Ex Vivo-Expanded Natural CD4+CD25+ Regulatory T Cells Synergize With Host T-Cell Depletion to Promote Long-Term Survival of Allografts

Foxp3⁺CD4⁺CD25⁺ natural regulatory T (nT_reg) cells have been shown in immunodeficient mice to suppress allograft rejection after adoptive cotransfer. We hypothesized that immunotherapy using ex vivo -expanded nT_reg could suppress allograft rejection in wild-type mice. Donor alloantigen (alloAg) specificity of naive splenic nT_reg was enriched in vitro by culturing with anti-CD3/CD28-coated Dynabeads plus bone marrow-derived dendritic cells (BM-DC) in the presence of interleukin (IL)-2 or IL-2 plus transforming growth factor (TGF)-β. On average, 96.2% fresh CD4⁺CD25⁺ nT_reg were intracellular Foxp3⁺. By d+20 in culture, 6.4% nT_reg were Foxp3⁺ following expansion with IL-2 alone, and 14.4% or 19.7% nT_reg were Foxp3⁺ when expanded with IL-2 plus 0.5 or 2.5 ng/mL TGF-β, respectively. In vitro , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg exerted stronger donor alloAg-specific suppression than cells with IL-2 alone in mixed lymphocyte reaction (MLR) assays. In vivo , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg expressed high-level Foxp3 following infusion, effectively overcame acute rejection and induced long-term survival of donor but not third-party heart allografts in peritransplant host T-cell-depleted mice. Long-term surviving allografts were noted to possess Foxp3⁺ graft-infiltrating cells of exogenous and endogenous origins. In conjunction with transient host T-cell depletion, therapeutic use of ex vivo -expanded nT_reg may be a practical means of preventing acute allograft rejection.     

Islet Transplantation for Brittle Type 1 Diabetes: The UIC Protocol

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1–3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460   080 ± 418   330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537   495 ± 190   968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2–3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets .     

Heart transplantation in insulin–treated diabetic patients with diabetes–related complications

Heart transplantation is the most effective therapy for end-stage heart failure in patients with diabetes mellitus (DM). However, diabetes-related complications (DRCs) are a relative contraindication for heart transplantation. Nevertheless, the increasing prevalence of both DM and congestive heart failure makes it necessary to perform heart transplantation even in those patients with advanced DM. We performed a retrospective analysis on long-term survival in 47 patients with insulin-treated DM and DRCs (group 1). Survival rate and causes of death were compared with data of a group of heart transplant recipients without DM (n = 1061, group 2). Mean follow-up time of all heart transplant recipients was 68.2 months (range: 0-204 months). Overall mortality during follow-up was 42.9%. Long-term survival did not differ significantly between study groups, but tended to be shorter in group 1 than in group 2 (P = 0.07). In group 1, steroid-free immunosuppressive therapy was associated with a higher percentage of long-term survivors compared with no steroid-free immunosuppression. Our data demonstrate that long-term survival is acceptable in heart transplant recipients with preoperatively diagnosed DM and DRCs. Consequently, advanced DM should no longer be a relative contraindication for heart transplantation.     

Emergency Medical Service (EMS) systems in developed and developing countries

OBJECTIVES: To compare patient- and injury-related characteristics of trauma victims and pre-hospital trauma care systems among different developed and developing countries. METHOD: We collated de-identified patient-level data from national or local trauma registries in Australia, Austria, Canada, Greece, Germany, Iran, Mexico, New Zealand, the Netherlands, the United Kingdom and the United States. Patient and injury-related characteristics of trauma victims with injury severity score (ISS) >15 and the pre-hospital trauma care provided to these patients were compared among different countries. RESULTS: A total of 30,339 subjects from one or several regions in 11 countries were included in this analysis. Austria (51%), Germany (41%) and Australia (30%) reported the highest proportion of air ambulance use. Monterrey, Mexico (median 10.1min) and Montreal, Canada (median 16.1min) reported the shortest and Germany (median: 30min) and Austria (median: 26min) reported the longest scene time. Use of intravenous fluid therapy among advanced EMS systems without physicians as pre-hospital care providers, varied from 30% (in the Netherlands) to 55% (in the US). The corresponding percentages in advanced EMS systems with physicians actively involved in pre-hospital trauma care, excluding Montreal in Canada, ranged from 63% (in London, in the UK) to 75% in Germany and Austria. Austria and Germany also reported the highest percentage of pre-hospital intubation (61% and 56%, respectively). CONCLUSION: This study provides an early look at international variability in patient mix, process of care, and performance of different pre-hospital trauma care systems worldwide. International efforts should be devoted to developing a minimum standard data set for trauma patients.     

Does the presence of extranodal extension in pathological stage B1 nonseminomatous germ cell tumor necessitate adjuvant chemotherapy?

PURPOSE: The presence of extranodal extension identified at primary retroperitoneal lymph node dissection has been associated with an increased risk of disease recurrence, and as such these patients are sometimes treated with adjuvant chemotherapy. We decided to evaluate the significance of extranodal extension on disease-free survival in patients with pathological stage B nonseminomatous germ cell tumor who did not receive adjuvant chemotherapy. MATERIALS AND METHODS: A retrospective review of our testicular cancer database was performed to identify all patients with clinical stage A nonseminomatous germ cell tumor who underwent primary retroperitoneal lymph node dissection and were found to have retroperitoneal metastasis with 5 or fewer involved nodes and no metastatic node larger than 2 cm. No patient received adjuvant chemotherapy, and all had a minimum followup of 24 months. A single pathologist (LC), who was blinded to clinical outcome, reviewed the retroperitoneal nodal package to identify the presence or absence of extranodal extension, defined as cancer perforating through the lymph node capsule into perinodal tissue. RESULTS: A total of 80 patients were identified with a median followup 48 months, and a 2 and 5-year disease-free survival of 75%. Extranodal extension was present in 23 patients and absent in 57 patients with a median followup of 54 and 44 months, respectively. The 5-year disease-free survival for patients with and without extranodal extension was 74% and 75%, respectively (p=0.67). CONCLUSIONS: We were unable to detect any prognostic significance of extranodal extension in patients found to have retroperitoneal metastasis at primary retroperitoneal lymph node dissection.     

体外短波热疗联合前列腺灸及哈乐治疗非细菌性前列腺炎和前列腺痛疗效观察

目的 探讨慢性非细菌性前列腺炎（CNP）和前列腺痛（PD）的治疗方法。方法 应用体外短波热疗联合前列腺灸及α1A-肾上腺素能受体阻滞剂哈乐治疗CNP和PD患者26例，疗程8周。观察治疗前后前列腺炎症状评分（CPSI）与最大尿流率（MFR）变化。结果 有效率为80．8％。治疗前后CPSI和MFR均有显著改善（P〈0．05）。结论 体外短波热疗联合前列腺灸及哈乐治疗CNP和PD安全有效。     

Gene therapy and erectile dysfunction： the current status

Current available treatment options for erectile dysfunction （ED） are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 （PDE5） inhibitors （i.e. sildenafil, tadalafil and vardenafil） has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure ＂on demand＂ without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined （lacunar） spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.     

狭窄性腱鞘炎的分期治疗

狭窄性腱鞘炎（俗称扳机指,Triggering finger）是手外科的常见病,保守疗法仍是治疗该病的常用措施。本文对1999年3月-2004年6月就诊的125例患者根据病情程度将其分为3期,施以不同的治疗方法,取得了较好的疗效。现总结报告如下。1临床资料1·1一般资料本组共125例（146指）,男24例,女101例;年龄27⁷5岁,平均51岁。其中,拇指61指,食指19指,中指28指,环指33指,小指5指。发病至本次治疗间隔时间平均27周。1·2分期标准根据孙康等[1]对狭窄性腱鞘炎的分期:Ⅰ期,掌指关节掌侧局限性疼痛,并有压痛,但不出现弹响,主动伸屈活动正常;Ⅱ期,患指伸屈时产生弹响,但     

肺隔离症的诊治进展

肺隔离症是一种少见的先天性肺发育异常疾病，临床上常被误诊误治。近年来，其影像学诊断及治疗方法均有新的突破。本文重点论述肺隔离症的病因、分类、影像学诊断及治疗方法上的最新进展.     

甲泼尼龙对体外循环后患者液体平衡及临床结果的影响

目的评价甲泼尼龙对低温体外循环（CPB）后患者液体正平衡、术后心血管功能稳定性和临床结果的影响。方法择期瓣膜置换或修复术成年患者32例,ASAⅡ级或Ⅲ级,随机分为2组,每组16例,对照组（NS组）麻醉诱导后静脉注射生理盐水10ml;试验组（MP组）麻醉诱导后静脉注射甲泼尼龙10mg/kg10 ml。监测术中及术后血液动力学和呼吸功能,记录术后气管导管留置时间、ICU停留时间、住院天数、术后血管活性药的用量及术后并发症的发生情况。于手术结束时、术后6 h和20 h计算液体净平衡。结果2组胶体液净平衡比较差异无统计学意义（P＞0．05）;与NS组比较, MP组手术结束时和术后20 h晶体液净平衡降低,CPB后心输出量、心脏指数升高,而CPB后各时点体循环阻力降低,CPB后即刻氧合指数升高（P＜0．05）;2组气管导管留置时间、ICU停留时间、住院天数和术后血管活性药的用量差异无统计学意义（P＞0．05）。结论麻醉诱导后静脉注射10 mg/kg甲泼尼龙可降低低温CPB后患者液体正平衡,提高术后心血管功能的稳定性,在一定程度上改善肺的氧合功能。