Two cases of rt-PA with dual antiplatelet therapies with capsular warning syndrome

Rationale:Capsular warning syndrome (CWS) is a term to describe stereotyped lacunar transient ischemic attacks (TIAs). Patients with CWS are at high risk of developing completed stroke. However, the exact pathophysiology of CWS is still unclear, and there is no conclusive clinical strategy for CWS patients.Patient symptoms:Two cases of middle-aged men with hypertension, hyperlipidemia, and diabetes mellitus presented with fluctuating right-sided weakness, numbness, and dysarthria.Diagnoses:These two patients were diagnosed with CWS.Interventions:Recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (0.9 mg/kg) was administered first and treated with aspirin (100 mg) and clopidogrel (75 mg) after 24 h of rt-PA for 21 days following by aspirin (100 mg) alone.Outcomes:Both cases got favorable clinical outcomes of somatic symptoms. In addition, diffusion-weighted imaging (DWI or DW-MRI) showed that ischemic injury disappeared in case 1 while maintained within a reasonable range in case 2.Lessons:Early recognition and rt-PA/dual antiplatelet treatment may be an effective strategy for patients with CWS.     

Hyperacute Management of Ischemic Strokes: JACC Focus Seminar

Acute ischemic stroke is the leading cause of disability and among the leading causes of mortality worldwide. Intravenous tissue plasminogen activator has been a cornerstone for treatment of acute ischemic stroke for more than 20 years; however, its use is limited due to a narrow therapeutic window, several contraindications, and low efficacy to recanalize the artery in large vessel occlusion. Recently, the addition of endovascular mechanical thrombectomy of large artery occlusion has revolutionized the stroke treatment for most disabling strokes. The paper reviews updates to the thrombolytic treatment as well as catheter-based treatment, and results from recent trials in the selection of patients in an extended time window using perfusion imaging.     

Impact of Regular Physical Activity on Adipocytokines and Cardiovascular Characteristics in Spinal Cord–Injured Subjects

Objective

To investigate the relationship of carotid artery intima-media thickness (IMT) and cardiac structure and function with adipocytokines in sedentary (S-SCI) and physically active (PA-SCI) subjects with spinal cord injury (SCI).

估算的肾小球滤过率、血尿酸和纤维蛋白原与缺血性脑卒中溶栓后脑出血转化的关系及对结局的预测价值

目的探讨估算的肾小球滤过率(eGFR)、血尿酸(SUA)、纤维蛋白原(FIB)与缺血性脑卒中溶栓后脑出血转化及临床结局的关系。方法选取158例缺血性脑卒中用重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓患者,包括无脑出血转化121例、脑出血转化37例。采用Logistic回归方程分析rt-PA静脉溶栓后脑出血转化影响因素;对比不同早期神经功能患者eGFR、SUA、FIB水平;评价eGFR、SUA、FIB对早期神经功能恶化(END)的预测价值;比较不同eGFR、SUA、FIB水平患者的累积生存率。结果rt-PA静脉溶栓2 h、24 h后,脑出血转化者eGFR、SUA、FIB水平较无脑出血转化者降低(P<0.05)。Logistic回归分析显示,年龄、基线NIHSS评分、基线舒张压、大面积脑梗死及溶栓后2 h和24 h的eGFR、SUA、FIB均为rt-PA静脉溶栓后脑出血转化的影响因素(P<0.05)。END患者溶栓后2 h和24 h的eGFR、SUA、FIB均低于非END患者(P<0.05)。ROC曲线分析显示,溶栓后24 h的eGFR、SUA、FIB联合预测END的曲线下面积为0.809,大于任一单一指标,其灵敏度、特异度分别为80.95%、74.14%。生存分析结果表明,溶栓后24 h的eGFR、SUA、FIB高水平组的累积生存率高于低水平组(P<0.05)。结论eGFR、SUA、FIB与缺血性脑卒中预后密切相关,监测上述指标有助于脑出血转化诊断及END预测。     

尿激酶治疗血栓栓塞性疾病的效果研究

目的：研究尿激酶治疗血栓栓塞性疾病的临床效果。方法选取湛江市第二中医医院2012年6月—2014年6月收治的195例血栓栓塞性疾病患者,根据治疗方法不同分为两组,111例采用尿激酶治疗的患者设为尿激酶组,84例采用低分子肝素治疗的患者设为肝素组,比较两组效果和不良反应。结果尿激酶组肺栓塞（ PE）患者总有效率为78.44%,深静脉血栓形成（ DVT）患者总有效率为96.67%;肝素组 PE患者总有效率为60.98%, DVT患者总有效率为81.40%。两组比较差异有统计学意义（ P<0.05）。治疗后2周尿激酶组膝下15cm和膝上15cm健、患肢周径差均小于肝素组（ P<0.05）。尿激酶组不良反应发生率为5.41%,肝素组为2.38%,无黏膜或其他脏器出血病例,两组不良反应发生率比较,差异无统计学意义（ P>0.05）。结论尿激酶溶栓可提高血栓栓塞性疾病患者的疗效,且不良反应少。     

Decreased Plasminogen Activator Inhibitor-1 Levels in Coronary Artery Aneurysmatic Patients

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. Plasmin strongly stimulates pro-MMP enzyme conversion to the active form. Plasmin hyperactivity due to decreased plasminogen activator inhibitor-1 (PAI-1) may cause MMP over activity and coronary aneurysms. The aim of this study was to investigate the association between PAI-1 and presence of coronary aneurysms. METHODS: Twenty-three patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Twenty-two patients without coronary aneurysm were selected as a control group (Group 2). PAI-1 was measured in peripheral venous blood. RESULTS: The plasma PAI-1 level was lower in the coronary artery aneurysmatic patients compared to the control group (8.41 +/- 4.28 vs. 13.32 +/- 10.05 ng/ml, p = 0.037). Serum C-reactive protein (CRP) values were not significantly different between groups (3.83 +/- 1.08 vs. 4.01 +/- 1.35 mg/l, p >0.05). CONCLUSION: Increased matrix degrading enzyme activity can cause arterial wall destruction through increased proteolysis of extracellular matrix proteins. Unregulated plasmin hyperactivity due to decreased inhibition by PAI-1 may play an important role in coronary aneurysm formation.     

肝硬化患者血浆中尿激酶型纤溶酶激活物的检测及其意义

目的 探讨肝硬化患者血浆尿激酶型纤溶酶激活物(uPA)、尿激酶型纤溶酶激活物受体(uPAR)、纤溶酶原激活物抑制剂-1(PAI-1)的变化及其意义。 方法 确诊的72例乙型肝炎后肝硬化患者,Child-pugh分级A级23例(A组),B级29例(B组),C级20例(C组)。6例健康志愿献血者为正常对照组。酶联免疫吸附实验测定血浆uPA、uPAR、PAI-1的变化。并同时检测血透明质酸(HA)、Ⅳ型胶原(C Ⅳ)、Ⅲ型前胶原(PC Ⅲ)、血浆白蛋白、胆红素、凝血酶原时间及其活动度改变。 结果 随着肝硬化的进展,血浆uPA、uPAR、PAI-1逐渐增加,HA、PC Ⅲ也明显增加。Child C组患者血浆uPA、uPAR、PAI-1水平(μg/L)分别为1.88±0.64、4.82±2.02和52.60±16.87,A组分别为1.36±0.43、3.03±1.48和24.09±7.14,B组分别为1.79±0.62、4.80±2.22和41.40±17.52,C组与A、B组比较,t值为2.81～7.38,P值均<0.01。A组血浆uPA与PC Ⅲ呈负相关(r=-0.4785,P<0.05);C组PAI-1与HA呈正相关(r=0.5447,P<0.01)。 结论 肝硬化晚期,虽然血浆uPA、PAI-1增加,但总的效应表现为uPA相对不足,肝基质纤维降解受抑制,血浆uPA、PAI-1与肝硬化发展密切相关。     

Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.     

Urokinase type plasminogen activator receptor expression in colorectal neoplasms

Background—The urokinase type plasminogenactivator receptor (uPAR) may play a critical role in cancer invasionand metastasis.
Aims—To study the involvement of uPAR incolorectal carcinogenesis.
Methods—The cellular expression and localisationof uPAR were investigated in colorectal adenomas and invasivecarcinomas by in situ hybridisation, immunohistochemistry, and northernand western blot analyses.
Results—uPAR mRNA expression was found mainly inthe cytoplasm of dysplastic epithelial cells of 30% of adenomas withmild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A(72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPARwas detected in dysplastic epithelial cells of 14% of adenomas and incarcinomatous cells of 49% of invasive carcinomas. uPAR mRNA andprotein concentrations were significantly higher in severe than in mildor moderate dysplasia (p<0.05); they were notably higher in Dukes'stage A than in severe dysplasia (p<0.05), and significantly higher inDukes' stage B than in stage A (p<0.05), but those in stage B werenot different from those in stage C or in metastatic colorectalcarcinomas of the liver.
Conclusions—Colorectal adenoma uPAR, expressedessentially in dysplastic epithelial cells, was upregulated withincreasing severity of atypia, and increased notably during thecritical transition from severe dysplasic adenoma to invasivecarcinoma. These findings implicate uPAR expression in the invasive andmetastatic processes of colorectal cancer.

Keywords:urokinase type plasminogen activator receptor; colorectal adenoma; colorectal cancer; adenoma-carcinoma sequence