胶质瘤中CD105与VEGF、Ki-67表达的相关性

目的探讨胶质瘤中CD105与血管内皮生长因子(VEGF)、Ki-67表达的相关性。方法对58例胶质瘤和10例正常脑组织标本采用免疫组化法检测CD105、VEGF、Ki-67蛋白表达情况并分析其相关性。结果①在正常脑组织中CD105、VEGF和Ki-67均表达阴性,且与各级胶质瘤的表达相差显著(P<0.01)。②Ⅰ～Ⅳ级胶质瘤CD105标染的微血管密度(CD105-MVD)分别为(6.33±2.97)个/视野、(10.69±2.88)个/视野、(19.13±5.14)个/视野和(25.13±5.51)个/视野,不同级别的胶质瘤间差异显著(P<0.01),且其表达与病理分级呈正相关(r=0.834,P<0.01)。③Ⅰ～Ⅳ级胶质瘤VEGF阳性细胞百分率分别为(15.00±3.39)%、(20.26±9.64)%、(36.19±10.75)%和(55.94±11.69)%,除Ⅰ、Ⅱ级之间外,其余各级别胶质瘤间相差显著(P<0.01),且其表达与胶质瘤病理分级呈正相关(r=0.836,P<0.01)。④Ⅰ～Ⅳ级胶质瘤Ki-67标记指数(Ki-67LI)分别为(4.20±1.30)%、(5.32±2.08)%、(9.88±3.24)%和(22.25±6.68)%,除Ⅰ、Ⅱ级之间外,其余各级别胶质瘤间相差显著(P<0.01),且其表达与胶质瘤病理分级呈正相关(r=0.872,P<0.01)。⑤CD105-MVD与VEGF阳性细胞百分率、Ki-67LI均呈显著正相关(r1=0.671,r2=0.699,P<0.01)。结论胶质瘤中CD105-MVD与VEGF阳性细胞百分率、Ki-67LI均有显著相关性,提示其可作为判断胶质瘤恶性程度的指标。     

胶质瘤组织中CD105与Ki-67表达的相关性

目的探讨胶质瘤组织中CD105与Ki-67表达的相关性。方法对58例胶质瘤和10例正常脑组织标本采用免疫组织化学方法检测CD105和Ki-67蛋白表达情况,并分析其相关性。结果①正常脑组织CD105蛋白表达阴性,而各级胶质瘤组织均有CD105蛋白阳性表达。高倍视野(×200倍)下Ⅰ～Ⅳ级胶质瘤组织CD105标染的微血管密度(CD105-MVD)分别为(6.33±2.97)个/视野、(10.69±2.88)个/视野、(19.13±5.14)个/视野和(25.13±5.51)个/视野,随病理分级提高逐渐增高(r=0.834,P<0.01),且不同级别胶质瘤间差异显著(P<0.01)。②Ⅰ～Ⅳ级胶质瘤组织Ki-67标记指数(Ki-67LI)分别为(4.20±1.30)%、(5.32±2.08)%、(9.88±3.24)%和(22.25±6.68)%,随病理分级升高逐渐增高(r=0.872,P<0.01),与正常脑组织比均有显著性差异(P<0.01)。除Ⅰ、Ⅱ级胶质瘤间无明显差异(P>0.05)外,其他各级别胶质瘤间均相差显著(P<0.01)。③CD105-MVD与Ki-67LI呈显著正相关(r=0.699,P<0.01)。结论胶质瘤组织中CD105-MVD与Ki-67LI有显著相关性,提示其可作为判断胶质瘤恶性程度的指标。     

CD105在胶质瘤组织中的表达及其意义

目的探讨CD105在胶质瘤组织中的表达及其意义。方法对58例胶质瘤和10例正常脑组织标本采用免疫组织化学方法检测CD105蛋白表达情况,同时与干细胞相关抗原(CD34)表达情况作对比分析。结果①正常脑组织CD105蛋白表达阴性,而各级胶质瘤组织均有CD105蛋白阳性表达。高倍视野(×200)下Ⅰ～Ⅳ级胶质瘤组织CD105标染的微血管密度(CD105-MVD)分别为(6.33±2.97)个/视野、(10.69±2.88)个/视野、(19.13±5.14)个/视野和(25.13±5.51)个/视野,随病理分级提高逐渐增高(r=0.834,P<0.01),且不同级别各组间均差异显著(P<0.01)。②胶质瘤及正常脑组织均有CD34蛋白阳性表达。高倍视野(×200)下Ⅰ～Ⅳ级胶质瘤组织CD34标染的MVD(CD34-MVD)分别为(10.60±4.72)个/视野、(16.65±4.40)个/视野、(28.53±7.72)个/视野和(38.95±7.98)个/视野,随病理分级升高逐渐增高(r=0.571,P<0.05),除Ⅰ级胶质瘤与正常脑组织[(9.80±3.52)个/视野]及Ⅱ级胶质瘤间CD34-MVD无明显差异(P>0.05)外,其他不同级别胶质瘤各组间差异均有显著性(P<0.01)。③CD105-MVD较CD34-MVD与胶质瘤病理分级具有更紧密的联系(u>1.96,P<0.05)。结论CD105优于CD34,可作为胶质瘤特异性血管内皮细胞标记物并用于测定肿瘤血管生成。     

Stathmin在脑胶质瘤血管内皮细胞中的表达及意义

目的 观察Stathmin及CD105在脑胶质瘤血管内皮细胞中的表达,探讨其在脑胶质瘤血管形成中的作用. 方法 用SP免疫组化法检测10例正常脑组织和78例脑胶质瘤血管内皮细胞中Stathmin和CD105蛋白表达,并通过检测肿瘤微血管密度(MVD)分析肿瘤血管形成.结果 正常脑组织血管内皮细胞中Stathmin和CD105均无表达,脑胶质瘤血管内皮细胞中二者均呈高表达;随着胶质瘤病理级别的增高,Stathmin和CD105表达上调,MVD值增高,Stathmin-MVD和CD105-MVD与脑胶质瘤病理分级均成正相关(r=0.912,P<0.05;P<0.936,P<0.05);且Stathmin-MVD和CD105-MVD之间也存在正相关(r=0.996,P<0.05). 结论 Stathmin与CD105在脑胶质瘤血管内皮细胞中均呈高表达,在肿瘤微血管形成过程起重要作用.     

CD44s和MT1—MMP mRNA在人脑胶质瘤中的表达及其意义

目的分析MT1-MMPmRNA和CD44蛋白的表达与脑胶质瘤恶性程度的关系。方法采用原位杂交和免疫组化方法检测42例人脑胶质瘤和8例正常脑组织中,CD44s蛋白和MT1-MMPmRNA的表达。结果①CD44s蛋白表达在Ⅲ-Ⅳ级脑胶质瘤与在正常脑组织、Ⅰ～Ⅱ级脑胶质瘤之间有显著的差异(P<0.01);②MT1-MMPmRNA的表达水平与肿瘤的级别呈正相关(P<0.01);在Ⅲ-Ⅳ级脑胶质瘤与在正常脑组织、Ⅰ～Ⅱ级脑胶质瘤之间其表达均有显著性差异(P<0.01)。③CD44s蛋白表达与MT1-MMPmRNA表达呈正相关(r=0.895,P<0.01),二者均与肿瘤的恶性程度呈正相关(P<0.01)。结论CD44s和MT1-MMP与脑胶质瘤的发生发展密切相关。     

内皮抑素和血管内皮生长因子在脑胶质瘤中的表达及意义

目的探讨内皮抑素(ES)和血管内皮生长因子(VEGF)在人脑胶质瘤中的表达和意义。方法采用免疫组织化学方法,对45例脑胶质瘤和5例正常脑组织标本中ES和VEGF的表达进行测定。结果Ⅲ-Ⅳ级胶质瘤中ES和VEGF表达水平明显高于Ⅰ-Ⅱ级胶质瘤和正常脑组织,差异有显著性意义(P<0.01);Ⅰ-Ⅱ级胶质瘤中VEGF表达水平显著高于正常脑组织(P<0.05);胶质瘤中ES与VEGF的比值和胶质瘤的分级呈负相关。结论ES和VEGF的协同作用可能在人脑胶质瘤细胞侵袭性生长及恶性发展中起重要作用,且有可能与胶质瘤的恶性程度及预后有关。     

钙粘素、Ki67和p16在人脑胶质瘤中的表达及意义

目的探讨钙粘素(E-cd)、p16和Ki67在人脑胶质瘤中的表达及意义。方法采用免疫组织化学方法检测53例胶质瘤和12例正常脑组织中的E-cd、p16蛋白和Ki67的表达。结果E-cd和p16在正常脑组织中的阳性表达率均为100%;E-cd在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为53.6%、20.0%,p16在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为57.1%、24.0%,E-cd和p16在Ⅰ-Ⅱ级胶质瘤中的表达明显高于在Ⅲ-Ⅳ级胶质瘤中的表达(P<0.05),而低于正常脑组织中的表达(P<0.01);E-cd和p16二者在胶质瘤中的表达呈正相关(P<0.05);Ki67在正常脑组织中无表达。Ki67在Ⅰ-Ⅱ级胶质瘤中阳性率(3.15%±1.67%)明显低于Ⅲ-Ⅳ级胶质瘤中的阳性率(14.37%±4.89%),两胶质瘤组与对照组之间的阳性细胞率差异非常显著(P<0.01)。结论E-cd、p16和Ki67在胶质瘤的发生发展过程中可能起重要作用,并且对评估胶质瘤的恶性度及预后有重要意义。     

人脑胶质瘤中CD133的表达及其意义

目的 探讨CD133 mRNA在人脑胶质瘤组织中的表达及其与病理分级的相关性.方法 用半定量逆转录聚合酶链反应法(RT-PCR)对43例胶质瘤患者、16例正常脑组织标本(均为急性颅脑损伤患者行内减压术切除的脑组织)进行CD133 mRNA检测.结果 (1)43例胶质瘤组织中CD133 mRNA表达全部呈阳性,而16例正常脑组织标本中仅有1例CD133 mRNA表达呈弱阳性.病例组和正常对照组CD133 mRNA的阳性率分别为100%和6.25%.病例组和对照组CD133 mRNA表达阳性率差异有统计学意义(P＜0.01).(2)在病例组中,参照1993年WHO分级标准分为Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级组,计算分组的标本CD133 mRNA与β-actin mRNA灰度比值.Ⅰ级和Ⅲ、Ⅳ级之间差异有统计学意义(P＜0.01),Ⅲ、Ⅳ级之间CD133 mRNA表达均高于Ⅰ级;Ⅱ级和Ⅲ、Ⅳ级之间差异有统计学意义(P＜0.01),Ⅲ、Ⅳ级之间CD133 mRNA表达均高于Ⅱ级.(3)相关性分析:CD133 mRNA表达量与胶质瘤病理分级呈正相关性(r=0.987,P＜0.001).结论 检测胶质瘤组织中CD133 mRNA的表达可用于胶质瘤患者的诊断及恶性程度和预后的判断.     

胶质瘤Polo样激酶1的表达与肿瘤细胞增殖活性及预后的关系

目的探讨Polo样激酶1(PLK1)在人脑胶质瘤组织上的表达及其与胶质瘤细胞增殖活性、临床病理和预后的关系。方法应用免疫组化法检测47例胶质瘤和8例正常脑组织中的PLK1和增殖细胞核抗原(PCNA)的表达,并随访病人。结果正常脑组织未见PLK1明显表达。Ⅰ～Ⅱ级、Ⅲ级和Ⅳ级脑胶质瘤中PLK1表达阳性率分别为64.3%、93.8%和100%,Ⅲ和Ⅳ级分别与Ⅰ～Ⅱ级比较差异有显著性意义(P<0.05)。PLK1表达与胶质瘤病理级别和PCNA表达均呈正相关(r=0.424,P<0.05;r=0.745,P<0.01)。PLK1高表达组和低表达组患者两年生存率分别为41.4%(12/29)和72.2%(13/18),差异显著(P<0.05)。结论PLK1在胶质瘤的发生发展和增殖中起重要作用,与肿瘤分化程度和患者预后密切相关。     

动态对比增强磁共振在脑胶质瘤病理级别中的诊断价值

目的探讨动态对比增强磁共振(DCE-MRI)在界定脑胶质瘤病理级别中的诊断价值。方法回顾分析南阳市第二人民医院2014-11—2016-09经临床或者病理证实为脑胶质瘤患者39例,男25例,女14例,年龄14~70(46±12)岁。病理分级Ⅱ级19例,Ⅲ级11例,Ⅳ级9例。采用免疫组化的方法对每例手术样本进行CD105-微血管密度(CD105-MVD)检测。采用Mann-Whitney U-test对不同级别胶质瘤的Ktrans、Ve和CD105-MVD进行差别验证。采用Pearman相关性分析Ktrans和Ve与CD105-MVD的相关性。结果 Ktrans、Ve和CD105-MVD在低级神经胶质瘤(LGG)和高级神经胶质瘤(HGG)之间有显著的统计学差异(P=0.001、P0.001、P0.001)。病理分级Ⅱ级的Ktrans、Ve和CD105-MVD明显低于Ⅲ级和Ⅳ级。在高级别胶质瘤中Ktrans与CD105-MVD,Ve与CD105-MVD均呈正相关(P0.001、P0.001)。结论 DCE-MRI在无创评估部分神经胶质瘤的MVD中具有一定的作用,值得普及。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.