头孢氨苄和头孢哌酮对肾功能及环孢素血浓度的影响

观察了头孢氨苄对肾移植术后患者的肾功能和环孢素血浓度的影响。42例患者在服用头抱氨苄期间,血尿素氮(BUN)、血清肌酐(SCr),环孢素血浓度比合并用药前分别增加2.55％、6.86％及30.56％,比停用头孢氨苄后分别增加17.59％,39.94％及35.80％。而在32例肾移植术后患者进行的另一项研究则表明,合并用头孢哌酮期间。BUN,SCr、环孢素血浓度与用药前、停药后相比几乎没有改变。提示在肾移植木后抗感染治疗可优选头孢哌酮。     

肾移植患者环孢素A肝毒性作用的回顾性研究

目的：了解环孢素Ａ在肾移植患者肝功能受损中的作用和长期服用对患者的影响。方法：回顾性分析了３组资料：（１）１９７８年７月至１９８４年应用二联免疫抑制治疗（硫唑嘌呤＋泼尼松）的肾移植患者８３例，１９８５～１９９１年应用三联免疫抑制治疗（环孢素Ａ＋硫唑嘌呤＋泼尼松）的肾移植患者５８０例；（２）１９９４年１月至１９９７年８月进行的肾移植患者５１９例；（３）随访服用环孢素Ａ免疫抑制治疗８年以上患者６８例，     

Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis

We studied the effects of cytomegalovirus (CMV) infection on 301 cardiac transplant recipients who were treated during the cyclosporine era of immunosuppression (1980 to the present). These patients received varying combinations of cyclosporine, azathioprine, prednisone, rabbit antithymocyte globulin, and OKT3 as their immunosuppressive therapy. Two hundred ten patients were free of CMV infection (non-CMV group). During the same period CMV infection developed in 91 patients, as manifested by a fourfold IgG serologic titer rise, demonstration of CMV inclusion bodies in tissue, or positive cultures for the virus (CMV group). The rate of graft rejection was significantly higher in the CMV group. Graft atherosclerosis was significantly more severe in the CMV group as judged by angiographic criteria or by pathologic study. Patient survival rates were significantly lower in the CMV group. Death caused by graft atherosclerosis was significantly more common among patients in the CMV group. Finally, the graft loss rate (from either death or retransplantation for atherosclerosis) was significantly greater in the CMV group. These data demonstrate that CMV infection in cardiac transplant recipients is associated with more frequent rejection, graft atherosclerosis, and death.     

肾移植患者高尿酸血症与痛风的研究进展

高尿酸血症在肾移植患者中较为常见，在接受环孢素A(CsA)治疗的患者中发病率更高。尿酸升高的原因多与药物治疗时间的长短有关，与剂量、血药浓度、血肌酐水平无明显相关性。肾移植患者痛风的发生率较低，其确切的病因目前尚不清楚。肾移植术后高尿酸血症和痛风的处理，目前尚有争议，作者对肾移植患者高尿酸血症和痛风作一综述。     

浅谈中西医结合系统防治急性移植物抗宿主病

急性移植物抗宿主病(aGvHD)是异基因造血干细胞移植受者一个重要的致死因素,防治aGvHD的关键在于阻止大量细胞因子引发对受者的剧烈免疫反应和组织器官损伤。文章分别归纳了当前中医与西医对aGvHD的理论研究,并进一步探讨了天然免疫抑制剂雷公藤内酯、苦参碱等与经典西药免疫抑制剂环孢素A联用防治a GvHD的研究,最后发现将经典的免疫抑制疗法结合中医药理论以扶正固本兼攻毒袪邪之药方配合移植患者治疗,可能有助于控制a GvHD的发生和发展。因此,提出中西医结合系统防治aGvHD的策略,希望为缓解移植并发症提供新的思路。     

Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients. We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus. Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

     

Primary hypertriglyceridemia with borderline high cholesterol and elevated apolipoprotein B concentrations. Comparison of gemfibrozil vs lovastatin therapy

A common pattern of dyslipidemia is elevated levels of plasma triglyceride, borderline high total cholesterol, reduced high-density lipoprotein, and increased apolipoprotein B. This pattern of dyslipidemia frequently is associated with premature coronary heart disease. Nicotinic acid is the drug of first choice for this pattern. In this study, gemfibrozil and lovastatin were compared for their effects on the overall lipoprotein profile in 13 men with this type of dyslipidemia. Both drugs significantly reduced very-low-density lipoprotein and intermediate-density lipoprotein cholesterol levels, and both modestly raised high-density lipoprotein cholesterol levels. Gemfibrozil therapy, however, failed to reduce total cholesterol or total apolipoprotein B levels, whereas lovastatin therapy lowered levels of total cholesterol by 28%, low-density lipoprotein cholesterol by 33%, and total apolipoprotein B by 32%. Moreover, lovastatin therapy caused greater declines in lipoprotein cholesterol ratios than gemfibrozil therapy. Lovastatin thus seems to have certain advantages over gemfibrozil for treatment of elevated plasma triglyceride levels accompanied by borderline high total cholesterol and raised apolipoprotein B levels; therefore, lovastatin therapy should be considered as one approach for management of this condition.     

Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.     

尸肾移植术后移植肾动脉狭窄发病原因分析

目的探讨尸体肾移植术后移植肾动脉狭窄(TRAS)的可能发病原因。方法对尸体肾移植术后18例TRAS患者与未发生TRAS的566受者有可能影响TRAS发生的多个因素进行统计分析。结果(1)TRAS患者的肾移植术后急性排斥反应发生率显著高于非TRAS者(66.67% vs5.48% , P<0.01);(2)发生与未发生TRAS的受者在术前透析方式、糖尿病发病、供肾冷缺血时间、供肾动脉数、供肾侧、供肾动脉吻合方式、术后免疫诱导用药、术后口服免疫维持治疗、术后巨细胞病毒感染以及发病时血脂等诸方面均无显著差异。结论肾移植术后TRAS的发生与移植术后急性排斥反应的发生有密切关系。     

尸肾移植术后移植肾动脉狭窄发病原因分析

OBJECTIVE: To explore the possible causes of transplant renal artery stenosis (TRAS) in cadaveric transplant recipients. METHOD: We retrospectively analyzed multiple factors that may contribute to TRAS (including the patients' age, presence of diabetes, cold ischemic time, acute rejection episode, cytomegalovirus infection, serum cholesterol, LDL cholesterol, pre-operative dialysis, number of donor renal arteries, which side of donor kidney, type of surgical anastomosis, different protocols of inductive and maintenance drug therapy) in 18 recipients with transplant renal artery stenosis after cadveric renal transplantation from Jan. 2000 to Dec. 2001 in comparison with another 566 non-TRAS recipients who underwent the transplantation during the same period. RESULTS: There was a higher incidence of acute rejection in the TRAS group than non-TRAS group (66.67% vs 5.48%, P<0.01), and no significant difference was noted between TRAS and non-TRAS cases in terms of the pre-operative dialysis, presence of diabetes, cold ischemic time, number of donor renal arteries, whith side of donor kidney, type of surgical anastomosis, different protocols of inductive and maintenance drug therapy, cytomegalovirus infections and serum and LDL cholesterols. CONCLUSION: The occurrence of TRAS in cadaveric allografts is associated with acute graft rejection episode, suggesting the importance of the treatment of acute graft rejection in the prevention of TRAS.     

Effects of cyclosporine therapy on plasma lipoprotein levels

Accelerated atherosclerosis is a leading cause of death in long-term survivors of heart and renal transplantation and may be exacerbated by the frequent occurrence of posttransplant hyperlipidemia. Attempts to define the mechanism for hyperlipidemia in transplant recipients are confounded by dramatic changes in metabolism and nutritional status after transplantation, as well as by treatment with multiple immunosuppressive and antihypertensive drugs. To avoid these pitfalls and to determine if cyclosporine alone adversely affects lipid levels, we measured lipoprotein levels in a prospective, double-blind, randomized, placebo-controlled trial of cyclosporine in 36 men with amyotrophic lateral sclerosis. Plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein B levels were measured at baseline, 2 weeks, 1 month, and 2 months. Significant increases of 21% in total cholesterol, 31% in low-density lipoprotein cholesterol, and 12% in apolipoprotein B levels occurred only in the cyclosporine group. Cyclosporine therapy alone adversely affects plasma lipoprotein levels by increasing total cholesterol levels, primarily due to an increase in low-density lipoprotein cholesterol level.     

Kidney

Conversion from cyclosporine to tacrolimus for the treatment of chronic allograft nephropathy , Clinical diagnosis and treatment of BK virus infection in renal transplant recipients , Clinical study on avascular necrosis of the femoral head in 24 renal transplantation patients , Clinical and histopathological analysis in living donor kidney transplantation recipients, Evaluation of the early-stage safety of livingrelated kidney transplant donors , Living-related donor kidney transplantation101 cases reports     

肝脏活检在异基因造血干细胞移植中的应用

目的评价肝脏活检在异基因造血干细胞移植（Allo—HSCT）后肝功能损害患者中的诊断及治疗意义。方法病例选自北京大学人民医院血液病研究所1999年2月至2004年1月所做的10例Allo—HSCT并接受肝脏活检的患者,男5例,女5例。年龄15～56岁（中位34．5岁）。其中白血病8例,骨髓异常增生综合征1例,重症再生障碍性贫血1例。移植方式包括非血缘骨髓移植1例,同胞全相合Allo—HSCT6例,单倍体移植1例,脐带血移植2例。预处理方案,采用全身照射加环磷酰胺2例,非全身照射方案8例。移植物抗宿主病全部采用环胞菌素A加短程甲氨蝶呤加霉酚酸酯方案。移植前供受者常规接受肝功能及乙肝、丙肝病毒检测。10例患者均接受经皮肝穿刺活检,得到肝组织标本分别经苏木素-伊红和Masson染色在光学显微镜下观察及免疫组织化学检测。结果10例患者Allo—HSCT后出现肝功能损害的时间为2～5个月,中位3．8个月。移植前7例患者HBV、HCV检测阳性,移植后仍阳性。移植前后3例患者HBV、HCV检测全部阴性,临床诊断为移植物抗宿主病（GVHD）肝损害。10例患者在出现肝功能损害时,9例伴有不同程度慢性GVHD（cGVHD）其他表现。10例患者均根据临床诊断采用初始治疗后,肝功能改善不好。分别于Allo—HSCT后4～12个月（中位5．5个月）行肝脏活检。病理结果3例肝炎病毒阴性者为cGVHD肝损害,其余7例为肝炎病毒感染合并cGVHD肝损害。3例单纯诊断为cGVHD肝损害患者,经调整抗GVHD药物后,肝功能恢复;其余7例患者采用抗病毒及调整免疫抑制剂等综合治疗,结果2例肝功能恢复并存活。5例死亡,其中2例在治疗中肝功能改善不好,因合并肺部感染死亡,3例因肝功能衰竭,肝昏迷死亡。结论Allo—HSCT后,对于临床诊断肝脏GVHD肝损害而治疗效果不好的患者,肝脏活检可起到鉴别诊断和指导进一步治疗的作用。肝炎病毒感染与GVHD肝损害合并存在者预后差。肝活检对指导治疗具有一定局限性,还需结合临床及病理制订治疗方案。     

肾移植术后应用普乐可复(FK506)逆转环孢素A(CsA)引起肝功能损害的临床研究

目的 :观察普乐可复 (FK5 0 6 )替换环孢素A(CsA)在防治尸肾移植术后药物性肝损害的有效性和安全性。方法 :选择 2 5例尸肾移植术后应用CsA出现肝功能异常而肾功能正常患者 (移植术后 2个月～ 36个月 ,年龄 2 3岁～ 5 8岁 ) ,以FK5 0 6切换CsA ,FK5 0 6初始剂量及维持剂量以患者体重、移植后时间、病情及全血FK5 0 6血药浓度进行相应调整 ,同时予以保肝治疗。结果 :将CsA切换成FK5 0 6治疗 2周～ 4周后 ,患者肝功能指标 (血清ALT、D BIL及I BIL)呈明显下降趋势。 8周～ 10周后 ,19例患者肝功能恢复正常 ,6例接近正常 ,换药前后比较差异有显著性 ,P <0 0 5。肾功能 (血清Cr、BUN)换药前后比较差异无显著性 ,P >0 0 5。以上病例继续随访 3个月～ 6个月 ,肝功能、肾功能全部维持正常。结论 :对CsA引起肝功能损害的尸肾移植患者应用FK5 0 6替换治疗是安全有效的。     

肾移植受者神经精神损害影响因素分析

目的 初步探讨肾移植受者（ＲＴＲ）神经精神损害（ＮＰＤ）的影响因素及其发病机制。方法 对２０５例ＲＴＲ的临床资料进行回顾性分析。结果 本组病例的ＮＰＤ发生率为３８％,类型包括：脑脓肿、昏迷、颅神经损害、抽动、肌无力、脊神经损害、神经衰弱症状群、精神症状和震颤。排斥反应、高血压、肝损害、医院感染、ＣｓＡ中毒和应用大剂量甲基泼尼松为本组ＮＰＤ的主要影响因素（Ｐ〈０．０１）;旨血症、高尿酸血症、高血糖、     

移植肾功能延迟恢复的临床研究

目的 探讨肾移植术后移植肾功能延迟恢复(DGF)的病因及诊治方法.方法 回顾性分析15例肾移植术后DGF患者的临床资料及诊治过程.15例DGF的病因不同,在血液透析的基础上,分别给予急性排斥反应冲击治疗、调整免疫抑制剂,近期移植肾切除后再次原位移植等方法进行治疗.结果 15例患者术后发生急性排斥8例;急性肾小管坏死5例;移植肾静脉血栓1例;环孢素A肾毒性1例,所有患者经治疗.肾功能在术后10～35 d恢复正常.随访0.5～3年,无并发症发生.结论 DGF是肾移植术后常见并发症之一,主要原因是急性排斥和急性肾小管坏死,区别不同原因采用相应治疗,可获得满意疗效.     

Hepatitis B surface antigenemia in renal transplant recipients. Increased mortality risk.

To determine effects of circulating hepatitis B surface antigen (HBsAg) on patient survival following renal transplantation, we studied 168 recipients of cadaveric grafts in whom HBsAg status was defined at transplantation by comparison of survivorships determined by actuarial life-table methods. Survival in HBsAg-positive recipients, as compared with those who were HBsAg-negative at the time of transplantation, was markedly diminished. Although graft survival appeared to be favored in the HBsAg-positive group in the early posttransplant period, the apparent protective effect was lost at nine months after grafting and thereafter, due to increased mortality in the HBsAg-positive recipients. Deaths in the antigenemic subjects were principally due to infections other than hepatitis and to cardiovascular events. We conclude that preexisting HBs antigenemia forebodes an ominous outcome for immunosuppressed renal transplant recipients, although hepatic disorders do not account for most deaths.     

环孢霉素A在眼科应用中的研究分析

目的探讨环孢霉素A在眼科中的应用,以供临床参考。方法分析环孢霉素A在眼科干眼病、防止翼状胬肉复发、角膜移植以及带状疱疹引起的角膜炎的应用效果,对环孢霉素A进行研究,总结其药物应用。结果环孢霉素A在眼科干眼病、防止翼状胬肉复发、角膜移植以及带状疱疹引起的角膜炎的应用效果均较为显著,患者不良反应较少,疗效较好,安全性较高。临床应用时可采用滴眼液、脂质体、眼膏等制剂。结论环孢霉素A在眼科中的应用范围较为广泛,如何研制新的载体材料,减少其毒副作用,是该药物研究的方向。     

多模式部分肝移植关键技术及其临床应用

针对目前全世界肝脏移植的瓶颈问题——供肝匮乏,课题组提出了一种新的肝移植方式——部分肝移植,取得了一系列原创性成果。与国内外同类研究比较,主要有以下发现和创新点:①确立了对移植物的选择标准和右半肝移植物静脉回流的重建方式;②比较了带或不带肝中静脉的右半肝移植物的活体肝移植的术后结果,确定了带肝中静脉的右半肝移植物的安全性和必要性;③首次在国内开展劈离式肝移植治疗终末期肝病患者,并保持国内单中心最大病例数;④首次在国内开展不同血型两供一受活体肝移植并获成功,该手术方式为受体提供了更大重量的肝脏,最大限度地保证了供体的安全;⑤在国际上率先报道了中国肝移植人群免疫抑制剂霉酚酸药代动力学变化规律,首次建立了霉酚酸完全暴露的简化计算公式,并首次比较了活体肝移植和全肝移植霉酚酸药代动力学的差异。该研究成果获2010年国家科技进步二等奖。     

肾移植术后感染新型冠状病毒1例

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient’s symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.