No abstract

To assess the utility of various indicators of biotin status, marginal biotin deficiency was induced experimentally in normal adults. Ten subjects consumed a diet that contained enough avidin to bind seven times more biotin than that in the diet. Blood and 24-h urine samples were collected before the diet began and twice weekly thereafter for 20 d. The urinary excretion and serum concentration of biotin and its two principal inactive metabolites bisnorbiotin and biotin sulfoxide were determined after HPLC separation with an avidin-binding assay. The urinary concentration of 3-hydroxyisovaleric acid, an indicator of reduced activity of a biotin-dependent enzyme, was quantitated by gas chromatography-mass spectrometry. The urinary excretion of 3-hydroxyisovaleric acid increased significantly (P < 0.0001). For all subjects, the urinary excretion of both biotin and bisnorbiotin decreased significantly (P < 0.0001 for each). In contrast, the mean serum concentration of biotin did not decrease significantly (P = 0.06). These data provide evidence that the urinary excretion of 3-hydroxyisovaleric acid and the urinary excretion of biotin are early and sensitive indicators of biotin deficiency and that the serum concentration of biotin is not.

No abstract

Long-term PEG therapy is safe and is well accepted by children with chronic constipation with and without encopresis.

No abstract

Combination therapy successfully shunted thiopurine metabolites to a more favorable pattern. Reversible neutropenia was the most common side effect (2 patients). Long-term prospective studies are needed in this patient population.

Seventy-four children (43 with chronic constipation, 31 with constipation and encopresis) treated with polyethylene glycol 3350 (PEG) for longer than 3 months were studied to assess long-term efficacy. The mean duration of PEG therapy was 8.4 months (range, 3-30). Weekly stool frequency, stool consistency, and symptoms associated with constipation improved significantly with PEG therapy in all 74 patients. In 31 children with encopresis, soiling ceased completely in 16 patients and frequency of soiling decreased significantly in all others. The average effective long-term dose of PEG was 0.7 g/kg/day. Long-term PEG therapy is effective for the treatment of chronic constipation with and without encopresis in children.

The epidermal growth factor (EGF) receptor is an important mediator of intestinal epithelial cell proliferation. We studied cell-surface localization of this molecule in Caco-2 cells and characterized cellular responses to apical or basolateral EGF stimulation. 125I-labeled EGF bound almost exclusively to a 180-kDa molecule, existing as a single high-affinity population by Scatchard analysis. On basolateral membranes 13- to 15-fold more ligand binding was seen. Apical/basolateral differences were not significantly altered by incubation with either blocking antibody to EGF receptor or transforming growth factor-alpha (TGF-alpha) neutralizing antibody. Even though apical EGF receptors were demonstrated, only basolateral membrane stimulation with EGF increased tyrosine kinase activity and enhanced uptake of [3H]thymidine. Continuous exposure to EGF during culture significantly increased monolayer DNA content. These data demonstrate that Caco-2 cell proliferation is driven solely by basolateral membrane EGF receptor, despite the presence of lesser amounts of this molecule on the apical surface. Differences between apical and basolateral membrane receptor expression are not the result of polarized secretion of TGF-alpha or other EGF receptor ligands.