移植物转染反义细胞外信号调节激酶-2基因减轻慢性移植物血管病

目的 研究转染反义ERK2基因对慢性移植物血管病的抑制作用及其机制.方法 构建含有反义ERK2基因和带有LacZ基因的腺病毒载体.以BN大鼠为供者,Lewis大鼠为受者,制作大鼠腹主动脉移植模型.ERK2组接受转染反义ERK2基因的腹主动脉移植,LacZ组接受转染LacZ基因的腹主动脉移植,对照组接受不进行处理的腹主动脉移植.移植后60 d,取各组移植血管和血清样本,以2,3-二羟基丙醛-3-磷酸脱氢酶(GAPDH)为内参照,计算ERK2条带灰度与GAPDH条带灰度的比值(ERK2/GAPDH,即为ERK2的相对表达强度);测量移植血管内膜厚度(I)和中膜厚度(M),计算I/(I+M)之百分比;检测移植血管平滑肌细胞(VSMC)的数目和分布;检测血清血小板源性生长因子-BB(PDGF-BB)的浓度.结果 对照组、LacZ组和ERK2组ERK2/GAPDH的比值分别为1.21±0.15、1.02±0.06和0.47±0.09,后者显著低于前二者(P<0.05).对照组和LacZ组移植血管呈典型的移植物血管病表现,两组I/(I+M)比值分别为84.1%和79.9%;ERK2组移植血管呈移植动脉内膜炎表现,该组I/(I+M)比值为13.7%,显著低于前两组(P<0.05).对照组和LacZ组内膜增厚处散在分布大量VSMC,计数分别为(71.3±9.2)个和(76.4±11.3)个;ERK2组内膜处VSMC计数为(34.8±5.3)个,明显少于前两组(P<0.05).对照组和LacZ组受者血清PDGF-BB浓度分别为(1075±70)pg/ml和(1200±25)pg/ml,ERK2组为(626±27)pg/ml,ERK2组明显低于对照组和LacZ组(P<0.05).结论 转染反义ERK2基因可减轻慢性移植物血管病,并延缓其进展,其机制可能与VSMC增殖和迁移受到抑制以及PDGF-BB表达下调有关.     

移植抗原特异性转基因CD8+T细胞对白细胞介素2的依赖性

目的研究白细胞介素2（IL-2）在调节移植抗原特异性转基因CD8^＋T细胞介导的免疫排斥反应中的作用。方法将经荧光染科CFSE标记后的C57BL／6小鼠和2CTg小鼠（CD4敲除鼠）淋巴细胞分别植入经致死剂量γ射线照射过的两组DBA／2J小鼠体内，检测CD4^＋与CD8^＋T细胞在体内分裂增殖的时相，并用胞浆内IL-2标志染色方法测定活化后T细胞表达IL-2的能力。以Balb／c小鼠为供者，糖尿病2CTg小鼠和2C Tg-IL-2KO小鼠（IL-2敲除鼠）为受者，进行胰岛细胞移植。观察CD8^＋ T细胞在介导移植排斥中的作用。结果DBA／2J小鼠输注了C57BL／6小鼠的淋巴细胞后，CD4^＋与CD8^＋T细胞分裂增殖均非常明显，前者表达大量IL-2，后者则不表达。DBA／2J小鼠输注了2CTg小鼠的淋巴细胞后。在完全没有CD4^＋T细胞存在的情况下，CD8^＋T细胞仍明显分裂增殖并大量表达IL-2。2CTg和2CTg—IL-2KO小鼠移植胰岛细胞后，前者迅速发生排斥反应，胰岛移植物的平均存活时间仅为8d，而后者胰岛移植物的平均存活时间〉50d。结论CD8^＋T细胞在产生和利用IL-2时有很大的可塑性。CD4^＋T细胞存在时，CD8^＋T细胞能有效利用CD4^＋T细来源的IL-2进行分裂增殖，在缺乏CD4^＋T细胞时，则利用自身来源的IL-2进行分裂增殖；移植抗原特异性CD8^＋T细胞的效应功能完全依赖于IL-2，排斥反应由CD8^＋T细胞介导时，阻断IL-2／IL-2受体通路可诱导移植物长期存活。     

TGF-β1基因修饰的未成熟树突状细胞对小肠移植大鼠外周血及移植肠浸润T细胞的影响

目的探讨经转化生长因子-β1（TGF-β1）基因修饰的未成熟树突状细胞（imDC）预处理大鼠小肠移植受体后的外周血及移植肠浸润T细胞的变化及意义。方法选用近交系F344／N和BN大鼠建立全小肠异位移植模型，实验分4组（每组24只）：同基因移植组（BN-BN组）、异基因移植组（F344／N-BN组）、异基因移植＋TGF-β1基因转染imDC组（F344／N-BN＋TGF-β1组）和异基因移植＋TGF-β1基因转染imDC＋FK506组（F344／N-BN＋TGF-β1＋FK506组）。各组大鼠分别于术后3、5、7d各处死6只，获取大鼠静脉血和移植肠。应用免疫组化SABC法检测受体鼠外周血及移植肠CD4^＋、CD8^＋、CD25^＋细胞和IL-4的表达。同时行移植肠组织病理学检查并观察大鼠生存情况。结果TGF-β1修饰的DC细胞能显著抑制外周血及移植肠浸润淋巴细胞CD4^＋、CD8^＋及CD25^＋的表达，并提高IL-4的表达；显著延长受体大鼠的生存时间，但移植肠仍有排斥反应的病理组织学征象。结论TGF-β1修饰的DC通过影响受体外周血及移植肠浸润T细胞对大鼠小肠移植发挥免疫抑制作用。     

血红素氧合酶-1基因治疗减缓移植物血管病及机制

目的 观察血红素氧合酶-1(HO-1)基因治疗减缓同种移植物血管病的效果,探讨其机制.方法 以BN-Lewis大鼠血管移植为对象,依据基因治疗方案分为4组:同系对照组、空白对照组、载体对照组、腺病毒介导的HO-1( AdHO-1)组.移植后2个月,观察各组移植物纤维化和内膜增生,检测T细胞(CD3+)、B细胞(CD45RA)和巨噬细胞(CD68+)浸润数量,逆转录-聚合酶链反应(RT-PCR)和Western blot检测移植物HO-1基因和蛋白的表达,酶联免疫吸附试验(ELISA)法检测受体血清白细胞介素(IL)-10的浓度.结果 同系对照组无移植物血管病表现,空白对照组和载体对照组大量纤维沉积,AdHO-1组纤维沉积轻微.血管内膜/(内膜+中膜)百分比4组分别为7.6％、81.4％、85.9％、15.9％.每400倍视野浸润细胞数4组分别为T细胞(9.2±1.6、92.3±11.6、89.6±17.8、39.3±10.1)、B细胞(3.6±1.1、72.6±11.8、66.6±10.9、30.6±9.9)、巨噬细胞(7.5±1.2、78.5 ±21.7、72.5 ±19.8、34.5±18.7).血清IL-10浓度4组分别为(50.2±20.1)、(40.2±11.1)、(38.6±19.3)、(481.2 ±69.1)ng/L.AdHO-1组与空白对照组和载体对照组间差异有统计学意义(P＜0.05).AdHO-1基因治疗增高了移植血管HO-1基因和蛋白的表达.结论 AdHO-1基因治疗减缓同种移植物血管病,移植物纤维化和内膜增生明显减轻.AdHO-1基因治疗下调了T细胞、B细胞和巨噬细胞在移植物中的浸润,增加了HO-1和IL-10的表达,IL-10-HO-1通路的活化可能是移植血管得到保护的重要原因.     

移植物转染血红素氧合酶-1基因抑制慢性移植物血管病

目的探讨移植物转染血红素氧合酶-1（HO-1）基因对慢性移植物血管病的影响。方法克隆HO-1基因，并构建含有HO-1基因的重组腺病毒载体（Ad-HO-1），实验分为4组：A组为同系移植对照组，供、受者均为Lewis大鼠，无特殊处理；B组为同种移植对照组，Lewis大鼠接受未经处理的BN大鼠胸主动脉移植；C组为同种移植空载体对照组，Lewis大鼠接受以空载体（不含HO-1基因）处理的BN大鼠的胸主动脉移植；D组为同种移植实验组，Lewis大鼠接受转染HO-1基因的BN大鼠的胸主动脉移植。于移植后60d取移植动脉，进行组织形态学观察，测量内膜厚度；免疫组化和逆转录聚合酶链反应检测HO-1在移植动脉中的表达。结果A组移植动脉形态正常；B组、C组移植动脉呈移植物血管病表现，血管内膜显著增厚，D组移植动脉呈内膜炎改变，内膜厚度与B组、C组相比，差异有统计学意义（P〈0．01）。免疫组化及RT-PCR检测显示，与A组、B组和C组相比，D组移植动脉可以检测到HO-1基因及其蛋白表达。结论在移植血管中预先转染HO-1基因，能明显缓解移植动脉的纤维化进程以及内膜的增生，对慢性排斥反应所致的移植物血管病具有抑制作用。     

腺病毒介导的血红素氧合酶-1基因治疗对同种移植物慢性排斥反应损伤的保护作用

目的探讨腺病毒介导的血红素氧合酶-1（AdHO-1）基因治疗对同种移植物慢性排斥反应损伤的保护作用及其机制。方法选用血管移植和肾脏移植两种慢性排斥反应模型,对同种血管移植物和肾脏移植物进行体外AdHO-1基因转染,分析慢性排斥反应发生时移植物的结构和功能变化、目的基因和蛋白的表达以及免疫系统的相应反应。结果AdHO-1基因治疗缓解了慢性排斥反应对同种肾脏移植物的损伤,但弱于对血管移植物的保护效应;空载病毒加剧了同种肾脏移植物的损伤;AdHO-1基因治疗可减少慢性排斥反应发生时移植物内巨噬细胞和CD4^＋细胞的浸润。结论AdHO-1基因治疗可能通过保护移植物、下调免疫反应、诱导免疫偏移等作用减轻同种移植物的慢性排斥反应损伤。     

移植物中CD4+CD25+T细胞的表达与异基因造血干细胞移植后移植物抗宿主病的相关性

异基因造血干细胞移植是治疗恶性血液病的有效手段之一，而其并发症移植物抗宿主病（GVHD）严重影响患者的预后和生存质量。近年来已有研究表明，去除移植物中的CD4^＋CD25^＋T细胞，移植后aGVHD的发生率上升。这说明移植物中CD4^＋CD25^＋T细胞表达水平与GVHD的发生相关。因此，我们对移植物中CD4^＋CD25^＋T细胞亚群比例与受者GVHD的发生进行了初步研究。报告如下。     

联合应用CTLA-4Ig及抗ICOS单克隆抗体延长小鼠移植胰岛存活时间

目的探讨共刺激信号阻断剂细胞毒T淋巴细胞相关抗原4免疫球蛋白（CTLA-4Ig）及抗共同刺激分子ICOS单克隆抗体（ICOSmAb）对移植胰岛功能的影响。方法以BALB／c小鼠为供者，C57BL／6糖尿病小鼠为受者，进行同种胰岛细胞移植。将移植后的小鼠随机分成4组，每组10只。ICOS组：移植后1、3、5d腹腔内注射ICOSmAb 100μg／kg；CTLA4组：移植后0、2、4d腹腔内注射CTLA-4Ig50μg／kg；联合阻断组：移植后腹腔注射CTLA-4Ig和ICOSmAb，用法同CTLA4组和ICOS组；对照组：单纯胰岛移植，不注射CTLA-4Ig和ICOSmAb。观察术后移植物存活时间和移植胰岛的病理改变；逆转录聚合酶链法（RT-PCR）检测移植胰岛组织中白细胞介素2（IL-2）、白细胞介素10（IL-10）mRNA的表达情况；应用流式细胞仪检测CD4^＋、CD8^＋T淋巴细胞表达情况。结果联合阻断组的小鼠移植胰岛存活时间较其它3组明显延长，移植胰岛的细胞形态经光镜检查接近正常。联合阻断组与其它3组比较，IL-2mRNA表达减少，差异有统计学意义（P〈0．05），IL-10mRNA的表达差异无统计学意义（P〉0．05）；移植术后21d，CD4^＋、CD8^＋T淋巴细胞表达上调不明显。结论应用CTLA-4Ig和ICOSmAb联合阻断CD28和共同刺激分子ICOS，可以明显的抑制排斥反应，延长移植胰岛的存活时间及存活率。     

槐耳颗粒对小鼠心脏移植物生存期的影响

目的探讨槐耳颗粒对小鼠心脏移植后移植物生存期的影响及其可能机制。方法槐耳颗粒在小鼠心脏移植术后每天予以6mg／g体重槐耳清膏灌胃处理；移植排斥对照组和同系移植对照组灌清水；术后5d或移植排斥终点收集供心做石蜡病理切片行HE染色及免疫荧光检查。结果移植排斥对照组供心平均存活时间为（8．0±0．53）d，槐耳颗粒组供心平均存活时间为（6．0±0．26）d，两组差异有统计学意义（P〈0．001）。槐耳颗粒组和移植排斥对照组供心心肌变性坏死、大量CD8^＋T细胞浸润及FasL表达。而同系移植对照组阴性。结论小鼠心脏移植术后槐耳清膏灌胃移植物生存期缩短，其可能与其增强CD8^＋T细胞浸润及FasL表达有关。     

供肝局部转染人细胞毒性T淋巴细胞相关抗原4免疫球蛋白的重组腺相关病毒诱导大鼠同种肝移植免疫耐受

目的 利用人细胞毒性T淋巴细胞相关抗原4免疫球蛋白的重组腺相关病毒（rAAV-hCTLA41g）局部基因转染供肝诱导大鼠同种肝移植免疫耐受。方法 供体为DA大鼠，受体为LEW大鼠，分为以下4组：（A）同基因对照组（LEW-LEW）；（B）生理盐水对照组；（C）rAAV-EGFP（增强型绿色荧光蛋白）对照组；（D）rAAV-hCTLA41g灌注组。大鼠原位肝移植前6周，经门静脉灌注采用血管夹闭法对供肝进行基因转染。结果 D组大鼠平均生存期显著高于C组（10．8±1．0）d及B组（11．6±1．1）d，B组与D组间，C组与D组间，生存期差异有统计学意义（P〈0．01）。D组血浆及移植肝中可以持续检测到hCTLA41g的表达。术后1周移植肝病理检查显示B组、C组均有严重免疫排斥反应，免疫组织化学显示大量CD4^＋、CD8^＋T淋巴细胞浸润；而D组仅有轻、中度炎症反应，少量CD4^＋、CD8^＋T淋巴细胞浸润。结论 移植术前6周对供肝体内经门静脉灌注采用血管夹闭技术基因转染rAAV-hCTLA41g可以诱导大鼠同种肝移植免疫耐受。     

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.