MVD、VEGF及Ki-67在颅咽管瘤中的表达与意义

目的探讨颅咽管瘤中MVD、VEGF及Ki-67表达与意义。方法根据病理亚型、形态学特征及复发情况,将47例颅咽管瘤按不同分类方法分为成釉质细胞型30例,鳞状乳头型17例;原发31例,复发16例;实性为主肿瘤10例,囊性为主肿瘤37例。SP法检测肿瘤标本MVD、VEGF及Ki-67表达,统计分析不同分类的组间表达差异。结果鳞状乳头型肿瘤MVD、VEGF的表达明显高于成釉质细胞型(均P0.001),而Ki-67在两种病理亚型之间无显著差异(P0.05);囊性为主的肿瘤中VEGF表达明显高于实性为主的肿瘤(P=0.018),而MVD、Ki-67在两种形态学分组之间无显著差异(均P0.05);原、复发组间MVD、VEGF及Ki-67均无显著差异(均P0.05)。在本组颅咽管瘤中,MVD与VEGF显著相关(P=0.014),两者均与Ki-67无显著相关(均P0.05)。结论 MVD、VEGF的测定可为颅咽管瘤的血管发生提供依据,VEGF的表达与肿瘤囊性结构形成密切相关,单独检测MVD、VEGF和Ki-67其中一项指标不能预测颅咽管瘤复发。     

血管内皮生长因子和Ki-67在人脑星形细胞瘤中的表达及相关性

目的 研究血管内皮生长因子(VEGF)和Ki-67抗原在人脑星形细胞瘤中的表达及二者的相关性.方法 应用免疫组化S-P法检测30例正常脑组织和60例人脑星形细胞瘤(Ⅰ～Ⅱ级28例,Ⅲ级20例,Ⅳ级12例)中VEGF和Ki-67的表达.结果 VEGF和Ki-67在正常脑组织中均不表达,而在各级别的人脑星形细胞瘤中均有表达,差异有统计学意义(P<0.05).VEGF和Ki-67的表达在高级别星形细胞瘤中均明显高于低级别星形细胞瘤,差异均有统计学意义(P<0.05),且VEGF与Ki-67的表达呈正相关(r=0.310,P<0.05).结论 VEGF和Ki-67的表达可为人脑星形细胞瘤的恶性程度和临床病理分级提供重要的依据.     

血管内皮生长因子、细胞周期相关核抗原Ki-67抗体和p53表达水平与脑膜瘤术后瘤周水肿的相关性研究

目的 探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)、细胞周期相关核抗原Ki-67抗体和p53的表达水平对脑膜瘤术后瘤周水肿(Pedtumoral brain edema,PTBE)的影响.方法 选取2007年1月-2016年7月于本院就诊的脑膜瘤手术患者159例...     

VEGF、PCNA、Ki-67、P53表达与垂体腺瘤侵袭性的相关研究

目的 研究VEGF、PCNA、Ki-67、P53在垂体腺瘤中的表达,探讨其与垂体腺瘤侵袭性的关系.方法 采用SP免疫组化技术,检测45例垂体腺瘤中VEGF、PCNA、Ki-67、P53的表达,并计数MVD,结合影像、手术及病理结果等进行统计学分析.结果 (1)垂体腺瘤中VEGF、PCNA、P53表达在非侵袭性与侵袭性组之间差异有统计学意义(P＜0.05),Ki-67在非侵袭性与侵袭性组之间无统计学意义(χ2=0.020,P＞0.05);(2)垂体腺瘤中VEGF、MVD的表达与垂体腺瘤病理分型之间有一定关系,在垂体腺瘤PRL病理型组中有统计学意义(χ2=9.396,P＜0.05),PCNA、P53、Ki-67的表达在病理分型PRL、GH组中无统计学意义.结论 (1)VEGF、PCNA、P53的表达在非侵袭性与侵袭性组之间有统计学意义,可作为判断垂体腺瘤侵袭性的重要指标;Ki-67的表达在非侵袭性与侵袭性组之间无统计学意义,Ki-67更多地反映恶性肿瘤的增殖性及预后;(2)VEGF、MVD在垂体腺瘤PRL病理型组中有统计学意义,PCNA、P53、Ki-67在病理分型PRL、GH组中无统计学意义,提示血管密度的改变不能完全代表垂体腺瘤的侵袭性,或者仅在垂体腺瘤某些病理型中可以代表一定的侵袭性.     

脑膜瘤缺氧诱导因子-lα表达与瘤周血管生成及病理级别的关系及意义

目的探讨脑膜瘤缺氧诱导因子-lα(HIF-lα)表达与瘤中血管生成及病理级别之间的关系,探讨HIF-lα在脑膜瘤发生和发展中的作用,为治疗脑膜瘤提供理论依据。方法选取脑膜瘤标本45例,正常脑组织标本10例(均为重型颅脑损伤急症行内减压术)作为对照。采用免疫组化ElivisionTMplus两步法,检测缺氧诱导因子-lα在脑膜瘤标本和正常脑组织标本中的表达,以人原始造血细胞(CD34)标记肿瘤微血管,用微血管密度(MVD)作为血管生成指标测定肿瘤血管生成,比较缺氧诱导因子-lα表达与血管生长及病理级别关系。结果45例脑膜瘤组织切片中有23例表达HIF-1α,染色阳性率为51.1%,HIF-1α在正常脑组织及脑膜瘤Ⅰ级、Ⅱ级、Ⅲ级中的阳性表达率分别为0.00%、32.00%、66.67%和87.50%。在各个级别的脑膜瘤及正常脑组织中,HIF-1α的阳性表达率间差异有显著性(P<0.05)。正常脑组织组、I、II和III级脑膜瘤组中的MVD值分别为10.34±2.78,17.25±2.69,20.43±5.20和30.79±5.64,MVD值随着脑膜瘤级别的升高逐渐增加。HIF-lα表达程度与MVD呈正相关。结论缺氧诱导因子-lα表达强度与脑膜瘤血管生成可能有关,为治疗脑膜瘤提供了新的思路。     

单中心107例脑膜瘤临床病理分析

目的探讨脑膜瘤WHO分级与预后的相关性以及免疫组化相关指标在各级中的表达。方法回顾性分析2013年03月～2018年12月间我院手术治疗的107例脑膜瘤患者的病理及预后资料,参照第4版WHO神经肿瘤分类标准将其分级,分析病理分级和复发的关系。采用组织化学及免疫组织化学染色测定波形蛋白(Vimentin)、上皮膜抗原(EMA)、S-100、细胞角蛋白(AE1/AE3)、GFAP以及Ki-67指数在肿瘤中的表达。结果WHOⅠ级99例,Ⅱ级5例,Ⅲ级3例,包括11种亚型。Ⅰ级脑膜瘤无进展生存时间(PFS)明显高于Ⅱ、Ⅲ级(P均0.05),Ⅱ、Ⅲ级脑膜瘤PFS无显著差异(P0.05)。Vimentin阳性107例,EMA阳性103例,S-100阳性13例,AE1/AE3阳性25例,GFAP均为阴性,上述各项指标在WHO分级中无显著差异(P均0.05)。Ki-67指数随肿瘤级别增高而增高(P0.01)。结论 WHO分级与脑膜瘤无进展生存时间密切相关,而Ki-67和肿瘤的良恶性相关,可作为鉴别良恶性脑膜瘤的重要分子标志物。     

脑膜瘤内的血管分布和血管生成与HIF-1α、VEGF的关系

目的 探讨脑膜瘤内部的血管分布以及缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)与脑膜瘤血管生成的关系. 方法 选取中山大学附属一院和中山市人民医院神经外科自2010年5月至2011年3月间手术切除并经病理证实的人脑膜瘤标本15例,收集每例标本硬膜鼠尾征处、基底中心、瘤中央、瘤缘4个不同部位的脑膜瘤组织,每个部位分别连续切片3张,应用免疫组化染色检测CD34、VEGF、HIF-1α的分布和表达. 结果 CD34主要表达在细胞膜和细胞浆,染色呈棕黄色颗粒,VEGF定位于肿瘤细胞胞浆内,而HIF-1α主要在细胞核,少量在胞浆.尾征和瘤缘部位MVD、VEGF、HIF-1α的表达高于基底中心和瘤中央,差异有统计学意义(P＜0.05).脑膜瘤MVD与VEGF、MVD与HIF-1α、VEGF与HIF-1α表达之间均呈正相关关系(r=0.960,P=0.040;r=0.964,P=0.036;=0.998,P=0.002). 结论 脑膜瘤外周部的血管生成比中央区丰富;HIF-1α、VEGF在诱导并促进脑膜瘤的血管生成方面发挥一定作用.     

整合素α3在脑膜瘤中的表达及生物学意义

目的探讨整合素α3在脑膜瘤中的表达及其生物学意义.方法免疫组织化学法检测43例脑膜瘤、5例正常硬脑膜及5例蛛网膜中整合素α3以及Ki-67的表达.结果整合素α3在Ⅰ级及Ⅱ、Ⅲ级脑膜瘤中的表达阳性率分别为80%、37.5%,有显著性差异(P＜0.05);整合素α3的表达与Ki-67标记指数有相关关系.正常硬脑膜及蛛网膜中,整合素α3呈弱、中阳性表达,Ki-67呈阴性表达.结论整合素α3参与脑膜瘤的增殖调控,随着整合素α3表达的减少,肿瘤细胞的增殖活性升高,恶性程度增加;并与脑膜瘤的侵袭性有关.     

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。     

45例脑膜瘤的临床病理和免疫组化分析

目的 探讨脑膜瘤(meningioma)的临床病理特点和免疫组织化学表达特征.方法 对45例脑膜瘤进行临床、病理形态观察分型及生物学行为分级,同时应用EMA、Vimentin、CD34、CK、S-100、GFAP、Ki-67抗体进行免疫组化染色.结果 45例脑膜瘤中,年龄35～73岁,中位年龄57岁,脑膜瘤皮细胞型20例,纤维型11例,非典型性5例,其他类型9例,低危险性脑膜瘤中以皮细胞型为主,EMA呈阳性表达,Vimentin表达阴性或弱阳性,Ki-67＜2%,高危险性脑膜瘤以非典型性为主,EMA呈阴性或弱阳性表达,Vimentin表达阳性,Ki-67＞5%.结论 EMA是诊断脑膜瘤的重要指标,Vimentin和Ki-67是脑膜瘤危险程度的参考辅助指标.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.