载5-氟脲嘧啶聚己内酯纳米粒子对人胆管癌细胞的体外杀伤作用

目的:探讨聚己内酯载5-氟尿嘧啶(5-FU)纳米粒子对人胆管癌细胞株的体外杀伤作用、安全性及机制。方法:超声乳化法制备载5-FU聚己内酯纳米粒子(5-FU-PCL-NP),观察空载纳米粒子的体外溶血及5-FU-PCL-NP的体外药物释放情况,检测5-FU-PLA-NP对人胆管癌细胞株Hccc-9810增殖抑制及凋亡诱导作用。结果:5-FU-PCL-NP成功合成,其载药率为15.1%,包封率为41.9%,溶血试验阴性,5-FU-PCL-NP体外释放5-FU缓慢,其72 h释放率为62.9%。与单纯5-FU比较,5-FU-PCL-NP对Hccc-9810细胞的增殖抑制作用明显增强,IC50明显降低[(1.32±0.12)μg/m L vs.(2.5±0.39)μg/m L],促Hccc-9810细胞凋亡作用明显增强(均P0.05)。空载纳米粒对Hccc-9810细胞凋亡无明显影响(P0.05)。结论:载5-FU聚己内酯纳米粒子5-FU-PCL-NP具有良好的药物缓释效应,可延长5-FU的作用时间窗,对胆管癌细胞有较好的体外杀伤作用,且生物安全性好。     

七叶皂苷钠对胆管癌细胞株Hccc9810增殖和凋亡的影响

目的 观察七叶皂苷钠对人胆管癌细胞株Hccc9810增殖和凋亡的影响.方法 运用细胞染色、噻唑蓝(MTT)比色法、流式细胞术和实时荧光定量聚合酶链反应(PCR)等技术观察不同浓度(0、10、20、40 μmol/L)七叶皂苷钠对胆管癌细胞增殖、细胞周期和凋亡的影响.结果 七叶皂苷钠呈时间剂量依赖性抑制胆管癌细胞Hccc9810的增殖,其24、48、72 h的50％抑制浓度(IC50)分别为:(45.34±2.12)、(33.00±1.92)、(25.00±1.65) μmol/L;G1期比例从(49.49±1.22)％上升到(70.20±1.52)％;胆管癌细胞形态发生典型凋亡特征性改变,凋亡率随浓度的升高从20.54％上升到62.56％,差异均有统计学意义(P＜0.05).结论 七叶皂苷钠通过阻滞细胞周期和诱导细胞凋亡而抑制胆管癌细胞Hccc9810增殖.     

金属卟啉化合物对人前列腺癌细胞PC-3的光动力杀伤作用

目的:研究水溶性金属卟啉化合物对人前列腺癌细胞PC 3的光动力学杀伤作用,探讨金属卟啉的光动力 学杀伤作用抗肿瘤的机制。　方法:合成水溶性金属卟啉化合物5,10,15,20 四(N 甲基 4 吡啶基)锰卟啉四碘盐 后,采用四甲基偶氮唑蓝比色法和膜联蛋白/碘化丙锭双标记流式细胞术分别检测不同浓度的金属锰卟啉化合物 (0、0.1、1、10μmol/L)在不同时间(0、15、30、45min)的高压汞灯(40W)照射下,对PC 3细胞的生长活性和凋亡的 影响。　结果:锰卟啉浓度在0～10μmol/L、光照0～30min范围内,其对PC 3细胞的增值抑制作用和诱导PC 3 细胞的凋亡作用均随着浓度增加和光照时间的增加而增强,但大剂量(10μmol/L)、高能量照射(光照45min)时主 要导致PC 3细胞坏死。　结论:水溶性金属卟啉化合物5,10,15,20 四(N 甲基 4 吡啶基)锰卟啉四碘盐的光动 力作用在体外能诱导PC 3细胞凋亡,有效杀伤PC 3细胞,其杀伤效果在锰卟啉浓度为0～10μmol/L、光照0～30 min范围内与锰卟啉的浓度和光照射剂量呈正相关,这可能是卟啉的光动力学疗法抗肿瘤作用的机制。     

ICOS基因转染对CIK细胞杀伤胆管癌细胞作用的研究

目的 探讨转染可诱导共刺激分子(inducible co-stimulator, ICOS)基因对细胞因子诱导杀伤(cytokine. induced killer, CIK)细胞杀伤胆管癌细胞的作用.方法 构建含ICOS基因的腺病毒载体并转染给CIK细胞(CIK-ICOS细胞组),单纯CIK及CIK-EGFP细胞为对照组,观察3组CIK细胞体外增殖与凋亡情况以及对胆管癌细胞的杀伤作用;ELISA法检测3组CIK细胞上清液中IFN-γ、IL-2及TNF-α的表达.建立胆管癌移植瘤的SCID小鼠模型,按随机数字表法将40只SCID小鼠分为生理盐水对照组、CIK、CIK-EGFP、CIK-ICOS细胞治疗组,观察转染ICOS基因的CIK细胞对小鼠胆管癌细胞的杀伤作用.结果 CIK-ICOS细胞组体外增殖明显强于CIK及CIK-EGFP细胞组;培养第20天CIK-ICOS与CIK细胞凋亡率分别为0.69%和2.90%,第23天分别为0.89%和4.92%;在不同效靶比CIK-ICOS细胞组杀伤效应均显著高于CIK与CIK-EGFP细胞组(F=13.37,6.46,25.51,P<0.05);CIK-ICOS细胞组上清液中IFN-γ的浓度为(49.50±4.73)μg/L,显著高于CIK细胞组(30.53±3.73)μg/L及CIK-EGFP细胞组(30.12±2.64)μg/L(F=38.89,P<0.05).CIK-ICOS细胞治疗组小鼠肿瘤生长速度明显低于CIK与CIK-EGFP细胞治疗组,肿瘤坏死面积明显大于CIK与CIK-EGFP细胞治疗组,瘤内CIK细胞数量最多.结论 CIK细胞在体内外均具有杀伤胆管癌细胞的作用.转染ICOS基因后,CIK细胞体外存活时间延长、增殖能力增强、IFN-γ的表达增多,其在体内外抗胆管癌作用明显增强.     

γ-氨基丁酸对胆管癌细胞株QBC_(939)增殖和侵袭转移的影响

目的 观察γ-氨基丁酸(GABA)对胆管癌细胞株QBC_(939)增殖、凋亡和侵袭转移的影响.方法 取GABA母液,用含10%胎牛血清的1640培养液稀释,配成浓度为1、10、100、1000μmol/L为实验组;对照组仅加入与实验组相同体积的完全培养液.采用MTT比色法观察GABA对人胆管癌细胞株QBC_(939)增殖的作用,流式细胞仪检测GABA对胆管癌细胞株QBC_(939)凋亡的影响,Transwell小室分析GABA对胆管癌细胞侵袭能力的影响,明胶酶谱法分析GABA对胆管癌细胞株QBC_(939)分泌的基质金属蛋白酶(MMP)活性的影响,放射免疫分析法检测cAMP含量.采用单因素方差分析.结果 GABA浓度由1 μmol/L增至1000 μmol/L,GABA对胆管癌细胞的抑制率由2.6%增至26.8%;细胞凋亡率由4.80%±0.04%增至28.03%±0.01%;穿透Matrigel胶的能力由(60±10)个减至(43±4)个,均呈剂量依赖性(F=7.833,83.765,7.598,P<0.05).同时胆管癌细胞分泌的MMP-2和MMP-9活性下降,cAMP含量增加,与对照组比较差异有统计学意义(F=9.507,9.148,27.418,P<0.05).结论 GABA可能通过受体后信息介导途径,诱导细胞凋亡,并减弱胆管癌细胞株QBC_(939)的侵袭转移能力,可能与其抑制基质蛋白酶MMP-2和MMP-9的活性有关.     

逆转录病毒介导的双自杀基因对肝内胆管癌细胞杀伤作用的实验研究

目的观察逆转录病毒介导的双自杀基因对肝内胆管癌细胞HCCC-9810的杀伤作用，探讨肝内胆管癌的基因治疗方法。方法在脂质体的介导下将含有双自杀基因的逆转录病毒载体PwzlneoCDglytk导人包装细胞PA317，经G418筛选后大量培养产病毒的阳性克隆PA317／CD tk细胞株，收集病毒上清，转染HCCC-9810细胞，再次经G418筛选，获得稳定表达双自杀基因的HCCC-9810／CD tk细胞株。用RT-PCR检测双自杀基因的表达。给予前体药物5-氟胞嘧啶(5-flourocytosine，5-FC)和(或)无环鸟苷(ganciciovir，GCV)后，用MTT法测定转基因组及未转基因组HCCC-9810细胞的存活率。结果双自杀基因在HCCC-9810细胞中可稳定表达，联合使用5-FC和GCV对细胞增殖的杀伤作用及旁杀伤效应高于单独使用5-FC或GCV。结论逆转录病毒介导自杀基因可有效杀死肝内胆管癌细胞，双自杀基因较单一自杀基因具有更强的抗肿瘤作用。     

胆汁酸对胆管癌细胞株QBC939中IL-6表达与细胞活力的影响

目的 探讨不同胆汁酸对胆管癌细胞株QBC939中IL-6的表达和细胞活力的影响.方法 分别使用不同浓度的游离胆汁酸以及其对应的甘氨酸结合型胆汁酸作用于胆管癌细胞株QBC939,药物浓度分别为:胆酸(CA)800 μmol/L、脱氧胆酸(DCA)100 μmol/L、鹅脱氧胆酸(CDCA)100 μmol/L、甘氨胆酸(GCA)1200 μmol/L、甘氨脱氧月胆酸(GDCA)200 μmol/L以及甘氨鹅脱氧胆酸(GCDCA)300 μmol/L.以MTT法检测不同胆汁酸刺激24、48、72 h后胆管癌细胞活力的变化,并以ELISA法检测肿瘤细胞中IL-6表达的改变.结果 DCA、CDCA、GCDCA作用48 h后,肿瘤细胞活力比值(A处理组/A对照组)分别为0.61、0.58和1.26;作用72 h后,CA、DCA、CDCA、GCA、GDCA和GCDCA各组肿瘤细胞活力比值分别为0.48、0.50、0.42、1.29、1.30和1.41;与对照组相比,以上各组细胞活力变化均具有统计学意义(P＜0.05).对照组肿瘤细胞培养48和72 h后,IL-6表达量分别为(198±32)ng/L和(323±34)ng/L,CA、DCA、CDCA、GCA、GDCA和GCDCA作用48 h后IL-6的表达量分别为(106±33)ng/L、(88±29)ng/L、(116±54)ng/L、(413±21)ng/L、(587±32)ng/L和(366±30)ng/L,作用72 h后IL-6表达量分别为(123±66)ng/L、(45±21)ng/L、(74±45)ng/L、(792±13)ng/L、(1310±22)ng/L和(845±18)ng/L;与对照组相比,以上各组IL-6表达量变化均具有统计学意义(P＜0.05).结论 游离胆汁酸CA、DCA和CDCA能减少胆管癌细胞IL-6的表达,并抑制细胞活力;而结合胆汁酸GCA、GDCA和GCDCA能增加胆管癌细胞IL-6的表达,并促进细胞活力.胆汁酸能通过IL-6途径改变胆管癌细胞活力.     

1,25二羟维生素D3对胆管癌细胞系QBC939增殖和凋亡的影响

目的 探讨1,25二羟维生素D3[1,25(OH)2 D3]对胆管癌细胞系QBC939的体外增殖及凋亡的影响.方法 将不同浓度的1,25(OH)2 D3与胆管癌细胞系QBC939共同培养,采用MTT法测定细胞增殖能力、显微镜观察细胞形态学的改变、流式细胞仪检测细胞周期与凋亡、免疫细胞化学观察bcl-2的表达.结果 0.1～0.5μmol/L的1,25(OH)2 D3对胆管癌细胞QBC939有抑制作用,呈剂量依赖性.经1,25(OH)2 D3作用72h后细胞G1期比例升高,S期比例下降,其中0.5μmol/L组细胞G1期由(50.3±1.0)%上升至(65.5±3.2)%,S期由(39.4±0.5)%下降至(23.6±0.7)%;并且可诱导细胞产生凋亡,0.5μmol/L组作用后细胞凋亡率由0.5%上升至24.6%;bcl-2的表达下调.结论 1,25(OH)2 D3能抑制胆管癌细胞系QBC939增殖并诱导细胞凋亡,其引起凋亡的机制可能与下调bcl-2的表达相关.     

肝内胆管癌细胞系ICC-9810与肝细胞癌细胞系SMMC-7721蛋白质组学比较

目的 比较肝内胆管癌细胞系ICC-9810、肝细胞癌细胞系SMMC-7721及正常肝细胞系L02的蛋白质表达,筛选胆管细胞癌和肝细胞癌的标志蛋白.方法 收集体外培养的肝内胆管癌细胞系ICC-9810、肝细胞癌细胞系SMMC-7721及正常肝细胞系L02细胞,细胞裂解液处理后提取蛋白.应用表面增强激光解吸离子化(SELDI)蛋白质芯片技术同时使用IMAC3和WCX2两种芯片检测肝内胆管癌细胞系ICC-9810、肝细胞癌细胞系SMMC-7721及正常肝细胞系L02的蛋白质谱.用PBSII-C型蛋白质芯片阅读机读取数据,采用Proteinchip Software 3.0.2软件分析数据.结果 与L02细胞比较,有12个蛋白质在两种肝癌细胞系中均出现明显的变化,其中4个蛋白高表达,8个蛋白低表达.比较两种肝癌细胞系的蛋白质谱,发现7个蛋白在ICC-9810细胞中高表达,10个蛋白低表达;11个蛋白在SMMC-7721细胞中高表达.在L02和ICC-9810细胞中去磷酸化蛋白17 175 Da表达较多,而在SMMC-7721细胞中磷酸化蛋白17 255 Da表达较多.结论 肝内胆管癌、肝细胞癌与正常肝细胞的差异蛋白表达为寻找肝肿瘤标志物提供了重要线索.17 255 Da蛋白的磷酸化/去磷酸化可能与肝细胞癌的发生有关.     

MicroRNA-7对HCCC9810细胞增殖、迁移和侵袭的研究

目的探讨MicroRNA-7(miR-7)对于肝内胆管癌细胞HCCC9810增殖、迁移、侵袭能力的影响。方法利用实时定量PCR对于肝内胆管癌病人的癌组织和癌旁组织,以及正常肝内胆管上皮细胞和肝内胆管癌细胞HCCC9810中miR-7表达水平的验证;培养人肝内胆管癌细胞HCCC9810,将其分为研究组(miR-7 mimics)和阴性对照组(miR-7 NC),分别进行miR-模拟物以及miR-阴性序列的转染,效率验证后,通过CCK-8实验,EDU实验,克隆形成实验,以及划痕和Transwell实验分别验证两组细胞的增殖、迁移和侵袭的能力。结果肝内胆管癌病人中癌组织miR-7的表达水平低于癌旁组织,肿瘤细胞HCCC9810 miR-7表达水平低于正常胆管上皮细胞;细胞转染效率验证显示,miR-7 mimics组HCCC9810细胞中miR-7的相对表达水平远高于miR-7 NC组,差异具有统计学意义(P<0.05);与miR-7NC相比,miR-7 mimics组细胞的增殖、迁移以及侵袭能力被明显抑制,差异均有统计学意义(均P<0.05)。结论miR-7在肝内胆管癌中表达水平下调,而且过表达miR-7能够抑制肿瘤细胞的增殖、迁移以及侵袭过程。     

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.