hIL-2基因修饰人肝细胞的腹腔移植抗肿瘤作用

目的　探讨hIL 2基因修饰人肝细胞腹腔移植的抗肿瘤作用。方法　采用鼠尾胶原包裹转hIL 2基因人肝细胞并移植入癌性腹水型小鼠模型腹腔,观察移植 1、4、7、10 d后小鼠脾淋巴细胞的增殖反应、脾淋巴细胞杀伤活性、血清hIL 2浓度及移植小鼠生存期。结果　移植4 d后,小鼠血清hIL 2浓度达到(76 2±2 2) pg/ml,脾淋巴细胞的增殖反应 OD值和脾淋巴细胞杀伤活性达到峰值,分别为(0 674±0 046)%和(35 6±1 9)%,与对照组和 L 02 细胞移植组相比,差别均有非常显著意义(P<0 05);移植 L 02/IL 2 肝细胞的小鼠生存率显著高于对照组和 L 02 细胞移植组(P=0 0003)。结论　IL 2基因修饰肝细胞移植于腹腔,可上调淋巴细胞的增殖和杀伤功能,达到抗肿瘤的目的,对肝细胞结合转基因的应用研究有积极意义。     

腺病毒载体携带全长人乙肝病毒表面前S2蛋白抗体基因在体外的表达

目的　构建携带全长人乙肝病毒表面PRES2 蛋白抗体基因的腺病毒载体 ,观察其在体外的表达。方法　将全长 2 5 70bp人乙肝病毒表面PRES2 蛋白抗体基因克隆入 5型腺病毒穿梭质粒载体 ,在 2 93细胞中重组产生重组腺病毒 ,体外感染CHO细胞 ,感染复数 (MultiplicityofInfec tionVirus/Cell)为 2 0 ,获得表达产物 ,并测定其亲和力。结果　TCID5 0法测定重组腺病毒滴度为(2 .1× 10 10 )pfu/ml。病毒感染CHO细胞后 ,表达蛋白经蛋白质印迹分析证实为全长人源化抗体。抗体亲和力常数为 (2 .16± 0 .2 0 )× 10 8L/mol。结论　全长人乙肝病毒表面PRES2 蛋白抗体基因腺病毒载体成功构建和表达全长高亲和力人源化抗体 ,为乙型肝炎治疗提供了一个全新的途径。     

Caspase-8和Fas抗原调控化疗诱导的人肝癌细胞凋亡

目的　探讨Fas抗原和Caspase 8在化疗诱导人肝癌细胞凋亡中的调控作用。方法　用 1× 10 -2 mol/L浓度的氟尿嘧啶处理HepG2细胞 ,分别作用 4、8、16、2 4h。免疫细胞化学法检测Fas抗原的表达。用荧光试剂盒检测Caspase 8的活性。流式细胞仪检测氟尿嘧啶或抗 Fas 抗体诱导的肝癌细胞凋亡百分率 ,以及加入Caspase 8活性抑制剂IETD FMK后凋亡百分率的变化。 结果　氟尿嘧啶诱导HepG2细胞凋亡后 ,与对照组比较 ,Fas抗原表达强度增加 (P <0 0 1) ,Caspase 8活性升高 (P <0 0 1)。Fas抗原表达和Caspase 8活性随着氟尿嘧啶作用时间的延长而逐步升高 ,至 16h后达到高峰 ,然后下降 ,但仍显著高于对照组 (P <0 0 1)。Fas抗原的表达与Caspase 8活性变化呈显著正相关 (r =0 96 9,P <0 0 1)。表达增强的Fas抗原具有转导凋亡信号的功能 ,借此抗 Fas 抗体增强了氟尿嘧啶诱导的HepG2细胞凋亡。Caspase 8活性抑制剂IETD FMK能阻断Caspase 8活化而抑制氟尿嘧啶或抗 Fas 抗体诱导的HepG2细胞凋亡 ,实验组和抑制剂组比较 ,细胞凋亡百分率有显著性差异 (P <0 0 1)。结论　氟尿嘧啶诱导HepG2细胞经Fas依赖途径凋亡。Caspase 8活性上调在该凋亡过程中发挥重要作用。     

聚丙烯酰胺水凝胶注入兔体的免疫效应研究

目的　观察注射性聚丙烯酰胺水凝胶 (PAMHG)注入实验兔体的免疫效应。方法　采用间接免疫荧光法或双抗体夹心ELISA法 ,监测PAMHG注入兔体前后T淋巴细胞亚群、NK细胞活性、IL 2和sIL 2R表达水平。结果　PAMHG注入兔体前 ,CD3+ 和CD4 + T淋巴细胞表达水平分别为(17.8± 5 .9) %和 (9.6± 3.5 ) % ;PAMHG注入兔体后 3个月 ,表达水平分别为 (2 4 .3± 5 .6 ) %和 (15 .8± 4 .7) %。注入前后比较有显著差异 (P <0 .0 1)。 3个月后表达水平逐渐下降 ,与术前比较差异无显著意义 (P >0 .0 5 )。PAMHG注入兔体前 ,CD8+ T淋巴细胞表达水平为 (6 .2± 2 .4 ) % ,与注入后 3个月为 (8.5± 4 .2 ) %比较仅略有上升 ,两者比较P >0 .0 5。注入兔体前、后CD4 + CD8+ 比值均在正常范围(1～ 2 )。NK细胞活性仅于注入兔体 1个月为 (2 5 .3± 6 .8) % ,较注入前 (18.0± 9.7) %升高 (P <0 .0 5 ) ,俟后NK细胞活性逐渐下降 ,与注入前比较差异无显著性意义 (P >0 .0 5 )。IL 2和sIL R表达水平于注入兔体前后差异无显著性意义 (P >0 .0 5 )。结论　PAMHG用作软组织填充剂 ,仅在机体内引起短时异物排斥 ,可渐与组织相容 ,不会引起严重免疫功能失调     

人肝癌细胞器官特异性转移与基质金属蛋白酶分泌的关系

目的　探讨不同转移潜能的人原发性肝癌细胞系基质金属蛋白酶 (MMPs)分泌与器官特异性转移的关系。方法　将C5 7BL/6小鼠的肺、脾组织粗提物与高低转移潜能的人肝癌细胞系MHCC97 H和MHCC97 L共培养 ,明胶酶谱法检测其分泌上清MMPs表达水平 ,并用荧光免疫染色法比较MMP 9的表达。结果　在无血清培养液培养条件下 ,MHCC97 H和MHCC97 L细胞均分泌较少MMP 9(2 .1± 0 .2 ,1.4± 0 .1) ,不分泌MMP 2 ;但MHCC97 H细胞分泌活性型MMP 9(17.4± 2 .2 )显著高于MHCC97 L细胞 (6.7± 0 .2 ,P <0 .0 0 1)。与肺组织粗提物孵育后 ,MHCC97 H和MHCC97 L细胞分泌MMP 9、活性型MMP 9和MMP 2均显著高于无血清培养液条件下MMPs分泌 (P <0 .0 0 1) ;MHCC97 H细胞分泌MMP 9(18.8± 1.2 )、活性型MMP 9(10 0 .1± 1.1)、MMP 2 (2 2 .4± 1.3 )均显著高于MHCC97 L细胞 (7.8± 0 .3 ,40 .8± 2 .2 ,8.2± 0 .4,P <0 .0 0 1)。脾组织粗提物孵育后的MHCC97 H和MHCC97 L细胞不分泌MMPs。荧光免疫细胞化学法检测MMP 9表达位于MHCC97 H细胞核周和细胞浆 ,而在MHCC97 L细胞未见明显的MMP 9表达。结论　不同转移潜能的人肝癌细胞分泌MMPs差异与其侵袭转移能力相关。肺组织粗提物促进不同转移潜能的人肝癌细胞分泌MMPs可能与其器官特异性     

半胱氨酸酶-3在依托利酸诱导肝癌细胞凋亡中的作用

目的　探讨选择性环氧合酶 (COX)抑制剂依托利酸 (etodolac)诱导肝癌SMMC772 1细胞凋亡的分子机制。方法　采用流式细胞术、DNA琼脂糖凝胶电泳法测定细胞凋亡情况 ;West ernblotting法检测不同浓度etodolac处理后凋亡相关蛋白Bcl 2、Bax表达的变化 ;并以流式细胞术检测半胱氨酸酶 3 (Caspase 3 )酶活性的变化。 结果　流式细胞术显示etodolac(0、0 .2 5、0 .5 0、1.0 0、2 .0 0mmol/L)作用SMMC772 1细胞 48h后 ,对照处理组 (0mmol/L)没有出现凋亡峰 ,其余各组(0 .2 5、0 .5 0、1.0 0、2 .0 0mmol/L)出现明显的凋亡峰 ,其凋亡率分别为 (16.3± 3 .1) %、(19.9±3 .6) %、(2 2 .9± 3 .2 ) %、(3 1.2± 3 .3 ) % (P <0 .0 0 1) ;DNA琼脂糖凝胶电泳出现明显的DNALad der ;不同浓度etodolac处理后凋亡相关蛋白Bcl 2表达下降 ,Bax表达增加 ;随着etodolac处理浓度的增加 ,表达活性Caspase 3的细胞百分率分别为 (3 .61± 0 .3 2 ) %、(2 .93± 0 .15 ) %、(10 .2 9±0 .3 9) %、(2 7.3 3± 1.2 8) %、(5 7.40± 1.69) % (P <0 .0 0 1)。结论　选择性COX 2抑制剂可能通过调节Bcl 2、Bax蛋白表达活化Caspase 3 ,从而诱导肝癌SMMC772 1细胞凋亡。     

重组人内皮细胞抑制素腺病毒载体的构建及其应用

目的　构建表达人内皮细胞抑制素 (Endostatin)的重组腺病毒载体 ,并进行活性检测。方法　将含有IL3分泌肽的人Endostatin全长cDNA插入穿梭质粒pAdCMV产生重组质粒pAd IL3 Endo ,通过脂质体介导与 pBHG1 0共转染 2 93细胞 ,经同源重组产生重组腺病毒Ad IL3 Endo。体外转染人结肠癌SW62 0细胞并观察其上清对人脐静脉内皮细胞 (HUVEC)生长的影响。结果　扩增到的Ad IL3 Endo的滴度为 4 .3× 1 0 1 2 空斑形成单位 (pfu) /L ,多聚酶链反应 (PCR)显示在转染的细胞中有人EndostatincDNA的存在 ,Westernblot显示转染细胞上清中有人Endostatin蛋白表达 ,台盼蓝染色显示其上清作用 72h后HUVEC的生长被抑制了 67% (P <0 .0 5)。结论　所制备的重组人Endostatin腺病毒载体能有效表达具有生物学活性的人Endostatin ,为进一步的研究奠定了基础     

抑制蛋白激酶Cα活性增加TNF-α对小鼠肝癌细胞毒性的实验研究

目的探讨肿瘤坏死因子α(tumor necrosis factor α,TNF-α)及联合蛋白激酶Cα (protein kinase C alpha,PKC-α)抑制剂Go6976对小鼠肝癌(H22)细胞凋亡的影响。方法将处于对数生长期的H22细胞分成两组,每组分四部分,一组仅以不同浓度的TNF-α(0,20、40、60 ng／ml)处理,另一组TNF-α处理同时以Go6976(4．6 nmol／ml)抑制PKC-α活性,分别于4 h,8 h,16 h采用流式细胞仪检测小鼠肝癌细胞的凋亡率,Western blotting方法检测PKC—α和磷酸化PKC-α蛋白的表达情况。结果 TNF-α(0、20、40、60 ng／ml)处理H22细胞4 h,细胞凋亡率分别为2．44％±0．31％、 1．80％±0．32％、2．73％±0．14％、3．05％±0．78％,PKC-α和磷酸化PKC-α表达无显著改变;同时用 TNF-α和Go6976处理H22细胞,凋亡率、PKC-α和磷酸化PKC-α的表达与单独使用TNF-α的结果相似。TNF-α处理8 h,细胞凋亡率分别为2．11％±0．43％、1．83％±0．31％、3．40％±0．47％、6．05％± 0．78％,PKC-α及磷酸化PKC-α的表达随TNF—α浓度增加而上调;TNF—α处理同时抑制PKC-α活性,细胞凋亡率显著升高,分别为2．90％±0．39％、7．76％±0．35％、11．43％±1．05％、12．96％± 2．44％,PKC-α和磷酸化PKC-α表达相应下调。仅以TNF-α处理或TNF—α处理同时抑制PKC-α活性16 h,其结果与8 h的结果基本一致;于Go6976抑制细胞PKC-α活性组,TNF-α60 ng／ml时细胞凋亡率较TNF-α40 ng／ml时有所下降,但坏死细胞的比例却明显升高。结论 TNF-α上调PKC—α和磷酸化PKC-α表达;抑制PKC-α活性,显著增加TNF-α对H22细胞的细胞毒性。     

抑癌基因PTEN与人大肠癌转移的相关性研究

目的　探讨抑癌基因PTEN的表达在大肠癌转移侵袭过程中的作用。方法　 (1)应用Nothernblot和免疫组织化学的方法检测 47例大肠癌组织中PTENmRNA和蛋白的表达 ,分析其与大肠癌转移的关系。 (2 )利用Westernblot法检测不同转移潜能的大肠癌细胞系内PTEN蛋白的表达水平 ,说明PTEN蛋白的表达对大肠癌细胞转移潜能的影响。 (3 )用阳离子脂质体作载体 ,将PTEN基因转染大肠癌细胞株LOVO后 ,采用计数细胞悬液加到粘附底物后 2 0和 12 0min的细胞贴壁数用以测定细胞粘附能力 ,采用Costar的浸润小室检测PTEN基因转染前后细胞的浸润能力。结果　 (1)在有淋巴结及远处转移的大肠癌组织中 ,PTENmRNA和蛋白的表达显著低于无转移者 ;(2 )转移潜能高的LOVO细胞PTEN的表达量通过显著低于转移潜能较低的HT 2 9、LS 174T ;(3 )LOVO、转染 pcDNA3 .0 PTEN的细胞 (LOVO/pcDNA3 .0 PTEN )在特异性粘附底物(Laminin)上 2 0min时贴壁率分别为 (18.6± 1.4) %和 (13 .9± 0 .5 ) % (P <0 .0 5 ) ,12 0min时贴壁率分别为 (71.2± 2 .5 ) %和 (5 6.0± 1.6) % (P <0 .0 5 ) ;(4 )采用Costar的浸润小室对LOVO、LOVO/pcDNA3 .0 PTEN细胞的浸润能力分析结果显示 :细胞悬液静置培养 6h后 ,对照细胞LOVO浸润穿透多聚碳膜的细胞数为 (1     

X射线激发Cu-Cy介导的光动力对人结肠癌细胞的杀伤作用研究

目的:探讨X射线激发Cu-Cy介导的光动力对人结肠癌SW620细胞的体外杀伤效应及其作用机制。方法:用不同浓度(0~100 mg/L)Cu-Cy联合或不联合低剂量X线照射处理SW620细胞后,采用CCK8法检测并光镜观察细胞的生长活性;JC-1染色检测线粒体膜电位;Annexin V FIFC/PI双染法检测细胞的凋亡率;Western blot检测凋亡相关蛋白Bax、Bcl-2及自噬相关蛋白LC3B、P62的表达;透射电镜观察细胞的超微结构。结果:与空白对照SW620细胞(0 mg/L Cu-Cy,无X线照射),Cu-Cy联合X线照射处理的SW620细胞生长活性明显降低,并呈一定的浓度依赖性(部分P0.05),且细胞凋亡率明显升高、线粒体膜电位下降细胞的比例明显增加、Bax与LC3B-II蛋白表达明显升高,Bcl-2与P62蛋白表达明显降低(均P0.05)、细胞内自噬体增多;单纯X射线照射和单加Cu-Cy处理的SW620细胞以上指标均无明显改变。结论:X线激发Cu-Cy介导的光动力能有效抑制人结肠癌SW620细胞体外生长活性,机制可能与其诱导细胞凋亡和自噬有关。     

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.