错配修复蛋白表达缺失在结直肠癌中的意义

目的检测结直肠癌组织中错配修复（MMR）蛋白表达情况，探究错配修复缺陷（dMMR）与患者临床病理特征的相关性及其对预后的影响。 方法回顾性收集2019年1月至2021年5月于攀枝花市中心医院就诊且行根治术治疗的214例结直肠癌患者临床资料及病理组织标本进行研究。采用免疫组织化学染色法和免疫印迹法分别检测临床肿瘤组织、对应癌旁正常组织中MMR蛋白（hMSH2、hMSH6、hMLH1、hPMS2）的表达情况，任一蛋白表达缺失则判定为dMMR。分析MMR蛋白表达与患者临床病理特征的相关性；Pearson检验结直肠癌组织中四种MMR蛋白表达缺失的相关性；绘制Kaplan-Meier生存曲线，分析dMMR对患者预后生存的影响。 结果（1）四种MMR蛋白阳性染色均主要分布于细胞核中，呈棕黄色或棕褐色。结直肠癌组织中dMMR发生率为15.4%（33/214），显著高于对应癌旁正常组织的3.3%（7/214），差异有统计学意义（χ²=18.642，P<0.001）。hMLH1蛋白表达缺失25例，hPMS2 20例，hMSH2 12例，hMSH6 9例；MMR蛋白常协同表达缺失，以hMLH1/hPMS2协同缺失为主。（2）dMMR与肿瘤位置有关，多位于右半结肠；错配基因功能正常（pMMR）患者则多位于直肠和左半结肠，表现为高-中分化腺癌。hMLH1表达缺失多为中-低分化腺癌，与肿瘤直径、分化程度和TNM分期密切相关；hMSH2表达缺失与肿瘤直径密切相关；hPMS2表达缺失与分化程度、TNM分期及浸润深度密切相关；hMSH6表达缺失与肿瘤形态密切相关（均P<0.05）。（3）结直肠癌组织中四种MMR蛋白表达缺失呈正相关关系，以hMLH1/hPMS2、hMSH2/hMSH6协同表达缺失最为显著（P<0.05）。（4）dMMR患者的术后累积总生存率为84.8%，显著高于pMMR患者的61.3%，差异有统计学意义（Log-rank χ²=2.985，P=0.043）。 结论结直肠癌组织中dMMR发生率高于癌旁正常组织，在右半结肠癌患者中比例更高，以hMLH1/hPMS2协同表达缺失较为多见；dMMR患者预后更好。dMMR对于判断结直肠癌临床恶性程度、选择治疗方案及预测患者预后有重要意义。     

遗传性非息肉病性结直肠癌hMLH1和hMSH2蛋白表达与其临床病理特征及预后的关系

目的探讨错配修复(MMR)基因hMLH1和hMSH2的蛋白表达与遗传性非息肉病性结直肠癌(HNPCC)临床病理特征及预后的关系。方法应用免疫组化方法(Elivision-两步法)检测48例符合修订后的《Bethesda指南》的HNPCC患者中hMLH1和hMSH2蛋白的表达情况,并定义两者同时表达阳性为MMR蛋白表达,分析其表达与HNPCC临床病理特征及预后的关系。结果 hMLH1蛋白的表达缺失率为20.83(10/48),高于hMSH2蛋白的表达缺失率(8.33%,4/48),Ρ<0.05;MMR蛋白的表达阳性率为70.83%(34/48)。MMR蛋白表达与肿瘤的浸润深度相关(Ρ<0.05)。MMR蛋白表达缺失与表达正常者的总生存率分别为85.71%(12/14)和85.29%(29/34),两者生存曲线比较差异无统计学意义(Ρ>0.05)。结论 hMLH1蛋白的表达缺失率高于hMSH2蛋白,hMLH1和hMSH2蛋白表达缺失与肿瘤的浸润深度相关,与患者的预后无关。     

结直肠腺癌中Galectin-3、Fascin-1和β-catenin蛋白表达与其临床病理特征的关系

目的探讨Galectin-3、Fascin-1和β-catenin蛋白在结直肠腺癌(colorectal carcinoma,CRC)组织中的表达及其与临床病理特征的关系。方法应用微波-EliVisionTM(MW-EliVisionTM)免疫组织化学染色技术检测60例CRC、30例结直肠腺瘤和30例正常结直肠黏膜组织中Galectin-3、Fascin-1和β-catenin蛋白的表达,分析其与CRC临床病理特征的关系。结果 Galectin-3、Fascin-1和β-catenin蛋白表达阳性率在CRC组织中分别为68.3%(41/60)、53.3%(32/60)和81.7%(49/60);在腺瘤组织中分别为46.7%(14/30)、30.0%(9/30)和43.3%(13/30);在正常黏膜组织中分别为20.0%(6/30)、3.3%(1/30)和13.3%(4/30),三者在三种组织中表达阳性率间的差异均有统计学意义(P<0.05)。三者的表达与CRC的TNM分期、浸润程度和淋巴结转移有关(P<0.05,P<0.01);Galectin-3和β-catenin蛋白的表达与CRC分化程度有关(P<0.05),而Fascin-1蛋白表达与CRC分化程度无关(P>0.05);三者的表达均与患者年龄、性别及肿瘤大小无关(P>0.05)。Galectin-3蛋白与Fascin-1和β-catenin蛋白表达呈正相关(r=0.728,P<0.01;r=0.696,P<0.01);β-catenin蛋白与Fascin-1蛋白表达呈正相关(r=0.507,P<0.01)。结论 Galectin-3、Fascin-1和β-catenin蛋白在CRC组织中的高表达与其高侵袭能力和淋巴结转移有一定相关性,可作为潜在预测结直肠癌浸润和转移的指标。     

早期直肠癌中p53和hMLH1的表达

目的探讨p53基因和hMLH1基因的突变是否是直肠癌发生的早期事件之一。方法用PV-9000二步法免疫组化检测技术对我院2003年2月至2009年7月期间的32例早期直肠癌、32例直肠腺瘤及30例正常直肠黏膜组织石蜡切片进行p53和hMLH1基因蛋白表达的检测。结果①正常直肠黏膜组织、直肠腺瘤组织及早期直肠癌组织中p53蛋白表达阳性率分别为0(0/30)、59.38%(19/32)及68.75%(22/32),其在直肠腺瘤组织和早期直肠癌组织中的p53蛋白表达阳性率差异无统计学意义(P0.05),但二者均明显高于其在正常直肠黏膜组织中的表达(P0.01);hMLH1蛋白在前述三种组织中的表达阴性率分别为0(30/30)、12.50%(4/32)和50.00%(16/32),其在早期直肠癌组织中的表达阴性率明显高于在直肠腺瘤组织和正常直肠黏膜组织中的表达(P0.01)。②在直肠腺瘤组织和早期直肠癌组织中p53阳性表达同时合并hMLH1阴性表达者分别占9.38%(3/32)及37.50%(12/32),二者间差异有统计学意义(P=0.008)。③p53阳性表达和hMLH1阴性表达均与早期直肠癌的分化程度有关(P0.05),而均与患者的性别、年龄、肿瘤最大径、浸润深度及大便潜血均无关(P0.05)。④p53阳性表达与腺瘤的增生程度有关(P=0.009),hMLH1阴性表达与腺瘤的增生程度无关(P0.05)。结论 p53基因和hMLH1基因的同时突变致癌作用明显,可能是直肠癌发生的早期事件之一。     

组织芯片检测技术在遗传性非息肉性结直肠癌家系筛选中的价值

目的研究组织芯片在遗传性非息肉性结直肠癌(HNPCC)家系筛选中的价值。方法将22例HNPCC家系中结直肠癌患者和15例散发性结直肠癌患者的肿瘤组织蜡块制作组织芯片,免疫组化方法检测hMLH1、hMSH2蛋白表达。结果常规免疫组化检测HNPCC组hMLH1或hMSH2阴性68.2%(15/22);散发性结直肠癌组hMLH1阳性14例、阴性1例(6.7%),hMSH2全部阳性。组织芯片检测HNPCC组hMLH1或hMSH2阴性77.2%(17/22);散发性结直肠癌组hMLH1阳性13例、阴性2例(13.3%);hMSH2全部阳性。应用常规免疫组化和组织芯片方法检测hMSH2其结果一致。对hMLH1常规免疫组化和组织芯片技术检测进行比较,P>0.05;差异均无统计学意义。结论组织芯片检测技术是一种高通量的筛选方法,适合于回顾性HNPCC家系筛选。     

β-catenin在结直肠癌组织的表达及临床意义

目的　探讨β-catenin(β-连环素 )在结直肠癌发生、发展中的作用。 方法　应用免疫组化法检测 2 5例正常结直肠粘膜和 65例结直肠癌组织中 β-catenin的表达。 结果　正常结直肠粘膜β-catenin蛋白表达几乎全部定位于细胞膜上。结直肠癌组织 β -catenin表达的特征发生改变 ,细胞膜表达有不同程度的缺失 ,而细胞浆和细胞核异位表达明显增加。结直肠癌 β -catenin异位表达率为 63 .1 % ,细胞膜表达缺失率为 70 .8%。结直肠癌β -catenin的异位表达率与肿瘤分化程度、临床分期和淋巴结转移有关 ,低分化腺癌明显高于高分化腺癌 (P <0 .0 1 ,Dukes’A +B期明显低于Eukes’C +D期 (P <0 .0 5 ) ,有淋巴结转移组明显高于无淋巴结转移组 (P <0 .0 5 )。结论　β-catenin蛋白的异常表达在结直肠癌发生、发展过程中可能具有重要作用 ,是判断结直肠癌侵袭、转移和预后的良好指标     

散发性结直肠癌APC、K-ras、p53、MMR基因突变检测

目的探讨结直肠癌中APC、K-ras、p53、MMR基因突变模式。方法应用酚/氯仿法提取48例结直肠癌组织及其相应正常黏膜组织的DNA,用聚合酶链反应（PCR）、单链构象多态性分析（SSCP）和DNA测序等方法检测APC基因第l5外显子突变密集区（mutation cluster region,MCR）区段、K-ras、p53和MMR基因的突变。结果hMLH1未发生突变,APC、K-ras、p53基因和hMSH2的突变率分别为37.5%（18/48）、43.8%（21/48）、35.4%（17/48）和4.2%（2/48）。APC、K-ras、p53或hMSH2基因突变率高达91.7%（44/48）。APC、K-ras,p53基因均发生突变的发生率为4.2%（2/48）。结论结直肠癌的发生、发展并不完全遵循由正常结直肠黏膜上皮细胞向腺瘤和侵袭性癌转化的过程,可能存在其他结直肠癌发病机制。     

β-catenin在结直肠癌中的表达及生物学意义

目的探讨β-catenin在结直肠癌（colorectal cancer,CRC）组织的表达及其生物学意义.方法选取2001年2月～2001年9月在北京大学临床肿瘤学院手术治疗的36例CRC患者,以免疫组织化学S-P法检测β-catenin在癌组织及相应的对照正常组织中的表达,并分析β-catenin的表达与CRC临床病理因素之间的相关性,用逆转录-聚合酶链式反应（RT-PCR）法比较β-cateninmRNA在癌组织及相应正常组织之间的差异.结果83.3%的肿瘤组织β-catenin表达阳性,5.6%的自身对照正常组织表达阳性（P＜0.01）;β-catenin的表达与肿瘤的肿瘤分化程度及TNM分期之间具有显著相关性（分别为r=-0.880,P=0.009;r=-0.796,P=0.026）.结论β-catenin蛋白表达与TNM分期及肿瘤分化程度之间具有显著相关性.β-catenin蛋白在CRC中的高表达可能并非由于其生成增加,而可能是降解减少所致.     

白细胞介素-6及微卫星不稳定在溃疡性结肠炎相关性结直肠癌中的表达及意义

目的分析溃疡性结肠炎(UC)相关性结直肠癌(UC-CRC)中白细胞介素-6(IL-6)及微卫星不稳定(MSI)情况并探讨其在UC患者癌变过程中所起的作用。方法回顾性分析了鄂东医疗集团2013年1月至2019年1月期间收治的符合纳入标准的17例UC-CRC患者及55例散发性结直肠癌(SCRC)患者术后病理标本资料并检测其癌组织标本中错配修复(MMR)蛋白hMLH1、hPMS2、hMSH2、hMSH6的表达情况;同时检测30例对照(非UC、UC-CRC、SCRC患者)、43例UC、17例UC-CRC及55例SCRC患者的血清中IL-6水平,并对SCRC及UC-CRC患者的癌组织中IL-6与MMR蛋白表达做相关性分析。结果 17例UC-CRC的癌组织标本中出现错配修复基因缺失(dMMR)7例(41.2%),其中hMLH1和hPMS2蛋白表达缺失、hMSH2和hMSH6蛋白表达缺失存在明显相关性(P0.001);UC-CRC组患者血清中IL-6水平明显高于UC组(t=4.97,P0.001)及SCRC组(t=5.26,P=0.006)。由于病例数较少,未对UC-CRC癌组织中dMMR与IL-6蛋白表达进行统计学分析,而在SCRC癌组织中未发现dMMR与IL-6蛋白表达有关(rs=0.04,P=0.77)。结论与SCRC类似,MSI同样参与了UC-CRC的发生及发展过程,UC-CRC的MMR蛋白缺失更常见于hMLH1与hPMS2、hMSH2与hMSH6的共同表达缺失,未发现IL-6参与了结直肠癌的MSI相关癌变机制,而从有限的病例初步推测IL-6可能参与了UC-CRC患者MSI的发生。     

结直肠癌组织中CD44v6和β-catenin蛋白的表达及其临床意义

目的探讨结直肠癌组织中CD44v6和β-catenin蛋白表达及其意义。方法采用微波-EliVisionTM免疫组化染色方法检测60例结直肠癌组织中CD44v6和β-catenin的表达情况,并分析其与临床病理参数尤其与结直肠癌浸润转移的关系。结果阳性表达物质CD44v6主要在细胞膜和细胞质,β-catenin主要在细胞质。60例结直肠癌CD44v6和β-catenin蛋白阳性表达率分别为71.7%和81.7%。两者均与肿瘤的临床TNM分期、浸润程度、淋巴结转移及术后复发有关;上述参数各分组间差异有统计学意义(P0.05)。结论联合检测CD44v6-和β-catenin蛋白表达对了解结直肠癌的生物学行为和判断患者预后有一定的实用价值。     

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.