神经上皮肿瘤中端粒酶活性及其调节

目的 研究神经上皮肿瘤的端粒酶活性及其RNA和人端粒酶逆转录酶（h TERT)的表达水平,为其临床诊断和治疗开拓思路。方法 改良端粒重复序列扩增法及RT－PCR法检测65例神经上皮肿瘤患者肿瘤标本的端粒酶活性及其RNA和hTERT表达水平,并与8例正常脑组织的标本进行对照。结果 神经上皮肿瘤端粒酶阳性率为61．5％（分别r＝0．607,r＝0．678,均P＜0．01）。结论 端粒酶活性及hTERT与神经上皮肿瘤恶性程度有关;hTERT是调节端粒酶活性的关键酶。     

膀胱癌组织端粒酶活性的研究

目的　探讨膀胱癌组织端粒酶活性的临床意义。　方法　应用银染端粒重复序列扩增法检测 42例膀胱癌及其癌旁组织的端粒酶活性。　结果　 3例正常膀胱组织端粒酶表达均阴性 ;42例膀胱癌组织中端粒酶表达阳性 35例 (83 .3 % ) ,癌旁组织端粒酶表达阳性 7例 (16 .7% ) ;浸润癌或有淋巴结或远处转移者端粒酶表达阳性率高于非浸润癌或无转移者 ,但差别无显著性意义 (P >0 .0 5 )。　结论　端粒酶是膀胱癌较理想的肿瘤标记物之一。     

膀胱癌端粒酶活性的研究

目的 :探讨端粒酶活性和膀胱癌之间的关系。方法 :采用在PCR基础上建立的TRAP ELISA法对30例膀胱癌及 9例切缘组织和 7例正常膀胱组织中端粒酶活性进行半定量的研究。结果 :膀胱癌组总阳性率为83.3% (2 5 / 30 ) ,与切缘组 11.1% (1/ 9)和对照组 0 .0 % (0 / 7)相比差异有极显著性意义 (P <0 .0 1) ;后两者之间差异无显著性意义 (P >0 .0 5 )。端粒酶阳性表达率和表达强度与患者年龄、性别、病变部位、肿瘤大小、手术方式等无显著性相关 (P >0 .0 5 ) ,而端粒酶表达强度与细胞病理分级具有相关性 (P <0 .0 5 )。结论 :膀胱肿瘤的端粒长度和端粒酶活性对于判断疾病的恶性程度、预后、监测微小残瘤病灶和预示早期复发均有积极的意义     

膀胱肿瘤端粒酶活性及细胞凋亡的研究

目的　探讨端粒酶活性及细胞凋亡与膀胱癌临床生物学行为及预后的关系。　方法　分别采用端粒酶活性试剂盒和末端脱氧核苷酸转移酶介导缺口末端标记 (TUNEL)法对 5 6例膀胱癌标本进行端粒酶活性和细胞凋亡的检测 ,并结合临床资料进行分析。　结果　 5 6例膀胱癌标本端粒酶活性阳性率为 89 3 % (5 0 / 5 6 ) ,细胞凋亡指数为 (4 5 2± 14 4) % ;端粒酶活性强度及细胞凋亡指数与年龄、性别、肿瘤大小、数目等无关 (P >0 0 5 ) ;与肿瘤分级、分期及预后有关 (P <0 0 1) ,即端粒酶活性越高或 (和 )细胞凋亡越少 ,则肿瘤“瘤级”、“瘤期”高者预后较差。端粒酶活性强度与细胞凋亡指数呈明显的负相关 (r=- 0 6 9,P <0 0 1)。　结论　膀胱癌端粒酶活性及细胞凋亡与肿瘤分级、分期及预后有关 ,端粒酶活性及细胞凋亡的检测有助于膀胱癌的临床分析及预后的评估     

端粒酶抑制剂与丝裂霉素C联合应用对膀胱癌的作用

目的:探讨端粒酶抑制剂对荷瘤小鼠肿瘤生长的影响及与化疗药物的协同作用。方法:应用端粒酶抑制剂齐夫多啶(AZT)联合化疗药物丝裂霉素C(MMC)治疗小鼠移植性膀胱癌(T24),观察其对抑瘤率、肿瘤端粒酶的表达及对肿瘤细胞凋亡的影响。结果:AZT、MMC、MMC加AZT的抑瘤率分别为12. 1%、29. 6%和43. 6%,AZT与MMC均能抑制肿瘤生长,并且AZT与MMC联用明显优于两者单独应用(P<0. 05 )。采用TUNEL法检测肿瘤细胞凋亡指数分别为(20. 23±0. 89)%、(8. 04±0. 12)%和(24. 09±1. 81)%。肿瘤端粒酶活性检测显示各组端粒酶阳性率分别为36. 5%、43. 6%和11. 8%,与对照组比较,AZT、MMC均有减少肿瘤端粒酶活性的作用(P<0. 05)。结论:MMC及AZT均能抑制小鼠膀胱癌T24细胞的生长及降低其端粒酶活性,诱导细胞凋亡,二者联用有相加作用。     

尿液端粒酶活性在膀胱癌诊断和监测复发中的意义

目的　探讨检测尿液中端粒酶活性在膀胱癌诊断和监测复发中的意义。　方法　采用PCR ELISA法检测 4 6例膀胱癌患者尿液中的端粒酶活性 ,并观察其中 2 0例术后尿液端粒酶活性变化及与复发的关系。　结果　膀胱癌患者术前尿液端粒酶活性 0 .6 0± 0 .5 6 ,明显高于对照组 0 .18± 0 .0 8,P <0 .0 0 1,肿瘤切除后恢复正常 ,肿瘤复发前再次上升 ;端粒酶活性随肿瘤恶性程度的增加逐渐升高 ;术前端粒酶活性与早期复发无关。　结论　尿液端粒酶活性检测在膀胱癌诊断中有参考价值 ,与膀胱癌恶性程度相关 ,可能成为监测肿瘤复发的重要辅助手段。     

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目的　研究在乳腺肿瘤增殖过程中端粒酶活性与细胞周期素D1(CyclinD1)表达的相互关系。 方法　10 0例乳腺癌和 5 6例良性乳腺肿瘤 ,采用TRAP银染法检测端粒酶活性 ,以流式细胞术检测CyclinD1水平。 结果　正常乳腺组织中无端粒酶活性表达 ,CyclinD1水平仅为 (1 5 8± 0 4 5 ) ,恶性肿瘤组织中有较高活性的端粒酶表达和较高水平的CyclinD1表达。端粒酶活性随乳腺癌恶性程度的增加而逐渐增高 ,同时CyclinD1水平也随之而逐渐增高。无论是良性乳腺肿瘤还是恶性乳腺肿瘤 ,端粒酶表达阳性组的CyclinD1水平皆显著高于端粒酶表达阴性组。结论　乳腺肿瘤端粒酶的活性与CyclinD1水平相关 ,乳腺肿瘤端粒酶的激活可能与CyclinD1高表达相关。     

端粒酶活性表达在肾恶性肿瘤中的临床意义

目的　探讨端粒酶活性表达在肾恶性肿瘤中的临床意义。　方法　采用端粒酶 PCR ELISA法检测 3 1例肾恶性肿瘤、3 1例肿瘤旁组织和 6例正常肾组织标本端粒酶活性 ,按不同的临床病理参数分组分析。　结果　 3 1例肾恶性肿瘤组织端粒酶表达阳性率 80 .6% ,肿瘤旁组织及正常肾组织端粒酶表达均阴性 ,差异有显著性意义 (P <0 .0 1) ;病理分级Ⅰ级者端粒酶表达阳性率 58.3 %(7/ 12 ) ,Ⅱ级者阳性率 91.7% (11/ 12 ) ,Ⅲ～Ⅳ级者阳性率 10 0 .0 % (7/ 7) ,Ⅱ～Ⅳ级者端粒酶表达明显高于Ⅰ级者 (P <0 .0 5) ;RobsonⅠ期阳性率 77.8% (14 / 18) ,Ⅱ期阳性率 81.8% (9/ 11) ,Ⅲ～Ⅳ期 2例均阳性 ;T1N0 M0 期 3例均阳性 ,T2 N0 M0 期阳性率 79.2 % (19/ 2 4) ,T3N0 M0 期阳性率 66.7% (2 / 3 ) ,T2 N2 M0期 1例阳性 ,端粒酶表达与肿瘤临床分期无明显相关 (P >0 .0 5)。　结论　端粒酶活性检测结合病理检查对肾恶性肿瘤的早期诊断及预后判断有重要价值。     

大肠癌与端粒酶活性相关性的研究

目的　探讨端粒酶活性在大肠癌发生、发展以及浸润转移中的意义。方法　应用端粒重复扩增 (TRAP)及免疫组织化学法对 30例大肠癌、癌旁组织、正常大肠组织及 2 0例大肠腺瘤性息肉组织端粒酶活性、端粒酶催化亚基蛋白 (hTERT)的表达进行检测。结果　端粒酶活性在癌组织中检出率明显高于其他组织 (P <0 .0 5) ;大肠癌组织端粒酶活性与淋巴结是否有转移之间关系密切 ,伴淋巴结转移大肠癌端粒酶阳性表达率明显高于无淋巴结转移者 (P <0 .0 5)。结论　端粒酶活性与大肠癌的发生发展以及浸润转移密切相关 ,检测端粒酶活性对临床预测大肠癌淋巴结转移趋势、评价恶性程度和判断预后均有重要意义     

突变型端粒酶逆转录酶基因转染对膀胱癌细胞T24增殖的影响

目的　探讨转染缺失突变的人端粒酶逆转录酶 (hTERT)基因对膀胱癌细胞株T2 4端粒酶活性和体外增殖的影响 ,为膀胱肿瘤基因治疗提供新的基因靶点。　方法　采用DNA 磷酸钙共沉淀法 ,将绿色荧光蛋白基因标记的含突变型hTERT真核表达载体 pEGFP hTERT导入人膀胱癌细胞株T2 4中。应用荧光显微镜、端粒酶PCR ELISA法、与衰老相关的 β 半乳糖苷酶染色、软琼脂集落形成试验、裸鼠皮下成瘤试验等方法动态观察转染细胞中端粒酶活性及对细胞恶性表型的影响。　结果　在转染 pEGFP hTERT细胞中可见与突变型hTERT基因融合的绿色荧光蛋白稳定表达于细胞核内 ,转染细胞端粒酶活性降低 ,衰老相关 β 半乳糖苷酶表达增加 ,软琼脂中集落形成减少 ,裸鼠成瘤性降低。与转染空载体组及未转染组细胞相比 ,差别有显著性意义 (P <0 .0 5 )。　结论　转染突变型人端粒酶逆转录酶基因hTERT能抑制膀胱癌细胞T2 4的端粒酶活性 ,促进其衰老并逆转膀胱癌细胞的恶性表型 ,对膀胱肿瘤基因治疗具有潜在的临床应用价值     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.