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,对阳件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.     

C4d联合外周血抗体对移植肾患者预后的预测价值

目的:探讨移植肾病理及预后与C4d及外周血抗体的相关性。方法:选择52例有完整病理资料的移植患者。用冰冻切片通过间接免疫荧光法进行C4d染色,采用Luminex技术检测外周血人类白细胞抗原(HLA)抗体、组织相容性复合体Ⅰ类相关链A(MⅠCA)抗体。随访1年,分析C4d与外周血抗体及移植肾病理的关系以及对移植肾功能的影响。结果:C4d阳性者HLA抗体阳性率88.9%,C4d阴性者HLA抗体阳性率40%;C4d阳性者HLA抗体阳性率高于C4d阴性者(P=0.003)。C4d阳性者肾小球炎比例较高(P=0.023);HLA抗体阳性者移植肾血管炎及动脉内膜增厚发生率较阴性者明显增高(P0.05);MⅠCA抗体阳性、阴性移植肾病理形态差异无统计学意义。单独C4d阳性者与阴性者肾小球滤过率(GFR)差异无统计学意义;C4d伴随外周血HLA或MⅠCA抗体阳性者较单独C4d阳性者GFR下降更明显(P0.05)。结论:对于急性排异的患者,C4d阳性伴外周血HLA或MⅠCA抗体阳性较单独C4d对移植肾预后更有预测价值。     

肾移植术后HLA抗体对移植肾预后的影响

目的：探讨肾移植后产生HLA抗体的影响因素,以及这些抗体对移植肾肾功能的影响。方法：采用Luminex技术检测92例肾移植后患者外周血HLA抗体,并随访1年时间,研究抗体和移植肾预后的关系。结果：HLA抗体的阳性率为58.7%,HLA-Ⅰ类抗体在女性更易产生,而HLA-Ⅱ类抗体的产生和性别无关,但和移植后时间有关,移植后时间越长,HLA抗体阳性率越高;并且发现,移植前诱导治疗采用多克隆抗体者HLA抗体产生的机会较小。在移植肾预后方面,HLA-Ⅱ类抗体和移植肾晚期失功相关,而单独HLA-Ⅰ类抗体的出现和移植肾晚期失功关系不大,HLA-Ⅰ类和HLA-Ⅱ类抗体同时存在对移植肾有协同破坏作用,移植肾生存率最低。多因素分析表明,HLA-Ⅰ类和Ⅱ类抗体同时出现移植肾失功的风险为阴性者的7.9倍（OR=7.9,95%CI：3.2～30.1）,而HLA-Ⅱ类抗体阳性者移植肾失功的风险为阴性者的5.1倍（OR=5.1,95%CI：1.1～24.2）。结论：肾移植术后HLA抗体和移植肾预后密切相关,而HLA-Ⅱ类抗体和移植肾晚期失功相关。     

移植肾长期存活受者体内人白细胞抗原抗体对移植肾功能的影响

目的:分析移植肾长期存活的受者体内人白细胞抗原(human leukocyte antigen,HLA)抗体的变化及其对移植肾功能的影响。方法:采用酶联免疫吸附法对92例接受环孢霉素等为基础免疫治疗方案的肾移植受者进行HLA抗体检测,观察HLA抗体对移植肾长期存活的影响。结果:92例患者中,移植前检出HLA-Ⅰ类抗体27例,HLA-Ⅱ类抗体16例;移植10年后检出HLA-Ⅰ类抗体12例,HLA-Ⅱ类抗体18例。移植肾长期存活患者的HLA-Ⅰ类和HLA-Ⅱ类抗体均为移植后新出现的HLA抗体。根据移植10年后HLA抗体检测的结果,将移植肾长期存活的肾移植受者分为HLA抗体阳性组(n=23)和阴性组(n=69),两组患者的估计肾小球滤过率(eGFR)分别为(66.52±14.52)mL/(min.1.73 m2)和(69.09±25.54)mL/(min.1.73 m2),组间差异无统计学意义(P>0.05)。92例患者中,有3例(3.26%)检出供者特异性抗体,检出率显著低于普通肾移植人群。结论:肾移植术后移植肾长期存活的患者体内的HLA抗体均为移植后产生,移植前的致敏抗体均已消失。移植肾长期存活的肾移植患者体内HLA抗体存在与否对移植肾功能的影响低微。     

潍坊地区无偿献血者HLA抗体和HNA抗体检测情况分析

目的:通过随机抽样检测潍坊地区无偿献血者血清HLA抗体及HNA抗体阳性率,评估在潍坊献血人群中开展HLA及HNA抗体筛查的必要性.方法:随机选取有输血、妊娠、移植等免疫史的无偿献血者208例作为实验组,选取无上述免疫史的无偿献血者168例作为对照组,运用流式荧光微珠法对两组标本进行HLA抗体和HNA抗体检测,运用统计分...     

人类白细胞抗原抗体在非血缘脐血移植中的作用

随着非血缘脐血移植(UC BT)在临床越来越多的应用,以及相关检测技术的发展,患者体内的脐血人类白细胞抗原(HLA)抗体对UCBT疗效的影响受到广泛关注.笔者拟就近年关于HLA抗体,尤其是供者特异性HLA抗体(DSA)对UCBT影响的研究进行综述.     

异基因造血干细胞移植后急性移植物抗宿主病的发生及其危险因素的探讨

目的　探讨异基因造血干细胞移植 (allo HSCT)后急性移植物抗宿主病 (aGVHD)的发生率与预后的关系及其危险因素。方法　总结了 118例患者 12 0次的allo HSCT的临床资料。结果　 6 3例患者发生了aGVHD ,累积发生率为 5 2 .5 7%。其中轻度aGVHD (Ⅰ～Ⅱ度 ) 4 6例 ,累积发生率38 91% ,重度aGVHD(Ⅲ～Ⅳ度 ) 17例 ,累积发生率 14 .17%。 12 0例次患者移植后 2年时总的累积疾病复发率为 14 .14 % ,其中无aGVHD组和轻度aGVHD组的累积复发率分别为 12 .4 8% (6例 )和 2 0 .5 3%(9例 ) ,重度aGVHD(Ⅲ～Ⅳ度 )组无一例复发 ,但无统计学意义 (P >0 .0 5 )。无aGVHD组和轻度、重度GVHD组患者 2年时的生存率分别为 6 1.4 0 % ,6 4 .0 8%和 17.6 5 % ,重度aGVHD组预后较差 (P <0 .0 1)。非血缘关系移植 ,HLA配型不合为发生aGVHD的危险因素。而与患者的年龄、性别、移植方式、疾病种类、分期、供受者性别和血型、输入细胞数等因素无关。结论　aGVHD是HSCT的重要并发症 ,发生时间越早 ,症状越重 ,预后越差。非血缘关系移植 ,HLA配型不合为发生aGVHD的危险因素。     

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.     

再次肾移植患者HLA与PRA的关系研究

目的 研究再次肾移植患者人类白细胞抗原(HLA)与群体反应性抗体(PRA)的关系.方法 选择行再次肾移植手术的患者30例检测PRA.PRA检测采用ELISA法筛选HLA-Ⅰ类、Ⅱ类混合抗原板和鉴定板.结果 根据肾移植手术时间分为3组:移植肾存活8年以上组患者3例,HLA错配2个抗原者1例,错配4个抗原者2例,无PRA生成;移植肾存活5年以上组患者10例,HLA错配4个抗原者6例和错配2个抗原者3例,肾功能正常,PRA阴性,错配3个抗原者1例,PRA阳性;移植肾存活3年以上组患者17例,HLA错配1个抗原和2个抗原者各1例,PRA阳性,HLA错配3个抗原者3例,其中1例PRA阳性,HLA错配4个抗原者7例,1例术前和术后均有抗Ⅱ类抗体,4例PRA阴性,2例PRA阳性,HLA错配5个抗原者5例,4例PRA阴性,1例PRA阳性.结论 HLA配型是维系移植肾长期存活的重要因素,而HLA抗体对移植肾长期存活和移植肾功能的影响具有重要作用.     

实体器官移植失败患者HLA和HPA抗体筛查及特异性分析

目的了解广州地区实体器官移植失败患者中HLA抗体和HPA抗体的分布和特异性,初步探索HLA抗体及HPA抗体与实体器官免疫性排斥反应的相关性。方法随机收集广州地区实体器官移植失败患者标本136例,利用Lifecodes Life Screen Deluxe(LMX)筛查标本的HLA抗体,阳性者再分别利用LIFECODES LSATMClassⅠ和LIFECODES LSATMClassⅡ(Single Antigen)鉴定抗体特异性;利用Lifecodes PAKR 2LE对HPA抗体进行筛查,阳性标本利用MAIPA进行最终确证。结果广州地区136例实体器官移植失败患者中,抗-HLA阳性率55.15%(75/136),其中HLA-Ⅰ类抗体出现频率为38.97%(53/136),HLA-Ⅱ类抗体出现频率为42.65%(58/136)。HLA-Ⅰ类抗体中出现频率较高的分别是抗-A~*02 35.85%(19/53)、抗-B~*15 47.17%(25/53)和抗-Cw~*07 28.30%(15/53),HLA-Ⅱ类抗体出现频率最高者是抗-DRB1~*04 39.66%(23/58)和抗-DQB1~*03 46.55%(27/58)。此外,检出HPA-5bb抗体一例。结论初步探讨了广州地区实体器官移植失败患者HLA抗体及HPA抗体的分布情况,证实HLA抗体与移植后的免疫排斥反应密切相关。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.