金黄地鼠前列腺分泌蛋白对输卵管液糖蛋白的影响

目的:在整体水平探讨前列腺分泌蛋白对金黄地鼠输卵管液中糖蛋白的影响。方法:金黄地鼠雄鼠依据手术方式的不同分为3组,分别为假手术组(SH)、附属性腺全去组(TX)和腹前列腺组(VP)(仅存前列腺)。收集与各手术组交配后不同时间点(交配后0.5、2、4、6h)的输卵管液(每一时间点及每一组,n=3),输卵管液蛋白经SDS-聚丙烯酰胺凝胶电泳,考马斯亮蓝或阿仙蓝染色分析,应用蛋白电泳印迹后与系列某一种特异性糖基专一性结合凝集素反应,分析糖蛋白的变化。结果:不同组雄鼠交配及不同时间点收集输卵管液蛋白电泳谱类似,约15条主要条带。凝集素结合谱示,麦胚凝集素(WGA)结合的相对分子质量(Mr)为32000、35500、47000、52000糖蛋白见于6h VP组输卵管液,而6h TX组可见Mr为81000、128000条带;与豌豆凝集素(PSA)结合Mr为37500、32000糖蛋白仅见于6h VP组,而6h TX组缺乏;仅6h VP组可见与双花扁豆凝集素(DBA)结合Mr为52000、47000糖蛋白,而6h TX组缺乏。而0.5、2、4h时间点收集的输卵管液各凝集素结合谱相似。结论:前列腺分泌蛋白可影响修饰交配6h后的输卵管液中含乙酰氨基葡萄糖、N-乙酰半乳糖胺/半乳糖和甘露糖糖链的糖蛋白。这些糖蛋白可能在胚胎的发育过程中起作用。     

金黄地鼠腹侧前列腺来源蛋白结合精子表面的实验研究

目的:探讨前列腺分泌蛋白是否可结合于精子表面。方法:以金黄地鼠作为研究对象,应用间接免疫荧光和亲和素标记的蛋白转印方法检测前列腺分泌蛋白是否可结合于精子。制备的抗前列腺粗提取物多克隆抗体,间接免疫荧光技术检测体外与前列腺分泌物孵育的附睾精子,以及体内分别与含前列腺及去除前列腺雄鼠交配后收集的子宫腔内和输卵管腔内精子的前列腺成分抗原。前列腺提取物经电泳分离转膜后和生物素标记附睾精子膜蛋白作用,测定在体外前列腺分泌蛋白能否与附睾精子膜结合。实验分为对照组、附属性腺全去组、腹侧前列腺组、去除腹侧前列腺组。结果:前列腺抗原成分的免疫反应局限在精子体中部表面,而精子头、颈部未见阳性反应。在体外(80±5)%附睾精子与前列腺分泌蛋白结合,在体内与对照组雄鼠交配后收集的子宫腔内精子与前列腺分泌蛋白结合精子阳性率为(30.0±4.6)%,与去除腹侧前列腺组(3.6±1.4)%比较差异有显著性(P<0.01),在体内与对照组雄鼠交配后收集的输卵管腔内精子与前列腺分泌蛋白结合精子阳性率为(16.0±3.6)%,与去除腹侧前列腺组精子(3.2±1.4)%比较差异有显著性(P<0.01)。前列腺分泌蛋白的电泳印记膜与生物素标记附睾精子膜蛋白孵育后显色分析结果可见5条阳性反应带。结论:金黄地鼠的前列腺分泌蛋白可结合于精子体中部表面,前列腺分泌蛋白中至少有5个组分可与精子膜蛋白结合。     

胆管癌胆汁中糖蛋白的糖链结构特点

目的：探讨与胆管癌相关的胆汁糖蛋白的糖链结构特点。方法：对15例胆管癌胆汁及10例良性胆道疾病的胆汁蛋白进行蛋白质电泳考马斯亮蓝及银染色，并用4种识别不同糖链结构的辣根过氧化酶标记的凝集素（ConA-HRP,WGA-HRP,LCA-HRP,DSA-HRP）进行凝集素印迹分析。结果：胆管癌胆汁和良性胆汁蛋白SDS－PAGE谱基本相同，ConA结合的胆管癌相关糖蛋白有4种（－138，－122，－108，－101kDa)，WGA结合胆管癌相关糖蛋白1种（－201kDa);LCA结合胆管癌相关糖蛋白1种（－122kDa);DSA结合胆管癌相关糖蛋白3种（－201，－163，－122KDa)。结论：胆管癌胆汁中一些糖蛋白的糖链结构发生了改变，主要表现为唾液酸含量增加及天线数，高甘露糖型糖链增多，可能与胆管上皮的恶性转化有关。     

半乳糖凝集素3抑制剂对大鼠椎间盘软骨终板细胞基质金属蛋白酶-3、趋化因子（C-C基元）配体3及聚蛋白多糖表达的影响

目的 探讨半乳糖凝集素3对大鼠椎间盘软骨终板细胞基质金属蛋白酶-3(MMP-3)、趋化因子(C-C基元)配体3(CCL3)、聚蛋白多糖表达的影响.方法 将P2代大鼠软骨终板细胞分为2组,一组加入含25μmol/L GB1107半乳糖凝集素3抑制剂(抑制剂组),另一组加入等体积空白溶剂(对照组),采用MTT法检测2组12 h、24 h及48 h细胞的增殖情况;于加入溶剂后24 h收集2组细胞,采用实时荧光定量PCR法检测细胞中MMP-3、CCL3及聚蛋白多糖的mRNA表达水平,采用蛋白质印迹法检测细胞中MMP-3、CCL3及聚蛋白多糖的蛋白表达水平.结果 抑制剂组大鼠软骨终板细胞的细胞增殖活性加入抑制剂后12 h开始随时间延长不断降低,加入抑制剂后12 h、24 h、48 h各时间点的细胞增殖活性均低于对照组,差异有统计学意义(P<0.05).抑制剂组大鼠软骨终板细胞中MMP-3、CCL3及聚蛋白多糖的mRNA和蛋白表达水平均低于对照组,差异有统计学意义(P<0.05).结论 抑制半乳糖凝集素3可降低大鼠终板细胞中MMP-3、CCL3及聚蛋白多糖的表达,提示半乳糖凝集素3可能通过调节细胞外基质的降解、炎性细胞浸润和合成代谢共同影响椎间盘退行性变进程.     

CAPD患者腹膜透析置换液及肝硬化患者腹水的蛋白质组的研究

目的：分析持续性非卧床腹膜透析（CAPD）患者24h时腹膜透析置换液及肝硬化患者腹水的蛋白质组,找出差异蛋白。方法：分别收集4位CAPD患者24h腹膜透析置换液及肝硬化患者1000～1500ml腹水进行超滤浓缩后行2-D胶双向电泳检测及图像、质谱分析。结果：实验成功得到了两组病人的蛋白电泳图,电泳图中存在明显差异蛋白点,选取20个点行质谱分析后得到15个点的肽指纹图,在蛋白质组数据库中将获得混合物肽片段质量数据输入数据库中进行检索。结果表明12、13、14点为视黄醇结合蛋白,17点为糖基化蛋白HC。结论：腹膜透析置换液和腹水之间确实存在蛋白质组的差异,经质谱分析证实视黄醇结合蛋白是其中之一,即腹膜透析置换液中存在视黄醇结合蛋白。     

不同脑保护方法下主动脉术后脑脊髓液S100β及IL-6的变化

目的通过对主动脉手术围手术期脑脊髓液生化指标变化的比较,评价两种不同脑保护方法的效果。方法2004年11月至2005年4月接受手术治疗的主动脉瘤患者14例,其中I型主动脉夹层11例,Ⅲ型主动脉夹层2例,假性胸腹主动脉瘤1例。在单纯深低温停循环（DHCA）下行胸降主动脉替换5例（DHCA组）;在DHCA结合选择性顺行脑灌注（ASCP）下行主动脉弓部置换9例（ASCP组）。于术前及术后0、6、12、24、48和72h检测脑脊髓液S10013蛋白（S100β）及白细胞介素6（IL-6）水平。结果ASCP组停循环时间长于DHCA组。两组脑脊髓液中S100β及IL-6的术前水平无显著差别。两组S100β于术后12h达到峰值;术后6—72h各时间点两组S100β水平差异有统计学意义（P〈0．05）。两组IL-6分别于术后12h和0h达到峰值;术后6h及12h两组IL-6水平差异有统计学意义（P〈0．05）。结论在两种脑保护方法下主动脉手术中发生的缺氧性脑损伤均属轻型。DHCA结合单侧ASCP具有比单纯DHCA更好的脑保护效果,围手术期的脑损伤较轻。     

金属硫蛋白对离体心脏细胞凋亡和NO、NOS表达的影响

目的 探讨金属硫蛋白（Mr）与离体心脏细胞凋亡和一氧化氮（NO）、一氧化氮合酶（NOS）的关系。方法 Wistar大鼠16只，分为2组：对照组（c），腹腔注射蒸馏水0．5ml24h后取离体心脏灌注HTK心脏保护液，4℃保存3h后建立Langendorff灌注模型，灌注KH液2h；实验组（E）腹腔注射3．6％ZnSO4（1．5ml／ks）24h后取离体心脏，处理方法同C组。测定心肌MT含量、心肌细胞凋亡率、NO、NOS的含量。结果 MT含量E组明显较C组增高（P〈0．05），心肌细胞凋亡率E组明显低于C组（P〈0．01），琼脂糖凝胶电泳检测DNA片段梯E组与C组比较，光密度明显减弱（P〈0．01），E组与C组比较，NO、NOS的含量明显增多（P〈0．01）。MT含量与凋亡细胞率呈负相关（r=-0．96，P〈0．01），与心肌组织中NO含量呈正相关（r=0．97，P〈0．01）。结论 心肌MT可增加心肌中NO、NOS的表达，减少再灌后心肌细胞凋亡的发生。     

前列腺增生和前列腺癌患者血、尿中PSA糖链结构的改变及意义

目的探索前列腺癌的早期诊断和答别诊断的新依据。方法收集前列腺增生和前列腺癌患者空腹第一次晨尿和血标本各90份和30份，随机分为3组，用PSA抗体亲和层析柱提纯尿液和血液中的PSA，用辣根过氧化物酶（HRP）标记的凝集素SNA（sambucus nigra agglutinin）做探针，连接到已固定在膜上纯化的PSA的糖链，榆测已结合的HRP来代表PSA糖链与凝集素的结合力，用增强化学发光法（ECL）检测已结合的HRP的结合力，其数值用发光单位（LLU）来表示。结果用HRP标记的凝集素SNA-HRP作探针检测前列腺癌和前列腺增生血中PSA时，前列腺癌血中平均LLU仅为前列腺增生血中PSA的18．3％，与SNA—HRP的结合力两者之间有明显差异（P〈0．001）；而在尿液中两者无明显差异（P〉0．05）。说明前列腺癌血中PSA糖链结构中唾液酸残基表达较前列腺增生明显减少。结论前列腺癌患者血中PSA糖链结构与前列腺增生相比发生改变，其中糖链结构中唾液酸残基表达的改变可能为今后前列腺癌的早期诊断和鉴别诊断提供新的依据。     

不同营养支持途径对烧伤大鼠肠粘膜上皮细胞周期的影响

目的：探讨肠道喂养及静脉营养对烧伤早期肠粘膜上皮细胞周期的影响。方法：66只烧伤大鼠随机分为肠道喂养组（EF组）及静脉营养组（PN组），分别采用灌喂和颈外静脉输入方法给予等氮、等热卡的营养液。每组设伤后6、12、24、48、72h5个观察时相点，每时相点6只大鼠，并设正常对照（6只）。采用流式细胞技术进行空、回肠粘膜上皮细胞周期分析，以Western blot法检测肠粘膜细胞周期蛋白D1、E及细胞周期蛋白依赖性激酶（CDK）2、4的表达。结果：（1）肠粘膜上皮GO／G1期细胞百分比的变化：在空肠粘膜，伤后72h时EF组明显低于PN组（P＜0．05）；在回肠粘膜，6、12、48、72h时EF组与PN组比较，差异有显性意义（P＜0．05）；（2）伤后48．72h时EF组S期细胞百分比均显高于PN组（P＜0．05－0．01）；（3）肠粘膜细胞周期蛋白D1表达的变化：与对照值比较，EF组在伤后24h及PN组在伤后48h明显增高（P＜0．05），72h时EF组显高于PN组（P＜0．05）；（4）EF组肠粘膜细胞周期蛋白E的表达在伤后72h显高于对照值和PN组（P＜0．05）；（5）PN、EF组肠粘膜CDK2的表达与对照值比较以及PN、EF两组间比较，差异均无显性意义（P＞0．05），EF组CDK4的表达在72h明显增高（P＜0．05）。结论：烧伤后早期肠道喂养能加速肠粘膜上皮细胞周期的进程以及受损肠粘膜的修复与更新。细胞周期蛋白及CDK在其中起重要作用。     

人类精浆中明胶结合蛋白的分子多样性

研究人类精浆中各种蛋白质的分子特征是了解这些蛋白质的生理和病理功能的必要步骤。据预测,人类精浆中的明胶结合蛋白（由纤维粘连蛋白[FN]和其相关分子组成）对男性不育十分重要,所以本文研究了该蛋白的免疫糖生化特征。将精液参数正常的研究对象的精浆在明胶琼脂糖凝胶上分离,用SDS-PAGE和免疫印迹（不同FN的抗体）分析。用蛋白质芯片技术结合表面增强激光解吸电离飞行时间质谱（SELDI—TOF—MS）技术（亲水性、疏水性和金属亲和芯片）来鉴定分离到的分子的多样性。用甘露醇、海藻糖和硅铝酸特异的植物血凝素和半乳糖凝集素-1检测碳水化合物组成。结果表明分离到的蛋白质组成与已知的FN一致,免疫反应试验也验证了这一结果。这些蛋白质中具有肝磷脂结合力的蛋白质优先集中于小分子成分中。实验发现了一些特别片段的磷酸化和糖基化现象。植物血凝素与带有明胶结合位点的片段（尤其是Ricinus communis凝集素-1）的结合力强于带有FN细胞结合位点的片段。实验还发现了少量能与唾液酸糖苷化和特有伴刀豆球蛋白A以及Lensculinaris凝集素结合的蛋白质成分。半乳糖凝集素-1与分离到的物质无任何反应。深入了解正常人类精浆中FN的分子多样性和它们与已知FN分子可能的相似及不同之处,是将这些特征应用于临床之前首当其冲的一步。     

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.     

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.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.