胰肾联合移植后的免疫抑制治疗

背景:胰肾联合移植已经被公认为是糖尿病(包括1 型和2 型)合并终末期尿毒症的有效治疗手段,由于胰腺为高免疫原性器官,合理的免疫抑制治疗是保证胰腺移植成功的关键.目的:探讨胰肾一期联合移植后免疫抑制药物的合理应用.方法:纳入2005-01/2009-06 在中山大学附属第一医院器官移植中心完成胰肾一期联合移植的患者9 例,其中男5 例,女4 例,胰液引流均采用空肠引流方式.术后采用白细胞介素2 单克隆抗体诱导的四联免疫抑制方案:白细胞介素2 单克隆抗体+他克莫司+麦考酚酸+激素,并逐渐过渡至单用他克莫司维持治疗.回顾性分析以上9 例患者围手术期及长期随访情况.结果与结论:胰肾一期联合移植后,除1 例早期死亡外,其余8 例患者移植后1 周内肌酐降至正常水平,移植后停用胰岛素时间为(11.5±3.5) d,空腹血糖恢复至正常时间为(15.4±6.3) d.8 例患者随访4～50 个月期间,共有4 例发生移植肾急性排斥,其中1 例在接受床边血液透析过程中并发心脑血管意外后家属放弃治疗,其余3 例患者经抗胸腺细胞球蛋白或激素冲击治疗后移植肾功能均逆转恢复,随访过程中未发现移植胰腺排斥.说明胰肾联合移植是治疗糖尿病合并终末期糖尿病肾病的有效方法,术后早期采用白细胞介素2 单克隆抗体诱导的四联免疫抑制方案并逐渐过渡至单用他克莫司维持治疗是安全的.     

胰肾联合移植后的免疫抑制治疗

背景：胰肾联合移植已经被公认为是糖尿病（包括1型和2型）合并终末期尿毒症的有效治疗手段,由于胰腺为高免疫原性器官,合理的免疫抑制治疗是保证胰腺移植成功的关键。目的：探讨胰肾一期联合移植后免疫抑制药物的合理应用。方法：纳入2005-01/2009-06在中山大学附属第一医院器官移植中心完成胰肾一期联合移植的患者9例,其中男5例,女4例,胰液引流均采用空肠引流方式。术后采用白细胞介素2单克隆抗体诱导的四联免疫抑制方案：白细胞介素2单克隆抗体＋他克莫司＋麦考酚酸＋激素,并逐渐过渡至单用他克莫司维持治疗。回顾性分析以上9例患者围手术期及长期随访情况。结果与结论：胰肾一期联合移植后,除1例早期死亡外,其余8例患者移植后1周内肌酐降至正常水平,移植后停用胰岛素时间为（11.5±3.5）d,空腹血糖恢复至正常时间为（15.4±6.3）d。8例患者随访4～50个月期间,共有4例发生移植肾急性排斥,其中1例在接受床边血液透析过程中并发心脑血管意外后家属放弃治疗,其余3例患者经抗胸腺细胞球蛋白或激素冲击治疗后移植肾功能均逆转恢复,随访过程中未发现移植胰腺排斥。说明胰肾联合移植是治疗糖尿病合并终末期糖尿病肾病的有效方法,术后早期采用白细胞介素2单克隆抗体诱导的四联免疫抑制方案并逐渐过渡至单用他克莫司维持治疗是安全的。     

Role of color Doppler sonography in post-transplant surveillance of vascular complications involving pancreatic allografts

PurposeTo evaluate the role of color Doppler ultrasonography in the postoperative surveillance of the vascular complications involving pancreas allografts.MethodsA retrospective analysis of a consecutive series of 223 pancreas transplantations was performed. All recipients received antithrombotic prophylaxis, which was tailored to the individual's estimated risk of thrombosis. All patients were monitored with daily color Doppler ultrasonography during the first post-transplant week and thereafter whenever clinically indicated. Vascular complications were defined as all thrombotic events requiring: increased anticoagulant therapy, angiography with fibrinolytic therapy, or repeat surgery.ResultsThe overall patient survival rates at one, three, and five years after transplantation were 94.7%, 93.3%, and 91%, respectively. The overall graft survival rates at the same time points were 87.4%, 79.6%, and 75.6%, respectively. In 28 of the 223 cases (12.5%) graft thromboses were diagnosed with Doppler ultrasound within the first 10 days after transplantation. In 3 cases, graft pancreatectomies were performed because of a complete loss of blood flow in the parenchyma. An attempt to rescue the graft was made in 18 patients. Fourteen of these grafts were saved and are still functioning (77.7%); and 4 rescue attempts failed and the grafts were subsequently explanted (32.3%).ConclusionColor Doppler ultrasound is a suitable tool for postoperative surveillance of pancreas transplant recipients. Its use can lead to early diagnosis and timely treatment of vascular complications.     

肾移植后雷帕霉素免疫抑制剂转换方案应用12例

目的:总结分析肾移植后转换为雷帕霉素免疫抑制方案的初步经验.方法:回顾性分析2008-01/2009-03 12例因急性排斥反应、移植肾肾病、肝功能损害及齿龈增生等因素,由神经钙蛋白抑制剂为主的免疫抑制方案转换为以雷帕为主的免疫抑制方案的临床资料,转换方案的选择:①方案1,快速转换方式:第1天神经钙蛋白抑制剂减50%,1周完全停用神经钙蛋白抑制剂;雷帕霉素4 mg起,2 mg维持.②方案2:第1天停用霉酚酸酯,神经钙蛋白抑制剂不调整或减半,雷帕霉素4 mg起,2 mg维持,5 d后复查血药浓度,调整排斥用药.结果:快速代谢性患者5例,4例选用第2种方案,血肌酐平均下降30 μmol/L,且他克莫司/环孢素A+雷帕霉素可调整到目标浓度,无排斥反应再次发生,1例出现肺部感染后治愈;1例选用第1种方案,转换后短期血肌酐下降明显,后出现严重腹泻,且就医意识差,未及时诊治致移植肾失功.1例因肝功能持续异常选用第1种转换方案,转换后肝功能在2个月后完全正常.3例因血肌酐爬行性升高选用第1种转换方案,转换2个月后血肌酐平均下降23 μmol/L,且稳定在该水平,但1例蛋白尿显著增加.2例因齿龈增生明显选用第1种方案转换后,复查3个月症状明显好转,血肌酐稳定.1例因既往有脾功能亢进,术后口服环孢素或他克莫司达目标浓度后,均出现严重的骨髓抑制选用第1种方案转换后,复查3个月症状明显好转,血肌酐稳定.3例有不同程度血脂升高,9例未见明显血脂升高现象.结论:对于快速代谢型肾移植患者,转换为雷帕霉素为较好的选择,主要通过早、中、晚3次口服抗排斥药物保持有效的抗排斥药物浓度,同时增加神经钙蛋白抑制剂类抗排斥药物的浓度,有利于排斥的纠正和预防.急性排斥不是转换雷帕霉素的绝对禁忌证,但转换雷帕霉素后,神经钙蛋白抑制剂浓度应保持在相对较高的浓度,保持有效的抗排斥作用.     

胰液膀胱引流式胰肾联合移植长期存活15例随访

背景：胰肾联合移植是治疗1型糖尿病合并终末期肾病的首选疗法,但由于移植风险高,并发症多,国内开展并不广泛。目的：总结胰液膀胱引流式胰肾联合移植长期存活的临床经验,观察其远期效果并分析影响因素。方法：对15例患者行胰液膀胱引流式胰肾联合移植,均采用心脏死亡的供体。HLA配型平均为2.13。均选择胰液膀胱引流式和体循环回流血管吻合方式,免疫抑制剂方案均用他克莫司,霉酚酸酯和泼尼松治疗。观察移植后患者移植物肾功能、血糖、淀粉酶等及并发症。结果与结论：最短随访8.5个月,最长随访105.5个月,平均住院时间为37.7（13～82）d。移植后13例患者胰腺功能恢复,2例于移植后即切除移植胰腺。移植后除1例患者肾脏功能延迟恢复外,其余患者肾脏功能立即恢复。2例患者因慢性排斥反应丢失移植胰腺和移植肾。移植后主要并发症为排斥反应,返流性胰腺炎和血栓形成。提示胰肾联合移植是治疗终末期糖尿病并发肾功能衰竭的一种安全而有效地治疗方法,其远期效果理想,完善的围移植期管理、预防和及时处理并发症、合理应用免疫抑制剂是影响患者和移植物长期存活的重要因素。     

Morbidity during regular dialysis treatment and after renal transplantation (author's transl)]

Renal transplantation was associated with a lesser degree of morbidity than chronic dialysis treatment in a group of 48 patients with end-stage renal failure. Morbidity was defined as total days of in-patient hospitalization divided by total days of risk. The morbidity during chronic intermittent dialysis, with a mean observation time of 296.1 (20 to 2255) days, was 11.8%, whereas after renal transplantation, with a mean observation time of 1004.0 (131 to 2400) days, only 7.6% of all days at risk were spent in hospital. Morbidity rises to 38.1% during chronic dialysis if all dialysis days on an out-patient basis are considered as hospitalization days. Morbidity was lowest (3.8%) in patients sent home for the first time with a functioning graft. Cardiac complications and fluid lung were the most common causes for morbidity during haemodialysis treatment; morbidity after renal transplantation was mainly due to renal rejection and infections under non-specific immunosuppression. Social and occupational rehabilitation was better after renal transplantation than during haemodialysis treatment. It can be concluded from these data that with regard to the quality of life renal transplantation is the preferable alternative in the management of end-stage renal failure.     

Doppler ultrasound in the diagnosis of renal allograft rejection and in monitoring the effect of treatment

Thirty-six consecutively transplanted renal allograft patients were prospectively monitored with ultrasound-Doppler examinations three times weekly during the first 3 weeks after transplantation. Although triple-immunosuppressive therapy consisting of cyclosporin A, azathioprine and prednisolone was used, acute rejection occurred in 11 patients. Nine patients had immediate onset of graft function and no rejection. Ten patients had acute tubular necrosis (ATN) without any signs of rejection and were treated with dialysis for 1-3 weeks after transplantation. Thrombosis of the renal artery was diagnosed in four patients. During rejection episodes pulsatility index (PI) was above normal range in all patients. In patients with mild to moderate ATN and PI was normal throughout the clinical course whereas two patients with severe ATN but no signs of rejection in the kidney biopsy also had high PI. It is concluded that serial Doppler velocity examination after kidney transplantation is a non-invasive, cheap and reliable method for monitoring of the graft. The method can be used in the early diagnosis of rejection, and it is of special value in monitoring grafts without function.     

Differential effect of donor-specific blood transfusions after kidney, heart, pancreas, and skin transplantation in major histocompatibility complex-incompatible rats

BACKGROUND: Donor-specific blood transfusion prior to transplantation has been demonstrated to prolong allograft survival. This study compared the effect of donor-specific blood transfusion after kidney, heart, pancreas, and skin allotransplantation in congenic rats of reciprocal strain combinations across a major histocompatibility complex barrier. STUDY DESIGN AND METHODS: Whole donor-specific and third-party blood was administered to the prospective graft recipients 14 and 7 days before the transplantation of kidney, heart, pancreas, and skin. Rejection was defined by cessation of organ-specific function (i.e., uremia, cessation of heartbeat, and recurrence of diabetes). The survival of skin grafts was monitored visually. All allografts were histologically assessed immediately after rejection or at the end of a 100-day observation period. RESULTS: Donor-specific blood transfusion leads to permanent acceptance of all renal allografts. LEW.1U heart allografts were accepted by LEW.1A recipients, but they were rejected in the reciprocal situation. Survival of pancreas and skin allografts was not significantly prolonged. Third-party blood had no effect on allograft survival. CONCLUSION: The beneficial effect of donor-specific blood transfusion depends on both the kind of transplanted organ and the genetic incompatibility involved. The precise mechanisms responsible for the remarkable organ-specific differences remain unknown.     

Screening of anti-B cell antibodies in the sera of renal transplant recipients by using Daudi cell line.

In order to examine the presence of antibodies against B cells, 83 sera obtained from 55 renal transplant recipients were screened by microcytotoxicity test using Daudi cell line. Out of 83 samples, 12 were pretransplant sera, 62 were post-transplant sera and 9 were from the patients whose grafts has been removed due to rejection. For the purpose of improving the reliability of the tests, 5 different rabbit complements were selected and cytotoxicity tests with them were carried out simultaneously. Pretransplant sera without blood transfusion did not show any cytotoxicity against Daudi cells. Although 42% of post-transplant sera showed cytotoxicity against Daudi cells, cytotoxic activity of the sera showed no relation with the occurrence of rejection episodes. Three serum samples out of 5 patients whose grafts had been removed due to rejection showed strong cytotoxicity against Daudi cells and the sera of 2 other patients did not. There was no relation between the cytotoxicity against Daudi cells and antibodies against Epstein-Barr virus capsid antigen in the post-transplant sera.     

Avoiding calcineurin inhibitors in the early post-operative course in high-risk liver transplant recipients: The role of extracorporeal photopheresis

The aim of this work is to report on the results of a single-center, prospective study on the feasibility of calcineurin-inhibitor (CNI)-staggered immunosuppression by use of extracorporeal photopheresis (ECP) in liver transplant (LT) recipients at risk of renal and neurological complications. Patients were matched on a 1:1 basis with historical controls on standard CNI immunosuppression. ECP patients were treated with ECP plus antimetabolites and/or steroids, while CNIs were withheld until clinically indicated. Thirty-six patients were evaluated: 18 ECP patients and 18 controls. ECP was tolerated in 100% of cases. CNI were introduced at a median of 8 days (4-55) in 17 ECP patients, while one patient was on a fully CNI-sparing regimen 22 months after LT. Acute rejection occurred in 27.7% patients in ECP (5/18) versus 16.7% in controls (3/18) (P = ns) with a shorter time to rejection in ECP (36 +/- 31.3 days vs. 83.6 +/- 65.6 days; P = ns). All rejection episodes were amenable to medical treatment. Neurological and renal complications occurred in 22.2% (4/18) of patients in either group, but led to in-hospital mortality in 3 patients among controls versus 1 in ECP (P = ns). One-, 6-, and 12-month survival rates were 94.4, 88.1, and 88.1% in ECP versus 94.4, 77.7, and 72.2% among controls (P < 0.0001). ECP seems to allow for management of high-risk LT recipients in the early post-transplant course and reduction of CNI-related mortality. Continued data validation is favored to assess the impact of ECP on long-term graft and patient survival.     

Long-term graft survival with or without donor-specific transfusion in cyclosporine era in one haplo-identical living-related renal transplant recipients beyond the first year: a 19-year experience

With improvement in immunosuppressive drugs, the beneficial role of donor-specific blood transfusion (DST) in the preconditioning of renal allograft recipients has been diminished. This retrospective study was conducted to investigate the influence of DST on long-term graft survival in successful one haplotype-mismatched kidney transplantation in the cyclosporine (CsA) era at Iwate Medical University. Between August 1983 and October 1996, 52 one haplotype-mismatched living related first renal transplants were performed. Fifty grafts survived beyond the first year after transplantation. These 50 patients were divided into two groups according to maintenance immunosuppression, 12 kidney graft recipients received azathioprine (AZA), prednisolone (PSL), CsA, and DST, and 38 recipients received AZA, PSL and CsA. Our DST protocol consisted of three transfusions of 30 ml of donor-specific buffy-coat at 4-week intervals, without immunosuppressive coverage. In recipients receiving DST and CsA, the 5-, 10-, and 13-year graft survival rates were 100%, 83%, and 67%, respectively. In recipients without DST, the 5-, 10-, and 13-year graft survival rates were 95%, 74%, and 69%, respectively. There was no significant difference between the two groups in long-term graft survival. In conclusion, DST and CsA combination treatment in our protocol may not induce long standing donor-specific immunologic hyporesponsiveness. Other strategies are expected to induce immunotolerance.     

Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes

OBJECTIVE: Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK. RESEARCH DESIGN AND METHODS: We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis. RESULTS: Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035). CONCLUSIONS: Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.     

Urinary protein/creatinine ratio as an indicator of allograft function following live related donor renal transplantation

In a study of 656 urine specimens from 53 consecutive recipients of live related donor renal allografts we found an excellent correlation between the protein content of 24-h urines and protein/creatinine ratio (Up/Ucr) in overnight urine samples. Using this ratio, we evaluated proteinuria up to 180 days after renal transplantation (overnight urine samples analysed, n = 2745). Heavy proteinuria in the immediate post-operative period had no prognostic significance. Eighty-nine percent of all clinically observed acute rejection episodes were accompanied by an increase over baseline of Up/Ucr; in 56.5% of these episodes elevation of Up/Ucr preceded that of serum creatinine. However, as a marker of rejection the usefulness of this parameter was limited owing to large number of false positive elevations. In 50 recipients whose grafts survived for more than 3 mth, proteinuria was graded into minimal, moderate and heavy. Renal function at the end of six months was good in all patients who exhibited proteinuria with Up/Ucr less than 100 mg/mmol creatinine. Persistent proteinuria with Up/Ucr above 100 mg/mmol preceded significant deterioration of graft function. Therefore, a protein-creatinine ratio of 100 mg/mmol can be considered as an apparent cut-off to differentiate stable from deteriorating graft function in long term evaluation of transplant recipients.     

肾移植后人类白细胞抗原抗体检测的临床意义

目的：了解肾移植受者的抗人类白细胞抗原（HLA）IgG抗体水平及其对肾移植效果的影响。方法：应用莱姆德抗原板和混合抗原板通过微量酶联免疫吸附法检测685例患者的抗HLA特异性IgG 抗体。结果：685例肾移植受者中HLA－IgG抗体阳性者占12％，致敏受者移植后排斥反应发生率为50％，明显高于HLA－IgG抗体阴性受者（P＜0．01），而移植物存活率则显著低于HLA－IgG抗体阴性受者（P＜0．01），移植后HLA－IgG抗体水平升高组，其排斥发生率和移植物丢失率分别为82％和77％，均显著高于HLA－IgG抗体无变化组（P＜0．01），而排斥逆转率则显著低于后者（P＜0．01）。结论：HLA－IgG抗体是预测受者HLA免疫致敏的一个敏感指标；动态监测HLA－IgG抗体水平的变化对临床筛选合适供者，减少排斥反应，提高移植物存活率重要意义。     

The current state of pancreas transplantation

The first pancreas transplant in 1966 demonstrated that a pancreas allograft could reestablish euglycemia independent of exogenous insulin in patients with type 1 diabetes mellitus. Early outcomes were poor, and application of the procedure was limited. In the 1980s, innovations in immunosuppression therapy and surgical management of pancreatic exocrine secretions combined with careful candidate selection resulted in dramatic improvements in patient and graft survival. In the 1990s, the incorporation of additional new anti-rejection agents into immunosuppression protocols resulted in a further decrease in the incidence of acute rejection, affording more freedom in surgical management of exocrine drainage. The vision for the future of transplantation for the treatment of diabetes is focused on the percutaneous infusion of pancreatic islets, thus eliminating the need for surgical revascularization of a pancreas allograft, yet reestablishing regulation of glucose metabolism.     

胰肾一期联合移植术后影像学检查

目的 探讨胰肾一期联合移植(SPK)术后影像学检查的临床价值。方法 于1998年12月至2000年1月期间的5例SPK术后的影像学检查中，5例均行胸片及彩色多普勒血流图(CDFI)检查，其中2例行数字减影血管造影检查。结果 在SPK术后影像学检查的阳性结果中，胸片诊断为肺部感染者2例，CDFI诊断急性排异反应2例，DSA诊断移植胰腺的供血动脉内血栓者1例。4例患者已健康存活了2年左右，其中1例因移植胰腺血管内血栓形成，于术后33天切除移植胰腺。1例因排斥反应于术后第47天死于急性心功能衰竭。结论 胸片与CDFI检查是SPK术后并发症的非侵袭性的首选诊断方法，DSA检查是SPK术后血管并发症合理而可靠的诊疗手段。     

Res配型在致敏受者肾移植中的应用

目的：探讨致敏受者经HLA-氨基酸残基配型（Res 配型）后行肾移植的效果。方法：对13例移植前群体反应性抗体(PRA)水平较高的患者按照美国 UCLA组织配型中心所确定的中国汉族人Res 配型标准进行供、受者筛选,以常规方法进行肾移植，术前未行血浆置换。结果：13例患者, 无1例发生超急排斥反应；9例术后5天内移植肾功能恢复正常；3例术后1月内各出现一次移植肾急性排斥反应（发生率23.1%），1例经M.P., 2例经OKT3治疗后逆转；1例发生急性肾小管坏死，经血液透析过渡后，于术后3周肾功能逐渐正常。按Res配型原则，供、受者0、1、2和3个位点错配分别为1例(7.7%)、3例(23.1%)、7例(53.8%)和2例(15.4%)，明显高于传统HLA六抗原配型结果。结论: Res配型可以显著提高供受者相配率，对缩短等肾时间，减少移植肾的排斥反应，提高移植肾的存活率具有重要意义。     

小鼠胚胎胰腺移植治疗糖尿病

背景：胚胎胰腺组织具有来源广泛,β细胞增殖分化能力强,低免疫排斥性等优点。目的：探索小鼠胚胎胰腺组织的分离技术,观察其对糖尿病模型小鼠的血糖调节作用。方法：体视显微镜下分离E11.5~E16.5C57BL/6小鼠胰腺组织。链唑霉素诱导雄性C57BL/6小鼠建立糖尿病模型,随机分为2组：移植组模型小鼠肾被膜下移植5个E16.5胰腺组织,假手术组模型小鼠肾被膜下注入0.05mLRPMI1640培养液。移植组小鼠血糖水平≤11.2mmol/L后,利用IPGTT和IPITT方法检测移植后胚胎胰腺组织的内分泌功能,并摘除移植物观察血糖变化。结果与结论：体视显微镜下可分离出较完整的E11.5~E16.5小鼠胰腺组织,≤E12.5d小鼠胚胎胰腺组织的形态和颜色均难以与周围组织分辨,需根据其与毗邻脏器的关系仔细辨别;〉E12.5d的小鼠胚胎胰腺已初具形态,颜色略发白。组织学和ELISA分别显示胚胎胰腺组织可表达并分泌胰岛素,其表达强度随发育时间逐渐增加。E16.5小鼠胰腺组织移植能有效地控制受体的血糖水平,使受体的体质量和糖耐量恢复正常;胚胎胰腺在受体的肾被膜下可生长发育,摘除的移植物胰岛素和胰高血糖素的表达均较移植前增强。说明胚胎胰腺组织可能成为治疗糖尿病的种子来源。     

Alternative Medicines Toxicology: A Review of Selected Agents

Abstract

Experience with organ procurement from poisoned donors in brain death status is still limited in comparison with other etiologies. From 1963 to 1993, 2769 grafts (heart 141, kidney 1922, liver 623, pancreas 43) were performed in our Universitary Hospital. Since 1975, among 1174 patients admitted to the ICU for acute poisoning, 12 patients who developed brain death status were considered for organ donation. The toxics involved were: methaqualone (1), benzodiazepines (1), benzodiazepines plus tricyclic antidepressants(2), barbiturates (2), insulin (2), carbon monoxide (1), cyanide (I), methanol (1), and acetaminophen (1). Exclusion criteria for organ removal were applied according to the nature of the toxin and the general criteria used for organ donation. The organs removed were: heart 5, heart valves for graft bank 2, kidneys 22, liver 4, pancreas 2, pancrease islet cells 2. Pertinent follow-up was obtained in 23 of 32 recipients. Immediate outcome was favorable in 20/23 patients (85%). Three patients died either from stroke, heart failure or preexisting encephalopathy. Two patients died from either chronic hepatic or renal graft rejection. None of these events could be directly related to a toxic origin. The one year survival rate of 75% is similar to that observed in the population who received organs from nonpoisoned donors. Organ procurement can be considered in few selected cases of acute poisoning. The accuracy of the diagnosis of irreversible brain damage is essential in this setting.     

Significance of thymus differential ratio in immunologic status of graft tolerance

LEW with BDE-heart graft received 0 (control), 15, or 40 mg cyclosporine (CsA)/kg b. wt. per day. On postoperative days 3, 5, 7, 10, and 14 in four animals each weight and cell count of thymus and spleen were determined, and thymus and spleen cell subpopulations were examined with monoclonal antibodies. The same tests were performed in FiS heart graft recipients without immunosuppression and ungrafted LEW which received 15 or 40 mg CsA. We expressed alterations in thymocyte subpopulations by using the differentiation ratio (DR), i.e., differentiated in % of all T-cells and by the ratio of helper to suppressor/cytotoxic T-cells (Th-Ts/c). In graft rejection the thymus showed no significant change in DR or Th-Ts/c. However, in the CsA-induced graft tolerance DR was elevated and at the same time Th-Ts/c declined, both showing maximum values on days 5 and 7 and a return to normal thereafter. FiS graft recipients exhibited similar thymus alterations as tolerant recipients, but less marked. In CsA-treated ungrafted LEW, elevation of DR was slight after 15 mg but very strong after 40 mg CsA (93% on day 7), and it did not return to normal in the latter group. Th-Ts/c was decreased in these ungrafted animals, but not as strongly as in tolerant graft recipients. Such thymus alterations were not observed in graft rejection. Spleen weights were strongly increased in graft rejection and unchanged in graft tolerance. Splenic Ts/c and Th-Ts/s were increased in CsA-treated tolerant recipients but not in graft rejection. We conclude that elevation of DR and decline of thymic Th-Ts/c in the initial postoperative phase are indicators of graft tolerance in organ recipients.