芹黄素提高胸苷激酶基因系统治疗前列腺癌疗效的研究

目的　观察芹黄素 (apigenin)对前列腺癌 (PC)细胞PC 3m生长的影响及其对单纯疱疹胸苷激酶 /更昔洛韦 (HSV tk/GCV)系统“旁观者效应”的调控 ,寻求增强该系统对PCa疗效的途径。方法　四甲基偶氮唑盐比色法 (MTT法 )检测 1、10、10 0 μmol/Lapigenin对PC 3m细胞生长的影响 ,观察 10 μmol/Lapigenin预处理后GCV对tk基因阳性 (tk+ )比例为 10 %和 5 %的混合细胞的杀伤作用及 18 α 甘草次酸 ( 18 α glycyrrhetinicacidAGA)对其影响 ,并检测apigenin联合GCV的杀伤效应。结果　Apigenin可抑制PCa细胞增殖 ,呈时间和剂量依赖关系 (P <0 .0 5 0 ) ;低浓度( 10 μmol/L) apigenin预处理对PC 3m细胞增殖无影响但可使“旁观者效应”明显增强 (P <0 .0 0 1) ,10 μmol/L和 10 0 μmol/LGCV对tk+ 为 10 %细胞的杀伤率由 ( 16.15± 1.64 ) %和 ( 2 3 .46± 3 .2 1) %提高到 ( 4 5 .89± 3 .2 8) %和 ( 5 9.86± 2 .44 ) % ,该作用可被AGA抵消。联合应用apigenin和GCV后杀伤率更为显著 ,达 ( 62 .5 8± 4.2 9) %和 ( 83 .16± 3 .72 ) %。结论　Apigenin不仅可以直接杀伤PC细胞 ,还可通过增强HSV tk/GCV系统“旁观者效应” ,发挥间接杀瘤效应 ,从而提高该系统治疗PC疗效。     

自杀基因联合全反式维甲酸治疗对前列腺癌PC-3细胞旁观者效应的影响

目的 观察单纯疱疹病毒胸苷激酶(HSV-TK)/丙氧鸟苷(GCV)系统联合全反式维甲酸(ATRA)对人雄激素非依赖性前列腺癌PC-3细胞旁观者效应的影响.方法 噻唑蓝(MTT)比色法检测HSV-TK(Ad-TK)/GCV系统对PC-3细胞的杀伤力.流式细胞仪检查连接蛋白(Cx)43阳性细胞数.结果 单纯Ad-TK/GCV系统对PC-3细胞旁观者效应在TK+:TK-细胞混合比例为5:5时明显出现(P<0.05),而联合ATRA后,在TK+:TK-细胞混合比例为3:7时就明显出现(P<0.05).Ad-TK/GCV联合ATRA处理PC-3细胞后,在细胞抑制率均达到约50%时,其TK+PC-3细胞混合比例可降低20%.ATRA(10-6 moL/L)处理PC-3细胞1、3、5 d后,Cx43阳性细胞率由10.5%分别升高为25.8%、50.8%和62.4%(P<0.01).结论 ATRA可能通过增强基于Cx43的旁观者效应,从而提高Ad-TK/GCV系统对前列腺癌的杀伤效应.     

人端粒酶逆转录酶启动子调控腺病毒介导的胸苷激酶基因治疗膀胱癌的实验研究

目的　观察人端粒酶逆转录酶(hTERT)启动子调控腺病毒介导的单纯疱疹病毒胸苷激酶基因/丙氧鸟苷(HSV tk/GCV)自杀基因系统体外对人膀胱癌的选择性杀伤效应。　方法　利用不同感染复数(MOI)的重组腺病毒携带增强型绿色荧光蛋白(EGFP)基因感染膀胱癌细胞253J和人成纤维细胞MRC 5,荧光显微镜下观察其感染效率。利用携带不同启动子的重组腺病毒Ad hTERT HSV/tk以及Ad CMV HSV/tk感染253J和MRC 5细胞,加入不同浓度GCV,MTT法观察受染细胞的存活率。　结果　重组腺病毒Ad hTERT EGFP能特异性转染253J细胞,其转染效率随重组病毒的MOI增加而升高(P<0. 01),MOI为1时转染率为8. 3%,MOI为1000时转染率达100. 0%;应用GCV处理后,Ad CMV HSV/tk对253J和MRC 5细胞均有杀伤作用,而Ad hTERT HSV/tk只杀伤253J细胞(P<0. 001),随着MOI和GCV浓度增加, 253J细胞存活率明显降低(P<0. 01),MOI为1、GCV浓度为1μmol/L时存活率为95. 4%,MOI为100、GCV浓度为1000μmol/L时存活率仅为6. 1%,并有旁观者效应。　结论　重组腺病毒携带EGFP报告基因可准确、简便地确定转染效率,hTERT启动子调控的重组腺病毒介导的HSV tk/GCV自杀基因系统对人膀胱癌细胞有靶向杀伤作用。     

野甘草醇对胸腺激酶依赖的更昔洛韦阻断前列腺癌进展的增效作用

目的 观察野甘草醇(SDC)在人端粒酶逆转录酶(hTERT)启动子调控腺病毒介导的单纯疱疹病毒胸腺激酶基因/更昔洛韦(HSV-tk/GCV)自杀基因系统对人前列腺癌细胞的杀伤作用中的增效作用.方法 测定胸苷激酶(TK)活性,应用高效液相色谱( HPLC)法测定三磷酸更昔洛韦(GCV-TP)在肿瘤细胞内的浓度,将不同配伍浓度的SDC、Ad-hTERT-HSV-tk、更昔洛韦(GCV)应用于前列腺癌细胞,观察体外对前列腺癌细胞的杀伤作用、旁杀伤效应.结果 SDC对转染Ad-hTERT-HSV-tk的LNCaP、PC3细胞的TK酶活性影响不明显.应用高效液相色谱法分析,以单加GCV组的GCV-TP浓度计作100％.在加入0.04μmolSDC后,GCV-TP浓度与不加SDC比较提高到(101.0±1.5)％,但差异无统计学意义(P＞0.05);加入5倍治疗剂量0.20 μmol SDC后,GCV-TP浓度提高到(106.0±4.5)％,差异有统计学意义(P＜0.05).并进一步通过细胞实验证实,SDC对Ad-hTERT-HSV-tk+ GCV杀伤前列腺癌细胞无明显增效作用,但是旁杀伤效应增加明显.结论 SDC对胸腺激酶依赖的GCV阻断前列腺癌进展有一定的增效作用,将天然药物SDC与我们构建的具有肿瘤特异性的重组腺病毒Ad-hTERT-HSV-tk以及GCV联合应用,可以达到增效减毒的目的.     

脂质体介导的HSV-TK基因治疗人膀胱癌

目的探讨HSV－TK基因/GCV系统对人膀胱癌细胞的杀伤作用．方法以潮霉素磷酸转移酶和HSV-HK的融合基因（HyTK）作为目的基因,利用阳离子脂质体将其转入膀胱癌细胞株,检测其表达及GCV对转基因细胞的杀伤作用。结果RT-PCR检测证实HyTK在转基因细胞的表达,MTT法测定示GCV对EJ／HyTK细胞有明显的杀伤作用;其IC50值为2.4mg／L,而对其亲代EJ细胞无明显毒性（P＜005）。按不同比例混合EJ／HyTK细胞和亲代EJ细胞,发现GCV不仅能杀伤转入TK基因的细胞,而且对其周围未转基因的膀胱细胞存在旁观者效应。结论HSV－TK基因／GCV系统可作为膀胱癌基因治疗的一种有效方法。     

全反式维甲酸增强单纯疱疹病毒胸苷激酶基因对前列腺癌PC-3细胞旁观者效应的研究

目的观察全反式维甲酸（ATRA）对单纯疱疹病毒胸苷激酶基因结合更昔洛韦（HSV-tk／GCV）旁观者效应的增强作用及与Cx43表达的关系。方法用携带HSV-tk基因的腺病毒液感染人前列腺癌PC-3细胞，半定量逆转录．聚合酶链反应（RT-PCR）检测HSV-tk基因整合情况，噻唑蓝（MTr）方法观察ATRA对前列腺癌PC-3，PC-3／TK‘细胞旁观者效应，RT-PCR检测AT-RA诱导Cx43mRNA表达的作用。结果ATRA显著提高PC-3／TK对GCV的敏感性。在100p．mol／L更昔洛韦（GCV）作用下，以10“mmol／LATRA与不加ATRA的作用比较，在PC-3，PC-3／TK不同比例混合的各组中，细胞的存活率明显降低，差异有统计学意义（P〈0．05）。并观察到10“mmol／LATRA对GCV旁观者效应的增强作用。RT-PCR结果表明，经ATRA处理的PC-3细胞，其Cx43mRNA的相对拷贝数比值增高约10倍。结论前列腺癌PC-3细胞中，10^-6mmol／LATRA具有明显增强HSV-tk／GCV旁观者效应的作用。其主要机制是通过ATRA在转录水平诱导Cx43mR-NA表达上调，导致旁观者效应的增强     

胸苷激酶基因系统杀伤前列腺癌细胞的流式细胞术分析

目的：探讨单纯疱疹病毒胸苷激酶／更昔洛韦（HSV－TK／GCV）自杀基因系统诱导人前列腺癌细胞死亡的机制。方法：利用脂质介导的基因转染技术将携带HSV－TK基因的EB病毒表达载体导入激素非依赖性人前列腺癌（HRPC）细胞系PC-3m并给予GCV，采用流式细胞术（FCM）观察PC－3m细胞周期变化以及细胞坏死和凋亡情况。结果：HSV－TK／GCV系统可使PC－3m细胞周期S期比例升高，高浓度GCV组尤其明显，S期细胞比例由16．73％升至33．60％；10和100μmol/L GCV作用72h后，PC-3m细胞可出现较为明显的细胞坏死和凋亡，比例分别为13．54％、12．45％、34．70％和10．11％。结论：细胞坏死和凋亡均参与了HSV－TK／GCV系统诱导的PCa细胞死亡，以细胞坏死比例稍高；TK自杀基因系统杀伤前列腺癌细胞时可能不依赖于其p53表达背景，因而具有更广阔的应用前景。     

腺病毒介导HSV-TK／GCV自杀基因系统靶向性治疗前列腺癌实验研究

目的观察腺病毒介导单纯疱疹病毒胸苷激酶基因／丙氧鸟苷（HSV-TK／GCV）自杀基因系统在人端粒酶逆转录酶（hTERT）启动子调控下对人前列腺癌细胞的靶向性体外杀伤效应。方珐利用不同感染复数（MOI）的重组腺病毒携带增强型绿色荧光蛋白（EGFP）基因感染前列腺癌细胞LNCaP和人成纤维细胞MRC-5,荧光显微镜下观察其感染效率;利用携带不同启动子的重组腺病毒Ad-hTERT-HSV／TK以及Ad-CMV-HSV／TK感染LNCaP和MRC-5细胞,加入不同浓度GCV,MTT法观察受转染细胞的存活率。结杲重组腺病毒Ad-hTERT-EGFP能特异地转染LNCaP,其转染效率随重组病毒的MOI增加而升高（P〈0.01）,MOI为1时转染率为8.3％,MOI为1000时转染率达100％;应用GCV处理后,Ad-CMV-HSV／TK对LNCaP和MRC-5细胞均有杀伤作用,而Ad-hTERTp-HsV／TK只杀伤LNcaP（P〈0.001）,随着MOI和GCV浓度的增加,LNCaP细胞存活率明显降低（P〈0.01）,MOI为1和GCV浓度为1μmol／L时存活率为95.4％,MOI为100和GCV浓度为1000μmol／L时存活率仅为6.1％,并有旁观者效应。结论重组腺病毒携带EGFP报告基因可准确、简便地确定转染效率;hTERT启动子调控的重组腺病毒介导的HSV-TK／GCV自杀基因系统对人前列腺癌细胞有靶向杀伤作用。     

全反式维甲酸提高激素非依赖性前列腺癌自杀基因治疗的旁观者效应

目的:观察全反式维甲酸(ATRA)提高单纯疱疹病毒胸苷激酶(HSV-TK)/丙氧鸟苷(GCV)系统体内外抗激素非依赖性前列腺癌的旁观者效应。方法:应用四甲基偶氮唑蓝(MTT)法测定细胞存活率来反映ATRA处理前后HSV-TK/GCV系统治疗PC-3细胞的旁观者效应;荷前列腺癌裸鼠模型随机分为4组,观察各组移植瘤生长状态和组织病理学改变。结果:在达到明显旁观者效应时,HSV-TK/GCV需要TK+PC-3细胞数为50%,而ATRA联合HSV-TK/GCV需要TK+PC-3细胞数仅为30%,两者比较差异显著(P<0.05)。HSV-TK可以抑制移植瘤生长,但ATRA+HSV-TK抗前列腺癌发生显效可提前1周,而且效果更显著(P<0.05)。结论:ATRA可增强HSV-TK/GCV系统治疗激素非依赖性前列腺癌的旁观者效应。     

腺病毒载体介导的双自杀基因对人胆管癌细胞QBC939的体外杀伤实验

目的观察腺病毒介导的胞嘧啶脱氨酶/单纯疱疹病毒-1-胸苷激酶(CD/TK)双自杀基因对人胆管癌细胞 QBC939的体外杀伤作用。方法 CD/TK 克隆入穿梭载体成为 pAdtrack-CMV-CD/TK,与骨架载体 pAdeasy-1在细菌内同源重组为 pAd-CD/TK,经 PacⅠ酶切,293细胞包装、扩增、纯化后,体外转染人胆管癌细胞 QBC939,并给予前药5-FC 或 GCV,观察其体外杀伤效果。结果含 CD/TK 基因的重组腺病毒鉴定正确,扩增纯化后,病毒滴度为1×10~(11)颗粒/ml。重组腺病毒对 QBC939细胞在感染倍数(m.o.i)为100时的转染效率为90%,在 m.o.i50感染时,0.1mmool/L的5-FC 及10 μmol/L 的 GCV 对 QBC939细胞的杀伤率为80%,明显高于单用5-FC 与 GCV 的效应。结论双自杀基因以腺病毒为载体对人胆管癌细胞转染效率高,体外杀伤效应明显。腺病毒介导的双自杀基因治疗有望成为治疗胆管癌的有效方法。     

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.