自体骨屑移植颏部充填动物模型的建立

目的:设计及建立自体骨屑移植颏部充填的动物模型,评价此动物模型的可行性,为临床自体骨屑移植提供实验资料和理论依据。方法:实验于2006-06/12在南方医科大学南方医院实验动物中心完成。选用同窝健康40周杂种犬4只,全麻后取下颌角区切口,分离咬肌暴露下颌角,切取部分下颌角区下颌骨,用电动打磨机磨碎成骨屑。在下颏部切口,分离至下颏骨膜处,将骨屑移植至下颏部下颌骨区,清洗沉淀后,将富含松质骨的骨屑移植至下颏部下颌骨区,并用牙科钻在下颏骨移植区处打孔3个,深达松质骨,建立动物模型。术后当时、术后4,8,12周观察犬进食活动情况,进行下颌骨X射线检测,全麻下活体取材行骨组织苏木精-伊红染色常规组织学检查,并观察移植骨屑的稳定性。结果:4只犬全部进入结果分析,无脱失。①手术后动物进食活动正常。②植骨区X射线观察结果:术后4周骨密度低于正常下颌骨;8周时骨形状基本和正常一致,皮质连续骨密度略低于正常;12周时缺损两端与植骨区无明显界限。③植骨区组织学观察结果:术后4周时可见新生的骨小梁,但排列紊乱;8周时骨小梁形成的编织骨已逐渐向板层骨过渡;12周时植骨区基本形成板状骨,骨质较厚。④移植骨屑的稳定性及活动度:术后4周,所移植骨屑的稳定性较好,不能活动。结论:实验成功建立了自体骨屑移植颏部充填的动物模型,以骨屑为支架,可以很快形成新生骨,与颏部下颌骨融合良好,结构稳定,提示模型有效、可靠。     

相关信号转导分子在创伤性兔膝骨关节炎发病中的变化

目的:在创伤性兔膝骨关节炎的发病机制中关节软骨细胞凋亡、诱导型一氧化氮合酶、基质金属蛋白酶组织抑制因子3、尿激酶型纤溶酶原激活物及其受体蛋白均会发生一些变化,观察其相关特征,从而确立骨关节炎"细胞通讯"的病理机制。方法:实验于2004-07/2006-07在兰州大学第一附属医院中心实验室及甘肃中医学院实验室完成。①实验动物:将36只健康青紫蓝家兔(雌雄各半)随机分成正常组、模型组各18只。②实验方法:模型组用硫喷妥钠30mg/kg腹腔麻醉,在无菌条件下取双侧膝关节内侧切口长约3cm,直视下探查关节腔无原发病变后,用眼科剪伸入切断前后交叉韧带、内侧副韧带、完整切除内侧半月板进行造模,正常组不作任何处理。③实验评估:运用流式细胞分析法、免疫组化法分别于6、8周两个时期进行DNA倍体含量、基质金属蛋白酶组织抑制因子3、尿激酶型纤溶酶原激活物及其受体蛋白、诱导型一氧化氮合酶蛋白阳性强度观察。结果:参加实验36只家兔,进入结果分析20只。①诱导型一氧化氮合酶蛋白表达:6周时各组间差异无显著性,8周时模型组损伤胶原化区与各组间差异显著(P<0.05)。②基质金属蛋白酶组织抑制因子3蛋白表达:6周时各组间比较差异有显著性,正常组6周和8周比较差异有显著性(P<0.05)。③细胞凋亡情况:8周时正常组与模型组DNA比率差异有显著性、但细胞凋亡均数差异无显著性。④尿激酶型纤溶酶原激活物及其受体蛋白表达:6,8周时各组间比较差异有显著性;正常组与模型组损伤胶原化区、正常组与模型组增殖肥厚区、正常组与模型组无损伤区;损伤胶原化区与增殖肥厚区、损伤胶原化区与无损伤区间差异有统计学意义(P<0.05);正常组和模型组6周和8周比较差异均有显著性(P<0.05)。结论:骨关节炎病理机制中存在破坏与修复相互拮抗平衡的分子"多轴心机制"。     

缺氧诱导因子1α在大鼠急性缺血心肌组织中的变化

目的:了解缺氧诱导因子1αmRNA和蛋白质在大鼠急性缺血心肌组织中表达的变化规律。方法:实验在南通大学生物技术系,江苏省神经生物学重点实验室完成。①实验分组:雄性SD大鼠78只,其中42只大鼠随机分为7组,每组6只,分别设为空白对照组(0h)和缺血0.5h,1h,1.5h,2h,3h,4h组,检测缺氧诱导因子1αmRNA表达变化。另外36只大鼠随机分为6组,每组6只,分别设为空白对照组(0h)和缺血1h,2h,4h,5h,6h组,检测缺氧诱导因子1α蛋白表达变化。②实验方法:通过结扎大鼠左冠状动脉前降支,构建左室心肌缺血模型。术中心电图等证明结扎成功后,分别在上述不同时间点取缺血心肌组织,分别运用反转录聚合酶链式反应法和免疫组织化学方法检测缺血心肌组织中缺氧诱导因子1αmRNA和蛋白质的表达变化。结果:缺氧诱导因子1αmRNA和蛋白质在正常大鼠心肌中微量表达,心肌缺血后表达明显增高,并随缺血时间变化而变化。0.5h缺氧诱导因子1αmRNA表达显著增加(P<0.05),1.0～2.0h达到高峰(P<0.01),以后逐渐下降并趋向基线。心肌缺血后1h缺氧诱导因子1α蛋白质表达明显上升(P<0.05),4h达到高峰(P<0.01),随缺血时间延长表达回降。结论:缺氧诱导因子1α在缺血心肌组织中高表达。缺氧诱导因子1α在大鼠缺血心肌组织中表达的上调,可能参加了心肌缺血的代偿机制,有助于改善心肌供血。     

经紫外线预照射移植猪皮片覆盖烧伤创面时间的观察

目的:观察经紫外线预照射移植猪皮片对烧伤创面覆盖时间的影响。方法:选择2004-01/2005-12四川攀枝花钢铁有限责任公司职工总医院烧伤科收治的需要植皮的烧伤患者35例,患者均知情同意。按随机数字表法分为2组,紫外线预照射组18例,对照组17例。紫外线预照射组使用的猪皮片经过40W紫外线预照射,波长为253.7nm,灯管距猪皮30cm,照射时间2h;对照组使用的移植猪皮片未做紫外线预照射。将移植猪皮片真皮面覆盖于切削痂创面上,加压包扎,用手术刀片打洞以利引流。观察整体猪皮片的存活时间,在术后5,10,15d取0.2cm×0.3cm大小的整层猪皮制成匀浆,检测相关生化因子水平:应用双抗体夹心酶联免疫吸附法测肿瘤坏死因子α含量,应用鲎法测内毒素含量,应用黄嘌呤氧化酶法测超氧化物歧化酶活性,应用硫代戊巴比妥酸法测丙二醛含量。移植猪皮片出现外观苍白,与创面分离,融解脱落均视为失效。结果:35例烧伤患者全部进入结果分析,无脱落。①紫外线预照射组猪皮平均烧伤创面覆盖时间为(18.3±2.4)d,显著高于对照组(13.7±3.1)d(P<0.05)。覆盖猪皮术后15d,紫外线预照射组有3例移植猪皮片失效,对照组有9例移植猪皮片失效。②随时间延长,两组患者覆盖猪皮片局部组织匀浆肿瘤坏死因子α、内毒素、丙二醛含量均呈升高趋势,术后10d和15d紫外线预照射组显著低于对照组(P<0.01)。两组患者覆盖移植猪皮片局部组织匀浆超氧化物歧化酶活性随时间延长均呈下降趋势,术后10d和15d紫外线预照射组显著高于对照组(P<0.01)。结论:紫外线预照射新鲜猪皮用于覆盖烧伤创面能明显延长创面保护时间,其作用途径可能与减轻局部组织脂质过氧化反应程度及炎性因子水平有关。     

Use of a generally applicable tissue factor--dependent factor V assay to detect activated protein C-resistant factor Va in patients receiving warfarin and in patients with a lupus anticoagulant

The original activated partial thromboplastin time-based assay for activated protein C (APC)-resistant factor Va (FVa) requires carefully prepared fresh plasma and cannot be used in patients receiving warfarin or in patients with antiphospholipid antibodies. A new test is described here that circumvents these limitations and distinguishes without overlap heterozygotes for APC-resistant FVa from persons with normal FV. A diluted test plasma is incubated with an FV-deficient substrate plasma and tissue factor and then clotted with Ca2+ or Ca2+ plus APC. Test results are independent of the FV level or the dilution of the test plasma used. Of 39 controls, 37 gave normal results. Two controls (5%) gave results indicative of APC resistant FVa and on DNA analysis were found to be heterozygous for FV R506Q. Twenty of 21 randomly selected patients receiving warfarin gave normal results. In the single patient with abnormal results, heterozygous FV R506Q was confirmed by DNA analysis. Two of 15 patients with protein S deficiency and 5 of 29 patients with a lupus anticoagulant had abnormal results. APC resistance caused by FV R506Q was confirmed in the five of these seven patients available for DNA analysis. APC-resistant FVa was also detected in 10 of 21 (46%) stored plasma from unrelated patients with venous thrombosis and negative earlier evaluation for a lupus anticoagulant or a deficiency of protein C, protein S, or antithrombin, which confirms a high incidence of this defect among patients with venous thrombosis.     

Prolonged versus standard gemcitabine infusion: translation of molecular pharmacology to new treatment strategy

Gemcitabine is frequently used in the treatment of patients with solid tumors. Gemcitabine is taken up into the cell via human nucleoside transporters (hNTs) and is intracellularly phosphorylated by deoxycytidine kinase (dCK) to its monophosphate and subsequently into its main active triphosphate metabolite 2',2'-difluorodeoxycytidine triphosphate (dFdCTP), which is incorporated into DNA and inhibits DNA synthesis. In addition, gemcitabine is extensively deaminated to 2',2'-difluorodeoxyuridine, which is largely excreted into the urine. High expression levels of human equilibrative nucleoside transporter type 1 were associated with a significantly longer overall survival duration after gemcitabine treatment in patients with pancreatic cancer. Clinical studies in blood mononuclear and leukemic cells demonstrated that a lower infusion rate of gemcitabine was associated with higher intracellular dFdCTP levels. Prolonged infusion of gemcitabine at a fixed dose rate (FDR) of 10 mg/m2 per minute was associated with a higher intracellular accumulation of dFdCTP, greater toxicity, and a higher response rate than with the standard 30-minute infusion of gemcitabine in patients with pancreatic cancer. In the current review, we discuss the molecular pharmacology of nucleoside analogues and the influence of hNTs and dCK on the activity and toxicity of gemcitabine, which is the basis for clinical studies on FDR administration, and the results of FDR gemcitabine administration in patients. These findings might aid optimal clinical application of gemcitabine in the future.     

Prophylactic gastrostomy tubes for patients receiving radical radiotherapy for head and neck cancers: A retrospective review

Patients undergoing radical radiotherapy for head and neck cancers often experience significant complications. We sought to evaluate the impact of prophylactic gastrostomy tubes (PGTs) among these patients on four easily evaluable adverse outcomes, namely, absolute weight loss, percentage weight loss, admissions for nutritional reasons and treatment interruptions. A retrospective review was carried out on patients undergoing radical radiotherapy for primary head and neck cancers from September 1999 to October 2005 at the Wellington Blood and Cancer Centre (n = 71). PGTs were placed in 7 (10%) patients. Patients with PGTs were compared with the patients without PGTs (the control group) by univariate and multivariate analyses. By univariate analysis, there was no significant difference in absolute or percentage weight loss between those with PGTs and the control group. By multivariate analysis, those with PGTs lost 5.2% (P = 0.016) less weight than the control group. There were no significant differences between the two groups with regard to admissions for nutritional reasons or treatment interruptions. The use of PGTs can reduce weight loss in patients undergoing radical radiotherapy for head and neck cancers, and its use should be further evaluated in future studies.     

Natural history of growth hormone receptor deficiency

Rosenbloom AL, Martinez V, Kranzier JH, Bachrach LK, Rosenfeld RG, Guevara-Aguirre J. Natural history of growth hormone receptor deficiency. Acta Pædiatr 1999; Suppl 428: 153–6. Stockholm. ISSN 0803–5326
This review discusses the natural history of growth hormone receptor deficiency (GHRD) in relation to epidemiology, mortality, growth, certain aspects of body composition, and intellectual development. The majority of affected individuals are of Semitic origin and 90% come from the Indian peninsula, the Middle East, or elsewhere in the Mediterranean. There is a twofold increased mortality before the age of 7 years for children with GHRD. Affected adults may have increased cardiovascular risk resulting from increased total cholesterol and low-density lipoprotein cholesterol, unrelated to adiposity or insulin resistance. Intrauterine growth is affected minimally, if at all. Within a genetically homogeneous population in Ecuador, postnatal growth effects are as variable as in a large genetically heterogeneous population. There is no influence of parental heights. Areal bone mineral density is reduced in adults with GHRD, but estimated volumetric bone density (bone mineral apparent density) is normal. Intellectual development is unaffected by GHRD. □ Body composition, growth, growth hormone receptor deficiency, insulinlike growth factor I deficiency, intellectual development, Laron syndrome, natural history     

Relation of basic and clinical research on foetal and neonatal thyroid pathology to neonatal thyroid screening

In this short review the importance is emphasized of basic and clinical research in regard to the interpretation of screening results. This review covers foetal thyroid physiology during the first 48 h of life, the importance of thyroid hormones for normal brain development, the definition of a critical period which might explain intellectual abnormalities in 10-15% of detected hypothyroid children and the importance of autoimmunity in the aetiology and diagnosis of transient congenital hypothyroidism.     

应用无支架Medtronic生物瓣行主动脉瓣替换

评估无支架Ｍｅｄｔｒｏｎｉｃ生物瓣作主动脉瓣替换的安全性和临床效果。方法以冠状动脉开口下方植入技术用无支架Ｍｅｄｔｒｏｎｉｃ生物瓣作主动脉瓣替换共８５例。易除左、右冠状动脉空运保留完整的无冠窦,全部采用连续缝合方法。结论无支架Ｍｅｄｔｒｏｎｉｃ生物瓣作主动脉瓣替换效果良好,适用于年龄超过７５岁以及伴有狭小动脉根部的病人。