Antibodies to hepatitis C virus in autologous blood donors

Hepatitis C virus (HCV) is the major cause of posttransfusion hepatitis. Two anti-HCV enzyme immunoassay (EIA) kits and one recombinant immunoblot assay (RIBA) were used to test serum samples of 1476 donations from 692 autologous blood donors to assess the prevalence of anti-HCV and its relationship to transfusion history. Of all autologous blood donations, 23 (1.6%) reacted when tested with one EIA kit and 29 (2.0%) reacted when tested by the other EIA kit. Of the autologous donors, 12 (1.78%) reacted by the first EIA kit and 14 (2.02%) by the second. Discrepancies in the EIA results from different donations by the same donor were seen in seven donors. The RIBA was positive or indeterminate in 33 percent of the EIA-reactive donations and in 41 percent of EIA-reactive donors. All RIBA-positive and -indeterminate samples reacted with both EIA kits. There was no significant difference in the EIA-reactive rates of autologous and first-time homologous blood donors. Previously transfused autologous blood donors had a higher anti-HCV EIA-reactive rate than nontransfused autologous donors, but the difference was not significant. In regard to hepatitis C, the use of autologous blood for homologous transfusion appears to be as safe as the use of blood from first-time homologous donors. Universal testing of previously transfused patients for hepatitis C appears premature at this time. Discrepant anti-HCV EIA results from different donations from the same individual have implications regarding donor deferral.     

单剂半量赛尼哌预防移植肾急性排斥的临床观察

目的观察单剂半量赛尼哌对肾移植急性排斥(AR)的预防作用及安全性评估。方法选择同期肾移植病人187例,根据术后肾功能恢复情况及术前是否使用赛尼哌分为A/90例、B/73例、C/11例、D/13例4组,其中A、B组移植后肾功能恢复良好,即术后1周血肌酐<176.6μmol/L,C、D组术后出现移植肾功能延迟恢复,术后1周血血肌酐>353μmol/L。A、C两组术前2h静滴赛尼哌25mg(0.5mg/kg)和口服霉酚酸酯0.75g,B、D组仅口服霉酚酸酯0.75g;术后四组病人均予甲基强的松龙500mg×3d冲击,常规强的松、环孢霉素A和霉酚酸酯三联抗排斥治疗。观察术后6个月内AR发生率、发生时间、强度及排斥逆转率,同时观察胃肠道反应、感染及血液系统损害等副作用。结果A组13例(14.4%)发生AR,B组18例(24.6%),C组6例(54.5%),D组7例(53.8%),A组AR发生率明显低于B、C、D三组(P均<0.01);B组AR发生率显著低于C、D组(P<0.01),C、D组差异不显著(P>0.05),A组排斥开始时间3-9d(6.2±3.2d)较B组2-8d(4.5±3.1d)、C组2-7d(4.3±4.2d)、D组2-9d(3.9±3.5d)明显延迟(P均<0.05)。但B、C、D三组排斥开始时间无明显差异(P>0.05)。A组AR经强化治疗均逆转,B组16例逆转,另2例失败,C组5例逆转,1例因移植肾排斥破裂出血切除,D组5例逆转,2例失败;C、D组各2例于术后13-32d再次排斥,经甲基强的松龙强化治疗逆转。感染、胃肠道反应及血液系统损害四组差异不显著(P均>0.05)。结论移植后肾功能恢复良好病人,术前25mg赛尼哌可显著降低AR发生率,且安全性好。但对于移植肾功能延迟恢复病人,术前25mg赛尼哌并不能有效预防排斥发生。     

A prospective microbiologic surveillance program to detect and prevent the transfusion of bacterially contaminated platelets

After two patients received bacterially contaminated platelet transfusions, a prospective surveillance program was instituted to perform Gram staining and microbiologic culturing of platelets at the time of transfusion. In 12 months, 3141 random-donor platelet pools (prepared from 14,481 units) and 2476 single-donor apheresis units were cultured. All single-donor apheresis units were sterile, but 6 (0.19%) of the random-donor pools were found to be bacterially contaminated, with 1 unit of 5 in the pool being the source in each case. Contaminants were Staphylococcus epidermidis (4 cases), Bacillus cereus (1), and Staphylococcus aureus (1) at counts of 0.5 × 10(2) to 10(11) colony-forming units per mL in platelet pools and 10(3) to 10(13) colony-forming units per mL in source units. The contamination rate for units transfused at < or = 4 days (1.8/10,000) was significantly lower than that at 5 days (11.9/10,000; p < 0.05), as was the magnitude of contamination (p < 0.05). Use of the pretransfusion Gram stain on 4- and 5-day-old platelet pools was 100 percent sensitive (4/4 true positives) and 99.93 percent specific (1 false positive) in detecting contaminated pools. These data define the extent and magnitude of platelet bacterial contamination and demonstrate the efficacy of the pretransfusion Gram stain on platelet units stored for 4 and 5 days in preventing the transfusion of heavily contaminated units. It is concluded that the risk of platelet contamination is related to the duration of component storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

腹腔镜膀胱癌根治加回肠膀胱术

目的:总结腹腔镜下膀胱癌根治加回肠膀胱术的手术方法及临床疗效。方法:2003年6月～2007年5月共行25例腹腔镜下根治性全膀胱切除、双侧盆腔淋巴结清扫加回肠膀胱术,患者平均年龄68岁,全膀胱切除和盆腔淋巴结清扫均在腹腔镜下完成,标本自下腹部小切口取出后,体外切取末端回肠10～15cm,近端闭合并与双侧输尿管吻合,远端造口于右下腹壁。结果:所有手术均顺利完成,手术时间210～320min,平均270min。术中出血220～1000ml,平均460ml。平均每例清扫淋巴结数10个,淋巴结阳性率16.2%,手术切缘均阴性。术后3～5天肠道功能恢复,1例因粘连性肠梗阻于术后1周再行手术探查松解粘连。术后2～3周拔除单J管,无肠漏及尿漏并发症发生。随访2～30个月,1例死于原发病转移,无腹壁造口狭窄发生,3例术后B超或造影显示单侧轻度肾积水和轻度输尿管扩张。结论:腹腔镜膀胱癌根治术具有创伤小,恢复快等优点,但手术难度较大,手术技术要求较高。回肠膀胱术手术操作相对简单,并发症少,可作为腹腔镜膀胱癌根治术后尿流改道可选方式之一。     

Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDA) remains a lethal human malignancy with historically limited success in treatment. The role of aberrant Notch signaling, which requires the constitutive activation of γ-secretase, in the initiation and progression of PDA is well defined and inhibitors of this pathway are currently in clinical trials. Here we investigated the in vivo therapeutic effect of PF-03084014, a selective γ-secretase inhibitor, alone and in combination with gemcitabine in pancreatic cancer xenografts. PF-03084014 treatment inhibited the cleavage of nuclear Notch 1 intracellular domain and Notch targets Hes-1 and Hey-1. Gemcitabine treatment showed good response but not capable of inducing tumor regressions and targeting the tumor-resident cancer stem cells (CD24⁺CD44⁺ and ALDH⁺ tumor cells). A combination of PF-03084014 and gemcitabine treatment resulted tumor regression in 3 of 4 subcutaneously implanted xenograft models. PF-03084014, and in combination with gemcitabine reduced putative cancer stem cells, indicating that PF-03084014 target the especially dangerous and resilient cancer stem cells within pancreatic tumors. Tumor re-growth curves plotted after drug treatments demonstrated that the effect of the combination therapy was sustainable than that of gemcitabine. Notably, in a highly aggressive orthotopic model, PF-03084014 and gemcitabine combination was effective in inducing apoptosis, inhibition of tumor cell proliferation and angiogenesis, resulting in the attenuation of primary tumor growth as well as controlling metastatic dissemination, compared to gemcitabine treatment. In summary, our preclinical data suggest that PF-03084014 has greater anti-tumor activity in combination with gemcitabine in PDA and provides rationale for further investigation of this combination in PDA.     

Characterization and toxicology evaluation of zirconium oxide nanoparticles on the embryonic development of zebrafish,Danio rerio

Zirconia oxide nanoparticles (ZrO₂NPs) are known to be one of the neutral bioceramic metal compounds that has been widely used for their beneficial applications in many biomedical areas, in dental implants, bone joint replacements, drug delivery vehicles, and in various industrial applications. To study the effects of ZrO₂NPs on zebrafish model, we used early life stages of the zebrafish (Danio rerio) to examine such effects on embryonic development in this species. ZrO₂NPs were synthesized by the sol-gel method, size about 15–20?nm and characterized by SEM, EDX, XRD, FTIR, UV-Vis Spectra. In this study, zebrafish embryos were treated with ZrO₂NPs 0.5, 1, 2, 3, 4, or 5?μg of nanoparticles/ml during 24–96?hour post fertilization (hpf). The results showed that ≥0.5–1?μg/ml of ZrO₂NPs instigated developmental acute toxicity in these embryos, causing mortality, hatching delay, and malformation. ZrO₂NPs exposure induced axis bent, tail bent, spinal cord curvature, yolk-sac, and pericardial edema. A typical phenotype was observed as an unhatched dead embryo at ≥1?μg/ml of ZrO₂NPs exposure. This study is one of the first reports on developmental toxicity of zebrafish embryos caused by zirconium oxide nanoparticles in aquatic environments. Our results show that exposure of zirconium oxide nanoparticles is more toxic to embryonic zebrafish at lower concentrations. The results will contribute to the current understanding of the potential biomedical toxicological effects of nanoparticles and support the safety evaluation and synthesis of Zirconia oxide nanoparticles.     

A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer

Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic.