抗供者特异性抗体与肾移植后的急性排斥反应

目的：大部分肾移植失败的患者体内都存在抗HLA抗体。检测抗供者特异性HLA抗体在肾移植受者体内的表达,并分析其在预测排斥反应中的作用。 方法：2006-10/2008-03郑州人民医院器官移植科采用酶联免疫吸附法检测179例肾移植受者血清中的抗供者特异性HLA抗体以及群体反应性抗体水平,群体反应性抗体> 10%为阳性,群体反应性抗体阳性受者即致敏受者。检测移植后2个月内早期急性排斥反应的发生率,统计分析群体反应性抗体及抗供者特异性HLA抗体与移植后早期急性排斥反应的关系。 结果：肾移植前血清抗供者特异性HLA抗体阳性50例受者的急性排斥反应率发生率为66%,移植前血清群体反应性抗体阳性56例受者的发生率为25%,两者比较差异具有显著性意义(P < 0.01),抗供者特异性HLA抗体水平与急性排斥反应的发生具有更强的相关性。移植前血清抗供者特异性HLA抗体阳性受者的急性排斥反应发生率显著高于抗供者特异性HLA抗体阴性受者(66%,11%,P < 0.01)。体内含抗HLA-Ⅱ类抗体受者的急性排斥反应发生率显著高于含HLA-Ⅰ类抗体的受者(78.1%,43.8%,P < 0.05)。 结论：抗供者特异性HLA抗体是肾移植前筛选致敏受者的重要指标,抗供者特异性HLA抗体阳性患者移植后更容易发生急性排斥反应。     

肾移植患者群体反应性抗体水平与移植肾急性排斥的关系

背景：目前众多实例和资料证实，群体反应性抗体的存在与否及该抗体的致敏程度对于是否发生排斥反应及移植物存活率的高低、移植后器官功能的实现都有着重要意义。 目的：检测肾移植受者术前、术后群体反应性抗体水平,并结合患者临床排异情况,分析肾移植患者术前、术后群体反应性抗体水平与急性排斥反应的关系。 设计、时间及地点：回顾性病例分析，于1998-09/2000-05在北京首都医科大学附属北京友谊医院泌尿科肾移植研究室完成。 对象：选择在北京友谊医院接受肾移植的633例患者，男348例，女285例，年龄16~67岁。 方法：采用美国One Lambda 公司和德国Biotest公司淋巴细胞冷冻板，检测患者术前和术后一两个月内血清中的群体反应性抗体。 主要观察指标：术前及术后患者群体反应性抗体水平、临床排斥反应发生情况。 结果：移植前群体反应性抗体阴性591例，移植后群体反应性抗体阳性164例，61例术后发生急性排斥反应，占10.3%；移植前群体反应性抗体阳性42例，移植后30例发生了急性排斥反应，占71.4%，12例未发生急性排斥反应。肾移植术前群体反应性抗体阴性与阳性术后发生排斥反应比较差异有非常显著性意义(P < 0.001)；肾移植前后群体反应性抗体均为阴性患者427例，术后24例发生了急性排斥反应，占5.6%；肾移植后群体反应性抗体阳性164例，70例发生了急性排斥反应，占42.7%。肾移植前群体反应性抗体阴性与术后群体反应性抗体阳性并发生排斥反应的比较差异有非常显著性意义(P < 0.001)。术前群体反应性抗体阴性和阳性与术后排异与否的相关系数为0.612，术后群体反应性抗体阴性和阳性与术后排异与否的相关系数为0.685，二者在P=0.01水平有明显相关性。 结论：群体反应抗体对预测移植肾的急性排斥反应具有重要的意义。术前、术后群体反应性抗体阳性患者，术后发生急性排斥的概率较高；而术前、术后群体反应抗体阴性的患者发生急性排斥的概率较低。     

肾移植受者血清sFas和sFasL变化及在早期急性排异反应预测中的应用

背景：细胞凋亡在移植免疫和移植物功能丧失发生过程中起十分重要的作用,其中Fas/FasL系统被认为是细胞凋亡参与肾移植的急性排异反应过程的主要途径之一。 目的：分析肾移植受者术后血清sFas和sFasL水平变化及其在预测早期急性排异反应中的应用价值。 方法：肾移植受者80例分为肾功能稳定组(49例)、急性排斥反应组(23例)和环孢素A中毒组(8例)。另选择性别、年龄与肾移植受者相匹配的健康体检者50例为对照组。肾移植受者术后均常规使用环孢素A+硫唑嘌呤+泼尼松三联免疫抑制治疗。发生急性排斥反应时给予每日甲基强的松龙6~8 mg/kg冲击治疗,3 d为1个疗程。采用ELISA法检测患者手术前后的血清sFas和sFasL水平。 结果与结论：肾移植组患者手术前的血清sFas和sFasL水平均明显高于对照组(P < 0.05)。急性排斥反应组血清sFas、sFasL水平高于相同时间段肾功能稳定组(P < 0.05)。环孢素A中毒的肾移植患者术后各时间点血清sFas、sFasL水平变化与肾功能稳定组基本相同,差异无显著性意义。提示动态监测血清sFas、sFasL水平可能对早期诊断及鉴别诊断肾移植急性排斥反应具有重要参考价值。     

sCD30与肾移植后的急性排斥

背景：很多实验已证实,可溶性CD30可作一种除群体反应型抗体以外的新的分子标志物来评估移植受者移植前免疫状况。 目的：比较sCD30与群体反应性抗体对预测肾移植后急性排斥反应发生的影响。 设计、时间及地点：回顾性病例分析,于2007-01/2008-01在郑州人民医院器官移植科完成。 参试者：接受肾移植的患者120例。 方法：检测120例肾移植前患者血清sCD30与群体反应性抗体浓度,移植后患者接受钙调神经磷酸酶抑制剂的免疫抑制疗法。移植后6个月内的急性排斥反映判断采用肾穿刺活检,确诊患者是否发生了急性排斥反应。 主要观察指标：通过检测移植前后sCD30,群体反应性抗体水平,观察患者sCD30、群体反应性抗体与急性排斥关系。 结果：总的急性排斥反应发生率为15.8%(19/120),sCD30与群体反应性抗体检测均阳性患者与两项都是阴性的患者相比急性排斥反应发生率显著提高(42%和7%,P =0.001)。群体反应性抗体阴性患者中若检测出sCD30呈阳性,发生急性排斥反应的概率会显著升高(21%和5%,P =0.019)。致敏组人群检测结果阳性率较高。 结论：sCD30的高表达与肾移植后急性排斥反应有关。     

外周血CD4+CD25highTreg细胞的比例变化在肾移植受者术后免疫监测中的临床应用研究

目的 研究外周血CD4+CD25highTreg细胞(regulatory T cell,Treg)比例对肾移植受者免疫力的影响,为CD4+CD25highTreg细胞的比例变化作为评估移植受者免疫状态及作为预测排斥反应和感染的特异性指标提供实验依据。方法 肾移植受者52例按肾移植术后恢复情况分为免疫力正常组26例,发生排斥反应组17例,发生感染组9例,用流式细胞仪检测外周血CD4+CD25highTreg细胞的比例,所得结果进行相关分析。结果 发生急性排斥反应组CD4+CD25highTreg细胞比例较免疫力正常组显著降低（p〈0.05）,发生感染组外周血CD4+CD25highTreg细胞的比例较正常组显著升高（p〈0.01）,均有统计学意义。FK-506和CsA分别对CD4+CD25highTreg细胞比例的影响没有显著性差异。结论 肾移植术后受者外周血CD4+CD25highTreg细胞比例与受者免疫状态密切相关。CD4+CD25highTreg细胞比例的变化可以反应机体的免疫状态的变化,其升高或降低可以作为预测肾移植受者术后发生感染或排斥反应的指标之一。     

肾移植术后尿液DYZ-1检测的临床意义

背景：对移植受者尿液成分进行定期监测可以作为判断移植肾功能、状态的一种方法。 目的：分析肾移植受者尿液中供者细胞出现与急性排斥反应的关系及临床意义。 方法：选取60例供者为男性、受者为女性的肾移植受者,分为移植后早期检测组40例、急性排斥组10例、移植后功能稳定组10例。定期提取尿液中细胞DNA,利用PCR检测Y染色体上特异的基因片段DYZ-1。 结果与结论：在手术第1日受者的尿液中可检测到供者细胞DNA,随着时间的延长,尿液中供者细胞DNA量逐渐减少,至术后1个月,有8例受者的尿液中供者细胞DNA消失,其中1例发生急性排斥反应;另外32例受者的尿液中仍有供者细胞DNA的出现,其中7例发生了急性排斥反应;存活3个月以上发生急性排斥反应10例患者,7例尿液标本中能检测到供者细胞DNA,对急性排斥者进行治疗后1个月,71.4%转为阴性;而在稳定期的10例肾功能良好受者,仅1例受者尿液中DYZ-1基因阳性。提示对肾移植受者尿中供者细胞DNA的进行定期检测,可以作为监测急性排斥反应发生及预后的一种手段。     

再次免疫应答导致肾移植后早期严重急性体液排斥反应

背景：国内外有关预防高致敏受者肾移植后发生超急性、急性排斥反应提高人肾存活率取得满意效果,然而临床对群体反应性抗体检测阴性既往致敏受者肾移植后发生再次免疫应答研究则罕见报道。 目的：探讨群体反应性抗体阴性的既往致敏受者肾移植后早期发生严重急性体液性排斥反应机制,为其早期诊断和治疗既提供参考依据。 方法：选择21例群体反应性抗体阴性术后早期发生严重急性体液性排斥的首次肾移植患者,动态分析移植后14 d内反映急性体液性排斥的相关指标,包括IgG型抗HLA抗体,病理苏木精-伊红染色、C4d及细胞表面分子原位检测。 结果与结论：21例患者既往均有输血或妊娠史;18例患者移植后第7天抗HLAⅠ类IgG抗体阳性率>80%,11例于移植后第7天抗HLA Ⅱ类IgG抗体> 80%;5例女性患者于移植后第5~8天发生移植肾破裂,抗HLAⅠ类和Ⅱ类IgG抗体均>96%;21例受者均检出抗供者特异性抗体(DSA),13例(61.90%)供、受者存在HLA-A2和HLA-A11的错配并产生对应DSA,包括5例移植肾破裂受者;病理组织形态学均有不同程度急性损伤,免疫组化可见管周毛细血管区(PTC)C4d沉积,原位染色CD34(+)、CD68(+)、CD4(+)。提示移植前群体反应性抗体监测不能完全反映受者的预致敏状态;移植后早期监测群体反应性抗体可预测和诊断既往致敏受者急性体液性排斥的发生;C4d、CD68(+)作为其的辅助诊断指标,可提高诊出率;HLA-A2和HLA-A11在既往致敏受者是高危致敏基因。     

内皮微粒在肾移植急性排斥反应中的诊断作用

背景：血管内皮细胞的变化与移植排斥反应的关系极为密切，内皮微粒脱落于激活或凋亡的内皮细胞，能直接而特异地反映血管内皮细胞的变化，检测血浆中内皮微粒对肾移植排斥反应的诊断监测具有一定的理论和实际意义。 目的：探讨肾移植急性排斥反应时循环内皮微粒的数量和表型的变化及与急性排斥反应之间的关系。 方法：建立同基因和同种异基因大鼠腹腔原位肾移植模型；移植后5 d苏木精-伊红染色观察肾组织的病理学改变，并进行Banff评分；采用免疫组化法检测肾组织中细胞间黏附分子1表达；采用流式细胞术检测血浆中CD144+内皮微粒数量及细胞间黏附分子1+/CD144+内皮微粒的数量；分析内皮微粒的数量和表型与肾组织病理变化的关系。 结果与结论：与同基因移植组比较，异基因移植组Bnaff评分明显增加(P < 0.01)，肾组织中细胞间黏附分子1表达明显增强(P < 0.01)；与同基因移植组比较，异基因移植组CD144+内皮微粒的数量和携带细胞间黏附分子1的内皮微粒的水平明显增加(P < 0.01)。内皮微粒的数量与移植肾急性排斥反应的程度呈正相关(P < 0.01)，携带细胞间黏附分子1内皮微粒的水平与移植肾脏中细胞间黏附分子1的表达呈正相关(P < 0.01)。提示肾移植后对内皮微粒数量和表型进行检测对诊断急性排斥反应的发生有一定意义。     

肾移植后早期监测环孢素A血药浓度峰值的临床意义

背景：近几年有报道,检测环孢素A的峰浓度可以更准确地反映环孢素A在体内的药代动力学变化,指导移植后的临床用药比检测谷浓度更合理,而对大样本临床资料统计的研究报道较少。 目的：探讨肾移植后早期监测环孢素A血药浓度峰值对判定环孢素A抗排异疗效及毒副作用的临床意义。 方法：采用单抗免疫荧光偏振法同步监测环孢素A全血谷浓度和峰浓度,回顾性分析78例肾移植受者,移植后观察6个月,48例未发生任何移植后并发症设为正常组,16例发生急性排异反应设为急性排斥反应组,14例出现药物性损害设为药物损害组,观察各组谷浓度及峰浓度在患者发生急性排斥反应或药物毒性时的变化。 结果与结论：移植后各时间段发生急性排异患者环孢素A谷浓度与未发生的比较,差异无显著性意义(P > 0.05),而各时间段发生急性排斥反应患者环孢素A峰浓度明显低于正常组(P < 0.05)。移植后1个月内,发生药物性肝损害、肾中毒患者谷浓度和峰浓度均明显高于未发生的(P < 0.05)。移植后2~6个月,药物性肝损害、肾中毒组谷浓度与常组比较差异无显著性意义(P > 0.05),而峰浓度明显高于正常组(P < 0.05)。提示,监测环孢素A峰浓度能有效预测肾移植后急性排异反应的发生;移植后2~6个月监测环孢素A峰浓度能有效预测肾移植后药物性肝损害、肾中毒的发生。     

不同亲属活体供肾移植94例的临床疗效探讨

目的：探讨不同亲属活体供肾移植的临床疗效。 方法：回顾性分析1999年3月至2008年10月94例亲属活体供肾移植的供、受者临床资料,其中父母给子女供肾35例,兄弟姐妹间供肾53例（含同卵双生姐妹间供肾1例）,妻子给丈夫供肾6例。 结果：所有供者术后恢复良好;所有受者肾功能均恢复正常后出院,其中父母给子女供肾4例受者发生急性排斥反应;兄弟姐妹间供肾3例受者发生急性排斥反应;夫妻间供肾受者中,1例术后第3 d发生加速排斥反应导致肾功能恢复延迟,于术后第5周恢复正常,1例发生急性排斥反应。急性排斥反应经甲泼尼龙冲击或抗淋巴细胞球蛋白治疗后全部逆转。术后随访6个月至10年,所有供者肾功能正常;94例受者中,死亡2例,1例术后2年死于呼吸衰竭,1例术后7年死于心力衰竭。其余受者2例发生慢性移植肾肾病。 结论：亲属活体供肾移植组织配型好、排斥反应发生少、移植肾长期存活率高,其中以血缘亲属供肾移植效果更佳。     

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.     

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.     

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.     

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.     

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.