前药热化疗对裸鼠转基因结肠癌肝转移的靶向作用

目的 探讨组织特异性胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝转移的靶向治疗效果.方法 脂质体法转CD基因至人结肠癌LoVo细胞株.45只BALB/c裸鼠采用经门静脉注射转CD基因LoVo细胞(LoVo-CEACD,0.2 mL,107/L)至裸鼠体内建立模型后,随机分为3组,每组15只,即对照组、前药治疗组及前药热疗组.3组分别经腹腔注射42℃生理盐水和38℃5-FC及42℃5-FC.5-FC剂量为500 mE/(kg·d),连续21 d后,待动物自然死亡,观察自然生存期、肝脏转移率、肝脏转移结节数;切取肝脏转移瘤组织,正常肝组织及胃、肺、胰腺、小肠、大肠组织,行RT-PCR检测各组织CD基因表达,观察各组织病理学变化、肿瘤细胞凋亡指数.结果 目的基因在肝脏转移瘤组织中能有效表达,在正常肝组织及胃、肺、胰腺、小肠、大肠组织中无表达.3组的自然生存期分别为(25.80±3.65),(34.27±4.08).(41.87±3.91)d;肝脏转移率分别为100.0%(15/15).40.0%(6/15),13.3%(2/15);平均肝脏转移结节数分别为(2.93±1.16),(0.80±1.01).(0.20±0.56)个.前药治疗组和前药热疗组的自然生存率明显长于对照组(P<0.05);3组间的肝脏转移率两两比较,差异均有统计学意义(均P<0.05).肿瘤细胞凋亡指数(AI)分别为4.59%,9.87%,17.4%,各组比较,差异均有统计学意义(P<0.05).结论 组织特异性CD/5-FC系统热化疗对裸鼠结肠癌肝转移有明显的靶向抑制作用.     

原位基因治疗联合前药热化疗治疗结肠癌肝转移的实验研究

目的:探讨胞嘧啶睨氨酶(CD)基因联合5-氟胞嘧啶(5-FC)热化疗对裸鼠结肠癌肝转移的治疗效果.方法:30只BALB/c裸鼠经门静脉注射人结肠癌Lovo细胞建立结肠癌肝转移模型,随机分为转基因组和非转基因组,每组15只.转基因组:经腹腔注射病毒上清(0.2 mL/d,共5d)进行原位基因转染;非转基因组经蝮腔注射生理盐水(0.2 mL/d,共5d),2组同时腹腔注射42℃500 mg·kg-1·d-1)5-FC.治疗21 d后将动物处死,观察肝脏转移率和转移结节数,PCR法检测目的基因在肿瘤组织的整合,RT-PCR法检测目的基因在肿瘤组织的表达,观察肿瘤病理学变化.结果:目的基因成功转染并在肿瘤组织中有效表达.转基因组与非转移基因组肝脏转移率分别为26.7%(4/15)、100.O%(15/15),2组比较差异有统计学意义(P<0.05),肝脏转移结节数分别为0.60±0.83、2.40±0.99(P<0.001).镜下转基因组肝内转移癌细胞变性,染色体消失,可见凋亡小体,而非转基因组未见明显变化.结论:原位基因治疗联合前药热化疗对裸鼠结肠癌肝转移有明显抑制作用.     

两种异位种植结肠癌肝转移动物模型的比较

目的建立并对比两种异位种植结肠癌肝转移小鼠模型。方法以1×106个/mL小鼠结肠癌细胞株(CT26)0.2mL对BALB/c小鼠分别行肝门静脉注射法,脾脏种植切除脾脏法构建结肠癌异位种植肝转移动物模型。术后待小鼠自然死亡,比较两种动物模型的肝转移率和成瘤效果、肺转移率以及小鼠生存期的差异。结果肝门静脉注射法与脾脏种植切除脾脏法相比,前者在肝转移率、肝脏成瘤效果和肺转移率方面高于后者,后者在小鼠生存时间和操作难易程度方面优于前者。结论本研究建立并对比了两种具有高转移率的结肠癌肝转移小鼠模型,肝门静脉法在肝转移率和肝脏成瘤效果方面更具优势,适合对肝转移率和取材要求较高的实验研究;而脾脏种植切除脾脏法则更适合验证周期较长的药物实验。     

前药热化疗对裸鼠结肠癌肝转移的作用

目的 观察胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝转移的作用.方法 45只裸鼠随机分为3组,分别给予不同的治疗方法,观察各组肝转移率、肝转移瘤数目、病理学变化、肿瘤细胞凋亡指数,检测肿瘤组织中CD基因的表达情况.结果 对照组、5-FC治疗组、5-FC热疗组平均肝脏转移瘤数和肝脏转移率分别为4.6000±1.2649、2.2000±0.9189、0.5000±0.8498;100%、40%、20%;肿瘤细胞凋亡指数平均为4.59%、9.87%和17.40%,5-FC热疗组可见较多的凋亡小体形成.结论 CD/5-FC系统热化疗对裸鼠转CD基因LoVo细胞结肠癌肝转移有明显的抑制作用.     

不同途径裸鼠大肠癌肝转移模型的比较

目的建立并比较四种不同途径的裸鼠大肠癌肝转移模型,从而根据不同需要选择较为理想的裸鼠模型。方法 BALB/c(nu/nu)裸鼠共80只随机分为4组(每组20只),分别经脾脏背膜下、肝脏背膜下、盲肠浆膜下、门静脉注射5×10~6个HCT116细胞建立大肠癌肝转移模型,观察并记录各组小鼠生存状态,小鼠死亡后进行剖腹探查观察腹腔内肿瘤生长、肝脏转移情况,对肿瘤组织进行常规病理组织学观察。结果脾脏被膜下注射组、肝被膜下注射组、盲肠浆膜下注射组注射位置均成功成瘤;肝转移率:脾被膜下注射组为94.7%,盲肠浆膜下注射组为44.4%,门静脉注射组为66.7%;各模型的原发肿瘤及转移瘤均为典型的低分化腺癌。肝被膜下注射组肿瘤进展迅速,门静脉注射组围手术期死亡率高,盲肠浆膜下注射组生存时间较长。结论四种模型具有各自的优势和缺点,应根据实验需要来选择恰当的动物模型。     

沉默STC2对裸鼠结肠癌模型中肝转移瘤形成情况及IL-10和VEGF表达水平的影响

目的建立结肠癌肝转移裸鼠模型,探讨斯钙素2(Stanniocalcin 2,STC2)在结肠癌肝转移中的作用。方法利用慢病毒载体将shRNA转染入HCT116细胞以沉默STC2,构建沉默STC2的HCT116细胞系,并用Western Blot验证沉默STC2效果,建立结肠癌肝转移动物模型,分析STC2在结肠癌肝转移中的作用。将24只雄性Balb/c裸鼠随机分为实验组及对照组,每组12只。实验组将沉默STC2的HCT116细胞系—HCT116p LL3.7-STC2注射入Balb/c裸鼠脾脏并保留脾脏建模;对照组将未沉默STC2的HCT116细胞系—HCT116p LL3.7-Con注射入Balb/c裸鼠脾脏并保留脾脏建模。观察两组Balb/c裸鼠肝转移瘤形成情况,采用免疫组织化学方法检测Balb/c裸鼠肝脏内转移瘤中IL-10和VEGF的表达。结果 Western Blot实验提示造模成功,沉默STC2的实验组细胞HCT116p LL3.7-STC2中STC2蛋白量的表达少于对照组细胞HCT116p LL3.7-Con。实验组肝转移瘤发生率为41.67%(5/12),对照组为91.67%(11/12),组间差异有统计学意义(P0.05)。实验组肝转移瘤数量少于对照组(P0.05),两组肝转移瘤大小和肝脏重量的差异均无统计学意义(均P0.05)。实验组肝转移瘤中IL-10及VEGF表达水平均低于对照组(均P0.05)。结论在裸鼠模型中,将STC2沉默后的结肠癌细胞肝转移潜能下降,且其肝转移瘤中IL-10及VEGF的表达水平低于未沉默者。     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

目的 探讨组织特异性胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝脏转移的影响.方法 将45只裸鼠按随机数字表法分为3组:对照组、非热疗组、热疗组,每组15只.门静脉注射法建立结肠癌肝脏转移动物模型,3组分别给予不同的治疗方法.采用χ2检验和单因素方差分析3组肝脏肿瘤转移率、转移数目;观察各组病理学变化、肿瘤细胞凋亡指数;荧光定量RT-PCR和Westernblot检测肿瘤组织中CD基因的表达情况.结果 对照组、非热疗组、热疗组肝脏平均转移癌结节数目和转移率分别为(4.6±1.3)、(2.2±1.0)、(0.5±0.8)个和100.0%、60.0%、13.3%,3组比较差异有统计学意义(F=25.898,χ2=5.208,19.548,5.168,P<0.05);肿瘤细胞凋亡指数平均为4.6%、9.9%和17.4%.热疗组可见大量细胞空泡变性、坏死、溶解现象,有较多的凋亡小体形成.3组均可以检测到CD基因的表达.结论 组织特异性CD/5-FC系统热化疗对转CD基因结肠癌LoVo细胞裸鼠肝脏转移有明显的抑制作用.     

裸鼠原位种植大肠癌肝转移三种建模方法的比较

目的 比较3种不同的人大肠癌裸鼠原位种植肝转移模型,建立稳定有效的人大肠癌裸鼠原位种植肝转移模型.方法 逐步传代法皮下成瘤传5代,采用84只BALB/C-nu/nu裸鼠,随机分为4组,结肠原位荷包缝合法和结肠原位纤维蛋白胶黏合法和结肠微注射1×106和1×105SW1116细胞法建立大肠癌裸鼠原位种植肝转移模型.各组裸鼠死亡后立即解剖观察原位以及肝脏、肺、脾脏、胰腺、肠系膜等脏器组织的转移并且进行苏木素-伊红(HE)染色进行镜下观察有无转移.结果 荷包缝合组和纤维蛋白胶组结肠原位种植肝转移成功率均为100%比微注射法50.0%和14.3%高,纤维蛋白胶法比其他两种方法所形成的结肠原位肿瘤和肝转移瘤均大而多.HE染色表明肝转移肿瘤性质与结肠原位种植瘤相同.结论 结肠原位纤维蛋白胶黏合法比较其他二种原位种植肝转移模型的手术成功率高,肝转移率高、操作简单.     

门静脉注射白细胞介素-12治疗肝转移肿瘤的实验研究

目的　探讨通过门静脉系统局部应用白细胞介素 12 (IL 12 )对于肝转移肿瘤的治疗作用。方法　通过门静脉注射 2× 10 5个MCA 2 0 5肿瘤细胞建立小鼠肝转移肿瘤模型 ,同时脾脏被移植到皮下 ,作为反复多次向门静脉系统注射的途径。第 3～ 7天 ,0 1μgIL 12通过腹腔或脾脏注射 ,同时对照组中通过脾脏注射等体积的平衡盐水。第 2 1天检查肝转移肿瘤的情况。结果　在肝转移模型中 ,IL 12腹腔注射组和IL 12脾脏注射组的肝脏重量 (1 33± 0 0 8)g和 (1 2 9± 0 0 7)g明显小于对照组 (1 92± 0 17)g ,P <0 0 5 ,IL 12腹腔注射组和IL 12脾脏注射组的肝脏转移结节数目 (1 5 3± 0 5 8,0 6 0± 0 89)明显少于对照组 (18 2 5± 5 71,P <0 0 5 )。在IL 12脾脏注射组中 (n =6 ) ,3只小鼠的肝脏肿瘤完全消失。结论　通过门静脉系统局部应用IL 12是治疗肝转移肿瘤的有效方法。     

苏拉明对裸鼠原位种植人胃癌生长和肝转移的抑制作用

目的 :研究苏拉明 (Suramin)对裸鼠原位种植人胃癌生长和肝转移的抑制作用 ,并探讨其对胃癌细胞凋亡的影响。方法 :建立裸鼠原位种植胃癌生长与转移裸鼠模型。随机分为 4组。种植后第 1周开始 ,分别自腹腔注射生理盐水 (对照组 )、5 -氟脲嘧啶 (30mg/kg·d ,5 -FU组 )、Suramin制剂 (15mg/kg·d ,Suramin组 )、5 -FU与Suramin联合应用 (5 -FU30mg/kg·d ,Suramin 15mg/kg·d ,5 -FU加Suramin组 ) ,每天一次 ,共用 6周。种植后第7周处死动物 ,测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度 (MVD)、胃癌细胞凋亡指数 (AI) ,观察肿瘤细胞肝转移情况。结果 :对照组、5 -FU组、Suramin组和 5 -FU加Suramin组的原位肿瘤瘤重分别为 1.32 g± 0 .37g、0 .71g±0 .34g、0 .36 g± 0 .15 g和 0 .18g± 0 .11g ;抑瘤率分别为 0 %、46 .2 %、72 .7%和 85 .6 %;肝转移率分别为 91.7%、33.3%、16 .7%和 0 %。MVD分别为 13.7± 5 .6、11.8± 4.2、4.1± 2 .3和 1.8± 1.2 ;AI分别为 3.14%± 1.95 %、7.2 3%± 3.87%、10 .15 %± 3.94%和 18.13%± 9.75 %。与对照组相比 ,5 -FU组、Suramin组加 5 -FU加Suramin组胃癌生长和肝转移受到明显抑制 (P     

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.