血红素氧合酶1对大鼠心肌细胞急性损伤的保护作用

目的 了解血红素氧合酶1(HO-1)对脂多糖(LPS)诱导的心肌细胞损伤的保护作用及其机制. 方法分离培养SD乳鼠心肌细胞,根据细胞悬液中所加刺激物的不同分为对照组(A组):常规培养;LPS组(B组):培养液中加入终浓度为30 μmol/L的LPS,作用1 h;LPS+氯化血红素(heroin)组(C组):加入终浓度为5 μmol/L的heroin,作用1 h后再加入30 μmol/L的LPS作用1 h;LPS+ZnPP组(D组):加入终浓度为3 μmol/L的ZnPPⅨ,作用1 h后再加入30 μmol/L的LPS作用1 h.硫代巴比妥酸比色法及黄嘌呤氧化酶法测定各组心肌细胞乳酸脱氢酶(LDH)、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;检测心肌细胞节律、存活率及凋亡率;用反转录-PCR法检测HO-1 mRNA表达;蛋白质印迹法检测心肌细胞HO-1、肿瘤坏死因子α(TNF-α)、核因子кB(NF-кB)的表达. 结果 B、C、D组LDH和MDA值分别为(113±15)、(79±13)、(154±22)U/L和(1.88±0.36)、(1.16±0.32)、(2.84±0.44)mmol/L,高于A组[(69±10)U/L、(0.87±0.25)mmol/L,P<0.05],而以上3组的SOD值[(17.8±1.8)、(22.5±2.4)、(13.4±1.5)U/mL]却低于A组[(24.3±3.6)U/mL,P<0.05].B、C、D组心肌细胞节律,凋亡率均高于A组(P<0.05),存活率低于A组(P<0.05).B、C、D组心肌细胞HO-1 mRNA表达均高于A组(P<0.05),其中C组最高.B、C、D组心肌细胞HO-1、TNF-α、NF-кB值均高于A组(P<0.05),其中C组的HO-1值最高,D组TNF-α、NF-кB值最高. 结论 LPS对心肌细胞有明显的损伤作用.HO-1可能通过抗炎性反应、减轻氧化应激以及减少细胞凋亡途径,对心肌细胞产生保护作用.     

小剂量氯胺酮预处理对大鼠肠缺血/再灌注后肝脏血红素加氧酶-1表达的影响

目的 观察小剂量氯胺酮对血红素加氧酶-1 (heme-oxygenase 1,HO-1)在大鼠肠缺血/再灌注(ischemia/reperfusion,I/R)后肝脏中表达的影响,并对其可能的保护机制作一初步探讨. 方法 48只雄性成年SD大鼠按随机数字表法分为A组(氯胺酮10 mg/kg术前30 min腹腔注射+假手术)、B组(盐水0.2 ml术前30 min腹腔注射+假手术)、C组(氯胺酮10 mg/kg术前30 min腹腔注射+小肠I/R)、D组(盐水0.2 ml术前30 min腹腔注射+小肠I/R)、E组(锌原卟啉5 mg/kg、氯胺酮10 mg/kg术前30 min腹腔注射+小肠I/R)、F组(锌原卟啉5 mg/kg、盐水0.2 ml术前30 min腹腔注射+小肠I/R),每组8只.小肠I/R造模组大鼠通过夹闭肠系膜上动脉60 min,然后松血管夹,于再灌注6h后取材,测定肝组织丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活性;采用免疫组化法测定肝组织HO-1的表达和定量;光镜下观察肝脏病理学改变;取外周静脉血测血清谷丙转氨酶(glutamic-pyruvic transaminase,GPT)、谷草转氨酶(glutamic-oxaloacetic transaminase,GOT). 结果 A、B两组间各项数据比较差异无统计学意义(P＞0.05);各缺血造模组大鼠肝组织MDA含量:C组[(2.69±0.35) μmol/g]、D组[(4.62±0.36) μmol/g]、E组[(4.35±0.24) μmol/g]、F组[(4.74±0.34) μmol/g]与B组[(1.08±0.26) μmol/g]比较,显著升高;SOD活力:C组[(129±6) μU/L]、D组[(102±5) μU/L]、E组[(99±4)μU/L]、F组[(96±6)μU/L]与B组[(133±7) μU/L]比较,显著下降;血清GOT、GPT含量:C组[GPT(212±21) U/L,GOT(129±16) U/L]、D组[GPT(416±33) U/L,GOT(362±15)U/L]、E组[GPT(407±29) U/L,GOT(359±14) U/L]、F组[GPT(414-±40) U/L,GOT(366±16) U/L]与B组[(GPT(53±9) U/L,GOT(83±7) U/L]比较,显著升高;HO-1表达:C组(0.472±0.126)、D组(0.324±0.078)、E组(0.337±0.092)、F组(0.328±0.083) OD与B组(0.078±0.010) OD比较,显著上调(P＜0.05或P＜0.01);与D组比较,C组血清GPT、GOT、肝组织MDA含量均显著降低,SOD活力显著上升,HO-1表达上调(P＜0.05);与D组比较,E组、F组血清GPT、GOT及MDA、SOD值差异无统计学意义(D0.05);E组和C组比较,血清GPT、GOT,肝组织MDA含量显著升高,SOD活力显著下降,HO-1表达下调(P＜0.05). 结论 小剂量氯胺酮预处理能减轻肠I/R后造成的肝脏损伤,这种作用在一定程度上是通过上调HO-1的表达来实现的.     

血红素氧化酶-1介导脂联素在脓毒症肺损伤中的保护作用

目的 探讨血红素氧化酶-1(heme oxygenase,HO-1)介导脂联素(adiponectin,APN)在脓毒症肺损伤中的保护作用.方法 80只雄性Wistar大鼠采用随机数字表法分为4组(每组20只):对照组(C组)、脓毒症模型组(LPS组)、脂联素预处理组(APN组)和HO-1抑制剂锌原卟啉IX(zinc protoporphyrin IX,ZnPP IX)干预组(Zn组).各组分别于腹腔注射脂多糖(lipopolysaccharide,LPS) (20 mg/kg)或0.9％氯化钠溶液后6h,采用酶联免疫吸附法检测血清中肿瘤坏死因子(tumor necrosis factor-alpha,TNF-α)和白介素(interlukin-6,IL-6)的含量.采用分光光度法测定一氧化氮(nitric oxide,NO)浓度、肺组织丙二醛(malonaldehyde,MDA)和髓过氧化物酶(myeloperoxidase,MPO)活性变化.采用实时荧光定量聚合酶链反应(real-time PCR)法检测肺组织HO-1、诱导型一氧化氮合成酶(inducible nitric oxide synthase,iNOS)mRNA的表达水平.观察5d内大鼠生存情况,并绘制生存曲线. 结果 与C组比较,LPS组、APN组和Zn组血清TNF-α [(321.3±11.2)、(132.5±10.2)、(311.7±12.4)vs (52.1±1.4)] ng/L、IL-6[(2 229.26±210.25)、(1 134.14±11.24)、(2 028.27±167.04)vs(55.38±0.23)] ng/L、NO[(103±10)、(79±8)、(97±9)vs(48±3)] μmol/L和肺组织匀浆MDA[(16.209±0.151) 、(5.943±0.310)、(13.238±0.326)vs(3.081 ±0.017)] μmol/g、MPO[(12.42±0.46)、(6.77±0.14)、(10.45±0.21)vs(2.74±0.06)] U/g水平显著升高(P＜0.05),生存率显著下降(20％ vs 100％;70％ vs 100％;30％ vs 100％,P＜0.05);与LPS组比较,APN组血清TNF-α [(132.5±10.2)vs (321.3±11.2)] ng/L、IL-6 [(1 134.14±107.13)vs(2229.26±210.25)] ng/L、NO[(79±8)vs (103±10)] μmol/L和肺组织匀浆MDA[(5.943±0.310)vs (16.209±0.151)] μmol/g、MPO [(6.77±0.14)vs (12.42±0.46)] U/g水平显著降低(P＜0.05),肺组织HO-1 mRNA[(8.73±0.24)vs(1.54±0.03)]显著升高(P＜0.05),iNOS mRNA[(1.42±0.15)vs(2.01±0.10)]显著下降(P＜0.05),生存率显著增高(70％ vs 20％,P＜0.05);与APN组比较,Zn组血清TNF-α[(311.7±12.4)vs(132.5±10.2)] ng/L、IL-6[(2 028.27±167.04)vs(1 134.14±107.13)]ng/L、NO[(97±9)vs(79±8)] μmol/L和肺组织匀浆MDA[(13.238±0.326)vs(5.943±0.310)] μmol/g、MPO[(10.45±0.21)vs(6.77±0.14)] U/g水平显著升高(P＜0.05),肺组织HO-1 mRNA[(2.66±0.14)vs (8.73±0.24)]显著下降(P＜0.05),iNOS mRNA[(2.06±0.23)vs(1.42±0.15)]显著升高(P＜0.05),生存率显著下降(30％ vs 70％,P＜0.05). 结论 HO-1可能介导了APN在脓毒症性肺损伤中的保护作用.     

大剂量盐酸氨溴索对脂多糖致小鼠急性肺损伤的影响

目的 研究大剂量盐酸氨溴索(沐舒坦)对脂多糖(lipopolysaccharides,LPS)所致小鼠急性肺损伤(acute lung injury,ALI)的治疗作用.方法 雄性BALB/C小鼠24只,采用随机数字表法随机分为3组(每组8只):生理盐水组(A组)、LPS组(B组)、LPS±沐舒坦处理组(C组).B组和C组予以LPS(2 g/L)3 mg/kg气管滴入制成ALI模型,A组予以等体积生理盐水气管滴入作为对照.6h后,C组按100 mg/kg经尾静脉注入沐舒坦,A组和B组予以等体积的生理盐水,24 h后重复给药.造模后48 h收集肺泡灌洗液,测定灌洗液中脂氧素A4、肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-10、蛋白含量,并行多形核细胞计数;测定各组的肺湿/干重比、肺组织中性粒细胞髓过氧化物酶(myeloperoxidase of leukocytes,MPO)含量;苏木精-伊红(hematoxylin-eosin,HE)染色观察小鼠肺组织病理形态学变化.结果 造模48 h后C组肺泡灌洗液中脂氧素A4[(332±19) ng/L] 、IL-10含量[(36±-6)ng/L]高于B组[(273±25)、(9±3)ng/L] (P＜0.01);C组TNF-α[(243±65) ng/L]、蛋白含量[(0.328±0.037) mol/L]、多形核细胞计数[(39.99±14.41)×104/ml]低于B组[(391±105) ng/L、(0.444±0.283) mol/L、(137.94±28.98)×104/ml](P＜0.01);C组肺组织湿/干重比(3.65 ±0.18)及MPO含量[(6.4±0.4)U/G]低于B组[(4.37±0.58)、(137.9±29.0) U/g)](P＜0.01);C组肺组织病理改变较B组明显减轻.结论 100 mg/kg沐舒坦对LPS所致小鼠ALI有一定治疗作用,这一作用可能与促进炎症消退有关.     

乌司他丁对大鼠机械通气肺损伤时γ-氨基丁酸信号通路的影响

目的探讨乌司他丁对大鼠机械通气引起的呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)时γ-氨基丁酸(GABA)信号通路的影响。方法选取健康成年雄性Wister大鼠36只,采用随机数字表法分为三组:正常对照组(C组)、机械通气肺损伤组(VILI组)和机械通气肺损伤+乌司他丁处理组(UTI组),每组12只。VILI组与UTI组采用VT40ml/kg机械通气4h的方法制备大鼠VILI模型。机械通气前1h,UTI组腹腔注射乌司他丁1×10~5 U/kg,C组和VILI组给予等容量生理盐水。收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),检测BALF中白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的浓度;取肺组织,检测湿/干重比(W/D)、肺组织IL-1β、TNF-α和ICAM-1 mRNA的表达;采用免疫组化与Western blot法检测肺组织GAD与GABAA受体的表达量,观察病理学结果并进行肺损伤评分。结果与VILI组比较,UTI组W/D(6.7±2.4vs.8.5±2.3)、肺损伤评分[(6.9±2.3)分vs.(11.8±2.7)分]明显降低(P0.05);BALF中IL-1β[(56±11)ng/L vs.(77±15)ng/L]、TNF-α[(105±29)ng/L vs.(158±37)ng/L]及ICAM-1[(205±46)ng/L vs.(293±61)ng/L]浓度明显降低(P0.05);肺组织IL-1β(1.81±0.26vs.2.58±0.34)、TNF-α(1.61±0.15vs.2.94±0.27)、ICAM-1(1.74±0.27vs.2.79±0.31)mRNA表达量明显降低(P0.05);GAD(0.44±0.08vs.0.18±0.04)和GABAA(0.30±0.09vs.0.15±0.04)受体表达量明显增加(P0.05)。结论乌司他丁可减轻大鼠机械通气引起的呼吸机相关性肺损伤,其机制可能与激活γ-氨基丁酸信号通路有关。     

胰腺肿瘤缺血再灌注加微球栓塞后血清细胞因子的变化

目的探讨胰腺缺血再灌注加微球栓塞对鼠胰腺癌血清肿瘤坏死因子（TNF）-α、白细胞介素-1（IL-1）和λ-干扰素（IFN-λ）含量及肿瘤生长的影响。方法大鼠胰腺尾部胰腺肿瘤形成后,阻断及开放胰腺尾部主要供血血管脾下动脉各30min,并经脾下动脉注入微球栓塞微血管,然后结扎脾下动脉。分别于术前及术后14d采用酶联免疫吸附法测定血清TNF-α、IL-2和IFN-λ的含量及观察胰腺肿瘤体积的变化。结果胰腺肿瘤缺血再灌注加微球栓塞组（E组）术前血清TNF-α、IFN-λ和IL-2的含量和胰腺肿瘤体积与阳性对照组（B组）和胰腺肿瘤缺血组（C组）及胰腺肿瘤缺血再灌注组（D组）之间比较差异均无显著性（P>0.05）。术后14dE组血清TNF-α、IFN-λ和IL-2的含量〔（79.5±8.7)ng/L、(106.0±10.8)ng/L、(346.1±13.1)ng/L〕明显高于B组〔（30.5±3.5)ng/L、（76.7±5.8）ng/L、（137.5±8.1）ng/L〕、C组〔（53.6±6.3）ng/L、（91.4±7.3）ng/L、（203.4±7.9）ng/L〕和D组（P<0.01）;且D、E组肿胰腺瘤体积也明显小于B、C组。结论胰腺肿瘤缺血再灌注加微球栓塞可导致鼠胰腺肿瘤血清TNF-α、IFN-λ和IL-2含量明显升高,并可使胰腺肿瘤体积明显缩小,其效果明显优于单纯的胰腺肿瘤缺血或胰腺肿瘤缺血再灌注。     

创伤性肺损伤核因子-κB和细胞因子的变化及糖皮质激素的影响

目的探讨创伤性急性肺损伤(ALI)肺泡巨噬细胞(PAM)核因子(NF)-κB的活化和细胞因子的释放及地塞米松(Dex)的抑制作用.方法将24只大耳白兔随机分为正常对照组、创伤组、Dex干预组.用凝胶电泳迁移率改变分析法(EMSA)和酶联免疫吸附(ELISA)法分别检测PAM核提取物中NF-κB的活性和PAM培养上清液中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-10的含量.结果 NF-κB活性和TNF-α、IL-6、IL-10的含量创伤组分别为(2987.85±163.85)ng/L、(235.6±30.8)ng/L、(398.8±243.6)ng/L、(246.4±30.5)ng/L,较对照组比较均显著增高(P＜0.01或P＜0.05);Dex组NF-κB(1968.27±69.42)ng/L、TNF-α为(168.2±48.8)ng/L、IL-6为(210.3±28.6)ng/L较创伤组比较明显降低(P＜0.01),但IL-10(227.2±38.6)ng/L无明显变化(P>0.05).结论 NF-κB激活和分泌高水平细胞因子在创伤性ALI的发生、发展过程中起着重要作用;Dex发挥抗炎作用与其对NF-κB的活性和细胞因子的调节作用密切相关.     

脂多糖对人工关节无菌性松动的影响

[目的]探讨脂多糖(LPS) 促进人工关节松动的可能性.[方法]采集40 例人体外周血,分离单核细胞(MOs),分组培养,A 组(对照组):仅MOs;B 组:MOs+ 超高分子聚乙烯微粒(UHMWPE,未去除LPS);C 组:MOs+LPS;D 组:MOs+UHMWPE(去除LPS);E组:MOs+UHMWPE(去除LPS)+ LPS.培养48 h后,放免法测定上清中肿瘤坏死因子α(TNF-α)、白介素6( IL-6)的含量.[结果]E组TNF-α、IL-6含量明显高于A、B、C、D组(P<0. 05);B组TNF-α、IL-6较D组增高(P<0. 05).[结论]LPS对UHMWPE刺激TNF-α、IL-6分泌有协同的作用,增强了UHMWPE的溶骨效应.     

磷霉素氨丁三醇散对慢性细菌性前列腺炎模型大鼠前列腺组织TNF-α、IL-8、IL-6含量的影响

目的:探讨磷霉素氨丁三醇散(FT)对慢性细菌性前列腺炎模型大鼠肿瘤坏死因子-α(TNF-α)、白介素8(IL-8)、白介素6(IL-6)表达水平的影响。方法:70只雄性SD大鼠随机分为7组,每组10只。A组:假手术组;B组:模型对照组;C组:阳性对照组[左氧氟沙星:100 mg/(kg·d),30 d];D组:FT低剂量、14 d疗程组[200 mg/(kg·d),14 d];E组:FT低剂量、7 d疗程组[200 mg/(kg·d),7 d];F组:FT高剂量、14 d疗程组[300 mg/(kg·d),14 d];G组:FT高剂量、7 d疗程组[300 mg/(kg·d),7 d],各组均采用灌胃给药。实验结束后留取各组大鼠前列腺组织,制作病理切片并使用酶联免疫吸附实验(ELISA)检测各组大鼠前列腺组织匀浆中TNF-α、IL-8、IL-6的含量。结果:与空白对照组比较,模型组大鼠前列腺组织匀浆中的TNF-α、IL-8、IL-6含量均明显升高,差异均有统计学意义[(19.83±6.1)ng/g prot vs(32.93±6.21)ng/gprot,(8.26±0.52)ng/g prot vs(16.2±2.84)ng/g prot,(1.55±0.11)ng/g prot vs(2.51±1.06)ng/g prot,P0.05或0.01];与模型组[(32.93±6.21)ng/g prot、(16.2±2.84)ng/g prot]相比,各治疗组大鼠前列腺组织匀浆中的TNF-α、IL-8含量[(20.54±5.78)ng/g prot、(21.95±6.48)ng/g prot、(23.8±6.93)ng/g prot、(19.97±2.58)ng/g prot、(21.97±3.38)ng/g prot;(12.43±3.64)ng/g prot、(11.11±2.86)ng/g prot、(12.43±4.02)ng/g prot、(8.83±1.32)ng/g prot、(12.68±1.97)ng/g prot]明显降低,差异具有统计学意义(P0.05或0.01);各治疗组大鼠前列腺组织匀浆的TNF-α、IL-8、IL-6含量与阳性对照组比较差异均无统计学意义(P0.05);F组大鼠前列腺组织匀浆中的IL-6的表达量较模型组显著减少[(2.51±1.06)ng/g prot vs(1.76±0.46)ng/g prot,P0.05],其余治疗组及阳性对照组前列腺组织匀浆中的IL-6的表达与模型组比较均无显著性差异(P0.05),但较模型组均有下降趋势。结论:FT通过抑制TNF-α、IL-8、IL-6的表达,减轻前列腺组织的炎症反应,达到治疗大鼠CBP的目的,为临床研究提供了实验依据。     

丙泊酚对内毒素性急性肺损伤大鼠血清TNF-α、IL-1β及IL-10的影响

目的探讨内毒素性急性肺损伤(ALI)大鼠用丙泊酚后处理对血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10影响。方法雄性SD大鼠96只,随机均分为四组,每组24只。脂多糖(LPS)致伤组(B组)、丙泊酚低剂量治疗组(C组)和丙泊酚高剂量治疗组(D组)经尾静脉注射LPS 5 mg/kg制作ALI模型;之后生理盐水对照组(A组)和B组泵入生理盐水,C、D组分别注射丙泊酚2、4 mg/kg后再分别泵入4、8 mg.kg-1.h-1。分别在制模后1、2、3、4 h抽取动脉血测定TNF-α、IL-1β及IL-10的水平。结果制模后各时点A组大鼠TNF-α、IL-1β和IL-10含量均明显低于其它三组(P<0.05或P<0.01)。制模后1、2 h B组TNF-α、IL-1β和IL-10含量明显高于C、D组(P<0.01),C组IL-1β和IL-10含量明显高于D组(P<0.05或P<0.01)。制模后3、4 h B组IL-1β和IL-10含量仍明显高于C、D组(P<0.01),C组显著高于D组(P<0.01)。结论丙泊酚可以显著抑制ALI大鼠血清TNF-α、IL-1β及IL-10上升的程度。     

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.     

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.     

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.     

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.     

Utilisation des médicaments prokinétiques en réanimation : indications et limites ?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.