前列腺癌骨转移血清蛋白质组学研究

目的:应用蛋白质组学双向凝胶电泳和质谱技术筛选前列腺癌骨转移血清标志物。方法:收集前列腺癌伴骨转移、不伴骨转移各5例血清样本。血清样品用除白蛋白试剂盒除去血清中的白蛋白后进行双向凝胶电泳,ImageMaster 2D Platinum软件分析,有意义的差异蛋白质点行基质辅助激光解析离子化飞行时间质谱(MALDI-TOF-MS)鉴定。结果:双向凝胶电泳显示,前列腺癌骨转移组血清蛋白中有15个斑点与前列腺癌无骨转移组有显著差异,前列腺癌骨转移患者血清中10个蛋白质表达水平显著增加,5个蛋白质表达水平显著下降。5个差异蛋白点进行胶内原位酶解,肽质量指纹图谱分析成功得到了3个蛋白质肽质量指纹图谱,并查询数据库初步鉴定了该3个蛋白质分别为锌α2糖蛋白、结合珠蛋白和载脂蛋白CⅢ。结论:双向凝胶电泳结合质谱鉴定是血清差异蛋白质组学研究的可靠平台和有力工具。所鉴定出的蛋白质与前列腺癌骨转移的发生、发展有关,可能是前列腺癌骨转移潜在的血清标志物。     

大鼠横断性损伤坐骨神经后近端神经干分泌液的蛋白质组学分析和生物活性检测

目的　探讨横断性周围神经近侧神经的分泌功能 ,分泌液的蛋白质成分及其对运动神经元生长的影响。方法　建立大鼠坐骨神经横断后神经近端室、神经远端室以及混合室 (近加远端神经 )收集室模型。用蛋白质双向电泳技术和质谱分析法分析 3种收集室内液体 (收集液 )的蛋白质成分 ,并以 3种收集液培养脊髓前角运动神经元。结果　大鼠坐骨神经断端的混合室、近端室和远端室均有淡黄色清亮液体 ,其蛋白质浓度分别为 ( 5 .45± 1.2 )mg/ml ,( 3 .87± 0 .7)mg/ml和 ( 5 .68± 1.5 )mg/ml。收集液蛋白质双向电泳结果显示 3组蛋白质图谱的图案模式相似。混合室、近端室和远端室组分别检测到 10 98± 3 4,985± 47和 10 2 1± 3 6个点。蛋白质点主要分布在pH4～ 8,分子量在2 5～ 90kD的范围内。应用 3组神经断端收集液培养运动神经元发现 ,3种收集液所培养的运动神经元的细胞存活数、神经元的胞体面积、突起长度总体上大于对照组 ;实验组之间无明显差异。结论　( 1)大鼠坐骨神经横断后 ,其近端神经干具有与远端神经干相似的分泌功能 ;( 2 )蛋白质双向电泳图谱的图案显示 3种收集室的蛋白质具有同源性 ;( 3 ) 3种收集液都能促进运动神经元的存活和生长 ,且近端室和远端室收集液的作用没有差别。     

创伤性休克后血浆黏附分子的变化及不同复苏液的影响

目的　探讨创伤性休克兔中性粒细胞黏附分子CD11b、血清可溶性细胞间黏附分子(sICAM ) 1的动态变化及不同复苏液的影响。方法　 72只创伤性休克模型兔分为 6组 ,林格氏液组按失血量 2倍输入乳酸林格氏液 ,其他各组按 6ml/kg分别输入右旋糖酐 40、70 6代血浆、7.5 %氯化钠和 2 0 %白蛋白。分别采用流式细胞仪、酶联免疫吸附法检测CD11b、sICAM 1表达值。结果　各实验组休克 1hCD11b及sICAM 1表达增高 ,与对照组比较差异有显著性 (P <0 .0 5 ) ,并于12h达最高值 (林格氏液组 85 .6± 12 .1,60 9.3± 10 1.3 ;高渗盐组 77.5± 10 .3 ,5 18.5± 87.2 ;白蛋白组 78.2± 10 .7,5 2 2 .4± 88.3 ;P <0 .0 1)。高渗盐和白蛋白组 2 4、48hCD11b和sICAM 1分别为5 9 .2± 6.9,5 4.6± 5 .9;3 60 .1± 68.4,2 74.4± 40 .1;5 8.9± 6.4,5 5 .0± 5 .8;3 5 2 .6± 65 .3 ,2 70 .2±3 8.2 ,较林格氏液组 (72 .3± 10 .1,65 .8± 8.3 ;5 0 2 .6± 84.5 ,3 42 .4± 63 .1)降低 (P <0 .0 5 ) ;高渗盐和白蛋白组 (8.3 % )复苏 48h动物死亡率较林格氏液组 (4 1.7% )低 (P <0 .0 5 )。结论　创伤性休克时PMNCD11b和sICAM 1表达增加 ;采用 7.5 %氯化钠或 2 0 %白蛋白复苏时表达值及死亡率较乳酸林格氏液低。     

氯沙坦对自发性2型糖尿病KKAy小鼠肾小球蛋白表达谱的影响

目的 利用比较蛋白质组学双向电泳技术研究体系来观察血管紧张素受体拮抗剂(ARB)氯沙坦对自发性2型糖尿病KKAy小鼠肾小球蛋白表达谱的影响.方法 8周龄自发性2型糖尿病KKAy小鼠随机分为氯沙坦治疗组(饮用水中喂入氯沙坦粉末10 mg+kg-1·d-1)和非治疗组;8周龄C57BL/6小鼠作为正常对照组.饲养12周后,经胸主动脉磁珠灌流分离肾小球,提取肾小球蛋白.DIGE最小荧光标记法标记,行二维荧光差异凝胶电泳.应用Typhoon多功能成像系统扫描凝胶,DeCyder 2D差异分析软件进行图像分析.采用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)鉴定差异表达蛋白质.结果 KKAy小鼠的体质量、血糖和尿白蛋白排泄率较正常对照C57BL/6小鼠显著升高(均P＜0.05),氯沙坦治疗显著改善2型糖尿病KKAy小鼠尿白蛋白肌酐比[(539.71±100.23)mg/g比(728±177.19) mg/g]、肾小球基底膜增厚和系膜基质增生等肾脏病理损害,而对血糖无影响.通过DeCyder 2D差异分析软件,发现KKAy氯沙坦治疗组与KKAy非治疗组肾小球内表达差异大于1.1倍的蛋白质斑点62个.经肽质量指纹图分析,鉴定出41种蛋白质.其中表达上调的蛋白28种,包括甘油激酶、亚硫酸盐氧化酶、甘氨酸脒基转移酶、腺苷高半胱氨酸酶等;表达下调的蛋白质13种,包括3-巯基丙酮酸硫基转移酶、ATP合酶亚单位d、60 000热休克蛋白、线粒体应激蛋白70(又名75 000葡萄糖调节蛋白,GRP75)等.有6种蛋白在20周龄KKAy小鼠和C57BL/6小鼠肾小球内存在差异表达,氯沙坦治疗抑制了其在糖尿病状态下的表达变化,包括丙酮酸脱氢酶复合物的二氢硫辛酰赖氨酸残基乙酰基转移酶组分、琥珀酰辅酶A连接酶[GDP-形成]亚单位β、ATP合酶亚单位d、GRP75、核苷二磷酸盐结合部分X模体19和硒结合蛋白1.结论 氯沙坦可明显减轻KKAy小鼠尿白蛋白排泄率和肾脏病理损害;可抑制糖尿病状态下肾小球ATP合酶亚单位d、GRP75、硒结合蛋白1等蛋白的表达变化;可能通过减少线粒体活性氧簇产生,抑制氧化应激反应发挥其肾脏保护作用.     

Th1/Th2细胞因子对器官移植排斥反应的影响

目的:研究Th1/Th2细胞因子对同种异系小鼠心脏移植存活时间的影响.方法:使用野生型BALB/c小鼠作为供体,野生型B6小鼠、IL-4基因去除B6小鼠及IFN-γ基因去除B6小鼠作为受体,行腹部异位小鼠心脏移植.部分IL-4基因去除小鼠、IFN-γ基因去除小鼠联合应用α-半乳糖神经酰胺(α-galactosylceramide,α-GalCer),以获得更强的Th1/Th2偏移.比较移植物存活时间.向野生型、IL-4基因去除及IFN-γ基因去除B6小鼠腹腔内注射供体小鼠脾细胞,提取受体小鼠脾脏CD8<'8>T细胞行淋巴细胞毒试验.结果:IFN-γ基因去除组小鼠的移植物存活时间为(6.40±0.55)d,联合应用α-GalCer组移植物存活时间为(8.00±1.15)d.IL-4基因去除组小鼠的移植物存活时间为(8.00±1.00)d,联合应用α-GalCer组移植物存活时间为(8.60±1.34)d.淋巴细胞毒试验显示IFN-γ基因去除小鼠的CD8+T细胞毒性明显增强.结论:Th1/Th2细胞因子与排斥反应之间并不存在简单的对应关系.     

2例膜性肾病患者足细胞内陷性病理改变的观察

我科观察45例原发性膜性肾病的超微结构，包括Ⅰ～Ⅲ期，其中男17例，女28例，平均年龄（42．4±11．5）岁，尿蛋白（3．5±1．7）g／d，血肌酐（68．88±22．28）umol／L，血浆白蛋白（29．7±7．O）g／L。其中2例患者超微结构显示足细胞伸入基底膜中。     

谷氨酰胺颗粒对创伤患者蛋白代谢的影响

目的　观察服用谷氨酰胺颗粒对创伤、烧伤及大手术患者蛋白代谢的影响及可能发生的不良反应。方法　采用随机、双盲对照法 ,将受试患者分为谷氨酰胺 (glutamine,GLN)组和安慰剂对照(placebo,P)组 ,每组 6 0例 ,两组患者采用等氮、等热卡的营养支持。GLN组口服或管饲GLN 0 5 g·kg-1·d-1,对照组使用同等剂量的安慰剂 (甘氨酸 ) ,疗程为 7d。比较各组患者血浆GLN浓度、蛋白代谢、肝肾功能及不良反应发生率 ,对烧伤患者还观察了创面愈合情况和住院时间。结果两组患者血浆GLN浓度、血浆蛋白含量均明显低于正常值 ,而尿氮排量则明显增高。两组比较 ,GLN组患者使用谷氨酰胺颗粒 7d后血浆GLN浓度明显增高 (5 92 5 0± 185 2 3μmol/Lvs.4 0 7 4 1± 190 2 2 μmol/L) ,增幅达4 5 4 3% (P <0 0 1)。与之对应 ,血浆前白蛋白 (0 2 9± 0 10 g/Lvs.0 2 4± 0 0 7g/L)、转铁蛋白 (5 4 4±3 0 3g/Lvs.3 6 0± 2 0 2 g/L)含量均显著高于P组 ,升幅分别为 2 0 83%、5 1 11% (P <0 0 1) ,而尿氮排量则明显低于P组 (6 78± 4 78g/dvs.9 38± 6 0 2g/d) ,降幅为 2 7 78% (P <0 0 1)。血浆总蛋白、白蛋白含量、血尿常规及肝肾功能两组差异无显著意义 (P >0 0 5 )。少数患者出现轻微不良反应 ,如恶心、腹     

骨肉瘤与良性骨肿瘤差异蛋白质组学研究

[目的]比较骨肉瘤与良性骨肿瘤蛋白质组学差异,探寻骨肉瘤特异性标记物.[方法]分别提取5例骨肉瘤肿瘤标本和5例良性骨肿瘤总蛋白,进行双向电泳,重复3次;银染、扫描后进行ImageMaster 2DE软件分析以发现差异蛋白并对差异蛋白质点进行MS+ MS/MS质谱鉴定,获取肽质指纹图谱并在NCBI数据库中找到匹配蛋白质.[结果]所获得的双向电泳银染图谱重复性较好,骨肉瘤组织蛋白质点数约为1 296±179,骨良性肿瘤组织蛋白质点数约为1 098±152,明显差异的蛋白质点38个,其中12个被成功鉴定,7个蛋白质在骨肉瘤中表达上调,其中热休克蛋白60、应激诱导磷酸化蛋白1在骨良性肿瘤中表达缺失;5个蛋白质在骨肉瘤中表达下降,以锚定蛋白下降最明显.[结论]蛋白质组学的分析能成功的发现骨肉瘤与骨良性肿瘤的差异蛋白质,为寻找骨肉瘤特异标记物提供依据.     

添加重组人生长激素的营养支持对严重多发伤患者营养状况的影响

目的观察添加重组人生长激素（recombinant human growth hormone，rhGH）的营养支持对严重多发伤患者营养状况的影响。方法45例严重多发伤（ISS〉25）患者随机分为三组，每组15例。三组均行标准营养支持，其中两组在术后48h行添加rhGHE分别为0．2和0．4IU／（kg·d）]的营养支持14d，第三组为对照组。不同时间点测定患者氮平衡试验、血浆前白蛋白水平和安全性指标（血糖、血Na^＋与血总13、T4）。结果严重多发伤患者各实验组术后第3、5天氮平衡分别为（-1．28±3．190）、（5．45±2．00）和（-0．18±2．55）、（6．11±1．60），均较对照组（-5．17±1．68）、（-1．08±3．31）明显增高（P〈0．01）；各实验组术后第9天、第16天的血浆前白蛋白水平分别为（180．19±27．15）、（194．44±50．82）和（194．94±29．65）、（194．11±16．17），均较对照组（117．42±19．10）、（135．63±28．31）明显增高（P〈0．01）。而实验组组间比较氮平衡和前白蛋白水平在各时间点的差异无统计学意义。术后第9天、第16天安全性指标水平三组之间差异均无统计学意义。结论严重多发伤患者在术后48h添加rhGH的营养支持可显著改善其营养状况，rh．GH在0．2和0．4IU／（kg·d）剂量下应用是安全的。     

复杂腹腔感染对白蛋白合成速率的影响

目的探讨复杂腹腔感染对白蛋白合成速率的影响。方法前瞻陆收集2009年12月至2010年10月间南京军区南京总医院普通外科研究所收治的肠瘘合并复杂腹腔感染病例（感染组,8例）;另选取同期8名年龄、性别、BMI相匹配的健康志愿者作为对照组。受试者在空腹状态下经外周静脉给予首剂量无菌L-[ring-^2H5]-苯丙氨酸溶液（4μmol／kg）,继之以6μmol·kg^-1·h^-1的速度持续输注6h。输注前和输注后的每小时取3ml动脉血：通过GC-MS测定血浆游离氨基酸和掺入到白蛋白中L-[ring^2H5]．苯丙氨酸的同位素丰度。结果感染组患者血清总蛋白和白蛋白浓度分别为（62．2±1．0）g／L和（32．5±4．0）g／L,显著低于对照组[（74．2±1．7）g／L和（46．1±2．6）g／L;均P〈0．05]。感染组患者C反应蛋白、白细胞计数和体温3项全身炎性反应指标均高于对照组（均P〈0．05）。感染组患者白蛋白合成速率为（5．3±1．6）％／d,显著低于正常对照组的（7．8±1．2）％／d,差异有统计学意义（P〈0．05）。血浆游离氨基酸谱显示,感染组患者血浆谷氨酸高于对照组．苯丙氨酸和脯氨酸低于对照组（均P〈0．05）。结论复杂腹腔感染可明显抑制白蛋白合成,是腹腔感染患者低白蛋白血症的原因之一。     

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.