Mechanisms of anterior vaginal wall support failure

阴道前壁支撑失效的机制

• 批准号: 7620401
• 负责人: JOHN O.L. DELANCEY
• 金额: $ 23.81万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-10 至 2010-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7620401
• 关键词: 3-Dimensional; Affect; Anterior; Anterior vaginal wall prolapse; Apical; Area; Bilateral; Biomechanics; Bladder; Caliber; Characteristics; Computer Simulation; Connective Tissue; Control Groups; Cystocele; Data; Defect; Failure; Female; Frequencies; Functional disorder; Funding; Impairment; Individual; Lead; Linear Regressions; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Modeling; Muscle; National Institute of Child Health and Human Development; Normal Range; Operative Surgical Procedures; Organ; Patients; Pattern; Pelvic Floor Disorders; Pelvic Floor Muscle; Pelvis; Peripheral; Play; Population Control; Positioning Attribute; Progress Review Group; Property; Ptosis; Recurrence; Research; Research Personnel; Rest; Role; Severities; Shapes; Side; Site; Speculums; Stretching; Support System; Symptoms; Techniques; Testing; Textiles; Time; Urodynamics; Vagina; Vaginal Prolapses; Woman; advanced disease; hymen; insight; instrument; muscular structure; novel; programs; theories

DESCRIPTION (provided by applicant): Anterior vaginal wall prolapse (AVP), clinically known as cystocele, is the most common form of pelvic organ prolapse. The NICHD Female Pelvic Floor Disorders workgroup and NIDDK'S Bladder Progress Review Group have identified a critical need for pathophysiology research in these conditions. Competing hypotheses have been proposed to explain how anterior vaginal wall connective tissue support (CIS) failure results in AVP; midline stretching of the vaginal wall vs. peripheral detachment in the paravaginal and apical areas of support. However, these theories do not incorporate observations from our previous funding cycle that pubococcygeal muscle (PCM) damage is 4 times more common in women with prolapse. This study proposes to test mechanistic hypotheses that the occurrence and magnitude of AVP is not explained by a single mechanism but involves the interaction of different connective tissue failures sites and also PCM impairment. We will use MRI techniques and novel 3-D computer modeling to individually measure and compare the status of each site of support in 150 women with AVP and 150 controls. In Aim 1 we will: a) measure origin to insertion distances for paravaginal and apical supports and longitudinal and transverse diameters of the vaginal wall at maximum Valsalva to determine the contribution of CTS failures at these sites to the presence of AVP, b) determine the sites where each individual with AVP has measures outside the normal range found in controls and c) use linear regression models to determine how the number of CTS site defects and severity of CTS failure at each site affects AVP size. In Aim 2 we will: a) determine how muscle impairment interacts with CTS failure in explaining the occurrence and size of AVP by measuring muscle structure and function in both groups, b) examine the role that PCM impairment plays in determining AVP severity beyond the contribution of the CTS and c) determine whether patterns of CTS failure (e.g. single failure, multiple failures or different combinations of failure) relate to PCM impairment. Aim 3 will use biomechanical analysis of muscle and connective tissue interactions in computer-based models of CTS and PCM to investigate patterns of muscle and connective support site failures that lead to AVP. These insights are needed to advance disease mechanisms research in order to reduce the 30% recurrence rate with surgery, and develop preventative strategies to lessen the need for surgery in 400,000 women a year.

描述(申请人提供)：阴道前壁脱垂(AVP)，临床上称为膀胱膨出，是最常见的盆腔器官脱垂形式。NICHD女性盆底疾病工作组和NIDDK的膀胱进展回顾小组已经确定了在这些情况下进行病理生理学研究的迫切需要。已经提出了相互竞争的假说来解释阴道前壁结缔组织支持(CIS)失败是如何导致AVP的；阴道壁的中线拉伸与阴道旁和顶端支持区域的外周分离是如何导致的。然而，这些理论并没有纳入我们上一个资金周期的观察结果，即耻骨尾部肌肉(PCM)损伤在患有脱垂的女性中是普通人的4倍。这项研究建议检验机械假说，即AVP的发生和程度不是由单一的机制解释的，而是涉及不同结缔组织失效部位和PCM损伤的相互作用。我们将使用MRI技术和新颖的3-D计算机建模来单独测量和比较150名AVP组和150名对照组女性每个支撑点的状态。在目标1中，我们将：a)测量阴道旁和根尖支架的起点到插入距离以及最大Valsalva时阴道壁的纵径和横径，以确定这些部位的CTS失败对AVP存在的贡献；b)确定AVP的每个个体在哪些部位的测量结果超出对照的正常范围；c)使用线性回归模型来确定每个部位的CTS部位缺陷的数量和CTS失败的严重程度如何影响AVP的大小。在目标2中，我们将：a)通过测量两组的肌肉结构和功能，确定肌肉损伤与CTS故障如何相互作用来解释AVP的发生和大小，b)检查PCM损伤在确定CTS以外的AVP严重程度中所起的作用，以及c)确定CTS故障的模式(例如，单个故障、多个故障或不同的故障组合)是否与PCM损伤相关。Aim 3将在基于计算机的CTS和PCM模型中使用肌肉和结缔组织相互作用的生物力学分析，以研究导致AVP的肌肉和结缔组织支持部位失效的模式。需要这些见解来推进疾病机制研究，以便通过手术降低30%的复发率，并开发预防策略，以减少每年40万妇女对手术的需求。