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We examined full-thickness rectal biopsies from 30 children who had chronic constipation, including 5 children with constipation associated with clinical symptoms of intestinal pseudo-obstruction. Biopsies from 9 patients who required colonic interposition and from 7 with Hirschsprung's disease were used as controls. Tissues were evaluated for muscularis mucosae thickness (in mm), for absolute circular and longitudinal muscle layer thicknesses and their ratio, and for the intensity of neural vasoactive intestinal peptide (VIP) immunohistochemical staining. Atrophy of the rectal musculature with focal muscle fiber vacuolation or muscle fiber disappearance was found in all children with chronic constipation. Muscularis mucosae thickness was increased (P < .01) and the circular-to-longitudinal muscle ratio was decreased in the constipation group, with the greatest degree of atrophy being demonstrated in the circular layer. Two of the patients had additional biopsies up to 9 years after the first that illustrate progressive myopathic changes over time. This study demonstrates muscular atrophy in the rectum of children with chronic constipation. Besides primary idiopathic disease, potential etiologies include chronic distention, denervation, functional obstruction from obstipation, alteration in gut hormones, and toxic, ischemic, or neural injury.

ABSTRACT. ~Xarnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age ( p = 0.035 and 0.026, respectively).Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon ( p = 0.0006), insulin ( p = 0.0001), and g1ucagon:insulin ratio ( p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal g1ucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns. (Pediatr Res 32: 312-316,1992) Abbreviations PEG, polyethylene glycol SCAC, short-chain acylcarnitine ANOVA, analysis of variance NB, newborn group S, suckling group W, weaning group FW, fully weaned group plays a critical role in the metabolic transition from carbohydrate to lipid-derived energy (2, 3) because hepatic glycogen stores become rapidly depleted and endogenous gluconeogenesis is inadequate in the first 24 h of life (4, 5). As such, carnitine insufficiency has been shown to impair lipid utilization in premature newborns (6, 7). The human newborn is especially susceptible to develop carnitine insufficiency because of low levels in premature infants (8), inadequate dietary intake of carnitine (9), and insufficient endogenous synthesis (10).One marker of the switch from glucose to lipid utilization in the newborn is the increase in hepatic carnitine concentrations compared with the fetus (4). In newborn rats, the Cfold rise in hepatic carnitine has been shown to coincide with enhanced ketone production. Although the origin of hepatic carnitine in newborns has not been fully established, because endogenous synthesis is limited, dietary sources appear to be important. Human and rat milk carnitine concentrations peaked in the first few days after parturition (4, 1 1). In 5-d-old rats, the contribution of milk carnitine to heart (41%) and liver (49%) carnitine stores was substantial (12). We hypothesized that intestinal a...