肾移植后抗HLA和MICA抗体对移植肾慢性排斥反应的影响

背景：体液免疫是影响移植肾长期存活的重要因素之一,抗HLA类抗体和抗MICA抗体在诱发慢性移植肾排斥反应中发挥了重要作用。 目的：探讨肾移植受者血清抗HLA抗体及MICA抗体与术后移植肾慢性排斥反应及存活率的相关性及其临床意义。 设计、时间及地点：病例对照分析,2001-01/2006-06南方医科大学附属珠江医院器官移植科。 对象：选择接受肾移植后长期随访的患者60例,男32例,女28例,年龄25~73岁,平均(45.3±10.8)岁。将移植肾慢性排斥反应受者34例设为排斥组,同期手术移植肾功能仍稳定的26例受者设为对照组。 方法：应用One Lambda混合抗原板通过酶联免疫吸附试验检测受者肾移植前血清中的抗HLA抗体,于2007-01/07月检测受者术后抗体情况,对阳性血清进一步用抗原板检测抗体阳性率及其特异性。采用免疫磁珠流式细胞仪液相芯片技术对肾移植者术前后进行抗MICA抗体测定;采用序列特异性引物聚合酶链反应技术进行HLA基因分型。 主要观察指标：①肾移植患者手术前后抗HLA抗体滴度及特异性的动态变化。②受者术后抗MICA抗体合成情况。③移植肾功能。④移植受者及移植物的存活率。 结果：在60 例肾移植受者中,抗体阴性者27例,抗体阳性者33例,阳性率为55%,其中抗HLA 抗体阳性12例,抗HLA 和MICA 抗体均阳性7 例,抗MICA 抗体阳性14例。慢性排斥组的抗HLA 抗体阳性率显著高于移植肾功能稳定组(P < 0.01);慢性排斥组和肾功能稳定组MICA抗体阳性受者分别为16例（47.1%）和5例（19.2%）,两者比较具有显著性差异(P < 0.05);抗体阳性患者血清肌酐明显高于抗体阴性者,其中抗HLA和MICA抗体均阳性者肌酐水平显著高于单一抗体阳性者(P < 0.05)。 结论：抗HLA抗体介导的体液性排斥反应在诱发慢性移植肾排斥中发挥了主要作用。同时,抗MICA抗体可与内皮细胞上表达的多态性MICA抗原作用,也可导致移植物的慢性损伤。     

经背腰十二肋小切口活体供肾37例：安全性效果评价

背景：活体供肾肾移植关系到供受者双方的生命,要求手术确保供受者安全,手术风险大,技术要求高,为保证供者的安全,如何选择供肾的切取方式十分关键。 目的：总结37例经背腰十二肋切口亲属活体供肾切取术的临床经验,评价其效果及安全性。 方法：选择广西中医学院附属瑞康医院移植泌尿外科2007-06/2008-08完成亲属活体供肾移植患者40例,其中37例采用经背腰十二肋小切口术式切取亲属活体供肾,回顾分析供、受者相关的临床资料。同期随机抽取尸肾移植40例,将亲属活体间肾移植受者与尸肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率、外科相关并发症发生率等方面进行比较。 结果与结论：37例手术均成功,供肾切取手术时间仅1.0~2.0 h,供肾热缺血时间约15 s,冷缺血时间1.0~2.0 h,术中出血不多,围手术期间未发生外科及内科并发症。受者术后肾功能恢复快,1周左右血肌酐水平均可降至正常。随访至今,所有供、受者均正常生存,移植肾功能均保持在正常范围。活体肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率等方面均显著低于尸肾移植。提示经背腰十二肋切口开放切取供肾手术除了有手术时间、热缺血时间短等优点外,在手术安全性方面也有一定的优势,亲属活体肾移植供肾质量高,术后人/肾存活率高。     

亲属活体供肾与同期尸体肾移植40例比较

背景：近年亲属活体间肾移植数量明显增加,供肾者的安全性及亲属活体供肾的移植质量受到日益重视。 目的：总结40例亲属活体供肾移植的临床经验,评价其效果及安全性。 方法：广西中医学院附属瑞康医院移植泌尿外科在2007-06/2008-08共完成亲属活体供肾移植40例,回顾分析供、受者相关的临床资料。同期随机抽取尸肾移植40例,将亲属活体间肾移植受者与尸肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率、外科相关并发症发生率等方面进行比较。 结果：所有供者手术时间仅1.0~2.0 h,供肾热缺血时间15 s左右,冷缺血时间1.0~2.0 h,围手术期间未发生外科及内科并发症。受者术后肾功能恢复快,前3 d尿量500~1 000 mL/h,1周左右血肌酐水平均可降至正常。随访至今,所有供、受者均正常生存,移植肾功能均保持在正常范围。活体肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率等方面均显著低于尸肾移植。开放切取供肾手术时间短、热缺血时间短,在手术安全性方面也有一定的优势。 关健词：亲属活体供肾;肾移植;供肾切取方式;临床分析;安全性     

亲属活体肾移植供者选取策略及围手术期的处理体会

目的：探讨亲属活体肾移植供者选取策略及围手术期处理体会。 方法：选择中南大学湘雅二医院泌外器官移植科完成的活体肾移植供受者126对。126名供者中,男32名,女94名,年龄28~64岁。父母捐给子女61例,兄弟姐妹之间捐献56例,夫妻之间捐献6例,儿子捐给父亲1例,侄子捐给舅舅1例,岳母捐给女婿1例。回顾性总结126例亲属活体肾移植供者的手术经过及术后恢复情况。 结果：受者发生肾功能延迟恢复1例;发生急性排斥反应2例,经抗淋巴细胞球蛋白治疗后得到有效控制;供者术后发生肠梗阻1例,予保守治疗后痊愈;1例供者术后发生阻塞性肺炎,经支纤镜吸痰、雾化吸入稀释痰液、鼓励咳痰、行肺部理疗并适当延长抗生素使用时间,肺部感染得到有效控制;1例供肾肾周脂肪组织中发现曼氏迭宫绦虫裂头蚴,术后供受者均服用吡喹酮,随访1年,血嗜酸性粒细胞计数正常,肾周B超未发现异常;供肾结石3例,2例受者随访2年结石无明显增大,亦未出现移植肾积水、肾功能受损害等表现,1例受者于移植后9个月突然出现尿量减少,行经皮肾穿刺输尿管镜下钬激光碎石术,肾功能恢复正常,术后复查移植肾无残石;5例供者术前检查发现单侧肾囊肿,手术选取有囊肿的一侧肾脏,术中对囊肿施行去顶或去盖术,术后供受者均定期随访肾脏B超,平均随访3年,受者移植肾未发现新发囊肿,供者孤立肾亦未发现囊肿;1例供者出院后生活条件较差,生活无节制,于术后3个月患肺结核,至结核病医院治疗,结核病病情好转后无明显诱因猝死,未尸检;几乎所有供者术后均有一过性血肌酐升高,经长期随访,肌酐均恢复至术前正常水平。 结论：亲属活体肾移植供者的选取要结合具体情况综合考虑,“对供者无害”是首要原则。     

肾移植术后超延迟肾功能恢复15例治疗体会

背景：肾脏移植患者急性排斥反应已不再成为术后的主要并发症，延迟肾功能恢复和慢性移植肾肾病仍然是移植患者术后需要面对的问题。 目的：总结分析15例术后发生超延迟肾功能恢复的肾移植患者资料，探讨临床经验及治疗对策。 方法：对肾移植后发生超延迟肾功能恢复患者15例进行回顾性分析。15例患者移植后均采用常规剂量的半量(环孢素A 3.0~4.0 mg/kg，他克莫司0.5~1 mg/kg)，并定期监测血药浓度，随时调整免疫用药剂量，采用血液透析/连续性肾脏替代治疗。分析超延迟肾功能恢复诱因，患者观察患者肾功能恢复情况。 结果与结论：术中低血压、供肾热缺血时间过长、早期急性排斥反应、环孢素中毒、外科并发症、动脉粥样硬化致移植肾血液灌流不足可能为患者超延迟肾功能恢复的诱因。患者术后由少尿期开始进入多尿期时间最长者为108 d，平均32~108 d。肾功能正常8例(血清肌酐78~135 μmol/L)，肾功能轻度异常5例(血清肌酐135~300 μmol/L)，血清肌酐> 300 μmol/L者2例。随访时间最长1例11年，至今移植肾功能正常。结果提示，肾移植后尽早行移植肾穿刺活检及移植肾彩超，根据结果采取综合治疗并制订个体化治疗方案可以使大多数的患者移植肾功能恢复正常。     

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。     

夫妻间肾移植10例临床分析

为总结夫妻间肾移植经验，探讨近期效果，回顾性分析了2005-10/2008-06上海长征医院器官移植科10例夫妻间肾移植临床及随访资料，随访时间为6~38个月。所有供者均为妻子，年龄29~42岁，平均(34.4±4.0)岁，身体健康，均为开放手术取肾，7例取左肾，3 例取右肾。受者均为首次肾移植，年龄30~45岁，平均年龄(35.8±4.6)岁，原发病均为慢性肾小球肾炎。供受者ABO血型相同，HLA配型5个抗原错配2例，完全错配8例。术后采用环孢素A或他克莫司、霉酚酸酯及强的松三联抗排斥治疗。所有供者移植后1周内出院，出院时血肌酐平均(78.9±15.2) μmol/L，随访期间肾功能均正常。受者移植后2例发生急性排斥反应，经激素冲击抗排斥治疗后逆转，无移植肾功能延迟恢复及其他并发症。出院时血肌酐(98.1±30.1)μmol/L，随访期间肾功能稳定。总之，夫妻间肾移植具有较好的近期效果，在缺少尸体或亲属供肾的情况下，夫妻间肾移植可以作为尿毒症患者早期肾移植治疗的选择。     

蛋白A免疫吸附防治高致敏肾移植受者急性排斥12例

为探讨蛋白A免疫吸附治疗对高致敏肾移植受者急性排斥反应的防治作用，选择2006-01/2008-01郑州人民医院器官移植科收治的肾移植高致敏受者12例。对12例群体反应性抗体> 50%的肾移植受者术前行蛋白A免疫吸附治疗4~6次，平均每周1次，术前1 d行蛋白A免疫吸附1次，术后发生急性排斥反应则立即给予蛋白A免疫吸附治疗，观察其急性排斥反应的发生情况及不良反应。12例高致敏患者移植后均未发生超急性排斥反应，有2例患者均在移植后数日内突发少尿，血肌酐迅速上升。经病理提示间质炎性细胞浸润，伴有水肿，肾小管周围淋巴细胞积聚，毛细血管有单核细胞浸润及动脉内膜炎和小血管坏死，诊为急性排斥反应，再次查群体反应性抗体，此2例患者群体反应性抗体均再度明显升高，Ⅰ类平均3.8%，Ⅱ类平均19.2%，立即行蛋白A免疫吸附结合大量甲泼尼松龙冲击治疗，成功逆转排斥反应，肾功恢复正常，复查群体反应性抗体Ⅰ类平均降至8.3%，Ⅱ类降至5.2%。所有患者均随访1年以上，移植肾功能良好。提示蛋白A免疫吸附能迅速清除患者体内的抗体，降低群体反应性抗体水平，预防急性排斥反应发生。     

高龄亲属活体供肾移植7例中长期效果：同一机构2年资料回顾分析

背景：随着肾移植中肾供体的短缺,“边缘”供肾提供了一条缓解途径。 目的：观察高龄亲属活体供肾移植的安全性和中长期临床效果。 方法：回顾性分析随访36~64个月的7例≥65岁亲属活体供肾移植的供者和受者的临床资料。 结果与结论：供、受者移植后均恢复顺利,无严重并发症。受者1周内移植肾功能正常、供者肾功能较术前略有增高、但均在正常范围内。无排斥反应发生。5例人/肾正常存活36~64个月;2例移植后≥1年死亡。供者均正常存活,无蛋白尿、高血压,肾功能正常。提示≥65岁高龄亲属活体供肾应经过严格筛选,部分可为临床扩大供肾来源。     

老龄供者亲属肾移植120例

背景：为了保证老龄供肾的移植效果，应当慎重选择供者。国内活体肾移植开展较晚，对老龄亲属供肾移植经验仍较欠缺。 目的：对老龄供肾亲属肾移植的效果和安全性进行分析。 方法：纳入120例行活体肾移植的供、受者资料进行回顾性分析，其中夫妻间供肾12例，父母供给子女75例，其他亲属供肾33例，供者 55岁以上52例。比较老年供者和非老年供者移植前血清肌酐值，移植后肾功能恢复状况及并发症发病率等，同时对2组受者的移植前后血清肌酐及并发症进行比较。 结果与结论：两组供者移植后肾功能恢复良好，无显著性差异；两组受者在移植后1周，1个月，1年内比较血清肌酐差异无显著性意义，急性排斥发病率差异亦无显著性意义。提示，老龄供者制定合理入选标准，对供者是安全的，受者和移植肾近期效果良好。     

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.