Muehlmann M.,Ludwig Maximilians University of Munich |
Koerte I.K.,Ludwig Maximilians University of Munich |
Laubender R.P.,Institute of Medical Informatics |
Steffinger D.,Ludwig Maximilians University of Munich |
And 5 more authors.
Investigative Radiology | Year: 2013
Objectives: The aim of this study was to investigate the relationship between the pressure setting of the ventriculoperitoneal (VP) shunt valve and a magnetic resonance (MR)-based estimate of intracranial pressure (ICP) in children with shunt-treated hydrocephalus without clinical signs of shunt malfunction. Materials and Methods: Institutional review board approval was obtained before the study, and all subjects and/or their legal guardians provided written informed consent. In this prospective study, 15 consecutive patients (median age, 8.25 years; range, 2.2-18.4 years; 6 girls and 9 boys) with shunt-treated hydrocephalus without signs of shunt malfunction were examined with retrospectively gated phase contrast sequences to quantify arterial inflow, venous outflow, and cerebrospinal fluid (CSF) flow to and from the cranial vault. The ratio of the maximal intracranial volume change and the pulse pressure gradient change was used to derive MR-ICP. Spearman ρ was used to test for the association of setting of the shunt valve opening pressure and MR-ICP. Results: Shunt valve opening pressure settings and MR-ICP were positively correlated (Spearman ρ = 0.64, P < 0.01). Median MR-ICP was 8.67 mm Hg (interquartile range [IQR], 1.59 mm Hg) and median setting of the VP-shunt valve was 6.62 mm Hg (IQR, 1.47 mm Hg). The median MR-ICP was 1.9 mm Hg (IQR, 0.73 mm Hg) higher than the setting of the shunt valve. Conclusion: There is a positive correlation between MR-ICP and VP shunt valve opening pressure setting. The systematically higher assessment of MR-ICP is most likely a result of outflow resistance within the shunt tubing system and well within the known fluctuation rates of VP shunt systems. © 2013 by Lippincott Williams & Wilkins.
PubMed | Helmholtz Center Munich, Innsbruck Medical University, University Utrecht, Swiss Tropical and Public Health Institute and 3 more.
Type: Journal Article | Journal: Allergy | Year: 2016
High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways.DNA from mattress dust and nasal samples of 86 school age children was analyzed by 454 pyrosequencing of the 16S rRNA gene fragments. Based on operational taxonomic units (OTUs), bacterial diversity and composition were related to farm exposure and asthma status.Farm exposure was positively associated with bacterial diversity in mattress dust samples as determined by richness (P = 8.1 10The stronger inverse association of asthma with bacterial diversity in mattress dust as compared to nasal samples suggests microbial involvement beyond mere colonization of the upper airways. Whether inhalation of metabolites of environmental bacteria contributes to this phenomenon should be the focus of future research.
PubMed | Hannover Medical School, Medical University of Graz, Emma Childrens Hospital, University of Mannheim and 11 more.
Type: | Journal: Thorax | Year: 2016
Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort.We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015.Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6months or (1b) before the age of 5years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects.Overall long-term (>5years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.
Peters M.,Ruhr University Bochum |
Kauth M.,Ruhr University Bochum |
Kauth M.,Protectimmun GmbH |
Scherner O.,Protectimmun GmbH |
And 6 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010
Background: Extract from cowshed dust (CDE) is a source of immunomodulating substances. We have previously shown that such substances protect from experimental allergic disorders in a mouse model of asthma. Objective: The objective of this study was to identify immunomodulatory molecules in extracts of dust from an allergy protective farming environment. Methods: Polysaccharides were isolated from CDE and plants by chromatography and precipitation with specific reagents. Polysaccharides were then characterized by nuclear magnetic resonance spectroscopy. Subsequently, the allergy-protective potential of isolated polysaccharides was tested in a mouse model of asthma. Results: The authors demonstrate that plant arabinogalactans are contained in CDE in high concentrations. The source of this arabinogalactan is fodder, in particular a prevalent grass species known as Alopecurus pratensis. Treatment of murine dendritic cells with grass arabinogalactan resulted in autocrine IL-10 production. Interestingly, these dendritic cells were not able to induce an allergic immune response. Furthermore, intranasal application of grass arabinogalactan protected mice from developing atopic sensitization, allergic airway inflammation and airway hyperreactivity in a mouse model of allergic asthma. This allergy-protective effect is specific for grass arabinogalactan because control experiments with arabinogalactan from gum arabic and larch revealed that these molecules do not show allergy-protective properties. This is likely because of structural differences because we were able to show by nuclear magnetic resonance spectroscopy that although they are predominantly composed of arabinose and galactose, the molecules differ in structure. Conclusions: The authors conclude that grass arabinogalactans are important immunomodulatory substances that contribute to the protection from allergic airway inflammation, airway hyperresponsiveness, and atopic sensitization in a mouse model of asthma. © 2010 American Academy of Allergy, Asthma & Immunology.
PubMed | Hospital General Universitario Gregorio Maranon, University of Helsinki, University of Melbourne, Dr von Hauner Childrens Hospital and University of Basel
Type: | Journal: Tuberculosis (Edinburgh, Scotland) | Year: 2016
Recent reports indicate an ongoing BCG shortage that may influence immunisation practice. This study aimed to determine current availability of BCG vaccine across Europe, and implications on immunisation practices and policies in Europe.Web-based survey among Paediatric Tuberculosis Network European Trials Group (ptbnet) members, between May and October 2015.Twenty individuals from 13 European countries participated. Ongoing shortages were reported in eight countries routinely using BCG (8/11, 73%). As a consequence of the shortage, BCG was not given as completely unavailable in some countries (2/8, 25%), was given only whenever available (1/8, 13%), or only in certain regions of the country (1/8, 13%). Strategies reported to reduce loss of immunisation were administration to selected high-risk individuals (2/8, 25%), or cohorting vaccinees on specific days to maximise the use of multi-dose vials (3/8, 38%). Authorities in two countries each were considering a change of manufacturer/supplier (2/8, 25%).The BCG shortage in Europe leads to significant changes in immunisation policies including changes of BCG vaccine strain and manufacturer. In addition, infants and children eligible for immunisation are at risk of not receiving BCG. To ensure necessary BCG immunisations, collaboration between national health agencies and vaccine manufacturers is crucial.
Blaschek A.,Dr Von Hauner Childrens Hospital |
Decke S.,Ludwig Maximilians University of Munich |
Albers L.,Ludwig Maximilians University of Munich |
Schroeder A.S.,Dr Von Hauner Childrens Hospital |
And 8 more authors.
Cephalalgia | Year: 2014
Aim: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. Methods: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. Results: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5% and 9.6%. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95% CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95% CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95% CI 0.87-1.69). Conclusion: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine. © International Headache Society 2014.
Weidlich S.,Dr von Hauner Childrens Hospital |
Bulau A.-M.,Dr von Hauner Childrens Hospital |
Schwerd T.,Dr von Hauner Childrens Hospital |
Althans J.,Dr von Hauner Childrens Hospital |
And 4 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014
OBJECTIVES: The function of interleukin (IL)-37 has not been resolved. We recently showed that IL-37 suppresses colonic inflammation in mice. To gain more insight into its relevance in human disease, we investigated the expression of IL-37 in the intestine of pediatric patients with chronic inflammatory bowel disease (IBD). METHODS: Intestinal biopsies were obtained from children with IBD (18 Crohn disease [CD], 14 ulcerative colitis [UC] and 11 controls) during endoscopy and analyzed for IL-37 expression by immunohistochemistry and real-time polymerase chain reaction. Results were correlated with immunostaining for IL-18 and IL-17, messenger RNA (mRNA) levels of pro- and anti-inflammatory cytokines, and clinical parameters. RESULTS: IL-37 protein was detected in epithelial cells and submucosal lymphoid cells of patients with CD and UC as well as healthy controls. IL-37 protein expression tended to be higher with submucosal lymphoid cell infiltration of patients with CD and UC and correlated with histological severity score of inflammation. IL-18 showed a staining pattern similar to that of IL-37, whereas staining for IL-17 revealed distinct positive cells scattered in the submucosal layer. mRNA expression of IL-8, IL-17, and IL-10 was upregulated in patients with CD and UC. mRNA levels of IL-18 and IL-37 were not significantly elevated compared with controls. Levels of IL-37 and IL-18 mRNA showed a positive correlation in the CD group. CONCLUSIONS: IL-37 protein is expressed in healthy and diseased bowel tissue. IL-37 and IL-18 show a similar expression pattern and correlate at mRNA levels. Future studies are warranted to delineate the specific contribution of IL-37 to modulate chronic bowel inflammation in humans. Copyright © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Grote V.,Dr von Hauner Childrens Hospital |
Theurich M.,Dr von Hauner Childrens Hospital
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014
Purpose of review: This article will summarize recent progress in research in the area of complementary feeding as it relates to childhood obesity. Newly emerged findings demonstrate how research on contributing factors has shifted. Examining nutrient and caloric intakes alone has failed to answer the critical question, 'Why are some children obese, whereas others are not?' Recent research explores parental attitudes, beliefs and parental feeding styles as contributing factors. RECENT FINDINGS: Studies examining the impact of specific macronutrients on obesity risk may have partially uncovered a link between consistently high protein intakes during infancy and an elevated obesity risk, at least until the second year of life. However, this relationship was not evident in all studies evaluated in a systematic review this year. Childhood obesity is not linked to any specific types of foods or food groups during the complementary feeding period. Adherence to dietary guidelines is associated with increased lean body mass, but not BMI or fat mass. Complementary feeding practices, socioeconomic and other family dynamics at least partially explain obesity risk. SUMMARY: As young infants are dependent on adults for nourishment, parental attitudes and beliefs about infant nutrition and actual feeding practices directly influence infant nutritional status. Early nutrition interventions to prevent obesity should take nutrition belief systems, parental feeding styles, socioeconomic and educational status, among other characteristics into consideration. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Langemeier J.,Hannover Medical School |
Schrom E.-M.,University of Würzburg |
Rabner A.,Technion - Israel Institute of Technology |
Radtke M.,Hannover Medical School |
And 10 more authors.
EMBO Journal | Year: 2012
Biallelic mutations in the untranslated regions (UTRs) of mRNAs are rare causes for monogenetic diseases whose mechanisms remain poorly understood. We investigated a 3′UTR mutation resulting in a complex immunodeficiency syndrome caused by decreased mRNA levels of p14/robld3 by a previously unknown mechanism. Here, we show that the mutation creates a functional 5′ splice site (SS) and that its recognition by the spliceosomal component U1 snRNP causes p14 mRNA suppression in the absence of splicing. Histone processing signals are able to rescue p14 expression. Therefore, the mutation interferes only with canonical poly(A)-site 3′ end processing. Our data suggest that U1 snRNP inhibits cleavage or poly(A) site recognition. This is the first description of a 3′UTR mutation that creates a functional 5′SS causative of a monogenetic disease. Moreover, our data endorse the recently described role of U1 snRNP in suppression of intronic poly(A) sites, which is here deleterious for p14 mRNA biogenesis. © 2012 European Molecular Biology Organization.
Gersting S.W.,Dr Von Hauner Childrens Hospital |
Staudigl M.,Dr Von Hauner Childrens Hospital |
Truger M.S.,Dr Von Hauner Childrens Hospital |
Messing D.D.,Dr Von Hauner Childrens Hospital |
And 4 more authors.
Journal of Biological Chemistry | Year: 2010
Protein misfolding with loss-of-function of the enzyme phenylalanine hydroxylase (PAH) is the molecular basis of phenylketonuria in many individuals carrying missense mutations in the PAH gene. PAH is complexly regulated by its substrate L-Phenylalanine and its natural cofactor 6R-L-erythro-5,6,7,8- tetrahydrobiopterin (BH4). Sapropterin dihydrochloride, the synthetic form of BH4, was recently approved as the first pharmacological chaperone to correct the loss-of-function phenotype. However, current knowledge about enzyme function and regulation in the therapeutic setting is scarce. This illustrates the need for comprehensive analyses of steady state kinetics and allostery beyond single residual enzyme activity determinations to retrace the structural impact of missense mutations on the phenylalanine hydroxylating system. Current standard PAH activity assays are either indirect (NADH) or discontinuous due to substrate and product separation before detection. We developed an automated fluorescence-based continuous real-time PAH activity assay that proved to be faster and more efficient but as precise and accurate as standard methods. Wild-type PAH kinetic analyses using the new assay revealed cooperativity of activated PAH toward BH4, a previously unknown finding. Analyses of structurally preactivated variants substantiated BH 4-dependent cooperativity of the activated enzyme that does not rely on the presence of L-Phenylalanine but is determined by activating conformational rearrangements. These findings may have implications for an individualized therapy, as they support the hypothesis that the patient's metabolic state has a more significant effect on the interplay of the drug and the conformation and function of the target protein than currently appreciated. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.