外科性黄疸对T细胞和NK细胞活性的影响

目的　探讨黄疸对外周血T细胞和自然杀伤 (NK)细胞的活性的影响。方法　通过应用CD系列单克隆抗体对 2 0例术前黄疸患者外周血T细胞和NK细胞的活性进行检测 ,观察免疫功能改变。结果　良性黄疸组CD3 (65 .0 9± 6.5 2 )、CD4(4 0 .5 8± 5 .82 )及NK(16.62± 6.91)细胞活性与对照组相比下降明显 (P <0 .0 5 ) ;CD8(3 5 .40± 6.0 7)细胞活性上升 (P <0 .0 5 )。恶性黄疸组CD3 (62 .44± 7.2 8)、CD4(3 0 .0 1± 6.89)及NK(16.2 3± 7.0 2 )细胞活性同样下降明显 (P <0 .0 5 ) ;且良恶性黄疸组CD4(3 0 .0 1± 6.89)细胞活性比较有显著性意义 (P <0 .0 5 )。而黄疸持续时间仅对CD4(分别为 2 3 .43± 3 .70 ,3 0 .0 1± 6.89)有影响。结论　良恶性黄疸能降低T淋巴细胞和NK细胞的活性 ,对机体免疫功能产生一定的影响。     

肾移植稳定病人淋巴细胞表面淋巴细胞功能相关抗原-1、L-选择素的表达

目的　研究尸肾移植后稳定病人淋巴细胞表面淋巴细胞功能相关抗原 1(CD11a)、L 选择素(CD62L)表达的动态变化。方法　利用单克隆抗体 流式细胞仪荧光免疫技术 ,测定 10例肾移植后稳定病人不同时间外周血淋巴细胞CD11a、CD62L抗原表达 ,并以 10例移植前病人对照。结果　肾移植前组CD11a、CD62L抗原表达率分别为(77.3±16.3 ) %和(3 8.5±16.8) %。移植后 3、6、9、15d时CD11a抗原表达率分别为 (2 7.9±9.2 ) %、(2 8.5±7.7) %、(2 2 .9± 8.9) %和(5 6.2±17.1) % ,均低于术前组 (P <0 .0 5 ) ;CD62L分别为(3 1.5±14 .5 ) %、(3 3 .5± 12 .8) %、(42 .0±15 .3 ) %和(5 3 .8±15 .7) % ,与术前组比较差异无显著性 (P>0 .0 5 )。结论　淋巴细胞CD11a、CD62L表达水平和肾移植病人免疫状态密切相关。免疫抑制剂能明显抑制淋巴细胞CD11a表达 ,这可能是其预防早期排斥反应的重要机制之一。     

肝癌疫苗激活的肿瘤浸润性淋巴细胞治疗原发性肝癌的研究

目的探讨经冷冻的肝癌疫苗激活的肿瘤浸润性淋巴细胞 (s TIL)治疗原发性肝癌的作用。方法 2 6例原发性肝癌患者使用s TIL治疗 ,并检测治疗前后其CD3、CD4、CD8、CD4/CD8比值、自然杀伤细胞 (NKC)活性和血清白细胞介素 2受体 (sIL 2R)水平的变化 ,计算 1、2、3年生存率 ,并与对照组相比较。结果应用s TIL患者 ,其第 19天、30天的CD3、CD4、CD4/CD8比值和NKC活性分别为 5 5± 3、76± 5 ;2 8 3± 1 6、44 6± 2 3;1 19± 0 2 2、2 2 1± 0 36 ;9 8± 1 2、17 4± 2 2。与对照组比较明显升高 (P <0 0 1)。而CD8和血清sIL 2R明显下降 ,分别为 2 4 9± 1 4、2 1 1± 1 2 ;5 6 9± 90、15 0± 31(P <0 0 1)。其 3年生存率为 88% ,与对照组 (5 7% )比较明显升高 (P <0 0 5 )。结论应用s TIL治疗原发性肝癌 ,能明显地提高原发性肝癌患者的免疫功能和远期疗效     

1,25-(OH)_2D_3对小鼠皮肤移植后脾T细胞亚群、MLR及NK细胞活性的影响

目的　探讨 1,2 5 二羟维生素D3 [1,2 5 (OH) 2 D3 ]抑制机体免疫功能的机理 ,为用于临床抗排斥治疗提供实验依据。方法　建立不同系小鼠间皮肤移植的动物模型。术日将实验小鼠随机分为四组 ,均用小鼠灌胃器给药。对照组 :每日 2 0ml/kg生理盐水 ;维生素D3 (VD3 )组 :单独应用 1,2 5 (OH) 2 D3 2 .5 μg·kg-1·d-1;环孢素A(CsA)组 :单独应用CsA 2 5mg·kg-1·d-1;VD3 +CsA组 :联合应用VD3 +CsA ,按VD3 组和CsA组用药剂量给药。术后 10d ,测定小鼠脾的T细胞亚群、单向混合淋巴细胞反应 (MLR)、自然杀伤细胞 (NK)活性。结果　VD3 组的移植皮片存活时间 (13.13±1.13)d ,明显长于对照组的 (9.75± 0 .89)d ;CD3+ 、CD4 + T细胞百分率 4 0 .19%± 4 .2 5 %、2 4 .6 5 %±3.4 7%均明显低于对照组 4 8.70 %± 7.19%、 33.5 5 %± 4 .34% ,P <0 .0 1;对BALB/C鼠的MLR(0 .95± 0 .12 )明显低于对照组 (1.19± 0 .2 2 ) ,P <0 .0 5 ;NK细胞的活性与对照组小鼠比较 ,差异无显著性。结论　 1,2 5 (OH) 2 D3 能延长小鼠皮肤移植的存活时间 ,其抑制机体免疫功能的作用是通过减少CD3+ 、CD4 + T细胞的数量及抑制T细胞功能而发挥的 ,对NK细胞活性无明显影响。     

CD4+CD25+调节性T细胞、Foxp3 mRNA及可溶性白细胞介素2受体检测在肾移植中的意义

目的 观察肾移植患者外周血中CD4+CD25+调节性T细胞水平及其表面特异性标志物Foxp3和可溶性白细胞介素2受体（sIL-2R）的变化，探讨其在诊断移植肾急性排斥反应中的作用和价值。 方法 选取42例维持性血液透析接受同种异体肾移植治疗的患者及30例健康体检对照者。在患者移植前、移植后1、2、4、8周或发生排斥反应时，以流式细胞仪检测外周血中CD4+CD25+调节性T细胞水平；荧光定量PCR检测Foxp3 mRNA表达；双抗体夹心酶联免疫吸附法（ELISB）检测血浆中sIL-2R水平。 结果 (1)移植后第1、2、4、8周急性排斥反应组CD4+CD25+调节性T细胞、Foxp3 mRNA水平明显低于同期未发生排斥的肾功能稳定组，而sIL-2R水平却显著高于肾功能稳定组。(2)血液透析患者外周血CD4+CD25+调节性T细胞[(9.22±3.53)%]、Foxp3 mRNA[（0.82±0.36）×10-3]及sIL-2R[（856.30±108.24） U/ml]水平与健康对照组[分别为(6.09±1.99)%、(0.50±0.28)×10-3、(247.35±11.24) U/ml]比较，差异均有统计学意义(P < 0.01)。(3)肾移植后随着肾功能的恢复，外周血CD4+CD25+调节性T细胞[(16.53±4.14)%]、Foxp3 mRNA[(4.97±1.94)×10-3]显著升高(P < 0.01)，而sIL-2R[（463.72±31.23）U/ml]水平明显降低(P < 0.01)。(4)当发生急性排斥反应时，CD4+CD25+调节性T细胞[(12.18±2.86)%]、Foxp3 mRNA[(3.15±1.22)×10-3]显著降低(P < 0.01)，而sIL-2R[(748.36±115.41) U/ml]水平明显升高(P < 0.01)，并且这些变化早于Scr的变化。(5)患者移植前后外周血CD4+CD25+调节性T细胞百分率与Foxp3 mRNA水平均呈正相关（分别为r ＝ 0.904、0.932，P < 0.01），但与sIL-2R水平无相关。 结论 外周血CD4+CD25+调节性T细胞、Foxp3 mRNA及sIL-2R水平的测定均可以作为肾移植患者移植后发生急性排斥反应的早期预测指标，并可判断预后。     

雌激素对去势大鼠下丘脑5-羟色胺2C及5-羟色胺6受体亚型mRNAs的影响

目的　观察雌激素对大鼠下丘脑 5 羟色胺 2C(5 HT2C)及 5 羟色胺 6(5 HT6)受体亚型mRNAs的影响。　方法　实验动物分为对照组 (C组 )、去势后又分为注射雌二醇组 (E+组 )和不注射雌二醇组 (E- 组 ) ,后两组分别在处理后 3、6、9、1 2d时提取下丘脑标本。实验采用反转录 聚合酶链反应 (RT PCR)。　结果　 5 HT2C受体亚型在E+组下丘脑的表达分别为C组 (1 0 0 % )的 (1 3 0 .6± 3 .1 ) %、(1 3 1 .0± 3 .1 ) %、(1 1 6.7±3 .2 ) %、(1 1 4 .7± 2 .6) % ,前两者与C组比较有显著差异 (P <0 .0 5) ;5 HT2C受体亚型在E- 组的表达分别为C组的 (1 2 9.8± 3 .2 ) %、(1 74.0± 6.1 ) %、(1 85.3± 5.9) %、(1 3 7.9±4.0 ) % ,均与C组存在显著差异 (分别为P <0 .0 5、P <0 .0 1、P <0 .0 1、P <0 .0 5) ;E+组与E- 组在去势后 6、9和 1 2d时差异显著 (P <0 .0 1 )。 5 HT6 受体亚型在E+组下丘脑的表达分别为C组的 (1 0 1 .2± 3 .6) %、(1 1 2 .6± 4.2 ) %、(1 1 5.9± 3 .7) %、(1 1 7.4± 4.1 ) % ,与C组比较无显著差异 (P >0 .0 5) ;5 HT6 受体亚型在E- 组的表达分别为C组的 (1 0 5.8± 4.1 ) %、(1 1 5.2± 4.4) %、(1 1 8.7± 5.4) %、(1 1 4 .7± 3 .2 ) % ,与C组比较无显著差异(P >0 .0 5) ;5 HT6 受?     

HER2×CD3双抗体治疗过度表达HER2基因裸鼠乳腺癌及其机制

目的　探讨基因工程HER2×CD3双特异性抗体 (BsAb)对过度表达HER2 /neu基因人乳腺癌的治疗效果及其作用机制。方法　建立人乳腺癌异位种植转移模型。 48只裸鼠皮下接种人乳腺癌细胞株BT 474后 ,随机分成 4组 (n =12 ) ,1周后开始 ,分别腹腔内注射磷酸盐缓冲液(PBS ,1ml ,对照组 )、效应细胞 +抗CD3单克隆抗体 (Anti CD3McAb) (0 .85mg/kg ,CD3McAb组 )、效应细胞 +抗HER2单克隆抗体Herceptin(0 .85mg/kg ,Herceptin组 )、效应细胞 +HER2×CD3双特异性抗体 (0 .3 5mg/kg ,BsAb组 ) ,每周 2次 ,共用 3周。第 8周末处死动物 ,测量种植处肿瘤体积、抑瘤率、观察癌细胞转移情况 ,应用Northernblot方法检测HER2 /neumRNA的表达。结果　各组均成瘤 ;BsAb组、Herceptin组、抗CD3组、对照组肿瘤体积和抑瘤率分别为(0 .10± 0 .0 2 )、(0 .2 1± 0 .0 7)、(0 .5 4± 0 .0 5 )、(0 .84± 0 .11)cm3 和 88.1%、75 .0 %、3 7.9%、0 ;腋窝淋巴结转移率分别为 0、16.7%、45 .5 %、10 0 % ;肝转移率分别为 0、16.7%、3 6.4%、75 .0 % ;Northernblot印迹分析示HER2×CD3双特异性抗体明显抑制HER2 /neumRNA表达。Herceptin组和BsAb组乳腺癌生长和转移受到明显抑制 (P <0 .0 5 ) ,尤以BsAb组最明显 (P <0 .0 5 )。结论　基     

高强度聚焦超声治疗VX2骨肿瘤的免疫变化

目的　探讨高强度聚焦超声 (HIFU )治疗骨肿瘤前后的免疫学变化。方法　将新西兰大白兔分为HIFU治疗组 (2 3只 )及正常对照组 (10只 ) ,对HIFU治疗组兔建立VX2移植性骨肿瘤模型 ,2周后接受HIFU治疗 ,于不同时间处死 ,免疫组织化学染色观察HSP70表达的变化 ,并在治疗前后抽血检测CD2 5变化。结果　治疗前肿瘤组织HSP70阳性表达细胞数量少 ,治疗后即刻直到 2 1d一直呈强阳性表达且阳性表达的细胞数明显增加。治疗前CD2 5为 7.83± 2 .0 3与正常兔 13 .18± 3 .47比较差异有显著性 (P <0 .0 5 ) ;治疗后增高为 15 .5 5± 2 .69,与治疗前比较差异有非常显著性 (P <0 .0 1)。结论　HIFU治疗后骨恶性肿瘤组织HSP70、CD2 5的数量增多 ,可递呈特异性抗原给T细胞 ,刺激T细胞增殖 ,提高机体抗肿瘤的免疫作用     

肝癌合并肝硬化患者肝癌切除后机体免疫状态的变化

目的探讨肝癌合并肝硬化患者癌灶切除前后机体免疫状态的变化。方法以肝硬化患者为对照组 ,采用流式细胞技术 (FCM)及ELISA方法分析 18例中晚期肝癌合并肝硬化患者癌灶切除前后外周血T细胞亚群CD4、CD8、CD4 /CD8及Th1/Th2细胞因子IFN γ、IL2、IL10蛋白水平的变化。结果　肝癌切除术后CD4 (33± 3) %、CD4 /CD8(1 1± 0 1)、IL2 (71± 11)pg/ml、IFN γ(90± 15 )pg/ml回升 ,高于术前水平〔CD4 (2 9± 4 ) %、CD4 /CD8(0 9± 0 3)、IL2 (5 7± 15 )pg/ml、IFN γ(78± 13)pg/ml〕 ,但仍低于肝硬化组〔CD4 (37± 4 ) %、CD4 /CD8(1 3± 0 2 )、IL2 (82± 15 )pg/ml、IFN γ(10 4± 2 2 )pg/ml〕(P <0 0 1或P <0 0 5 ) ;CD8(32± 3) %、IL10 (70± 9)pg/ml下降 ,低于术前〔CD8(35± 6 ) %、IL10(81± 15 )pg/ml〕水平但高于肝硬化组〔CD8(2 9± 2 ) %、IL10 (6 1± 10 )pg/ml〕(P <0 0 5 )。结论　癌灶切除后 ,机体免疫功能有明显改善。但仍未恢复到肝硬化患者的水平。     

外周血淋巴细胞穿孔素和颗粒酶B在肾移植急性排斥诊断中的价值

目的　探讨外周血淋巴细胞 (PBLs)中穿孔素 (P)和颗粒酶B (GB)表达水平在同种异体肾移植急性排斥诊断中的价值。　方法　定量RT PCR方法测定 10例肾移植患者移植前后PBLs中P和GB的表达情况 ,并对 3例患者急性排斥反应前后的P和GB表达情况进行对比分析。　结果　 10例患者肾移植前后P的相对表达量分别为 2 3 5± 42和 2 16± 3 5 ,GB分别为 62± 2 3和 5 7± 2 6,差异均无显著性意义 (P >0 .0 5 )。 3例发生急性排斥反应后P、GB相对表达量分别为 193 2± 3 2 6和 489± 5 7,均显著高于发生排斥反应前 (P <0 .0 0 1)。　结论　定量RT PCR测定外周血淋巴细胞中穿孔素和颗粒酶B表达可以较敏感预测肾移植急性排斥反应的发生 ,具有临床诊断参考价值     

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 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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.