Faculty Bibliography

BACKGROUND/UNASSIGNED:When an exclusively breastfed infant develops hematochezia, the pediatrician may recommend elimination of dairy and soy products from a mother's diet, but there is limited scientific evidence to indicate that altering the maternal diet will lead to resolution of the problem. RESEARCH AIM/UNASSIGNED:To estimate the likelihood that maternal dairy and soy avoidance will resolve rectal bleeding in an exclusively breastfed infant. METHODS/UNASSIGNED:This was a prospective, longitudinal, one-group pre/post study involving mothers of exclusively breastfed infants at least 2 weeks but less than 6 months of age with a positive stool guaiac test in the absence of an intestinal lesion or other explanation for the blood. Participants agreed to follow a dairy and soy elimination/rechallenge protocol, maintain a food diary, and have their infant re-tested at 3-week intervals to determine the outcome of the dietary changes. One participant was lost to follow-up, leaving a final sample size of N = 19. RESULTS/UNASSIGNED:All infants continued to test positive for blood in the stool after their mothers eliminated foods containing dairy or soy. Therefore, 0% (0/19) of infants responded to their mother's restricted diet, 95% confidence interval (one-sided [0%, 15%]). CONCLUSION/UNASSIGNED:Given these results, we must call into question the rationale for advising breastfeeding mothers to eliminate dairy and soy from their diet in response to their infant's unexplained rectal bleeding.

OBJECTIVES:: Infants with milk protein intolerance are usually switched to a casein hydrolysate or amino acid based formula, which they continue to receive until one year of age, when they are rechallenged with a cow's milk or soy protein formula. To investigate whether some of these infants actually become tolerant sooner, this study gathered preliminary data for establishing an empirical timetable for the resolution of milk protein intolerance. METHODS:: This prospective, longitudinal cohort study enrolled infants <4 months of age receiving either breast milk or a cow's milk or casein hydrolysate formula who presented to a pediatric subspecialty practice over an 18-month period and had a positive stool guaiac test. After having been successfully switched to a casein hydrolysate or amino acid formula, infants who had guaiac-negative stools for at least 2 consecutive months were rechallenged with the formula that had necessitated the most recent switch. RESULTS:: Of the 25 patients enrolled in the study, 16 completed the food challenge and data collection protocol. Negative stool guaiac tests following rechallenge indicated resolution of milk protein intolerance by the time subjects reached an average age of 6.7 +/- 1.0 months (mean +/- SD). By the age of 7 months, 12 of the 16 infants had resolved, the remainder having resolved by 10 months. CONCLUSIONS:: It may be reasonable to treat infants with milk protein intolerance for 2-3 months with a hypoallergenic formula, then rechallenge them at 6 months of age, usually without causing recurrence of the hematochezia. Rechallenging before 12 months old could result in cost savings to families and insurers.

OBJECTIVES/OBJECTIVE:ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. METHODS:129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. RESULTS:In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. CONCLUSIONS:PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways.

OBJECTIVE:To determine the prevalence of antibodies associated with celiac disease and biopsy-proven celiac disease in children with autoimmune thyroid disease. STUDY DESIGN/METHODS:A total of 302 patients with positive anti-thyroid antibodies were prospectively studied. Total immunoglobulin A (IgA) and tissue transglutaminase-IgA (tTG-IgA) levels were obtained. Those with a positive tTG-IgA titer were offered biopsy for definitive diagnosis of celiac disease. RESULTS:A total of 4.6% of subjects with autoimmune thyroid disease had positive tTG-IgA titers. The prevalence of biopsy-confirmed celiac disease was 2.3%. Our population was enriched with patients with type 1 diabetes mellitus (4.3%) and Down syndrome (3.4%). Excluding individuals with these co-morbidities, the prevalence of celiac disease in autoimmune thyroid disease is 1.3%, similar to that of the general population. The positive predictive value of biopsy-proven celiac disease in patients with autoimmune thyroid disease and positive tTG-IgA titer was 54%. CONCLUSION/CONCLUSIONS:The increase in prevalence of celiac disease in autoimmune thyroid disease in our study was largely caused by enrichment with co-morbidities. Without comorbidities or symptoms, screening for celiac disease may not be justified in this population. The specificity of tTG-IgA titer for the diagnosis of celiac disease was decreased in patients with autoimmune thyroid disease compared with the general population.

PURPOSE OF REVIEW/OBJECTIVE:This review summarizes recent advances about the role of microsomal triglyceride transfer protein in plasma and tissue lipid homeostasis. RECENT FINDINGS/RESULTS:Microsomal triglyceride transfer protein emerged as a phospholipid transfer protein and acquired triacylglycerol transfer activity during evolution from invertebrates to vertebrates. These activities are proposed to participate in 'nucleation' and 'desorption' steps during the biosynthesis of primordial apoB-containing lipoproteins. Microsomal triglyceride transfer protein also transfers phospholipids to the glycolipid antigen presentation molecule CD1d. Under physiologic conditions, plasma apoB-containing lipoproteins and microsomal triglyceride transfer protein expression exhibit diurnal variations synchronized by food and light. Microsomal triglyceride transfer protein is regulated at the transcriptional level. HNF4alpha is critical for its transcription. Other transcription factors along with coactivators and corepressors modulate microsomal triglyceride transfer protein expression. Reductions in microsomal triglyceride transfer protein mRNA and activity are related to steatosis in HCV-3 infected patients. CCl4 induces steatosis by enhancing proteasomal degradation of microsomal triglyceride transfer protein and can be partially avoided by inhibiting this degradation. Chemical antagonists cause hepatosteatosis, but this was not seen in the absence of fatty acid binding protein. SUMMARY/CONCLUSIONS:Microsomal triglyceride transfer protein is a target to lower plasma lipids and to reduce inflammation in certain immune disorders. More knowledge is required, however, regarding its regulation and its role in the biosynthesis of apoB-containing lipoproteins and CD1d.