胆管癌抗原肽对转染全长野生型p53的树突状细胞免疫功能的影响

目的研究胆管癌抗原肽对转染全长野生型p53的树突状细胞(wtp53DC)免疫功能的影响。方法先将全长野生型p53导入脂质体内并转染小鼠骨髓来源的DC,然后用胆管癌抗原肽修饰wtp53DC,检测这种树突状细胞的抗原提呈功能。结果抗原肽修饰的wtp53DC和单纯DC的上清3种细胞因子含量明显增加,分别为(545.2±12.1)ng/L,(511.1±13.3)ng/L,(537.1±11.1)ng/L(P<0.05);wtp53DC刺激小鼠脾脏T细胞增殖水平明显高于对照组(P<0.01);该细胞高表达B7-1、B7-2、MHC-Ⅰ、MHC-Ⅱ(P<0.05);能够特异性地杀伤胆管癌细胞,杀伤率81.6%。结论全长野生型p53基因转染+胆管癌抗原肽联合修饰树突状细胞能诱导小鼠细胞毒性T淋巴细胞的特异性。     

胆管癌肿瘤裂解物修饰和p53基因导入对树突状细胞免疫效应的影响

目的　研究胆管癌裂解物对转染全长野生型p5 3的树突状细胞 (DC)免疫功能的影响。方法　用腺病毒作为介质 ,将全长野生型 p5 3转染入DC ,然后用胆管癌裂解物修饰已转染全长野生型 p5 3的DC(Lywtp5 3DC) ,检测这种DC表面分子B7-1、B7-2、MHC -Ⅰ、MHC -Ⅱ表达的高低 ,诱导特异的细胞毒性T淋巴细胞 (CTLs)的能力 ,对小鼠的免疫保护和对动物模型治疗作用。结果　经流式细胞仪检测胆管癌裂解物刺激的wtp5 3DC表面高表达B7-1( 86.70± 0 .0 7)、B7-2 ( 18.77± 0 .0 8)、MHC -Ⅰ ( 87.2 0± 0 .0 5 )、MHC -Ⅱ ( 5 6.70± 0 .0 7) ,而单纯DC这些分子是低表达的 ;Lywtp5 3DC能够特异性地杀伤胆管癌细胞 ,杀伤率为 81%。Lywtp5 3DC治疗组和其它组在肿瘤生长的直径大小之间有显著差异 (P <0 .0 5 ) ,在Lywtp5 3DC治疗组中 ,肿瘤生长明显减慢。结论　全长野生型 p5 3基因转染 胆管癌裂解物联合修饰的DC能诱导CTLs的特异性 ,显著地提高DC的抗原提呈功能 ,体外能诱导高效而特异的抗胆管癌免疫效应。     

胃癌抗原肽Hsp70复合物对转染全长野生型p53的树突状细胞免疫功能的影响

目的 应用联合修饰的树突状细胞(DC)在体外诱导高效而特异的抗胃癌免疫效应。方法 先将全长野生型p53导入脂质体内并转染小鼠骨髓来源的DC,然后用胃癌抗原肽-HSP70复合物等因素修饰已转染全长野生型 p53的 DC(wt-p53 DC),检测这种DC诱导小鼠脾脏淋巴细胞特异的细胞毒性T淋巴细胞(CTLs)的能力,分泌细胞因子功能,以及表面分子表达的高低。结果Western blot检测转染小鼠 p53cDNA的 BMDC及其培养上清中均可以检测到 p53表达;细胞因子含量明显增加(P<0.05),而的其他组的细胞因子含量与对照相比,无显著变化;经流式细胞仪(FACS)检测 wt-p53DC表面高表达 B7-1、B7-2、MCH-Ⅰ、MCH-Ⅱ;脾淋巴细胞经刺激后,能够特异性地杀伤胃癌细胞,杀伤率为91.6％。结论 全长野生型p53基因转染+抗原肽联合修饰DC能诱导小鼠细胞毒性T淋巴细胞的特异性,显著提高DC的抗原提呈功能。     

肝癌细胞裂解物致敏DC疫苗诱导的肿瘤特异抗瘤效应

目的　研究肝癌细胞裂解物致敏的树突状细胞 (DC)疫苗诱导的体内、外抗瘤效应。方法　体外实验 :将肿瘤细胞裂解物致敏的DC与T细胞共培养 ,4d后收获致敏的T细胞 ,观察其对野生型肿瘤细胞的杀伤反应并检测培养液中的IFN γ分泌情况。体内实验 :观察肿瘤细胞裂解物致敏的DC疫苗对小鼠皮下肝癌发生的抑制作用。结果　在效 :靶比分别为 5 0 .0∶1.0、2 5 .0∶1.0、12 .5∶1.0时 ,肝癌细胞裂解物致敏的DC组与DC组诱导的肿瘤杀伤活性分别为 (4 5 .7±3 .2 ) %对 (2 6.5± 2 .5 ) % ;(3 1.0± 2 .7) %对 (14 .3± 3 .3 ) % ;(2 7.8± 1.7) %对 (9.9± 0 .6) % (在各效靶比 ,P <0 .0 1) ,混合细胞培养上清液中IFN γ浓度则为 (2 60 3 .3± 2 60 .0 )ng/L对 (5 0 1.0±5 0 .0 )ng/L。在体内则可有效抑制小鼠皮下肝癌的发生。结论　肝癌细胞裂解物致敏的DC疫苗可以诱导肿瘤特异的抗瘤效应     

树突状细胞激活的肿瘤浸润性淋巴细胞体外特异性抗小鼠肝癌研究

目的树突状细胞(DC)是目前已知的功能最强的抗原提呈细胞(APC),可以向包括肿瘤浸润性淋巴细胞(TIL)在内的T淋巴细胞提呈抗原,并诱发细胞毒T淋巴细胞(CTL)反应。本文旨在探讨H22细胞和B16细胞全细胞性抗原致敏的树突状细胞激活的肿瘤浸润性淋巴细胞体外抗小鼠肝癌活性。方法从小鼠四肢长骨骨髓中获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白介素-4(IL-4)和肿瘤全细胞性抗原致敏DC,然后用DC激活TIL,观察TIL在体外对H22细胞、Hepal-6细胞和B16细胞的杀伤活性。结果经H22细胞全细胞性抗原致敏的DC激活的TIL具有很高的对H22细胞杀伤活性,杀伤率为(71·31±3·11)%,明显高于其对Hepal-6和B16细胞的杀伤活性[杀伤率分别为(50·11±3·03)%,(30·31±2·89)%];也明显高于未经H22细胞全细胞性抗原致敏的DC激活的TIL、DC激活的脾淋巴细胞和未经DC激活的脾淋巴细胞对H22细胞杀伤活性[杀伤率分别为(49·80±3·21)%,(48·76±3·60)%和(19·23±2·71)%]和对Hepal-6细胞杀伤活性[杀伤率分别为(39·4±3·21)%,(38·62±2·87)%和(18·73±2·40)%]以及对B16细胞杀伤活性[杀伤率分别为(26·38±2·51)%,(25·82±2·70)%和(18·34±3·01)%],同时经B16细胞全细胞性抗原致敏的DC激活的TIL(来源于H22瘤体)也可诱导相对较低的对B16细胞的特异性细胞杀伤活性。结论来源于H22瘤体的TIL经H22细胞全细胞性抗原致敏的DC激活后可产生很强的针对H22细胞的特异性杀伤活性,明显高于其他各组,说明DC能诱导TIL产生高效而特异的体外抗小鼠肝癌免疫。     

乳腺癌细胞抗原肽修饰树突状细胞的抗肿瘤作用

目的探讨经重组乳腺癌热休克蛋白70(heat shock protein 70,HSP70)抗原肽复合物修饰后的树突状细胞(dendritic cell,DC)的抗肿瘤作用。方法冻融法获取BALB/C小鼠4T1乳腺癌细胞抗原肽,体外重组HSP70-4T1抗原肽复合物。检测BALB/C小鼠DC经该复合物修饰成熟后IL-12和TNFa的分泌。检测修饰后成熟的DC对BALB/C小鼠脾淋巴细胞的增殖作用及增殖后淋巴细胞对4T1细胞的杀伤功能。BALB/C小鼠注射修饰成熟DC,观察该方法对4T1乳腺癌株的抑制作用。结果0.75μg抗原肽与HSP70结合,可使1×10~6DC成熟;成熟后的5×10~3DC可激活2×10~6小鼠脾淋巴细胞。与直接用HSP70-4T1复合物刺激脾细胞比较,DC途径抗原肽的用量减少40倍。增殖后淋巴细胞对4T1细胞杀伤率为(60.24±6.23)%。接种该DC能有效地抑制肿瘤的生长。结论重组乳腺癌热休克蛋白70-抗原肽复合物能够诱导DC成熟,成熟后的DC能激活淋巴细胞并抑制肿瘤生长。该途径能有效降低肿瘤免疫治疗时抗原肽的使用剂量。     

反义IDO-AFP基因融合修饰树突状细胞抗肝癌免疫作用

目的探讨反义IDO-AFP基因融合修饰树突状细胞(DC)后,DC通过调控色氨酸代谢达到高效、特异性抗肝癌作用。方法采用细胞培养方法,从小鼠骨髓中获得DC,用反义IDO核酸和AFP基因融合的载体,转染入DC内,检测转染入融合基因DC的对T细胞增殖的影响和体外对肝细胞癌的免疫应答的改变。以~(51)Cr释放法测定细胞毒性T淋巴细胞(CTL)杀伤活性。制作小鼠肝癌模型,分别予以反义IDO-AFP修饰的DC、单纯DC、空白对照组进行治疗,检测血清中自细胞介素(IL)-10、干扰素(IFN)-7水平；CD4、CD8和IFN-7和IL-10双阳性细胞比例,观察其抑制肿瘤的效果。结果反义IDO-AFP修饰的DC可激活小鼠脾淋巴细胞；能对肝癌细胞株H22细胞进行特异性杀伤,杀伤率为89．3%,显著高于单纯DC、生理盐水(空白对照组)组的34．7%和8．9% (P均＜0．01)而对艾氏腹水瘤细胞无效；反义IDO-AFP修饰DC组色氨酸含量为(17．8±1．2)μm,而单纯DC组和空白对照组的色氨酸为(6．2±0．6),um和(5．2±1．2)μm,表明反义IDO-AFP修饰DC可明显增加培养液中的色氨酸。使Thl细胞比例上升,抑制体内肿瘤的生长。结论反义IDO-AFP基因融合修饰树突状细胞后,DC通过调控色氨酸代谢达到高效、特异性抗肝癌的目的,可成为一种有效的瘤苗。     

gp96多肽复合物树突状细胞疫苗诱导的体外抗胃癌实验研究

目的研究gp96多肽复合物树突状细胞(DC)疫苗特异性抗胃癌的免疫反应。方法应用层析技术从胃癌组织中提取gp96多肽复合物,制备gp96多肽复合物DC疫苗;采用流式细胞仪检测gp96多肽复合物DC疫苗表面分子的表达;ELISA检测gp96多肽复合物DC疫苗致敏的效应 T淋巴细胞分泌IFN-γ和IL-10的水平;51Cr释放实验检测gp96多肽复合物DC疫苗诱导的特异性对胃癌细胞的杀伤效应。结果gp96多肽复合物DC疫苗表面分子CD1α(79．3±4．1)％、CD80 (84．3±2．4)％、CD83(85．7±3．2)％和HLA-DR(83．4±2．9)％的表达显著增高;对原代培养胃癌细胞的杀伤率(58．5±10．7)％显著高于对SGC 7901细胞的杀伤率(24．0±4．2)％,两者相比差异有统计学意义,P<0．01;对HepG2细胞(13．8±2．8)％则无明显杀伤作用。DC疫苗诱导的效应T淋巴细胞分泌IFN-γ(2875±178)pg／ml的量明显增加,分泌IL-10(36±7)pg／ml的量显著降低。结论 gp96多肽复合物DC疫苗能诱导出较强的对自体胃癌细胞的杀伤作用,且具有高度特异性。     

肺癌抗原负载的树突细胞体外诱导细胞毒性T淋巴细胞的杀瘤作用

目的探讨不同方式肺癌抗原负载的树突状细胞(DC)在抗肿瘤免疫中的作用。方法取肺癌患者外周静脉血体外诱导和培养DC,分别以肺癌细胞总RNA转染DC(转染组)、肺癌细胞融合DC(融合组)和肺癌细胞冻融抗原负载DC(冻融组),以未负载抗原的DC(未负载组)和T细胞组作为对照,比较各组(每组n=6)DC诱导的细胞毒性T淋巴细胞(CTL)对肺癌细胞A_(549)的杀伤率(%)。结果转染组、融合组、冻融组、未负载组和T细胞组的杀伤率分别为(73．2±5．9)%、(61．6±6．2)%、(55．3±6．9)%、(22．3±6．1)%和(19．8±6．3)%(P＜0．05)；其中转染组、融合组和冻融组高于未负载组和T细胞组(P＜0．05)；转染组和融合组之间差异无统计学意义(P＞0．05),但两者均大于冻融组(P＜0．05)。RNA转染DC所需的肿瘤细胞数仅是冻融及融合方式的1/5和1/6。结论3种肺癌抗原负载DC方式均有诱导效应细胞杀伤靶细胞的增效作用,而以肺癌细胞总RNA转染方式为佳。     

白细胞介素-18与癌细胞裂解物修饰的树突状细胞疫苗对胰腺癌的免疫治疗作用

目的　观察经白细胞介素 18(IL 18)和胰腺癌细胞裂解物修饰的树突状细胞 (DC)疫苗对胰腺癌荷瘤小鼠的免疫治疗作用。方法　用药物诱导制成BALB/c小鼠的胰腺癌模型。通过IL 18和癌细胞裂解物修饰小鼠DC(MTSC4) ,制成DC疫苗 ,检测各组血清中细胞因子IL 18、干扰素γ(IFN γ)的浓度 (分为DC IL18 裂解物组 ,DC 裂解物组 ,DC IL 18组 ,DC组 ,PBS组 ) ,研究了其对小鼠胰腺癌的免疫治疗作用。结果　DC IL18 裂解物组中IL 18与IFN γ的浓度 ( 2 161± 43 9)μg/L和 ( 4 3 5± 72 ) μg/L ,与其余各组比较差异有显著性 (P <0 .0 5 ,P <0 .0 1)。DC IL18 裂解物组接种胰腺癌细胞后 5 0d均未见移植肿瘤形成 ,与其余各组比较差异有非常显著性 (P <0 .0 1)。对胰腺癌细胞的细胞毒作用以DC IL18 裂解物组最强 ,DC 裂解物组次之 ,DC IL18组较弱 ,其余 2组则缺乏 (P <0 .0 1)。DC IL18 裂解物组的小鼠的生存期比他各组明显延长 ,且肿瘤的重量比其他各组明显减轻 (P <0 .0 1,P <0 .0 5 )。结论　IL 18和胰腺癌细胞裂解物修饰的DC疫苗对胰腺癌荷瘤小鼠有明显的免疫治疗作用。     

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.