正常妊娠与重度子痫前期孕妇房室结构及左心室舒张功能的多普勒评价

目的探讨应用超声心动图血流多普勒评价正常妊娠与重度子痫前期孕妇左心房结构及左心室舒张功能变化的临床意义。方法测量106例重度子痫前期重度患者（观察组）及106例正常妊娠者（对照组）孕晚期心脏各项数值。测量左侧房室（LAD、LVD）大小、室壁厚度[室间隔厚度（IVST）、左心室后壁厚度（LVPWT）]、心输出量（CO）、左心室重量指数（LVMI）、二尖瓣血流（MV）舒张早期与舒张晚期最大流速（E）,A和E峰下降时间（DT）,并计算E/A最大流速比。测量等容舒张期时间（IVRT）。肺静脉血流（PV）频谱,分别测量收缩期、舒张期与心房收缩期反向波的最大峰速S、D与Ar。肱动脉收缩与舒张压。结果观察组舒张功能指标二尖瓣口血流舒张早期峰值流速及其与舒张晚期峰值流速比值显著低于对照组（P〈0.05）;而二尖瓣舒张晚期充盈峰、肺静脉心房收缩期反响血流充盈峰、相对室壁厚度、左心室等容舒张时间均显著高于对照组（P〈0.05）。结论彩色多普勒超声心动图将肺静脉血流频谱与二尖瓣前向血流频谱结合,可较全面评价左心室舒张功能,具有临床诊断价值。     

超声检测血管内皮功能在缺血性心肌病患者中的应用价值

目的 探讨超声检测血管内皮功能在缺血性心肌病患者中的应用价值.方法 收集62例缺血性心肌病(ICM)患者持续治疗随访1年,并招募40名健康者作为对照.ICM患者在入选时和随访1年后分别行超声心动图[左心室射血分数(LVEF)、每搏输出量(SV)、左心室短轴缩短率(LVFS)、左心室等容舒张时间(IVRT)、二尖瓣舒张早期血流峰值速度/二尖瓣舒张晚期血流峰值速度(E/A)比值]、血流介导血管舒张功能(FMD)检查及血浆一氧化氮(NO)、内皮素-1(ET-1)检测,对照者仅在入选时行以上检查.结果 ICM组入选时LVEF、SV、LVFS、IVRT、E/A、FMD、NO、ET-1较对照组存在显著差异(P<0.05);随访1年后,ICM患者的LVEF、SV、E/A值、FMD值较入选时升高,而IVRT较前降低(P<0.05).入选时ICM患者的LVEF、LVSF值与FMD呈正相关,IVRT与FMD呈负相关(P<0.05);随访1年后,其LVEF、LVSF、E/A值与FMD呈正相关(P<0.05).随访前后差值△LVSF与入选时的FMD值呈正相关关联,而△IVRT与之呈负相关(P<0.05).结论 超声血管内皮功能FMD检查对缺血性心肌病患者当前心功能及将来心功能变化具有一定的评估预测价值.     

不同左心室舒张功能状态的冠心病患者左心房容积与功能研究

目的 应用实时三维超声心动图(RT-3DE)评估左心室不同舒张功能状态的冠心病患者左心房容积与功能并探讨三维测量的左心房参数与左心室舒张功能分级的关系.方法 80例冠心病患者根据左心室不同舒张功能状态分成舒张功能正常组、松弛功能降低组、假性正常化组及限制性充盈障碍组,各20例.比较4组左心房最大容积(LAVmax)、左心房收缩前容积(LAVpre)、左心房最小容积(LAVmin),体表面积校正后得出LAVmax指数、LAVpre指数、LAVmin指数,计算左心房总排空分数(LAVtEF)、左心房被动排空分数(LAVpEF)、左心房主动排空分数(LAVaEF).结果 在左心室舒张功能异常各组中,二尖瓣频谱的二尖瓣血流舒张早期速度峰值E/心房收缩期速度峰值(A)、E/二尖瓣环舒张早期峰值速度(Em)、E/左心室舒张早期血流传播速度(Vp)随着舒张功能障碍加重而增加,而E峰减速时间(DT)随着舒张功能障碍加重而降低(均P＜0.05)；LAVmax、LAVpre、LAVmin、LAVmax指数、LAVpre指数、LAVmin指数随舒张功能降低而增加,LAVtEF随舒张功能降低而降低(P＜0.05)；E/Em、E/Vp、DT与RT-3DE测量LAVmax指数、LAVpre指数、LVAmin指数、LAVtEF显著相关(r=0.75、0.70、0.73、-0.79；r =0.75、0.68、0.72、-0.83；r=-0.70、-0.69、-0.67、0.74,均P＜0.05).LAVmax指数≥34 ml/m2,LAVtEF≤30％诊断左心室充盈压增高(即E/Em＞ 15),其敏感度和特异度分别为85.7％、65.6％及85.1％、81.6％.结论 RT-3DE测量左心房容积与功能各项参数有助于临床更准确地评价左心室舒张功能.     

体外反搏对高血压性心脏病舒张功能的影响

目的 探讨体外反搏对高血压性心脏病舒张功能的影响.方法 随机将104例高血压性心脏病患者分为两组,其中52例在常规药物治疗基础上加用体外反搏治疗为反搏组,52例应用常规药物治疗为对照组,治疗前后进行彩色多普勒超声检测.结果 治疗后,左心室等容舒张时间(IVRT),左房室瓣舒张早期充盈E峰速率(E),左房室瓣舒张晚期充盈A峰速率(A),E峰速率/A峰速率(E/A),E峰减速时间(DT)等左室舒张功能指标明显改善(P＜0.01).左室心肌重量指数(LVMI)明显降低(P＜0.01).反搏组各项左室舒张功能指标改善优于对照组(P＜0.05).结论 体外反搏治疗可显著改善高血压性心脏病左心室舒张功能并可使左室重构发生逆转.     

静脉注射硝酸酯类对急性心肌梗死早期左心室舒张功能的影响

目的观察硝酸甘油(NTG)及二硝基山梨醇酯(IDN)在急性心肌梗死(AMI)患者对左心室舒张功能的疗效。方法根据超声心动图二尖瓣血流频谱将AMI患者28例分为3组:2>E/A>1(A组);E/A<1(B组);E/A>3(C组)。用二尖瓣和肺静脉血流频谱作为观察指标。结果二尖瓣:静注NTG或IDN后,C组可显著降低E/A比值及E峰下降速率(均P<0.05);而A,B2组患者对上述参数均无影响;肺静脉:静注IDN后,3组均可使肺静脉血流频谱S/D比值显著升高(均P<0.05),Ar负向峰值速率显著下降(均P<0.05);但NTG对这2项参数无明显影响。结论在AMI早期,静脉注射硝酸甘油和二硝基山梨醇酯均可改善左心室舒张功能。     

组织多普勒成像技术(DTI)评价尿毒症患者左心室舒张功能的研究

目的 探讨组织多普勒成像技术(DTI)在评价尿毒症患者心脏舒张功能中的价值.方法 对33例尿毒症患者采用脉冲波多普勒法测量二尖瓣口前向血流速度参数:舒张早期峰值速度(E)、舒张晚期峰值速度(A),计算E/A比值;利用组织多普勒成像(DTI)技术,测量左室侧壁、前壁、下壁、室间隔的二尖瓣环水平DTI参数:舒张早期峰值速度(Em);舒张晚期峰值速度(Am);计算Em/Am比值.对比分析两种检测方法.结果 病例组E/A正常例数与异常例数间差异有统计学意义(P<0.05),Em/ Am正常例数与异常例数间有显著的统计学差异(P<0.01).结论 DTI技术可以实时定量地反映心肌运动的方向与速度,准确、客观地评价左心室舒张功能,有效避免频谱多普勒检查中存在的假性正常化现象.     

N-端B型钠尿肽前体在左室舒张功能减退时的变化

目的 探讨心脏疾病患者左室舒张功能减退时血清N-端B型钠尿肽前体(NTproBNP)的变化.方法 应用脉冲波多普勒测量左室功能正常组(30例)、二尖端血流频谱"假性正常"组(36例)和左事舒张功能减退对照组(32例)患者二尖瓣瓣尖舒张早期最大血流速度(E)、晚期最大血流速度(A)及二者比值(E/A);同时应用多普勒组织成像(DTI)测量平均舒张早期峰值速度(Ve)、平均舒张晚期峰值速度(Va),并计算二者比值(Ve/Va),并同期测定血清N-proBNP.结果 血清NT-proBNP浓度随左室舒张功能减低而升高,NT-proBNP浓度与Ve/Va呈负相关r=-0.62(P＜0.01).结论 血清NT-proBNP可为无症状性左室舒张功能异常提供一种无创性估测的新方法.     

类风湿关节炎30例左心室功能组织多普勒成像分析

目的 应用组织多普勒成像技术评价类风湿性关节炎患者的左心室功能.方法 选取类风湿性关节炎患者30例,正常对照组30例,分别进行超声心动图检查,测量常规左心室功能指标(射血分数EF、左室短轴缩短率FS、二尖瓣口血流速度比值E/A),并采用组织多普勒成像技术测量二尖瓣环运动频谱收缩期Sa峰、舒张早期Ea峰、舒张晚期Aa峰的峰值速度,Ea/Aa比值及Tei指数.结果 类风湿关节炎组与正常对照组相比,两组之间常规左室功能指标(EF、FS、E/A)差异无统计学意义(P＞0.05),而类风湿关节炎组Ea/Aa比值减低、Tei指数增高,两组之间差异有统计学意义(P＜0.05).结论 组织多普勒成像技术可早期评价类风湿关节炎患者的左心室功能受损情况,有助于临床及时制订相应的治疗措施,从而有效改善类风湿关节炎患者预后.     

多普勒组织成像和脉冲多普勒技术在评价高血压病患者左心室舒张功能中的应用

目的探讨多普勒组织成像和脉冲多普勒技术在评估原发性高血压病患者左心室舒张功能的应用价值。方法选取高血压病患者58例作为应用多普勒组织成像（DTI）及脉冲多普勒（PWD）技术检测2组二尖瓣环舒张期运动速度（Ve、Va）及二尖瓣口血流频谱,并进行对比研究。结果舒张早期血流速度（E）及E/A（舒张晚期血流速度）比值小于对照组,差异均有统计学意义（P〈0.05）。舒张早期峰值速度（Ve）及Ve/Va（舒张晚期峰值速度）比较,高血压组均小于对照组,差异均有统计学意义（P〈0.05）;且与二尖瓣血流频谱E/A比值高度成正相关,对照组与高血压组r值分别为0.81和0.74。结论高血压患者在发生左心室肥厚前已有心室舒张功能异常;DTI技术与PWD技术结合,可以为评估左室舒张功能提供更客观的诊断依据。     

超声心动图对肺静脉血流频谱评价冠心病患者左室舒张功能的价值

目的应用彩色多谱勒超声心动图研究冠心病患者肺静脉血流频谱对左室舒张功能的临床应用价值.方法选择冠心病患者和健康正常人各50例,应用彩色多普勒超声心动图记录二尖瓣血流频谱,并选择测量参数:舒张早期峰值(Ep)、舒张晚期峰值(Ap)、速度时间积分(Ei、Ai)、等容舒张时间(IRT)及左房(LA);记录肺静脉血流频谱,并选择测量参数;收缩期峰值(Sp)、舒张早期峰值(Dp)、舒张晚期峰值(ap)及其速度时间积分(Si、Di、ai),对各组数据进行比较统计学分析.结果冠心病组ap、ai较正常组显著增大,Si、Dp、Di和Dp/ap、Di/ai值明显减小,ap ai增大幅度与左室舒张功能明显相关.结论肺静脉血流可直观反映冠心病患者左心房内的压力状态,其频谱特征与二尖瓣口血流频谱结合评价左室舒张功能较用二尖瓣口血流频谱一种方法更加准确可靠.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。