Pathophysiology of Anorectal Disorders

肛门直肠疾病的病理生理学

基本信息

批准号：
9210079
负责人：
ADIL E. BHARUCHA
金额：
$ 34.58万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9210079
关键词：
Address Adrenergic Agents Adrenergic Antagonists Adult Affect Agonist Anus Biofeedback Chronic Circular layer of muscularis propria of anal canal Clinical Clip Clonidine Constipation Controlled Study Data Defecation Devices Diagnosis Diagnostic Diagnostic tests Diarrhea Discipline of obstetrics Disease Disease Management Elasticity Epidemiology Fecal Incontinence Fissure in Ano Functional disorder Human Hybrids Hypertension Impairment Injury Intestines Knowledge Lateral Left Magnetic Resonance Elastography Magnetic Resonance Imaging Manometry Measurement Measures Motion Patient Care Patients Pattern Pelvic floor dysfunction Pelvic floor structure Pelvis Pharmaceutical Preparations Pharmacology Phenotype Positioning Attribute Process Provider Relaxation Resolution Rest Sensorimotor functions Symptoms Testing Therapeutic Studies Visceral Woman Work accurate diagnosis alfuzosin anorectal disorder base clinical Diagnosis design experience improved in vivo innovation insight laxative multidisciplinary nerve supply novel novel strategies portability pressure public health relevance rectal sphincter ani muscle structure

项目摘要

DESCRIPTION (provided by applicant): Defecatory disorders (DD), which commonly cause chronic constipation, are diagnosed by clinical features supplemented by abnormal anorectal tests, and should be managed by pelvic floor retraining by biofeedback therapy rather than by laxatives. DD are attributed to "maladaptive" pelvic floor contraction during defecation. This paradigm overlooks the contribution of visceral disturbances (e.g., increased anal resting pressure or anal hypertension). Biofeedback therapy is not widely available and there are no pharmacological approaches to manage DD currently. Anorectal tests are not widely available, and the accuracy of a key diagnostic test, i.e. a negative rectoanal gradient (rectal < anal pressure), during simulated evacuation is questionable because many asymptomatic subjects also have a negative gradient. We have identified 3 distinct phenotypes (i.e. "high anal", "low rectal" and "hybrid") which are defined by the magnitude of rectal pressure and anal relaxation during evacuation. Thus, the "high anal" pattern is defined by normal rectal pressure (propulsive force) but impaired anal relaxation during evacuation. The high anal phenotype is also characterized by high anal resting pressure (anal hypertension). Based on preliminary studies, our hypotheses are that: (1) Anal hypertension is associated with reduced anal distensibility, increased internal anal sphincter stiffness, and impaired evacuation in DD. Anal distensibility and stiffness will be evaluated by anal balloon distention and magnetic resonance elastography (MRE) respectively and rectal evacuation will be assessed by dynamic pelvic MRI in 60 healthy subjects and 60 patients with DD. (2) α1- adrenergic tone contributes to anal hypertension in DD. We will evaluate the effects of an α1-adrenergic antagonist on anal pressures in 36 healthy subjects and 36 patients with DD, and on symptoms in 36 patients with DD, and (3) Rectal pressure is higher and rectoanal pressure measurements are more accurate for identifying DD in the seated than the left lateral position (3a) and rectoanal pressures can be accurately measured by portable manometry (3b). We will compare pressures measured by high resolution and portable manometry in the seated and left lateral positions in 60 healthy subjects and 60 patients with DD; pelvic floor motion and rectal evacuation will be evaluated by dynamic MRI. A multi-disciplinary collaborative team will apply innovative approaches to address these hypotheses in a highly refined manner. Each study is designed to improve patient care in humans.

描述（由应用程序提供）：通常引起慢性便秘的缺乏障碍疾病（DD）是由补充异常厌食直肠测试的临床特征诊断出来的，应通过生物反馈治疗而不是通过泻药来管理骨盆底培训。 DD归因于排便期间的“适应不良”骨盆底收缩。该范式忽略了内脏障碍的贡献（例如，肛门静压或肛门高血压增加）。生物卫生疗法并不广泛，目前没有药理方法来管理DD。厌食直肠测试并不广泛，并且关键诊断测试的准确性，即阴性正直梯度（直肠<肛门压），在模拟疏散期间，由于许多不对称受试者也具有负梯度，因此值得怀疑。我们已经确定了3种不同的表型（即“高肛门”，“低直肠”和“杂种”），这些表型是由直肠压力和疏散期间的直肠压力和肛门弛豫的大小来定义的。这是由正常直肠压力（推进力）定义的“高肛门”模式，但撤离期间肛门松弛受损。高肛门表型也以高肛门静息压力（肛门高血压）为特征。基于初步研究，我们的假设是：（1）肛门高血压与肛门的可扩张性降低，内部肛门括约肌刚度增加以及DD疏散受损有关。肛门自由裁量和刚度将分别通过肛门气球酌处权和磁共振弹性图（MRE）评估，直肠疏散将通过60名健康受试者和60名DD患者的动态骨盆MRI评估。（2）α1-肾上腺素能张力有助于DD中的肛门高血压。我们将评估α1-肾上腺素能拮抗剂对36名健康受试者和36例DD患者的肛门压力的影响，以及36例DD患者的症状，（3）直肠压力更高，并且比左后位置（3A）和直肠压力更准确，直肠压力更准确，可以识别坐着的DD（3A）和直肠压力。我们将比较60名健康受试者和60例DD患者的座椅和侧面位置高分辨率和便携式测量法测量的压力；骨盆底运动和直肠疏散将通过动态MRI评估。一个多学科的合作团队将采用创新的方法以高度完善的方式解决这些假设。每项研究旨在改善人类的患者护理。