合并危险因素肾移植受者18例应用西罗莫司的观察

摘要：评价服用环孢素A肾移植受者合并危险因素时,应用西罗莫司为主要免疫抑制剂的临床效果及安全性。纳入应用标准的18例受者,将环孢素A 转换为以西罗莫司为主要免疫抑制剂的抗排斥治疗,环孢素A在1周内迅速撤除,西罗莫司的目标血药浓度为5~8 µg/L,随访观察移植肾功能、并发症和不良反应。环孢素A转换为西罗莫司时距移植后时间为5~108个月,随访4~31个月,发生急性排斥反应1例,经甲基泼尼松龙冲击治疗后逆转;环孢素A相关肾毒性4例,转换后血清肌酐均正常;慢性移植肾肾病5例,1例发生移植肾失功,另4例肌酐转换前为(327.4±105.0) μmol/L,转换后6个月下降为(215.6±42.3) μmol/L (P < 0.05);2例急性难治性移植肾排斥逆转;环孢素A相关肝毒性5例,其中环孢素A相关肾、肝毒性2例,肝功能恢复正常4例,改善1例;2例骨质疏松症安全撤除皮质激素;2例移植后恶性肿瘤,手术治疗后转换为西罗莫司,随访11~16个月病情稳定。西罗莫司主要不良反应为高脂血症、白细胞减少及慢性腹泻。提示以环孢素A为主要免疫抑制剂的肾移植受者合并一个或多个危险因素时,转换为西罗莫司是一种较为安全有效的选择。     

西罗莫司对肾移植受者的转换治疗

背景：新一代的强效免疫抑制剂西罗莫司具有肾毒性少、抗增殖、抗肿瘤等作用，能够减少肾移植受者的肝肾毒性和严重感染等不良反应。 目的：验证以神经钙蛋白抑制剂为主要免疫抑制方案出现一种或多种危险因素时，应用西罗莫司转换治疗方案的有效性及其安全性。 设计、时间和地点：回顾性病例分析，于2003-06/2006-12在解放军南京军区南京总医院解放军肾脏病研究所完成。 对象：肾移植后转换以西罗莫司为主的免疫抑制剂治疗的患者93例，男59例，女34例，年龄(38±11)岁。神经钙蛋白抑制剂肾中毒者13例、神经钙蛋白抑制剂肝毒性者26例、移植后糖尿病11例、慢性移植肾肾病33例、移植后并发肿瘤10例。 方法：所有患者治疗方案都采用快速转换法，即2周内撤除神经钙蛋白抑制剂，口服环孢素A或他克莫司后4 h，口服西罗莫司，单次首剂负荷剂量6 mg，之后维持剂量1.0~2.0 mg/d。在服用第1剂西罗莫司后的5~7 d检测第1次西罗莫司浓度，目标质量浓度6~10 μg/L。 主要观察指标：动态观察西罗莫司转换后的血肌酐水平、急性排斥反应发生率、移植肾的丢失率、肺部感染和死亡率等。 结果：西罗莫司转换治疗后，神经钙蛋白抑制剂肾毒性和肝毒性患者症状明显好转，血浓度维持在(5.1±1.2) μg/L，血肌酐由(297.72±150.28) μmol/L降至(123.76±44.2) μmol/L，转换后肝功能恢复(24例，92.3%)。高糖血症患者9例恢复正常，2 例改善；17例血肌酐下降大于原肌酐水平的25%，有效率为51.5%；10例肿瘤发生于肾移植后6~43个月，8例稳定无复发，2例死亡。西罗莫司转换治疗6个月内发生急性排斥反应3例。并发症主要包括高脂血症和蛋白尿。3例死亡，6例返回透析治疗，2例移植肾摘除。转换治疗3年人肾存活率分别为90.9%和75.8%。 结论：使用神经钙蛋白抑制剂的肾移植受者时出现一种或多种危险因素时，切换成西罗莫司和霉酚酸酯免疫抑制方案后不良反应减少。     

神经钙蛋白阻滞剂减量联合西罗莫司治疗慢性移植肾肾病

背景：西罗莫司具有明确的抗增殖特性而无肾毒性，可能在慢性移植肾肾病的防治方面发挥作用，但以其为基础的免疫抑制方案治疗慢性移植肾肾病尚无统一标准。 目的：探讨神经钙蛋白阻滞剂减量联合西罗莫司治疗慢性移植肾肾病的效果。 设计、时间及地点：回顾性病例分析，于2005-05/2007-05在解放军第三军医大学大坪医院野战外科研究所完成。 对象：选取同期收治的经病理学检测证实的慢性移植肾肾病患者69例，免疫抑制剂方案为他克莫司+霉酚酸脂+强地松19例，环孢素+霉酚酸脂+强地松43例，环孢素+硫唑嘌呤+强地松7例，其中他克莫司用量1.0~4.0 mg/d，环孢素用量100~ 325 mg/d，霉酚酸脂用量500~1 500 mg/d，强地松用量2.5~15 mg/d。西罗莫司为美国惠氏制药公司产品，批号H20050066。神经钙蛋白阻滞剂他克莫司为日本藤泽药品工业株式会社产品，批号X980596；环孢素为杭州中美华东制药有限公司产品，批号H10960122。 方法：将他克莫司或环孢素剂量减少2/3，加用西罗莫司2 mg/d，根据血药浓度监测调整西罗莫司用量达到常规目标谷浓度的1/2，其余免疫抑制剂霉酚酸脂、硫唑嘌呤及醋酸泼尼松用量维持不变，随访6个月。 主要观察指标：24 h尿量、血清肌酐、内生肌酐清除率、24 h尿蛋白的变化；部分患者移植肾再次活检病理学表现。 结果：与使用前比较，69例患者使用西罗莫司6个月后24 h尿量、内生肌酐清除率明显升高（P < 0.05或0.01），血清肌酐值、24 h尿蛋白含量显著下降（P < 0.01）。使用西罗莫司6个月后4例患者接受再次穿刺活检，病理学上可见以间质炎性细胞浸润为特点的排斥反应减轻，而以微动脉管壁增厚和玻璃样变性为特点的神经钙蛋白阻滞剂肾毒性反应变化不大。 结论：神经钙蛋白阻滞剂减量联合西罗莫司治疗慢性移植肾肾病是一种安全有效的方法，其原因可能与两者联合应用后产生的协同性免疫抑制作用及减少神经钙蛋白阻滞剂肾毒性有关。     

肾移植后西罗莫司致不良反应的文献分析

背景：西罗莫司是一新型免疫抑制剂,肾毒性小,已在中国用于防治肾移植后排斥反应。 目的：分析肾移植后应用免疫抑制剂西罗莫司所致不良反应的临床特征和相关因素。 方法：计算机检索2002/2009中国知网数据库、万方数据资源的中国期刊全文数据库国内文献收载的西罗莫司不良反应报道资料,检索词“西罗莫司、肾移植”,采用文献计量学方法进行统计、分析。纳入近年中国国内报道的西罗莫司临床应用及安全性方面的研究论文,要求其中不良反应报告的病例在性别、年龄、不良反应表现等方面详细具体。排除综述类文献及不良反应报告过于简单的病例资料。 结果与结论：共选入文献15篇,患者500例,其中发生不良反应病例合计468例次。468例不良反应中高脂血症发生最多(182例,占38.9%),其次为感染和发热 (62例,占13.2%),肝功能异常 (54例,占11.5%)等。提示西罗莫司主要不良反应为高脂血症、感染和肝功能异常等,不良反应发生与血药浓度等因素相关,定期监测血药浓度,合理调整用量,可增加西罗莫司应用的有效性及安全性。 关键词：西罗莫司;不良反应;文献分析;肾移植;免疫抑制剂     

亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的应用

背景：亲属活体肾移植供、受者移植前准备充分,供肾热、冷缺血时间较短,HLA配型的组织相容性好,移植后排斥反应发生率低,为亲属活体供肾肾移植后采用低剂量免疫抑制剂方案提供了可能性。 目的：探讨亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的安全性和有效性。 方法：选取2006-01/2008-06在南京医科大学第一附属医院肾移植中心行亲属活体供肾移植的受者38例,移植后常规使用环孢素A/他克莫司+吗替麦考酚酯+泼尼松的三联免疫抑制方案。将38例患者随机分为两组：CNI常规剂量组(n=18),移植后初始药物剂量为环孢素A 6 mg/(kg•d)或他克莫司0.12 mg/(kg•d);CNI低剂量组(n=20),术后初始药物剂量为环孢素A 4 mg/(kg•d)或他克莫司0.08 mg/(kg•d);两组吗替麦考酚酯和泼尼松使用剂量相同。移植后密切随访,比较两组患者移植后不同时期的肾功能以及急性排斥反应、肺部感染、肝功能损害、肾毒性等并发症的发生情况。 结果与结论：随访12个月,CNI常规剂量组重度肺部感染死亡1例,CNI低剂量组无死亡病例。两组移植肾功能及急性排斥反应发生率比较差异均无显著性意义(P > 0.05);CNI低剂量组肝功能损害、钙调蛋白酶抑制剂肾毒性发生率显著低于CNI常规剂量组 (P < 0.05)。此外,采用低剂量钙调蛋白酶抑制剂免疫抑制方案明显减轻了亲属肾移植患者的经济负担。说明亲属活体供肾移植后采用低剂量钙调蛋白酶抑制剂的免疫抑制剂方案安全、有效。     

低剂量他克莫司为基础四联免疫抑制方案在肾移植中的应用：4年随访结果

背景：免疫抑制药物日新月异的发展及药物应用存在较大的个体差异使得目前国内外对于肾移植后免疫抑制的选择和应用剂量等仍无法达成完全统一的共识。 目的：观察以低剂量他克莫司为基础的四联免疫抑制剂方案的免疫抑制效能、保护肾功能的作用和安全性。 方法：以他克莫司+酶酚酸酯+泼尼松龙(方案1)为对照组；将方案1中他克莫司和酶酚酸酯减量为方案2，以方案2+西罗莫司为组1；方案2+咪唑立宾为组2。检测3组受者肾移植后第2，4周、6个月及1年时淋巴细胞对供体树突状细胞的反应强度；每6个月测定1次受者尿转化生长因子β1；移植后每1~3个月检查肝肾功能、血尿常规、血糖，随访时间为4年。 结果与结论：3组急性排斥反应发生率及感染发生率无显著差异；移植4周，组1，组2的反应强度明显低于对照组 (P < 0.05)；移植1年，组1、组2尿转化生长因子β1浓度均显著低于对照组(P < 0.05)；移植2年，组1、组2血肌酐和肌酐清除率降低值均显著低于对照组(P < 0.05)；组1、组2肝功损害、高血糖等不良反应发生率均低于对照组 (P < 0.05)。提示与常规剂量他克莫司为基础的三联免疫抑制方案相比，低剂量他克莫司为基础的四联免疫抑制方案能够发挥同样的免疫抑制效果，同时能减轻移植肾纤维化进程，改善移植肾功能，减少严重不良反应发生率，更有利于移植肾长期存活。     

钙调神经蛋白抑制剂引起的肾毒性：肾移植术后的早期预防和治疗

目的：就近年来国内外预防和治疗钙调神经蛋白抑制剂肾毒性的方法进行综述。 方法：应用PubMed检索及CNKI中国期刊全文数据库检索系统,以“环孢素A,他克莫司,钙调神经蛋白抑制剂肾毒性”和“Ciclosporine A,Tacrolimus,CNIS drug-induced chronic nephrotoxicity”为关键词检索相关文献。时间范围为1980-01/2010-01。选择文章主要内容与钙调神经蛋白抑制剂肾毒性直接相关、针对性强、代表性好、相关领域权威杂志的文章共44篇进行综述。 结果：环孢素A与他克莫司做为常用的免疫抑制剂,明显改善了器官移植者的生活质量和生存率,如果要取得移植肾的长期存活,必须考虑到导致移植物丧失功能的病因学问题。目前,已经证明慢性移植物肾病和钙调神经蛋白抑制剂的肾毒性是导致移植肾丧失功能的主要原因,而同时钙调神经蛋白抑制剂肾毒性在慢性移植物肾病的自然病程中又起到了重要的作用。 结论：目前没有有效预防和治疗钙调神经蛋白抑制剂肾毒性的手段。移植术后早期减少钙调神经蛋白抑制剂用量或撤除,或许是预防钙调神经蛋白抑制剂肾毒性更好的选择。     

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。     

同一移植中心2年间亲属活体肾移植38例安全性评估

背景：国内活体器官供者的安全性令人关注,供者移植后并发症,受者移植效果不理想或失败的病例有所发生。因此,必须重视活体肾移植,保证供者的生命安全和生活质量。 目的：探讨亲属活体肾移植的安全性。 方法：回顾性分析38对亲属活体肾移植供受者的临床资料,总结治疗经验。38例供者移植前明确身份,完善检查,充分告知治疗方案,合理手术。38例受者移植前充分透析,改善全身状况后行肾移植,移植后给予他克莫司或环孢素A、霉酚酸酯、皮质激素的三联基础免疫抑制方案治疗。观察肾移植后供受者肾功能变化、并发症发生率,以及受者急性排斥反应发生情况。 结果与结论：亲属活体肾移植等待时间短、花费较少、长期存活率高的优势是明显的,供者的近期和远期风险都很小。尽管如此,进行亲属活体肾移植仍要充分评估供受者的风险,保证供受者的安全。     

Sirolimus may not cause neurotoxicity in kidney and liver transplant recipients

Neurotoxicity associated with calcineurin inhibitors cyclosporin A and tacrolimus is established. Sirolimus is a new agent related to tacrolimus, but its mechanism of action differs. The authors reviewed 202 transplant recipients treated with sirolimus from 2001 to 2004. They found no evidence of neurotoxicity with sirolimus therapy for up to 18 months (range, 15 days to 3 years). Sirolimus could be considered a substitute immunosuppressant for patients with cyclosporin A or tacrolimus neurotoxicity.     

Treatment with everolimus is associated with a procoagulant state

Introduction

Renal transplant recipients are at increased risk of venous thromboembolic events, which is in part caused by their treatment with maintenance immunosuppressive drugs. Because we observed an increased incidence of venous thromboembolic events in renal transplant recipients treated with the mTOR inhibitor (mTORi) everolimus, we aimed to identify prothrombotic mechanisms of this immunosuppressive drug.

Materials and Methods

In a single center study, nested in a multi-center randomized controlled trial, we measured parameters of coagulation, anti-coagulation and fibrinolysis in renal transplant recipients, receiving the mTORi everolimus (n = 16, mTOR group) and compared them to a similar patient group, receiving a calcineurin inhibitor and/or mycophenolate sodium (n = 20, non-mTOR group). All patients were at least 6 months following transplantation with a stable transplant function.

Results

The use of an mTORi was associated with significantly higher levels of von Willebrand factor, prothrombin fragment 1 + 2, thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 as compared to a non-mTORi based immunosuppressive regimen.

Conclusions

Treatment with an mTORi leads to increased endothelial activation, thrombin formation and impaired fibrinolysis in renal transplant recipients. This suggests an increased risk of thrombotic events in renal transplant recipients treated with mTOR inhibitors. A prospective study to establish the precise risk of thrombotic events in these patients is urgently needed.     

移植肾穿刺病理组织中抗体介导的排斥反应

背景：体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。 目的：对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。 方法：选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD(美国)活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。 结果与结论：84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

Alternative Tacrolimus and Sirolimus Regimen Associated With Rapid Resolution of Posterior Reversible Encephalopathy Syndrome After Lung Transplantation

BackgroundNeurotoxicity is a significant complication of calcineurin inhibitor use, and posterior reversible encephalopathy syndrome has been reported. Limited data exist on the use of alternative immunosuppression regimens in the management of posterior reversible encephalopathy syndrome in transplant recipients.MethodsWe present the immunosuppression management strategy of a girl who underwent bilateral lung transplantation for cystic fibrosis 6 months earlier, then suddenly developed a grand mal seizure due to posterior reversible encephalopathy syndrome diagnosed by magnetic resonance imaging of the brain. In an effort to reduce her tacrolimus dose, an alternative immunosuppressant regimen combining tacrolimus and sirolimus was used.ResultsAfter the modification of her immunosuppressant regimen, there was rapid clinical improvement with no further seizures. Her brain findings had resolved on magnetic resonance imaging 2 months later. Over the next 6 months, allograft function remained stable and surveillance transbronchial biopsies found no allograft rejection on the combined sirolimus and tacrolimus therapy.ConclusionsTacrolimus-associated neurotoxicity resolved in a lung transplant recipient with a combined tacrolimus and sirolimus regimen. This combined therapy appears to be an effective alternative for lung transplant recipients that allow them to receive the benefits of both drugs but at lower doses, which reduces the risk for adverse effects.     

Rapamycin: brain excitability studied in vitro

Neurological complications are common in transplant recipients treated with immunosuppressant calcineurin inhibitors. Rapamycin, a macrolide antibiotic, was suggested as an alternative agent in patients who develop calcineurin inhibitor associated neurotoxicity, including seizure attacks. The aim of the present study was to test the effect of rapamycin on the bioelectrical activity and evoked field excitatory postsynaptic potentials (fEPSP) in CA1 area of hippocampal tissues and compare its effect with FK506, a calcineurin inhibitor agent. Application of rapamycin at different concentrations neither affected the bioelectrical activity nor changed fEPSP magnitude. In contrast, FK506 elicited epileptiform burst discharges and significantly enhanced fEPSP magnitude. This study supports the suggestion that rapamycin could be used as an alternative to calcineurin inhibitors in the event of neurotoxicity.     

In vitro thromboxane synthesis of depleted blood platelets following renal transplantation

Renal transplant rejection is associated with platelet activation in vivo which may lead to partially alpha- and delta-granule-depleted platelets that continue to circulate. These "exhausted" platelets are hemostatically defective. To quantitate the extent of platelet granule depletion following kidney transplantation, we determined intraplatelet levels of beta-thromboglobulin (beta TG), platelet factor 4 (PF4), and serotonin (5-hydroxytryptamine, 5-HT) ex vivo in Triton X-100-treated platelet lysates. To explore biochemical alterations of partially depleted platelets, we studied platelet thromboxane A2 (TXA2) synthesis in citrated platelet-rich plasma (PRP) upon stimulation with thrombin or collagen in 45 recipients of renal allografts and 10 healthy volunteers. The patients were divided into subjects with acute and chronic allograft rejection (N = 15), those with compensated renal failure after kidney transplantation but without evidence of allograft rejection (N = 15), and those with functioning renal transplant (N = 15). The mean intraplatelet content of beta TG (38.6 +/- 4.2 micrograms/10(9) platelets), PF4 (11.8 +/- 1.8 micrograms/10(9) platelets), and 5-HT (274 +/- 31 ng/10(9) platelets) in patients with acute or chronic renal allograft rejection was significantly lower than in other recipients of kidney transplants or healthy volunteers (beta TG: 59.9 +/- 4.7 micrograms/10(9) platelets; PF4: 20.4 +/- 2.3 micrograms/10(9) platelets; 5-HT: 461 +/- 48 ng/10(9) platelets; p less than 0.005 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral reticulum cell sarcoma after multiple renal transplants

A case is reported of a 34 year old white male with chronic renal failure secondary to glomerulonephritis who received four renal transplants over a period of five years. He died 25 months after the fourth transplant. Necropsy revealed a reticulum cell sarcoma-microglioma of the brain. The possibility that multiple transplants may have had a synergistic effect in the development of a malignant cerebral lymphoma in this patient is briefly discussed in the light of the current theories concerning the pathogenesis of the tumours in transplant recipients and in the context of the present therapeutic approach to graft rejection.     

来氟米特用于肾移植患者长期维持治疗20例

背景：来氟米特作为一种新型免疫抑制剂广泛应用于治疗自身免疫性疾病,它兼有免疫抑制作用和抗病毒活性,初步临床观察提示它可用于器官移植抗排斥治疗,但长期疗效尚不清楚。 目的：评价来氟米特+环孢霉素(或他克莫司)+泼尼松三联药物对肾移植受者维持治疗的长期效果。 设计、时间及地点：回顾性病例分析,2002-12/2007-03在解放军第四五五医院,解放军南京军区肾脏专科中心完成。 对象：选取肾移植术后超过1个月且肾功能正常者。来氟米特治疗组：用氟米特替换霉酚酸酯或硫唑嘌呤患者20例,移植时年龄16~47岁,平均(32.6±8.7)岁,其他免疫抑制剂与对照组相同。对照组：同期肾移植患者41例,年龄17~57岁,使用霉酚酸酯+环孢素A/他克莫司+泼尼松为维持治疗。 方法：来氟米特起始剂量为50 mg/d,应用3~5 d后给予20 mg/d 维持;泼尼松维持剂量为10 mg/d;环孢素A或他克莫司剂量根据其血药浓度进行调整。前3个月每月复查肝功能、肾功能和血常规,以后根据患者情况1~3个月复查1次。 主要观察指标：来氟米特治疗组和对照组移植肾和患者生存率,及来氟米特不良反应。 结果：来氟米特组观察时间平均(27.7±21.6)个月。继续维持来氟米特治疗肾功能稳定7例,血肌酐翻倍或肾功能丢失2例,失访1例,退出10例。来氟米特组人、肾生存率分别为1年100%和100%,3年100%和94%,5年79%和78%。对照组人、肾生存率分别为1年95%和95%,3年90%和88%,5年90%和77%。死亡原因：来氟米特组2例移植肾失功后放弃透析治疗;霉酚酸酯组2例带功死于肺部感染,2例于移植肾失功后因经济困难放弃治疗。来氟米特不良反应：早期脱发3例,皮疹2例,恶心3例,贫血2例。 结论：用来氟米特+钙调素抑制剂+泼尼松三联治疗和霉酚酸酯+钙调素抑制剂+泼尼松三联治疗的肾移植受者5年的临床结果无明显差别。     

Testosterone-induced enhancement of male medial preoptic tissue transplant volume in female recipients: a possible neuronotrophic action

To characterize further the action of gonadal hormones on the development of the brain, this study was designed to test the ability of testosterone treatment to modify the volume of male brain tissue transplants in female recipients. One-day-old females, in addition to having either medial preoptic area (MPOA) or caudate nucleus (CN) tissue from neonatal males bilaterally implanted into their own MPOA, also received a subcutaneous injection of either 200 micrograms testosterone propionate (TP) or oil concurrently, and on the following 4 days. All recipients were sacrificed at 30 days of age postnatally. An analysis of male transplant volumes indicated that MPOA transplants in oil-treated recipients were substantially reduced in size (0.06 +/- 0.01 mm3) compared with the initial transplant volume of 0.19 mm3. However, MPOA transplants in recipients treated with TP showed a 79% increase above the initial transplant volume (to 0.34 +/- 0.05 mm3). The resulting 5- to 6-fold difference in MPOA transplant volume between oil and TP treated animals was highly significant. In sharp contrast, the same TP treatment to recipients receiving male CN transplants resulted in no enhancement of transplant volume. Therefore, transplants involving a brain area known to concentrate 3H-labeled testosterone neonatally (i.e. the MPOA) responded to TP treatment with an enhancement of volume which was not observed for transplants consisting of brain tissue not known to concentrate 3H-labeled testosterone (i.e. the CN). The above results suggest that testosterone is a 'neuronotrophic' agent during development that acts specifically on cells within steroid-sensitive brain areas, perhaps to prevent neuronal death within these areas.     

Neurological complications of organ transplantation

Over the last thirty years, organ transplantation has become a practical treatment option for many otherwise fatal diseases. New immunosuppressive agents, advances in tissue matching, and improvements in surgical technique have increased both the number and type of transplants performed. Kidney, bone marrow, heart, lung, liver, and pancreas transplants are now used regularly in the treatment of end-stage disease. However, these advances have come at a price. Transplant recipients are subject to numerous complications, many of which involve the nervous system. Depending on the type of organ transplanted, 30 to 60% of transplant recipients experience neurological problems. Most neurological complications, especially those related to immunosuppression, are common to all transplant types; other complications are associated predominantly with specific transplant types. This report reviews the general categories of neurological complications as well as the specific problems associated with each kind of transplant.