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152 Chapter 7 healthy adults and adults with slow-transit constipation. 13,17 Specifically, we hypothesized that both children and adults with intractable constipation would display similar motor abnormalities prior to and after a meal, indicating that the potential neuropathy identified in adults is also present in children. METHODS Study population All children scheduled for colonic manometry for evaluation of chronic intractable functional constipation at our tertiary referral center (Emma Children’s Hospital/Academic Medical Center, Amsterdam, The Netherlands) between January 2014 and June 2015 were potentially eligible for the study. Children with intractable constipation underwent colonic manometry as part of standard care. Children had tomeet the following criteria for inclusion: (i) fulfilled the Rome III criteria for functional constipation 18 , (ii) aged between 0 and 18, and (iii) failed response to intensive treatment (high dosage of osmotic and stimulant laxatives, colonic lavage). Patients were excluded if they had constipation with a known organic cause. Colonic transit studies were not routinely performed in these children. Many parents were reluctant to allow their children to stop taking medications to allow a transit study to be conducted out of fear for deterioration of symptoms. As such, colonic transit was only measured in nine children. We adopted a radiopaque marker study where a capsule with 10 radiopaque markers was ingested on six consecutive days with an abdominal X-ray on day 7. Colonic transit time was calculated by multiplying the number of intra-abdominal markers by the constant 2.4. The 2.4 represents the ratio between the period in which the examination was performed (144 h) and the number of markers ingested ( n = 60). 19 Anorectal manometry studies were performed in 13 of 18 children. As with the colonic transit studies, some parents were reluctant for their children to undergo this test. In this procedure, anal squeeze and resting pressures were measured as was the presence of a rectoanal inhibitory reflex (RAIR). All adults were recruited and studied at Flinders Medical Centre, Adelaide, South Australia, Australia. The recruitment of healthy adults has been described elsewhere. 17 In summary, subjects had to be aged 19–75 years and had normal bowel habits, defined as having between three bowel movements a day and one bowel movement every three days, with no symptoms of rectal evacuatory difficulty or other gastrointestinal symptoms. All adult participants gave written, informed consent, and the studies were approved by the Human

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