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Sankt Gallen, Switzerland

Wiegand S.,Charite - Medical University of Berlin | Keller K.-M.,German Clinic for Diagnostics | Robl M.,University of Gottingen | L'Allemand D.,Childrens Hospital of Eastern Switzerland | And 3 more authors.
International Journal of Obesity | Year: 2010

Objective:Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort.Methods:In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16 390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 Ul -1). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis.Results:In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (<12 vs ≥12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 Ul-1 was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight3.2; boys vs girls OR=2.3).Conclusion:In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care. © 2010 Macmillan Publishers Limited All rights reserved. Source

Tinner E.M.,University of Bern | Hoesli I.,University of Basel | Jost K.,University of Basel | Schobi N.,Childrens Hospital of Eastern Switzerland | And 8 more authors.
Journal of Pediatrics | Year: 2013

Objective: To assess the efficacy of paracetamol (acetaminophen) for neonatal pain relief. Study design: Randomized, double-blind placebo-controlled trial in 3 Swiss university hospitals. Term and near-term infants (n = 123) delivered by forceps or vacuum were randomized to receive 2 suppositories with paracetamol (60/80/100 mg in infants <3000 g/3000-4000 g/>4000 g birth weight) or placebo at 2 and 8 hours of life. Pain and discomfort during the first 24 hours was assessed by the échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] score. The response to the subsequent heel prick for metabolic screening at days 2-3 of life was investigated by the Bernese Pain Scale for Neonates (BPSN). Results: The échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] pain scale ratings after assisted vaginal delivery were low and declined within 4 hours of life (P < .01) irrespective of paracetamol administration. At 2-3 days of life, BPSN scores after heel prick were significantly higher in infants who had received paracetamol, compared with controls, both when BPSN were scored by nurses at the bedside (median [IQR] 4 [2-7] vs 2 [0-5], P = .017) or off-site from videos (4 [2-8] vs 2 [1-7], P = .04). Thirty-five of 62 (57%) infants treated with paracetamol cried after heel prick, compared with 25 of 61 (41%) controls (P = .086). Conclusions: Infants born by assisted vaginal delivery have low pain scores in the immediate period after birth. Paracetamol given to newborns soon after birth may aggravate a subsequent stress response. Copyright © 2013 Mosby Inc. Source

L'Allemand-Jander D.,Childrens Hospital of Eastern Switzerland
International Journal of Obesity | Year: 2010

Childhood overweight (body mass index (BMI)90th centile) poses a major public health problem in so far as adult diseases manifest themselves already during childhood. In this review, after examining the prevalence of metabolic and cardiovascular diseases, the issue of whether BMI or other clinical parameters are valid tools to predict co-morbidities in children is discussed. Data of 2001-2008 are reviewed, including several studies conducted on more than 260 000 overweight and obese children in Germany and Switzerland. Apart from non-metabolic co-morbidities, namely musculoskeletal complications and attention deficit/hyperactivity disorders in up to 74% and up to 58% of overweight children, respectively, at least one cardiovascular and metabolic risk factor was seen in 52% of the overweight children, mostly high blood pressure (35%) with increased left ventricular mass or arterial stiffness. Signs of fatty liver disease or dyslipidemia were found in up to 29 and 32% of the children, respectively. Type 2 diabetes was found in less than 0.7% of the children, and an elevated fasting glucose or glucose intolerance in 3%. Irrespective of BMI, the quality of fat and protein intake predicted hypertension or insulin resistance, and fructose predicted lower (and more atherogenic) particle size of low-density lipoprotein-cholesterol. Out of the adiposity markers, waist circumference was closely correlated with insulin resistance and the components of the metabolic syndrome. In conclusion, risk factors are found in more than half of the overweight children, most frequently high blood pressure or dyslipidemia, and were mainly related to waist circumference, but also to BMI and fat mass. Even in the presence of normal BMI, screening for cardiovascular risk factors is advocated in each child with elevated waist circumference, but its cut-off points still remain to be validated. The increased occurrence of orthopedic and psychiatric complaints may detrimentally influence health-related lifestyle and obesity therapy. © 2010 Macmillan Publishers Limited All rights reserved. Source

Rueegg C.S.,University of Bern | Rueegg C.S.,University of Lucerne | Barben J.,Childrens Hospital of Eastern Switzerland | Hafen G.M.,University of Lausanne | And 4 more authors.
Journal of Cystic Fibrosis | Year: 2016

Background Newborn screening for CF started 01/2011 in Switzerland. We investigated the parents' opinions about the information received, their feelings, and overall approval of the screening. Methods This is a prospective questionnaire survey of all parents of positively screened children. Parents were phoned by CF-centres and invited for diagnostic investigations. They completed a questionnaire after the visit to the CF-centre. Results From 2011–2013, 246 families received the questionnaire and 138 (56%) replied. Of these 77 (60%) found the information received at birth satisfactory; 124 (91%) found the information provided in the CF-centre satisfactory. Most parents (n = 98, 78%) felt troubled or anxious when the CF-centre called, 51 (38%) remained anxious after the visit. Most parents (n = 122; 88%) were satisfied with the screening, 4 (3%) were not, and 12 (9%) were unsure. Conclusions The smooth organisation of the screening process, with personal information by a CF specialist and short delays between this information and the final diagnostic testing, might have contributed to reduce anxiety among parents. Most families were grateful that their child had been screened, and are happy with the process. © 2015 European Cystic Fibrosis Society Source

Winkler F.,Charite - Medical University of Berlin | Kleinau G.,Leibniz Institute for Molecular Pharmacology | Tarnow P.,Charite - Medical University of Berlin | Rediger A.,Charite - Medical University of Berlin | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Activating mutations in the TSHR gene were found in patients suffering from nonautoimmune hyperthyroidism. In the past, it was assumed that thyroid hyperplasia is due to constitutive activation of the Gs/adenylyl cyclase signaling pathway; however, the physiological role of the Gq/11 pathway in this context remains unclear. Objective: In this study, we investigated molecular details of the TSHR in a patient with nonautoimmune and nongoitrous hyperthyroidism. Results: We detected a heterozygous mutation in exon 10 of the TSHR gene leading to an exchange of a cysteine residue for tryptophan at amino acid position 636 in transmembrane helix 6. Functional characterization of the mutant receptor revealed a slight reduction of the cell surface expression and TSH induced cAMP accumulation compared to the wild type. Additional observations included a constitutive activation of the Gs-mediated signaling pathway and a simultaneous nearly complete loss-of-function for the Gq/11 pathway after bovine TSH stimulation. Studies on TSHR models suggest significant changes of important amino acid interactions and the overall helix arrangement caused by mutation C636W. Conclusion: We report a patient in whom a TSHR mutation leads to nonautoimmune hyperthyroidism due to a mutation that constitutively activates the Gs signaling pathway but additionally completely inhibits the Gq/11 pathway. The absence of goiter in the patient suggests that the Gq/11 pathway is related to thyroid growth and that different signaling pathways are mediated and regulated by TSH. These functional data could be confirmed by reproducible findings of two siblings with a constitutive activation for both pathways. Copyright © 2010 by The Endocrine Society. Source

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