Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in wisconsin: a statewide population-based study

Kugathasan, Subra; Judd, Robert H.; Hoffmann, Raymond G.; Heikenen, Janice B.; Telega, Gregorz; Khan, Farhat Ullah; Weisdorf-Schindele, Sally; Pablo, William San; Perrault, Jean; Park, Roger; Yaffe, Michael R.; Brown, Christopher; T., Rivera-Bennett, Maria; Halabi, Issam; Martínez, Alfonso Martín; Blank, Ellen L.; Werlin, Steven L.; Rudolph, Colin D.; Binion, David G.

doi:10.1067/s0022-3476(03)00444-x

Cited by 554 publications

(436 citation statements)

References 29 publications

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“…Moreover, in pediatric patients a higher male-to-female ratio was not demonstrated, which seems to be confined to Crohn's disease (CD). 9 The low rate of family history (7,2%), found in Portuguese patients could reflect an increasing incidence of IBD, among a population not considered at high risk in the past, but now facing new environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Ulcerative colitis in a Southern European country: A national perspective

Portela

Magro²,

Lago³

et al. 2010

Inflammatory Bowel Diseases

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Section: Discussionmentioning

confidence: 99%

Ulcerative colitis in a Southern European country: A national perspective

Portela

Magro²,

Lago³

et al. 2010

Inflammatory Bowel Diseases

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“…37 Recent genetic studies have implicated primary defects in mucosal innate immunity that then lead to chronic, relapsing and remitting T-cell-predominant gut inflammation. 1 We asked whether the GH-dependent STAT5b transcription factor, which we have recently linked to growth failure in colitis, might also regulate mucosal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Signal Transducer and Activator of Transcription 5b Promotes Mucosal Tolerance in Pediatric Crohn's Disease and Murine Colitis

Han

Osuntokun

Benight

et al. 2006

The American Journal of Pathology

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Growth hormone (GH) regulates anabolic metabolism via activation of the STAT5b transcription factor and reduces mucosal inflammation in colitis.Peroxisome proliferator-activated receptor (PPAR) ␥ suppresses mucosal inflammation and is regulated by GH through STAT5b. We hypothesized that the GH:STAT5b axis influences susceptibility to colitis via regulation of local PPAR␥ abundance. Colon biopsies from children with newly diagnosed Crohn's disease (CD) and controls were exposed to GH in short-term organ culture. Trinitrobenzene sulfonic acid (TNBS) administration was used to induce colitis in STAT5b-deficient mice and wildtype controls , with and without rosiglitazone pretreatment. GH receptor , STAT5b , PPAR␥ , and nuclear factor B activation and expression were determined. Epithelial cell GH receptor expression and GH-dependent STAT5b activation and PPAR␥ expression were reduced in CD colon. STAT5b-deficient mice exhibited reduced basal PPAR␥ nuclear abundance and developed more severe proximal colitis after TNBS administration. This was associated with a significant increase in mucosal nuclear factor B activation at baseline and after TNBS administration. Rosiglitazone ameliorated colitis in wild-type mice but not STAT5b-deficient mice. GHdependent STAT5b activation is impaired in affected CD colon and contributes to chronic mucosal inflammation via down-regulation of local PPAR␥ expression. Therapeutic activation of the GH:STAT5b axis therefore represents a novel target for restor- Current evidence suggests that Crohn's disease (CD) is caused by loss of tolerance to the enteric flora, leading to chronic inflammation and intestinal damage.1 Increased epithelial nuclear factor B (NF-B) activity and consequent chemokine expression are fundamental molecular features of this loss of tolerance. Increased NF-B DNAbinding activity has been attributed to increased binding of the p50 and p65 subunits.2 Importantly, disease activity in mice with colitis due to 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration was inhibited by antisense oligonucleotides that inhibit p65 expression.2 These studies suggest a critical role for NF-B in mediating expression of proinflammatory factors, which are central to the pathogenesis of CD. Although much less is known regarding the regulatory transcription factors that may promote mucosal tolerance, recent studies have suggested that both STAT5a/b and peroxisome proliferator-activated receptor (PPAR) ␥ may play a role.Colonic mRNA expression of the STAT5b transcription factor is down-regulated in affected segments in adults with CD and ulcerative colitis.3 However, the functional significance of this is not known. Moreover, whether GHdependent STAT5b tyrosine phosphorylation and DNA binding are reduced in affected CD colon has not been determined. Current data suggest that the closely related STAT5a and STAT5b transcription factors are required, in

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“…56 Disease rates are highest in Westernized countries, and the incidence rate in children is increasing. [57][58][59][60] The incidence of pediatric Crohn disease is ϳ7 new cases per 100 000 children per year. 60 In addition to the usual symptoms of diarrhea, abdominal pain, weight loss, anemia, and rectal bleeding, children may exhibit growth failure years before disease diagnosis.…”

Section: Crohn Diseasementioning

confidence: 99%

“…[57][58][59][60] The incidence of pediatric Crohn disease is ϳ7 new cases per 100 000 children per year. 60 In addition to the usual symptoms of diarrhea, abdominal pain, weight loss, anemia, and rectal bleeding, children may exhibit growth failure years before disease diagnosis. 61,62 Anorexia, malabsorption, and increased metabolic demands all contribute to poor growth.…”

Section: Crohn Diseasementioning

confidence: 99%

Glucocorticoid-Induced Osteoporosis in Children: Impact of the Underlying Disease

Leonard

2007

Pediatrics

110

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Glucocorticoids inhibit osteoblasts through multiple mechanisms, which results in significant reductions in bone formation. The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion. Although decreased bone mineral density has been described in various pediatric disorders that require glucocorticoids, and a population-based study reported increased fracture risk in children who require Ͼ4 courses of glucocorticoids, some of the detrimental bone effects attributed to glucocorticoids may be caused by the underlying inflammatory disease. For example, inflammatory cytokines that are elevated in chronic disease, such as tumor necrosis factor ␣, suppress bone formation and promote bone resorption through mechanisms similar to glucocorticoid-induced osteoporosis. Summarized in this review are changes in bone density and dimensions during growth, the effects of glucocorticoids and cytokines on bone cells, the potential confounding effects of the underlying inflammatory-disease process, and the challenges in interpreting dual-energy x-ray absorptiometry results in children with altered growth and development in the setting of glucocorticoid therapy. Two recent studies of children treated with chronic glucocorticoids highlight the differences in the effect of underlying disease, as well as the importance of associated alterations in growth and development. S166LEONARD by guest on May 10, 2018 http://pediatrics.aappublications.org/ Downloaded from D URING CHILDHOOD AND adolescence, skeletal development is characterized by gender-, maturation-, and race-specific increases in cortical dimensions and trabecular density. The 2000 National Institutes of Health Osteoporosis Prevention, Diagnosis, and Therapy Consensus Development Conference identified bone accrual during childhood as a critical determinant of lifelong skeletal health. The authors of the resulting consensus statement 1 specifically called for research to determine the impact of chronic diseases and glucocorticoid therapy on bone accrual in children.Glucocorticoid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis in adults and is the result of profound effects of glucocorticoids on bone cells. 2 Glucocorticoids inhibit osteoblastogenesis and promote osteoblast apoptosis, which results in significant reductions in bone formation. 3 Studies in adults have demonstrated that glucocorticoids cause rapid, dose-dependent bone loss and increased fracture risk. 4 The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion.Glucocorticoids are used in myriad pediatric diseases. Decreased bone mineral density (BMD) has been described in various pediatric disorders that require glucocorticoids, including asthma, juvenile rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and organ trans...

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Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in wisconsin: a statewide population-based study

Cited by 554 publications

References 29 publications

Ulcerative colitis in a Southern European country: A national perspective

Ulcerative colitis in a Southern European country: A national perspective

Signal Transducer and Activator of Transcription 5b Promotes Mucosal Tolerance in Pediatric Crohn's Disease and Murine Colitis

Glucocorticoid-Induced Osteoporosis in Children: Impact of the Underlying Disease

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