肉瘤样肾细胞癌组织中P53基因突变

为了明确Ｐ５３基因突变与肾癌发生发展的关系，采用Ｎｏｒｔｈｅｒｎｂｌｏｔ方法和免疫组织化学方法对３７例肾癌新鲜标本进行Ｐ５３基因检测。结果显示：７例Ｐ５３ｍＲＮＡ表达明显高于正常对照，９例（２４．３％）Ｐ５３蛋白过表达；３７例肾癌组织中３例为肉瘤样肾细胞癌或组织中含肉瘤样癌细胞成分，此３例（１００．０％）均有Ｐ５３ｍＲＮＡ和Ｐ５３蛋白过表达，都有肾门或腹膜后淋巴结转移；３４例透明细胞和颗粒细胞癌中４例（１１．８％）Ｐ５３ｍＲＮＡ高表达，６例（１７．６％）Ｐ５３蛋白过表达，其中１例有肾静脉癌栓，１例有肾门淋巴结转移，另１例取自切口转移癌组织。结果表明：肉瘤样肾细胞癌中有频繁的Ｐ５３基因突变，可能是肾癌细胞向肉瘤样癌细胞转化的关键因素之一。     

P53和C—fos蛋白在肾细胞癌中的表达

用免疫组织化学方法对６２例石蜡包埋的肾细胞癌标本中的Ｐ５３和Ｃ－ｆｏｓ蛋白进行检测。结果；Ｐ５３和Ｃ－ｆｏｓ蛋白表达均位于肿瘤细胞的细胞核内，其中Ｐ５３蛋白阳性３８例占６１．３％，Ｃ－ｆｏｓ蛋白阳性３３例占５３．２％。Ｐ５３蛋白和肾细胞癌的病理学分类无关，但Ｐ５３和Ｃ－ｆｏｓ蛋白随透明细胞癌的分期升高而高表达，并和预后有密切关系。     

VHL基因与肾细胞癌

肾细胞癌细胞遗传学研究显示染色体３Ｐ杂合性缺失及易位起主要作用，近年来对３Ｐ２５－Ｐ２６区域ＶＨＬ基因克隆定位成功，发现ＶＨＬ基因具有肿瘤抑制基因的特征，野生型ＶＨＬ蛋白与转录延伸因子Ｅｌｏｎｇｉｎ的Ｂ、Ｃ亚单位结合、阻断Ｅｌｏｎｇｉｎ ＡＢＣ复合体形成，从而调控基因转录，ＶＨＬ突变与肾透明细胞癌关系密切，为肾细胞癌的基因诊断和治疗开拓了广阔前景。     

肾癌p53蛋白表达及其点突变相关研究

目的探讨肾细胞癌发病机制中致癌基因突变规律。方法以ｐ５３蛋白表达及其点突变率为实验观测指标,对以往１１６例各类肾肿瘤以免疫组化ＡＢＣ法检测病理切片的ｐ５３表达。并以ＰＣＲＳＳＣＰ观测５９外显子点突变,并以１２例非瘤新鲜肾组织作对照。结果三类恶性肾细胞癌的ｐ５３阳性表达率介于４２％～５４％之间,且随癌细胞恶性度增加及分期增加而升高,而良性瘤及正常肾组织为阴性。点突变率介于２５％～７１％之间,与恶性度及分期相关。第９外显子点突变率明显高于其它区域,良性瘤及正常肾无点突变。结论肾癌发病机制与ｐ５３基因突变密切相关。ｐ５３蛋白阳性表达与其点突变相辅并存,协同一致,二者阳性率与生存期及预后密切相关     

肾细胞癌P53,c—erbB—2癌蛋白高表达与预后的关系

应用突变型Ｐ５３、ｃ－ｅｒｂＢ－２抗体和微波炉抗原修复法对３１例肾细胞癌进行免疫组化研究。结果显示突变型Ｐ５３和ｃ－ｅｒｂＢ－２癌蛋白的高表达阳性率分别为３５．５％和７４．２％；阳性患者的５年存活率２７．２％和４３．５％，而阴性患者的５年存活率则分别为７０．０％和８７．５％。提示突米型Ｐ５３、ｃ－ｅｒｂＢ－２的高表达可能与肾细胞癌的预后有关（Ｐ＜０．０５），并可能成为肾细胞癌的恶性标志和预后的辅助     

肾细胞癌bc1－2、P53、ER、PR的表达及临床意义

为了更好地选择估价肾细胞癌预后的指标，应用免疫组化技术检测５４例肾细胞癌中ｂｃ１－２、Ｐ５３蛋白及雌、孕激素受体的表达。ｂｃ１－２阳性３８例（７０．４％），Ⅰ、Ⅱ级肿瘤阳性３３例，Ⅲ、Ⅳ级肿瘤阳性５例（Ｐ＜０．０５）；Ｐ５３蛋白阳性１０例（１８．３％），对照组无一例阳性（Ｐ＜０．０５）；ＥＲ、ＰＲ阳性分别为２９例（５７．７％）、３９例（７３．７％）。ｂｃ１－２蛋白表达与ＥＲ、ＰＲ呈正相关（Ｐ＜０．０１，ｒ＝０．４５２），与Ｐ５３蛋白表达呈负相关（Ｐ＜０．０１，ｒ＝－０．４２１）。结果提示：ｂｃ１－２蛋白的表达有助于肾细胞癌预后的评估     

肾细胞癌P53、c－erbB－2癌蛋白高表达与预后的关系

应用突变型Ｐ５３、ｃ－ｅｒｂＢ－２抗体和微波炉抗原修复法对３１例肾细胞癌进行免疫组化研究。结果显示突变型Ｐ５３和ｃ－ｅｒｂＢ－２癌蛋白的高表达阳性率分别为３５．５％和７４．２％；阳性患者的５年存活率分别为２７．２％和４３．５％，而阴性患者的５年存活率则分别为７０．０％和８７．５％。提示突变型Ｐ５３、ｃ－ｅｒｂＢ－２的高表达可能与肾细胞癌的预后有关（Ｐ＜０．０５），并可能成为肾细胞癌的恶性标志和预后的辅助指标之一。     

多药耐药基因产物在肾细胞癌组织中的表达及意义

应用免疫组织化学方法检测４４例肾细胞癌组织中的多药耐药基因产物Ｐ糖蛋白的表达。结果６３．６％的肾细胞癌有Ｐ－ＧＰ表达。根据组织病理学分型，发现不同类型的肾细胞癌Ｐ－ＧＰ表达有所不同、颗粒细胞癌Ｐ－ＧＰ表达率为９０．９％，混合型癌为７５．０％，乳头状腺癌为５０．０％，透明细胞癌为４７．８％。     

P16抑癌基因在肾癌组织中的表达及临床意义

为了探讨Ｐ１６抑癌基因与肾癌生物学行为的关系，采用免疫组化法检测了４５例肾癌组织和２５例癌旁肾组织中Ｐ１６基因的表达。结果：癌旁肾组织Ｐ１６阳性率（８０．０％）显著高于肾癌组织（５１．１％）。Ｐ１６阳性率在Ⅰ、Ⅱ和Ⅲ级肿瘤中分别为７８．６％、４７．４％和２５．０％（Ｐ＜０．０５）；在Ⅰ、Ⅱ和Ⅲ～Ⅳ期肿瘤中分别为６８．４％、５３．３％和１８．２％（Ｐ＜０．０５），显示Ｐ１６表达阳性率随肾癌病理分级、临床分期的上升而降低。Ｐ１６阳性与阴性表达组间３、５年生存率均存在显著性差异。提示抑癌基因Ｐ１６在防止肾癌的发生和发展中起着重要作用，可作为肾癌生物学行为及预后评估的参考指标。     

VHL基因与肾细胞癌

肾细胞癌细胞遗传学研究显示染色体３Ｐ杂合性缺失及易位起主要作用，近年来对３Ｐ２５－Ｐ２６区域ＶＨＬ基因克隆定位成功，发现ＶＨＬ基因具有肿瘤抑制基因的特征，野生型ＶＨＬ蛋白与转录延伸因子Ｅｌｏｎｇｉｎ（ＳⅢ）的Ｂ、Ｃ亚单位结合，阻断ＥｌｏｎｇｉｎＡＢＣ复合体形成，从而调控基因转录。ＶＨＬ基因突变与肾透明细胞癌关系密切，为肾细胞癌的基因诊断和治疗开拓了广阔前景     

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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

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.