Apheresis in thoracic organ transplantation.

The beneficial addition of cyclosporine and tacrolimus to the immunosuppressive armamentarium have unfortunately only partially solved the problems of acute and chronic rejection in thoracic organ transplantation. Apheresis techniques offer creative avenues for modifications of allograft rejection. Plasmapheresis can be used for mechanical reduction of alloantibody burdens in highly sensitized patients and permit transplantation in an otherwise almost hopeless situation and can also be used on a short-term basis for the treatment of acute humoral rejection. Extracorporeal photochemotherapy holds promise as a possibly synergistic adjunct to conventional therapy and may even reduce the severity of graft vasculopathy. The increasing availability of highly specific column immunoadsorption techniques may further increase the applicability of apheresis in transplantation.     

Eosinophilic myocarditis in patients awaiting heart transplantation

OBJECTIVE: To determine the possible causative agents of eosinophilic or hypersensitivity myocarditis in patients awaiting heart transplantation. DESIGN: Consecutive patient series. SETTING: Large university-affiliated hospital. PATIENTS: A total of 190 consecutive patients who had heart transplantation at our center. INTERVENTIONS: The myocardium of the explanted heart was examined for a mixed inflammatory cell infiltrate containing an identifiable component of eosinophils. The relative quantity of each cell type was evaluated by a semiquantitative grading system (scored 0 to 3). The clinical findings and medications were reviewed, and patients were followed after heart transplantation. MEASUREMENTS AND MAIN RESULTS: Eosinophilic myocarditis (EM) was found in the explanted heart in 14 patients (7.4%). Myocardial infiltration by eosinophils ranged from mild (n = 6), often focal involvement to marked (n = 8), usually multifocal or widespread involvement. Twelve patients (86%) had peripheral blood eosinophilia before transplant, and in ten (71%), the eosinophil count at least doubled. Loop or thiazide diuretics were used in all 14 patients, and angiotensin-converting enzyme inhibitors were used in 12. Preoperative characteristics were similar in patients with and without EM, except for a higher frequency of inotropic support and assist devices in EM patients. Dobutamine was used in 12 (86%) and dopamine in seven (50%; one with dopamine alone), and one patient (7%) received neither dopamine nor dobutamine. In two patients receiving dobutamine and one receiving dopamine, tapering or discontinuation of the inotropic infusion resulted in a significant diminution of the peripheral eosinophilia and the EM before transplantation. Postoperative survival in patients with and without EM was similar at 8 yrs (50% +/- 13% and 54% +/- 4%, p =.34). No patient in this study has had EM on biopsy after transplant. CONCLUSIONS: EM is a complication of multiple drug therapy in patients awaiting heart transplantation, and should be suspected when peripheral blood eosinophilia is present or the eosinophil count increases by at least two-fold. EM may be related to intravenous inotropic therapy, and this is the first study to document improvement in myocardial pathology after inotropic drug withdrawal. Hypersensitivity to thiazide and loop diuretics, angiotensin-converting enzyme inhibitors, and antibiotics must also be considered. Survival after heart transplantation is not impaired, and postoperative steroid therapy may prevent EM.     

Health related quality of life in patients awaiting heart transplantation

Quality of life is an important outcome measure in patients with end-stage heart failure waiting for heart transplantation. The purpose of this study was to investigate the relationship between aspects of quality of life and physiological and psychosocial variables in patients with end-stage heart failure. A total of 123 patients participated in the study. The functional status was assessed with New York Heart Association (NYHA) functional classification, a 6-minute walk test (6 MWT) and peak oxygen uptake (pVO(2)). Health related quality of life (HRQOL) was measured with Medical Outcomes Study, 36-item Short Form Survey (SF-36), and Minnesota Living with Heart Failure Questionnaire (MLHFQ). Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) were used to assess psychological symptoms. A significant relationship was found between HRQOL (SF-36 and MLHFQ) and functional status (NYHA, 6 MWT and pVO(2)) (p < 0.05). Psychological symptoms (BDI) were associated with HRQOL (p < 0.05). In addition to clinical derangements, functional limitation and psychological distress can lead to limitations in activities of daily life through impairment of quality of life. It would be helpful to evaluate psychological symptoms and quality of life in patients with end-stage heart failure besides routine clinical evaluations.     

Selection of patients for kidney organ transplantation.

Renal transplantation is a viable alternative for most patients with end-stage renal disease, either before or after the institution of dialysis. Evaluation of potential recipients is necessary before transplantation and is mandatory to exclude patients who are likely to have a poor outcome. Such evaluation also may identify special problems and conditions in patients with end-stage renal disease who will require intervention before transplantation. Identification and evaluation of each transplant donor is also very important. Although organs from related living donors usually have better long-term function, survival, and fewer complications, most efforts in the transplantation community are spent attempting to extend the survival of cadaver kidney transplants. This goal could be accomplished by increasing availability of cadaver organs, improving histocompatibility of donor-recipient pairs, and improving available immunosuppressive therapy.     

Management of patients with preformed reactive antibodies who are awaiting cardiac transplantation.

Patients with elevated levels of preformed reactive antibodies to HLA antigens have higher rates of organ rejection than do patients without such antibodies. Consequently, before proceeding with transplantation, many medical centers do prospective cross-matching, that is, mix lymphocytes from the organ donor with sera from the prospective organ recipient, to determine whether a higher rejection rate or an immediate episode of rejection will occur. The problem has been compounded by the increased frequency of preformed reactive antibodies in patients with ventricular assist devices who are awaiting cardiac transplantation. Performing a prospective cross-match can be time-consuming and often is impossible because of the unstable condition of the organ donor or travel logistics, leading to increased costs for transplantation and longer waiting times for recipients. A variety of treatments are used in cardiac transplantation programs in attempts to reduce the concentration of preformed reactive antibodies. Each of these treatments has accompanying complications and considerations for the transplant team. Each treatment must also be assessed for therapeutic response. Options for managing patients with preformed antibodies and a case report are presented.     

Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation

Objective: To determine the pharmacokinetics and pharmacodynamics of the neuromoscular blocking agent atracurium besylate in patients with fulminant hepatic failure (FHF).Design: Open study of patients receiving atracurium infusions to facilitate mechanical ventilation.Setting: Intensive care unit in a tertiary referral university teaching hospital.Patients: Ten encephalopathic patients with FHF reuiring mechanical ventilation while awaiting orthotopic liver transplantation. Three patients died before transplantation could be performed, three died after transplantation, and four survived following successful transplantation.Methods: Plasma, urine and dialysate fluid were analysed for atracurium and its metabolites using HPLC. Neuromuscular blockade was measured using transcutmeous ulnar nerve stimulation and an accelerometer. Electroencephalography and liver function tests were performed daily.Results: Patients received atracurium infusions for a period ranging from 38 to 217 h. Six patients required continuous arteriovenous haemodiafiltration (CAVHD) to replace renal function. Atracurium mean steady state clearence was 8.6 ml/min/kg, and train-of-four recovery ratio, to 75% took 63 min (range 32–108). Laudanosine clearance was markedly reduced in the non-survivors; the half-life was 38.5 hrs compared with 5.3 h in the 4 patients who underwent successful transplantation. Laudanosine accumulation could be observed in all patients before transplantation, but kinetics returned to normal after successful transplantation. The highest laudanosine level recorded was 6,860 ng/ml. There was no evidence of adverse central neurological effects attributable to laudanosine. CAVHD did not contribute significantly to clearance of atracurium or its metabolites.Conclusions: Atracurium kinetics and dynamics are nearnormal even in patients with fulminant hepatic failure and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantation of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment.     

肝移植术前等待患者的死亡原因分析

目的 调查分析住院等待肝移植患者的死亡原因,为加强肝移植术前等待患者的管理提供方向和依据.方法 回顾性分析我院2003年1月-2007年6月住院等待肝移植手术期间死亡的63例患者等待时间、治疗过程和死亡原因.结果 63例患者的平均住院等待时间为(32.53±17.21)d,重症加强治疗病房(ICU)住院时间为(12.75±9.77)d.等待期间上消化道出血、意识障碍、感染的发生率分别为47.62%、39.68%和74.60%.主要死因感染性休克和感染性多器官功能衰竭(MOF)以及曲张静脉破裂出血的病死率分别为39.68%和26.98%.血液净化治疗对肝性脑病治疗有效.结论 当前肝移植术前等待住院患者的主要死亡原因是感染和致命性上消化道出血.     

Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation

Objective: To determine the pharmacokinetics and pharmacodynamics of the neuromoscular blocking agent atracurium besylate in patients with fulminant hepatic failure (FHF). Design: Open study of patients receiving atracurium infusions to facilitate mechanical ventilation.     

预致敏受者尸体肾移植术后的急性排斥反应

目的：预致敏肾移植受者的增加已是目前肾移植成功的重大影响因素。观察人类白细胞抗原氨基酸残基配型及新型免疫抑制剂治疗方案对预致敏患者肾移植术后急性排斥反应的治疗效应，寻找提高移植物存活率的最佳方案。方法：选择2003—01／2005—08在首都医科大学附属北京友谊医院行肾移植手术的患者396例，患者均知情同意。分组：①预致敏组（n=32）：即术前致敏患者。采用诱导治疗（抗淋巴细胞球蛋白100mg／d，3～7d）＋三联免疫抑制剂维持治疗方案（他克莫司＋霉酚酸酯＋激素）。②对照组（n=364）：未致敏患者。采用三联免疫抑制剂维持用药方案。比较两组患者肾移植术后6个月内急性排斥反应发生率、移植肾功能延迟恢复发生率及移植肾，患者1年存活率，同时分析人类白细胞抗原氨基酸残基配型对移植肾急性排斥反应的影响。结果：396例患者全部进入结果分析。①两组患者肾移植术后急性排斥反应发生率差异无显著性意义（P〉0．05）。预致敏组患者移植肾功能延迟恢复发生率显著高于对照组（P〈0．01）。②两组患者1年存活率差异无显著性意义（P〉0．05）。预致敏组患者1年移植肾存活率低于对照组（P〈0．05），如果去除患者死亡因素的影响，两组患者1年移植肾存活率差异无显著性意义（P〉0．05）。③预致敏组患者人类白细胞抗原氨基酸残基相配率高于对照组（P〈0．05）。预致敏组中氨基酸残基配型3-4错配患者的急性排斥反应发生率显著高于0-2错配患者（P〈0．01），高度致敏患者（移植术前群体反应抗体〉50％）急性排斥反应发生率显著高于低度致敏患者（群体反应抗体10％-20％）（P〈0．01）。结论：供受者之间良好的人类白细胞抗原氨基酸残基分型及采用新型免疫抑制药物治疗方案，对预防及减轻致敏患者移植术后急性排斥反应疗效确切，并可以缩短致敏患者等待移植手术的时间。     

Safety and efficacy of preoperative donation of blood for autologous use by patients with end-stage heart or lung disease who are awaiting organ transplantation

Many patients are, perhaps inappropriately, denied the benefits of autologous blood transfusion, because they are thought to be too ill to donate blood safely. The safety and efficacy of autologous blood donation by selected patients with end-stage heart or lung disease who are awaiting organ transplantation were studied to determine if even these critically ill patients could be suitable candidates for autologous blood donation. Seventy-two adults awaiting heart or lung transplantation were evaluated for autologous blood donation in a hospital-based blood collection facility. Phlebotomy was performed if the patient met the required medical eligibility protocol, and if he or she consented to participate. Units of blood were separated into packed red cells and plasma and stored in a frozen state. Of 48 heart transplant candidates, 31 (65%) were each able to donate 1 to 8 units of blood. The median number of exposures to allogeneic components was 1 for patients who donated and 7 for nondonors (p = 0.0141). Among patients who donated, 54 percent required allogeneic components, as compared to 88 percent of nondonors (p = 0.0968). Of 24 lung transplant candidates, 15 (63%) made 1 to 6 donations each. The median number of exposures to allogeneic components was 0 for donors and 2 for nondonors (p = 0.1871), but only 45 percent of donors required allogeneic components, as compared to 100 percent of nondonors (p = 0.0418). No serious complications during or following phlebotomy were observed. It is concluded that autologous blood donation by patients with end-stage heart or lung disease may be safe.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current problems in organ transplantation.

Organ transplantation has evolved over the past 30 years, although 'new' and 'old' problems remain unsolved, which from a personal point of view, might be summarized as: i) the transfusion effect; ii) HLA matching and pre-graft sensitization of the potential recipient; iii) immunosuppressive drugs; iv) the pathogenesis of chronic rejection; v) infections; vi) de novo cancers. The aim is to attain a state of specific immunological tolerance without the use of immunosuppressive drugs.     

静脉滴注免疫球蛋白对肾移植患者群体反应抗体的影响(英文)

背景:很多方法可降低群体反应抗体致敏患者的群体反应抗体水平,其中血浆置换或免疫吸附法脱敏法是比较常用的,但这些方法副作用较多。目的:拟观察肾移植前静脉滴注免疫球蛋白对肾移植患者血清群体反应抗体的影响。设计、时间及地点:以2003-01/2006-11重庆医科大学附属第一医院肾移植中心的57例等待肾移植的群体反应抗体致敏患者为对象的前后对照,病例分析。对象:群体反应抗体致敏患者57例,年龄21～65岁,群体反应抗体值平均(46.7±29.5)%。方法:所有患者在接受肾移植前以5g/d剂量静脉滴注免疫球蛋白,2周为1个疗程。2个疗程之间间隔1周。在给予静脉滴注免疫球蛋白前和疗程结束立即应用酶联免疫吸附反应方法各检测1次血清群体反应抗体水平。主要观察指标:血清群体反应抗体水平。结果:应用免疫球蛋白后群体反应抗体降为非致敏84%(48/57),完全未降5%(3/57),部分下降11%(6/57)。用药后群体反应抗体下降0～61%,平均(38.4±16.3)%。57例患者肾脏移植前淋巴细胞毒试验<10%,均未出现超急性排斥反应。结论:静脉滴注免疫球蛋白预治疗是理想的降低肾移植致敏性的方法,且副作用小。     

等待肺移植患者生存质量及其相关影响因素的调查

目的调查等待肺移植患者生存质量及其相关因素,为制订提高等待肺移植患者生存质量的措施提供理论依据。方法采用简明健康问卷(short form36health survey questionnaires,SF-36)、焦虑自评量表(self-rating anxiety scale,SAS)、抑郁自评量表(self-ratingdepression Scale,SDS)和领悟社会支持量表(perceiving social support scale,PSSS)对55例等待肺移植患者进行调查。采用Stepwise法对影响等待肺移植患者生存质量的相关因素进行分析。结果等待肺移植患者SF-36各维度得分为(23.18±37.53)-(74.57±26.02)分,低于常模(均P<0.001);SAS及SDS得分分别为(48.09±9.06)分及(52.18±9.98)分,高于常模(均P<0.01);PSSS社会总支持因子得分为(5.56±1.04)分,家庭内支持因子得分高于家庭外支持因子(P<0.05)。呼吸困难和抑郁是影响患者生存质量的主要因素。结论等待肺移植患者的生存质量较低,其生存质量受多种因素的影响,呼吸困难和抑郁是其主要影响因素。因此,医护人员应从患者的生理及心理方面进行有效的干预,以提高患者的生存质量。     

Telephone-adapted Mindfulness-based Stress Reduction (tMBSR) for patients awaiting kidney transplantation

BackgroundPatients with progressive kidney disease experience increasing physiologic and psychosocial stressors and declining health-related quality of life (HRQOL).MethodsWe conducted a randomized, active-controlled, open-label trial to test whether a Mindfulness-based Stress Reduction (MBSR) program delivered in a novel workshop-teleconference format would reduce symptoms and improve HRQOL in patients awaiting kidney transplantation. Sixty-three transplant candidates were randomized to one of two arms: i) telephone-adapted MBSR (tMBSR, an 8-week program of meditation and yoga); or ii) a telephone-based support group (tSupport). Participants completed self-report questionnaires at baseline, post-intervention, and after 6-months. Anxiety, measured by the State-Trait Anxiety Inventory (STAI) post-intervention served as the primary outcome. Secondary outcomes included: depression, sleep quality, pain, fatigue, and HRQOL assessed by SF-12 Physical and Mental Component Summaries (PCS, MCS).Results55 patients (age 54 ± 12 yrs) attended their assigned program (tMBSR, n = 27; tSupport, n = 28). 49% of patients had elevated anxiety at baseline. Changes in anxiety were small and did not differ by treatment group post-intervention or at follow-up. However, tMBSR significantly improved mental HRQOL at follow-up: + 6.2 points on the MCS - twice the minimum clinically important difference (95% CI: 1.66 to 10.8, P = 0.01). A large percentage of tMBSR participants (≥ 90%) practiced mindfulness and reported it helpful for stress management.ConclusionsNeither mindfulness training nor a support group resulted in clinically meaningful reductions in anxiety. In contrast, finding that tMBSR was more effective than tSupport for bolstering mental HRQOL during the wait for a kidney transplant is encouraging and warrants further investigation.ClinicalTrials.gov NCT01254214.     

Expectations and outcomes in organ transplantation.

Research is needed on the frequency of bad outcomes in transplantation. Allocation policies and professional or institutional self-interest may affect the incidence of bad outcomes, and the need for reform is stressed. Transplant recipients who have had a bad outcome often continue to receive aggressive care. The humanistic care of patients having bad outcomes requires attention to advance directives, discussion with patient and family of alternatives to aggressive treatment, and provision of an option for home hospice care. Finally, it must be reemphasized that the average typical good outcome is extraordinarily good, restoring function of a vital organ, extending and improving quality of life, and sometimes restoring near-normal health. In no way should the fact of bad outcomes reduce our commitment to producing good outcomes.     

肺移植手术等待期间患者心理状态及护理干预的研究进展

<正>国外肺移植术发展的主要障碍是供体严重短缺,美国大多数肺移植中心登记等待肺移植的时间是18-24个月[1],荷兰公布的术前等待期平均为468d,据加拿大安大略省的资料显示,由于供体短缺,每年有20%-25%的患者在等待中死亡[2-3]。     

Critical decisions in selecting an intravenous immunoglobulin product.

Use of intravenous immunoglobulin (IVIG) therapy has expanded enormously in the past two to three decades, targeting a large number of autoimmune and inflammatory disorders as well as primary immunodeficiency disease, human immunodeficiency virus, and Kawasaki disease. Increased use, particularly at higher doses and in older patients, has presented certain challenges related to safety and tolerability. All IVIGs are not the same. They differ in manufacturing processes, methods of virus elimination, and final composition. Carefully evaluating patient risk factors and matching them to potential IVIG product risks and benefits are becoming increasingly important in the selection of a particular IVIG.     

Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration

The natural compound amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) amygdalin infusion. All patients had also continuously ingested amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous amygdalin treatments. The time period between each i.v. application ranged between 4–6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. amygdalin administration was 34.74 μg/L, which increased significantly to a mean value of 66.20 μg/L after i. v. amygdalin application. In contrast, lactate decreased significantly from 1266 μmol/L pre-infusion to 868 μmol/L post-infusion. Increasing i.v. amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by amygdalin administrators, i.e. after chronic oral amygdalin intake and then again after a closely subsequent intravenous amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.     

Management of dyslipidemia in patients after solid organ transplantation

The increase in organ transplantation has led to primary care physicians assuming a greater role in the provision of health care. Cardiovascular disease is the leading cause of mortality in transplant patients. The risk factors for cardiovascular disease do not differ from the nontransplant population, except that there is increased prevalence of these risk factors in the transplant population. Post-transplant hyperlipidemia is extremely prevalent, partly because of the underlying condition causing the need for transplantation and partly because of the side effects of immunosuppressant agents. Although there are no large, cardiovascular event outcome trials demonstrating a benefit for lipid-lowering therapy in the transplant population, there is robust literature supporting this treatment in the nontransplant population, and numerous smaller trials in transplant patients have demonstrated the safety and efficacy of lipid-lowering therapy. This article reviews the evidence and treatment options for currently available lipid-lowering therapy in solid-organ transplant patients.