4-1BBL基因转染对小鼠体内胃癌细胞生长的影响

目的观察共刺激分子4-1BBL基因导入小鼠胃癌MFC细胞后在小鼠体内诱导的抗肿瘤效应以及对小鼠免疫状况的影响。方法用脂质体法把pMKITneo/4-1BBL和pMKITneo质粒导入615小鼠胃癌细胞MFC内,再用MFC、MFC/pMKITneo和MFC/4-1BBL细胞分别接种615小鼠,观察其成瘤情况,并测定肿瘤细胞的凋亡率及外周血的CD4~+、CD8~+T细胞和NK细胞的含量。结果4-1BBL基因转染后的胃癌MFC细胞在615小鼠体内成瘤所需的时间长、瘤体的重量轻；且MFC/4-IBBL组的癌细胞凋亡率(22．45±4．11)%明显高于MFC组(18．47±3．34)%及MFC/pMKITneo组(17．87±4．04)%(P＜0．05)；MFC、MFC/pMKITneo组小鼠外周血CD8~+T、NK细胞数明显低于正常对照组和MFC/4-1BBL组(P＜0．05),且MFC、MFC/pMKITneo两组间差异无统计学意义(P＞0．05)。结论4-1BBL基因导入胃癌MFC细胞后能够提高荷瘤机体的免疫能力、延缓肿瘤的发生、抑制肿瘤的发展、促进肿瘤细胞的凋亡。     

环孢素A和他克莫司对裸鼠体内移植的肺癌A549细胞的生物学行为的影响

目的 研究环孢素A(CsA)和他克莫司(Tac)对裸鼠体内移植的肺癌A549细胞的生长及凋亡的影响,并探讨其可能机制.方法 用肺癌A549细胞建立Balb/c小鼠移植瘤模型,分为3组实验.对照组,不给予任何免疫抑制剂;CsA组,腹腔注射CsA;Tac组,腹腔注射Tac.根据各组小鼠瘤体积变化绘制移植瘤生长曲线,根据终末瘤质量计算影响率.以细胞侵袭实验研究各组小鼠肺癌细胞迁移能力的改变.用细胞凋亡原位末端标记法检测细胞凋亡情况.荧光定量逆转录聚合酶链反应检测肿瘤细胞凋亡抑制基因(Bcl-2)mRNA和肿瘤细胞凋亡促进基因(Bax) mRNA的表达.结果 CsA组和Tac组移植瘤增长迅速,质量和体积均高于对照组(P＜0.05),2组的影响率分别为19％(P＜0.05)和25％(P＜0.05).CsA组和Tac组肿瘤细胞的迁移能力均明显高于对照组(P＜0.01,P＜0.01).对照组肿瘤凋亡指数为(0.049±0.008)％,CsA组为(0.009±0.001)％,Tac组为(0.007±0.001)％,对照组高于CsA组和Tac组(P＜0.05,P＜0.05).与对照组相比较,CsA组和Tac组肿瘤细胞中Bcl-2 mRNA的表达较高(P＜0.05),Bax mRNA的表达较低(P＜0.05).结论 CsA和Tac对裸鼠体内移植的肺癌A549细胞的生长均有促进作用,会增强肿瘤细胞的侵袭力,其机制可能与影响肿瘤细胞凋亡相关.     

早期肠内免疫营养对烫伤小鼠肠道免疫功能的影响

目的 了解早期免疫强化肠内营养对烫伤小鼠肠道免疫功能的影响.方法 选择24只雄性BALB/c小鼠制作20%TBSAⅢ度烫伤模型,采用简单随机法分成2组.每组12只.普通营养组:于伤后2 h开始经口灌喂普通肠内营养剂;免疫营养组:方法同前,在普通营养剂基础上加入谷氨酰胺和精氨酸.2组营养剂糖、脂肪、蛋白质供热比均为82:3:15,热量与氮之比为150:1.每只小鼠营养摄入按732.2 kJ·kg-1·d-1计算,第1天摄入标准量的1/3,第2天摄入标准量的1/2,第3天起摄入全量,每天的计划量分4～6次喂完.2组营养摄入为等氮、等热量、等体积.小鼠连续灌喂7d后处死,取全段小肠.另取10只同品系小鼠作为健康对照组,同法取材.记录肠集合淋巴结细胞总数,通过流式细胞仪检测淋巴结中CD3+、CD4+、CD19+及凋亡细胞变化,双抗体夹心酶联免疫吸附测定法检测肠IgA变化.结果 健康对照组、普通营养组、免疫营养组小鼠肠道淋巴结细胞总数分别为(4.5±0.6)×106、(2.3±0.4)×106、(3.8±0.5)×106个,与健康对照组比较,后2组细胞数明显减少(P＜0.05).但免疫营养组高于普通营养组(P＜0.05);3组小鼠肠道淋巴结CD3+、CD4+、CD19+细胞数比较情况类似于淋巴结细胞总数.健康对照组、普通营养组、免疫营养组淋巴细胞凋亡率分别为(4.8±2.1)%、(12.7±2.4)%、(8.0±1.7)%,与健康对照组比较,后2组小鼠细胞凋亡率明显增加(P＜0.05),但免疫营养组低于普通营养组(P＜0.05).健康对照组、普通营养组、免疫营养组肠IgA水平分别为(42±7)、(35±6)、(38±6)μg/cm,与健康对照组相比,后2组水平明显减低(P＜0.05),但免疫营养组高于普通营养组(P＜0.05).结论 用强化免疫营养剂进行早期肠内营养,可以改善烫伤小鼠肠道免疫功能.     

抑制Tregs增强DC/HCC融合疫苗诱导抗肝癌免疫反应的研究

目的 通过抑制荷瘤小鼠体内调节性T细胞(TregFoxp3+),探讨其增强DC/HCC融合细胞疫苗诱导抗肝癌免疫作用的相关机制.方法 皮下建立小鼠肝癌模型,24只小鼠随机分为4组:(1)环磷酰胺联合疫苗组[环磷酰胺(CTX)+ VAC];(2)疫苗组(VAC);(3)单纯环磷酰胺组(CTX);(4)对照组.各组治疗后,取外周血测定CD8+及CD4+淋巴细胞比例,同时取肿瘤组织及脾脏组织分别行苏木素-伊红(HE)染色和免疫组织化学观察肿瘤坏死和CD8+细胞及Treg+细胞的浸润,并用细胞计数试剂盒(CCK-8)检测脾脏淋巴细胞特异性细胞毒T淋巴细胞(CTL)活性.结果 与其他各组比较,CTX+ VAC组外周血CD4+及CD8+细胞比例增高[ CTX+ VAC:17.50％、14.69％;VAC:16.17％、13.07％;CTX:12.17％、11.59％;对照组:12.24％、11.16％];肿瘤组织可见大量肿瘤细胞坏死,脾脏组织中Foxp3+细胞浸润减少,CD8+细胞浸润增高,CTL对肿瘤细胞杀伤作用明显增强(P＜0.05).结论 通过CTX抑制荷瘤小鼠微环境及外周血中的Treg细胞,可以明显增强DC/HCC融合疫苗对肿瘤的杀伤作用.     

次级淋巴趋化因子(SLC/CCL21)基因与肿瘤裂解产物构建树突状前列腺癌瘤苗的抗肿瘤免疫作用研究

目的 探讨转染次级淋巴趋化因子基因的树突细胞(DC)瘤苗在小鼠前列腺癌中的抗肿瘤效应.方法 通过脂质体法将次级淋巴趋化因子基因转染至小鼠骨髓来源的树突状细胞,构建DC瘤苗;逆转录-聚合酶链反应检测SLC;种瘤24 d后SLC组的瘤体平均体积为(1430±86)mm3,45 d后仍有50%的荷瘤小鼠存活,与其他两组比较差异有统计学意义(P＜0.05);免疫组织化学荧光染色可见SLD组中CD4+、CD8+T细胞和CD11+DC的浸润率分别为(15.24±0.67)%、(¨.02±0.73)%和(14.50±0.51)%,与DC组比较差异有统计学意义(P＜0.05).结论 转染SLC的DC瘤苗能有效诱导抗肿瘤的免疫效应,其免疫效应是通过趋化大量CD4+、CD8+T细胞及CD11+DC至肿瘤部位而发挥作用.     

膀胱癌错配修复基因hMSH2表达的研究

目的 探讨错配修复基因hMSH2在膀胱移行细胞癌中的表达情况及其与肿瘤细胞增殖、凋亡的关系.方法 采用免疫组化法检测101例膀胱移行细胞癌错配修复基因hMSH2以及细胞增殖抗原Ki-67的表达情况,原位末端标记(TUNEL)法检测肿瘤细胞凋亡情况.结果 hMSH2表达于非膀胱肿瘤尿路上皮及部分膀胱移行细胞癌的细胞核,膀胱移行细胞癌组低表达率较非膀胱肿瘤膀胱组织组高(P=0.004,＜0.05);膀胱移行细胞癌pT2-pT4组中hMSH2的低表达率比pTis-pT1组的低表达率高(P=0.016,＜0.05);G1、G2、G3三组间低表达率的总体差别有统计学意义(P=0.033,＜0.05),G1+G2组与G3组之间差别有统计学意义(P=0.036＜0.05);有无淋巴结转移组差别无统计学意义(P=0.317).hMSH2弱表达组与强表达组间凋亡指数(AI)均值差异非常显著(P＜0.01),Ki-67标记指数(Ki-67 LI)均值差异不显著(P＞0.05),AI/KI值差异经统计学分析具有统计学意义(P＜0.05).结论 hMSH2基因突变或功能缺失与膀胱移行细胞癌的发生有关,可能系肿瘤发生过程中的重要事件,并可能与肿瘤细胞凋亡有关,而与增殖活性无关.     

携带4-1BBL基因的胃癌细胞总RNA转染树突状细胞疫苗的研究

目的 观察携带4-1BBL基因的胃癌细胞总RNA转染树突状细胞疫苗,在小鼠体内诱导的抗肿瘤效应以及对小鼠免疫力的影响.方法 用脂质体法把pMKITneo/4-1 BBL质粒导入小鼠胃癌细胞MFC内,再提取此细胞的总RNA并转染至树突状细胞内制备MFC/4-1BBL/DC疫苗;把MFC细胞注射于20只615小鼠皮下建立荷瘤小鼠胃癌模型,并随机分为对照组、DC组、MFC/DC组和MFC/4-1BBL/DC组,每组5只;在MFC细胞接种后第7、14天给予相应DC疫苗治疗,于肿瘤细胞接种后第21天,处死实验动物,测量瘤重、测定肿瘤细胞的凋亡率及外周血的CD4+、CD8+T细胞和NK细胞的含量.结果 MFC/4-1BBL/DC组小鼠平均瘤重(2.06±0.39)g显著低于对照组(3.82±0.57)g、DC组(3.63±0.51)g、MFC/DC组(2.67±0.32)g(P＜0.05);且MFC/4-1BBL/DC组肿瘤细胞凋亡率(28.58±2.84)%明显高于MFC/DC组(25.03±1.88)%、DC组(20.66±2.71)%及对照组(19.09±2.73)%(P＜0.05);MFC/4-1BBI/DC组小鼠外周血CID4+T、NK细胞数明显高于对照组和其他治疗组(P＜0.05).结论 携带4-1BBL基因的胃癌细胞总RNA转染树突状细胞疫苗能够提高荷瘤机体的免疫能力、抑制肿瘤细胞的生长、促进肿瘤细胞的凋亡.

Abstract：

Objective To observe the induced anti-tumor effects and immune state in vivo by the transfection of dendritic cell vaccine into the total RNA of gastric cancer cells carrying 4-1BBL gene.Methods The liposome-mediated pMKITneo/4-1BBL gene was inserted into the MFC gastric cancer cells,and the cell total RNA was extracted and transfected into dendritic cells to make the MFC/4-1BBL/DC vaccine.After MFC cells were injected into the 615 mouse to establish tumor-bearing mouse model,and those 20 mice were randomly divided into control group,DC group,MFC/DC group,MFC/4-1BBL/DC group.The dendritic cell vaccine was subcutaneously injected on the day 7 and 14 after inoculation of tumor cells,and on the day 21 animals were killed and tumor weight was measured,tumor cell apoptosis rate was assayed and the contents of CD4 +,CD8 + T cells and NK cells in peripheral blood were analyzed.Results The mean tumor weight in MFC/4-1BBL/DC group (2.06 ±0.39) g was significantly less than that in control group (3.82 ±0.57) g,DC group (3.63 ±0.51 ) g,MFC/DC group (2.67 ±0.32) g (P ＜0.05).Moreover the apoptosis rate in MFC/4-1BBL/DC group (28.58 ± 2.84 ) % was significantly higher than that in MFC/DC group (25.03 ± 1.88)%,DC group (20.66 ±2.71 )% and control group ( 19.09 ±2.73 )% (P ＜0.05).The percentage of CD4 + T,NK cells in MFC/4-1BBL/DC group was significantly higher than in other groups ( P＜0.05).Conclusion The transfection of dendritic cell vaccine into the total RNA of gastric cancer cells carrying 4-1BBL gene can increase immunity of the bearing tumor mice,inhabit tumor growth and promote tumor cell apoptosis.     

姜黄素对直肠癌CD133+肿瘤干细胞样细胞群体放疗增敏作用的研究

目的 探讨姜黄素对体外、体内直肠癌CD133+肿瘤干细胞样细胞群放疗敏感性的影响.方法 采用免疫磁珠分选法对直肠癌HRT-18细胞进行干细胞分选后随机分成姜黄素组、放疗组、姜黄素联合放疗组,应用MTT法检测24、48和72 h各组细胞生长抑制情况;采用Annexin V/PI双染流式细胞仪检测各组细胞凋亡情况.将分选的CD133+直肠癌细胞移植于裸鼠右脚垫建立移植瘤模型,将模型鼠分为姜黄素组、放疗组、姜黄素联合放疗组,每组8只,观察瘤体动态生长情况并用原位末端标记技术检测瘤体内细胞凋亡情况.结果 低剂量姜黄素联合放疗对直肠癌CD133+肿瘤干细胞样细胞群(24 h生长抑制率:18.7％±1.7％)较放疗组(14.6％±1.0％)具有明显的生长抑制作用(P＜0.01);姜黄素联合放疗组细胞凋亡率(28.8％±3.7％)与放疗组(13.1％±1.4％)比较差异有统计学意义(P＜0.01);治疗6d时,姜黄素联合放疗组的瘤体体积为(521 ±79) mm3,与放疗组的(717 ±134) mm3比较差异有统计学意义(P＜0.01);姜黄素联合放疗组瘤体细胞凋亡指数(26.1％±3.3％)较放疗组(12.0％±2.1％)明显增高,两者比较差异有统计学意义(P＜0.01).结论 姜黄素可显著提高CD133+肿瘤干细胞样细胞群的放疗敏感性.     

1-甲基色氨酸对胰腺癌荷瘤鼠中调节性T细胞数量变化的影响

目的 观察1-甲基色氨酸(1-MT)对胰腺癌荷瘤鼠中调节性T细胞(Treg)数量变化的影响,比较树突状细胞(DC)疫苗与1-MT联合应用前后抗肿瘤作用的强弱.方法 建立小鼠胰腺癌模型;利用流式细胞术检测荷瘤鼠应用1-MT前后肿瘤组织周围引流淋巴结(TDLNs)及脾脏中CD4~+ CD25~+T细胞占CD4~+T比例;荧光定量聚合酶链反应(PCR)测量Foxp3在TDLNs及脾脏mRNA水平;利用肿瘤细胞裂解物冲击DC制备DC疫苗,并根据是否与1-MT联合应用分组(各组均为n=8);观测各组肿瘤体积的差异.结果 应用1-MT后,荷瘤鼠CD4~+ CD25~+ T细胞占CD~+T细胞的比例明显低于未应用组(TDLNs)分别为(16.01±2.21)%和(25.00±2.16)%(P<0.05);脾脏分别为(13.11±1.93)%和(22.14±2.33)%(P<0.05,P<0.01);应用1-MT组Foxp3 mRNA表达水平显著低于未应用组,应用1-MT组相对表达值:TDLNs0.947±0.216、脾细胞1.198±0.347,而未应用组分别为:1.927±0.256、1.798±0.237(P<0.05);1-MT+DC疫苗组肿瘤生长显著受到抑制,第36天肿瘤体积为(789.0±111.0)mm~3;显著小于DC疫苗组、1-MT组及对照组,肿瘤体积分别为:(1768.0±251.3)、(1854.0±192.1)、(1899.0±201.2)mm~3(P<0.01).结论 1-MT可以有效抑制胰腺癌荷瘤鼠癌组织周围引流淋巴结及脾脏CD4~+ CD25~+ Treg细胞的数量增加,从而增强DC疫苗抗肿瘤作用.     

吉西他滨化疗对免疫健全小鼠Panc02胰腺癌的作用以及对免疫环境的影响

目的 建立免疫健全小鼠Panc02胰腺癌皮下种植瘤模型.利用该模型观察吉西他滨化疗对免疫健全小鼠胰腺癌的作用以及对全身及肿瘤局部免疫环境的影响.方法 利用C57BL/6J小鼠同源Panc02胰腺癌细胞建立皮下种植瘤模型.待肿瘤生长至75 ～ 100 mm3时,将荷瘤小鼠分为化疗组和对照组.化疗组利用吉西他滨50 mg/kg腹腔内注射化疗,每周2次,共4周.绘制肿瘤生长曲线,最终称量荷瘤小鼠体质量、肿瘤重量及脾脏重量.流式细胞计数检测外周血与肿瘤组织中10个免疫细胞群的变化.实时荧光定量反转录-聚合酶链反应检测荷瘤小鼠脾脏及肿瘤组织中7种细胞因子水平.免疫组织化学法及Western blot检测CD34及淋巴管内皮透明质酸受体-1(LYVE-1)蛋白表达,并计数肿瘤组织中微血管密度(MVD)及淋巴管密度(LVD).结果 化疗组肿瘤体积明显小于对照组,在各个时间点比较差异有统计学意义(P＜0.05).化疗组荷瘤小鼠体质量明显小于对照组[(21.00±1.88)g比(28.36±1.06)g,P＜0.01].化疗组终末肿瘤重量明显小于对照组[(641.67 ±289.92) mg比(1 492.00±462.73)mg,P＜0.01].化疗组与对照组脾脏重量比较差异无统计学意义(P＞0.05).化疗后外周血中CD11c+树突状细胞增多[(22.93±2.26)％比(16.53±2.68)％,P＜0.05],CD11b+ Gr-1+髓系来源抑制细胞(MDSC)减少[(3.00±0.10)％比(7.03±0.32)％,P＜0.01].化疗后肿瘤组织中CD3+T淋巴细胞[(10.70±1.21)％比(21.10±3.54)％,P＜0.01]及MDSC[(5.10 ±2.11)％比(10.50±0.72)％,P＜0.05]减少,而树突状细胞[(17.13±3.21)％比(10.43±1.60)％,P＜0.05]、CD19+B细胞[(17.13±2.68)％比(7.90±1.87)％,P＜0.01]、Gr-1+粒细胞[(79.50 ±5.86)％比(46.00±3.75)％,P＜0.01]、CD3+NK1.1+自然杀伤T细胞(NKT)[(9.77±1.56)％比(4.90±1.81)％,P＜0.05]增多.化疗后脾脏中白细胞介素-4 (IL-4)表达升高(P＜0.05),而肿瘤坏死因子-α(TNF-α,P＜0.05)及IL-2(P＜0.01)表达下降.化疗后肿瘤组织中IL-4及转化生长因子(TGF)-β表达升高(P＜0.05),而IL-6、干扰素(IFN)-γ、TNF-α及IL-2表达均下降(P＜0.05或P＜0.01).化疗后肿瘤组织中MDSC效应产物精氨酸酶-1(Arginase-1)明显下降(P＜0.05).化疗后肿瘤组织中MVD(18.47±2.61比30.40±3.92,P ＜0.05)及LVD(6.66±2.77比16.27±2.02,P＜0.01)均下降.结论 吉西他滨可以抑制小鼠Panc02胰腺癌生长以及肿瘤组织中淋巴管及血管的生成,但也诱导产生了肿瘤局部和全身的免疫抑制效应,以肿瘤局部免疫抑制作用尤为明显.化疗诱导产生的免疫抑制效应以及肿瘤血管生成减少导致的肿瘤组织中血药浓度下降,可能是影响胰腺癌疗效的重要原因,有望成为提高胰腺癌化疗效果的重要靶点.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.