结直肠癌表观沉默蛋白Bmi1与Notch信号通路调控的关系

目的 探讨人结直肠癌中表观沉默蛋白Bmi1和Notch1的蛋白表达与结直肠癌病理特征的关系,观察Notch通路对结直肠癌细胞增殖凋亡及Bmi1表达的影响。方法 应用免疫组织化学技术(SP法)检测85例结直肠癌组织及其邻近正常肠黏膜中Notch1及Bmi1的蛋白表达;将Notch1通路中γ-分泌酶抑制剂DAPT,作用于结肠癌SW480细胞株,运用噻唑蓝(MTT)比色法检测细胞增殖状态;流式细胞仪观察其对细胞凋亡的影响,Western blot检测ICN及Bmi1蛋白的表达。结果 结直肠癌组织中Notch1和Bmi1蛋白表达的阳性率明显高于正常肠黏膜(P＜0.05),分别为61.2％ (52/85)对15.3％ (13/85)和56.5％ (48/85)对17.6％ (15/85);Bmi1表达率与Notch1表达率呈正相关(r =0.625,P＜0.01),并与肿瘤分化程度、分期及淋巴结转移有关(P＜0.05);阻断Notch1通路(DAPT)可抑制SW480细胞的增殖,诱导其凋亡,作用12、24、36 h后其增殖抑制率分别为13.1％、17.5及22.6％,而凋亡率为32.7％、45.6％及67.2％;同时Notch1胞内活性段ICN随作用时间延长而下降,而Bmi1表达水平也逐渐降低。结论 结直肠癌中Bmi1与Notch1表达密切相关,阻断Notch通路可抑制Bmi1表达,同时可抑制结肠癌细胞的增殖,促进其凋亡。     

结直肠癌组织中Ezrin和E-cadherin蛋白的表达特点及意义

目的:探讨结直肠癌组织中Ezrin和钙黏素E(E-cadherin)蛋白的表达及其与临床病理因素的关系.方法:应用免疫组织化学光/微波(LW/MW)-EliVisionTM法,检测100例结直肠癌组织中Ezrin和E-cadherin的表达情况,并分析其与结直肠癌浸润转移等的关系.结果:Ezrin和蛋白在结直肠癌组织中的阳性表达明显高于正常黏膜,而E-cadherin蛋白在正常黏膜中的阳性表达高于结直肠癌组织(P＜0.05).Ezrin的高表达与结直肠癌浸润深度、淋巴结是否转移有关(P＜0.05);而与TNM分期、分化程度无关(P＞0.05).E-cadherin的表达与结直肠癌分化程度、TNM分期、浸润深度及淋巴结是否转移有关(P＜0.05).二者在结直肠癌组织中的表达呈显著负相关(r=-0.673,P＜0.01).结论:Ezrin和E-cadherin蛋白在结直肠癌的发生、发展中起着重要作用,联合检测可为结直肠癌浸润转移和预后的判断提供理论依据.     

p-21活化激酶-1、Snail在结直肠癌侵袭与转移中的作用

目的 观察p-21活化激酶-1(PAK1)、Snail在结直肠癌侵袭与转移中的作用.方法 采用荧光原位杂交和免疫组织化学方法分别检测60例结直肠癌患者的正常结直肠黏膜与结直肠癌组织中PAK1和Snail的表达,分析两者在结直肠癌中表达的意义以及相关性.结果 PAK1 mRNA、Snail mRNA在结直肠癌中的表达率分别为70.00％ (42/60)和73.33％ (44/60),均显著高于正常对照组(P＜0.05);PAK1 mRNA在Dukes不同分期中表达差异有统计学意义(x2=6.0708,P ＜0.05),在有淋巴结转移的结直肠癌中表达显著高于无淋巴结转移的结直肠癌(x2=5.8764,P＜0.05);Snail mRNA在Dukes不同分期中表达差异有统计学意义(x2=6.7930,P＜0.05),在有淋巴结转移的结直肠癌中表达显著高于无淋巴结转移的结直肠癌(x2=6.2130,P＜0.05);PAK1和Snail蛋白在结直肠癌组织中的表达呈正相关(r =0.319 24,P＜0.05).结论 PAK1和Snail的高表达与结直肠癌的侵袭和转移有关;PAK1和Snail在结直肠癌侵袭和转移过程中可能存在相互促进作用.     

GPAA1在结直肠癌中表达增强及其意义

目的 通过检测GPAA1在结直肠癌组织中的表达以探讨其与结直肠癌增殖、侵袭、转移的关系.方法 取新鲜结直肠癌原发灶组织(52例)、正常结直肠黏膜(52例)和肝转移灶组织标本(11例)分别行免疫组织化学检测;实时定量PCR检测每个组织样本中GPAA1基因表达水平;高表达GPAA1 mRNA结直肠癌组织和低表达GPAA1 mRNA结直肠癌组织行原代细胞培养,将培养获得的原代细胞进行Boyden小室体外增殖、侵袭实验.结果 52例结直肠癌患者标本经免疫组织化学检测,GPAA1在结直肠正常肠黏膜、癌原发灶、肝转移灶中的表达阳性率分别为21.15% ( 11/52)、55.76% (29 /52)、和72.73% ( 8/11).GPAA1在结直肠癌原发灶、肝转移灶中表达阳性率均高于正常肠黏膜组织(P＜0.01).通过实时定量PCR检测发现GPAA1 mRNA表达水平在结直肠癌原发灶、肝转移灶中均高于结直肠正常肠黏膜(P＜0.01);在肝转移灶中的GPAA1 mRNA水平高于癌原发灶(P＜0.05);高表达GPAA1 mRNA的原代细胞穿透Matrigel微孔滤膜细胞数明显高于低表达GPAA1 mRNA组.结直肠癌组织中GPAA1 mRNA的表达水平与组织分化程度相关,而与年龄、性别及Dukes分期无明显相关,(P<0.05).结论 GPAA1表达增强与结直肠癌的发生、侵袭、转移有密切关系.     

PUMA和BIM表达与结直肠癌浸润转移及预后的关系

目的 研究BH3-only蛋白家族中p53上调凋亡调控因子(PUMA)和与bcl-2相互作用的细胞死亡调解因子(BIM)在结直肠癌组织中的表达及其与结直肠癌侵袭、转移和预后关系.方法 采用免疫组化染色方法(EnVision),检测PUMA和BIM蛋白在30例正常大肠黏膜、30例大肠腺瘤及142例结直肠癌组织中的表达.分析PUMA、BIM蛋白表达与患者临床病理特征、预后及化疗耐药相关蛋白[P-糖蛋白(P-gp)、谷胱甘肽S转移酶-π(GST-π)]的相关性.结果 PUMA蛋白在结直肠癌组织中的阳性表达率为82.4％,低于其在大肠腺瘤和正常大肠黏膜组织中的阳性表达率(均为96.7％)(x2=3.93、3.93,P＜0.05).BIM蛋白在结直肠癌组织中的阳性表达率为62.7％,明显低于其在大肠腺瘤组织中和正常大肠黏膜的阳性表达率(90.0％和96.7％)(x2 =8.42、13.29,P＜0.01).PUMA蛋白与BIM蛋白在结直肠癌组织中的表达呈正相关(r=0.747,P=0.000).PUMA蛋白的表达与肿瘤的分化程度(x2 =11.87)、浸润深度(x2=11.59)、淋巴结转移(x2=12.82)、TNM分期(x2=33.47)以及P-gp表达(x2=18.30)有关(P＜0.05),而与患者的年龄、性别、肿瘤大小、病理组织学类型以及GST-π表达无关(P＞0.05).BIM蛋白的表达与分化程度(x2=16.19)、淋巴结转移(x2=14.95)、TNM分期(x2=52.66)以及P-gp表达(x2 =10.60)有关(P＜0.05),而与患者的年龄、性别、肿瘤大小、浸润深度、病理组织学类型以及GST-π表达无关(P＞0.05).PUMA、BIM阳性表达者的术后1、3、5年生存率明显高于阴性表达者(x2=6.10、27.60,P＜0.05).淋巴结转移(RR=0.238)、TNM分期(RR=7.895)、PUMA(RR=1.691)和BIM蛋白的表达(RR =0.440)可作为结直肠癌独立的预后指标(P＜0.05).结论 PUMA、BIM在结直肠癌中的表达与结直肠癌的侵袭、转移和预后明显相关.PUMA和BIM蛋白表达降低的结直肠癌患者病期晚、预后差.     

Twist与E-cadherin在结直肠癌中的表达及其意义

目的探讨Twist和E-cadherin蛋白在结直肠癌组织中的表达及其可能的机理、相互作用以及与结直肠癌预后的关系。方法应用免疫组化SP法检测63例结直肠癌组织以及21例正常结肠黏膜组织中Twist和E-cadherin蛋白的表达,并分析其与结直肠癌临床病理特征和患者预后的关系。结果 Twist蛋白在结直肠癌组织中的表达阳性率为66.7%(42/63),而在正常结直肠黏膜组织中的表达阳性率为14.2%(3/21),前者高于后者(P0.01);E-c adherin蛋白在结直肠癌组织中的表达阳性率为20.6%(13/63),而在正常结直肠黏膜组织中的表达阳性率为81.0%(17/21),前者低于后者(P0.01)。两者的表达与肿瘤的分化程度及T、N和M分期均相关(P0.05)。相关性分析显示,Twist和E-cadherin蛋白的表达呈负相关关系(r=-0.215,P=0.039)。结论 Twist和E-cadherin蛋白的表达可能与结直肠癌的发生发展和侵袭转移相关,并可作为评价结直肠癌生物学行为和预后的重要指标。Twist和E-cadherin蛋白表达呈负相关关系提示,在上皮-间质转化过程中可能是通过抑制E-cadherin蛋白的表达来实现的。     

TMSG-1蛋白在结直肠癌中的表达及意义

目的探讨TMSG-1蛋白在结直肠癌组织中的表达及其与肿瘤病理特征的关系。方法采用免疫组织化学SP法检测98例结直肠癌组织中TMSG-1蛋白的表达,同时选取76例结直肠正常组织作对照。结果 TMSG-1蛋白在结直肠癌和正常结直肠组织中主要表达在细胞质,少量胞核可见着染。76例正常结直肠黏膜组织中TMST-1蛋白均表达阳性,其中11例呈弱阳性,65例强阳性表达。在98例结直肠癌中,32例TMST-1蛋白表达阴性,23例弱阳性表达,43例呈强阳性。两者表达差异有统计学意义(P<0.05)。在结直肠癌患者中TMSG-1蛋白表达与年龄、性别、肿瘤部位、肿瘤大小无明显相关(P>0.05),与肿瘤的浸润深度,分化程度、淋巴结转移及远处转移有明显负相关(P<0.05)。结论 TMSG-1蛋白低表达与结直肠癌恶性程度及肿瘤转移有密切相关,这为结直肠癌治疗提供新的治疗靶点且有可能成为判断结直肠癌细胞浸润及转移的重要预后指标。     

Skp2、p27kip1蛋白在结直肠癌中的表达及其意义

目的 探讨Skp2蛋白在结直肠癌发生、发展中的作用及其与p27kip1蛋白表达的关系.方法 应用免疫组织化学法结合计算机图像分析检测结直肠癌(80例)、腺瘤(20例)、正常组织(20例)中Skp2蛋白和p27kip1蛋白的表达.结果 由正常结直肠黏膜、腺瘤到癌,Skp2阳性表达率为0%、55%、93.8%,呈上升趋势(P＜0.01);p27kip1阳性表达率为100%、95%、87.5%,呈下降趋势(P＜0.05).结直肠癌中Skp2表达与p27kip1表达呈负相关(r=-0.311,P＜0.01).Skp2蛋白在癌组织中的表达与结直肠癌的分化程度、淋巴转移有关(P＜0.05).结论 结直肠癌skp2蛋白过表达与p27kip1蛋白降解有关,Skp2蛋白过表达可能是结直肠癌发生、发展的原因之一.     

整合素α5β1和血管内皮生长因子在结直肠癌中的表达及临床意义

目的 探讨结直肠癌中整合素α5β1和血管内皮生长因子(VEGF)的表达与各临床病理因素的关系,以及两者在结直肠癌中表达的相关性.方法 对116例结直肠癌患者采用原位杂交染色方法检测正常结直肠黏膜及结直肠癌组织中α5β1和VEGF的表达.结果 结直肠癌组织中α5β1和VEGF的表达阳性率分别为56.00％和61.29％,正常结直肠黏膜两者表达的阳性率分别为4％、6％,与正常结直肠黏膜中的表达阳性率比较差异有统计学意义(P＜0.05);α5β1及VEGF两者表达与性别、年龄、肿瘤大小无明显相关(P＞0.05),在组织学分化差、淋巴结转移、Dukes'分期高者α5β1和VEGF表达率增高,而且浸润深度较深者VEGF表达率增高,与对照组比较差异有统计学意义(P＜0.05);在结直肠癌组织中α5β1表达和VEGF表达呈正相关(rs=0.63,P＜0.01).结论 α5β1和VEGF在结直肠癌组织中表达增高,提示其参与结直肠癌的发生、发展.     

结直肠癌Dll-1/Notch信号传导通路的研究

目的 研究Dll-1/Notchl信号传导通路与结直肠癌病理学特征的关系,明确此通路对结直肠癌细胞增殖及凋亡的影响.方法 应用固定化蛋白质印迹法检测63例结直肠癌组织及其邻近正常肠黏膜中Dll-1及Notch1蛋白表达;用Notch1通路中γ-分泌酶抑制剂DAPT作用于结肠癌细胞系SW480,MTT法检测细胞增殖状态,流式细胞仪观察其对细胞凋亡的影响,固定化蛋白质印迹法检测Notch1胞内活性段及其靶基因产物Hes-1和Bcl-2蛋白的表达.分别采用独立样本t检验、配对样本t检验及单因素方差分析.结果 结直肠癌组织中Notch1和Dll-1蛋白表达水平分别高于正常肠黏膜的1.75及2.21倍(t=2.554,P=0.012及t=3.565,P=0.005);二者表达与肿瘤分化程度(t =2.463,P=0.017及t=2.390,P=0.019)、分期(t=2.675,P=0.007及f=2.310,P=0.021)及淋巴结转移(t =2.229,P=0.021及t=2.210,P=0.023)有关.用γ-分泌酶抑制剂DAPT阻断Notch1通路可抑制SW480细胞的增殖,诱导其凋亡;同时NICD和Bcl-2的表达水平随作用时间延长而降低.结论 Dll-1及Notch1的高表达与结直肠癌病理学特征密切相关,阻断Notch1通路可抑制Bcl-2表达,同时可抑制结肠癌细胞的增殖,并诱导其凋亡.     

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.     

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.     

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.     

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.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.