Pathophysiology of Anorectal Disorders

肛门直肠疾病的病理生理学

• 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
• 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

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（由申请人提供）：排便障碍（DD），通常导致慢性便秘，通过临床特征和异常肛门直肠检查来诊断，应该通过生物反馈疗法进行盆底再训练而不是泻药来治疗。DD是由于排便时盆底“不适应”收缩所致。这种模式忽略了内脏紊乱的影响（例如，肛门静息压力增加或肛门高压）。生物反馈疗法尚未广泛应用，目前也没有药物治疗DD的方法。肛门直肠检查并不普遍，而且一项关键诊断测试的准确性，即在模拟排泄过程中直肠直肠负梯度（直肠<肛门压）的准确性值得怀疑，因为许多无症状的受试者也有负梯度。我们已经确定了3种不同的表型(即：“高肛门”、“低直肠”和“混合型”)，这是由排泄过程中直肠压力的大小和肛门松弛程度来定义的。因此，“高肛门”模式的定义是正常的直肠压力（推进力），但在排泄过程中肛门松弛受损。高肛门表型还以高肛门静息压（肛门高压）为特征。根据初步研究，我们的假设是：(1)肛门高压与肛门膨胀性降低、内肛门括约肌僵硬增加有关。60名健康受试者和60名DD患者分别采用肛门球囊扩张和磁共振弹性成像（MRE）评估肛门膨胀性和僵硬性，并通过动态盆腔MRI评估直肠排泄。(2)α1-肾上腺素能张力与DD肛门高压有关。我们将评估α1-肾上腺素能拮抗剂对36名健康受试者和36名DD患者肛门压力的影响。(3)直肠压力较高，与左侧侧卧位相比，直肠肛管压力测量更准确地识别DD (3a)，便携式测压仪可以准确测量直肠肛管压力（3b）。我们将比较60名健康受试者和60名DD患者的高分辨率和便携式测压仪在坐位和左侧卧位测量的压力；盆底运动和直肠排泄将通过动态MRI评估。一个多学科合作团队将采用创新的方法，以高度精细的方式解决这些假设。每项研究都是为了改善人类的病人护理。