Comparison of Combination Plasmapheresis/IVIg/Anti-CD20 Versus High-Dose IVIg in the Treatment of Antibody-Mediated Rejection

Different strategies appear to improve the success in treatment of antibody-mediated rejection (AMR), although no one best method has yet emerged. The objective of this study was to compare the efficacy of the combination of Plasmapheresis/intravenous immunoglobulin (IVIg)/anti-CD20-based regimes versus high-dose IVIg alone in the treatment of AMR. Group A (12 patients) was treated with high-dose IVIg between January 2000 and December 2003; group B (12 patients) was treated by Plasmapheresis/IVIg/anti-CD20 between January 2004 and December 2005. Graft survival at 36 months was 91.7% in group B versus 50% in group A (p = 0.02). Donor-specific human leukocyte antigens (DSA) levels detected by Luminex single antigen (Luminex SA) and ELISA, 3 months postrejection are significantly lower in group B than in group A: DSA ELISA class 2 score 6–8 (p = 0.02), DSA mean intensity of fluorescence (MFI) max (p = 0.009) and DSA mean MFI (p = 0.0004). The persistence of elevated DSA levels posttreatment is more frequent in patients with graft loss as compared to those with preserved renal function: score 6–8 on ELISA (p = 0.04); mean MFI (p = 0.00009) and MFImax (p = 0.018). We conclude that: (1) high dose IVIg alone is inferior to Plasmapheresis/IVIg/anti-CD20 as therapy for AMR and (2)DSA postrejection can be quantified using solid phase assays, showing that 3 months after AMR, DSA levels are higher in patients with graft loss.     

HLA Class I Antibodies Provoke Graft Arteriosclerosis in Human Arteries Transplanted into SCID/Beige Mice

Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro , those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.     

前路钢板复合BMP2同种异体骨移植治疗无脊髓损伤型外伤性颈椎滑脱

目的 探讨颈前路减压、椎体间植骨支撑融合、钢板内固定术治疗无脊髓损伤型外伤性颈椎滑脱的手术方法 及疗效.方法 手术治疗50例无脊髓损伤型外伤性颈椎滑脱,采取复合BMP2同种异体骨移植支撑融合、钢板内固定术.结果 术后全部病例经随访观察,症状获得改善,加例完全恢复.植骨在3个月内牢固融合,术后6个月47例重返工作,3例残留手指麻木.颈椎椎间高度、生理曲度维持良好、无钢板、螺钉折断、滑脱等并发症.结论 颈前路减压、椎体间植骨融合、钢板内固定术治疗外伤性颈椎滑脱,临床疗效满意.植骨融合手术操作简单,钢板内固定术后颈椎即刻稳定,有助于早期功能锻炼,减少外固定时间,防止植骨块塌陷,保持椎问高度及颈椎的生理前曲,有利于提高手术远期效果.     

关节突入路椎间融合内固定治疗复发性腰椎间盘突出症29例

腰椎间盘突出症术后复发率为3%～9%[1],常需再次手术.由于术后椎管内外的瘢痕增生,局部解剖关系紊乱,神经根及硬膜囊与瘢痕组织粘连,给二次手术带来困难,我科自2005年2月一2007年12月,采用关节突入路,椎间cage联合椎弓根钉系统固定融合,治疗复发性腰椎间盘突出症29例,取得良好疗效,报告如下:     

Fibula and tibia fusion with cancellous allograft vitalised with autologous bone marrow: first results for infected tibial non-union

Background and aims  Autogenous bone grafting has been used in reconstructing bone defects and in stimulating fracture healing, producing high healing rates in the treatment of infected tibial non-unions. A novel therapeutic alternative is now available known as “vitalised allograft”, a cancellous bone graft procured from femoral heads from living human donors and “vitalised” through the injection of autologous bone marrow. The aim of this study is to summarise the initial results of the fibula and tibia fusion using vitalised cancellous allograft in the treatment of infected tibial non-unions. Patients and methods  We initiated a follow-up of 15 prospective non-randomized patients who received a vitalised allograft in the treatment of infected tibial non-unions in order to produce bony union. The patients included 13 men and 2 women with an average age of 48 years. All patients received a multi-stage surgical approach. After establishing an infection-free environment, allogenic cancellous bone grafting was performed, intended as the final surgical procedure in fibula and tibia fusion. Our follow-up included a clinical and radiographic investigation of the calf in four planes. We analysed union-rate and time required for bony consolidation, as well as recurrent infections, re-fractures, potential graft-resorption, and time needed for graft and bone remodelling. Results  With an average follow-up of 17.1 months, infection control was obtained in 14 of 15 patients, producing an infection arrest rate of 93.3%. Radiographs indicated consolidation in 11 out of 15 cases, with a union rate of 73.3%. Bone union was achieved on average in 17.1 weeks. Conclusions  Fibula and tibia fusion with allogenic cancellous bone grafting, vitalised through autogenic bone marrow, could well become an innovative treatment option for infected tibial non-unions. We need, however, to analyse a higher number of cases over a longer follow-up period in order to assess more accurately recurrent infections and re-fractures.     

腺病毒介导人白介素-10转基因对大鼠同种异体移植血管IL-2、TNF-α的影响

目的:观察腺病毒介导人白介素-10(hIL-10)转基因对大鼠同种异体移植血管IL-2、TNF-α的影响及其可能的作用机制。方法:以Wistar大鼠为供体,SD为受体,采用颈动脉显微外科原位吻合技术,将经直接浸泡法转染腺病毒介导hIL-10的离体供血管植入受体血管。随机分为3组:I组(空白对照组,n=9),II组(空载体组,n=10),III组(基因转染组,n=10)。移植后5d,观察移植物病理组织学变化及免疫排斥级别;RT-PCR、ELISA、免疫组化染色检测移植血管hIL-10基因产物;免疫组化染色检测IL-2、TNF-α。结果:基因转染组移植血管有效地表达特异性hIL-10基因产物。与对照组比较,急性排斥级别降低(P<0.01);IL-2、TNF-α的表达量明显下降(P<0.01)。结论:腺病毒介导人白介素-10转基因能有效地下调IL-2、TNF-α表达,诱导移植血管局部免疫抑制状态,抑制同种异体移植血管的急性排斥反应。     

Subsidence of Cylindrical Cage (AMSLU? Cage) : Postoperative 1 Year Follow-up of the Cervical Anterior Interbody Fusion

Objective

There are numerous reports on the primary stabilizing effects of the different cervical cages for cervical radiculopathy. But, little is known about the subsidence which may be clinical problem postoperatively. The goal of this study is to evaluate subsidence of cage and investigate the correlation between radiologic subsidence and clinical outcome.

Methods

To assess possible subsidence, the authors investigated clinical and radiological results of the one-hundred patients who underwent anterior cervical fusion by using AMSLU™ cage during the period between January 2003 and June 2005. Preoperative and postoperative lateral radiographs were measured for height of intervertebral disc space where cages were placed. Intervertebral disc space was measured by dividing the sum of anterior, posterior, and midpoint interbody distance by 3. Follow-up time was 6 to 12 months. Subsidence was defined as any change in at least one of our parameters of at least 3 mm.

Results

Subsidence was found in 22 patients (22%). The mean value of subsidence was 2.21 mm, and mean subsidence rate was 22%. There were no cases of the clinical status deterioration during the follow-up period. No posterior or anterior migration was observed.

Conclusion

The phenomenon of subsidence is seen in substantial number of patients. Nevertheless, clinical and radiological results of the surgery were favorable. An excessive subsidence may result in hardware failure. Endplate preservation may enables us to control subsidence and reduce the number of complications.     

CD8(+) T cells mediate aortic allograft vasculopathy under conditions of calcineurin immunosuppression: role of IFN-gamma and CTL mediators

We have developed a model of aortic allograft vasculopathy (AV) that uses mouse strains that are fully disparate at Class I, Class II and minor histocompatibility antigens. Acute rejection is ablated with therapeutic doses of the calcineurin inhibitor Cyclosporine A (CyA). In this way we successfully mimic human disease. Using this model we have demonstrated, with cell transfer models using highly purified T cell populations, that calcineurin inhibitors ablate CD4(+) T cell effector mechanisms. As such, in the presence of calcineurin inhibition, graft vasculopathy is dependent on CD8(+) T cell effector mechanisms. In this study we examine the etiology of graft vasculopathy by these CD8(+) T cells in the presence of calcineurin inhibition. We transferred CD8(+) T cells from CyA treated IFN-gamma deficient mice into immunodeficient mouse recipients of aortic allografts to demonstrate that IFN-gamma production by CD8(+) T cells is essential for the development of AV in the presence of calcineurin inhibition. Using two models of CTL ablation we also demonstrated that CTL activity by CD8(+) T cells is essential for the development of AV in the presence of calcineurin inhibition. This is in contrast to models without calcineurin inhibitor immunosuppression where either pathway is capable, by itself, of inducing AV. These data indicate that although calcineurin inhibition ablates CD4(+) T cell effects and weakens CD8(+) T cell pathways, the antigenic challenge of the graft is enough to induce sufficient responsiveness from CD8(+) T cells to induce robust AV.     

不同植骨材料椎间融合效果的实验研究

目的观察不同植骨融合材料在兔腰椎椎体间脊柱融合的愈合情况,探讨不同的植骨材料替代自体骨用于腰椎椎体间融合的可能性。方法试验组分5组：空白对照组、自体骨组、同种异体骨组、生物陶瓷+自体骨组、重组人骨形态发生蛋白（rhBMP-2）复合体组。椎体间移植后4、8、12周,通过大体观察、手法检测、影像学、生物力学和组织学方法评价脊柱愈合情况。结果术后12周,大体及手法检测显示空白对照组不能自行达到脊柱融合,融合率为0％（0/12）;自体骨组脊柱融合率为83.3%（10/12）;同种异体骨组为66.7%（8/12）;生物陶瓷+自体骨组融合率为66.7%（8/12）;rhBMP-2复合体组为100%（12/12）,组织学显示成骨早,新骨形成量大,降解快,生物力学测试结果表明,自体骨组与同种异体骨组和生物陶瓷+自体骨组差异无统计学意义(P＞0.05),rhBMP-2复合体组优于其它组(P＜0.05)。结论同种异体骨、生物陶瓷+自体骨、rhBMP-2复合体均能替代自体骨行脊柱椎体间融合,rhBMP-2复合体更能促进脊柱愈合,提高脊柱愈合的生物力学强度。     

自制颈椎翼型钛网的生物力学评价

目的对自行研制的中下颈椎前路内固定装置——新型翼型钛网进行生物力学测试,评价其生物力学稳定性,为产品初步临床应用提供理论依据。方法取25具新鲜青年男性尸体颈椎标本,制成5种状态脊柱功能单位(FSU)的试验模型：正常颈椎组、失稳颈椎模型组、髂骨植骨组、钢板+髂骨植骨组和新型翼形钛网组,每组5具标本。利用脊柱三维运动分析系统依次测定各组在不同运动状态下颈椎节段(C4-6)运动范围(ROM)变化,进行统计分析,比较新型翼形钛网组与单纯髂骨组、钢板+髂骨组对失稳颈椎的稳定作用。结果生物力学测试表明,新型翼形钛网内固定系统可以对失稳颈椎提供有效的稳定作用,与失稳颈椎节段的运动范围比较差异有显著性(P＜0.01),其抗前屈和抗后伸功能超过正常颈椎(P＜0.05),而其抗旋转抗扭曲功能与钢板系统存在一定差距(P＜0.05)。 结论新型翼形钛网内固定系统具有较好的生物力学稳定性,可以对中下颈椎前路减压融合提供有效的稳定作用。