Understanding Mechanisms of Normal and Disordered Defecation

Study includes a screening visit and a study day. During the initial screening visit for this
study, subjects will complete three (3) questionnaires about their bowel symptoms, overall
health, and anxiety and depression. A blood sample (about 4 tablespoons) will be drawn to
study the relationship between genes and certain bowel habits. Subjects will be asked to
provide a single stool sample to look at the bacteria in the stool.

Before the study, subjects will receive 1 to 2 Fleet's enemas to clean the rectum. After
receiving the Fleet's enema (administered through a small plastic tube in the rectum), a swab
attached to a small rectal catheter will be used to brush the lining of the rectum and obtain
a stool specimen. Then, rectal and anal pressures will be measured by placing a small
catheter (plastic tube) in the rectum, and withdrawing it slowly. Rectal sensation will be
measured by inflating a small balloon in the rectum.

There are 2 procedures (rectal barostat study and fecomanoflowmetry), each of which lasts
approximately 90 minutes. During the rectal barostat study, contractions will be recorded
with a balloon inserted into the rectum and inflated. After the barostat study is completed,
your rectum will be filled with a small amount of paste. Two thin catheters will be inserted
into the anus to measure pressures and electrical activity (electromyography or EMG). Then,
you will be asked to sit on a commode, contract (squeeze) your anal muscles, blow into a
balloon, and expel the paste into the commode.

Inclusion Criteria

- Male and female volunteers aged 18-80 years.

- Able to provide written informed consent before participating in the study.

- Able to communicate adequately with the investigator and to comply with the
requirements for the entire study.

- Individuals with chronic constipation for 1 year, with 2 or more of the following
symptoms for 3 months or longer: <3 bowel motions/week, straining ≥ 25% of time, hard
or lumpy stools ≥ 25% of time, anal digitation ≥ 25% of time, incomplete evacuation ≥
25% of time, feeling of anorectal blockage ≥ 25% of time.

- Able to provide written informed consent before participating in the study.

- Able to communicate adequately with the investigator and to comply with the
requirements for the entire study.

Exclusion Criteria

- Clinical evidence of significant cardiovascular, respiratory, renal, hepatic,
gastrointestinal, hematological, neurological, psychiatric or other disease that may
interfere with the objectives of the study and/or pose safety concerns.

- Current symptoms of a functional gastrointestinal disorder assessed by questionnaire.

- Putative risk factors for pelvic floor trauma: i.e. six or more vaginal deliveries,
birthweight >4500gms (macrosomia), or known 3rd or 4th degree perineal tear.

- Medications that are likely to alter gastrointestinal motility: e.g., opiates and
anticholinergic medications; a stable dose of thyroxine and low doses of tricyclic
agents (e.g., up to amitriptyline (50 mg daily).

- Active rectal inflammation, cancer; perianal sepsis; history of pelvic radiation,
rectosigmoid surgery or inflammatory bowel disease.*

- Anxiety or depression as assessed by the Hospital Anxiety and Depression
Questionnaire.

- Pregnant women, prisoners and institutionalized individuals.