急性移植物抗宿主病发生过程中供者T细胞迁移和归巢的机制

供者T细胞向次级淋巴器官的迁移以及活化的供者T细胞向急性移植物抗宿主病（aGVHD）靶器官的迁移归巢是aGVHD发生的关键环节之一,深入认识供者T细胞的归巢机制对aGVHD的防治具有重要意义。本文就供者T细胞向次级淋巴器官的迁移,活化的供者T细胞向aGVHD靶器官的归巢,供者调节性T细胞向aGVHD靶器官的归巢和aGVHD过程中T细胞迁移归巢机制及其研究前景等进行了综述。     

心脏死亡器官捐献供者家属应对压力的探讨

目的：探讨压力理论对心脏死亡器官捐献供者家属面临的伦理问题的指导性意义,缓解供者家属焦虑状态,争取可供移植器官的来源。方法收集我院54例潜在捐献者资料,分析捐献者家属心理压力的来源,探讨压力理论对缓解压力,加强供者家属对伦理问题应对的作用。结果54例潜在捐献者中同意捐献者35例,成功捐献22例。结论压力理论可应用于今后心脏死亡器官捐献供者家属管理中,为争取更多可移植器官提供保障。     

Aggressive organ donor management protocol

As of August 2007, 96 900 people are awaiting organ transplantation in the United States, while only 28 930 transplants were performed in 2006. With such a large gap between organ need and organ availability, it is inevitable that many will die while awaiting transplantation. This organ shortage has become a national public health crisis, and as a response, the United States Department of Health and Human Services launched the Organ Donation Breakthrough Collaborative, an ambitious campaign to dramatically increase the number of transplantable organs. One of the suggested strategies involves maximizing the number of organs obtained from the available cadaveric "brain dead' donor pool by using donor management protocols that optimize and treat the profound physiological disturbances that are associated with brain death. The use of these standardized and aggressive donor management protocols has been shown to increase the number of transplanted organs and prevent the number of donors lost due to medical failures. A protocol-driven approach by a dedicated organ donor management team should be considered a key component of any program designed to bridge the gap between organ supply and demand.     

p53基因转移至移植心脏的安全性

背景:课题组前期实验表明野生型p53基因具有抑制移植心脏冠状动脉内膜增厚的作用。目的:研究腺病毒介导的野生型p53基因转移至移植心脏的安全性。方法:以Wistar大鼠为供体,SD大鼠为受体建立大鼠腹腔异位心脏移植模型,在取出供心后,经供心冠状动脉分别注射携带野生型p53基因的重组腺病毒液、携带β-半乳糖酐酶基因的重组腺病毒液和生理盐水800μL,4℃静置30min后进行心脏移植。结果与结论:移植后5d,重组腺病毒液组的供心冠状动脉组织可见野生型P53蛋白的表达。移植后28d,未见受体大鼠血液生化学指标异常和重要脏器的病理性改变,RT-PCR扩增未见腺病毒E1A区产物。说明在心脏移植中,将腺病毒介导的野生型p53基因转移至移植心脏是安全的。     

Inhalational anesthesia for organ procurement: potential indications for administering inhalational anesthesia in the brain-dead organ donor

Organs needed for transplantation far outweigh their availability. There is minimal research regarding perioperative care of the brain-dead organ donor during the procurement procedure. Current research attributes a great deal of organ damage to autonomic or sympathetic storm that occurs during brain death. Literature searches were performed with the terms brain death, organ donor, organ procurement, anesthesia and organ donor, anesthesia and brain death, anesthesia and organ procurement, inhalational anesthetics and organ procurement, and inhalational anesthetics and brain dead. Additional resources were obtained from reference lists of published articles. The literature review showed there is a lack of published studies researching the use of inhalational anesthetics in organ procurement. No studies have been published evaluating the effect of preconditioning with inhalational agents (administering 1.3 minimal alveolar concentration of an inhalational agent for the 20 minutes before periods of ischemia) in the brain-dead organ donor population. Further studies are required to determine if administration of inhalational anesthetics reduces catecholamine release occurring with surgical stimulation during the organ procurement procedure and whether this technique increases viability of transplanted organs. Anesthetic preconditioning before the ischemic period may reduce ischemia-reperfusion injury in transplanted organs, further increasing viability of transplanted organs.     

The brain-dead patient or a flower in the vase? The emergency department approach to the preservation of the organ donor.

Transplantation has been incorporated into the treatment of patients with end-stage diseases of most major organ systems in recent years. However, organ supply is the greatest limitation to organ transplantation. Among the factors that can enhance organ supply, donor management has received the least attention. The importance of establishing an acceptable method of rapidly and accurately determining brain death in potential donors cannot be overemphasized. With an increased awareness of donor management issues and the application of a rational physiological approach, the supply of functional organs for transplantation can be increased. Rapid and continuing resuscitation of clinically brain-dead trauma victims is mandatory. This review addresses the evaluation and management of the organ donor within the emergency department. Common management problems (hypotension, arrhythmias, diabetes insipidus, oliguria, and coagulopathy) are discussed in detail. An aggressive, proactive approach to the medical management of the potential donor is recommended in order to limit the number of medical failures and maximize the number of organs donated.     

异基因脐血干细胞移植后STR基因座位的表达分析

本研究分析杜氏型肌营养不良（DMD）病人异基因脐带血干细胞移植后STR基因座位的表达。利用PCR—SSO方法检测患者、供者HLA-A、B、DR位点，并利用STR—PCR方法检测术后各个器官的STR-基因位点的表达情况。结果表明：患者与供者在HLA中、低分辨情况下A、B、DR位点全相合，患者的胸骨骨髓显示为供者独立植入，脾、左上肺、前臂、肌舌、左肝、胃、右颞叶、膈肌、右支气管、左心室、右肾均为嵌合状态。结论：造血干细胞移植术后，供者的基因可在实体器官表达，形成嵌合状态.     

A novel extracorporeal kidney perfusion system: a concept model

The number of patients awaiting kidney transplantation has more than doubled in the past decade while the number of available donor organs has seen only a modest increase, leading to a critical shortage of organs. In response to this extreme shortage, the criteria for accepting organs have been modified to include marginal donors such as non-heart beating donors (NHBD). In these kidneys, determining viability is important for success of transplantation. Therefore, a study was undertaken to develop a system that would allow the extracorporeal assessment of function and compatibility of the donor organ before the patient is exposed to the risks associated with surgery. Following bilateral nephrectomy, the kidneys of 10 pigs (approximately 30 kg) were connected to a commercially available hypothermic pulsatile kidney perfusion apparatus. This system was modified to allow for normothermic pulsatile renal perfusion using the potential recipient's blood, via vascular access. These kidneys were perfused with the animal's blood for a minimum of two hours while various parameters were monitored. Perfusion pressures were kept between 60 and 90 mmHg, which correlated to flows between 70 and 150 mL/min. A decrease in perfusion pressure with a concomitant rise in flow over the two-hour period served as a good predictor of a viable and compatible graft. The modified kidney preservation system allows the normothermic, pulsatile extracorporeal perfusion of donor kidneys with the ability to monitor resistance to flow and urine production. This model also allows observation of the kidney for signs of hyperacute rejection. Further research needs to be conducted in order to determine if the system represents a methodology to increase the pool of available donor organs.     

Effect of a specialized pediatric institutional setting on organ recovery from potential donors.

BACKGROUND: The relationship between accessibility to the full range of subspecialty care available at freestanding pediatric hospitals and organ donor management and recovery rates has not been studied. OBJECTIVE: To examine current rates of recovery of organs from children for transplantation at free-standing pediatric hospitals versus all other hospitals. METHODS: Data from the hospitals served by Mid-America Transplant Services from January 2000 to July 2003 were reviewed. Organ recovery rates from freestanding children's hospitals were compared with the rates from other types of institutions. Patients were included if their organs were considered medically suitable at the time of referral for donation. RESULTS: Overall, 66% (210/318) of the potential organs were recovered. The type of institution in which the potential donor was managed did not influence the proportion of organs recovered: 67% (96/144) at freestanding children's hospitals versus 66% (114/174) at all other hospitals. A greater proportion of livers were recovered at other donor institutions than at children's hospitals (100% vs 85%, P< or =.01). CONCLUSION: The organ recovery rate from potential pediatric donors is low. In general, this rate does not appear to be affected by the type of managing pediatric institution except for liver recovery, which favors institutions that are not freestanding children's hospitals. The low rate of recovery suggests that although suitable donors are identified, appropriate referrals are made, and families provide consent for donation, major obstacles remain to the successful recovery of organs.     

供体淋巴细胞在GVHD模型小鼠组织器官中迁移和分布的动态观察

本研究应用小鼠GVHD模型探讨异基因T淋巴细胞在移植受体体内的迁移和分布。将C57BL／6的骨髓细胞和转基因荧光C57BL／6小鼠的脾淋巴细胞输入经8Cy全身照射的BALB／c小鼠，建立eGFP标记供体淋巴细胞的GVHD小鼠模型；应用荧光显微镜和流式细胞术观测GVHD模型中eGFP^＋细胞的分布；ELISA法检测GVHD靶组织中趋化因子MIP—1α水平的改变。结果表明：①输入脾细胞和骨髓细胞第8天后出现GVHD临床及病理表现；②CVHD模型中，受体鼠肝、皮肤、肠、脾、肺、舌有eGFP^＋细胞浸润；③GVHD小鼠肝、脾eGFP^＋细胞中CD4^＋、CD8^＋细胞比例均逐渐升高；④GVHD鼠脾、肝组织中MIP—1α水平升高，脾中MIP-1α水平高峰出现于移植后第3天，肝中MIP—1α水平高峰出现于移植后第7天。结论：除肝、肠、皮肤外，肺、舌可能也是GVHD靶器官。肝、脾组织中供体淋巴细胞浸润伴随MIP—1α水平的升高。     

Consequences of cold ischemic injury of kidneys in clinical transplantation.

Cold storage allows the effective utilization of organs retrieved for transplantation. However, prolonged cold ischemia contributes to organ damage and increases patients' morbidity and mortality and health care cost. Using recent data from the United Network for Organ Sharing, this paper examines the outcomes of live donor and deceased donor kidney transplants in relation to cold ischemia time.     

Engineering tissues, organs and cells

Patients suffering from diseased and injured organs may be treated with transplanted organs; however, there is a severe shortage of donor organs that is worsening yearly, given the ageing population. In the field of regenerative medicine and tissue engineering, scientists apply the principles of cell transplantation, materials science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy, including the use of amniotic and placental fetal stem cells. This review covers recent advances that have occurred in regenerative medicine and describes applications of these technologies using chemical compounds that may offer novel therapies for patients with end-stage organ failure.     

Legal and ethical issues related to nonheart beating organ donation

Major breakthroughs in immunosuppressant medication and advances in surgical techniques have increased the number of successful transplantations, but the demand for organs far outweighs the supply. People continue to die while waiting for donor organs to become available. Nonheart beating organ donation is a means of increasing the supply of organs to be transplanted. It is based on cardiac cessation criteria. This article explores the ethical and legal considerations, as well as implications for perioperative nurses. AORN J 77 (May 2003) 973-976.     

Non-heart-beating organ donation: process and review

To combat the national shortage of donor organs and meet the needs of more than 60,000 patients awaiting transplant, many organ procurement organizations have reevaluated non-heart-beating organ donation (NHBD) as one solution. Non-heart-beating donation is the process by which organs are recovered from patients after the pronouncement of death by cardiopulmonary criteria. Recent media reports have misled health care providers to believe that this is a new donation procedure; however, NHBD provided the foundation for modern clinical transplantation. This article describes non-heart-beating donor evaluation criteria, the donation process, associated ethical considerations and the role of the advance practice nurse in assisting families with this end-of-life decision. A case study will be presented followed by a summary of transplant recipient patient and graft survival outcomes.     

Organ procurement in children —surgical,anaesthetic and logistic aspects

To cover the need in paediatric organ transplantation, every potential donor should be considered as a multi-organ donor. Successful transplantation may be performed with kidneys retrieved from very young infants, even anencephalic neonates if the en-bloc technique using both kidneys is used. Regarding the liver, paediatric donors can be accepted from one month of age while livers harvested from older children and even young adults can be transplanted into small children after ex-vivo reduction of the size of the graft. Multi-organ procurement from the same donor provides valuable organs if the anaesthetic management of the donor is appropriate. Active transplant programs needs international cooperation which is made possible by the organ exchange organizations.     

Acquired transplant tolerance

Increasing the acceptance rate of organs is the central goal of transplantation research. Long-term survival of vascularized organs without chronic immunosuppressive therapy has been achieved in experimental animals. In humans, the possibility of achieving immunological tolerance and a drug-free state has been reported occasionally in patients who after withdrawal of immunosuppressants because of major toxicity still cary a functioning graft. It has been proposed that organ transplant implies a migratory flux of donor ‘passenger’ leukocytes out of the graft into the recipient tissue or organs, to establish a persistent condition of ‘microchimerism’. Although there is evidence that the same migratory mechanisms apply to all organ grafts, migration of ‘passenger’ leukocytes is less in kidney and heart than in liver. To enhance the acceptance of organs less tolerogenic than liver, perioperative infusion of donor bone marrow has been attempted to increase the donor ‘passenger’ leukocyte load. It has been suggested that the established microchimerism is not only associated with long-term acceptance of the graft, but it also plays an active role in induction and maintenance of donor-specific unresponsiveness. However, the intimate mechanism(s) responsible for prolonged graft survival in this setting remain speculative. Experimental evidence is also available that the thymus plays a major role in the development of self-tolerance and is critical in the induction of acquired tolerance to exogenous antigens. It has been reported that after intrathymic injection of donor cells clonal deletion of maturing thymocytes occurs and is the major mechanism in the induction of donor-specific tolerance, since peripheral T-cell component would be devoid of alloreactive population. Studies are warranted in the near future to explore whether the thymus technique can be employed to prolong survival or induce tolerance to allograft in humans. An interesting novel strategy for transplant tolerance is also the oral administration of alloantigens, which has been recently applied to the cardiac transplant model in rat. All these approaches will have a major impact in the near future on transplant medicine, opening new perspectives to obtain indefinite graft survival.     

Drug abusers and poisoned patients: a potential source of organs for transplantation?

One of the major constraints to transplantation of solid organs is lack of availability of grafts and any attempt to use all available donors is to be welcomed. We address the possibility of expanding the transplant donor pool by inclusion of more patients who have suffered intoxication with drugs premortem. Particularly important in this context is the exclusion of organ-specific damage, and also infective risk to the potential recipient due to viral causes in the donor.      

A donation to life: organ procurement.

1. Only 15% of brain dead patients become organ donors. This is due to a lack of public education regarding the benefits of organ donation, lack of recognition of potential donors, poor donor management, and unfortunately, even the reluctance of health-care workers to approach families with the choice to donate. 2. Once the patient has been officially accepted as an organ donor and the consents have been signed, the donor goes through a thorough evaluation involving physician consultations and lab work, and the medical history is reviewed for possible complications. 3. As many as four surgical teams may be involved in organ procurement, and good communication between nurses, physicians, and coordinators is vital to promote successful recovery of donor organs.     

Critical care issues in lung and heart transplantation

Although much has been accomplished in HTx and LTx in the past few decades, much remains to be conquered. It is an ever-changing, always fascinating field. Though science and technology know no limits, the primary limitation of HTx and LTx continues to be the availability of donor organs. One can only hope that further advances in educating the public will help close the large gap between the list of those waiting and the organs available for transplantation.