Isolated Limb Infusion for Malignant Melanoma: Predictors of Response and Outcome

Purpose

Isolated limb infusion (ILI) is an alternative to isolated limb perfusion (ILP) for the treatment of unresectable limb melanoma recurrence. The aims of this study were to determine the response rates of unresectable local and/or in-transit melanoma of the upper or lower limb to ILI and to identify factors predictive of survival.

Methodology

A prospective database identified 74 patients (35 male and 39 female) with local and/or in-transit melanoma recurrence without metastatic disease who underwent hyperthermic ILI with melphalan at a single institution between January 1996 and December 2008. Three patients could not be evaluated for response. Median follow-up was 34 months.

Results

Of the 74 patients, the majority had N2c disease (57/74, 67%), while 17/74 (33%) patients had N3 disease. Median maximum temperature achieved was 38.1°C and median tourniquet time was 32.5 min. Wieberdink III/IV complications occurred following 7/74 (10%) ILI and were associated with higher limb volumes and higher total melphalan dose. Complete response (CR) was seen following 17/71 (24%) ILI and the partial response rate was 30% (22/71). The median duration of CR was 43 months. Univariable analyses found that limb volume >8.0 l and maximum limb temperature >38.5°C were the only independent factors predictive for a CR following ILI. Multivariate analyses identified CR and positive lymph nodes as the only independent prognostic factors for melanoma-specific survival.

Conclusions

Patients who obtain CR have significantly improved survival compared with nonresponders. The challenge remains to improve CR rates and prospectively identify responders.     

International milestones 1985

In three studies we investigated denial and related concepts ('phenomena of make believe’, ‘psychic numbing’, ‘blotting out the idea’ and ‘veil of denial') as the predominant human psychological responses to the nuclear war threat. We found support for this assertion within the subjects’ emotional reactions of overwhelming fear and sadness. To reduce the paralyzing effect of the denial response, we suggest three steps: immersing ourselves in the negative affect, presenting moderate fear arousal messages, and promoting active involvement.     

Towards the twenty‐first century

It is suggested that the change in thought and technology in France, North America and England in the late 18th century is paralleled in the change in contemporary modes of behaviour and ways of looking at the self. The philosophy articulated at that time was by the philosophers of the Enlightenment and poets of Romanticism. Contemporary psychologies are concerned with the structure of the individual psyche and with social organization.

In this nuclear age we are threatened by nuclear war, over‐population and ecological imbalance, with irreversible destruction of living and technological resources. The contemporary philosophical and technological changes are on a global basis, as is the current conflict reflecting a war of man against himself. This can lead to either complete annihilation of humanity or to a re‐appraisal through a holistic approach to ourselves and our planet, based on internationalism.     

Building world democracy through the UN

The evolution of autonomous units of organized human society from tribes to sovereign nation‐states has been paralleled by a belief in a need for global unification under a religious or secular authority.

A modern alternative to the subordination of nation‐state sovereignty to a higher authority is to restrain the excesses of the established world system by institutionalizing in the United Nations a democratic voice for the world public's opinions. This could be done by means of: (1) a UN Second ('we the peoples') Assembly or related proposal; (2) a UN Parliamentary Assembly to represent national parliaments; (3) an assembly representative of non‐governmental organizations affiliated with the UN or its Agencies and other bodies; (4) a UN‐grassroots system for information‐sharing and dispute‐solving.

The paper summarizes the principles of these approaches, and outlines in more detail the multidisciplinary basis of the concept of a UN Second Assembly, the Penrose method for equitable voting power or distribution of seats in a world assembly, and the work of the International Network for a UN Second Assembly (INFUSA) including the initiative for a series of international Conferences on A More Democratic United Nations (CAMDUN).     

缺氧复合氰化钠中毒对大鼠脑组织单胺类神经递质含量的影响

目的观察缺氧复合氰化钠(NaCN)中毒对大鼠脑组织单胺类神经递质含量的影响。方法128只雄性SD大鼠随机分为平原组和高原组,每组64只。平原组大鼠在常规实验室内处理,高原组于模拟海拔4 000m的高原低压舱内连续缺氧暴露3d,每天23.5h。高原组和平原组大鼠分别在模拟高原条件和平原条件下经腹腔注射NaCN 3.6mg/kg,于中毒0、0.5、2、6h麻醉取脑,冰上分离海马和纹状体组织,离心提取组织内蛋白质。HPLC法测定大鼠脑纹状体和海马组织多巴胺(DA)、去甲肾上腺素(NE)和5-羟色胺(5-HT)含量。结果平原组大鼠NaCN中毒0.5、2、6h脑纹状体和海马组织的DA、NE和5-HT含量与中毒0h比较变化不明显。高原组大鼠脑纹状体DA、NE、5-HT含量和海马组织NE、5-HT含量在NaCN中毒2h或6h与0h比较均显著下降。与平原组比较,高原组纹状体DA、NE、5-HT和海马组织NE、5-HT含量均明显降低(P<0.05或0.01)。结论高原缺氧后脑组织单胺类神经递质含量明显降低,而氰化物中毒可进一步加剧这一改变。     

叶酸-白蛋白包覆阳离子纳米脂质载体的制备及体内外评价

合成叶酸-白蛋白靶向材料,通过薄膜分散法制备白蛋白包覆阳离子脂质纳米载体(BSA-cNLCs)和叶酸-白蛋白包覆阳离子脂质纳米载体(FA-BSA-cNLCs)。对两者粒径、外观、包封率、载药量、体外细胞摄取、血液和肿瘤药代动力学和药效学进行考察。结果表明,BSA-cNLCs和FA-BSA-cNLCs粒径分别为81.4和79.8 nm,Zeta电位分别为+5.12和+3.74 mV,透射电镜照片表明两者均为圆整的类球形结构。两者紫杉醇包封率都大于97%,载药量在3.7%左右。体外细胞试验证实,高表达叶酸受体的SKOV3对FA-BSA-cNLCs的摄取显著高于BSA-cNLCs,说明FA-BSA-cNLCs对SKOV3具有明显的靶向性。血液及肿瘤药代动力学显示两者体内药代动力学行为无明显差异,证实表面修饰叶酸不影响制剂的体内行为。药效学试验显示,BSA-cNLCs和FA-BSA-cNLCs抑瘤率分别为72.08%和80.75%。可见FA-BSA-cNLCs在一定程度上提高了体内外抗肿瘤疗效,在肿瘤的治疗中具有较好应用前景。     

基于脑血管重建的血管内皮生长因子缓释微球制备及性质研究

目的制作用于脑血管重建研究的血管内皮生长因子(VEGF)缓释微球并研究其性质。方法采用W1/O/W2复乳溶剂挥发法制作VEGF-聚乳酸-羟基乙酸共聚物(PLGA)微球和载罗丹明B微球;使用扫描电镜观察其表面形态结构;采用微量蛋白测定法测定微球中药物的载药量和包封率,并对微球的体外释药性能进行研究;将用罗丹明B标记的微球注入大鼠颞肌组织,分别于第10天和第30天取颞肌组织行冰冻切片,倒置荧光显微镜下观察。结果扫描电镜观察到微球表面光滑无孔隙,粒径为4~10μm;微球载药量及包封率的测定显示其平均载药量为(25.50±1.57)%,平均包封率为(85.07±0.15)%,累积释放率可达80%以上;微球在颞肌组织中可持续存在30 d以上。结论 VEGF-PLGA微球能稳定长时间释放VEGF,可用于脑血管重建研究。     

支气管内超声引导针吸活检术对肺门、纵隔淋巴结肿瘤和结核的诊断价值

目的探讨支气管内超声引导针吸活检术（EBUS-TBNA）在肺门、纵膈淋巴结恶性肿瘤和结核诊断中的应用价值。方法回顾性分析2013年1月至2016年9月在四川大学华西医院呼吸内镜中心接受EBUS-TBNA检查的553例患者的临床及病理资料,统计EBUS-TBNA对肺门、纵膈淋巴结肿瘤和结核的诊断敏感性、特异性和准确率。结果EBUS-TBNA诊断肺门、纵膈淋巴结恶性肿瘤的敏感性、特异性和准确率分别为89.2%（263/295）、100.0%（247/247）和94.1%（510/542）。针吸活检组织查见肉芽肿诊断结核的敏感性、特异性和准确率分别为65.0%（76/117）、97.2%（385/396）和89.9%（461/513）。标本组织行抗酸染色和TB-PCR的102例中,查见抗酸杆菌或TB-PCR任一项阳性诊断结核的敏感性、特异性和诊断准确率为63.7%（58/91）、90.9%（10/11）和66.7%（68/102）。结论EBUS-TBNA诊断肺门和纵膈肿瘤具有较高的敏感性和特异性,并可联合抗酸染色和TB-PCR联合诊断肺门和纵膈淋巴结结核。     

AAV-TGFβ1的构建及其与AV-TGFβ1对髓核细胞蛋白多糖合成影响的比较

目的探讨转化生长因子β1腺相关病毒表达系统(AAV-TGFβ1)的构建及其与转化生长因子β1腺病毒表达系统(AV-TGFβ1)对髓核细胞蛋白多糖合成影响的比较。方法采用PCR技术扩增转化生长因子β1(TGFβ1)基因,并于其两端分别连接EcoRI和SalI酶切位点。将TGFβ1基因亚克隆于腺相关病毒(AAV)载体中,并经酶切和测序分析进行鉴定。AAV-TGFβ1病毒被包装并转染H293细胞,通过免疫荧光检测AAV介导的目的基因表达。利用AAV-EGFP病毒检测AAV对髓核细胞的转染效率。AAV-TGFβ1和AV-TGFβ1分别转染髓核细胞后,通过Antonopulos法检测蛋白多糖的合成。结果测序分析证明TGFβ1序列与NCBI Gene Bank所报道的一致。经酶切鉴定证实AAV-TGFβ1重组质粒被成功构建。AAV可介导TGFβ1高效表达并高效转染髓核细胞。AV-TGFβ1可快速一过性地促进髓核细胞蛋白多糖合成,而AAV-TGFβ1可稳定促进蛋白多糖合成。结论AAV-TGFβ1病毒被成功构建并可稳定地促进髓核细胞蛋白多糖的合成。