Nejat S.,Astrid Lindgren Childrens Hospital |
Buxbaum C.,Astrid Lindgren Childrens Hospital |
Eriksson M.,Astrid Lindgren Childrens Hospital |
Bennet R.,Astrid Lindgren Childrens Hospital
Pediatric Infectious Disease Journal | Year: 2012
BACKGROUND: Increasing international migration has changed the epidemiology of tuberculosis (TB) in Europe. Little is published on clinical manifestations and epidemiology in children in this new era. METHODS: Clinical and laboratory data on all children with TB in Stockholm between 2000 and 2009 were entered into a database and retrospectively completed with information from case records. Population data, including parents' country of birth, were obtained from Statistics Sweden. RESULTS: TB was diagnosed in 147 children <18 years of age (78 confirmed, 12 probable, 57 possible). Fifty-six children (38%) presented clinically, and 91 were identified by screening procedures. Ninety children (61%) were born in high-endemic countries and 38 in Sweden to parents from such countries. The incidence was 451/100,000 person years among children born in Somalia, 44 among those born in other high-endemic countries, and 13 among Swedish-born children with parents from high-endemic countries. All but 1 of the 19 Swedish-born children with Swedish parents belonged to a single outbreak. Median age was 12 years. Severe, adult-type TB was predominantly observed in adolescents, whereas young children presented mild, primary disease that was diagnosed at the time of screening. The 78 positive cultures were traced back to 67 strains. Resistance to any first-line drug was present in 25% of the strains, of which 4 were multidrug resistant. CONCLUSIONS: Active TB in Stockholm is common in children born in high-endemic countries, especially Somalia. The most severe cases are seen in adolescents. The high prevalence of antimicrobial resistance is a cause for concern. Copyright © 2012 by Lippincott Williams & Wilkins.
Dahlin M.,Astrid Lindgren Childrens Hospital |
Mansson J.-E.,Molndal Hospital |
Amark P.,Astrid Lindgren Childrens Hospital
Epilepsy Research | Year: 2012
The ketogenic diet (KD) is a non-pharmacological treatment of medically refractory epilepsy in children. Its mechanisms of action are still unclear but monoamine neurotransmitters have been proposed to be involved. Norepinephrine, dopamine, and serotonin are known to modulate seizure susceptibility in many animal models. We examined whether the concentrations of norepinephrine, dopamine, and serotonin metabolites were affected by the KD in children with pharmacoresistant epilepsy. The metabolites of norepinephrine, HMPG, of dopamine, HVA, and of serotonin, 5-HIAA, were analyzed in cerebrospinal fluid (CSF) before and 3 months after starting the KD. Twenty-six children (mean age 5.9 years) participated. Twenty-one children had generalized epilepsy and five partial. CSF was sampled by lumbar puncture. Seizure frequency before and during the diet was determined. Highly significant changes were found for HVA (p= 0.0002) and 5-HIAA (p= 0.004), which were both decreased during the KD compared to before diet. The levels of HMPG were unchanged. However, no differences were found between response groups. Valproate medication affected the levels of HMPG during diet with decreased levels in children on valproate and increased in those not on valproate (p= 0.04). Our study indicates that the KD significantly alters the levels of metabolites of dopamine and serotonin but with a stable ratio HVA/5-HIAA in the CSF of children with refractory epilepsy, which finding may be of importance for the mechanism of action. © 2011.
Wang L.,Max Planck Institute for Molecular Biomedicine |
Benedito R.,Max Planck Institute for Molecular Biomedicine |
Bixel M.G.,Max Planck Institute for Molecular Biomedicine |
Zeuschner D.,Max Planck Institute for Molecular Biomedicine |
And 8 more authors.
EMBO Journal | Year: 2013
In mammals, postnatal haematopoiesis occurs in the bone marrow (BM) and involves specialized microenvironments controlling haematopoietic stem cell (HSC) behaviour and, in particular, stem cell dormancy and self-renewal. While these processes have been linked to a number of different stromal cell types and signalling pathways, it is currently unclear whether BM has a homogenous architecture devoid of structural and functional partitions. Here, we show with genetic labelling techniques, high-resolution imaging and functional experiments in mice that the periphery of the adult BM cavity harbours previously unrecognized compartments with distinct properties. These units, which we have termed hemospheres, were composed of endothelial, haematopoietic and mesenchymal cells, were enriched in CD150+ CD48- putative HSCs, and enabled rapid haematopoietic cell proliferation and clonal expansion. Inducible gene targeting of the receptor tyrosine kinase VEGFR2 in endothelial cells disrupted hemospheres and, concomitantly, reduced the number of CD150+ CD48- cells. Our results identify a previously unrecognized, vessel-associated BM compartment with a specific localization and properties distinct from the marrow cavity. © 2013 European Molecular Biology Organization.
Van'T Hooft I.,Astrid Lindgren Childrens Hospital |
Norberg A.L.,Karolinska Institutet
NeuroRehabilitation | Year: 2010
In a pilot study we examined the feasibility of a condensed version of the Swedish Memory and Attention Re-Training on children treated for medulloblastoma combined with a structured coaching programme for their parents. Parental coaching contained the translation of the child's new skills into daily life, and education regarding their own stress mechanisms. Before and after intervention we assessed the children's cognitive performance, social relations and self image as well as their parents stress. All three families continued the programme without interruption. Observations revealed that this condensed version of the programme was more stressful to participants. However, several aspects of the children's attention and memory performance improved from pre to post-training assessment. In addition, all of the children reported enhancement of their social relations and self image. Initially, symptoms of parental stress were pronounced for the three mothers, but fairly low for the fathers. After training and coaching, the stress level of both mothers and fathers was low. Our findings encourage full scale studies examining whether this combination of condensed cognitive training and specific coaching programme for parents may influence not only the children's cognitive performance but also their social relations, self image and their parents stress. © 2010-IOS Press and the authors. All rights reserved.
Sonesson S.-E.,Astrid Lindgren Childrens Hospital |
Eliasson H.,Astrid Lindgren Childrens Hospital |
Conner P.,Astrid Lindgren Childrens Hospital |
Wahren-Herlenius M.,Karolinska Institutet
Ultrasound in Obstetrics and Gynecology | Year: 2014
Objective To distinguish between blocked atrial bigeminy (BB) and incomplete atrioventricular block with 2:1 conduction (2:1 AVB) can be very difficult, especially in the mid-term fetus. Making a correct diagnosis has important clinical implications, as their prognosis and management differ markedly. Our objective was to investigate whether analysis of isovolumetric time intervals could improve Doppler echocardiography in differentiating these conditions. Methods Sixteen fetuses with sustained BB or isolated 2:1 AVB, diagnosed at our tertiary center from 2002 to 2012, were reviewed retrospectively. Doppler recordings of left ventricular in- and outflow, including mitral and aortic valve movements, were used to measure isovolumetric contraction (ICT) and relaxation (IRT) time intervals. ICT reference values obtained from 104 normal pregnancies were used for comparison. Results Ten fetuses had BB and six 2:1 AVB. Five of the AVB cases were anti-Ro antibody positive and one had long QT syndrome (LQTS). ICT was systematically shorter in BB than in antibody-mediated 2:1 AVB. Nine of 10 cases with BB had an ICT below -2 SD and the five with antibody-mediated 2:1 AVB had values at or above +2 SD. All 15 fetuses with either BB or antibody-mediated AVB had an IRT of < 70 ms, as opposed to a markedly prolonged IRT (105 ms) in the LQTS case. Conclusion Measurement of ICT can improve the differential diagnosis between BB and antibody-mediated 2:1 AVB. Fetuses with BB or antibody-mediated AVB are unlikely to have IRT measurements exceeding 70 ms and, when this is observed, LQTS should be considered a more likely diagnosis Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Mogensen N.,Karolinska Institutet |
Larsson H.,Karolinska Institutet |
Lundholm C.,Karolinska Institutet |
Almqvist C.,Karolinska Institutet |
Almqvist C.,Astrid Lindgren Childrens Hospital
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011
Background: Cross-sectional studies report a relationship between childhood asthma and attention-deficit hyperactivity disorder (ADHD) symptoms, but the mechanisms are yet unclear. Our objective was to investigate the longitudinal link between childhood asthma and the two dimensions of ADHD (hyperactivity-impulsivity, HI, and inattention, IN) in adolescence. We also aimed to explore the genetic and environmental contributions and the impact of asthma medication. Methods: Data on asthma, HI and IN, birth weight, socioeconomic status, zygosity, and medication were collected from the Swedish Medical Birth Register and through parental questionnaires at ages 8-9 and 13-14 years on 1480 Swedish twin pairs born 1985-1986. The association between asthma at age 8-9 and ADHD symptoms at age 13-14 was assessed with generalized estimating equations, and twin analyses to assess the genetic or environmental determinants were performed. Results: Children with asthma at age 8-9 had an almost twofold increased risk of having one or more symptom of HI (OR 1.88, 95% CI 1.18-3.00) and a more than twofold increased risk to have three symptoms or more of HI (OR 2.73, 95% CI 1.49-5.00) at age 13-14, independent of asthma medication. For IN, no significant relationship was seen. Results from twin modeling indicate that 68% of the phenotypic correlation between asthma and HI (r = 0.23, 0.04-0.37) was because of genetic influences. Conclusions: Our findings suggest that childhood asthma is associated with subsequent development of HI in early adolescence, which could be partly explained by genetic influences. Early strategies to identify children at risk may reduce burden of the disease in adolescence. © 2011 John Wiley & Sons A/S.
Lundeberg S.,Astrid Lindgren Childrens Hospital |
Lundeberg S.,Karolinska Institutet
Paediatric Anaesthesia | Year: 2015
Morphine, paracetamol and local anesthetics have for a long time been the foremost used analgesics in the pediatric patient by tradition but not always enough effective and associated with side effects. The purpose with this article is to propose alternative approaches in pain management, not always supported up by substantial scientific work but from a combination of science and clinical experience in the field. The scientific literature has been reviewed in parts regarding different aspects of pain assessment and analgesics used for treatment of diverse pain conditions with focus on procedural and acute pain. Clinical experience has been added to form the suggested improvements in accomplishing an improved pain management in pediatric patients. The aim with pain management in children should be a tailored analgesic medication with an individual acceptable pain level and optimal degree of mobilization with as little side effects as possible. Simple techniques of pain control are as effective as and complex techniques in pediatrics but the technique used is not of the highest importance in achieving a good pain management. Increased interest and improved education of the doctors prescribing analgesics is important in accomplishing a better pain management. The optimal treatment with analgesics is depending on the analysis of pain origin and analgesics used should be adjusted thereafter. A multimodal treatment regime is advocated for optimal analgesic effect. © 2014 John Wiley & Sons Ltd.
Lagercrantz H.,Astrid Lindgren Childrens Hospital |
Changeux J.-P.,Institute Pasteur Paris
Seminars in Perinatology | Year: 2010
The newborn shows several signs of consciousness, such as being awake and aware of him/herself and mother. The infant processes olfactory and painful inputs in the cortex, where consciousness is believed to be localized. Furthermore, the newborn expresses primary emotions such as joy, disgust, and surprise and remember rhymes and vowels to which he or she has been exposed during fetal life. Thus, the newborn infant fulfills the criteria of displaying a basic level of consciousness, being aware of its body and him/her-self and somewhat about the external world. Preterm infants may be conscious to a limited degree from about 25 weeks, when the thalamocortical connections are established. © 2010 Elsevier Inc.
Lundeberg S.,Astrid Lindgren Childrens Hospital |
Roelofse J.A.,University of the Western Cape |
Roelofse J.A.,University College London
Paediatric Anaesthesia | Year: 2011
Sufentanil is a potent synthetic opioid. Like other opioids, sufentanil creates a stable hemodynamic environment in cardiovascularly compromised pediatric patients. Clearance, expressed as per kilogram, is increased in children compared to adults. The P450 CYP3A4 enzyme is responsible for the major metabolic N-dealkylation pathway. Enzyme activity is reduced in neonates but the maturation of sufentanil clearance is not described. The free active fraction is affected by age because of the reduced α1-acid glycoprotein plasma concentrations in neonates. Intranasal administration of sufentanil is a possible option for premedication, procedural sedation and analgesia in children, as this option has been found to be safe and effective. Studies concerning the pharmacokinetics and dynamics of sufentanil administered as a bolus or continuous infusion in children are few. © 2010 Blackwell Publishing Ltd.
Hertting O.,Astrid Lindgren Childrens Hospital |
Shingadia D.,Great Ormond Street Hospital
Journal of Infection | Year: 2013
Although childhood tuberculosis has declined dramatically in the UK over the last century, it is now increasing again and globally childhood tuberculosis still accounts for a significant proportion of the tuberculosis disease burden. Children may present with non-specific symptoms, and because of the paucibacillary nature of disease and the difficulty of producing sputum samples, tuberculosis in children is often difficult to diagnose. Apart from the traditional diagnostic methods, like chest X-ray, tuberculin skin testing and mycobacterial staining or culture, new diagnostic strategies have been developed. In particular, immune-based diagnostics, such as interferon-gamma release assays, have now been introduced for clinical use. However these tests do not offer substantial improvements in sensitivity over tuberculin skin testing for the diagnosis of active disease. Further research is needed to develop better diagnostic tests for tuberculosis in children. © 2013 The British Infection Association.