长链非编码RNA小核仁RNA宿主基因22靶向作用于微小RNA-27a-3p/胰岛素样生长因子-1信号轴对三阴性乳腺癌细胞侵袭能力的影响

目的观察三阴性乳腺癌细胞中长链非编码RNA小核仁RNA宿主基因22(SNHG22)靶向作用于微小RNA(miR)-27a-3p/胰岛素样生长因子-1对细胞侵袭能力的影响。方法选取2019年6月至2022年3月河北医科大学第二医院甲状腺乳腺外科收治30例三阴性乳腺癌及其癌旁组织标本作为研究对象, 采用荧光定量聚合酶链反应(PCR)分析癌及癌旁组织中SNHG22和miR-27a-3p的表达变化;将SNHG22过表达质粒和miR-27a-3p模拟物(mimics)分别转染至三阴性乳腺癌MDA-MB-231细胞中, 利用细胞侵袭实验观察两者对细胞侵袭能力的影响;利用生物信息学软件及双荧光素酶报告基因分析SNHG22和miR-27a-3p的关系及miR-27a-3p的下游靶基因。将miR-27a-3p mimics、miRNA阴性对照(miR-NC)分别与SNHG22共转染后, 观察上调miR-27a-3p表达对过表达SNHG22的MDA-MB-231细胞侵袭能力的影响。两组间比较采用t检验。结果荧光定量PCR实验结果显示, SNHG22在三阴性乳腺癌组织中的表达水平(3.184±1.800)明...     

微小RNA-30a-5p激活Wnt/β-连环蛋白信号通路对胃癌细胞增殖与侵袭的作用机制

目的探讨人微小RNA(has-miR)-30a-5p调控Wnt/β-连环蛋白(β-catenin)信号通路对胃癌细胞增殖及侵袭的影响及其作用机制。方法体外培养胃癌MKN-45细胞;在所研究胃癌细胞系中使用小干扰RNA(siRNA)转染建立miR-30a-5p的敲除和过表达模型, 胃癌MKN-45细胞分为3组:miR-30a-5p小干扰RNA(miR-30a-5p inhibitor)组, miR-30a-5p过表达RNA组和空白对照组(NC), 荧光定量聚合酶链反应(qPCR)和蛋白质印迹法(Western blot)检测Wnt/β-catenin信号通路相关标志物Cyclin D1(CCND1)基因的表达水平;双荧光素酶报告基因实验验证miR-30a-5p与Wnt信号通路下游关键基因CCND1的靶向调节关系;在培养的胃癌细胞MKN-45中加入Wnt/β-catenin信号通路抑制剂-银杏双黄酮, 分为miR-30a-5p inhibitor组、miR-30a-5p inhibitor+银杏双黄酮组、miR-30a-5p Inhibitor NC组及miR-30a-5p Inhibit...     

微小RNA-30a-5p抑制胃癌增殖与侵袭的机制

目的探讨人微小RNA(has-miR)-30a-5p调控Frizzled 2(FZD2)基因激活Wnt/β-连环蛋白(β-catenin)信号通路对胃癌细胞增殖及侵袭的作用机制。方法体外培养胃癌MKN-45细胞;在胃癌细胞系中使用小干扰RNA(siRNA)转染建立微小RNA(miR)-30a-5p的敲除和过表达模型, 胃癌MKN-45细胞分为3组:miR-30a-5p小干扰RNA(miR-30a-5p inhibitor)组, miR-30a-5p过表达RNA(miR-30a-5p mimics)组和空白对照组(negative control, NC), 荧光定量聚合酶链反应(qPCR)、蛋白质印迹法(Western blot)检测miR-30a-5p的直接靶基因FZD2基因及Wnt/β-catenin信号通路下游关键基因c-myc的表达水平;双荧光素酶报告基因实验验证miR-30a-5p与直接靶基因FZD2的靶向调节关系;在培养的胃癌细胞MKN-45中加入Wnt/β-catenin信号通路抑制剂-银杏双黄酮, 分为miR-30a-5p inhibitor组、miR-30a-5p i...     

瘢痕疙瘩microRNA表达谱的筛选及miR-199a-5p生物功能的初步研究

目的 探讨并筛选出瘢痕疙瘩相关微小RNAs(miRNAs),检测其对瘢痕疙瘩成纤维细胞(keloid fibroblasts,KF)增殖的影响.方法 收集手术切除瘢痕疙瘩及正常皮肤组织标本各8例,采用基因芯片检测瘢痕疙瘩与正常皮肤组织差异表达的miRNA,并采用qRT-PCR验证,在瘢痕疙瘩成纤维细胞株中转染miRNA模拟物,模拟细胞中成熟miRNA的高表达,用EdU检测方法检测其对瘢痕疙瘩成纤维细胞增殖的影响.结果 ①通过芯片检测发现包括miR-199a-5p在内的17个差异表达的miRNAs.②qRT-PCR验证结果显示miR-199a-5p表达下调,与芯片检测结果相一致.③miR-199a-5p模拟物转染组与阴性对照组EdU的阳性率分别为(20.72±2.50)％和(27.68±4.92)％,miR-199a-5p模拟物转染组瘢痕疙瘩成纤维细胞的增殖率下降(t=2.183,P=0.047).同时,细胞的生长周期分布也发生改变,MiR-199a-5p模拟物转染组S期与G2/M期细胞百分比分别为(33.93±1.30)％和(10.87±0.80)％,阴性对照组分别为(31.39±0.79)％和(9.27±0.46)％,差异有统计学意义(P＜0.05).结论 ①瘢痕疙瘩中miRNA的差异表达有组织特异性;②miR-199a-5p在瘢痕疙瘩中的显著低表达,可影响瘢痕疙瘩成纤维细胞周期分布,抑制瘢痕疙瘩成纤维细胞增殖,提示miR-199a-5p可能参与了瘢痕疙瘩成纤维细胞增殖的调控.     

微小RNA-219a-5p通过靶向卷曲蛋白4抑制激素性股骨头坏死中骨髓间充质干细胞的增殖和成骨分化

目的观察微小RNA(microRNA,miR)-219a-5p在骨髓间充质干细胞(BMSC)中的表达及其对细胞增殖和成骨分化的影响。方法选取在2019年1月至2020年1月期间于河南省人民医院骨科接受髋关节置换的16例激素性股骨头坏死患者及9例股骨颈骨折不愈合患者分别作为实验组及对照组,提取股骨近端BMSC,利用实时定量反转录聚合酶链反应(RT-qPCR)检测miR-219a-5p和卷曲蛋白4(FZD4)在细胞中的表达水平。荧光素酶活性检测验证miR-219a-5p和FZD4的相互作用关系。利用细胞转染技术和miR-219a-5p的模拟物、抑制剂、FZD4发卡RNA(shRNA)来调控BMSC中miR-219a-5p和FZD4的表达水平。细胞计数试剂盒(CCK-8)增殖实验检测BMSC的增殖活性,茜素红染色评估BMSC的成骨分化能力。利用统计与制图软件(GraphPad Prism)统计分析实验数据。采用方差分析(ANOVA)和t检验确定计量资料各组间差异的统计学意义,计数资料的组间比较采用方差检验。结果miR-219a-5p在实验组BMSC中的相对表达量为6.03±1.39,而在对照细胞中的相对表达水平仅有1.01±0.21,两组之间差异有统计学意义(t=10.351,P<0.01)。利用数据库TargetScan预测得到miR-219a-5p的下游靶基因FZD4,RT-qPCR结果提示FZD4在实验组细胞中的表达水平为1.09±0.55,在对照组细胞中相对表达量达到4.61±1.08,两组之间差异有统计学意义(t=10.376,P<0.01)。皮尔森(Pearson)线性分析显示miR-219a-5p和FZD4在BMSC中表达水平呈负相关[r=-0.631,95%可信区间(CI):-0.763、-0.498,P<0.01]。下调实验组中miR-219a-5p的表达后,FZD4的水平升高4.34倍(t=8.426,P<0.01),而在对照组细胞中上调miR-219a-5p的表达后,FZD4的表达水平下降4.75倍,差异均有统计学意义(t=8.667,P<0.01)。荧光素酶活性检测证实了miR-219a-5p与FZD4之间的结合关系。CCK-8实验结果显示实验组BMSC培养24、48、72 h后的吸光度值分别为0.27±0.05、0.48±0.05、0.63±0.04显著低于对照组的BMSC的0.46±0.05、0.96±0.08、1.51±0.11,两组之间差异具有统计学意义(t=9.776,P<0.01)。抑制实验组中miR-219a-5p表达后细胞的增殖活性明显提高,而同时敲低FZD4的表达则会逆转上述作用。同样地,将miR-219a-5p模拟物转染对照组细胞,细胞增殖活性明显抑制。茜素红染色显示对照组细胞的阳性染色面积/总面积为0.58±0.05,明显高于实验组的0.22±0.04,差异有统计学意义(t=7.610,P<0.01)。在实验组细胞中转染miR-219a-5p抑制剂可以增强细胞的成骨分化能力,但FZD4 shRNA抵消了miR-219a-5p抑制剂对成骨能力的强化作用,且上调正常BMSC中miR-219a-5p的水平可以阻止其成骨分化过程。结论miR-219a-5p在激素性股骨头坏死BMSC中高表达,FZD4介导了miR-219a-5p对BMSC增殖及成骨分化的抑制作用。     

微小RNA-148a-3p对肝癌树突状细胞活化的影响及其机制

目的探讨微小RNA(miR)-148a-3p对肝癌树突状细胞活化的影响及其机制。方法分离肝癌患者外周血树突状细胞, 通过双荧光素酶报告验证miR-148a-3p和细胞因子信号转导抑制因子1(SOCS1)的靶向关系。树突状细胞分为4组:对照组、miR-148a-3p组、SOCS1组和miR-148a-3p+SOCS1组。通过转染miR-148a-3p类似物和/或SOCS1质粒来实现过表达。检测各组细胞中miR-148a-3p和SOCS1蛋白、抗原呈递蛋白(CD11c和CD86)、白细胞介素-6(IL-6)、干扰素-α(IFN-α)的表达水平和树突细胞迁移能力。多组间的差异采用单因素方差分析(ANOVA), 组间两两比较采用SNK-q检验。结果 miR-148a-3p组的miR-148a-3p水平高于对照组(4.21±0.38比1.00±0.07, t=66.461, P<0.05), SOCS1组的SOCS1蛋白表达水平显著高于对照组(2.91±0.25比1.00±0.08, t=58.212, P<0.05)。miR-148a-3p+SOCS1组的SOCS1蛋白水平显著高于...     

MicroRNA-133a-5p调控c-met表达对胆管癌细胞迁移和侵袭的影响

目的:探讨MicroRNA-133(miR-133)在胆管癌细胞系中的表达,研究miR-133基因表达在胆管癌细胞迁移和侵袭过程中的作用。方法:利用实时荧光定量PCR(RT-PCR)技术测定分析miR-133及其不同成熟体(miR-133b、miR-133a-3p、miR-133a-5p)在胆管癌QBC939细胞系中的表达。将胆管癌QBC939细胞系经转染后分为三组:自然生长组(空白对照组),细胞转染无关序列组(阴性对照组)以及细胞转染Anti-miR-133a-5p组(干扰组),利用RT-PCR检测各组胆管癌QBC939细胞系中miR-133a-5p、c-met的表达。然后利用Transwell小室法分别检测分析干扰miR-133a-5p基因表达对胆管癌QBC939细胞系迁移和侵袭能力的影响。结果:RT-PCR检测miR-133不同成熟体miR-133b(0.74±0.07)、miR-133a-3p(0.99±0.12)、miR-133a-5p(1.00±0.06)中的表达,其中miR-133a-5p在胆管癌QBC939细胞系中表达量最高(P0.05)。RT-PCR实验证实干扰组QBC939细胞系中miR-133a-5p(0.70±0.08)表达显著低于对照组(1.43±0.34);干扰组QBC939细胞系中c-met(0.09±0.02)表达也显著低于对照组(1.01±0.07),差异有统计学意义(P0.01)。Transwell小室实验证实干扰组中胆管癌QBC939细胞系迁移(69.5±8.3)和侵袭(19.3±3.3)能力明显低于对照组,差异均有统计学意义(P0.01)。结论:MicroRNA-133a-5p的低表达可以明显减弱c-met的表达,同时可以抑制胆管癌QBC939细胞系的迁移和侵袭能力,miR-133a-5p有可能成为胆管癌基因表达调控的新靶点。     

微小RNA-19a-3p通过调控转录因子ETS样蛋白3对乳腺癌细胞阿霉素耐药的影响

目的探讨微小RNA(miR)-19a-3p在乳腺癌细胞阿霉素耐药中的作用及其机制。方法以人乳腺癌细胞MDA-MB-231为研究对象, 根据转染物的不同, 将细胞分为对照组、miR-NC组(转染miR-19a-3p mimics阴性对照miR-NC)、miR-19a-3p mimics组(转染miR-19a-3p mimics)和miR-19a-3p mimics+si-转录因子ETS样蛋白3(ELK3)组[共转染miR-19a-3p mimics和ELK3小干扰RNA(siRNA)]。实时定量反转录聚合酶链反应(RT-qPCR)检测细胞中miR-19a-3p的表达, RT-qPCR和蛋白质印迹法(Western blot)检测细胞中ELK3的mRNA和蛋白表达, Western blot法检测细胞中P-糖蛋白(P-gp, ABCB1)的表达, 分别用不同浓度的阿霉素(0、5、10、25、50 nmol/L)处理各组细胞, 细胞计数试剂盒(CCK-8)法检测细胞增殖能力, 评价各组细胞对阿霉素的药物敏感性。多组间均数比较采用单因素方差分析, 组间两两比较采用LSD-t法。结果 miR-1...     

结核病患者外周血单核细胞miR-146a表达

目的研究miR-146a在结核病患者外周血单个核细胞中的表达水平和临床意义。方法采用Trizonl一步法从结核病患者、结核病潜伏感染者和健康对照外周血单个核细胞提取总RNA,荧光定量PCR测定miR-146a的表达。同时使用荧光定量PCR测定样本中肿瘤坏死因子受体相关因子6、白细胞介素受体相关激酶1和肿瘤坏死因子的表达。结果肺结核患者外周血单核细胞miR-146a表达较结核潜伏感染和健康对照者显著下降,而潜伏感染者miR-146a表达水平(4.49±0.61)与对照组(4.57±0.25)没有差异。同时,miR-146a下游靶基因TRAF6、IRAK-1以及TNF-α表达在活动性肺结核患者中较结核潜伏感染和健康对照者增加。结论与健康对照和潜伏感染者相比,miR-146a在结核病患者外周血单个核细胞中表达显著下降,推测miR-146a有可能成为鉴别活动性结核和结核潜伏感染新的标记物。     

IgA肾病外周血B淋巴细胞微核糖核酸差异表达及临床意义

目的通过检测人外周血B淋巴细胞微核糖核酸(microRNA)的差异表达,并分析其与IgA肾病临床病理特点、IgA1分子O-糖基化异常之间的关系,探索microRNA在IgA肾病发病中的可能机制。方法收集7例IgA肾病患者及4例正常人外周血5 ml,磁珠法分选出CD19~+B淋巴细胞,提取RNA,采用表达谱芯片筛选差异表达的microRNA。在另外29例IgA肾病患者和16例正常对照者中,对候选microRNAs用实时荧光定量聚合酶链反应(quantificational real-time polymerase chain reaction,QRT-PCR)进行验证,并分析它们与临床病理、IgA1分子半乳糖缺陷(galatose-defecient IgA1,Gd-IgA1)水平的关系。结果 IgA肾病患者外周血B淋巴细胞microRNA表达明显异常,其中85个明显上调,30个明显下调。对5个候选microRNA:miR-3189-5p、let-7g-5p、miR-4258-5p、miR-4695-3p及miR-99b-5p,进一步验证显示,其表达水平在IgA肾病患者与正常对照之间差异无统计学意义(P0.05)。且上述5个microRNA表达量与IgA肾病患者的临床病理指标没有明显的相关性。IgA肾病组血清IgA1、Gd-IgA1明显高于正常对照(P0.05或P0.01)。5个候选microRNA:miR-3189-5p、let-7g-5p、miR-4258-5p、miR-4695-3p及miR-99b-5p的水平与IgA肾病患者IgA1分子O-连接半乳糖缺陷之间没有明显相关性。结论 IgA肾病患者和正常人外周血CD19~+B淋巴细胞microRNA表达谱存在明显差异。初步验证显示miR-3189-5p、let-7g-5p、miR-4258-5p、miR-4695-3p及miR-99b-5p的表达水平在IgA肾病患者与正常对照之间差异无统计学意义,且与IgA肾病的临床病理特点和Gd-IgA1之间无明显相关性,提示这5个microRNA可能不是参与IgA肾病发病和进展的重要microRNA。     

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.     

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.     

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.     

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.