Journal of Pediatric Gastroenterology and Nutrition

41:493563 October 2005 Lippincott Williams & Wilkins, Philadelphia

Abstracts

North American Society of Pediatric

Gastroenterology, Hepatology, and Nutrition
Annual Meeting
October 2022, 2005
Salt Lake City, Utah

POSTER SESSION I Conclusion: There was considerable variability in EMA and TG levels
for each Marsh grade, so that an individual level could not be utilized to
THURSDAY, OCTOBER 20, 2005 predict histological severity. The data show that as a group, increasing
5:00 PM 7:00 PM severity of the histological lesion in celiac disease was associated with
increased levels of both IgA EMA and TG antibodies.
Celiac Disease
TABLE 1. Endomysial antibody titer and Marsh Grade
1* Marsh Grade 0 I & II IIIa IIIb & IIIc
SEVERITY OF HISTOLOGICAL CHANGES IN CELIAC Mean titer (SD) 122 (502) 978 (3665) 4603 (10759) 6173 (11678)
DISEASE CORRELATES WITH IGA ENDOMYSIAL AND Sample size 53 39 17 40
TISSUE TRANSGLUTAMINASE ANTIBODY LEVELS
Holly Wimpee2, Kris Leiferman2, John Zone2, Molly OGorman1, Daniel TABLE 2. Tissue transglutaminase level and Marsh Grade
Jackson1, Christopher Hull2, Linda Book1. 1Pediatrics, University of
Utah, Salt Lake City, UT; 2Dermatology, University of Utah, Salt Lake Marsh Grade 0 I & II IIIa IIIb & IIIc
City, UT.
Mean units (SD) 12.6 (18.8) 22.4 (28.1) 40.7 (98.9) 75.8 (77.8)
Background: Although IgA endomysial antibodies (EMA) and tissue Sample size 21 21 9 25
transglutaminase (TG) are sensitive and specific serologic tests for
the diagnosis of celiac disease, there is limited information on the
association of the magnitude of antibody level with the severity of the 2
histological abnormalities of the intestine.
Purpose: To determine if EMA and TG titers correlate with the severity LACK OF CORRELATION OF COPY NUMBER OF HLA
of histological changes in patients with celiac disease. DQA1A*05 DQB1*02 AND TISSUE TRANSGLUTAMINASE
Methods: We identified 148 children from our laboratory database that LEVELS IN UNTREATED CELIAC DISEASE
had EMA, TG and intestinal biopsies performed. IgA EMA was deter- Stephanie Klein1, Susan Neuhausen2, Linda Book1, Charles Hoff 1,
mined by indirect immunofluorescence with results expressed as a dilu- John Zone1. 1University of Utah, Salt Lake City, UT; 2University of
tional titer with positivity determined at 1:5. IgA TG was determined by California Irvine, Irvine, CA.
an enzyme linked human immunosorbent ELISA assay with results
expressed in standardized units. A modified Marsh histological grading Background: Celiac Disease is an autoimmune disorder of the small
system was used to describe the duodenal biopsies: Type 0 normal, I intestine characterized by intolerance to gluten. More than 90% of the
increased intraepithelial lymphocytes (IEL), II hyperplastic crypts, IIIa patients with celiac disease have the human leukocyte antigen DQA1*05
partial villus atrophy, IIIb subtotal villus atrophy, IIIc total villous atrophy. DQB1*02. A gene dosage effect has been proposed for this high-risk
Results: Mean values for EMA (Table 1) and TG (Table 2) genotype. In CD, there is an autoimmune response to the enzyme tissue
progressively increased with increasing Marsh score. transglutaminase, causing the production of immunoglobulin A
autoantibodies, which are quantitative and resolve with improvement
*Posters of Distinction. of intestinal inflammation after adherence to a gluten-free diet.

493
494 NASPGHAN ANNUAL MEETING
Methods: Blood samples were collected from relatives of patients with
known celiac disease as part of a family study to identify genes for
celiac disease. These patients were screened for immunogloglobulin A
endomysial antibodies. Positive sera were then evaluated for quanti-
tative levels of immunoglobulin A tissue transglutaminase antibodies
and HLA genotyping was performed.
Results: One hundred sixteen family members were found to be positive
for immunoglobulin A endomysial antibodies. Tissue transglutaminase
levels for this group had a mean of 111 (6SD 93) with a range of 4-258.
There was no correlation between IgA tTG levels and age or sex of the
patients. Twelve patients had no copies of DQA1*05DQB1*02,82 had 1
copy, and 22 had 2 copies. The means for IgA tTG Ab levels for the 3
groups were (1) zero copies, mean = 129 Units (2) one copy, mean = 111
units (3) two copies, mean = 100 units. There were no statistical differ-
ences between the IgA tTG Ab levels in the 3 groups or when or when the
presence of the DQB1*02 genotype alone was evaluated.
Conclusion: HLA genotype, although it is strongly correlated with CD
and does not correlate with the level of IgA tTG Ab.
3 47/53-89%;PPV 8/14-57%;NPV 47/47-100%). There were 15 values
CELIAC DISEASE IN PAKISTANI CHILDREN WITH
PERSISTENT DIARRHEA
Sina Aziz1, Rana Muzaffar2, Mirza N. Zafar3, Ayesha Mehnaz4,
Muhammad Mubarak5, Zaigham Abbas6, Syed A. Naqvi7, Adeeb H.
Rizvi8. 1Pediatric gastroenterology and hepatology, SIUT, Karachi,
Pakistan; 2Immunology, SIUT,DMC, Karachi, Pakistan; 3Biochemistry,
SIUT, Karachi, Pakistan; 4Pediatrics, CHK,DMC, Karachi, Pakistan;
5
Pathology, SIUT,DMC, Karachi, Pakistan; 6Gastroenterology,
SIUT,DMC, Karachi, Pakistan; 7SIUT,DMC, Karachi, Pakistan;
8
SIUT,DMC, Karachi, Pakistan.
Introduction: Celiac disease (CD) an immune-mediated enteropathy
caused by permanent sensitivity to gluten in genetically susceptible indi-
viduals. Data from Pakistan is meager. Children with persistent diarrhea
(PD), treated as Protein calorie malnutrition with and without infective
diarrhea, do not improve and are labeled as failure to thrive (FTT).
Objectives: To document CD in children with FTT and/or PD.
Setting: Pediatric GI and Nutrition, SIUT and CHK.
Duration: Two year.
Sample Size: 49.
Sampling Technique: Non-probability, purposive sampling. Inclusion
criteria children with PD age range one to 18 years.
Exclusion Criteria: Infective causes of diarrhea.
Study Design: Descriptive study.
Data Collection Procedure: Both sexes were included. Information in
proformas was demographic data, weaning practices, breast feeding and
family history. Investigations included lab workup tissue transglutaminase
and antigliadin antibody (tTG, AGA), HLA typing, EGD with biopsy and
anthropometric data. SPSS 10 was used for analysis of data. Diagnostic
criteria for CD was March type 2 or 3 with positive tTG and or AGA.
Results: 49 patients of FTT and/or PD were included. 49% were males.
Majority breast fed (88%). Thirty four (66%) had history of PD, 38
(74%) had significant history of weight loss. Thirty two (65%) short
stature was present. Protuberant abdomen in 53%. FTT in 30 (58%). In
40% weaning was started at 6 months of age. tTG was positive in 47%
with biopsy confirmed for CD in 30(61%) marsh type 2, 3 which co-
related with positive serological tests for CD (tTg, AGA). HLA typing
in 18 patients showed DQ2 type.
Conclusion: CD is an existing yet undiagnosed problem in our
pediatric population. Children may have PD and or FTT with CD.
Key Words: celiac disease, Pakistan, HLA type.
4 of their patients with autoimmune thyroid disease have CD. Eight
THE USEFULNESS OF SCREENING CELIAC DISEASE (CD)
ANTIBODIES IN CLINICAL PRACTICE
Michael J. Pettei, Lisa Iofel, Toba A. Weinstein, Jeremiah J. Levine.
Pediatrics, Schneider Childrens Hospital, NSLIJHS, New Hyde Park, NY.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Purpose: Due to the reported higher prevalence of CD than previously
suspected, there has been more frequent screening with CD Abs. The
recent (6/04) NIH Conference on CD noted that most of the sensitivity
and specificity data for CD serologic tests have been obtained from
studies conducted in a research setting, and suggested reasons why
these tests may perform less well in the clinical setting. The purpose
of this study was to ascertain the performance of AGA-G & A Abs,
TTG-A Ab, and AEA in a peds clinical setting.
Methods: The charts of 328 pts. (9mo-19yo) who underwent UED in
a recent 6 mo. period were reviewed. Those with any of the above CD
tests, an IgA level and sm. bowel bx. were tabulated. Those with IgA
defic. or known CD were excluded.
Results: There were 70 pts. with 8 having an init. Dx. of CD.
There were 70 AGA-IgG: 47 were (+) 7 with CD and 23 were (2)
0 with CD (Sens. 7/7-100%; Spec. 23/63-37%; PPV 7/47-15%; NPV
23/23-100%). There were 68 AGA-IgA: 24 were (+) 5 having CD
and 44 were (2) 3 with CD (Sens. 5/8-63%;Spec. 41/60-68%;PPV
5/24-21%;NPV 41/44-93%). There were 61 TTG-IgA: 14 were (+) 8
having CD and 47 were (2) none with CD (Sens. 8/8-100%;Spec.
for AEA: 1 was (+) 1 having CD and 14 were (2) 0 having CD (Sens.
1/1-100%; Spec. 14/14-100%; PPV 1/1-100%; NPV 14/14-100%).
Conclusion: Both AGA Abs were less reliable in practice than prior
assessments. The high false (+) rates (low PPV) of both AGA Abs make
them unacceptable in practice resulting in undue anxiety on the part of
pts. and families, and potentially unnecessary referrals and bxs. While the
sensitivity and specificity of the TTG-A was similar to prior assessments,
in practice the poor PPV of the test can give rise to many unnecessary
(43%) sm. bowel bxs. The AEA is the most promising for practice but the
number of values, 14, is too small to generalize. It would seem at this
point that in practice a TTG-A and AEA with an IgA level should be
obtained as the initial screening test until more clinical data is obtained.
5
DO PATIENTS WITH AUTOIMMUNE THYROID DISEASE
ALSO HAVE CELIAC DISEASE?
Farrah Lazare1, Thomas Wilson2, Andrew Lane2, Anupama Chawla1.
1
Pediatric Gastroenterology, University Hospital at Stony Brook, Stony
Brook, NY; 2Pediatric Endocrinology, University Hospital at Stony
Brook, Stony Brook, NY.
A limited number of studies suggest an increased incidience of celiac
disease (CD) in individuals with autoimmune thyroid disease. We sought
to determine the prevalence of tTG-IgA antibodies associated with CD
and the prevalence of CD in patients with autoimmune thyroid disease in
the United States. Our results will also be compared with the results
obtained in Europe.
Methods: 50 pediatric patients with autoimmune thyroid disease
participated in this study. After written informed consent was obtained,
blood was drawn to determine their tissue transglutaminase IgA (tTG-
IgA) levels and total IgA levels. If the tTG-IgA levels were positive, an
endoscopy and biopsy were performed to confirm the diagnosis of CD.
Results: Four of our patients (8%) had positive tTG-IgA. Of those, 3
underwent endoscopy. One (2%) of our patients was diagnosed with CD
based on the histopathology using the Marsh Criteria. Two patients
biopsies were negative, and one patient refused endoscopy. Our results
showed a lower correlation between autoimmune thyroid disease and
CD than do the results from the European literature which showed
a range from 1440%. However, we did find a higher correlation (2%)
of positive tTG-IgA in those patients with autoimmune thyroid disease
than in the normal population in the US which is 0.40.9%.
Discussion: European literature suggests that approximately 1440%
percent of our patients had positive tTG-IgA which was significantly
higher compared to normal populations. However, only 2% of our
autoimmune thyroid patients also have CD. tTG-IgA positivity by itself
should not be interpreted as diagnostic of CD. However, because there is
a higher chance of having CD with autoimmune thyroid disease than
 NASPGHAN ANNUAL MEETING
those who do not, we also recommend measuring tTG-IgA levels in
patients with autoimmune thyroid disease. This must be followed by
histopathological examination for CD when tTG-IgA is positive.
6 proliferation and IEC killing. Presence of NKG2C+ IEL was associated
FAILURE TO RESPOND TO HEPATITIS B VACCINE IN
CHILDREN WITH CELIAC DISEASE
Seung-Dae Park1,2, James Markowitz1, Michael Pettei1, Toba Wein-
stein1, Steven Swiss3, Cristina P. Sison4, Jeremiah Levine1. 1Pediatrics,
North Shore-Long Island Jewish Health System, New Hyde Park, NY;
2
Pediatrics, Juntendo Nerima Hospital, Tokyo, Japan; 3Pathology,
North Shore-Long Island Jewish Health System, New Hyde Park, NY;
4
Biostatistics Unit, North Shore-Long Island Jewish Research Institute,
Manhasset, NY.
Objectives: Celiac disease (CD) has strong association with specific
human leukocyte antigen (HLA) haplotypes B8, DR3, DQ2 and DQ8.
These haplotypes are often found in people who do not respond to
hepatitis B virus (HBV) vaccine. The aim of this study is to determine
whether children with CD fail to respond to HBV vaccine more
frequently than children without CD.
Study Design: This was a prospective study which compared the response
to HBV, tetanus, rubella and Haemophilius Influenza type b (Hib) vaccines
between children with CD and age/sex-matched controls.
Results: There were 26 CD subjects and 18 age/sex-matched controls in
the study. There was a significantly higher proportion of subjects in the
CD group (14/26) with failed response to HBV vaccine than control
(2/18) (53.9% vs. 11.1%; p , 0.005). Subjects with CD were 9.33 times
more likely to test negative for the HBsAb than control (95% CI:
1.8,49.1). All subjects in both groups were positive for the rubella
antibodies. There was only one subject in the CD group who was
negative for tetanus antibody and none in the control group (3.9% vs.
0%; p = 1.0). There were fewer subjects in the CD group with negative
response to Hib than the control group (33.3% vs. 44.4%; p = 0.53).
Conclusion: Children with CD respond less frequently to HBV
vaccines compared to age/sex-matched control.
7*
SELECTIVE EXPRESSION OF NKG2C IN
INTRAEPITHELIAL LYMPHOCYTES(IEL): A BASIS FOR IEL
PROLIFERATION AND EPITHELIAL CELL KILLING IN
CELIAC DISEASE (CD)
B. Meresse1, C. Ciszewski1, M. Setty2, S. Curran1, M. Tretiakova1, T.
Krausz1, L. Lanier4, E. Ebert5, P. H. Green6, S. Guandalini2, B. Jabri.
1
Pathology, University of Chicago, Chicago, IL; 2Pediatric Gastroen-
terology, University of Chicago, Chicago, IL; 3Medicine, University of
Chicago, Chicago, IL; 4Microbiology & Immunology, UCSF, San
Francisco, CA; 5Medicine, UMDNJ, New Brunswick, NJ; 6Medicine,
Columbia University, New York, NY.
Introduction: IEL expansion, malignant transformation and epithelial
cell(IEC) killing are hallmarks of CD. Recent studies suggest the NK
receptor, NKG2D, is crucial for IEC destruction, though it cannot
mediate proliferation and cytokine secretion. Linked with DAP10, an
adaptor molecule with a PI3-kinase binding motif, it cannot recruit
ZAP70, a kinase required for transcriptional events. Normally, IEL do
not express NKG2C/DAP12, a receptor complex capable of recruiting
ZAP70 and inducing cytokine secretion. HLA-E, the NKG2C ligand, is
a non classical MHC I molecule induced by IFNg on IEC.
Methods: IEL and IEC were isolated from duodenal biopsies of 31
patients with CD (20 villous atrophy, 11 on GFD .1 year) and 10
controls biopsied for functional issues or had gastric bypass. Expression
of TCRab, NKG2C+ and DAP12 by IEL and HLA-E by IEC was
examined in normal, active and GFD patients. NKG2C mediation of IEL
proliferation, IFNg secretion and epithelial cell killing was determined.
TCR repertoire of NKG2C+ T cells was studied by polymerase chain
reaction and sequencing.
495
Results: Percentages of NKG2C+ T cells was significantly higher in
active CD (mean = 19.8 6 5.8, p , 0.02) and GFD (mean = 10.7 6 23.2,
p , 0.05) compared to normal (mean = 3.8 6 2.3). NKG2C+ IEL
expressed DAP12 and led to ZAP70 activation, IFNg secretion, IEL
with increased HLA-E expression by IEC. TCR analysis of NKG2C+ IEL
revealed a highly oligoclonal TCR repertoire.
Conclusions: NKG2C/DAP12 induction in CD proposes a basis for
IEL proliferation and IEC killing. Further studies are warranted to
determine if NKG2C expression in more severe CD may set the stage
for malignant transformation of IEL.
8
CELIAC DISEASE AND PREVALENCE OF FRACTURES
Rabin Persad1,2, Iqbal H. Jaffer1, Robert M. Issenman1,2. 1Pediatrics,
McMaster University, Hamilton, ON, Canada; 2Hamilton Health
Sciences, Hamilton, ON, Canada.
Introduction: The fracture risk in adults with CD has been estimated,
with some studies showing a three-fold increase as compared to control
populations. Osteoporosis is thought to play a significant role, and
occurs with a prevalence rate of about 40% in adult patients with CD.
There are several reports detailing bone mineral density (BMD) changes
in children with CD, however to our knowledge there is limited data
describing the risk of fractures in pediatric patients with CD.
Aims: The primary objective of this study was to assess the prevalence
of fractures in children with CD as compared to their healthy siblings.
Method: A self- administered questionnaire that was previously used
for patients with inflammatory bowel disease (IBD) was modified for
CD. Celiac disease was defined as presence of total or partial small
intestinal villous atrophy and positive serology (TTG &/or EMA).
Patients were identified by reviewing the pathology database for total or
partial small intestinal villous atrophy, compatible with CD. Those
patients with positive serology (TTG &/or EMA) and whom the
principal authors followed were then mailed a questionnaire concerning
broken bones. A reminder was mailed after 6 weeks to non-
responders. The control group consisted of healthy siblings of patients
with CD. The research ethics board approved this study.
Results: A total of 100 patients with celiac disease were identified. 58
patients with CD and 51 controls returned their questionnaire;
a response rate of 58%. 11 patients with CD (19%) and 16 controls
(31%) had recollection of fractures (p , 0.2).
Conclusions: There was no overall increased fracture risk in patients
with celiac disease. However the response rate was poor, and the total
numbers small making it difficult to assess for significant differences in
fracture rates. Prospective studies are needed prior to targeting this
group of patients for routine osteoporosis screening and treatment.
9
NEWER DOUDENAL BIOPSY NORMS FOR DIAGNOSIS OF
CELIAC DISEASE TO DECREASE FALSE POSITIVE RATE IN
APPARENTLY NORMAL CHILDREN DATA FROM A
TERTIARY CARE CENTRE
Ajay K. Jain1, Prem Arora2, Santosh K. Mittal2. 1Pediatrics, Medical
College of Georgia, Augusta, GA; 2Pediatrics, Maulana Azad Medical
College, New Delhi, India.
Introduction: Celiac disease continues to be an important cause of
diarrhea, malnutrition and failure to thrive around the world. Various
criteria used for diagnosis of celiac disease are not specific and may be
found in conditions like giardiasis, tropical sprue, infectious gastroen-
teritis and food hypersensitivity. Many of these conditions are quite
prevalent in children and biopsy normograms for apparently normal
children are not yet well defined.
Methods: 142 children were enrolled into the study. Duodenal biopsy
specimens of 51 children (Group A) not having any clinical, serological
or endoscopic evidence of celiac disease were compared with 50
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
496 NASPGHAN ANNUAL MEETING

children (Group B) with proven celiac disease as per the following Constipation and Colonic Motility
criteria: Number of intraepithelial lymphocytes (IEL) per 100 epithelial
cells (IEL/100EC), Villous atrophy, Crypt Hyperplasia, Villous:Crypt 11
(V/C ratio), Inflammatory infiltration of the lamina propria and any
other findings. INTERNAL ANAL SPHINCTER ACHALASIA: RELATIONSHIP
Results: The mean value of IEL/100EC in Group A was 19.42 (range WITH COLONIC DYSMOTILITY AND MANOMETRIC
762, SD 10.14) and in Group B was 56.4 (range 4187, SD 12.23). RESPONSE TO BOTULINUM TOXIN INJECTION
Villous atrophic changes (mild to total) were seen in 7 (13.72%) and Leonel Rodriguez, Alex Flores. Floating Hospital for Children,
29 (56.8%) children in Group A and Group B respectively. Crypt Boston, MA.
hyperplasia was present in 7.8% in Group A and 14% in Group B. No
patients in Group A had a V/C ratio less than 1 as compared to 12 (24%) Background: Internal anal sphincter achalasia (IASA) is defined as the
children in Group B. More than 93% children in Group A had absence of full relaxation of the internal anal sphincter (IAS) after rectal
inflammatory infiltration of lamina propria (including neutrophils). balloon dilatation, usually associated with elevated IAS resting
Giardia was present in 6.9% of all children. pressure, also known as ultra short segment Hirschsprungs disease.
Conclusion: 40 IEL/100EC can be taken as the upper limit of normal. Objective: Describe our experience with the use of botulinum toxin in
V/C ratio less than 1, villous atrophy (moderate to severe) and crypt IASA and the manometric changes in resting pressure and relaxation of
hyperplasia support the diagnosis of celiac disease. Inflammatory the IAS in IASA before and after botox injection.
infiltration of lamina propria was quite prevalent in Group A children Methods: Patients diagnosed with IASA by anorectal manometry
which may be due to high incidence of clinical and subclinical gastro- received an intrasphincteric injection of 60100 U of botulinum toxin
intestinal infections and was not specific or diagnostic for celiac (botox) divided in aliquots in 4 quadrants. Anorectal manometry was
disease. repeated immediately after injection and resting pressure and percent-
age of IAS relaxation after rectal balloon dilatation were estimated.
Medical records were reviewed to obtain clinical information.
10 Results: 14 patients (6 female) were diagnosed as having IASA.
2 patients were previously diagnosed as Hirschsprungs and underwent
A REAPPRAISAL OF CELIAC SCREENING a pull through. Pre-botox mean resting pressure was 64 mmHg and after
Gary Fanjiang, Aubrey Katz. Pediatric Gastroenterology & Nutrition, rectal balloon distention was 33 mmHg. Pre-botox mean percentage of
Tufts-New England Medical Center, Boston, MA. relaxation was 50%. Post-botox mean resting pressure was 32 mmHg
and after rectal balloon dilatation was 0. Post-botox mean percentage of
Purpose: Tissue transglutaminase IgA (TTG) is currently considered relaxation was 100%. 7 patients reported important clinical improve-
the best available screening test for celiac disease. We evaluate the ment of the constipation at a mean follow up of 5.5 weeks, 3 patients
positive predictive value (PPV) of TTG and endomysial IgA (EMA) for reported at least some improvement, 2 patients had no improvement and
the diagnosis of celiac disease. 2 patients were lost of follow up. At long term follow up (26 y)
Methods: The charts of 122 patients who screened positive for celiac 6 patients were diagnosed as having colonic neuropathy, 5 by colonic
disease with TTG and/or EMA were reviewed. Only patients with manometry.
duodenal biopsies were included. Asymptomatic patients were screened Conclusions: Our study demonstrates the efficacy of intrasphincteric
because of family history or comorbid diagnoses such as diabetes or botox injection to decrease the mean resting pressure and induction of
hypothyroidism. Biopsies were characterized using Marsh criteria. PPV full relaxation of the IAS. Prospective studies are needed to evaluate
and 95% confidence intervals (CI) were calculated. the long-term clinical efficacy of botox injection and the relationship
Results: Ninety-five patients had positive TTG (TTG.20), with 59 of IASA with colonic dysmotility.
confirmed biopsies (PPV = 0.62). Eighteen of 26 asymptomatic TTG
positive patients were true positives (PPV = 0.69). Forty-one of 69
symptomatic TTG positive patients were true positives (PPV = 0.59). 12
Forty-nine TTG positive patients had levels .100, with 44 confirmed
biopsies (PPV = 0.90). Thirty-eight TTG positive patients had levels USE OF THE RECTO-SIGMOID INDEX (RSI)
.150, with 37 confirmed biopsies (PPV = 0.97). Forty-one patients had TO DIAGNOSE HIRSCHSPRUNGS
a positive EMA, with 36 confirmed biopsies (PPV = 0.88). Eleven of 12 DISEASE (HD)
patients who screened positive with both TTG and EMA had confirmed Reinaldo Garcia, C. Arcement, L. Hormaza, M. L. Haymon, C. Velazco,
biopsies (PPV = 0.92). R. Brown, J. N. Udall, P. Tyson, H. Correa, J. Congeni, K. Ward, E.
Conclusion: EMA seems to have a greater PPV compared to TTG. Schmidt-Sommerfeld. LSUHSC/Childrens Hospital, New Orleans, LA.
Increasing the cutoff for TTG to 100 or 150 increases its PPV to a level
comparable to EMA. There is little difference in the PPV of TTG for RSI in an unprepared barium enema is an objective measurement to aid
screening symptomatic patients versus those screened only because of in the diagnosis of neonatal HD. It has also been used in other age
family history or comorbid diagnoses. This data suggests using both groups, but published data beyond the newborn period are sparse. In
TTG and EMA for screening celiac disease and that screening does not order to determine its reliability and accuracy compared with the
obviate the need for duodenal biopsies. transitional zone (TZ) in different age groups, we reviewed barium
enemas and pathology reports of patients with suspected HD during
a 5 year period.
TABLE 1. Celiac screening positive predictive values 107 patients who had a barium enema (BE) and a diagnostic rectal
biopsy were subdivided into three different age groups: neonates ,1
N True (+) PPV month of age (n = 15), infants 1 to 12 months (n = 29) and children .1
TTG (+) (TTG . 20) 95 59 0.62 (CI = 0.520.72) year (n = 63). Three pediatric radiologists independently and blindly
Asymptomatic TTG (+) 26 18 0.69 (CI = 0.480.86) reviewed the contrast enemas. The RSI (diameter of rectum: sigmoid
Symptomatic TTG (+) 69 41 0.59 (CI = 0.470.71) colon ,1 or .1) and the presence or absence of a transitional zone were
TTG . 100 49 44 0.90 (CI = 0.780.97) compared with the biopsy findings.
TTG . 150 38 37 0.97 (CI = 0.870.99) A total of 16 patients with and 91 without HD were evaluated. The RSI
EMA (+) 41 36 0.88 (CI = 0.740.96) agreed with the biopsy result in 85 cases (79.4% CI 0.70-0.88). The
TTG (+) and EMA (+) 12 11 0.92 (CI = 0.640.98) sensitivity of the RSI in infants . month of age was 100% and the
specificity 79% with a negative predictive value (NPV) of 100%.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
Similar results were found in patients older than 1 year of age. In the 16
patients with HD the RSI was diagnostic in 12, but only 9 of the 16 had
an evident TZ. 13 patients had recto-sigmoid HD, their RSI was
suggestive of HD in 12 cases (92% CI 0.601.00). In five of the patients
without a TZ in the BE and aganglionosis in the biopsy, the RSI was ,1.
The three radiologists agreed on the RSI in 85 of the 107 contrast
enemas studies (79.4% CI 0.700.89).
No difference in sensitivity, specificity and NPV was found between the
RSI and the TZ. Both radiological signs had a higher NPV in infants and
children compared with neonates. The positive predictive value was low
in all age groups.
The RSI does not provide any additional statistical benefit compared
with the TZ to detect or exclude HD. In the neonatal period, as opposed
to later in life, a normal BE appears to be unreliable in excluding HD.
13
CONSTIPATION PRACTICES OF PEDIATRICIANS
AND FAMILY PRACTITIONERS
Douglas G. Field, Laurie Yuncker, Keith Williams. Pediatric GI and
Nutrition, Penn State Childrens Hospital, Hershey, PA.
Constipation is a problem encountered frequently by physicians. This
problem accounts for approximately 3% of visits to pediatricians (Peds)
and 10% to 25% of visits to pediatric gastroenterologists (Peds GI).
NASPGHAN developed a clinical practice guideline to help medical
care providers in the evaluation and treatment of infants and children
with constipation. This study evaluated referring physicians manage-
ment of infants and children with constipation and encopresis to see if
these treatment styles are consistent with NASPGHAN guidelines.
Methods: Questionnaires regarding the treatment of constipation and
encopresis in infants and children were mailed to 1130 referring
physicians. There was a 28.5% response rate.
Results: In comparison to family physicians (FPs), Peds reported seeing
more infants and children with constipation/encopresis, had a higher level
of comfort in treating these patients, treated for longer periods of time and
referred a smaller percentage of their children to Peds GI. The most
common reason for referral to Peds GI is a lack of patient response to
prescribed therapy. Suppositories and prune juice are used most often by
all physicians to cleanout infants with constipation. Most FPs and Peds
use some form of laxative, stool softener or prune juice as maintenance
therapy in infants. About 35% of the physicians use enemas to cleanout
children over one year of age. Peds use more polyethylene glycol
electrolyte solution as both cleanout and maintenance therapy in this age
group. FPs use more senna as a cleanout and prescribe a high fiber diet as
maintenance therapy more often than Peds. Finally, FPs use psychiatric
counseling for the treatment of encopresis more often than Peds.
Conclusion: Peds and FPs differ in their method of treatment of infants
and children with constipation and encopresis. Although many
physicians follow the NASPGHAN recommendations, there is a lack
of uniformity in the treatment of these infants and children. We propose
that better education of primary care physicians may lead to better
treatment and outcome in infants and children with constipation.
14
BODY MASS INDEX DISTRIBUTION IN A
TERTIARY-CARE CONSTIPATION CLINIC
Joseph A. Skelton1,2, Stephanie Mullin1, Maureen Otto1, Jingnan
Mao1, Peter Havens1,2. 1Pediatrics, Medical College of Wisconsin,
Milwaukee, WI; 2Childrens Research Institute, Milwaukee, WI.
Introduction: Obese adults have an increased frequency of gastroin-
testinal complaints. A single study has shown an increased prevalence
of constipation in overweight children. Risk factors for overweight
coincide with risk factors for constipation (poor diet, lack of physical
activity). The aim of this study was to determine if children treated for
constipation at a tertiary-care constipation clinic have a higher body
mass index as compared to the general population.
497
Methods: Retrospective study of children followed in the Childrens
Hospital of Wisconsin Constipation Clinic, from January, 2002 to
December, 2004, querying computer records for age at first visit, height,
weight, race, ethnicity, and insurance category. Only children with
functional constipation were included in this analysis. BMI, BMI
percentile for age, and BMI z-score were calculated using National
Center for Health Statistics tools. BMI z-score distribution of our clinic
population was compared to that of the National Health and Nutrition
Examination Study (NHANES) from 20002001.
Results: 1345 children were treated during this time period. 90% were
age ,12 years, 54% male, 44% minority, and 32% Medicaid. Mean
BMI z-score was 0.53 (SD 6 1.2) The prevalence of children of at risk
for overweight and overweight was 14.1% and 18.5%, respectively, and
were associated with non-white race (p = .001), male gender (p = .03),
and Medicaid insurance (p = .0005). The BMI z-score was higher in
patients treated in the constipation clinic than in the NHANES data set
(See Table).
Conclusion: Children age 2 through 12 years treated in this tertiary-
care constipation clinic had higher BMI z-scores than age matched
controls from the NHANES data set. When constipation is seen, it is
important to consider the possibility of being overweight.
BMI BMI Wilcoxon
Age N z-score N z-score test,
(years) CHW CHW SD NHANES NHANES SD p-value
26 661 0.35 1.2 808 0.17 1.5 0.005
712 552 0.67 1.2 1170 0.5 1.1 0.0007
1318 132 0.74 1.1 1802 0.56 1.1 0.03
Overall 1345 0.53 1.2 3780 0.46 1.2 0.07
15
THE VALUE OF REPEAT ANORECTAL
MANOMETRY IN INFANTS
Rita Steffen, Robert Wyllie, Marsha Kay, Barbara Kaplan, Hupertz
Vera, Lori Mahajan. Pediatric Gastroenterology, Cleveland Clinic
Foundation, Cleveland, OH.
Neonates and infants with constipation or a history of delay in passage
of meconium are often seen for anorectal manometry to screen for short
segment Hirschsprung disease. Anorectal manometry is also difficult to
perform in this age group, which also includes premature infants, due to
motion artifact and the small size of the anal sphincter complex within
the anal canal. When the morphology of the rectoanal inhibitory reflex
is equivocal, we recommend repeating the anorectal manometry within
the next one or two weeks. In some cases, anorectal manometry may be
done weekly or biweekly until the mature and fully reproducible
rectoanal inhibitory reflex is established.
The presence of a normal RAIR rules out Hirschsprung disease and
makes suction rectal biopsy unnecessary to perform. Although bleeding
which is usually minimal is the most frequent complication of rectal
biopsy, obtaining inadequate submucosal tissue to make or exclude
a diagnosis of Hirschsprung disease is also common, requiring a second
suction rectal biopsy or a referral for a full thickness rectal biopsy by
a pediatric surgeon. Other complications, which are serious, have been
reported, including hemorrhage requiring transfusion. These may be
avoided entirely in the clinical situation of an infant with the equivocal
RAIR is restudied and is later found to have a normal RAIR.
We looked at the previous 100 anorectal manometry reports of infants
less than one year of age done to rule out Hirschsprung disease.
Repeating the manometry was recommended in 18 infants, as the RAIR
was deemed equivocal. In all but one infant who went on to have
a diagnosis of Hirschsprung disease by rectal biopsy, the second
manometric screening showed the development of a normal RAIR in
16, and a third manometry showed a normal RAIR in one infant.
Performing these motility tests in infants may be time consuming and
requires patience, but repeating the manometry has been shown to be of
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
498 NASPGHAN ANNUAL MEETING
value to us in our clinical practice. Serial manometry will obviate the
need to perform suction rectal biopsies in many infants.
16
CAN WE REDUCE THE DURATION OF COLONIC
MANOMETRY STUDY IN CHILDREN?
Manu R. Sood, Steven Werlin, Colin D. Rudolph. Pediatrics, Medical
College of Wisconsin, Milwaukee, WI.
Introduction: Colonic manometry (CM) is a useful investigation in
evaluating children with chronic intractable constipation. The two
recognized features of normal colonic manometry include: increase in
colonic contractions after a meal (gastrocolonic reflex) and high
amplitude propagating contraction (HAPC).
Methods: We performed retrospective chart review of 45 colonic
manometry studies performed since 2001. Fasting recording for at least
60 min, postprandial recording for another 60 min and bisacodyl
stimulation was performed in all pateints. The study was approved by
the hospital IRB.
Results: 33/45 patients presented with intractable constipation, 8 with
obstructive symptoms without a mechanical cause and 4 with painful
defecation. We recorded spontaneous HAPCs in 13% of the patients,
77% had HAPCs following Bisacodyl stimulation. Ten studies were
abnormal, in 7 patients no abnormality was present during the fasting
phase and in 3 simultaneous low amplitude contraction were recorded.
Following Bisacodyl, HAPCs failed to propagate beyond transverse
colon in 4, simultaneous contractions were recorded in 5 and 1 patient
had no contractions. In 7 of these 10 patients no increase in colonic
contractions was observed following a meal and 8 patients with
a normal study we were unable to reliably assess for an increase in
colonic contractions following a meal.
Conclusion: The most reliable feature of a normal colonic manometry
is the HAPC. Patients with normal HAPCs following bisacodyl
stimulation are unlikely to have colonic motility abnormalities. Because
of the time constraints the a motility index is usually not calculated for
clinical studies and manual evaluation to assess postprandial increase in
colonic motility is observer dependent and unreliable. Further it is also
difficult to make a child eat a standardize meal during the study. We
propose that colonic motility studies should include a fasting phase for
1 hour followed by Bisacodyl stimulation.
17
CLINICAL GUIDELINES FOR CONSTIPATION IN
CHILDREN ARE PRIMARY CARE PHYSICIANS
TAKING NOTE?
Yoram Elitsur, Autunm Morales, Mary DiFillippo, Chris McKeand. Pedi-
atrics, Gastroenterology Division, Marshall University, Huntington, WV.
Introduction: Constipation is one of the most common referred diseases
to the pediatric gastroenterology clinic. A panel of experts has recently
published guidelines for the treatment of constipation in children.
Aim: To investigate the adherence to constipation clinical guidelines by
the primary care physicians (PCP) practicing in West Virginia.
Methods: A short questionnaire was mailed to all available WV PCPs
who treat pediatric patients. The survey consisted of questions in the
following areas: demographics, physical examination practices, therapy,
and referral patterns.
Results: A total of 718 surveys were mailed, 221 (31%) returned, but
only 210 were completed appropriately. Physicians distribution in-
cluded: 112 (53%) family practitioners (FP), 78 (37%) pediatricians
(PD), 5 (2%) physician assistants, and 15 (7%) had other specialties.
Among all clinic visits, 70% of PCP reported the diagnosis of consti-
pation in less than 10% of their patients. Rectal examination (REx) was
performed by 51% of PCP in less than 20% of their pts. Over 60% of
PCP spent less than 30 mins at the initial or f/u visits. Most PCP are
treating constipation with a combination therapy including: laxatives,
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
high fiber, and behavioral modifications. Of the various laxatives, 64%
used osmotic drugs, 45% used stimulants, 51% used lubricants, and
51% used lavage laxatives. Most of PCP (85%) refer pts based on
treatment failure and 19% for parental pressure. Most PCP (58%)
expected to co-manage the patient along with the specialist. The
published clinical guideline for constipation was known to only 22% of
PCP of whom only 8% had actually read it. When compared with FP
physicians, PD reported a higher rate of constipation in their clinics (p =
0.0138), used more lavage solution for therapy (p = 0.000), and were
more familiar with the clinical guidelines (p = 0.007).
Conclusion: Most PCP do not follow the clinical guidelines for
constipation in children which may decrease their treatment efficacy.
An educational campaign of constipation in children is clearly warranted.
Gastroesophageal Reflux
18
MII + PH PROBE AND CORRELATION WITH
TRACHEAL PEPSIN ASPIRATES IN 6 PATIENTS WITH
MODERATE TO SEVERE PERSISTENT ASTHMA
Peter C. Wilmot, Vani Gopalareddy, Zhaoping He, Laura Bolling,
Mansi Shah, Devendra Mehta. Gastroenterology and Nutrition, Alfred I
duPont Hospital for Children, Wilmington, DE.
Introduction: Coexistence of asthma, GER and mircroaspiration have
been proposed previously. Non-acid reflux measures and availability of
airway pepsin as markers of microaspiration have become recently
available. We present the first series of cases from a retrospective chart
review.
Methods: Six patients (range 5 to 15 years) with moderate to severe
asthma who had bronchoscopy as well as combined MII + pH probe
studies (all greater then 18 hours) as part of their evaluations were
reviewed. Pulmonary aspirates were assayed for pepsin. None had
clinical suspicion of oral aspiration or radiological evidence of
aspiration. One had history of TEF repair and one was subsequently
diagnosed with a mild CF by genotype. All patients had impedance pH
studies performed off acid suppression medications. NASPGHAN
criteria for acid GER, number of MII episodes (up to the cervical
esophagus) and symptom index for cough was recorded. Pepsin was
assayed using floreroscein isothiocyanate casein. Normal airway
aspirates are undetectable for pepsin.
Results: All cases had positive airway pepsin (range 12.7 to 78 ng/ml).
One case met criteria for acid GER. The 6 patients had mean of 42.5
(range 20 to 60) acid and non-acid MII episodes. Four of the six patients
had minimal acid reflux events. There was a high degree correlation of
MII with subsequent coughing events. Three of the five patients had
symptoms index (SI) scores of greater then 40% for cough. Three of the
four patients with high SI were mostly non-acid reflux events (range
57% to 100% nonacid MII events).
Conclusion:
1. Positive tracheal pepsin aspirates seen in these patients support
microaspiration as a cause of chronic lung disease.
2. Persistent asthma and MII events are associated temporally with
cough. This supports GER and microapiration in association of
moderate to severe asthma.
3. Non-acid events in this sample were more commonly associated with
symptoms, suggesting previous studies assessing acid GER only
may be invalid.
19
EVALUATION OF INFANTILE ACID AND
NONACID GASTROESOPHAGEAL REFLUX
UTILIZING COMBINED PH MONITORING AND
IMPEDANCE MEASUREMENT
Adria A. Condino1,2, Judith Sondheimer1,2, Zhaoxing Pan1,2, Jane
Gralla1,2, Darryl Perry1,2, Judith A. OConnor1,2. 1The Childrens
 NASPGHAN ANNUAL MEETING
Hospital, Denver, CO; 2University of Colorado Health Sciences Center,
Denver, CO.
Objective: Characterize the proportion of acid and nonacid esophageal
reflux events in young infants with suspected gastroesophageal reflux
(GER) utilizing combined pH - multichannel intraluminal impedance
(MII) monitoring. Determine the symptom index correlation with nonacid
reflux and acid reflux events.
Study Design: Prospective study of children, ages two weeks to one
year, referred to The Childrens Hospital of Denver Gastroenterology
clinic for evaluation of GER. Exclusion criteria were congenital
anomalies or syndromes, cerebral palsy, mental retardation, and
pulmonary or cardiac disease. The children were admitted to The
Childrens Hospital General Clinical Research Center for a 20-hour pH-
MII study. Acid suppression was either never used or discontinued
2 weeks prior to testing.
Results: 34 infants were enrolled from 2/2004 to 2/2005. Ages ranged
from 2 months to 11 months, mean = 6.1 (20 females/14 males). 1890
reflux events were detected by MII, and 588 reflux events detected by
pH probe alone. The percent of reflux that was acid was 47% (888
events) vs. 53% (1002 events) nonacid reflux events. The proportion
of nonacid reflux decreased with age (p , 0.0001 by Pearson Chi-
square test) and with increasing time elapsed from last meal. There
were 958 total symptoms recorded. The most frequently reported
symptom was fussiness/pain which correlated with nonacid reflux
events 24.6% and acid reflux 25.2%. The proximal height of a reflux
was predictive for symptoms of fussiness/pain, arching, and burping.
Conclusion: MII detects more reflux events than pH monitoring alone.
The proportion of nonacid reflux to acid reflux events in infants is more
similar to adults than previously reported. Although combined pH-MII
esophageal monitoring identifies more reflux events, it does not improve
clinical correlation with all symptoms.
20
EVALUATION OF GASTROESOPHAGEAL REFLUX IN
PEDIATRIC ASTHMA PATIENTS BY INTRAESOPHAGEAL
MULTICHANNEL IMPEDANCE-PH MONITORING
Adria A. Condino1,2, Judith Sondheimer1,2, Zhaoxing Pan1,2, Jane
Gralla1,2, Darryl Perry1,2, Judith A. OConnor1,2. 1Pediatrics, The
Childrens Hospital, Denver, CO; 2University of Colorado Health
Sciences Center, Denver, CO.
Objective: To determine the proportion of acid and nonacid reflux
events in pediatric patients with asthma suspected of having gastro-
esophageal reflux (GER) utilizing combined multichannel intraluminal
impedance and pH (MII-pH). The secondary objective was to determine
the correlation of respiratory symptoms with nonacid and acid reflux
events (respiratory symptom index).
Methods: Prospective study of children with asthma, age five months to
six years, referred by the pulmonologists to the GI department of The
Childrens Hospital of Denver for evaluation of GER. Exclusion criteria
were congenital anomalies, cerebral palsy, mental retardation, or
cardiac disease. Children were admitted to The Childrens Hospital
Clinical Research Center for 20-hour MII-pH study. Acid suppression
was discontinued 2 weeks prior to testing.
Results: 24 children (7 female/17 male) were enrolled from 3/04 to
2/05. Age range was 567 months (mean, 33 months). A total of 1184
reflux events was detected by combined MII-pH, while pH probe
detected 419 additional events without impedance changes diagnostic
of reflux. The percent of nonacid MII detected reflux events was 51%
(605 events) vs. 49% (579 events) acid reflux events. The proportion of
nonacid reflux events decreased with the time elapsed from the last
meal (p , 0.0001 by Pearson Chi-square test). There was no associa-
tion between age and the proportion of nonacid refluxes (p = 0.56).
There were 555 total symptoms recorded. The most frequent symptom
was cough (331 reports) 9.4% of cough episodes were associated
with nonacid reflux events and 17.2% were associated with acid reflux
events.
499
Conclusion: The proportion of nonacid and acid reflux events in children
with asthma is similar to adults with GER. MII-pH monitoring detects
more reflux events than pH probe alone. Although combined MII-pH
esophageal monitoring identifies more reflux events, it does not increase
the detection of a clinical correlation of all symptoms with reflux.
21
THE MULTICHANNEL INTRALUMINAL IMPEDANCE IN
INFANTS WITH GASTRO-ESOPHAGEAL REFLUX
Emilia J. Cohen Sabban, Marina Orsi, Barbara Branchesi, Daniel
DAgostino. Gastroenterologia Infantil, Hospital Italiano, Buenos
Aires, Argentina.
The 24 hour pH-study was considered the gold standard to study gastro-
esophageal reflux in children but normal pH scores were obtained despite
non acid reflux. There is a new method, the Multichannel Intraluminal
Impedance (MII) which is able to evaluate the movement of liquid or gas
throughout the esophagus independent of the quality of the refluxate.
Aim: To evaluate the (MII) in relation to the 24 hour esophageal
monitoring to diagnose gastroesophageal reflux (GER) in a group of
infants under eighteen months of age.
Material and Methods: From January to May 2005, 32 infants with
a median age of 2 months were studied because of a clinical
presentation and a barium X-ray fluoroscopy which suggested gastro-
esophageal reflux. The evaluation was performed with a Sleuth
Monitoring Recorder using a catheter with 6 impedance sensors and
one pH probe located at the distal end. The results of the pH monitoring
were evaluated according to the Boix-Ochoa score and for the MII, the
symptom correlation .75% was the cut -off value was considered for
the acid or non-acid reflux episodes.
Results: MII + pH study + : 7 patients
MII + pH study 2 : 7 patients
MII 2 pH study 2 : 16 patients
MII 2 pH study + : 1 patient.
MII Sensitivity: 87.5% Especificity: 68.2% PPV: 50% NPV: 93.7%
p 0.01 The infants with pathologic MII had a median value of 59.6%.
Most episodes (66.6%) were of pure liquid and 40.5 % of them reached
the maximum height, they went up to the proximal esophagus.
Conclusions: The Multi-Channel Intraluminal Impedance resulted a very
good method to evaluate gastresophageal reflux because is capable of
diagnosing acid episodes but also the non-acid ones that are not detected
by the conventional 24 hour pH monitoring. This is a preliminary study in
a small group of babies. Further work will necessary to better understand
the multiple implications of this novel tool.
22
THE SENSITIVITY OF MULTI-CHANNEL INTRALUMINAL
IMPEDANCE (MII) COMPARED TO PH PROBE IN THE
DETECTION OF GASTROESOPHAGEAL REFLUX
Rachel Rosen, Candace Lord, Samuel Nurko. Motility Unit, Childrens
Hospital Boston, Boston, MA.
Multi-channel intraluminal impedance (MII) has become an important
tool in the evaluation of gastroesophageal reflux (GER) but the sensitivity
of the device has not been compared to the gold standard pH probe.
Aim: To determine the sensitivity of MII as compared to pH probe in
the detection of GER episodes in children.
Methods: We conducted a prospective study of 25 untreated children
(NT) undergoing pH-MII. We used the following definition of
sensitivity for the pH probe: (# acid + pH-only events)/(# acid + pH-
only + non-acid events). We used the following definition for the
sensitivity of MII: (# acid + non-acid events)/(# acid + pH-only + non-
acid events). To see if the sensitivity of pH probe and MII differed if the
study was performed while on acid suppression therapy (AS), additional
tracings of 25 children on acid suppression therapy were retrospectively
reviewed.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
500 NASPGHAN ANNUAL MEETING
Results: The mean ages in the NT and AS groups were 6.2 6 5.3 yrs
and 7.2 6 5.6 yrs, respectively. 60% of NT group had normal pH probes
compared to 84% in the AS group. 1845 episodes were detected in the
NT group of which 42.1%, 31.4% and 26.5% were acid, non-acid and
pH-only; 1702 episodes were detected in the AS group of which 25.1%,
50.3% and 24.6% were acid, non-acid and pH-only (p , 0.0001). The
sensitivities of the pH probe and MII in the NT group were 80.6 6
18.2% and 76.1 6 13.5% respectively (p = 0.41). The sensitivities of the
pH probe and MII in the AS group were 47.2 6 36.0% and 80.3 6
21.1% respectively (p = 0.005).
Conclusion: The sensitivity of the pH probe is identical to that of MII
in the patients not taking acid suppression therapy. However, if the
studies are performed while on therapy, the sensitivity of MII exceeds
that of the pH probe and may be a better tool to evaluate GER.
23*
THE ACCURACY AND TOLERABILITY OF THE BRAVO
CATHETER-FREE PH CAPSULE IN PATIENTS BETWEEN
THE AGES OF 4 AND 18 YEARS
Joseph M. Croffie. Pediatrics, Indiana University, Indianapolis, IN.
Objective: The aim of this study was to determine if the capsule is
comparable to the catheter in pH recording and to determine how it
compares to the catheter in terms of tolerability in children.
Methods: A total of 66 children undergoing esophageal pH testing
were recruited for the study. 10 each from ages 4 to 6, 7 to 10, and
greater than 10 years were tested simultaneously with the catheter and
the capsule. 6 from similar age groups were tested with the catheter
alone or the capsule alone. The capsule was placed 87% of the distance
measured endoscopically from the incisors to the G-E junction. The
catheter was positioned using Strobels equation and adjusted as needed
based on position on chest xray. The catheter recorded for 24 hours and
was removed. The capsule recorded for 48 hours. A chest xray was
obtained on day 14 to verify capsule detachment. Subjects graded
tolerance (activity level, appetite and satisfaction with the test) on
a scale of 1 to 5, 5 being well tolerated. A 24 hr reflux index was
generated from data collected by the catheter and a 24 hr and 48 hr
reflux index was generated from data collected by the capsule. Student
t Test and Mann-Whitney test were used to compare reflux index and
tolerability between the catheter and capsule.
Results: Patients ages ranged from 4 to 16 years. All completed the
study without complications. 1 patient with the capsule complained of
severe chest pain for several hours after placement which resolved with
acetaminophen+ codeine. There was no statistically significant
difference between the mean reflux indices obtained simultaneously
with the catheter and capsule (p = 0.0665 day 1 of capsule vrs catheter,
p = 0.4885 24 hr vrs 48 hrs of capsule). The capsule was better tolerated
than the catheter: Appetite (3.53 vrs 2.72 p = 0.013), Activity (3.66 vrs
2.33 p = 0.001), overall satisfaction (4.31 vrs 3.11 p = 0.0003).
Conclusion: The Bravo pH capsule was as accurate as the conventional
pH catheter in recording esophageal acid exposure. It was better
tolerated than the conventional catheter by all age groups studied.
24
THE CLEARANCE OF GASTROESOPHAGEAL
REFLUX IS INFLUENCED BY THE PRESENCE OF
ACID REFLUX AND AGE
H Mousa1, F Woodley1, J Hayes2, Melissa Metheney1. 1Division of
Gastroenterology, Childrens Hospital, Columbus, OH; 2Center for
Biostatistics, Ohio State University, Columbus, OH.
Prolonged bolus contact time (BCT) and reduced clearance of gastro-
esophageal reflux (GER) are indicators of esophageal dysfunction.
Aim: To investigate whether acid GER has an impact on the
BCT/clearance of refluxate.
Methods: 35 children (20M/15F, 2.5 wks18.5 yr) underwent a 24 hr
dual multichannel intraluminal impedance/pH studies. Children were
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
divided into; group A (,2 yr, n = 20)and group B (.2 yr, n = 15). Each
child was suspected of having GER-related symptoms. A pH study was
considered abnormal or pH(+) if the pH was ,4 for .6% in subjects
.1 yr and .12% in subjects ,1 yr old. BCT was defined as the duration
(sec)of reflux in the most distal impedance channel. Clearance rates
were expressed as mean BCT with confidence interval. Data were
analyzed using analysis of variance.
Results: pH studies were abnormal in 19 subjects (12 from group A,
7 from group B). Clearance of non-acid GER was more efficient in
subjects with pH (+) in comparison to those with pH (2) {16.6[14.5,
19.1] vs 22.8[19.9, 26.1], p = .02} with no significant difference in the
clearance of acid GER. The more efficient clearance of non-acid AGER
in subjects with pH (+) was found in older children (p = 0.029), not in
the younger group (p = .382). Among subjects with pH (+), older
children had more effective clearance of GER than younger children
{15.6[13.2, 18.5] vs 21.7[18.3, 25.7] p = .00059} and acid GER
{16.1[12.8, 20.2] vs 24.5[19.5, 30.8] p = .00093}. In children with no
evidence of abnormal acid reflux, there was no difference in the
clearance of GER, acid GER and non acid GER between older and
younger subjects.
Conclusions: Older children with acid reflux tend to have more
efficient volume clearance of GER and acid GER than younger ones.
Regardless of age, volume clearance of non acid GER is more efficient
in children with significant acidification of distal esophagus compared
to control. In children younger than 2 years old, the presence or absence
of acid reflux has no impact on the clearance of acid GER or non acid
GER.
25
PREVALENCE OF GASTROESOPHAGEAL REFLUX
DISEASE (GERD) IN OVERWEIGHT AND
OBESE CHILDREN
Misaa Ayad2, Iqbal H. Jaffer1, Rabin Persad1,2, Robert M. Issenman1,2.
1
Pediatrics, McMaster University, Hamilton, ON, Canada; 2Hamilton
Health Sciences, Hamilton, ON, Canada.
Introduction: More than 30% of children in the western nations are
overweight or obese. GERD is increasingly recognized in children, as
a cause of morbidity. The association of gastroesophageal reflux (GER)
in adults with obesity has been suggested but remains controversial. The
data in the pediatric population is even more limited and contradictory.
Aim: The aim of the study was to evaluate the relationship between the
BMI (kg/m2), and histologically confirmed reflux esophagitis in
children.
Method: This is a retrospective study of upper endoscopies done in the
period of January 1st, 1998May 31, 2004. Using the key word
esophagitis, we identified all patients less than 18 years of age with
histological evidence of esophagitis from the institutional pathology
database. Medical charts were then reviewed and data extracted.
Patients with neurological abnormalities, anatomical abnormalities,
inflammatory bowel disease, chronic medical illness and patients less
than age one were excluded.
Results: 136 patients were identified, 30 children were excluded. The
M:F ratio of the 104 study subjects was 71:33. Of these, 33 (M:F-26:7)
had BMI .85%, with 17 (M:F-15:2) having a BMI .95% of age
adjusted scores.
Discussion: Although obesity has been presumed to predispose patients
to GERD, in our study 32% of patients with histological evidence of
esophagitis is were overweight (BMI .85%) and 16% were obese (BMI
.95%). This is similar to recently published norms for children in our
community but indicate an unexplained difference in male:female ratio.
Conclusion: Children with endoscopic established esophagitis do not
appear to have a higher than expected prevalence of overweight and
obesity compared to community norms. However, overweight and
obese children may still be subject to higher prevalence of symptoms. A
prospective cross sectional control study to screen children for
overweight and obesity and identify the prevalence of GER using
a validated questionnaire is envisioned.
 NASPGHAN ANNUAL MEETING
26
TOLERANCE AND RELIABILITY OF WIRELESS PH
MONITORING IN CHILDREN
Jay Hochman, Cathy Simms, Stan Cohen, Dinesh Patel. Childrens
Center for Digestive Health Care, Atlanta, GA.
Objectives: The purpose of this study was to determine whether the
placement of a wireless capsule pH monitoring system improved the
reproducibility and patient comfort of pH probe studies in children.
Methods: The records of 50 children who underwent wireless
pH monitoring were retrospectively reviewed. Among this group, 44
children (27 males and 17 females) met inclusion criteria. The average
age was 11.8 years, with a range from 6 years to 19 years. Each of these
patients had a capsule placed 6cm above the squamocolumnar junction
and underwent pH telemetry for 2 days. In addition, 38 of the 44
families were contacted for follow-up to determine the tolerability of
the catheter-free monitoring.
Results: Data analysis revealed that the overall reproducibility of
a single 24-hour period was 77%. Studies were considered reproducible
if the reflux index was normal (pH , 4 for less than 5% of study period)
or abnormal on both study days. Using McNemars Exact test, we found
no significant difference between the two days (p = 0.11). Ten of 44
patients had conflicting results on day 1 compared with results on day 2.
The majority (68%) of patients reported some degree of discomfort
during the study; however, this pain was generally mild. 95% of parents
would be willing to have their child undergo pH monitoring in the future
with the wireless pH monitoring.
Conclusions: Catheter-free prolonged esophageal pH monitoring is
feasible in children older than 6 years of age. A lack of consistent
reproducibility in sequential 24-hour recordings with this technique
concurs with findings using the conventional catheter methodologies.
The catheter-free system is often associated with discomfort during the
study, but these symptoms were generally well-tolerated.
27
PROLONGED PH MONITORING WITH A CATHETER-FREE
SYSTEM IN CHILDREN BEING EVALUATED FOR
EXTRA-INTESTINAL MANIFESTATIONS OF
GASTROESOPHAGEAL REFLUX (GER)
Toba Weinstein, Elizaveta Iofel, Jeremiah Levine. Schneider Childrens
Hospital, New Hyde Park, NY.
Purpose: Children with chronic cough, hoarseness, and/or chronic
respiratory symptoms are often referred for evaluation of gastroesoph-
ageal reflux disease (GERD). As part of the evaluation an upper
endoscopy and/or ambulatory 24 hour pH probe are often performed.
The aim of this study was to evaluate the effectiveness of the BRAVO
pH system, a catheter-free pH testing system that measures esophageal
pH for up to 48 hours, in diagnosing GERD in pts with extra-intestinal
symptoms.
Methods: The medical records of all pts who underwent catheter-free
pH monitoring between 10/02 and 5/05 were reviewed. Indications for
the procedure and medication usage were recorded. In each pt
esophageal biopsies were obtained. The pH capsule was placed
approximately 5 cm above the proximal border of the lower esophageal
sphincter. All pts were re-endoscoped immediately following capsule
placement to document attachment.
Results: 20 pts (13M,7F), mean age 13.3 6 2.8 yrs (range 8.917.4)
underwent endoscopy and pH capsule placement for extra-intestinal
manifestations. 8/20 (40%) pts had documented esophagitis. Of pts with
documented esophagitis, 75% (6/8) had a catheter-free pH study
consistent with GERD (DeMeester score .14.7), but only 50% of pts
had a positive study on both days. Of patients without documented
esophagitis, 6/12 (50%) had a catheter-free pH study consistent with
GERD, but only 50% of pts had a positive study on both days. There
was no statistical difference noted in age or pt weight between groups.
30% (6/20) of pts who were referred for evaluation of GER were found
501
to have documented GERD based on one day of data vs 60% (12/20)
based on 2 days of data, increasing diagnostic utility by 100%.
Conclusion: This study suggests that having 2 days of data is better
than studying a single 24 hr period in pts with extra-intestinal mani-
festations of GERD. The ability to perform prolonged esophageal pH
determination in children increases the likelihood of finding pathologic
GER episodes and may significantly improve diagnostic yield.
28
ESOPHAGITIS AND 24-HOUR PHMETER ON
CHILDREN WITH GASTROESOPHAGEAL
REFLUX DISEASE
Carlos A. Velasco, Maira P. Sanchez. GASTROHNUP, University of
Valle, Cali, Colombia.
Introduction: GERD in children may in 50% get complicated with
esophagitis. The monitoring of the 24-hours intraesophageal pH (24h-
pH) is the gold standard for the GERD diagnosis.
Objective: To determine the possible relation between the histopath-
ological findings of esophagitis and the 24h-pH on children with GERD.
Materials and Methods: Transversal section descriptive observational
study on children below 14 years old from the Hospital Universitario del
Valle and the Hospital Infantil Club Noel in Cali, Colombia were
studied. Data about identification (age and gender), symptoms (di-
gestive and/or respiratory), weight, 24h-pH (parameters and relation-
ship with symptoms) and the histopathology (esophagitis associated to
GERD) was obtained from the clinical record. It was considered global
malnutrition (MNT) when the deficit weight/age was . of 10%
according to the NCHS. The results were expressed as an average and
standard deviation, and for finding association (table of 2 3 2) OR and
X2 were used, being p , 0.05 significant.
Results: 49 children were included in the study, their ages oscillated
between 4 months and 13 years old (5 years 3 months 6 3 years
8 months); 26 were boys; showing as predominant symptoms the
respiratory 26.5% and digestive 8.16%; with global MNT of 34.6%. Out
of the 49 24h-pH (reflux index 3.06 6 3.12%; # of acid episodes 59.45
6 57.92; # of acid episodes .5# 0.98 6 1.79 and duration of the longest
episode 8.16 6 12.72 minutes), 27 were abnormal by parameters and 18
were abnormal by association with symptoms. The histopathological
findings reported esophagitis associated to GERD in 15 (31%) children.
We did not find relation between the histopathological findings and the
result of the 24h-pH (p , 0.05).
Conclusion: Despite that we did not find relation between the
histopathological findings and the result of the 24h-pH, it is still
mandatory for children with GERD to include 24h-pH by parameters in
their studies (RI, # acid episodes, # episodes .5# and duration of the
longst episode) and by association with symptoms (digestive and/or
respiratory) and the high digestive endoscopy with biopsy taking
(esophagitis due to GERD).
29
PSYCHOLOGICAL CHARACTERISTICS IN FAMILIES
OF CHILDREN WITH GASTROESOPHAGEAL
REFLUX DISEASE
Carlos A. Velasco, Angela M. Jimenez. GASTROHNUP, University of
Valle, Cali, Colombia.
Introduction: GERD in infants may be understood as a psychological
problem.
Objective: To describe the psychological characteristics in families of
children with GERD.
Materials and Methods: 11 children (224 months) from the Hospital
Infantil Club Noel in Cali, Colombia were included.
Results: 6 girls, parentss age (1841 years old); parents living
together between 013 years; 6 with mternal step brothers; 5 living in
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
502 NASPGHAN ANNUAL MEETING
common-law marriage and 3 married and living together, respectively;
7 were non planned pregnancy; all were wanted pregnancy; 8 had
serious illnesses background and hospitalizations; 6 mothers were self
defined as anxious and nervous; 3 with mothers in a psychiatric
treatment; 6 with nursing from mother and one never had it.
Discussion: The observation of children with GERD and their families
has allowed us to begin the understanding inherent to the illness and all
those fears, expectancies and defenses thar are characteristic of it. Thus,
the emotional conflict due to the loss of control of the external world, its
regularities and predictions is evident, and this leads to the anxiety
increase when facing the physcical illness of the child. During the
semistructured interviews carried out with the families of the children
with GERD, recurrent characteristics that allude to a series of
manifestations proper of the person when is threaten by factors on
which does not have control have been found. In that sense, a series of
defenses that are conveniente at that moment for bearing the pain and
the incapacity that the childs illness represents are observed. Among
the most remarkable defenses are: negation, dissociation, intellectual-
ization, projection and regression, manifestations which main compo-
nent is the loss of control and the inability to provide the child the
protection s/he requires. Therefore, the knowledge that the pediatrician
has about the psychological capabilities of both the child and the family,
as well as the recognition of the emotional threat that the illness implies
to the parents will result in an extra support in order to protect the health
and make the process a little more tolerable.
30
KNOWLEDGE, ATTITUDES AND PRACTICE
STYLES OF NORTH AMERICAN PEDIATRICIANS:
GASTROESOPHAGEAL REFLUX DISEASE
Diego Diaz1, Harland S. Winter2, George D. Ferry3, Richard B.
Colletti , Steven J. Czinn6, Rudolph D. Colin5, William Cochran7,
4
Benjamin D. Gold1. 1Emory University, Atlanta, GA; 2Massachucetts
General Hospital, Boston, MA; 3Baylor College of Medicine, Houston,
TX; 4University of Vermont, Burlington, VT; 5Medical College of
Wisconsin, Milwakee, WI; 6Case Western Reserve University, Cleve-
land, OH; 7Geisinger Clinic, Danville, PA.
NASPGHAN launched a provider and public education campaign in
2002 to raise awareness of gastroesophageal reflux disease (GERD). To
determine effectiveness of campaign messages, we conducted a knowl-
edge, attitudes and practice styles survey (KAPS) of pediatric providers.
Understanding the spectrum of management styles of GERD in chil-
dren is critical to achieve better health outcomes and reduce healthcare
costs.
Methods: The KAPS questionnaire was administered to 6,000 randomly
selected members of the American Academy of Pediatrics.
Results: 1245 members responded; 82% worked in a primary care
setting and 18% in subspecialty practices. Overall, 66% order
diagnostic testing in routine practice, 54% start testing for GERD in
neonates, and 38% after 1 month of age. The most common tests
ordered were barium esophagram (45%) and esophageal pH monitoring
(37%). 82% would treat GERD with acid suppression before ordering
diagnostic testing; 74% recommended H2 blockers for an empirical
trial, yet 19% believed acid suppression was best achieved by H2
blockers. If acid suppression was indicated, only 36% followed
guideline recommendations for therapy duration and 52% for dosing.
92% recommended anti-reflux surgery only as a last resort. Overall,
69% of providers believed the amount of GERD related information
available was not enough. Primary sources of information were journals
(86%) and conferences (69%). Respondents who were not aware of
available GERD Practice Guidelines ranged from 74%92%.
Conclusion: Pediatric providers appear to frequently order diag-
nostic testing and treatment for GERD, yet knowledge about GERD
among this random sample was limited. Moreover, a significant
number of providers were not aware of different guideline publica-
tions available.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
31
GASTROESOPHAGEAL REFLUX DISEASE (GERD)
IMPAIRS THE QUALITY OF LIFE IN
PEDIATRIC PATIENTS
Vasundhara Tolia1, Lynette Essenmacher2, Joel Ager2. 1Gastroenter-
ology, Hepatology & Nutrition, Childrens Hospital of Michigan,
Detroit, MI; 2Outcomes Research, Wayne State University, Detroit, MI.
Introduction: A prospective study of factors affecting the quality of
life (QOL) issues was performed in children and adolescents with
GERD using an 11 page questionnaire which was completed by the
parent or parent/child.
Methods: The questionnaire was given to 190 patients diagnosed to
have GERD by endoscopy/w/biopsy to be returned in a stamped, self-
addressed envelope. These were normal children without other
neurologic, anatomic or surgical co-morbidities. Some components of
the questionnaire addressed the QOL issues related to eating, school and
sports attendance and their association with GERD symptoms, concerns
regarding outcome, need for ongoing medications and tests (eg; scope).
Entries into a microsoft access database were analyzed with SAS. This
study was approved by IRB.
Results: 88 questionnaires (35 M, 51 F) were returned. Mean age of the
total cohort was 9.0 years (range 218 years). There were 57 caucasians,
20 African Americans and 5 others. 59% of patients experienced
symptoms with intake of citrus foods, tomato products, chocolate, fried
foods, carbonated beverages and foods at fast food restaurants. 49%
reported worsening of symptoms with some of the above foods as well
as dairy in 17%. 38% were symptomatic during meals and 61% after
meals. 45% had symptoms associated with sleep and in 31% reflux
symptoms occurrred with sports or exercise. School attendance and/or
performance was adversely affected in 27% of this cohort. Children
were also concerned that their illness will not resolve (75%), upset
about not being able to eat what they wanted (68%) without feeling sick
and 59% were bothered about the need to take medications.
Conclusions: A variety of foods worsen the symptoms in children with
GERD during and after meals. These children are concerned about need
for treatment, tests and outcome. GERD impairs QOL in pediatric
patients by affecting their school performance and disturbs sleep.
32
UTILIZATION OF ESOPHAGEAL PH MONITORING
AND ADHERENCE TO NASPGHAN GUIDELINES AT
CHILDRENS HEALTHCARE OF ATLANATA (CHOA)
Conrad R. Cole1, Tom Sternberg1, William F. Meyers2, Benjamin D.
Gold1. 1Pediatrics, Emory University, Atlanta, GA; 2Pediatrics,
Childrens Healthcare of Atlanta, Atlanta, GA.
NASPGHAN published guidelines for primary care providers recom-
mending use of 24h-pH Monitoring (pHM) tests for the evaluation of
gastroesophageal reflux (GER) in children.
Objective: Our aim is to measure current adherence/compliance with
guidelines as a baseline for Quality Improvement Initiative (QII) at
CHOA.
Methods: All 295 patients medical records (ages: 1220 months),
undergoing pHM during 2003 were abstracted for relevant demograph-
ically descriptive and biometrically appropriate data including Reflux
Index (RI) and Esophageal Clearance (EC). Each of these continuous
variables was converted into categorical variables with two-outcomes
(normal/abnormal) based on published norms and where appropriate,
adjusted for age. Furthermore, indication, reported symptoms, pre-
sumptive diagnosis and referring providers specialty were also
evaluated, so as to be able to impute the test as being NASPGHAN
guidelines compliant or not. This imputation was the result of a panel of
5 gastroenterologists using the majority of the panels decision
regarding NASPGHAN compliance.
Results: 186 children (28.5%) had pHM tests that were in adherence to
guidelines for recommending tests while 109 patients (37%) were
 NASPGHAN ANNUAL MEETING 503

recommended for non-testing. 84 children (28%) had abnormal RI of on H2RAS had stepped up to PPIS, while 2 patients on PPIS had
whom only 54 (64%) were flagged in compliance with guidelines; stepped down to H2RAS, thereafter 12 patients were lost to follow up.
implying that 30 (36%) with abnormal RI would have been missed. The sequential and follow up data are shown in Table 1 and 2.
Similarly, 164 (55%) children had abnormal EC, of whom 103 (63%) Conclusion: Longitudinal data suggests that continuous treatment is
were appropriately selected by guidelines; implying that 61 (37%) with needed even in the absence of other predisposing factors in normal
abnormal EC would have been missed. children .2 yrs in age with GERD. Prospective Long Term studies are
Conclusion: Adherence to NASPGHAN guidelines recommendations needed to understand the natural history of GERD in Children.
at this hospital has mixed results for predicting test results for both RI
and EC; exhibiting limited sensitivity and low specificity.
TABLE 1. PPIS- 22 patients
Step down No Lost to
33 Years PPIS to H2RAS RX followup
SYMPTOMS OF REFLUX ARE NOT ALWAYS 1 22 2 0 O
REFLECTIVE OF PERSISTENT GASTROESOPHAGEAL 2 20 0 0 0
REFLUX: A PEDIATRIC STUDY USING 3 13 2 0 5
SIMULTANEOUS IMPEDANCE-PH MONITORING
Rita Steffen. Pediatric Gastroenterology, Cleveland Clinic Foundation,
Cleveland, OH. TABLE 2. H2RAS- 32 patients

Symptoms may persist in children thought to have gastroesophageal Step up No Lost to

reflux (GER) despite ongoing treatment. In a small pediatric group on
GER therapy, we noted absence of temporal association between
reported symptoms on one hand and acid or non-acid reflux events on
the other.
Using Multichannel Intraluminal Impedance-pH monitoring (MII-pH,
Sandhill Scientific), we evaluated 8 pediatric patients on GER therapy
who had persistent symptoms. All patients had at least 20 hours of
monitoring. Reported symptoms and both acid and non-acid reflux
episodes were analyzed. Acid suppression was complete in 4 patients
(group 1) and incomplete in 4 (group 2).
Out of 193 noted symptoms, 128 (66.3%) did not coincide with acid or
non-acid reflux. The symptom sensitivity index was 33.6%. Group 1
reported more symptoms overall and more symptoms associated with
nonacid reflux than did group 2 (22 % vs. 8%, P = 0.029).
Our observations warrant further evaluation of the etiology of reported
symptoms commonly attributed to persistent reflux despite therapy,
and also further study of the role of better acid suppression and
prokinetics.
34
CLINICAL PRESENTATION AND LONG TERM
OUTCOME OF GASTROESOPHAGEAL REFLUX DISEASE
IN CHILDREN AND ADOLESCENTS
Grace I. Onimoe, Vasundhara Tolia, Ron Thomas. Gastroenterology,
Childrens Hospital of Michigan, Detriot, Michigan, MI.
Objective: A retrospective review of pediatric patients diagnosed with
GERD with long term follow up to study presenting symptoms,
associated conditions, response to treatment and need to step up or step
down from initial treatment.
Design/Methods: Chart review was performed on patients diagnosed
with GERD by Esophagogastroduodenoscopy (EGD) and biopsy.
Duration of treatment with Histamine receptor antagonists (H2RAS)
and Proton pump inhibitors (PPIS), need for step up or step down and if
Rx was discontinued was assessed.
Inclusion Criteria: Children .2 yrs at diagnosis.
Exclusion Criteria: Children with neurologic and esophageal
anatomic abnormalities.
Results: 54 patients (28 Females), ages ranging from 2.5 to 17 years
(mean 6 SD-8.55 6 4.34) were identified.
The most common presenting symptoms were chronic abdominal pain
(61.1%),Vomiting (14.9%) and heartburn (5.6%). 8 patients had asthma.
BMI range was 13.80 to 42.80 (mean = 22.34).
After a one to four year follow up period (mean = 3.27), all patients
responded to treatment and its modifications. 32 patients were started on
H2RAS and 22 patients on PPIS. After the second year of Rx, 9 patients
Years H2RAS to PPI RX followup
1 32 6 O 0
2 26 3 O 0
3 15 1 O 7
35
THE TREATMENT OF REFRACTORY BENIGN
ESOPHAGEAL STRICTURES USING REMOVABLE
SILICONE STENTS
Theodore H. Stathos, Steven S. Rothenberg, Aziz J. Yazdi, Jose M.
Barrios, Sandra Kay. Pediatric Gastroenterology, Mother and Child
Hospital at Presbyterian/St. Lukes Medical Center, Denver, CO.
Esophageal strictures are a common problem in the pediatric
population. Common causes include scaring from caustic ingestions,
chronic gastroesophageal reflux disease and from the repair of
esophageal atresia (EA) or tracheoesophageal fistula (TEF). Up to
90% of these strictures are readily treatable using common esophageal
dilation techniques.
Others remain refractory to dilatation and typically require frequent
repeated dilatation or surgical resection. Silicone stents have success-
fully been used for the treatment of adults with refractory strictures.
We suggest that the use of silicone stents in children with refractory
strictures should be equally safe and successful, and report our
experience.
Ten children (ages 6 mo to 18 yr) with refractory esophageal strictures
were selected based on re-stricturing of the esophageal lumen following
multiple dilations. The Polyflex Esophageal Stent (Boston Scientific)
placement was done endoscopically with fluoroscopic guidance under
general anesthesia (phase 1). After 46 months the stents were
endoscopically removed and a larger diameter stent was placed (phase
2). The second stent was left in place for another 46 months. Removal
after a total of 812 months was the goal in all patients.
Ten children have had stents placed with good success. Five of the Ten
patients have had the stent(s) removed and no longer require dilatations.
Three patients remain in phase 1, two are in phase 2, all continue to
tolerate the stents well. Proximal migration of a stent was observed in 2
of the patients and endoscopic removal with subsequent replacement
was easily accomplished in both.
The treatment of benign esophageal strictures using silicone removable
stents is both safe and effective in a limited study of children with
benign esophageal strictures. The Polyflex esophageal stents are easily
used with minimal invasiveness. More patients are needed to deter-
mine with greater accuracy the long-term success and tolerance of this
procedure.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

504 NASPGHAN ANNUAL MEETING
36
PEPSIN IN THE AIRWAY-MARKER FOR
REFLUX ASPIRATION
Vani V. Gopalareddy, Zhaoping He, Laura Bolling, Mansi Shah,
Devendra I. Mehta. Gastroenterology, Alfred I. duPont Hospital for
Children, Wilmington, DE.
Objectives: Patients with Gastroesophageal reflux disease (GERD) can
have chronic lung disease. A diagnostic tool to measure reflux aspira-
tion is currently lacking. The aim of this study is to determine whether
presence of gastric pepsin in airway can be used as a marker of
microaspiration of refluxed gastric contents.
Method: Tracheal samples from 22 children undergoing bronchoscopy
for pulmonary problems was assayed for gastric pepsin using
fluoroscein isothiocyanate casein. Retrospective chart review for GERD
symptomatology and/or diagnostic test (PH probe study, endoscopy)
was done. PH probe done in 6/22, one positive, Endoscopy was done in
12/22 patients, 6 had esophagitis. Lipid laden macrophages (LLM) done
in 8/22, one was positive.
Results: Primary diagnosis included chronic cough, cystic fibrosis,
asthma, bronchopulmonary dysplasia, recurrent pneumonia. 10 males
and 12 females. Ages ranged from 3 months to 15years. Pepsin levels
ranged from 0 ng/ml to 367 ng/ml (with a cut off value of .6.5 ng/ml
for positive assay) in 17/22 patients (77% positive) with chronic
respiratory symptoms. GERD was present in 14/22 patients (63%).
Fishers exact test, two-tailed analysis showed no correlation between
reflux symptoms and pepsin in airway (microaspiration) (P = 0.30).
Conclusions: Microaspiration of gastroesophageal reflux contents can
happen in the absence of obvious GERD symptoms in patients with
chronic lung disease. Pepsin is a better marker of aspiration than lipid
laden macrophages.
TABLE 1. GERD and Pepsin (analysis for correlation)
GERD positive GERD negative Total
Pepsin positive 12 5 17
Pepsin negative 2 3 5 and found that cigarette smoking, alcohol, and NSAIDs were risk
Total 14 8 22
37
THE 24 HOUR PH-STUDY IN CHILDREN WITH
DIGESTIVE OR RESPIRATORY SYMPTOMS
RELATED TO GASTROESOPHAGEAL REFLUX
Emilia J. Cohen. Sabban, Marina Orsi, Carla Venturi, Eduardo
Mullen, Daniel DAgostino. Gastroenterologia Infantil, Hospital
Italiano, Buenos Aires, Argentina.
The 24 hour pH monitoring was considered the gold standard to
evaluate gastro-esophageal reflux disease. The presence of normal ph
results related to pathological gastroesophageal reflux has been
reported. The existence of non-acid events, not detected by the ph
probe created a shadow into a well established diagnostic tool.
Aim: To evaluate the correlation of the 24 hour pH-study with the
presence of esophagitis in children with respiratory or digestive
symptoms related to GERD.
Material and Methods: Since December 2001 to May 2005, 84
children suspected of GERD because of a clinical history and a positive
upper GI x-Ray. In all of them, an upper endoscopy was performed and
multiple biopsies were taken. Immediately after, a 24 hour monitoring
was done. The studies were divided into normal or pathological
according to the Vandenplas score. The biopsies were informed by two
different pathologists in a blinded manner.
The patients were divided according clinical presentation
Group I: 54 children with digestive symptoms.
Group II: 30 children with respiratory symptoms.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Results: Group I: Sensitivity 63%; Specificity: 37.5%; PPV: 85.2%;
NPV: 15%; Square chi 0.97; P N/S.
Group II: Sensitivity: 63.6%; Specificity: 25%; PPV: 70%; NPV: 20%;
Square chi 0.34; P N/S.
Conclusions: The 24 hour pH study resulted a poor predictor of
esophageal mucosal damage in both groups of children with gastro-
esophageal reflux. New methods are required to establish a correct
diagnosis in a more accurate manner in this prevalent disease.
TABLE 1. Children with digestive symptoms
Esophageal Esophageal
damage positive damage negative
pH monitoring positive 29 5
pH monitoring negative 17 3
TABLE 2. Children with respiratory symptoms
Esophageal Esophageal
damage positive damage negative
pH monitoring positive 14 6
pH monitoring 8 2
38
ASSOCIATION OF FOOD AND DRINKS WITH
GASTROESOPHAGEAL REFLUX SYMPTOMS
IN ADOLESCENTS
Asim A. Mohammed1, M. Dahlberg1, G. Namachivayan1, T. S.
Gunasekaran1,2. 1Lutheran General Childrens Hospital, Park Ridge,
IL; 2Loyola University Medical Center, Maywood, IL.
Gastroesophageal Reflux (GER) is a common GI disorder. We reported
a prevalence of 38% of esophageal GER symptoms among adolescents
factors for these symptoms. Now we are analyzing if certain foods and
drinks are associated with GER symptoms.
Aim:
1. To find out the association between GER symptoms and spicy foods,
citrus fruit drinks, chocolate drinks, and 12 caffeinated and 15 non-
caffeinated carbonated drinks.
2. To confirm if NSAIDs, alcohol, caffeine use, and smoking are risk
factors.
Method: A cross sectional survey was given to 1418 year old students.
The survey had questions on presence of esophageal (heartburn,
regurgitation and dysphagia) and respiratory (cough and shortness of
breath) symptoms of GER over the past year and intake of above
mentioned food and drinks. Data was analyzed by chi square.
Results: 1082 surveys received. Mean age 15.5 years, 51% female,
Ethnic distribution 41.5% Caucasians, 29.2% Asians, 11.1% Hispanics,
5.8% African Americans, and 12.4% others. GER symptom prevalence
was 51%. Sex and ethnic differences for GER symptoms were not
significant. Adolescents drinking coffee, certain caffeinated, carbonated
drinks (Barqs Root Beer, Dr. Pepper, Mountain Dew, and cola) and
certain caffeine-free carbonated drinks (Diet Rite, Sprite, Caffeine Free
Coke, Barqs Root Beer, and A&W Root Beer) were found to have
significant association with GER symptoms (p , 0.05). Tea, spicy foods,
citrus fruit drinks, and chocolate drinks were not associated with GER
symptoms. Esophageal symptoms were associated with fewer carbon-
ated drinks than respiratory symptoms. As we showed earlier, NSAIDs
(p , 0.001), alcohol (p = 0.003) and cigarette smoking (p , 0.001) were
again found to have significant association with GER symptoms.
Conclusion: Coffee, 4/12 carbonated, caffeinated drinks and 5/15
carbonated caffeine free drinks were found to be associated with GER
symptoms. Cigarette smoking, alcohol, and NSAIDs use were sig-
nificant for GER symptoms as shown earlier.
 NASPGHAN ANNUAL MEETING 505

39* Findings: GER was identified in 5 of 5 patients tested by BRAVO pH

testing. Esophagitis was seen in 3 of 6 patients biopsied. See tables below.
PHARMACOKINETICS OF MULTIPLE DOSES OF Conclusions:
ESOMEPRAZOLE IN PEDIATRIC PATIENTS AGED 1. Gastroesophageal reflux can be tested in children with autism using
1 TO 11 YEARS WITH SYMPTOMS OF wireless BRAVO pH probe technology.
GASTROESOPHAGEAL REFLUX DISEASE 2. Aggresive or self-injurious behavior may be a manifestation of pain
Jianguo Li , June Zhao1, Jennifer E. Hamer-Maansson1, Tommy
1
from GER and should prompt consideration of further investigation.
Andersson1, Marta Illueca1, Per Lundborg2. 1AstraZeneca R&D, 3. Further study of non-classic GI symptoms needs to be considered in
Wilmington, DE; 2AstraZeneca R&D, Molndal, Sweden. children with autism.

Purpose: To determine the pharmacokinetics (PK) of esomeprazole

after repeated oral doses in pediatric patients with gastroesophageal TABLE 1. Demographics and symptoms
reflux disease (GERD) symptoms.
Methods: In this single-center, open-label study (D9614C00099), Patient Age, yrs Symptoms at presentation
children aged 15 years inclusive received esomeprazole 5 or 10 mg,
AS 8 History of GER, regurgitation, Chest pain,
and children aged 611 years inclusive received esomeprazole 10 or
Sleep disturbance, Aggressive behavior,
20 mg once daily for 5 days. Plasma esomeprazole was measured using
Self-injurious behavior (SIB)
normal-phase liquid chromatography and UV detection in blood
JG 11 History of GER, Pressing on chest,
samples taken ,30 minutes before and 0.5, 1, 1.5, 2, 3, 4, and 6 hours
Aggressive behavior, Unexplained crying
after dosing on day 5 (presumed steady state).
JB 19 Posturing episodes, Eructation
Results: Of these children, 55% were boys. In the younger children,
CR 10 Posturing episodes, Eructation
AUC and Cmax with the 10-mg dose were more than twice that with the
ND 13 Apparent pain, Aggressive behavior
5-mg dose, and t1/2lz was nearly twice that observed with the 5-mg
RS 10 Aggressive behavior, SIB
dose. In the older children, AUC and Cmax with the 20-mg dose were
approximately twice that with the 10-mg dose; t1/2lz and tmax were
comparable. With the 10-mg dose, t1/2lz was similar in both age groups.
The mean apparent clearance (Cl/F) adjusted for body weight was TABLE 2. Findings: Endoscopic histology and
.50% higher in 15-year-old than in the older children. All doses were pH probe results
well tolerated; 2 mild adverse events were reported.
Conclusions: The difference between the lower and higher doses in Endoscopic pH probe pH probe
overall exposure (AUC) was greater in the younger than in the older histology results Day 1 results Day 2
children. Comparison of the 10-mg dose of esomeprazole in the 2 age Patient findings (DeMeester score) (DeMeester score)
groups suggests that 15-year-old children metabolize esomeprazole
AS Acute Esophagitis 75.1 50.8
more rapidly per body weight than 611-year-old children.
JG Normal Histology 34.8 21.9
JB Acute Severe 42.5 37.6
Aged 15 years Aged 611 years Erosive
Esophagitis
Esomeprazole Esomeprazole Esomeprazole Esomeprazole CR Normal Histology 19.7 23.1
5 mg (n = 6) 10 mg (n = 8) 10 mg (n = 7) 20 mg (n = 6)
ND Normal Histology 22.7 7.9
Mean weight (kg)* 21.0 (5.76) 14.7 (3.32) 33.3 (12.5) 29.6 (6.91) RS Acute Severe Not tested Not tested
AUC (mmol;h/L) 0.74 (0.36) 4.83 (2.56) 3.70 (2.05) 6.28 (2.71) Erosive due to due to
Cmax (mmol/L) 0.62 (0.38) 2.98 (0.69) 1.77 (0.96) 3.73 (1.21) Esophagitis esophagitis esophagitis
tmax (h)* 1.33 (0.41) 1.44 (0.42) 1.79 (0.64) 1.75 (0.42)
t1/2lz (h) 0.42 (0.13) 0.74 (0.36) 0.88 (0.35) 0.73 (0.21)
pH probe results are reported by DeMeester score. DeMeester score
Cl/F/kg (L/h/kg) 0.40 (0.19) 0.25 (0.21)
normal is less than 14.72.

*Arithmetic mean (SD); Geometric mean (SD).

40 Nutrition, Absorption and Malabsorption

GASTROESOPHAGEAL REFLUX IN
CHILDREN WITH AUTISM: HOW DO CHILDREN
PRESENT AND CAN ONE TEST
THESE CHILDREN?
Timothy M. Buie. Pediatric GI, MGH, Boston, MA.
Background: Gastroesophageal Reflux (GER) is primarily diagnosed by
symptom description. Children with autism have core difficulty commu-
nicating and atypical social relatedness. For this reason, identification of
GER in autistic children may be difficult. The prevalence of GER in
autism remains unknown, but several reports identify esophagitis as a
finding in autistic children undergoing endoscopy.
Aims: To evaluate autistic children with GI complaints and aggression
or self-injurious behavior in order to determine if these behaviors may
be symptoms of GER.
Methods: Six consecutive autistic children (ages 819 years) under-
going endoscopy and scheduled for BRAVO (wireless) pH probe were
evaluated for histology and pH meter results.
41
ANALYSIS OF MACRONUTRIENT INTAKE ON
PARENTERAL NUTRITION-ASSOCIATED CHOLESTASIS
(PNAC) IN PREMATURE INFANTS WEIGHING
6001000 GRAMS
Jonathan Blau, Shanthy Sridhar, Susan Mathieson, Anupama Chawla.
Pediatrics, Stony Brook University, Stony Brook, NY.
Introduction: Parenteral feeding has historically been a significant
cause of PNAC in premature neonates. Studies examining the causes of
PNAC have produced conflicting results. Increased protein/nonprotein
calorie ratios, glucose, and lipid concentrations have all been implicated
as possible causes of PNAC. However, these studies were done in the
pre-Trophamine (neonatal-specific amino acid TPN formulation) era.
We analyzed the parenteral macronutrient intake of cholestatic vs. non-
cholestatic premature infants receiving Trophamine to assess any
causative role of these macronutrients.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

506 NASPGHAN ANNUAL MEETING
Methods: A retrospective chart review of 25 cholestatic and 25 non-
cholestatic TPN-dependent premature neonates weighing 6001000
grams was conducted. Cholestasis was defined as a serum Total
Bilirubin (TB) of greater than or equal to 2 mg/dl, with a Direct
Bilirubin (DB) of greater than or equal to 20 percent of the TB. Average
daily TPN macronutrient compositions were analyzed over a 2-week
period to examine if the protein, lipid, and carbohydrate intakes played
a role in the development of PNAC. Statistical analysis was performed
using student t-tests.
Results: All nutritional parameters did not differ significantly between
the 2 groups. Renal function as evaluated by BUN and Creatinine also
did not differ. However, the duration of TPN therapy and length of
hospital stay were statistically different.
Conclusions: PNAC seemed to be independent of macronutrient
composition of TPN. Adequate protein intake did not affect renal
function. Therefore, providing adequate macronutrient intake should
not be limited in this patient population as suggested by previous studies
in the pre-Trophamine era.
*P-value ,0.05 Cholestasis Non-cholestasis P-value
Total intake (kcal/kg) 64.20 6 7.93 62.85 6 8.87 0.51
Total Protein intake (g/kg) 2.37 6 0.28 2.37 6 0.34 1.00
Total Lipid intake (g/kg) 1.96 6 1.57 1.96 6 0.52 1.00
Glucose infusion
Rate (mg/kg/min) 6.54 6 1.26 6.38 6 1.50 0.62
Length of hospital
stay (days) 92.48 6 26.44 78.72 6 19.92 0.02*
Duration of TPN
therapy (days) 46.64 6 24.25 22.68 6 7.96 ,0.01*
42
EFFECTS OF EARLY ENTERAL FEEDING ON
FECAL ELASTASE 1 AND PLASMA SECRETIN
LEVELS IN LOW BIRTH WEIGHT INFANTS
Toshiaki Shimizu, Noritsugu Kaneko, Mitsuyoshi Suzuki, Kyoko
Tanaka, Koichi Shinohara, Seigo Shiga, Yuichiro Yamashiro. Department
of Pediatrics, Juntendo University, Tokyo, Japan.
Background: Enteral feeding is known to be effective on the
development of gut hormone secretion and pancreatic exocrine
function, but the effects of extremely early enteral feeding are not clear.
Aim: We examined the effects of extremely early enteral feedings on
the postnatal changes in pancreatic exocrine function and gut hormone
secretion in very low birth weight (VLBW) infants.
Methods: We measured the fecal elastase 1 and plasma secretin
concentrations at four different periods during the first 28 d of life in
VLBW infants, with extremely early enteral feeding starting within 24 h
of birth, as well as in control infants.
Results: Fecal concentrations of elastase 1 at 7, 14 and 28 d after birth
were significantly higher than those at 1 or 2 d in both the early
feeding and control groups. Fecal elastase 1 levels in the early feeding
group were significantly higher than those in the control group at 7
and 14 d after birth. The plasma concentration of secretin at 14 d after
birth was significantly higher than that at 1 or 2 d and 7 d after birth
in the early feeding group. No significant differences in plasma
secretin levels were detected between the early feeding and control
groups at 1 or 2 d, 7 d and 28 d after birth, but a significant difference
in the secretin level was observed between the two groups at 14 d after
birth.
Conclusions: Our results suggest that extremely early enteral feedings
may play an important role in the development of pancreatic exocrine
function and secretin secretion in the early period of life in VLBW
infants. To examine the long-term effects of extremely early enteral
feedings, we should examine the clinical outcome in VLBW infants
over longer periods.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
43
INTESTINAL FAILURE. IS IT REVERSIBLE?
C. Torres1, D. Sudan2, S. Raynor2, J. Botha2, W. Grant2, A. Langnas2.
1
Pediatrics - GI, University of Nebraska, Omaha, NE; 2Surgery,
University of Nebraska, Omaha, NE.
To analyzed the role of an Intestinal Rehabilitation Program (IRP) at the
University of Nebraska in the treatment of advance intestinal failure
during the last 4 years. 46 patients with short bowel syndrome, TPN
dependent, referred for liver/small bowel transplant, after evaluation,
were assigned to be treated instead by our IRP. Indications for treatment
in the IRP were: 1.Infants with no liver disease that had .15 cm of
bowel. 2. Children with .40 cm of bowel with elevated bilirubin but
normal INR. 3. Children with advanced liver disease/portal hyperten-
sion but normal INR, who had . than 60 cm of bowel and abnormal but
potentially repairable intestinal anatomy. Height, weight Z score,
platelet count, albumin, and bilirubin were obtained at the beginning
and end of the study Table 1.
Of the 46 patients, 25 had 40 different surgical intestinal repairs
(12 Bianchi, 11 Intestinal obstruction repaired, 5 takedown, 3 fistulas
repaired, 9 tapering/step enteroplasty). 32 had hyperbilirubinemia
(7 had cirrhosis, 13 advanced bridging fibrosis, and 12 portal fibrosis).
27 normalized the serum bilirubin with treatment. 4 patients died (3 for
sepsis, one for Influenza). 6 required transplantation. 2 are listed for
transplant. Of the remaining 34 IRP patients, 24 were weaned from
TPN (3 with cirrhosis) 10 patients are in process of weaning (2 of them
with stable cirrhosis). Survival of the IRP patients is 91%. Growth
has continued along the same curve. 25% exhibited significant catch up.
With an aggressive medical/surgical approach, even patients with
intestinal failure and advanced liver disease, can avoid transplantation.
IRP patients improved liver function and nutritional parameters with
the ability to discontinue TPN while maintaining growth. Early referral
of these patients to specialized centers prior to the development of
advanced liver disease is recommended.
Median
(range) Bilirubin Albumin HZ WZ Platelets
First 5 (0.1 to 3.0 (2 to 22.2 (24.2 21.2 (24.4 190 (19
26.4) 3.8) to 1.2) to 21.5) to 565)
Last 0.3 (0.1 3.7 (2.5 21.4 (22.9 20.6 (23.8 264
to 4.6) to 4.5) to 20.81) to 3) (96617)
44
INFECTION ASSOCIATED TO PERCUTANEOUS
CATHETER FOR PARENTERAL NUTRITION AT A
NEONATAL INTENSIVE CARE UNIT
Alexandra Cossio, Liliana C. Morales, Patricia Velez. Neonatal Unit,
Fundacion Valle del Lili, Cali, Colombia.
Introduction: The infection is the main complication during the
administration of TPN. It is necessary to measure rates and risk of
institutional infection.
Objective: To estimate the incidence and infection risk of percutaneous
catheters used at the administration of TPN.
Materials and Methods: A prospective cohort of 480 percutaneous
catheters for TPN was monitored between 1998 and 2001 at a level
IV Hospital; definitions of infection associated to catheter of the
CDC were used. The incidence was calculated as follows: number of
infections associated to central catheter 3 100/Catheter Total days; for
the categorical variables Fisher Test was applied; the variables of
remaining and duration of catheter, Kruskal-Sallis was applied. OR raw
and ajusted between infection, weight, remaining and catheter duration
was calculated by logistic regression. The first infection event was taken
into account.
 NASPGHAN ANNUAL MEETING
Results: The incidence was 0.65/100 catheter days, the children below
1.500 gr got infected (77%), Staphylococcus epidermis was found (34.2%)
and Klebsiella pneumoniae (22.8%). There were no significant differ-
ences between infection and complications at the moment of passing the
catheter. Statistically significant differences among infected ones com-
pared to the group of not infected in the variables weight when entering,
remaining and catheter duration were found. When adjusting the infection
according to the weight and remaining the association was not significant.
Conclusions: Vigilance about the appearing of infection due to catheter
on neonates must be increased; the ones with lower weight show higher
risk to acquire an infection. It is important to establish measurements
that reduce to the minimum the appearance of infections on these
children.
45
OUTCOMES OF LOW-BIRTH-WEIGHT INFANTS
WITH SURGICAL SHORT BOWEL SYNDROME
Conrad R. Cole1, Nellie I. Hansen2, Thomas Ziegler1, Barbara J.
Stoll1. 1Emory University, Atlanta, GA; 2Research Triangle Institute,
Research Triangle Park, NC.
Short bowel syndrome (SBS) is a devastating clinical problem in low
birth weight neonates.
Aims: To determine 1) incidence of SBS in very low birth weight
(VLBW; ,1500 g) infants; 2) incidence, morbidity, mortality and
growth in extremely low birth weight (ELBW; ,1000 g) infants.
Methods: Data were prospectively collected from infants born
01/01/02-06/30/04 who survived .12 hours and received care at 16
NICHD Neonatal network centers. They were followed until hospital
discharge/death/120 days. ELBW survivors were evaluated for follow-
up (f/u) at 1822 months corrected age. The distribution of and risk
factors for developing surgical SBS were evaluated.
Results: Cohort consisted of 8681 VLBW infants. 105(1.2%) had
surgical SBS (0.32.5% across centers). Relative risk of SBS was
inversely related to birth weight (BW) (p , 0.001). 13% of infants with
NEC had SBS compared to 0.3% of those without (p , 0.001). 3695
ELBW infants were classified as SBS (1.8%), Medical NEC without
SBS (4%), Surgical NEC without SBS (5.1%), No NEC or SBS
(89.1%). There were more male infants with SBS (p = 0.014). During
the initial hospital stay, SBS infants were more likely to develop sepsis,
severe intraventricular hemorrhage (IVH), patent ductus arteriosus
(PDA) and be treated with steroids for BPD. More SBS infants (36%)
died during the initial hospitalization than those without NEC or SBS
(22%), but less than infants with Surgical NEC without SBS (52%).
1060 children have completed the f/u visit. Compared to other groups,
more infants with SBS were tube fed and had been re-hospitalized at f/u.
There was no difference between the weights of SBS infants and other
infants at f/u. However, SBS infants had lower length and head
circumference than infants without NEC or SBS (p , 0.05).
Conclusion: ELBW infants with SBS have higher mortality during the
initial hospital stay. Lower BW, NEC, PDA, IVH and postnatal steroid
use were associated with SBS. At f/u, these children were more likely to
have lower length and head circumference. This suggests the need for
intensive nutritional therapy in these children.
46
COMPLICATED INTESTINAL FAILURE IN THE
TRANSPLANT ERA
Kishore R. Iyer1, Timothy Sentongo2, Lisa Keys1, Kim Kazmerski1,2,
Valeria Cohran2, Annie Xoomsai2, Margaret Richard1. 1Surgery,
Childrens Memorial Hospital, Chicago, IL; 2Gastroenterology, Chil-
drens Memorial Hospital, Chicago, IL.
Aim: We report our initial experience with a multidisciplinary intestinal
rehabilitation and transplantation program (IRP), over a 2 year period.
507
Methods: Retrospective chart review and review of clinical, laboratory,
nutritional and pathological data identified patients with intestinal
failure who had received prolonged parenteral nutrition (PN). We de-
fined PN associated cholestasis (PNAC) as a total bilirubin .3.0 mg%
and sepsis as at least 2 positive bacterial isolates or a single fungal
isolate from blood in a 2 year period. Hospital stay and charges were
computed for the same period.
Results: 56 patients met study criteria, over the 2 year period.
14 patients had functional causes of intestinal failure and 42 patients
had short bowel syndrome due to anatomic causes. 39 patients were on
PN at the start of the study period. 22 of these achieved full intestinal
adaptation and 6 achieved partial autonomy from PN. 17 patients met
criteria for bacterial sepsis. 7 of these patients also had episodes of
fungemia. 29 patients met criteria for PNAC. Three of the patients died,
representing all the deaths in the series. Of the remainder, all but one has
achieved full biochemical and functional liver recovery. Recovery
followed isolated small bowel transplant in 1 patient and 1 patient
received an isolated liver. Mean hospital charges for the septic patients
over the 2 year period of study were $1016721.06 compared to mean
charges of $183228.39 for the stable patients (p = 0.0001). Mean
charges for patients without PNAC were $175055.3 compared to
$662624.2 for patients with liver dysfunction (p = 0.007). Sepsis had an
adverse impact on adaptation (p , 0.005) though liver dysfunction had
no detectable impact.
Conclusions: Our data suggest that patients with complicated intestinal
failure have overall good survival and nutritional outcomes. While
PN-related complications clearly affect hospital charges, only sepsis
appears to have a definite impact on nutritional outcome within our
limited study period.
47*
A 10 YEAR REVIEW OF PEDIATRIC INTESTINAL FAILURE
PATIENTS IN NORTHERN ALBERTA
Karr-Hong Lee, Hien Q. Huynh, Rhonda Rosychuk, Justine Turner,
Linda Casey. Pediatrics, University of Alberta, Edmonton, AB, Canada.
Objectives: Having intestinal transplantation at our centre, we aim to
determine prognostic factors for children with intestinal failure (IF) in
our region.
Methods: We conducted a retrospective review of children treated from
94-04 who met our criteria for IF - dependence on parenteral nutrition (PN)
for more than 100 days or diagnosed with IF who died prior to 30 days of
PN. ANOVA, Kaplan-Meier method, and Fishers test were used.
Result: 44 children were treated for IF at our centre (19942004). 11
infants died before the first month of life - early death IF (EDIF). 33
children required PN for more than 100 days - long-term PN IF (LTIF). 22
had necrotizing enterocolitis, followed by 8 gastroschisis. EDIF patients
had lower birth weight (p = 0.013), gestational age (p = 0.025) and gut
length (p = 0.000) compared to the LTIF patients. Main cause of death in
EDIF patients were withdrawal treatment (n = 8). Liver failure (n = 5) and
sepsis (n = 4) were causes of death in LTIF. LTIF also had an increase in
number of septic episodes prior to death. Of the 33 LTIF, 12 died, 17 were
weaned from PN, 3 were on PN at the time of the study and 1 was
transferred. There were no significant differences in demographics
between the deceased and adapted LTIF. Of the 29 LTIF children with
known outcome, 25 were diagnosed with short bowel syndrome (SBS). 11
patients died, 14 patients were survived and weaned from PN. LTIF with
gut length ,40 cm had less than 20% cummulative survival vesus .70%
in those with gut length .40 cm. From 150 days onward, a rising trend
for TBIL, AST/ALT were seen in those deceased, while a plateau or
resolving trend for those adapted. The deceased had a significantly greater
proportion of patients with an AST .100 U/l, ALT .150 U/l, TBIL
.150 umol/l, ALB ,30 g/l, and Platelet ,100 000. only 2 deceased
LTIF patients reached below 40 kcal/kg of PN use.
Conclusions: Infants who survived more than 100 days, intestinal
length ,40 cms, rising TBIL more than 150 umol/l with rising trans-
aminases, recurrent sepsis and needing .40 kcal/kg of PN were poor
prognostic factors.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
508 NASPGHAN ANNUAL MEETING
48
THE EFFECT OF EATING IODIZED SALT FORTIFIED
BREAKFAST ON THE INTELLIGENCE QUOTIENTS OF
PRIMARY SCHOOL STUDENTS: A RANDOMIZED
DOUBLE BLIND CONTROLLED TRIAL
Maria Cristina M. Gorospe, Melchor Victor G. Frias. Pediatrics, De La
Salle University Medical Center, Dasmarinas, Philippines.
Objective: To determine the effect of iodized salt fortified breakfast on
the IQ scores of primary school children.
Setting: A private, semi urban school.
Study Design: Randomized double blind controlled trial.
Participants: All 230 children, Grades 1 to 3, ages 6 to 9 years old of
the private elementary school were screened. 120 students met the
inclusion criteria, 8 were dropped out. 58 children were randomly
assigned to receive iodized salt and 54 to receive non iodized salt.
Outcome Measures: Improvement in IQ was considered if there was
a noted difference of at least 5 points between pre test and post test. The
participants scholastic performances were also compared.
Statistical Analysis: Statistical analysis was performed using
SPSSPS+ and Epi- Info (version 6.0) software. Characteristics of
patients upon entry to the study were compared using paired t test.
Improvements in IQ and scholastic performances were assessed by
using a 232 table chi square test. Risk ratio at 95% confidence interval
was also calculated. Linear regression and logistic regression were done
in cases of significantly different variables at baseline.
Results: All 4 components of Stanford Binet Intelligence test were
noted to have significantly improved after iodized salt was incorporated
to the breakfasts of school aged children for 2 months. Overall IQ scores
also improved significantly. Significant improvement was noted on
academic grades on the following subjects: English, Filipino, Math,
Civics and MAPE. On the other hand, there was no noted improve-
ment of grades in CBA and science. Academic average significantly
improved after the intervention period.
Conclusion: Children given iodized salt fortified food, resulting to
increased urinary iodine concentrations, have a significant improvement
on the IQ scores and scholastic grades than did the group with no
iodized salt food fortification.
49
GASTROINTESTINAL SYMPTOMS AND
INTESTINAL DISACCHARIDASE ACTIVITIES IN
CHILDREN WITH AUTISM
Rafail I. Kushak, Harland S. Winter, Nathan S. Farber, Timothy M. Buie.
Pediatric GI/Nutrition, Massachusetts General Hospital, Boston, MA.
Autistic children frequently suffer from diarrhea, abdominal pain, food
intolerance and other gastrointestinal problems (GIP) that may
contribute to their behavioral symptoms.
Aim: To determine disaccharidase activities in autistic (AI) and non-
autistic individuals (NAI) with different GIP.
Methods: Specific activities for lactase, sucrase, maltase, and
palatinase were studied in duodenal biopsies from 308 AI and
206 NAI selected for endoscopy based on a suspicion of GIP.
Disaccharidase activities were analyzed for all patients based upon
clinical report or diagnosis of diarrhea, abdominal pain, food sensitivity,
failure to thrive (FTT), constipation, GER, or a combination of
symptoms. Within each diagnostic category, activities for AI and NAI
were determined. Cut off values for lactase, sucrase, maltase, and
palatinase deficiency were correspondingly 15, 25, 100, and 5 U/g
protein. Disaccharidase activities in intestinal biopsies were determined
by Dahlqvist method; protein level was measured by Bradford method.
Results: The frequency of GIP among AI and NAI was: diarrhea, 38 vs
18 %; abdominal pain, 36 vs 59 %; food sensitivity, 14 vs 11%;
constipation, 4 vs. 0.5%; GER, 3 vs. 11%; FTT, 2 vs. 6%; diarrhea with
abdominal pain, 6 vs 5%; diarrhea with food sensitivity, 6 vs 3%; and
abdominal pain with food sensitivity, 4 vs 3%. AI with diarrhea (n = 206)
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
demonstrated significantly lower maltase (P , 0.05) activity than NAI
with diarrhea. Frequency of lactase deficiency in AI with FTT (n = 5) was
significantly higher (80% vs 25%; P , 0.05) than in NAI with FTT and
frequency of palatinase deficiency in AI with diarrhea was significantly
higher than in NAI (28% vs 11%; P , 0.05) with the same GIP. AI and
NAI with other GIP had similar frequency of disaccharidase deficiencies.
Conclusion: Clinical indications for endoscopy based on GIP differ in
AI and NAI. The clinical relevance of maltase deficiency in behavioral
issues of AI with diarrhea needs to be determined. For most AI with
GIP, the frequency of disaccharidase deficiency does not appear to differ
from NAI.
50
EFFECT OF A FORMULA WITH ADAPTED
PROTEIN PROFILE ON INTESTINAL MICROBIOTA
AND GROWTH OF INFANTS
Rochat Florence1, C. A. Brown3, C. Hager1, G. Puccio2, A. Fazzolari-
Nesci , D. Barclay1, F. Haschke4. 1Nestec, Lausanne, Switzerland;
2
2
Neonatologia, Instituto di Ostetricia e Ginecologia dellUniversita,
Palermo, Italy; 3Nestle, Glendale, CA; 4Nestle, Vevey, Switzerland.
The protective effect of the breast-milk may be partly attributed to the
characteristics of the intestinal microbiota provided by this mode of
nutrition. The microbiota of formula-fed infants differs from that of
breast-fed infants. Although the main bifidogenic effect of breast-milk has
been attributed to the non-protein fraction, it is now recognized that it is
due to a complex set of inter-acting factors, among which the type and
level of protein (standard formula 2.5 g; human milk 1.8 g/100 Kcal).
Aims: To evaluate if a formula with an adapted protein profile, enabling
an amino acid profile more similar to human milk (consistent with the
international recommendations) may provide similar growth and
intestinal microbiota compared to human milk.
Subjects and Methods: Non-randomized parallel study in healthy
newborn infants less than 28 d of age (21 breast-fed, 27 bottle-fed). The
bottle-fed infants received ad libitum a NAN formula with adapted
protein profile (1.8 g/100 kcal), and were followed until the age of 120 d.
The breast-fed infants were exclusively breast-fed from birth to 60 6 3 d
of age. Anthropometric data and fecal bacteria counts (Bifidobacteria,
Lactobacilli and Enterobacteria; evaluated by FISH and/or by plating
techniques) were measured.
Results: The test formula with adapted protein profile provided satis-
factory growth up to 120 d compared to the Euro-Growth data, and
favored the bifidobacteria population to reach a level similar to that of
the breast-fed infants at 60d. Fecal bifidobacteria counts in bottled-fed
vs. breast-fed infants obtained by FISH and culture plates were 8.6 6
0.6 vs. 8.8 6 0.8 (p = 0.33) and 7.2 6 3.3 vs. 7.8 6 3.2 log cfu/g of
feces (p = 0.53), respectively. Likewise, the other bacterial populations
were not affected by the mode of feeding.
Conclusion: Infants fed a starter formula with adapted protein profile
had normal growth and intestinal microbiota similar to that of breast-fed
infants.
51
ANTHROPOMETRIC NUTRITIONAL STATUS
IN CHILDREN HIV POSITIVE WITH
VERTICAL TRANSMISSION
Carlos A. Velasco, Pio Lopez, Leydi J. Contreras. GASTROHNUP,
University of Valle, Cali, Colombia.
Introduction: The anthropometric measurement is very important in
order to observe the deterioration of the nutritional status of HIV
positive children.
Objective: To determine the anthropometric nutritional status of HIV
positive children with vertical trnasmission from Hospital Universitario
del Valle in Cali, Colombia.
Materials and Methods: Descriptive study of transversal section on
HIV positive children with vertical transmission of the HUV in Cali,
 NASPGHAN ANNUAL MEETING
Colombia. Data regarding identification, age, gender, stage, viral
burden and CD4 percentage, weight and height were taken from the
clinical record. According to the charts of the NCHS of the USA,
children wre classified as global malnutrition (MNT) when their
deficit for weight/age was .10%; chronic MNT when their deficit for
height/age was .5% and acute MNT when their deficit weight/height
was .10%. The data is presented as average and standard deviation.
Results: 43 children between 9 months and 12 years old (6 years 4
months 6 2 years 8 months) were included, 22 boys. According to the
stage of the illness were, in frequency order, 13 C3 (30.2%); 5 A2 and
B1, respectively; 4 A1, 4 B2 and 4 C, respectively; 3 C2 and 1 A3 and
B3, respectively. Their viral burden were between 49 and 971000
(115270 6 253787) and their percentage of CD4 (n = 40) between 7 and
1100% (58.05 6 170.75%). The weight was between 6 and 31 kg
(17.5 6 5.8 kg) and the height between 65 and 138.4 cm. (107.4 6
26.4 cm.). Thirty one (72%) showed global MNT (219.72 6 12.68),
1 showed a severe global MNT with a deficit .40%; 29 (67%) showed
chronic MNT (27.32 6 4.98), 1 showed severe chronic MNT with
a deficit .15% and 15 (35%) showed acute MNT (25.96 6 8.66).
Conclusions: HIV positive children with vertical transmission of the
Pediatric Clinic of HIV/AIDS at the HUV in Cali, Colombia, according
to the analyzed parameter, namely weigth for the age, height for age
and weight for height, show 72% of global MNT, 67% chronic MNT
and 35% acute MNT, which may become this small children group
highly vulnerable, reason why the planning of a timely and adequate
nutritional support for their nutritional recovery is fundamental.
52*
ELEVATED VITAMIN B12 LEVELS IN CHILDREN
WITH SHORT BOWEL SYNDROME AND
INTESTINAL DYSMOTILITY
L. Mattis , R. Young2, J. Hampsey1, D. Antonson2, J. Vanderhoof 2,
1
J. Saavedra1. 1Pediatrics, Johns Hopkins Hospital, Baltimore, MD;
2
Pediatrics, University of Nebraska, Omaha, NE.
Vitamin B12 deficiency in patients with intestinal disease has been
attributed to malabsorption, ileal resection, and small bowel bacterial
overgrowth (SBBO). To the best of our knowledge, elevated serum
vitamin B12 (VB12) levels in children with intestinal disease have not
previously been reported. We report the incidence of elevated VB12
levels in this population.
Methods: Laboratory and demographic data were collected for patients
with short bowel syndrome (SBS) and intestinal dysmotility (ID)
followed in the clinics at 2 institutions. Those who received tube
feedings or a combination of parenteral nutrition (PN) and enteral
nutrition (EN) for .3 months and whose VB12 levels were routinely
monitored were included.
Results: A total of 139 subjects were identified and medical records
reviewed. 96 instances of elevated VB12 levels (.900 pg/ml) were
identified in 46 (33%) of 139 subjects; 20 instances of low VB12 levels
(,150 pg/ml) were identified in only 7(5%). Elevated VB12 levels ranged
from 903.2000 pg/ml (limit of detection). Age range at initial high
VB12 level: 3-286 months; mean: 60 months. Primary diagnoses: SBS
(33), gastroschisis (4), pseudo-obstruction (5), IBD (3), microvillus
inclusion disease/SB transplant (1). 33(72%) had partial or complete ileal
resection; 31(67%) had resection of ileocecal valve (ICV). 32(33%) of
elevated VB12 levels were found in 15 subjects while receiving no PN
and no VB12 enterally beyond that in commercial formulas.
Conclusions: Most children with SBS and ID receiving adequate
nutrition have normal VB12 levels. Elevated VB12 levels were
significantly more frequent (p , 0.05) than low levels, even in cases of
ileal and ICV resection. These findings are contrary to the belief that
VB12 deficiency is common in intestinal disease. Given that the source of
VB12 (or its analogues) in humans is only dietary intake or bacterial
synthesis in the gut lumen, we speculate that synthesis of VB12 from
SBBO and absorption in the SB is responsible for the frequency of
elevated VB12 levels in this population.
509
53*
KINETIC ANALYSIS OF STARCH DIGESTION
REVEALS MAJOR ROLE OF SUCRASE-ISOMALTASE
AND INHIBITION OF MALTASE-GLUCOAMYLASE
BY MALTOTRIOSE
Buford L. Nichols1, Roberto Quezada-Calvillo1,2, Claudia Robayo1,
Stephen Avery1, Bridget Adams3, Robert Baker3, Susan Baker3, Ursi
Lugenbuhl4, Edwin Sterchi4. 1Pediatrics, Baylor College of Medicine,
Houston, TX; 2CIEP-FCQ, UASLP, San Luis Potosi, Mexico;
3
Pediatrics, State University of New York, Buffalo, NY; 4IMB,
University of Bern, Bern, Switzerland.
Food starch digestion is a complex process. Glucose oligomers (GO)
resulting from digestion by amylases, are terminally digested to free
glucose by intestinal Maltase-Glucoamylase (MGAM) and Sucrase-
Isomaltase (SI).
Aims: 1. To define the relative roles of MGAM and SI in terminal starch
digestion using kinetic models with maltose, maltotriose, and mixed
GO (Polycose) as substrates; 2. To compare the model to experimental
data using immunoisolated human MGAM and SI activities. MGAM
and SI activities from pooled Nonidet P-40/ DOC solubilized human
duodenal biopsy homogenates were immunoisolated with monoclonal
antibodies on protein A beads. Protein purification was assessed by
Western blots. Enzyme activities against maltose, maltotriose and GO
(Polycose) were assayed on the beads by the TGO method. Mathe-
matical models were constructed using Michaelis-Menten equations.
MGAM and SI account for .90% of biopsy maltase, maltotriase and
GOase activities. MGAM contributed only 36 % of maltase and 22%
of GOase. Km for maltose was higher for SI (40 mM) than for MGAM
(3.7 mM); however, apparent Vmax for SI was .2 X MGAM. This
difference was visualized on Western blots. Maltotriose caused
substrate inhibition of MGAM with Km of 20 and Ki of 1.8 mM, while
SI had a Km of 22 mM and no inhibition. MGAM activities for GO
resembled those observed with Maltotriose with respect to substrate
inhibition. Kinetic modeling of the activities with maltose and
maltotriose correlated with experimental data from isolated MGAM
and SI. Modeling of GO hydrolysis correlated only at low concen-
trations because other inhibitions occur at high concentrations.
Conclusions: 1. .90% of GO digestion is by MGAM and SI. 2. Kinetic
models prove that SI accounts for .66% of GO digestion at con-
centrations .10 mM. 3. Maltotriose at concentration .6 mM causes
substrate inhibition of MGAM.
54*
WHEY-BASED PEPTIDE DIET ALTERS
GASTROINTESTINAL IMMUNITY AND INFLAMMATION
IN PIGLETS WITH A COMPROMISED
GASTROINTESTINAL TRACT
Kelly A. Tappenden, Bianca A. Maples, Brian M. Chung. Nutr Sci,
University of Illinois, Urbana, IL.
Providing nutrition support to pediatric patients with a compromised
gastrointestinal tract (GI) is clinically challenging. While enteral
nutrients are preferred, the optimal nutrient composition of formulas
is evolving. Two proteins currently used in commercial formulas are
whey and casein, which are known to differ in gastric emptying rate and
antioxidant amino acid precursors. We hypothesized, in a pediatric
model of intestinal injury, that provision of a whey hydrolysate diet
would enhance GI immunity, while reducing inflammation, when
compared to diets containing either intact proteins or casein hydroly-
sate. Shortly following weaning, piglets (8.55 6 0.11 kg, n = 20)
underwent gastrostomy placement and banding of the superior
mesenteric artery to restrict blood flow to baseline fasting levels. For
7 days following surgery, piglets received continuous enteral infusions
with isoenergetic, isonitrogenous formulas containing: 1) intact proteins
(POLY); 2) whey-hydrolysate with a low amount (,1 %) of free AA
(WHEY), or 3) casein-hydrolysate with a high amount (40%) of free AA
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
510 NASPGHAN ANNUAL MEETING
(CASEIN). Body weight did not differ between groups at any time.
Compared to CASEIN, WHEY reduced colonic enterocyte sloughing
(p = 0.0013), duodenal (p = 0.017) and colonic (p = 0.002) edema, and
jejunal lacteal dilation (p = 0.005). White blood cell count, plasma
C-reactive protein, and intestinal glutathione concentration were not
altered by dietary treatment; however, liver glutathione concentration
tended (p = 0.088) to be highest in the WHEY group. Compared to
CASEIN, WHEY increased (p = 0.019) malondialdehyde concentration
in the jejunum. Similarly, plasma interleukin (IL)-1b (p = 0.014) and
interferon-g (p = 0.020) were increased in WHEY versus CASEIN,
however IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor-a were
not altered by diet. In summary, these results indicate that provision of
a whey-based peptide diet augments various aspects of GI immunity and
inflammation. The protein composition of enteral formulas provided
during compromised intestinal function requires further study.
55
NPC - LINKS TO DYSLIPIDEMIA BUT NOT
CARDIOVASCULAR RISK
Diana Volpert1, Tilla S. Worgall2, Marc C. Patterson1, Ira A. Tabas3,
Richard J. Deckelbaum1. 1 Pediatrics, New York-Presbyterian,
New-York, NY; 2Pathology, New York-Presbyterian, New-York,
NY; 3Medicine, New York-Presbyterian, New-York, NY.
Following our previous studies showing increased cardiovascular
disease (CVD) risk and dyslipidemia in Niemann-Pick A and B carriers
we assessed if CVD and dyslipidemia are increased in carriers and
affected patients for Niemann-Pick type C (NPC) compared to the
normal population. CVD in parents (n = 33) and first degree relatives
of NPC patients (n = 56) was assessed using a validated CVD
questionnaire. Fasting plasma lipoprotein profiles (total cholesterol and
triglyceride (TG), LDL-cholesterol and HDL-cholesterol levels) were
assessed in 58 individuals (40 heterozygous, 15 male, 25 female; and 17
homozygous, 8 female, 9 male). Of 33 heterozygous only 1 had history
of stroke and none had history of myocardial infarct (MI). Of 56
grandparents 7 had a history of stroke and 9 had a history of MI, but
only 1 had a history of premature MI (age 54). In heterozygote carriers
mean total cholesterol levels and mean LDL-C levels were abnormally
high (.200 mg/dl for cholesterol and .130 mg/dl for LDL-C).
Surprisingly 18/40 heterozygous had abnormally elevated TG levels for
this age group (.150 mg/dl). HDL-C levels were low (,40 mg/dl) in
6/40 heterozygote carriers No correlation was found between BMI and
TG levels in the heterozygous subjects. In the homozygous NPC patients
mean total cholesterol and LDL-C levels were normal for age. HDL-C
was low (,40 mg/dl) in 53% and 47% had high TG for age (.130 mg/dl).
These results indicate that NPC affected patients and carriers have
abnormal lipid profiles, but despite dyslipidemia there is no evidence
for increased cardiovascular risk in NPC carriers. We hypothesize that
NPC genotypes link to abnormalities in TG and/or HDL metabolism.
56
CHARACTERIZATION OF THE CLINICAL SPECTRA
AMONG CHILDREN REFERRED TO A
MULTIDISCIPLINARY FEEDING AND SWALLOWING
DISORDERS PROGRAM
A. Scheimann1, R. Carvalho1, J. Biscoe2, P. Wang2, R. Katz1, E.
Reinhardt3, C. Gulotta2. 1Pediatrics, Johns Hopkins School of
Medicine, Baltimore, MD; 2Behavioral Psychology, Kennedy Krieger
Institute (KKI), Baltimore, MD; 3Nursing, Kennedy Krieger Institute
(KKI), Baltimore, MD.
Feeding problems are commonly reported in infants and children. As
feeding requires integration of multisystem skills, underlying medical
issues may impact upon feeding.
Methods: Retrospective chart review of all patients (pts) seen in the
KKI Feeding and Swallowing Disorders Clinic between 19982003.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Children admitted to the feeding program prior to 1998 were excluded.
Data collected included birth history (hx), family hx, diet hx, past
medical hx, diagnostic evaluation and physical exam findings.
Results: Data was collected on 190 pts (54% male). The mean age at
the time of feeding evaluation was 39.4(628) months. The mean height
z-score was 21.62(61.5); mean weight z-score was 21.35(61.3). 54%
of pts had foods excluded from their diet. 51.7% of pts were on
combined tube & oral feeds; 12.4% of pts received only tube feeds.
The most commonly used tube feedings included pediassure (45%),
peptamen junior (8.7%), neocate (4.3%) and neocate 1+ (3.6%). 43% of
pts were on an H2-blocker; 26.5% of pts were on a proton pump
inhibitor. 60.2% of pts underwent endoscopic evaluation. 61.7% of pts
underwent a videoflouroscopic swallow study. The table below lists
underlying medical conditions.
Conclusion: Underlying medical problems were reported in the
majority of pts with feeding difficulties.
Underlying medical problems
Diagnosis % of patients
Gastroesophageal Reflux Disease 29.6
Developmental Delay 21.4
Allergic Symptoms 11.3
Lung Disease 10.4
Congenital GI abnormality 6.7
Congenital Heart Disease 3.9
Genetic Disease 3.1
Motility Disorder 1.9
Behavioral Disorder 1.7
ENT 1.7
57
CLINICAL PRESENTATION OF CHILDREN WITH FOOD
ALLERGIES IN A FEEDING AND SWALLOWING
DISORDERS PROGRAM
A. O. Scheimann1, R. Carvalho1, C. Gulotta2, J. Biscoe2, P. Wang2, R.
Wood1. 1Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD;
2
Behavioral Psychology, Kennedy Krieger Institute (KKI), Baltimore,
MD.
Feeding problems and allergies are commonly seen in children.
Minimal published data exists regarding allergic symptoms in children
with feeding problems.
Methods: Retrospective chart review of children seen in the Feeding
and Swallowing Disorders Clinic between 19982003. Children
admitted to the feeding program prior to 1998 were excluded. Data
collected included birth history (hx), past medical hx, family hx, diet
hx, physical findings and diagnostic evaluation (endoscopy and
allergy testing). Students t-test was used to compare groups.
Results: A total of 27 (13.4%) patients (pts) with allergies (A) were
identified out of 201 pts seen in the Feeding and Swallowing clinic.
Mean gestational age (GA) for A was 34.1 weeks (w) (67) vs. 35.1 w
(66) for other feeding pts (p , 0.0001). Mean age of onset of food
refusal was 9.1 months (m) (611) for A vs. 6.7 m (6 9.6) for other pts
(p = 0.01). Mean age at the time of clinic evaluation was 46.1 m (631)
for A vs. 39.44 m (628) for other feeding pts (p , 0.0001). 2% of pts
with A had evidence of eczema on physical examination vs. 7% of the
other pts seen in the feeding clinic. Food allergy was considered in
differential diagnosis for 31.8% of pts seen in clinic. 26.8% of pts seen
in clinic had foods eliminated from their oral diet. Commonly
eliminated foods included egg (9.6%), milk (18.4%), peanut (7.4%),
soy (13.2%), and wheat (7.4%). Allergic reactions reported included
urticaria (6%), eczema (17%), vomiting (54%), and diarrhea (23%).
7.96% of pts seen in the feeding clinic were receiving an amino-acid
based formula; 10.4% of pts seen in the feeding clinic were receiving
 NASPGHAN ANNUAL MEETING 511

a hydrolysate. 6.8% of clinic pts had recently received an inhaled patients, we offered LAGB to MO adolescents at our institution. The
steroid; 4.3% of pts had recently received oral steroids. RAST testing goal of this study is to report our early results in these adolescents.
was obtained in 25.37% of pts seen in clinic. Endoscopy was performed Hypothesis: LAGB is a safe and effective procedure in both MO adults
in 61.7% of pts. and adolescent.
Conclusion: Allergies are commonly seen in feeding pts. Pts appear to Methods/Results: Between December 2001 and March 2005, 10
present at an earlier GA with later onset of food refusal. adolescents and 506 adults meeting NIH bariatric criteria underwent
LAGB. Outcome measures including BMI (Kg/m2) (body mass index),
% EWL (excess weight loss), operative time, length of stay and
58* complications are reported as mean 6 SD and tabulated below. Of note,
HIGH PREVALENCE OF OBESITY IN HOMELESS no mortality nor nutritional complications were seen.
BALTIMORE CHILDREN AND THEIR CAREGIVERS Conclusions: LAGB as a treatment for MO is an effective and safe
Kathleen B. Schwarz1, Beth Garrett1, Jenifer Hampsey1, Douglas weight loss procedure with short operative time, brief hospital stay and
Thompson2. 1Pediatrics, Johns Hopkins University School of Medicine, no mortality in both patient populations. The reoperative rate for pouch
Baltimore, MD; 2Maryland Medical Research Institute, Baltimore, MD. enlargement is however higher in adolescent patients. To reduce the
incidence of pouch enlargement, we have incorporated new post-
operative management approaches into the treatment protocol for our
At the present time obesity is one of the most pressing public health ongoing FDA-sponsored trial of LAGB in MO adolescents.
issues in America. We therefore performed simple anthropometric
assessments of homeless Baltimore children 218 years of age and their Adolescent Adult p value
caregivers to determine the prevalence of obesity in this population and
to assess demographic correlates of obesity. Sixty-eight children and 40 Age (yrs) 18 (1620) 41 (2165) 0.6
caregivers were enrolled in the study. Child BMI was related to caregiver Preop BMI 49 6 8 47 6 8 0.8
BMI and correlates of normal child BMI (below the age-specific 85th Operative time (min) 55 6 22 66 6 26 0.8
percentile of BMI) vs high BMI were assessed. For adults BMI was Lenght of stay (hs) 12 6 6 22 6 25 0.8
classified as normal (18.524.9), 2529.9 (overweight) and 30 or greater
Follow up BMI post op %EWL BMI post op %EWL
(obese).
Results: Twemty-five (42%) of the children had a high BMI. The 3 months 42 6 9 27 6 19 42 6 7 18 6 11 0.7
average adult BMI was in the obese range (33.14, range 29.9836.31) 6 months 36 6 11 51 6 32 39 6 8 31 6 16 0.5
and none of the caregivers were in the normal range. Child BMI was 12 months 37 6 10 50 6 26 37 6 8 40 6 23 0.8
positively correlated with caregiver BMI (r = 0.43), a significant 18 months 34 6 7 57 6 23 37 6 6 39 6 19 0.6
association even after accounting for the clustering of children within Pouch 3 (30%) 58 (11%) 0.1
caregivers (p = 0.0002). The association of selected caregiver enlargement 2 (20%) 9 (2%) 0.004
characteristics with classification of child BMI is shown in the table (PE) reoperations reoperations
below. While none of these caregiver characteristics was significantly
associated with the classification of child BMI, there were trends toward
children with high BMI scores having less educated heavier mothers.
Conclusion: Public health programs for the ~14 million homeless adults 60
and children in the US should focus on obesity prevention and treatment.
WHERE DOES THE PAKISTANI PEDIATRIC
POPULATION LIE ON NCHS GROWTH
Caregiver Children with Children with CENTILE CHARTS
characteristics normal BMI high BMI Sina Aziz , Deneize A. Puri2, Kehkashan Z. Hossain3, Faiza Hussain4,
1

Syed A. Naqvi5, Adeeb H. Rizvi6. 1Pediatrics, SIUT, DMC, Karachi,

Did not finish high school 56% 42% Pakistan; 2Nutrition, SIUT, DMC, Karachi, Pakistan; 3Nutrition, SIUT,
Income ,$10K 59% 58% DMC, Karachi, Pakistan; 4Nutrition, SIUT, DMC, Karachi, Pakistan;
5
Responsible for .2 children 59% 42% SIUT, DMC, Karachi, Pakistan; 6SIUT, DMC, Karachi, Pakistan.
HCV positive 29% 17%
BMI 31.1 (610.0) 35.0 (69.3) Introduction: Hospitals government and private in Pakistan are in need
Weight (kg) 84.0 (625.8) 96.1 (624.6) for standard growth charts for children. These charts are essential to
Height (cm) 165.2 (67.7) 166.9 (67.9) document that the child is appropriate for height and weight in relation
Ever used injection drugs 12% 9% to age. Presently we are using charts not developed in Pakistan.
Depression score 6.1 (63.6) 6.7 (65.0) Institutions are using NCHS or UK charts. Genetic factors and nutrition
influence height and weight of children. Hence, we planned this study
for Pakistani children as height and weight plotted on NCHS centiles
59* may not be a true reflection of our pediatric population.
Objective: to measure height and weight of Pakistani school going
LESSONS FROM THE INITIAL US EXPERIENCE children. To document where Pakistani pediatric population plot on
IN GASTRIC BANDING FOR THE TREATMENT OF NCHS charts. Children were of different ethnic and middle socio-
ADOLESCENT MORBID OBESITY economic background.
Aixuan Holterman1, Veronica Gorodner2, Santiago Horgan2, Allen Methodology: Population based cross-sectional epidemiological,
Browne1, Mark Holterman1, Nancy Browne1, Micheal Batista2, multicenter study (multiple schools).
Frederico Moser2. 1Pediatric Surgery, U of Illinois at Chicago, Setting: Government and private schools of Karachi.
Chicago, IL; 2General surgery/Minimally Invasive Surgery, U of Subjects: Healthy school-going children 2 to 18 years.
Illinois at Chicago, Chicago, IL. Duration of the Study: Three months.
Sample Size: 2,245.
Background: Morbid obesity (MO) affect .15% of adolescents in the Outcome Measures: Anthropometric measurement (height and
US and its incidence is on the rise. Laparoscopic adjustable gastric weight).
banding (LAGB) is a restrictive bariatric surgical procedure which has Results: P5, P25 and P50 centiles for height and weight of Pakistani
been shown to provide weight loss and improve obesity-related comor- children were below NCHS. However, P95 for boys and girls weight
bidities in the adults. After refining the surgical technique in our adult and height did not differ markedly in Pakistani and NCHS centiles.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

512 NASPGHAN ANNUAL MEETING
Conclusion: Height and weight of Pakistani children is below NCHS
centile.Children plotting near P95 NCHS, indicates that obesity may be
a serious concern, further studies are required. This pilot study indicates
the need for development of centile charts for Pakistani pediatric
population. We are in process of doing further such a study, with greater
sample size, nation wide and of children from all socio-economic and
ethnic background.
Key Words: height, weight, centile, Pakistani children, NCHS.
61*
ARM VS. WEIGHT AND HEIGHT INDEXES IN THE
DIAGNOSIS OF THE NUTRITIONAL STATUS IN CHILDREN
AND ADOLESCENTS WITH CHRONIC LIVER DISEASE
Erika Hurtado-Lopez1,2, Alfredo Larrosa-Haro1,2, Rocio Macias-
Rosales1, Enrique Romero-Velarde2, Carmen Bojorquez-Ramos1.
1
Gastroenterology and Nutrition, Hospital de Pediatria, Guadalajara,
Mexico; 2Instituto de Nutricion Humana, Universidad de Guadalajara,
Guadalajara, Mexico.
Introduction: Anthropometric assessment of the nutritional status may
be inaccurate in children with advanced chronic liver disease (CLD) due
to liver and spleen enlargement, ascitis and distal edema. Arm
anthropometrics may be a diagnostic alternative in these patients.
Objective: To compare arm vs. conventional anthropometric indexes in
the nutritional diagnosis of children and adolescents with CLD.
Methods: Design. Cross-sectional. Setting. A referral pediatric hospital
n = 79 Inclusion. Age 2194 months, diagnosis of CLD. Variables:
Liver function tests, pediatric end stage liver disease score (PELD);
anthropometrical indexes: weight for height, height for age, mid arm
circumference, tricipital skinfold; total, muscular and fat arm areas.
Methods Conventional anthropometric technique and instruments,
criteria of normality . or ,2DE, NCHS reference pattern. Statistics
Frequencies, %, chi-square, Fisher test, means, SD, Student t.
Results: 54% females, mean age 72.6 months. Diagnosis: Biliary
atresia 27.8%, idiopatic CLD 12.7%, Alagille syndrome 8.9%. Liver
damage: Infants had higher PELD scores, 60% had esophageal varices,
58% liver fibrosis and 28% cirrhosis.
Nutritional Status: 24 to 62% had growth impairment, being infants
and preschooler the most affected groups. Weight for height ,22SD
was identified in 8 to 20% age groups. Arm indexes identified cases
,22DE from 12 to 85%, being infants and preschoolers the most
frequently affected. Arm indexes significantly identified more cases
,22DE in all age groups than weight for height.
Conclusions: Growth impairment was identified in all age groups. Arm
indexes identified more cases ,22 DE than weight for height and
weight for age. Arm indexes may become a better anthropometric tool
for the diagnosis of nutritional status in children with CLD and may
predict better the degree of liver damage than indexes that weight and
height indexes.
62
METHODOLOGICAL ALGORITHM FOR
PLANNING NUTRITIONAL TREATMENT FOR
HOSPITALIZED CHILDREN IN A PEDIATRIC NUTRITION
UNIT WITH LIMITED RESOURCES
Rafael J. Garcia1, Eduardo Sagaro. Gonzalez1, Ronoel Penalver.
Valdes2. 1Servicio de Gastroenterology, Hospital Universitario Juan
Manuel Marquez, Habana, Cuba; 2Medico General Basico, Policlinico
Docente de Calabazar, Habana, Cuba.
Background: In countries with limited resources, enteral nutrition in
undernourished hospitalized children has a lower risk of sepsis and is
most economical.
Objective: We report an approach that has been tested for four years
and permits decisions resulting in maximizing limited resources.
Methods: A total of 367 children with compromised nutritional status,
ages three months to 16 years were admitted to the Nutrition Unit.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Following informed consent, anthropometric measurements (weight,
length or height, mid-arm circumference and triceps skinfold thickness)
and physiological variables (hemoglobin, mean corpuscular hemoglo-
bin concentration, blood sugar, total protein and albumin) were obtained
at admission and discharge. Clinical, anthropometric and biochemical
assessment of the nutritional status were made by the Nutrition Team to
determine the type of feeding and formula that would be used for
nutritional support. Weekly clinical and anthropometric assessments
were made up to the time of discharge.
Results: The largest groups of patients were admitted with digestive
diseases (23.5%) or cancer (18,6%). The variables with the greatest
significant difference were weight and triceps skinfold thickness (p ,
0.001). One to 5 year old children had the highest increase in weight and
height (mean differences value 3.15 kg and 2.48 cm). Significant
differences were also found in hemoglobin in children 1 to 6 years and
in albumin in children ages 6 to 15 years. Polymeric formulas were used in
43% of patients; 13% received semi-elemental formula. The most common
adverse effects were refusal of formula (13%) and vomiting (10%).
Conclusions: A multidisciplinary approach along with anthropometric
measurements, hemoglobin and albumin is beneficial in allocating
valuable resources in an hospital environment with greatly limited
resources.
PLENARY SESSION I
FRIDAY, OCTOBER 21, 2005
9:00 AM 10:00 AM
63
TEMPORAL-SPATIAL REGULATION OF
APOPTOSIS IN EXPERIMENTAL BILIARY ATRESIA
Nissa I. Erickson, Pranavkumar Shivakumar, Gregg Sabla, Sujit
Mohanty, Jorge A. Bezerra. Gastroenterology, Hepatology, and Nutri-
tion, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH.
Background: Biliary atresia results from a fibrosing cholangitis that
leads to bile duct obstruction. Recent studies using a mouse model of
rhesus rotavirus (RRV)-induced biliary atresia demonstrate increased
TNF-alpha levels in liver. Based on the established role of TNF-alpha in
apoptosis, we hypothesized that RRV triggers bile duct apoptosis in
experimental biliary atresia.
Methods: Balb/c mice were inoculated with RRV or saline on day 1 of
life, and the liver and EHBD were studied at days 218. Hepatic
mononuclear cells were isolated for gene expression analysis by real-
time PCR. TUNEL and active caspase-3 assays were performed on
paraffin-embedded liver and EHBD sections, while mRNA expression
of caspases was assessed using snap-frozen samples.
Results: RRV infection resulted in obstruction of the EHBD after day 6.
At this time, there was a marked increase in mRNA expression of
FasL, perforin, and granzyme B in hepatic mononuclear cells compared
to controls (p , 0.02). From days 618, intrahepatic portal tracts
consistently showed higher numbers of TUNEL-positive cells than
controls (p , 0.02). To investigate temporal dynamics of apoptosis in
the EHBD, we counted TUNEL-positive cells at days 214. TUNEL
labeling was localized to duct epithelial cells at day 4 and peaked
in cells occluding the duct lumen at day 5 (mean 6 SD: 20.9 6 4.3 vs.
0.53 6 0.29; p , 0.01). The active caspase-3 assay confirmed these
results, showing maximal cell staining at day 5. mRNA expression of
caspases-1 and -4 was higher in both liver and EHBD, with fold changes
ranging from 2.07.4.
Conclusions: RRV challenge induces: 1) the expression of pro-
apoptotic molecules in hepatic mononuclear cells, 2) infiltration of
portal tracts with TUNEL-labeled cells, and 3) a peak in TUNEL and
active caspase-3 labeling in the EHBD at the time of obstruction. These
results support a pathogenic role for apoptosis in experimental biliary
atresia.
 NASPGHAN ANNUAL MEETING
64
THE POPULATION PREVALENCE OF FATTY LIVER
Jeffrey B. Schwimmer, Reena Deutsch, Joel Lavine, Cynthia Behling.
Pediatrics, UCSD, San Diego, CA.
Background and Aim: Fatty Liver disease is increasingly diagnosed in
children but the prevalence remains unknown. To date, the prevalence
has been estimated based upon surrogate measures such as liver
chemistry and/or ultrasound. The aim of this study is to determine the
prevalence of fatty liver as diagnosed by histology in a population-based
sample of children free from clinical selection bias.
Methods: Study subjects were all children (n = 954) age 2 to 19
(mean = 15 y) who died of external causes (accident, homicide, suicide)
within 48 hours of injury and underwent an autopsy by the San Diego
County Medical Examiner from 1993 to 2003. The racial and ethnic
distribution was identical to that of San Diego County: Asian 8%,
Black 12%, Hispanic 35%, Native American Indian 1%, White 44%.
We collected clinical data and reviewed liver biopsies. Fatty liver was
defined as greater than or equal to 5% of hepatocytes with macro-
vesicular steatosis.
Results: Fatty liver was present in 14% of study subjects. Fatty liver
prevalence increased significantly with age ranging from 1% for ages 2
4 up to 15% for ages 1519. Boys were 67% more likely than girls to
have fatty liver. In addition race and ethnicity influenced fatty liver;
fatty liver was significantly more prevalent in Hispanics (19%) than
non-Hispanic white children (10%) and significantly less common in
children of black race (5%). The highest rate of fatty liver was seen in
obese children (35%). The overall prevalence of fatty liver in the
County of San Diego adjusted for age and gender was 8.1% which
represents an estimated 62,827 children age 219.
Conclusion: This population-based study of liver histology demon-
strates that fatty liver is the most common liver abnormality in children
age 219. The presence of macrovesicular hepatic steatosis in 1 out of
every 12 children has important ramifications for the long-term health
of children and young adults. The major risk factors for fatty liver are
male gender, Hispanic ethnicity, and obesity. These findings should
guide efforts to elucidate the genetic and environmental factors
underlying fatty liver in high risk populations.
65
ZEBRAFISH VPS33B, AN ORTHOLOG OF THE GENE
RESPONSIBLE FOR HUMAN ARTHROGRYPOSIS-RENAL
DYSFUNCTION-CHOLESTASIS SYNDROME, REGULATES
BILIARY DEVELOPMENT DOWNSTREAM OF THE ONECUT
TRANSCRIPTION FACTOR HNF-6
Randolph P. Matthews1,2, Nicolas Plumb-Rudewiez3, Kristin Lorent4,
Paul Gissen5, Colin Johnson5, Frederic Lemaigre3, Michael Pack4,6.
1
Division of GI and Nutrition, The Childrens Hospital of Philadelphia,
Philadelphia, PA; 2Department of Pediatrics, University of Pennsylva-
nia School of Medicine, Philadelphia, PA; 3Hormone and Metabolic
Research Unit, Catholic University of Louvain, Brussels, Belgium;
4
Department of Medicine, University of Pennsylvania School of
Medicine, Philadelphia, PA; 5Section of Medical and Molecular
Genetics, University of Birmingham, Birmingham, United Kingdom;
6
Department of Cell & Developmental Biology, University of
Pennsylvania School of Medicine, Philadelphia, PA.
Arthrogryposis-renal dysfunction-cholestasis syndrome (ARC) is a rare
cause of cholestasis in infants. Causative mutations in vps33b, a gene
that encodes a Class C vacuolar sorting protein, have recently been
reported in ARC patients. We have identified a zebrafish vps33b
ortholog that is expressed in developing liver and intestine. Knockdown
of vps33b causes bile duct paucity and impairs intestinal lipid absorp-
tion, thus phenocopying digestive defects characteristic of ARC. In
contrast, neither motor axon nor kidney epithelial defects typically seen
in ARC could be identified in vps33b deficient larvae. Biliary defects in
vps33b deficient zebrafish larvae closely resemble the bile duct paucity
513
associated with knockdown of the onecut transcription factor, hnf-6.
Consistent with this, reduced vps33b expression was evident in hnf-6
deficient larvae and in larvae with mutation of vhnf1, a downstream
target of hnf-6. Zebrafish vhnf1, but not hnf6, increases vps33b expres-
sion in zebrafish embryos and in mammalian liver cells. Electrophoretic
mobility shift assays suggest that this regulation occurs through direct
binding of vhnf1 to the vps33b promoter. These findings identify
vps33b as a novel downstream target gene of the hnf-6/vhnf1 pathway
that regulates bile duct development in zebrafish. Further, they
show that tissue-specific roles for genes that regulate trafficking of
intracellular proteins have been modified during vertebrate evolution.
POSTER SESSION II
FRIDAY, OCTOBER 21, 2005
12:15 PM 2:15 PM
Basic Science
66
A NOVEL PRIMATE MODEL FOR HELICOBACTER PYLORI
PATHOGENESIS AND VACCINE DEVELOPMENT
Sundeep Arora1, John Nedrud2, Steven Czinn1,2. 1Pediatric GI,
Rainbow B & C Hosp, Cleveland, OH; 2Pathology, Case Western
Reserve University, Cleveland, OH.
Introduction: Helicobacter pylori, a gram-negative spiral bacterium,
infects half the worlds population and has been associated with peptic
ulcers and gastric cancers. Many non-human primates are naturally
colonized with helicobacter species and we sought to characterize
gastric bacterial infection of baboons.
Materials and Methods: Baboons at the Oklahoma University Health
Sciences Center are maintained in three groups. 1) Free living animals
in half-acre corrals housing 60 to 70 animals. 2) Specific pathogen free
(SPF) animals,hand reared from birth. These animals are regularly
tested for simian viruses and animals that test positive are removed to
traditional caging (SPF dropout animals) and are exposed to corral
baboons. 46 animals from each group were endoscoped and biopsies
were obtained for culture, histopathology and Steiner (silver) staining.
Blood was also obtained.
Results: 1) SPF animals had a normal appearing mucosa on endoscopy.
The SPF dropout group was noted to have erythematous gastric mucosa
with thickened pyloric folds. The corral baboons had a similar
appearance to the SPF dropout group and 2 of 5 animals exhibited
ulcers in the pyloric region. 2) The biopsies from all animals failed to
grow out any bacteria with characteristics typical of H. pylori (colony
morphology, urease,catalase,oxidase positivity), although occasionally
some biopsies did yield unidentified colonies. 3) Examination of steiner
stained sections revealed that the two non-SPF groups were moderately
to heavily colonized with a spiral bacteria consistent with H. heilmanii
or a related organism. 4) Histopathology of SPF animals was consistent
with gross endoscopic appearance (normal healthy mucosa). The SPF
dropout animals had minimal to very mild inflammation. The corral
animals exhibited moderate to severe patchy infiltration of mononuclear
cells, PMNs and small lymphocyte aggregates.
Conclusions: The results suggest that the baboon may be an excellent
model to study H. pylori pathogenesis. Efforts are also underway to
infect the SPF animals with H. pylori.
67
RBM19 IS EXPRESSED IN THE STEM CELL
COMPARTMENT OF THE INTESTINAL EPITHELIUM
James A. Lorenzen1, Benedatta Bonacci1, Rachel E. Palmer3, Clive
Wells2, Jian Zhang1, Daniel A. Haber3, Allan M. Goldstein4, Alan M.
Mayer1. 1Pediatrics/Gastroenterology and Childrens Research In-
stitute, Medical College of Wisconsin, Milwaukee, WI; 2Cell Biology,
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
514 NASPGHAN ANNUAL MEETING
Medical College of Wisconsin, Milwaukee, WI; 3Cancer Center,
MGH/HMS, Charlestown, MA; 4 Pediatric Surgery, MGH/HMS,
Charlestown, MA.
The epithelium of the intestine is characterized by its ability to
continuously regenerate. Renewal of the epithelium relies upon
coordinately regulating the proliferation and the differentiation of cells
as they ascend the crypt-villus axis. Whereas cells in the crypt are
proliferating and poorly undifferentiated, the terminally differentiated
cells of the villus have irreversibly withdrawn from the cell cycle. To
better understand the regulatory mechanisms that govern the decision to
proliferate versus differentiate, we are examining Rbm19. Rbm19 is an
RNA binding protein that we originally identified as being essential for
intestinal morphogenesis and differentiation in the zebrafish (Mayer
et al, Development 130:3917). Here, we extend these findings to include
an analysis of Rbm19 expression during vertebrate intestinal develop-
ment and differentiation of the CACO-2 cell line. In the undifferentiated
embryonic gut tube, Rbm19 is expressed throughout the epithelium
becoming localized to the crypts of Lieberkuhn in the adult intestine.
Consistent with its expression in the crypt compartment, Rbm19
exhibits widespread expression in human colorectal carcinoma tissue.
In CACO-2 cells, Rbm19 is found predominantly in the nucleolus.
When CACO-2 cells undergo confluence-induced cell cycle arrest,
Rbm19 expression declines which recapitulates its absence from the
terminally differentiated cells of the villus. We also observe a decline in
the expression of nucleophosmin and nucleolin, two other prominent
nucleolar proteins with a role in ribosome biogenesis. Significantly,
there is not a concomitant loss of the nucleolus when these cells are
examined by electron microscopy. Based on these data, we suggest that
the nucleolus may be a potential locus for regulating the prolifer-
ation/differentiation cell fate decision in the intestinal epithelium.
68*
TARGET OF RAPAMYCIN (TOR) MEDIATES THE
ENDODERM-INTESTINE TRANSITION IN ZEBRAFISH
Khadijah Makky, Alan N. Mayer. Pediatrics, MCW, Milwaukee, WI.
Introduction: Formation of intestinal villi from undifferentiated
endodermal epithelium requires tightly regulated processes of cell growth
and differentiation. The molecular signaling that regulates theses pro-
cesses is currently unknown. The target of rapamycin (TOR) is a key
regulator of cell growth and proliferation, integrating both extracellular
growth cues and intracellular nutrient status. TOR mediates cellular
growth via signaling to p70 S6 kinase (p70S6K) and 4E-BP1, resulting in
the translation of proteins required for various anabolic functions.
Hypothesis: We tested the hypothesis that TOR signaling may play
a key role in the endoderm-intestine transition.
Methods and Results: Using zebrafish as a model, we treated embryos
with rapamycin, a known TOR inhibitor, and observed arrested
development at the primitive gut tube stage. This effect is mediated by
the proteins FKBP12 and TOR, since addition of FK506 (a drug that
competitively binds FKBP12) rescued intestinal maturation. Knock-
down of p70S6K, a downstream component positively regulated by
TOR, mimics the phenotype observed upon TOR inhibition. The eIF 4E
binding protein (4EBP) is negatively regulated by TOR; concordantly,
morpholino knockdown rescued the inhibition of TOR by rapamycin.
Finally, morpholino knockdown of the upstream negative regulator of
TOR, TSC2, stimulated intestinal differentiation.
Conclusion: Taken together, these findings support the hypothesis and
provide novel evidence for a link between organogenesis in the
vertebrate digestive tract and the TOR signaling pathway.
69*
mTOR SIGNALING IS A COMPONENT OF INTESTINAL
REPAIR IN PIGLET ROTAVIRUS ENTERITIS
Jon M. Rhoads1, Bob Harrell2, Ben Corl2, Xiao M. Niu2, Lori Gatlin2,
Oulayvanh Phillips2, Anthony Blikslager3, Jack Odle2. 1Pediatrics,
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Ochsner for Children, New Orleans, LA; 2Animal Sciences, North
Carolina State University, Raleigh, NC; 3Anatomy & Physiology -
College of Veterinary Medicine, North Carolina State University,
Raleigh, NC.
Recent identification of the mTOR pathway as a key regulator of amino
acid sensing, mRNA translation, and protein synthesis led us to investi-
gate its role in viral diarrhea. We hypothesized that during rotavirus
enteritis, malnutrition would reduce jejunal protein synthetic rate and
mTOR signaling via its immediate downstream target, ribosomal p70 s6
kinase (p70s6k).
Methods: Newborn Yorkshire piglets were artificially fed from birth
and half were infected with porcine rotavirus on d5 of life. Study groups
included controls, infected, infected/50% protein-calorie malnour-
ished, and infected and treated with arginine (ARG, 0.3 g/kg/d) and/or
rapamycin (1 mg/m2).
Results: At the peak of diarrhea (on days 3 and 5 post-inoculation),
western blotting revealed four-fold induction of p70s6k phosphorylation
and p70s6k level (p , 0.05) compared with uninfected tissue. In vitro
jejunal protein synthetic rate increased 2-fold (p , 0.05) during infection.
Malnutrition did not alter the level of p70s6k activation or the increase in
gut permeability caused by infection. Immunolocalization revealed that
infection produced a major induction of cytoplasmic p70s6k and of
nuclear phospho-p70s6k in the crypt and lower villus. In vitro jejunal
protein synthesis and p70s6k phosphorylation increased 3-fold in
response to L-arginine. In vivo, rapamycin treatment of infected piglets
increased gut permeability 2.5-fold, while ARG reversed the rapamycin
effect, did not impact the diarrhea, and enhanced staining of phosphor-
ylated p70s6k and ribosomal protein S6 over the entire villus epithelium.
Conclusions: Rotavirus infection resulted in increased jejunal protein
synthesis and activation of mTOR in the crypt. Intestinal activity of
mTOR/p70s6k was not influenced by malnutrition, but was enhanced
by ARG.
70
ROLE OF mTOR SIGNALING IN INTESTINAL
CELL MIGRATION
Jon M. Rhoads1, Xiao M. Niu1, Jack Odle2, Lee Graves3. Pediatrics,
Ochsner for Children, New Orleans, LA; 2Animal Sciences, North
Carolina State University, Raleigh, NC; 3Pharmacology, University of
North Carolina, Chapel Hill, NC.
We previously showed that intestinal cell migration, the initial event in
epithelial restitution, is accelerated by L-arginine (ARG). We also
found that cycloheximide, rapamycin, wortmannin, and intracellular
Ca++ chelation inhibited the response to ARG. In this study, we
investigated if the ARG response is mediated through the mammalian
target of rapamycin (mTOR), which regulates translation of mRNAs
bearing a 5-oligopyrimidine sequence and acts as an amino acid sensor.
Methods: We used amino acids as prototypic activators of mTOR in
IEC-6 cells and we used serum as a recognized stimulator of intestinal
cell migration. Assays included razor wounding-stimulated migration,
western blotting, and immunohistochemistry.
Results: (1) ARG activates mTOR/p70s6k, NO production, and
migration. However, neither leucine (LEU, which activates
mTOR/p70s6k but does not produce NO) nor the nitric oxide (NO)
donor detaNONOate (which does not activate mTOR) enhances cell
migration. (2) The combination of LEU (4 mM) + NONOate (25 uM)
enhances migration similarly to ARG (P , 0.01). (3) ARG activates
p70s6k immunocytochemical staining in cytoplasm, phospho-p70s6k in
the nucleus, and phospho-ribosomal protein S6 in the cytoplasm. Also,
phosphorylated p70s6k migrates from nucleus to the cytoplasm after
ARG stimulation.
We conclude that stimulators of the mTOR pathway stimulate intestinal
cell migration; inhibitors of the mTOR pathway inhibit intestinal cell
migration; p70s6k is activated in the nucleus; and ribosomal protein S6 is
activated in the cytosol. These results are consistent with translational
 NASPGHAN ANNUAL MEETING
regulation via mTOR/p70s6k playing an important role in arginine-
stimulated intestinal epithelial restitution.
71
VIRULENT FRANCISELLA TULARENSIS LPS CAN
STIMULATE THE HUMAN INNATE IMMUNE SYSTEM
Riad M. Rahhal1, Micheal Apicella2, Gail Bishop3. 1Pediatrics, Univ.
of Iowa, Iowa City, IA; 2Microbiology, Univ. of Iowa, Iowa City, IA;
3
College of Medicine, Univ. of Iowa, Iowa City, IA.
Introduction: Francisella tularensis is a highly virulent gram negative
bacterium classified as a Class A potential bioweapon. It can cause
several clinical features depending on the route of infection. The
oropharyngeal and typhoidal types constitute about 25% of all cases.
Mortality is very high especially with the typhoidal type if not
recognized and treated early. Children less than 10 years of age are more
likely to get infected. A vaccine was developed based on studies in mice
with an attenuated Francisella tularensis strain. This vaccine has not
been adequately protective in humans against the virulent strains and is
not approved for use in the US.
Hypothesis: Virulent Francisella tularensis LPS can stimulate human B
cells and macrophages.
Methods: Highly purified LPS from virulent type B Francisella
tularensis was used to stimulate human peripheral B cells and human
derived macrophages.
Results: We have demonstrated a stimulatory role for virulent
Francisella tularensis LPS in human peripheral B cells with cytokine
and immunoglobulin production. TNF-alpha and IL-6 production was
noted by ELISA assays at 4 and 24 hours respectively. IgM production
showed similar, although less pronounced, patterns as compared to E coli
LPS over 12 days. Furthermore, we found differences in response
between human peripheral B cells and mouse splenocytes and mouse cell
lines. Mouse cells were not stimulated by virulent Francisella tularensis
LPS to generate inflammatory cytokines. Human macrophages re-
sponded to LPS stimulation by producing IL-6 and TNF-alpha in a dose
response fashion. Compared to E coli LPS, virulent Francisella tularensis
LPS produced less inflammatory cytokines in human macrophages.
Conclusion: Virulent Francisella tularensis LPS can stimulate mem-
bers of the human innate immune system. We hope this information will
pave the way towards development of a more effective vaccine against
virulent Francisella tularensis.
72
REGULATED TRAFFICKING OF TRANSFORMING
GROWTH FACTOR b RECEPTORS AND LIGAND IN
POLARIZED EPITHELIAL CELLS
John Barnard, Qin Huang. Pediatrics, Columbus Childrens Hospital
and The Ohio State University College of Medicine, Columbus, OH.
Gastrointestinal epithelial cells form tight junctions that spatially
separate apical and basolateral cell membrane domains. These domains
harbor functionally distinct proteins that contribute to cellular
homeostasis and tissue morphogenesis. Transforming growth factor b
(TGFb) is a critical regulator of gastrointestinal epithelial cell growth
and differentiation. Functional assays of vectorial TGFb signaling,
immunofluorescence staining, ELISAs, and biotinylation assays were
used to determine membrane localization of TGFb receptors and
vectorial ligand secretion in polarizing Caco-2 cells, a colon cancer cell
line. These results were compared to the nontransformed Madin-Darby
Canine Kidney (MDCK) cell line. Cells were grown on Transwells to
a transepithelial resistance of 200 ohms/cm2 or greater. In both Caco-2
and MDCK cells, addition of 2 ng/ml of TGFb to the basolateral
medium resulted in phosphorylation of Smad2 within 20 minutes. No
phosphorylation was observed when TGFb was added to the apical
chamber, indicating receptor signaling is localized in the basolateral
membrane. In support of this, immunofluorescence results show that
the type I TGFb receptor localizes to the basolateral membrane.
515
Biotinylation assays show that the type II TGFb receptor also localizes
to the basolateral membrane domain. Secretion of TGFb1 from MDCK
and Caco-2 cells into the apical or basolateral medium was measured by
ELISA. Interestingly, secretion was exclusively apical in the non-
transformed MDCK line and basolateral in the transformed Caco-2
cells. Collectively, these results show basolateral domain specificity in
localization of the TGFb receptor signaling apparatus in gastrointesti-
nal epithelial cells. Ligand is also differentially sorted, although
differences were observed between a nontransformed kidney cell line
and a transformed colon cell line. These observations have important
implications for understanding the biology of TGFb in polarized
epithelia and in the design of therapeutics that target TGFb function.
Clinical Sciences
73
FECAL CALPROTECTIN AND COWS MILK
PROTEIN ALLERGY IN INFANTS
John Pohl, Lynn Azuma, Matthew Watts, David Easley. Pediatric
Gastroenterology, Scott and White, Temple, TX.
Calprotectin, a 36.5 kiloDalton protein released into the intestinal
lumen by macrophages and neutrophils, has been shown to be useful in
determining disease activity and treatment response in intestinal
inflammatory conditions such as inflammatory bowel disease. Cows
milk protein allergy (CMPA) is a common gastrointestinal problem of
infancy associated with rectal bleeding, emesis, diarrhea, and eczema.
We hypothesized that fecal calprotectin is a useful screening test to
evaluate for resolution of CMPA in infants. A pilot trial was performed
in six infants less than 90 days of age with rectal bleeding and other
symptoms consistent with cows milk protein allergy. Fecal calprotectin
levels were determined by ELISA assay at baseline, 3, and 6 weeks after
placement on a protein hydrolysate formula. All infants improved
clinically and rectal bleeding resolved within 6 weeks after conversion
to a hydrolysate formula. Initial fecal calprotectin levels ranged from
1351537 mg/L (mean 557 mg/L) and decreased to a range of 42
219 mg/L (mean 163 mg/L) after 6 weeks on protein hydrolysate
formula. A control patient with no symptoms of CMPA maintained
fecal calprotectin values between 97 and 129 mg/L throughout the study.
The results of this pilot trial suggests that fecal calprotectin may be
a useful screening test for treatment response to protein hydrolysate
formula; however, further studies with a larger number of patients are
necessary to determine the utility of this test in infants with CMPA.
74
AN INFANT WITH AUTOIMMUNE ENTEROPATHY AND
STOMACH INVOLVEMENT: RESPONSE TO TACROLIMUS
Rita Steffen, Alex Green, Robert Wyllie, Marsha Kay, Barbara Kaplan,
Vera Hupertz, Lori Mahajan, Lisa Feinberg. Pediatric Gastroenterol-
ogy, Cleveland Clinic Foundation, Cleveland, OH.
A female infant presented in the first month of life with failure to thrive,
emesis, and protracted diarrhea. Biopsies revealed marked duodenal
villous atrophy with surface epithelial lymphocytosis, consistent with
autoimmune enteropathy. She also had a large gastric ulcer, showing
stomach involvement for the first time in a pediatric case of autoimmune
enteropathy. She was also successfully treated with three months of
tacrolimus and methylprednisolone, which will be continued for one year.
Her duodenal epithelium has healed along with her stomach.
At 17 days of life this infant girl was referred for failure to thrive. During
the neonatal period she was treated for necrotizing enterocolitis, which
presented with gross blood in the stool. She was vomiting despite formula
changes, and diarrhea began at this time. Laboratory studies demonstrated
hypoalbuminemia. Her stools were negative for pathogens, but positive
for alpha-1-antitrypsin, thus protein-losing enteropathy. Her intestinal
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
516 NASPGHAN ANNUAL MEETING
biopsies are detailed above, and the gastric ulcer was quite large, measuring
2.0 3 3.0 cm. Its pathology exhibited focal neutrophilic epithelial injury
with an increase in the number of chronic inflammatory cells.
After a poor response to steroids, the patient was tapered off and
subsequently started on oral tacrolimus (FK506, Fugi-sawa Pharmaceut-
icals, Tokyo, Japan) with a serum concentration goal of 1215 nag/ml. She
responded to tacrolimus and had repeat endoscopic biopsies demonstrating
healing of the gastric ulcer and normal small bowel brush border and
lamina propria. She is receiving all of her nutrition through her digestive
tract. Her gastric mucosa also healed with the immunosuppressive therapy.
To our knowledge, this is the first reported case of autoimmune enteropathy
in a child that had stomach involvement.
75
PREVALENCE OF CRYPTOSPORIDIUM SPP.
BY ELISA TEST IN HEALTHY CHILDREN
FROM CALI, COLOMBIA
Carlos A. Velasco, Diana Velez, Victor Duenas, Pio Lopez, Tania Caro,
Consuelo Rojas, Paola Neuta. GASTROHNUP, University of Valle,
Cali, Colombia.
Introduction: Cryptosporidium spp. (C. spp) is a protozoan is the fifth
cause for diarrhea in Colombia.
Objective: To determine the prevalence of C. spp in feces of healthy
children under 10 years old by ELISA test.
Materials and Methods: Transversal section descriptive observational
study was carried out from Centro de Salud Lourdes in Cali, Colombia.
Data like identification, age, gender, signs, symptoms, anthropometric
measurements, as well as hygienic conditions (drinking water consump-
tion, disposal of feces and home pets presence) were taken from their
clinical record. The identification of the C. spp in feces was carried out
through ELISA. For this analysis, statistic test were carried out, based
on the X2, and due to the low expected prevalence, the exact test of
Fisher, the odds ratio and the relative risk.
Results: 100 healthy chindren below 10 years old were included
(average age 4 years 2 months); 97% stratum 1 and 2; 50% both gender.
30% of the children live in stacking conditions; 84% live in urban zones;
95% have drinking water and 85% have an appropriate disposal of feces.
52% have some kind of animal and 63% attend the kinder garden or
school. The prevalence of C. spp in feces was 4% (0.147.89% 95% CI).
The major prevalence was associated to a non-appropiate feces disposal
(OR 0.157 p = 0.106) and to the female gender (p = 0.117). The 25% of
the ELISA + tests showed a certain level of malnutrition.
Conclusion: The prevalence of the C. spp for the studied population
sample was 4%, statistically equal to the prevalence for similar samples of
healthy children found in Colombia and other developing countries. The
presence of C. spp does not seem to be related to specific symptoms. The
association study with social-demographic-type variables suggests that
the non appropiate feces disposal is related to higher protozoa prevalence.
the anthropometric assessment indicates that malnutrition in children with
C. spp is lower (25%) than in children with no C. spp (40.6%).
76
DOES HELICOBACTER PYLORI CAUSE INFANTILE
HYPERTROPHIC PYLORIC STENOSIS (IHPS)?
Ahmed Dahshan1, G. K. Donovan1, Issam M. Halabi1, Richard Ranne2,
Mary Li2, William Illig3. 1Department of Pediatrics, Oklahoma
University Health Sciences Center-Tulsa, Tulsa, OK; 2Department of
Pediatric Surgery, Saint Francis Hospital, Tulsa, OK; 3Department of
Pathology, Saint Francis Hospital, Tulsa, OK.
H. pylori has been recognized in the last two decades as etiologically
related to gastritis, peptic ulcer disease and gastric cancer. IHPS has
been described over two centuries ago and presents with projectile non
bilious vomiting in the first few weeks of life. A 6 week old boy
presented to us with hematemesis, his endoscopic evaluation revealed
pyloric stenosis and H. pylori gastritis. A recent paper hypothesized that
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
H. pylori causes some cases of IHPS, based on its epidemiologic and
clinical features. We performed this study to evaluate the possible
relationship between IHPS and H. pylori.
Prospective enrollment of infants diagnosed with IHPS before un-
dergoing pyloromyotomy was arranged. Upper GI endoscopy with
biopsy was performed. The endoscopic appearance of the pylorus was
noted to validate endoscopic features of IHPS.
A total of 16 infants were evaluated, 15 boys, mean age of 42 days (R
21104). The index Case had H. pylori like organisms and chronic active
gastritis on biopsy. 4 had chronic active gastritis without H. pylori. 6
more had focal or mild chronic gastritis without H. pylori. The remaining
5 were within normal limits. All patients had negative rapid urease test.
Subsequent immune histochemical staining for biopsies with chronic
active gastritis was negative for H. pylori. Commonest endoscopic
findings of IHPS were thickened prominent asymmetric pyloric folds and
pin-hole pylorus that could not be intubated by the pediatric endoscope.
H. pylori was not shown to be present in most patients with IHPS. The
presence of H. pylori like organism in the gastric mucosa in our index
case and finding of chronic active gastritis in several others may indicate
the possibility of an acquired infectious etiology for IHPS in some cases.
The pathogenesis of IHPS may need to be reexamined. Endoscopic
diagnosis of IHPS is possible and could be a valuable tool in equivocal
cases before surgical exploration.
77
PARTICIPATION IN PLACEBO CONTROLLED
TRIALS: FAVORABLE PARENTAL PERCEPTIONS
ARE INDEPENDENT OF STUDY OUTCOME
Nader Youssef, Maria Perez, Eric Lazar, Joel Rosh. Pediatric
Gastroenterology, Goryeb Childrens Hospital, Morristown, NJ.
Aim: There is a paucity of placebo controlled trials (PCTs) in pediatric
GI. Investigators have concerns that parents will poorly perceive PCTs.
The aim of this study was to identify differences between parental
perceptions in families who successfully completed (CO) a clinical trial
compared to those who were non-completers (NC).
Methods: Parents of both CO and NC children enrolled in 1 of 3 pediatric
GI studies performed in the prior 1 year were eligible. Reasons for NC
were screen failures, adverse events and treatment failures. 117 parents of
120 children were identified and sent a questionnaire eliciting perception
regarding participation in clinical research. Questionnaires were coded for
anonymity, sent 6 months after participation ended; and returned to
investigators who had not met the family. Demographics, reasons for
participation, risk/benefit perception, and consent process were assessed.
Results: Eighty-eight (75%) parents returned the survey. Parent
characteristics included: maternal responders (98%), English as primary
language (97%), and education beyond high school (85%). There were
no significant differences in responses found between completers (CO,
n = 49; 63%) and non-completer (NC, n = 29; 37%) (Table). Of 29
families who did not respond back, 7 (24%) were NC.
Conclusions: PCTs are well received by parents regardless of whether
or not their child had direct benefit from the study. Satisfaction from
participation in research is not stratified by successful completion of
a PCT. These results should encourage investigators that PCTs in
pediatric GI can result in a high degree of parental satisfaction. Strongly
Agree or Agree (%).
Non-
Factor Completers completers Significance
Research Important 100 97 p = ns
Minimal risk to child 94 69 p = ns
Perceived benefit for child 90 72 p = ns
Others might benefit 100 100 p = ns
More attention in study 59 41 p = ns
Reassuring researcher 100 90 p = ns
 NASPGHAN ANNUAL MEETING
78
PROTON PUMP INHIBITORS IN INFANTS
T. Iarocci1, H. Tan1, J. Singer1, J. Barron1, A. Bakst2, E. Pilzer3,
D. Patel3. 1HealthCore, Wilmington, DE; 2TAP Pharmaceuticals, Lake
Forest, IL; 3Childrens Center for Digestive Healthcare, Atlanta, GA.
Objective: Practice guidelines on pediatric gastroesophageal reflux
(GER) include acid suppression for infants meeting certain criteria.
Though proton pump inhibitors (PPIs) are not approved for infants aged
,12 months, this study examined off-label PPI use. Findings presented
here are not intended to support such use.
Methods: This retrospective observational study used data from 1999
2004 from 4 US health plans. Infants aged ,12 months with $1 PPI
pharmacy claim were identified. Charts were reviewed in a subset.
Results: Identified infants (N = 2,469) were 58% male and 19% were
born pre-term. PPI use rose 7.5-fold from 19992004; lansoprazole and
omeprazole were used almost exclusively. The group tested for GER
(8%) had more defects and pre-term births. Pre-index diagnoses included
GER, difficulty feeding (23%), respiratory infection (23%), colic (20%),
and food allergies (10%). Pre-index H2 blockade was evident in 58%;
metoclopramide in 38%. Index PPI was identified at age 03 months in
50%; 47 months in 35%. Provider specialty appeared to be associated
with PPI duration. In the chart subset (n = 405), rationale for PPI use
included: (not mutually exclusive) GER (92%), colic/fussy (38%),
problems feeding (25%) and respiratory concerns (11%).
Conclusions: PPI use in the study population increased steadily from
19992004. Fussiness, feeding difficulties, and respiratory concerns
were commonly seen prior to starting PPI. As more infants receive PPI,
clinical trials may help to evaluate safety and efficacy in this population.
1999* 2000 2001 2002 2003 2004*
Prevalence 63 91 148 214 408 470
(per 100,000
insured
infants)
PPI Claimants 46 157 301 467 947 551
Insured Infants 73,567 173,087 204,064 218,056 232,100 117,336
*Data in 1999 was limited to 3 health plans, while 4 health plans are
represented in subsequent years. Data for 2004 was updated to the 2nd
or 3rd quarters, depending on plan. Infants eligible for pharmacy
claims for $1 day during the year were counted in the denominator of
the prevalence calculations.
79*
HIGH RESOLUTION ULTRASOUND TO EXAMINE
THE EFFECT OF TRACTION ON THE ESOPHAGUS FOR
ESOPHAGEAL ATRESIA REPAIR
Khalid M. Khan1, Allen Sabati2, Shaun Mallery3, Rebecca Lai3, Tara
Kendall , John Foker4. 1Pediatrics, University of Minnesota, Minne-
2 the presenting manifestations of PTLD in pediatric heart transplant
apolis, MN; 2Medical School, University of Minnesota, Minneapolis,
MN; 3Medicine, Hennepin County Medical Center, Minneapolis,
MN; 4Surgery, University of Minnesota, Minneapolis, MN.
At our center long-gap esophageal atresia is managed by applying
traction to the esophageal ends prior to repair. The esophageal pouches
undergo up to a five fold increase in length. We examined the effect of
traction on the esophagus after traction.
Method: High-frequency catheter probe ultrasound was used to
measure the muscularis propria, mucosa and submucosa in 18 children
during endoscopy. Those having undergone traction (n = 11) were
compared to short-gap atresia cases, where traction was not required
(n = 7). The catheter was passed through the accessory channel of
a standard endoscope or alongside a smaller endoscope and advanced
under direct vision. Water was infused for acoustic coupling. Measure-
517
ments were taken 24 cm above the lower esophageal sphincter and
24 cm above the anastomosis. Measurements taken within the nearest
0.10 mm from printed images.
Results: The long-gaps were younger, mean age 2.1 (2.4) vs. 4.1 (4.9)
years, 14/18 were male. In general the long-gaps underwent endoscopy
for post repair anastomotic dilatation and short-gaps for routine follow-
up. In 2/11 long-gaps the lower esophagus could not be examined. The
thickness of the muscularis propria of the esophagus below the
anastomosis were similar in long and short-gaps; 0.7 (0.2) vs. 0.7
(0.1) mm respectively. The thickness of the muscularis propria above
the anastomosis in long-gap atresia was greater than in the shorter gaps;
0.8 (0.2) vs. 0.7 (0.2) mm, p . 0.05. The mucosa and submucosa
combined, were of similar thickness in long and short-gaps below the
anastomosis, 1.0(0.3) vs. 1.0 (0.1) mm respectively and above the
anastomosis, 1.0 (0.2) vs. 1.0 (0.2) mm respectively.
Conclusion: The esophageal structure appears to be preserved after
traction is applied to achieve primary repair of long-gap esophageal
atresia. The catheter ultrasound can be effectively used to examine the
esophageal structure in small children.
80
GASTROINTESTINAL MANIFESTATIONS OF POST
TRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN
PEDIATRIC HEART TRANSPLANT PATIENTS
Evelyn Baghdasraian1, Khiet Ngo1, Richard Chinnock2, Manoj Shah1,
George Yanni. 1Pediatric Gastroenterology, Loma Linda University
School of Medicine, Loma Linda, CA; 2Pediatric Heart Transplant,
Loma Linda University School of Medicine, Loma Linda, CA.
Background and Aims: Post-Transplant Lymphoproliferative Disease
(PTLD) is a significant cause of morbidity and mortality in children
undergoing solid organ and bone marrow transplantation. Early
recognition of its clinical manifestations plays a major role in developing
the management plan and hence achieving an excellent patient and graft
survival rate. Clinical manifestations of PTLD are usually non-specific
and can be easily missed. The aim of this study is to explore the clinical
manifestations of PTLD with particular interest in the gastrointestinal
signs and symptoms in our study group at our institution.
Method: A chart review of pediatric heart transplant patients who were
diagnosed with PTLD from 1997 to 2004.
Results: Eighteen children (mean age 8.9 years, M:F ratio of 10:8) with
PTLD were identified. Thirteen patients (72%) presented with
gastrointestinal manifestations (GI), nine of whom (70%) had
additional non-GI signs and symptoms (fever, cervical adenopathy,
myalgia, skin manifestations). Four patients (22%) presented with only
GI manifestations. Seven patients (38%) presented with abdominal
pain, six patients (33%) presented with altered bowel habit (con-
stipation and/or diarrhea), and five patients (27%) presented with lower
gastrointestinal bleeding. Five patients (28%) presented with non-GI
manifestations of which cervical adenopathy was the predominant sign.
Conclusions: 1) Common gastrointestinal signs and symptoms can be
recipients. Heart transplant patients with PTLD may present with GI
manifestations as the sole clinical features. 2) The association of the
gastrointestinal manifestations with the generalized non-specific symp-
toms (fever, skin rash, and lymphadenopathy) in pediatric heart transplant
patients should alert the clinician to a possible diagnosis of PTLD.
81
FEEDING CHILDREN WITH IMPAIRED AIRWAY
PROTECTION - SCREENING FOR PULMONARY DISEASE
WITH CT SCANNING OF THE CHEST
Richard J. Noel1, Amy L. Delaney2, Robert B. Beecher2, Joan C.
Arvedson2, Colin D. Rudolph1. 1Ped. GI and Nutrition, Med. Coll. of
Wisc., Milwaukee, WI; 2Speech and Language Pathology, Child. Hosp.
of Wisc., Milwaukee, WI.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
518 NASPGHAN ANNUAL MEETING
The pulmonary health of children with impaired airway protection
during a swallow is assumed to be in peril when oral feeds are
continued. Gastric feeding access is believed to minimize pulmonary
injury, but does not allow for the development and progression of
swallowing skills. We propose that in the absence of detectable
pulmonary pathology, oral feedings continue with appropriate medical
and speech pathologist supervision. Computed tomography (CT)
scanning of the chest identifies pulmonary pathology with greater
sensitivity than physical examination, chest radiography, or pulmonary
function testing. We describe the utility of this test for the screening of
children who aspirate and feed orally.
Methods: Orally feeding children with aspiration on videofluoroscopic
swallow study (VFSS) were identified retrospectively. Screening CT
scans recorded 5 mm sections; if pathology was detected, resolution
was increased as required. Clinical data, including VFSS and chest CT
scan data were gathered.
Results: Seven cases were identified; 71% were female. Age at
diagnosis of aspiration was 10.2 6 6.2 months (mean 6 stdev). All
patients had a normal pulmonary physical examination. Patients had 1
3 VFSS and 13 CT scans, depending on length of follow-up. Age at
last evaluation was 17.8 6 6.8 months (mean 6 stdev). Six cases
continue to eat orally without pulmonary pathology; of these, two have
made marked progress with regard to their swallowing mechanics and
airway protection. The seventh case was noted to have radiographic
signs of pulmonary disease despite absence of clinical lung disease,
prompting a gastrostomy and regulation of oral feeds.
Conclusion: Continuation of oral feeding and appropriate therapy in
children who aspirate can result in improved swallowing mechanics and
airway protection. Computed tomography is a sensitive screen for
pulmonary complications of chronic aspiration and decreases the
calculated risk of oral feeding in this situation.
82
THE FREQUENCY OF DIFFUSE INFLAMMATION IN
CHILDREN WITH PRIMARY AND SECONDARY ULCERS
Walter Sipe1, Roberto Gugig1, Ferrell Linda2, Orit Elkayam1, Melvin
Heyman1, Betsy Haas-Beckert1, John D. Snyder1. 1Pediatrics, UCSF,
San Francisco, CA; 2Pathology, UCSF, San Francisco, CA.
Background: Few recent large population studies are available on
childhood ulcers. We could find no data on whether childhood ulcers
result from a focal or more diffuse inflammatory process and whether
the distribution of inflammation differs for primary (PU, no known
associated disease) and secondary (SU, associated with known causes,
e.g. Crohn disease) ulcers. To answer these questions, we evaluated the
biopsy results of children with ulcers diagnosed by endocopy.
Methods: Retrospective chart reviews were performed on children who
underwent upper GI endoscopy between 1/1/1994 and 12/31/2002.
Endoscopy photographs and biopsy results were reviewed for each case.
An average of 2 duodenal and 3 gastric biopsies were obtained from
each patient. Ulcers were defined as erosions of gastric or duodenal
mucosa with a defined crater. Inflammation was defined using standard
histologic criteria.
Results: 1705 upper GI endoscopies with biopsies were performed in
1364 patients over the 9 years. The mean age (SD) of the patients was
7.9 (5.9) years; 55% were male. Ulcers were identified in 72 patients
(5%). Histologic findings were available for 69 of the children with
ulcers, including 20 with PU and 49 with SU. The presence and degree
of inflammation associated with PU and SU is summarized in the Table.
The majority (61%) of patients with ulcers had no associated
inflammation and there was no significant difference between gastric
and duodenal or PU and SU. No pattern of diffuse inflammation and
disease diagnosis was apparent.
Conclusions: In our population, diffuse inflammation was an un-
common finding in children with either primary or secondary ulcers of
the stomach or duodenum.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Primary Secondary
Inflammation Gastric Duodenal Gastric Duodenal
None 5 5 23 9
Mild, focal 1 5 5 1
Diffuse 2 2 6 5
TOTAL 8 12 34 15
83*
THE EFFECT OF APROTININ ON BLOOD LOSS
AND INTESTINAL ISCHEMIA, AS MEASURED BY
INTESTINAL FATTY ACID BINDING PROTEIN
(IFABP), DURING POSTERIOR SPINAL FUSION
(PSF) SURGERY IN CHILDREN
Raman R. Sreedharan, Dalal Tonob, Zhaoping He, Dev Mehta. GI and
Nutrition, AI duPont Hospital for Children/Thomas Jefferson Univer-
sity, Wilmington, DE.
Major blood loss is a complication of PSF surgery in children, but its
effect on intestinal perfusion is not completely understood. Aprotinin is
a serine protease inhibitor used in major surgeries to reduce blood loss.
Also, aprotinin has been shown to have a protective effect on the
splanchnic circulation. IFABP, a cytosolic protein in small intestinal
enterocytes, is a sensitive marker in blood for early intestinal ischemia.
Method: In an open-labeled study, 9 children (4# & 5$) received
aprotinine during PSF surgery (treatment group) and 12 historically
matched children (2# & 10$) acted as controls (non-treatment group).
In all these cases, intra-operative vital signs were maintained within
acceptable limits and the blood loss was recorded. The mean age and
weight of the treatment group was 13.5 yrs & 31.97 kg and that of the
non-treatment group was 13.75 yrs & 28.97 kg respectively. Serum
samples were collected during surgery, post-op day 1 and post-op day 2
for IFABP estimation using an ELISA technique.
Results: Mean blood loss during surgery for the treatment group was
1772 mls (59.54 mls/kg) compared to 3387 mls (127.4 mls/kg) for the
non-treatment group (p = 0.01). The mean peak serum IFABP level for
the treatment group was 401.2 ng/ml compared to 563.5 ng/ml for the
non-treatment group (p . 0.01). When analyzed after combining the
two groups, the peak serum IFABP levels and the blood loss showed
statistical significance (p , 0.0001).
Conclusions: Aprotinin is effective for reducing blood loss during PSF
surgeries in children. There is a correlation between intra-operative
blood loss and the levels of IFABP suggesting intestinal ischemia.
Direct effect of aprotinin on the splanchnic flow appears to be less
relevant here. Future studies with larger sample size are required to
predict clinical outcomes.
84*
PREVALENCE OF GASTROENTEROLOGICAL
SYMPTOMS IN COMMUNITY CHILDREN.
A PROSPECTIVE SCHOOL STUDY
Miguel Saps1, Carlo Di Lorenzo2. 1Pediatric Gastroenterology
Hepatology and Nutrition, Childrens Memorial Hospital, Chicago,
IL; 2Pediatric Gastroenterology, Childrens Hospital of Columbus,
Columbus, OH.
Background: Previous epidemiologic studies of common GI symptoms
have relied on office samples or cross-sectional data based on patients
recall. These methods may lead to bias and inaccurate estimates.
Aims: To examine the prevalence of GI symptoms in school-age children.
Importance: This is the first prospective community study assessing the
prevalence of common GI symptoms in school-age American children.
 NASPGHAN ANNUAL MEETING
Methods: All 4th and 5th grade students attending a middle-size urban
school were asked to participate in a prospective cohort study. From 2
6/2004, the children completed confidential weekly surveys using
previously validated self-report questions assessing the presence and
severity of abdominal pain, constipation, diarrhea, nausea, vomiting,
and chest pain during the previous week plus 2 questions on headaches
and limb pain to investigate somatization and co-morbidities.
Results: 48 children (32 boys), out of 92 Caucasian children, age 911
years participated to the study. An average of 43 children responded
each week (3548). Data were obtained during 16 weeks on 690
(90.5%), out of 768 possible children/weeks. Sixty percent (4689%)
reported at least one GI symptom weekly. The prevalence of weekly GI
symptoms was: abdominal pain 46% (2872%), nausea 28% (1759%),
constipation 18% (739%), diarrhea 17% (1124%) and vomiting 5%
(013%). Abdominal pain was significantly more prevalent during the
first than in the last month of the study (p , 0.001). There was no
significant variation in monthly prevalence of any other symptom.
Abdominal pain persisted for 4 weeks or more in 23% of children and
for 12 weeks in 8%. No child missed school due to persistent GI
symptoms.
Conclusion: GI symptoms are common among school age children.
There seems to be a seasonal variation of abdominal pain. The high
prevalence of GI symptoms not interfering with school attendance
underscores their benign nature. The investigation demonstrates the
feasibility of prospective school studies in children.
85
A SINGLE CENTER TASTE PREFERENCE STUDY
OF RANITIDINE (ZANTAC) SYRUP VERSUS RANITIDINE
EFFERVESCENT TABLETS (ZANTAC EFFERDOSE)
IN CHILDREN
Vanessa Ameen, Greg Giguere, Bonnie Pobiner. Glaxo SmithKline,
Research Triangle Park, NC.
The H2 receptor antagonist ranitidine hydrochloride (Zantac) is
approved for the treatment of GERD and erosive esophagitis in children
1 month of age and older. A low strength Zantac EFFERdose formu-
lation is available in a 25 mg effervescent tablet to facilitate use in
smaller children and infants.
Objective: To compare taste preference of two Zantac preparations
(EFFERdose dissolved in water, or Syrup) in healthy children 4 to 8
years of age and their adult caregivers.
Methods: A randomized, single-blind, cross-over taste test trial was
conducted in 102 children and 102 parents/legal guardians. All subjects
received a single 45 mg dose of each Zantac preparation. After tasting
the first preparation, subjects cleansed their mouth, waited 5 minutes,
and tasted the second preparation. After tasting both preparations
children were asked, Now that you have tasted both medicines, which
one of these medicines do you think tastes better? Adults were asked
four questions to assess whether they would administer the medication
to the children.
Results: Of the children who sampled both preparations, 71% (72/102)
preferred the taste of EFFERdose compared to 29% (30/102) who
preferred the Syrup (p , 0.001). The majority of adults responded
that they preferred to administer Zantac EFFERdose based on taste
(Table). Adverse events consistent with product labeling were mild and
were reported in four children and three adults: headache (n = 3),
drowsiness (n = 1), stomachache/cramps (n = 2), and bloating/gas
(n = 1).
Conclusion: The taste of Zantac EFFERdose dissolved in water is
preferred over Zantac Syrup. Better taste acceptance may facilitate ease
of administration and compliance in pediatric patients. Percent of
caregivers (n = 102) who responded affirmatively to questions regarding
administration of Zantac EFFERdose (dissolved in water) or Zantac
Syrup based on taste.
519
EFFERdose Syrup
Would give to an infant 1 month or older 52% 23%
Believed that child would take medicine 51% 25%
Taste would make it easy to give to child 53% 22%
Caregiver preferred to give
to child based on taste 71% 29%
Functional Disorders and Motility Disturbances
86
BELIEFS AND NEED FOR EDUCATION IN
SCHOOL NURSES ON RECURRENT ABDOMINAL
PAIN OF CHILDHOOD. OPPORTUNITY TO DEVELOP
AN THERAPEUTIC ALLIANCE?
Nader Youssef, Thomas Murphy, Charlotte Intile, Joel Rosh. Pediatric
Gastroenterology, Goryeb Childrens Hospital, Morristown, NJ.
Aim: Recurrent abdominal pain (RAP) of childhood affects up to 20%
of children. RAP has significant consequences including frequent
school absence and physician evaluation. Initial assessment of RAP is
often made at the school nurse (SN) level. The aim of this study is to
determine what knowledge and beliefs SNs have regarding RAP.
Methods: 425 SNs selected from the New Jersey School Nurses
Association Directory. SNs were sent a 21-item questionnaire eliciting
their perceptions regarding RAP in children. The definition of RAP was
3 episodes of abdominal pain interfering with activity for 3 months in
the past year. Questionnaires were coded for anonymity. SN experience,
knowledge on RAP, disease perception, knowledge of medicines, and
need for education were assessed.
Results: There were 131 (31%) questionnaires returned and RNs
accounted for 95% of respondents. Over 98% reported seeing children
with RAP. More than 10 visits/ month for RAP was reported by 31% of
SNs. Of respondents, 77% felt that an extensive evaluation by an MD is
needed but only 23% believed that medication would help RAP.
Communication with MDs about RAP was considered poor by 84% of
SNs. SNs reported that 70% of children with RAP were faking the pain
or seeking attention. Children with RAP were considered sad (35%) or
lazy (38%). SNs recommendations for RAP include: rest (94%), go to
bathroom (90%), back to class (68%) and sent home (48%). Mean total
nursing experience was 26.1 + 14 years with a mean school nurse
experience of 11.1 + 21 years.
Conclusions: Despite extensive experience, SNs have negative views of
children with RAP. SNs may inadvertently contribute to the increased
social stigmata felt by children with RAP who might feel their
complaints are not taken seriously. Focused education initiatives of SNs
and better communication from MDs may allow for enhanced partner-
ships. Implementation of strategies at the SN level to reduce conse-
quences of RAP including school absenteeism should be explored.
87
ABDOMINAL PAIN: IS THERE A SEASONAL PATTERN?
Miguel Saps1, Cheryl Blank2, Seema Khan3, Rohan Patel1, BU Li1,
Carlo Di Lorenzo4. 1Pediatric Gastroenterology, Hepatology and
Nutrition, Childrens Memorial Hospital, Chicago, IL; 2Pediatric
Gastroenterology, Childrens Hospital of Pittsburgh, Pittsburgh, PA;
3
Pediatric Gastroenterology, A.I. du Pont Hospital for Children,
Wilmington, DE; 4Pediatric Gastroenterology, Childrens Hospital of
Columbus, Columbus, OH.
Background: We have previously identified a seasonal variation in the
prevalence of abdominal pain (AP) in school-age children at the
community level.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
520 NASPGHAN ANNUAL MEETING
Aims: To investigate the seasonal pattern of consultations for AP in
pediatric gastroenterology clinics at different institutions.
Methods: The number of outpatient consultations with the diagnosis of
AP (ICD-9 789) and the total number of outpatient consultations was
obtained from 2 tertiary care institutions (Childrens Hospital of
Pittsburgh, Childrens Memorial Hospital in Chicago) for the years
200104. Rates were compared across time periods (period 1: mo
FebruaryApril vs. period 2: mo JuneAugust) and across cities. In
order to assess seasonal variation of comorbidities we analyzed the ratio
of consultations for headaches (HA) (ICD-9 784) from one of the
centers.
Results: The data reveals a similar seasonal pattern every year with
a significantly higher ratio of consultations for AP in the winter
months and a lower number during summer time in both institutions
in 7/8 analyzed periods (,0.005). No significant variation was found
in 1/8 periods. A similar and significant pattern was found for the
diagnosis of HA every year (p , 0.002) in Pittsburgh with the
exception of 2001.
Discussion: The pathogenesis of functional gastrointestinal disorders
remains unknown. Stress, infections and other environmental factors
could play a role. Our data reveals a similar pattern regardless of the
geographical location. The fact that a similar curve was found in distant
locations with the same academic year, relativizes the role of the
environment and makes a possible influence of school stressors more
likely. The similar seasonal pattern found for other somatic complaints
(HA) reinforces a possible role of stress.
Conclusion: We have demonstrated a seasonal variation on the
prevalence of AP.
88*
THE PRIMARY CARE PHYSICIANS APPROACH TO
FUNCTIONAL ABDOMINAL PAIN IN CHILDHOOD
Mark Fishbein, Brad Bernard, Christopher Ehrlich. Pediatrics, SIU
School of Medicine, Springfield, IL.
Objectives: Recurrent abdominal pain in children was defined initially
by Apley and updated recently by Rome II criteria. The intent of the
Rome II criteria is to provide greater insight into functional disorders of
the gastrointestinal tract. Since markers for these disorders are lacking,
diagnostic evaluations may vary. In this investigation, the individual
approach of the primary care physician to the child with functional
abdominal pain (as defined by Rome II criteria) is explored both in
a hypothetical and clinical setting.
Study Design: A clinical vignette and survey involving the evaluation
of a hypothetical school-aged child with prototypical functional
abdominal pain was distributed to area primary care physicians (n =
201 completed). Physician preference regarding subsequent diagnostic
testing and their anticipation of positive yield was determined through
Likert scale (1 to 5 numeric ranking). Options for testing were organ
specific including urinary tract (urinalysis and urine culture), kidney
(serum electrolytes), liver (serum liver chemistries), pancreas (serum
amylase and lipase), upper GI tract (upper GI x-ray), intestinal (ova and
parasite, upper GI with small bowel follow through), and abdominal
generalized (abdominal x-ray, ultrasound, CT with or without contrast).
The actual physician approach for functional abdominal pain was
determined through chart review of children referred to gastroenterol-
ogy clinic (n = 103).
Results: Physicians favored limited organ-specific testing, with
urinalysis, preferred most. Physicians with extreme anticipation of
a positive yield requested more testing than their non-anticipatory
counterparts (5.7 6 2.2 vs. 2.0 6 2.0, p , 0.001). Ultrasound was the
only diagnostic test requested with greater frequency in actual subjects
than hypothetical (31 vs. 18%, p , 0.005).
Conclusion: In accordance with published guidelines, physicians
requested minimal testing for functional abdominal pain. Increased
ultrasound requests in the clinic setting may be more reflective of the
need for reassurance rather than seeking an organic etiology.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
89*
FRUCTOSE INTOLERANCE IN CHILDREN
PRESENTING WITH ABDOMINAL PAIN
R. E. Gomara, M. S. Halata, L. J. Newman, H. E. Bostwick, S. H.
Berezin, L. Cukaj, M. C. See, M. S. Medow. Pediatrics, New York Medical
College, Valhalla, NY.
Fructose consumed as high fructose corn syrup in soda, fruit juices, or
candy is also present in many fruits. While glucose is completely
absorbed by active transport, fructose is absorbed by facilitated
diffusion which is capacity limited. In small quantities, most dietary
fructose is completely absorbed. Unabsorbed fructose may serve as an
osmotic load and may be fermented by anaerobic bacteria producing
hydrogen, methane, carbon dioxide and short chain fatty acids resulting
in abdominal pain, bloating, flatus and diarrhea. The effects of fructose
ingestion in children have not been described. We therefore determined
the prevalence of fructose intolerance in children with unexplained
chronic GI symptoms, to establish whether results of the fructose breath
test are influenced by the amount of fructose. We administered a
Fructose Breath Test to children presenting with persistent, unexplained
abdominal pain. Subjects randomly received a 1, 15 or 45 gram
challenge of fructose and breath hydrogen was measured with
a Quintron 12i GasAnalyzer for 3 hours following ingestion. Breath
test results were considered positive when breath hydrogen was 20 ppm
greater than baseline and fructose ingestion was accompanied by
symptoms of gas, abdominal pain or diarrhea.
Results: To date 27 subjects have been enrolled with an average age of
13.1 6 3.85 years; 45% male and 55% female. None of the subjects who
received 1 gram were positive; 20% who received 15 grams and 50%
who received 45 grams were positive (7 of 27 were positive). All
subjects regardless of the breath test results were asked to restrict
subsequent dietary fructose intake. Among the group that had a positive
test, 60% reported improvement of their GI symptoms within 2 weeks
while the group that tested negative did not.
Conclusion: Fructose malabsorption may be a significant problem in
children and management of dietary intake can be effective in reducing
symptoms of abdominal pain, bloating, flatus and diarrhea.
90
ESOPHAGEAL MOTILITY DISTURBANCES IN
CHILDREN WITH RETT SYNDROME: CORRELATION
WITH X-LINKED METHYL CPG BINDING PROTEIN
(MECP2) GENE MUTATIONS
John E. Fortunato1, Anil Darbari1, John Desbiens1, Geni Bibat2,
Sakkubai Naidu2, Carmen Cuffari1. 1Peds GI, Johns Hopkins
University, Baltimore, MD; 2Neurogenetics, Kennedy Kreiger Institute,
Baltimore, MD.
Background: Preliminary studies in children with Rett syndrome have
shown that proximal mutations on the MeCP2 gene associate well with
severe gastrointestinal manifestations, including oropharyngeal dyspha-
gia and failure to thrive (J Child Neuro 2003).
Aim: To correlate esophageal motor abnormalities with MeCP2 gene
mutations.
Methods: Females with Rett syndrome (n = 12) with a mean age of
9.1 years (range 514) had esophageal manometry performed using
a flexible solid-state catheter (MMS USA, Inc.). Pressure readings were
obtained after both dry and water swallows using three solid-state
pressure transducers spaced 5 cm apart. Esophageal manometry tracing
were correlated with MeCP2 mutations and GI disturbances.
Results: Patients with proximal MeCP2 mutations demonstrated
a higher incidence of failure to thrive (p , 0.05). This was associated
with high pressure esophageal peristalsis (N: 40100 mmHg), and
inappropriate LES relaxation (N: 90100%).
Conclusions: MeCP2 gene mutations are associated with both clinical
GI manifestations and esophageal dysmotility. Failure of LES relaxation
and high peak esophageal pressures may explain feeding problems
 NASPGHAN ANNUAL MEETING 521

associated with Rett syndrome. Ongoing studies are further needed to Background: Radionuclide scintigraphy using technetium-99 m sulfur
correlate genotypic with clinical phenotype. colloid in milk formula is the most common method used to evaluate
gastric emptying times. However, normative data in infants is limited, and
previous studies have examined gastric emptying times primarily in
Failure infants with gastro-esophageal reflux or abnormal anatomy. Because
to % LES LES Peak
Reflux thrive Dysphagia relaxation resting pressure gastric emptying studies are useful to decide medical therapy or consider
surgery, we decided to analyze gastric emptying data with the aim of de-
Proximal Mutation termining normative data for infants with normal anatomy and no reflux.
T158M 0 0 0 88 40 71 Materials and Methods: The infants included in this study presented
T158M 1 1 0 71 24 201 with symptoms of ALTE, vomiting or FTT. A retrospective analysis of
T158M 1 1 1 38 26 192 gastric emptying using the radionuclide scintigraphy studies performed
R133C 0 0 0 100 21 57 on all infants less than one year of age at UCLA between January 1999
Deletion E3/E4 0 1 1 62 22 71 and January 2005. This study included infants had to have been ruled
out for reflux using a 2448 hour intra-esophageal pH monitoring study,
Distal Mutation
normal anatomy on UGI series and be on a cows milk formula diet. Of
R306H 0 0 0 38 19 193
the 259 infants identified, 32 met the criteria.
R306C 1 0 0 44 29 89
Results: The mean percent cleared 95% C.I. is as follows:
R270X 0 0 1 94 15 61
26.6% (66.2%) at 15 minutes, 37.9% (66.5%) at 30 minutes, 45.2%
807 Deletion 1 0 1 94 21 182
(67.1%) at 45 minutes, 52.3% (67.1%) at 60 minutes, and 66%
1163 del 26 1 0 0 100 14 94
(67.2%) at 90 minutes.
Del/Insert E4 1 0 1 75 48 73
Conclusions: Infants less than 1 year of age with no documented reflux
No Mutation 0 0 0 97 27 35
on 24 hour pH monitoring, no anatomic abnormalities and on cows milk
formula were found to have a T1/2 of approximately 60 minutes and 66%
gastric clearance at 90 minutes on a technetium-99 m sulfur colloid study.
91 These values establish possible normative values for gastric emptying
times in this population.
THE ROLE OF CLINICAL AUTONOMIC TESTING IN
PEDIATRIC GASTROINTESTINAL DISORDERS 93
Gisela Chelimsky1, Thomas Chelimsky2. 1Pediatric Gastroenterology,
Rainbow Babies & Childrens Hospital, Cleveland, OH; 2Division of EFFECT OF PYLORIC INJECTION OF BOTULINUM TOXIN
Autonomic Disorders, Department of Neurology, University Hospitals IN CHILDREN WITH GASTROPARESIS
of Cleveland and Case Western Reserve University, Cleveland, OH. Alysa Muniz-Crim, Sabina Sabharwal, Leonel Rodriguez, Alejandro
Flores. Floating Hospital for Children, Boston, MA.
Background: Despite increasing utilization among adults, clinical
autonomic testing has not been widely embraced in children, and its Background: Clinical efficacy of endoscopic injection of botulinum
utility has not been reported. A few case reports and small series discuss toxin into the pylorus has been reported in adults for the treatment of
the role of POTS in functional abdominal pain. gastroparesis, its effect on gastric emptying in children remains to be
Methods: Utilizing an IRB approved protocol, we reviewed our described.
experience with autonomic testing in all patients less than 18 years old Objectives: Describe our experience with the use of botulinum toxin in
over the last 12 years. We reviewed the testing interpretation, and the the treatment of gastroparesis in children and its effect on gastric
referring clinician and hospital records. We ranked the utility of the test emptying.
from 1 to 5 in regard to mechanistic and etiologic diagnoses, and choice Methods: Retrospective study including patients diagnosed with
of treatment. gastroparesis by clinical features and gastric emptying time (GET)
Results: The chief reason for referral to the autonomic laboratory was measured by scintigraphy that underwent pyloric injection of
a gastrointestinal complaint in 87/231 referrals (38%). Mean age was botulinum toxin. GET was repeated after botox injection, t 1/2 was
12.6 6 4 years, range 0.6 to 17 years. There were 80 autonomic screens estimated and was compared with previous GET; clinical improve-
(Valsalva and deep breathing responses, Tilt study, axon reflex ment was also evaluated when available.
sweating) and 9 thermoregulatory sweat tests. The most common Results: 6 patients (3 male, mean age 15.3 years) diagnosed with
referral diagnoses were: undiagnosed abdominal pain in 60%, dizziness gastroparesis underwent pyloric injection of 100 units of botulinum
in 16%, possible cyclic vomiting syndrome in 16%, nausea in 8%, and toxin. 5 of 6 patients did not reach t 1/2 during the study time prior to
diarrhea in 7%. The most common diagnoses made by testing were botox injection. T 1/2 for the remaining patient prior to botox injection
postural tachycardia syndrome (55%), autonomic neuropathy (22%), was 244 minutes. All 6 patients demonstrated improvement of GET.
orthostatic hypotension (8%), and vasodepressor syncope (5%). The test Mean t 1/2 following botox injection was 69.8 minutes. Mean time of
was helpful in defining a presumed mechanism of presenting symptoms post-botox GET was 16.2 days (435 days). All patients reported some
and guiding medication choice in 86% of patients, and aided in improvement in clinical symptoms, two of who reported considerable
elucidating the underlying disease process in 49%. reduction in symptoms.
Conclusion: Autonomic testing is valuable in the assessment of Conclusions: Endoscopic pyloric injection of botox is effective in
pediatric functional gastrointestinal disorders, guiding treatment in the improving GET in children; clinical improvement is less dramatic,
majority of cases. In almost half the patients, it is also helpful in prospective studies are needed to evaluate its long-term clinical efficacy.
unearthing an etiologic diagnosis. Given the known high prevalence of
such disorders in children, greater use of autonomic testing may provide Liver Diseases
more insight into the optimal management of these patients.
94*
92* HEPATIC CHOLESTEROL ACCUMULATION
GASTRIC EMPTYING TIMES IN CHILDREN AND APOPTOSIS IN THE NPC12/2 MOUSE
UNDER 1 YEAR OF AGE Eduardo Beltroy, James Richardson, Jay Horton, Stephen Turley,
Jamil Abou-Harb, Jorge Vargas, Mini Mehra. Peds GI, UCLA, Los John Dietschy. UT Southwestern Medical Center at Dallas,
Angeles, CA. Dallas, TX.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

522 NASPGHAN ANNUAL MEETING
Background: Niemann-Pick type C (NPC) disease is an autosomal
recessive lipid storage disorder that results from a defect in intracellular
trafficking of cholesterol which leads to accumulation of unesterified
cholesterol within the late endosome-lysosome compartment in
virtually every organ. Apoptosis is important in normal development,
maintenance of tissue homeostasis, as well as in elimination of damaged
or infected cells. In vitro studies have suggested that loading of
macrophages with unesterified cholesterol can trigger apoptosis via
both the Fas ligand pathway with release of cytochrome c and activation
of the caspase pathway.
Methods: Matching mutant (npc12/2) and wild type (npc1+/+) mice
were weaned at 19 days to a low cholesterol chow diet. Hepatic
cholesterol content and plasma ALT and AST activities were
measured in groups of mice at different ages ranging from 1 to
75 days. Liver tissue of both npc12/2 and npc1+/+ animals at 75
days of age was stained with H&E, and also subjected to TUNEL
assay for apoptosis. Other liver samples were used for measurement
of mRNA expression of several proteins using quantitative real-
time PCR.
Results: In the npc12/2 mice, whole liver cholesterol content increased
almost linearly as a function of age from 0.80 to 34.37 mg compared to
0.35 to 3.31 mg in the npc1+/+ controls over 75 days. This was
associated with a progressive elevation in the ALT and AST activities.
Liver histology at 75 days revealed accumulation of amorphous
material in both hepatocytes and Kupffer cells, the presence of
apoptotic bodies, and the absence of inflammation. In the npc12/2
mice, the expression of two genes involved in apoptosis, caspase 1 and
caspase 6, in the liver was elevated 4.5- and 2.2-fold, respectively,
compared to the npc1+/+ mice. TUNEL assay confirmed the presence of
apoptotic bodies in the npc1+/+ mice.
Conclusion: Cholesterol accumulation in the npc12/2 mouse is
associated with liver cell apoptosis; however, the question remains
wether cholesterol is in fact the sole offending agent.
95
LIVER MICROSOMAL TRIGLYCERIDE
TRANSFER PROTEIN IN A RAT
MODEL OF NONALCOHOLIC FATTY
LIVER DISEASE
Marcos E. Alfie, Jahangir Iqbal, Abha Kaistha, Stanley E. Fisher,
Mahmood M. Hussain. Pediatric GI, SUNY, Brooklyn, NY.
Nonalcoholic fatty liver (NAFLD) is one of the most common liver
diseases encountered in the United States. A net retention of lipids
within the hepatocytes is a prerequisite for the development of
NAFLD. The metabolic anomalies responsible for lipid accumulation
are not clear. Microsomal triglyceride transfer protein (MTP) plays an
important role in lipoprotein assembly and lipid transport. We
hypothesize that NAFLD is associated with a decreased MTP activity
with a subsequent failure to mobilize lipids from the hepatocytes
resulting in a net retention of fat. We tested our hypothesis in a SD
rat-model of NAFLD described by Lieber et al. After three weeks on
either a standard or a high fat-diet, (n = 6 per group) rats were
sacrificed; liver tissue and whole blood were collected. Plasma and
liver lipid levels were determined by enzymatic assay kits, MTP
activity was measured by a fluorescent assay as described by Athar
et al. As shown in table, rats fed a high fat diet had an increased
cholesterol and triglyceride (TG) liver content, and a decreased
plasma TG level as compared to controls; on the other hand, liver MTP
activity was similar in both groups. Thus liver MTP does not appear to
play a significant role in the development of steatosis in this specific
animal model of NAFLD. Additional mechanisms such as the role of
mitochondrial b-oxidation and reactive oxygen species are now being
investigated.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Regular High
diet fat diet P values
Plasma Lipids (mg/dl)
Cholesterol 57.8 6 3.9 58.4 6 20.2 (p = NS)
Triglycerides 45.9 6 14.1 17.6 6 7.4 (p , 0.002)
Liver Lipids (mg/g
of tissue)
Cholesterol 304.7 6 14.9 445.3 6 54.3 (p , 0.001)
Triglycerides 852.2 6 307 3057.5 6 709.7 (p , 0.0001)
MTP (as % of
transfer) 13.9 6 3.9 12.7 6 2.3 (p = NS)
96
PREDICTORS OF NON-ALCOHOLIC STEATOHEPATITIS
(NASH) IN OVERWEIGHT CHILDREN
Stacee M. Lerret2, Joseph Skelton1, Denise Kilway1, Grzegorz Telega1.
1
Gastroenterology, Medical College of Wisconsin, Milwaukee, WI;
2
Gastroenterology, Childrens Hospital of Wisconsin, Milwaukee, WI.
Introduction: The prevalence of obesity and its complications
increases in the pediatric population. Identification of the hepatic
complications of obesity is essential for development of treatment
protocols. Currently there are no accepted criteria for performing
diagnostic liver biopsy (LB) in obese pediatric patients. The aim of this
study was to evaluate utility of arbitrary lab criteria in prediction of
Non-alcoholic fatty liver disease (NAFLD) and/or NASH among
children referred to the NEW Kids Program TM, a weight management
program at CHW.
Methods: We recorded age, gender, race, weight, height, BMI,
aspartate aminotransferase (AST), alanine aminotransferase (ALT),
and fasting levels of: triglycerides, total cholesterol, LDL, HDL, and
insulin level. Guidelines used in decision to perform a LB in obese
patients include: (1) no evidence of other liver disease and (2) AST or
ALT greater than 200 iu/l or any elevation of AST or ALT for more than
6 months. We reviewed records of overweight children with a body
mass index (BMI) greater than 95% for age who underwent LB
according to our guidelines.
Results: The patients were selected out of a group of 284 overweight
patients (age 218 years). In this group 60 children (21%) demonstrated
an elevated ALT and 15 children (5%) demonstrated an elevated AST.
Out of this group eight children (3%) met the guidelines to perform
a LB. Age of biopsied children ranged from 8 to 17 years. 4 patients
were male, 4 female. Mean BMI of patients biopsied was 35.1 (6 7.3).
Conclusion: 100% of the children that met our guidelines for LB had
histological evidence of NASH. 87.5% had NASH with fibrosis or
cirrhosis. Determination of sensitivity and specificity of our criteria will
require prospective study. NASH is a chronic progressive liver disease
and is a major cause of morbidity and mortality in obese patients.
Establishment of pediatric guidelines for diagnosis of this disease is
necessary for the development of the treatment protocols.
97
EPIDEMIOLOGY OF ABNORMAL TRANSAMINASES
IN OVERWEIGHT CHILDREN
Grzegorz Telega1, Stacee M. Lerret2, Denise Kilway1, Joseph Skelton1.
1
Gastroenterology, Medical College of Wisconsin, Milwaukee, WI;
2
Gastroenterology, Childrens Hospital of Wisconsin, Milwaukee, WI.
Introduction: Prevalence of obesity increases in the pediatric
population. Among adult overweight patients abnormal transaminases
strongly correlate with features of metabolic syndrome (MS) such as
triglycerides (TG), LDL, insulin level and inversely correlate with
 NASPGHAN ANNUAL MEETING
HDL. The aim of this study was to evaluate whether biochemical
features of MS are associated with higher risk of elevated transaminases
in children referred to the NEW Kids ProgramTM, a weight-
management program at CHW.
Methods: Retrospective study of 284 overweight children 218 years
of age with a body mass index (BMI) greater than 95%. We recorded
age, gender, race, weight, height, BMI, aspartate aminotransferase
(AST), alanine aminotransferase (ALT), and fasting levels of:
triglycerides, cholesterol, LDL, HDL, and insulin.
Results: In our group, 56% were female. 117 (41%) were Caucasian,
and 107 (59%) ethnic/minority (38% African-American, 9% Latino,
12% Other). The mean BMI was 34 kg/m2 (range: 1777), and 24% had
a BMI .40 kg/m2. 57 children or 19.7% demonstrated an elevated ALT.
11 children or 3.9% demonstrated an elevated AST. Elevated transami-
nases did not correlate with age, gender, weight, height or BMI. Elevation
of ALT was statistically more common in Latino children. 145 (65%)
patients had an elevated serum insulin level. Despite the high prevalence
of hyperinsulinemia, elevation of transaminases did not correlate with any
of the biochemical features of MS.
Conclusion: Elevation of transaminases is a common abnormality in
overweight children. Our study underscores the importance of screening
of overweight children for elevated transaminases. We were not able to
establish a relationship between the biochemical features of MS and
elevated transaminases. Adult guidelines for liver biopsy in obese
patients based on biochemical features of the MS should not be used in
children. Possible explanation of our results is that development of non-
alcoholic fatty liver disease precedes the development of the MS.
98
HISTOLOGICAL EVALUATION IN CHILDREN WITH
NON-ALCOHOLIC STEATOHEPATITIS (NASH) AFTER
VITAMIN E THERAPY
Ruben E. Quiros-Tejeira1,2, Sandy Cope-Yokoyama3, Kelly D. Brown3,
Milton J. Finegold3, William J. Klish3. 1Pediatrics, University of
Texas - Houston, Houston, TX; 2Memorial Hermann Childrens
Hospital, Houston, TX; 3Texas Childrens Hospital, Baylor College
of Medicine, Houston, TX.
Treatment efforts in children with NASH have been focus on decreasing
serum aminotransferases with less emphasis in histopathologic changes.
Materials and Methods: 11 children with biopsy-proven NASH were
enrolled. Follow-up liver biopsy was done after 12 months of vit E
therapy (400800 IU daily). Data was prospectively recorded.
Results: 10 children underwent follow-up liver biopsy. One patient was
excluded because of diabetes mellitus needing insulin therapy. There
were 7 males. The mean age was 12.5 6 1.8 years. All children failed to
lose weight yet one decreased his BMI because of height increase.
Initial mean wt was 76.4 6 20.1 kg. The mean BMI was 34.9 6
6.7 kg/m2 with a mean delta BMI of 3.0 6 2.2. Initial mean liver
enzymes were as follows: ALT 179.2 6 123.1, AST 91.8 6 60.9 and
GGT 83.4 6 50.6. Mean delta ALT was 283.7 6 119.3 (p , 0.05).
Fasting insulin, glucose, HbA1C, cholesterol, triglycerides, CRP and
Ferritin level did not change significantly after vit E therapy. All
patients increased their baseline vit E level (p , 0.05). Overall, there
was no significant histological changes in steatosis, inflammation or
fibrosis. While inflammation grade improved in 2 patients, 6 remained
the same and 2 worsen. Regarding fibrosis staging: 7 children remained
the same, 1 improved and 2 worsen. Worsening in pathology was not
related to severity of weight gain (delta BMI) or delta vit E level.
Conclusions: While all children have demonstrated a uniform im-
provement in aminotransferase levels after vit E, a corresponding
decrease in histopathologic severity was not seen. This study also
prompts a concern about liver enzymes as true markers of therapeutic
success in NASH. Histological assessment should be considered while
evaluating different therapies in this disorder until better markers of
disease progression are validated. A larger, double blind, placebo
control study is need to evaluate the role of vit E in NASH.
523
99
SEX DIFFERENCES IN NON-ALCOHOLIC
STEATOHEPATITIS IN AN ANIMAL MODEL OF
SEDENTARY LIFESTYLE
Stephanie H. Abrams, Chantal Rivera, Hossein Tcharmtchi, C. Wayne
Smith. Pediatrics, Baylor College of Medicine, Houston, TX.
Obesity has reached epidemic proportions in North America and
worldwide. Non-alcoholic steatohepatitis (NASH), which includes
steatosis; inflammation; and fibrosis, affects up to 3% of the worlds
population. Previous studies have reported that male rodents exposed to
hindlimb unloading (HU) have pathology resembling NASH, a phe-
nomenon associated with elevated levels of portal endotoxin. This study
was designed to assess if sedentary lifestyle, modeled by HU, combined
with a high fat/high sucrose (HF/HS) diet causes endotoxin-dependent
inflammation and steatosis in females. It was hypothesized that, based
on the endotoxin-associated injury seen in alcoholic steatohepatitis,
females would have more severe inflammation and steatosis than males.
Male and female Wistar rats were fed standard laboratory chow or
HF/HS diet (15% of calories from casein, 37% from corn oil, and 41%
from sucrose) for 3 weeks. Subsequently, half of each group underwent
HU, with the remaining animals housed separately to control for
thermoregulation. Oil-red O stained liver sections were scored by
a pathologist blinded to the experimental groups/conditions. Chow fed
HU males and HF/HS fed HU males demonstrated a statistically
significant increase in inflammation and steatosis compared with
females. Consistent with these histological findings, serum ALT levels
were approximately 2-fold higher in males. Portal endotoxin levels
were statistically significantly increased in both male and female
HF/HS fed HU animals. Lipid peroxidation end-products measured in
liver homogenates were non-detectable in male controls, but were
significantly increased in male HU rats (p , 0.05). In contrast to their
male counterparts, adiponectin levels were statistically significantly
elevated in female HF/HS fed HU animals. It was concluded that the
combination of diet and sedentary behavior due to HU causes steatosis
and inflammation consistent with NASH in female adolescent rats. In
contrast to our hypothesis, males demonstrated an enhanced hepatic
inflammatory response.
100
MITOCHONDRIAL OXIDANT STRESS IN
EXPERIMENTAL NON-ALCOHOLIC
STEATOHEPATITIS (NASH)
Rohit Kohli, Xiaomin Pan, Padmini Malladi, Mark Wainwright,
Peter Whitington. Department of Pediatrics, Northwestern University,
Chicago, IL.
Background and Hypothesis: The hypothetical two hits leading to
NASH are insulin resistance and oxidative stress related to steatosis.
Experimental NASH can be produced by feeding mice a methionine and
choline deficient (MCD) diet, and exposing mouse AML-12 hepato-
cytes in vitro to MCD medium stimulates PI3-K dependent steatosis and
release of ALT, both without global oxidative stress. Early mitochon-
drial swelling suggests that focal oxidative stress may be involved. We
hypothesize that mitochondrial reactive oxygen species (mROS)
generation leads to impaired beta-oxidation, accumulation of toxic
acyl-CoA moieties and subsequent mitochondrial dysfunction. Further
toxic acyl-CoA moieties may be a therapeutic target for supplementa-
tion with carnitine.
Methods: AML-12 hepatocytes were exposed to MCD and control
(MC+) media 6 0.5 mM L-carnitine (CARN), and mROS generation
was evaluated by co-staining with fluorescent dyes, dihydroethidium
(DHE, a ROS specific vital dye) and DAPI for double-stranded DNA.
ROS generation was confirmed by a cell permeable superoxide
scavenger, Manganese benzoyl porphyrin chloride (MnTBAP). Female
A/J mice were fed MCD or MC+ diet 6 0.5% CARN in drinking water.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
524 NASPGHAN ANNUAL MEETING
mROS was measured by DHE staining in frozen liver sections obtained
on days 3, 7 and 14.
Results: DHE staining showed marked [ mROS activity within 30 min
of exposure of AML-12 hepatocytes to MCD medium, which dissipated
by 3 hr MCD exposure to levels in MC+ medium treated cells.
Incubating with MnTBAP before DHE staining reduced fluorescence,
confirming mROS generation. Supplementing with CARN substantially
reduced mROS generation in MCD treated cells as evidenced by Y DHE
fluorescence. [ hepatic mROS in MCD diet fed mice at all time points
was reduced by CARN supplementation as evidenced by Y DHE
fluorescence.
Conclusions: 1. Focal mitochondrial oxidative stress due to [ mROS
generation has a potentially important mechanistic role in experimental
NASH. 2. CARN may provide a targeted strategy to protect from mROS
stress and thus retard progression of NASH.
101
DEVELOPMENT OF A MULTI-CENTER,
RANDOMIZED CONTROLLED TRIAL FOR CHILDREN
WITH CHRONIC HEPATITIS C (PEDS-C)
Karen Murray2, Bruce Barton3, Regino Gonzalez-Peralta4, James
Rodrigue , John Shepherd5, Jay Hoofnagle6, Kathleen B. Schwarz1;
4
PEDS C Clinical Research Network. 1Johns Hopkins University School
of Medicine, Baltimore, MD; 2University of Washington, Seattle, WA;
3
Maryland Medical Research Institute, Baltimore, MD; 4University of
Florida, Gainesville, FL; 5UCSF, San Francisco, CA; 6NIDDK,
Bethesda, MD.
Chronic hepatitis C is usually asymptomatic in children, but significant
liver disease may occur. No large scale multi-center randomized
controlled trial has been performed in this unique group. Peginterferon
and ribavirin have been shown to be more effective than peginterferon
alone in adults with hepatitis C and is the standard of care. However,
ribavirin is a known teratogen, and preliminary data suggest that
peginterferon alone may be as effective as combination therapy in
children. We, therefore, have designed and initiated a randomized
controlled trial to determine the efficacy and safety of peginterferon
with and without ribavirin in children with chronic hepatitis C. An
initial FDA Orphan Products Grant evolved into a fully funded NIH
cooperative agreement with additional support from Roche Pharma-
ceuticals to establish a group of 11 Clinical centers and a Data
Coordinating Center (PEDS C). Protocol development issues included
an untreated control group, a compassionate combination treatment
arm, blinding and unblinding strategies, and definition of early viral
response. Other study elements were the selection of a central
laboratory and the development of an Automatic Response System to
facilitate patient registration and randomization. NIDDK sponsorship
allowed for the integration of additional investigator-initiated studies
not traditionally included in industry-sponsored trials including studies
of the effects of treatment on body composition, growth and neuro-
cognitive functioning. Finally, Ancillary Studies and Publication Policy
Guidelines were developed, and a PEDS C Website was constructed.
Since there have been few large-scale randomized controlled trials in
pediatric gastroenterology, lessons learned from this trial may assist in the
development of similar studies in this field.
102
IMPACT OF VACCINATION IN THE ELIMINATION OF
HEPATITIS B IN CHILDREN ,5 YEARS. (199204)
Carlos Castaneda1, G Delgado2, MA Galindo2. 1Section of Pediatric
Gastroenterology, National Institute of Gastroenterology, Havana City,
Cuba; 2National Dept of Epidemiology, Ministry of Public Health,
Havana City, Cuba.
After several decades of having an effective vaccine for the prevention
of hepatitis B (HB), this disease is still a world health problem,
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
especially in developing countries. In Cuba, the universal vaccination of
newborns was included since 1992 in the N.I.P. achieving + 95%
coverage. The immunization of 814 y was begun in 1994 at schools,
completing a group ,20 y in 2000. Our work presents the impact of this
strategy.
The HB Heberbiovac recombinant vaccine was used with high and
effective immunogenic level. The scheme for newborns is 3 doses at the
moments, 0, 1 and 6 m, with an average annual national coverage +
95%. The 0-1-2-12-month scheme was used for the children of infected
mothers by tests during pregnancy, without using the hyperimmune B
gamma globulin. The diagnosis criteria was clinical evidence of acute
viral hepatitis and HbsAg positive with ALAT elevated. Statistical data
is obtained by the N. H. S.
Ten yrs after the application of this strategy there a reduction in the
acute disease of 93.9% in the general population, 99.3% in ,15 y and
there were no reported cases in ,5 y since 2000, representing a 100%
reduction. This chart shows the impact of the Vaccination Program with
elimination of acute cases of HB in that age group. These results
demonstrate that it is possible to eliminate HB in infancy. AS the group
of vaccinated subjects gets older, the protected age groups will increase.
This raises the possibility of eliminating acute disease, and reduce the
mortality from cirrhosis and cancer hepatic. The continuity of this
program will make it possible for Cuba to be one of the first countries to
be close to eliminating HB.
TABLE 1. Cases of children under 5 years of age.
Cuba 19912004. By year
Years 1991 1992 1993 1994 199596 199798 1999 200004
Cases 72 66 48 31 33 7 1 0
This chart shows the impact of the Vaccination Program with
elimination of acute cases of hepatitis B in that age group.
103
WILSON DISEASE: CLINICAL EXPERIENCE AND
DIAGNOSTIC CHALLENGES AT THE CHILDREN
HOSPITAL OF COSTA RICA
Dr. Carlos Saenz Herrera, Gabriela Jimenez, Carlos Morales, Alfredo
Mora, Celina Guzman, Carolina Jimenez-Rivera. Hospital Nacional de
Ninos de Costa Rica, San Jose, Costa Rica.
Background: Diagnosing Wilson Disease (WD) is often a difficult
task. Diverse clinical and laboratory findings may help establish the
diagnosis. However, since there is no gold standard, liver biopsies are
necessary in many cases to assess severity of disease and often to
confirm it.
Aim: To describe clinical presentation and socio-demographic
characteristics of patients diagnosed with WD in our institution.
Methods: Retrospective chart review of all consecutive patients
discharged from our hospital carrying the diagnosis of WD from
January 1992 to March 2005.
Results: Thirty-five patients were discharged with the diagnosis of WD,
40% were female (n = 14) and 60% were male (n = 21). Mean age at
presentation was 10 years (515 years). Clinical presentation included
hepatic presentation in 57% (n = 20), hematological in 20% (n = 7),
neurological in 6% (n = 2) and six patients were asymptomatic siblings
screened for WD. There were four children (11%) who died from
fulminant hepatic failure. Kayser-Fleischer rings were present in 17.8%
of the patients (5 out of 28). Mean ceruloplasmin level was 36 mg/dl
(0177 mg/dl). The aspartate aminotransferase levels oscillated
between 20 and 2296 IU/L (mean = 135 IU/L) and the alanine
aminotransferase levels ranged between 10 and 1941 IU/L (mean =
135 IU/L). Urinary copper excretion values were available in 21 patients
and ranged between 4 and 1400 mg/24 hr (mean = 396 mg/24 hr). Liver
biopsies were available in 11 (31%) patients at diagnosis, only one had
cirrhosis and 6 showed moderate fibrosis. Three patients underwent
 NASPGHAN ANNUAL MEETING
liver transplantation and are still alive. The majority of the patients
received chelating therapy with D-Penicillamine and few of them in
combination with Zn.
Conclusions: There was predominance in males with a mean age of 10
years. Only a small number of patients presented with Kayser-Fleischer
rings and the majority of them had elevated basal urinary copper
excretion values. Liver biopsies are useful but not often performed.
Screening is important in first-degree family members.
104
CHOLESTATIC SYNDROMES AND ELEVATED
SWEAT ELECTROLYTES
John Lloyd-Still. Pediatrics, Rush University Medical Center,
Chicago, IL.
Background: ABC proteins bind directly to ion channels and alter their
confrontation and function. The MRP/CFTR subfamily is the largest of
the 30 human ABC proteins sequenced.
Results: In 1981 (1) we reported 2 siblings with Bylers syndrome
(PFIC1) who had normal sweat Cl which later went in the CF range.
Both succumbed after liver Tx. Pathology showed no evidence of CF.
This was confirmed in 1982 (2) when an infant with meconium
peritonitis (normal Cl) developed PFIC and elevated Cl; and in 1996 (3)
when 3/5 pts with PFIC had elevated sweat Na. We follow another pt
with confirmed PFIC1 with Cl in the CF range whose cholestasis
improved after bile diversion; CF mutations are negative. Our 4th pt had
gallstone cholecystitis at 2 yrs and persistently elevated alk. phos. His
sweat Cl remains in the CF range for 19 yrs. His course is compatable
with mild MDR3 disease. MDR3 transports phospholipids across the
biliary canalicular membrane and is localized to chromosome 7q21
adjacent to the CF gene. Some PFIC pts develop elevated sweat Cl and
pancreatic insufficiency (PI) post liver Tx (Knisely, personal communi-
cation) and PI complicates 42% with Alagilles syndrome. In 1985 (4) we
reported that PGE1 infusion elevated sweat Cl to the CF range, which
normalized after PGE1 was discontinued. Recently, a prostaglandin
transporter (MRP) has been identified. Lastly, a phylogenetic rooted tree
shows the aligned relationship between MDR1, MDR3 and CFTR (5).
Conclusions: These observations of ABC transporter dysfunction
suggest a common pathyway for sweat electrolyte elevation. There is
a relationship between CF, cholestatic syndromes and essential fatty
acids. More data is required on sweat Cl in cholestatis syndromes pre
and post liver Tx.
References:
1. J Pediatr 1981;99:580.
2. Pediatrics 1982;69:325.
3. Arch Dis Child 1996;75223.
4. J Pediatr 1985;106:953.
5. Biochem Biophys Acta 1999;1461:347.
105
PERCUTANEOUS LIVER BIOPSY PRACTICE
PATTERNS AMONG PEDIATRIC
GASTROENTEROLOGISTS IN NORTH
AMERICA: RESULTS OF A WEB-BASED SURVEY
Sanjoy Banerjee1, Jenifer Lightdale2, Warren Bishop1. 1Pediatric GI,
Childrens Hospital of Iowa, Iowa City, IA; 2Gastroenterology,
Childrens Hospital Boston, Boston, MA.
Percutaneous liver biopsy (PLB) practices vary widely among pediatric
gastroenterologists (GIs).
Aim: To document PLB practices among pediatric GIs in North
America.
525
Methods: 699 NASPGHAN members were invited by email to
participate in a web-based survey. Queries about practice preferences
used 5-pt Likert scales (1 = not at all, 5 = very important). Results were
tabulated, and variables were analyzed by x2.
Results: 474 invitations were viewed and 308 (65%) surveys
completed. 62% of all respondents reported practicing .10 yr, and
70% at academic centers. 59% described themselves as practicing GI
and hepatology vs. 5% hepatology exclusively. 36% of all respondents
perform no PLB, 58% #5 PLBs/mos, and 6% .5 PLBs/mos. Among
those who do not perform PLB, 65% refer to interventional radiologists
(IR), with medical indications, patient safety, and desire for real-time
ultrasound (US) reasons for referral with mean ratings .4. Among
those who perform PLBs, Bard-Monopty (39%) and Jamshidi needles
(34%) are preferred devices. 44% observe patients for up to 8 hrs post-
PLB while 56% admit overnight. In the same group, 36% report always
using US assistance vs. 20% who never do. Among those who use US,
patient safety, unusual anatomy, and inability to palpate/percuss liver
margins are factors that scored .4. GIs who do not use US gave mean
scores of #2 (1 = totally agree, 5 = totally disagree) for no proof of
necessity and no cost benefit. We found no differences between
academic vs. non, general GI vs. hepatology, or practice experience
#10 vs. .10 yr groups regarding preference for routine use of US, PLB
device, or overnight observation. Non-academic practitioners are more
likely to use US routinely (34/69 vs. 49/160, p = 0.01). General
pediatric GIs are more likely to refer to IR (73/292 vs. 0/16, p = 0.008).
Discussion: Significant variation in PLB practice exists among pediatric
GIs in North America. Further health services research may be useful to
understand this variation and determine best practices.
106
SEVERE ADVERSE CONSEQUENCES ASSOCIATED WITH
NON-ADHERENCE IN ADOLESCENT LIVER
TRANSPLANT RECIPIENTS
Rebecca Berquist, William Berquist, Iris Litt. Pediatrics, Stanford
University, Palo Alto, CA.
Background: Non-adherence is reported as a common behavior in
adolescent transplant recipients. Yet, the prevalence, morbidity and
mortality associated with this behavior is poorly described and
understood in the pediatric liver transplant population.
Aim: To determine the prevalence and adverse consequences associated
with non-adherence to immunosuppressive therapy in the adolescent
liver transplant population.
Methods: We reviewed the charts of ninety-eight patients from 1987 to
2002 who by December of 2002 had survived at least one year post-
transplant and were followed by the Pediatric Liver Transplant Service
at any point during their adolescent period (ages of 1221). Non-
adherence was defined as the voluntary admission of non-adherence by
the patient or reported non-adherence by a parent or heath care provider.
Results: Using the inclusion criteria, a total of 97 patients represented
the study sample. 37 subjects (38.1%) were defined as non-adherent and
60 (61.8%) were adherent. Non-adherence was significantly associated
with episodes of late acute rejection (P , .025) and with episodes of late
acute rejection as an adolescent (,.001). Non-adherence was also
significantly associated with re-transplantation and death secondary to
chronic rejection (P , .01, P , .025 respectively) using Chi-square
analysis.
Conclusions: Non-adherence to immunosuppressive therapy is a prev-
alent problem in the adolescent liver transplant population. The greater
incidence of late acute rejection, and death and re-transplantation
owing to chronic rejection in non-adherent patients suggests that
non-adherence is significantly associated with an increased risk of
morbidity and mortality. Further investigation of this issue is necessary
to identify risk factors to design the most effective intervention to
address this problematic behavior and to increase patient survival and
well-being.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
526 NASPGHAN ANNUAL MEETING
107
CHILDREN WITH AUTOIMMUNE HEPATITIS - ARE THEY
TAKING MEDICATIONS AS PRESCRIBED?
Nanda Kerkar1, R. Annunziato2, L. Foley1, J. Schmeidler2, C. Rumbo1,
S. Emre1, B. Shneider1, E. Shemesh2. 1Pediatrics and Transplant
Surgery, Mount Sinai Medical Center, New York, NY; 2Psychiatry,
Mount Sinai Medical Center, New York, NY.
Background and Aims: A key to successfully managing autoimmune
hepatitis (AIH) is maintaining stable immunosuppression. Although
adherence to medical recommendations is important in AIH, the extent
children actually follow the prescribed regimen is unknown. Those with
psychiatric symptoms related to their illness may not take medications
as it reminds them of their illness, a memory they may wish to avoid.
The aims were to assess: (i) adherence to medications (ii) relationship
between adherence and medical outcome and (iii) psychiatric risk
factors for non-adherence.
Methods: Data were obtained prospectively from consented pediatric
patients with a diagnosis of AIH (including those stable post OLT)
during one year of follow-up. To measure adherence we used an
electronic monitoring device (EM), which records each opening of
a pillbox. Post-OLT trough blood levels of Tacrolimus were recorded.
With regards to psychosocial predictors, we focused on disease-
related distress, using both a semi-structured, full psychiatric
interview, and a self-report posttraumatic stress (PTS) tool. The
chosen medical outcome measure was maximal ALT reading during
the year.
Results: 35 pediatric patients with a diagnosis of AIH (15 post-OLT)
were enrolled. Only 14 of them (40%) used their EM device and none
took their medications exactly as prescribed (EM range 2894% of
expected). EM readings correlated inversely with maximal ALT (p =
0.03, r = 20.59) and with PTS (p = 0.02, r = 20.70). Similarly, in the
post-OLT group, increased fluctuation in tacrolimus levels correlated
inversely with EM (p = 0.04, r = 20.72) and PTS (p = 0.03, r = 0.62).
Conclusion: Adherence can be assessed objectively. Non-adherence
was prevalent even though children/parents knew they were being
monitored. Because it correlated with higher maximal ALT, non-
adherence emerges as an important risk factor for poor outcome. PTS
symptoms correlated with non-adherence, and early intervention may
improve outcome.
108
DEVELOPMENTAL OUTCOME IN A COHORT OF
INFANT LIVER TRANSPLANT RECIPIENTS
Susan M. Gilmour1, Robin Adkins2, Charlene M. Robertson1.
1 contributing to decreased morbidity in the last four years. Diagnoses
Pediatrics, University of Alberta, Stollery Childrens Hospital,
Edmonton, AB, Canada; 2Pediatrics, Glenrose Rehabilitation Hospital,
Edmonton, AB, Canada.
Children with end-stage liver disease and liver transplantation (LT)
during the first 12 months of life are exposed to many potential
neurological insults during the most vulnerable period of brain growth.
We describe the developmental outcome in infants transplanted at the
University of Alberta, Stollery Childrens Hospital.
Methods: Infants #12 months of age who had a LT between 1990
2004 were registered and followed by the Complex Pediatrics Therapies
Project. The children were assessed between 6 to 12 months post-LT
with a neurological examination, audiology and administered the
Bayley Scales of Infant Development-II (BSID-II). The BSID-II
provides a Mental Development Index (MDI) which has a population
normative score of 100 6 15. Developmental delay is defined as a MDI
of ,70 and borderline delay 8470. The registry also recorded potential
predictive variables including age at LT, socioeconomic status (SES),
diagnosis, growth and serum bilirubin and ammonia.
Results: During this period, 27 grafts were transplanted into 24
recipients, with a patient survival of 21/24 (87.5%) and a graft survival
of 21/27 (77.8%). Follow-up was available on 18/21 (85.7%) survivors.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Etiology of the 18 children included biliary atresia n = 14 and other n =
4. The mean MDI was 77.1 # 16.9 (range 10949) with only 4 (22%)
children having a MDI .85 (normal development), 9 (50%) had a MDI
8470 (borderline delay) and 5 (28%) had a MDI ,70 (developmental
delay). Compared to the expected general population, prevalence of
borderline delay was 3 times and developmental delay 14 times the
expected rate. There was no correlation between MDI and the age at LT,
SES, diagnosis, growth and pretransplant serum bilirubin and ammonia.
Conclusion: End-stage liver disease and LT in infancy results in over
75% of children with borderline or developmental delay. All infants
should have thorough developmental assessments to enable them to
receive appropriate supports and learning environments to maximize
their potential.
109*
OUTCOME OF LIVER TRANSPLANTATION IN
INFANTS LESS 10 KG
Cynthia Kawai3, Rebecka Meyers2,3, Eric Scaife2,3, John Sorensen2,3,
Le Grande Belnap2,3, Willem Van der Werf2,3, Molly OGorman1,3,
Stephen Guthery1,3, Dan Jackson1,3, Linda Book1,3. 1Pediatrics,
University of Utah, Salt Lake City, UT; 2Department of Surgery,
University of Utah, Salt Lake City, UT; 3Liver Transplant Program,
Primary Childrens Medical Center, Salt Lake City, UT.
Background: The application of liver transplantation (Tx) now
includes small critically ill infants, with unique technical challenges.
Purpose/Methods: We retrospectively reviewed our experience from
19972005 in infants ,10 kg at the time of liver Tx regarding: patient
and graft survival, vascular complications, cause of death, and
diagnosis. We also compared outcomes for the first half and second
half of this time period.
Results: There were 34 infants mean 6.76 kg 6 1.29 (range 4.59 kg),
and mean age 277 6 116 days (range 43657 days) who underwent
liver Tx between 19972005. They represented 45% of all pediatric
transplants from our program. Overall patient survival was 91% and
graft survival 79% with follow up ranging from 4 months to 8.5 years.
Causes of death were two infants with multisystem organ failure within
three months of Tx, and one non-transplant related accidental death.
Vascular complications were one portal vein thrombosis, one hepatic
venous outflow obstruction; and 5 hepatic arterial thrombosis (HAT),
two with successful thrombectomies. In the first four-year period,
patient survival was 86% and graft survival 71%. In the second four-
year period patient survival was 100%, graft survival 19/21 (90%) with
no HAT. In addition to increased experience, avoidance of over-sized
grafts and arterial anastamosis to the aorta were likely factors
included biliary atresia 19 (56%), alpha 1-antitrypsin deficiency 4
(12%), neonatal hepatitis 3 (9%), ornithine transcarbamylase deficiency
3 (9%), hepatic tumor 2 (6%). Most infants 22/34 (65%) were listed as
UNOS Status 1, at the time of transplantation.
Conclusion: Critically ill infants represent a significant portion of the
pediatric liver transplant constituency. Despite significant technical
challenges, excellent outcomes can be achieved in this population.
110
PORTAL HYPERTENSION AFTER LIVER
TRANSPLANTATION: LONG TERM FOLLOW-UP
Simon C. Ling, Any Pfeiffer, Avitzur Yaron, Vicky L. Ng. Division of
Gastroenterology, Hepatology & Nutrition, The Hospital for Sick
Children, Toronto, ON, Canada.
Aim: To describe the long-term changes in the clinical and imaging
features of portal hypertension (PHT) following liver transplantation in
children.
Methods: Retrospective chart and database review of consecutive
children undergoing their first liver transplant at one institution between
 NASPGHAN ANNUAL MEETING
1993 and 2003. Details of clinical progress and ultrasound or CT
imaging were recorded at 1y post-transplantation and at last follow-up.
Results: Data were extracted on 112 children (median age at transplant
1.7 y, range 1 m17.9 y, 59 girls) who underwent 121 transplants.
Primary diagnoses included biliary atresia (n = 53), acute liver failure
(19), hepatoblastoma (9), TPN liver disease (4), Alagille syndrome (3),
tyrosinemia (3), sclerosing cholangitis (3) and others (18). Last follow-
up occurred at a median 3.4y after transplantation. Seventeen children
had died within 1y of transplant (median 47 days, range 1215 days)
and a further 3 died after longer follow-up (3.8 y6.8 y). Follow-up data
from ultrasound scans of 86 and 78 children at 1 y and at last follow-up,
respectively, are presented in the table. Ascites was mostly of minimal
volume. PV thrombosis was recognized in 1 child at 1 y and 2 children
at last follow-up. GI bleeding occurred in 5 children by last follow-up
and was due to portal vein (PV) thrombosis, arteriovenous fistula and/or
parenchymal disease.
Conclusion: The imaging features of PHT often persist long after liver
transplantation. Only a minority of children develop clinically
significant sequelae of PHT, which arises from both vascular and
parenchymal disease.
Before 1 y after Last
transplant transplant follow-up
Splenomegaly (%) 69.6 37.5 36.6
Ascites (%) 53.6 8.0 4.5
Collaterals (%) 41.1 12.5 13.4
Reversed flow in main PV (%) 10.7 0.0 0.0
GI hemorrhage (%) 21.4 0.9 4.5
111
COMPLICATIONS FOLLOWING LIVER
TRANSPLANTATION FOR HEPATOBLASTOMA
Matthew R. Riley, William Berquist, Melissa Hurwitz. Pediatric
Gastroenterology, Stanford University, Palo Alto, CA.
Background: While hepatoblastoma (HB) is the most common
primary malignant liver tumor of childhood, it is a rare indication for
orthotopic liver transplant (OLT). Little is known about optimal post-
OLT management and the incidence of complications following OLT
for HB.
Aim: To evaluate the incidence of complications following OLT for
unresectable HB, including renal failure, graft rejection, infection and
vascular thrombosis.
Methods: The medical records of all children receiving liver trans-
plants for hepatoblastoma between 2000 and 2005 at our institution
were reviewed.
Results: Twelve OLTs were performed on 9 patients. Four patients had
resectable local metastasis at the time of OLT (3 portal vein, 1
diaphragm). Average weight at OLT was 15.1 kg (range 524) and
average age was 49 months (range 3117). One death and 4 graft losses
occurred (3 vascular thromboses, 1 primary non-function). Complica-
tions during the first 100 days after OLT included peritonitis (7),
bacteremia (5), wound infection (4), wound dehiscence (1), urinary tract
infection (1) and thrombosis (2 hepatic artery, 2 portal vein, 1 inferior
vena cava). Five of these complications occurred while patients were
neutropenic. Three of the 4 patients who had at least one estimated
creatinine clearance (CrCl) of ,110 mL/minute before OLT required
either hemodialysis (HD) or hemofiltration (HF) after OLT. A drop in
CrCl during pre-OLT chemotherapy did not predict need for HD or HF.
No patient required HD more than 2 months after OLT. Three episodes
of rejection occurred during the first 100 days post-OLT. No episodes
of rejection occurred during periods of chemotherapy-induced neutro-
penia.
Conclusions: Children with unresectable HB undergoing OLT
comprise a small but complex patient population. Aggressive anti-
527
coagulation may be needed to prevent vascular thrombosis in this group.
CrCl ,110 mL/minute may be predictive of need for post-OLT HD or
HF. Despite post-OLT chemotherapy, few neutropenic complications
occurred. Low risk of rejection during periods of neutropenia may allow
for immunosuppressive dose reduction following chemotherapy.
112
IS IT CAROLIS OR BILIARY ATRESIA?
Dan W. Thomas1, F. Watanabe4, J. Derdoy1, D. Schofield3, S. Johnson1,
2 1
Y. Genyk . Pediatric GI, Childrens Hospital Los Angeles, Los Angeles,
CA; 2Pediatric Surgery, CHLA, Los Angeles, CA; 3Department of
Pathology, CHLA, Los Angeles, CA; 4Division of Liver Transplanta-
tion, Cedars Sinai Medical Center, Los Angeles, CA.
Background: Biliary atresia (BA) is typified by progressive cholestasis
in the first few weeks of life. Early recognition and surgical
portoenterostomy often abates further liver damage. BA is usually
isolated without familial occurence or co-existing congenital anoma-
lies. A few infants with BA have other congenital anomalies. We report
3 infants diagnosed with BA based upon clinical and liver biopsy
findings who underwent liver transplantation and were found to have
features of Carolis disease (CD) in their explants. CD frequently has
a familial occurrence with polycystic kidneys or congenital hepatic
fibrosis. Progressive liver disease can happen with CD, but is
uncommon in infants. Most patients have problems with portal and
systemic hypertension, or kidney dysfunction. All 3 infants were
referred and diagnosed with BA relatively late. None underwent
portoenterostomies because of their ages and/or advanced cirrhosis. BA
was diagnosed on initial liver biopsy done in 2 of the infants using
standard criteria of bile duct proliferation, intraductular bile plugs, and
portal fibrosis or biliary cirrhosis. CD was diagnosed in the explants by
the presence of microscopic segmental bile ductal ectasia with staghorn
duct fusion, rudimentary bile duct epithelium, and grossly by varying
degrees of fibrosis and biliary cysts. None of the patients had a family
history of liver or kidney disease.
Conclusion: Either these 3 children represent unusual examples of CD
and their liver biopsies and imaging studies were inaccurate, or these
cases typify the natural history of some cases of BA.
Patient data
Age BA Fract. EHBA on Age Fract. CD in
Sex diagnosed bili Alb biopsy Portoenterostomy transplanted bili Alb explant
M 5 mos 6/3 4.3 Y N 8 mos 7.5/5 2.9 Y
F 4.5 mos 7/4.9 3.7 Y N 10.5 mos 8.4/6 2.4 Y
M Uncertain NA NA ND N 9 mos 18.3/17 1.3 Y
113
CHILDHOOD CHOLEDOCHAL CYSTS: CLINICAL
PRESENTATION AND DIAGNOSTIC FINDINGS
Khiet Ngo, M. Shah, M. Klooster, M. Walters, J. McCracken, L. Gibbs, D.
Broome, G. Yanni. Pediatric Gastroenterology, Loma Linda University
School of Medicine, Loma Linda, CA.
Background: The risk of developing malignancies associated with
choledochal cysts (CC) increases with age, making timely recognition
and surgical intervention vital. There are only a limited number of
reports describing the presentation and diagnostic findings associated
with CC. We describe our experiences with six pediatric patients
diagnosed with CC.
Methods: A retrospective chart review of pediatric patients diagnosed
with CC.
Results: Summarized in Tables 1 and 2.
Conclusions: 1. Jaundice and cholestasis are common presentations of
CC in neonates and infants, while persistent chronic or acute abdominal
pain, abdominal tenderness, and vomiting are common presentations in
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528 NASPGHAN ANNUAL MEETING

young children. 2. Elevations in liver and pancreatic enzymes are also with saline (N = 13) on day of life 2. They were weighed daily and
frequently observed in our patients with CC. 3. Abdominal ultrasonog- examined for jaundice, bilirubinuria, pale (acholic) stools, and oily rectal
raphy is a reliable diagnostic tool for CC. MRI and/or CT/cholangiog- discharge or oily hair effect. Clinical cholestasis (stasis of bile flow) was
raphy, particularly with reconstructive imaging, may be useful in pre defined as acholic stools plus oily hair or oily rectal discharge. Mice were
operative planning and defining pancreatic involvement. Imaging sacrificed at 1, 2, or 3 weeks post-inoculation (pi), and blood and liver
studies may be less reliable for infants in predicting the particular type tissue were collected.
of CC. 4. ERCP remains a useful part of diagnosing and managing CC Results: Three animals which died within 4 days pi were excluded from
for our patients. the analysis. Of 25 animals inoculated with greater than 107 pfu live
RRV, 23 (92%) developed cholestasis by 9 days pi. Two developed
TABLE 1. Clinical features in children acholic stools transiently but no oily hair or oily discharge. Of
cholestatic animals, eight (25%) were sacrificed by post-inoculation
with choledochal cyst (pi) day 14, seven (30%) died by pi day 16, and 5 (22%) redeveloped
Age (yrs)/ pigmented stools between 14 and 15 days post-inoculation. At 1 week
Gender/ Signs & Alkaline T/D Amylase/ pi, the gallbladder and cystic duct appeared distorted in situ. At two and
Patient Ethnicity Symptoms AST/ALT Phosphatase Bilirubin Lipase three weeks pi, narrowing/blockage of the cystic and common bile duct,
distorted shape of the gallbladder, and green bile plugs in the liver were
1 3/F/ African Abdominal 140/126 582 5.2/3.2 474/420
American Pain/
seen. Histology showed hepatic necrosis and bile duct inflammation at
Tenderness
these time points. Animals injected with inactivated virus or with saline
2 6/F/ Hispanic Abdominal 82/111 299 6.5/4.0 699/1658
did not develop cholestasis.
pain/
Conclusions: Intraperitoneal injection of live RRV prior to 48 hours of
life leads to clinical and histopathological disease consistent with
Tenderness,
biliary atresia. Injection of a comparable dose of inactivated virus does
Vomiting
3 7/F/ Hispanic Abdominal 84/178 384 0.8/0.1 104/43
not cause biliary atresia.
pain/
Tenderness,
Vomiting Video and Capsule Endoscopy
4 2/F/ Asian Abdoinal 25/16 96 2.4/1.2 106/160
pain/ 115
distension,
Vomiting, CAPSULE ENDOSCOPY IN CHILDREN LESS
Diarrhea THAN 10 YEARS OF AGE
5 0.5/M/ Jaundice 53/78 301 6.8/4.8 13/18 Victor L. Fox. Gastroenterology and Nutrition Childrens Hospital,
Hispanic Boston, MA.
6 0.08/F/ Jaundice 54/63 296 4.5/3.0 Not
Caucasian available Background: Capsule endoscopy (CE) is the most desirable tool for
non-invasive imaging of suspected small bowel (SB) disease,
especially gastrointestinal bleeding (GIB). The Pillcam capsule
TABLE 2. Diagnostic modalities in children device has only been approved by the FDA for use in children 10
with choledochal cyst 18 years of age. Younger children may also benefit by this technology
but the technique, diagnostic yield, and safety in this age group have
MRI*/CT ERCP Operative not been studied.
cyst cyst diagnosis Methods: All CE cases at a single pediatric facility were retrospec-
Patient Ultrasound type type of cyst type tively reviewed to identify those involving children ,10 yrs of age.
Patient demographics, clinical indications, underlying diagnoses,
1 CC Type IV *IV V Not Performed technique for capsule placement, small bowel transit time (SBTT),
2 CC Type IV IV IV IV capsule findings, and complications were recorded.
3 Not Performed *IV IV Not Performed Results: 77 CE procedures were conducted between October 2002 and
4 Ascites IV IV IV May 2005. Twenty two (29%) were performed in 20 children ,10 yrs
5 CC Type IV *IV Not Performed I of age with mean age = 5.9 yrs (range 2 to 9) and mean weight = 22 kg
6 CC Type IV *IV Not Performed I (range 13 to 32). Primary indications were GIB (n = 19), suspected
polyp (n = 2), and malabsorption (n = 1). Diagnoses included vascular
anomalies (n = 9), Turners syndrome (n = 2), protein-losing
enteropathy (n = 2) and one of each: Tetralogy of Fallot, Peutz-Jeghers
syndrome, Cowden syndrome, alpha-1 antitrypsin deficiency, vasculi-
114 tis, portal hypertension, colonic duplication, and multivisceral trans-
plantation for microvillus inclusion disease. The device was
ROTAVIRUS-ASSOCIATED BILIARY ATRESIA IN A MURINE endoscopically placed into the duodenum in all but 3 children.
MODEL REQUIRES REPLICATING VIRUS Capsules reached the colon in 14 of 22 (64%) attempted procedures
Paula M. Hertel, Milton J. Finegold, Mary K. Estes. Baylor College of with a mean SBTT = 181 minutes (range 65 to 294). Capsules reached
Medicine, Houston, TX. the colon more often when procedures were limited to EGD (75%)
versus EGD + colonoscopy (45%). SB abnormalities detected in 14 of
Background: Biliary atresia (BA) is a progressive, irreversible 21(67%) completed procedures included vascular anomalies (n = 7),
obliterating disease of large bile ducts which results in severe liver varices (n = 1), ulcer/erosion (n = 4), polyps (n = 1), abnormal villi
disease and is the indication for more than 50% of pediatric liver (n = 2), and fresh blood (n = 4). Transient gastric retention was a single
transplantations performed. Rotavirus has been suggested to be the complication.
cause of some cases of BA. Conclusion: CE may be performed safely in young children after
Methods: Neonatal Balb/c mouse pups were injected intraperitoneally capsule ingestion or endoscopic placement with a high yield of
(ip) with live rhesus rotavirus (RRV) triple-layered particles (TLPs) abnormal findings. Simultaneous colonoscopy adversely affects SBTT
(N = 28), with comparable doses of inactivated RRV TLPs (N = 25), or resulting in less complete SB imaging.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
116
PEDIATRIC PERSPECTIVES ON PATENCY: INITIAL
REPORT OF A PEDIATRIC TRIAL EMPLOYING A
PATENCY CAPSULE WITH A SINGLE TIMER PLUG
Stanley A. Cohen, Cathy Simms. Childrens Center for Digestive
Healthcare, Atlanta, GA.
Capsule endoscopy (CE) has been well tolerated in patients with Crohns
Disease (CD) with minimal capsule retention. However, this safety
profile has not yet been well established in children and adolescents.
Methods: The Patency Capsule (PatCap) is an ingestible, dissolvable
capsule containing a radiofrequency identification tag and is the same
size as the PillCam SB Capsule. A timer plug erodes and allows
dissolution of the capsules body. The remaining fragments of the
capsule can pass even small orifices. An ongoing, single center,
prospective study evaluating the impact of CE on CD management used
the PatCap with a single timer plug to screen patients for inclusion.
Those passing the PatCap within 40 hrs were able to undergo CE within
the study. Those failing to pass the capsule within that time period could
have CE performed outside the study.
Findings: Twelve patients (ages 1218 years) ingested the PatCap. Five
excreted the PatCap within the set time of 40 hrs. (mean 20.8) and
proceeded with CE. Four patients who excreted the PatCap beyond the
allotted time also underwent CE (2 had a complete SB studies, and all 4
excreted the PillCam). In 2 patients, small bowel obstructive symptoms
required hospitalization. One underwent resection with the disinte-
grated capsule found distal to his strictured ileum. The other, whose
PatCap was never recovered, was discharged on medical therapy. Of the
other 10 PatCap, 1 was excreted intact at 12 hrs; 6 were disintegrating at
the time of passage (range 8.672.9 hrs); 2 were not returned. In the 1
patient passing the capsule after 130 hrs, the PatCap had disintegrated
completely. No apparent difference in age, height, weight, or eventual
diagnosis distinguished those who passed the PatCap in the allotted time
from those who did not.
Conclusion: This first pediatric and first US report of PatCap
experience demonstrates that patency evaluation may be useful in
pediatric CD where there is concern about potential retention of the
PillCam SB capsule. Further studies may show broader applicability.
117
WIRELESS CAPSULE ENDOSCOPY: INITIAL
PEDIATRIC EXPERIENCE
Franziska Mohr, Marsha Kay, Robert Wyllie, Lori Mahajan. Pediatric
Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH.
Background and Study Aims: Wireless capsule endoscopy (WCE)
allows painless imaging of the small bowel without radiation and aids in
the diagnosis of obscure small bowel disease in adults. To date there is
only very limited data regarding the use of WCE in pediatric patients
and endoscopic deployment has not been reported in children. The aim
of our study was to determine the indications, feasibility, outcome and
complications of WCE in children.
Patients and Methods: An IRB approved retrospective chart review of
17 patients (11 F: 6 M) with a mean age of 14.8yrs (7.619.2 yrs) and
mean weight of 49.2 kg (2484.2 kg) undergoing WCE was performed.
Indications included possible Crohns (CD) disease in 13, assessment of
degree of involvement in 2 known IBD patients and occult bleeding in
2. 13 patients swallowed the capsule without difficulty. Endoscopic
deployment was performed in the remaining 4 patients using a through-
the-channel WCE deployment device.
Results: All studies were successfully completed. Mean small bowel
transit time was 266 min. (76510 min.). The capsule was positioned at
the IC valve at the end of the study in 2 patients and passed without
complication in all. No complications were encountered during or after
the procedure. 7 studies (41.2%) showed abnormalities: small bowel
lesions consistent with Crohns disease in 5 patients (29%), enterobiasis
in 1 patient (5.8%) and gastritis in 1 (5.8%) patient. In addition a small
529
2 mm polyp was identified in one of the patients with CD. The findings
on capsule endoscopy altered the management in 5 patients (29%) by
either establishing a new diagnosis or initiating a change of therapy and
eliminated additional testing in 5 additional patients (29%).
Conclusions: WCE is a valuable diagnostic tool in children with
suspected small bowel disease particularly in Crohns disease not
confirmed by conventional testing. WCE can be performed safely in
young or small pediatric patients. The capsule can be endoscopically
deployed in those patients unable to swallow the device because of
patient age, size or impaired swallowing.
118
WIRELESS CAPSULE ENDOSCOPY: EXPERIENCE
AT A TERTIARY CHILDRENS HOSPITAL
Kenneth K. Lee. Pediatrics, Division of Pediatric Gastroenterology,
Childrens Hospital of Wisconsin, Medical College of Wisconsin,
Milwaukee, WI.
Background: Wireless capsule endoscopy (WCE) is a relatively new
technique to directly visualize the small bowel whose use is rapidly
expanding. WCE has been increasingly used in pediatric patients, but
published data in this group is limited. The pediatric experience in WCE
at one tertiary childrens hospital is described.
Methods: Records of ten pediatric patients who underwent WCE at
Childrens Hospital of Wisconsin Feb 2005May 2005 were retrospec-
tively reviewed and abstracted for indications, placement method,
findings, and complications.
Results: The patients included 5 males and 5 females, age range 516
years (mean 12 years). Presenting symptoms included abdominal pain
(5), anemia (3), joint pain/arthralgia (4), vomiting (2), pelvic abscess
(1), and nausea (1). None had signs of overt gastrointestinal bleeding.
All had esophagogastroduodenoscopy (EGD) and colonoscopy per-
formed prior to WCE referral and all were normal, including ileum.
Nine patients underwent upper gastrointestinal (UGI) and small bowel
follow-through (SBFT) contrast studies; 6 were normal. Five patients
required EGD placement in the duodenum. 8/10 WCEs were success-
fully completed and demonstrated the entire small bowel. One of the
2 patients with incomplete WCE retained the capsule and was sub-
sequently found to have an idiopathic ileal stricture. No other significant
complications were reported. 8/10 WCEs showed no small bowel
abnormalities. The other 2 WCEs showed small bowel ulcerations and
erosions suggestive of Crohns disease (CD), including the 5-year-old
patient. The colonoscopy biopsy specimens of one of these patients,
previously interpreted as normal, were re-reviewed and granulomas and
chronic inflammation consistent with CD was found. Symptoms in both
resolved with CD treatment.
Conclusions: WCE is a useful diagnostic tool for small bowel
disorders. The indications for WCE continue to evolve and increased
experience with WCE in pediatric patients is needed to both define its
indications and delineate its capabilities and limitations.
119*
CAPNOGRAPHY DETECTS SUB-CLINICAL ALTERED
RESPIRATORY EVENTS NOT DETECTED BY ROUTINE
MONITORING IN CHILDREN UNDERGOING EGD WITH
PROCEDURAL SEDATION
Khiet Ngo, M. Klooster, G. Yanni, M. Shah. Pediatric Gastroenterology,
Loma Linda University School of Medicine, Loma Linda, CA.
Introduction: Capnography measures and displays in continuous
waveform exhaled carbon dioxide concentration. Microstream capnog-
raphy (mCAP) is a non-invasive method of capnography using a
modified oxygen nasal cannula. This study compares the effectiveness
of mCAP and conventional monitoring in detecting respiratory changes
for pediatric patients undergoing EGD with deep sedation.
Methods: The authors completed a prospective observational study.
Altered Respiratory Events (AREs) were defined as any abnormality in
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
530 NASPGHAN ANNUAL MEETING
mCAP waveform for .15 seconds or if events were associated with
esophageal intubation/extubation. An independent clinician observed for
any clinical changes and interventions, and recorded data collected by
conventional monitoring (Pulse oximetry [POX], vital signs) and mCAP.
Results: Forty four patients (M:F = 22:22, mean age 8.8 years) were
enrolled. Patients were premedicated with 0.01 mg/kg of atropine and
given an average of 0.16 mg/kg of versed and 1.6 mg/kg of ketamine. A
total of 179 AREs were documented. All 179 AREs were detected by
mCAP while POX detected 15 AREs. Of the 15 AREs detected by POX,
14 were detected by mCAP on average 15 seconds earlier. Two hundred
and five identifiable clinical changes were associated with 168 of the
AREs (78 esophageal intubation/extubation, 80 gag, 14 cough, 18
agitation, 2 breath holding, 13 procedure related), while 11 AREs had
no clinical change. Eighty six interventions were required as a con-
sequence of AREs (10 increased oxygen, 34 suction, 28 additional
sedation, 12 withdrawl of endoscope, 2 reposition).
Conclusions: Sub-clinical AREs are common in children undergoing
EGD with deep sedation. The majority of these AREs are detected by
mCAP but not by conventional monitoring. Most of these sub-clinical
AREs are associated with identifiable clinical changes. The use of
mCAP with conventional monitoring and POX increases the sensitivity
of monitoring in children undergoing procedure related sedation.
120
COMPLICATIONS OF PEDIATRIC
UPPER ENDOSCOPY
Kalpesh Thakkar, Hashem El-Serag, Mark A. Gilger. Pediatrics, Baylor
College of Medicine, Houston, TX.
Background: Esophagogastroduodenoscopy(EGD) is an essential
diagnostic and therapeutic procedure performed to evaluate gastroin-
testinal disorders in children. Although generally safe, EGD has
the potential for complications. There is scarce pediatric data on
complication rates.
Purpose: To determine the frequency of complications in pediatric
EGD using the national endoscopic database, PEDS-CORI (Pediatric
Endoscopy Database System - Clinical Outcomes Research Initiative).
Methods: The PEDS CORI database was queried regarding unplanned
interventions and complications during EGDs done in patients aged 0
18 years from 11/1/99 through 12/31/03. The database was queried for
the indication of the EGD, ASA (American Society of Anesthesiologists)
class, gender, age, and type of complication corresponding to each EGD
included in the study. The type of complications were divided into
cardiopulmonary, gastrointestinal, and other. Data was analyzed using
logistic regression to identify characteristics associated with increased
complications(MH Test of Trend).
Results: 10,236 procedures were included in the study. There were 239
complications (2.3%). The most common complications were oxygen
desaturation (136, 56.9%), transient hypoxia (55, 23%), and gastrointes-
tinal bleeding (28, 11.7%). Complication rates were higher in the youngest
age group (see table). Complication rates also increased with higher ASA
class (p = 0.0004). Complications were found in 126 females (2.5%) vs.
113 (2.3%) in males (p = 0.28).
Conclusions: Complications of pediatric upper endoscopy are rare. The
most common complications are related to hypoxia. There is
a significantly higher complication rate in the first year of life and in
patients with ASA class IV+.
Complication rate by age group
Age group (years) Total N Any comp N (%) p value
01 1640 58 (3.5%) 0.0001
25 1805 57 (3.2%)
610 2473 58 (2.4%)
1114 2602 37 (1.4%)
1517 1716 29 (1.7%)
M-H Test of Trend p-value ,0.0001.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
121
ENDOSCOPY BLUES
Ahmed Dahshan, G. K. Donovan. Department of Pediatrics, Oklahoma
University Health Sciences Center, Tulsa, OK.
Severe methemoglobinemia resulting from the use of topical benzo-
caine has been reported in adults as a rare complication.
We report a case of severe acquired methemoglobinemia resulting from
topical use of benzocaine spray (Hurricaine, Beutlich Pharmaceuticals,
Waukegan, IL) during diagnostic upper gastrointestinal endoscopy in
a 3 year old boy with repeated episodes of hematemesis three weeks
post tonsillectomy. He developed marked cyanosis and became
increasingly agitated immediately after completion of his unremarkable
endoscopic procedure that was performed under intravenous sedation.
He did not respond to maximum supplemental oxygen and had
increased respiratory effort. His pulse oximetry dropped to 85% but
simultaneous arterial blood gas analysis showed marked hypoxemia
(PO2 = 29%) and severe methemoglobinemia (methemoglobin = 39%).
His cyanosis and altered mental status promptly resolved after
intravenous administration of methylene blue.
In patients with methemoglobinemia, pulse oximetry tends to overestimate
the actual oxygen saturation and is not entirely reliable.
Post tonsillectomy bleeding is a rare but occasionally serious complication
that could occur weeks after the surgery, although it is more common to
occur in the first few days. Physicians should remain aware of the
possibility of its late onset.
This case illustrates the severity of acquired methemoglobinemia that may
result from even small doses of topical benzocaine and highlights the fact
that prompt treatment of the disorder can be lifesaving. We question the
rationale for routine use of topical anesthetic spray for sedated upper GI
endoscopy in children. By bringing the attention of endoscopists to this rare
but serious complication, we hope that it will result in its improved
recognition and possible prevention.
122
PATIENT RATINGS BY ENDOSCOPY UNIT
PROVIDERS USING THE AMERICAN SOCIETY OF
ANESTHESIOLOGISTS (ASA) PHYSICAL STATUS
CLASSIFICATION SCALE
Jenifer Lightdale1, Clarissa Valim1, Adrienne Newburg1, Lisa Heard1,
Steven Zgleszewski2, Victor Fox1. 1Gastroenterology and Nutrition,
Childrens Hospital Boston, Boston, MA; 2Anesthesiology, Childrens
Hospital Boston, Boston, MA.
The American Society of Anesthesiologists (ASA) Classification Scale
is a standard used to document physical status of patients undergoing
endoscopy outside of an operating room setting. There is known lack of
uniformity among anesthesiologists in assigning ASA scores.
Aim: To compare inter-rater reliability of ASA scores assigned by
different providers in a pediatric endoscopy unit (EU).
Methods: As part of a quality improvement initiative, anesthesiologist
ASA scores of children scheduled to receive propofol in our EU (5/04
2/05) were compared using k-statistics to independent ratings of the
same cohort by an endoscopist (MD), and an endoscopy nurse (RN).
Demographics, including GI and non-GI diagnoses, were analyzed
using 95% confidence intervals (CIs) and point estimates.
Results: ASA ratings of 104 children (51 male; mean age 12)
undergoing EGD (48), colonoscopy (13) and EGD/colons (43) were
compared. Patient symptoms included GER (56%), abdominal pain
(49%), diarrhea (25%) and GI bleeding (25%). 15% had confirmed IBD.
49% had .1 non-GI diagnosis, e.g. asthma (5%). Although anesthesi-
ologists rated more patients as ASA II (Table 1), overall agreement was
fair (k = 0.57, p , .001). When compared pairwise, there was poor
agreement of anesthesiologist vs. MD (k = .32, CI = 0.150.49) and vs.
RN (k = 0.28, CI = 0.110.45). MD and RN ratings had good
consistency (k = 0.77, CI = .63.90). RNs and MDs were more likely to
 NASPGHAN ANNUAL MEETING
disagree if patients had .1 non-GI dx(p = 0.07); disagreements with
anesthesiologists were not associated with # non-GI diagnoses.
Discussion: ASA ratings of children undergoing endoscopy vary
between clinical providers in our endoscopy unit. Variability in ASA
scores may limit its usefulness as a standard of care. (Supported by
AHRQ K08 HS-13675.)
Endoscopy unit provider ASA II ratings p chronic diarrhea. Recorded data included the age and gender of the
Anesthesiologist vs. Endoscopist 49% vs. 29% ,.05
Anesthesiologist vs. RN 49% vs. 29% ,.05
Endoscopist vs. RN 29% vs. 29% =1.00
123
OUTCOMES OF PEDIATRIC ENDOSCOPIES AT A
TERTIARY CARE CENTER IN SOUTHEASTERN US
Shehzad Saeed1, John Boyle1. 1Peds GI, University of Alabama,
Birmingham, AL; 2Pediatric Gastroenterology and Nutrition Sciences,
University of Alabama at Birmingham, Birmingham, AL.
There exists a perception that different geographical areas tend to have
variations in diagnoses, especially for eosinophilic gastrointestinal
diseases (EGID).
Objective: Our objective was to review endoscopic procedures
performed at a large tertiary care referral center to give a frequency of
diagnosis in the Southeastern US.
Methods: Retrospective review of endoscopic procedures performed at
The Childrens Hospital of Alabama between 3/036/04, performed by
2 gastroenterologists, was downloaded from the Olympus database.
Biopsy reports were reviewed for final diagnosis.
Results: 575 endoscopies were performed during this period. 421 of
these were esophagogastroduodenoscopies (EGD), 139 were colonos-
copies, and 15 were sigmoidoscopies. The indications for these
procedures were abdominal pain, dyspepsia, weight loss, diarrhea, GI
bleeding, refractory constipation/encopresis, and celiac disease screen-
ing. A patient could have been diagnosed with more than one diagnosis
at the same time. The frequency of final diagnoses were: 1) EGID-
(Eosinophilic esophagitis, gastritis, duodenitis, ileitis and colitis)-35%;
2) Reflux esophagitis-21 %; 3) Chronic gastritis-13%; 4) Peptic
duodenitis-4%; 5) Nodular lymphoid hyperplasia of the colon-4%; 5)
Crohns disease-3.5%; 6) Chronic gastritis-3.5%; 7) Juvenile polyps-
3%; 8) Candida esophagitis-3%; 9) Infections and 10) Proctitis-2%
each; 11) UC, and 12) Celiac disease-1% each. Rest of the diagnosis
comprised of foreign body removal, PEG placement, and variceal
sclerotherapy/banding. 42% of EGDs and 20% of colonoscopies were
normal.
Conclusions: By far the largest final diagnosis on endoscopic proce-
dures in a large referral center in the Southeastern US is that of
eosinophilic gastrointestinal disease. A multicenter collaborative effort
in the Southeastern US may be needed to corroborate these findings.
124
ROLE OF DIAGNOSTIC UPPER ENDOSCOPY
IN INFANTS AND CHILDREN: A RETROSPECTIVE
STUDY OVER A TWO-YEAR PERIOD
Tamara Feldman, Yolanda Rivas. Pediatric Gastroenterology, Mon-
tefiore Medical Center, Bronx, NY.
Introduction: The criteria for diagnostic upper endoscopies vary
among pediatric gastroenterologists. We undertook a retrospective
examination of our patient population over a 2-year period and
reviewed the indications for diagnostic upper endoscopy and
531
correlated the clinical impression with the endoscopic findings and
histopathology.
Methods: In this retrospective study, we reviewed the data of 297 upper
endoscopies performed in 272 children ranging from 1 month to 21
years of age between June 2003 and May 2005 at the Childrens
Hospital at Montefiore. The indications for endoscopy included:
abdominal pain, upper gastrointestinal bleeding, foreign body ingestion,
failure to thrive/weight loss, vomiting/gastroesophageal reflux, and
patient at the time of endoscopy, the indication for the endoscopy, and
the endoscopic and histopathologic findings for each upper endoscopy
performed.
Results: The most common indication for endoscopy in children up to
age 2 was vomiting/gastroesophageal reflux followed by chronic
diarrhea in 31% and 23% of cases, respectively. Abdominal pain was
the most common indication for endoscopy in children above the age of
2 in 64% of cases. There was direct correlation between clinical
impression and endoscopic and histopathologic findings in 82% and
86% of cases, respectively. Endoscopic evidence of ulcerative disease
was found in 10% of cases. On histopathology, eosinophilic enteropathy
was found in 10% of cases, H. pylori gastritis in 6% of cases, and
Crohns gastritis in 4% of cases. Normal histopathology was found in
14% of cases. No complications were reported.
Conclusion: Our experience indicates that upper endoscopy is
a valuable tool in the evaluation of upper gastrointestinal disease in
infants and children. In our patient population there was a high
correlation between the clinical impression/indication for endoscopy
and the endoscopic and histopathologic findings.
125
INDICATIONS FOR ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY IN CHILDREN
AND ADOLESCENTS
Miriam V. Louthan1, Angela Peters1, Whitney Jones2, John T. Stutts1.
1
Pediatrics, Division of Gastroenterology, University of Louisville,
Louisville, KY; 2Medicine, Division of Gastroenterology, University of
Louisville, Louisville, KY.
Background: Endoscopic retrograde cholangiopancreatography
(ERCP) is increasingly utilized in the management of pancreatic and
biliary diseases in pediatric practice. Few studies exist evaluating the
utility of ERCP in this setting.
Methods: We performed a retrospective chart review utilizing an
electronic medical record system to review all ERCPs performed in
children at our center over an 18 month period.
Results: We reviewed 23 ERCPs performed in 18 children ages 5 to 18
years by 3 experienced adult gastroenterologists. Of these procedures
the indications were as follows: 9 for choledocholithiasis, 5 for chronic
pancreatitis, 5 for stent removal or follow-up of previous ERCP
findings, 2 for severe acute pancreatitis following abdominal trauma
and 2 for primary sclerosing cholangitis. The majority of procedures
(82%) were both diagnostic and therapeutic. Of the 9 initial procedures
performed for indications other than choledocholithiasis, 100% led to
a new diagnosis improving management and 5 (55%) were therapeutic.
Almost all (89%) cases for choledocholithiasis were therapeutic. In 3
cases (13%), post ERCP pancreatitis developed and this resulted in an
average of 3.7 days inpatient care post ERCP, but resolved without
serious consequences in all 3 cases. There were no failed procedures
due to technical difficulties with cannulation.
Conclusions: The primary indication for ERCP performed in children
in our center was biliary disease, most often choledocholithiasis. The
majority of procedures were both diagnostic as well as therapeutic and
most procedures significantly impacted the management of the child.
Post ERCP pancreatitis was rare and resolved without long-term
consequences. Therefore, ERCP is safe and useful in the diagnosis and
treatment of pediatric biliary and pancreatic diseases.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
532 NASPGHAN ANNUAL MEETING

126 is characterized by intractable GERD symptoms resistant to acid

suppression treatment or obstructive symptoms such as dysphagia or
NUMBER OF PROCEDURES PERFORMED BY food impaction. Complete elimination of intact protein using elemental
FELLOWS AT THE MIDPOINT OF THEIR TRAINING formulas is the current therapeutic gold standard. However, the poor
AND REPORTED CONFIDENCE taste of amino acid-based formulas interferes with oral compliance and
Emory Collins. Pediatric Gastroenterology, University of Michigan, often necessitates administration via nasogastric or gastrostomy tubes.
Ann Arbor, MI. Aim: To compare retrospectively the clinical and histological responses
to a six food elimination vs. elemental diet.
This addresses three specific aims: 1) Record the number of procedures Methods: Children (aged ?-?) with isolated esophageal eosinophilia
completed by fellows at the midpoint of their training. 2) Determine if (.20 eos/hpf) were treated either with an elimination diet (excluding
a correlation exists between the number of procedures performed and cow milk, soy, egg, wheat, peanut/tree nut and sea food) or exclusively
confidence. 3) To determine if the size of the training program impacts elemental amino acid-based diet. Clinical and histologic responses after
the number of procedures performed. at least 6 weeks were assessed.
During training, fellows master a rapidly expanding field of knowledge Results: Of 50 children (42 males) ages 117 years, 30 were treated
and develop proficiency in diagnostic and therapeutic procedures. with elimination diet (mean 6.2) and 20 with elemental diet (mean 6.7).
Guidelines have been written by NASPGHAN that establish minimum Clinical improvement was seen in 29/30 on elimination diet and all 20
numbers of procedures necessary to gain competence.1 One cohort of on elemental diet. Significant reductions from pre-therapeutic esopha-
fellows was surveyed to gather data regarding details of training programs, geal eosinophil counts were observed in both groups (Table 1).
the number of procedures performed and confidence in their procedure Conclusions: The clinical and histological response to selective
ability at the midpoint of their fellowship training. Specifically, fellows elimination diet is comparable to that seen in children treated with an
reported on paracentesis, esophageal dilation, variceal banding, sclero- elemental diet. Elimination diet, although challenging, circumvents the
therapy, liver biopsy, and polypectomy. The response rate was 66% poor taste and required tube administration associated with the
totaling 33 completed surveys. By the midpoint of training, fellows had elemental diet.
completed between 6 and 31% of the minimum number of procedures
required for assessing competence as established by the NASPGHAN TABLE 1. Comparison of histopathological response in
guidelines. There is a positive correlation between the number of children with elemental and elimination diet
procedures completed and confidence. Fellows in training programs with
three or less full-time faculty perform the same number of procedures as Significant No change
trainees in programs with seven or more full-time faculty members. Normal improvement Partial (no
(Decrease (Decrease improvement change Pre- Post-
Type No. of in eos in eos (Decrease in in eos biopsy biopsy
1. Rudolph, C. D. & Winter, H. S. (1999). NASPGN guidelines for of diet subjects .80%) 5080%) eos 150%) count) (mean) (mean) P-value
training in pediatric gastroenterology. NASPGN Executive Council,
NASPGN Training and Education Committee. Journal of Pediatric Elemental 20 15 3 0 2 51.6 12.9 ,0.001
Gastroenterology & Nutrition. 29 Suppl 1:S126. Elimination 30 21 4 4 1 80.8 15.7 ,0.0001

Achieving procedure competence

Esophageal Banding or Liver
Paracentesis dilation sclerotherapy biopsy Polypectomy
128
Minimum Number
ESOPHAGEAL FOREIGN BODIES AND EOSINOPHILIC
for Competence 5 15 15 20 20
ESOPHAGITIS IN THE PEDIATRIC POPULATION: DID YOU
Percent of Fellows 16% 22% 6% 31% 6%
REALLY GET THE WHOLE STORY?
Surpassing
Nader Youssef, Patrick Vannelli, John Openheimmer, Joel Rosh.
Minimum
Goryeb Childrens Hospital, Morristown, NJ.
Minimum number for Competence: the threshold number of
procedures to assess competence per NASPGHAN Guidelines1. Aim: Acute non-food impactions of the esophagus usually present in
young children and are not associated with significant mucosal
abnormalities. Eosinophilic esophagitis (EE) is an emerging entity with
POSTER SESSION III presenting symptoms of dysphagia and reflux-symptoms resistant to
acid suppressing medications and may predispose to food impactions.
SATURDAY, OCTOBER 22, 2005 The aim of this study was to define the association of eosinophilic
7:45 AM 9:45 PM esophagitis with foreign bodies of the esophagus in children.
Methods: A retrospective review of consecutive endoscopic procedures
performed at a regional center from 12/1999 to 12/2004 was performed.
Eosinophilic Disorders 73 patients (59 male, aged 5.9 yrs, range 6 mo to 16 yrs) who presented
with foreign body obstruction of the esophagus requiring endoscopic
127 evaluation were identified. Foreign bodies were classified as food
impactions (FI) and non-food impactions (NFI). Proximal obstruction
COMPARISON OF CLINICAL AND was defined as the cricopharyngeal cuff or above. Abnormal gross
HISTOPATHOLOGICAL RESPONSES TO endoscopic findings included erythema, exudates, ulceration, edema,
ELIMINATION VS. ELEMENTAL DIETS IN CHILDREN ringed appearance and furrowing of the mucosa. Histological findings
WITH EOSINOPHILIC ESOPHAGITIS consistent with EE included .20 eosinophils/HPF. Prior symptoms
Amir F. Kagalwalla1,2, Maria Manuel-Rubio1, Hector Melin-Aldana1,2, included history of difficulty swallowing, heartburn, vomiting, or
Sally Ritz1, Timothy Sentongo1,2, Rohan Patel1, Therese Hess1, B Li1,2. abdominal pain.
1
Pediatrics, Childrens Memorial Hospital, Chicago Illinois, IL; Conclusions:
2
Northwestern Universitys Feinberg School of Medicine, Chicago, IL. 1. In previously asymptomatic older males who present with esopha-
geal foreign body obstruction, eosinophilic esophagitis is likely.
Eosinophilic esophagitis (EE) is a newly described and increasingly 2. Children with non-food impactions have at least a 30% chance of
diagnosed disorder of chronic eosinophilic esophageal inflammation. It having evidence of EE.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING 533

3. All patients who present with an acute obstruction of the esophagus Symptoms in pediatric patients with eosinophilic esophagitis (EE) can
should be evaluated by biopsy either at the time of presentation or be severe. Mucosal biopsies with .20 eosinophils per high power field
shortly thereafter as this will further guide management. is the diagnostic criteria. Accepted treatments of elemental diets, and
Results: swallowed/systemic steroids try to eradicate the eosinophil and improve
Food Non-food symptoms. This report describes 12 patients (11 males), mean age of
impaction impaction Significance 12.5 yrs (range 1 to 21 yrs), with the diagnosis of EE, who are symptom-
free with only conservative treatments for a mean observation period of
# of patients 22 51 p , 0.05 3.9 years (range 1 to 6.3 years). All 12 patients are atopic, 7 had
Age (years) 11.2 + 3.1 4.7 + 3.5 p , 0.05 multiple food allergies. These 7 all fulfilled diagnostic criteria for EE
Gender 96% male 64% male p , 0.05 elsewhere and enrolled in an elemental formula protocol, but could not
Obstruction Location 8% proximal 58% proximal p , 0.05 remain compliant. They refused these formulas and the use of
Gross findings 74% 12% p , 0.05 systemic/inhaled steroids. These 7 had upper endoscopies here, and 5
.20 eosinophils /HPF 89% 33% p , 0.05 other new patients also fulfilled diagnostic criteria. Eleven patients had
prior GI symptoms 15% 6% p = ns visible abnormalities of furrowing, 6 also had white plaques, 1 had
cobblestoning, 4 had ulcerations, 1 looked normal. Our initial biopsies
all confirmed EE. All 12 patients were offered treatments with proton-
pump inhibitors (PPI) and/or restricted diets. They all improved. Over
129 this interval, 9/12 patients require a PPI. Three patients have stopped the
THE ROLE OF NON-ACID REFLUX IN PATIENTS PPI, 2 of these have also fully expanded their diets, 1 remains restricted.
WITH EOSINOPHILIC ESOPHAGITIS: A STUDY USING Ten of 12 symptom-free patients had a follow-up endoscopy during the
MULTI-CHANNEL INTRALUMINAL IMPEDANCE (PH-MII) observation period and 7 of these had persistent EE. The esophageal
Rachel Rosen, Glenn Furuta, Candace Lord, Samuel Nurko. Motility mucosa of three of the oldest patients (mean age of 19.3 years), with the
Unit, Childrens Hospital Boston, Boston, MA. longest diagnosis of EE, reverted grossly and on biopsy to a more
normal mucosa with a low number of eosinophils. These 3 remain
symptom-free on a PPI. For nearly 4 years thus far, 9/12 patients with
Background: Eosinophilic esophagitis (EE) is a clinicopathological EE are symptom-free on conservative treatments. None have developed
disease that typically affects the proximal and distal esophagus. Clinical strictures, a small-caliber esophagus, or have required dilation. These
evidence suggests a role for food or aero-allergens, but the impact of non- observations suggest that the esophagus can retain apparently normal
acid reflux in patients with EE is uncertain. function while densely infiltrated with eosinophils for nearly 4 years,
Aim: To determine whether non-acid reflux is increased in patients and the diagnosis of EE does not appear to be permanent. Further
with EE. observations are warranted.
Methods: This is a retrospective study in which pH-MII tracings of
children with well-defined clinicopathological features of EE were
compared to children with GERD and patients with no evidence of
pathologic reflux (controls). GERD patients had reflux symptoms in Gastrointestinal Polyps and Tumors
addition to abnormal pH recordings with a reflux index .6%. Children
with EE had a normal pH probe and demonstrated esophageal eosinophilia 131
(.20 eos/HPF) that did not respond to 8 weeks of proton pump inhibition.
A REMINDER THAT RECTAL BLEEDING
Patients referred for evaluation of respiratory symptoms with normal
CAN BE CANCER
esophageal biopsies, a normal pH probe, and no symptoms of GERD were
Jyoti Ramakrishna. Pediatric GI & Nutrition, UMMHC, Worcester, MA.
used as controls. Reflux profiles were compared using ANOVA.
Results: Consecutive pH-MII tracings from 10 patients with EE, 10
patients with GERD and 9 controls were reviewed. Results are shown We know rectal bleeding in children, unlike adults, seldom means cancer.
(mean 6 std) in the table below. No statistically significant differences were Lewis et al report 8 children with colorectal cancer over 25 years across
found between EE patients compared to controls. Patients with GERD had 3 large referral centers in Alabama. Karnak et al from Turkey similarly
significantly more acid and pH-only reflux compared to EE and controls. report 20 cases over 25 years. Younger patients with colorectal cancer
Conclusions: Non-acid reflux does not seem to play a role in the often have advanced disease and a poor prognosis, attributed to a low
pathogenesis of EE. Antigenic stimulation may occur during initial index of suspicion and delay in diagnosis. This report is on 2 patients seen
topical passage of foodstuffs/aeroallergens or as a result of systemic at our hospital. HB: 15 yr male presented Nov 2001 to the ED with a 3 day
exposure rather than during reflux. history of RLQ pain, vomiting and dizziness. There was no reported
diarrhea or bleeding. Past history: treated for iron deficiency anemia 3 yr
prior, normal HCT 2 yr prior. Soc history: immigrated from El Salvador
EE GERD Control P Value 2 yrs ago. Family history: noncontributory. Labs: HCT 24.1 (3749%),
MCV 67.5 (7898 FL), normal albumin and prealbumin. Growth: Height
Age (yr) 10.5 6 6.8 6.2 6 3.8 7.8 6 6.8 0.28
- 25th percentile, weight - 75th, no weight loss. SBFT and CT showed an
% time ,4 2.8 6 1.9% 11.3 6 4.3% 2.6 6 1.9% ,0.0001
abnormal area of distal ileum and a hypodensity in the liver. Colonoscopy
# pH-only episodes 7.7 6 5.9 22.1 6 14.1 13.6 6 11.2 0.02
upto the terminal ileum showed a narrow area with lymphoid aggregates;
# acid episodes 24.9 6 20.0 47.4 6 17.1 28.4 6 16.5 0.02
a laparoscopic evaluation showed a matted area of distal small bowel with
# non-acid episodes 4.7 6 3.3 7.5 6 5.3 6.8 6 4.6 0.36
some lymph nodes, peritoneal studding including the falciform ligament
# full column episodes 11.4 6 14.6 17.7 6 13.6 10.8 6 13.1 0.48
and surface of the liver. Pathology revealed poorly differentiated
% full column episodes 32 6 21% 30 6 15% 23 6 20% 0.55
adenocarcinoma of unclear origin. Palliative chemotherapy was given
and the patient died within a few months. KL: 12 yr white male treated
successfully for non-Hodgkins lymphoma 3 years prior, presented in
130 March 2002 with pallor and tiredness. Intermittent complaints of rectal
bleeding predated his lymphoma, treatment for constipation led to
IMPROVE SYMPTOMS, OR CLEARANCE OF EOSINOPHILS? resolution of bleeding. He had no abdominal pain or obstructive
WHAT IS THE END-POINT FOR TREATMENT OF symptoms. Labs: Hgb 7.3 (1316 g/dl), MCV 62. CT abd and pelvis
EOSINOPHILIC ESOPHAGITIS IN CHILDREN? revealed a 6cm mass and 2 smaller ones in the liver. Open biopsy was
Kevin J. Kelly. Pediatrics, Temple Univ, School of Medicine, performed looking into recurrence of his lymphoma. Pathology showed
Philadelphia, PA. a metastatic adenocarcinoma likely of GI origin. He was guaiac positive

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

534 NASPGHAN ANNUAL MEETING

and colonoscopy revealed rectal masses, biopsies showed poorly

Affected Current Age at 1st Presenting Total Polyp
differentiated adenocarcinoma. He underwent surgery and chemother- member age symptom symptom no/type/location Outcome
apy, but liver and pancreatic metastases finally took their toll. He died in
Sep 2003. FAMILY ONE: unique BMPR1A mutation in exon 8 at the 3 end of gene (Y425X)
Father 44 yrs 5 yrs Rectal bleeding Numerous subtotal
colectomy
7 yrs
Daughter 21 yrs 4 yrs Passed polyp 5/ sess/ sigmoid
132* & cecal
Daughter 16 yrs 10 yrs Passed polyp 4/ ped/ sigmoid dysplastic
PRESENCE OF MATRIX METALLOPROTEINASES histo
IN THE URINE AND TISSUE OF PATIENTS WITH Son 19 yrs 14 yrs IBS symptoms TNTC/ ped/ R.L subtotal
JUVENILE POLYPS colon 19 yrs: colectomy
Michael A. Manfredi1,4, Victor L. Fox1, Jonathan N. Glickman5, David 1/ ped/ pouch 18 yrs
Zurakowski , Marsha A. Moses3,4. 1Gastroenterology and Nutrition,
2
Pat GF 60 yrs 40 yrs polyps subtotal
Childrens Hospital Boston, Boston, MA; 2Surgery, Childrens Hospital expired colectomy
Boston, Boston, MA; 3Surgery, Harvard Medical School, Boston, MA; Pat GGF 56 yrs colon cancer
4
The Vascular Biology Program, Childrens Hospital Boston, Boston, expired
MA; 5Pathology, Childrens Hospital Boston, Boston, MA. FAMILY TWO: MADH4 mutation
Mother 42 yrs 18 yrs None, polyps 20/ ped/ cecal
Juvenile Polyposis Syndrome (JPS) is a condition characterized by the found during & rectal
formation of multiple juvenile polyps in the colon and an increased Surveillance
risk of gastrointestinal adenocarcinoma, warranting repeated colonos- Son 17 yrs 3 yrs Rectal TNTC/ ped & sess/ subtotal
copy of affected individuals and screening of family members at risk. bleeding R.L colon colectomy
In contrast, patients with one or few solitary juvenile polyps are Adenomatous 14 yrs
thought to have a benign condition. Distinguishing between these two changes
conditions remains difficult in the absence of reliable non-invasive Mat GM 31 yrs 27 yrs Colon subtotal
biomarkers of polyp growth. Juvenile polyps are highly vascularized expired cancer/ colectomy
tissue. Matrix Metalloproteinases (MMPs) are responsible for the cecal metastatic
degradation of extracellular matrix and basement membrane proteins disease
and are required for angiogenesis. We therefore hypothesized that
MMPs may play a role in juvenile polyp development and may serve as GF, grandfather; GGF, great grandfather; GM grandmother; TNTC, too
non-invasive biomarkers for polyp growth and development. In this numerous to count; sess, sessile; ped, pedunculated.
preliminary study, we analyzed 20 urine samples collected prospectively Families with JPS can show variable presentation and course in regards
from 10 subjects with known or suspected juvenile polyps who presented to their disease phenotype. Assigning, or eliminating, the diagnosis of
to the endoscopy unit for colonoscopic evaluation and 10 age and sex- JPS in children and young adults from affected families should not be
matched controls. Urinary MMPs were analyzed by zymography and based on the presence or absence of symptoms. Genetic testing can offer
protein tissue expression via immunohistochemistry (IHC) on polyps. a definitive diagnosis in JPC families that carry a known mutation and
Greater than 90% of urines from polyp patients tested positive for MMPs, can allow for early surveillance and preventive care.
which was statistically significant compared to normal controls. IHC
demonstrated that MMPs were detected at high levels in the epithelium
and lamina propria in polyp tissue compared to normal colonic tissue. 134
These data are the first to demonstrate the presence of MMPs in the urine
DOES GEOGRAPHIC VARIATION IN THE
and tissue of juvenile polyp patients. Current studies are focused on
DISTRIBUTION OF APC GENE MUTATION ACCOUNT
determining the role of MMPs in polyp development and as novel urinary
FOR PHENOTYPIC VARIATION IN FAMILIAL
biomarkers of this disease. [DK007477 (W.I. Lencer), 2PO1CA45548
ADENOMATOUS POLYPOSIS?
(M. A. Moses)]
Rosemary J. Young1, Julie Stoner2, Henry T. Lynch3, Thomas M.
Attard1,3. 1Pediatrics, University of Nebraska Medical Center, Omaha,
NE; 2Preventive and Societal Medicine, University of Nebraska
133 Medical Center, Omaha, NE; 3Preventive Medicine, Creighton
University, Omaha, NE.
PHENOTYPIC VARIATION IN FAMILIES WITH
JUVENILE POLYPOSIS SYNDROME (JPS) Background: Familial Adenomatous Polyposis (FAP) has an incidence
Steven H. Erdman1,3, Thomas W. Prior2. 1Gastroenterology/Hepatol- of 1 in 8,000. Children may present with FAP related intestinal and
ogy/Nutrition, Childrens Hospital, Columbus, OH; 2Department of extraintestinal complications in the first and second decade of life.
Pathology, The Ohio State University, Columbus, OH; 3Department of Clinical manifestations of FAP vary depending on the pattern of gene
Pediatrics, The Ohio State University, Columbus, OH. mutation and the population being described. Herein we investigate the
geographic differences in APC mutation distribution in patients with
Familial Juvenile Polyposis Syndrome (OMIM 174900) is the most FAP across Europe, North America and Asia.
common of the hamartomatous polyp syndromes involving mutation of Methods: 15 publications (12 European, 3 Asian) describing the APC
MADH4 or BMPR1A in up to 30% of affected patients. In this mutations detected by polyposis registries in 471 patients with FAP
autosomal dominant disorder, ~75% of presenting probands will have from 122 families were included; the mutations were categorized by
an affected parent with the remaining 25% representing new mutations. segmental involvement and classified by country/continent of origin.
Within each family, marked variation in age at first symptoms, polyp These were compared with the APC mutation distribution in 392 FAP
number, and distribution can be seen. This variation among affected patients from the United States diagnosed between 19912002 though
family members with identical mutations has diagnostic implications testing (PCR, PGGE) by Labcorp Corporation.
for younger undiagnosed family members that may not have symptoms. Results: There were significant differences across the 3 geographical
We present two JPS families with hamartomatous polyps who illustrate areas in terms of location mutation, Pair-wise comparisons suggest that
this variation in disease expression. there are no significant differences in location distribution between

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
Europe and Asia (p = 0.12), there are significant differences between
Europe and North America (p = 0.004), and there are marginally
significant differences between Asia and the United States (p = 0.03).
Conclusions: There are regional differences in the pattern of APC
mutation detected in patients with FAP; the increased frequency of
segment 1 mutation compared to segment 3 mutation in North America
compared to Asia and Europe may explain the observed clinical features
of FAP in the United States including the relatively increased incidence
of upper gastrointestinal tract involvement in Asian patients.
135
AN INTERNET BASED PEDIATRIC RESIDENT
QUESTIONNAIRE ON KNOWLEDGE ON HEREDITARY
GASTROINTESTINAL POLYPOSIS SYNDROMES
Thomas M. Attard1,3, Julie Stoner2, Yongyue Qi2, Henry T. Lynch3.
1
Pediatrics, University of Nebraska, Omaha, NE; 2Preventive Medi-
cine, University of Nebraska Medical Center, Omaha, NE; 3Hereditary
and Preventive Medicine, Creighton University, Omaha, NE.
Background: Patients with hereditary gastrointestinal polyposis
syndromes present usually in the first two decades of life with
hematochezia (FAP, JP) or intestinal obstruction (PJS) or anemia.
Patients at risk of polyposis syndromes require continued surveillance.
Physicians taking care of children should be able to recognize and
competently manage these patients including their need for referral for
endoscopy. Herein we present our findings on US pediatric and
medicine pediatrics residents familiarity with gastrointestinal polyposis
syndromes based on an internet-administerd questionnaire.
Methods: This study was exempt from IRB approval. The program
directors at all 196 pediatric, medicine pediatric programs throughout the
US were asked to allow their residents to participate in an anonymous
internet based questionaire testing their practice on, and knowledge of
polyposis syndromes in children; 43 sites consented. The questionnaire
was forwarded to the residents as a hyperlinked interactive web-page by
e-mail. Questions addressed clinical practice (2) and tested knowledge (15)
based on information included in 2 out of 3 standard pediatric textbooks.
Results: The respondents included 323 residents; 290 pediatric, 33
medicine-pediatrics. Medicine-pediatrics residents were more likely to
inquire on family history of polyposis or early onset colorectal cancer
during health care maintenance (HCM) visits (P = 0.02, 0.03) than
pediatric residents. Most residents (91%) would refer newly diagnosed
children with polyposis to genetic counselling. Factual knowledge on
polyps and polyposis syndromes varied widely by syndrome (15%
[FAP]80% [PJS] correct) but not by year of training.
Discussion: Our study suggests that a greater emphasis should be
placed on resident education on the identification and correct
management of gastrointestinal polyps and polyposis syndromes
including inquiry on pertinent family history during HCM visits.
136
FAMILIAL ADENOMATOUS POLYPOSIS IN CHILDREN
UNDER 10; PRESENTATION AND CLINICAL OUTCOME:
WHO GOES TO COLECTOMY?
Thomas M. Attard1,2, Rosemary J. Young1, Alan G. Thorson2, Susan
T. Tinley , Henry T. Lynch2. 1Pediatrics, University of Nebraska,
2
Omaha, NE; 2Hereditary and Preventive Medicine, Creighton
University, Omaha, NE.
Background: Familial Adenomatous Polyposis (FAP) is an autosomal
dominant inherited predisposition to early development of colorectal
cancer (CRC) and increased risk of other, including extraintestinal,
malignancies. Children aged less than 10 years are at a heightened risk of
hepatoblastoma and may also present with polyps and rarely with CRC.
Heirein we describe our experience as a multidisciplinary pediatric
hereditary gastrointestinal polyposis clinic.
Methods: A cross-sectional analysis including demographic, clinical
presentation and course, gene mutation testing, endoscopic-histololgic
535
findings and surgical outcome of all patients suspected or confirmed
with FAP presenting in the first decade of life and followed by the
multidisciplinary Pediatric Hereditary Polyposis Clinic at the Univer-
sity of Nebraska Medical Center and Creighton University.
Results: 22 children (M;11) including 3 sibling pairs presented with
suspected or confirmed FAP, 2 were discharged from follow up following
negative APC gene mutation testing, all the rest continued to be tested
for elevated ? afetoprotein and ultrasound of the abdomen throughout
the first decade of life. 12 patients presented with symptoms, 6 had de-
novo FAP, 7 had gastrointestinal hemorrhage and went on to endoscopy,
4 patients were referred for colectomy, all 4 harbored APC gene
mutation at codon 1309. The age at referral to colectomy was earlier
for patients with 1309 mutation compared to patients who harbored
other mutations or were untested (mean 8.6 years vs. 16 years P = 0.03).
Conclusions: Children with FAP under the age of 10 may present
presymptomatically for disease surveillance. De-novo and inherited
FAP associated with APC gene mutation at codon 1309 entails a risk of
a more aggressive phenotype; early colectomy may be indicated in
children harboring this gene mutation.
137
NATURE VS NURTURE; DISEASE EXPRESSION IN
JUVENILE POLYPOSIS SYNDROME MAY BE INFLUENCED
BY EXOGENOUS FACTORS AND COMORBID DISEASE
Thomas M. Attard1,2, Carmen Cuffari2, Henry T. Lynch3. 1Pediatrics,
University of Nebraska, Omaha, NE; 2Pediatrics, Johns Hopkins
School of Medicine, Baltimore, MD; 3Hereditary and Preventive
Medicine, Creighton University, Omaha, NE.
Juvenile Polyposis Syndrome (JP) is inherited as an autosomal
dominant trait and predisposes to gastrointestinal hamartomatous
polyps and increased risk of colorectal cancer(CRC). Excess circulating
growth hormone and, to a lesser extent, exogenously administered growth
hormone have been implicated in the development of colorectal and
extraintestinal neoplasia. Adenomatous transformation is reported in up to
25% of polyps in patients with JP but is poorly understood. Herein we
describe the clinical course of two siblings with JP wherein one sibling was
treated with growth hormone.
Case Report: Two siblings are followed through the Hereditary
Polyposis Clinic (CU/JHH) for management of JP diagnosed in the
family, including the father who developed colon cancer in the fourth
decade of life. The younger siblinig was also diagnosed with Turners
Syndrome (45XO) and was started on growth hormone (somatrem,
somatotropin) from age 6 through age 14; she presented with rectal
bleeding associated with multiple colorectal polyps from age 8 years
and evidenced dysplastic transformation in multiple polyps from age
13. She was subsequently diagnosed with celiac disease based on upper
endoscopic - histologic and serology findings. The older sibling
presented at age 7 with hematochezia that was secondary to multiple
colorectal juvenile polyps. This sibling had continued endoscopic
surveillance and demonstrated a similar polyp burden as the sister but
without evidence of dysplasia up through the present time (age 18).
Discussion: Our patients illustrate the phenotypic variability in the
disease expression of the same gene mutation in JP, the dysplastic
transformation observed in the child treated with growth hormone and
found to have celiac disease may be a chance observation or may be
indicative of an increased risk of adenomatous transformation and
potentially CRC from either exogenous growth hormone or celiac disease.
138
INFLAMMATORY POLYPS WITH EBV-RELATED
LYMPHOPROLIFERATVE DISEASE IN A CHILD
WITH IPEX SYNDROME
Kristin D. Peterson1, Thomas M. Attard1,2, Lawrence Jung2, James M.
Gulizia3. 1Pediatrics, University of Nebraska, Omaha, NE; 2Pediatrics,
Creighton University, Omaha, NE; 3Pathology, University of Nebraska,
Omaha, NE.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
536 NASPGHAN ANNUAL MEETING
Background: IPEX Syndrome (Immune Dysregulation, Polyedocrin-
opathy and Enteropathy, X-linked) is caused by mutation in the FOXP3
gene. Autoimmune enteropathy has been reported and contributes to the
associated failure to thrive. Immunomodulatory agents including
cyclosporine have been successfully used in selected patients. In-
flammatory polyps may complicate chronic colitis and may give rise to
symptoms including bleeding and abdominal pain.
Case Report: A 13 yr old Caucasian male presented with a long-
standing history of abdominal pain, gastrointestinal hemorrhage and
iron deficiency anemia (Hb 10.8 g/dL, MCV61.9fL, RDW 23.5, serum
Fe 4 mcg/dL), he had been treated with FK506 (5.9 ng/mL range 3.9 to
9.0 from 11/97 to present) and IVIG. Upon enteroscopy, he was found to
have active Candida esophagitis and chronic, focally active gastritis.
Colonoscopy showed chronic active pancolitis with sparing of the
transverse colon, severe colitis in the sigmoid, rectosigmoid colon with
numerous inflammatory polyps which on biopsy - polypectomy were
found to have prominent lamina propria expansion with acute and
chronic inflammatory cells including a marked lymphocytoplasmacytic
infiltrate. Immunophenotypic staining showed admixed B-cells
(CD20+) and T-cells (CD3+), and in-situ hybridization revealed promi-
nent EBV-positive lymphoid cells. The patient had partial symptomatic
relief following multiple polypectomies during the initial colonoscopy.
Mesalamine and decreased immunomodulatory therapy are being
attempted to improve the colitis and inflammatory polyposis, respectively.
Conclusion: This is the first reported development of EBV-related
inflammatory polyposis complicating chronic colitis in a child with
IPEX Syndrome, this complication has to be borne in mind when
monitoring the long term effects of immunomodulatory therapy in these
and other immunosuppressed patients.
139
THE COMBINED ENDOSCOPIC-SURGICAL
PROCEDURE FOR POLYP CLEARANCE IN PEUTZ
JEGHERS SYNDROME
Emilia J. Cohen Sabban, Marina Orsi, Veronica Busoni, Jorge Olmos,
Pablo Lobos, Eduardo Mullen, Daniel DAgostino. Gastroenter-
ologia Infantil, Hospital Italiano, Buenos Aires, Argentina.
Peutz-Jeghers syndrome is an autosomal dominant disorder character-
ized by melanocytic macules of the lips, buccal mucosa, and digits;
multiple gastrointestinal hamartomatous polyps; and an increased risk
of various neoplasms. The first concern for pediatricians is the possi-
bility of multiple or extensive intestinal resections because of small
bowel intussusceptions.
Aim: To evaluate a combined endoscopic-surgical procedure for the
follow-up and treatment of children with Peutz-Jeghers Syndrome.
Materials and Methods: an upper GI is performed under general
anesthesia to remove all polyps, followed by a videocolonoscopy. When
the scope has reached the ileocecal valve a small laparotomy is
performed and the the scope is then manually guided trhough all the
small bowel up to the jejunum. The observation of the entire gut allows
a complete resection of polyps. Since 1999 up to 2004, 11 of these
procedures have been performed in 8 children with a median age of 11
years (r 620 yrs). 5 had a history of at least one intussusception, 2 were
admitted to the hospital due to severe anemia, abdominal cramps and
mucocutaneus pigmentation. Only one presented a typical anal polyp
protrusion.
Results: In all of the eight patients, more than 10 polyps were resected
in each session, and none required further surgical intervention at that
point. In 4 of the patients, the histology of one of the polyps showed
adenomatous transformation and an adenocarcinoma was detected in
the eldest boy.
Conclusions: The combined endoscopic and surgical procedure is
a safe technique for complete polyp resection, prevents further multiple
resections or enterotomies allowing for longer asymptomatic periods
and helps detect pre-malignant or malignant lesions at an earlier stage
with the consequent benefits for the patient.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
140
USE OF CAPSULE ENDOSCOPY IN SCREENING
PEDIATRIC PATIENTS WITH HAMARTOMATOUS
POLYP SYNDROMES
Adam Mezoff2,1, Daniel Pruedhomme2,1, Sonia Michail2,1, Cathy
Hodges , Tonya Milliken1. 1GI, Childrens Medical Center, Dayton,
1
OH; 2Pediatrics, Wright State Univ School of Med, Dayton, OH.
Introduction: Capsule endoscopy (CE) studies in adults have
demonstrated the superiority of CE versus other modalities in eval-
uating lesions of the small intestine. Pediatric reports have primarily
focused on evaluating patients for occult Crohns disease and GI
bleeding. We present two patients with hamartomatous polyp syn-
dromes that benefited from the utilization of CE as a screening tool.
Methods and Patients: CE was performed on two patients utilizing the
Given Pillcam system. Patient #1 had known Puetz-Jegher syndrome,
patient #2 had known Cowdens syndrome.
Results: Patient #1 had ongoing occult GI bleeding despite standard
upper and lower GI endoscopy with polyp removal, and upper GI/small
bowel series. The CE study performed on this patient demonstrated
a large polypoid lesion in the proximal jejunum that was previously
undiscovered, and subsequently removed during push enteroscopy. The
removal of this lesion resulted in resolution of the patients occult
bleeding. Patient #2 had Cowdens Syndrome with gastric polyp on
initial presentation. Her CE demonstrated potential small bowel polyps
which were removed with push enteroscopy, and subsequently
identified as lymphatic structures. These structures were not detected
by conventional radiologic studies.
Discussion: Capsule endoscopy (CE) is a new diagnostic modality,
found superior to Upper GI series, CT enteroclysis, and push
enteroscopy in evaluating lesions in the small intestine. In both of our
patients, CE provided a road map identifying the location of polypoid
lesions amenable to removal by push enteroscopy in children with
hamartomatous polyp syndromes.
Conclusion: CE is a well tolerated study that helps identify small
bowel abnormalities in patients with hamartomatous polyp syndromes
that may be amenable to endoscopic removal. CE should be considered
as the modality of choice for the screening evaluation of these children.
Inflammatory Bowel Disease
141
VARIATION IN INITIAL EVALUATION AND
TREATMENT OF PEDIATRIC CROHN DISEASE
R Colletti1, R Baldassano2, D Milov3, P Margolis4. Pediatric IBD
Network for Research and Improvement for PIBDNet5, 1University of
Vermont, Burlington, VT; 2CHOP, PHL, PA; 3Nemours, ORL, FL;
4
UNC, CH, NC; 5Office@PIBDNet.org, BTV, VT.
Background: Variation in care can be due to overuse, underuse
or misuse of diagnostic and therapeutic interventions. There are no data
available on the variation in care of pediatric Crohn disease (CD).
Aim: To identify variation in a collaborative network of pediatric
gastroenterologists (PG).
Methods: In a PIBDNet prospective cohort of CD patients, PG enrolled
patients who were starting treatment with 6-mercaptopurine (6MP) or
azathioprine (AZA). They provided care as usual and completed patient
encounter forms on the PIBDNet Data Collection web site.
Patients: Preliminary data from 30 sites are presented on 57 patients
(717 yr, 65% male, 91% Caucasian, 16% Jewish). 15% had
involvement of the esophagus, 75% ileum, 81% colon, 32% perine-
um, and 5% extraintestinal. 47% were underweight, 58% were taking
daily prednisone, and CRP was elevated in 64%. By the Physician
Global Assessment CD was inactive in 11%, mild in 35%, moderate in
51% and severe in 3%.
 NASPGHAN ANNUAL MEETING
Results: Diagnostic studies in which care was uniform included CBC,
performed by 100% of PG, LFT 98%, ESR 96%, colonoscopy 95%,
calprotectin 4% and NOD2 4%. Less uniformly performed evaluations
included upper endoscopy 89%, small bowel series or CT scan 76%, stool
pathogens 75%, CRP 67%, TPMT 61%, pANCA or ASCA 44%, eye
exam 14% and DEXA bone scan 11%. There was variation in therapeutic
interventions, including treatment with mesalamine 63%, a vitamin
supplement 43% and probiotic 9%. The dose of mesalamine was between
23 and 112 mg/kg/d. The starting dose of AZA was between 0.65 and
2.29 mg/kg/d and for 6MP was between 0.37 and 1.85 mg/kg/d.
Conclusion: There is considerable variation in diagnostic and thera-
peutic interventions in the management by PG of Crohn disease. While
some variations are due to patient needs or preferences, many variations
are likely due only to habitual differences in practitioner style.
Standardization of care, with systematic studies of planned variations
(randomized studies) can lead to increased knowledge and improved
outcomes.
142
VARIATION IN INITIAL 6-MERCAPTOPURINE
DOSAGE IN CROHN DISEASE
R. Baldassano1, R. Colletti2, D. Milov3, P. Margolis4. Pediatric IBD
Network for Research and Improvement for PIBDNet5, 1Childrens
Hospital of Philadelphia, PHL, PA; 2UVM, BTV, VT; 3Nemours, ORL,
FL; 4UNC, CH, NC; 5Office@PIBDNet.org, Burlington, VT.
Background: Variation in care can be due to overuse, underuse or
misuse of diagnostic and therapeutic interventions. 6-mercaptopuprine
(6MP) and its prodrug azathioprine (AZA) have efficacy in Crohn
disease (CD). Measurement of thiopurine methyltransferase (TPMT)
prior to starting treatment can identify normal genotype or phenotype
patients to whom the recommended dose (6MP 1.01.5 mg/kg/d) can be
administered.
Aim: To determine the variation in care by pediatric gastroenterologists
in administering 6MP and the effect of measuring TPMT.
Methods: In a prospective cohort of CD patients by PIBDNet, pediatric
gastroenterologists enrolled patients who were starting treatment with
6MP or AZA. They provided care as usual and completed patient
encounter forms via the PIBDNet Data Collection web site.
Patients: Preliminary data from 30 sites are presented on 57 patients
(717 yr, 65% male, 91% Caucasian, 16% Jewish). 15% had involvement
of the esophagus, 75% ileum, 81% colon, 32% perineum, and 5%
extraintestinal. 47% were underweight, 58% were taking daily
prednisone, and the CRP was elevated in 64%. By the Physician
Global Assessment CD was inactive in 11%, mild in 35%, moderate in
51% and severe in 3%. The most common indication for 6MP/AZA
treatment was early or induction therapy.
Results: 12 patients (21%) were treated with AZA and 45 patients
(79%) with 6MP. Of the 45 patients treated with 6MP, TPMT was
measured in 30 (67%); in 24 the TPMT was normal and in 6 the TPMT
was heterozygous or intermediate. Of patients in whom the TPMT was
normal, the dose was between 1.0 and 1.5 mg/kg/d in 67% (mean starting
dose 1.18 mg/kg/day; range 0.751.85). In contrast, of patients without
TPMT measurement, the dose was between 1.0 and 1.5 mg/kg/d in only
30% (mean starting dose 0.97 mg/kg/day; range 0.371.55) (p = 0.04).
Conclusion: There is considerable variation in the selection of drug,
measurement of TPMT and dosage prescribed. Patients in whom TPMT
had not been measured were less likely to receive the recommended
dose of 6MP.
143*
PIBDNETTHE PEDIATRIC IBD NETWORK FOR
RESEARCH AND IMPROVEMENT
D. Milov1, R. Baldassano2, R. Colletti3, P. Margolis4. Pediatric IBD
Network for Research and Improvement for PIBDNet5, 1Nemours,
Orlando, FL; 2CHOP, PHL, PA; 3UVM, BTV, VT; 4UNC, CH, NC;
5
Office@PIBDNet.org, BTV, VT.
537
PIBDNetthe Pediatric IBD Network for Research and Improvement is
a collaborative network where all pediatric gastroenterologists in North
America can work together to integrate cohort studies, quality
improvement, standardization of care, randomized clinical studies and
translational research to reduce morbidity and improve the health care
and well-being of children with inflammatory bowel disease (IBD). The
PIBDNet Data Collection Web Site is a secure online system for data
entry, storage and analysis. In response to an email in July 2004, 365
NASPGHAN members expressed an interest in participating in
PIBDNet. After 10 months, 64 sites with 194 Network Physicians had
obtained IRB approval. 114 Network Physicians, from 56 sites in 32
states and provinces, had completed the Network Physician De-
mographic Information Form online, 93% from the USA, 4% from
Canada, and 3% from Australia. 74% were male, 18% were in private
practice, 6% in solo practice. Network Physicians have between 0 and
16 others in their group (mean 5.8, median 4) who take care of children
with IBD. 48% reported having a registry of all of their IBD patients,
but only 25% used a registry for patient management. 32% manage their
patients with Crohn disease during a regularly scheduled clinic
designed for children and adolescents with IBD, and 29% have
a multidisciplinary clinic. 32% use an electronic medical record to
record clinical information about their patients. 90% felt confident
about their knowledge of IBD. 75% felt the system in which they
worked (the practice setting, multidisciplinary support, information
technology, communications with patients and families) was helpful to
providing comprehensive care to their patients with IBD. 89% felt
personally satisfied with the care they were providing to their patients
with IBD. Enrollment of patients is underway. PIBDNet has attracted
a diverse and representative group of pediatric gastroenterologists who
are interested in clinical research and efforts to improve the quality of
care for children with IBD.
144
INFLIXIMAB AND PEDIATRIC
ULCERATIVE COLITIS
Gary Fanjiang, George Russell, Aubrey Katz. Pediatric Gastroenter-
ology & Nutrition, Tufts-New England Medical Center, Boston, MA.
Purpose: We evaluate the indications for infliximab to treat pediatric
patients with ulcerative colitis (UC) and report long-term follow-up.
Methods: The charts of 27 pediatric patients with UC who were treated
with infliximab were reviewed. All patients would have otherwise been
candidates for colectomy. The acute group included patients with new
onset UC refractory to IV steroids for 57 days and patients with non-
steroid dependent UC with a fulminant exacerbation; the chronic group
included patients with chronic steroid dependent UC. Lichtiger colitis
activity index (LCAI) was measured for all patients at 0, 1, and 2
months after infliximab. Patients were regarded as successfully treated
if they remained off steroids and avoided colectomy.
Results: The acute and chronic groups included 16 and 11 patients
respectively. The acute group had a mean LCAI score of 11.4 at
induction and a mean net change of 11.1 after 2 months. The chronic
group had a mean LCAI score of 11.2 and a mean change of 5.7. The
acute group had a significantly greater net LCAI change than the
chronic, p = 0.001. The net LCAI change in the patients treated
successfully was not significantly different than those who failed, p =
0.43. The mean follow-up time from last infliximab was 13 months.
Infliximab was successful in 75% of patients in the acute group and 27%
in the chronic. Infliximab is no longer required in 80% of patients (83%
of acute; 67% of chronic) who were successfully treated. These patients
had a mean of 10 infusions and a mean follow-up of 10 months from last
infliximab.
Conclusion: 1) Infliximab appears to be effective for patients with
acute UC refractory to IV steroids and non-steroid dependent UC with
fulminant exacerbation. 2) Patients with steroid dependent UC respond
less well to infliximab. 3) Infliximab could be first line therapy for
severe UC although further study is needed. 4) Patients successfully
treated with infliximab can discontinue therapy and maintain their
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
538 NASPGHAN ANNUAL MEETING

remission, possibly only needing the induction phase of infliximab measurement. For each visit laboratory results, CS and AZA dose, and
therapy. clinical indicators of disease activity were recorded.
Results: The incidence of disease exacerbations per year was 55% less
in the study group (0.18 6 0.05 vs. 0.40 6 0.07, 95% CI 17%, 76%, p =
145 0.009). The study group patients received 73% less CS while on a stable
dose of AZA for more than 120 days (p , 0.0001) and had lower
INFLIXIMAB IMPROVES ALBUMIN SYNTHESIS pediatric Crohn,s disease activity index (median 5 vs. 10, p = 0.011) or
RATE IN PEDIATRIC CROHNS DISEASE simple clinical colitis activity index (mean 0.9 6 0.3 vs. 2.6 6 0.5, 95%
Steven Steiner, Marian Pfefferkorn, Joseph Fitzgerald, Scott Denne. CI 0.6 to 2.9, p = 0.003) scores. No difference was noted between the
Indiana University School of Medicine, Indianapolis, IN. groups in in-patient utilization or surgery rate. Study group patients
received higher stable dose of AZA (median 2.4 vs. 1.7 mg/kg,
Background: Children with Crohns disease frequently have dis- p , 0.0001) and these patients also had more dose adjustment (median
turbances in growth. Serum albumin levels are found to be below +0.8 vs. +0.4 mg/kg, p = 0.005). A 6-thioguanine nucleotide level of
normal in many children with active Crohns disease. Tumor necrosis $200 pmol/8 3 108 RBCs was associated with lower lymphocyte count
factor-alpha (TNF-a) may contribute to growth disturbance and (p = 0.03) and increased chance of disease remission (97/145 vs.
decreases in serum albumin levels. Although infliximab, a TNF-a 58/72, p = 0.04).
antibody, is an effective therapy for Crohns disease in children, there Conclusion: AZA dose adjustment using a 6-MP metabolite assay
are no data regarding its effects on albumin synthesis. results in appropriate selection of drug dosage, improved control of
Aim: To characterize changes in albumin synthesis following the initial disease activity, and decreased CS usage.
dose of infliximab in children with Crohns disease.
Methods: Children with active Crohns disease scheduled for their
initial dose of infliximab underwent outpatient metabolic assessment
immediately before and two weeks following infliximab infusion. Using
147
the stable isotope [d5] phenylalanine, albumin enrichment was mea- PHARMACOKINETICS AND PHARMACODYNAMICS
sured, and rates of fractional and absolute albumin synthesis were OF NATALIZUMAB IN A PHASE 2 STUDY OF
calculated. Measurements were made in both the fasting and ADOLESCENT PATIENTS WITH CROHNS DISEASE
parenterally fed states. Pre- and post- infliximab measurements were John Grundy, Wei-jian Pan, Subra Kugathasan, Fides Nagpala,
compared using the paired t-test. Deborah Hilton, Julie Taylor, Ronald Goldblum, Michele Libonati,
Results: Eleven children completed the study. Their mean age was 14.8 Regina Daniels, Jeannie Giacchino. Elan Pharmaceuticals, San Diego,
yr, mean serum albumin was 3.6 g/dL, and mean PCDAI score was 21 CA.
before infliximab therapy. In response to infliximab, during fasting,
there was no change in fractional albumin synthesis rate (9.0%/d Background/Aims: Natalizumab, a humanized monoclonal IgG4
to 9.1%/d) (p = 0.93), and no change in absolute albumin synthesis antibody to a4 integrin, reduces transmigration of leukocytes from the
rate (142.3 mg/kg/d to 142.6 mg/kg/d) (p = 0.88). During parenteral peripheral circulation to inflamed tissues, resulting in an increase in the
nutrition infusion, however, the fractional albumin synthesis rate number of peripheral blood lymphocytes. Natalizumab pharmacokinetics
increased from 10.3%/d to 12.7%/d (p = 0.06), and the absolute (PK) and pharmacodynamics (PD) were evaluated in adolescent
albumin synthesis rate increased from 171.0 mg/kg/d to 212.3 mg/kg/d patients (1117 years of age; n = 38) with moderate to severe Crohns
(p = 0.05). disease (CD).
Conclusions: Although no significant difference in fasting albumin Methods: This open-label study evaluated 3 monthly natalizumab IV
synthesis rates were observed following infliximab therapy in children infusions (3 mg/kg). PK and PD assessments following infusions 1 and
with Crohns disease, fractional albumin synthesis and absolute albumin 3 included measure of natalizumab serum concentrations, a4 integrin
synthesis increased by 24% in the parenterally fed state. Infliximab may receptor percent saturation of peripheral blood mononuclear cells, and
have an important effect on hepatic synthetic function, with subsequent absolute counts of lymphocytes.
positive effects on healing and growth. Results: Selected natalizumab PK parameter summary statistics are
shown below.
The apparent elimination half-life (t) of natalizumab appeared
146 somewhat shorter in adolescents (#4.6 days) relative to adults ($6.4
days; Phase 3 study results). Over the course of each evaluated monthly
OPTIMIZING AZATHIOPRINE DOSE USING dosing interval, mean a4 integrin receptor percent saturation fell from
6-MERCAPTOPURINE METABOLITE LEVELS IMPROVES a peak of approximately 93% to #34%, and median change in absolute
DISEASE OUTCOME AND REDUCES CORTICOSTEROID lymphocyte count from baseline fell from a peak increase of 106%
USE IN PEDIATRIC PATIENTS WITH INFLAMMATORY 122% to 45%65%. Improvement in CD occurred in most patients.
BOWEL DISEASE Conclusions: Open-label natalizumab 3 mg/kg once monthly was
Sanjoy Banerjee, Warren Bishop. Pediatric Gastroenterology, Chil- associated with clinical benefits but provided relatively low trough
drens Hospital of Iowa, Iowa City, IA. serum levels and corresponding suboptimal PD effects. Evaluation of
other natalizumab dose regimens in adolescents may be warranted.
Objectives: We have used the PRO-PredictRx Metabolite test
(Prometheus Labs) to customize azathioprine (AZA) dosing in pediatric
patients with inflammatory bowel disease (IBD) since 2001. We Summary Cmax Ctrough AUCN/t t CL
Infusion Statistics (mg/mL) (mg/mL) (mg;hr/mL) (hr) (mL/hr)
evaluated whether AZA dose adjustment using this assay resulted in
better selection of the drug dose, improved control of disease activity, 1 N 38 38 38 38 38
and decreased corticosteroid (CS) use. Mean (SD) 63.8 (18.7) 0.6 (0.9) 9034 (3435) 94.9 (29.3) 17.37 (5.51)
Methods: This is a retrospective chart review of 101 patients with IBD Range 40.5114.3 03.3 4300-18638 48.7170.6 5.6334.10
who were on a stable dose of AZA for at least 4 months. The study Median 57.4 0 (BLQ) 8313 92.3 17.43
group (n = 64, 75% Crohn,s disease [CD], 25% ulcerative colitis [UC], 3 N 30 30 30 30 30
median age 14.7 yr) consisted of patients who received AZA and had 6- Mean (SD) 70.3 (24.3) 0.9 (1.5) 9792 (4051) 111.0 (59.2) 17.64 (9.05)
mercaptopurine (6-MP) metabolite levels measured. The control group Range 42.0163.8 0.06.1 262218225 47.4262.7 7.4552.72
(n = 37, 76% CD, 24% UC, median age 14.1 yr) consisted of patients Median 66.7 0 (BLQ) 10535 96.3 17.06
who were treated with AZA before the use of 6-MP metabolite

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
148*
A RANDOMIZED, MULTICENTER,
OPEN-LABEL STUDY TO EVALUATE THE SAFETY
AND EFFICACY OF INFLIXIMAB IN PEDIATRIC
PATIENTS WITH MODERATE-TO-SEVERE
CROHNS DISEASE
Jeffrey Hyams1, Wallace Crandall2, Subra Kugathasan3, Robert
Heuschkel4, Anne Griffiths5, Stanley Cohen6, James Markowitz7, Allan
Olson8, Jewel Johanns8, Robert Baldassano9. 1Connecticut Childrens
Medical Center, Hartford, CT; 2Columbus Childrens Hospital,
Columbus, OH; 3Medical College of Wisconsin, Milwaukee, WI;
4
Royal Free Hospital, London, United Kingdom; 5The Hospital for Sick
Children, Toronto, ON, Canada; 6Childrens Center for Digestive
Health Care, Atlanta, GA; 7North Shore-LIJ Health System, New Hyde
Park, NY; 8Centocor, Inc., Malvern, PA; 9Childrens Hospital of
Philadelphia, Philadelphia, PA.
Introduction: A study was conducted to evaluate the safety and
efficacy of IFX in pediatric pts with CD.
Methods: Pts aged 617 years, with moderate-to-severe CD (Ped
Crohns Disease Activity Index [PCDAI] .30) despite treatment with
an immunomodulator 6 corticosteroids were enrolled and received
5 mg/kg IFX via IV infusion at wks 0, 2, and 6. The primary endpoint,
clinical response at wk 10, was defined as a decrease of $15 in the
PCDAI and a PCDAI value ,30. Non-responders were discontinued.
Pts who achieved clinical response to induction therapy were
randomized (1:1) to receive IFX 5 mg/kg q8 wks (Group I) or q12
wks (Group II) through wk 46. Pts who lost response in the maintenance
phase were eligible for a higher or more frequent dose of IFX. The final
safety and efficacy visit for the study occurred at wk 54. Secondary
efficacy endpoints included clinical response at wk 54 and clinical
remission at wks 10 and 54. Clinical remission was defined as a PCDAI
score of #10. Physical development (patient growth), quality of life (as
measured by the IMPACT III questionnaire), corticosteroid use, and
bone metabolism were assessed.
Results: 103 of the 112 pts who received IFX therapy were randomized
at wk 10 to receive either IFX q8 or 12 wks. No deaths, malignancies, or
delayed hypersensitivity reactions were reported. One case of
anaphylaxis was reported. The most common SAEs were related to
CD. Efficacy through wk 54 will be presented in the two treatment
groups.
Conclusion: The safety results are consistent with those noted in the
adult ACCENT 1 trial.
149
ANTIBODIES TO A NOVEL FLAGELLIN (CBIR1) ADDS
CLINICAL UTILITY TO THE DIAGNOSIS AND
DIFFERENTIATION OF PEDIATRIC IBD
Marla Dubinsky1,2, Ling Mei2, Carol Landers2, Lirona Katzir1,
Sharmayne Farrior1, Iwona Wrobel1, Antonio Quiros1, Ron Bahar1,
Ghassan Wahbeh1, Bruce Grill1, Gary Silber1, Drew Kelts1, Michelle
Pietzak1, Saied Dallazadeh1, Eric Vasiliauskas1, Charles Nelson3, Robert
Hershberg4, Yang Huiying2, Jerome Rotter2, Stephan Targan2. 1Western
Regional Pediatric IBD Research Alliance, Los Angeles, CA; 2Cedars-
Sinai Medical Center, Los Angeles, CA; 3University of Alabama,
Birmingham, AL; 4Dendreon Corporation, Seattle, WA.
Background: Approximately 2/3 of IBD patients are positive for
antibodies to microbial and auto-antigens. A novel antibody; anti-
CBir1, may have unique diagnostic properties and phenotypic
associations in children. The Western Regional Pediatric IBD Research
Alliance examined the added utility of anti-CBir1 in the diagnosis and
differentiation of pediatric IBD patients as compared to previously
defined antibodies: ASCA, OmpC, I2 and pANCA.
Methods: Sera from 331 pediatric IBD patients (111 UC, 220 CD) were
tested by ELISA for anti-OmpC, anti-I2, ASCA, anti-Cbir1 and
539
pANCA. Quantitative and qualitative expression of antibody markers
was evaluated.
Results: Anti-CBir1 was present in 55% of CD vs. 15% of UC (p ,
0.001). 41% of anti-CBir1 (+) UC patients were also positive for .1
CD-related antibody. Anti-CBir1 was present in 53% of ASCA(2) CD
patients and in 52% (31/60) of patients negative for all antibodies. The
most CBir1 reactive CD subset was OmpC+/I2+ (74%, median = 49)
and least reactive was ASCA + (56%, median = 31). 13.5% of pANCA
(+) only UC patients were anti-CBir1 (+) as compared to 35% of
pANCA(+) only CD patients (p = 0.03). Both pANCA and anti-CBir1
levels were higher in pANCA (+) CD vs. UC (median pANCA: 46.6 vs.
70.0; p = 0.003, and median anti-CBir1: 21 vs. 12 p , 0.0001).
Conclusions: Anti-CBir1 increased detection of CD cases negative for
all other antibodies. Cbir1 reactivity added to the differentiation of
pANCA+ CD from pANCA+ UC and can minimize misdiagnosed CD
colitis patients. Both the presence and magnitude of anti-CBir1
reactivity adds to the clinical utility of presently known antibodies in
pediatric IBD.
150
FAMILIAL EXPRESSION OF SEROLOGICAL
IMMUNE RESPONSES IN PEDIATRIC IBD
Marla Dubinsky1,2, Ling Mei2, Carol Landers2, Lirona Katzir1,
Sharmayne Farrior1, Iwona Wrobel1, Antonio Quiros1, Ron Bahar1,
Ghassan Whabeh1, Bruce Grill1, Gary Silber1, Michelle Pietzak1, Eric
Vasiliauskas1, Saied Dallalzadeh1, Drew Kelts1, Charles Elson3, Robert
Hershberg4, Huiying Yang2, Stephan Targan2, Jerome Rotter2. 1Western
Regional Pediatric IBD Research Alliance, Los Angeles, CA; 2Cedars-
Sinai Medical Center, Los Angeles, CA; 3University of Alabama,
Birmingham, AL; 4Dendreon Corporation, Seattle, WA.
Background: IBD specific serological immune responses are an
important nexus of environmental factors and host genetics. Studies
suggest that pANCA, ASCA and more recently OmpC may represent
familial immunologic traits expressed in unaffected family members.
The Western Regional Pediatric IBD Research Alliance studied the
quantitative and qualitative expression of serological immune responses
in unaffected parents of pediatric IBD patients.
Methods: Sera were collected from 92 trios (56 CD, 36 UC), and tested
by ELISA for antibodies to microbial antigens: anti-OmpC, anti-I2,
ASCA and anti-CBir1 and autoantigens: pANCA. Associations
between affected children and their parents for quantitative and
qualitative expression of antibodies and correlation analyses were
conducted.
Results: The qualitative expression of antibodies in parents was higher
then controls for anti-OmpC (p = 0.05) and anti-CBir1 (p , 0.05).
Levels of anti-OmpC (p , 0.0001) and anti-CBir1 (p , 0.05) were
higher in parents of affected IBD patients than controls regardless of
proband expression. Levels of OmpC were significantly higher in
parents whose CD offspring were OmpC + (p = 0.04) compared to
OmpC (2) probands. This OmpC association was not seen for UC.
Antibody levels for OmpC (r = 0.35; p = 0.008), I2 (r = 0.26; p = 0.05)
and CBir1 (r = 0.24; p-0.07) correlated between parents and CD
offspring, suggesting familial expression of antibodies. Gender did not
influence expression.
Conclusion: Both the quantitative and qualitative expression of
immune responses to microbial antigens is increased in the parents of
pediatric CD patients, suggesting that the immune dysregulation
observed in such patients is a familial trait.
151
INFLAMMATORY BOWEL DISEASE (IBD) IN
AFRICAN AMERICAN CHILDREN
Alexandra Eidelwein1, Kristin Fiorino1, Richard Thompson2, Carmen
Cuffari1, Vivian Abadom1, Maria Oliva-Hemker1. 1Pediatric Gastroen-
terology, Johns Hopkins University School of Medicine, Baltimore, MD;
2
Biostatistics, Bloomberg School of Public Health, Baltimore, MD.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
540 NASPGHAN ANNUAL MEETING
Introduction: Limited data is available regarding the clinical course of
IBD in African Americans (AA). The aim of our study was to compare
the disease presentation and course between AA and Caucasian (Cauc)
children with IBD.
Methods: Medical records were reviewed from 1/199112/2000 of AA
and Cauc pts treated at the Johns Hopkins Hospital. Data collected
included: demographics, age at diagnosis, symptom duration, family
history, and disease phenotype. Markers of disease severity included
ESR, use of corticosteroids, immunomodulators and infliximab, and
need for IBD-related surgeries.
Results: Of the 245 pts 58 (23.6%) were AA and 187 (76.3%) Cauc.
Mean age at dx was 12.5y 6 4.0 in AA and 11.5y 6 4.5 in Cauc. Mean
duration of symptoms was 0.95y (AA) and 0.89y (Cauc). 12.8% Cauc
and 6.9% of AA were diagnosed before age 6y (OR [95%CI] = 1.98 [0.6,
8.2]). 36.4% Cauc and 17.5% AA had a family hx of IBD (p = 0.006).
AA with CD had a higher risk of perianal disease, 17.6% compared to
10.6% in Cauc (OR [95%CI] = 1.8 [0.5,5.8). AA were more likely to
progress to fistulizing or stricturing CD than Cauc (29.2% vs 11.3%,
p = 0.05). Mean ESR of AA was 47.5 mm/h vs 28.8 mm/h in Cauc (p ,
0.001). The risk of surgeries was higher in AA than in Cauc (OR
[95%CI] = 1.4 [0.5, 3.7). More AA received steroids and infliximab (p =
0.035 and 0.037). Cauc were more likely to receive immunomodulators
within 3 months after diagnosis (OR [95%CI] = 2.18 [0.65, 9.37]).
Conclusions: Our study suggests that compared to Cauc, AA children
have a lower family history of IBD and a lower risk of being diagnosed
before the age of 6y. However, AA appear to have a more severe clinical
course with a higher ESR at presentation, an increased risk of fistulizing
and stricturing disease, a greater exposure to steroids and infliximab,
and a higher risk of undergoing surgery. Larger studies are needed to
delineate whether these differences are valid or whether racial
disparities exist in access to medical care and in disease management.
152
MANAGEMENT OF DISTAL RECTAL STRICTURES
IN CROHNS DISEASE; DIGITAL DILATION, TOPICAL
APPLICATION OF MITOMYCIN AND AT-HOME DILATION
Asim A. Mohammed1, T. S. Gunasekaran1,2, Sharon Brown1. 1Lutheran
General Childrens Hospital, Park Ridge, IL; 2Ronald McDonald
Childrens Hospital, Loyola Medical Center, Maywood, IL.
About 23% of Crohns patients have rectal strictures. Management of
these strictures may require endoscopic dilation, stricturoplasty or
partial colon resection. Distal rectal and anal strictures pose additional
challenges in surgical treatment because of its location. We present 3
patients with distal rectal strictures treated by digital dilation, topical
application of mitomycin at stricture site and regular at-home dilation.
Method: 3 patients, 18, 17, 12 years were diagnosed with Crohns
disease at ages of 10, 15 and 9 years respectively. They had Crohns
disease of the ileum and colon. They were treated with mesalamine, 6-
mercaptopurine and infliximab. 27 years after the diagnosis, the
patients presented with rectal bleeding, difficulty in defecation and
passing ribbon like stools. The rectal strictures were diagnosed on Hospital Boston, Boston, MA.
digital examination or colonoscopy. Gentle 5 days preparation done.
Under deep sedation with propofol, colonoscopy was performed, fibrotic
3 mm stricture was noted at 5 cm from the anal verge. Balloon dilatation
failed to open the stricture. Following this a digital dilation was done. The
index finger was inserted to its base, stricture was opened to a diameter of
about 15 mm and topical application of mitomycin (0.3 mg/ml) was done.
Abdominal x-ray after dilation showed no evidence of perforation. In the
recovery room, patients and parents were taught to do the dilatation with
a 14 mm Hegar dilator, which continued at-home daily.
Result: Patients tolerated the procedure well. A follow up of 4
18 months showed no relapse of the rectal strictures and the stool caliber
was normal.
Conclusion: Digital dilatation of rectal strictures is a safe treatment for
distal rectal strictures. At-home dilatation by patient or parent is a safe
for preventing the recurrence of these strictures. Topical application of
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
mitomycin may have an added benefit in managing these difficult distal
rectal strictures.
153
PROTEIN INHIBITOR OF ACTIVATED STAT3 (PIAS3)
INHIBITS SKELETAL MUSCLE GROWTH HORMONE (GH)
SIGNALING IN EXPERIMENTAL COLITIS
Lee Denson, Xiaonan Han, Erin Bonkowski. Gastroenterology,
Hepatology, and Nutrition, Cincinnati Childrens Hospital Medical
Center, Cincinnati, OH.
Background: GH regulates lean body mass (LBM) via activation of the
STAT5 transcription factor and up regulation of IGF-1 gene expression.
LBM is reduced in Crohns disease; the molecular basis for impaired GH
action in skeletal muscle in colitis is not known. PIAS3 binds to
STAT3/5 transcription factors, preventing STAT3/5 transcription factor
binding to target gene cis elements. We hypothesized that PIAS3 would
inhibit GH signaling in skeletal muscle in colitis by preventing STAT5
DNA binding.
Methods: DEXA was used to determine body composition in IL-10-/-
mice with colitis and wild type (WT) controls before and after chronic
GH administration. Circulating IGF-1 was determined by ELISA, and
tissue IGF-1 expression was determined by real time PCR. STAT5
activation and DNA binding were assessed by western blot and EMSA,
while PIAS3 abundance and PIAS3:STAT5 association were de-
termined by immuno-precipitation and western blot.
Results: LBM was reduced in IL-10-/- male mice with colitis relative to
WT controls. The percent LBM increased with chronic GH adminis-
tration to WT controls, but not IL-10-/- mice with colitis, confirming
a physiologic resistance to GH action in skeletal muscle. Both skeletal
muscle IGF-1 RNA expression and circulating IGF-1 levels were
reduced in mice with established colitis. GH dependent STAT5 tyrosine
phosphorylation and nuclear translocation were not impaired in skeletal
muscle of mice with colitis. However, GH dependent STAT5 DNA
binding to an IGF-1 gene promoter cis element was significantly
reduced. PIAS3 nuclear abundance and PIAS3:STAT5 association were
significantly increased in skeletal muscle of colitic mice, relative to WT
controls.
Conclusions: Male IL-10-/- mice with colitis exhibit reduced LBM and
local GH resistance which is due to increased PIAS3:STAT5 association
leading to reduced STAT5 DNA binding and IGF-1 expression.
Targeted therapies which reduce skeletal muscle PIAS3 abundance
may be beneficial in terms of restoring LBM in colitis.
154
IMPACT OF ACUTE STEROID TREATMENT ON
MEMORY, EXECUTIVE FUNCTION, AND MOOD IN
PEDIATRIC INFLAMMATORY BOWEL DISEASE
Christine Mrakotsky, Athos Bousvaros, Lyvia Chriki, Elyse Kenney,
Peter Forbes, Eva Szigethy, Deborah Waber, Richard Grand. Childrens
Introduction: Corticosteroids, which are critical for therapy of
pediatric inflammatory bowel disease (IBD), can adversely affect the
nervous system, changing sleep, appetite, and mood. Less is known,
however, about their impact on cognition and memory, especially in
children. We investigated the effects of high-dose steroids on memory,
cognition and mood in children with IBD.
Methods: Children (age 817) with IBD on high-dose steroids
($30 mg/day prednisone) (N = 14: 7 CD, 7 UC) were compared to those
off steroids for $6 months (N = 15; 13 CD, 2 UC). Assessment included
the Wide Range Assessment of Memory and Learning (WRAML
Stories), Childrens Memory Scale (CMS Faces), Rey Osterrieth Complex
Figure (ROCF), Trails, Behavior Rating Inventory of Executive Functions
(BRIEF)-self and parent report, Child Behavior Checklist (CBCL)/Youth
Self-Report (YSR), and measures of IQ, pain and sleep.
 NASPGHAN ANNUAL MEETING 541

Results: The high-dose steroid group (M = 40 mg, range 3075 mg) had
poorer short-term memory for details, slower speed, and reported more
problems with working memory, shifting, mood, and sleep (p = .075)
(Table). Demographics, IQ, and pain level were comparable between
groups. Sleep problems accounted partly for group differences.
Conclusions: Steroids affect short-term memory, speed, executive
function and mood in children treated acutely for IBD. The impact of
steroid-related sleep problems on memory and mood should be
considered when helping patients manage drug side effects. Longitu-
dinal studies are warranted to examine the reversibility of these effects.
Steroid Control
Mean 6 SD Mean 6 SD p psleep
with IBD. These risk factors for depression should be assessed routinely
in outpatient medical clinics to enhance comprehensive care for these
patients.
156
SIBLING SUPPORT IN PEDIATRIC INFLAMMATORY
BOWEL DISEASE (IBD)
Debra Lobato2, Yana Wember2, Wendy Plante2, Linda Shalon1, Jack
Nassau , Nancy Miller1, Kathy Scorpio1, Janet Trotta1, Neal LeLeiko2.
2
1
Pediatrics, Hasbro Childrens Hospital/Brown Medical School,
Providence, RI; 2Psychiatry, Hasbro Childrens Hospital/Brown
Medical School, Providence, RI.

WRAML Stories Details Objective: A supportive family environment is an important predictor of

Immediate Recall 12.8 6 1.8 14.1 6 2.2 .084 ns psychological outcomes and medication adherence in pediatric chronic
ROCF Details conditions, including IBD. Siblings are a fundamental part of a childs
Immediate Recall 23.7 6 8.4 28.6 6 6.1 .084 ns familial and social network, yet little is known about siblings
CMS Faces involvement in IBD care. This ongoing pilot study examines the relation-
Immediate Recall 35.6 6 5.8 38.7 6 3.6 .066 .058 ship between healthy siblings support with IBD care and the quality of
Trails 26.5 6 9.2 20.7 6 4.7 .046 ns life and treatment adherence of children and adolescents with IBD.
BRIEF_SR Method: Participants to date include 12 child and adolescent patients
Working Memory 47.4 6 8.9 42.3 6 6.0 .063 ns with IBD (83% Crohns disease) recruited through a Pediatric GI
BRIEF_SR Shifting 52.7 6 7.5 43.1 6 6.8 .003 .095 specialty clinic. IBD patients (age range: 1117 years; M = 13.7) were
CBCL Internalizing 58% female, 83% Caucasian, and had well-controlled disease by parent
Problems 58.2 6 9.9 45.9 6 8.9 .001 ns report (75% had not experienced a flare-up in over a year). One healthy
YSR Internalizing sibling (age range: 1018 years; M = 13.2) from each family was
Problems 52.0 6 9.0 45.2 6 10.2 .106 .015 randomly selected for reference; 58% were older than the IBD patient.
IBD patients completed measures of IBD-specific quality of life
(IMPACT-II), IBD medication adherence (completed conjointly with
parent), and sibling support with IBD care. The sibling support measure
155* assessed the IBD patients perceived frequency of and attitude toward
a healthy siblings involvement in IBD care.
PREDICTORS OF DEPRESSIVE SEVERITY IN
Results: Greater frequency of sibling support with IBD care was
ADOLESCENTS WITH INFLAMMATORY
associated with better overall quality of life (r = .56, p = .06), better
BOWEL DISEASE
body image (r = .57, p , .05), and fewer concerns about IBD treatment
Eva Szigethy1,2, Elyse Kenney1, Johanna Carpenter1, Athos Bous-
(r = .61, p , .05) in IBD patients. IBD patients who reported a positive
varos1, David R. DeMaso1,2. 1Childrens Hospital, Boston, MA;
2 attitude toward sibling support also reported fewer difficulties with
Harvard Medical School, Boston, MA.
treatment management (r = 2.67, p , .05).
Conclusion: Preliminary findings suggest that sibling support in IBD
Introduction: Pediatric inflammatory bowel disease (IBD) is a chronic care may be associated with higher quality of life and medication
physical illness with high rates of depression and family dysfunction. adherence in children and adolescents with IBD. Findings may have
This study explores those physical and psychosocial factors that may important implications for family-based interventions in pediatric IBD.
predict depressive severity in adolescents with Crohns disease (CD) or
ulcerative colitis (UC).
Methods: Youth (ages 1117) with IBD (N = 193) were recruited from 157
a gastroenterology clinic. Parent and child completed the Childrens
Depression Inventory (CDI) during their medical appointment. IBD DIFFERENTIAL EFFECT OF ANXIETY ON PAIN
severity was obtained using standardized measures and current steroid PERCEPTION IN CHILDREN WITH IBD AND
dose was recorded. Subjects (N = 43) with CDI scores $9 were given FUNCTIONAL GASTROINTESTINAL
the Family Adaptability and Cohesion Evaluation Scale, the Brief DISORDERS UNDERGOING COLONOSCOPY
Symptom Inventory, and the Life Events Checklist to assess family Wallace Crandall, Timothy Halterman, Laura Mackner. Columbus
functioning, parental psychopathology, and life stressors, respectively. Childrens Hospital, Columbus, OH.
Results: For the 193 screened subjects, a comparison of depressive
severity in three age groups (1113, 1415, 1617), revealed that Purpose: To compare pain and anxiety scores between children with
subjects aged 1617 had significantly higher CDI scores than those inflammatory bowel disease (IBD), and those with functional gastro-
1113 (p = .033). In a comparison of CDI scores across three IBD intestinal disorders (FGDs) undergoing colonoscopy, and to examine
disease severity ratings (inactive, mild, moderate/severe), subjects with the role of anxiety in predicting reports of pain.
moderate/severe disease activity scored significantly higher on the CDI Methods: 20 children with IBD and 20 children with FGDs, aged 10 to
than the other groups (p = .016). Youth scoring .30 on the Pediatric 18 years, undergoing colonoscopy, completed pain and anxiety ques-
Crohns Disease Activity Index had significantly higher CDI scores than tionnaires prior to the procedure, and a pain questionnaire 48 hours
those scoring #30 (p = .012). Depressive scores were significantly post procedure. Parents completed a demographics form. The pain
increased in those patients on steroids versus those not on steroids (p = questionnaire assessed current and usual pain intensity via Likert scales
.033). For adolescents with a CDI score $9, a significant negative (0 = no pain to 10 = severe pain). Participants indicated pain location via
association between CDI score and lower family functioning was found, a drawing distinguishing four abdominal quadrants and pain description
but no relationship between depressive severity and either life stressors via a checklist of eight descriptors.
or parental psychopathology. Results: Children with IBD had a mean pain duration of 11.8 weeks, vs.
Conclusions: More active disease, corticosteroid therapy, and family 82.1 weeks in the FGDs group (p , 0.01). Children with FGDs
dysfunction are valid predictors of depressive severity in adolescents endorsed a greater total number of the pain descriptors than did children

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

542 NASPGHAN ANNUAL MEETING
with IBD (3.65 vs. 1.70, p , 0.001). There were no differences in pain
intensity at the time of colonoscopy between groups. However, the
FGDs group reported higher usual pain severity (7.13 vs. 5.33, p ,
0.01), and greater pain severity 48 hours after the colonoscopy (2.20 vs.
0.53, p , 0.05). No differences in anxiety were reported at the time of
colonoscopy. However, higher levels of anxiety were associated with
higher pain scores at the time of colonoscopy in children with IBD, but
not in children with FGDs. Forty-eight hours after colonoscopy, anxiety
was not a predictor of pain in either group.
Conclusions: Children with FGDs report a longer duration of pain prior
to colonoscopy, endorse more descriptors of their typical pain, and
describe more severe usual and post-procedure pain as compared to
children with IBD. In contrast, pain symptoms at the time of
colonoscopy were similar between groups. In the IBD group, those
with more anxiety reported worse pain at the time of colonoscopy, but
anxiety did not play a role in the pain reports of the FGD group.
158
THE MISSION IS REMISSION: A WEB-ENABLED
SELF-MANAGEMENT PROGRAM FOR PEDIATRIC
IBD TARGETING HEALTH-RELATED QUALITY
OF LIFE
Anthony R. Otley, Patrick McGrath, Barbara Christensen. Pediatric
Gastroenterology, Dalhousie University, Halifax, NS, Canada.
Background: Psychological and information-based interventions can
positively impact health-related quality of life (QOL) in patients with
chronic disease.
Aim: To test a web-enabled home program (IBDC) of self-manage-
ment, information, and peer support for pediatric IBD patients and their
parents.
Methods: In a series of n-of-1 studies, 40 patients (and 40 parents) were
assessed during standard care and subsequently, IBDC care. Patients were
enrolled with active disease, followed for two months to achieve
remission, then entered six month control period with standard care, and
finished with six month of IBDC intervention. The primary outcome was
QOL, measured by IMPACT-III, with secondary outcomes of disease-
specific knowledge (the IBD-KID), adherence to therapy, perceived stress
and health care utilization.
Results: Of 40 enrolled patient/parent dyads, data was available for
analysis from the first seven dyads. For the 7 patient participants, mean
age was 14.6 6 2 yrs, 5 Crohns disease (CD), 2 ulcerative colitis (UC).
At study entry, mean PCDAI for CD patients was 30.5 6 10, and UC
disease activity index of 2.5 6 2 for UC. By start of IBDC, all patients
were in remission, although at end 1 each of UC and CD had active
disease. The mean IMPACT score at start of the IBDC for those with
inactive disease throughout was 161 6 12, and 164 6 9 at study
completion. For those with active disease at study completion, the
values were 138 6 37 and 140 6 30 respectively. Disease-related
knowledge, as measured by IBD-KID, was 15 6 5 at entry into IBDC,
and 17 6 4 at completion. Satisfaction questionnaires completed by
patients and parents uniformly provided strongly positive endorsements
of the program, although debriefing at study completion raised issues
about appeal of computer game.
Conclusions: Participants were uniformly and strongly supportive of
the IBDC intervention. Preliminary results show positive trends, but
final results for all 40 patient/parent dyads are required to assess the true
impact on QOL and other outcomes of this innovative intervention.
159
DEVELOPMENT OF A WEB-BASED
SELF-MANAGEMENT PROGRAM FOR TEENS
WITH IBD AND THEIR PARENTS: THE
MISSION IS REMISSION
Anthony R. Otley, Barbara Christensen, Patrick McGrath. Pediatric
Gastroenterology, Dalhousie University, Halifax, NS, Canada.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Background: IBD adversely affects health-related quality of life
(QOL) in children with IBD. Self-management interventions positively
impact the QOL of patients in other chronic illnesses.
Aim: To design and construct a web-enabled evidence based home
program (IBDC) of self-management, information, and social support
for pediatric IBD patients and their parents.
Methods: Content was developed by pediatric gastroenterologists,
nurses, psychologists, and dieticians, together with computer scientists
with website development and gaming expertise. A pilot study in 40
patients (and 40 parents) is targeting the following outcomes: QOL,
disease-specific knowledge, adherence to therapy, perceived stress and
health care utilization.
Results: Program development completed with website accessible via
Internet by participants using unique usernames and passwords. Content
is divided into 12 sessions, including disease-related knowledge and
therapies; stress and pain management techniques. Information is
imparted using text, flash animation and medical illustration, videos,
and games to reinforce program content. Content is individualized
based on disease type, treatments received, and can be targeted to
reinforce areas of concern on the part of the patient, family or health
care team. Participants (patient and one parent) work through each
session and interact with a para-professional coach by phone who
reinforces key session points and acts to ensure participants questions
are answered. Other website features include: peer-group chat rooms;
a journal feature and message board; a News section where items of
interest to participants will be posted; and private mail where the
participant and coach can leave messages for each other. Outcome
measures are completed online for immediate database entry. Testing
and focus groups have demonstrated high levels satisfaction by
participants.
Conclusions: The web-based IBDC provides tertiary health services in
a forum that is accessible to families without limitations of distance or
school/work schedules.
160
QUALITY OF LIFE AND DISEASE SEVERITY IN PEDIATRIC
INFLAMMATORY BOWEL DISEASE
James M. Perrin1, Karen Kuhlthau1, Aziz Chughtai1, Harland S.
Winter1, Robert N. Baldassano2, Stanley A. Cohen4, George D. Ferry3,
Benjamin D. Gold4, Melvin B. Heymann5, Barbara S. Kirschner6.
1
Pediatrics, MassGeneral Hospital for Children, Boston, MA; 2Child-
rens Hospital of Philadelphia, Philadelphia, PA; 3Baylor College of
Medicine, Houston, TX; 4Childrens Healthcare of Atlanta, Atlanta,
GA; 5University of California San Francisco, San Francisco, CA;
6
University of Chicago, Chicago, IL.
Background: Validating measures of quality of life (QoL) includes
assessing the relationship of clinical subscales with other indicators of
disease severity, as well as the relationship of more general subscales
with other general QoL measures.
Objective: To determine associations of quality of life (QoL) in
pediatric inflammatory bowel disease (IBD) with disease severity and
other QoL measures.
Design/Methods: Cross-sectional survey of children and youth ages
817 years and their parents attending any of six US IBD centers.
Sample: Subjects recruited from either existing registry of age-eligible
subjects or on visits to participating centers.
Measures: General (PedsQL) and IBD-specific (Impact-35) quality of
life measures, assessing both childrens and parents views; age, gender,
condition (ulcerative colitis [UC] or Crohns disease [CD]); and
a severity index for each condition.
Results: Data from 212 subjects, 157 with CD and 55 with UC, indicate
good mean levels of general QoL (PedsQL; mean child score: 80.5). All
Impact-35 subscales were significantly negatively associated with
clinical severity (correlations varying from 2.22 to 2.67 [all p ,
0.02]). Highest associations were with symptom scores. Similarly,
scores on the IBD-specific measure correlated well with the general
QoL measure, especially for social and emotional functioning.
 NASPGHAN ANNUAL MEETING
Conclusions: These findings help to validate this measure of QoL in
pediatric IBD. The correlations found in this sample indicate the
accuracy of the symptom and social and emotional subcales. The levels
of association indicate that several subscales measure domains other
than severity and broaden the assessment of change in IBD care or in
clinical trials.
161
MEASURING QUALITY OF LIFE IN INFLAMMATORY
BOWEL DISEASE
James M. Perrin1, Karen Kuhlthau1, Aziz Chughtai1, Harland S.
Winter1, Robert N. Baldassano2, Stanley A. Cohen3, George D. Ferry4,
Benjamin D. Gold3, Melvin B. Heymann5, Barbara Kirschner6.
1
Pediatrics, MassGeneral Hospital for Children, Boston, MA;
2
Childrens Hospital of Philadelphia, Philadelphia, PA; 3Chil-
drens Healthcare of Atlanta, Atlanta, GA; 4Baylor College of
Medicine, Houston, TX; 5 University of California San Francisco,
San Franscisco, CA; 6 University of Chicago, Chicago, IL.
Background: Measuring quality of life (QoL) has increasing
importance for children with chronic conditions. Recent work has led
to development of QoL measures for pediatric inflammatory bowel
disease (IBD).
Objective: To develop a parent measure for pediatric IBD, determine
factors arising from application of QoL measures, and examine
congruence of parent and child assessments.
Design/Methods: Cross-sectional survey of children and youth ages
8-17 years and their parents attending any of six US IBD centers.
Sample: 212 subjects (157 with Crohns disease [CD] and 55 with
ulcerative colitis [UC]) recruited from either existing registry of age-
eligible subjects or on visits to participating centers.
Measures: General (PedsQL) and IBD-specific (Impact-35) quality of
life measures, assessing both childrens and parents views; age and
gender. Factor analysis of parent and child responses and comparison
between parent and child assessments.
Results: Both parent and child IBD-specific responses had best results in
four-factor solutions. Parent factors included acute symptoms/problems,
feelings about IBD and its treatment, long-term concerns, and body image.
Children and youth had similar factors, except for issues with friends
rather than long-term concerns. We found high correlations between
parent and subject on most QoL scales, although correlations decreased
with age for the general QoL scales, more for estimates of general health
and school functioning than for social or emotional functioning.
Conclusions: This study provides further characteristics of a QoL
measure specific to pediatric IBD and adds a comparable parent
measure. It indicates key factors associated with QoL in this condition.
Supported in part by NIH Grant DK 062927.
162
IBD KNOWLEDGE QUESTIONNAIRE
Muhammad A. Qureshi1, Vernon M. Chinchilli1. 1Pediatric Gastroen-
terology and Nutrition, Penn State College of Medicine, Hershey, PA;
2 sports activities compared with their siblings.
Department of Health Evaluation Sciences, Penn State College of
Medicine, Hershey, PA.
Specific Aim: Our study provides preliminary validation of the IBD
Knowledge Questionnaire; a brief measure that assesses ones
knowledge of inflammatory bowel disease (IBD).
Background: There is no instrument available to assess the knowledge
of IBD. In our previous work we found sibling (sib) functioning
correlates with knowledge of IBD, but the instrument was not validated.
Method: We designed a disease-specific, self-administered questionnaire
(Q) consisting of 44 questions (two questions were repeated twice each to
assess the sensitivity of this measure). Q was divided into seven categories;
systemic symptoms, bowel symptoms, medications, nutrition, disease
itself, growth and quality of life. The Q was administered to pediatric (ped)
gastroenterologists (GI), pediatricians, ped/non ped residents, medical
543
students, parents of IBD affected families, parents of non-IBD affected
families by mass email or paper version. Statistical methods included one
way ANOVA with Tukeys studentized range test for multiple compar-
isons of the scores among the seven types of responders, Cronbachs alpha
for assessing consistency of items within categories, and Cohens kappa
for assessing agreement among replicated items.
Results: Ped GI scored the highest (mean = 42.1) and parents of non-
affected families scored the lowest (mean = 31.5), which was statistically
significant. Parents of affected families scored just as well as non
pediatric residents and better than medical students, although not sig-
nificantly (means of 38.7, 38.4, and 36.2, respectively). Cronbach alpha
statistics ranged between 0.35 and 0.67, indicating good consistency of
items within categories. Kappa statistics ranged between 0.81 and 0.89,
indicating excellent agreement among replicated items on the Q.
Conclusion: This pilot study demonstrates that the proposed IBD
Knowledge Questionnaire delineates very well among categories of
individuals with different levels of knowledge, and has potential as
a tool for ascertaining an individuals knowledge about pediatric IBD.
163
LIFE INTERESTS AND ACTIVITY INDEX (LIAI) OF
CHILDREN AND ADOLESCENTS WITH INFLAMMATORY
BOWEL DISEASE (IBD)
Robert M. Issenman1,2, Iqbal H. Jaffer1, Rabin Persad1,2, Chris
Radoja2. 1Pediatrics, McMaster University, Hamilton, ON, Canada;
2
Hamilton Health Sciences, Hamilton, ON, Canada.
Introduction: We have previously described that children attending the
Pediatric IBD clinic to be relatively happy, well adjusted individuals
with high self esteem (when healthy) compared to community controls.
This study focussed on achievement levels of patients attending our
clinic compared to sibling controls.
Methods: A comparative survey was mailed to 200 patients and
families concerning the activities their children with IBD and healthy
sibling controls were involved in. Families were asked to rate those
activities for level of achievement.
Results: 102 out of 200 surveys (51%) were returned representing 194
children (M:F 91:103, Mean Age 14 years). 102 of 194 (53%)
(51 males, 51 females) children had IBD and 92 (47%) were healthy
siblings (40 males, 52 females). The average age was 14 years. Activities
were assigned one point per activity weighted on a four point scale
representing level of achievement (1 = Recreational, 2 = House/School
Leagues, 3 = City Representative, 4 = Regional). Scores ranged from
023. The overall average activity index rating was 6.55. The average
activity index rating was 7.24 for children with IBD [min, max = 0, 23]
and 5.78 [0, 21] for siblings. The average activity index rating for males
and females was similar (Males = 6.85 [0, 23], Females = 6.28 [0, 21]).
Discussion: The LIAI of Pediatric IBD patients was found to be higher
than that of their healthy siblings (7.24 vs. 5.78) though not statistically
significant because of the diverse range of interests and activities. Many
children are involved in sports and music. Many volunteer or are
involved within their religious communities as well. They are more
involved with sports and volunteering, and equally involved with non-
Conclusions: We have shown that, when healthy, children with IBD are
actively involved in diverse activities; in some cases more so than their
healthy siblings. This perspective is valuable when counselling parents
of newly diagnosed patients.
164
PANCREATITIS AS THE PRESENTING SYMPTOM OF
CROHNS DISEASE
Jyoti Ramakrishna1, Amanda Goddard2. 1Pediatric GI & Nutrition,
UMMHC, Worcester, MA; 2Univ of Mass Med School, Worcester, MA.
Pancreatitis is known to be associated with Crohns disease (CD). There
is one prior report of a child admitted with acute pancreatitis found to
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
544 NASPGHAN ANNUAL MEETING
have CD during the same hospital admission. We are reporting two
pediatric cases of CD who presented with pancreatitis. Case 1 (ST)
13 yr old male of Cambodian origin, presented Jan 2004 with four days
of epigastric pain, nausea, vomiting and fever. Past history: poor weight
gain. Lab results: lipase 138 (050 U/L), amylase 389 (25125 U/L),
hematocrit 33.7 (3749%), hemoglobin 10.9 (13.016.0 g/dL), MCV
68.2 (7898 FL), platelets 744 (140440 th/mm3), ESR 94 (0
10 mm/hr), iron 10 (50150 ug/dL), albumin 1.7 (3.25.2 (g/dL). U/S
revealed a sludge filled gallbladder and an edematous pancreas.
EGD/colonoscopy revealed perianal fistulae; friable, nodular and
ulcerated mucosa in the terminal ileum with pathology of chronic
active ileitis. Case 2 (KB) 13 yr old black male, presented Aug 2004
with acute onset abdominal and back pain, and vomiting. Past history of
weight loss, recent iron deficiency anemia, pt was to be scheduled for
colonoscopy for G+ stool. Exam revealed diffuse/epigastric abdominal
pain, guarding. Hematochezia was noticed in hospital. Lab results: lipase
372.4 (050 U/L), amylase 602 (25125 U/L), hematocrit 28.7 (37
49%), hemoglobin 9.0 (13.016.0 g/dL), MCV 61.6 (78-98 FL), platelets
458 (140440 th/mm3), ESR 46 (010 mm/hr), ferritin 15.2 (23.9
336 mg/mL), iron 10 (50150 ug/dL), albumin 2.5 (3.25.2 g/dL),
prealbumin 9.2 (1840 mg/dL). Imaging supported pancreatitis with no
cholelithiasis. Colonoscopy revealed segmental areas of friability,
apthous ulcers and mucosal edema scattered through the colon, a
segmental area of psuedopolyps, ulceration and friability in the
proximal right colon. A small opening posterior to the anus without
induration, redness or discharge was also seen. Biopsy showed chronic
active colitis in the cecum, right colon, transverse colon and left colon
consistent with CD.
In both patients iron deficiency anemia, low albumin, and poor growth
in the recent past, led to the suspicion of CD.
165
PEDIATRIC INFLAMMATORY BOWEL DISEASE
PRESENTING AS EOSINOPHILIC ILLEOOCILITIS
Shehzad Saeed1, John Boyle1, Cary Cavender1, David Kelly2.
1
Pediatric Gastroenterology, University of Alabama, Birmingham,
AL; 2Departement of Pathology and Laboratory Medicine, University
of Alabama, Birmingham, AL.
Eosinophilic gastroenterocolitis is a descriptive term designating
eosinophilic infiltration of the gastrointestinal tract. It is increasingly
being recognized, and some data suggests more prevalence of intestinal
eosinophilia in the Southern states. We report a series of 5 patients who
underwent endoscopic evaluation at a tertiary care center for abdominal
pain, diarrhea, GI bleeding, short stature and weight loss,who would have
been diagnosed with eosinophilic ileocolitis based on histology from
endoscopic biopsies, and were found to have Crohns disease on small
bowel series.
Methods: Records of endoscopies at Childrens Hospital of Alabama
were retrospectively reviewed. These procedures were performed
between March 2003 and June 2004. Total of 568 procedures were
reviewed, performed by 3 gastroenterologists. Diagnosis of EGID was
based on histologic review of biopsies. EGID was defined as a)
Density of eosinophils in lamina propria- b) Presence of intraepithelial
eosinophils on surface or crypts, and c) Extent of eosinophilic degran-
ulation. Patients identified with infections were excluded.
Results: Of these 568 procedures, 15 were excluded for infectious or
inflammatory colitides. 104 patients were initially diagnosed with EGID.
Of these, 35 patients had symptoms suggestive of IBD but 30 had normal
serology (Prometheus Labs- ANCA/ASCA IgA/IgG) and/or small bowel
series {15/30 were both SBFT and serology negative}. 5 would have been
diagnosed with eosinophilic ileocolitis based on histology but were found
to have Crohns disease on abnormal small bowel series with illeal disease.
Conclusions: Finding of eosinophilc gastrointestinal disease should
prompt evaluation for IBD, especially utilizing radiological modalities.
These patients may need to be followed closely since some of them may
go on to develop IBD.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
166
GENDER DIFFERENCES IN PEDIATRIC
CROHNS DISEASE (CD)
Neera Gupta1, Melvin B. Heyman1, Alan G. Bostrom1, Benjamin D.
Gold3, George D. Ferry4, Harland S. Winter2, Stanley A. Cohen3, Oren
Abramson6, Robert N. Baldassano5, Barbara S. Kirschner7. 1Univer-
sity of California, San Francisco, San Francisco, CA; 2MassGeneral
Hospital, Boston, MA; 3Emory University, Atlanta, GA; 4Baylor
College of Medicine, Houston, TX; 5Childrens Hospital of Phila-
delphia, Philadelphia, PA; 6Kaiser Permanente Medical Center, Santa
Clara, CA; 7University of Chicago, Chicago, IL.
Background: We found female (F) pediatric patients with CD are at
increased risk for first intestinal resection compared to males (M) in our
large multicenter registry. We determined whether additional gender
differences exist in pediatric CD.
Methods: We conducted a retrospective, cohort study using the
Pediatric IBD Consortium Registry. Data collected from Jan 2000 to
Nov 2003 were analyzed to compare the course of CD in 566 M and 423
F using the Fishers Exact Test and Cox Proportional Hazards Modeling.
Results: Mean follow-up time was 3.6 6 3.1 years. M and F did not
differ by age at diagnosis (dx) (p = .61), race/ethnicity (p = .41), location
of disease at dx (p = .47), presence of a granuloma on histology
(p = .21), or presence of abnormal ASCA levels (p = .74). A higher
proportion of F (4.0%) compared with M (1.4%) presented with mouth
sores (p = .01). At the time of dx, a higher proportion of F (74.6%) had
hypoalbuminemia compared with M (54.7%) (p = .01). Differences did
not exist by gender for presence of elevated WBC (p = .23), abnormal
HCT (p = .79), or abnormal ESR (p = .87) at the time of diagnosis. The
risk for developing erythema nodosum in F was 2.81 times the risk in M
(95% CI = 1.057.47; p = .04). F were at decreased risk for growth
failure (Hazard Ratio (HR) = 0.28; 95% CI = 0.120.63; p = .002).
The risk of requiring treatment with Cyclosporine in F was 4.52
times the risk in M (95% CI = 1.2516.43; p = .02). The risk of
requiring treatment with 5-ASA in F was 0.88 times the risk in M
(95% CI = 0.771.01; p = .08). Gender did not predict treatment with
remicade (p = .73).
Conclusions: Gender differences, including hormonal and genetic
influences on the presentation and progression of disease in pediatric
CD, should be further investigated.
Supported in part by NIH grants DK060617 and DK00762.
167
US ESTIMATES AND OUTCOMES OF CHILDREN
AND ADOLESCENTS HOSPITALIZED WITH
ULCERATIVE COLITIS
Stephen Guthery, Molly OGorman. Linda Book, Pediatrics, University
of Utah and Primary Childrens Medical Center, Salt Lake City, UT.
Randomized trials in children are needed to assess the efficacy of novel
therapeutic agents in hospitalized patients with ulcerative colitis (UC).
However, there are limited data describing the epidemiology and
outcomes of severe ulcerative colitis in children.
Purpose: To estimate the number and outcomes of US children
hospitalized with ulcerative colitis.
Methods: We analyzed the Kids Inpatient Database, a nationwide and
stratified probability sample of 2.5 million hospital discharges from the
year 2000 of children 20 years and younger. Ulcerative colitis was
defined as discharges 18 years and younger, with a discharge ICD-9
diagnosis code of 556.0556.9 in the first position. Those undergoing
colectomy were identified using the ICD-9 code 45.8 as the principal
procedure performed during hospitalization. Weighted estimates (6SD)
are reported, and represent US national estimates.
Results: A total of 7.3 million discharges were available for analysis.
2,277 (6209) children 18 years and younger were hospitalized for
ulcerative colitis. 893 (6106) were hospitalized for 7 days or longer,
 NASPGHAN ANNUAL MEETING
and 207 (645) underwent total abdominal colectomy. Among the 2,784
reporting hospitals, twenty reported more than 10 cases of UC
requiring 7 days or longer of hospitalization.
Conclusions: Approximately 40% of all children hospitalized for UC
required 7 days or longer of hospitalization, and 9% required colectomy.
UC cases requiring prolonged hospitalization are relatively rare and
widely distributed. These data clearly demonstrate that clinical trials
designed for the treatment of refractory colitis will require a multi-
institutional collaborative network.
168
THE CHANGING PATTERN OF PEDIATRIC IBD AT
BRITISH COLUMBIA CHILDRENS HOSPITAL
Vered Pinsk, Daniel A. Lemberg, Collin Barker, Richard Schreiber,
David M. Israel, Kevan Jacobson. Pediatrics, British Columbia
Childrens hospital, Vancouver, BC, Canada.
Background: Epidemiologic studies suggest an increase in incidence of
Inflammatory Bowel Disease (IBD) in children. British Columbia
Childrens Hospital (BCCH) is in a unique position as the only tertiary
referral centre for pediatric patients in the province, with all practicing
pediatric gastroenterologists at this site.
Aim: To compare incidence and clinical characteristics of pediatric
IBD patients referred to BCCH between 19901994 and 20002004.
Methods: A retrospective chart review was undertaken with at
diagnosis data collected from medical charts of all patients #16 years
of age diagnosed with IBD at BCCH between 19901994 and 2000
2004. Data on age, gender, ethnicity, family history of IBD, type and
extent of disease and surgical intervention was collected. Provincial
population statistics were obtained from Statistics Canada. The
diagnosis and classification of disease was based on standard clinical,
endoscopic, radiological and histological criteria.
Results: Seventy patients were diagnosed with IBD during 19901994,
equivalent to an incidence rate 1.69/105 (1.18/105 for CD, 0.46/105 for
UC and 0.05/105 for IC) in contrast to 298 patients diagnosed during
20002004, corresponding to an incidence rate of 7.21/105 (5.06/105 for
CD, 1.14/105 for UC and 1.01/105 for IC). Twenty three percent of
children diagnosed were #6 years (1990-1994) compared to 8.8 %
(20002004), (OR 3.11, CI 1.56, 6,19), 24% were diagnosed with upper
gastrointestinal disease vs. 40%, 24.3% had surgery vs. 8.1% (OR
3.662, CI 1.842, 7.282). No differences were observed in the male to
female ratio, ethnic distribution, duration of symptoms prior to
diagnosis, and family history from either cohort.
Conclusions: Children diagnosed with IBD during 19901994 in
BCCH tended to be younger, and more likely to undergo surgery. The 4-
fold increase in incidence of IBD at BCCH likely reflects change in
referral pattern in addition to an increase in incidence, whereas the
increase in upper GI disease likely reflects a change diagnostic practice.
169
PEDIATRIC INFLAMMATORY BOWEL DISEASE: THE
BRITISH COLUMBIA EXPERIENCE
Vered Pinsk, Daniel A. Lemberg, Rosario Leonor, Collin Barker,
Richard Schreiber, David M. Israel, Kevan Jacobson. Pediatrics,
British Columbia Childrens hospital, Vancouver, BC, Canada.
Background: Limited data is available regarding incidence and preva-
lence of inflammatory bowel disease (IBD) in the Canadian Pediatric
population. Epdemiologic studies suggest an increase in prevalence of
IBD. British Columbia Childrens Hospital (BCCH) is uniquely positioned
as the only pediatric tertiary care hospital in the province with all
provincial pediatric gastroenterologists practicing at this site.
Aim: To investigate epidemiology and clinical characteristic of IBD in
children referred to BCCH between 1985 and 2005.
Methods: A review was undertaken with at diagnosis data collected from
medical charts of all patients #16 years diagnosed with IBD at BCCH
between the study period. Age, gender, ethnicity, family history of IBD,
545
type and extent of disease were included. Provincial population statistics
were obtained from Statistics Canada. Diagnosis and classification of
disease was based on standard clinical, endoscopic, radiological and
histological criteria.
Results: A total of 570 children were diagnosed with IBD; 391(68.6%)
with Crohn disease (CD), 114 (20%) with Ulcerative Colitis (UC) and
56 (9.8 %) with Indeterminate Colitis (IC). The incidence rate for IBD
between years 20012005 was 7.21/105 (5.06/105 for CD, 1.14/105 for
UC and 1.01/105 for IC). The median age at diagnosis was 12 6 3.63
(SD) years (range 0.816 years) and the male to female ratio was 1.20:1.
Seventy nine percent of the population was Caucasian (4.2% Ashkenazi
Jews), 12.9% East Indian, 2.8% Asian and 5% additional visible
minorities. A family history of IBD was evident in 36.3% of children
(36% 1st degree, 64% 2nd degree). Twenty two percent of the CD
cohort had isolated colonic disease.
Conclusion: The incidence rate and extent of disease of the pediatric
IBD cohort of British Columbia are similar to published pediatric IBD
data, while the high incidence of family history is not well reported.
Moreover, the study found a disproportionate distribution of IBD in the
ethnically diverse population of British Columbia.
170*
NOD2 MUTATIONS PREDICT PHENOTYPIC CHANGES IN
GROWTH IN PEDIATRIC CROHN#S DISEASE
Douglas A. Jacobstein, Jennifer Young, Emily Maksimak, Linda B.
Hurd, Petar Mamula, Robert N. Baldassano, Jonathan E. Markowitz.
The Childrens Hospital of Philadelphia, Philadelphia, PA.
Background: The etiology of Crohn#s disease is multifactorial,
including environmental and genetic influences. Recent linkage analy-
sis revealed a susceptibility gene to Crohn#s disease, NOD2/CARD15,
which is hypothesized to play a role in the innate immune response
of the gut to bacteria. The purpose of this study was to identify
any significant phenotypic expressions of Crohn#s patients with
NOD2/CARD15 mutations.
Methods: Chart reviews of 99 pediatric patients with Crohn#s disease
with NOD2/CARD15 genetic analysis were performed. Data including
age at presentation, age at diagnosis, weight/height (including z-score),
disease location, disease behavior, and NOD2/CARD15 gene variant
were recorded.
Results: NOD2/CARD15 mutations were found in 33 of 99 (33.3%)
patients. Allele-specific NOD2/CARD15 variants were found to be
significantly correlated with growth parameters. Carriers of allele
R702W were found to have both decreased height and weight at
diagnosis compared to non-carriers of NOD2/CARD15 mutations (p =
0.0064, p = 0.0163). Carriers of the G908R allele had increased height
at diagnosis when compared to non-carriers of NOD2/CARD15
mutations (p = 0.0348). No associations were found between carriers
of NOD2/CARD15 variants and age at diagnosis, disease location, and
disease behavior. A trend toward ileal involvement was observed.
Conclusions: Height and weight parameters were associated with
allele-specific NOD2/CARD15 variants. The R702W variant may be
responsible for abnormal height and weight at diagnosis, while the
G908R allele may confer decreased risk of height derangements.
Further study of allele-specific phenotypes may help to confirm these
findings and may reveal other associations that aid in understanding the
role of NOD2/CARD15 in Crohn#s disease.
171*
IBD5 IS STRONGLY ASSOCIATED WITH PEDIATRIC ONSET
CROHNS DISEASE (CD): CONFIRMATION BY
FAMILY-BASED ASSOCIATION & CASE CONTROL
ANALYSIS FROM A PROSPECTIVE POPULATION-BASED
NORTH AMERICAN COHORT
Subra Kugathasan1, U. Babusukumar1, E. McGuire1, T. Wang2, J.
Nebel , U. Broeckel1. 1Dept of Peds, Medical College of WI,
1
Milwaukee, WI; 2Biostats, Medical College of WI, Milwaukee, WI.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
546 NASPGHAN ANNUAL MEETING
IBD5 locus is strongly associated with adult onset CD. Recently,
mutations of OCTN1/OCTN2 and the combined OCTN1 & 2 (TC
diplotype) within the IBD5 locus have been implicated with
susceptibility to CD in adults. To confirm this association, we
genotyped IBD5 variants in our population based pediatric onset CD
cohort by using family based associations (TDT) and case control
designs. DNA was genotyped from 245 CD children and their parents
from our IBD cohort and from 548 control children. Allele frequencies
were calculated for OCTN1 & 2 and 2 haploytpe tagging SNPs
(IGR2198, IGR2230). Mean age of onset was 12 yrs. Among the
pediatric onset CD, a significant association (TDT) was found with
OCTN1 (F 8.1, p , 0.004) and OCTN2 (F 9.54, p , 0.002). All markers
tested were in tight linkage disequilibrium with one another. Logistic
regression showed TC homozygosity was significant for CD risk (OR
1.7, 95% CI (1.12.7), p , 0.05). Case control analysis showed a
significant association (p , 0.05) between cases and control for TC
homozygosity.
Conclusions: We confirm strong association for OCTN1, OCTN2 &
its corresponding TC diplotype for CD susceptibility in our large
independent, population based, pediatric onset North American CD
cohort. OCTN1 and OCTN2 as another susceptibility gene in children
with CD will enhance our ability to study 1) gene-gene interactions with
CARD15; 2) genotype-phenotype correlations in pediatric onset CD.
IBD5 Marker Transmitted/untransmitted F P
OCTN1 65/41 8.09 0.0047
OCTN2 73/46 9.54 0.0021
IGR2198 58/44 3.16 0.076
IGR2230 71/48 7.06 0.0082
172*
CARD15 & IBD5 DO NOT CONTRIBUTE TO CROHNS
DISEASE (CD) SUSCEPTIBILITY IN AFRICAN-AMERICAN &
HISPANIC CHILDREN; A MULTI-CENTER STUDY
U. Babusukumar1, V. Tolia3, A. Loizides2, T. Wang4, E. McGuire1, G.
Kofman2, R. Rajasingham1, U. Broeckel1, S. Kugathasan1. 1Dept of
Peds, Medical College of WI, Milwaukee, WI; 2Albert Einstein College
of Medicine & Childrens Hospital at Montefiore, New York, NY;
3
Wayne State School of Medicine & Childrens Hospital of Michigan,
Detroit, MI; 4Division of Biostatistics, Medical College of Wisconsin,
Milwaukee, WI.
The incidence of CD has been increasing among non-Caucasians in the
US where 25% are ethnic minorities according to the 2000 US census.
Very little information is available on racial/ethnic differences related to
the recently discovered genes CARD15 & IBD5. We studied phenotypic
and genotypic characteristics in 76 ethnic minority children with CD
(58 African-American (AA), 18 Hispanic) from 3 pediatric centers and
compared these to 237 Caucasian CD children. Genotyping for
CARD15 (R702W, G908R, and 1007fsinsC) and IBD5 (OCTN1,
OCTN2) were performed in CD and in large control samples from
Caucasian (n = 601), AA (n = 124), and Hispanic (n = 124) children.
Disease location and behavior were similar among the three groups.
However, significantly lower frequencies of CARD15 mutations were
seen in AA (p , 0.0001) and Hispanic (p , 0.0001) CD children
compared with Caucasian CD children. CARD15 among control
populations also showed significance for both AA (p , 0.001) and
Hispanics (p = 0.03) compared to Caucasians. Significantly lower
frequencies of IBD5 mutations were also seen in AA CD children
compared to Caucasian CD children (p , 0.02).
Conclusions: Conclusions: Phenotypic features of CD are similar
among African-American and Hispanic children compared with
Caucasians. CARD15 & IBD5 do not increase CD susceptibility among
AA and Hispanic children. In the general population, CARD15 & IBD5
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
among AA and Hispanics are lower compared with Caucasians. Future
genetics studies will be crucial, not only in understanding how IBD
genes differentially alter CD susceptibility and progression among
various ethnic and racial groups, but also as a basis for more effective
management of these disorders.
173*
INFLAMMATORY BOWEL DISEASE SEROLOGIC
MARKERS IN CHILDREN; CORRELATION WITH
CLINICAL FINDINGS: A REPORT BY THE PEDIATRIC
IBD COLLABORATIVE GROUP
Sonia Michail1, Jeffrey Hyams2, Adam Mezoff1,2, Anthony Otley2, Joel
Rosh2, David Mack2, Athos Bousvaros2, Subra Kugathasan2, M.
Pfefferkorn2, Vasundhara Tolia2, Jonathan Evans2, Robert Wyllie2,
Robert Rothbaum2, J. del Rosario2, M. Olivia-Hemker2, Anne
Griffiths2, Sandra Hale2, James Markowitz2. 1Wright State University,
Dayton, OH; 2Pediatric IBD Collaborative Group, New York, NY.
Introduction: Several serologic markers including ASCA, anti-OmpC,
and pANCA characterize patients with Crohn disease (CD).
Aim: To determine whether these markers are found more commonly in
different sub-groups of pediatric CD patients and whether they correlate
with clinical course.
Methods: Data were obtained from the prospective observational
registry of the Pediatric IBD Collaborative Research Group.
Results: One hundred and forty six patients with CD had complete data
available for study. 61 (42%) were ASCA positive, 23 were pANCA
positive (16%) and 22 were anti-OmpC positive (15%). Four patients
(2.7%) were ASCA/ANCA positive, 14 children (9.6%) were
ASCA/OmpC positive, and one child (0.7%) was positive for all three.
Children who were ASCA positive were more likely to be .10 years
(95.1% versus 78.8%, p = 0.006) and have disease in the terminal ileum
(90.2% versus 71.8% p = 0.007). Children who were ASCA negative
were more likely to have left sided colonic disease (72.9% versus
27.1%, p = 0.031). Thirteen children were identified with perianal
fistulae and none of them were pANCA positive. All children who
were anti-OmpC positive while being ASCA negative (n = 7) had CD
involving the ascending and transverse colon. 90% of ASCA-/pANCA+
patients had left-sided colon disease, while 25% ASCA+/pANCA+ had
left-sided colon disease (p = 0.021). There was no difference in race,
gender, disease severity at diagnosis, or response to subsequent therapy.
ASCA positivity did not predict the use of infliximab therapy or surgical
intervention in the first year post-diagnosis.
Conclusions: ASCA positive children with CD are more likely to be
.10 years old and to have disease in the terminal ileum, while those
ASCA negative are more likely to have left sided colonic disease. The
presence or absence of ASCA was not helpful in predicting clinical
course.
174*
LACTOBACILLUS GG INHIBITS THE INTESTINAL
TRANSEPITHELIAL MIGRATION OF NEUTROPHILS
Sonia Michail, Frank Abernathy. Pediatric Gastroenterolgy and
Nutrition, Wright State University/The Childrens Medical Center,
Dayton, OH.
Inflammatory bowel disease (IBD) is often characterized by neutrophil
migration across the intestinal epithelium forming cryptitis and crypt
abscess. The migration of neutrophils is associated with clinical disease
activity as well as intestinal epithelial barrier dysfunction. Therefore,
conditions that reduce the neutrophil migration can be of clinical
benefit. Lactobacillus GG is a probiotic agent with good colonization
and adherence ability to the gastrointestinal tract. The goal of this study
is to determine whether Lactobacillus GG is capable of reducing the
transepithelial migration of neutrophils across cultured intestinal
epithelial cells. Fluorescently labeled neutrophils were allowed to
migrate in the basolateral to apical direction across inverted T-84
 NASPGHAN ANNUAL MEETING
intestinal epithelial monolayers under fMLP chemotactic gradient in the
presence or absence of the probiotic. The number of migrated neutrophils
was calculated by comparing fluorescence to known cell densities.
Several concentrations of Lactobacillus GG in the mid log phase were
used (range 1061010). Conditioned media and heat-killed lactobacilli
were utilized to determine if viability and secreted substances from the
probiotic were a factor in influencing neutrophil migration. The results
of this study show a significant reduction of transepithelial migration of
neutrophils in the presence of live Lactobacillus GG at a concentration of
108 (395 6 34 3 103 and 238 6 38 3 103, p , 0.05, n = 12). Heat-killed
L. GG and conditioned media failed to inhibit neutrophil migration. We
conclude that Lactobacillus GG is capable of inhibiting the trans-
epithelial migration of neutrophils at a specific probiotic dose. This effect
is not mediated by a secreted substance from the probiotic agent and
requires the presence of viable bacteria.
175
CD4+ T-LYMPHOCYTE ATP LEVELS:
A SENSITIVE MARKER FOR INFLIXIMAB INDUCED
IMUNNOSUPPRESSION IN PEDIATRIC
PATIENTS WITH IBD
Shervin Rabizadeh, Alexandra Eidelwein, Maria Oliva-Hemker,
Carmen Cuffari. Department of Pediatrics, Division of Pediatric
Gastroenterology and Nutrition, The Johns Hopkins University School
of Medicine, Baltimore, MD.
Introduction: Infliximab has proven efficacy in both the induction and
maintenance of remission in inflammatory bowel disease (IBD).
Although treatment dosing and frequency has been established, some
patients require treatment optimization based on breakthrough symp-
toms. A recent study in solid organ transplantation has shown that
CD4+ T-cell lymphocyte levels are sensitive sub-clinical markers of
immune activation, and can be used to effectively modulate immuno-
suppressant therapy.
Aim: To correlate CD4+ ATP levels and ESR with responsiveness to
infliximab therapy in pediatric patients with IBD.
Methods: Serial CD4+ ATP levels (20) and ESR values (17) were
obtained at the time of infliximab infusion. The CD4+ ATP levels were
preformed by CylexTM (Kowalski et al. Clinical Transplantation,
2003).
Results: The patients with a mean age of 15.9 years were on
maintenance infliximab therapy (5 mg/Kg). 50% had Crohn disease,
40% had ulcerative colitis, and 10% had indeterminate colitis. CD4+ T-
lymphocyte cell ATP levels, but not ESR, correlated with increasing
dosing frequency of infusions (p , 0.04; Pearson Correlation) Table 1.
Conclusion: High CD4+ ATP levels may reflect sub-optimal immuno-
suppression in some patients on standard dosing frequency of infliximab
infusions. Future prospective controlled studies are needed to determine
if CD4+ ATP levels can guide maintenance infliximab therapy in order
to achieve clinical remission.
Time between CD4+ ATP
infliximab infusion (wks) mean (ng/mL) SEM
2 248 131
4 367 56
6 436 155
8 479 78
.8 615 126
Optimal immunosuppression was defined as CD4+ ATP ,400 ng/mL.
176*
DETERMINANTS OF ALTERED BODY COMPOSITION IN
CHILDREN WITH CROHN DISEASE AT DIAGNOSIS
Meena Thayu, Robert N. Baldassano, Jon M. Burnham, Mary B.
Leonard. Childrens Hospital of Philadelphia, Philadelphia, PA.
547
Crohn disease (CD) is characterized by malabsorption, growth failure
and low body mass index (BMI). CD may have distinct effects on lean
mass (LM) and fat mass (FM) that are not captured by BMI. The
objectives of this study were to quantify LM and FM in patients with
incident CD, compared with healthy controls, and to identify
determinants of LM and FM deficits. Whole body LM and FM were
assessed using dual energy x-ray absorptiometry in 78 subjects with
CD (56% M, 10% black) and 632 controls (49% M, 38% black), ages
521 yr. Height (Ht) and BMI were converted to age and gender specific
z-scores using national reference data. Gender specific z-scores for
LM-for-Ht (LM-Ht) and FM-for-Ht (FM-Ht) were derived using linear
regression in the controls, and adjusted for race. Incident CD subjects
had significantly decreased Ht and BMI z-scores (Table) and delayed
sexual maturation (p , 0.001), compared with controls. CD was asso-
ciated with significantly lower LM-Ht z-scores. Adjustment for Tanner
stage attenuated LM-Ht deficits; however, LM-Ht deficits remained
significant (M p , 0.05; F p , 0.001). LM deficits increased with
greater Tanner stage in females with CD, compared with controls (test
for interaction, p , 0.01). FM-Ht z-scores were significantly lower in
females with CD, and these deficits persisted after adjustment for
Tanner stage, compared with controls. In CD subjects, LM-Ht and
FM-Ht Z-scores were significantly lower in females compared with
males. LM-Ht and FM-Ht z-scores were not associated with growth
failure, duration of symptoms, presence of upper tract disease nor
anemia. In summary, CD was associated with significant reductions
in LM in males and females, and FM in females at diagnosis. A
prospective study addressing the impact of therapies on LM and FM is
underway.
Crohn disease Controls p-value
Ht Z Score*
Male 20.27 6 1.14 0.14 6 0.89 ,0.01
Female 20.35 6 1.08 0.23 6 0.85 ,0.001
BMI Z Score*
Male 20.29 6 1.17 0.18 6 0.99 ,0.01
Female 20.78 6 1.01 0.29 6 0.88 ,0.001
LM-Ht Z-Score**
Male 20.39 (20.72, 20.07) ,0.05
Female 20.91 (21.26, 20.56) ,0.001
FM-Ht Z-Score**
Male 0.02 (20.29, 0.33) 0.90
Female 20.63 (20.97, 20.29) ,0.001
*Mean 6 SD, **Mean (95% CI).
177
PREVALENCE OF ANEMIA IN INCIDENT
PEDIATRIC CROHN DISEASE
Meena Thayu, Mary B. Leonard, Robert N. Baldassano, Petar Mamula.
Childrens Hospital of Philadelphia, Philadelphia, PA.
Crohn disease (CD) is characterized by chronic inflammation,
malabsorption, and extranintestinal manifestations including anemia,
due to poor dietary intake, decreased iron absorption, and intestinal
blood loss. The prevalence of anemia in pediatric patients with CD at
the time of diagnosis has not been well characterized. The objectives of
this prospective cross-sectional study were to determine the prevalence
of anemia in children with newly diagnosed CD prior to initiation of
therapy, and to identify disease characteristics associated with anemia
in CD. 78 CD subjects (56% male, 10% black), 518 years of age, were
enrolled within 2 weeks of diagnosis. All patients had colonoscopy, and
75 patients had esophagoduodenoscopy. Anemia was defined as
a hemoglobin (Hgb) , the 5th percentile based on age and gender
reference values. Disease activity was assessed by the Pediatric CD
Activity Index (PCDAI) and body composition (lean mass and fat mass)
by DXA. Abnormal growth was defined as weight loss of $10% or $1
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
548 NASPGHAN ANNUAL MEETING

channel decrease in height within 2 years prior to diagnosis. Subject and Inpatient therapies
disease characteristics were compared in anemic and non-anemic
subjects using x2 and t-tests. Anemia was present in 77% of CD CD-US CD-Canada UC-US UC-Canada
N = 38 N = 11 FET N = 11 N=8 FET
subjects. Mean Hgb was 11.5 6 1.4 g/dL, (range 8.515.1). Mean
PCDAI scores and erythrocyte sedimentation rates (ESR) were IV Steroids (%) 30 (78.9) 4 (36.4) 0.012 10 (90.9) 8 (100) 0.579
significantly higher in anemic compared with non-anemic subjects IV Antibiotics (%) 16 (42.1) 2 (18.2) 0.136 2 (18.2) 2 (25) 0.574
(Table). Presence of upper gastrointestinal tract (UGT) disease on Parenteral Nutr (%) 11 (28.9) 4 (36.4) 0.450 6 (54.5) 6 (75) 0.337
endoscopy was significantly associated with anemia. Anemia was not Enteral Nutrition (%) 3 (7.9) 2 (18.2) 0.311 0 0
associated with gender, duration of symptoms, body composition, RBC Transfusion (%) 4 (10.5) 1 (9.1) 0.689 4 (36.4) 1 (12.5) 0.267
growth parameters, nor a history of abnormal growth at the time of Infliximab (%) 16 (42.1) 2 (18.2) 0.136 4 (36.4) 0 0.085
diagnosis. In summary, the majority of patients with incident CD were
anemic; UGT disease, ESR, and PCDAI were significantly associated
with anemia. An ongoing prospective study is addressing the impact of
CD therapies on anemia. 179
FECAL CALPROTECTIN DIFFERENTIATES
BETWEEN CHILDREN WITH ACTIVE INFLAMMATORY
Total Anemic Non-anemic p-value
BOWEL DISEASE (IBD) AND HEALTHY CHILDREN
UGT disease, % 88 93 72 #.05 Dorota Walkiewicz1, Steven Werlin1, Daryl Fish1, Patrick Hanaway2,
ESR (mm/hr)* 26.3 (21.5, 31.1) 30.4 (24.8, 36.0) 12.72 (6.7, 18.7) #0.005 Subra Kugathasan1, Nita Salzman1. 1Pediatrics, Medical College of
PCDAI* 37.8 (33.6, 42.0) 40.2 (35.3, 45.0) 29.4 (21.4, 37.3) #0.05 Wisconsin, Milwaukee, WI; 2Genova Diagnostics, Asheville, NC.

*Mean (95% CI). Background: Calprotectin is a calcium- binding protein released by

myelomonocytic cells during inflammation. Fecal calprotectin (FC) is
elevated in patients with IBD and may fluctuate according to disease
activity.
178 Aims: 1) Compare levels of FC in healthy children to those with IBD.
2) Compare FC levels within the IBD group (flare vs. remission).
RESOURCE UTILIZATION FOR CHILDREN WITH NEWLY
Methods: FC was measured by ELISA using 134 stool samples (37
DIAGNOSED INFLAMMATORY BOWEL DISEASE
from healthy controls, 76 from Crohn disease (CD) patients and 21
E. Utterson1, S. Boslaugh1, R. Rothbaum1,2, J. Hyams2, J. Markowitz2,
from ulcerative colitis (UC) patients). Normal FC level was defined as
A. Griffiths2, S. Moyer2, J. Rosh2, D. Mack2, J. Evans2, S. Kugathasan2,
,50 mcg/g of stool. Disease activity in 32 IBD patients (56 samples)
M. Pfefferkorn2, A. Mezoff2, V. Tolia2, A. Otley2, N. LeLeiko2, M. Oliva-
was assessed by the physician global assessment within 2 weeks of sample
Hemker2, R. Wyllie2, A. Bousvaros2, J. Fernando delRosario2, S. Hale2.
1 submission. The Harvey-Bradshaw index (HBI) was calculated in CD
Washington University, St. Louis, MO; 2Pediatric IBD Collaborative
patients. Analysis was performed using the Wilcoxon rank sum test.
Research Group, Hartford, CT.
Results: See Table 1. As a group IBD patients had higher FC levels than
healthy controls (p , 0.0001). Patients with active IBD had sig-
Purpose: To describe resource utilization in the first year after nificantly higher FC levels than controls with no overlap in FC
diagnosis for children with IBD in the US and Canada. concentrations (p , 0.0001). FC levels were higher in disease flare than
Methods: Data originated from the Pediatric IBD Collaborative remission (p , 0.0001); however there was some overlap in FC levels
Research Group Registry, a prospective, observational study of children (p , 0.0001). The correlation coefficient between the HBI and FC
,16 yrs with newly diagnosed IBD. Patient evaluation/treatment are levels in patients with CD was 0.36, p , 0.02.
dictated by each physician and not by protocol. Resources studied
included: office visits, endoscopy beyond diagnostic procedures,
hospitalizations and inpatient therapies. ANOVA and Fishers exact Age Median Mean FC
test (FET) compared data between US and Canada. range FC FC range
Results: 385 patients (264 Crohns disease (CD), 95 ulcerative colitis Disease N (years) (mcg/g) (mcg/g) SD (mcg/g)
(UC) and 26 indeterminate colitis (IC)) completed one year of follow-
up. Data are shown for CD and UC. 71 patients were hospitalized at IBD (CD + UC) 97 820 1193 1539 1738 177500
least once. Most patients were hospitalized 15 days total (mean 11.6, CD/Flare 19 819 2557 3214 2186 8387500
median 5.5, range 183). CD/Remisson 25 819 1293 1373 1630 177500
Conclusions: In the first year after IBD diagnosis, 68% of children had UC/Flare 4 818 2491 2819 1610 12954999
#5 office visits. Only 10% underwent endoscopy beyond primary UC/Remission 8 820 517 764 869 582596
diagnostic procedures, ,20% were hospitalized and only 4% of CD and Control 37 516 43 88 152 16750
3% of UC patients had a surgical procedure. The resource utilization for
these patients was no different in the US compared to Canada, except Conclusions: FC levels can be used to differentiate children with active
for greater IV steroid use for hospitalized CD patients in the US. IBD from healthy controls. FC levels failed to clearly differentiate
disease flare from remission in IBD patients. There is not a clear
Outpatient visits and endoscopic procedures relationship between HBI and FC as a predictor of relapse. Further
investigation of the predictive value of FC in determining relapse in
CD-US CD-Canada ANOVA/ UC-US UC-Canada ANOVA/ a cohort with clinical remission is needed.
N = 198 N = 66 FET N = 63 N = 32 FET

Mean Office Visits 4.75 4.73 0.939 4.79 4.41 0.493

range range range range 180*
111 18 112 19
Patients with
UTILITY OF INFLAMMATORY MARKERS
EGD (%) 19 (9.6) 4 (6.1) 0.272 3 (4.8) 1 (3.1) 0.586
VERSUS SEROLOGIC MARKERS IN SCREENING FOR
Pts. with
INFLAMMATORY BOWEL DISEASE
colonoscopy (%) 21 (10.6) 6 (9.1) 0.466 5 (7.9) 1 (3.1) 0.337
Nasha N. Sabery, Dorsey Bass. Pediatric Gastroenterology, Lucille
Packard Children Hospital at Stanford University, Palo Alto, CA.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
Objectives: Our objective was to compare sensitivity and specificity of
IBD serology (ASCA, ANCA, OMP-C) with hematocrit and ESR in
a referred patient population with suspected IBD.
Methods: Medical records of patients who had IBD serology
performed at Prometheus Laboratories 9/20029/2004 were retrospec-
tively reviewed. Patients were divided into 4 categories: those with
ulcerative colitis (UC), Crohns disease (CD), indeterminate colitis (IC),
and Control Group. Patients were categorized based on clinical
evaluation by board certified pediatric gastroenterologists based on
clinical, radiologic, endoscopic, and pathologic criteria.
Results: 220 patients seen in LPCH GI clinic had IBD serology
performed. Forty-five children were found to have IBD (18 with UC, 25
with CD, and 2 with IC). Prevalence of IBD was 20%. 72% of patients
with UC had had positive serology for PANCA while 17% had positive
ASCA. In patients with CD, 28% had positive PANCA, while 32% had
positive ASCA
Conclusions: As a screening strategy, measurement of ESR and
hematocrit is more sensitive and less costly than serologic testing.
While IBD serology may be helpful in determination of IBD types, it
must be placed in context of other clinical and radiological findings.
Sensitivity Specificity
ANCA or ASCA 57% 93%
OMPC 9% 97%
ESR + ANEMIA 53% 97%
ESR or ANEMIA 86% 77%
Using values of IgA .20, IgG .40, pANCA Elisa .12, IFA DNAse
sensitive, OMP-C .16.5, ESR .20.
181
GRANULOMA PREVALENCE AND DISTRIBUTION IN
PEDIATRIC CROHNS DISEASE: IMPORTANCE OF UPPER
ENDOSCOPY AND TERMINAL ILEAL BIOPSIES
V. De Matos, D. A. Piccoli, R. N. Baldassano, P. Russo The Childrens
Hospital of Philadelphia, University of PA School of Medicine,
Philadelphia, PA.
Background: Descriminating Crohns colitis from ulcerative colitis is
a problem. A granuloma is a pathognomonic finding of CD. The
presence and prevalence of granulomas in pediatric patients with CD
has not been fully characterized.
Methods: To study the frequency and distribution of granulomas in
pediatric CD we evaluated all patients undergoing colonoscopy from
1/98 to 12/04. Histology and patient charts were reviewed for all
patients with a TI biopsy. Patients with a diagnosis of CD who had
upper tract, TI and colon biopsies were included in this study. The
presence and site of granulomas were recorded.
Results: 1728 colonoscopies with TI biopsies were performed in 1403
patients. 366 of these patients have CD. 299/366 CD patients had
biopsies from EGD, TI and colon. 43.8% (131/299) had at least one
granuloma identified. Granulomas were identified in the following
specimens: esophagus 1.3%; stomach 14.4%; duodenum 3%; TI 26.7%;
colon 21.7% of all patients. In the 131 granuloma positive CD patients,
the distribution is as follows:
EGD only 14.5%; EGD + TI 3.8%
TI only 22.9%; TI + colon 20.6%
Colon only 19.1%; EGD + colon 6.9%; All 3 sites 12.2%.
Summary: 1) Granulomas are identified commonly (43.8%) in
pediatric CD patients fully evaluated by endoscopy. 2) The upper tract
was the only site of identified granulomas in 14.5% of patients. 3) The
TI was the only site of identified granulomas in 22.9% of patients. 4)
Colonoscopy alone would have identified granulomas in only 58.8% of
patients who had granulomas identified in this study. Upper tract
biopsies and TI biopsies are essential for identifying granulomas in
nearly half (41.2%) of all pediatric CD patients.
549
Conclusions: EGD with biopsy, and TI intubation with biopsy
markedly increase the likelihood of identifying granulomas in pediatric
CD. In some patients this may help discriminate CD from UC. This data
supports a complete endoscopic evaluation with biopsies including
EGD and TI intubation for all patients with possible IBD.
182
DLG5-113A MUTATION IS STRONGLY ASSOCIATED WITH
MALE GENDER BUT PROTECTIVE IN FEMALES IN
PEDIATRIC ONSET CROHNS DISEASE (CD)
Subra Kugathasan1, Umesh Babusukumar1, Tao Wang3, Erin
McGuire1, Ulrich Broeckel2. 1Department of Pediatrics, Medical
College of Wisconsin, Milwaukee, WI; 2Human Molecular Genetics
Center, Medical College of Wisconsin and Childrens Hospital of
Wisconsin, Milwaukee, WI; 3Division of Biostatistics, Medical College
of Wisconsin, Milwaukee, WI.
Genome wide scanning identified a potential IBD locus on Chromo-
some 10 in European IBD cohort. Recently, the 113A mutation within
the DLG5 gene (Drosophila Discs Large Homolog 5) at 10q23 has been
linked to CD in adults. Since the susceptibility risk of this gene in early
onset CD is not known, we have examined the contribution of DLG5
(113G to A) and its interaction with gender in a pediatric onset
population based CD cohort. The mean age of onset in CD was 12.2 yrs.
240 CD & 479 controls were genotyped for DLG5-113A missense
mutation by taqman technology. Only Caucasian samples were studied.
Parental DNA was typed and joint linkage/association was tested by
transmission disequilibrium test (TDT). Potential genotype-gender
interaction was detected by performing logistic regression with
adjustment for gender. The overall allele frequency for DLG5-113A
was 8.5 % in CD and 10.3% in controls. When analyzed separately for
gender effects in CD, allele frequencies were 10.2% in males (n = 142)
and 6% in females (n = 98). In controls, the allele frequencies were
8.3% for males (n = 240) and 12.3% for females (n = 239). A strong
male gender effect (p = 0.0013) was seen for CD susceptibility and, in
contrast, a protective effect (p = 0.18) was seen in females with CD.
Again, gender/DLG5 113A mutation interaction was significant (p =
0.016) for males. TDT show no significant association (p = 0.16) with
our relatively small sample size of CD trios (n = 112). Conclusions:
DLG5 113A mutation seems to confer CD susceptibility for the male
gender, but a protective effect for females in our cohort of pediatric
onset CD. This may explain the predominance of male over female CD
incidence (1.9:1 ratio) seen in early onset CD, as previously published
(J Pediatr 2003:143). This intriguing finding needs confirmation in
large, independent IBD cohorts.
Pancreas and Cystic Fibrosis
183
HYPERAMYLASEMIA AND LIPASEMIA IN
PEDIATRIC DIABETIC KETO-ACIDOSIS
J. Antonio. Quiros, James Marcin, Nathan Kuppermann, Farid
Nasroladeh, Nicole Glaser. Dept. of Pediatrics, UC Davis Childrens
Hospital, Sacramento, CA.
Background: Elevated amylase and lipase occur in approximately 16
60% of patients presenting with diabetic ketoacidosis (DKA).
Postulated causes of enzyme elevation in this setting include ischemia,
autoimmune pancreatic injury, artificial elevation of serum enzyme
levels by decreased renal function, generation of macroforms of these
enzymes and non-pancreatic enzyme release.
Study Design and Methods: We sought to determine the possible
cause of amylase and lipase elevation in patients with DKA by
prospectively measuring laboratory values among consecutive children
admitted with DKA to three tertiary Childrens Hospitals. In the first
24 hrs of admission we measured serum pH, lipase, amylase, amylase
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
550 NASPGHAN ANNUAL MEETING
isoenzymes, chemistries and renal function tests. Data was analyzed
using chi-square analysis and Student t-test when appropriate.
Results: Hyperlipasemia was present in 21/68 (31%) and hyper-
amylasemia in 16/68 (23%) in the first 24 hours post admission. 13%
had both enzymes elevated. There was a significant association between
the degree of acidosis and both amylase and lipase enzyme elevation
(p , 0.05). Elevated BUN was associated with higher serum levels of
amylase (p = 0.02) and lipase (p = 0.07). Amylase isoenzyme analysis
was performed in 32 patients (47%). Lipase and pancreatic amylase
elevation occurred in 3/31 (9.7%). Acidosis and elevated BUN were
also associated with total and pancreatic amylase elevation (p , 0.05).
Abdominal pain was present in 41 (60%) of patients. There was no
association between abdominal pain and elevated pancreatic enzymes.
Discussion: Elevated lipase and amylase in pediatric patients with
DKA is common and not always associated with abdominal pain.
Dehydration and severity of disease, which potentially lead to decreased
organ perfusion and reduced glomerular filtration, may result in
elevated amylase and lipase values. This is independent of biochemical
pancreatitis in most cases and due to systemic ischemic injury and
decreased metabolism and excretion.
184
ESSENTIAL FATTY ACID DEFICIENCY AND THE
CLINICAL RELEVANCE OF THE TRIENE:TETRAENE
RATIO IN CHILDREN WITH CYSTIC FIBROSIS
Asim Maqbool1, Joan Schall1, Babette Zemel1, Birgitta Strandvik2,
Virginia A. Stallings1. 1GI and Nutrition, The Childrens Hospital of
Philadelphia-University of Pennsylvania School of Medicine, Phila-
delphia, PA; 2Pediatrics, Institute for Women & Childrens Health,
Goteburg University, Goteburg, Sweden.
Background: Essential fatty acid (EFA) deficiency has been well
documented in patients with cystic fibrosis (CF) and may be due to
impaired absorption, increased turnover, or both. EFA deficiency
(EFAD) is defined as a triene:tetraene (T:T; Eicosatrienoic [ETA]:
Arachidonic [AA] acids) ratio of .0.04.
Aims: To describe EFAD and serum FA levels in a cohort of pre-
adolescent children with CF & pancreatic insufficiency (PI) compared
to age & sex-matched healthy control subjects with similar T:T ratio.
Methods: Children (6.0 to 8.9y) with CF&PI were enrolled from 13 US
CF Centers as part of a longitudinal study of nutritional & pulmonary
status. Serum FA were assessed for all subjects. The coefficient of fat
absorption (%COA) was calculated from 7-day weighed food records
and 3-day stool collection for children with CF. EFA levels & %COA
were examined in relation to discrete T:T ratios, either ,0.02 or .0.04
(Table).
Results: 77 children with CF&PI (8.4 6 0.9y.o.; 39F) & 23 healthy
controls (8.4 6 1.1 y.o.; 13F) participated. 17% (13) of children with CF
had a T:T ratio .0.04.
Conclusions: 17% of our study children with CF,PI & mild lung disease
had EFAd by the T:T ratio.Children with CF & similar T:T ratio as the
healthy control children had significantly different EFA & FA status.
Subjects with CF & EFAd had the poorest fat absorption & FA
status.Supported by R01 HL57448, GCRC (M01RR00240), Swedish
Research Council (4995) & Nutrition Center at CHOP.
T:T ratio, select fatty acids (mole%), ratios and %COA.
T:T
(ETA:AA) N(%) LA aLA AA DHA ETA AA:DHA %COA
Controls ,0.02 23(100) 25 6 3 0.16 6 0.06 10.9 6 1.3 3.0 6 1.4 0.12 6 0.05 4.3 6 1.6
CF ,0.02 37(48) 23 6 2 0.20 6 0.07 8.5 6 1.4 6 0.12 6 0.04 6.5 6
1.6** 0.5** 1.9**
.0.04 13(17) 19 6 0.19 6 6.8 6 1.0 6 0.52 6 7.2 6
2** 0.05 1.6** 0.3** 0.3** 1.2**
Mean 6 SD. Controls v CF: *p , 0.05, **p , 0.001. EFA ,0.02 v EFA .0.04, p , 0.01,
p , 0.001. LA, Linoleic acid; aLA, alinolenic acid; DHA, Docosahexaenoic acid.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
185
FREQUENCY OF DELTA F508 MUTATION IN CHILDREN
AND ADOLESCENTS WITH ACUTE PANCREATITIS AND
ACUTE RECURRENT PANCREATITIS
Carmen A. Sanchez-Ramirez2,1, Alfredo Larrosa-Haro2,1, Rocio
Macias-Rosales2,1, Alejandra Villa-Gomez1,2, Elsa Martinez-Puente1,2.
1
Gastroenterology and Nutrition, Hospital de Pediatria, Guadalajara,
Mexico; 2Unidad de Investigacion en Epidemiologia Clinica, IMSS,
Guadalajara, Mexico.
Introduction: Mutations in the cystic fibrosis (CF) gene in children
with recurrent pancreatitis (RP) have been recently described. The aim
of this study was to compare the frequency of the mutation DF508 in
children and adolescents with acute pancreatitis (AP) vs. recurrent
pancreatitis (RP).
Methods: n = 39. Setting: Pediatric hospital. Design: Analytic cross-
sectional study. Dependent variable: type of pancreatitis (AP y RP).
Independent variables: DF508 mutation. Identification of the mutation
DF-508 was performed with DNA extraction from blood samples and
tested for DF508 amplified by the polymerase chain reaction. Statistical
analysis: Chi-square and Fisher test, means, SD, Student t. p values
, 0.05 were considered as significant.
Results: Mean age 120.8 months, 18 females. There were no differences
in age, gender, ileus, jaundice, shock, severity of the pancreatitis, obesity,
abdominal trauma, biliary stone disease, hepatitis, and drug ingestion
among the 39 patients under study. The symptoms and signs of
pancreatitis in both groups showed differences: in AP 26 (93%) had
episodes of abdominal pain and in RP 11 (100%), with no significant
differences. Nausea, vomiting and fever were more frequent in the AP
group (p , 0.05). No DF508 mutations were detected in the 39 cases
studied in the current series. Comparison of the frequencies of DF508
mutation in the current series with data from series of pediatric patients
with AP, RP from other countries, suggests that it is possible the existence
of demographic variability in its frequency: Oralewska identified this
mutation in 16.6% of 18 Polish children (p , 0.05); and Corpino found
this mutation in 8.3% of 12 cases of British children (p . 0.05).
Conclusion: The absence of the DF508 mutation in our patients with
RP and AP compared with the findings from Poland and British
series probably mean geographic and demographic differences in gene
distribution.
186
CHARACTERISTICS OF VALPROIC ACID
INDUCED PANCREATITIS
Daryl L. Fish, Steven L. Werlin. Pediatrics, Medical College of
Wisconsin, Milwaukee, WI.
Background: Pancreatitis is a known adverse reaction to valproic acid
(VPA) in children, but pediatric published series are small.
Aims: To describe VPA induced acute pancreatitis in children.
Methods: Chart review of all children diagnosed with VPA induced
pancreatitis at the Childrens Hospital of Wisconsin from 19962004. The
diagnosis of pancreatitis was based on a 3-fold elevation of serum amylase
or lipase with appropriate clinical correlation.
Results: 22 patients had VPA pancreatitis (mean age 10 yrs, range 218;
male, 11). None had a prior episode of pancreatitis, recent abdominal
trauma or gallstones. Symptoms included abdominal pain/tenderness 18
(82%), vomiting 16 (73%), abdominal distention 7 (32%) and fever 6
(23%). Median serum amylase and lipase at diagnosis were 325 IU/L
(normal ,81; range 14-815) and 5255 IU/L (normal ,208; range 316
17,874) respectively. Amylase and lipase were .3X normal in 64% and
89 6 7
100% respectively. Radiographic confirmation of pancreatitis was made
in 79% of obtained studies. 7 (30%) had concurrent hepatitis. Median
77 6
12
AST and ALT were 35 (range 14685) and 29 (range 5227)
respectively. GGT was obtained in 6 and elevated in 4 (range 139
1461). The median duration of hospitalization was 6 days. Mean VPA
dosage was 45 mg/kg/day (range 1488). Average duration of VPA usage
 NASPGHAN ANNUAL MEETING 551

prior to onset of pancreatitis was 32 months (range 284). Mean VPA Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are
level at diagnosis was 73 ug/mL (range 5207). Of the 5 (23%) patients at risk for vitamin A deficiency due to chronic fat malabsorption. This
who continued on VPA, pancreatitis resolved in all but one, who died cross-sectional study describes the serum retinol levels and vitamin A
6 days after admission. 3 of those had recurrences and the fourth had intake of preadolescent children, 8.0 to 11.9 years of age, with CF and
3 subsequent admissions for vomiting with no serum pancreatic enzymes PI cared for under current practice standards from 13 US CF centers.
or radiographic imaging. 2 (9%) patients died from enterococcus septic Serum retinol levels, assessed by HPLC, were compared with those of
shock (1) and necrotizing pancreatitis (1). The clinical course did not 593 age-equivalent children from the National Health and Nutrition
differ from children with pancreatitis from other causes. Examination Survey 19992000 (NHANES). Dietary data was
Conclusions: VPA pancreatitis is common and idiosyncratic. Lipase is measured from 7-day weighed food records. Detailed supplement data
a more sensitive marker than amylase. The clinical course does not were obtained by interview. Preformed and total vitamin A intake was
differ from other etiologies of pancreatitis. Mortality is high (9%). VPA compared with the Recommended Dietary Allowance (RDA), Upper
should be discontinued and not restarted after an episode of pancreatitis. Limit (UL), and CF recommendations, by age (8.08.9 and 9.0-11.9
years). The 73 subjects with CF had mild to moderate lung disease
187 (FEV1 91 6 13 %) and mild to moderate steatorrhea (coefficient of fat
absorption 85 6 13%, n = 70). Serum retinol was 52 6 13 mg/dL
THE INADEQUACIES OF MRCP COMPARED TO ERCP AS A (range: 2698), which was significantly greater than levels from
TOOL FOR THE DIAGNOSIS OF PANCREATIC DUCT NHANES (37 6 10 mg/dL, p , 0.001). One subject had a serum level
ABNORMALITIES IN CHILDREN below the NHANES 5th %ile (26.7 mg/dL) while 47% (n = 34) had
Raman R. Sreedharan, Karoly Horvath, Zhaoping He, Lisa States, levels above the NHANES 95th %ile (51.3 mg/dL). All of the 8.08.9
Thomas Kowalski, Dev Mehta. GI and Nutrition, AI duPont Hospital year group and 83% of the 9.011.9 year group took supplements.
for Children/ Thomas Jefferson University, Wilmington, DE. Intake is summarized in Table 1. While vitamin A supplements may be
needed to prevent deficiency, the high serum retinol levels and vitamin
Endoscopic Retrograde Cholangio-Pacreatography (ERCP) is consid- A intake in this study suggest that current care standards may provide
ered as the gold standard investigation for the diagnosis of biliary tract excess vitamin A, particularly as preformed retinol.
(BT) and pancreatic duct (PD) abnormalities. Eventhough Magnetic
Resonance Cholangio-Pancreatography (MRCP) is used extensively as Age: 8.08.9 Years Age: 9.011.9 Years
an alternate to ERCP, there is no data in pediatric literature establishing N = 33 58%# N = 40 45%#
the usefulness of MRCP compared to ERCP. Mean 6 % RDA % Subjects % Subjects Mean 6 % RDA % Subjects % Subjects
Method: Retrospective study comparing the MRCP and ERCP findings in SD 95% Mean 6 .UL .CF Rec SD 95% Mean 6 .UL .CF Rec
Vitamin A CI % SD 95% Preformed/ Preformed/ CI % SD 95% Preformed/ Preformed/
21 children (10# & 11 $) diagnosed with pancreatico-biliary disorders Source Preformed CI Total Total Preformed CI Total Total
during the period 19992005. MRCP was done prior to ERCP in all cases.
Secretin stimulation during MRCP was not used in any of the cases. The Diet 755 6 273 189 6 68 12/33 0/0 867 6 376 145 6 63 0/3 0/0
mean age was 10.9 yrs (range 3.018.25 yrs). ERCP and MRCP reports 658852 165213 747987 124165
85 6 10 89 6 8
were analyzed under two categories: 1) anatomical visualization of PD &
Supplement 2322 6 1561 581 6 390 82/88 18/18 2161 6 1601 360 6 267 60/60 18/23
BT and 2) pathology of PD & BT. The MRCP findings were then correlated
17692875 442719 16492673 275446
with the corresponding ERCP findings and scored as full, partial or no 83 6 23 82 6 9
correlation. Combined 3077 6 1654 769 6 413 94/100 18/42 3028 6 1685 505 6 281 65/78 28/55
Results: 17 of the 21 patients underwent PD cannulation during ERCP 24913663 623916 24893567 415595
and 15 showed PD abnormalities of which none were detected by 84 6 14 85 6 7
MRCP. 19 of the 21 patients underwent BT cannulation during ERCP
and 11 had BT abnormalities of which 90.9% was detected by MRCP. Microgram retinol activity equivalents (mg RAE) per day RDA = 400 mg, UL =
900 mg, CF Rec = 3000 mg, RDA = 600 mg, UL = 1700 mg, CF Rec = 3000 mg.
Table below shows the percentage of MRCP studies that showed full,
partial or no correlation to the ERCP findings.
Conclusions: These data demonstrate that MRCP imaging is a good
investigation in children to visualize the BT anatomy and for detecting 189*
pathological changes of the BT. In contrast, MRCP imaging showed very
poor sensitivity to delineate the PD anatomy and was not able to diagnose USEFULNESS OF NON-BREATH-HOLD
the pathological changes reported by ERCP. Inter- operator variability and ONE SHOT MAGNETIC RESONANCE
lack of secretin stimulation during MRCP may have contributed to the CHOLANGIOPANCREATOGRAPHY FOR THE
poor performance. EVALUATION OF CHOLEDOCHAL CYST IN CHILDREN
Mitsuyoshi Suzuki, Toshiaki Shimizu, Takahiro Kudo, Ryuyo Suzuki,
Yoshikazu Otsuka, Satoru Nagata, Yuichiro Yamashiro. Department of
Full Partial No Pediatrics, Juntendo University, Tokyo, Japan.
correlation correlation correlation
MRCP to ERCP n (%) (%) (%)
Objective: The aim of this study was to clarify the usefulness of
ANATOMY PD 17 17.64 47.05 35.29 magnetic resonance cholangiopancreatography (MRCP) for the
BT 19 78.94 21.05 0.00 diagnosis of choledochal cyst in children, and to evaluate for the
PATHOLOGY PD 15 0.00 0.00 100.00 ability to depict clearly abnormal union of the pancreaticobiliary
BT 11 90.90 0.00 9.09 junction (AUPBJ), dilatation or abnormalities of the main pancreatic
duct, and protein plug or stone with choledochal cyst.
Subjects and Methods: During the past 10 years, 33 patients (age
188 range, 1 month-18 years; mean age, 4.8 years; 26 girls and 7 boys) who
were diagnosed as choledochal cyst by abdominal sonography or
VITAMIN A STATUS IN PREADOLESCENT computed tomography underwent non-breath hold MRCP using a half-
CHILDREN WITH CYSTIC FIBROSIS AND Fourier, single-shot, fast spin-echo imaging method. The detection rate
PANCREATIC INSUFFICIENCY in MRCP of choledochal cyst, AUPBJ, dilatation or abnormalities of the
Rose C. Graham-Maar, Joan I. Schall, Babette S. Zemel, Virginia A. main pancreatic duct, and protein plug or stone were compared with
Stallings. GI & Nutrition, The Childrens Hospital of Philadelphia, those of endoscopic retrograde cholangiopancreatography (ERCP) or
Philadelphia, PA. intraoperative cholangiopancreatography (IOCP).

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

552 NASPGHAN ANNUAL MEETING
Results: In all 33 patients, MRCP could detect choledochal cyst that
contains 13 of cystic dilatation and 20 of fusiform dilatation. Detection
rate of main pancreatic duct was 62.2% (20/32), AUPBJ was 53.3%
(16/30), dilatation or abnormalities of the main pancreatic duct was
75.0% (3/4), and protein plug or stone was 76.9% (10/13). In under 2
year old patients (group A), the detection rate were significantly lower
than those of in over 2 year old patients (group B) (main pancreatic
duct; 16.6% (1/6) vs 73.1% (19/26): p , 0.01, AUPBJ: 0.0% (0/7) vs
66.7% (16/24): p , 0.05, and protein plug or stone; 0.0% (0/2) vs 90.9%
(10/11): p , 0.05). Detection rate of AUPBJ in the patients with
fusiform dilatation was superior to that in the patients with cystic
dilatation (70% (14/20) vs 20% (2/10): p , 0.05).
Conclusion: Above two year old patients with choledochal cyst,
MRCP is useful for surgical planning and should be first choice to
confirm the diagnosis and accuracy visualization of anatomical
structure of pancreaticobiliary system and potential complication.
ORAL ABSTRACT PRESENTATIONS
SATURDAY, OCTOBER 22, 2005
10:00 AM 12:00 PM
Basic Science
190
SOY-LIPID DERIVED STIGMASTEROL SUPPRESSES FXR
TARGET GENES BSEP AND FGF-19 IN HUMAN
HEPATOBLASTOMA (HEPG2) CELLSPOTENTIAL
ROLE IN TOTAL PARENTERAL NUTRITION-ASSOCIATED
CHOLESTASIS (TPNAC)
Beth A. Carter1,2, Daniel R. Prendergast1,2, Richard J. von Fursten-
berg1,2, Saul J. Karpen1,2. 1Baylor College of Medicine, Houston, TX;
2
Texas Childrens Liver Center, Houston, TX.
Background: The etiology of TPNAC is unknown but may involve an
impairment in bile acid (BA) secretion leading to intracellular
accumulation of BAs. BSEP, the 1 bile salt exporter on the canalicular
membrane of the hepatocyte, has an FXR element in its promoter
upregulated by the potent FXR ligand chenodeoxycholic acid (CDCA).
We previously reported that stigmasterol acetate (StigAc), a phytosterol
component of soy lipid in IV fat solutions, antagonizes BA-activated
BSEP in a 1 mouse hepatocyte model. Fibroblast growth factor-19
(FGF-19), like BSEP, has an FXR response element in its promoter and
has previously been implicated in the suppression of BA biosynthesis
(Holt et al, Genes and Dev, 2003).
Purpose: To test the effect of stigmasterol on BA-activated FXR target
genes in a human cell line.
Methods: HepG2 cells were grown to 80% confluency followed by
24 hr treatments in 0.25% charcoal stripped media: Vehicle alone,
chenodeoxycholic acid (CDCA) 100 mM alone, StigAc 10 mM alone, or
CDCA 100 mM + StigAc 10 mM. Cells were harvested, RNA isolated,
and QRTPCR performed to determine the relative expression of the
human FXR target genes BSEP and FGF-19 normalized to 18s RNA
expression.
Results: As expected, the potent FXR ligand, CDCA, activated BSEP
mRNA expression ~300-fold over vehicle-treated cells. StigAc alone
had no effect on BA-activated HepG2 cells, while cells co-treated with
CDCA + StigAc suppressed BA-activated BSEP mRNA by ~50%.
StigAc similarly suppressed BA-activated FGF-19 expression in HepG2
cells (~70% suppression).
Conclusion: The high serum levels of stigmasterol in infants with
TPNAC may contribute to hepatotoxicity by interfering with the
hepatoprotective pathways orchestrated by FXR (i.e. BA-induced
upregulation of BSEP and FGF-19 mediated suppression of BA
synthesis). These findings further delineate our molecular model of
TPNAC in infants on longterm TPN.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
191
PEPTIDE-BASED DIET WITH LOW AMOUNT OF
FREE AMINO ACIDS ENHANCES GASTROINTESTINAL
STRUCTURE AND FUNCTION IN PIGLETS WITH
COMPROMISED GASTROINTESTINAL TRACT
Kelly A. Tappenden, Bianca A. Maples, Brian M. Chung. Nutr Sci,
University of Illinois, Urbana, IL.
Polymeric diets support intestinal structure and function more
effectively than hydrolysate diets; however, hydrolysate diets are
known to enhance tolerance during intestinal dysfunction. We
hypothesized, in a pediatric model of intestinal injury, that provision
of a peptide-based diet with a low amount of free amino acids (AA)
would enhance intestinal structure and function compared to diets
containing either intact proteins or peptides with a high proportion of
free AA. Within two weeks of weaning, piglets (8.55 6 0.11 kg, n = 20)
underwent gastrostomy placement and banding of the superior
mesenteric artery to restrict blood flow to baseline fasting levels. For
7 days following surgery, the piglets received continuous enteral
infusions with isoenergetic, isonitrogenous complete nutrient formulas
containing: 1) intact proteins (POLY); 2) whey-hydrolysate with a low
amount (,1%) of free AA (LAA), or 3) casein-hydrolysate with a high
amount (40%) of free AA (HAA). Body weight did not differ between
groups at any time, and piglets gained 261 6 22 g/day. Jejunal weight
(g/kg body wt) was 35% higher (P = 0.048) in LAA compared to HAA,
but did not differ from POLY. Within the jejunum, the percentage of the
intestine comprised of mucosa was 2030% greater (P = 0.005) in LAA
and HAA compared to POLY. However, treatment did not alter weight or
mucosal abundance of the duodenum, ileum, or colon. LAA increased
(P = 0.018) duodenal sucrase activity compared to HAA and POLY,
whereas both peptide-based diets increased (P = 0.034) jejunal lactase
activity compared to POLY. In summary, these data indicate that
peptide-based diets do stimulate the structure and function of a
compromised intestine when compared to intact protein diets, and
certain additional advantages may be garnered with diets containing
a higher ratio of peptides: free AA. Provision of a whey peptide-based
enteral formula with a low amount of AA may provide appropriate
mucosal stimulation while maintaining enteral tolerance during in-
testinal dysfunction.
192
TREATMENT OF EXPERIMENTAL FORMS OF
IBD BY THE ADMINISTRATION OF NFkb BINDING
SITE DECOY OLIGONUCLEOTIDES
Ivan J. Fuss, Stefan Fichtner-Feigl, Jan Preiss, Atsushi Kitani, Warren
Strober. Mucosal Immunity Section, National Institutes of Health,
Bethesda, MD.
Crohns disease and ulcerative colitis, result in major health care
problems. Unfortunately, existing treatment for both diseases are
associated with a number of serious, long-term side effects and
therefore different methods of treatment are needed. One such approach
involves the targeting of NF-KB, a transcription factor that is necessary
for the cellular production of several key inflammatory cytokines that
drive the inflammation of IBD.
Methods: To test this, we administered double-stranded decoy
oligonucleotides (ODN) targeting the consensus sequences of NF-KB
(by either an intra-rectal or intra-peritoneal route) to mice with several
forms of colitis (acute/chronic TNBS-colitis, Oxazolone-colitis).
Results: We showed that administration of ODN packaged in a viral
envelope derived from the hemagglutinating virus of Japan (HVJ-E)
both prevented and treated acute TNBS-colitis as verified by weight
loss, histopathology, downmodulation of cytokine production (IL-12,
IFN-g and TNF-a) and decreased NF-KB DNA-binding activity. In
addition, we showed that NF-KB decoy ODN administration was an
effective treatment of chronic TNBS-colitis and in this case not only
 NASPGHAN ANNUAL MEETING
downmodulated the production of the above inflammatory cytokines but
also, reversed the development of fibrosis. In contrast, neither
scrambled ODN nor decoy ODN administered in the absence of HVJ-
E had any effect. In both models, NF-KB decoy treatment resulted in
CD4 Tcell apoptosis, suggesting that the durable effect was secondary
to activation induced cell death of inflammatory effector cells. Finally,
we showed that NF-KB decoy ODN also prevented the development of
oxazolone-colitis and led to downmodulation of Th2 cytokines, such as
IL-4 and IL-13, indicating that it is applicable to a Th2-mediated
disease process as well such as UC.
Conclusion: In each case, decoy administration led to resolution of
inflammation, this plus the ease of administration to inflamed tissue
suggest a therapeutic potential applicable to both human IBD.
193
MARKED BILE DUCT PROLIFERATION IN
MICE HETEROZYGOUS FOR LUNATIC FRINGE
AND JAG1 MUTATIONS
Matthew J. Ryan, Dorian M. Hall, Lara A. Silvis, Anthony Nelson,
Nancy B. Spinner, Kenro Kusumi, Kathleen M. Loomes. Childrens
Hospital of Philadelphia, Philadelphia, PA.
Background: The Notch signaling pathway is involved in cell fate
determination in many organs. JAG1, encoding a ligand in the Notch
pathway, has been identified as the disease gene for Alagille Syndrome
(AGS), characterized by bile duct paucity and other manifestations.
Mice heterozygous for mutations in both the Notch2 receptor and Jag1
ligand have a phenotype similar to AGS. Notch signaling is regulated by
three mammalian Fringe genes. These genes encode glycosyltrans-
ferases that modify the activation of the Notch receptor by the ligand.
To examine the role of the Lunatic Fringe (Lfng) gene in modifying
Jag1 ligand function, we carried out genetic analysis of double
heterozygous mice (Jag1tm1Grid/+; Lfngtm1Rjo/+, abbreviated as J1LF).
Methods: Liver sections from both J1LF and control mice were
examined by H&E staining. Bile ducts were identified by cytokeratin
staining, and blood vessels were stained with Factor VIII antibody. Mice
were evaluated as newborns and 5-week old adults. Quantitative real time
RT-PCR for Hes1, a downstream effector in the Notch pathway, was
performed to measure Notch signaling.
Results: Adult J1LF mice had a significant increase in the number
of bile ducts in the portal tracts, when compared to their single
heterozygous and wild type littermates. Numbers of blood vessels in
portal tracts were not significantly different between J1LF and control
mice. Gross examination revealed that the extrahepatic biliary tree was
intact. In adult J1LF livers with bile duct proliferation, real time PCR
demonstrated a 4 to 8 fold increase in Hes1 expression levels over wild
type and single heterozygous controls. However, in the newborn period,
J1LF mice did not display a significant difference in the numbers of bile
ducts.
Conclusions: Jag1/Lfng double heterozygous mice have a striking
proliferation of bile ducts in the adult liver. These differences arise
postnatally, pointing to a role for Lfng in regulating Jag1-Notch
signaling in bile duct growth and maturation and LFNG as a potential
modifier gene for AGS.
194
GROWTH HORMONE RESTORES PEROXISOME
PROLIFERATOR ACTIVATED RECEPTORg
EXPRESSION IN COLITIS
B. Osuntokun, X. Han, N. Benight, E. Bonkowski, L. Denson.
Gastroenterology, Hepatology & Nutrition, Cincinnati Childrens
Hospital Medical Center, Cincinnati, OH.
Background: Growth hormone (GH) regulates cell function through
activation of the STAT5b transcription factor, and promotes mucosal
healing in colitis. Peroxisome proliferator-activated receptor gamma
(PPARg) is as an anti-inflammatory factor in colitis, and is up regulated
553
by GH through STAT5b. We hypothesized that PPARg would be down
regulated in colitis, and that GH would restore PPARg expression.
Methods: Colon GH dependent STAT5b activation and PPAR g
expression were determined in children with newly diagnosed CD and
healthy controls. Interleukin-10 deficient (IL10-/-) mice with colitis and
healthy wild type (WT) controls received single dose GH or chronic GH
administration for 14 days. Colon STAT5b activation and PPARg
expression were determined. T84 human colon carcinoma cells were
treated with TNFa 6 GH, and STAT5b activation was determined.
Results: STAT5b activation and PPARg expression were down regulated
in colon epithelial cells (CEC) and laminar propria mononuclear cells
(LPMC) of children with CD, relative to healthy controls. Colon STAT5b
activation and PPARgexpression were increased in CEC and LPMC by
both single dose and chronic GH administration in WT mice. IL-10-/-
mice exhibited elevated basal STAT5b activation and PPARg expression
in LPMC. However, as in CD, STAT5b activation and PPARg expression
were reduced in CEC; these were resistant to up regulation following
single dose GH treatment. With chronic GH administration,CEC STAT5b
activation and PPARg expression did increase in IL10-/- mice, although
this remained lower than in WT controls. TNFa pre-treatment inhibited
GH mediated STAT5b activation in T84 cells, reproducing the relative GH
resistance observed in CEC in colitis.
Conclusion: PPARg expression is reduced in CEC of affected colon in
CD and in experimental colitis. Chronic GH administration partially
restores PPARg expression via increased STAT5b activation. GH
mediated up regulation of PPARg therefore constitutes a novel
therapeutic target in CD.
195
A NOVEL PHENOTYPE OF LIVER STEM CELLS
USING CD133 EXPRESSION
Carl B. Rountree1,2, Shundi Ge2, Judy Zhu2, Lora Basrky2, Gay
Crooks2. 1Gastroenterology, CHLA, LA, CA; 2GISCT Program, CHLA,
LA, CA.
Controversies exist over the phenotype of oval cells (OCs), liver stem
cells, and their role in liver regeneration. The goal of this study is to
establish the phenotype of OCs. This study compares the proliferation
of OCs using two methods of liver damage: 3,5-diethoxycarbonyl-1-4-
dihyrdo-collidine (DDC) and 2-acetylaminofluorene with carbon
tetrachloride (AAF/CCL4). C57/B6 and immune deficient b2Mnull
NOD/SCID mice were fed a DDC 0.1% diet or gavaged AAF with an
injection of CCL4 and studied at defined intervals to determine the
time course of injury. H&E staining, immunohistochemistry (IHC)
co-staining for cytokeratin and BRDU, and IHC for A6, an OC marker
all demonstrated proliferation of OCs in DDC damaged livers. These
studies indicate that DDC injury is a useful model for future study of
OCs. Cytospin of liver non-parenchymal (NP) cells, non-hepatocytes,
reveals cells that express A6, c-Met (the Hepatocyte Growth Fac-
tor receptor) and aFP (a marker of liver regeneration). Flow cytometry
(FACS) analysis determined the percentage of each OC marker
as a proportion of CD45- NP cells in DDC damaged livers. (CD45 is a
marker of mature hematopoietic cells). CD45- NP (non-hematopoietic)
cells expressing CD34 and Thy-1, previously described OC markers,
were significantly increased. In addition, CD133+ cells, a marker not
previously associated with OCs, were significantly increased in the
CD45- NP fraction. CD45+ and CD45- cells expressing these markers
were isolated from NP cells for RT-PCR analysis. CD133 + CD45- cells
have strong RNA expression of albumin, c-Met, aFP, and HNF4a (a
transcription factor of early liver development). The other fractions of
CD45- cells, which express Thy-1 or CD34, did not share the same
profile of liver gene expression. CD45+ hematopoietic cells do not
express liver genes like albumin or HNF4a. Using H&E, IHC and
FACS, a comparison of two methods of liver damage demonstrates that
DDC is the most efficient method to induce OC proliferation. These
studies indicate that murine OCs are within the CD45- fraction of liver
NP cells that express the novel marker, CD133.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
554 NASPGHAN ANNUAL MEETING

196 Results: Rats that received pH 4.0 injections as neonates developed

visceral hyperalgesia with a significant increase in the visceromotor
ANTI-INFLAMMATORY MECHANISMS OF ENTERIC response (CRD $20 mmHg, p , 0.05). The spontaneous firing of SL-S
HELMINTH THERAPY IN MURINE COLITIS (20.6 6 4.5 imp/s), but not SL-A (6.4 6 5.4 imp/s) neurons in the
Thomas L. Sutton1, K. B. Madden2, A. Zhao3, J. E. Elfrey3, B. A. Tuft1, C. pH 4.0 group was higher than control (1.8 6 0.1 and 4.3 6 2.3 imp/s,
A. Sullivan1, J. F. Urban4, T. Shea-Donohue3. 1WRAMC, Washington, respectively, p , 0.01). The responses of SL-S neurons to CRD in the
DC; 2USUHS, Bethesda, MD; 3UMd SOM, Baltimore, MD; 4USDA, pH 4.0 group were also higher at all distension pressures (p , 0.01).
Beltsville, MD. SL-A neurons did not differ from controls. Amitriptyline signifi-
cantly decreased the spontaneous activity of sensitized SL-S neurons
Recent studies showed that Trichuris suis ova therapy improved (17.6279 6 1.9 vs 5.96 6 2.0, p , 0.01) and the response to CRD at all
symptoms in IBD patients. pressures (p , 0.02) but had no effect on SL-A neurons.
Aims: To determine the protective mechanism of helminth infection on Conclusion: Nociceptive somatic stimulation in neonatal rats results in
colitis-induced changes in immune and epithelial cell function. chronic visceral hyperalgesia. Sensitization occurs through sustained
Methods: BALB/c mice received intrarectal saline or TNBS spinal neurons that can be modulated by amitriptyline.
(2 mg/mouse; 40% ETOH) and studied 4 days (d) later. Separate
groups of mice received oral Heligmosomoides polygyrus (Hp), saline Clinical Science
or TNBS at 14d, and studied at 18d. Colonic mucosae were mounted in
Ussing chambers to measure mucosal permeability (R, resistance) and 198
secretion to 5-HT, histamine (HIS), and PAR1 or 2 agonists. Colonic
expression of IFNg, TNFa, IL-13, IL-4, PAR1, PAR2, and histamine 4 NEONATAL HEMOCHROMATOSIS (NH) DUE TO GESTATIONAL
(H4) receptor (present on immune cells) was assessed by real-time PCR. ALLOIMMUNITY: DETECTION OF MATERNAL
Results: TNBS upregulated IFNg, TNFa, and H4 expression, induced ALLOANTIBODY AND PREVENTION OF RECURRENCE
mucosal damage, and depressed secretory responses (table). Hp elevated Peter F. Whitington, Padmini Malladi, Susan Kelly. Pediatrics,
IL-13 and IL-4 expression, increased mucosal R and decreased responses Northwestern University, Chicago, IL.
to PAR1. Hp infection prevented TNBS-induced upregulation of Th1
cytokines and H4 expression, and normalized responses to 5-HT and Background: NH is a severe fetal liver disease. We hypothesized that
PAR2. Hp-induced increases in mucosal R and Th2 cytokine expression NH is an alloimmune gestational disease and showed that treatment
persisted after TNBS. PAR expression was unchanged in all groups. with high-dose IVIG during gestation prevents lethal recurrence
Conclusions: The protective mechanism of enteric infection against (Lancet 2004;364:16908). The aims of this study were: 1. Identify
TNBS-induced colitis involves downregulation of inflammatory mediator the fetal target of alloimmunity in order to develop a serologic test for
expression and improved colonic function. These findings underlie the alloantibody; and 2. Extend the trial of gestational treatment in order to
clinical improvement seen in IBD with helminth therapy. further determine its effectiveness.
Methods and Results: Subjects were women whose last pregnancy
Resistance HIS 5-HT PAR 1 PAR 2 ended in a bona fide case of NH; controls were unaffected women and
n$4 (V cm2) (mA/cm2) (mA/cm2) (mA/cm2) (mA/cm2) spouses of subjects. IgG isolated by protein-A sepharose binding was
tested for immunoreactivity with fetal liver proteins by western blot and
CONTROL 19 6 1 42 6 10 89 6 10 70 6 14 40 6 8
2-D PAGE immunoblot. IgG from NH subjects consistently reacted at
TNBS 22 6 3 17 6 4* 34 6 10* 14 6 3* 15 6 2*
high dilution with a specific protein in fetal (but not adult) human,
Hp 26 6 4* 4 6 3* 60 6 17 14 6 3* 20 6 5
mouse and calf liver, whereas control IgG at low titer at most weakly
Hp + TNBS 29 6 4*f 8 6 3* 96 6 23f 13 6 5* 40 6 7f
detects this protein, which is tentatively identified as a fetal isoform of
*p , 0.05 vs CONT; fp , 0.05 vs TNBS. hemeoxygenase-1 (HO-1). This protein isolated from fetal calf liver is
being used to develop a sandwich immunoassay for quantitative, high
throughput determination of alloantibody. Subjects were offered
197 gestational treatment (IVIG 1g/kg weekly from 18 wks gestation) in
subsequent pregnancies. To date, 29 subjects have enrolled. All 25
A NEW MODEL OF VISCERAL HYPERALGESIA babies born to date survived with medical care alone (p , 0.00001
IN NEONATAL RATS versus previous gestations); 5 women are currently receiving treatment;
Adrian Miranda, Shachar Peles, Colin Rudolph, Enisa Hodzic, Jyoti N. and 1 subject suffered miscarriage at 18 weeks before treatment began.
Sengupta. Pediatrics, Medical College of Wisconsin, Milwaukee, WI. We became aware after the fact that a woman beginning off-protocol
treatment at 2425 weeks had a severely affected baby who died. She
Introduction: During development, the spinal cord is vulnerable to subsequently tested strongly positive for alloantibody.
permanent structural and functional alterations in pain pathways. We Conclusions: NH is often the result of maternal alloimmunity against
aimed to investigate alterations in visceral sensation that result from fetal liver and recurrence can be prevented by high-dose IVIG during
noxious somatic stimulation during the neonatal period. We hypothe- gestation, beginning at 18 weeks or earlier. We speculate that depletion of
sized that spinal neurons undergo permanent sensitization in areas of fetal hepatic HO-1 activity results in loss of cellular antioxidant and
viscero-somatic convergence and that this sensitization can be sensitivity to iron-induced oxidant injury.
attenuated by amitriptyline.
Methods: Neonatal Sprague-Dawley rats received saline injections 199
(0.1 ml) of pH 4.0 or pH 7.4 in the gastrocnemius muscle on alternate
days (total 6). A third group received needle prick only, while a forth WATER AND BIOFILM TRANSMISSION OF
group was left naive (n = 10 per group). A stimulus response function to HELICOBACTER PYLORI (HP) IN RURAL
graded colorectal distension (CRD) (10-80 mmHg) was recorded at age GUATEMALAN HOUSEHOLDS
8-12 weeks. Extracellular single-unit recordings from spinal neurons Michael J. Kowolick1, Sherie A. Dowsett1, Luis Archila3, Ana-Maria
(L1-L4) were performed in adult pH 4.0 injected rats and compared to Solorzano , Beatriz Lopez4, Carlos Mendoza4, Alejandro D. Thomp-
3

naive controls. Neurons were sub-classified as short latency abrupt
(SL-A, n = 24) or short latency sustained (SL-S, n = 23). The
spontaneous activity and response to graded CRD was recorded for each
neuron. Recordings were repeated following administration of amitrip-
tyline (6 mmol/kg, i.v.).
son2, Marilyn L. Owens2, Milton Brown2, Benjamin D. Gold2.
1
Dentistry, Indiana Univ. Sch of Med., Indianapolis, IN; 2Pediatrics,
Emory Univ. School of Med., Atlanta, GA; 3Univ. Mariano Galvez,
Guatemala City, Guatemala; 4Center for Health Studies, MERTU,
Guatemala City, Guatemala.

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
Introduction: Modes of Hp transmission remain incompletely
characterized, particularly extra-human reservoirs (e.g. water, biofilms).
Methods: We previously demonstrated Hp presence in dental plaque
and tongue dorsum of a high proportion (86%) of persons in San Juan la
Laguna, an indigenous Mayan population of western Guatemala. No hot
running water is available. All households utilize standing water from
rain collection, or pipe/carry water from the lake. To determine the
presence of Hp in water or biofilms, we collected water and biofilm
samples from households previously surveyed with serology (Hp
antibodies) and PCR of dental plaque for Hp infection. Water sources
obtained were from storage vessels, pipes (spout, bend) and biofilm
swabs from each source. All samples were tested for coliforms,
including Escherichia coli. After DNA extraction from water samples
and swabs, PCR and nested-PCR methods were performed in two
independent labs for presence of Hp.
Results: 8 households had Hp-infected persons by serology and oral
evaluation; 4 households evaluated had all persons negative by
serology and few oral sites contained Hp DNA. All samples from
standing water, pipes and vessels were positive for fecal coliforms and
E. coli. Using conventional and nested-PCR, a greater proportion of
standing water samples (65%) than swab samples (29%) were positive
for Hp DNA (p , 0.002); yet swabs from deep pipe sections had more
Hp than pipe spouts.
Conclusion: Hp appears to be present in both water and biofilm in
households where infected persons reside in rural Guatemala. A greater
degree of Hp appears to be present in the standing water samples than in
biofilm swabs in this village. Future research is needed to elucidate
potential mechanisms for eliminating Hp from water and biofilms to
prevent person to person and environment-person spread of Hp in
endemic regions.
200
BIOAVAILABILITY OF A NOVEL WATER-SOLUBLE
VITAMIN E FORMULATION IN
MALABSORBING PATIENTS
Konstantinos Papas1, John Kalbfleisch2, Ricky Mohon3. 1Yasoo Health
Inc., Johnson City, TN; 2Biometry and Medical Computing, Section of
Medical Education, Quillen College of Medicine, East Tennessee State
University, Johnson City, TN; 3Department of Pediatrics, Quillen
College of Medicine, East Tennessee State University, Johnson City, TN.
Background: In cystic fibrosis (CF), pancreatic insufficiency and
a diminished bile acid pool cause malabsorption of important nutrients
and dietary components leading to deficiency, poor nutritional status
and oxidative stress. Of particular significance is the malabsorption of
fat-soluble nutrients and antioxidants, which are important for normal
immune and neurological function. CF patients are often deficient in
these compounds despite supplementation with the current standard of
care therapy.
Objective: Compare the pharmacokinetic profile of this water-soluble
vitamin E formulation (Aqua-E) with an oil-based softgel formulation
in a malabsorbing patient population.
Design: Patients with CF who had documented malabsorption were
recruited for participation in this pharmacokinetic study. Patients that
met inclusion and exclusion criteria discontinued vitamin E supple-
mentation, except for that in a multivitamin, for 7 to 21 days prior to the
day of dosing. Patients were randomized to a single dose of 20 ml of
Aqua-E or 3 oil-based softgels which contained equivalent amounts of
tocopherols. Blood was drawn from patients at time 0, 2, 4, 8, 24, 48 and
168 hours and analyzed for tocopherols.
Results: Eight patients were enrolled in the study and randomized
to Aqua-E or softgels. The primary outcome, the absorption of g-
tocopherol in Aqua-E (AUC = 115 mg/ml*hrs), was significantly greater
than that of oil-based softgels (AUC = 27 mg/ml*hrs, p = 0.015). Total-
tocopherols (a + g + d) in Aqua-E (AUC = 294 mg/ml*hrs) showed
a strong trend toward increased absorption compared to that of oil-
based softgels (AUC = 117 mg/ml*hrs, p = 0.069).
555
Conclusion: This novel water-soluble formulation showed a marked
and statistically significant increase in absorption of g-tocopherol in
malabsorbing CF patients as compared to an oil-based formulation.
201
INCREASED INCIDENCE OF MATRIX
METALLOPROTEINASES IN THE URINE OF
PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Michael A. Manfredi1,4, David Zurakowski2, Thomas R. Walker1, Paul A.
Rufo1, Victor L. Fox1, Marsha A. Moses3,4. 1Gastroenterology and Nutrition,
Childrens Hospital Boston, Boston, MA; 2Surgery, Childrens Hospital
Boston, Boston, MA; 3Surgery, Harvard Medical School, Boston, MA; 4The
Vascular Biology Program, Childrens Hospital Boston, Boston, MA.
Matrix Metalloprotein (MMPs) are enzymes involved in the degradation
of extracellular matrix (ECM) and basement membrane proteins.
Dysregulated degradation of ECM is characteristic of a number of
pathologic conditions including cancer. It has been suggested that
MMPs may also play a role in the pathogenesis of Inflammatory Bowel
Disease (IBD) by mediating the mucosal breakdown in response to the
inflammatory cascade. We have previously demonstrated that urinary
MMPs are independent predictors of disease status in cancer patients.
We therefore hypothesized that urinary MMPs may also be markers of
disease activity in patients with IBD. In this study, we analyzed 56 urine
samples that were collected prospectively from 28 subjects with known
or suspected IBD who presented to the endoscopy unit for colonoscopic
evaluation. Urinary MMPs were analyzed in patients with IBD by
zymography and compared to 28 age, sex-matched controls. The
percentage of subjects with elevated urinary MMP levels differed
significantly (P , 0.0001) in patients with IBD and each IBD subgroup
(Crohns disease or Ulcerative Colitis) compared to controls. Multiple
logistic regression revealed that expression of MMP-2 (P = 0.005) and
MMP-9 NGAL (P , 0.0001) are significantly higher in patients with
IBD, independent of age and gender. Estimated odds of having IBD are
over 16 times higher for individuals who are positive for MMP-2 (odds
ratio = 16.8, lower 95% confidence interval (CI) = 2.4) and over 100
times higher in those positive for MMP-9 NGAL (odds ratio = 105.6,
lower 95% CI = 12.3). These data are the first demonstration that the
presence of urinary MMPs can predict disease status in patients with
IBD and may therefore represent novel non-invasive biomarkers of this
disease. [Supported by NIH/NIDDK T32 DK007477 (W.I. Lencer),
2PO1CA45548 (M. A. Moses)].
202
PRIMARY SCLEROSING CHOLANGITIS IN
CHILDHOOD IS ASSOCIATED WITH ABNORMALITIES
IN CYSTIC FIBROSIS-MEDIATED CHLORIDE
CHANNEL FUNCTION
Harpreet Pall1,2, Maureen M. Jonas1, Deborah A. Dasilva2, Kimberly
M. Potvin2, Steven D. Freedman2. 1Division of Gastroenterology,
Childrens Hospital Boston, Boston, MA; 2Division of Gastroenterol-
ogy, Beth Israel Deaconess Medical Center, Boston, MA.
Recent work by our group has shown an increased prevalence of CFTR
abnormalities in adults with primary sclerosing cholangitis (PSC).
Aim: To determine whether PSC in childhood is associated with
abnormalities in CFTR based on functional testing with nasal trans-
membrane potential difference (NTPD) and sweat chloride concentration.
Methods: 19 subjects with PSC diagnosed in childhood were recruited
to undergo NTPD testing. Inclusion criteria included age of onset of
PSC ,18 years and current age $12 years. Mean 6 SD in mV was
calculated for maximum baseline PD and following intranasal infusion
of amiloride and chloride free medium with isoproterenol. These data
were compared with healthy control reference ranges. All subjects had
sweat chloride concentration determined by quantitative pilocarpine
iontophoresis.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
556 NASPGHAN ANNUAL MEETING
Results: 14/19 subjects were male, and ages ranged from 1225 years.
17 subjects had IBD, and 4 had autoimmune hepatitis/PSC overlap
syndrome. Maximum baseline PD was normal at 226.5 6 7.0 (reference
range: 224 6 8). The response to inhibition of sodium uptake
(4Amiloride) was normal at 15.0 6 6.9 (reference range: 12 6 5).
CFTR chloride channel function (4Chloride free + isoproterenol) was
markedly diminished at 28.6 6 8.2 (reference range:221 6 9), and the
2 subjects without IBD had values of 213.3 and 212.8. Only six of the
nineteen subjects had NTPD results (4Chloride free + isoproterenol)
#212. Sweat tests were normal in 16 subjects and in 3 subjects values
were in the intermediate range (4060 mmol/L).
Conclusions: There is a high prevalence of CFTR-mediated ion
transport dysfunction in our subjects with PSC. Complete DNA
analyses for CFTR gene mutations is ongoing and will provide further
information. A matched group with IBD and no PSC is undergoing
identical testing to determine if CFTR dysfunction is linked to IBD
alone in childhood. (Supported by Thrasher Research Fund and GCRCs
at Childrens Hospital Boston and BIDMC).
203
GENE EXPRESSION PROFILES IN CHILDREN WITH
NEWLY DIAGNOSED CROHNS DISEASE
Alexandra Eidelwein1, Feng Wu2, Hannah Lee3, Shukti Chakravarti2,
Shyam Biswal3, Carmen Cuffari1, Maria Oliva-Hemker1. 1Pediatric
Gastroenterology, Johns Hopkins Univ. School of Medicine, Baltimore,
MD; 2Medicine, Johns Hopkins Univ. School of Medicine, Baltimore,
MD; 3Environmental Health Sciences, Bloomberg School of Public
Health, Baltimore, MD.
Introduction: Identification of novel genes involved in early Crohns
disease (CD) may lead to a better understanding of disease
pathogenesis. We evaluated gene expression profiles in colonic mucosa
of children with newly diagnosed CD.
Methods: Two colonic biopsies were obtained from patients (pts) with
GI symptoms undergoing colonoscopy. Total RNA was isolated from 5
pts with histopathologically confirmed moderate to severe CD and from
6 children with normal histology (controls). Pts had not been exposed to
any CD medications. RNA purification and amplification were
performed prior to microarray analysis using Affymetrix Human
Genome U133 Plus 2.0 Array,containing ~31,836 unique entries. Data
analysis for comparison between pts and controls using dChip Analyzer,
included signal difference $100, fold change $1.5, present call
.50%, t test, p value , 0.05.
Results: Mean ages of pts and controls were 14.2 y and 14.6 y. Mean
ESR was 42 mm/hr in pts and 3 mm/hr in controls. 66 genes were
differentially up-regulated in CD including lipocalin 2 (LCN2), S100
calcium binding protein, TGM2, CXCL2, CXCL3, IFITM, B-factor
properdin, dual oxidase 2 (DUOX2), SPINK4, SLC2A3, TIMP1,
NNMT, SDCCAG33, RIS1, COL6A3 with functions involved in
inflammation, immune response, metabolism, cell cycle regulation,
transcription, oncogenesis and remodeling. 27 genes, mainly involved
in metabolism and inflammation, were down-regulated in CD including
prostaglandin D2 receptor (PTGDR), SLC16A9, HSD17B2, APOBE-
C3A, SLC38A4, TRPM7, ZNF124, ATP-binding cassette B1 (MDR).
Conclusion: Microarray analysis of colonic biopsies from newly
diagnosed children with CD revealed multiple differentially expressed
genes. Examination of the gene patterns expressed in early CD may
provide useful information for improved disease characterization,
development of diagnostic markers and for future therapeutic targets.
204
CONTRIBUTION OF SUSCEPTIBILITY GENES TO
PEDIATRIC ONSET INFLAMMATORY BOWEL DISEASE
T. Walters1, M. Silverberg2, P. Sherman1, P. Lewinger2, Anne Griffiths1.
1
GI/Nutrition, Hospital for Sick Children, Toronto, ON, Canada;
2
GI/Nutrition, Mount Sinai Hospital, Toronto, ON, Canada.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Background/Aims: Heritability (relative contribution of genes vs
environment to disease pathogenesis) appears greater in early- versus
late-onset inflammatory bowel disease (IBD). We evaluated the contri-
bution and phenotypic correlations of confirmed (NOD2/CARD15) or
suggested (OCTN1 and OCTN2) susceptibility genes in a single center
population of patients diagnosed at age #17 years.
Methods: 380 probands with both familial and sporadic IBD (total
251 CD, 107 UC, indeterminate 22), their parents, and 42 affected sibs
were studied. Genotyping was performed for 5q31 (IBD5) locus
markers: IGR 2096, IGR 2198, IGR 2230, SLC22A5 (OCTN2), and
SLC22A4 (OCTN1) and the 3 risk alleles of CARD15 (R702W, G908R
and 1007fsinsC). Data were analyzed by transmission disequilibrium
testing using FBAT (family-based association test). North American
IBD Genetics Consortium definitions were used for phenotyping.
Results: 66% patients were non-Jewish Caucasian; 23% Jewish
Caucasian; 8% Asian. 24% of CD and 14% of UC probands had
affected first degree relative(s). UC was extensive in 77%, left-sided in
21%. CD macroscopically involved small bowel (sb) only (54%); sb and
colon (34%); colon only (14%). At most recent follow-up CD was
inflammatory (74%) stricturing (9%) and internal penetrating (17%).
18% had developed perianal fistula(e).
FBAT demonstrated no associations with pediatric onset UC. Very
strong association was evident between pediatric onset CD involving
small bowel and CARD15 1007 fsinsC (p = 0.000001). All IBD5
markers including OCTN gene polymorphisms demonstrated strong
association to CD (any location) in non-Jewish families. All IBD5
markers were in strong linkage disequilibrium with one another.
Conclusions: Of the three common CD-associated CARD15 poly-
morphisms, 1007 fsinsC most influences the early development of CD.
Markers of the IBD5 risk haplotype are associated with early onset CD,
but linkage disequilibrium precludes definitive acceptance of OCTN as
the IBD gene within this locus.
205
GROWTH HORMONE IN PEDIATRIC
CROHNS DISEASE
Melvin B. Heyman, Elizabeth Garnett, Janet M. Wojcicki, Selna
Kaplan. Pediatrics, University of California, San Francisco, CA.
Background: Poor growth is reported in 40% of pediatric patients with
Crohns disease (CD) resulting in short stature as adults. We determined
clinical efficacy of human growth hormone (GH) in pediatric CD
patients with growth failure 6 steroid dependency.
Methods: 6 boys and 4 girls (mean age 12.6 6 4.5 [SD] [range 4.8
19.6] yrs) with unfused growth plates were enrolled; 4 were pre-
pubescent. In addition to their individual therapies, all patients received
open label GH 0.043 mg/kg/day SQ injection for one year. Assessments
made at baseline, 2, 4, and 8 weeks, 3, 6, 9 and 12 months. Data were
analyzed by paired t-tests and analysis of variance for repeated
measures using STATA 7.0.
Results: Mean growth velocity increased from 2.68 6 1.47 [range 0.7
4.6] cm/yr at baseline to 8.52 6 4.80 [range 2.417.4] at 6 months and
8.06 6 3.75 [1.914.3] cm/yr at 1 year of GH (p = 0.004). Height Z
scores increased by 0.79 6 0.47 (p = 0.002); weight Z scores increased
by 0.57 6 0.56 (p = 0.02). DXA scans at 1 yr revealed mean increase
lumbar spine T scores of 0.61 6 0.39 (p , 0.001) above baseline.
Percent body fat (by DXA scan) decreased in 8 patients, while mean
BMI increased in all patients (p = 0.02), suggesting increased lean body
mass. Serum alkaline phosphatase levels correspondingly increased in
all subjects (p = 0.004). Levels of IGF-1 (p = 0.002) and IGF-BP3 (p =
0.007) increased. Of the 5 patients taking prednisone at the start of the
study, 4 were completely weaned within the first month of treatment and
did not require further prednisone during the year of GH. The Pediatric
Crohns Disease Activity Index (PCDAI) varied throughout the study
period in all subjects.
Conclusion: GH is beneficial in pediatric Crohns disease patients
exhibiting poor growth and poor bone mineralization. Further studies
are needed to determine the ideal timing and combination of therapies
 NASPGHAN ANNUAL MEETING
for pediatric Crohns patients exhibiting poor growth and the role for
GH as a primary therapy for children and adolescents with CD.
Supported in part by NIH grants DK 060617, DK 007762, and
M01RR01271 and by the Genentech Center for Clinical Research in
Endocrinology.
ORAL ABSTRACT PRESENTATIONS
SATURDAY, OCTOBER 22, 2005
2:00 PM 3:30 PM
Mucosal Immunity
206
EARLY EFFECTS OF GLIADIN ON HUMAN INTESTINAL
MUCOSA AND INTESTINAL CELL LINES
Maria Grazia. Clemente1, Sandro Drago1,2, Ramzi El. Asmar1,6, Maria
Rosaria Di. Pierro1,2, Anna Sapone1, Manjiusha Thakar1, Giuseppe
Iacono3, Antonio Carroccio3, Cinzia DAgate4, Tarcisio Not5, Lucia
Zampini6, Carlo Catassi1,6, Alessio Fasano1. 1Pediatrics, University of
Maryland, Baltimore, MD; 2Bionat Italia S.r.l., Palermo, Italy;
3 activated by acetylcholine (1 uM).
Clinica Medica University of Palermo, Palermo, Italy; 4Policlinico-
University of Catania, Catania, Italy; 5IRCCS Burlo Garofolo Trieste,
Trieste, Italy; 6Dipartimento Scienze Materno-Infantile, University
Politecnico delle Marche, Ancona, Italy.
Background & Aims: The mechanism(s) of interaction of gliadin with
intestinal epithelial cells are still largely unknown. Based on our recent
discovery of zonulin, a modulator of intestinal tight junctions, and its up-
regulation in celiac disease, we elected to establish whether gliadin has
any immediate effect on the zonulin pathway.
Methods: Both ex vivo human small intestines and intestinal cell
monolayers were exposed to gliadin, and zonulin release and changes in
paracellular permeability were monitored in the presence and absence
of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement,
and zonula occludens-1 re-distribution were evaluated by immunoflu-
orescence microscopy.
Results: Zonulin receptor positive IEC6 and Caco 2 cells exposed to
gliadin released zonulin with subsequent zonulin binding to the cell
surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1
protein-protein interaction, and increased monolayer permeability.
Pretreatment with the zonulin antagonist FZI/0 blocked these changes.
When exposed to luminal gliadin, intestinal biopsies from celiac
patients in remission expressed a sustained luminal zonulin release and
increase in intestinal permeability that was blocked by FZI/0 pre-
treatment. Conversely, biopsies from non-celiac patients demonstrated
a limited, transient zonulin release which was paralleled by a reduction
in intestinal TEER that never reached the level of permeability seen in
CD tissues. Chronic gliadin exposure caused a down-regulation of both
ZO-1 and occludin gene expression.
Conclusions: Gliadin activates the zonulin system irrespective of the
genetic predisposition to autoimmunity, leading to increased intestinal
permeability to macromolecules.
207
FUNCTIONAL EXPRESSION OF THE
EXTRACELLULAR CALCIUM-SENSING RECEPTOR
(CAR) ON AN ESOPHAGEAL EPITHELIAL CELL LINE
(HET-1A) AND IN HUMAN ESOPHAGUS
Christopher Justinich1,2, N. Mak2, D. A. Kalafus2, C. Wells2, M.
Blenerhassett3,2, R. J. MacLeod3,2. 1Pediatrics, Queens University,
Kingston, ON, Canada; 2GI Diseases Research Unit, Queens
University, Kingston, ON, Canada; 3Physiology, Queens University,
Kingston, ON, Canada.
557
Background: Human esophageal epithelial cells are regularly exposed
to luminal contents and acid. The mechanisms that protect esophageal
epithelium from this noxious environment are unknown. In other areas
of the gastrointestinal tract CaR helps maintain epithelial homeostasis.
The CaR is a G-protein coupled receptor that is activated by calcium
and polyamines. This study was designed to determine the location and
functional significance of CaR in the esophagus.
Methods: CaR fluorescent immunostaining was performed on formalin
fixed esophagus. Calcium and other CaR agonists were used to
stimulate HET-1A cells, with IL-8 measured by ELISA. Calcium
imaging was performed by loading HET-1A with Fluor 4 and measuring
changes in fluorescence with CaR activation. Interfering RNA against
the CaR was used to antagonize the effects of the CaR.
Results: CaR immunoreactivity was robust in the esophageal basal layer
and diminished in the non-replicating cells of the differentiated surface
layer. CaR expression was confirmed in HET-1A cells by RT-PCR and
immunocytochemistry. Extracellular Ca2+ stimulated secretion of the
multifunctional cytokine IL-8 from HET-1A cells in a dose dependent
manner (EC50~2.3 mM). Other CaR agonists including Mg2+ (20 mM),
and spermine (110 mM) stimulated IL-8 secretion. Extracellular Ca2+
and spermine caused Ca2+ mobilization using Fluo-4 microspectro-
flurometry. HET-1A cells transiently transfected with siRNA directed
against CaR did not exhibit Ca2+-stimulated increases in IL-8 secretion
and intracellular Ca2+ release but demonstrated these responses when
Conclusion: The CaR is present on basal cells of the human esophagus
and in HET-1A cells. Activation of the CaR on these cells mobilizes Ca2+
and leads to cytokine secretion. CaR is a new marker for basal esophageal
cells and may play a protective role in esophageal homeostasis.
208
THE FC-RECEPTOR NEONATAL (FCRN) TRAFFICS
THROUGH THE COMMON ENDOSOME IN MUCOSAL
EPITHELIAL CELLS
Elizabeth H. Yen1, M. Kothe1, J. Wagner1, W. I. Lencer2,1. 1Childrens
Hospital, Boston, MA; 2Harvard Medical School, Boston, MA.
FcRn binds and traffics IgG bidirectionally across mucosal epithelial
barriers where it acts in immune surveillance. The mechanism(s) of
transport across polarized epithelial cells are unknown. Here, we
describe a GFP tagged FcRn model in MDCK-II cells that faithfully
reproduces FcRn function in IgG transport. We examine the in-
tracellular pathway of FcRn transport at steady state and in living cells.
Methods: HA tagged human FcRn fused to GFP was transfected into
MDCK cells stably expressing human b2microglobulin. Cell surface
expression was measured by selective cell surface biotinylation. IgG
transport was measured using recombinant human IgG1 specific for the
hapten NIP and assayed by ELISA. Immunofluorescence and live cell
imaging was performed on polarized MDCK cells using spinning disc
confocal microscopy.
Results: Polarized MDCK cells stably expressing FcRn-GFP exhibit
basolateral polarity of FcRn at the cell surface, identical to that found
for wild type FcRn. The FcRn-GFP clones transport human NIP-IgG
bidirectionally across the monolayer with the same efficiency as MDCK
cells expressing wild type FcRn. Competition with excess rabbit IgG
blocks NIP-IgG transport in both directions (8095%), showing that
IgG transport is specific for FcRn. In fixed cells, the bulk of FcRn-GFP
is located in intracellular vesicles and almost fully colocalizes with the
transferrin receptor. FcRn-GFP does not colocalize with LAMP-1a. In
living cells, FcRn localizes to mobile vesicles near the apical membrane
and in the basolateral cytoplasm. The FcRn-vesicles are strictly sorted
away from the lysosomal compartment labeled with LysoTracker Red.
Conclusion: These results define an epithelial cell line for visualizing
FcRn trafficking in real time. The cell line reproduces the physiology of
FcRn-dependent IgG transport at mucosal surfaces. We find that
FcRn traffics through the common endosome, and strictly avoids the
late endosome/lysosome. These results are consistent with results from
non-polarized cells and with the proposed biology of FcRn function.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
558 NASPGHAN ANNUAL MEETING
209
EFFECT OF GLUTEN-CONTAINING DIET ON SERUM
ZONULIN AND INTESTINAL PERMEABILITY IN TYPE 1
DIABETES CHILDREN AND THEIR RELATIVES
Anna Sapone1, Debra Counts2, Deborah Kryszak1, Teresa Palese2,
Carlo Catassi3,1, Lucia Zampini3, Yves Nordmann2, Giovanni Valen-
tino Coppa3, Alessio Fasano1. 1Mucosal Biology Research Center,
University of Maryland, Baltimore, MD; 2Pediatrics, University of
Maryland, Baltimore, MD; 3Dipartimento Scienze-Materno Infantile,
Universita Politecnico Delle Marche, Ancona, Italy.
The trigger of the autoimmune destruction of pancreatic beta cells in
Type 1 diabetes (T1D) is unclear. One theory is that antigens absorbed
through the gut may be involved. A gut protein, zonulin, opens tight
junctions and allows paracellular absorption of macromolecules. We
have shown that zonulin is increased in the serum of a subset of patients
with T1D and their first degree relatives. To determine if dysregulation
of the zonulin pathway is involved in the pathogenesis of T1D, we have
measured serum zonulin levels and intestinal permeability (IP) before
and after a gluten containing meal in both T1D children (=17) and in
their relatives (=56). Zonulin serum levels were measured by sandwich
ELISA, IP was determined by measurement of both serum and urine
contents of both lactulose and mannitol following their oral adminis-
tration. We found an increase in serum zonulin (53%) and IP (47%) in
T1D subjects compared to controls (4% and 0%, respectively), and
a significant relationship between elevation of zonulin and increased IP
(p = 0.026). All subjects had elevation of zonulin at baseline and post-
meal,and all had a further IP increase 1-hour post-meal that was
statistically higher in T1D subjects (5.6 fold) than their relatives (2.7
fold, p , 0.01). There was no relationship between serum glucose and
zonulin levels. In conclusion, serum zonulin levels correlate with
increased IP in children with T1D and their first degree relatives. Our
data suggest that increased serum zonulin is is indicative of abnormal
gut permeability that can be exacerbated by gluten ingestion in children
with T1D. Based on our animal studies, we postulate a temporal rela-
tionship between increased serum zonulin and the development of T1D.
210
CELL PROLIFERATION RATES IN EOSINOPHILIC
ESOPHAGEAL DISORDERS
Swati B. Gadewar1, Karoly Horvath2. 1Pediatric Gastroenterology,
University of Maryland, Baltimore, MD; 2Pediatric Gastroenterology,
Alfred I. duPont Hospital for Children, Wilmington, DE.
Eosinophilic inflammation in the esophagus is associated with reflux
esophagitis (RE), eosinophilic gastroenteritis (EGE) and eosinophilic
esophagitis (EE). Eosinophilic esophagitis (EE) is a new entity
characterized by characteristic endoscopic and histological findings. It
is not known if EE represents a part of the spectrum of EGE or if it is
a separate entity with different pathogenesis. To date, no absolute
diagnostic criteria for EE exist. In publications the number of
eosinophils/HPF varies (.5, others .20).
Aim: To compare eosinophils and cell proliferation rate in the
esophageal biopsies in the 3 diseases by using Ki67 monoclonal
antibody. Ki67 is a protein, which is vital for cell proliferation, localized
in the nucleus and is a marker of cell mitosis.
Methods: Esophageal biopsies of patients with RE (n = 11), EE (n =
16), EGE (n = 11) and normal controls (n = 8) were included in the
study. Biopsy slides were stained with Ki67 monoclonal antibody. The
number of Ki67 positive cell was counted per high power field (40X).
Digital pictures were taken. Two investigators independently counted
the cell numbers
Results: Inter-observer variance was not significant in the various
counting (p = 0.110.22). One SD value for the number of eosinophils
in patients with EE was 14 cells/HPF. The Table below shows the
numbers (mean 6 SEM) and the results of statistical analysis.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
Conclusions: The cell proliferation rate (Ki67 activity) in the
esophagus was significantly higher in patients with EE compared to
patients with EGE (p = 0.022), RE and control patients. This may
suggest that EE is separate disease entity and not part of the spectrum of
EGE. The importance and long-term consequence of the increased
proliferation rate warrants further investigation.
TABLE 1. Results of statistical analysis
RE EGE EE Controls
Eos/HPF 060 15.6 6 5.4 37.4 6 5.8* 060
Ki67+/HPF 29.3 6 7.25 45.6 6 11.2 78.7 6 10.5* 25.6 6 4.5#
p values: *EGE vs. EE = 0.02; #EE vs. RE = 0.0008.
211
INHIBITION OF ZONULIN-MEDIATED
INCREASED INTESTINAL PERMEABILITY BLOCKS
PROGRESSION FROM PRE-CLINICAL AUTOIMMUNITY
TO TYPE 1 DIABETES IN BB/WOR RATS
Anna Sapone1, Klara Margaretten1, Barbara Whalen3, Dennis
Guberski , Blake Paterson2, Alessio Fasano1. 1Mucosal Biology Research
3
Center, University of Maryland, Baltimore, MD; 2Alba Therapeutics,
Baltimore, MD; 3Biomedical Research Models Inc., Worcester, MA.
We have recently reported the causal role of zonulin, a protein involved in
intestinal permeability modulation, in the pathogenesis of Type 1 diabetes
(T1D) in BB/Wor diabetic prone (BBDP) rats. To determine whether oral
zonulin inhibition can preserve functional and anatomic beta cell
integrity, BBDP rats were studied after seroconversion (age 5254 days).
Animals were randomized to orally receive either placebo or treatment
with the zonulin inhibitor AT1001. At the disease endpoint (fasting blood
glucose .250 mg/dl), BBDP rats that developed T1D were euthanized
and blood and tissue samples collected. AT1001-treated rats that did not
develop T1D were re-randomized at age 120 days in two groups: a) drug
withdrawal arm and b) continued treatment with AT1001; they were
followed for 100 additional days. Serum zonulin, autoantibodies, and
glucose levels were monitored throughout the study. Insulitis was blindly
evaluated by two investigators. AT1001 treatment reduced the cumulative
incidence of T1D by 45%. None of the animals that continued AT1001
treatment developed T1D, while 33% of those in which AT1001 was
withdrawn developed T1D. AT1001 treatment did not affect serum zonulin
levels. Conversely, autoantibodies were reduced in AT1001-treated rats that
did not develop T1D as compared to untreated animals that developed the
disease. Histological analysis of the pancreas revealed classic signs of active
or end-stage insulitis in untreated rats that developed T1D. Conversely,
AT1001-treated animals showed evidence of perivascular inflammation
without insulitis and a process of repair and regeneration. Beta cell preserva-
tion was confirmed by specific staining showing presence of a normal
number of beta cells in AT1001-treated animals as compared to few residual
cells in untreated rats that developed T1D. Based on these results, we
conclude that zonulin inhibition prevents autoimmune beta cell destruction.
MEDICAL STUDENT AND PEDIATRIC
RESIDENT ABSTRACT PRESENTATIONS
SATURDAY, OCTOBER 22, 2005
3:45 PM 5:45 PM
212
INTESTINAL MUCIN GENE MODULATION IN VIVO USING
ORALLY ADMINISTERED PROBIOTIC BACTERIA
Natalie S. Godwin, Lucie Hyde, David R. Mack. Childrens Hospital of
Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON,
Canada.
 NASPGHAN ANNUAL MEETING
Cell culture studies demonstrate innate protective mechanisms of
intestinal epithelial cells, such as modulation of mucin gene expression,
may be regulated by selective probiotic bacteria. Mucins are large
complex glycoproteins that can bind enteric pathogens to limit their
access to the intestinal mucosa. The mucin genes responsible for the
majority of mucin secretion are MUC2 and MUC3 in the large and
small intestine, respectively. In this study we investigated if rats fed
probiotic organisms increased mucin expression in a regional and time-
specific manner within the intestinal tract. Lactobacillus rhamnosus
R0011 or Bifidobacterium bifidum R0071 were added to the water of
Sprague-Dawley rats on a daily basis and either 107 or 109 CFU/day
were ingested. Following 2, 5 and 10 day administrations, animals were
sacrified and intestinal segments were excised for RNA isolation and
histology. rMUC2 and rMUC3 mRNA were analyzed via Taqman RT-
PCR, and protein levels were confirmed by using immunohistochemical
analysis with an antibody to the C-terminus region of rMUC3. Results
show that with the administration of B. bifidum, rMUC3 expression in
jejunum was greater after 2 days (204 6 42% control, mean 6 SE)
when compared to jejunal expression levels at 10 days (72 6 17%
control, p , 0.05). By 10 days, rMUC3 expression was similar to
baseline levels (p . 0.05). Similar results were found in ileal segments.
Rats fed probiotics had similar rMUC2 expression in colonic segments
(1.08 6 0.12% control, p . 0.05) as control animals not receiving
probiotics. Results were similar with L. rhamnosus administration. No
concentration dependent alteration in rMUC3 gene expression was
demonstrated. Inmmunohistochemical staining of jejunal segments
showed a direct correlation between mucin gene expression and mucin
protein expression in response to the administration of B. bifidum.
Orally administered probiotics demonstrate site specific and time-
dependent effects on mucin expression and may offer an inducible
means of protection for the intestinal tract.
213
POLYETHYLENE GLYCOL (PEG 3350) CLEANING
PROTOCOL FOR COLONOSCOPY IN CHILDREN- A
WEEKEND ORDEAL?
Shaista Safder, Yoram Elitsur. Pediatrics, Gastroenterology Division,
Marshall University, Huntington, WV.
Background: Inadequate colon preparation is a significant obstacle in
performing colonoscopy, and is directly related to poor patient
compliance. Recently, a lavage solution (PEG 3350, Miralax) was
found adequate for colon preparation in children (J Pediatr 2004).
Objective: (1) To assess Miralax solution for colon preparation in
children over an extended weekend. (2) Assess the value of clinical
markers to predict adequate colon cleaning.
Methods: In a prospective study, children scheduled for colonoscopy
were prepared with Miralax solution (1.5 gms/kg/day, ,100 g/day) for
4 days with no adjunct medications or enemas. Patients completed a
questionnaire which included demographic data, amount (g) consumed,
#stools/day, stool consistency, and side effects. Colon preparation
was assessed immediately after colonoscopy procedure using a stan-
dard colon assessment: Grade 1: poor, Grade 2: fair, Grade 35:
adequate/ excellent (Gastrointest Endo 2002).
Results: 99 children were included in the study with a mean age of
11.9 yrs. Side effects were seen in 31 children (29 abdominal pain,
4-vomiting). Seven children were excluded for protocol deviation.
Colon preparation was found to be adequate to excellent (grade35) in
72 (84%) children, and poor to fair (grade12) in 15 (16%) children.
Liquid stool consistency on days 3 & 4 was significantly associated
with adequate (grade .3) colon preparation (p , 0.012: Sen-96%,
PPV-87%). Average stool number above 5 per day within the last two
days was significantly associated with adequate (grade .3) colon prep-
aration (p , 0.038, Sen-60%, PPV-92%).
Conclusion: 1. Liquid stool consistency and number of stools
averaging over 5 per day, in the last 2 days of preparation, are good
markers for adequate colon preparation in children undergoing
559
colonoscopy. 2. These markers may predict colon preparation prior to
procedure and may reduce incomplete colonoscopy in children. 3.
Weekend colon preparation with Miralax is safe and has excellent
compliance in children undergoing colonoscopy procedure.
214
INCIDENCE OF EOSINOPHILIC
ESOPHAGITIS IN BIOPSIED PATIENTS:
A RETROSPECTIVE REVIEW
Joyce Lee, Susan Baker, Robert Baker. Pediatrics, State University of
New York, Buffalo, NY.
Introduction: Although widespread epidemiological data for eosino-
philic esophagitis (EOE) has yet to be established, numerous reports
indicate an apparent rise in the incidence of EOE in recent years. This
study was undertaken to 1) establish the incidence of EOE in biopsied
patients in Western New York during two distinct periods and 2)
determine if there exists an increase in the incidence of EOE between
these two periods.
Methods: We retrospectively evaluated all esophageal biopsies
obtained at the Women and Childrens Hospital of Buffalo, New York
during the periods 198088 and 200102. A consistent group of
reviewers examined each specimen to diagnose EOE, gastroesophageal
reflux disease (GERD), or other esophageal disease based upon
a defined set of histologic criteria.
Results: In total, 1,049 esophageal biopsies from 527 patients were
reviewed. Between 198088, 257 biopsies from 204 patients were
evaluated. Of these, 5 patients met the criteria for EOE, 43 for GERD,
53 for other esophageal disease, and 103 were within normal limits.
Between 200102, 792 biopsies from 323 patients were evaluated. Of
these, 11 patients met the criteria for EOE, 121 for GERD, 43 for other
esophageal disease, and 148 were within normal limits. No statistically
significant change in the incidence of EOE was observed between groups
(chi-square = 0.6647, p = 0.4149). A statistically significant increase in
the incidence of GERD was observed from 198088 to 200102 (chi-
square = 15.0337, p = 0.0001).
Conclusions: This study describes trends in esophageal disease within
the select geographic area of Western New York over a 23 year period.
This study failed to demonstrate a change in the incidence of EOE
across the study period. Any apparent increase in the incidence of EOE
in recent years may be due in part to increased disease awareness and
diagnostic accuracy rather than to a true increase in disease incidence.
This study further shows an increase in the incidence of histologic
GERD across the study period. This is an unexpected finding that
warrants further investigation.
215
SEROLOGICAL ANALYSES OF UNAFFECTED
PRESUMED GENE CARRIERS OF CELIAC DISEASE
Adam Traintor1, Christopher Hull1, Susan Neuhausen2, Linda Book1,
John Zone1. 1Pediatrics, University of Utah, Salt Lake City, UT;
2
University of California Irvine, Irvine, CA.
Celiac disease (CD) is known to be familial but its inheritance pattern is
not fully understood. Serologic tests are used to identify at risk individuals
in CD families. We defined presumed gene carriers for celiac disease as
individuals testing negative for IgA endomysial antibody, who have both
a CD affected parent, sibling or cousin and a CD affected child. We
hypothesized that presumed CD gene carriers would have unique
serological profiles.
Methods: We measured and compared IgG and IgA tissue trans-
glutaminase (tTG), endomysial antibody (EMA) antigliadin antibody
(GA) and total serum IgA in presumed gene carriers, HLA DQ2+ organ
donors, and Red Cross blood donors.
Results: There were no significant differences in EMA, GA, or IgA tTG
levels in controls and presumed carriers. Presumed gene carriers had
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
560 NASPGHAN ANNUAL MEETING

significantly elevated total serum IgA levels compared to DQ2 and blood Conclusions:
donor controls (Table 1). The levels of IgG tTG were also significantly 1. More than one-half of patients with pediatric ulcerative colitis
above those of the controls (Table 2). present with moderate-severe disease.
Conclusion: Higher total serum IgA levels in CD family members who 2. Mesalamine monotherapy can be considered for steroid-free in-
are presumed gene carriers could be an indication of an accelerated duction in the majority of newly diagnosed pediatric UC patients
mucosal immune response. The increased IgG tTG levels, indicates including those who present with moderate-severe disease.
a slight tendency towards an immune response to transglutaminase 3. The presence of anemia, elevated sedimentation rate and pancolitis
antigen. However, the data clearly indicate that no test is clinically may have influenced the use of steroids more than clinical
useful in differentiating presumed gene carriers from controls and there characteristics or PGA.
does not appear to be a unique serologic pattern differentiating the 4. Large, prospective studies are needed to validate these findings.
presumed gene carrier family member.
TABLE 1. Serum IgA levels (mg/dL) 217
Presumed HLA DQ2 Red cross 3D MODEL TO DETERMINE PARAMETERS FOR
gene carriers positive blood donors PERFORMING PERCUTANEOUS LIVER
BIOPSIES IN CHILDREN
Sample size 40 38 43 David Petersen, J. Antonio. Quiros, James Marcin, Sandra Gorges,
Median 268 102 100 Richard Quan. Dept. of Pediatrics, UD Davis Childrens Hospital,
SD 312 102 172 Sacramento, CA.
p values (compared to presumed p , 0.001 p = 0.0015
gene carriers)
Background: Percutaneous needle biopsy (PLB) is routinely used to
aid the diagnosis of liver disease in children. The size of the biopsy
specimen is important to ensure an accurate diagnosis. A model to test
TABLE 2. IgG tTG levels safety parameters for PLB in children has not been developed.
Methods: Abdominal CT scans performed in children were analyzed
Presumed gene HLA DQ2 Red cross and 3D reconstructions of the liver and surrounding structures were
carriers positive blood donors created. Coronal and transverse cross sectional images were modified to
Sample size 40 38 43 create two oblique images. The intersection of these planes created
Median 5 4 5 a line from the 9th intercostal space at the midaxillary line, toward the
SD 7.5 6.3 12.3 xyphoid process. We hypothesized that the ideal distance for a blind
p values (compare to presumed p , 0.001 p = 0.0402 percutaneous liver biopsy that maximizes the specimen size and
gene carriers) minimizes inadvertent injury could be determined from the CT images.
Measurements 30 degrees off the transverse and coronal axis were taken
to control for procedural variations.
Results: A total of 70 abdominal CT scans were analyzed in children
216 118 years of age. Six measurements were performed in each model
ROLE OF MESALAMINE MONOTHERAPY reconstruction, 3 in the transverse and 3 in the coronal axis. Data was
IN THE INDUCTION OF REMISSION OF PEDIATRIC segregated by age groups and stratified by weight (see Table).
ULCERATIVE COLITIS Additionally, through the anatomical models developed, we determined
Uma Phatak1, Nader N. Youssef1,2, Joel R. Rosh1,2. 1Pediatric what extra-hepatic structures are at risk of injury from PLB in patients
Gastroenterology, Atlantic Health System, Morristown, NJ; 2Pediat- of varying size, ages and anatomies. Discussion: This pilot study shows
rics, UMDNew Jersey Medical School, Newark, NJ. it is possible to develop standards for liver biopsy in children .1y of
age. Data collected from this study could help in developing prospective
trials and improve the diagnostic quality of PLB.
Background: Mesalamine is indicated for the treatment of mild-
moderately active ulcerative colitis (UC) and is often started in
moderate-severe disease once remission is achieved with cortico- Mean distance SD P value
steroids.
Aim: To determine whether pediatric patients presenting with Age ,3 y 10.5 60.8 ,0.01
moderate-severely active UC can successfully be put into remission Age 3-8 y 11.7 60.8 ,0.01
with mesalamine monotherapy. Age .8 y 13.6 61.4 ,0.01
Methods: A retrospective chart review of all pediatric patients with Weight ,20 kg 9.9 60.9 ,0.01
non-fulminate UC managed through induction at a regional pediatric Weight .20 kg 12.0 61.4 ,0.01
IBD center. Induction was defined as resolution of rectal bleeding.
Presentation was classified as mild, moderate or severe using ACG
guidelines and physician global assessment (PGA). Clinical, laboratory
and endoscopic findings were recorded for patients induced only with 218
mesalamine (MES) and those given steroids (STER).
Results: A total of 73 pediatric UC patients were studied. 47 (64.4%) DIGITAL RECTAL EXAMINATION FOR
achieved remission with MES alone (average age = 10.03 years; range CONSTIPATION: A LOST ART?
1.515.5 years; 24 male) compared to 26 given STER (average age = Shaista Safder, Mary Rewalt, Yoram Elitsur. Pediatrics, Gastroenter-
11.8 years; range 2.517.5 years; 14 female). Mean MES dose was ology Division, Marshall University, Huntington, WV.
53.3 mg/kg/day (range 22108 mg/kg/day). Of the total 73 patients,
53% had an initial PGA of moderate or severe: 18 MES (24.1%) v. 21 Background: Constipation is the most common disease referred to the
(28.8%) STER p = ns. Pancolitis was present in 65% of all patients: pediatric gastroenterology clinic, reaching up to 30% of all clinic
MES 25 (35.2%) v. 22 STER (30.1%) p = ns. Mean sedimentation rate referrals. The limited number of pediatric gastroenterologists in WV
was higher in STER (34.2; range 690) than MES (14.6; range 151) may limit the access of patients to this specialty. The new patient
p , 0.05. Hemoglobin at presentation ,10.0 g/dl was seen in 4 (8.5%) backlog and the rural nature of the State put a significant medical and
MES v. 7 (27%) STER p = 0.08. travel burden on the patients families. Digital rectal examination is the

J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005

 NASPGHAN ANNUAL MEETING
sole direct examination which can assess constipation and its
complications.
Objective: To investigate the frequency of rectal examination
performed in children referred to the pediatric GI clinic for constipation,
encopresis, and/or rectal bleeding.
Methods: All children referred to the GI clinic for those diagnoses
were evaluated for: demographics, diagnosis at referral, performance
of digital exam by the primary care physician (PCP), previous ther-
apy, digital exam findings by the specialist, and final diagnosis and
treatment.
Results: 94 children were included in this study. The mean age was 7.5 yrs
with a M/F ratio of 1:0.6. The median round trip traveling time for
patients was 2.66 hrs. The diagnosis at referral was constipation/encop-
resis in 82%, rectal bleeding in 13% and other in 5%. Rectal exam by
PCP prior to referral was performed only in 16% children vs. 96% by
the specialist (p , 0.000). Rectal exam by the specialist revealed the
following diagnoses: fecal impaction in 19%, anal fissure in 21%, hard
stool in 11%, empty ampulla in 15%, hemorrhoids in 4%, and anterior
anal displacement in 2%. Laxative treatment was given by the PCP in 64
(69%) pts., and rectal enema in 29 (31%) pts. Lavage solution treatment
(PEG 3350) was prescribed in only 29 (31%) children.
Conclusion: Digital rectal examination in children with constipation is
under performed by PCPs. This practice may cause misdiagnosis and
unjustified referral resulting in a high medical expense and long travel
time for the patient. We postulate that an educational campaign for PCP
on the diagnosis and treatment of constipation in children will improve
the patient#s standard of care and decrease unnecessary referrals.
219
DIFFUSE ESOPHAGEAL SPASM IN CHILDREN
John M. Rosen, Teri Lavenbarg, Jose Cocjin, Paul E. Hyman.
Pediatrics, University of Kansas Medical Center, Kansas City, KS.
Diffuse esophageal spasm (DES) causes chest pain and/or dysphagia in
adults but is rarely reported in children. We defined DES as
simultaneous contractions associated with .10% of swallows and
mean simultaneous contraction amplitude .30 mmHg (Castell, 2004).
We reviewed charts of 278 subjects 018 years of age after esophageal
manometry. Results included normal motility 61%, nonspecific
esophageal motility disorder 20%, DES 13% (n = 36), and achalasia
4%. Of 24 subjects ,5 years, chief complaints were food refusal (14),
vomiting (3), choking (3), retching (1), and no symptoms (3). Of 12
subjects .5 years, chief complaints were chest pain (4), dysphagia (3),
vomiting (2), food refusal (2), and retching (1). Food refusal was more
common in infants and toddlers than in children and teens (p , 0.05).
Esophageal manometry was the only motility test in 14 subjects; 22
subjects were evaluated with antroduodenal (15) or colonic manometry
(3) or both (4). Of these 22 subjects, 9 were diagnosed with DES only,
and 13 were diagnosed with generalized motility disorders. Prior to
manometry, 25 subjects (69%) had surgery for symptoms: 20 gastro-
stomies, 13 fundoplications, 3 pyloroplasties, 1 Collis gastroplasty, and
1 gastrojejunostomy. Comorbid medical conditions, often multiple,
were found in 33 subjects: idiopathic developmental delay (7), heart
malformation (7), Downs Syndrome (6), cerebral palsy (4), seizures (2),
and neuropathic pseudoobstruction (2). Mitochondrial myopathy,
chromosome 3p25 deletion, chromosome X q26-28 duplication, mixed
connective tissue disease, holoprosencephaly, Rett Syndrome, Charcot-
Marie-Tooth disease, Ehlers-Danlos Syndrome, Hirschsprungs disease,
and celiac disease were each found in one subject. Follow up treatment
modalities and effects were variable. We conclude that DES in infants and
children is not rare. DES should be considered when children present with
food refusal, dysphagia, chest pain, or unexplained vomiting. DES in
infants and children rarely presents without comorbidity. We speculate
that early diagnosis and treatment may prevent unnecessary surgery in
some cases.
561
APGNN Abstracts
Presented During Poster Session II,
Friday, October 21, 2005
220
PEDIATRIC CROHNS DISEASE: THE ASSOCIATION
OF NOD2/CARD15 GENOTYPE, GROWTH DELAY
AND BONE DISEASE
L. Hurd, D. Jacobstein, J. Markowitz, P. Mamula, I. Ahmad, E.
Maksimak, R. Baldassano. The Childrens Hospital of Philadelphia,
Philadelphia, PA.
Strong evidence suggests that genetic factors play a role in the
development of Crohns disease (CD). The recently discovered
susceptibility gene, NOD2/CARD15, has been associated with the
pathogenesis of CD and the disorders diverse clinical manifestations.
Growth delay is a prominent feature of pediatric CD. NOD2/CARD15
variants may affect the nutritional condition and growth of children.
Among the most important aspects of pediatric CD are bone growth,
bone density, and the predisposition to osteoporosis in adulthood.
Aims: The aims of this study were to define the relationship between
NOD2/CARD15 variants, growth delay and bone disease in children by
analyzing genotype/phenotype relations, and to determine the clinical
significance of NOD2/CARD15 variants.
Methods: Phenotypic information and NOD/CARD15 test results were
collected from 98 children with CD. The associations between the
presence of NOD2/CARD15 mutations (G908R, R702W, or 1007fs)
and the following parameters were analyzed: disease location, height,
weight, and bone density.
Results: NOD2/CARD15 variants were found in 33 of 98 (34%)
patients. A trend for ileal disease was observed in children carrying
a NOD2/CARD15 mutation (P = 0.085). Furthermore, there was
a tendency for NOD2/CARD15-variant positive patients to possess
lower weight z-scores at disease onset (20.61 versus 20.33, P = 0.28)
as well as lower bone density z-scores (21.90 versus 21.34, P = 0.19),
although data did not attain statistical significance. No difference was
found in the mean height z scores at disease onset in patients with
and without a NOD2/CARD15 variant (2.48 and 20.42, respectively,
P = 0.79).
Conclusions: In this study of genotype/phenotype correlation in
pediatric CD patients, data suggests that NOD2/CARD15 mutations
may indirectly impact patients bone density and weight. A potential
mechanism by which polymorphisms may affect these patterns is
through the ileal disease phenotype. Therefore, NOD2/CARD15 testing
may be a useful tool in predicting disease course and in developing new
and improved preventive and therapeutic paradigms. However, further
examination is required to make a sound conclusion regarding the
pathogenesis of growth delay and susceptibility for bone dis-
ease. (Supported by a generous grant from the Heineman Foundation).
221
QUALITY OF LIFE OF CHILDREN WITH
CONSTIPATION AND ENCOPRESIS AND IMPACT OF
PEDIATRIC NURSE PRACTITIONER INTERVENTION
M. Kinservik. Medical College of Wisconsin, Milwaukee, WI.
Constipation and encopresis are common in childhood. At least 3% of
all visits to a pediatric practice and 25% of all visits to a pediatric
gastroenterology clinic are for constipation and encopresis. Studies
have found that over 50% of childhood constipation persists 35 years
after medical intervention, making this a chronic problem for some
children. Families often report to care providers that the childs
constipation has taken over their lives. However its effect on the childs
quality of life (QOL) and the impact on the childs family have not been
studied in young children. The purpose of this study was to discover 1)
if constipation and encopresis affect QOL of these children and their
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
562 NASPGHAN ANNUAL MEETING
families and 2) if an intervention by a pediatric nurse practitioner
(PNP), who specializes in the treatment of constipation, would improve
the childs QOL. Subjects: 25 subjects age 25 years were recruited
from children who presented for care in Constipation Clinic.
Methods: Multiple descriptive methods were used to explore the
phenomena of the QOL of constipated preschool children and their
families. These methods included a QOL measure, a qualitative
interview using specific interview questions, observations of the parent
and child during the encounter and the usual data collected in a clinic
visit. The QOL measure was repeated 68 weeks after the initial
assessment to determine if the childs QOL improved after treatment by
specialized PNPs. Triangulation of all of the methods improved the
likelihood that the qualitative findings were credible.
Results: The significant findings of this study included 1) the child and
familys QOL was adversely affected by the childs constipation, 2)
parental worry was correlated with lower QOL scores on the pretest, 3)
pain was the most common physical symptom associated with
constipation that parents reported in the qualitative interview, and 4)
improvement on the childs QOL scores after one intervention by a PNP
who specializes in the treatment of childhood constipation.
Conclusions: Chronic constipation in toddlers and preschool children
places a significant physical, social and emotional burden on the child
and family. In this small study, the childrens QOL improved when their
constipation was treated by PNPs, who specialize in treatment of
children with constipation. In spite of the small sample size, these
findings should provide a starting point for further research on this
subject.
222
THE DEVELOPMENT AND UTILIZATION OF TRIAGE
PATHWAYS IN OUTPATIENT GASTROINTESTINAL CARE
K. Hlywiak, M. Czyzewski, I. Kunz, S. Mize, P. Scales, T. Thompson, M.
Mascaranas, R. Verma. The Childrens Hospital of Philadelphia,
Philadelphia, PA.
The Division of Gastroenterology and Nutrition at our institution
receives approximately 20 urgent/emergent patient referrals from
community physicians on a daily basis. Outpatient GI care is provided
at 10 sites located in the community. In an effort to triage severity of
illness and to educate the staff in the community practices, pathways
were developed recognizing that staff with varying levels of expertise
and background accept and facilitate these calls. The goals of the
project were: Acquire and review appropriate/specific patient history
information including history growth data, previous testing; decrease
the number of staff phone calls to acquire patient information; provide
MD offices with testing suggestions/rationale prior to the visit; and
provide consistent pathways for outpatient GI staff regarding triage,
treatment, medications.
Methods: We conducted an e-mail survey among the outpatient nurses,
PNPs, physicians and clinical coordinators to identify common urgent
referral diagnoses. The results identified gastroesophageal reflux, rectal
bleeding, and failure to thrive as the three most common referral
diagnoses. Triage pathways were devised and included triage questions,
red flags that would warrant Emergency Department referrals,
treatment goals and clinical reference data for clinicians. The triage
pathways were reviewed by nurse/physician teams and the outpatient
staff prior to use. Pathways were implemented in the outpatient network
and were utilized by 4 RNs and 2 non-nursing clinic coordinators.
Results: Pathways were evaluated at 3 intervals. Verbal feedback was
solicited from staff at 2 and 4 months. A written evaluation at 6 months
included a scale 15 with 5 being the most beneficial. Overall
usefulness of the triage sheets was rated as 45. Evaluators identified
decreased time spent in acquiring information and utilization as
a resource as being most valuable.
Conclusions: The goals of the project were met. The acquisition of
information, and as a reference guide in providing patient care. This
project facilitated collaboration between physicians, nurses and out-
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005
patient clinic coordinators. Staff found the triage pathways to be
valuable and recommended the development of additional triage
pathways for GI complaints such as abdominal pain, constipation and
screening for celiac disease.
223
PREDICTORS OF NON-ALCOHOLIC
STEATOHEPATITIS (NASH) IN OVERWEIGHT CHILDREN
S. Lerret, J. Skelton, D. Kilway, G. Telega. Gastroenterology,
Childrens Hospital of Wisconsin, Milwaukee, WI; Gastroenterology,
Medical College of Wisconsin, Milwaukee, WI.
The prevalence of obesity and its complications is increasing in the
pediatric population. Identification of the hepatic complications of
obesity is essential for development of treatment protocols. Currently,
there are no accepted criteria for performing diagnostic liver biopsy
(LB) in obese pediatric patients. The aim of this study was to evaluate
the utility of arbitrary laboratory criteria in prediction of non-alcoholic
fatty liver disease (NAFLD) and/or NASH among children referred to
the NEW Kids Program, a weight management program at our
institution.
Methods: We recorded age, gender, race, weight, height, body mass
index (BMI), aspartate aminotransferase (AST), alanine aminotransferase
(ALT), and fasting levels of: triglycerides, total cholesterol, LDL, HDL,
and insulin level. Guidelines used in decision to perform a LB in obese
patients include: (1) no evidence of other liver disease and (2) AST or
ALT greater than 200 iu/L or any elevation of AST or ALT for more than
6 months. We reviewed records of overweight children with a BMI
greater than 95% for age who underwent LB according to our guidelines.
Results: The patients were selected out of a group of 284 overweight
patients (age 218 years). In this group, 60 children (21%) demonstrated
an elevated ALT and 15 children (5%) demonstrated an elevated AST.
Out of this group, eight children (3%) met the guidelines to perform
a LB. Age of biopsied children ranged from 8 to 17 years. 4 patients
were male and 4 were female. Mean BMI of patients biopsied was 35.1
(67.3).
Conclusions: 100% of the children that met our guidelines for LB had
histological evidence of NASH. 87.5% had NASH with fibrosis or
cirrhosis. Determination of sensitivity and specificity of our criteria will
require a prospective study. NASH is a chronic progressive liver disease
and is a major cause of morbidity and mortality in obese patients.
Establishment of pediatric guidelines for diagnosis of this disease is
necessary for the development of treatment protocols.
224
ELEVATED VITAMIN B12 LEVELS IN CHILDREN
WITH SHORT BOWEL SYNDROME AND
INTESTINAL DYSMOTILITY
L. Mattis, R. Young, J. Hampsey, D. Antonson, J. Vanderhoof, J.
Saavedra. Johns Hopkins University, Baltimore, MD; University of
Nebraska, Omaha, NE.
Vitamin B12 deficiency in patients with intestinal disease has been
attributed to malabsorption, ileal resection, and small bowel bacterial
overgrowth (SBBO). To the best of our knowledge, elevated serum
vitamin B12 (VB12) levels in children with intestinal disease have not
previously been reported. We report the incidence of elevated VB12
levels in this population.
Methods: Laboratory and demographic data were collected for patients
with short bowel syndrome (SBS) and intestinal dysmotility (ID)
followed in the clinics at 2 institutions. Those who received tube
feedings or a combination of parenteral nutrition (PN) and enteral
nutrition (EN) for .3 months and whose VB12 levels were routinely
monitored were included.
Results: A total of 139 subjects were identified and medical records
reviewed. 96 instances of elevated VB12 levels (.900 pg/ml)
 NASPGHAN ANNUAL MEETING
were identified in 46 (33%) of 139 subjects; 20 instances of low VB12
levels (,150 pg/ml) were identified in only 7(5%). Elevated VB12
levels ranged from 9032.2000 pg/ml (limit of detection). Age range at
initial high VB12 level:3286 months; mean: 60 months. Primary
diagnoses: SBS (33), gastroschisis (4), pseudo-obstruction (5), IBD (3),
microvillus inclusion disease/SB transplant (1). 33 (72%) had partial or
complete ileal resection; 31 (67%) had resection of ileocecal valve
(ICV). 32 (33%) of elevated VB12 levels were found in 15 subjects
while receiving no PN and no VB12 enterally beyond that in
commercial formulas.
563
Conclusions: Most children with SBS and ID receiving adequate
nutrition have normal VB12 levels. Elevated VB12 levels were
significantly more frequent (p , 0.05) than low levels, even in cases of
ileal and ICV resection. These findings are contrary to the belief that
VB12 deficiency is common in intestinal disease. Given that the source of
VB12 (or its analogues) in humans is only dietary intake or bacterial
synthesis in the gut lumen, we speculate that synthesis of VB12 from
SBBO and absorption in the SB is responsible for the frequency of
elevated VB12 levels in this population.
Note: * after the final id indicates Poster of Distinction.
J Pediatr Gastroenterol Nutr, Vol. 41, 4, October 2005