Efficacy of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis in children.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to be beneficial in reducing disease activity in adult patients with primary sclerosing cholangitis (PSC). However, there has been little published regarding PSC in children and no studies investigating the efficacy of UDCA as a treatment for PSC. METHODS: This retrospective study included 10 children who were found to have the diagnosis of PSC during the past 15 years at the Texas Children's Hospital and Herman Hospital, both in Houston, Texas. The male:female ratio was 8:2, the median age of onset was 12 years (range, 1-17 years), and eight patients had coexistent inflammatory bowel disease (IBD; six ulcerative colitis, one Crohn's disease, one unspecified). At the time of diagnosis, five patients were asymptomatic, all of whom had IBD with elevated liver enzymes and three of whom had hepatomegaly. Nine patients were treated with UDCA. The one patient who did not receive UDCA was lost to follow-up soon after diagnosis. The mean dose of UDCA was 17 mg/kg with the doses ranging from 9 to 37 mg/kg. RESULTS: There were no side effects from the medication recorded for any of the patients. These patients showed a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase at 1, 3, 6, 15, and 20 months after treatment. CONCLUSIONS: This study demonstrates that children with PSC treated with UDCA have significant improvements in liver biochemical indices. However, the long-term effect of UDCA on clinical outcome is unknown.

Symptomatic hyperammonemia caused by a congenital portosystemic shunt.

A child with trisomy 21 had altered mental status and hyperammonemia at presentation and was found to have a congenital portosystemic shunt as a result of a congenital abnormality of the portal venous system. Anomalies of the portal venous system leading to portosystemic shunting, although they are infrequent, should be considered in the differential diagnosis of hyperammonemia.

Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia.

This is a case report and review of the literature on the blue rubber bleb nevus syndrome. The clinical features of the syndrome are discussed, with emphasis on chronic gastrointestinal bleeding and resulting anemia. A new therapeutic modality, colonoscopy with laser photocoagulation, is recommended as a safe, effective, and less invasive method of controlling bleeding from colonic hemangiomas than surgical resection and repeated transfusions. This technique is less helpful for patients with prominent involvement of the small intestine.

Effects of pH alterations and hypoxia on isolated human intestine.

Effects of hypoxia and pH alterations on the spontaneous contractions and responses to cholinergic stimuli or KCl were investigated in isolated human intestines. The longitudinal strip of human intestine showed spontaneous contractions. The spontaneous contraction was abolished by hypoxia with nitrogen gas substitution (95% N2 and 5% CO2) but not by substitution with acidic (pH 6.53) or alkaline (pH 7.75) solution. Contractile responses to acetylcholine (ACh) were not altered by treatment with hypoxia or pH alterations. KCl (10 mM)-induced contraction was inhibited by hypoxia but not by pH alterations. Transmural electrical stimulation elicited a transient contraction that was blocked by tetrodotoxin or atropine. Contractions induced by electrical stimulation at a low frequency (5 Hz) was not altered by hypoxia or pH alterations. The metabolic pathway related to energy generation and utilization for the spontaneous contraction and KCl-induced contraction seems to be more dependent on oxygen supply than that for ACh-induced contraction. The contractile mechanism in human intestine seems to be resistant to pH alterations.

The effects of chronic prednisone administration on intestinal receptors for 1,25-dihydroxyvitamin D3 in the dog.

Glucocorticoid inhibits intestinal calcium absorption. To further explore the mechanism of this inhibition, we studied dogs during the administration of oral prednisone (1.2-1.5 mg/kg X day) for 20 to 28 weeks in comparison to untreated dogs. Prednisone administration had no effect on serum 25-hydroxyvitamin D concentrations, but was accompanied by a fall in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations from 87 +/- 20 pM (control) to 62 +/- 28 pM (prednisone-treated; P less than 0.01). Cytosol prepared from the duodenal, jejunal, and ileal mucosa of control dogs was found to contain a specific 3.2S [3H]1,25-(OH)2D3 binder analogous to the binder that has been observed in the intestine of other species and in other tissues. The apparent concentration of this binder decreased progressively from duodenum to ileum. Prednisone administration increased the apparent duodenal concentration of the binder from 170 +/- 91 (control) to 363 +/- 124 fmol/mg protein (prednisone-treated; P less than 0.025). The intestinal content of calcium-binding protein also declined progressively from the duodenum to the ileum, but was not affected by prednisone administration. These data suggest that events other than alterations in intestinal 1,25-(OH)2D3 receptors must mediate the inhibition of intestinal calcium absorption during chronic glucocorticoid administration.

Immunocytochemical localization of rat intestinal vitamin D-dependent calcium-binding protein.

Vitamin D-dependent calcium-binding protein (CaBP) was localized in intestinal tissue sections obtained from rats raised under three different nutritional conditions: a normal vitamin D-replete diet, a vitamin D-free diet followed by supplementation with vitamin D3, or a vitamin D-free diet without additional supplementation. An indirect immunoperoxidase technique, with immunocontrols, was used to visualize the specific sites of CaBP. CaBP was visualized only in the cytoplasm of absorptive cells. In the duodenum of animals raised on a normal diet, CaBP was present in absorptive cells from the upper crypt region to the villus tips. In the jejunum, many fewer absorptive cells contained CaBP, while in the ileum only random absorptive cells near the villus tips contained CaBP. In rats raised on a vitamin D-deficient diet then supplemented with vitamin D3, CaBP was present in cells at the full depth of the crypts and in absorptive cells along the total villus length in the duodenum. Rats raised on the same deficient diet but without supplementation with additional vitamin D exhibited no CaBP in crypt cells nor in absorptive cells more than half way up the villi. Absorptive cells higher on the villi contained immunoreactive CaBP but the intensity of immunostaining and number of CaBP-containing cells was markedly reduced compared to the vitamin D-supplemented group.

Rat intestinal vitamin D-dependent calcium-binding protein: immunocytochemical localization in incisor ameloblasts.

Antiserum raised against the 10,000-Dalton vitamin D-dependent calcium-binding protein (CaBP10) from rat intestine was used to localize CaBP10 immunocytochemically in histological sections of rat mandible using an indirect immunoperoxidase method. Ameloblasts in the zone of maturation, along the continuously erupting incisor, contained CaBP10 throughout their cytoplasm. It was present in both smooth-ended ameloblasts and ruffle-ended ameloblasts. CaBP10 was not found in earlier developmental stages of ameloblasts or in other cells involved in tooth formation, i.e., odontoblasts, pulpal cells, cells of the stellate reticulum, papillary layer, and outer dental epithelium. The presence of CaBP10 in ameloblasts suggests that the vitamin D-endocrine system may have a direct effect on tooth formation in addition to the indirect effect of maintaining the required levels of serum calcium and phosphorus required for mineralization.

Experimental protein malnutrition decreases calcium-binding protein in rat intestinal mucosa.

Calcium-binding activity was measured in duodenal mucosal homogenates of rats 50 days after weaning onto a protein-deficient diet providing 3-4 g of protein per kilogram of body weight per day compared to control animals, who were fed an isocaloric diet providing 9-12 g of protein per kilogram of body weight per day. Calcium-binding activity was decreased (44% of control) further than can be explained by the decrease in intestinal mucosal weight (70% of control) or supernatant protein content (80% of control). The results suggest that the decrease in calcium-binding activity reflects decreased synthesis of the vitamin D-dependent calcium-binding protein (CaBP) as an adaptive response to the stunted growth associated with protein malnutrition.

Intestinal calcium-binding protein in the baboon (Papio cynocephalus).

1. Calcium-binding protein (CaBP) has been isolated from baboon (Papio cynocephalus) intestinal mucosa by gel filtration and ion-exchange chromatography. 2. Similarity in electrophoretic behavior, size and charge and immunologic structure are demonstrated between the baboon CaBP and CaBPs isolated from other species. 3. Baboon intestinal CaBP is resistant to neuraminidase digestion.

Intestinal calcium binding protein in uremia.

In order to assess the usefulness of intestinal biopsies as indicators of end-organ responsiveness to vitamin D in uremic patients, calcium binding activity and calcium binding protein (CaBP) content were measured in intestinal biopsies from 12 uremic patients (glomerular filtration rate less than 5.0 ml/min) and 12 adult controls. Values for both were found to vary with the site of biopsy, highest values being obtained in the duodenal bulb, with lower values distally. Values for activity correlated with values for CaBP content in both normals and uremics and no difference was observed between groups. Levels of calcium binding activity and content of CaBP did not correlate with serum immunoreactive parathormone levels, but were directly related to circulating 25-hydroxycholecalciferol (25-OHD) levels. The data show that intestinal CaBP is normal in activity, quantity, and affinity for calcium in malabsorbing uremic patients, and are consistent with the hypothesis that calcium malabsorption in uremia is unrelated to deficiency of intestinal calcium binding protein.