dimer)、抗凝血酶－Ⅲ（AT－Ⅲ）、血浆血小板α－颗粒膜蛋白140（GMP－140）采用酶联免疫吸附试验（ELISA）法，组织型纤溶酶原激活物（t-PA)、纤溶酶原激活剂抑制物（PAI）采用发色底物法。结果 与对照组比较，糖尿病无并发症组Fg、FPA、vWF、GMP-140水平显著增高（P＜0.05),AT-Ⅲ、D-dimer、t-PA、PAI差异无显著性；糖尿病有并发症组Fg、FPA、vWF、D-dimer、PAI、GMP－140水平显著增高（P＜0.01)，AT－Ⅲ、t-PA水平显著降低（P＜0.01)。结论 糖尿病时，凝血、抗凝血、血小板、纤溶等系统发生了显著变化，因此测定上述指标，对指导临床治疗、监测病情、预防血栓形成具有一定价值。     

缺血性脑卒中并发下肢深静脉血栓形成的相关因素同期住院4 320例中发病率1.16%

目的分析缺血性脑卒中并发下肢深静脉血栓形成患者的资料,探讨其发生原因.方法山东省血栓病防治中心1993-10/2004-12收治缺血性脑卒中患者4 320例,其中合并下肢深静脉血栓形成患者50例,分析其发生率,年龄及并发症,发生部位与时间及类型等临床特点及血液指标血友病因子、血小板表面α颗粒膜蛋白、凝血酶原片断1+2、纤溶酶原和纤溶酶原激活物抑制物活性等的变化.另选择同期健康查体者50例为对照组,也检测凝血、抗凝和纤溶系统分子标志物各指标,两组进行对比.结果所有100例被试者均进入结果分析.①缺血性脑卒中并发下肢深静脉血栓形成发生率1.16%(50/4 320).②年龄及并发症50例中65岁以上的占60%;伴发疾病中以高血压、高血脂最常见;发热、尿潴留、应用脱水药物等是主要诱发因素.③发生部位、时间及类型80%(40/50)发生在瘫痪侧肢体;发生在脑梗死后1周以内的8例,2～4周内发生的30例,4～8周的7例,6个月以内3例,1年以内2例;14例为中央型,36例为周围型.④凝血、抗凝和纤溶功能与正常人比较与对照组相比,缺血性脑卒中并发下肢深静脉血栓形成患者的血管性血友病因子、血小板表面α颗粒膜蛋白、凝血酶原片断1+2水平、纤溶酶原激活物抑制物活性均明显升高,而抗凝血酶活性、总蛋白S含量、蛋白C活性、纤溶酶原活性均明显降低,差异均有非常显著性意义(P＜0.01～0.001).结论随年龄增大,血栓形成的发病率逐步增高,高血压、糖尿病及高血脂是血栓形成的危险因素.老年脑血管病患者偏瘫肢体制动,血液呈高凝状态是下肢深静脉血栓形成的主要因素.提示临床工作中应对高龄、长期卧床、存在高凝状态的缺血性脑卒中偏瘫患者,及早给予针对瘫痪肢体的功能训练,应用必要的抗凝药物,防止下肢深静脉血栓形成的发生.     

缺血性脑卒中并发下肢深静脉血栓形成的相关因素同期住院4320例中发病率1．16％

目的：分析缺血性脑卒中并发下肢深静脉血栓形成患者的资料，探讨其发生原因。方法：山东省血栓病防治中心1993-10／2004-12收治缺血性脑卒中患者4320例，其中合并下肢深静脉血栓形成患者50例，分析其发生率，年龄及并发症，发生部位与时间及类型等临床特点及血液指标血友病因子、血小板表面a颗粒膜蛋白、凝血酶原片断1+2、纤溶酶原和纤溶酶原激活物抑制物活性等的变化。另选择同期健康查体者50例为对照组，也检测凝血、抗凝和纤溶系统分子标志物各指标，两组进行对比。结果：所有100例被试者均进入结果分析。①缺血性脑卒中并发下肢深静脉血栓形成发生率：1．16％(50／4：320)。②年龄及并发症：50例中65岁以上的占60％；伴发疾病中以高血压、高血脂最常见；发热、尿潴留、应用脱水药物等是主要诱发因素。③发生部位、时间及类型：80％(40／50)发生在瘫痪侧肢体；发生在脑梗死后1周以内的8例。2～4周内发生的30例，4～8周的7例，6个月以内3例，1年以内2例；14例为中央型。36例为周围型。④凝血、抗凝和纤溶功能与正常人比较：与对照组相比，缺血性脑卒中并发下肢深静脉血栓形成患者的血管性血友病因子、血小板表面α颗粒膜蛋白、凝血酶原片断l+2水平、纤溶酶原激活物抑制物活性均明显升高，而抗凝血酶活性、总蛋白S含量、蛋白C活性、纤溶酶原活性均明显降低，差异均有非常显著性意义(P&;lt;0．0l～0．001)。结论：随年龄增大，血栓形成的发病率逐步增高，高血压、糖尿病及高血脂是血栓形成的危险因素。老年脑血管病患者偏瘫肢体制动。血液呈高凝状态是下肢深静脉血栓形成的主要因素。提示临床工作中应对高龄、长期卧床、存在高凝状态的缺血性脑卒中偏瘫患者，及早给予针对瘫痪肢体的功能训练，应用必要的抗凝药物，防止下肢深静脉血栓形成的发生。     

复发性缺血性脑卒中患者血纤溶系统的变化及其临床意义

目的：探讨复发性缺血性脑卒中患者血纤溶系统变化的临床意义。方法：观察41例复发缺血性脑卒中、58例初发缺血性脑卒中患者及42例健康对照组血液组织型纤溶酶原激活物（tPA)，纤溶酶原激活物抑制剂（PAI－1），纤溶酶的（Plg)，纤溶酶（Plm)及纤维蛋白原（Fig) 含量。结果：复发性缺血性脑卒中与初发缺血性脑卒中患者血tPA-1水平均明显高于对照组，初发缺血性脑卒中患者Plg明显升高，与对照组比较有显著差异；血纤维蛋白原水平在复发中风组明显高于初发中风组和对照组。TPA－1与房颤和中风家族史呈正相产；Plm与冠心病心绞痛呈正相关。结论：缺血性脑卒中的复发与多种危险因素有关，其中血纤维蛋白原水平的增加和纤溶功能的降低在复发中起着重要作用；降低血纤维蛋白原的水平和纠正降低的血纤溶功能在预防缺血性脑卒中的复发方面有重要意义。     

心肌梗死患者介入术前后血小板活化及纤溶功能的变化

目的 观察急性心肌梗死（AMI）患者冠状动脉介入术后外周循环血中血小板活化及凝血-纤溶功能的变化。方法 采用ELISA检测PTCA和冠状动脉内支架术前后血小板表面α-颗粒膜蛋白（GMP-140），血管性假血友病因子（vWF)，组织纤溶酶原激活剂（t-PA)，纤溶酶原激活剂抑制物-1（PAI-1），D-二聚体（D-D）的含量。结果 35例急性心肌梗死患者PTCA术后10分钟，GMP-140，tPA和vWF明显增高，术后24小时vWF仍显著增高，结论 AMI患者介入术后血小板活化和纤溶功能均出现改变。     

Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults

We have developed a reliable and validated radio-enzymatic method for the assay of L-carnitine and acylcarnitines, using a modification of existing methods. The sensitivity of the assay is 10 mumol/l using 10 microliters of plasma or urine. It is also suitable for measurements of carnitine in a 10 mg sample of liver or muscle obtained by percutaneous biopsy. The use of N-ethylmaleimide in the reaction mixture together with an excess of [1-14C]acetyl CoA ensures that the reaction proceeds to completion and a linear response is obtained. Using this method control ranges have been established for plasma and urine carnitine concentrations in healthy children and adults, and for the carnitine content of liver and muscle in adults. No significant difference was found between fasting and post-prandial plasma carnitine levels. An age-related increase was found in urinary total carnitine and acylcarnitine concentration throughout childhood. These data provide a reliable basis for studies of patients with abnormal carnitine and acylcarnitine metabolism, distribution and excretion.     

Activity of amikacin and ampicillin in succession and in combination

One strain each of Escherichia coli and Streptococcus faecalis were exposed to amikacin and ampicillin in combination as well as in succession. Exposure to ampicillin for 1 hr followed by amikacin for 3 or 4 hr had the greatest antibacterial activity when the antibiotics were applied in succession. The least effective exposures for both organisms were 1 hr to amikacin followed by 3 or 4 hr to ampicillin. Exposure to the antibiotics in combination each at 1 MIC had the overall greatest antibacterial activity. Simultaneous exposure to the antibiotic combination does not necessarily mean simultaneous activity of both ampicillin and amikacin on the E. coli. The cell wall autolytic activities produced by ampicillin are triggered within 10 min after physical contact with the bacteria. In contrast, amikacin requires at least 30 min after physical contact to manifest its activity on the ribosome. Although physical exposure to both antibiotics in the combination is simultaneous, the specific activity of each is in fact sequential, with ampicillin acting first. This explains the synergistic effect of the combination. It appears, therefore, that the synergistic or antagonistic affect of a drug combination is determined by the sequence and timing of the antibacterial manifestations of its components.     

纤维支气管镜在儿童咯血诊断与治疗中的应用

目的 评价纤维支气管镜术在儿童咯血病因诊断及治疗中的价值以及安全性.方法 应用用日本产Olympus BF 3c-40纤维支气管镜(最小外径3.6 mm)给58名咯血原因不明的患者行纤维支气管镜检查,并予镜下局部止血治疗.判断出血部位、观察病变情况和出血的原因、临床表现、其他辅助检查、治疗及转归等进行综合分析.结果 引起咯血的主要疾病为气管支气管、肺部的炎症24例(41.3%)、支气管内膜结核12例(20.7%)、支气管异物8例(13.7%)、特发性肺含铁血黄素沉着症7例(12.1%)、支气管扩张4例(6.9%)、心肺血管发育异常1例,原因不明2例.诊断阳性率为96.5%.镜下发现有活动性出血18例,镜下局部止血治疗后显效者10例,有效者8例,有效率为100%.术中并发短暂低氧血症(SaO2＜85%,＜20 s)15例,加大吸氧流量后均改善;术后发热3例均为低热,24 h后热退.结论 纤维支气管镜检查可明确出血部位及原因并可进行局部治疗,且安全的有效.     

Sites of in vivo extraction and interconversion of testosterone and androstenedione in dogs

The interconversion and extraction of testosterone and androstenedione across and within different tissues or areas have been studied by the constant infusion technique. The results were calculated using the (3)H/(14)C ratios and radioactive concentrations of testosterone and androstenedione obtained from afferent and efferent blood and tissues at equilibrium. In each tissue studied, the interconversion between testosterone and androstenedione inside the tissue was significantly higher than the corresponding interconversion across the tissue. The pulmonary contribution to the total interconversion between testosterone and androstenedione was far more important than that of any of the other tissues studied. The hepatic metabolic clearance rates of testosterone and androstenedione were not different from their metabolic clearance rates in the mesenteric area. The extraction of each of these compounds, although not negligible, was lower in the kidney and the femoral bed compared with the extraction in the liver and the mesenteric area. Finally, with the possible exception of the liver, testosterone and androstenedione were more completely metabolized when they originated from the cells than from afferent blood.The evaluation of these different tissue transfer constants provides more precise information concerning the relative importance of different sites in the metabolism of these interconverting hormones.     

Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation

BACKGROUND: The serine protease inhibitor aprotinin and plasminogen inhibitor tranexamic acid are used in coronary artery bypass graft (CABG) surgery to reduce bleeding. Clinicians may consider these agents as readily substitutable regarding their pharmacological profiles. OBJECTIVE: These agents were evaluated in assays of hemostasis to elucidate their underlying mechanism(s) of action. METHODS: In human plasma, effects on both clot fibrinolysis and coagulation were spectrophotometrically quantified in vitro. Rat-tail bleeding and arteriovenous shunt thrombus formation models were conducted in vivo. RESULTS: Fibrinolysis was inhibited by aprotinin (IC(50), 0.16 +/- 0.02 micromol L(-1)) and tranexamic acid (IC(50), 24.1 +/-1.1 micromol L(-1)). In vivo, aprotinin dose-dependently reduced rat-tail bleeding time (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1 )h(-1) infusion); tranexamic acid reduced bleeding time (minimal effective dose, 100 mg kg(-1) h(-1)). In vitro, coagulation time was doubled by aprotinin at 3.2 +/- 0.2 micromol L(-1), while tranexamic acid showed no effect at concentrations up to 3 mmol L(-1). Aprotinin inhibited thrombus formation in vivo in a dose-dependent manner (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1) h(-1) infusion). Conversely, tranexamic acid dose-dependently increased thrombus formation and thrombus weight (minimal effective dose, 100 mg kg(-1 )h(-1) infusion). CONCLUSIONS: These data show that aprotinin and tranexamic acid have differential effects on hemostasis and are not necessarily substitutable with respect to mechanism of action. Although both agents have been shown to reduce bleeding in patients undergoing CABG, their divergent effects on thrombus formation observed in vitro and in vivo should be critically evaluated clinically.     

Noradrenaline and Adrenaline in Blood and Urine in a Case of Phaeochromocytoma

A case of phaeochromocytoma is described in which X-ray investigation and pharmacodynamical tests with tetraethyl-ammonium and Regitin were non-informative. The diagnosis was established by the increased excretion of catechols with the urine (1010–2400 μg noradrenaline and 16–19 μg adrenaline per 24-hour period).

Estimation of catechols in samples of the blood and of the urine from the same period showed an average blood level of 3.6 μg/100 ml noradrenaline and a corresponding urinary output of 110 μg per hour.

The high systolic and diastolic blood pressure, the electrocardiographic changes, the increased basal metabolic rate, the response to the glucose tolerance test, sweating, eosinopenia and fatigue are explained as symptoms and signs of hypernoradrenalinemia.

Biological estimation of the catechols in the tumor, which weighed 40 g, showed 590 μg/g noradrenaline and 12 μg/g adrenaline.

After operation the blood pressure and the level of the urinary catechols returned to normal.     

Population pharmacokinetics and pharmacogenetics of alcohol in Chinese and Indians in Singapore

What is known and Objective:  Interindividual variability in alcohol pharmacokinetics is influenced by a number of factors, including polymorphisms in genes mediating alcohol pharmacology, ethnicity, sex and body size. Several studies have evaluated the population pharmacokinetics of alcohol from breath alcohol measures. None of these studies, however, have evaluated ethnicity and alcohol‐metabolizing enzyme genotypes as covariates in their population pharmacokinetic modelling. We aimed to develop a population pharmacokinetic model using clinical and genetic factors and to identify covariates that influenced interindividual variability in alcohol clearance and volume of distribution. Methods:  Hundred and eighty healthy subjects (90 Chinese and 90 Indians; 45 males and 45 females from each ethnic group) ingested a vodka–orange juice mixture to simulate social drinking. Subjects were genotyped for the ADH1B (Arg48His), ALDH2 (Glu504Lys) and CYP2E1 (c.‐1293G>C and c.‐1053C>T) polymorphisms. A base pharmacokinetic model was developed using the nonmem software (NONMEM Project Group, University of California, San Francisco, San Francisco, CA, USA) to determine the alcohol clearance and volume of distribution. The model was extended to include covariates that influenced the between‐subject variability. Results and Discussion:  Body weight and sex significantly influenced absorption rate and volume of distribution of alcohol. Body weight and ADH1B Arg48His polymorphism significantly influenced alcohol clearance. The Michaelis–Menten elimination rate (V_max) was decreased by 10% in homozygous ADH1B*1/*1 subjects. Ethnicity was not determined to be a significant covariate in the final population pharmacokinetic model. What is new and Conclusion:  Gender and body weight were covariates that contributed most to explaining the observed interindividual alcohol pharmacokinetic variability. Of the four SNPs examined in this study, only ADH1B Arg48His polymorphism had a significant, though modest, effect on the pharmacokinetics of alcohol.     

Safety and efficacy of linezolid in 16 infants and children in Japan

Linezolid, an oxazolidinone antibiotic, exhibits a broad spectrum of activity against Gram-positive bacteria. It has been licensed for adult use in Japan since 2006 for MRSA infections, and has also been used off-label for pediatric patients. At our university hospital, a total of 16 infants and children (including one non-Japanese Asian) were administered linezolid owing to infection with multidrug-resistant Gram-positive bacteria, after consent had been provided. All patients had severe underlying diseases or indications for surgery. Eighty-eight percent of the causal microorganisms were methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus and all were sensitive to linezolid. Linezolid was administered because the antecedent anti-MRSA medications were ineffective or contraindicated, or intravenous-to-oral switch therapy was requested owing to cardiac or orthopedic surgical-site infections. The median duration of administration was 13 days (range 3-31 days). The overall efficacy was 91 % (10/11) in those for whom efficacy could be evaluated. Only two patients (both teen-aged) encountered linezolid-related adverse effects (13 %, 2/16). One patient showed elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), requiring that administration be withdrawn, but enzyme levels returned to normal after the patient had been switched to vancomycin. The other patient showed transiently decreased platelet counts. Linezolid is considered generally safe and effective for children in Japan, especially for those who cannot use other anti-MRSA medications or those who require oral antibiotics for infections with multidrug-resistant Gram-positive bacteria.