西罗莫司与钙调磷酸酶抑制剂联合方案在慢性移植肾肾病中的应用

目的 探讨西罗莫司(SRL)与减低剂量的环孢素A(CsA)或他克莫司(Tac)联合方案在慢性移植肾肾病(CAN)中的应用.方法 53例无特定病因所致的CAN患者,在原CsA(或Tac)+吗替麦考酚酯(MMF)+泼尼松(Pred)的免疫抑制方案上加用SRL(四联方案),其中CsA(或Tac)和MMF的用量减少25％～50％.治疗12个月,观察受者血肌酐、肾小球滤过率(GFR)、血胆固醇、血甘油三酯、尿蛋白等的改变.结果 四联方案治疗前患者血肌酐为(161.51±106.48)μmol/L,治疗后1个月为(138.47±67.74) μmol/L,治疗后6个月为(126.51±56.21)μmol/L,治疗后12个月为(123.43±54.18)μmol/L.与治疗前相比较,治疗6个月和12个月后,差异有统计学意义(P＜0.05,P＜0.01).四联方案治疗前患者GFR为(0.754±0.302) ml/s,治疗后1个月为(0.868±0.358)ml/s,治疗后6个月为(0.952±0.347) ml/s,治疗后12个月为(1.007±0.394) ml/s.治疗6个月和12个月后,患者GFR与治疗前相比较,差异有统计学意义(P＜0.05,P＜0.01).治疗1、6和12个月后,患者血胆固醇和甘油三酯与治疗前相比较,差异均无统计学意义(P＞0.05,P＞0.05).四联方案治疗前患者尿蛋白阳性率为9.4％,治疗后1个月为13.2％,治疗后6个月为22.6％,治疗后12个月为26.4％.治疗12个月后蛋白尿阳性率与治疗前相比较,差异有统计学意义(P＜0.05).结论 应用SRL+ CsA(或Tac)+ MMF+ Pred四联方案改善了CAN患者的血肌酐和GFR,但增加了患者蛋白尿的发生率.     

肺移植100例临床分析

目的 探讨肺移植术后免疫抑制方案的安全性及有效性、术后并发症、死亡原因及其危险因素等.方法 回顾性分析100例肺移植受者的临床资料.100例受者中,单肺移植72例,双肺移植28例,61例在体外循环支持下完成,其中常规体外循环(CPB)5例,体外膜肺氧合(ECMO) 56例.2007年之前53例受者使用环孢素A(CsA)+吗替麦考酚酯(MMF)+皮质激素的三联免疫抑制方案预防排斥反应(CsA组),随后47例采用他克莫司(Tac)+ MMF+皮质激素的三联免疫抑制方案(Tac组),所有受者均使用了达利珠单抗或巴利昔单抗进行免疫诱导治疗.结果 受者术后1、2、3、5年累积存活率分别为73.3％、61.6％、53.5％和40.7％,CsA组受者存活时间为(36.57±3.44)个月,Tac组受者存活时间为(35.00±2.33)个月,两组比较,差异无统计学意义(P＞0.05).术后主要死亡原因包括原发性移植物功能丧失(PGD)、急性排斥反应(AR)、闭塞性细支气管炎(BOS)、感染等.CsA组AR和BOS的发生率明显高于Tac组(P＜0.05),但Tac组术后新发糖尿病的发生率显著高于CsA组(P＜0.05).等级相关分析显示,AR与BOS的发生呈正相关(相关系数=0.340,P＜0.01).单因素和多因素COX比例风险回归模型分析结果均显示,使用循环支持,原发病为特发性肺间质纤维化,术后出现AR、BOS和感染等因素会降低受者的存活时间(P＜0.05).结论 肺移植术后以CsA或Tac为主的免疫抑制方案均是有效的免疫抑制措施.术后加强随访、及时处理出现的并发症是延长受者存活时间和改善受者生存质量的关键.     

肾移植后胰岛素抵抗的危险因素以及与代谢综合征关系的临床研究

目的 探讨肾移植术后发生胰岛素抵抗(IR)的危险因素以及与代谢综合征的关系.方法 对133例肾移植受者进行前瞻性观察,患者移植前无糖尿病病史,入组时未发生急性排斥反应和免疫抑制剂肾毒性,无蛋白尿,肝、肾功能正常,无严重感染.术后采用环孢素A(CsA)、霉酚酸酯(MMF)和泼尼松(Pred)预防排斥反应者108例(CsA组),采用他克莫司(Tac)、MMF和Pred预防排斥反应者19例(Tac组),采用西罗莫司者6例.1年后进行血、尿生化及体格检查,并计算体重指数(BMI)和稳态模型胰岛素抵抗指数(HOMA-IR).随机抽取普通社区人群200名作为对照.结果 肾移植受者的代谢综合征发生率为33.1%(44/133),显著高于普通社区人群的15%(30/200),差异有统计学意义(P＜0.05).肾移植受者中超重/肥胖者(BMl≥24 kg/m2)39例,其HOMA-IR和代谢综合征发生率明显高于BMI正常者(P＜0.05,P＜0.01).Tac组的空腹血糖为(6.19±1.61)nmml/L,HOMA-IR为0.95±0.53,均高于CsA组的(5.50±1.17)mmol/L和0.68±0.56,差异有统计学意义(P＜0.05,P＜0.05),且HOMA-IR与血Tac浓度存在正相关(r=0.521,P＜0.05).合并代谢综合征的肾移植受者的HOMA-IR为1.01±0.56,显著高于无代谢综合征者的0.58±0.53(P＜0.01);高甘油三酯血症、高胆固醇血症以及高血压者的HOMA-IR水平明显升高(P＜0.05).结论 超重/肥胖以及使用Tac(尤其是血Tac浓度较高时)是引起肾移植受者IR的危险因素,而IR与肾移植后的代谢综合征关系密切.     

DCD供者CYP3A5基因型对肝移植受者术后他克莫司个体化用药的指导意义

目的 研究心脏死亡器官捐赠(DCD)供者的CYP3A5基因型对肝移植受者术后早期Tac起始用量的指导意义,为Tac的使用提供个体化方案.方法 选择2010年3月至2013年3月接受DCD供肝移植,且与供者CYP3A5基因型不相同的受者36例,将受者分为实验组和对照组.两组受者术后均采用Tac+吗替麦考酚酯+泼尼松的三联免疫抑制方案,实验组受者根据供者CYP3A5基因型的不同调整Tac的起始用量,对照组受者按照传统方法经验给药.两组受者吗替麦考酚酯和泼尼松的使用无差别.结果 术后7d,实验组受者的血Tac浓度为(7.47±1.83)μg/L,达目标血Tac浓度的受者占72.2％(13/18),对照组为(8.68±5.14)μg/L,达目标血Tac浓度的受者占38.9％(7/18),两组比较,差异有统计学意义(P＜0.05).实验组需要调整Tac剂量的受者占22.2％,而对照组受者占55.6％,两组比较,差异有统计学意义(P＜0.05).术后3个月内,实验组与对照组急性排斥反应发生率分别为22.2％(4/18)和27.8％(5/18),Tac不良反应发生率分别为11.1％(2/18)和22.2％(4/18),实验组均低于对照组,但差异均无统计学意义(P＞0.05).结论 根据DCD供者CYP3A5基因型的不同,可以科学调整Tac的初始剂量,使肝移植受者术后尽早达到目标血Tac浓度,减少排斥反应发生率和降低Tac不良反应,实现Tac的个体化用药.     

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.     

环孢素A转换为他克莫司对慢性移植肾肾病患者的治疗效果

目的 探讨由环孢素A(CsA)转换为他克莫司(Tac)为主的免疫抑制方案对慢性移植肾肾病(CAN)患者的治疗效果.方法 选择接受同种肾移植后发生CAN的患者153例,患者肾移植后均采用CsA、吗替麦考酚酯(MMF)及泼尼松(Pred)的免疫抑制方案.根据是否以Tac替换CsA将患者分为两组.(1)CsA组:45例,进入研究后患者维持原免疫抑制方案.(2)Tac组:108例,进入研究后将CsA转换为Tac,停用CsA后立即开始服用Tac,MMF和Pred的用法同CsA组.对所有患者随访12个月,观察人/移植肾存活率、急性排斥反应发生率、移植肾功能、24 h尿蛋白定量、移植肾穿刺病理学活检及免疫抑制剂的不良反应等指标.结果 随访12个月时,CsA组和Tac组患者存活率均为100%,移植肾存活率分别为86.6%和93.5%(P＜0.05);急性排斥反应发生率分别为4.4%(2/45)和3.7%(4/108)(P＞0.05),6例发生急性排斥反应的患者均经甲泼尼龙冲击治疗3 d后逆转.Tac组患者移植肾功能明显改善,并且出现重度蛋白尿、重度肾间质纤维化和肾小管萎缩的患者比例较CsA组显著减少(P＜0.05).Tac组有13.8%(15例)的患者出现轻度血糖增高,发生率显著高于CsA组的4.4%(2例)(P＜0.05);Tac组有22.2%(24例)的患者发生高血压,发生率显著低于CsA组的55.6%(25例)(P＜0.05);17例因使用CsA而出现牙龈增生和多毛症者,经转换治疗后,症状均明显好转.结论 由CsA转换为Tac为主的免疫抑制方案能够显著改善CAN患者的移植肾功能,延缓CAN的发展,转换过程中未发生严重Tac不良反应并且改善了使用CsA时出现的不良反应.

Abstract：

Objective To investigate the effect of conversion from cyclosporine A (CsA) to tacrolimus (Tac) on chronic allograft nephropathy (CAN). Methods 153 CAN patients undergoing kidney transplantation received CsA, mycophenolate mofetil (MMF) and prednisone (CsA-MMF-Pred) regimen after kidney transplantation, and divided into 2 groups according to whether CsA were maintained in the immunosuppressive regimen: CsA + MMF + Pred group (CsA group, n = 45); Tac + MMF + Pred group (Tac group, n = 108). The patients were followed up with patient/kidney survival rate, acute rejection incidence, renal function, 24-h proteinuria and adverse events of immunosuppressive drugs for 12 months. Results Compared with CsA group, the transplanted kidney survival rate was significantly higher in Tac group (93. 5 % vs 86.6 %, P＜0. 05). Acute rejection (AR) was diagnosed in 4. 4 % (2/45) of recipients in CsA group and 3. 7 % (4/108) in Tac group (P＞0. 05) respectively. Acute rejection (2 cases in CsA group and 4 in Tac group) was reversed by 500 mg of methylprednisolone for consecutive 3 days, and the patients in Tac group showed a significantly lower degree of interstitial fibrosis and tubular atrophy (IF/TA) (P＜0. 05).Renal allograft functions and 24-h proteinuria during a follow-up period of 12 months were significantly improved in Tac group (P ＜ 0. 05). Incidence of mild hyperglycemia in Tac Group (13.8 %, 15/108) was significantly higher than in CsA group (4.4 %, 2/45), and that of hypertension in Tac group (22. 2 %, 24/108) was significantly lower than in CsA group (55.6 %,25/45). CsA-related side effects (such as hirsutism and gingival hypertrophy) in 17 patients were greatly improved after conversion from CsA to Tac treatment. Conclusion The conversion from CsA to Tac on the patients with CAN can improve renal allograft function, retard the progression of renal allograft dysfunction, reduce the incidence of CsA-related side effects and not generate serious adverse effects of Tac.     

不同免疫抑制剂对肾小球系膜细胞增殖的影响

目的 探讨不同免疫抑制剂对受损的肾小球系膜细胞增殖的影响.方法 在体外用细胞松弛素B可逆性地损害处于增殖期的大鼠肾小球系膜细胞株(HBZY-1细胞),然后将细胞分成5组:对照组,仅加入橄榄油10 μl;环孢素A(CsA)组,加入CsA 3μg/ml(2.5 mmol/L);他克莫司(Tac)组,加入Tac 1μg/ml;吗替麦考酚酯(MMF)组,加入MMF 0.3μg/ml;西罗莫司(SRL)组,加入SRL10 ng/ml.在药物处理后6、12和24 h时,采用专业图像分析软件对各组不同时间点的系膜细胞进行形态观察、计数和增殖情况分析.结果 药物处理后,各组HBZY-1细胞的形态均有所恢复.处理后6 h时,除Tac组HBZY-1细胞数明显高于对照组外,其余各组与对照组之间的差异均无统计学意义(P＞0.05).12 h时,各组HBZY-1细胞数之间的差异均无统计学意义(P＞0.05).24 h时,对照组和MMF组之间细胞数的差异无统计学意义(P＞0.05);而其余各组的细胞数均显著增高,与对照组、MMF组以及与组内其他时点相比较,差异均有统计学意义(P＜0.05),其中尤以CsA组和Tac组的细胞数量增加最为显著,SRL组增加的幅度低于CsA组和Tac组(P＜0.05).结论 CsA、Tac、SRL和MMF均可不同程度地减轻受损大鼠肾小球系膜细胞的损伤和促进其恢复,但是其中CsA和Tac明显地促进了细胞的增殖,SRL促细胞增殖作用不明显,而MMF则几乎不引起系膜细胞增殖.     

肾移植受者血他克莫司浓度对外周血自然杀伤细胞及其受体的影响

目的 研究肾移植受者血他克莫司(Tac)浓度对外周血自然杀伤(NK)细胞及其受体的影响.方法 将2007年12月至2009年7月间的60例受者纳入研究,术后受者均采用以Tac为基础的免疫抑制方案.根据术后6个月监测到的血Tac浓度将受者分为低浓度组和高浓度组[各为30例,术后6个月时血Tac浓度分别为(6.84±1.72)和(11.88±2.59)μg/L],另以20名健康志愿者作为对照组.术前和术后6个月,采用流式细胞术检测NK细胞及其抑制性受体(CD85j和CD158d)和活化性受体( CD94、NKG2D)的表达情况,采用酶联免疫吸附试验法检测免疫耐受分子分泌型HLA-G5( sH LA-G5)的表达水平.结果 术前低浓度组和高浓度组受者外周血NK细胞绝对值均较对照组显著降低(P＜0.05),术后6个月时低浓度组和高浓度组NK细胞比例及绝对值较对照组均显著降低(P＜0.05),低浓度组NK细胞绝对值显著高于高浓度组(P＜0.05).术前两组间CD85j、CD158d、CD94、NKG2D表达的差异均无统计学意义(P＞0.05);术后6个月时低浓度组和高浓度组CD85j和CD158d的表达较术前升高,CD94和NKG2D的表达下降,而低浓度组CD85j和CD158d的表达显著高于高浓度组(P＜0.05).经Spearman系数统计,CD85j和CD158d与sHLA-G5呈正相关(P＜0.01),NKG2D与sHLA-G5呈负相关(P＜0.01).结论 肾移植受者血Tac浓度与外周血NK细胞数量及其受体的表达具有相关性,低血Tac浓度受者的NK细胞数量及其抑制性受体的表达升高,仍然能有效保护移植肾功能.     

无症状性动静脉瘘肾移植受者闭瘘后左心形态和功能的变化

目的 观察无症状性动静脉瘘肾移植受者闭瘘后左心形态和功能的变化.方法 连续选取2007年3月至2011年3月间符合病例纳入标准的无症状性动静脉瘘肾移植受者60例,采用随机表法将受者分为闭瘘组及对照组,每组各30例.超声心动图检查两组受者,比较组内和组间受者的心输出量(CO)、心脏指数(CI)、射血分数(EF)、左心室舒张末期容积(LVEDV)、左心室质量指数(LVMI)的变化及差异.结果 肾移植术后12个月,闭瘘组及对照组受者CO、LVEDV和LVMI较移植前均降低(P＜0.05,P＜0.01,P＜0.05),CI也呈降低趋势(P＞0.05),而EF较移植前升高(P＜0.01).与术后12个月(闭瘘前)相比较,闭瘘组受者术后18个月(闭瘘后6个月)的CO、CI、LVEDV和LVMI进一步降低(P＜0.01,P＜0.05,P＜0.05,P＜0.05),而EF进一步升高(P＜0.05).对照组术后18个月的CO、CI、LVEDV、LVMI和EF与移植后12个月时相比较,差异均无统计学意义(P＞0.05).闭瘘组术后18个月的CO为(4.4±0.8)L/min,CI为(3.0±0.8)L·min-1·m-2,LVEDV为(110.0±17.4)ml,LVMI为(114.7±42.5)g/m2,均明显低于同期对照组的检测结果(P＜0.01,P＜0.05,P＜0.05,P＜0.05) ;闭瘘组术后18个月的EF为(75.2±7.4)％,明显高于同期对照组的结果(P＜0.05).结论 透析患者的左心功能均在肾移植后得到改善,左心肥大有所恢复,闭瘘后左心功能改善及左心肥大的恢复更为明显.     

肾移植后早期受者BK病毒DNA拷贝数的影响因素研究

目的 探讨肾移植后早期受者BK病毒的负荷状况及其影响因素.方法 检测80例同种异体肾移植受者血清和尿液中的BK病毒DNA拷贝数,并且分析肾移植临床常见的参数对BK病毒负荷的影响.结果 80例中,BK病毒血症阳性者为7例(占8.75％),BK病毒尿症阳性者为30例(占37.5％).＞50岁组受者血清和尿液中BK病毒DNA拷贝数都明显高于≤50岁组(P＜0.05);他克莫司组血清BK病毒DNA拷贝数高于环孢素A(CsA)组(P＜0.05),前组受者血清BK病毒负荷高峰时间在术后14个月,而后者在术后10个月.两组尿液BK病毒负荷高峰时间提前,Tac组为术后2个月,CsA组为术后8个月.结论 年龄＞50岁、正在服用他克莫司可能为BK病毒再次激活及BK病毒肾病的高危因素.     

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.     

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.     

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.     

Intraoperative autotransfusion is associated with modest reduction of allogeneic transfusion in prosthetic hip surgery

Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r²=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.     

缺氧对肾小管上皮细胞分泌外泌体的影响

目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    （1）常氧（21% O₂）及缺氧（1% O₂）分别处理大鼠肾小管上皮细胞（NRK-52E）48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。（2）在共培养实验中,以不同浓度（1、10、50、100、300 mg/L）的常氧外泌体、缺氧外泌体分别干预脂多糖（LPS）诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验（ELISA）法分别检测巨噬细胞白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型氮氧化物合酶（iNOS）水平;使用Western印迹法检测巨噬细胞磷酸化（p）STAT/STAT及细胞因子信号传导抑制蛋白1（SOCS1）的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA（microRNA,miR）的表达差异。 结果    （1）离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。（2）缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌（均P＜0.01）,同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达（均P＜0.01）;对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高（P＜0.05）。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。     

In Vitro Function and Durability Assessment of a Novel Polyurethane Heart Valve Prosthesis

Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy: A controlled randomised trial

Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O₂ flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg^?1· h^?1 vs. 6.6 ± 4.8 μg · kg^?1· h^?1), a lower O₂ supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO₂ was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.