WHITE BLOOD CELLS, EXERCISE, AND CHILDREN: INITIAL MECHANISMS

白细胞、运动和儿童：初始机制

• 批准号: 7606633
• 负责人: DAN M COOPER
• 金额: $ 2.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606633
• 关键词: Acoustics; Adult; Air; Alkaline Phosphatase; Animals; Anthropometry; Architecture; Arts; Biochemical; Biolectric Impedance; Body Composition; Body Regions; Bone Density; Bone Mineral Contents; Cardiac; Child; Clinical; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnosis; Disadvantaged; Dose; Dual-Energy X-Ray Absorptiometry; Elasticity; Electric Conductivity; Energy Metabolism; Environment; Epimysium; Evaluation; Event; Exercise; Fatty acid glycerol esters; Femur; Fracture; Funding; Gene Mutation; Goals; Grant; Growth; Human; Imagery; Infant; Institution; Intervention; Intervention Studies; Ionizing radiation; Journals; Leukocytes; Life; Literature; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Metabolic Bone Diseases; Methods; Minerals; Modeling; Morphologic artifacts; Movement; Muscle; Neonatal; New England; Newborn Infant; Outcome; Patients; Perinatal; Physiologic calcification; Plethysmography; Potassium; Pregnancy; Premature Infant; Process; Property; Prospective Studies; Purpose; Rattus; Reporting; Research; Research Design; Research Personnel; Resources; Respiratory Diaphragm; Risk; Scanning; Serum; Skeletal Muscle; Skin; Skinfold Thickness; Son of Sevenless Proteins; Source; Spectrum Analysis; Structure; Techniques; Thick; Third Pregnancy Trimester; Time; Tissues; Tracer; Ultrasonography; United States National Institutes of Health; Work; attenuation; base; bone; bone strength; clinically relevant; concept; cost; density; humerus; indexing; insight; instrument; muscle hypertrophy; myostatin; neonate; physical property; sound; subcutaneous; validation studies

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding the dynamic changes in body composition in the perinatal and early neonatal period has been a major of focus of neonatal research for over a century. At no time in the life of humans is energy expenditure for growth so large and the process of new tissue development so rapid. Measurements of body composition and energy expenditure are essential if we are to gain insights into the mechanisms of how interventions like assisted exercise influence body composition in premature babies. For many reasons involving technical, ethical, and feasibility factors, making accurate measurements of both body composition and energy expenditure has remained a singular challenge in this field (1), and the armamentarium available for these important indexes of growth are limited in the context of the newborn. Current techniques include: anthropometry, total body electrical conductance, tracer dilution, total body potassium, bioelectrical impedance, magnetic resonance imaging and spectroscopy, acoustic plethysmography, air displacement, Dual Energy X-ray Absorptiometry (DEXA), Quantitative ultrasound (QUS), and regional ultrasonography of skeletal muscle and fat mass (2-8). Of these methods, some combination of DEXA, QUS, and regional ultrasonography is the most promising and feasible. QUS and muscle ultrasound are noninvasive, can be performed at the bedside (no need to transport the infant), have no ionizing radiation, and can be performed multiple times during the course of an intervention study. However, the determinants of QUS are complex and their relationship to bone structure and density have yet to be fully clarified. Both QUS and muscle sonography provide data on regions of the body, and it may not be possible to extrapolate the regional data to total body bone mineral density or muscle mass-a key outcome when considering the impact of assisted exercise. In contrast, DEXA can measure both bone mineralization and body composition, and these measurements can be made for the whole body and regionally. But the disadvantages of DEXA are also substantial: the baby must be studied with a minimum of movement artifact (often, a daunting challenge for a typical, unsedated neonate), and the baby must be transported to the DEXA unit rendering it difficult to perform multiple measurements in a growing, hospitalized premature baby. Finally, DEXA does involve a minimal (probably negligent) dose of ionizing radiation which can hinder recruitment. Thus, to optimize our measurements of body composition and bone mineralization in the prospective study, we plan a Methods Validation Study designed to compare the three following techniques: " DEXA " Bone Quantitative Ultrasound " Muscle Ultrasound As a result of this study, we will be able to determine the optimal combination of these three methods, or, if possible, information from QUS and muscle ultrasonagraphy alone are powerful enough to meet our objectives. DEXA: is a scanning technique that measures the differential attenuation of two x-rays as they pass through the body. DEXA has become the state-of-the-art method to estimate body composition for research purposes in adult humans [e.g., (9)]. DEXA scans measure total and regional body bone mineral content (BMC), bone mineral density (BMD), fat-free mass (FFM), and fat mass (FM). DEXA scanning has been used in infants, and our Project Consultant, Dr. Winston Koo, has done much of the pioneering work in establishing the instrumental, clinical, and analaytical approaches necessary for reproducible and accurate use of DEXA scanning for the measurement of body composition in infants (10; 11). QUS: Metabolic bone disease is a relatively common event in preterm infants because the greatest period of bone mineral accretion ordinarily occurs during the last trimester of pregnancy, and this is difficult to reproduce in the extrauterine environment (12; 13). Currently, its diagnosis is based primarily on biochemical evaluation of serum alkaline phosphatase and radiological evidence of osteopenia and/or fractures, and in some cases, on measurements of bone mineralization by DEXA (14). The use of DEXA in the clinical setting, however, is limited by its relatively high cost and the need to transport the patient to the instrument, making it relatively unfeasible for very small or sick infants, i.e., the very ones most at risk of developing metabolic bone disease. QUS measurement of bone SOS has recently become a viable alternative, and there is a substantial body of literature demonstrating its utility in assessing bone strength in infants (15-20), children (21) and adults (22; 23). QUS is predicated on the concept that the propagation of sound waves through a medium depends upon the physical properties of that medium (Figure 3). Therefore, the denser the medium, the faster the sound waves propagate through it. In addition to bone density, bone SOS is also determined by other bone properties, such as cortical thickness, elasticity and micro-architecture, and may, in conjunction with DEXA, provide a more clinically relevant picture of bone strength (24; 25). QUS is relatively inexpensive, portable, noninvasive, involves no ionizing radiation, and has, in initial studies, been shown to correlate accurately with measurements by DEXA (26; 27). Muscle Ultrasound: A major goal of this study is to assess muscle and fat mass in the newborn and preterm infant. Ultrasound (US) imaging is a useful technique for visualization of skeletal muscle tissue (28), and has been extensively used in adults (29) and more recently in children (30) and infants (31) [where it is increasingly used to measure volume of the diaphragm as well (32)]. US imaging is a portable, noninvasive method that does not involve ionizing radiation. Clear visualization of the muscle boundaries is possible since the epimysium surrounding the muscle is highly reflective and the bone echo is strong and distinct. This gives the added advantage of directly quantitating lean muscle mass compared to more indirect methods like skinfold thickness, which can include the skin and subcutaneous fat (33). In a recent New England Journal of Medicine report (34), muscle ultrasound was used to assess muscle hypertrophy in a baby with a myostatin gene mutation, and it has been used successfully to gauge cardiac and skeletal muscle mass in small animals such as the rat and small shorebirds (35; 36). A key question is whether regional measurement of bone strength or muscle/fat distribution, as will be done by the QUS and muscle ultrasound techniques, can be useful in gauging total body lean and fat distribution. We will be able to answer this question in the proposed Methods Validation Study. We have reason to be optimistic, for example, our Project Consultant Dr. Winston Koo and coworkers (37) showed in the piglet model that bone mineral content variables obtained from DEXA of the humerus and femur were highly correlated with whole body DEXA results.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 一个多世纪以来，了解围产期和新生儿早期身体成分的动态变化一直是新生儿研究的重点。 在人类一生中，生长所需的能量消耗从未如此之大，新组织的发育过程也从未如此迅速。 如果我们要深入了解辅助运动等干预措施如何影响早产儿身体成分的机制，那么身体成分和能量消耗的测量至关重要。 由于涉及技术、伦理和可行性因素的多种原因，准确测量身体成分和能量消耗仍然是该领域的一个独特挑战 (1)，并且可用于这些重要生长指标的设备在新生儿的背景下是有限的。 目前的技术包括：人体测量学、全身电导、示踪剂稀释、全身钾、生物电阻抗、磁共振成像和光谱学、声体积描记法、空气置换、双能 X 射线吸收测定法 (DEXA)、定量超声 (QUS) 以及骨骼肌和脂肪量的区域超声检查 (2-8)。 在这些方法中，DEXA、QUS 和局部超声检查的某种组合是最有前途和可行的。 QUS和肌肉超声是无创的，可以在床边进行（无需运送婴儿），没有电离辐射，并且可以在干预研究过程中多次进行。 然而，QUS的决定因素很复杂，它们与骨结构和密度的关系尚未完全阐明。 QUS 和肌肉超声检查都提供身体区域的数据，但可能无法将区域数据推断为全身骨矿物质密度或肌肉质量（在考虑辅助运动的影响时这是一个关键结果）。 相比之下，DEXA 可以测量骨矿化和身体成分，并且这些测量可以针对整个身体和局部进行。 但 DEXA 的缺点也很明显：必须以最少的运动伪影来研究婴儿（对于典型的、未镇静的新生儿来说，这通常是一项艰巨的挑战），并且必须将婴儿运送到 DEXA 装置，这使得对正在成长的住院早产儿进行多次测量变得困难。 最后，DEXA 确实涉及最小（可能是疏忽）剂量的电离辐射，这可能会阻碍招募。 因此，为了在前瞻性研究中优化我们对身体成分和骨矿化的测量，我们计划进行一项方法验证研究，旨在比较以下三种技术： ” 地塞米松 骨定量超声 ” 肌肉超声检查 这项研究的结果是，我们将能够确定这三种方法的最佳组合，或者，如果可能的话，仅来自 QUS 和肌肉超声检查的信息就足以满足我们的目标。 DEXA：是一种扫描技术，可测量两束 X 射线穿过身体时的衰减差异。 DEXA 已成为估计成年人身体成分用于研究目的的最先进方法 [例如 (9)]。 DEXA 扫描可测量全身和局部身体骨矿物质含量 (BMC)、骨矿物质密度 (BMD)、去脂质量 (FFM) 和脂肪质量 (FM)。 DEXA 扫描已用于婴儿，我们的项目顾问 Winston Koo 博士在建立可重复且准确地使用 DEXA 扫描测量婴儿身体成分所需的仪器、临床和分析方法方面做了许多开创性工作 (10; 11)。 QUS：代谢性骨病是早产儿中相对常见的事件，因为骨矿物质积累的最大时期通常发生在妊娠的最后三个月，而这在宫外环境中很难重现（12；13）。目前，其诊断主要基于血清碱性磷酸酶的生化评估和骨质减少和/或骨折的放射学证据，在某些情况下，基于 DEXA 测量的骨矿化 (14)。 然而，DEXA 在临床环境中的使用受到其相对较高的成本和需要将患者运送到仪器的限制，这使得它对于非常小的或患病的婴儿（即最有可能患代谢性骨病的婴儿）来说相对不可行。 骨 SOS 的 QUS 测量最近已成为一种可行的替代方案，并且有大量文献证明其在评估婴儿 (15-20)、儿童 (21) 和成人 (22; 23) 骨强度方面的实用性。 QUS 所依据的概念是声波在介质中的传播取决于该介质的物理特性（图 3）。因此，介质越致密，声波在其中传播的速度越快。除骨密度外，骨 SOS 还由其他骨特性决定，例如皮质厚度、弹性和微结构，并且可以与 DEXA 结合，提供更具临床相关性的骨强度图 (24; 25)。 QUS 相对便宜、便携、无创、不涉及电离辐射，并且在初步研究中已被证明与 DEXA 测量结果准确相关 (26; 27)。 肌肉超声：这项研究的一个主要目标是评估新生儿和早产儿的肌肉和脂肪量。超声 (US) 成像是一种用于骨骼肌组织可视化的有用技术 (28)，已广泛用于成人 (29)，最近又用于儿童 (30) 和婴儿 (31) [其中也越来越多地用于测量膈肌体积 (32)]。 超声成像是一种便携式、非侵入性方法，不涉及电离辐射。由于肌肉周围的肌外膜具有高度反射性并且骨回声强烈且清晰，因此可以清晰地观察到肌肉边界。与皮褶厚度（包括皮肤和皮下脂肪）等更间接的方法相比，这提供了直接定量瘦肌肉质量的额外优势 (33)。 在最近的《新英格兰医学杂志》报告中 (34)，肌肉超声被用来评估肌生长抑制素基因突变婴儿的肌肉肥大情况，并且已成功用于测量大鼠和小滨鸟等小动物的心脏和骨骼肌质量 (35; 36)。 一个关键问题是，通过 QUS 和肌肉超声技术进行的骨强度或肌肉/脂肪分布的区域测量是否可用于测量全身瘦肉和脂肪分布。 我们将能够在拟议的方法验证研究中回答这个问题。 我们有理由乐观，例如，我们的项目顾问Winston Koo博士和同事（37）在仔猪模型中显示，从肱骨和股骨的DEXA获得的骨矿物质含量变量与全身DEXA结果高度相关。