抑癌基因P16在肾脏肿瘤中的表达及意义

为探讨抑癌基因Ｐ１６与肾脏肿瘤临床病理及预后的关系，采用免疫组织化学ＳＰ法对５３例肾癌组织中Ｐ１６基因进行检测。结果显示，５３例肾肿瘤Ｐ１６基因表达的阳生率为３７．７３％，其阳性表达与肿瘤的病理分级，临床分期及预后均密切相关，有显著性差异。     

Fascin蛋白在肾细胞癌中的表达及临床意义

目的观察Fascin蛋白在肾细胞癌中的表达情况,并探讨其表达与肿瘤生物学行为及临床病理指标的关系。方法用免疫组织化学方法检测109例肾细胞癌组织、20例肾脏良性肿瘤和20例正常肾脏组织中Fascin蛋白和Ki-67的表达,分析Fascin蛋白表达与不同临床病理指标及Ki-67表达之间的关系。结果109例肾细胞癌中有58例（53．2％）Fascin蛋白呈阳性表达,20例肾脏良性肿瘤和20例正常肾脏组织中的阳性表达例数分别为2例（10．0%）和0例（0%）,肾细胞癌中Fascin蛋白表达与肾脏良性肿瘤和正常肾脏组织中Fascin蛋白表达比较差异均有统计学意义（均P〈0．01）。肾细胞癌组织中Fascin蛋白表达与肿瘤组织学分级、临床分期、淋巴结转移以及Ki-67表达均呈正相关（均P〈0．01）;与肿瘤组织学分类无相关性（P〉0．05）。结论Fascin蛋白在肾细胞癌中表达上调且和肿瘤的恶性程度及侵袭行为有关。Fascin蛋白表达与病理分级和临床分期结合能够更好地判断肾细胞癌的预后,且其有可能成为肾细胞癌治疗的一个新靶点。     

胃癌中p16、p53蛋白表达与细胞增殖、浸润、转移及预后的关系

目的 探讨p16、p53蛋白表达与胃癌细胞增殖、浸润、转移及预后的关系。方法 应用免疫组化S－P法研究100例胃癌，20例中、重度异型增生，16例萎缩性胃炎和10例正常胃黏膜p16、p53蛋白和增殖细胞核抗原（PCNA）的表达。结果 正常胃黏膜p16阳性率为80％,p53未表达。萎缩性胃炎、异型增生和胃癌组织中p16阳性率分别为68．8％、35％和43％；p53阳性率分别为12．5％、25％和56％。p16在胃癌中的阳性率与预后明显相关（P＜0．05）；p53阳性率与肿瘤病理分级、Lanren分型有显著相关（P＜0．05），与预后关系密切（P＜0．01）。从正常胃黏膜到病变组织PCNA指数逐渐上升，以异型增生、胃癌细胞增殖显著（P＜0．01），癌细胞PCNA指数p16阴性组，p53阳性组高于对照组，与肿瘤大小、浸润浓度密切相关（P＜0．05）。p16、p53阳性表达具有协同性（P＜0．05）。结论 胃黏膜中、重度异型增生有较高的增殖活性，基因水平上已表现出癌变特性，是癌变发生过程中的一个重要阶段。p16、p53蛋白表达在胃癌的发生发展中起重要作用，可作为判断预后的可靠指标。     

抑癌基因FHIT和PTEN的表达与胆囊癌临床病理因素的关系

为探讨脆性组氨酸三联体（FHIT）基因和与张力蛋白同源、第10染色体丢失的磷酸酶基因（PTEN）与胆囊癌临床病理因素之间的关系。笔者采用免疫组织化学SP法检测53例原发性胆囊癌和25例慢性胆囊炎中PTEN和FHIT蛋白的表达。结果示在胆囊癌中，FHIT和PTEN蛋白阳性表达率分别为28.3%(15/53)和43.4%(23/53)，而在25例慢性胆囊炎组织中FHIT和PTEN蛋白阳性表达率分别为88.0%（22/25）和100%（25/25），其差异均有统计学意义（P＜0.05）。FHIT蛋白的表达与肿瘤分化程度及预后有关（P＜0.05），而PTEN蛋白的表达则与Nevin分期、肿瘤分化程度及预后有关（P＜0.05）。提示抑癌基因FHIT，PTEN的低表达在胆囊癌的发生、发展中起重要作用；检测FHIT，PTEN蛋白的表达有助于判断病情及预后。     

膀胱移行细胞癌组织中p53和血管内皮生长因子表达的关系及临床意义

目的研究p53和血管内皮生长因子（VEGF）在膀胱移行细胞癌（BTCC）组织中的表达及与BTCC临床参数的关系。方法免疫组织化学LDP法检测86例BTCC组织及10例正常膀胱组织中p53蛋白及VEGF的表达。BTCC病理分级（WHO）：G126例，G248例，G312例；临床分期（UICC）：浅表性66例，浸润性20例；随访10个月一8年，复发30例。结果BTCC组织中p53与VEGF阳性表达率分别为46．5％（40／86）和66．3％（57／86）。正常膀胱组织p53及VEGF均无表达。p53表达与VEGF表达呈明显正相关（P〈0．05）；二者均与BTCC的组织学分级显著相关（P〈0．05）；浸润性肿瘤阳性表达率明显高于浅表性肿瘤（P〈0．01）。p53阳性和VEGF阳性表达的肿瘤复发迅速，p53阴性而VEGF阳性表达较阴性表达者预后差。结论p53和VEGF与BTCC组织学分级和预后密切相关。BTCC是典型的血管依赖性病变，p53可能通过p53-VEGF调节旁路途径促进BTCC的肿瘤血管形成，联合检测p53和VEGF的表达可作为判断BTCC生物学行为及预后的重要指标。     

P53，C—erbB—2和bcl—2基因在膀胱癌中的表达及意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌组织中异常表达与肿瘤病理分级和临床分期之间的关系。方法：应用免疫组织化学方法检测96例膀胱移行细胞癌标本中P53,C－erbB-2和bcl-2基因的表达水平。结果：96例膀胱移行细胞癌标本中P53,C－erbB-2,bcl-2基因的阳性表达率分别为60．4％,66．7％和81．3％,P53,C－erbB-2和bcl-2异常表达与膀胱癌的病理分级和临床分期之间的差异有统计学意义（P＜0．01）,结论：P53,C－erbB-2和bcl-2基因异常表达在膀胱癌发生发展中起重要作用。肿瘤的多基因分析比单基因分析更有价值,为临床病理诊断及估计预后和复发提供了参考指标。     

肾细胞癌VHL基因改变与VEGF表达的关系及意义

目的：探讨肾细胞癌VHL基因异常与血管内皮生长因子（VEGF）表达的关系及意义。方法：应用聚合酶链反应（PCR）加单链构象多态性分析（SSCP）、多聚合酶链反应（Multiplex-PCR)及免疫组织化学方法检测42例肾细胞癌、18例远离肿瘤的正常肾脏及10例正常肾脏组织中VHL基因突变、异常甲基化及VEGF的表达。结果：肾癌组织中VHL基因改变（61．9％）与正常肾脏组织（3．6％）比较差别有显著性意义（P＜0．005）,VHL基因失活与肾癌组织类型及临床分期相关,与病理分级无关。VEGF在肾癌组织（64．3％）与正常肾组织（21．4％）中的表达差别有显著性意义（P＜0．005）,肾癌组织中VEGF表达与组织类型无关,与病理分级及临床分期相关,随病理分级及临床分期的升高而增高。VHL基因改变与VEGF表达间存在显著的相关性（P＜0．05）。结论：VHL基因在肾细胞癌中具有高频突变率,可负向调节VEGF的表达。     

膀胱移行细胞癌组织中p16、p53和PCNA的表达及其意义

目的:探讨p16、p53蛋白及PCNA在膀胱移行细胞癌的表达及其与病理分级和临床分期关系.方法:采用免疫组化SABC法并结合图像分析方法检测40例膀胱移行细胞癌中p16、p53蛋白及PCNA的表达.结果:3种蛋白在膀胱肿瘤中的表达与正常膀胱组织均有显著差异.p16与病理分级及临床分期呈负相关,p53、PCNA与病理分级呈正相关.结论:p16与p53可作为膀胱移行细胞癌分化程度和预后判断的参考指标,而PC-NA可作为预后判断辅助指标.     

联合评估凋亡相关蛋白Survivin和突变型p53在膀胱移行细胞癌中的表达及意义

目的：探讨凋亡相关蛋白Survivin和突变型p53在膀胱移形细胞癌（BTCC）中的表达及其临床意义。方法：应用SP免疫组织化学法检测50例BTCC及10例正常膀胱黏膜组织石蜡切片中Survivin和p53表达的情况,结合临床资料进行分析。结果：Survivin在BTCC的肿瘤标本中的阳性表达率为76％（38／50）,而正常对照组中无一例呈阳性表达;Survivin的表达与BTCC的组织学分级、预后显著相关（二者均P〈0．05）,但与临床病理分期无关（P〉0．05）;p53在13TCC肿瘤标本中的阳性表达率为68％（34／50）,与对照组阳性表达率30％（3／10）相比有统计学意义（P〈0．05）。p53的表达与BTCC组织学分级、临床分期及复发相关（均P％0．05）;相关性分析表明,BTCC肿瘤组织中Survivin的表达与p53表达呈正相关（r=0．317,P〈0．05）。结论：Survivin在BTCC组织中选择性表达,与BTCC的分化程度及复发密切相关;p53蛋白在BTCC中的表达与分级、分期及复发相关,联合评估Survivin和p53蛋白对于判断BTCC预后有重要临床指导意义。     

肾癌生物学行为与p16基因改变及蛋白表达的关系

目的：探讨p16基因改变在肾细胞癌发生发展中的作用及临床意义。方法：采用聚合酶链反应（PCR）加单链构象多态性分析（SSCP）、多重对照聚合酶链反应（multiplex-PCR)、双重对照PCR反应及链霉菌亲和物素蛋白－生物素酶标免疫组织化学（S－P法）检测42例肾细胞癌组织、18例远离肿瘤的正常肾脏及10例正常肾脏组织中p16基因异常及p16蛋白的表达情况。结果：p16基因改变在肾癌（30．95％）及正常肾脏组织（3．51％）差异有非常显著性（P＜0．01），其蛋白表达在肾癌（57．14％）及正常肾脏组织（89．29％）差异亦有显著性（P＜0．005），p16基因改变及蛋白表达与肾细胞癌组织学类型无关，p16蛋白表达与病理分级、临床分期相关。结论：p16基因失活在肾癌的发生发展中起着重要作用，其作用是通过不同的失活机制引起的p16蛋白表达缺如或功能丧失而实现；p16基因及蛋白的检测可作为肾癌的辅助诊断、判断恶性程度参考指标。     

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.