深低温冷存的吻合血管同种异体长骨移植的实验研究

目的：探讨深低温冷存的吻合血管异体长骨治疗大块骨缺损的效果。方法：32只兔随机分成3组：A组12只，用深低温冷存的吻合血管作异体骨移植；B组12只，深低温冷存的吻合血管异体移植术后4周用免疫抑制剂环孢素A（Cyclosporine A CsA);C组8只作新鲜的吻合血管异体骨移植。术后2、4、8、12周摄X线片，第3周取外周血栓测自发性淋巴母细胞生成率，第8周取外周血检测白细胞介素2（IL－2），并于12周通过灌注墨汁等检测吻合血管的通畅情况，并对移植骨进行组织学检测。结果：A、B2组术后12周两端可达骨性连接（愈合），而C组仅1例近端达骨连接且明显延迟。术后3周A、B2组自发性淋巴母细胞生成与未移植兔比值均＜2。术后8周外周血IL－2活性，C组最高，A组次之，B组最低，且任意2组之间均有显著性差异（P＜0．01）。术后12周，A、B2组血管通畅率无显著性差异（P＞0．05）。组织切片中可见移植骨与受区两端有骨小梁连接。结论：深低温冷存吻合血管异体长骨可修复大块骨缺损；深低温冷存和CsA可协同抑制吻合血管异体长骨移植的排斥反应。     

Endothelial nitric oxide synthase expression in ischemia-reperfusion injury after living related-donor renal transplantation

Ischemia-reperfusion injury during renal transplantation has been linked to early graft dysfunction and late graft failure. Nitric oxide (NO), produced by NO synthase (NOS), participates in the recovery from ischemia. We correlated the intensity of graft immunoreactivity for the endothelial NOS isoform (eNOS) during early reperfusion with graft function in 25 children receiving grafts from related donors. Renal allograft biopsy specimens were obtained before transplantation, 1 h after renal artery reperfusion, and 1 year after transplantation. Immunohistochemical staining for eNOS occurred mainly within the endothelium of glomerular capillaries and peritubular capillaries as well as in tubule cells. The mean intensity score for eNOS staining (0-9) was 3.0+/-1.4 before transplantation, 4.5+/-1.9 at 1 h, and 3.3+/-1.9 at 1 year (baseline vs 1 h, P<0.05). Creatinine clearance (ml/min) in patients with a 1-h eNOS score of below 5 and of at least 5, respectively, was 77.1+/-28.4 vs 104.3+/-25.3 at 1 month, 78.7+/-33.4 vs 105.2+/-24.4 at 3 months, 64.7+/-30.1 vs 100.1+/-25.3 at 1 year, 58.2+/-31.3 vs 84.7+/-18.8 at 3 years, and 71.2+/-19.7 vs 78.3+/-23.1 at 5 years ( P<0.05 for 1 month, 1 year, and 3 years). We concluded that elevated eNOS expression after reperfusion in living related-donor renal transplantation enhances the recovery from renal ischemia and, consequently, reduces late graft deterioration.     

同种异体骨与自体骨移植治疗青少年脊柱侧凸的比较研究

[目的]观察同种异体骨移植与自体骨移植治疗青少年脊柱侧凸的临床效果.[方法]对1996～2006年本科收治的63例青少年脊柱侧凸患者的临床资料,采用回顾性"病例-对照"研究方法进行分析,A组(同种异体骨移植组)32例,10～15岁,平均12.2岁;Cobb's角38°～113°,平均62°;B组(自体髂骨移植组)31例,年龄9～14岁,平均12.4岁;Cobb's角41°～105°,平均54°.所有患者均选择中华长城椎弓根内固定系统经后路矫正,术后定期随访并对临床效果进行评估.[结果]出院后2个月即开始随访,随访时间18～24个月,平均26个月;亦无严重并发症发生;A组的手术时间、失血量较B组患者减少,组间具有统计学意义(P＜0.01).[结论]两组患者具有相似的临床效果,在严格掌握适应证,充分术前准备、正确手术操作、及时术后处理的前提下,同种异体骨移植能够有效替代自体髂骨移植治疗青少年脊柱侧凸.     

Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation

Moore J, Tomson CRV, Tessa Savage M, Borrows R, Ferro CJ. Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation.
Clin Transplant 2011: 25: 406–416. © 2010 John Wiley & Sons A/S. Abstract: The impact of disordered mineral and bone metabolism following kidney transplantation is not well defined. We studied the association of serum phosphate and calcium concentrations, and surrogate measures of arterial stiffness (augmentation index: AIx and Timing of the reflected wave: Tr), with long‐term kidney transplant recipient and allograft survival. Prevalent adult renal transplant patients (n = 270) were prospectively studied over a median 88‐month follow‐up. Detailed demographic, clinical and laboratory data, in addition to both peripheral and central non‐invasive blood pressure measurements, were recorded. Higher serum phosphate and calcium levels were associated with increased all‐cause mortality (HR: 1.21; 95% CI 1.09,1.35, p < 0.001 and HR: 1.22; 95% CI 1.01,1.48; p < 0.04, respectively; adjusted Cox model) and death‐uncensored graft loss (p < 0.001 and p = 0.03, respectively). In addition, serum calcium and phosphate were associated with death‐censored graft loss on univariable analysis (p < 0.001 and p = 0.02, respectively), but did not retain significance on multivariable analysis. AIx and Tr were not associated with mortality or graft loss on multivariable analysis. This is the first report to demonstrate that both higher serum phosphate and calcium levels are associated with increased mortality in kidney transplant recipients. It highlights the need for randomized trials assessing current interventions available for improving disordered mineral–bone metabolism post transplantation.     

Periprosthetic fracture of the proximal tibia after lateral unicompartmental knee arthroplasty

We report a case of periprosthetic fracture of the proximal tibia after lateral unicompartmental knee arthroplasty following a trivial fall. At the time of surgery, the components were found to be loose; and there was a large uncontained tibial defect with bone loss and communition at the fracture site. The patient was treated by revision total knee arthroplasty and proximal structural tibial allograft, with a satisfactory result at 5-year follow up. Our case illustrates that a bone-conserving unicompartmental knee arthroplasty, if complicated by a periprosthetic fracture, can also present with a difficult surgical problem. Attention to preoperative planning and to availability of structural allograft for such difficult cases is recommended.     

同种异体髂骨结合钢板在颈椎前路手术中的应用

[目的]探讨同种异体髂骨块植骨结合前路钢板在颈椎前路椎间植骨融合中的应用效果。[方法]对68例颈椎前路减压植骨融合的患者应用同种异体髂骨块植骨结合前路钢板，记录手术时间、术中出血量及定期X线片等资料，并与同期自体髂骨块植骨结合前路钢板的32例对照组的相关资料进行比较。[结果]同种异体髂骨块植骨结合前路钢板组与同期自体髂骨块植骨结合前路钢板组比较，手术时间以及手术出血量较后者显著减少（P〈0．05），随访1年，两组均成功实现椎体间骨融合，但前者融合时间较后者显著延长（P〈0．05），两组无1例发生钢板断裂或螺钉松动、滑脱。[结论]同种异体髂骨块植骨结合前路钢板，手术时间短，术中出血少，植骨可顺利融合，是颈椎前路手术较好的术式。     

Renal allograft biopsies in the era of C4d staining: the need for change in the Banff classification system.

C4d immunostaining in the peritubular capillaries (PTC) is a marker of antibody-mediated rejection (AMR). We evaluated the histopathologic diagnoses of 388 renal transplant biopsies since the implementation of routine C4d immunostaining at our center. Of these, 155 (40%) biopsies had evidence of acute cellular rejection (ACR), out of which 119 (77%) had pure ACR, 31 (20%) had ACR with concomitant features of AMR, and five (3%) had ACR with focal C4d staining. Sixty-four (16%) biopsies exhibited features of AMR [33 (52%) pure AMR, and 31(48%) concomitant AMR and ACR]. One hundred and fifty-five (40%) biopsies had features of interstitial fibrosis and tubular atrophy (IFTA). Of these, 20 (13%) had concomitant AMR [13 (8.5%) had pure AMR and seven (4.5%) had concomitant ACR and AMR]. Creatinine at the time of biopsy was higher in patients with mixed ACR and AMR and the clinical behavior of mixed lesions is more aggressive over time. Despite having a lower serum creatinine at the time of biopsy, patients with IFTA experienced gradual decline in graft function over time. The pathologic findings in renal allograft biopsies are often mixed and mixed lesions appear to have more aggressive clinical behavior. These findings suggest the need for change in the Banff classification system to better capture the complexity of renal allograft pathologies.     

Immune response to perforated and partially demineralized bone allografts

Immune responses have been shown to be involved in the pathogenesis of clinical complications of cortical bone allografts. In an attempt to reduce the immunogenicity of these allografts, we evaluated cortical bone allografts modified by laser perforation and partial demineralization transplanted orthotopically into sheep tibiae. The recipient animals were divided into three groups, of eight animals each, according to the type of cortical allograft that was transplanted: group 1, no treatment (control); group 2, demineralization only; and group 3, laser perforation and partial demineralization. All animals were tissue-typed by biochemical definition of MHC class I molecules, using unidimensional isoelectric focusing and Western blotting. Mismatches of donors and recipients were assessed by testing samples of each donor and recipient pair in parallel and by comparing their individual bands. Donor-specific alloantibodies were detected by a similar technique, using an enzyme-linked immunosorbent assay (ELISA) format. Negative controls were included in all tests. All grafts were poorly immunogenic, whether they were untreated, processed by partial demineralization, or processed by both laser perforation and partial demineralization. Only two recipient animals showed a transient, antibody-mediated donor-specific immune response. One of these animals had received a control allograft, whereas the other animal had received a laser-perforated and partially demineralized bone allograft. All of the grafts in this study, including control grafts, were stripped of soft tissues and their bone marrow was removed; cellular sources of alloantibody stimulation may have been eliminated by these processes. The results of this study suggest that immune responses to bone allografts may be reduced by removing the bone marrow and adjacent soft tissues. The processing of cortical bone allografts by laser perforation and partial demineralization appeared to have little effect on immune responses.     

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen

Abstract:  Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.
Methods:  Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
Results:  No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 ± 0.5 mg/dL vs. 1.4 ± 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 ± 0.5 g/L vs. 0.1 ± 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).
Conclusion:  In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.     

Unaltered Graft Survival and Intragraft Lymphocytes Infiltration in the Cardiac Allograft of Cxcr3−/- Mouse Recipients

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3^−/- mice. Interestingly, in our hands, neither of the independently derived Cxcr3^−/- lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-γ production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3^−/- recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.