Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

Role of extracellular adenosine triphosphate in the cytotoxic T- lymphocyte-mediated lysis of antigen presenting cells

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma- activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.     

A prediction model for complete remission upon reinduction for patients with acute myeloid leukemia after failure of anthracycline and cytarabine standard chemotherapy

The aim of this study was to investigate clinical parameters that might predict complete remission (CR) following reinduction therapy in patients with acute myeloid leukemia (AML). We retrospectively analyzed outcomes in 142 patients who failed to achieve CR with standard anthracycline-plus-cytarabine induction chemotherapy (IND1) and who received the same regimen as a reduction therapy (IND2). The CR rate after reinduction was 54%. Multivariate analysis showed that the presence of peripheral blood (PB) blasts on the day of commencement of IND2 and ≥20% blasts in an interim BM sample taken during IND1 (C1-INT-BM) were independent risk factors for failure of remission. Our scoring system for prediction of CR after reinduction (CRAR score) included a favorable chromosome risk group, absence of PB blasts on the day of commencement of IND2, and ≤21% blasts in the C1-INT-BM. This scoring system predicted that the rates of CR in the four subgroups would be 92.1%, 68.9%, 29.5%, and 7.3%, respectively, in good agreement with observed CR rates. The CRAR scoring model might be associated with the possibility of achieving CR after reinduction, and may be helpful in choosing alternative strategy for AML patients refractory to standard induction chemotherapy, although further prospective validation is required.     

亲属活体肾移植18例报告

目的：总结亲属活体肾移植的临床经验，以期提高该技术的安全性及疗效。方法：选择2005—11／2006—12解放军第一七五医院收治的亲属活体肾移植患者18例，均知情同意。受体均为慢性肾小球肾炎；供体年龄24-74岁，17例有血缘关系，另一例为妻子供肾。均行经腰开放手术取肾，左侧供肾15例，右侧供肾3例。术后受体采用环孢素A＋霉酚酸酯＋激素三联低剂量免疫抑制剂方案。结果：①所有供体在术后10d左右出院，均无严重并发症且肾功能正常。②16例受体均在术后1-3d内移植肾功能恢复正常，另2例因供肾迷走血管损伤在术后5d左右血肌酐下降到200μmol／L，1个月左右稳定在160μmol／L。1例他克莫司仅服0．5-0．75mg／d，于术后5个月出现急性排斥反应。1例术后2个月出现环孢素A急性肾毒性（血药浓度谷值为343μg，L）。2例出现药物性肝炎。结论：亲属活体肾移植术较为安全，排斥反应少，结果满意。免疫抑制剂宜采用低剂量方案。     

不同孔径纳米羟基磷灰石人工骨修复兔桡骨缺损效果比较

目的:纳米级的羟基磷灰石材料与人体内组织成分更为相似,具有更佳的生物性能。评价不同孔径的多孔纳米羟基磷灰石人工骨的骨缺损修复能力,从而筛选出适合的孔径以达到骨传导功能与生物力学性能的良好统一。方法:实验于2005-10/2006-10在深圳市第二人民医院中心实验室完成。①实验材料:纳米羟基磷灰石人工骨以硝酸钙和磷酸二氢铵为原料,采用溶胶-絮凝法制备粉体,运用压力成型、木模成型和浸渍成型分别制得孔隙分布均匀的孔径分别为50～150μm、100～250μm和300～500μm的多孔纳米羟基磷灰石人工骨。②实验动物:雄性新西兰大白兔60只随机分为植入50～150μm孔径材料组、植入100～250μm孔径材料组、植入300～500μm孔径材料组、空白对照组,每组15只。实验过程中对动物处置符合动物伦理学要求。③实验方法:制备双侧桡骨骨缺损动物模型,然后用3种不同孔径的纳米羟基磷灰石人工骨材料植入骨缺损处进行修复,空白对照组不植入任何材料。④实验评估:术后4,8和12周分别行大体标本观察、X射线片观察、扫描电镜观察及生物力学测试,比较各组材料修复骨缺损的能力。结果:实验动物均进入结果分析。①X射线片检查结果:术后4周、8周、12周,植入100～250μm孔径材料组X射线评分高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。②生物力学检测结果:术后4周、8周、12周,植入100～250μm孔径材料组生物力学强度高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。③扫描电镜观察结果:植入100～250μm孔径材料组成骨效果明显优于植入50～150μm,300～500μm孔径材料组和空白对照组。结论:纳米羟基磷灰石人工骨具有良好的成骨能力,但其骨修复能力受孔径因素的影响,孔径100～250μm的纳米羟基磷灰石人工骨材料成骨能力较好。     

异硫氰酸荧光素标记动态观察天花粉蛋白对黑色素瘤B16细胞的损伤

目的:应用异硫氰酸荧光素标记天花粉蛋白,在激光共聚焦显微镜下直接观察天花粉蛋白进入黑色素瘤B16细胞的动态过程并分析其对黑色瘤B16细胞的损伤作用。方法:实验于2003-08/2004-08在南通大学神经再生重点实验室完成。将常规传代培养的黑色素瘤B16细胞用胰酶消化,以5×109个/L的浓度种植于24孔培养板。将天花粉蛋白、异硫氰酸荧光素-天花粉蛋白、异硫氰酸荧光素-牛血清白蛋白分别加入培养细胞中,终浓度为50mg/L,同时加入等量生理盐水作为正常对照组,每组再分别设3,6,12h不同孵育时间组。异硫氰酸荧光素标记天花粉蛋白后,利用激光共聚焦显微镜观察异硫氰酸荧光素-天花粉蛋白进入细胞的过程及其荧光强度,CCK-8细胞毒性实验评估各组细胞存活率、并用单细胞凝胶电泳及hoechst33258染核观察天花粉蛋白对黑色素瘤B16细胞致DNA损伤作用。结果:①终浓度50mg/L的异硫氰酸荧光素-天花粉蛋白孵育3h时已经进入黑色素瘤细胞,6h时进入细胞量达到最高,12h时已轻度下降,各时间点比较差异有统计学意义(P<0.01)。异硫氰酸荧光素-天花粉蛋白组与异硫氰酸荧光素-牛血清白蛋白组荧光强度差异有显著性(P<0.01)。②终浓度50mg/L异硫氰酸荧光素-天花粉蛋白、天花粉蛋白孵育黑色素瘤细胞3,6h后利用单细胞电泳和Hoechst33258染色未观察到核形态的变化;但孵育6h后CCK-8细胞毒性实验显示活细胞数量明显下降;孵育12h后出现DNA损伤的特征性彗星尾现象,并观察到明显的核浓缩和边集现象,出现特征性凋亡小体。结论:孵育6h时天花粉蛋白进入细胞量最多,但并没有明显的细胞DNA损伤的作用,而孵育12h时产生明显的细胞毒作用和凋亡的发生。     

上海市0～6岁小儿佝偻病的现状调查

目的:了解上海市小儿佝偻病的现状及影响因素。方法:2005年春季以整群和分层随机抽样法抽取上海市部分城区0～6岁小儿821名,采取问卷调查方法了解小儿的生活环境、饮食习惯、户外活动、营养状况、既往疾病史及母亲的妊娠情况等。佝偻病的诊断以1996年国家卫生部颁布的"婴幼儿佝偻病防治方案"为诊断标准。结果:取得完整有效资料769名,其中男童396名,女童373名;集居儿童456名,散居儿童313名。①小儿佝偻病患病率为17.3%(133/769),其中男童患病率为17.4%、女童为17.2%。②佝偻病与喂养方式(母乳喂养的患病率为13.0%、混合喂养的患病率为17.5%、人工喂养的患病率为25.2%)、鱼肝油添加(按时添加维生素D的患病率为13.5%、偶加或未加维生素D的患病率为32.5%)、居住环境(居住在市区的患病率为23.6%、居住在郊区的患病率为10.6%;集居儿童患病率为13.8%、散居儿童患病率为22.4%)、户外活动时间(经常户外活动的患病率为12.9%、偶尔户外活动的患病率为31.8%)、反复呼吸道感染(小儿有反复呼吸道感染的患病率为26.9%、无反复呼吸道感染的患病率为12.9%)、母孕期缺钙(母孕期有缺钙的患病率为33.2%、无缺钙的患病率为12.0%)等因素有关(P<0.01)。结论:上海市小儿佝偻病患病率有上升趋势。影响因素与城市环境污染、母乳喂养减少、年轻父母科学育儿知识缺乏等有关。     

Characterization of antimicrobial resistance and class 1 integrons found in Escherichia coli isolates from humans and animals in Korea

OBJECTIVES: Antimicrobial resistance and class 1 integrons found in Escherichia coli isolates from humans and animals in Korea were characterized. METHODS: E. coli isolates were examined for susceptibility to antimicrobial agents. Integrase genes were amplified. Gene cassette regions for classes 1 and 2 integrons were amplified and sequenced. Conjugal transfer and Southern hybridization were performed to determine the genetic localization of class 1 integrons. The clonal relationship of E. coli isolates carrying an identical cassette array was analysed by PFGE. RESULTS: Commensal E. coli isolates from animals were highly resistant to commonly used antimicrobial agents such as tetracycline, sulfamethoxazole, streptomycin, ampicillin and carbenicillin. Integrons were most prevalent in commensal E. coli isolates from poultry (44%), followed by clinical isolates from humans (33%), commensal isolates from swine (23%) and humans (13%). dfrA17-aadA5, dfrA12-orfF-aadA2 and aadA1 were found most frequently in E. coli isolates from humans, poultry and swine, respectively. Class 1 integrons were mostly located in conjugative plasmids. E. coli isolates carrying an identical cassette array were phylogenetically unrelated. CONCLUSIONS: The use of antibiotics is strongly associated with antimicrobial resistance. E. coli isolates from different sources may select a specific gene cassette by antibiotic selective pressure, which results in differences in class 1 integrons. The horizontal transfer of class 1 integrons through conjugative plasmids seems to be responsible for wide dissemination of a particular type of class 1 integron.     

氯磷酸二钠表面改性羟基磷灰石血清蛋白吸附行为的改变

目的:观察二磷酸盐药物对羟基磷灰石进行表面改性后对材料表面蛋白吸附的影响。方法:实验于2005-06/08在口腔生物医学工程教育部重点实验室完成。①将羟基磷灰石制成10mm×10mm×2mm大小的块状,共48块,随机分为实验组与对照组,每组24块。②实验组羟基磷灰石与氯磷酸二钠复合制成氯磷酸二钠-羟基磷灰石,对照组不复合氯磷酸二钠,用乙醇和蒸馏水超声波清洁,干燥备用。③将两组标本分别置入100g/L小牛血清(蛋白吸附溶液)和0.2mol/LPBS磷酸缓冲液(对照吸附溶液)中浸泡吸附,每种溶液中12块。④通过X射线光电子能谱分析检测和蛋白质电泳对两组材料表面吸附的蛋白进行对比分析。结果:①X射线光电子能谱分析检测提示吸附小牛血清后,实验组和对照组表面氮元素百分含量分别是(9.83±1.33)%和(10.11±1.67)%,差异无显著性意义(P>0.01)。②十二烷基磺酸钠-聚丙烯酰胺凝胶电泳提示两组材料均可以吸附大量白蛋白,实验组表面吸附的白蛋白要少于对照组。③双向电泳提示两组材料表面吸附的蛋白相对分子质量均大于50000;对照组吸附的酸性蛋白量要多一些,实验组表面吸附的碱性蛋白和中性蛋白要多一些;偏酸性的蛋白中,β球蛋白和玻璃粘连蛋白在实验组表面吸附量较对照组表面多。结论:氯磷酸二钠复合羟基磷灰石对材料表面吸附蛋白的种类有一定影响,但对总量没有明显影响。