• Research & Education (20100712)


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    • Abstract: Pediatric gastroenterology, hepatology and nutrition 1. Celiac Disease and Type 1 Diabetes Mellitus in Children. Organization ... Pediatric gastroenterology, hepatology and nutrition 4. 5. Adverse Events Leading to Modification of Therapy in a Large Cohort of ...

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Research profile
Karolinska University Hospital
Research & Education
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Pediatric gastroenterology, hepatology and
nutrition
Karolinska University Hospital
Research & Education
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Celiac Disease and Type 1 Diabetes Mellitus in Children
Organization
Pediatric Gastroenterology and Nutrition, Dept of Woman and Child Health.
Principle investigators
Lena Grahnquist
Grants awarded by
The Sällskapet barnavård, HKH Kronprincessan Lovisa’s foundation, Gastroenterologiska Föreningen and
AstraZeneca AB, and Sigurd and Elsa Goljes Memory foundation.
Research profile
We study the prevalence of positive serological tests for celiac disease and biopsy-confirmed celiac disease
in a large population of children with type 1 diabetes mellitus attending the Astrid Lindgren Children’s
Hospital during 1995–2004.
Among 1151 children registered, 8 children had a known celiac disease before the onset of diabetes, 3
children underwent intestinal biopsy prior to the serological test due to symptoms, and a total of 836
children were screened for celiac disease. Among the screened children, at least 155 had one abnormal
serological test result, 82 underwent biopsy, and celiac disease was confirmed in 66 children. Out of these
66 children more than half had no record of gastrointestinal symptoms.
The prevalence of biopsy-confirmed celiac disease was shown to be 9 %. Twelve children should have
performed a biopsy, but didn’t, and about 25 % of the registered patients never underwent serological
screening for celiac disease.
We now offer approximally 200 children and young adults, that were patients at the clinic at that time,
serological testing for celiac disease (tTGA).
Fundamental resources
A unique patient material with diabetic children that has been screened for celiac disease since 1995.
During this period, the incidence of celiac disease in Sweden changed dramatically. Hence this material can
contribute to an improved knowledge about the temporal onset and the cause of these diseases which
subsequently may lead to better care.
Collaboration
Eva Örtqvist, MD, PhD, Senior Consultant at the Diabetes and Endocrinological Unit at the Astrid
Lindgren Children’s Hospital.
2010-07-17 Pediatric gastroenterology, hepatology and nutrition 1
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Crohn’s disease in children - etiological, clinical and
prognostic aspects
Organization
Pediatric Gastroenterology and Nutrition, ALB. Department of Woman and Child Health, Karolinska
Institutet.
Principle investigators
Maja Ideström
Grants awarded by
SLL (FOUU/ALF), Sällskapet Barnavård, Bengt Ihre’s research foundation and Odd Fellows Stockholm.
Research profile
Crohn’s disease is a chronic inflammatory bowel disease which strikes children and young adults. Still
there are many things not known concerning etiology, clinical course and prognosis.
Through studying genetic differences between patients and healthy controls as well as histopathology and
disease characteristics of various stages of the disease and correlate the findings to the disease outcome and
progress among our patients, the knowledge and understanding of the disease can increase.
We have studied the NOD2/CARD15-gene and the IL-6-gene and correlated the findings to disease
extension/ severity and growth retardation, respectively. The importance of granuloma findings and age of
the patient has also been studied.
Hopefully, we can through increased knowledge better anticipate the needs of each patient, and
individualize the anti-inflammatory treatment already at an early stage after diagnosis. This might lead to
better long term prognosis and improvements in the quality of life.
Collaboration
Carlos Rubio, Clinical pathology and Fredrik Granath, Clinical statistics, both at Karolinska University
Hospital in Solna. Pediatric gastroenterologists and researchers in London and Paris.
More information can be found in these important scientific articles:
1. Idestrom M, Rubio C, Granath F, Finkel Y, Hugot P. CARD15 mutations are rare in Swedish pediatric
Crohn disease. J Pediatr Gastroenterol Nutr. 2005 Apr;40(4):456-60.
2. Meinzer U, Idestrom M, Alberti C, Peuchmaur M, Belarbi N, Bellaiche M,
Mougenot JF, Cezard JP, Finkel Y, Hugot JP. Ileal involvement is age dependent in pediatric Crohn's
disease. Inflamm Bowel Dis. 2005 Jul;11(7):639-44.
3. Sawczenko A, Azooz O, Paraszczuk J, Idestrom M, Croft NM, Savage MO, Ballinger AB, Sanderson
IR. Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the -174
IL-6 G/C polymorphism in children. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13260-5.
2010-07-17 Pediatric gastroenterology, hepatology and nutrition 2
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Inflammatory Bowel Disease in Children – Studies of
Immunological Mechanisms, Diagnostic and Prognostic
Methods, and Treatment
Organization
Dept of Gastroenterology and Nutrition, Dept of Woman and Child Health.
Principle investigators
Ulrika L. Fagerberg, Consultant, PhD.
Grants awarded by
Mayflower Charity Foundation for Children, Stockholm County Council (ALF), The Swedish Society of
Medicine, Bengt Ihre´s Foundation, Ruth and Richard Juhlin´s Foundation.
Research profile
Since the beginning of the 1990s the incidence of pediatric inflammatory bowel disease (IBD) has more
than doubled in Sweden and, in particular, a growing number of children have been diagnosed with
Crohn´s disease (CD). The reason for this increase is not known, but data suggest that a number of
interacting factors such as heredity, environmental factors and immunological dysfunction contribute to the
disease.
We conduct research in pediatric IBD with focus on immunological mechanisms, as well as diagnostic and
prognostic methods. By studying calprotectin (a protein abundant in neutrophils) and excretion of
calprotectin in stool, we have been able to establish fecal calprotectin as an appreciated routine method in
both suspected and confirmed IBD. In our studies the method had a sensitivity of 95% for detection of
colorectal inflammation and was more reliable compared to routine inflammatory markers in blood.
The results also showed that the concentration of calprotectin in stool correlated well to endoscopic colonic
disease activity in children with active IBD, and that the concentrations of fecal calprotectin normalized at
complete microscopic mucosal healing. This means that we are now able to study the healing effects of
different IBD treatments without performing colonoscopy repeatedly.
X-ray has been used to investigate the involvement of inflammation in the intestines but the method has
several disadvantages such as the exposure of radiation. To avoid this we now study the use of magnetic
resonance imaging in pediatric IBD.
By using flow cytometry and studying the presence of antibodies in the blood in children with ulcerative
colitis and Crohn´s disease, we are now studying the prognostic and differential diagnostic significance of
these methods.
Collaboration
Research groups in Clinical Chemistry, Clinical Immunology, Radiology, and Pathology at Karolinska
University Hospital, Karolinska Institutet and Uppsala University Hospital.
More information can be found in these important scientific articles:
1. Fecal Calprotectin Levels in Healthy Children Studied With an Improved Assay
Fagerberg UL, Lööf L, Merzoug RD, Hansson L-O, Finkel Y. Journal of Pediatric Gastroenterology and
Nutrition 2003;37:468-472.
2. Colorectal Inflammation is Well Predicted by Fecal Calprotectin in Children with Gastrointestinal
Symptoms. Fagerberg UL, Lööf L, Myrdal U, Hansson L-O, Finkel Y.
Journal of Pediatric Gastroenterology and Nutrition 2005;40:450-455.
3. Fecal Calprotectin - A Quantitative Marker of Colonic Inflammation in Children with Inflammatory
Bowel Disease. Fagerberg UL, Lööf L, Lindholm J, Hansson L-O, Finkel Y. Journal of Pediatric
Gastroenterology and Nutrition 2007;45(4):414-420.
4. Fecal Calprotectin in Children With Special Reference to Inflammatory Bowel Disease in Children.
Fagerberg UL. http://diss.kib.ki.se/2007/978-91-7357-013-8/thesis.pdf.
2010-07-17 Pediatric gastroenterology, hepatology and nutrition 3
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5. Adverse Events Leading to Modification of Therapy in a Large Cohort of Patients with Inflammatory
Bowel Disease. Hindorf U, Lindqvist M, Hildebrand H, Fagerberg UL, Almer S. Alimentary Pharmacology
& Therapeutics 2006 Jul 15;24(2):331-42.
2010-07-17 Pediatric gastroenterology, hepatology and nutrition 4
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Responsible Editor
Chief of Research & Education Sten Lindahl
Karolinska University Hospital
S-171 76 Stockholm
Telephone +46-8-517 700 00
www.karolinska.se


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