肝癌患者外周血AFP mRNA表达的临床意义

目的:探讨肝细胞肝癌(HCC)患者外周血AFP mRNA表达在血行播散中的意义.方法:抽取30例HCC患者外周静脉血5ml,应用RT-PCR对血中AFP mRNA进行扩增检测,并与各对照组比较.结果:30例HCC患者中,AFP mRNA的阳性率为46.7%(14/30);AFP mRNA的表达阳性率与肝癌TNM分期、肿瘤大小、有无门脉癌栓及有无肝外转移有显著的相关性(P＜0.05),而与血清AFP水平无关(P＞0.05).结论:AFP mRNA是反映原发性肝癌患者血中是否存在肝癌细胞的灵敏指标.     

IGF-Ⅱ、IGFBP-2在肝癌病人血清的表达及其对评价经皮肝动脉化疗栓塞治疗效果的意义

目的 检测原发性肝癌(简称肝癌)病人血清IGF-Ⅱ、IGFBP-2的表达,探讨经皮肝动脉化疗栓塞(transhepatic artery chemoembolization,TACE)治疗前后IGF-Ⅱ、IGFBP-2表达水平变化的临床意义.方法 采用ELISA法检测正常人群与肝癌病人以及肝癌病人TACE治疗前后血清IGF-Ⅱ和IGFBP-2的表达水平.采用电化学发光法测定肝癌病人TACE前后血清AFP的表达水平;对比两组人群及肝癌病人TACE治疗前后血清IGF-Ⅱ、IGFBP-2表达水平差异,比较肝癌病人血清IGF-Ⅱ、IGFBP-2表达水平与AFP表达水平的相关性.结果 在正常人群与肝癌病人两组血清IGF-Ⅱ、IGFBP-2水平存在显著差异(F=32.63,P＜0.01;F=26.84,P＜0.01),肝癌病人血清IGF-Ⅱ、IGFBP-2表达水平明显高于正常人群组(P＜0.01).血清IGF-Ⅱ、1GFBP-2和AFP诊断肝癌的敏感性分别为61.22%、53.06%和73.46%,特异性分别为79.78%、76.53%和85.39%.AFP阴性肝癌病人IGF-Ⅱ和IGFBP-2阳性检出率分别为38.46%和61.53%.肝癌病人组血清IGF-Ⅱ、IGFBP-2水平与AFP呈正相关(r=0.446,P＜0.01;r=0.180,P＜0.05).肝癌病人采用IGF-Ⅱ、IGFBP-2和AFP单独检测的阳性率分别为61.22%、53.06%和73.46%,而采用血清IGF-Ⅱ+IGFBP-2+AFP联合检测的阳性率则高达93.87%.TACE治疗前血清IGF-Ⅱ和IGFBP-2水平显著高于TACE治疗后,差异有统计学显著性(P＜0.05).结论 检测正常人群和肝癌病人血清IGF-Ⅱ、IGFBP-2表达水平有助于肝癌的早期诊断,可弥补AFP阴性病人之诊断不足;肝癌病人TACE前后血清IGF-Ⅱ、IGFBP-2表达水平检测和AFP一样可用于TACE治疗临床疗效的评价.     

肝癌患者血清中聚糖蛋白3检测的临床意义

目的 探讨血清聚糖蛋白3(GPC3)在肝癌研究中的临床应用价值.方法 应用生物素-链霉亲和素系统亲和力高的特点建立双抗体夹心酶联免疫吸附试验(ELISA)方法,检测681份不同人群血清中的GPC3.结果 (1)肝硬化组(42.9%)、肝癌组(41.4%)、肝癌复发组(61.1%)患者血清GPC3阳性率与正常人组(4.1%)及乙肝组(8.6%)差异有统计学意义(P<0.01);肝细胞型肝癌组(HCC)血清GPC3阳性率(45.9%)高于胆管细胞型肝癌组(ICC)(20.9%)(P<0.05);HCC组中直径≤3 cm的小肝癌及AFP≤20μg/L的肝癌血清中GPC3阳性率分别为36.0%、41.9%;AFP≤<20μgs/L且直径≤3 cm的小肝癌患者血清GPC3阳性率为44.4%(4/9).(2)联合血清AFP及GPC3,可将单独应用AFP时提示肝癌复发从77.7%提高到88.9%.(3)结肠癌肝转移病例血清中GPC3的阳性率为28.6%.(4)手术切除术前及术后2～16 d内HCC患者血清中GPC3的变化多样.(5)24例HCC组织GPC3阳性20例,其中血清GPC3阳性率为50%.结论 血清中GPC3的测定作为一种新的肿瘤标志物在肝癌的诊断特别是早期诊断、提示复发、转移及评价手术治疗效果中可能均有一定的意义.     

Pokemon在肝硬化结节中的动态表达及意义

目的 观察Pokemon在不同时期肝硬化结节中的表达水平,探讨Pokemon动态变化与肝硬化结节癌变之间的关系.方法 应用实时定量逆转录-聚合酶链反应(RT-PCR)法检测30例直径＞1 cm肝硬化结节组织中Pokemon水平,分4次进行,时间分别为初次确诊肝硬化结节组织(＞1 cm)之时、之后0.5、1.0、1.5 y.同时对该肝硬化结节进行常规病理检查.结果 4次检测Pokemon阳性表达率分别为96.67%(29/30)、96.55%(28/29)、100.00%(27/27)、95.45%(21/22)(P＞0.05).Pokemon表达水平在0 y与0.5 y、1.0y与1.5 y组间差异无统计学意义(P＞0.05),后两组表达水平明显高于前两组(P＜0.05).相关肝硬化结节的0.5、1.0、1.5 y癌变率分别0.00%(0/29)、14.29%(4/28)、33.33%(9/27).结论 初次确诊之时及之后0.5 y的肝硬化结节组织中Pokemon表达水平显著低于确诊之后1、1.5 y的水平.Pokemon表达水平与肝硬化结节癌变密切相关.动态监测肝硬化结节Pokemon表达水平可能有助于发现肝硬化结节癌变.     

Pokemon在肝细胞癌、肝细胞癌远处转移、肝硬化和健康人群外周血中的表达及意义

目的观察Pokemon在肝细胞癌（HCC）、肝细胞癌远处转移、肝硬化患者和健康人群外周血中的表达特征及其影响因素。分析Pokemon作为HCC诊断、预测转移复发标记物的价值。方法研究对象分4组（n=40）。HCC合并乙型肝炎后肝硬化行肝移植患者、HCC远处转移合并乙型肝炎后肝硬化、乙型肝炎后肝硬化及健康人群各抽外周血2ml 1次。用实时定量逆转录一聚合酶链反应（RT-PCR）法检测Pokemon mRNA的表达。结果（1）Pokemon在HCC、肝硬化和健康人群外周血中的表达差异元统计学意义（P〉0．05）。（2）HCC远处转移组Pokemon表达量、表达比例明显高于其余各组（P〈0．05）。（3）HCC外周血中Pokemon表达水平与性别、年龄、HBSAG、HBV．DNA、AST、ALT、AFP无关（P〉0．05）。结论HCC患者外周血中的Pokemon表达水平不高；肝硬化、健康人群组也可能存在Pokemon的表达。HCC远处转移组Pokemon表达水平明显高于HCC肝移植、肝硬化和健康人群组。监测外周血中Pokemon表达水平可能有助于诊断和预测HCC远处转移。     

人宫颈癌致癌基因和Pokemon在肝细胞癌中的表达及其相关性

目的 观察人宫颈癌致癌基因(HCCR)和Pokemon在肝细胞癌中的表达水平,探讨两者间的关系.方法 应用实时定量逆转录-聚合酶链反应(RT-PCR)法检测41例肝癌组织、43例癌旁组织及其相应44例血液标本、3例肝硬化组织及其相应的3例血液标本以及3例正常肝组织中HCCR、Pokemon的表达水平,分析肝细胞癌(HCC)患者血液样本中HCCR、Pokemon表达水平与临床指标的关系.结果 肝癌、癌旁、肝硬化及正常肝组织HCCR阳性表达率分别为100.00%、97.67%、100.00%、100.00%;Pokemon阳性表达率分别为97.56%、97.67%、100.00%、100.00%.但HCCR、Pokemon在各类组织中的表达水平差异有统计学意义(P<0.05),肝细胞癌、癌旁、肝硬化、正常肝等组织中的表达水平呈递减趋势.肝细胞癌患者血液中HCCR、Pokemon阳性率分别为79.55%及50.00%.两者的表达水平显著相关.结论 HCCR和Pokemon可能可以做为HCC相关的肿瘤标记物.HCCR和Pokemon在肝细胞癌患者中存在某种程度的关系.     

原发性肝癌患者介入治疗前后血清GPC3水平检测的临床价值

目的:了解原发性肝癌(hepatocellar carcinoma,HCC)介入治疗前后GPC3的浓度变化和临床价值.方法:采用ELISA法检测HCC、肝硬化、正常人血清GPC3浓度.结果:51例HCC患者、16例肝硬化患者、正常人组血清GPC3浓度分别为(3 939.72±2 801.92)、(619.08±542.80)和(534.24±500.20)pg/mL,前者与后二者比较差异有统计学意义(P<0.05),但其表达与血清甲胎蛋白(alpha-fetoprotein,AFP)无显著相关性;32例HCC患者介入治疗后高转移复发倾向组血清GPC3浓度为(4 418.00±3941.96)pg/mL,低转移复发倾向组血清GPC3浓度为(534.44±910.56)pg/mL,二者比较差异有统计学意义(P<0.05);缓解组、稳定组、恶化组血清GPC3浓度分别为(571.64±288.72)、(2 521.76±2340.76)、(4 812.84 4-1 858.64)pg/mL,3组两两比较差异均有统计学意义(P<0.05).结论:GPC3在HCC患者血清中的检出率高,特异性强,其表达与AFP无相关性,联合应用AFP及GPC3可提高诊断的灵敏度.GPC3与肿瘤复发转移、治疗效果有关.     

外周血γ-谷氨酰转移酶mRNA-H亚型与甲胎蛋白对原发性肝癌诊断及肝外转移意义的比较

目的　探讨外周血γ 谷氨酰转移酶 (GGT)mRNA H亚型及甲胎蛋白 (AFP)的表达与原发性肝癌 (HCC)诊断及肝外转移的关系。方法　以逆转录 聚合酶链反应方法检测HCC及对照组外周血GGTmRNA H亚型 ;运用放射免疫测定法检测外周血AFP水平。结果　 65例肝癌中 ,GGTmRNA H亚型阳性率为 46.2 %。小肝癌AFP阳性率 (3 0 .0 % )明显低于大肝癌 (75 .6% ) ;其余各组AFP阳性率无差异 (P >0 .0 5 ) ;有肝内转移 (82 .1% )、门静脉癌栓 (86.4% )及远处转移组(90 .0 % )其外周血GGTmRNA H亚型阳性率显著高于无肝内转移 (18.9% )、门脉癌栓 (2 5 .6% )及远处转移组 (3 8.2 % ) (P <0 .0 5 )。血清AFP值的高低与肝癌患者外周血GGTmRNA H的阳性率两者差异无显著性 (P >0 .0 5 )。结论　检测HCC患者外周血细胞GGTmRNA H亚型表达对估计有无血行播散和远处转移有临床实用价值。对血清AFP值低或阴性患者进行周围血GGTmRNA H测定可以显著提高肝癌诊断的敏感性和特异性     

肝细胞癌潜在血清标志物GRO-1和Thrombin的蛋白鉴定及其临床特征分析

目的 寻找自效的早期诊断及判断肝细胞癌(HCC)预后的血清标志物.方法 利用表面增强激光解吸离子化-飞行时间质谱(SELDI-TOF-MS)技术确定HCC患者血清蛋白表达谱.对HCC 81例、肝炎82例和健康志愿者80例血清标本蛋白表达谱进行比较,经高效液相色谱分离和质谱鉴定蛋白质序列.另取48例HCC、54例肝硬化、62例大肠癌、55例鼻咽癌、36例肺癌和42例健康志愿者血清,利用PS20免疫芯片和SELDI技术对候选标志物进行验证.荧光定量PCR技术检测55例HCC患者癌和癌旁组织,13例正常肝组织中候选标志物基因的表达情况,探讨它们与HCC患者临床预后的相关性.结果 检出两个HCC候选标志物凝血酶轻链(Thrombin light chain)和生长相关性癌基因编码蛋白(GRO-1).以这两个因子建立的HCC诊断模型敏感性和特异性均为89.6％,显著高于甲胎蛋白(AFP)单独检测敏感性和特异性(69％,83％).它们与AFP联合使用后的灵敏度和特异度更高(91.7％,92.7％),而对大肠癌、鼻咽癌、肺癌的敏感性均不超过50％.HCC 患者癌组织的GRO-1与Thrombin的表达具有显著相关性(r=0.73,P＜0.01),GRO-1表达与肝外转移及术后复发显著相关(P＜0.05),Thrombin的表达量与术后复发及AFP升高相关(P＜0.05).GRO-1和Thrombin高表达的患者术后5年生存率明显低于GRO-l低表达的患者.GRO-1表达量是影响HCC预后的独立影响因素.结论 Thrombin light chain和GRO-1是HCC的潜在血清标志物,并有希望成为HCC患者术后复发转移的预测指标.     

人血清高尔基体蛋白-73与乙肝病毒相关肝病关系的研究

目的 探讨血清高尔基体蛋白-73(GP73)与乙型肝炎病毒(HBV)相关肝病的关系及其对肝细胞癌(HCC)的诊断价值.方法 采用酶联免疫吸附测定(ELISA)法对慢性乙型肝炎患者(n=31)、肝硬化患者(n=60)、HCC患者(n= 71)、乙肝自愈者(n=21)及健康人群(n=42)进行血清GP73检测并其与其他临床指标的关系进行统计学分析.结果 HBV相关肝病组的GP73水平较乙肝自愈组和健康对照组明显升高(P＜0.01).在所有肝病患者中,肝硬化组GP73水平(231.13ng/ml)明显高于HCC患者治疗前组(117.63 ng/ml)(P＜0.01)与慢性乙肝组(93.09 ng/ml) (P＜0.01);HCC治疗前组与慢性乙肝组GP73水平近似,无统计学差异(P＞0.05);乙肝自愈与健康对照组GP73水平近似(分别为36.79 ng/ml和45.40 mg/ml),差异无统计学意义(P＞0.05).HCC手术患者术后组血清GP73(175.12 ng/ml)明显高于术前组(107.28 ng/ml) (P＜0.01).肝硬化组与HCC组中血清GP73水平随肝功能的降低而升高.采用甲胎蛋(AFP)与GP73的比值(AFP/GP73)制作诊断HCC的ROC曲线,曲线下面积:0.878 (95％ CI:0.817～0.938),cut＝off值为0.12时,敏感度78.87％,特异度86.21％,优于单独应用AFP检测.后者曲线下面积:0.826 (95％ CI:0.755～0.897),cut-off值为19.52时,敏感度为67.61％,特异度为85.12％.结论 HBV相关肝病患者血清GP73水平明显高于健康对照与乙肝自愈者,并与肝损害的程度成正相关.血清GP73联合AFP检测(AFP/GP73)诊断HCC,相对于AFP单独检测在敏感性及特异性上都有不同程度的提高.     

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.     

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.     

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.     

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.