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病生名词解释跨细胞液（transcellular fluid）跨细胞液是组织间液中的极少部分分布于一些密闭腔隙（关节囊、颅腔、胸腔、腹腔等）中，是由上皮细胞分泌产生的，为一特殊部分，也称第三间隙液。
水通道蛋白aquaporins (AQP)是一组广泛存在于生物界的构成水通道与水通透有关的细胞膜转运蛋白。
低容量性低钠血症hypovolemic hyponatremia又称为低渗性脱水，其特点是失Na+多于失水，血清Na+浓度〈130mmol/L，血浆渗透压〈280mmol/L，伴有细胞外液量的减少。
高容量性低钠血症hypervolemic hyponatremia又称为水中毒，其特点血清Na+浓度〈130mmol/L，血浆渗透压〈280mmol/L，是由于过多的水分在体内潴留造成细胞内、外液量都增多，并引起重要器官功能障碍。
低容量性高钠血症hypovolemic hypernatremia又称为高渗性性脱水，其特点是失水多于失Na+，血清Na+浓度〉150mmol/L，血浆渗透压〉310mmol/L，细胞外液量和细胞内液量均减少。
凹陷性水肿 (pitting edema)组织间隙中积聚的液体超过胶体网状物的吸附能力时，形成游离的液体，后者在组织间隙中具有高度的移动性，当液体积聚到一定量后，用手指按压该部位皮肤，游离液体便从按压点向周围散开，形成凹陷，称为凹陷性水肿，又称为显性水肿。
异位钙化在高钙或高磷血症时，体内多处可形成钙化，如血管壁、关节周围、软骨、肾、鼓膜钙化等，这些钙化灶引起相应器官的功能损害。
阴离子间隙 (anion gap,AG)AG指血浆中未测定的阴离子与未测定的阳离子的差值。
反常性酸性尿碱中毒时尿液一般呈碱性，但在缺钾等引起的代谢性碱中毒时，在远曲小管因Na+-H+交换加强，导致肾泌H+增多，故尿呈酸性，称之为反常性酸性尿。
分子病(molecular disease)是指由于DNA遗传性变异引起的一类蛋白质异常为特征的疾病。
FSS SeriesLow Profile Force SensorDESCRIPTIONThe FSS Series Force Sensor provides precise, reliable force sensing performance in a compact, commercial-grade package at a cost effective price. The sensor features a proven sensing technology that uses a specialized piezoresistive,micromachined silicon sensing element. The low power,unamplified, uncompensated Wheatstone bridge circuit design provides inherently stable mV outputs over the force range.Force sensors operate on the principle that the resistance of silicon-implanted piezoresistors will increase when theresistors flex under any applied force. The sensor concentrates force from the application, through the stainless steel ball, directly to the silicon-sensing element. The amount ofresistance changes in proportion to the amount of force being applied. This change in circuit resistance results in a corresponding mV output level change.The sensor package design incorporates patented modular construction. The use of innovative elastomeric technology and engineered molded plastics results in overforce capacities of up to three times the rated force. The stainless steel ball provides excellent mechanical stability and is adaptable to a variety of applications.The FSS Series Sensor delivered 20 million operations in Mean Cycles to Failure (MCTF) reliability testing at 50°C [122°F]. This test determines the number of possible sensor operations at full scale until failure.FEATURES AND BENEFITS∙ RoHS-compliant materials meet Directive 2002/95/ECallows use in industries requiring regulation compliance ∙ Low deflection (approx. 30 µm typical at full scale) helpsreduce measurement error∙ Direct mechanical coupling of the actuation ball to thesense element reduces coupling errors and keeps mechanical hysteresis to a minimum∙ Product rating of 20 million MCTF at 25 °C [77 °F], subjectto application variation, provides for consistent output over time and reduces repairs or replacements∙ Small size minimizes space on the printed circuit board(PCB)∙ Provides enhanced sensitivity without compromisingsignal integrity, resulting in low system noise and reducing measurement errors∙ Electrically ratiometric output accommodates supplyvoltage variations, leading to low ratiometricity error ∙ Low voltage supply allows for use in many batterypowered applications∙ High resistance to electrostatic discharge (ESD) meetsESD Sensitivity Classification Level 3B (8 KV), reducing special handling during assembly∙ Sensor output has low sensitivity to many mountingstressesPOTENTIAL APPLICATIONS Medical∙ Infusion pumps∙ Ambulatory non-invasive pumps ∙ Occlusion detection∙ Kidney dialysis machines ∙ Enteral pumpsIndustrial∙ Load and compression sensing ∙ Variable tension control ∙ Robotic end-effectors ∙ Wire bonding equipmentFSS Series2 11. All force-related specifications are established using dead weight or compliant force.2. The range of voltage excitation which can be supplied to the product to produce an output which isproportional to force but due to ratiometricity errors may not remain within the specified performance limits. Non-compensated force sensors, excited by constant current (1.5 mA) instead of voltage, exhibit partial temperature compensation of span.3. The output signal obtained when the zero force is applied to the sensor. Also known as "null" or "zero".4. The change in the null resulting from a change in temperature. It is not a predictable error as it can shift upand down from unit to unit. Change in temperature causes the entire output curve to shift up or down along the voltage axis.5. The algebraic difference between output signals measured at the upper and lower limits of the operating forcerange. Also known as "full scale output" or simply "span".6. The maximum deviation of product output from a straight line fitted to output measured over the operatingforce range. T he straight line through a set of points which minimizes the sum of the square of the deviations of each of the points from the straight line.7. The ratio of output signal change to the corresponding input force change. Sensitivity is determined bycomputing the ratio of span to the specified operating force range multiplied by the supply voltage being used.8. The maximum deviation in sensitivity due to changes in temperature over the operating temperaturerange, relative to sensitivity measured at 25 °C.9. The maximum difference between output readings when the same force is applied consecutively, underthe same operating conditions, with force approaching from the same direction within the operating force range.10. The maximum force which may safely be applied to the product for it to remain in specification once force isreturned to the operating force range. Exposure to higher forces may cause permanent damage to theproduct. Unless otherwise specified, this applies to all temperatures within the operating temperature range.1. The temperature range over which the product may safely be exposed without excitation or force applied. Under these conditions theproduct will remain in specification after excursion to any temperatures in this range. Exposure to temperatures beyond this range may cause permanent damage to the product.2. MCTF is a basic measure of reliability for a non-repairable device. It is the mean number of cycles to maximum operating force over whicha sensor can be expected to operate until failure. The mean value is determined statistically from a probability distribution for failures based upon test data. MCTF may vary depending on the specific application in which a sensor is utilized.Low Profile Force SensorHoneywell Sensing and Control311. Absolute maximum ratings are the extreme limits that the product can withstand without damage to the product.2. The temperature range over which the product may safely be exposed without excitation or force applied. Under these conditions, theproduct will remain in the specification after excursions to any temperature in this range. Exposure to temperatures beyond this range may cause permanent damage to the product.3. The maximum temperature and time to which the product may be exposed for processing of solder electrical connections.Figure 3. Packaging Dimensions (For reference only.) Short Tube: 43,9 mm [1.73 in] long, 5 units/tubeStandard Tube: 584 mm [22.99 in] long, 100 units/ tubeTape and Reel (mm)2.∙∙Sensing and Control Honeywell1985 Douglas Drive NorthGolden Valley, MN 55422 080809-2-ENFebruary 2013© 2013 Honeywell International Inc. All rights reserved.MISUSE OF DOCUMENTATIONWARRANTY/REMEDYHoneywell warrants goods of its manufacture as being free of defective materials and fa ulty workmanship. Honeywell’s standard product warranty applies unless agreed to otherwise by Honeywell in writing; please refer to your order acknowledgement or consult your local sales office for specific warranty details. If warranted goods are returned to Honeywell during the period of coverage, Honeywell will repair or replace, at its option, without charge those items it finds defective. The foregoing is buyer’s sole remedy and is in lieu of all other warranties, expressed or implied, including those of merchantability and fitness for a particular purpose. In no event shall Honeywell be liable for consequential, special, or indirect damages.While we provide application assistance personally, through our literature and the Honeywell web site, it is up to the customer to determine the suitability of the product in the application.Specifications may change without notice. The information we supply is believed to be accurate and reliable as of this printing. However, we assume no responsibility for its use.PERSONAL INJURYSALES AND SERVICEHoneywell serves its customers through a worldwide network of sales offices, representatives and distributors. For application assistance, current specifications, pricing or name of the nearest Authorized Distributor, contact your local sales office or:E-mail:*********************Internet:Phone and Fax:Asia Pacific +65 6355-2828+65 6445-3033 FaxEurope +44 (0) 1698 481481+44 (0) 1698 481676 FaxLatin America +1-305-805-8188+1-305-883-8257 FaxUSA/Canada +1-800-537-6945+1-815-235-6847+1-815-235-6545 FaxMouser ElectronicsAuthorized DistributorClick to View Pricing, Inventory, Delivery & Lifecycle Information:H oneywell:FSS1500NSR FSS1500NST FSS1500NGT FSS1500NGR。
[38]VanSlotenT，Schram M Understandingdepressionintype2diabetes：a biolo g icala pp roachin observationalstudies[J] F1000Res，2018，7：F1000[39]van der Heijden MM,van Dooren FE,Pop VJ,et aS.Effectsof exercise training on quality of life,symptoms of depression, symptoms of anxiety and emotional we ii-being in type2diabe-tesme l itus：as y stematicreview[J]Diabetolo g ia,2013,56(6)：1210-1225：40]萇静,山曦.老年2型糖尿病患者运动状况及干预策略:J].实用临床医药杂志，2017,21(16)：148-150.(收稿日期：2019-11-04)降脂治疗中LDL-C水平目标值的探讨何璐，王曦摘要：血脂异常是动脉粥样硬化心血管疾病(ASCVD)的独立危险因素，降低低密度脂蛋白-胆固醇(LDL-C)水平,可显著降低ASCVD的发病率,但LDL-C的目标值应该是多少仍有争议。
大多数研究证实,他汀类使LDL-C水平下降到调脂指南现有标准以下能使患者进一步受益，且降低至30mg/dl是安全的。
因此，提倡在临床实践中，将LDL-C水平降低到现有指南推荐的水平以下。
关键词：动脉粥样硬化；血脂异常;脂蛋白类，LDL文章编号：1008-0074(2021)01-95-04中图分类号：R543.5文献标识码：A Doi：10.3969/j.isn.1008-0074.2021.01.25Discussion of target value of LDL一C level in lipid一lowering therapy/HE Lu,WANG Xi//Department of Cardiology,First Affiliated Hospital of Chongqing Medical University,Chongqing,400000,ChinaCorresponding author：WANG Xi,E-mail：1874993260@Abstract:Dyslipidemia is an independent risk factor for atherosclerotic cardiovascular disease(ASCVD).Lowering level of low density lipoprotein—cholesterol(LDL-C)can significantly reduce morbidity of ASCVD,but the target valueofLDL-Cissti l controversial MoststudieshaveconfirmedthatstatinslowerLDL-Clevelbelowthecur-rent standards of guidelines,which can further benefit patients.And its safe to reduce LDL—C to30mg/dl.There-fore，itisrecommendedtoreduceLDL-Cleveltobelowtherecommendedlevelofexistingguidelinesinclinical practiceKey words:Atherosclerosis；Dyslipidemias；Lipoproteins,LDLSupported by fund project:Chongqing Basic Research and Frontier Exploration Project(Chongqing Natural Science Foundation)(cstc2018jcyjAX0058)血脂异常是动脉粥样硬化心血管疾病（atherosclerotic cardiovasculardisease,ASCVD）的独立危险因素,降低低密度脂蛋白-胆固醇（LDL-C）水平，可显著减少ASCVD 的发病，2016年欧洲心脏病学会（ESC）血脂异常管理指南仍强调将降低LDL-C作为最主要的治疗靶点，到目前为止,所有关于血脂防治的指南均将LDL-C作为首要治疗靶点。
机械通气临床应用指南中华医学会重症医学分会（2024年）引言重症医学是探讨危重病发生发展的规律，对危重病进行预防和治疗的临床学科。
器官功能支持是重症医学临床实践的重要内容之一。
机械通气从仅作为肺脏通气功能的支持治疗起先，经过多年来医学理论的发展及呼吸机技术的进步，已经成为涉及气体交换、呼吸做功、肺损伤、胸腔内器官压力及容积环境、循环功能等，可产生多方面影响的重要干预措施，并主要通过提高氧输送、肺脏爱护、改善内环境等途径成为治疗多器官功能不全综合征的重要治疗手段。
机械通气不仅可以依据是否建立人工气道分为“有创”或“无创”，因为呼吸机具有的不同呼吸模式而使通气有众多的选择，不同的疾病对机械通气提出了具有特异性的要求，医学理论的发展及循证医学数据的增加使对呼吸机的临床应用更加趋于有明确的针对性和规范性。
在这种条件下，不难看出，对危重病人的机械通气制定规范有明确的必要性。
同时，多年临床工作的积累和多中心临床探讨证据为机械通气指南的制定供应了越来越充分的条件。
中华医学会重症医学分会以循证医学的证据为基础，采纳国际通用的方法，经过广泛征求看法和建议，反复仔细探讨，达成关于机械通气临床应用方面的共识，以期对危重病人的机械通气的临床应用进行规范。
重症医学分会今后还将依据医学证据的发展及新的共识对机械通气临床应用指南进行更新。
指南中的举荐看法依据2024年ISF提出的Delphi分级标准(表1)。
指南涉及的文献依据探讨方法和结果分成5个层次，举荐看法的举荐级别依据Delphi分级分为A E级，其中A 级为最高。
表1 Delphi分级标准举荐级别A 至少有2项I级探讨结果支持B 仅有1项I级探讨结果支持C 仅有II级探讨结果支持D 至少有1项III级探讨结果支持E 仅有IV级或V探讨结果支持探讨课题分级I 大样本，随机探讨，结果清楚，假阳性或假阴性的错误很低II 小样本，随机探讨，结果不确定，假阳性和/或假阴性的错误较高III 非随机，同期比照探讨IV 非随机，历史比照和专家看法V 病例报道，非比照探讨和专家看法危重症患者人工气道的选择人工气道是为了保证气道通畅而在生理气道与其他气源之间建立的连接，分为上人工气道和下人工气道，是呼吸系统危重症患者常见的抢救措施之一。
测井资料常用英文代码表Microlog 1 Microlog 2 Acousticlog Density Compensated Dual-Spacing Neutron Log Caliper Bit Size Gamma Ray-Natural Radioactivity Spontaneous Potential Deep Investigation Induction Log Midium Investigation Induction Log Laterolog 8 Micro-Sphericlly Focused Log Laterolog Deep Laterolog Shallow Resistivity 4True Formation ResistivityResistivity 2.5 中子伽马 中子伽马 泥质含量 孔隙度 渗透率 含水饱和度 含油饱和度 束缚水饱和度 残余油饱和度 深侧向电阻率 LLD 浅侧向电阻率 LLS 4米梯度电阻率RT 地层真电阻率RT 感应电导率2.5 米梯 度电 阻率 R2.5 微梯度ML1 微电位ML2 声波时差AC 密度DEN 中子孔隙度CNL 井径CAL 钻头大小BS 自然伽马GR 自然电位SP 深感应电阻率ILD 中感应电阻率ILM 八侧向电阻率LL8 COND Conductivity NGR Neutron Gamma RaySH ShalePOR PorosityPERM PermeabilitySW Water SaturationSO Oil Saturation ofSWI Initial Water SaturationSOR Residual Oil Saturation微 球 形 聚 焦 电 阻 率 MSFL NEU Neutron斯仑贝谢 ( Schlumberger ) 常用英文缩写数控测井系统CSU Cyber Service Units 或Computerized Logging Units 声波时差DT Delta T密度RHOB Rho Bulk中子孔隙度NPHI Neutron Phi感应电导率CILD IL-Deep Conductivity井径CALS Caliper Size自然伽马能谱NGS Natural Gamma Ray Spectrolog铀URAN Uranium钍THOR Thorium钾POTA Potassium高分辨率地层倾角仪HDT High Resolution Dipmeter Tool地层学高分辨率地层倾角仪SHDT Stratigraphy High Resolution Dipmeter Tool地层压力RFT Repeat Formation Tester波形WF Wave Form微电阻率成像FMI Fullbore Formation Micro Imager Tool 阵列感应成像AIT Array Induction Imager Tool方位侧向成像ARI Azimuthal Resistivity Imager Tool偶极声波成像DSI Dipole Shear Sonic Image Tool超声波成像USI Ultrasonic Imager Tool核磁共振CMR Combination Magnetic Resonance模块式地层动态测试仪MDT Modular Formation Dynamics Tester测井曲线名称汇总GRSL—能谱自然伽马POR 孔隙度NEWSANDPORW 含水孔隙度NEWSANDPORF 冲洗带含水孔隙度NEWSANDPORT 总孔隙度NEWSANDPORX 流体孔隙度NEWSANDPORH 油气重量NEWSANDBULK 出砂指数NEWSANDPERM 渗透率NEWSANDSW 含水饱和度NEWSANDSH 泥质含量NEWSANDCALO 井径差值NEWSANDCL 粘土含量NEWSANDDHY 残余烃密度NEWSANDSXO 冲洗带含水饱和度NEWSANDDA 第一判别向量的判别函数NEWSAND DB 第二判别向量的判别函数NEWSAND DAB 综合判别函数NEWSANDCI 煤层标志NEWSANDCARB 煤的含量NEWSANDTEMP 地层温度NEWSANDQ 评价泥质砂岩油气层产能的参数NEWSANDPI 评价泥质砂岩油气层产能的参数NEWSAND SH 泥质体积CLASSSW 总含水饱和度CLASSPOR 有效孔隙度CLASSPORG 气指数CLASSCHR 阳离子交换能力与含氢量的比值CLASS CL 粘土体积CLASSPORW 含水孔隙度CLASSPORF 冲洗带饱含泥浆孔隙度CLASSCALC 井径差值CLASSDHYC 烃密度CLASSPERM 绝对渗透率CLASSPIH 油气有效渗透率CLASSPIW 水的有效渗透率CLASSCLD 分散粘土体积CLASSCLL 层状粘土体积CLASSCLS 结构粘土体积CLASSEPOR 有效孔隙度CLASSESW 有效含水饱和度CLASSTPI 钍钾乘积指数CLASSPOTV 10 0%粘土中钾的体积CLASSCEC 阳离子交换能力CLASSQV 阳离子交换容量CLASSBW 粘土中的束缚水含量CLASSEPRW 含水有效孔隙度CLASSUPOR 总孔隙度，UPOR=EPOR+BW CLASS HI 干粘土骨架的含氢指数CLASSBWCL 粘土束缚水含量CLASSTMON 蒙脱石含量CLASSTILL 伊利石含量CLASSTCHK 绿泥石和高岭石含量CLASSVSH 泥质体积CLASSVSW 总含水饱和度CLASSVPOR 有效孔隙度CLASSVPOG 气指数CLASSVCHR 阳离子交换能力与含氢量的比值CLASS VCL 粘土体积CLASSVPOW 含水孔隙度CLASSVPOF 冲洗带饱含泥浆孔隙度CLASSVCAC 井径差值CLASSVDHY 烃密度CLASSVPEM 绝对渗透率CLASSVPIH 油气有效渗透率CLASSVPIW 水的有效渗透率CLASSVCLD 分散粘土体积CLASSVCLL 层状粘土体积CLASSVCLS 结构粘土体积CLASSVEPO 有效孔隙度CLASSVESW 有效含水饱和度CLASSVTPI 钍钾乘积指数CLASSVPOV 100%粘土中钾的体积CLASSVCEC 阳离子交换能力CLASSVQV 阳离子交换容量CLASSVBW 粘土中的束缚水含量CLASSVEPR 含水有效孔隙度CLASSVUPO 总孔隙度CLASSVHI 干粘土骨架的含氢指数CLASSVBWC 粘土束缚水含量CLASSVTMO 蒙脱石含量CLASSVTIL 伊利石含量CLASSVTCH 绿泥石和高岭石含量CLASSQW 井筒水流量PLIQT 井筒总流量PLISK 射孔井段PLIPQW 单层产水量PLIPQT 单层产液量PLIWEQ 相对吸水量ZRPM PEQ 相对吸水强度ZRPM POR 孔隙度PRCO PORW 含水孔隙度PRCO PORF 冲洗带含水孔隙度PRCO PORT 总孔隙度PRCO PORX 流体孔隙度PRCO PORH 油气重量PRCO BULK 出砂指数PRCO HF 累计烃米数PRCO PF 累计孔隙米数PRCO PERM 渗透率PRCO SW 含水饱和度PRCO SH 泥质含量PRCO CALO 井径差值PRCO CL 粘土含量PRCO DHY 残余烃密度PRCO SXO 冲洗带含水饱和度PRCO SWIR 束缚水饱和度PRCO PERW 水的有效渗透率PRCOPERO 油的有效渗透率PRCOKRW 水的相对渗透率PRCOKRO 油的相对渗透率PRCOFW 产水率PRCOSHSI 泥质与粉砂含量PRCOSXOF 199＊SXO PRCOSWCO 含水饱和度PRCOWCI 产水率PRCOWOR 水油比PRCOCCCO经过PORT校正后的C/ O值PRCOCCSC经过PORT校正后的SI/CA值PRCOCCCS经过PORT校正后的CA/SI值PRCODCO油水层C/ O差值PRCOXIWA 水线视截距PRCOCOWA 视水线值PRCOCONM 视油线值PRCOCPRW 产水率（C/ O计算）PRCOCOAL 煤层CRAOTHR 重矿物的百分比含量CRASALT 盐岩的百分比含量CRASAND 砂岩的百分比含量CRALIME 石灰岩的百分比含量CRADOLM 白云岩的百分比含量CRAANHY 硬石膏的百分比含量CRA ANDE 安山岩的百分比含量CRA BASD 中性侵入岩百分比含量CRA DIAB 辉长岩的百分比含量CRA CONG 角砾岩的百分比含量CRA TUFF 凝灰岩的百分比含量CRA GRAV 中砾岩的百分比含量CRA BASA 玄武岩的百分比含量CRA常用测井曲线名称A1R1 T1R1 声波幅度A1R2 T1R2 声波幅度A2R1 T2R1 声波幅度A2R2 T2R2 声波幅度AAC 声波附加值AAVG 第一扇区平均值AC 声波时差AF10 阵列感应电阻率AF20 阵列感应电阻率AF30 阵列感应电阻率AF60 阵列感应电阻率AF90 阵列感应电阻率AFRT 阵列感应电阻率AFRX 阵列感应电阻率AIMP 声阻抗AIPD 密度孔隙度AIPN 中子孔隙度AMAV 声幅AMAX 最大声幅AMIN 最小声幅AMP1 第一扇区的声幅值AMP2 第二扇区的声幅值AMP3 第三扇区的声幅值AMP4 第四扇区的声幅值AMP5 第五扇区的声幅值AMP6 第六扇区的声幅值AMVG 平均声幅AO10 阵列感应电阻率AO20 阵列感应电阻率AO30 阵列感应电阻率AO60 阵列感应电阻率AO90 阵列感应电阻率AOFF 截止值AORT 阵列感应电阻率AORX 阵列感应电阻率APLC 补偿中子AR10 方位电阻率AR11 方位电阻率AR12 方位电阻率ARO1 方位电阻率ARO2 方位电阻率ARO3 方位电阻率ARO4 方位电阻率ARO5 方位电阻率ARO6 方位电阻率ARO7 方位电阻率ARO8 方位电阻率ARO9 方位电阻率AT10 阵列感应电阻率AT20 阵列感应电阻率AT30 阵列感应电阻率AT60 阵列感应电阻率AT90 阵列感应电阻率ATAV 平均衰减率ATC1 声波衰减率ATC2 声波衰减率ATC3 声波衰减率ATC4 声波衰减率ATC5 声波衰减率ATC6 声波衰减率ATMN 最小衰减率ATRT 阵列感应电阻率ATRX 阵列感应电阻率AZ 1 号极板方位AZ1 1 号极板方位AZI 1 号极板方位AZIM 井斜方位BGF 远探头背景计数率BGN 近探头背景计数率BHTA 声波传播时间数据BHTT 声波幅度数据BLKC 块数BS 钻头直径BTNS 极板原始数据C1 井径C2 井径C3 井径CAL 井径CAL1 井径CAL2 井径CALI 井径CALS 井径CASI 钙硅比CBL 声波幅度CCL 磁性定位CEMC 水泥图CGR 自然伽马CI 总能谱比CMFF 核磁共振自由流体体积CMRP 核磁共振有效孔隙度CN 补偿中子CNL 补偿中子CO 碳氧比CON1 感应电导率COND 感应电导率CORR 密度校正值D2EC 200 兆赫兹介电常数D4EC 47 兆赫兹介电常数DAZ 井斜方位DCNT 数据计数DEN 补偿密度DEN_1 岩性密度DEPTH 测量深度DEV 井斜DEVI 井斜DFL 数字聚焦电阻率DIA1 井径DIA2 井径DIA3 井径DIFF 核磁差谱DIP1 地层倾角微电导率曲线1 DIP1_1 极板倾角曲线DIP2 地层倾角微电导率曲线2 DIP2_1 极板倾角曲线DIP3 地层倾角微电导率曲线3 DIP3_1 极板倾角曲线DIP4 地层倾角微电导率曲线4DIP4_1 极板倾角曲线DIP5 极板倾角曲线DIP6 极板倾角曲线DRH 密度校正值DRHO 密度校正值DT 声波时差DT1 下偶极横波时差DT2 上偶极横波时差DT4P 纵横波方式单极纵波时差DT4S 纵横波方式单极横波时差DTL 声波时差DTST 斯通利波时差ECHO 回波串ECHOQM 回波串ETIMD 时间FAMP 泥浆幅度FAR 远探头地层计数率FCC 地层校正FDBI 泥浆探测器增益FDEN 流体密度FGAT 泥浆探测器门限FLOW 流量FPLC 补偿中子FTIM 泥浆传播时间GAZF Z 轴加速度数据GG01 屏蔽增益GG02 屏蔽增益GG03 屏蔽增益GG04 屏蔽增益GG05 屏蔽增益GG06 屏蔽增益GR 自然伽马GR2 同位素示踪伽马HAZI 井斜方位HDRS 深感应电阻率HFK 钾HMRS 中感应电阻率HSGR 无铀伽马HTHO 钍HUD 持水率HURA 铀IDPH 深感应电阻率IMPH 中感应电阻率K 钾KCMR 核磁共振渗透率KTH 无铀伽马LCAL 井径LDL 岩性密度LLD 深侧向电阻率LLD3 深三侧向电阻率LLD7 深七侧向电阻率LLHR 高分辨率侧向电阻率LLS 浅侧向电阻率LLS3 浅三侧向电阻率LLS7 浅七侧向电阻率M1R10 高分辨率阵列感应电阻率M1R120 高分辨率阵列感应电阻率M1R20 高分辨率阵列感应电阻率M1R30 高分辨率阵列感应电阻率M1R60 高分辨率阵列感应电阻率M1R90 高分辨率阵列感应电阻率M2R10 高分辨率阵列感应电阻率M2R120 高分辨率阵列感应电阻率M2R20 高分辨率阵列感应电阻率M2R30 高分辨率阵列感应电阻率M2R60 高分辨率阵列感应电阻率M2R90 高分辨率阵列感应电阻率M4R10 高分辨率阵列感应电阻率M4R120 高分辨率阵列感应电阻率M4R20 高分辨率阵列感应电阻率M4R30 高分辨率阵列感应电阻率M4R60 高分辨率阵列感应电阻率M4R90 高分辨率阵列感应电阻率MBVI 核磁共振束缚流体体积MBVM 核磁共振自由流体体积MCBW 核磁共振粘土束缚水ML1 微电位电阻率ML2 微梯度电阻率MPHE 核磁共振有效孔隙度MPHS 核磁共振总孔隙度MPRM 核磁共振渗透率MSFL 微球型聚焦电阻率NCNT 磁北极计数NEAR 近探头地层计数率NGR 中子伽马NPHI 补偿中子P01 第1 组分孔隙度P02 第2 组分孔隙度P03 第3 组分孔隙度P04 第4 组分孔隙度P05 第5 组分孔隙度P06 第6 组分孔隙度P07 第7 组分孔隙度P08 第8 组分孔隙度P09 第9 组分孔隙度P10 第10 组分孔隙度P11 第11 组分孔隙度P12 第12 组分孔隙度P1AZ 1 号极板方位P1AZ_1 2号极板方位P1BTN 极板原始数据P2BTN 极板原始数据P2HS 200 兆赫兹相位角P3BTN 极板原始数据P4BTN 极板原始数据P4HS 47 兆赫兹相位角P5BTN 极板原始数据P6BTN 极板原始数据PAD1 1 号极板电阻率曲线PAD2 2 号极板电阻率曲线PAD3 3 号极板电阻率曲线PAD4 4 号极板电阻率曲线PAD5 5 号极板电阻率曲线PAD6 6 号极板电阻率曲线PADG 极板增益PD6G 屏蔽电压PE 光电吸收截面指数PEF 光电吸收截面指数PEFL 光电吸收截面指数PERM-IND 核磁共振渗透率POTA 钾PPOR 核磁T2 谱PPORB 核磁T2 谱PPORC 核磁T2 谱PR 泊松比PRESSURE 压力QA 加速计质量QB 磁力计质量QRTT 反射波采集质量R04 0.4 米电位电阻率R045 0.45 米电位电阻率R05 0.5 米电位电阻率R1 1米底部梯度电阻率R25 2.5 米底部梯度电阻率R4 4米底部梯度电阻率R4AT 200 兆赫兹幅度比R4AT_1 47 兆赫兹幅度比R4SL 200 兆赫兹电阻率R4SL_1 47 兆赫兹电阻率R6 6米底部梯度电阻率R8 8米底部梯度电阻率RAD1 井径（极板半径）RAD2 井径（极板半径）RAD3 井径（极板半径）RAD4 井径（极板半径）RAD5 井径（极板半径）RAD6 井径（极板半径）RADS 井径（极板半径）RATI 地层比值RB 相对方位RB_1 相对方位角RBOF 相对方位RD 深侧向电阻率RFOC 八侧向电阻率RHOB 岩性密度RHOM 岩性密度RILD 深感应电阻率RILM 中感应电阻率RLML 微梯度电阻率RM 钻井液电阻率RMLL 微侧向电阻率RMSF 微球型聚焦电阻率RNML 微电位电阻率ROT 相对方位RPRX 邻近侧向电阻率RS 浅侧向电阻率SDBI 特征值增益SFL 球型聚焦电阻率SFLU 球型聚焦电阻率SGAT 采样时间SGR 无铀伽马SICA 硅钙比SIG 井周成像特征值SIGC 俘获截面SIGC2 示踪俘获截面SMOD 横波模量SNL 井壁中子SNUM 特征值数量SP 自然电位SPER 特征值周期T2 核磁T2 谱T2-BIN-A 核磁共振区间孔隙度T2-BIN-B 核磁共振区间孔隙度T2-BIN-PR 核磁共振区间孔隙度T2GM T2 分布对数平均值T2LM T2 分布对数平均值TEMP 井温TH 钍THOR 钍TKRA 钍钾比TPOR 核磁共振总孔隙度TRIG 模式标志TS 横波时差TT1 上发射上接受的传播时间TT2 上发射下接受的传播时间TT3 下发射上接受的传播时间TT4 下发射下接受的传播时间TURA 钍铀比U 铀UKRA 铀钾比URAN 铀VAMP 扇区水泥图VDL 声波变密度VMVM 核磁共振自由流体体积VPVS 纵横波速度比WAV1 第一扇区的波列WAV2 第二扇区的波列WAV3 第三扇区的波列WAV4 第四扇区的波列WAV5 第五扇区的波列WAV6 第六扇区的波列WAVE 变密度图WF 全波列波形ZCORR 密度校正值测井曲线代码一览表常用测井曲线名称测井符号英文名称中文名称Rt true formation resistivity. 地层真电阻率Rxo flushed zone formationresistivity 冲洗带地层电阻率lid deep in vestigate in duction log 深探测感应测井Ilm medium investigate induction log 中探测感应测井lls shallow investigate induction log 浅探测感应测井Rd deepinvestigate double lateral resistivity log深双侧向电阻率测井Rs shallow investigate double 浅双侧向电阻率测井lateral resistivity log RMLL micro lateral resistivity log 微侧向电阻率测井CON induction log 感应测井AC acoustic 声波时差DEN density 密度CN neutron 中子常用测井曲线名称测井符号 英文名称 中文名称Rt true formation resistivity. 地层真电阻率Rxo flushed zone formation resistivity 冲洗带地层电阻率Ild deep investigate induction log 深探测感应测井Ilm medium investigate induction log 中探测感应测井Ils shallow investigate induction log 浅探测感应测井Rd deep investigate double lateral resistivity log 深双侧向电阻率测井 Rs shallow investigate double lateral resistivity log 浅双侧向电阻率测井 RMLL micro lateral resistivity log 微侧向电阻率测井CON induction log 感应测井AC acoustic 声波时差DEN density 密度CN neutron 中子 SP spontaneous potential自然电位CALborehole diameter 井径K potassium 钾TH thorium钍Uuranium 铀 KTHgamma ray without uranium 无铀伽马NGR neutron gamma ray中子伽马 GR natural gamma ray自然伽马GR natural gamma ray 自然伽马SP spontan eous pote ntial 自然电位CAL borehole diameter 井径K potassium 钾TH thorium 钍U uranium 铀KTH gamma ray without uranium 无铀伽马NGR neutron gamma ray 中子伽马5700 系列的测井项目及曲线名称Star Imager 微电阻率扫描成像CBIL 井周声波成像多极阵列声波成像MACMRIL 核磁共振成像TBRT 薄层电阻率DAC 阵列声波DVRT 数字垂直测井HDIP 六臂倾角MPHI 核磁共振有效孔隙度MBVM 可动流体体积MBVI 束缚流体体积MPERM 核磁共振渗透率Echoes 标准回波数据T2 Dist T2 分布数据TPOR 总孔隙度BHTA 声波幅度BHTT 声波返回时间Image DIP 图像的倾角COMP AMP 纵波幅度Shear AMP 横波幅度COMP ATTN 纵波衰减Shear ATTN 横波衰减RADOUTR 井眼的椭圆度Dev 井斜。
Justification for the Use of Statins in Primary Prevention:An Intervention Trial Evaluating Rosuvastatin(JUPITER)—Can C-Reactive Protein Be Used to Target Statin Therapy inPrimary Prevention?Samia Mora,MD,MHS,and Paul M Ridker,MD,MPH*The most important action of3-hydroxy-3-methylglutaryl coenzyme A reductaseinhibitors(statins)is their ability to lower levels of low-density lipoprotein(LDL)cholesterol.Statins have proved highly effective in reducing the risk of cardiovascularevents in both primary and secondary prevention studies.However,the magnitude ofrisk reduction associated with statins is greater than that predicted on the basis ofLDL cholesterol lowering alone.A likely explanation for this effect is the anti-inflammatory action of statins.Following the observation that high-sensitivity C-re-active protein(hs-CRP)is a powerful predictor of cardiovascular events,investigatorsin the Cholesterol and Recurrent Events(CARE)and Air Force/Texas CoronaryAtherosclerosis Prevention Study(AFCAPS/TexCAPS)trials demonstrated that themagnitude of risk reduction associated with statin therapy was higher among thosewith elevated hs-CRP levels.In addition,there is accumulating evidence that statinslower plasma levels of hs-CRP in a manner largely independent of LDL cholesterollowering.In contrast,little benefit has been demonstrated for statin therapy in theabsence of both hyperlipidemia and inflammation.Justification for the Use of Statinsin Primary Prevention:an Intervention Trial Evaluating Rosuvastatin(JUPITER)isa large multinational,long-term,double-blind,placebo-controlled,randomized clin-ical trial designed to assess directly whether statin therapy(rosuvastatin20mg/day)should be given to apparently healthy individuals with low LDL cholesterol levels butelevated hs-CRP levels—a critical issue for the prevention of cardiovascular disease.Support for the concept behind the JUPITER trial is also now available from severalrecent trials comparing different intensities of statin therapy on disease progressionas well as clinical end points.These studies indicate that the hs-CRP level achievedafter initiation of statin therapy may be as important as the LDL cholesterol levelachieved.All of these data raise the possibility that hs-CRP could be used to targethigh-risk patients who may benefit from early statin use.Ongoing work will deter-mine whether hs-CRP reduction,independent of LDL cholesterol reduction,results ina net clinical benefit.©2006Elsevier Inc.All rights reserved.(Am J Cardiol2006;97[suppl]:33A–41A)Numerous avenues of research ranging from basic experi-mental evidence to population-based observational studies have led to the recognition that cardiovascular disease (CVD)involves a systemic inflammatory process.1Large epidemiologic studies carried out in diverse populations have repeatedly documented the association between high-sensitivity C-reactive protein(hs-CRP),an indicator of in-flammation,and CVD outcomes,independent of traditional cardiovascular risk factors.2However,it remains uncertain whether therapies that lower hs-CRP levels would also result in lower cardiovascular event rates.The3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins)are the most widely studied lipid-lower-ing agents and the most effective low-density lipoprotein (LDL)cholesterol–lowering medications.Statins lower LDL cholesterol and total cholesterol levels by approxi-mately20%to50%and have a lesser effect on lowering triglycerides(Ϸ10%to40%)and raising high-density li-poprotein(HDL)cholesterol(Ϸ5%to15%)levels.Most studies of the effect of statins on outcomes have shown that for approximately every1%reduction in LDL cholesterol level,there is an associated1%reduction in risk of clinical cardiovascular events.3Data from multiple large-scale randomized clinical trialsCenter for Cardiovascular Disease Prevention and Division of Cardio-vascular Disease,Department of Medicine,Brigham and Women’s Hos-pital,Harvard Medical School,Boston,Massachusetts,USA.Paul M Ridker is listed as a co-inventor on patents held by the Brighamand Women’s Hospital that relate to the use of inflammatory biomarkers incardiovascular disease.*Address for correspondence:Paul M Ridker,MD,MPH,Center forCardiovascular Disease Prevention,Brigham and Women’s Hospital,900Commonwealth Avenue East,Boston,Massachusetts02215.E-mail address:pridker@.0002-9149/06/$–see front matter©2006Elsevier Inc.All rights doi:10.1016/j.amjcard.2005.11.014support a similar relative risk reduction with statin therapyfor cardiovascular outcomes in both the primary and thesecondary prevention of CVD.This has led to the develop-ment of current international guidelines that focus on LDLcholesterol lowering as the primary target of therapy,tai-loring the level of optimal LDL cholesterol reduction to theindividual’s level of cardiovascular risk.3Several risk pre-diction models,such as the Framingham risk equations andthe European Systematic Coronary Risk Evaluation(SCORE),use traditional risk factors to estimate globalCVD risk in asymptomatic individuals.4,5However,mostUS women and a large proportion of US men are classifiedas low risk when the Framingham risk score,as recom-mended by the National Cholesterol Education ProgramAdult Treatment Panel III(NCEP ATP III)guidelines,isused to estimate risk in the primary prevention setting.Current US population estimates from the National Healthand Nutrition Examination Survey(NHANES)found that Ͻ1%of women had high-risk Framingham scores(10-year estimated risk for hard coronary events ofϾ20%)and only4%of women had intermediate-risk scores(10%to20%),compared with5%and29%in men,respectively.6Mean-while,the lifetime risk of developing CVD for both men andwomen is substantially higher—approximately1in3forwomen and1in2for men.7To improve cardiovascular risk stratification and detec-tion,an expert panel assembled by the Centers for DiseaseControl and Prevention(CDC)and the American HeartAssociation(AHA)provided a scientific statement onhs-CRP summarizing how it may be applied for clinicalcardiovascular risk assessment in primary prevention pop-ulations.8This report termed hs-CRP an independentmarker of cardiovascular risk and endorsed its use as part ofglobal risk prediction in asymptomatic individuals,particu-larly those deemed at intermediate risk for CVD by tradi-tional risk factors.8The panel also established a set of cutpoints to be used in clinical practice,with hs-CRP levels of Ͻ1mg/L considered low risk andϾ3mg/L,high risk.The Cholesterol And Recurrent Events(CARE)trialfirstdemonstrated that statin therapy also lowers plasma levelsof hs-CRP.9This has since been shown to be a class effect,with an approximate statin-mediated reduction of hs-CRPlevels of20%to30%.9,10However,the beneficial value oflowering hs-CRP that is independent of lowering LDL cho-lesterol is not so clear.The critical question then becomes whether inflamma-tory markers,such as hs-CRP,can be clinically useful inselecting patients who may benefit from statin therapy de-spite having normal LDL cholesterol values.This is thehypothesis driving Justification for the Use of Statins inPrimary Prevention:an Intervention Trial Evaluating Rosu-vastatin(JUPITER),a long-term,multinational,random-ized,double-blind,placebo-controlled study to assess rosu-vastatin20mg in the primary prevention of cardiovascularevents in15,000subjects with low LDL cholesterol levelsand elevated levels of hs-CRP.Role of Inflammation in Cardiovascular Disease Multiple large-scale prospective studies performed in a va-riety of populations have demonstrated that hs-CRP is a strong and independent predictor of CVD events,including myocardial infarction(MI),ischemic stroke,sudden cardiac death,and diabetes mellitus.11–22In the Physicians’Health Study,an epidemiologic study ofϾ22,000healthy middle-aged men with no clinical evidence of disease,increasing levels of hs-CRP at study entry were associated with up to a3-fold increase in risk of incident MI and a2-fold increase in risk of ischemic stroke.12When directly compared with other novel risk factors—including homocysteine,lipopro-tein(a),interleukin-6,intercellular adhesion molecule–1, and serum amyloid A—and standard lipid measures,hs-CRP has proved to be the single strongest predictor of cardiovascular risk in apparently healthy women.This is demonstrated in the Women’s Health Study(Figure1),with a relative risk ratio of4.4for the highest versus lowest quartile of hs-CRP.Moreover,the addition of hs-CRP to traditional choles-terol screening enhanced cardiovascular risk prediction and proved to be independent of LDL cholesterol,suggesting that elevated hs-CRP levels may be particularly useful for identifying asymptomatic individuals who may be at high risk for future cardiovascular events but who have average cholesterol levels.As shown in Figure2,the poorest event-free survival in women was among those with high LDL cholesterol and high hs-CRP levels,and the best event-free survival was among those with low LDL cholesterol and low hs-CRP levels.Notably,individuals with low LDL cholesterol levels but high hs-CRP levels were at higher risk than those with high LDL cholesterol levels but low hs-CRP levels.This importantfinding of higher risk associated with high hs-CRP/low LDL cholesterol is among the motivating factors behind the JUPITER trial because this population of apparently healthy individuals—usually missed by current screening guidelines—is being prospectively studied for the first time.Levels of hs-CRP add important prognostic information on cardiovascular risk not only at all levels of LDL choles-terol but also at all levels of the Framingham risk score (Figure3).With increasing levels of global coronary risk (Figure3,left),there was a graded and consistent relation with increasing levels of hs-CRP in a dose-response man-ner.This additional prognostic information is most clini-cally relevant for those asymptomatic individuals who are at intermediate risk for CVD based on their traditional risk factor profile(Framingham risk estimate of5%to20%for developing coronary artery disease over a10-year period). Currently,these individuals are not considered eligible for aggressive risk factor modification with statin therapy be-cause their LDL cholesterol levels are below the current therapeutic target of 3.36mmol/L(130mg/dL).3The JUPITER trial was designed to study just this population. The ability of hs-CRP to add prognostic information on34A The American Journal of Cardiology()Vol97(2A)January16,2006global cardiovascular risk after adjustment for all Framing-ham risk factors has been confirmed in 9major prospective studies (Figure 4).The hs-CRP marker has also been found to modify the risk associated with the metabolic syndrome,which en-compasses a number of proatherogenic,prothrombotic,and proinflammatory risk factors (abdominal obesity,el-evated triglycerides,low HDL cholesterol levels,high blood pressure,and high fasting glucose levels).16This finding may be because of the active role that adipocytes play in inflammatory vascular processes,particularly in central or abdominal tissue.The metabolic syndrome has been associated with increased cardiovascular risk and thus was identified as a target of therapy in NCEP ATP III.3Individuals with the metabolic syndrome are more likely to have high hs-CRP levels,and those with 1or2Figure 1.Risk factors for future cardiovascular events in apparently healthy women in the Women’s Health Study.Apo B ϭapolipoprotein B;CRP ϭC-reactive protein;HDL ϭhigh-density lipoprotein;IL-6ϭinterleukin-6;LDL ϭlow-density lipoprotein;SAA ϭserum amyloid A;sICAM-1ϭsoluble intercellular adhesion molecule–1;TC ϭtotal cholesterol.(Reprinted with permission from N Engl J Med .14)Figure 2.Kaplan-Meier curves depicting cardiovascular event-free survival according to 4groups based on high or low levels of C-reactive protein (CRP)and low-density lipoprotein (LDL)over 8years of follow-up in the Women’s Health Study.Low CRP was defined as beneath the study median of 1.52mg/L and low LDL as beneath the study median of 3.2mmol/L (123.7mg/dL).(Reprinted with permission from N Engl J Med .15)35AMora and Ridker/Can C-Reactive Protein Be Used to Target Statin Therapy in Primary Prevention?criteria for the metabolic syndrome have higher hs-CRP levels than those with none.In a study of Ͼ14,000apparently healthy women,me-dian hs-CRP levels for those with 0,1,2,3,4,or 5criteria for the metabolic syndrome were 0.68,1.09,3.01,3.88,and 5.75mg/L,respectively.16In individuals who met NCEP ATP III criteria for the metabolic syndrome,those with high levels of hs-CRP (Ն3mg/L)had worse event-free survival than those with low hs-CRP levels (Ͻ3mg/L).Figure 5shows cardiovascular event-free survival in analyses strati-fied by hs-CRP levels of Ͻ1,1to 3,and Ͼ3mg/L,which are cutoffs chosen to correspond with CDC recommenda-tions for differentiating low-,intermediate-,and high-risk groups.8As clearly shown,hs-CRP levels added informa-tion at all levels of the metabolic syndrome,just as prior data had demonstrated that hs-CRP added importantprog-Figure 3.C-reactive protein (CRP)adds independent prognostic information at all levels of the Framingham risk score (left )and all levels of low-density lipoprotein (LDL)cholesterol (right ).CV ϭcardiovascular.(Reprinted with permission from N Engl J Med .15)Figure 4.C-reactive protein was an independent predictor of cardiovascular risk in 9large prospective studies across diverse populations.ARIC ϭAtherosclerosis Risk in Communities;CHS ϭCardiovascular Health Study;EPIC ϭEuropean Prospective Investigation into Cancer and Nutrition;HPFS ϭHealth Professionals Follow-up Study;MONICA ϭMonitoring Trends and Determinants in Cardiovascular Disease;NHS ϭNurses’Health Study;PHS ϭPhysicians’Health Study;WHS ϭWomen’s Health Study.36A The American Journal of Cardiology ()Vol 97(2A)January 16,2006nostic information at all levels of LDL cholesterol and at all levels of the Framingham risk score.Although a number of different markers of inflamma-tion can provide useful information for predicting car-diovascular risk,acute-phase reactant hs-CRP is cur-rently the most accurate marker.23Inflammatory markers,such as soluble intercellular adhesion molecule–1and interleukin-6,are not readily measured in clinical set-tings,partly because of their instability and partly be-cause of measurement error.In contrast,several commer-cial assays with acceptable coefficients of variation are available for the measurement of CRP,and a program to standardize CRP testing is currently being developed by the CDC.8Emerging evidence also suggests that hs-CRP may not only be a useful marker of inflammation but may also play an active role in the pathogenesis of atherosclerosis (Figure 6).Specifically,CRP appears to be directly involved in augmenting the innate inflammatory response;inducing prothrombotic factors,such as plasminogen activator inhib-itor–1,proinflammatory adhesion molecules,and monocyte chemoattractant protein–1;and interfering with endothelial nitric oxide synthase.24–27Recent studies have shown that CRP is produced not only in the liver,as previously be-lieved,but also locally in other tissues,including smooth muscle cells from normal coronary arteries and diseased coronary artery bypass grafts.28,29Moreover,CRP trans-genic mice that were made to overexpress the human CRP gene developed significant thrombosis after arterial damage,suggesting that hs-CRP may be more than just a marker for atherosclerosis.C-Reactive Protein–Lowering Effects of Statins in Acute Coronary SyndromesUntil recently,it was not known whether the hs-CRP–lowering action of statins provided any clinical benefit be-yond their LDL cholesterol–lowering action.In 2studies published recently—the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL)and the Prava-statin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22(PROVE IT–TIMI 22)studies—the strongest evidence to date is provided for the independent cardiovascular benefits asso-ciated with statin-induced hs-CRP lowering.30,31These 2trials compared the effects of high-dose atorvastatin with those of low-dose pravastatin,demonstrating that lowering hs-CRP levels through intensive statin therapy reduced pro-gression of coronary plaque and risk of recurrent clinical events in patients with acute coronary syndromes.In PROVE IT–TIMI 22,there was a highly significant relative reduction of CVD events (16%)favoring high-dose statin therapy at a 2.5-year follow-up—although the benefit was seen as early as 30days from the start of therapy.31A prespecified analysis of PROVE IT–TIMI 22revealed similar and statistically independent relations between hs-CRP reduction and risk of recurrent coronary events and between LDL cholesterol reduction and risk of such events.When patients were divided into categories on the basis of final hs-CRP and LDL cholesterol levels achieved,those with hs-CRP levels reduced to Ͻ2mg/L had fewer recurrent events,regardless of the LDL cholesterol level achieved by statin therapy.As shown in Figure 7,the patients athighestFigure 5.C-reactive protein (CRP)adds important predictive value to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)metabolic syndrome.CVD ϭcardiovascular disease.(Reprinted with permission from Circulation .16)37AMora and Ridker/Can C-Reactive Protein Be Used to Target Statin Therapy in Primary Prevention?Figure 6.C-reactive protein (CRP)is likely more than just a marker for atherosclerosis,playing an active role in the pathogenesis of atherosclerosis.eNOS ϭendothelial nitric oxide synthase;ET-1ϭendothelin-1;LDL ϭlow-density lipoprotein;MCP-1ϭmonocyte chemoattractant protein–1;mRNA ϭmessenger ribonucleic acid;NO ϭnitric oxide;PAI-1ϭplasminogen activatorinhibitor–1.Figure 7.Cumulative incidence of recurrent coronary events in patients with acute coronary syndromes according to levels of C-reactive protein (CRP)and low-density lipoprotein cholesterol (LDL-C)achieved by statin therapy over a 2.5-year follow-up period.(Reprinted with permission from N Engl J Med .31)38A The American Journal of Cardiology ()Vol 97(2A)January 16,2006risk were those in whom both LDL cholesterol and hs-CRP remained elevated despite statin therapy.In patients whose LDL cholesterol was lowered to below study median (Ͻ1.8mmol/L [Ͻ70mg/dL])with statin use,those whose hs-CRP levels remained elevated had significantly higher recurrent event rates than those whose CRP levels were reduced to Ͻ2mg/L.Moreover,the correlation between hs-CRP re-duction and LDL cholesterol reduction achieved by statin use was small in both trials (correlation coefficient,0.1to 0.2).These findings suggest that the beneficial effects of statin therapy for secondary prevention of cardiovascular events may be as much a result of lowering hs-CRP levels as lowering LDL cholesterol levels.REVERSAL demonstrated that lowering hs-CRP levels in patients with coronary disease by intensive statin therapy resulted in reduced atherosclerotic lesion progression;in some patients there was even atheromatous regression,as measured by intravascular ultrasonography (Figure 8).These findings suggest that to maximize the benefit of statin therapy,physicians may need to monitor hs-CRP levels in addition to LDL cholesterol levels for secondary prevention of CVD.JUPITER will clarify whether such monitoring could also be beneficial for primary prevention.Justification for the Use of Statins in Primary Prevention:An Intervention Trial Evaluating Rosuvastatin (JUPITER)Because inflammation is an integral part of the underly-ing pathophysiology of atherosclerosis and hs-CRP is a useful clinical marker of this inflammatory process,animportant unresolved question is whether hs-CRP screen-ing combined with traditional lipid screening would pro-vide an improved strategy for statin use in primary pre-vention of CVD.The JUPITER trial was designed to answer this question.Several factors governed the de-sign.First,statin therapy has been repeatedly demon-strated to lower the risk of CVD events.Second,several studies have now shown statins to have a greater impact on lowering CVD risk in individuals with higher levels of inflammation.32,33As already noted,for example,inves-tigators in the CARE trial of secondary prevention found that the benefit of pravastatin was greater among subjects with elevated hs-CRP levels.32Similarly,in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)of primary prevention with lova-statin,the event reduction among those with low LDL cholesterol but high hs-CRP was virtually identical to that seen in patients with high LDL cholesterol.33Third,more than half of CVD events occur in individuals with LDL cholesterol levels that current guidelines do not consider eligible for therapy.And finally,because of the hs-CRP–lowering effects of statins,treating individuals with high hs-CRP levels but normal LDL cholesterol levels may extend the benefit of prophylactic statins.The primary objective of the JUPITER trial is to determine whether statin therapy (rosuvastatin 20mg/day)will reduce the rate of first major cardiovascular events,defined as the combined primary end point of cardiovascular death,MI,stroke,hospitalization for un-stable angina,or arterial revascularization among healthy individuals with low LDL cholesterol levels (Ͻ3.36Figure 8.High-sensitivity C-reactive protein (hs-CRP)lowering with aggressive statin therapy slowed atherosclerotic progression and resulted in regression of atheroma volume as measured by intravascular ultrasonography in patients with coronary disease in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL)trial.2ϭreduction greater than study median;1ϭreduction less than study median;LDL-C ϭlow-density lipoprotein cholesterol.(Based on data from N Engl J Med .30)39AMora and Ridker/Can C-Reactive Protein Be Used to Target Statin Therapy in Primary Prevention?mmol/L [130mg/dL])but high hs-CRP levels (Ն2mg/L).34Figure 9shows the basic JUPITER trial design.Asymp-tomatic individuals (men aged Ͼ55years,women aged Ͼ65years)who have no prior history of MI,stroke,or myocardial revascularization and who on initial screening are found to have LDL cholesterol levels Ͻ3.36mmol/L (130mg/dL)and hs-CRP levels Ն2.0mg/L are randomized in a double-blind manner to either rosuvastatin 20mg/day or placebo.All study participants are then observed over a period of 3to 4years for the development of a first cardio-vascular event.JUPITER has been designed to answer de-finitively whether those with average or low LDL choles-terol levels but high hs-CRP levels should be treated aggressively with statin therapy to lower their risk of CVD events.Secondary objectives of JUPITER are to evaluate whether rosuvastatin therapy lowers the incidence of type 2diabetes mellitus,bone fractures,and venous thromboem-bolism.Given the large sample size and the inclusion of a large number of women and minorities,the study will also provide an important tool for evaluating the safety of long-term rosuvastatin use in various racial and ethnic groups.ConclusionThe JUPITER trial is the first large-scale,multinational,double-blind,placebo-controlled clinical trial to investigate the effects of statins in the primary prevention of cardio-vascular events in individuals with low levels of LDL cho-lesterol who may be at risk because of their elevated hs-CRP levels.Trial results could provide an evidence base for the use of hs-CRP in addition to LDL cholesterol to guide statin therapy in primary prevention.Because of its potential impact on public health,this trial represents anextremely important step in understanding the links among inflammation,statin therapy,and CVD prevention—knowl-edge that could lead to substantial alterations in our ap-proach to cardiovascular prophylaxis and treatment.1.Libby P,Ridker PM,Maseri A.Inflammation and atherosclerosis.Circulation 2002;105:1135–1143.2.Bassuk SS,Rifai N,Ridker PM.High-sensitivity C-reactive protein:clinical importance.Curr Probl Cardiol 2004;29:439–493.3.Expert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.Executive summary of the third report of Na-tional Cholesterol Education Program (NCEP)Expert Panel on Detec-tion,Evaluation,and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).JAMA 2001;285:2486–2497.4.Wilson PW,D’Agostino RB,Levy D,Belanger AM,Silbershatz H,Kannel WB.Prediction of coronary heart disease using risk factor categories.Circulation 1998;97:1837–1847.5.Conroy RM,Pyorala K,Fitzgerald AP,Sans S,Menotti A,De Backer G,De Bacquer D,Ducimetiere P,Jousilahti P,Keil U,et al.Estimation of ten-year risk of fatal cardiovascular disease in Europe:the SCORE project.Eur Heart J 2003;24:987–1003.6.Ford ES,Giles WH,Mokdad AH.The distribution of 10-year risk for coronary heart disease among US adults:findings from the National Health and Nutrition Examination Survey III.J Am Coll Cardiol 2004;43:1791–1796.7.Lloyd-Jones DM,Wilson PW,Larson MG,Beiser A,Leip EP,D’Agostino RB,Levy D.Framingham risk score and prediction of lifetime risk for coronary heart disease.Am J Cardiol 2004;94:20–24.8.Pearson TA,Mensah GA,Alexander RW,Anderson JL,Cannon RO III,Criqui M,Fadl YY,Fortmann SP,Hong Y,Myers GL,et al.Markers of inflammation and cardiovascular disease:application to clinical and public health practice:a statement for healthcare profes-sionals from the Centers for Disease Control and Prevention and the American Heart Association.Circulation 2003;107:499–511.9.Ridker PM,Rifai N,Pfeffer MA,Sacks F,Braunwald E,for the Cholesterol and Recurrent Events (CARE)Investigators.Long-term effects of pravastatin on plasma concentration of C-reactive protein.Circulation 1999;100:230–235.10.Albert MA,Danielson E,Rifai N,Ridker PM.Effect of statin therapyon C-reactive protein levels:the pravastatin inflammation/CRP eval-uation (PRINCE):a randomized trial and cohort study.JAMA 2001;286:64–70.Figure 9.Schematic of the basic trial design for Justification for the Use of Statins in Primary Prevention:an Intervention Trial Evaluating Rosuvastatin (JUPITER),a large multicenter trial to answer definitively whether those with low cholesterol levels but high C-reactive protein (CRP)levels should be treated aggressively with statin therapy to prevent cardiovascular events.CABG/PTCA ϭcoronary artery bypass graft surgery/percutaneous transluminal coronary angioplasty;CAD ϭcoronary artery disease;CVD ϭcardiovascular disease;HbA 1c ϭhemoglobin A 1c ;LDL-C ϭlow density lipoprotein cholesterol;LFTs ϭliver function tests;MI ϭmyocardial infarction.40A The American Journal of Cardiology ()Vol 97(2A)January 16,200611.Kuller LH,Tracy RP,Shaten J,Meilahn EN.Relation of C-reactiveprotein and coronary heart disease in the MRFIT nested case-control study:Multiple Risk Factor Intervention Trial.Am J Epidemiol1996;144:537–547.12.Ridker PM,Cushman M,Stampfer MJ,Tracy RP,Hennekens CH.Inflammation,aspirin,and the risk of cardiovascular disease in appar-ently healthy men.N Engl J Med1997;336:973–979.13.Koenig W,Sund M,Frohlich M,Fischer HG,Lowel H,Doring A,Hutchinson WL,Pepys MB.C-reactive protein,a sensitive marker of inflammation,predicts future risk of 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Prevention?。
预测机械通气患者容量反应性的研究进展准确评估血管内容量状态和测量容量反应性在围手术期医学中变得越来越重要。
现在人们普遍认识到，补液不足和补液过多都对健康有害[1]，而且都会影响围手术期的康复。
容量反应性的定义在临床和研究环境中各不相同。
在手术室、急诊室和重症监护室环境中，对血液动力学不稳定的患者来说，基于综合的临床评估进行液体输注时，只有50%的患者是有容量反应性的[2-3]。
液体输注并不总是临床低灌注患者的正确治疗方法，对无容量反应者进行液体输注，相反会增加患者容量超负荷、全身和肺水肿以及组织缺氧的风险[4]。
在全身麻醉期间经常发生血流动力学波动，包括低血压和心输出量的减少，可能导致急性循环衰竭。
在这种情况下，液体输注是首选的治疗方法。
许多试验[5-7]已经被用来评估患者的容量反应性。
传统上被用来评估患者容量状态的静态指标，如中心静脉压和肺毛细血管楔压，在识别患者容量反应性方面可靠性较差[8]。
为了解决这个问题，近年来相继开发了一些通过测量心输出量的变化，以反应其引起的心脏前负荷瞬时变化的动态指标。
这些指标大多都基于心肺相互作用。
它们为容量反应性提供了更好的预测性[9,10]。
首先被发现的指标是脉压变异度（PVV）或每搏量变异度（SVV），然后发现的指标是下腔静脉内径变异度（ICVD）或颈内静脉内径变异度（IJVD）。
然而，所有这些指标只有在严格的条件下才是可靠的，这些条件限制了它们在许多临床情况下的使用。
其他指标，如被动抬腿试验（PLR）或呼气末阻塞试验（EEOT），也是评估机体循环容量的测量方法。
为了可靠地预测患者的容量反应性，医生必须综合每个指标各自的局限性和所使用的心输出量监测技术，在这些不同的动态指标中进行选择。
在这篇综述中，我们将汇总评估机械通气患者容量反应性方法中的最新发现。
1.基于心肺相互作用的动态测试1.心肺相互作用生理学动态指标是由机械通气和血管内容量之间的相互作用产生的。
December2003:397–412 Lead Review ArticleEvaluation of Insulin Sensitivity in Clinical Practice and in Research SettingsLais U.Monzillo,M.D.,and Osama Hamdy,M.D.,Ph.D.Insulin resistance is the core metabolic abnormal-ity in type2diabetes.Its high prevalence and its association with dyslipidemia,hypertension,hy-perinsulinemia,and high coronary and cerebro-vascular mortality put it in the forefront as the plausible target for aggressive intervention.Mea-surements of insulin sensitivity provide clinicians and clinical researchers with invaluable instru-ments to objectively evaluate the efficiency of both current and potentially useful interventional tools.Although several methods had been devel-oped and validated to evaluate insulin sensitivity, none of these methods can be universally used in all patients.Nonetheless,a method suitable for use in clinical or basic research may not neces-sarily be a practical method for use in clinical practice or for epidemiologic research.We re-viewed the currently used methods for assess-ment of insulin sensitivity.For each method,we summarized its procedure,normal value,cut-off value for defining insulin resistance,advantages and limitations,validity,accuracy for each patient population,and suitability for use in clinical prac-tice and in research settings.The methods re-viewed include fasting plasma insulin,homeo-static model assessment,quantitative insulin sensitivity check index,glucose-to-insulin ratio, continuous infusion of glucose with model as-sessment,indices based on oral glucose toler-ance test,insulin tolerance test,and the so called “gold standard”methods,the hyperinsulinemic euglycemic clamp and the frequently sampled–intravenous glucose tolerance test.Key words:insulin resistance,insulin sensitivity, clinical practice©2003International Life Sciences Institutedoi:10.1301/nr.2003.dec.397–412IntroductionInsulin resistance is a state in which physiologic concen-trations of insulin produce a subnormal biologic re-sponse.1It underlies abnormalities of glucose,lipid,and blood pressure homeostasis.2This cluster of metabolic abnormalities is referred to as the insulin resistance syndrome,syndrome X,or the metabolic syndrome,and is related to type2diabetes,obesity,hypertension,and dyslipidemia.3–5In fact,insulin resistance is present long before the clinical manifestations of the individual com-ponents of the syndrome.6–8Epidemiologic evidence indicates that insulin resistance is directly related to the risk of developing atherosclerosis and cardiovascular disease.9–11To clinically identify patients with the metabolic syndrome,the National Cholesterol Education Program Expert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults(Adult Treatment Panel III,ATP III)suggested that individuals having three or more of the following criteria are defined as having the metabolic syndrome:121.Abdominal obesity:waist circumferenceϾ40inchesin men andϾ35inches in women;2.Hypertriglyceridemia:Ͼ150mg/dL(1.69mmol/L);3.Low high-density lipoprotein(HDL)cholesterol:Ͻ40mg/dL(1.04mmol/L)in men andϽ50mg/dL(1.29mmol/L)in women;4.High blood pressure:Ն130/85mmHg;5.High fasting plasma glucose:Ն110mg/dL(Ն6.1mmol/L).A recent epidemiologic study among adults above age20 showed that the age-adjusted prevalence of the metabolic syndrome in the United States is23.7%,with a higher prevalence among minority populations.13Several clinical trials have shown that lifestyle mod-ification delays the progression to type2diabetes among individuals with impaired glucose tolerance;14–17how-ever,none of these studies included quantitative evalu-ation of insulin sensitivity as an integral component of the study design.It is possible that an improvement in insulin sensitivity can be achieved either through life-style modification18–21or pharmacologically with met-Drs.Monzillo and Hamdy are with the Clinical Research Center,Joslin Diabetes Center;Department of Medicine,Harvard Medical School,Boston,MA 02215,USA.formin22,23or thiazolidinediones.24–26The Food and Drug Association(FDA)has not approved either of these pharmacologic compounds for treatment of insulin resis-tance in nondiabetic individuals;however,the diagnosis of type2diabetes,hypertension,and dyslipidemia man-dates aggressive appropriate treatment with antidiabetic, blood pressure–lowering,and lipid-lowering agents aimed at reducing cardiovascular morbidity and mortal-ity.The rapidly growing epidemic of obesity and con-sequent insulin resistance has increased the interest in finding quantitative,accurate,and easy methods to eval-uate insulin sensitivity in both clinical research and clinical practice.Such a tool is not only useful for early identification of insulin resistance but also to assess the degree of success in treating this syndrome and its consequences.This review will summarize our current knowledge of the available methods used to evaluate insulin sensitivity in humans.The components of each method,its indications,and its limitations are discussed. Fasting Plasma Insulin ConcentrationOne of the most practical ways to estimate insulin resis-tance from the clinical perspective is to measure plasma insulin concentration after an overnight fast.As it is inexpensive and easy to do,it has been used in several population-based studies.27–30Very high plasma insulin values reflect the presence of insulin resistance.Despite the relatively good correlation between fasting plasma insulin and insulin sensitivity derived from the hyperin-sulinemic euglycemic clamp,measures of fasting plasma insulin explain no more than5to50%of the variability in insulin action seen in nondiabetic subjects.31,32This is because plasma insulin levels depend not only on insulin sensitivity,but also on insulin secretion,distribution,and degradation.33Moreover,with the development of diabetes,fasting plasma insulin levels tend to decrease owing to beta cell dysfunction.Therefore,plasma insulin levels in diabetic patients are valid reflection of both target tissue insulin resistance and diminishing insulin production.34This explains why fasting plasma insulin levels may accu-rately predict insulin sensitivity among normoglycemic patients than among those with impaired glucose toler-ance(IGT)or type2diabetes.32,35,36Another limitation to using fasting plasma insulin to predict insulin resis-tance is cross-reactivity between insulin and proinsulin. Proinsulin levels are high among insulin-resistant sub-jects with type2diabetes and IGT,37,38but not in people who are insulin resistant and normoglycemic.39 The commonly used radioimmunoassay(RIA) method has a lower specificity and sensitivity,and a higher interassay coefficient of variation,when com-pared with the two-site monoclonal antibody-based in-sulin assay methods(immuno-radiometric[IRMA],im-muno-enzymometric[IEMA],and immuno-fluorimetric [IFMA])methods.40,41The presence of anti-insulin an-tibodies in type1and type2diabetic patients,who are treated with human or animal insulin,can interfere with both the RIA and two-site monoclonal assay,unless removal of anti-insulin antibodies and antibody-bound insulin is performed.41,42The normal range for insulin levels using RIA is3to 32mU/L.43,44However,there is no defined cut-off value indicating insulin resistance.This lack of consensus stems partly from the various means used to define abnormal.In a population-based study examining the association between insulin levels and cardiovascular risk,Lindahl et al.8defined insulin resistance as a plasma insulin levelϾ7.2mU/ing the hyperinsulinemic euglycemic clamp as the reference standard,McAuley et al.45found that a fasting insulinϾ12.2mU/L predicted insulin resistance among normoglycemic adults. Laakso,32also using the hyperinsulinemic clamp in nor-moglycemic adults,arrived at a cut-off of18mU/L. Finally,defining the abnormal range as the upper10% percentile,Ascaso et al.46defined insulin resistance in nondiabetic individuals when plasma insulin levels were equal or greater than16.7mU/l(Table1).While these variations illustrate how study designs influences what insulin level is determined to represent insulin resistance, the lack of established standards for insulin assay proce-dures further complicates the issue.47Another limitation for measurement of fasting plasma insulin is the pulsatile mode of insulin secretion (pulses with a periodicity of10–15minutes,and ultra-dian oscillations periods of1to3hours).The periodicity, amplitude,and ultradian oscillations of insulin pulsesparison of Fasting Plasma Insulin Values and Insulin Assays Used to Assess Insulin Sensitivity in Different StudiesStudy Year Population Insulin Assay Insulin Resist Value Lindahl et al.81993General population RIAϾ7.2mU/L McAuley et al.452001General population RIAϾ12.2mU/L Laakso et al.321992Normoglycemic RIAϾ18mU/L Ascaso et al.462001Normoglycemic RIAՆ16.7mU/L RIAϭradioimmunoassay.vary in the fasting state,and are altered in IGT and in type2diabetes.41Because of these limitations,fasting plasma insulin levels are of limited value for clinical purposes,but have some utility as a research tool in population-based studies.The Homeostasis Model Assessment(HOMA)Because fasting insulin per se does not provide an accu-rate measure of insulin sensitivity in diabetic patients, efforts have been made to incorporate fasting plasma glucose in a formula to arrive at a better estimate of insulin-sensitivity.HOMA was developed by Matthews et al.48as a method for estimating insulin sensitivity from fasting serum insulin(FI)and fasting plasma glu-cose(FG)using the following mathematic formula: HOMA Insulin Resistance(HOMA IR)ϭFIϫFG/22.5FI is measured inU/mL and FG is measured in mmol/L.Low HOMA IR indicates high insulin sensitiv-ity,whereas high HOMA IR indicates low insulin sensi-tivity.In their original report,Matthews et al.found HOMA IR ranges between1.21and1.45in normal sub-jects and between 2.61and 2.89in insulin-resistant diabetic subjects.48However,further epidemiologic studies performed in the general population reported higher HOMA IR values of2.1,442.7,31and3.8.46 Because fasting insulin is a major component of the HOMA IR calculation,all previously mentioned limita-tions should apply to this formula.Three samples for fasting plasma insulin should be drawn5minutes apart to avoid errors that may arise owing to the pulsatile nature of insulin secretion.However,most studies use only one basal insulin measurement to calculate HOMA IR.HOMA IR correlates well with the glucose disposal rate derived from the hyperinsulinemic euglycemic clamp.49–53In addition,two authors found a good cor-relation between the HOMA IR and the insulin sensitivity index(S i)derived from the frequently sampled intrave-nous glucose tolerance test(FSIVGT).54,55By contrast, Anderson et al.35failed to demonstrate a good correla-tion between the two.Furthermore,some of the studies that initially demonstrated significant correlation be-tween the HOMA IR and the clamp-derived insulin sen-sitivity used a low insulin infusion rate of20 mU⅐m2Ϫ1⅐minuteϪ1during the clamp,which might not have completely suppressed the hepatic glucose pro-duction and may have created an error in calculating theglucose uptake by peripheral tissues.51,52One of the limitations of HOMA IR is the model assumption that insulin sensitivity in the liver and pe-ripheral tissues are equivalent,whereas it is known that they can differ considerably in the same individual.50 Furthermore,some data suggest that the accuracy of HOMA IR is limited by hyperglycemia.Those studies that demonstrated good correlations between HOMA IR and the clamp-derived insulin sensitivity in diabetic patients tended to enroll patients without significant hyperglyce-mia.48–50,52,53Mari et al.56failed to show a significant correlation between HOMA IR and clamp in type2dia-betic patients with higher glucose levels(mean basal plasma glucose of205mg/dL).In addition,Anderson et al.35and Brun et al.57found that the correlation between HOMA IR and S i derived from the FSIVGT weakened as glycemia increased.These results suggest a non-linear relationship between S i and HOMA IR.The coefficient of variation(CV)for HOMA IR is as high as31%,48which limits its use in clinical practice and clinical research.47Optimizing sample size and in-sulin assay method reduceHOMA IR CV to8to12%.49,51 In conclusion,HOMA IR is mostly useful for the evaluation of insulin sensitivity in euglycemic individu-als and in persons with mild diabetes;however,this index appears to offer little or no advantage over the fasting insulin concentration alone.31,45,58In patients with severe hyperglycemia or in lean diabetic patients with beta cell dysfunction,the HOMA IR may not be accurate.Its usefulness should therefore be restricted to large population-based studies that require a simple method to assess insulin sensitivity.Quantitative Insulin Sensitivity Check Index (QUICKI)QUICKI is another mathematic model available to esti-mate insulin sensitivity.59QUICKIϭ1/[log(I0)ϩlog(G0)],where I0is the fasting plasma insulin level inU/mL, and G0is the fasting plasma glucose level in mg/dL.The mean QUICKI for lean,obese,and obese-diabetic sub-jects are0.382,0.331,and0.304,respectively.59Al-though other studies have found a similar range for a normal healthy population of0.372and0.366,60,61one study showed a wider range between0.265and0.518.62 The mathematic difference between the QUICKI and the HOMA IR is that the former uses the reciprocal of the logarithm of both glucose and insulin to account for the skewed distribution of fasting insulin values.As expected,there is very good correlation between QUICKI and HOMA IR,63especially when the HOMA IR is log-transformed.59,62,64,65Although two studies failed to demonstrate any real advantage of QUICKI when compared with log HOMA IR,62,65other studies argue that QUICKI has the advantage of being applied to wider ranges of insulin sensitivity.61,63,64QUICKI was also shown to correlate well with the FSIVGT66and the hyperinsulinemic eu-glycemic clamp.58However,the correlation is weakerwhen insulin levels were low,as seen in non-obese insulin-sensitive subjects and diabetic patients with di-minished insulin production;59,60,62,65,67,68this is be-cause low insulin levels lead to variability in determined insulin concentrations and because of the oscillatory pattern of insulin secretion in healthy individuals.Other limitations to this mathematic method include its limited applicability for type1diabetic patients owing to lack of endogenous insulin secretion,59and its inaccuracy if conducted following exercise training.67In conclusion,the QUICKI may be a useful and simple tool for assessing insulin sensitivity in epidemi-ologic settings;it may offer some advantage over the HOMA IR,especially in obese and diabetic individuals with relatively preserved beta cell function.However, the model needs validation in a wider range of subjects with different glucose tolerance patterns in order to confirm its reliability for use in clinical practice and in research settings.Fasting Plasma Glucose-to-Insulin Ratio(G/I)G/I is another mathematic method that uses fasting plasma insulin and fasting plasma glucose to estimate insulin sensitivity.The higher the ratio,the more insulin-resistant an individual is.The index generally correlates well with other indi-ces of insulin sensitivity.1,45,69–75It correlated with in-sulin sensitivity indices derived from the oral glucose tolerance test(OGTT,rϭ0.82,PϽ0.05),1,71and FSIVGT(rϭ0,76,PϽ0.001).1,69,72Vuguin et al.72 found that a fasting G/I ratioϽ7provided87%sensitiv-ity and89%specificity for identifying low insulin sen-sitivity in young girls with premature adrenarche.In another study of white nondiabetic women with polycys-tic ovarian syndrome(PCOS),Legro et al.69found the G/I ratio to be the best screening test for insulin resis-tance.The authors showed that a cut-offϽ4.5provided an87%positive predictive value and94%negative predictive value in screening for insulin resistance in PCOS.G/I ratio was found to correlate well with HOMA IR(rϭ0.83,PϽ0.01),fasting insulin(rϭ0.95, PϽ0.001),73and QUICKI(rϭ0.91,PϽ0.0001)74in healthy individuals.Data on the correlation between G/I ratio and insulin sensitivity derived from the euglycemic clamp procedure are inconsistent;whereas two studies found a significant correlation,1,45another did not.50 Adding to the previously mentioned problems that in-clude precision of insulin assay,pulsatile pattern of insulin secretion,and cross reactivity with proinsulin,the major problem with using the G/I ratio is its inaccuracy in diabetic patients owing to defects in insulin secretion and high plasma fasting glucose.1,50,70,76In subjects with normoglycemia,G/I ratio offered little advantage over the1/insulin measure76or fasting insulin.45Moreover,it provides indirect information on whole-body sensitivitybut not on the effect of insulin in peripheral tissues.1Inconclusion,this index,like the previously describedindices,should be limited to the nondiabetic population.For research purposes,its superiority over the fastinginsulin is questionable.Continuous Infusion of Glucose with Model Assessment(CIGMA)Because of the inaccuracy that may result from low basalinsulin concentrations,an alternative mathematic methodwas proposed.This method assesses insulin sensitivitythrough the evaluation of the near–steady state glucoseand insulin concentrations after a continuous infusion ofglucose with model assessment.77This procedure mim-ics postprandial glucose and insulin concentrations.CIGMA not only provides information about glucosetolerance and insulin sensitivity,but also about beta celling a mathematic model of glucose ho-meostasis,glucose and insulin values are compared withknown physiologic data of glucose and insulin kinetics inresponse to glucose infusion that are derived fromhealthy lean subjects with no family history of diabetes.The glucose and insulin values used for CIGMA areobtained during the last15minutes of the60-minutecontinuous glucose infusion(5mg glucose⅐kg idealbody weightϪ1⅐minuteϪ1).Samples are collected at five-minute intervals,to avoid the oscillatory variation ininsulin concentration.The average is then compared withpredicted values from the computer model.The medianvalue for normal subjects is1.35and for diabetic patientswith mild hyperglycemia is4.0.77Although CIGMA has been used in several studiesto evaluate insulin resistance,78–83few studies havecompared CIGMA with other insulin sensitivity indices.In elderly normoglycemic patients,CIGMA significantlycorrelated with mean fasting plasma insulin concentra-tions.84Hermans et al.55compared CIGMA,HOMA IR,FSIVGT,and the insulin tolerance test(ITT),in subjectswith glucose tolerance ranging from normal to frankdiabetes.They found that CIGMA and HOMA IR wereable to discriminate differences in insulin sensitivityamong subjects as well as the FSIVGT and better thanthe ITT.Among the four methods,CIGMA was the bestdiscriminatory test in precision analysis.It is worthmentioning that CIGMA in this study derived from a2-hour test(compared with the original1-hour CIGMA).Other studies have also reported data from2-hourCIGMA.85,86Data aiming to validate CIGMA against the clamp-derived insulin sensitivity index are scarce.In the orig-inal article,CIGMA was shown to correlate well with theeuglycemic hyperinsulinemic clamp(rϭ0.87,P Ͻ0.0001)77in normal subjects and in diabetic patientswith mild hyperglycemia.However,the relationship be-tween CIGMA and the clamp was nonlinear for diabetic patients with severe insulin resistance.Nijpels et al.70 studied90subjects,most of them with normal or im-paired glucose tolerance,and found a modest correlation between CIGMA and the clamp-derived insulin sensitiv-ity(rϭ0.66;PϽ0.05).The CV of CIGMA ranges between17%84and20%.77There are two main advantages of CIGMA over HOMA IR.First,the insulin values that are measured in CIGMA are much higher than those in HOMA IR owing to the glucose stimulus;therefore,the high insulin inter-assay CV(10–15%)41,47that is problematic at low insu-lin a concentration is avoided.55Second,higher insulin concentration in CIGMA stimulates peripheral glucose uptake producing a steady-state glucose concentration, which is a better reflection of the peripheral insulin sensitivity.Although CIGMA is more physiologic,practical, cheaper,and less invasive than the FSIVGT and clamp procedure,the model incorrectly assumes that levels of insulin resistance at the liver and peripheral tissues are equal.Furthermore,in insulin-deficient subjects,where the insulin response is insufficient to stimulate glucose uptake,the interpretation of CIGMA is difficult.33As CIGMA is a procedure and not a simple test such as fasting insulin or the HOMA IR,its use in clinical practice is limited.Moreover,due to insufficient data comparing CIGMA against the“gold standard”euglycemic hyper-insulinemic clamp,its use in research settings should also be viewed with caution.The Oral Glucose Tolerance Test(OGTT) Because oral glucose tolerance is in part determined by sensitivity of peripheral tissues to insulin,the OGTT has been used to evaluate insulin release and the sensitivity of the peripheral tissue to the insulin action.Being a less costly and less labor-intensive procedure compared with the FSIVGT and the euglycemic clamp,the OGTT has been considered a practical method for epidemiologic studies,58for population screening,and for large-scale intervention trials.50,63,87Several indices to estimate in-sulin sensitivity have been derived from the four samples of insulin and glucose(0,30,60,and120minutes)taken after ingestion of75grams of glucose(Table2). Insulin Sensitivity Indices Based on the OGTT Levine et al.88was one of thefirst authors to use the product of the area under the curve for glucose(AUC G) and the area under the curve for insulin(AUC I)during the OGTT to derive an estimate of insulin sensitivity. Later,AUC I was used alone as an estimate.31,36,89Cederholm and Wibell Index90SIϭM/G⅐log I,where Mϭglucose load/120ϩ(0-h plasma glucose concentration–2-h plasma glucose concentration)ϫ1.15ϫ180ϫ0.19ϫbody weight/120;where Gϭmean plasma glucose concentration,and Iϭmean serum insulin.A normal reference value is79Ϯ14.Gutt et al.Index91ISI0,120ϭMCR/log MSI(mean serum insulin),uses the fasting(0min)and120min post-load insulin and glucose concentrations,where MCR(metabolic clear-ance rate)is m/MPG(mean plasma glucose),where mϭ(75000mgϩ[0min glucose–120min glucose]ϫ0.19ϫbody weight)/120min.The reference range for lean controls was89Ϯ39,for obese58Ϯ23,for IGT 46Ϯ12,and for diabetic patients23Ϯ19.Avignon et al.Index92Sibϭ108/(IϫGϫVD)⅐(normal rangeϭ11.99Ϯ1.43)Si2hϭ108/(I2hϫG2hϫVD)⅐(normal rangeϭ1.79Ϯ0.33), where Iϭfasting insulin,Gϭfasting plasma glucose, G2h and I2hϭplasma glucose and insulin at the second hour of the OGTT,and VDϭvolume distribution(150 mL/kg of body weight).An additional insulin sensitivity index(S i M)was derived by the average of the2,after multiplying S i b by a correcting factor:SiMϭ[(0.137ϫSib)ϩSi2h]/2(normal rangeϭ1.71Ϯ0.24). Matsuda et al.Index50ISI(composite)ϭ10,000/͙(FPGϫFPI)ϫ(GϫI), where FPGϭfasting plasma glucose,FPIϭfasting plasma insulin,and Gϭmean plasma glucose,and Iϭmean plasma insulin concentration.Belfiore et al.Index93ISIϭ2/(INSpϫGLYp)ϩ1,where INSp and GLYp are the insulinemic and glycemic areas of the person under study recorded during OGTT. Reference value in normal controls was around1,butmarkedly reduced in the obese and obese-diabetic sub-groups.Stumvoll et al.Index94MCR est(OGTT)ϭ18.8Ϫ0.271BMIϪ0.0052ϫI120Ϫ0.27ϫG90, where MCR est stands for metabolic clearance rate estimate derived from the OGTT,BMIϭbody mass index,I120ϭplasma insulin at120minutes OGTT,and G90ϭplasma glucose at90minutes OGTT.Mari et al.Index56OGIS180ϭ[637106(G(120)Ϫ90)ϩ1]Cl ogtt, where OGIS180ϭoral glucose insulin sensitivity,G120ϭplasma glucose at2h OGTT,andCl ogttϭ289DoϪ104[G(180)ϪG(120)/60]G(120)ϩ14.0103G(0)440I(120)ϪI(0)ϩ270, where Clϭglucose clearance in mL⅐minϪ1⅐mϪ2, Doϭoral glucose dose in g/m2,G(120)ϭplasmaTable2.OGTT-derived Indices to Estimate Insulin Sensitivity and their Correlation with the Euglycemic Hyperinsulinemic Clamp or Frequently Sampled Intravenous Glucose Tolerance Test(FSIVGT)in Various PopulationsFormulae Subjects Correlation with 1.AUC I NGT Euglycemic clamp89rϭ0.61,Pϭ0.001IST31rϭ0.79,PϽ0.001AUC II30min I2hrG30min G2hr NGT,IGT ITT36rϭϪ0.51,PϽ0.001rϭϪ0.43,PϽ0.001rϭϪ0.39,PϽ0.001rϭϪ0.28,Pϭ0.01rϭϪ0.38,PϽ0.0012.SIϭMGϫlog INGT,IGT,DMEuglycemic clamp90rϭ0.62,PϽ0.00013.ISI0,120ϭMCR/log MSI NGT,IGT,DM Euglycemic clamp91rϭ0.63,PϽ0.001 4.Sibϭ108/(f Iϫf GϫVD)NGT,IGT,DM FSIVGT92Si2hϭ108(I2hϫG2hϫVD)rϭ0.90,PϽ0.0001 SiMϭ[(0.137ϫSib)ϩSi2h]/25.ISI(Comp)ϭ10,000͙(FPGϫFPI)ϫ(GϫI)NGT,IGT,DMEuglycemic clamp50rϭ0.73,PϽ0.00016.ISIϭ2(INSpϫGLYp)ϩ1NGT,O,ODMEuglycemic clamp93rϭ0.96,PϽ0.0017.MCRestϭ18.8Ϫ0.271BMIϪ0.0052ϫI120Ϫ0.27ϫG90NGT,IGT Euglycemic clamp94rϭ0.80;PϽ0.000058.OGIS180ϭ[637106(G{120}Ϫ90)ϩ1]Cl ogtt L,O,IGT,DM Euglycemic clamp56rϭ0.73;PϽ0.0001 AUC Iϭarea under the insulin curve,NGTϭnormal glucose tolerance,IGTϭimpaired glucose tolerance,I30minϭ30minutes post-load insulin,I2hrϭ2hours post-load insulin,G30minϭ30minutes post-load glucose,G2hrϭ2hour post-load glucose, ITTϭinsulin tolerance test,SIϭinsulin sensitivity,Mϭglucose uptake rate in mg⅐minϪ1,Gϭmean glucose concentration,Iϭmean insulin concentration,DMϭtype2diabetes,ISI0,120ϭindex of insulin sensitivity from fasting and120minutes post OGTT insulin and glucose concentrations,MCRϭmetabolic clearance rate,MSIϭmean serum insulin,Sibϭinsulin sensitivity in the basal state,Si2hϭinsulin sensitivity at the second hour,f Iϭfasting insulin concentration,f Gϭfasting glucose concentration,VDϭ150mL/kg of body weight,SiMϭinsulin sensitivity index,ISI(Comp)ϭcomposite whole-body insulin sensitivity index,FPGϭfasting plasma g glucose,FPIϭfasting plasma insulin,Gϭglucose,Iϭinsulin,ISIϭinsulin sensitivity index,INSpϭinsulinemic area,GLYpϭglycemic area,MCRestϭmetabolic clearance rate estimate,OGISϭoral glucose insulin sensitivity,Doϭoral dose glucose,Cl ogttϭglucose clearance.glucose at120minutes OGTT,G(180)ϭplasma glucose at180minutes OGTT,G(0)ϭfasting plasma glucose, I(120)ϭinsulin levels at120minutes,and I(0)ϭfasting insulin.Reference values in lean controls ranged300–600mL⅐minϪ1⅐mϪ2.As shown in Table2,the insulin sensitivity mea-sures derived from these formulas correlate well with insulin sensitivity determined by the euglycemic clamp50,89,90,93and FSIVGT.93However,the correlation was weaker in type2diabetic patients50,92,94and in the IGT group.36,58Belfiore et al.93advocate that their for-mula should not be used in type2diabetic patients with significant insulin deficiency.On the other hand,Mari et al.formula(OGIS),56showed a positive correlation with the clamp data in type2diabetic patients(rϭ0.49,P Ͻ0.002).In addition to the inadequacy of this method in insulin deficient states,other problems should be consid-ered.First,during the oral glucose tolerance test suppres-sion of hepatic glucose production is minimal,confound-ing interpretation of the plasma glucose level.Thus,it is impossible to differentiate among whole-body,periph-eral,or hepatic insulin sensitivity separately using data from the OGTT.49Second,the insulin level achieved in response to an oral glucose load involves gut hormones, neural stimulation,and of course the integrity of the pancreatic beta cells.68For example it has been shown that after75grams of glucose,obese subjects exhibit insulin hypersecretion,95while type2diabetes patients show a blunted response.96Third,glucose homeostasis in the postprandial state depends partly on the suppression of glucagon secretion and partly on the rate of entry of ingested glucose into the circulation.This rate is deter-mined by the rate of gastric emptying and splanchnic glucose uptake.60,61Fourth,the OGTT is poorly repro-ducible.Several studies show only about50to65% reproducibility of the results of an OGTT.63,97,98 Despite these limitations,the OGTT may be used in clinical settings to assess insulin action and in large-scale clinical and epidemiologic studies.However,the glucose and insulin excursions in the OGTT should be inter-preted with caution in populations with varying glucose tolerance.The Insulin Tolerance Test(ITT)ITT was one of thefirst methods developed to assess insulin sensitivity in vivo.99In this method,afixed bolus of regular insulin(0.1U/kg body weight)is given intra-venously after an8-to10-hour fast.The plasma glucose decrement over60minutes is then measured.The faster the decline in glucose concentration,the more insulin sensitive the subject is.The slope of the linear decline in plasma glucose(K ITT)can be calculated by dividing 0.693by the plasma glucose half-time(50%from base-line,Figure1).100K ITTϭ0.693/t1/2ϫ100,where t1/2represents the half-life of plasma glucose decrease.Normal K ITT isϾ2.0%/minute and values Ͻ1.5are considered abnormal.This method gives an indirect estimate of overall insulin sensitivity.It has been shown to correlate with the euglycemic clamp(rϭ0.811,PϽ0.001)101in several studies.101–104Some of the drawbacks of this method include the supraphysi-ologic insulin dose used,102and also the fact that the test does not differentiate peripheral versus hepatic insulin resistance.A major limitation of this test is the risk of hypo-glycemia,particularly in normoglycemic subjects and in elderly diabetic patients.Moreover,hypoglycemia trig-gers counterregulatory hormonal responses,which may interfere with insulin sensitivity.A lower insulin dose method of0.05units/kg,or shortening the test to15 minutes was suggested as an attempt to decrease the risk of hypoglycemia.105–107The lower dose ITT has also been shown to correlate well with the clamp.105How-ever,some studies failed to demonstrate reduction of the risk of hypoglycemia in insulin sensitive sub-jects.55,108,109They also showed a higher CV(16and 31%)in comparison to the conventional dose ITT(6–9% CV).101,103,104,110The shorter version101,103evolved from the notion that the counterregulatory hormone re-sponse occurs only after20minutes of the insulin infu-sion.111–113The short ITT yielded a good correlation with the euglycemic clamp101,103,105and has been used in most of the recent studies.114–117In conclusion,the ITT should be used with great caution in insulin sensitive individuals because of the increased risk of hypoglycemia,even when thesmallerFigure1.Calculation of the KITT(percentage decline in plasma glucose concentration per minute)in nondiabetic subjects.100 The time(t1⁄2)required for the plasma glucose concentration to decline by50%(i.e.,from90to45mg/dL)was25minutes.From the equation,KITTϭ0.693/t1⁄2ϫ100,the K rate was determined to be2.77%.。
A BSTRACTObjective : To determine the accuracy of antepartum Amniotic Fluid Index (AFI) of <5 cm as a predictor of adverse outcome at birth in high-risk pregnancies.Study Design : Cross-sectional study.Place and Duration of Study : Obstetrics and Gynaecology Unit I, Holy Family Hospital and Railway Teaching Hospital Complex, Rawalpindi, from February 2003 to January 2004.Methodology : One hundred pregnant women at term gestation were studied. Each high-risk woman at term with an AFI of <5 cm admitted for delivery through emergency or outpatient department was labeled as predictor of poor outcome.The next high-risk pregnant woman at term with the same pregnancy complication but an AFI of > 5 cm was labeled as predictor of good outcome at birth. The subjects in both the groups were demographically matched and fulfilled the inclusion and exclusion criteria. The Apgar score was calculated at 5 minutes of birth. The newborns, with Apgar score <6 at 5 minutes of birth were labeled as diseased and > 6 were labeled as healthy. AFI was compared with Apgar score,using Chi-square and a p-value was calculated to determine the statistical significance. Sensitivity, specificity, efficiency and the predictive values of AFI at a cut off point of <5 cm as a predictor of adverse outcome at birth (Apgar score of <6 at 5 minutes of birth) in high-risk pregnancy were calculated.Results : Only 8 neonates of 50 women with low AFI had low Apgar score. Similarly, 6 neonates of 50 women with normal AFI had poor Apgar score. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and efficiency of AFI as test were 57.1%, 51.3%, 16%, 88% and 52% respectively.Conclusion : Low AFI is a poor predictor of adverse outcome for high-risk term patients. AFI is not a good screening test for high-risk pregnant women at term for birth of an infant with low Apgar score.Key words:Apgar score. Amniotic fluid index. High-risk term pregnancy.Low Amniotic Fluid Index in High-Risk Pregnancyand Poor Apgar Score at BirthSaadia Sultana 1, Muhammad Nadim Akbar Khan 2, Khalida Adeeb Khanum Akhtar 3and Muhammad Aslam 4Low AFI in high-risk pregnancy and poor Apgar score at birthSaadia Sultana, Muhammad Nadim Akbar Khan, Khalida Adeeb Khanum Akhtar and Muhammad AslamLow AFI in high-risk pregnancy and poor Apgar score at birthafter 40 weeks but has a poor sensitivity for adverse pregnancy outcome.19He also suggested, as in this study, that frequent use of USG at term may lead to increase obstetric intervention without improvement in perinatal outcomes.19An Italian study concluded that in pregnancies with oligohydramnios, the modality of delivery and neonatal outcome did not differ from those with normal AFV.20 Although there is a statistically significant association of AFI with induction of labour, there is no significant difference in mode of delivery and neonatal outcome between normal and low AFI groups. The sensitivity of an AFI <5 cm for the prediction of severe morbidity is unfortunately low. This means that any sign of deteriorating fetal condition might have prompted induction and immediate delivery. This selective confounding may have, to some extent, biased the perinatal outcomes. So a randomized clinical trial is necessary in which women with AFI <5 cm will be randomly assigned, either to immediate delivery or to expectant management, may provide a more definitive answer.The significant proportion of neonates with poor Apgar score has an AFI > 5 cm. It indicates that other tests of fetal well-being are necessary to detect the fetuses that are at risk of adverse outcome in the presence of normal AFI. Another reason of low sensitivity of AFI estimation may be due to the fact that colour Doppler ultrasound was not used. However, the use of colour Doppler imaging has been reported to overdiagnose oligohydramnios.21Use of 3-D USG and MRI may circumvent this problem and more accurate results can be obtained. An ultrasound may be inconclusive in fetuses with renal diseases that result in anhydramnios or oligohy-dramnios. In such cases, further investigation with MRI should be considered.22The only objective assessment of fetal well-being is neonatal acidosis. As suggested in a meta analysis, a multi-center study with sufficient power should be undertaken to demonstrate that a low AFI is associated with an umbilical arterial pH of < 7.10 Although antepartum or intrapartum oligohydramnios is not a predictor of adverse perinatal outcome in high-risk pregnant ladies, as measured by low Apgar score at 5 minutes, this may be reflective of aggressive antepartum and intrapartum management, which was provided to those patients. A more definitive answer may be obtained by a clinical trial in which women with AFI ≤ 5 cm will be randomly assigned either to immediate delivery or to expectant management.CONCLUSIONAFI is a poor predictor of adverse outcome for high-risk antepartum or intrapartum pregnant ladies. The only significant association between low AFI and labour induction reveals that the early intervention due to low AFI in high-risk parturients lead to more alert attitude of the obstetricians, which may lead to some confounding. The conclusion that AFI is not a good predictor of outcome may be reflective of aggressive antepartum or intrapartum management that the patients with oligohydramnios received.REFERENCES1.Nicolini U, Fisk NM, Rodeck CH, Talbert DG, Wigglesorth JS.Low amniotic pressure in oligohydramnios – is this cause ofpulmonary hypoplasia? Am J Obstet Gynecol1989; 161:1098-101.2.Brace RA, Wolf EJ. Normal amniotic fluid volume changesthroughout pregnancy. Am J Obstet Gynecol1989; 161:382-8.3.Murrey E, Keirse MJ. Assessment of fetal growth, size and well-being. A guide to effective care in pregnancy and childbirth. 3rded. Oxford: Oxford University Press; 2000.p.80-92.4. Phelan JP, Smith CV, Broussard P, Small M. Amniotic fluidvolume assessment with the four-quadrant technique at 36-42weeks gestation. J Reprod Med1987; 32:540-2.5. Moore TR, Cayle JE. The amniotic fluid index in normal humanpregnancy. Am J Obstet Gynecol1990; 162:1168-73.6. Florescu A, Koren G. Non-steroidal anti-inflammatory drugs forrheumatoid arthritis during pregnancy. Can Fam Physicians2005;51:961-2.7. Banks EH, Miller DA. Perinatal risks associated with borderlineamniotic fluid index. Am J Obstet Gynecol1999; 180:1461-3.8. Ghosh G, Marsal K, Gudmundsson S. Amniotic fluid index in lowrisk pregnancy as test for an admission to the labour ward. Acta Obstet Gynecol Scand2002; 81:852-5.9. Kawasaki N, Nishimura H, Yoshimura T, Okamura H. 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