A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases.

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.     

Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate.

Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. INTRODUCTION: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. MATERIALS AND METHODS: We measured the resistance to pull-out 1-mm-diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1-34), pamidronate or saline vehicle for 8 wk. The tibias were removed for microCT morphometry, followed by the evaluation of pull-out strength. RESULTS: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (-29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to-implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. CONCLUSIONS: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

骨髓间充质干细胞向肝细胞的横向分化

目的：综合分析骨髓间充质干细胞向肝细胞分化的研究现状及应用前景。资料来源：应用计算机检索Pubmed 2000—01／2005—04有关干细胞及其向肝细胞横向分化方面的文献，检索词“stem cell，hepatoeyte．transdifferentiation”，并限定文章种类为English。资料选择：对检索到的有关干细胞及其向肝细胞横向分化方面的文献进行整理，选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼：共检索到45篇相关文献，其中38篇符合要求，7篇为重复同一研究而排除。资料综合：利用骨髓间充质干细胞在肝损伤等病理状态下具有分化为肝细胞的特性，实现肝组织重建，纠正肝细胞代谢和合成功能障碍，为治疗肝炎、肝硬化、肝癌及肝代谢性疾病提供了新的策略。干细胞在肝病治疗中的应用无疑是对传统治疗方式的挑战。结论：多数学者的研究表明，干细胞具有分化为肝细胞及胆管细胞样细胞的潜能，但也有少数学者持否定意见。目前对于移植后干细胞是产生细胞融合还是分化作用尚存在争议。     

抗人热休克蛋白60效价增高提示急性心源性胸痛患者的一年预后不良

目的：探讨抗人热休克蛋白60或抗分枝杆菌热休克蛋白65抗体是否能够预测因急性心源性胸痛入院的患者一年预后不良。设计：前瞻性观察研究。地点：教学医院。患者：连续588例急诊收治的疑似急性心源性胸痛患者。主要观察指标：测定入院后晨起血样的抗人热休克蛋白60和抗分枝杆菌热休克蛋白65效价。出院后终点为冠心病死亡、非致死性心肌梗死、冠状动脉搭桥术、经皮穿刺腔内冠状动脉成形术、血管造影或因心脏缺血性胸痛加重再次入院。     

交锁髓内钉在四肢长管状骨骨折中的失误与处理

目的:探讨交锁髓内钉技术的临床疗效及并发症的主要原因和治疗效果。方法:1999年6月-2004年6月采用交锁髓内钉技术治疗四肢长管状骨骨折420例,男310例,女110例;其中股骨干骨折180例,胫腓骨双骨折160例,肱骨干骨折10例,股骨粗隆间骨折60例,股骨髁上骨折10例。年龄20~87岁,平均56岁。发生并发症30例,术中骨折端劈裂2例,钢丝捆扎后完成交锁;异位再骨折2例和术后再骨折2例,更换较长的髓内钉;髓内钉卡在髓腔内进退困难1例,捶击髓内钉尾端拔出髓腔;横向交锁失误12例,其中10例在术中发现退出锁钉重新完成交锁,2例在术后发现应用石膏外固定6周;术后发生主钉断裂2例,二次手术更换较粗的主钉;骨折端不稳定出现反常活动3例,应用石膏外固定6~8周;导针与钻头相嵌顿2例,通过捶击拔出钻头退出导针;腹壁软组织损伤4例进行理疗。结果:本组400例得到6~12个月的随访,骨折全部愈合。膝关节屈曲受限(<90°)4例,肩关节外展上举受限(<90°)1例。结论:交锁髓内钉技术治疗四肢长管状骨骨折临床疗效良好;粗劣的操作技术是发生并发症的主要原因;积极处理并发症可避免功能障碍的发生。     

老年人与青年人皮肤血流量比较研究

目的 判定增龄对皮肤血流量的影响。方法 用PIM2-LDPI检测皮肤血流量。结果 老年组前额、左手指背、命门穴部位皮肤血流量分别为:(1.94±0.86)V,(1.92±0.52)V和(0.71±0.19)V,与青年组比较差异无显著性。但是,老年男性在命门穴的皮肤血流量明显高于青年男性(P<0.05),老年女性前额的皮肤血流量明显降低(P<0.01)。男性比女性的皮肤血流量高。结论 皮肤血流量的差异无年龄相关性,男性组的皮肤血流量比女性组高。     

微波凝固对变应性鼻炎患者T淋巴细胞亚群的影响及意义

目的　探讨常年性变应性鼻炎 (PAR)患者细胞免疫功能状态及微波凝固治疗的作用机制。方法　观察组 2 5例PAR患者分别于微波治疗前以及治疗 1个月后应用免疫组化法检测鼻粘膜上皮和外周血CD3、CD4、CD8、CD4/CD8水平。健康对照组 1 5例亦作相应检测。结果　PAR患者治疗前鼻粘膜及外周血CD3、CD4明显高于正常人 ,CD8低于正常人 ,CD4/CD8比值升高 ,与正常人比较差异有显著性 (P <0 .0 5)。微波治疗后CD4明显减少 ,CD8升高 ,CD4/CD8接近于健康对照组。结论　PAR患者存在明显的细胞免疫功能障碍 ;微波局部凝固治疗可改善PAR患者的细胞免疫状况。     

改良Hardinge入路在非骨水泥全髋置换术中的应用

目的：对改良Hardinge入路行全髋置换进行评价。方法：对经改良Hardinge入路行非骨水泥全髋置换（THR－CL）术并获术后6个月以上随访的32例病人进行总结。结果：优良28例（88％），很好4例（12％），其中轻度跛行6例（19％），下肢不等长＞2cm1例（3％），改良Trendelenburg试验阳性3例（10％）。结论：此入路创伤小，暴露好，利于假体定位，易于控制下肢长度，术后外展肌功能恢复快。