Recent advance in therapies for age -related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age - related macular degeneration ( AMD ) is the leading cause of irreversible visual loss in elderly people among white - dominated population. At percent, treatment for AMD includes anti - vascular endothelial growth factor antibody ( Anti- VEGF ) drug treatment, photodynamic therapy ( PDT ) , topical application of triamcinolone acetonide ( TA ) and laser therapy ( nanosecond laser) etc. Through comparative analysis of different treatment methods of AMD, we review the mechanism, clinical efficacy, adverse events and cost effectiveness to provide the basis for clinical treatment.

Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients / 药学学报

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).

Alemtuzumab induction therapy in highly sensitized kidney transplant recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.</p><p><b>METHODS</b>In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.</p><p><b>RESULTS</b>Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05).</p><p><b>CONCLUSION</b>Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.</p>

Pathologic characteristics of lymphangiogenesis in renal transplants and its clinical implication / 第二军医大学学报

Objective: To investigate the pathologic characteristics of lymphangiogenesis in renal transplants and to analyze its clinical implication. Methods: The morphology and distribution of lymphangiogenesis were investigated by a biotin-streptavidin horseradish-peroxidase method with anti-podoplanin monoclonal antibody in 45 archival biopsies. The lymphatic vessel density (LVD) was calculated and the results were compared between different pathologic types and with the normal renal tissues. Results: Fewer podoplanin-positive lymphatic vessels were identified in the biopsies from the renal transplants with normal function, and the transplants had a similar morphological profile as normal renal tissues. More podoplanin-positive lymphatic vessels were observed in the transplants suffering acute rejection episode; the vessels mainly located around peripheral arteriole with different lumen sizes. Transplants with chronic rejection had the most podoplanin-positive lymphatic vessels with focal mononuclear infiltration and distended/ distorted lymphatic vessels. The lowest mean LVD (1.26±0.27) was observed in the biopsies from transplants with normal function, which was significantly different from those in the acute rejection and chronic rejection groups (P<0.05). The highest mean LVD was found in the chronic rejection group (20.76±5.30), which was significantly higher than those of the other 2 groups (P<0.01); no significant difference was observed between the transplants with normal function and the normal kidney. Conclusion: Lymphatic neoangiogenesis occurs in the renal transplant and its pathologic characteristics differs in the transplants with different rejection types.

Comparison of biologic activity of two anti-PSA/anti-CD3 bispecific single-chain antibodies / 中华男科学杂志

<p><b>OBJECTIVE</b>To study and compare the biologic activity of two anti-PSA/anti-CD3 bispecific single-chain antibodies.</p><p><b>METHODS</b>Flow cytometry (FCM) was used to detect the binding activity of two antibodies to CD3-positive cell line Jurkat and prostate carcinoma cell line LNCaP. The effect of the two antibodies in mediating tumor cell lysis in vitro was determined by using the 51Cr-release test. For in vivo evaluation of the two antibodies activity, a nude mouse model was used. The mice were inoculated with LNCaP prostate cancer cells.</p><p><b>RESULTS</b>FCM showed that both the antibodies could bind Jurkat and LNCaP cells with high specificity. The percentages of the cells bond by the bispecific single-chain antibodies were 56.3% and 55.4%, and those by the multivalent antibodies were 74.0% and 83.0% respectively. Both the antibodies mediated a specific lysis of LNCaP cells in vitro, with activated CTLs as effector cells, and significantly reduced tumor growth of nude mice in vivo as compared with the untreated controls and the group treated with CTLs only (P <0.05). The experiment also showed that the multivalent antibody had a better activity than the bispecific antibody in binding antigens, mediating lysis of LNCaP cells and reducing tumor growth (P < 0.05).</p><p><b>CONCLUSION</b>Both the anti-PSA/anti-CD3 bispecific single-chain antibody and multivalent antibody have good biologic activity, and the formation of the tetramerization of single-chain antibody can improve its biologic activity.</p>

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single-bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients.</p><p><b>METHODS</b>A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA < 10%, n = 30) and sensitized group (PRA > or = 10%, n = 26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. Chi(2) test and t test were used to analyze the data.</p><p><b>RESULTS</b>During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P = 0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P = 0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13 - 25 days (mean, 16.7 +/- 3.3) in the non-sensitized group and 14 - 29 days (mean, 16.2 +/- 3.1) in the sensitized group, respectively (P = 0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups.</p><p><b>CONCLUSION</b>Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.</p>

Renal transplantation in children, report of 21 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>The survival rate of cadaveric renal transplant in children has been improved following the development of transplantation technology and the application of immunosuppressive agents. In this study, the prognosis of renal transplantation, operative procedure and immunosuppressive agents administration in 21 children with end-stage renal disease (ESRD) were analyzed.</p><p><b>METHODS</b>From January 1985 to December 2001, 21 patients (9 males and 12 females with a mean age of 14 +/- 2 yr, mean body weight of 33.4 kg and mean height of 136.5 cm) received renal transplantation because of ESRD were enrolled in the study. The patients with an average GFR of 8.28 ml/min were managed with dialysis for 13.4 months in average pro-transplantation. All cadaveric kidneys were from adults, which included 1 donor with one HLA mismatch, 3 with two mismatches, 5 with three mismatches and 4 with four mismatches. All transplantations were performed with anastomoses of the adults' renal artery and vein to the children's iliac externa artery and iliac externa vein. Biological inducement therapy was given in 4 cases. At the first 3 - 5 days post-transplantation, methylprednisolone was administered [7 mg/(kg.d)]. All patients received baseline diploid or triple immunosuppression therapy of cyclosporin A [6 - 8 mg/(kg.d)] or FK506 [0.18 - 0.25 mg/(kg.d)], mycophenolate mofetil [MMF 10 - 15 mg/(kg.d)] or azathioprine [1 - 3 mg/(kg.d)] and prednisone [0.4 - 0.6 mg/(kg.d)]. High-dose methylprednisolone [10 mg/(kg.d)] was administered to control the acute rejection.</p><p><b>RESULTS</b>The renal function of patients was restored 5.6 days in average after transplantations. The 1st, 3rd and 5th year survival rates of recipient/graft were 95.2%/95.2%, 86.7%/73.3% and 72.7%/63.6%, respectively. One case had super-acute renal rejection, 5 cases had acute rejection, 3 cases had delayed graft function and 3 patients died. The longest survival time was 12 years. The major complications included hypertension (47.6%), diabetes (19.4%), infection (19.4%) and drug-induced hepatic injury (14.2%). Catch-up growth was seen in most of the pediatric recipients.</p><p><b>CONCLUSION</b>Renal transplantation is the most ideal method to treat children with ESRD, and the growth of the pediatric patients will be improved after transplantation. Adult donor kidneys adapt to the school age patient. And the protocol of immunosuppressive therapy (prednisone plus MMF and FK506) should be applied.</p>