ABSTRACT
BACKGROUND: An adverse intrauterine environment leads to permanent physiological changes including vascular tone regulation, potentially influencing the risk for adult vascular diseases. We therefore aimed to monitor responsive NOS3 expression in human umbilical artery endothelial cells (HUAEC) and to study the underlying epigenetic signatures involved in its regulation. RESULTS: NOS3 and STAT3 mRNA levels were elevated in HUAEC of patients who suffered from placental insufficiency. 5-hydroxymethylcytosine, H3K9ac and Histone 2A (H2A).Zac at the NOS3 transcription start site directly correlated with NOS3 mRNA levels. Concomitantly, we observed entangled histone acetylation patterns and NOS3 response upon hypoxic conditions in vitro. Knock-down of either NOS3 or STAT3 by RNAi provided evidence for a functional NOS3/STAT3 relationship. Moreover, we recognized massive turnover of Stat3 at a discrete binding site in the NOS3 promoter. Interestingly, induced hyperacetylation resulted in short-termed increase of NOS3 mRNA followed by deferred decrease indicating that NOS3 expression could become self-attenuated by co-expressed intronic 27 nt-ncRNA. Reporter assay results and phylogenetic analyses enabled us to propose a novel model for STAT3-3'-UTR targeting by this 27-nt-ncRNA. CONCLUSIONS: An adverse intrauterine environment leads to adaptive changes of NOS3 expression. Apparently, a rapid NOS3 self-limiting response upon ectopic triggers co-exists with longer termed expression changes in response to placental insufficiency involving differential epigenetic signatures. Their persistence might contribute to impaired vascular endothelial response and consequently increase the risk of cardiovascular disease later in life.
ABSTRACT
OBJECTIVE: Intussusception (IS) is one of the most common paediatric emergencies, and the best mode of conservative reduction and its exact incidence remains unclear. For different reasons, availability of reliable incidence data are useful and additionally may be fundamental to monitor potential effects of recently introduced rotavirus (RV) vaccines. METHODS: We performed a prospective German nationwide surveillance between January 1, 2006 and December 31, 2007, followed by separate collection of all IS cases in a random sample of 31 clinics for an unbiased estimation of underreporting. For case definition, the Brighton Collaboration (BC) criteria were applied. RESULTS: A total of 1200 children with at least 1 episode of IS were included. For children younger than 1 year the incidence was calculated to be 60.4/100,000 child-years. The risk for surgery increased 2-fold if the interval between onset of symptoms and first attempt of conservative reduction exceeded 5 hours (95% confidence interval [CI] 1.2-3.1). We also observed a 2.8-fold increased risk for surgery for hydrostatic (CI 1.2-6.4) and a 3.7-fold for barium enema reduction (CI 1.6-8.8) compared to pneumatic reduction. The level of specialisation of the hospital did not influence the success of conservative management. CONCLUSIONS: For children with IS a fast attempt of pneumatic reduction seems to be the optimal management. Considering the current practice we estimated that approximately 104 (CI 46-161) surgical interventions would be preventable in Germany every year. Also, conduction of reliable postmarketing monitoring of the new RV vaccines is now possible based on the provided incidence data.
Subject(s)
Intussusception/epidemiology , Intussusception/therapy , Adverse Drug Reaction Reporting Systems , Age Factors , Child , Child, Preschool , Cross-Sectional Studies , Female , Germany/epidemiology , Hospitals, Pediatric , Humans , Incidence , Infant , Infant, Newborn , Intussusception/surgery , Male , Population Surveillance , Practice Patterns, Physicians' , Prospective Studies , Risk Factors , Rotavirus Vaccines/adverse effects , Severity of Illness IndexABSTRACT
BACKGROUND: Currently there is much controversy whether to treat idiopathic facial palsy with corticosteroids with sparse data on the natural course of the disease in children. METHODS: We performed a prospective study on all children <15 years of age who were admitted to our unit for facial palsy between 1st July 1998 to 30th June 2008. All patients received a standardized work-up and follow-up. Therapy consisted of symptomatic treatment either with (in case of neuroborreliosis) or without a 14 day course of intravenous antibiotics. FINDINGS: 106 patients were included in our study. The calculated incidence for facial palsy was 21.1/100000/year for children <15 years. The incidence for neuroborreliosis (NB) in this age group was calculated to be 4.9/100000/year. The overall rate of complete recovery was 97.6% with significantly faster recovery in younger children and in patients with NB as compared to idiopathic facial palsy. Both patients with incomplete recovery were at least 14 years old and presented late in the course of the disease. CONCLUSION: Based on the rate of 97.6% spontaneous complete recovery we believe that the routine use of corticosteroids in children with facial palsy is not justified, unless there is new data from controlled trials in children.
