Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice

Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 x BALB/c)F(1) recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30-80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis.     

Acute Antibody-Mediated Rejection Following Heart Transplantation

Acute antibody-mediated rejection (AMR) in heart transplantation is often associated with hemodynamic compromise, and is associated with increased mortality and development of accelerated transplant coronary artery disease (TCAD). The diagnosis of AMR has historically been controversial and outcomes with aggressive immunosuppressive therapy including plasmapheresis and cyclophosphamide are poor. Advances in diagnostic techniques like the demonstration of immunopathologic evidence for antibody-mediated rejection by deposition of the complement split product C4d in tissue and detection of anti-HLA antibodies by flow cytometry will assist in further characterizing AMR. Immunosuppression targeting B-lymphocytes and use of m-TOR inhibitors to alter the predilection to develop TCAD and improve survival in AMR remains to be proven.     

Extremely High Association Between Appearance of HLA Antibodies and Failure of Kidney Grafts in a Five-Year Longitudinal Study

Longitudinal studies were conducted over a five-year period for HLA antibodies on 493 sera tested from 54 kidney transplant patients. HLA single antigen beads were employed to establish donor specificity of the antibodies. Only 3 of 22 patients without antibodies rejected a graft in contrast to 17 out of 32 patients with posttransplant antibodies (p = 0.003). Using a serum creatinine value of 4.0 mg/dL as the cut-off for a failed graft, 4 of 22 patients without antibodies failed compared to 21 of 32 with antibodies (p = 0.0006). Among patients with donor-specific antibodies (DSA) 13 of 15 failed (p = 0.000004). Even among patients with non-donor specific antibodies (NDSA), 8 of 17 failed (p = 0.05). Among patients who could be identified as making de novo antibodies (since they developed antibodies while not having antibodies for more than six months after transplantation), 6 of 11 failed (p = 0.03). Sequential testing for HLA antibodies shows that antibodies appear prior to a rise in serum creatinine and subsequent graft failure. The very strong association between the production of HLA antibodies after transplantation and graft failure indicates the importance of monitoring for posttransplant HLA antibodies.     

Complications Related to Dapsone Use for Pneumocystis Jirovecii Pneumonia Prophylaxis in Solid Organ Transplant Recipients

Dapsone, used for prevention of Pneumocystis jirovecii infections, has been reported to cause hemolytic anemia and methemoglobinemia; its tolerability in solid organ transplant recipients is not well described. We investigated dapsone-related adverse events in patients undergoing solid organ transplantation from 1999 to 2004. Transplant providers identified patients for the investigators who then reviewed the patients' hospital and outpatient records. Sixteen solid organ transplant recipients fit case definitions for dapsone-related hemolytic anemia (n = 11) or methemoglobinemia (n = 5). Median time from event to dapsone discontinuation was 15 days; all patients improved after drug discontinuation. G6PD enzyme activity was normal in all patients whose test results were available. Dapsone may be associated with hemolytic anemia or methemoglobinemia, even with normal G6PD levels. These events are often not promptly recognized, and drug discontinuation is delayed. Dapsone-related hemolytic anemia or methemoglobinemia should be considered in solid organ transplant recipients with unexplained anemia or hypoxia.     

对原发性骨质疏松诊断的一些看法

原发性骨质疏松的诊断首先要除外继发性骨质疏松。后者包括的范围很广，内容也很多，需要广博的内科学基础和辨证的逻辑思维才能予以正确鉴别。骨密度检查只能作为一种参考，而不能作为诊断原发性骨质疏松的唯一依据。     

Aortic valve endocarditis in an acutely rejecting orthotopic heart transplant recipient

Infective endocarditis is an infrequent but serious complication in heart transplant recipients. We report successful treatment for this serious complication.     

Pancreas and kidney transplantation: the San Raffaele Hospital (Milan, Italy) experience

Results of 33 simultaneous pancreas and kidney transplantations performed at the San Raffaele Hospital, Milan, Italy are presented. In 26 cases segmental neoprene duct-injected grafts were transplanted and in seven cases, duodenopancreatic bladder-drained grafts. Five-year patient, kidney and pancreas survival were respectively, 89%,72% and 58%. Five-year survival in patients with technically successful pancreas transplants was 73%. Thrombosis occured in 20% of cases. Mortality was 6% and overall morbidity 76%. Surgical complications were present in 51% of cases.     

肾脏疾病患者治疗前后血浆内皮素水平动态变化及其意义

目的 为了探讨肾脏疾病患者血浆内皮素水平与肾脏疾病病情程度的关系,为肾脏疾病治疗效果的评价提供依据.方法 采用放射免疫分析(RIA)观察了77例肾脏疾病患者治疗前后血浆内皮素水平的动态变化,并与60例正常对照组比较.结果 正常对照组血浆内皮素浓度为43.1±15.2ng/L,肾脏疾病患者治疗前血浆内皮素水平为161±83.8ng/L,治疗后为97.4±52.7ng/L,均高于正常对照组(P值均<0.001).肾脏疾病治疗后内皮素水平明显下降(P<0.001),与BUN,Cr水平的下降具有一定的相关性(相关系过分别为0.54,0.55).结论血浆内皮素水平随着肾脏疾病严重程度的增加而升高,血浆内皮素水平可作为肾脏疾病治疗效果评定的指标之一     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

7例肝细胞体内移植患者临床护理需求的探讨

目的观察肝细胞体内移植术的有效性与安全性,探讨相应的护理需求。方法从自愿捐献者的肝脏内分离纯化肝细胞,制成悬液,经股动脉插管行脾动脉灌注移植,观察治疗后肝衰竭患者的肝功能恢复率、恢复时间、治疗不良反应及患者心态变化,针对不良反应及患者心理给予完善护理,建立肝细胞体内移植术护理规范。结果7例肝衰竭患者治疗后,4例临床治愈,有效率为57.1%,胆红素、凝血酶原活动度改善50%以上的发生时间约在术后4周。术后患者不同程度出现恶心、呕吐(57.1%),少量腹水(57.1%),肝性脑病(42.9%),发热(42.9%),穿刺点皮下血肿(28.6%),肺部真菌感染(14.3%)。术后71.4%的患者有焦虑情绪。经过相应的临床及心理护理,症状均有不同程度的改善。结论肝细胞体内移植可延长终末期肝病患者生存期,但病情明显改善所需时间约4周,防治肝性脑病、预防穿刺点皮下血肿及运用心理护理消除患者焦虑情绪是重要的护理需求。