Acute ischemic stroke treatment and the occurrence of seizures

Background and objectives

Early intravenous treatment with recombinant tissue plasminogen activator (rt-PA) improves the outcome of patients with an acute ischemic stroke. This retrospective observational study analyses whether rt-PA treatment also prevents the occurrence of early- and late-onset seizures.

Patients and methods

Thirty-eight patients treated with rt-PA were compared to 269 receiving anticoagulants (ACs) and 769 on antithrombotics (ATs) for an acute cardiac- or thrombo-embolic stroke. The epidemiological and clinical data, and the vascular risk factors were determined in the three groups. The incidence, onset and types of seizures were compared.

Results

The patients treated with rt-PA had more severe stroke signs on admission and remained more dependent than those treated with ACs and ATs. The appearance of early-onset seizures was related to the severity of the stroke. The incidence of the late-onset ones tended to be low in the rt-PA group. None of the patients developed status epilepticus or epilepsy.

Conclusion

The occurrence of early-onset seizures in the rt-PA treated group is related to the severity of the stroke and not to the treatment modality. Thrombolysis prevents partly the occurrence of late-onset seizures, probably, by a better reperfusion of the ischemic brain regions.     

Cerebral embolism during elective carotid endarterectomy treated with tissue plasminogen activator: Utility of intraoperative EEG monitoring

Electroencephalography (EEG) is routinely used during elective carotid endarterectomy (CEA) for monitoring cerebral perfusion. The period most frequently associated with cerebral hypoperfusion is the one during the clamping of the carotid artery. We present a case whereby acute hypoperfusion, as detected by ipsilateral hemispheric slowing and attenuation of the fast frequencies on EEG, was detected in the period prior to clamping of the carotid artery. The acute changes were caused by a cerebral embolism. Following emergent treatment with intraoperative thrombolytic therapy with intra-arterial tissue plasminogen activator (t-PA) the EEG changes reversed fully. We discuss the utility of intraoperative EEG monitoring in the detection and treatment of cerebral embolism. The ability of EEG to intraoperatively measure the function of the at-risk cerebral cortex makes it not only a useful tool in detecting acute changes such as from a large embolism, but also in guiding necessary treatment by offering direct feedback in the absence of reliable imaging and clinical examination.     

Long-term stability of fibrinolytic factors stored at -80 °C

Introduction

Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits.

Materials and Methods

Plasma samples stored at -80 ^°C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n = 1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n = 1558) and re-analysed 2001 (n = 78) and 2005 (n = 828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1.

Results

Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R² = 0.01, PAI-1 antigen R² = 0.01 and tPA-PAI-1 complex R² = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R² 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R² 0.67 - 0.93).

Conclusions

This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.     

Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: A pilot study

Introduction

We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke.

Materials and methods

We included 66 patients with acute ischaemic stroke admitted between 1 and 7 hours after the onset of clinical symptoms. We collected plasma samples upon admission and on the two following days and measured AP-FXIII and subunit levels by ELISA. Clinical stroke severity was assessed by NIHSS stroke score.

Results

AP-FXIII could be detected in 34 patients upon admission (range 0.2-26.3 ng/ml), on day 1 in 15 patients (0.2-10.4 ng/ml), and on day 2 in 11 patients (0.1-15.1 ng/ml. AP-FXIII was higher in patients with severe stroke. Lower AP-FXIII levels upon admission were associated with clinical improvement. FXIII-A and FXIII-B subunit levels decreased significantly from day 0 to day 1.

Conclusions

For the first time, we detected AP-FXIII in patients upon an acute thrombotic event. The decrease in FXIII subunit levels during acute ischaemic stroke is evidence for ongoing coagulation activity and FXIII consumption. Our results suggest that FXIII activation and concomitant AP-FXIII release might be associated with an unfavourable short-term clinical outcome. Larger studies are needed to further investigate whether AP-FXIII might serve as a diagnostic and/or prognostic marker for acute thrombotic diseases.     

Effect of resveratrol on hemostatic properties of human fibrinogen and plasma during model of hyperhomocysteinemia

Resveratrol (3,4’, 5 - trihydroxystilben), a phenolic antioxidant synthesized in grapes and vegetables and presents in wine, has been supposed to be beneficial for the prevention of cardiovascular events. In this study the influence of resveratrol on the clot formation (using human plasma and purified fibrinogen) and the fibrin lysis during model of hyperhomocysteinemia was investigated. We induced this process using a reduced form of Hcys (at final dose of 0.1 mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 0.5 μM). The aim of our study in vitro was to investigate the modifications of human plasma total proteins after incubation with Hcys, HTL and resveratrol. We observed that HTL, like its precursor, Hcys stimulated polymerization of fibrinogen. Our present results also demonstrated that Hcys (0.1 mM) and HLT at lower doses than Hcys (0.5 μM) reduced the fibrin lysis in human plasma. Moreover, Hcys and HTL change the level of thiol and amino groups in plasma total proteins. Our results indicate that resveratrol reduced the toxicity action of Hcys and HTL on hemostatic properties of fibrinogen or plasma, suggesting its possible protector role in hyperhomocysteinemia - induced cardiovascular diseases.     

小剂量重组组织型纤维溶酶原激活剂治疗急性心肌梗死的疗效观察

目的观察重组组织型纤维蛋白激活剂栓体舒(recombinant tissue plasminogen activator,rTPA)在急性心肌梗死治疗中的临床疗效和不良反应。方法小剂量重组组织型纤维蛋白溶酶激活剂(栓体舒)50mg于90min内静脉注入,治疗急性心肌梗死患者72例,观察血管再通的临床指标、不良反应及病死率。结果梗死相关血管再灌注率75%,6周病死率4.17%,出血发生率14.17%。结论小剂量栓舒静脉溶栓治疗急性心肌梗死较安全有效。     

发病3～6h应用rt-PA静脉溶栓治疗急性脑梗死的有效性与安全性分析

目的探讨重组组织型纤溶酶原激活物(rt-PA)静脉溶栓治疗扩大时间窗至6 h的疗效与安全性。方法试验组选择发病3 h内的患者(A组)16例,3～6 h的患者(B组)10例做为观察对象,分别给予rt-PA(0.7 mg/kg)静脉溶栓治疗;另选择发病在0～6 h内未选择溶栓治疗的患者为对照组(16例)。试验组与对照组均给予奥扎格雷钠80 mg,1次/d,静点;舒雪宁20 mL,1次/d,静点;阿司匹林0.1 g,1次/d,口服治疗。评定患者治疗前、治疗后2 h、24 h、7 d、30 d的NIHSS评分及治疗后90 d的Barthel指数评分。治疗前、治疗后1 d查头部CT,判定是否出血(根据影像学判定是梗死后还是实质出血)并记录各组出血和死亡例数。结果试验组与对照组各自NIHSS评分治疗前无差别(P>0.05),治疗后各时间点比较有统计学意义(P<0.05),试验A组与B组治疗前后各时间点差别无统计学意义(P>0.05);试验组与对照组B I指数治疗前与治疗后90d比较差异有统计学意义。A组出血2例,1例为梗死后出血,1例为脑实质出血,死亡1例;B组出血1例,为梗死后出血,死亡0例;对照组出血1例,1例为梗死后出血,死亡1例。结论用rt-PA溶栓治疗,扩大时间窗至6 h,疗效确切,未增加出血几率。因此,将溶栓时间窗扩大至6 h可行。     

Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration

To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined," the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29), 92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in 3 samples for which the initial cytological diagnosis was "suspicious" and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis.     

狼疮肾炎热瘀证与临床病理的相关性研究

目的：研究狼疮肾炎热瘀证与临床及肾脏病理损害的相关因素分析。方法：分析30例狼疮肾炎热瘀证与30例狼疮肾炎非热瘀证的临床及肾脏病理资料。结果：狼疮肾炎热瘀证多见于SLE活动期,热瘀证组抗dsDNA阳性率、SLEDAI积分明显高于非热瘀证组（P〈0．01）,而补体G、C4明显低于非热瘀证组（P〈0．01）;除血浆tPA含量外,血浆纤维蛋白原（FIB）、D-二聚体、1型纤溶酶原激活物抑制物（PAI-1）含量在两组病人间存在统计学差异,热瘀证组明显高于非热瘀证组（P〈0．01～0．05）;热瘀证组肾脏病理的活动积分显著高于非热瘀证组;热瘀证组肾组织纤维蛋白原相关抗原（FRA）沉积程度明显强于非热瘀证组。结论：狼疮肾炎热瘀证与临床及病理损害有一定相关性,狼疮肾炎热瘀证与狼疮活动、肾脏病理活动、全身及肾脏局部高凝和纤溶低下有一定相关。     

Plasma PAI-1 levels are independently related to fatty liver and hypertriglyceridemia in familial combined hyperlipidemia, involvement of apolipoprotein E

BACKGROUND: Familial combined hyperlipidemia (FCHL) is a genetic form of dyslipidemia, which is characterized by an increased cardiovascular risk. The current study was conducted to investigate the relation of endothelial, inflammatory and fibrinolysis markers with the presence of hypertriglyceridemia and fatty liver in FCHL, in order to advance insight in their contribution to the cardiovascular risk profile. MATERIALS AND METHODS: Key plasma markers of low-grade inflammation, endothelial dysfunction and fibrinolysis were measured in 38 hypertriglyceridemic FCHL patients and 38 age and sex-matched spouses. The presence of fatty liver was determined with ultrasound. RESULTS: hsCRP, vWF, PAI-1, tPA and tPA/PAI-1 complex levels were significantly higher in hypertriglyceridemic FCHL patients compared to spouses (p<0.05). Subsequent analyses revealed that these increased levels were confined to FCHL patients with the fatty liver phenotype (n=25). Only PAI-1 and tPA levels were also elevated in the hypertriglyceridemic FCHL patients without fatty liver (n=13). Of interest, 11 hypertriglyceridemic non-FCHL patients with the E2/E2 genotype displayed significantly lower PAI-1 levels when compared to the overall FCHL population (p=0.001), implicating a role for apolipoprotein E in the relation of PAI-1 with plasma triglycerides. CONCLUSION: Markers of fibrinolysis were increased in all hypertriglyceridemic FCHL patients, whereas an increased state of endothelial dysfunction and inflammation was particularly observed in those hypertriglyceridemic FCHL patients who also have fatty liver. These results demonstrate the complex genesis of the unfavourable cardiovascular risk profile that is present in FCHL, and illustrate the potential risk of fatty liver above, and beyond hypertriglyceridemia per se.