复方积雪草防治局灶节段性肾小球硬化模型大鼠足细胞损伤的实验研究

目的:探讨复方积雪草对局灶节段性肾小球硬化(focal segmental glomerulo sclerosis,FSGS)模型大鼠足细胞裂孔膜蛋白nephrin、podocin表达的影响,阐述其延缓肾小球硬化的部分分子生物学机制。方法:采用左肾摘除+阿霉素重复静脉注射方法建立FSGS模型。复方组分别予高中低剂量复方积雪草膏剂灌胃;对照组予苯那普利混悬液;于第8周末留取24h尿蛋白定量,检测血肌酐(Scr)、尿素氮(BUN)、胆固醇(TC)、三酰甘油(TG)和血浆蛋白(Alb);留取右肾标本,光镜标本行HE染色;用免疫组化法观察裂孔膜蛋白nephrin和podocin表达;RT-PCR法检测肾组织nephrin和podocinmRNA表达。结果:各复方组24h尿蛋白定量及血Scr、BUN、TC、TG较模型组有显著改善,且与西药组疗效相似。RT-PCR及免疫组化结果显示模型组足细胞裂孔膜蛋白表达较正常组明显降低(P<0.05)。而各治疗组表达较模型组均有明显增加(P<0.05),且与正常组比较差异无统计学意义(P>0.05)。结论:复方积雪草能通过上调模型大鼠肾小球内nephrin和podocin分子表达,减轻足细胞损伤,延缓肾小球硬化。     

血必净对局灶节段性肾小球硬化大鼠的肾脏保护作用

目的：观察中药血必净注射液对局灶节段性肾小球硬化症（FSGS）大鼠转化生长因子-β1（TGF-β1）和血管内皮生长因子（VEGF）表达的影响，探讨血必净对FSGS大鼠的肾脏保护作用。方法：建立单侧肾切除加重复注射阿霉素的FSGS大鼠模型，分为血必净组、模型组，并设假手术组为对照组。检测各组大鼠第0、4、6、8周24h尿蛋白定量及血生化值，计算内生肌酐清除率（Ccr）；对肾组织进行病理形态学观察，计算肾小球硬化指数（SI）、肾小球细胞外基质与肾小球面积之比（ECM／GA），采用免疫组织化学方法检测肾组织TGF-β1、VEGF的表达。结果：与模型组相比，血必净治疗组大鼠尿蛋白排泄减少，肾脏病理改变明显减轻，肾组织TGF-β1、VEGF的表达减少。结论：血必净可以抑制局灶节段性肾小球硬化大鼠肾组织TGF-β1、VEGF的高表达，具有一定的肾脏保护作用。     

局灶节段性肾小球硬化症大鼠尿足细胞动态检测及其意义

目的建立局灶节段性肾小球硬化症(FSGS)大鼠模型,观察尿中脱落的肾小球足细胞的变化,并探讨其意义。方法FSGS组(n=7):采用左颈静脉插管一次性缓慢注射嘌呤霉素核苷酸(PAN,9mg/100g体重的方法建立)FSGS大鼠模型。正常对照组(n=5):注射等量生理盐水,实验周期20周。动态检测24h尿蛋白定量;间接免疫荧光方法动态检测尿沉渣足细胞特异性标志蛋白podocalyxin(PCX)、Wilm'stumor鄄1(WT鄄1);20周末肾组织光镜下观察肾小球病变;电镜观察肾小球足细胞的改变;免疫荧光染色观察肾小球内PCX和成熟足细胞特异性标志蛋白synaptopodin(PP44)的表达。结果FSGS组大鼠24h尿蛋白定量在第天较注射前明显升高,第312天达到高峰[(672.74±98.72)比(19.31±3.15)mg/24h,P<0.01),此后开始下降,于第6周接近注射前水平,持续至11周[(35.46±14.88)比(19.31±3.15)mg/24h,P=0.0238];从12周开始再度缓慢升高,持续高水平至20周,为注射前近7倍[(140.61±68.90)比(19.31±3.15)mg/24h,P<0.01]。FSGS组大鼠从12周开始,尿足细胞出现阳性(>1～5个/HP),持续至20周。光镜显示,30%～50%肾小球出现不同程度的局灶节段性硬化;电镜证实足突部分融合并可见足突与基底膜剥离。足细胞特异标记蛋白PCX、PP44在肾小球节段性硬化部位呈现节段性缺失。对照     

尿足细胞及其相关分子在肾小球疾病中的表达

目的：探讨尿液检测局灶节段性肾小球硬化足细胞损伤与其他足细胞病之间的特点和差异。方法：入选原发性局灶节段性肾小球硬化（KSGS）患者54例,膜性肾病（MN）23例及微小病变（MCD）12例,正常对照20例。免疫荧光法计数尿足细胞,荧光实时定量PCR法定量尿沉渣足细胞相关分子nephrin、podocin、synaptopodin mRNA的表达水平,Western印迹法检测尿液WilmsTumor1（WT1）蛋白水平,免疫荧光法检测肾脏组织podocalyxin的表达及分布。结果：（1）FSGS组、MN组、MCD组和对照组尿足细胞阳性率分别是63％、34．8％、33．3％和0,FSGS组与其余各组相比差异均有统计学意义（P〈0．05）。FSGS组足细胞脱落数目显著高于MCD组、MN组和对照组（P〈0．05）,伴足细胞尿FSGS患者与不伴足细胞尿FS—GS患者相比,24h尿蛋白和血清白蛋白（Alb）差异均有统计学意义（P〈0．05）。（2）FSGS组尿沉渣足细胞nephrin mRNA表达水平显著高于MCD和MN组（P〈0．05）;FSGS组尿沉渣足细胞podocinmRNA表达显著高于MCD组（P〈0．05）,与MN组相比有升高趋势但差异无统计学意义;尿沉渣足细胞synaptopodin mRNA表达各组间差异无统计学意义。尿沉渣足细胞nephrin、podocin．synaptopodin mRNA的表达与24h蛋白尿无相关性。（3）FSGS组尿WT1蛋白量显著高于MCD和MN组。部分足细胞阴性患者尿液检测到WT1分子。（4）FSC-S患者肾组织podocalyxin较对照组、MCD和MN有明显的节段缺失。结论：局灶节段性肾小球硬化病患者足细胞损伤严重,尿足细胞与FSGS疾病活动相关。尿沉渣足细胞nephrin mRNA表达可以把FSGS与MCD和MN区分开来,尿WT1蛋白可能是足细胞早期损伤指标。     

阿霉素诱导的局灶节段性肾小球硬化小鼠足细胞损伤的机制研究

目的构建阿霉素(ADR)诱导的局灶节段性肾小球硬化(FSGS)小鼠模型, 探究足细胞损伤的分子机制。方法取24只8周龄雄性BALB/c小鼠分为生理盐水组(对照组, n=6)和FSGS模型组(ADR组, n=18), 分别按照10 mg/kg的剂量尾静脉注射生理盐水和ADR, 采集注射ADR后的7、14、28 d小鼠以及注射生理盐水后的28 d小鼠的血液、尿液和肾组织, 检测血液和尿液中血肌酐﹑尿肌酐﹑尿蛋白含量, 将肾组织进行HE和MASSON染色, 观察其形态变化, 然后采用实时定量PCR和Western blot法检测肾皮质组织中Synaptopodin和RhoA的表达。结果与对照组比较, 注射ADR 7 d后, ADR组小鼠的尿蛋白与尿肌酐比值升高, 血肌酐水平升高, 差异均有统计学意义(均P<0.05);注射ADR 7 d后, 与对照组比较, ADR组小鼠的肾皮质组织中Synaptopodin 、RhoA的mRNA和蛋白质表达量均降低, 差异均有统计学意义(均P<0.05);注射ADR 28 d后, ADR组小鼠出现肾小球硬化程度恶化、肾小管损伤和间质病变纤维化, ...     

局灶节段性肾小球硬化的新病理分型

局灶节段性肾小球硬化(FSGS)由Rich在1957年首先描述,其发生率有逐年增高趋势.FSGS是一种临床病理综合征,其特点为蛋白尿,常为肾病性蛋白尿,同时伴局灶节段性肾小球硬化和足突的消失.疾病早期,仅部分肾小球(＜50%)和/或部分毛细血管襻(<50%)发生硬化性改变.随着病变进展,肾小球逐渐弥漫硬化,甚至出现球性硬化.     

霉酚酸酯对局灶节段性肾小球硬化大鼠肾脏的保护作用

目的观察霉酚酸酯对局灶节段性肾小球硬化大鼠残肾的保护作用。方法给予局灶节段性肾小球硬化大鼠霉酚酸酯（MMF）50mg·kg^-1·d^-1、雷公藤20mg·kg^-1·d^-1。8周后观察大鼠24h尿蛋白定量、血尿素氮（BUN）、血肌酐（SCr）、血浆白蛋白（Alb）的含量以及肾脏病理改变。结果两药均能减少尿蛋白，降低BUN。在肾脏病理上，局灶节段性肾小球硬化大鼠出现局灶性肾间质纤维化，肾小球硬化，用药后病变减轻，以MMF减轻更为显著。结论MMF能抑制局灶节段性肾小球硬化大鼠肾脏中细胞的异常增殖，减少间质纤维化及肾小球硬化，减少蛋白尿，减轻肾脏的损害。     

阿霉素诱导的局灶节段性肾小球硬化小鼠TGF-β/MAPK信号通路的表达

目的观察阿霉素(ADR)诱导的局灶节段性肾小球硬化(FSGS)模型小鼠肾脏转化生长因子-β1 (TGF-β1)/丝裂原活化蛋白激酶(MAPK)信号通路的表达。 方法将8周龄雄性BALB/c小鼠(18～23 g)分为实验组和对照组,用ADR尾静脉注射进实验组小鼠,生理盐水注射入对照组,分别收集各组小鼠血、尿及肾脏组织。利用ELISA方法检测尿蛋白及血清肌酐、尿素氮,观察肾脏病理改变,实时荧光定量PCR技术检测转化生长因子-β1(TGF-β1)、Smad7和IV型胶原(Col IV)mRNA水平,Western印迹方法检测磷酸化细胞外信号调节激酶(p-ERK1/2)和磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)的蛋白水平。采用Graphpad Prism 5软件对结果进行单因素方差分析,P<0.05为差异有统计学意义。 结果实验组显示在第3天出现24 h尿蛋白增多,第22天升高更明显,与对照组相比差异有统计学意义(t＝ 8.718,P<0.001);实验组中血清肌酐及尿素氮与对照组相比,第22天升高(t＝5.12,t＝11.7;P<0.001),第32天达高峰(t＝25.7,t＝16.21;P<0.001);肾脏病理：实验组第22天可见部分肾小球系膜基质增多和系膜细胞增生,第32天出现系膜基质和系膜细胞轻至中度增生,节段加重,伴足细胞损伤,且可发现血管袢和肾小球囊粘连,符合FSGS的病理特点;荧光实时定量PCR结果显示：实验组第22天时肾脏TGF-β1 mRNA水平明显高于对照组(q＝5.091,P<0.05),Col IV mRNA相对表达量随着诱导天数而增加,在第32天时达到最高,与对照组相比差异有统计学意义(q＝5.222,P<0.05);Smad7的表达量在第32天时显著减少,与对照组比较差异有统计学意义(q＝10.64,P<0.01),与第22天比较差异亦有统计学意义(q＝9.643,P<0.01);Western印迹结果显示,第22天实验组p-ERK1/2蛋白水平较对照组降低(q＝5.570,P<0.05),第32天较对照组降低更明显(q＝8.881,P<0.01);第22天实验组p-p38MAPK表达较对照组增加(q＝30.65,P<0.001),第32天p-p38MAPK较对照组比较差异仍有统计学意义(q＝31.76,P<0.001)。 结论FSGS模型小鼠TGF-β/MAPK信号通路的表达量较对照组相比明显增加,提示TGF-β/MAPK通路有可能被激活从而参与FSGS的发病过程。     

肾移植术后移植肾局灶性节段性肾小球硬化临床分析

目的分析肾移植术后发生移植肾局灶性节段性肾小球硬化(FSGS)患者的临床和病理特征。方法回顾性分析中山大学附属第一医院器官移植科2009年3月至2012年3月经移植肾穿刺活检确诊为FSGS的25例肾移植受者资料。根据FSGS患者预后分为好转组、未愈组和恶化组,分析3组患者在年龄、性别、伴发病、发病时间、活检时间、基础免疫抑制方案、穿刺时24 h尿蛋白定量、穿刺时血清肌酐水平、硬化肾小球百分比等方面是否存在差异,分析蛋白尿水平和肾功能不全程度与肾小球硬化程度的相关关系。两个连续型随机变量的关联性分析采用Pearson相关分析及Spearman秩相关分析,多组定量资料比较采用方差分析或Kruskal-Wallis秩和检验;多组定性资料比较采用χ2检验或Fisher确切概率法。结果好转组、未愈组、恶化组患者性别、年龄、伴发病(高血压和高脂血症)、发病时间(肾移植术后至FSGS发病的时间)、活检时间(FSGS发病至移植肾活检时的时间)、基础免疫抑制方案以及24 h尿蛋白定量差异均无统计学意义(P均0.05)。好转组、未愈组、恶化组患者穿刺时血清肌酐水平分别为(144±47)、(232±103)、(410±208)μmol/L,硬化肾小球百分比分别为(0.24±0.19)%、(0.56±0.23)%、(0.49±0.26)%,差异均有统计学意义(F=6.33和4.01,P均0.05)。25例肾移植术后FSGS患者尿蛋白定量与穿刺时血肌酐水平无明显相关(r=-0.019,P0.05);尿蛋白定量与肾小球硬化程度无明显相关(r=0.316,P0.05)。结论移植肾FSGS临床表现与原发FSGS相似,治疗困难,预后较差。移植后出现蛋白尿早期,应及时进行移植肾活检并给予相应治疗。     

槌果藤对局灶节段肾小球硬化鼠模型的治疗作用及作用机制的初步探讨

目的：探讨槌果藤对局灶节段肾小球硬化大鼠模型的治疗作用及作用机制。方法：通过左肾切除并阿霉素尾静脉注射的方法建立FSGS模型。按不同灌胃给药浓度将动物分为75g/L组（A组）、150g/L组（B组）、300g/L组（C组）、600g/L组（D组）,另两组分别为安慰剂对照组（E组）和假手术组（F组）。造模后4周给药,疗程4周。各组动物于治疗前后均分别测定24h尿蛋白定量、血常规、肾功能、谷丙转氨酶（ALT）、总蛋白（TP）、白蛋白（Alb）、胆固醇（TC）水平。治疗后取D、E、F组肾组织抽提总RNA,杂交高密度cDNA芯片并分析结果。结果：各槌果藤煎剂组治疗后24h尿蛋白水平均较治疗前显著下降,其中又以D组下降程度最为显著（P〈0.05）。同时各治疗组治疗后血浆白蛋白均较治疗前有显著上升,血胆固醇、肌酐、尿素氮水平均较治疗前有显著降低,而各治疗组治疗前后血红蛋白、白细胞总数、血小板数和谷丙转氨酶水平均无统计学差异（P〉0.05）。基因芯片检测结果显示与E组比较,D组有包括转化生长因子-β1（TGF-β1）、肿瘤坏死因子α（TNF-α）受体、足细胞相关蛋白（Podocin）、纤维连接蛋白等与FSGS发生发展密切相关的基因表达具有统计学差异。结论：本实验中不同浓度的槌果藤煎剂对FSGS大鼠模型均有减少尿蛋白的作用,其中以600g/L组为最强。观察期内各组均未发现骨髓抑制、肝损害等副反应。槌果藤可能通过下调TNF-α受体、EGF受体、TGF-β1、PDGF、纤维连接蛋白、肾特异性膜蛋白、足细胞相关蛋白Podocin以及ILK的基因表达,上调锌指蛋白216以及硒蛋白的表达等起到免疫调节、抗氧化、抗纤维化作用,其确切作用机制需要进一步研究。     

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.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

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.     

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.     

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.