Search

This longitudinal, prospective study sought to establish whether pediatric Crohn's disease (CD) and ulcerative colitis (UC) are associated with increased levels of cytogenetic damage and whether folate supplementation in combination with other treatments mitigates cytogenetic damage in children with inflammatory bowel disease (IBD). After a 1-mo treatment and folate supplementation, all clinical tests in CD (n = 24) and UC (n = 17) patients improved. Patients with CD were comparable in the cytogenetic response with controls (n = 28) assessed by micronucleus (MN) assay, but both groups differed from the UC group. While the MN frequency in epithelial cells slightly decreased from first to second observations in CD patients (p = 0.05) and controls (p = 0.11), an increase was observed in UC patients (p = 0.001). Similar changes were observed in blood lymphocytes resulting in significantly higher levels of the MNs and chromosome bridges in UC patients. These preliminary findings of a difference in chromosome damage between pediatric UC patients compared with CD patients and healthy controls warrant confirmation and expansion to determine (1) the role of cytogenetic damage in the pathogenesis of these diseases, (2) relative contribution of treatment and folate supplementation, and (3) potential links to the eventual development of cancer in some patients.

482 Safety and Efficacy of Velaglucerase Alfa in Gaucher Disease Type 1 Patients Previously Treated with Imiglucerase

169 Update on Enzyme Replacement Therapy (ERT) with Recombinant Human Arylsulfatase B (RHASB) for MPS VI (Maroteaux-Lamy)

Growth retardation is common in children with SCA, in spite of adequate dietary intakes. Previous studies have demonstrated elevated REE in children with SCA. An increased metabolic rate may be secondary to rapid hemolysis of sickled cells and the compensatory erythropoietic activity. The purpose of the current investigation was to determine whether the elevated REE in children with SCA can be normalized by RBC transfusion therapy. Five children aged 12 to 16 years (4 males, 1 female) were studied before and one week after a scheduled RBC transfusion. Measurements included anthropometics (height, weight), REE by indirect calorimetry, hemoglobin, reticulocyte count, and percent HgS. Growth failure was seen in 3 of 5 subjects who were below the 25% ile by NCHS standards for height. Pre-transfusion REE was significantly elevated above predicted REE (28%, p≤0.04, Wilcoxon matched-pairs signed-ranks test) consistent with reports in the literature. Surprisingly, REE increased further after RBC transfusion to 37% on average above predicted REE (pre versus post REE, p≤0.08) despite a significant decrease in erythropoietic activity (reticulocyte count: Δ = -9.3%, p≤0.04). Four of 5 subjects showed an increase in REE after RBC transfusion. The subject who had no change in REE demonstrated an increase one week after receiving a second RBC transfusion. Anemia improved after RBC transfusion with an increase in hemoglobin (Δ=1.5 g/dl, p≤0.04), and decrease in Hgb S (Δ=-31.4%, p≤0.04). These results suggest that REE is not correlated with erythropoietic activity in children with SCA and may, in fact, increase when RBC transfusion decreases erythropoietic activity. A possible explanation for this increase includes the hypothesis that a relatively hypoxic catabolic hypermetabolism exists prior to RBC transfusion that transitions in children with SCA to a more hypermetabolic anabolic state after RBC transfusion. If proven, this might explain the catch-up growth observed in children with SCA who receive chronic RBC transfusion therapy.

The everted gut sac technique was used to study adaptive changes in small intestinal handling and uptake of radiolabeled bovine serum albumin and ovalbumin during lactation in rats. Binding and uptake of both proteins by the gut sacs of lactating animals were significantly less, compared to controls (p less than 0.001, after 30 min of incubation). This change was reversible after lactation ceased. The differences could not be explained by oral immunization since there were no specific antibodies found in sera, mucosal extracts, or breast milk; prior exposure to the protein did not alter the observed differences. No differences in mucosal breakdown of bovine serum albumin could be demonstrated by precipitation with trichloroacetic acid (10%); an increase in breakdown of ovalbumin in the lactating animals was shown under the same conditions. The injection of prolactin produced differences in bovine serum albumin binding and uptake similar to the ones observed in the lactating group (p less than 0.01, after 30 min of incubation, compared to solvent-injected controls). Since food protein antigen binding, breakdown and uptake are functions of the local intestinal host defense, these findings suggest that there are adaptive changes of the gut mucosal barrier during lactation which decrease the transfer of dietary antigens from mother to infant. The adaptation of the maternal intestinal host defense was shown to be influenced by prolactin.

Undegraded carrageenan, a sulfated polygalactan macromolecule, is used as an emulsifier in ready-to-use infant formulas. Although undegraded carrageenan has not been shown to be transported across the intestine the safety of this food additive has recently been questioned because of its toxic effect on the intestine and liver of laboratory animals (Lancet 1:602, 1980). We have shown that intestinal macromolecular transport is increased early in life, therefore, newborns may be more susceptible to any toxic effect of carrageenan. To investigate the intestinal transport and toxicity of carrageenan in newborn animals, 40 mgm of carrageenan, a quantity present in 5 oz of formula, was given by gavage to newborn rabbits. Cardiac and portal blood were obtained four hours later. The stomach, small intestine and liver of animals were removed and homogenized. Double gel-diffusion with antiserum raised to λ-carrageenan was used to detect the presence of carrageenan in blood and tissue specimens. The results are expressed in animals positive for carrageenan/animals tested.

The present experiments examine the effect of antibody derived by placental transfer on the uptake of enteric antigen in the new born rabbit pup. Female New Zealand White rabbits were immunized with bovine serum albumin (BSA). Litters from immunized and non-immunized rabbits were examined either at birth, 24hrs., 48hrs., or 72 hrs. After obtaining serum all pups were gavaged with 100 mg of I125-BSA. Pups born to immunized mothers had circulating antibody before feeding while pups of unimmunized mothers had no detectable antibody to BSA. The fed animals were sacrificed 1, 2,3, or 4 hrs. later and sera were examined for the presence of BSA by electroimmunodiffusion. None of the 43 immunized pups had any BSA in their sera, whereas all 20 unimmunized pups had 6-15 ug/m1 of BSA. All animals had>2×104cpm/m1 of serum. Four immunized animals had radioactivity which appeared to be associated with circulating immune complexes. Radioactive material in the remaining immunized animals was

Antibodies, passively acquired from the mother, were previously shown to limit the circulation of antigen given enterically to newborn rabbits. In the present experiments, we tested the effect of passive immunization and enteric antigen challenge on uptake of bystander protein. Female rabbits were immunized with bovine gamma globulin (BGG). Litters from these animals were tested prior to suckling by the intragastric administration of bovine serum albumin (BSA) plus BGG (test) or ovalbumin (OVA) (control animals). Three hrs. later, serum from both groups was tested for immunoreactive BSA by radioimmunoassay. Test animals had significantly less serum iBSA than controls. In other experiments the same protocol was followed except for the addition of 14C-polyethylene glycol (14C-PEG). Three hrs. after challenge, the concentration of radioactivity in various segments of intestine was determined. There was less 14C-PEG in the small intestine of test compared to control animals. These findings suggest enteric antigen-antibody interaction in intact animals may limit contact of protein with the absorptive surface on the enterocyte and thus diminish uptake of bystander protein in the neonate.