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.

BACKGROUND:Endoscopic ultrasound (EUS) is a useful diagnostic and therapeutic tool in the pediatric population. Given the high accuracy and sensitivity of EUS, it is particularly effective in evaluating pancreaticobiliary disease. Published literature in the use of pediatric EUS is limited. Therefore we aimed to review the current literature for EUS indications, safety, and effectiveness for the pediatric population. DATA SOURCES/METHODS:English language articles on the use of pediatric endoscopic ultrasound in evaluating pancreaticobiliary diseases were retrieved from PubMed/ MEDLINE. RESULTS:We analyzed various retrospective studies and case series publications. Data were extrapolated for pediatric patients with pancreaticobiliary diseases. CONCLUSIONS:EUS offers superior imaging. It is comparible to magnetic resonance imaging and/or pancreatic-protocol computed tomography. In the current literature, there are a variety of pancreaticobiliary conditions where EUS was utilized to make a diagnosis. These include recurrent pancreatitis, congenital anomalies, microlithiasis, pancreatic pseudocysts, and pancreatic mass lesions. EUS was shown to be a safe and cost-effective modality with both diagnostic and therapeutic capabilities in the pediatric population. EUS is now increasingly being recognized as a standard of care when evaluating pancreaticobiliary conditions in children.

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: Infliximab, an anti-tumor necrosis factor (TNF) monoclonal antibody, might exert some of its long-term therapeutic effects in Crohn's disease (CD) by interacting directly with cells of the immune system such as monocytes and T lymphocytes via membrane TNF and by inducing apoptosis. Accordingly, the effects of inflix-imab on monocyte apoptosis and down-regulation of proinflammatory cytokines (reverse signaling) were assessed. METHODS: To assess apoptosis, monocytes from healthy individuals (controls) and CD patients were incubated in the presence or absence of infliximab or the apoptotic agent gliotoxin for 24 hours. Annexin V staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-FITC nick end labeling assay were used to measure early and late apoptosis. To measure the effects of infliximab on reverse signaling, monocytes from healthy individuals pretreated in vitro with infliximab were stimulated with lipopolysaccharide or staphylococcal enterotoxin A, and the induction of the proinflammatory cytokines, TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured by reverse transcription polymerase chain reaction. The effect of in vivo infliximab treatment of monocytes was similarly determined by comparing the responses of monocytes from CD patients before and immediately after infliximab infusion. RESULTS: Infliximab did not induce apoptosis of monocytes from either healthy individuals or CD patients but rather stabilized them. However, monocytes from healthy individuals treated with infliximab in vitro, or from CD patients infused with infliximab, produced significantly less TNF and other proinflammatory cytokines when stimulated with the bacterial products lipopolysaccharide and staphylococcal enterotoxin A. CONCLUSIONS: Apoptosis of monocytes is not responsible for the therapeutic effects of infliximab. However, some of the therapeutic effects of infliximab may be caused by its ability to down-regulate proinflammatory cytokines production by monocytes exposed to bacterial antigens

Perturbations in sex hormones occur in adults with liver disease; however, little is known about how liver disease affects hormone levels in children. To address this issue, we recruited 19 patients with portal hypertension and 21 non-hormone-deficient short children as controls. Serum sex hormones, sex hormone binding globulin (SHBG), IGF-I, IGFBP-3, gonadotropins, and thyroid hormones were measured; growth and pubertal status were recorded. There was no significant difference between groups for any of the sex hormones, SHBG, gonadotropins, or thyroid hormones. In contrast, IGF-I and IGFBP-3 were significantly lower among patients than controls, despite the fact that height SDS for the control group was significantly lower. We conclude from this cross-sectional study that children with portal hypertension do not have clinical evidence of growth failure or abnormal puberty, despite subtle changes in the growth axis

Patients with ulcerative colitis who undergo proctocolectomy and an ileal anal anastomosis (IPAA) require surveillance; dysplasia and carcinoma occur in both the small intestinal mucosa of the ileal pouch and the retained rectal mucosa as early as 2 yr after ileostomy closure. This study evaluated risk factors for carcinoma (eg, dysplasia, p53 overexpression, labeling index, and aneuploidy) in the small intestinal and rectal mucosa. Thirty patients (age 14-64 yr) with ulcerative colitis and IPAA were studied. The mean duration of ulcerative colitis prior to IPAA was 3 yr (range 6 mo-21 yr). Patients were followed by annual endoscopy and biopsies of the ileal pouch and rectal mucosa. Sections of small intestine and rectal mucosa were evaluated for inflammation and dysplasia, and by immunohistochemical stains Ki-67 (MIB-1) for a labeling index and for p53. Ploidy determination was performed by flow cytometry. Active inflammation of the small intestinal mucosa and the rectal mucosa was frequent and the labeling index of both the pouch and rectal mucosa was abnormal. Two patients had changes indefinite for dysplasia, one involving the small bowel mucosa of the pouch and the other the retained rectal mucosa. Fifteen of the 30 patients had overexpression of p53, 9 from the pouch, and 6 from the rectal mucosa. Overexpression of p53 was seen in both of the patients with indefinite dysplasia. Aneuploidy was noted in 3 patients: two from the pouch and one from the rectal mucosa. All aneuploidic specimens were p53-positive, but negative for dysplasia. In conclusion, most biopsies of the ileal pouch and rectal mucosa were inflamed. The labeling indexes of the small bowel and rectal mucosa were higher than normal. The risk factors for carcinoma (dysplasia, overexpression of p53, and aneuploidy) occurred in the small intestinal and the rectal mucosa. Overexpression of p53 was noted in 16 patients, dysplasia only in 2. Therefore, p53 overexpression and aneuploidy should be considered in the evaluation of surveillance biopsies of patients with ulcerative colitis with IPAA, whereas dysplasia is an insensitive marker

OBJECTIVE: To identify changes over the past decade in physicians' attitudes regarding the use of immunomodulatory agents for the treatment of children with inflammatory bowel disease (IBD), we surveyed the membership of the North American Society for Pediatric Gastroenterology and Nutrition and compared the responses to those from an identical survey performed in 1990. METHODS: Surveys were mailed to 718 physicians in January, 2000. All surveys returned by mid-February were analyzed, and results compared to those obtained in the 1990 survey. RESULTS: Thirty-nine percent (278/718) of surveys were returned, compared to 27% (105/385) in 1990. Overall, 93% of the current survey's respondents agreed with the statement 'immunomodulatory agents are effective in the treatment of children and adolescents with IBD.' Compared to 1990, significant increases (p < 0.0001) were noted in the percentage of respondents who prescribe immunomodulatory agents to children with all forms of IBD. Indications for immunomodulation that showed significant increases (p < 0.001) since 1990 included treatment of perianal and non-perianal fistulae; growth failure; use as initial, primary therapy; and use as prophylaxis against postoperative recurrence. 6-Mercaptopurine and azathioprine continue to be the agents prescribed by the greatest percentage of respondents. More physicians are willing to use immunomodulatory agents in children younger than 5 yr, and duration of use is longer than in 1990. Currently, physicians seem to favor the use of immunomodulatory agents over colectomy for children with either intractable ulcerative or Crohn's colitis. Most respondents remain concerned about potential bone marrow and immune suppression, but concerns regarding malignancy, teratogenicity, and infertility have lessened. CONCLUSION: These survey findings document that pediatric gastroenterologists have widely accepted the use of immunomodulators in the treatment of children and adolescents with IBD

BACKGROUND: Liver biopsy findings are important in diagnosing extrahepatic biliary atresia. Diffuse ductular proliferation is a characteristic finding. We describe four patients with conjugated hyperbilirubinemia in whom the initial liver biopsy findings showed a lack of ductular proliferation, despite subsequent development of biliary atresia. RESULTS: On initial biopsy, paucity of intrahepatic bile ducts was present in three of four patients, with a bile duct to portal space ratio of 0.3 to 0.4 (normal, 0.9-1.8). A normal bile duct to portal space ratio of 1.0 was observed in the fourth patient. Ductular proliferation became apparent in three subjects between 9 and 12 weeks of age, and biliary atresia was noted at the time of a Kasai portoenterostomy. The fourth child had well-developed biliary cirrhosis at liver transplantation. CONCLUSIONS: Changes characteristic of biliary atresia may appear even after 9 weeks of age. Bile duct paucity and normal bile duct to portal space ratio do not preclude the subsequent development of biliary atresia. Infants with unexplained conjugated hyperbilirubinemia and acholic stools should undergo sequential liver biopsies until clinical improvement occurs or until biliary atresia can be excluded from the differential diagnosis