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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.