Prothrombin, thrombin and prothrombin fragments in plasma of normal individuals and of patients with laboratory evidence of disseminated intravascular coagulation

With specific immunoassays for prothrombin, thrombin-anti-thrombin-III complex and for prethrombin-1 antigen, we measured the levels of these proteins in the plasma of normal individuals and patients suspected of having chronic disseminated intravascular coagulation (DIC). The normal level of prothrombin in plasma was found to be 110–212 mg/liter, and of thrombin-anti-thrombin-III complex and prethrombin-1 antigen approximately 1 μg/ml. In patients with suspected DIC, prothrombin levels, as measured by immunoassay and two-stage clotting assay, were decreased in 14 of 19 studied. Levels of thrombin-anti-thrombin-III complex were normal in all the patients and those of prethrombin-1 elevated in only two of 19. The lack of elevation of these products is probably due to the small amount of prothrombin activated in these patients. Decreased synthesis may account for the low levels of prothrombin observed in some. Measurement of the level of these products of prothrombin is therefore not useful in the diagnosis and management of patients with DIC.     

Multiple bilateral non-hemorrhagic cerebral infarctions associated with microscopic polyangiitis

Microscopic polyangiitis (MPA) is a systemic disorder that affects small vessels, such as arterioles, venules or capillaries. Cerebrovascular disease has been rarely reported in connection with MPA; this complication is usually associated with fatal hemorrhage or hemorrhagic conversion. We report a case of MPA with multiple bilateral non-hemorrhagic cerebral infarctions in a 66-year-old woman who was undergoing steroid pulse therapy. The diagnosis of MPA was based on the presence of painful mononeuritis multiplex, pulmonary fibrosis, and increased myeloperoxidase activity and on the biopsy of the sural nerve.     

Ropinirole induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in Wistar rats

Stroke is characterized by an initial ischemia followed by a reperfusion that promotes cascade of damage referred to as primary injury. The loss of mitochondrial function after ischemia, which is characterized by oxidative stress and activation of apoptotic factors is considered to play a crucial role in the proliferation of secondary injury and subsequent brain neuronal cell death. Dopamine D2 receptor agonist, Ropinirole, has been found to promote neuroprotection in Parkinson´s disease and restless leg syndrome. The current study was designed to test its efficacy in preclinical model of stroke. Previously it has been demonstrated that Ropinirole mediates its neuroprotection via mitochondrial pathways. Assuming this, we investigated the effect of Ropinirole on mitochondrial dysfunction, we have shown the positive effect of Ropinirole administration on behavioral deficits and mitochondrial health in an ischemic stroke injury model of transient middle cerebral artery occlusion (tMCAO). Male Wistar rats underwent transient middle cerebral artery occlusion and then received the Ropinirole (10 mg and 20 mg/kg b.w.) at 6 h, 12 and 18 h post occlusion. Behavioral assessment for functional deficits included grip strength, motor coordination and gait analysis. Our findings revealed a significant improvement with Ropinirole treatment in tMCAO animals. Staining of isolated brain slices from Ropinirole-treated rats with 2, 3,5-triphenyltetrazolium chloride (TTC) showed a reduction in the infarct area in comparison to the vehicle group, indicating the presence of an increased number of viable mitochondria. Ropinirole treatment was also able to attenuate mitochondrial reactive oxygen species (ROS) production, as well as block the mitochondrial permeability transition pore (mPTP), in the tMCAO injury model. In addition, it was also able to ameliorate the altered mitochondrial membrane potential and respiration ratio in the ischemic animals, thereby suggesting that Ropinirole has a positive effect on mitochondrial bioenergetics. Ropinirole inhibited the translocation of cytochrome c from mitochondria to cytosol reduces the downstream apoptotic processes. In conclusion, these results demonstrate that Ropinirole treatment is beneficial in preserving the mitochondrial functions that are altered in cerebral ischemic injury and thus can help in defining better therapies.     

Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged ≤ 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7–3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3–6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from ‘cryptogenic’ ischaemic events. Received: 13 January 1998 Received in revised form: 9 March 1998 Accepted: 23 March 1998     

Higher cerebral dysfunction in a case with atypical multiple sclerosis with concentric lesions

Abstract A patient with atypical multiple sclerosis (MS) with clear concentric structure was studied using high field magnetic resonance imaging (MRI). This case was considered to be Balo's concentric sclerosis. Magnetic resonance imaging showed diffuse multiple concentric demyelinating lesions in the bilateral centrum semiovales, which finally regressed with the necrotic lesions remaining when the patient was discharged. During his clinical course, he showed some higher cerebral dysfunctions, such as memory disturbance, constructual apraxia and acalculia. He was treated with glycerin, prednisone and rehabilitation; all of which were effective in his recovery. Over a 4 month period, the patient recoveredclinically, but some intellectual impairment remained.     

大鼠颈动脉狭窄伴多发脑梗死血管再通后脑组织MMP-9的动态变化

目的 应用可逆性大鼠颈动脉重度狭窄合并脑梗死模型,探讨颈动脉狭窄合并脑梗死血管再通后脑组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的动态变化.方法 采用针控线拴法和自体血栓制作可逆性大鼠颈动脉狭窄合并脑梗死模型,免疫组织化学染色及半定量脑内MMp-9的变化.结果 颈动脉重度狭窄合并脑梗死无再通组梗死侧脑组织MMP-9表达增加(P<0.05),1d开始明显增高,以后逐渐下降;5d出现第2个高峰.1d、2d、3d、5d、7d颈动脉狭窄合并脑梗死无再通组梗死侧MMP-9表达均高于非梗死侧(P<0.05);14d时颈动脉狭窄合并脑梗死无再通组梗死侧MMP-9表达与非梗死侧相比无统计学差异(P>0.05).颈动脉重度狭窄合并脑梗死再通组MMP-9表达1d开始升高;5d达高峰;7d和14d逐渐降低.与无再通组相比各时间点MMP-9的表达均有降低趋势,第1天时降低较明显(P<0.05).结论 大鼠颈动脉重度狭窄合并脑梗死无再通组和再通组梗死侧MMP-9表达均高于非梗死侧,且MMP-9的表达与血管再通有关.     

体外循环心脏术后重度脑损害临床分析

目的 探讨体外循环（Cardiopulmonary bypass,CPB)心脏术后重度脑损害的原因及防治方法。方法 分析18例CPB术后并发重度脑损害的诊治过程及预后。结果 脑缺氧综合征12例,硬脑膜外/下出血5例,脑实质出血1例,治愈11例,好转1例,死亡6例,结论 CPB中提高灌注流量和应用微栓过滤器是降低脑并发症的重要措施,上腔静脉逆行灌注和高压氧的应用是治疗脑气栓的有效方法,早期诊断和及时手术清除血肿是治疗硬脑膜外/下血肿的关键。     

Atrial fibrillation predicts good functional outcome following intravenous tissue plasminogen activator in patients with severe stroke

Objective

Atrial fibrillation (AF) is associated with poor outcome after intravenous thrombolysis probably due to greater pretreatment stroke severity. We conducted this retrospective study to determine whether AF is an independent predictor for clinical outcome in patients stratified by initial stroke severity.

Methods

A total of 143 acute ischemic stroke patients who received intravenous thrombolysis within 3 h after onset were enrolled. The patients were categorized according to the baseline stroke severity by National Institute of Health Stroke Scale (NIHSS) score (≤10 vs. >10) and the presence of AF or not. Favorable 90-day outcome was defined as a modified Rankin Scale (mRS) score < 2.

Results

Among the 100 patients with severe stroke (NIHSS > 10), those with AF (n = 52) had a higher proportion of favorable 90-day outcome than those without AF (31% vs. 8%, P = 0.005). After adjustment for age, baseline glucose level, and onset to treatment time, the difference remained significant (odds ratio 5.80, 95% confidence interval 1.63–20.68). In patients with mild stroke (NIHSS ≤ 10), no difference in clinical outcome was found between AF (n = 20) and non-AF (n = 23) groups.

Conclusion

Presence of AF was associated with favorable 90-day outcome following intravenous thrombolysis in patients with severe stroke at baseline, while the association did not exist in patients with mild stroke.     

急性脑梗死及其并发多脏器功能障碍综合征患者血清C反应蛋白水平的变化

目的　探讨急性脑梗死 (ACI)及其并发多脏器功能障碍综合征 (MODS)患者血清C反应蛋白(CRP)水平的变化及与MODS发生率的关系。方法　采用免疫透射比浊法测定 30名健康体检者 (正常对照组 )和 82例ACI患者血清CRP的含量 ,并对腔隙性脑梗死 (LCI)、急性单纯性脑梗死 (PACI)、ACI并发MODS患者的血清CRP水平进行比较。结果　ACI患者血清CRP水平与正常对照组比较显著升高 (P <0 0 1) ,PACI患者血清CRP水平显著高于LCI患者 ,ACI并发MODS患者又显著高于PACI患者 (均P <0 0 5 )。ACI患者MODS的发生率与血清CRP水平呈正相关 (r=0 94 ,P <0 0 5 )。结论　CRP与ACI及其并发MODS明显相关 ,血清CRP水平对判断ACI的预后是一个有效指标。     

Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular dysfunction and infarction during mild but not severe hyperglycemic stroke

We investigated mechanisms by which circulating factors during hyperglycemic (HG) stroke affect cerebrovascular function and the role of peroxynitrite in stroke outcome. Middle cerebral arteries (MCAs) were isolated from male Wistar rats and perfused with plasma from rats that were hyperglycemic for 5 to 6 days by streptozotocin and underwent either MCA occlusion (HG MCAO) or Sham surgery (HG Sham) compared with MCA perfused with physiologic saline (No plasma). Myogenic responses and endothelial function were compared in untreated MCA (n=8/group) or with inhibitors of NADPH oxidase (apocynin; n=8), peroxynitrite (FeTMPyP; n=8) or endothelin-1 (ET-1)(A) (BQ-123; n=8). Finally, animals were treated in vivo before reperfusion after mild (<68% cerebral blood flow (CBF) decrease) or severe (>68% CBF decrease) MCAO with FeTMPyP (n=12) or vehicle (n=12) and CBF and infarction measured. The HG MCAO plasma increased tone in MCA versus No plasma (P<0.05) that was reversed by FeTMPyP, but not by apocynin or BQ-123. The HG Sham plasma also increased tone in MCA (P<0.05) that was reversed by BQ-123 only. In vivo, FeTMPyP was neuroprotective during mild, but not severe ischemia. These results show that circulating factors in plasma can affect cerebrovascular function through peroxynitrite generation and ET-1. In addition, peroxynitrite decomposition improves stroke outcome acutely during mild, but not severe HG ischemia.     

老年大面积脑梗死合并多器官功能不全综合征102例分析

目的探讨老年大面积脑梗死合并多器官功能不全综合征(MODS)的临床特点及防治措施。方法回顾性分析1998年6月～2008年6月在北海市人民医院住院治疗的老年大面积脑梗死合并MODS患者的临床资料。结果本组患者102例,男79例,女23例,平均76.13±6.25岁;发生MODS时,各器官衰竭的易感性依次为肺、心、肾、外周循环、胃肠、肝、凝血功能,死亡率为62.75%。结论老年大面积脑梗死患者发生MODS时,肺、心、肾等器官最先受累,这时死亡率升高,需积极进行防治。     

A female case of West syndrome with remission of spasms following multiple cerebral hemorrhages

Multiregional wide-distribution hemorrhages of the left hemisphere occurred at 1 month of age in a girl with congenital factor V deficiency. At the age of 4 months, symmetrical spasms appeared in clusters and electroencephalography showed diffuse background attenuation in the left side and hypsarrhythmia only in the right. Brain CT scan showed that the left hemisphere including Rolandic area was completely infarcted. She was diagnosed with West syndrome and spasms were not controlled by anti-epileptic drugs. Following multiple intracerebral and subarachnoid hemorrhaging involving the right hemisphere at approximately 2 years of age, spasms and hemi-hypsarrhythmia abruptly disappeared, and complete remission of spasms persisted for 2 years. Taken together, the right-hemispheric cortex seemed to be primarily responsible for generation of symmetric spasms and hemi-hypsarrhythmia on electroencephalography. This case study failed to support the hypothesis that ictal discharges needs to be propagated from one to the other side though the corpus callosum in order to generate symmetric spasms. Rather, symmetric spasms can be explained by activation of subcortical structures such as the brain stem, ipsilateral spreading of electrographic discharges from the residual hemisphere, or intra-hemispheric propagation of ictal discharges.     

Neuroprotection following focal cerebral ischaemia with the NMDA antagonist dextromethorphan,has a favourable dose response profile

Abstract

Although N-methyl-D-Aspartate (NMDA) antagonists protect against focal cerebral ischaemia, there is concern that the high closes necessary for neuroprotection may cause unacceptable adverse effects. We studied the dose response characteristics of the clinically available NMDA antagonist dextromethorphan in a rabbit model of transient focal ischaemia. Thirty-three anaesthetized rabbits underwent occlusion of the left internal carotid and anterior cerebral arteries for 1 h followed by 4.5 h of reperfusion. One hour after the onset of ischaemia, they were treated with an i.v. infusion of varying doses of dextromethorphan or normal saline. Seventeen additional unanaesthetizednonischaemic rabbits received similar infusions of dextromethorphan to correlate brain with blood levels and to evaluate adverse effects. Rabbits with plasma dextromethorphan levels 500-1500 ng ml^–1 had a 64% reduction in ischaemic neuronal damage (p<0.05); those with levels >1500 ng ml^–1 showed 92% attenuation of neuronal damage and 65% decrease in ischaemic oedema (p < 0.01). Drug levels suggest that dextromethorphan’s neuroprotection is not mediated by its active metabolite dextrorphan. Unanaesthetized rabbits with plasma levels > 2500 ng ml^–1 demonstrated severe gait ataxia. These results demonstrate that systemic treatment with dextromethorphan after 1 h of focal ischaemia can significantly protect against cerebral damage if adequate plasma and brain levels are achieved. Dextromethorphan was concentrated 7-30 x in brain compared with plasma, and brain levels were highly correlated with plasma levels (r = 0.89). Neuroprotective doses of dextromethorphan were tolerated with only transient side effects. [Neurol Res 1993; 15:174–180]     

Effect of methylene blue on middle cerebral artery flow velocity in a patient with severe sepsis following clipping of a cerebral aneurysm

Introduction: The use of methylene blue, an inhibitor of guanylate cyclase, has been described in patients with septic shock who are unresponsive to inotropic agents. However, the effects of methylene blue on the human cerebral circulation are not known. Methods and Results: This article presents a case report of a 58-year old-female with a clinical presentation compatible with severe sepsis and increasing inotropic requirements following clipping of a cerebral aneurysm. Administration of methylene blue (2 milligrams/kilograms) intravenously was undertaken with monitoring of mean arterial pressure and middle cerebral artery flow velocity (FVm). The effect of methylene blue on mean arterial pressure occurred quite rapidly after initiation of the infusion, allowing downward titration of norepinephrine. Initially, FVm increased in association with an increase in mean arterial pressure, reaching its highest value halfway through the infusion. Subsequently, FVm decreased to baseline by the end of the monitoring period. The rise in mean arterial pressure and increase in FVm were accompanied by a reduction in cerebral vascular resistance assuming intracranial pressure, and the diameter of the insonated vessel was unchanged during and immediately after infusion of methylene blue. Conclusion: Methylene blue did not appear to have a major untoward effect on cerebrovascular resistance in this patient. The limited characterization of cerebrovascular effects provided by this article mandates the need for careful monitoring of cerebrovascular behavior and adequacy during use of methylene blue.     

急性脑梗死诱发SIRS及MODS时患者血清SOD含量变化研究

目的 探讨急性脑梗死(ACI)诱发全身炎症反应综合征(SIRS)及多器官功能障碍综合征(MODS)的发生率,以及血清中超氧化物岐化酶(SOD)含量变化在ACI诱发SIRS及MODS中的作用机制及临床意义. 方法 选取自2006年1月至2008年6月菏泽市立医院神经内科住院及门诊就诊的68例ACI患者.分为3组,其中急性单纯性脑梗死36例(SACI组),ACI诱发SIRS患者(SIRS组)32例,ACI诱发MODS患者(MODS组)24例,采用黄嘌呤氧化酶法测定血清SOD含量,另设28例到本院查体的健康人为正常对照组(NC组). 结果 (1)本组SACI诱发SIRS的发生率为88.9%,诱发MODS的发生率为66.7%;ACI诱发SIRS时MODS的发生率为75.0%.ACI诱发MODS时100%发生SIRS.(2)各组之间SOD含量比较差异有统计学意义(P<0.05),且血清SOD含量水平依次为MODS组相似文献   

The phenylpropanoid micronutrient chlorogenic acid improves clinical rating scores in rabbits following multiple infarct ischemic strokes: synergism with tissue plasminogen activator

The present study assessed whether chlorogenic acid (CGA), a phenylpropanoid molecule that has multiple mechanisms of action would be useful to attenuate behavioral deficits associated with embolic strokes using the rabbit small clot embolic stroke model (RSCEM). Quantal analysis for each treatment determines the quantity of microclots (mg) that produce neurologic dysfunction in 50% of a group of animals (P(50)), with intervention considered beneficial if it increases the P(50) compared to controls. CGA (50 mg/kg) injected 5 min post-embolization significantly increased behavioral function and the P(50) to 3.61+/-0.52 mg (n=19) compared to 1.58+/-0.15 mg (n=26) in controls. In addition, CGA also increased the P(50) to 2.57+/-0.28 mg (n=18) when administered 1 h post-embolization, but was ineffective when given 3 h following embolization (P(50)=1.22+/-0.24 mg, n=18). For combination studies with the thrombolytic tissue plasminogen activator (tPA), we used tPA at a standard dose of 3.3 mg/kg, which significantly increased the P(50) to 2.89+/-0.29 mg (n=17) when administered 1 h after embolization, but not 3 h after embolization (P(50)=1.54+/-0.27 mg, n=18). However, when tPA (3.3 mg/kg) was combined with CGA (50 mg/kg) and administered 3 h following embolization, there was a significant increase in behavioral function as evidenced by an increase in the P(50) value to 3.40+/-0.76 mg (n=23). In conclusion, as a mono-therapy CGA effectively reduced behavioral deficits when given up to 1 h following embolic strokes in rabbits. Moreover, there was a synergistic effect of the combination of tPA with CGA when administered 3 h following embolization. The results show that the therapeutic window for a standard effective dose of tPA could be increased by administration of CGA, suggesting that it may be most useful as a co-therapy with a standard thrombolytic treatment regimen.     

急性脑出血并发全身炎症反应综合征致多器官功能障碍综合征患者血清一氧化氮、一氧化氮合酶的变化

目的　探讨急性脑出血并发全身炎症反应综合征(SIRS)致多器官功能障碍综合征(MODS)的可能机制及一氧化氮(NO)、一氧化氮合酶(NOS)在急性脑出血致MODS发生发展中的作用。方法　观察急性脑出血并发SIRS及导致MODS的发生率。应用硝酸还原酶法及比色法动态监测73例急性脑出血患者血清NO及NOS的水平,并以20名健康人为对照。结果　脑出血并发SIRS的发生率为47. 95% (35 /73),其中74. 29% (26 /35)导致MODS。73例患者血清NO及NOS水平均明显高于正常对照组,且随病情的加重呈上升的趋势(均P<0. 01);重型MODS组较轻型组、死亡MODS组较存活组差异有极显著性(均P<0 01)。结论脑出血并发SIRS是导致MODS的主要机制,NO、NOS参与了脑出血并发SIRS及导致MODS的病理生理过程,并可作为一客观指标判断脑出血的病情及预后。