表阿霉素聚氰基丙烯酸正丁酯纳米粒治疗移植性肝癌

目的 观察表阿霉素聚氰基丙烯酸正丁酯纳米粒对移植性肝癌的治疗效果。方法 建立SD大鼠移植性肝癌动物模型，14d后，从中随机取12只，测定肿瘤的长短径，为治疗前的肿瘤体积。并将余下肿瘤模型大鼠随机分为4组，每组12只。除生理盐水组外，EPI组给表阿霉素每只1．67mg／kg体重，EPI—PACA—NP组给表阿霉素聚氰基丙烯酸正丁酯纳米粒每只相当于1．67mg／kg体重表阿霉素。PACA-NP组给空白纳米粒每只相当于EPI-PACA-NP组所给纳米粒不载药纳米粒的量。1周后记录肿瘤治疗后的生长率、肿瘤的坏死范围，存活天数，生命延长率。结果治疗后各组间肿瘤体积差异有统计学意义（P＜0．05），EPI—PACA—NP组的肿瘤体积和肿瘤生长率显著低于其他组（P＜0．01）。病理切片可见EPI—PACA—NP组可见肿块里有大面积无核结构，纤维组织替代，以重度坏死为主，无轻度坏死。与NS组和EPI组比较，EPI—PACA—NP组大鼠平均生存时间延长（P＜0．01）；且以EPI组作为对照组，则EPI—PACA—NP组大鼠的生命延长率增加80．95％。结论 尾静脉注射EPI—PACA—NP组肿瘤生长率明显降低、生命延长率显著提高（P＜0．01）。     

1-甲基色氨酸对荷肝癌小鼠皮下移植瘤生长的抑制作用

目的 观察1-甲基色氨酸(1-MT)对荷肝癌小鼠皮下移植瘤生长的抑制作用.方法 建立荷肝癌小鼠皮下移植瘤模型.实验分为hepG2组、空质粒组、吲哚胺2,3双加氧酶(IDO)生理盐水组、IDO 5-氟尿嘧啶(5-FU)组、IDO 1-MT组、IDO 1-MT和5-FU联合处理组,每组各8只.观测各组小鼠成瘤情况肿瘤体积差异以及常规病理检查变化,并采用免疫组化法检测肿瘤组织内IDO表达情况.结果 与hepG2和空质粒生理盐水组比较,IDO生理盐水组肿瘤体积大、生长快(P＜0.05).与IDO生理盐水组比较,5-FU组、1-MT组和联合处理组肿瘤体积较小、重量减轻,其抑瘤率分别为86.54％、79.95％、94.46％,差异有统计学意义(P＜0.05).其中联合用药组效果最好(P＜0.05),5-FU组与1-MT组两者间肿瘤体积变化无显著差异(P＞0.05).HE病理切片观察各处理组可见癌细胞密度减少,坏死区域增加.各处理组外周血甲胎蛋白(AFP)降低,差异有统计学意义(P＜0.05).结论 IDO可促进肝癌细胞的生长,参与了肝癌细胞的免疫逃逸;1-MT对人肝癌小鼠皮下移植瘤生长具有抑制作用,与化疗药联合应用效果更好.     

索拉菲尼对大鼠Walker-256移植性肝癌的治疗作用

目的探讨索拉菲尼(Sorafenib)对大鼠Walker-256移植性肝癌的治疗作用及机制。方法 Walker-256移植性肝癌大鼠随机分为4组(n=16):A组(对照组);B组(索拉菲尼低剂量组);C组(索拉菲尼中剂量组);D组(索拉菲尼高剂量组),另设E组(正常组,n=8)。所有大鼠于术后20d取静脉血,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆红素(TB)含量;分离出肝内瘤块,称量其质量、测量其体积,计算出肿瘤的质量抑制率、体积抑制率;采用免疫组织化学方法检测瘤旁组织血管内皮生长因子(VEGF)、微血管密度(MVD)水平,并对VEGF及MVD行双变量相关性分析;对索拉菲尼各组剩余8只大鼠,观察其生存时间。结果索拉菲尼各剂量组大鼠血清ALT、AST、TB普遍低于对照组(P0.05);C、D组大鼠瘤块体积、质量均小于A组,生存时间长于A组(P0.05);索拉菲尼各剂量组大鼠瘤旁组织肿瘤细胞坏死程度较A组明显,癌灶周边肝脏细胞受累坏死程度较A组轻;各剂量组瘤旁组织VEGF阳性率、MVD计数小于A组(P0.01);大鼠瘤旁组织VEGF与MVD高度相关(P0.01),相关系数rp=0.843。结论索拉菲尼通过抑制肝癌大鼠瘤旁组织VEGF合成,降低瘤旁组织微血管密度、抑制瘤旁组织微血管生成,从而抑制肿瘤生长,减轻肿瘤对正常肝细胞的损害作用及肝功损害,延长大鼠生存期限,对大鼠移植性肝癌具有积极的治疗作用。     

表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒在大鼠肝脏组织中的靶向研究

目的 制备表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒(EPI-PBCA-MNPS)并进行表征,进一步分析该药在大鼠肝脏分布情况,研究其靶向性。方法 在EPI-PBCA-NPS研究的基础上,采用微乳液反相界面聚合法制得表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒(EPI-PBCA-MNPS),然后表征;将SD雄性大鼠随机分为3组:A组为EPI组(表阿霉素组)、B组为EPI-PBCA-MNPS组;C组为EPI-PBCA-MNPS+磁场组,并分为两个亚组,实验中测定血浆中表阿霉素浓度即C非靶区肝组和测定肝脏内肝组织中表阿霉素浓度即C靶区肝组。每组15只,分别通过尾部静脉注射,观察各组靶向分布情况。采用SPSS 13.0统计软件进行数据统计处理,计量资料以x珋±s表示,采用t检验;计数资料采用χ~2检验。以P0.05为差异有统计学意义。所有数据均进行方差齐性检验及符合正态分布。检验水准a=0.05。结果 EPI-PBCA-MNPS粒径为(151.3±29.6)nm,分布均匀,胶体溶液长期稳定,平均包封率为(80.26±14.22)%,平均载药量为(14.64±2.13)%,饱和磁化强度为:0.34 KA/m;尾部静脉给药后,肝脏组织中表阿霉素浓度较高,其药物最高浓度提前至5 min,并明显减少了在脾中的分布情况,进一步使肝脏组织中的分布显著提高。在磁场环境中,C靶区肝组中表阿霉素浓度显著升高,并明显高于C非靶区肝、A组及B组(P0.05)。结论 EPI-PBCA-MNPS具有较好的磁感应性,大鼠静脉注射并在磁场环境中能够显著提高表阿霉素在靶肝区聚集的程度,并进一步降低表阿霉素在其他非靶肝区聚集的程度。     

选择性胆管栓塞与选择性门静脉栓塞对大鼠肝癌模型影响的实验研究

目的观察选择性门静脉栓塞和选择性胆管栓塞对大鼠种植性肝癌模型肿瘤及未栓塞侧肝组织影响。方法建立Walker-256大鼠移植性肝癌模型,随机分为三组,每组20只,分别进行选择性门静脉栓塞、选择性胆管栓塞及单纯剖腹手术(对照组),于术后1、2、3、4周各处死5只大鼠,检测肝叶重量、肿瘤大小和肝功能;免疫组织化学法检测瘤组织中Ki67表达,计算Ki67阳性率。CD31标记血管内皮细胞测肿瘤微血管密度。根据资料不同分别应用单因素方差分析和q检验进行统计学分析。结果选择性门静脉栓塞组、选择性胆管栓塞组与对照组比较,大鼠ALT、AST升高,未栓塞侧肝脏体积增大,P值均0.05或0.01。选择性门静脉栓塞组大鼠肝癌体积及癌组织Ki67阳性率大于其余两组(P0.05),选择性胆管栓塞组与对照组差异无统计学意义(P0.05)。微血管密度值三组间差异无统计学意义(P0.05)。结论选择性胆管栓塞和选择性门静脉栓塞均能够增加未栓塞侧肝体积,选择性门静脉栓塞效果更佳。选择性门静脉栓塞可促进栓塞侧大鼠移植性肝癌生长,选择性胆管栓塞对大鼠肿瘤生长无影响。     

磁性阿霉素隐形脂质体对裸鼠移植性人胃癌的靶向治疗

目的　探讨磁性阿霉素隐形脂质体靶向治疗裸鼠移植性人胃癌的疗效。方法　荷人胃癌的裸鼠为动物模型,尾静脉给药,肿瘤部位放置恒定磁场进行磁导向化疗。结果　磁性阿霉素隐形脂质体靶向MDL( )组对人胃癌的移植瘤有显著抑制作用,体积和瘤重抑瘤率分别为71%和70 % ,显著高于磁性阿霉素隐形脂质体非靶向MDL(- )组(5 7%、5 0 % )和游离阿霉素DOX组(33%、31% )(P <0 .0 5 ) ,空白组细胞凋亡率均低于各实验组,MDL( )组达4 2 % ,高于其他各组(P <0 . 0 5 )。实验期间DOX组体重一直未见增加,而MDL( )组体重平稳增加,且饮食、活动未见明显变化。结论　磁性阿霉素隐形脂质体作为一种新型抗肿瘤药物显示了良好的应用前景。     

靶向干扰骨架蛋白Transgelin抑制胰腺癌裸鼠移植瘤的生长

目的 探讨靶向干扰骨架蛋白Transgelin对人胰腺癌裸鼠移植瘤生长的影响.方法 设计并体外合成靶向Transgelin的短发夹RNA(shRNA)真核表达质粒,将其转染人胰腺癌细胞BxPC3,采用RT-PCR、Western印迹法检测转染前后Transgelin表达的变化.成功造模胰腺癌裸鼠24只,按皮下注入细胞不同均分为3组:实验组(接种BxPC3/shRNA)、阴性对照组(接种空质粒转染细胞BxPC3/Neo)和空白对照组(接种未转染细胞BxPC3).每周测量肿瘤大小,术后第28天处死所有裸鼠,计算瘤体体积,治疗前、后裸鼠体重的变化以及抑瘤率.免疫组织化学法检测移植瘤组织切片中Transgelin和增殖细胞核抗原(PCNA)蛋白的表达.结果 实验组、阴性对照组和空白对照组在各时间段的肿瘤体积增长差异有统计学意义(均P ＜0.05).实验组在第21,28天肿瘤体积显著小于阴性对照组和空白对照组(均P＜ 0.05).实验组第28天瘤重为(0.74±0.21)g,阴性对照组为(1.42±0.28)g,空白组为(1.59±0.24)g.实验组瘤重与阴性、空白对照组相比差异均有统计学意义(均P ＜0.05),抑瘤率达53.5％.实验组PCNA指数显著低于阴性对照组和空白对照组(均P＜0.05).结论 靶向封闭Transgelin基因能明显抑制胰腺癌细胞BxPC3在裸鼠体内的增殖及肿瘤生长.     

磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性

目的：观察磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性，并观察磁性白蛋白纳米粒在各脏器中的分布特征。方法：建立大鼠移植性肝癌模型。大鼠正中开腹，胃十二指肠动脉插管固定。实验组，肝肿瘤区外加磁场，肝动脉注射磁性阿霉素白蛋白纳米粒(相当于阿霉素0．5mg／kg)，磁场应用30min，移去磁场后，动物立即处死。对照组肝肿瘤区不加磁场，肝动脉注射同样剂量的纳米粒后30min处死。动物处死后，立即取肿瘤组织、非磁区正常肝组织、心、肾、脾、肺、小肠和胃作了计数，肿瘤组织、肝组织送病理切片检查。结果：肝肿瘤区应用磁场30min后，磁区肿瘤组织的放射活性较非磁区肝组织的放射活性明显增加，磁区肿瘤组织的放射活性为非磁区正常肝组织的放射活性的8．7倍。对照组在没有磁场存在的情况下，肿瘤组织的放射活性为正常肝脏的2．8倍。实验组肺的放射活性较对照组明显降低。肾、心、脾、小肠和胃两组之间无明显差异。另外，实验组脾、肺和胃与肿瘤组织的放射活性之比较对照组大为降低。注入纳米粒800%以上分布于肝脏。结论：在磁场的作用下，磁性阿霉素白蛋白纳米粒在大鼠移植性肝肿瘤中的聚集明显增加。即使肝肿瘤区没有外加磁场，由于肿瘤组织和正常肝组织血管密度的差异，磁性阿霉素白蛋白纳米粒在肿瘤组织中的分布明显高于正常肝组织。实验组脾、肺、胃与肿瘤组织的放射活性比值大大低于对照组，说明磁场的存在使这些脏器的相对药物暴露明显降低。     

肝癌姑息性切除术后裸鼠残癌模型的建立

目的 建立肝癌姑息性切除术(PR)后可研究残癌生物学特性变化的转移性裸鼠人肝癌原位移植瘤模型.方法 采用单肝叶双瘤源原位接种技术建立MHCC97H原位移植瘤模型,PR切除1瘤,观察5周.测量肿瘤大小,流式细胞术计数外周血循环肿瘤细胞数,荧光显微镜和苏木素-0伊红(HE)染色检测肝内、肺、腹腔转移等,免疫组织化学染色和Western blot检测脑和肿瘤组织Vimentin表达.结果 双瘤源接种成瘤率95.6％、PR成功率95.3％、裸鼠5周总体存活率90.2％.假手术组、肝部分切除术组、PR组肿瘤大小、循环肿瘤细胞数均依次升高,肝内转移率分别为15.4％、41.7％、83.3％,肺转移率分别为61.5％、91.7％、100.0％,腹腔转移率分别为23.1％、50.0％、83.3％(P值均＜0.05).手术组脑和肿瘤组织Vimentin表达均显著上调.结论 成功建立转移性裸鼠人肝癌原位移植瘤合并PR模型,可用于研究残癌生物学特性的变化.     

瘤内注射奥曲肽对大鼠移植性肝肿瘤PCNA表达的影响

目的：探讨奥曲肽瘤内注射对大鼠移植性肝肿瘤PCNA表达的影响。方法：30只大鼠移植性肝肿瘤模型随机分为奥曲肽组、盐水组、酒精组三组,分别瘤内注射奥曲肽0.02mg、生理盐水0.2mL、无水酒精0.2mL,3d及8d后分别测定肿瘤组织中增殖细胞核抗原（PCNA）的表达情况。结果：治疗3d后,奥曲肽组的PCNA表达低于无水酒精组和生理盐水组的表达（P〈0.05）。8d后,奥曲肽组的PCNA表达明显低于无水酒精组和生理盐水组的水平（P〈0.05）。结论：瘤内注射奥曲肽可抑制大鼠移植性肝肿瘤的生长。     

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.     

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.     

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.