Reutlingen, Germany
Reutlingen, Germany

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Huppke P.,University of Gottingen | Brendel C.,University of Gottingen | Kalscheuer V.,Max Planck Institute for Molecular Genetics | Korenke G.C.,Childrens Hospital | And 16 more authors.
American Journal of Human Genetics | Year: 2012

Low copper and ceruloplasmin in serum are the diagnostic hallmarks for Menkes disease, Wilson disease, and aceruloplasminemia. We report on five patients from four unrelated families with these biochemical findings who presented with a lethal autosomal-recessive syndrome of congenital cataracts, hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous or compound heterozygous mutations for all affected subjects in SLC33A1 encoding a highly conserved acetylCoA transporter (AT-1) required for acetylation of multiple gangliosides and glycoproteins. The mutations were found to cause reduced or absent AT-1 expression and abnormal intracellular localization of the protein. We also showed that AT-1 knockdown in HepG2 cells leads to reduced ceruloplasmin secretion, indicating that the low copper in serum is due to reduced ceruloplasmin levels and is not a sign of copper deficiency. The severity of the phenotype implies an essential role of AT-1 in proper posttranslational modification of numerous proteins, without which normal lens and brain development is interrupted. Furthermore, AT-1 defects are a new and important differential diagnosis in patients with low copper and ceruloplasmin in serum. © 2012 The American Society of Human Genetics.


PubMed | Martha Maria Hospital, Klinikum am Steinenberg, University of Ulm and RWTH Aachen
Type: | Journal: Trials | Year: 2015

The use of a laryngeal mask airway (LMA) in appropriate patients supports fast-track anesthesia with a lower incidence of postoperative airway-connected adverse events. Data on the most favorable anesthetic in this context, with the lowest rate of upper airway complications and fast emergence times, are controversial and limited. Desflurane seems to match these criteria best, but large randomized controlled trials (RCTs) with a standardized study protocol are lacking. Therefore, we aim to compare desflurane with other commonly used anesthetics, sevoflurane and propofol, in a sufficiently powered RCT. We hypothesize that desflurane is noninferior regarding the frequency of upper airway events and superior regarding the emergence times to sevoflurane and propofol.A total of 351 patients undergoing surgery with an LMA will be included in this prospective, randomized, double-blind controlled, multicenter clinical trial. The patients will be randomly assigned to the three treatment arms: desflurane (n = 117), sevoflurane (n = 117), and propofol (n = 117). The emergence time (time to state the date of birth) will be the primary endpoint of this study. The secondary endpoints include further emergence times, such as time to open eyes, to remove LMA, to respond to command and to state name. Additionally, we will determine the frequency of cough and laryngospasm, measured intraoperatively and at emergence. We will assess the postoperative recovery on the first postoperative day via the Postoperative Quality Recovery Scale.Despite increasing importance of cost-effective and safe anesthesia application, we lack proof for the most advantageous anesthetic agent, when an LMA is used. There are only a few RCTs comparing desflurane to other commonly used anesthetics (sevoflurane, propofol and isoflurane) in patients with LMA. These RCTs were conducted with small sample sizes, huge interstudy variability, and some also showed strong biases. The present multicenter RCT will provide results from a large sample size with a standardized study protocol and minimized bias, which is feasible in the clinical routine. Furthermore, we will expand our knowledge regarding the most favorable recovery on the first postoperative day, which impacts patients comfort after surgery.EudraCT Identifier: 2014-003810-96, 5 September 2014 ClinicalTrials.gov: NCT02322502, December 2014.


PubMed | Hopital University Necker Enfants Malades and Insitut, University of Manchester, Copenhagen University, Innsbruck Medical University and 12 more.
Type: Journal Article | Journal: Journal of inherited metabolic disease | Year: 2016

To describe current diagnostic and therapeutic strategies in organic acidurias (OADs) and to evaluate their impact on the disease course allowing harmonisation.Datasets of 567 OAD patients from the E-IMD registry were analysed. The sample includes patients with methylmalonic (MMA, n=164), propionic (PA, n=144) and isovaleric aciduria (IVA, n=83), and glutaric aciduria type 1 (GA1, n=176). Statistical analysis included description and recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. For some analyses, symptomatic patients were divided into those presenting with first symptoms during (i.e. early onset, EO) or after the newborn period (i.e. late onset, LO).Patients identified by newborn screening (NBS) had a significantly lower median age of diagnosis (8days) compared to the LO group (363days, p<0.001], but not compared to the EO group. Of all OAD patients 71% remained asymptomatic until day 8. Patients with cobalamin-nonresponsive MMA (MMA-Cbl(-)) and GA1 identified by NBS were less likely to have movement disorders than those diagnosed by selective screening (MMA-Cbl(-): 10% versus 39%, p=0.002; GA1: 26% versus 73%, p<0.001). For other OADs, the clinical benefit of NBS was less clear. Reported age-adjusted intake of natural protein and calories was significantly higher in LO patients than in EO patients reflecting different disease severities. Variable drug combinations, ranging from 12 in MMA-Cbl(-) to two in isovaleric aciduria, were used for maintenance treatment. The effects of specific metabolic treatment strategies on the health outcomes remain unclear because of the strong influences of age at onset (EO versus LO), diagnostic mode (NBS versus selective screening), and the various treatment combinations used.NBS is an effective intervention to reduce time until diagnosis especially for LO patients and to prevent irreversible cerebral damage in GA1 and MMA-Cbl(-). Huge diversity of therapeutic interventions hampers our understanding of optimal treatment.


PubMed | Northern General Hospital, Alderhey Childrens Hospital, Semmelweis University, Klinikum am Steinenberg and 56 more.
Type: Journal Article | Journal: Molecular genetics and metabolism | Year: 2015

There appears little consensus concerning protein requirements in phenylketonuria (PKU).A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics.The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day).The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.


Haske D.,Red Cross | Schempf B.,Cardiology | Gaier G.,Klinikum am Steinenberg | Niederberger C.,Klinikum am Steinenberg
Resuscitation | Year: 2013

Background: Current cardiopulmonary resuscitation (CPR) guidelines recommend airway management and ventilation whilst minimising interruptions to chest compressions. We have assessed i-gel™ use during CPR. Methods: In an observational study of i-gel™ use during CPR we assessed the ease of i-gel™ insertion, adequacy of ventilation, the presence of a leak during ventilation, and whether ventilation was possible without interrupting chest compressions. Results: We analysed i-gel™ insertion by paramedics (n= 63) and emergency physicians (n= 7) in 70 pre-hospital CPR attempts. There was a 90% first attempt insertion success rate, 7% on the second attempt, and 3% on the third attempt. Insertion was reported as easy in 80% (n= 56), moderately difficult in 16% (n= 11), and difficult in 4% (n= 3). Providers reported no leak on ventilation in 80% (n= 56), a moderate leak in 17% (n= 12), and a major leak with no chest rise in 3% (n= 2). There was a significant association between ease of insertion and the quality of the seal (r= 0.99, p= 0.02). The i-gel™ enabled continuous chest compressions without pauses for ventilation in 74% (n= 52) of CPR attempts. There was no difference in the incidence of leaks on ventilation between patients having continuous chest compressions and patients who had pauses in chest compressions for ventilation (83% versus 72%, p= 0.33, 95% CI [-0.1282, 0.4037]). Ventilation during CPR was adequate during 96% of all CPR attempts. Conclusions: The i-gel™ is an easy supraglottic airway device to insert and enables adequate ventilation during CPR. © 2013 Elsevier Ireland Ltd.


PubMed | University Hospital of Tuebingen and Klinikum am Steinenberg
Type: Case Reports | Journal: The Annals of thoracic surgery | Year: 2015

We herein present a new surgical technique in the treatment of an anomalous left coronary artery from the right coronary sinus in an 18-year-old patient with an intramural course of the left main coronary artery.


Stevanovic A.,RWTH Aachen | Rossaint R.,RWTH Aachen | Fritz H.G.,MarthaMaria Hospital | Froeba G.,University of Ulm | And 4 more authors.
European Journal of Anaesthesiology | Year: 2015

BACKGROUND: Desflurane's short emergence time supports fast track anaesthesia. Data on the rate of upper airway complications and emergence time when desflurane is used with laryngeal mask airway (LMA) are controversial and limited. OBJECTIVES: To compare recovery time variables and the rates of upper airway adverse events in patients with an LMA undergoing general surgery with desflurane, sevoflurane, isoflurane or propofol anaesthesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A systematic search for eligible RCTs in Embase (Elsevier) and in PubMed (National Library of Medicine) databases up to September 2013. ELIGIBILITY CRITERIA: RCTs investigating the rates of cough overall, cough at emergence, laryngospasm, time to eye opening, time to removal of the LMA, time to respond to command and time to state date of birth in patients with an LMA, during emergence from desflurane, sevoflurane, iso-flurane or propofol anaesthesia. RESULTS: Thirteen RCTs were included and analysed. We found a strong interstudy variability. There was no difference in the rates of upper airway events between desflurane and sevoflurane or between desflurane and a control group consisting of all the other anaesthetics combined. Comparing desflurane (n = 284) with all other anaesthetic groups (n = 313), the risk ratio [95% confidence interval (95% CI)] was 1.12 (0.63 to 2.02, P = 0.70). Cough at emergence was only measured in patients receiving desflurane (n = 148) and sevoflurane (n = 146): the risk ratio (95% CI) was 1.49 (0.55 to 4.02, P = 0.43). Laryngospasm was rare and there was no significant difference in its incidence when desflurane (n = 262) was compared with all other anaesthetics combined (n = 289; risk ratio 1.03; 95% CI 0.33 to 3.20, P = 0.96). The times of all emergence variables were significantly faster in the desflurane group than in all other groups. CONCLUSION: When using an LMA, upper airway adverse reactions in association with desflurane anaesthesia were no different from those noted with sevoflurane, isoflurane or propofol anaesthesia. Emergence from general anaesthesia with desflurane is significantly faster than all the other anaesthetics. Due to interstudy variations and the small size of the trials, further large-scale, multicentre studies are required to confirm or refute the results of this meta-analysis. © 2015 Copyright European Society of Anaesthesiology.

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