泥浴疗法治疗膝骨关节炎疼痛的荟萃分析

背景：泥浴疗法治疗膝骨关节炎一直受到研究者的重视,但其有效性在以往的各项研究中尚存在争议。 目的：分析研究泥浴疗法治疗膝骨关节炎疼痛的有效性。 方法：计算机检索 Pubmed/Medline 数据库以及手工检索相关文献的参考文献。所有检索截止至2013年3月9日。收集国内外公开发表的有关泥浴疗法治疗膝骨关节炎的随机对照试验和前瞻性对照试验。 结果与结论：纳入Meta分析的研究共7个,累计研究对象410例。治疗组和对照组的目测类比疼痛评分（标准化标准差[SMD]-0.74）和 WOMAC 疼痛评分（标准化标准差[SMD]-0.30）组间差异有显著性意义。可见泥浴疗法可改善膝骨关节炎疼痛的症状。但此结论有待更多高质量的随机对照试验进一步证实。     

中药塌渍疗法治疗膝骨关节炎有效性的Meta分析

[目的]系统评价中药塌渍疗法治疗膝骨关节炎的有效性和安全性。[方法]计算机检索PubMed、Cochrane临床对照试验中心注册数据库(Cochrane Central Register of Controlled Trails,CENTRAL)、中国期刊全文数据库(CNKI)、万方数据库和中国科技期刊全文数据库(VIP)自建库至2018年9月的相关文献,收集中药塌渍疗法治疗膝骨关节炎的随机对照试验(RCT)及半随机对照试验(CCT),对纳入研究利用Cochrane系统评价手册提供的偏倚风险评估工具进行文献质量评价,使用RevMan 5.3软件对数据进行Meta分析。[结果]共纳入6项研究,共220例病人。Meta分析结果显示:中药塌渍组的治疗有效率高于对照组,差异有统计学意义[RR=1.14,95%CI(1.07,1.21),P0.000 1];中药塌渍组病人的疼痛评分(VAS)低于对照组,差异有统计学意义[WMD=-0.91,95%CI(-1.42,-0.40),P=0.000 5]。[结论]中药塌渍疗法可提高膝骨关节炎病人的治疗有效率并减轻病人疼痛。但鉴于纳入文献方法学质量均不高,且多数研究未报告不良反应的发生情况,建议今后开展更多大样本的随机双盲对照试验进行进一步探究。     

早期活动对机械通气病人ICU获得性肌无力影响的累计Meta分析及试验序贯分析

[目的]应用累积Meta分析方法评价早期活动对机械通气病人重症监护病房(ICU)获得性肌无力(ICU-AW)的影响,并运用试验序贯分析检验Meta分析结果的真实性。[方法]计算机检索the Cochrane Library、PubMed、EMbase、中国知网(CNKI)、维普数据库(VIP)、万方数据库从建库至2019年9月25日公开发表的关于早期活动干预用于ICU机械通气病人的临床随机对照研究(RCT),由2名研究员独立筛选文献、评价文献质量并提取资料。对符合质量标准的研究按发表时间顺序进行累计Meta分析,同时采用试验序贯分析方法,评价研究结果的可靠性和真实性。[结果]共纳入12篇文献,包括研究对象979例。累计Meta分析结果显示:与常规护理比较,早期活动能够提高机械通气病人肌力,累计效应值SMD=1.47,95%CI(1.21,1.72);早期活动可降低ICU-AW发生率,累计效应值RR=0.31,95%CI(0.16,0.60);试验序贯分析结果显示:两指标虽未达到期望信息量,但累积的Z值线穿过了传统界值,同时跨过了试验序贯分析界值,说明可能两组疗效差异有统计学意义,且无须更多试验来证明。[结论]早期活动能够提高病人的肌力,减少ICU-AW的发生。     

可穿戴设备在膝关节置换术后患者康复中应用效果的Meta分析

目的:评价可穿戴设备对膝关节置换术后康复效果的影响。方法:计算机检索中国知网、万方、维普、PubMed、Cochrane Library数据库,搜集应用可穿戴设备对膝关节置换术后患者康复管理的RCT试验。2名研究者按纳入、排除标准独立筛选文献、质量评价和提取资料,对符合要求文献使用Stata12.2软件进行Meta分析。选择西安大略和麦克马斯特大学骨关节炎指数WOMAC评分、关节屈曲度ROM、计时起立-行走测试(TUGT)、视觉模拟评分VAS评分、步数作为结局指标。结果:最终纳入8篇文献进行Meta分析,共718例患者。Meta分析结果表明可穿戴设备应用于膝关节置换患者术后康复能够提高HSS评分(SMD=0.22,95%CI:-0.64~1.07,P<0.01)、ROM评分(SMD=0.64,95%CI: 0.13~1.15,P<0.01)及VAS评分(SMD=-0.18,95%CI-1.10~0.75,P<0.01),但在TUGT测试评分(SMD=-0.39,95%CI:-0.75~0.03,P>0.01)、WOMAC评分(SMD=1.37,95%CI:0.92~1.82,P>0.01)、术后步数方面效果不显著。结论:可穿戴设备在膝关节置换患者术后康复中对膝关节活动度、HSS评分和VAS评分改善明显,在一定程度上可有效提高其膝关节功能,加快康复进程。但对TUGT测评、WOMAC评分及步数方面效果尚不能确定。     

关节镜下清理术联合关节内透明质酸注射治疗膝关节骨关节炎有效性的系统评价

目的系统评价关节镜下清理术联合关节内透明质酸注射治疗膝关节骨关节炎的有效性。方法计算机检索The Cochrane Library、SCI、MEDLINE、EMbase、CBM和WanFang Data,查找所有关节镜下清理术联合关节内透明质酸注射(联合疗法)与二者任一单一疗法比较治疗膝关节骨关节炎的随机对照试验,检索时限均从建库至2012年。由2位研究者按照纳入和排除标准独立筛选文献、提取资料并评价质量后,采用RevMan 5.0软件进行Meta分析。结果最终纳入7个随机对照试验,共526例患者。Meta分析结果显示联合治疗与单用关节内透明质酸注射[RR=1.40,95%CI(0.99,1.98),P=0.06]或单纯关节镜下清理术[RR=1.09,95%CI(0.93,1.26),P=0.29]治疗膝关节骨关节炎的优良率相似,其差异无统计学意义。但单用关节内透明质酸注射治疗在改善患者Lysholm评分方面不及联合治疗,两组差异有统计学意义[MD=–14.81,95%CI(–17.55,–12.08),P<0.000 01]。结论关节镜下清理术联合关节内透明质酸注射治疗膝关节骨关节炎的优良率与单一疗法的差异无统计学意义,但Lysholm评分高于单用透明质酸注射治疗,联合疗法具有一定优势。受纳入研究数量和质量限制,上述结论尚需开展更多高质量的随机对照试验加以验证。     

太极治疗膝骨关节炎系统评价及meta分析

目的:系统评价太极对膝骨关节炎有效性及安全性。方法:检索Pubmed/Medline、Embase、Cochrane图书馆、OVID、中国知网、万方、中国医学生物文献数据库及手动检索相关参考文献,搜集太极治疗膝骨关节炎的随机对照试验研究,对纳入文献进行资料提取、方法学质量评价,并用Revman 5.0软件进行统计分析。结果:共纳入7例随机对照研究,包括367例患者。Meta分析结果显示:与对照组比较,太极对膝骨关节炎患者关节疼痛、关节僵硬、关节功能、躯体生活质量、步行速度改善效果更明显,差异具有显著性意义([SMD=-0.73,95%CI(-0.99,-0.14),P0.01)]、([SMD=-0.76,95%C(I-1.02,-0.50),P0.01)]、([SMD=-0.72,95%C(I-1.24,-0.20),P0.01)]、([SMD=0.71,95%C(I0.25,1.16),P0.01)]、([SMD=0.57,95%C(I0.11,1.02),P=0.01)]。与对照组比较,太极对膝骨关节炎患者平衡能力、精神生活质量、肌肉力量、BMI指数改善效果无显著性差异。太极治疗膝骨关节炎期间未出现相关严重不良事件。结论:太极对膝骨关节炎患者的关节疼痛、关节僵硬、关节功能、步行速度、躯体生活质量具有改善作用,其安全性良好。但今后还需进行多中心、大样本随机对照研究,及延长观测周期以为太极治疗膝骨关节炎提供更为可靠的依据。     

艾灸治疗失眠症临床随机对照试验的系统评价

目的:系统评价艾灸治疗失眠症的疗效。方法:计算机检索数据库中单纯艾灸与口服药物比较治疗失眠症的随机对照试验,采用Rev Man 5.2软件进行Meta分析。结果:最终纳入14个RCT,包括1186例患者。Meta分析结果示:艾灸组与口服药物组相比,总有效率[RR=1.19,95%CI(1.12,1.26),P0.00001]、PSQI减分率[RR=1.28,95%CI(1.05,1.55),P=0.004]、PSQI积分[SMD=-1.11,95%CI(-1.60,-0.61),P0.0001]差异具有统计学意义。亚组分析艾灸与口服西药相比,总有效率[RR=1.20,95%CI(1.12,1.28),P0.00001]差异具有统计学意义。结论:艾灸治疗失眠症有效。但纳入文献部分研究质量较低,部分主要疗效指标报道较少,缺乏足够的信息进行深入分析,需要更多高质量、大样本、多中心的随机对照试验来进一步验证。     

中药离子导入对膝骨关节炎疗效的Meta分析

[目的]探讨中药离子导入治疗膝骨关节炎的临床疗效。[方法]检索Cochrane Library、PubMed、EMBASE、中国生物医学文献数据库、中国知网(CNKI)、维普、万方数据库,检索时间从各数据库建库至2017年9月,收集中药离子导入治疗膝骨关节炎的随机对照研究。应用Revman 5.3软件进行统计学分析。[结果]本研究共纳入17篇文献,涉及膝骨关节炎病人1 933例。Meta分析结果显示:试验组总有效率高于对照组[OR=4.59,95%CI(3.32,6.35),P0.000 01];治疗后关节疼痛程度低于对照组[WMD=-1.14,95%CI(-1.52,-0.76),P0.000 01];关节功能优于对照组[WMD=13.08,95%CI(10.70,15.46),P0.000 01]。[结论]中药离子导入对膝骨关节炎有一定临床疗效,但需更多高质量、大样本的随机对照试验进一步证实,为临床治疗提供更真实可靠的依据。     

神经肌肉电刺激治疗膝骨关节炎疼痛的Meta分析

背景：膝关节骨关节炎早、中期的治疗方法以对症治疗为主,有研究表明神经肌肉电刺激用于膝关节骨关节炎的治疗能改善患者的疼痛评分,但目前对于其疗效仍存在争议。目的：评价神经肌肉电刺激治疗膝关节骨关节炎患者疼痛的疗效。方法：计算机检索Medline数据库和手工查找神经肌肉电刺激治疗膝关节骨关节炎相关文献的全文,所有检索截止至2014年7月3日。搜集国内外研究神经肌肉电刺激对膝关节骨关节炎患者疼痛评分影响的随机对照试验,2名研究人员独立按照纳入和排除标准筛选文献,采用Cochrane协作网提供的Revman 5.2软件进行Meta分析。结果与结论：共纳入5项随机对照试验,累计239例研究对象。Meta分析结果显示,与空白对照组相比,神经肌肉电刺激对减轻膝关节骨关节炎患者的疼痛无统计学意义[均数差=-0.40,95%置信区间（-1.34-0.54）,P=0.40]。结果表明,神经肌肉电刺激对改善膝关节骨关节炎患者的疼痛情况无明显疗效。但由于纳入的样本量较小,参数选择存在较大的差异,所以未来尚需大样本和高质量的随机对照试验对结果做进一步的证实。     

多模式超前镇痛在膝关节置换术康复护理中应用效果的Meta分析

[目的]系统评价多模式超前镇痛对膝关节置换术病人康复锻炼的影响。[方法]检索中国知网、万方、维普引文数据库以及PubMed,EMbase,MedLine英文数据库,获得国内外关于多模式超前镇痛对膝关节置换病人术后康复训练效果的随机对照试验,使用RevMan 5.3软件进行Meta分析。[结果]纳入8篇符合标准的文献,Meta分析结果显示:试验组术后72h内疼痛VAS评分比对照组低[SMD=-2.31,95%CI(-3.14,-1.49),P0.01],试验组术后3d、6个月病人膝关节活动度优于对照组[WMD=11.22,95%CI(10.75,11.69),P0.01;WMD=15.60,95%CI(12.51,18.68),P0.01],试验组术后6个月病人膝关节功能HSS评分比对照组病人改善明显[WMD=15.62,95%CI(13.63,17.61),P0.01]。[结论]多模式超前镇痛可缓解膝关节置换病人的术后疼痛,提高康复锻炼依从性,术后膝关节功能恢复效果好。     

重型乙型肝炎患者原位肝移植围手术期全身氧代谢的变化

目的 探讨重型乙型肝炎（乙肝）与其他肝病患者原位肝移植围术期全身氧代谢变化的特点。方法 12例重型乙肝患者为试验组。10例其他肝病患者为对照组。以咪唑安定、异丙酚、芬太尼、维库溴铵诱导全麻，术中吸入异氟醚维持麻醉。维库溴铵维持肌松，行改良背驼式原位肝移植术。左桡动脉穿刺测有创动脉压，右颈内静脉穿刺置入漂浮导管。分别于术前、无肝前10min、无肝期25min、新肝期30min和术毕监测动脉和混合静脉血氧分压（PaO2和Pv^-O2）、动脉和混合静脉血氧含量（CaO2和Pv^-O2）及动-静脉血氧含量差（CA-vO2）、氧供（DO2）、氧供指数（DO2I）、氧消耗（VO2）、氧耗指数（VO2I）、氧摄取指数（O2EI）和氧摄取率（O2ER）。结果 ①试验组：与术前相比，无肝前期Pv^-O2上升，Ca-vO2、O2EI、O2ER下降，DO2和VO2无明显变化；无肝期DO2、DO2I、VO2和VO2I均明显下降，DO2、VO2分别下降43％和21％，O2EI和O2ER均明显上升；新肝期PvO2上升，DO2和DO2I明显上升。VO2和VO2I回升至术前水平；术毕时DO2和DO2I依然高于术前水平。②对照组：无肝前期PvO2上升。DO2和VO2无明显变化，O2EI和O2ER下降；无肝期DO2、DO2I、VO2和VO2I均明显下降，DO2下降25％，VO2则下降12％；新肝期PvO2上升，Ca-vO2下降，DO2、DO2I明显上升，VO2和VO2I回升至术前水平；术毕时DO2和DO2I依然高于术前水平。结论肝移植围术期中，全身DO2变化大于VO2变化；重型乙肝患者的全身DO2和VO2变化较其他肝病患者剧烈。     

Inhibition of thromboxane A(2)-induced Cl(-) secretion by antidiarrhea drug loperamide in isolated rat colon

The antitumor drug irinotecan clinically causes severe diarrhea as a side effect. Thromboxane A(2) (TXA(2)), released by irinotecan, has been shown to be a novel physiological stimulant of Cl(-) secretion in the rat colon. Herein, we examined the effect of loperamide, an antidiarrhea drug, on Cl(-) secretion induced by irinotecan; 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)), a stable TXA(2) analog; and prostaglandin E(2) (PGE(2)) by using isolated mucosae of the rat colon. In the presence of atropine, loperamide in a concentration-dependent manner inhibited the Cl(-) secretion induced by irinotecan, STA(2), and PGE(2). However, the drug inhibited more effectively the irinotecan- and STA(2)-induced secretion (IC(50) = 0. 7 and 1.2 microM, respectively) than the PGE(2)-induced secretion (IC(50) = 23 microM). Naloxone, an opiate antagonist, did not affect the antisecretory action of loperamide. Similar to the case for loperamide, W-7, a specific calmodulin antagonist, inhibited more effectively the STA(2)-induced Cl(-) secretion (IC(50) = 5 microM) than the PGE(2)-induced secretion (IC(50) = 36 microM). W-5, a low-affinity calmodulin antagonist (a dechlorinated control analog of W-7), also inhibited the STA(2)-induced secretion, but this effect was much less than that of W-7. STA(2)-induced increase in the intracellular free Ca(2+) concentration of single colonic crypt cells was not affected by loperamide. We suggest that loperamide efficiently inhibits the TXA(2)-induced secretion by blocking the calmodulin system in the colonic epithelium. The present results may explain why coadministration of loperamide with irinotecan is clinically efficient for avoiding the irinotecan-induced side effect of diarrhea.     

Constitutive activity and ligand selectivity of human, guinea pig, rat, and canine histamine H2 receptors

Previous studies revealed pharmacological differences between human and guinea pig histamine H(2) receptors (H(2)Rs) with respect to the interaction with guanidine-type agonists. Because H(2)R species variants are structurally very similar, comparative studies are suited to relate different properties of H(2)R species isoforms to few molecular determinants. Therefore, we systematically compared H(2)Rs of human (h), guinea pig (gp), rat (r), and canine (c). Fusion proteins of hH(2)R, gpH(2)R, rH(2)R, and cH(2)R, respectively, and the short splice variant of G(salpha), G(salphaS), were expressed in Sf9 insect cells. In the membrane steady-state GTPase activity assay, cH(2)R-G(salphaS) but neither gpH(2)R-G(salphaS) nor rH(2)R-G(salphaS) showed the hallmarks of increased constitutive activity compared with hH(2)R-G(salphaS), i.e., increased efficacies of partial agonists, increased potencies of agonists with the extent of potency increase being correlated with the corresponding efficacies at hH(2)R-G(salphaS), increased inverse agonist efficacies, and decreased potencies of antagonists. Furthermore, in membranes expressing nonfused H(2)Rs without or together with mammalian G(salphaS) or H(2)R-G(salpha) fusion proteins, the highest basal and GTP-dependent increases in adenylyl cyclase activity were observed for cH(2)R. An example of ligand selectivity is given by metiamide, acting as an inverse agonist at hH(2)R-G(salphaS), gpH(2)R-G(salphaS), and rH(2)R-G(salphaS) in the GTPase assay in contrast to being a weak partial agonist with decreased potency at cH(2)R-G(salphaS). In conclusion, the cH(2)R exhibits increased constitutive activity compared with hH(2)R, gpH(2)R, and rH(2)R, and there is evidence for ligand-specific conformations in H(2)R species isoforms.     

Stabilization of Factor VIII in Plasma by the von Willebrand Factor: STUDIES ON POSTTRANSFUSION AND DISSOCIATED FACTOR VIII AND IN PATIENTS WITH VON WILLEBRAND''S DISEASE

In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII(AHF)) to that of the von Willebrand factor activity (ristocetin cofactor, VIII(VWF)) or factor VIII antigen (VIII(AGN)) is approximately 1, but ratios > 1 (e.g., VIII(AHF) > VIII(VWF) or VIII(AGN)) may be observed in some patients with von Willebrand's disease and in the "late" posttransfusion plasmas of patients with this disorder. The lability of VIII(AHF) was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37 degrees C. With normal plasmas, 77+/-12% (SD) of the original VIII(AHF) activity remained after incubation. VIII(AHF) was labile (e.g., 35-55% residual activity) in the "late" posttransfusion plasmas (VIII(AHF) > VIII(VWF)) of a patient with von Willebrand's disease, but not in the "early" posttransfusion plasmas (VIII(AHF) approximately VIII(VWF)). VIII(AHF) was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII(AHF) to VIII(VWF) were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was approximately 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIII(AHF). In both of these patients, and in the late posttransfusion plasmas, labile VIII(AHF) activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII(AHF) activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII(VWF) may serve to stabilize VIII(AHF) and this might explain the posttransfusion findings in von Willebrand's disease.     

Modified proteinase-activated receptor-1 and -2 derived peptides inhibit proteinase-activated receptor-2 activation by trypsin.

Trypsin activates proteinase-activated receptor-2 (PAR(2)) by a mechanism that involves the release of a tethered receptor-activating sequence. We have identified two peptides, FSLLRY-NH(2) (FSY-NH(2)) and LSIGRL-NH(2) (LS-NH(2)) that block the ability of trypsin to activate PAR(2) either in PAR(2)-expressing Kirsten virus-transformed kidney (KNRK) cell lines or in a rat aorta ring preparation. The reverse PAR(2) peptide, LRGILS-NH(2) (LRG-NH(2)) did not do so and FSY-NH(2) failed to block thrombin activation of PAR(1) in the aorta ring or in PAR(1)-expressing human embryonic kidney cells. Half-maximal inhibition (IC(50)) by FSY-NH(2) and LS-NH(2) of the activation of PAR(2) by trypsin in a PAR(2) KNRK calcium-signaling assay was observed at about 50 and 200 microM, respectively. In contrast, the activation of PAR(2) by the PAR(2)-activating peptide, SLIGRL-NH(2) (SL-NH(2)) was not inhibited by FSY-NH(2), LS-NH(2), or LRG-NH(2). In a casein proteolysis assay, neither FSY-NH(2) nor LS-NH(2) inhibited the proteolytic action of trypsin on its substrate. In addition, FSY-NH(2) and LS-NH(2) were unable to prevent trypsin from hydrolyzing a 20-amino acid peptide, GPNSKGR/SLIGRLDTPYGGC representing the trypsin cleavage/activation site of rat PAR(2). Similarly, FSY-NH(2) and LS-NH(2) failed to block the ability of trypsin to release the PAR(2) N-terminal epitope that is cleaved from the receptor upon proteolytic activation of receptor-expressing KNRK cells. We conclude that the peptides FSY-NH(2) and LS-NH(2) block the ability of trypsin to activate PAR(2) by a mechanism that does not involve a simple inhibition of trypsin proteolytic activity, but possibly by interacting with a tethered ligand receptor-docking site.     

Interaction of antimycobacterial drugs with the anti-Mycobacterium avium complex effects of antimicrobial effectors, reactive oxygen intermediates, reactive nitrogen intermediates, and free fatty acids produced by macrophages

The profiles of the interaction of antimycobacterial drugs with macrophage (MPhi) antimicrobial mechanisms have yet to be elucidated in detail. We examined the effects of various antimycobacterial drugs on the anti-Mycobacterium avium complex (MAC) antimicrobial activity of reactive oxygen intermediates (ROIs), especially of an H(2)O(2)-halogen (H(2)O(2)-Fe(2+)-NaI)-mediated bactericidal system, reactive nitrogen intermediates (RNIs), and free fatty acids (FFAs), which are known as central antimicrobial effectors of host MPhis against mycobacterial pathogens. We have found that certain drugs, such as rifampin (RIF), rifabutin (RFB), isoniazid (INH), clofazimine (CLO), and some fluoroquinolones, strongly or moderately reduced the anti-MAC activity of the H(2)O(2)-Fe(2+)-NaI system, primarily by inhibiting the generation of hypohalite ions and in part by interfering with the halogenation reaction of bacterial cell components due to the H(2)O(2)-Fe(2+)-NaI system. This phenomenon is specific to the H(2)O(2)-Fe(2+)-NaI system, since these drugs did not reduce the anti-MAC activity of RNIs and FFAs. From the perspective of the chemotherapy of MAC infections, the present findings indicate an important possibility that certain antimycobacterial drugs, such as rifamycins (RIF and RFB), INH, CLO, and also some types of fluoroquinolones, may interfere with the ROI-mediated antimicrobial mechanisms of host MPhis against intracellular MAC organisms.     

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals

This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.     

Assay of serum arylesterase activity by fitting to the reaction curve with an integrated rate equation.

BACKGROUND: Conventional enzyme activities make use of the initial reaction rate at high substrate concentrations. Because this is not always practical, alternative enzyme assays have been sought. METHODS: Reaction curve fitting with an integrated rate equation was investigated to assay serum arylesterase (ArE) activity using phenyl acetate (PA) and p-nitrophenol acetate (PNPA) as substrates. At a much lower initial concentration of substrate (S(0)), the simplified integrated rate equation for the ArE reaction was ln(S(0)/S(i))=(V(m)/K(m)+K(d))t(i). Treating S(0) as a parameter, the enzyme activity as V(m)/K(m) was estimated through nonlinear least square fitting to reaction curve, and the multiplication of V(m)/K(m) by K(m) produced V(m). Spontaneous hydrolysis of the substrate with a rate constant, K(d), served as the background for the estimation of V(m)/K(m). RESULTS: Substrate concentration at 8% of K(m) was well suited for the estimation of V(m)/K(m). With either substrate, the V(m)/K(m) showed a close relation to the percentage of substrate consumed, and was not affected by common systematic errors. With either substrate, the between-run precision for V(m)/K(m) was 6% (n>7), V(m)/K(m) was proportional to the amount of ArE and closely correlated with its initial rate. The upper limit of linearity by this integrated method was much higher than the initial rate method, while the detection limit was comparable. By using either V(m)/K(m) or the initial rate, there was negligible interference with ArE activity assay from triglycerides, bilirubin, and hemoglobin. CONCLUSIONS: These results indicate the feasibility of the integrated method for routine assay of serum enzyme activity.     

Beta(1)-selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for beta(1)-selective binding in resting and active states

(-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] is a highly selective beta(1)-adrenergic receptor (beta(1)AR) agonist. To study the binding site of beta(1)-selective agonist, chimeric beta(1)/beta(2)ARs and Ala-substituted beta(1)ARs were constructed. Several key residues of beta(1)AR [Leu(110) and Thr(117) in transmembrane domain (TMD) 2], and Phe(359) in TMD 7] were found to be responsible for beta(1)-selective binding of (-)-RO363, as determined by competitive binding. Based on these results, we built a three-dimensional model of the binding domain for (-)-RO363. The model indicated that TMD 2 and TMD 7 of beta(1)AR form a binding pocket; the methoxyphenyl group of N-substituent of (-)-RO363 seems to locate within the cavity surrounded by Leu(110), Thr(117), and Phe(359). The amino acids Leu(110) and Phe(359) interact with the phenyl ring of (-)-RO363, whereas Thr(117) forms hydrogen bond with the methoxy group of (-)-RO363. To examine the interaction of these residues with beta(1)AR in an active state, each of the amino acids was changed to Ala in a constitutively active (CA)-beta(1)AR mutant. The degree of decrease in the affinity of CA-beta(1)AR for (-)-RO363 was essentially the same as that of wild-type beta(1)AR when mutated at Leu(110) and Thr(117). However, the affinity was decreased in Ala-substituted mutant of Phe(359) compared with that of wild-type beta(1)AR. These results indicated that Leu(110) and Thr(117) are necessary for the initial binding of (-)-RO363 with beta(1)-selectivity, and interaction of Phe(359) with the N-substituent of (-)-RO363 in an active state is stronger than in the resting state.     

Accuracy of Continuous Central Venous Oxygen Saturation Monitoring in Patients Undergoing Cardiac Surgery

OBJECTIVE: Continuous assessment of central venous oxygen saturation (S(cevox)O(2)) with the CeVOX device (Pulsion Medical Systems, Munich, Germany) was evaluated against central venous oxygen saturation (S(cv)O(2)) determined by co-oximetry. METHODS: In 20 cardiac surgical patients, a CeVOX fiberoptic probe was introduced into a standard central venous catheter placed in the right internal jugular vein and advanced 2-3 cm beyond the catheter tip. After in vivo calibration of the probe, S(cevox)O(2), S(cv)O(2), mixed venous oxygen saturation (S(mv)O(2)) haemoglobin (Hb), body temperature, heart rate, central venous and mean arterial pressure, and cardiac index were assessed simultaneously at 30 min intervals during surgery and at 60 min intervals during recovery in the intensive care unit. Agreement between S(cevox)O(2), and S(cv)O(2) was determined by Bland-Altman analysis. Simple regression analysis was used to assess the correlation of S(cevox)O(2), and S(cv)O(2) to Hb, body temperature and haemodynamic parameters. RESULTS: Values of S(cevox)O(2) and S(cv)O(2) (84 data pairs during surgery and 106 in the intensive care unit) ranged between 45-89% and 43-90%, respectively. Mean bias and limits of agreement of S(cevox)O(2) and S(cv)O(2) were -0.9 (-7.9/+6.1)% during surgery and -1.2 (-10.5/+8.1)% in the intensive care unit. In 37.9% of all measured data pairs, the difference between S(cevox)O(2) and S(cv)O(2) was beyond clinically acceptable limits (>/=1 s.d.). Mean bias was significantly influenced by cardiac index. Sensitivity and specificity of S(cevox)O(2) to detect substantial (>/=1 s.d.) changes in S(cv)O(2) were 89 and 82%, respectively. CONCLUSIONS: In adult patients during and after cardiac surgery, the current version of the CeVOX device might not be the tool to replace S(cv)O(2) determined by co-oxymetry, although sensitivity and specificity of S(cevox)O(2 )to predict substantial changes in S(cv)O(2) were acceptable.