长期环孢菌素治疗与阿霉素有关的神经症状和昏迷

预防移植物排斥反应,长期使用环孢菌素(CsA)主要的副作用是肾毒性和高血压。据新的可靠证据,其毒性效应的主要靶位是血管的内皮细胞。作者在心脏移植病人长期     

2例心脏原位移植术后环孢素A浓度的监测

心脏移植（ｈｅａｒｔ ｔｒａｎｓｐｌａｎｔａｔｉｏｎ）是治疗终末期心脏病的一种重要疗法,自１９６７年南非Ｂａｒｎａｒｄ首次成功地进行了同种原位心脏移植术以来［１］,８０年代由于环孢素Ａ（ｃｉｃｌｏｓｐｏｒｉｎ Ａ）的问世［２］、心内膜心肌活检技术的应用、供心保存方法的改进,心脏移植的存活率显著提高。正确地进行免疫抑制治疗是关系到心脏移植受者术后能否长期存活的关键因素,而环孢素Ａ药物动力学个体差异大,不良反应明显,故监测环孢素Ａ的血药浓度对于指导临床免疫抑制剂的合理使用,减少急性排斥反应发生具有重要…     

原位心脏移植中免疫抑制剂的应用及环孢素A血药浓度监测

心脏移植是治疗终末期心脏病的一种主要疗法,急、慢 性排斥反应仍然是目前引起移植物功能丧失的主要原因, 正确地进行免疫抑制治疗是关系到移植受者术后存活的关 键因素。作者于1997年8月进行了1例心脏移植。现将有 关资料及环孢素A(CsA)分析结果作一报道。 1 临床资料 1.1 病例选择 1例男性患者,20岁,体重55kg。术前诊断为扩张型心 肌病,心功能Ⅲ～IV级,于1997年8月20日在全麻体外循 环下施行原位心脏移植。术后病人一般情况良好,生活可以     

颗粒酶在心脏移植急性排斥反应中的作用

心脏移植是治疗终末期心脏病的有效方法,虽然已有多种免疫抑制剂广泛应用于临床,但心脏移植的术后并发症主要仍是排斥反应,其中最常见的是急性排斥反应。     

心肌炎

心肌炎,尤其是病毒性心肌炎现已引起人们重视。以前在这方面只是少数基础研究者或临床医师所从事的工作,但以斯坦福大学为中心的心脏移植研究小组曾报告,在通过心内膜心肌活检确诊的心肌炎,使用治疗移植心脏的异体排斥反应的免疫抑制疗法,可使病理和临床表现改善。自从这项研究     

IL-10可防止器官移植排斥

美国亚拉巴马大学和佛罗里达大学的研究人员报告,能阻止血管情况恶化的白细胞介素10(IL-10)的生物学途径可使器官移植物排斥延迟多年。IL-10具有抗炎、免疫抑制和其他有助于保持血管正常的特性。慢性血管排斥是实体器官移植物丧失功能的主要原因。本次在大鼠模型中的研究还表明,一次肌肉注射由基因送递载体携带的IL-10能提供长期治疗作用。研究人员发现,IL-10是通过细胞间的血红素加氧酶依赖性(HO-1)生物学途径起作用的。这种1次注射方法的关键在于使用腺病毒相关病毒作为把IL-10送入体内的方式,可使IL-10持久地分泌到血流中。IL-10…     

再生障碍性贫血患者免疫抑制治疗对免疫T细胞亚群和血清因子水平的影响

目的：探讨再生障碍性贫血患者免疫抑制治疗的疗效及对免疫T细胞亚群和血清因子水平的影响。方法将200例再生障碍性贫血患者随机分为试验组和对照组各100例。所有患者给予基础治疗和密切护理,试验组联合免疫抑制治疗,对照组仅给予常规治疗。治疗半年后评价2组临床疗效,并检测患者免疫T细胞亚群和血清因子水平影响变化。结果试验组临床疗效高于对照组,CD3^＋、CD4^＋细胞数、CD4^＋／CD8^＋比值和sFas水平较对照组高, CD8^＋细胞数及IL－2、TNF－α、INF－γ水平较对照组低,差异均有统计学意义（P＜0．05）。结论再生障碍性贫血免疫抑制治疗疗效显著,促使患者免疫T细胞亚群和血清因子趋向于正常水平。     

2例原位心脏移植手术成功的体会

为总结同种异体原位心脏移植的治疗体会,对2例终末期扩张型心肌病患者进行心脏移植,采用双腔静脉吻合法。供体为急性脑死亡者,供心保护用4℃HTK液。供体与受体配置为受体群体反应性抗体(PRA)<10%,ABO血型符合输血原则。免疫抑制治疗采用赛尼哌(Daclizumab)诱导加环孢素A、霉酚酸酯、泼尼松三联方案。结果2例术后恢复顺利,未发生超急性或急性排斥反应,心、肾功能恢复正常,无感染发生,术后3周出院。结论:严格掌握手术适应证和有效心肌保护是心脏移植成功的关键。     

苏木药理作用研究进展

苏木(Caesalpinia sappan L.CAE)是我国的传统中药,为豆科云实属植物的干燥心材,有行血祛瘀,消肿止痛之功效.临床药理作用包括抗肿瘤、免疫抑制、抗心脏移植排斥反应、抗菌消炎、抗氧化作用,对心血管、中枢神经系统及降糖作用等.本文就近年来在苏木药理作用方面的研究成果作一综述.     

FDA批准普乐可复用于心脏移植受体患者

FDA于3月31日批准Astellas公司的普乐可复（Prograf）作为免疫抑制剂用于心脏移植受体患者以防止器官排斥反应的发生。这是Prograf获得FDA审批的第三个器官移植指征，Prograf现在被用于接受了肾脏或者肝脏移植手术的大部分患者的基本治疗。这一用于心脏移植受体的新指征对于Astellas公司来说是具有里程碑式的意义。     

Treatment of allograft vasculopathy in heart transplantation

Cardiac allograft vasculopathy remains one of the main causes of morbidity and mortality after heart transplantation, although its impact is becoming somewhat smaller as prophylactic measures are implemented. Advances in the understanding of the molecular and cellular mechanisms involved in the genesis and development of cardiac allograft vasculopathy are opening ways for new diagnostic and therapeutic strategies. Successful prophylaxis of the early stages of the disease has been demonstrated with the use of newer immunosuppressive agents, such as sirolimus and everolimus, that will probably be included in future protocols. For most patients with established cardiac allograft vasculopathy, currently available revascularisation methods and retransplantation are not appropriate options. Antiproliferative agents could provide significant improvement in terms of symptom relief and prognosis, but their definite value must be proven in well-designed trials.     

Treatment of allograft vasculopathy in heart transplantation

Cardiac allograft vasculopathy remains one of the main causes of morbidity and mortality after heart transplantation, although its impact is becoming somewhat smaller as prophylactic measures are implemented. Advances in the understanding of the molecular and cellular mechanisms involved in the genesis and development of cardiac allograft vasculopathy are opening ways for new diagnostic and therapeutic strategies. Successful prophylaxis of the early stages of the disease has been demonstrated with the use of newer immunosuppressive agents, such as sirolimus and everolimus, that will probably be included in future protocols. For most patients with established cardiac allograft vasculopathy, currently available revascularisation methods and retransplantation are not appropriate options. Antiproliferative agents could provide significant improvement in terms of symptom relief and prognosis, but their definite value must be proven in well-designed trials.     

Immunosuppression for lung transplantation: evidence to date

With the introduction of ciclosporin (cyclosporine) into routine clinical practice 20 years ago, lung transplantation has become an established treatment for patients with advanced lung disease. Most lung transplant recipients routinely continue to receive a triple-drug maintenance immunosuppressive regimen consisting of a calcineurin inhibitor, an antimetabolite and corticosteroids. The use of antibody-based induction therapy remains common, although there has been a shift away from T cell-depleting agents, such as antithymocyte globulin, towards anti-interleukin-2 receptor monoclonal antibodies. Recent years have seen the introduction of sirolimus and everolimus, immunosuppressive drugs that act by blocking growth factor-driven cell proliferation. While the newer immunosuppressive drugs have been rigorously evaluated in large randomised trials in kidney, liver and cardiac transplantation, such studies are lacking in lung transplantation. Despite a shift towards more potent immunosuppressive regimens that incorporate tacrolimus and mycophenolate mofetil, the development of chronic allograft rejection, as manifested by the bronchiolitis obliterans syndrome continues to negatively impact on the long-term survival of lung transplant recipients. This article reviews the evidence for the immunosuppressive regimens used during induction and maintenance of patients undergoing lung transplantation, and discusses current strategies in the management of chronic rejection.     

Everolimus: a proliferation signal inhibitor targeting primary causes of allograft dysfunction

Allograft dysfunction remains a major problem for long-term graft survival after kidney and heart transplantation. Current immunosuppressive regimens do not completely address the causes of allograft dysfunction which include acute rejection episodes, complications of immunodeficiency (for example, cytomegalovirus infection), nephrotoxicity from calcineurin inhibitors (cyclosporine and tacrolimus) and vascular remodeling and vasculopathy. Everolimus is a potent immunosuppressor that inhibits growth factor-stimulated proliferation of hematopoietic and nonhematopoietic cells, including vascular smooth muscle. Everolimus is indicated for the prophylaxis of acute rejection in kidney and heart transplant patients in a combined regimen with cyclosporine microemulsion and corticosteroids. Everolimus is formulated as both a tablet and a tablet for oral solution. It is rapidly absorbed and displays dose-proportional, stable pharmacokinetics. Everolimus has equivalent efficacy to mycophenolate mofetil in reducing the incidence of acute rejection after renal transplantation and superior efficacy to azathioprine after heart transplantation. Combination of everolimus with cyclosporine allows dose-reduction of cyclosporine while maintaining efficacy due to the synergistic immunosuppressive effects of the combination. Everolimus reduces intimal thickening of blood vessels to the graft and the incidence of allograft vasculopathy in heart transplantation. In both kidney and heart transplantation, the incidence of cytomegalovirus infection was lower in everolimus-treated patients compared with patients receiving the control treatment. Everolimus-related adverse events include elevated cholesterol and triglycerides, which respond to treatment, and decreased platelet count, which is transient. Nephrotoxicity may result from the combination of everolimus with full-dose cyclosporine but is mitigated by reducing the dose of cyclosporine. Everolimus is initiated at 0.75 mg b.i.d. with dose adjustments guided by therapeutic drug monitoring of predose blood levels. In clinical development trials, everolimus has demonstrated the ability to reduce the incidence of acute rejection episodes, cytomegalovirus infection and cardiac vasculopathy, thus addressing the primary causes of allograft dysfunction.     

Everolimus: an immunosuppressive agent in transplantation

Everolimus is a novel immunosuppressive agent related to sirolimus. It is a proliferation signal inhibitor with an improved pharmacokinetic profile and bioavailability compared with sirolimus. Everolimus has been shown to be as effective as mycophenolate mofetil in reducing acute rejection in renal transplantation. In cardiac transplant recipients, it is superior to azathioprine in reducing acute rejection and cardiac allograft vasculopathy. Its use is also associated with a decrease in cytomegalovirus infection. However, coadministration with calcineurin inhibitors requires careful dose adjustment to prevent renal toxicity. Antiproliferative effects of everolimus may abrogate the increased risk of malignancy seen in solid organ transplantation.     

Everolimus: an immunosuppressive agent in transplantation

Everolimus is a novel immunosuppressive agent related to sirolimus. It is a proliferation signal inhibitor with an improved pharmacokinetic profile and bioavailability compared with sirolimus. Everolimus has been shown to be as effective as mycophenolate mofetil in reducing acute rejection in renal transplantation. In cardiac transplant recipients, it is superior to azathioprine in reducing acute rejection and cardiac allograft vasculopathy. Its use is also associated with a decrease in cytomegalovirus infection. However, coadministration with calcineurin inhibitors requires careful dose adjustment to prevent renal toxicity. Antiproliferative effects of everolimus may abrogate the increased risk of malignancy seen in solid organ transplantation.     

Immunopharmacologic Therapy in Renal Transplantation

The long-term kidney allograft survival rate is still far from optimum. Conventional immunosuppressive drugs used to prevent allograft rejection are associated with significant side effects. Moreover, withdrawal of these agents is often associated with graft loss due to rejection. No treatment is available for chronic rejection. Graft tolerance is difficult to achieve in humans, and therefore a continued goal in organ transplantation is to develop immunosuppressive regimens that are associated with fewer side effects and decreased rates of rejection, and that promote graft tolerance. The advent of newer pharmacologic agents and bioreagents is expected to improve patient and graft survival rates.     

Immunosuppressive strategies and management

<正>Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival.However,chronic allograft failure,antibody mediated rejection,recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life.New immunosuppressive agents and protocols are being evaluated to combat these problems.Importantly, clinicians must work to manage post-transplant complications and avoid complex medication regimens,which will potentiate drug interactions and non-compliance.     

Immunosuppressive therapy in older cardiac transplant patients

Cardiac transplantation has become an established intervention for end-stage heart disease. Clinical outcomes in older cardiac transplant patients have improved over the last decade and are almost similar to those in younger patients. Nevertheless, morbidity and mortality due to infections, cancer and chronic allograft vasculopathy remain problematic. On the other hand, older transplant patients seem to have lower incidences of acute rejection episodes than younger patients. Conventional immunosuppression with calcineurin-inhibiting drugs, azathioprine and corticosteroids is responsible for a number of adverse effects. Although these adverse effects can also be seen in younger patients, tolerance to these agents seems to decrease with increasing age. In particular, diabetes mellitus, osteoporosis and chronic renal insufficiency are associated with higher morbidity and mortality in older cardiac transplant patients. As the elderly become an ever-increasing segment of the cardiac transplant population, new and innovative immunosuppressive strategies will have to be developed and applied.Currently, the availability of new immunosuppressive drugs means more individualised immunosuppressive protocols can be used. New antibodies for induction therapy, a choice between ciclosporin and tacrolimus, and the advent of mycophenolate mofetil as well as proliferation signal inhibitors (everolimus, sirolimus) have changed immunosuppressive protocols dramatically. Therefore, a generalised protocol for all patients has been replaced by individualised immunosuppression depending on the patient group. Moreover, protocols can be modified during follow-up depending on the individual patient's requirements and problems. Hypertension and hyperlipidaemia could be influenced by the selection of tacrolimus over ciclosporin, and weaning of corticosteroids might have a positive impact on osteoporosis or diabetes. There is also no clear evidence that tacrolimus is associated with a higher risk for new onset of diabetes. Chronic renal insufficiency can be managed with calcineurin inhibitor-free immunosuppression consisting of mycophenolate mofetil and proliferation signal inhibitors. Both everolimus and sirolimus also seem to have a protective effect against the onset of graft vasculopathy and some sorts of cancer after cardiac transplantation. As a general rule, however, older cardiac transplant patients should be treated with lower doses and fewer immunosuppressive drugs to avoid over-immunosuppression.     

Prevention and treatment of severe hemodynamic compromise in pediatric heart transplant patients

Allograft rejection is a leading cause of severe hemodynamic compromise in pediatric heart transplant patients. A triple-drug immunosuppression regimen, which includes a calcineurin inhibitor, antiproliferative agent, and corticosteroid, suppresses the immune system at multiple different levels for optimal graft protection while minimizing the adverse effects of any one particular agent. Some pediatric centers also use induction therapy with anti-T cell antibodies immediately following transplantation as additional rejection prophylaxis. These antibodies augment immunosuppression by either depleting the T cell pool or blocking interleukin-2 receptors on activated T cells. Despite the aggressive preventive measures outlined above, some pediatric heart transplant patients will develop severe hemodynamic compromise, most commonly due to fulminant rejection. Such patients require attention to, and optimization of, the four determinants of cardiac output (heart rate, preload, contractility and afterload) to stabilize the circulation until the rejection can be reversed. Careful administration of volume, diuretics, inotropes, and afterload-reducing agents will meet this goal. Patients with allograft rejection require augmentation of immune suppression to facilitate myocardial recovery. Corticosteroids form the cornerstone of treatment for both cellular and vascular rejection. In patients with refractory cellular rejection, conversion to mycophenolate mofetil or tacrolimus may be appropriate if these agents are not already being used for maintenance immunosuppression. Critically ill patients may additionally benefit from muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed specifically for humoral rejection is prescribed with the intention of suppressing new antibody formation, removing circulating antibody, and improving coronary blood flow. In addition to corticosteroids, cyclophosphamide and antithymocyte globulin or muromonab-CD3, along with plasmapheresis, may improve survival. Systemic heparinization should be considered to minimize coronary thrombosis in patients with humoral rejection. In the future, novel immunosuppressive agents may further assist in the prevention as well as treatment of severe hemodynamic compromise due to rejection in pediatric heart transplant recipients.