Plasma cell infiltrates in polyomavirus nephropathy

Polyomavirus (PV) associated nephropathy (PVAN) has become an important cause of allograft dysfunction. We studied plasma cells (PCs) – which have not yet been characterized – present in the cellular infiltrate of 20 PVAN cases using immunohistochemistry and morphometry. The results were correlated with morphological, clinical and anti‐BK virus serological findings. PC‐rich cellular infiltrates occurred in 50% of cases (>15% PCs in the cellular infiltrate) and in these IgM producing PCs were commonly seen (70%): IgM PC predominance in 50% of cases and a comparable number of IgM and IgG PCs in 20% of cases. We found a significant correlation not just between the absolute numbers (P < 0.034) and the percentage values of IgM PCs (P < 0.004 in relation to all cells) and the serum IgM‐Ab anti‐BKV activity, but also between the ratio of IgG/IgM PCs and the ratio of serum IgG/IgM‐Ab activities (P < 0.0001). We showed that IgM PC counts in biopsies correlate with titers of circulating anti‐BK virus IgM antibodies. Every case except one was C4d negative in peritubular capillaries (PTC). As IgG PCs characterize PC‐rich rejection cases, we suggest that in the presence of IgM PCs in PC‐rich infiltrate with PTC C4d negativity, a search for possible PVAN infection should be initiated.     

Basic and clinical research on intramural esophagography

Preoperative diagnosis of the penetration of esophageal cancer is important in its treatment. Lipiodol Ultra Fluid was injected into the oral side of the lesion, and after consideration of the state of its transfer linearly and histologically, the contrast medium had mostly transferred into the spaces between tissue. As a preoperative method of diagnosis, the ratio of the distance of transfer from the proximal edge of the tumor to the distal edge of the tumor in relation to the vertical length of the tumor was calculated and called the transfer ratio, and also (1) the distance from the assumed edge of tumor to the projecting portion in the inner cavity for the deepest part of the tumor was calculated, as was (2) the same calculation for the greatest penetration of contrast medium in the layer of adventitia, and the transfer ratio was multiplied by (2)/(1) and the result was called the section ratio. Using the transfer ratio and the section ratio, the preoperative depth of the invasion by the esophageal cancer was classified into four classifications: A0(sm), A0(pm), A1-2, and A3. The accuracy of diagnosis, comparing the preoperative diagnosis and the histological examination was: A0(sm): 100%, A0(pm): 75%, A1-2: 91.7%, A3: 80% and was 85.7% overall, showing very good result.     

Basic epidemiologic and statistical methods in clinical research.

Various study designs and approaches to statistical analysis in clinical research have their own underlying rationales and limitations for interpretation. This information is presented in an intuitive and accessible manner, relying minimally on basic algebra. Epidemiologic concepts of study design and interpretation, bias and confounding, hypothesis testing, and sample size and power are explained. Statistical tests and their appropriate applications are discussed for mean comparisons (t tests and ANOVA), percentages (chi-square), survival analysis, and correlation and regression. Applicable nonparametric tests are also introduced.     

Renal pathology and clinical presentations of polyomavirus nephropathy in simultaneous kidney pancreas transplant recipients compared with kidney transplant recipients

INTRODUCTION: The purpose of this study was to describe and compare the renal histopathology and clinical course of simultaneous kidney-pancreas transplant (SKP) recipients with kidney transplant (KT) recipients with polyomavirus nephropathy (PVN). METHODS: Between 1997 and 2002, 20 patients (7 SKP, 13 KT) were diagnosed with PVN. Clinical characteristics and outcomes of PV-N were correlated with histopathologic examinations of renal allograft biopsy and compared between SKP and KT recipients. RESULTS: There were no differences in demographics between SKP and KT recipients with PV-N. The mean time to PVN was 611 (172 to 1174) days posttransplant in SKP and 343 (83 to 720) days posttransplant in KT (P =.05). The serum creatinine at the time of diagnosis was similar between SKP and KT recipients. All patients were treated with reduction in immunosuppression. After a median follow-up of 2 years, the patient survival was 71% in SKP and 100% in KT. Four grafts (57%) were lost owing to PVN in SKP group and three grafts (23%) were lost owing to PVN in the KT group. More patients (43%) in SKP had a history of acute rejection prior to diagnosis of PVN compared to KT (8%) and biopsy-proven tacrolimus nephrotoxicity prior to PVN was more common in SKPT (86%) than in KT (8%) patients (P <.05). SKP patients with evidence of diffuse fibrosis and high total sum scores at time of presentation all subsequently lost their grafts. CONCLUSIONS: SKP recipients with PVN had a worse clinical course than KT recipients.     

脊柱骨母细胞瘤的基础与临床研究进展

骨母细胞瘤（osteoblastoma）是少见的原发性骨肿瘤,约占良性骨肿瘤的3%,占全部原发性骨肿瘤的1%;男性多见,男女之比约为2∶1;10~30岁的青少年和青年患者约占80%;其好发部位为脊柱,约占30%~40%,其次为长管状骨及手足骨[1、2]。在生物学上有潜在的局部侵袭性,切除不彻底容易复发,且有恶变倾向。从1956年被正式命名至今,其在世界各地均有报告,但绝大多数报告的病例数量较少,而关于脊柱病变的单独报告则更少,未见多中心、大样本的研究[3]。现就脊柱骨母细胞瘤的实验室研究、诊断、鉴别诊断与治疗进展综述如下。     

Teratocarcinoma: Basic research and its clinical relevance

Summary Both the mouse and the human teratocarcinoma model systems have contributed to knowledge of differentiation and oncodevelopmental markers. Of particular interest are antigens detected on human teratocarcinomas with alloantisera and biochemical analyses of human germ cells in various stage of maturation. Both methods offer promise of new tumor markers for testicular germ-cell cancer and perhaps of targets for contraceptive vaccines.     

Clinical utility of histological features of polyomavirus allograft nephropathy

BACKGROUND: The purpose of this study was to determine if histological features of polyomavirus allograft nephropathy (PVAN) are associated with the clinical presentation and outcomes of PVAN. METHODS: We examined the histological features of initial and follow-up biopsies of 20 kidney and kidney-pancreas transplant recipients with PVAN during a time prior to routine surveillance. The subjects' demographics, clinical characteristics, and outcomes were compared based upon classification of histological features of PVAN on initial biopsy. RESULTS: Diabetes mellitus (45%) and a history of tacrolimus-induced nephrotoxicity (35%) appeared to be prevalent in subjects with PVAN. Although histological severity of PVAN did not predict or correlate with the clinical course of PVAN, subjects with pattern C on initial PVAN biopsy presented later posttransplant, had higher serum creatinine level at presentation, and had significant allograft deterioration at follow-up than subjects with either pattern A or B on initial biopsy. Resolution of PVAN was noted in 60% of follow-up biopsies and occurred more frequently in subjects with pattern B on initial biopsy. Most subjects developed chronic allograft nephropathy after PVAN and viral clearance did not abrogate the progression to chronic allograft nephropathy. CONCLUSIONS: These data indicate that histologic patterns of PVAN may have clinical correlation to disease presentation and prognosis.     

Cost efficiency in the prospective diagnosis and follow-up of polyomavirus allograft nephropathy

Evaluation of urine cytology (UC) for decoy cells and quantitative determinations of viruria (urine viral load [UPCR])and viremia (viral load in blood [VLB]) have been proposed as surrogate markers of polyomavirus allograft nephropathy (PVAN). In this study, we present the experience with the concurrent evaluation of UC, UPCR, and VLB in 349 patients (940 sets of samples). Results were correlated with each other and with a previous, concurrent, or subsequent biopsy diagnosis of PVAN. Patients were followed up for a mean of 27 months posttransplantation. We conclude that both UC and UPCR are useful for screening of renal transplant recipients. Simultaneous performance of both UC and UPCR does not add useful clinical information. In patients with positive UC, performance of UPCR, however, can allow for the distinction between BK and JC polyoma viruses. Quantitative measurement of viremia is not indicated in patients lacking viruria because no patients with PVAN present with this combination of findings. In patients with viruria, a positive viremia strongly correlates with PVAN. Rationale selection of screening protocols based on the current knowledge of the infection and tailored to the available laboratory capabilities in each transplantation center can optimize the use of resources.     

Leflunomide treatment for polyomavirus BK-associated nephropathy after kidney transplantation

Polyomavirus-associated nephropathy (PVAN) affects 1-10% of kidney-transplant (KT) patients, with graft failure/loss in approximately 90% of cases. Reducing immunosuppression is the key treatment option, but addition of leflunomide may improve BK Virus (BKV) clearance and graft survival. In a prospective open-labeled study, 12 KT patients with biopsy-proven PVAN were treated with reduced immunosuppression and leflunomide. BKV viremia and graft function were followed. PVAN was diagnosed at 6 months (3-192) post-transplant; median serum creatinine concentration (sCC) was 189 micromol/l (92-265). After 16 months (8-30) of follow-up, the sCC was 150 micromol/l (90-378, NS). Renal function improved in six cases (50%), remained stable in two (16.6%) and deteriorated in four (33.4%), with graft loss in two (17%). Clearance of BKV viremia was observed in five (42%) cases. Side effects included anemia in six cases leading to leflunomide withdrawal in two patients, and mild thrombocytopenia. In KT patients diagnosed with PVAN, leflunomide plus reduced immunosuppression improved graft function in 66.6%, cleared BKV viremia in 42%, and resulted in side effects in 17%. This limited efficacy contrasts with other reports and falls short of expectation. We conclude that active screening, earlier diagnosis and intervention remain the cornerstones of treatment.     

Basic and clinical research in the AMC Renal Transplant Unit

Our research is aimed at characterization of the antiviral and allo-immune responses in kidney transplant recipients. In particular, we are interested in the differentiation, effector function and memory formation of T cells specific for the latent viruses cytomegalovirus (CMV) and BK virus (BKV) and in the impact of virus-specific immune responses on alloimmunity. Furthermore, we perform studies towards the most optimal, tailor-made immunosuppressive drug regimen and towards the impact of immunosuppression on infectious diseases; cognitive function and cardiovascular status of kidney transplant recipients.     

Successful pregnancy in renal transplant recipient with previous known polyomavirus nephropathy

Pregnancy after renal transplantation has become increasingly common. Studies in non-immunocompromised patients have shown that pregnant women have increased susceptibility to infection or reactivation of latent virus such as BK virus. To what extent a renal transplant recipient is at risk for reactivation of polyoma virus during pregnancy remains unknown. We hereby report successful pregnancy outcome in a renal transplant recipient with a known history of BK virus nephropathy treated with cidofovir i.v. To our knowledge, this is the first published experience with a successful pregnancy in renal transplant recipients with known history of polyomavirus-associated nephropathy.     

Ureteral stents: a novel risk factor for polyomavirus nephropathy

Polyomavirus virus nephropathy (PVN) is an important cause of renal allograft dysfunction. The risk factors for the development of PVN have not been completely elucidated. We investigated the hypothesis that ureteral trauma caused by placement of indwelling stents is an independent risk factor for PVN. Twenty cases of PVN were compared with 46 controls. Logistic regression was used to calculate odds ratios and to construct multivariate models. A total of 75% of cases and 35% of controls had stents placed during renal transplantation. In both univariate and multivariate logistic regression analyses adjusting for age, gender, deceased donor transplant, delayed graft function, tacrolimus and exposure to antibodies, the placement of a ureteral stent at the time of kidney transplantation was found to have a statistically significant association with developing PVN. Our findings reveal that the presence of a ureteral stent is associated with an increase in the risk of PVN.     

足外侧柱延长术的基础及临床研究进展

目的综述足外侧柱延长术(lateral column lengthening,LCL)的基础及临床研究进展。方法广泛查阅近年国内外LCL相关文献,并对其进行分析。结果 LCL作为治疗平足畸形的重要手术方式之一,包括两种术式——跟骨远端截骨延长术和跟骰关节撑开融合术,目前在治疗平足畸形时具体术式选择尚存在争议。结论 LCL临床广泛用于治疗平足畸形,但需要生物力学试验和大样本临床随访结果进一步验证疗效。     

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy

Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.     

烧伤创面愈合的理论探索与临床实践

The basic and clinical research in wound healing have made great progress in China in the past 50 years. The method of " intermingle skin transplantation" which was first advocated by surgeons of Ruijin Hospital in 1966 greatly reduced the amount of autologous donor skin, thus making the coverage of an extensive burn wound possible. This method is al so known as " Chinese therapy". In 1986,doctors of Jishuitan Hospital reported successful coverage of an extensive burn wound with mieroautografts and allogeneic skin. The basic research of wound healing has been carried out since 1992,a series of studies showed the characteristics of biological behaviours of cells in concern, extracellular matrix and growth factor, the mechanism underlying progressive injury in deep second burn wound, the effect of " skin island" and the local immune tolerance induced by it (which are the key factors of intermingle transplantation).The induction of local immune tolerance has now become the re search hot subject of skin transplantation immunology. Stem cell research in the field of wound healing has been extensively car ried out. The theory of " dermal template defection" has been proposed as one of the mechanisms of scar formation. On the other hand, great progress has been achieved in the treatment of bums on the basis of clinical researches. Doctors of PLA 304 hospital found that excision of eschar on patients with extensive deep burn injury at early shock stage greatly decreased the occurrence of complications and mortality. Doctors of Ruijin Hospital reported that healing of deep second burn wound could be improved by tangential excision of burn eschar within 24 hours after burn injury. Doctors of Xiang ya Hospital reported patients suffering from deep bums of the hands got satisfied functional restoration when treated with tangential excision of eschar while degraded dermal tissue could be retained with transplantation of autoskin grafts.     

Use of cidofovir in polyomavirus BK viral nephropathy in two renal allograft recipients

Polyomavirus BK viral allograft nephropathy is a potentially reversible cause of deteriorating function of kidney allografts. Initial treatment involves reducing immunosuppressive medications, with low-dose cidofovir an effective alternative in refractory cases. We describe two cases of BK viral allograft nephropathy responding to low-dose cidofovir after a reduction in immunosuppressive medications failed to clear the virus or stabilize the deterioration in renal function. There were no significant side-effects from this treatment in either patient.