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Konstanz, Germany

Pfeffer S.,University of Stuttgart | Maier T.,University of Stuttgart | Stricker E.,University Hospital of Tuebingen | Rall M.,University Hospital of Tuebingen | Trick M.,Klinikum Konstanz
Biomedizinische Technik | Year: 2012

The anesthesia workplace can be regarded as a complex human-machine-system (HMS). In this information-intensive "cockpit" the operator has to handle several devices. Not only visual but also auditory cues have to be integrated in the action-control-loop. It's obvious that in some stressful and complex situations, a perceptual and cognitive overloading of the anesthetist could occur and therefor inhibit an efficient and save interaction. The design of the interfaces and the form of information presentation has a significant impact on these aspects. The contribution presents the possibilities of the new methodical approach "iFlow Analysis" (information-flow) to observe cognitive ergonomics and informatory load in such HMS. In our exemplary observation we used an eyetrackingsystem to evaluate the user interactions in a simulated scenario and in a field (thyroidectomy and exploratory laparotomy) situation. All incoming visual and auditory signals were observed during the procedure of anesthetic guidance. The interactions have been integrated in the so called iFlow Chart to evaluate the density of information presentation. In addition informatory load has been measured by the dynamic changes of pupil size. © 2012 by Walter de Gruyter Berlin Boston.

Czekelius P.,Klinikum Konstanz | Wenzel H.,Independent Health Economic Consultant
Zeitschrift fur Geburtshilfe und Neonatologie | Year: 2016

Introduction: Crowther et al. 3 analysed the effectivity of magnesium tocolysis in preventing preterm birth. They conclude that there is no evidence for protection. In its latest guidelines, based on this Cochrane analysis, the German Association of Gynaecology and Obstetrics (DGGG) does not recommend any more the use of magnesium for tocolysis. Magnesium tocolysis is said neither to delay nor to prevent preterm birth. Moreover, magnesium could be responsible for increased mortality in infants. These conclusions are mostly based on the research of Mittendorf et al. 4. In a Cochrane study from 2014, which in principal was identical to the study mentioned above 3, Crowther et al. 6 confirm the previous findings and conclusions. Method: Having successfully applied magnesium tocolysis for many years, these surprising conclusions led us to review the soundness of the publications mentioned above. Combining the practical experience of many years with the results of a comprehensive literature retrieval, we finally contrasted this knowledge with the findings of the aforementioned publications that caused the DGGG to withdraw the recommendation for magnesium. Results: To draw binding consequences from a meta-analysis is possible only when stringent quality guidelines are observed. The studies that were included in the Cochrane review of Crowther et al. 3 are very heterogeneous and are not suitable for concluding on poor or even lacking effectiveness of magnesium tocolysis. Furthermore, the cases of infant deaths, as stated by Mittendorf et al. 4, are very unlikely caused by magnesium. Conclusion: When including studies in a meta-analysis special attention has to be given to the relevance and unbiased selection of studies. To prevent any misjudgment, a thorough knowledge of the included studies seems essentiell. There is not sufficient evidence to withdraw the recommendation for applying magnesium tocolysis as a preventive measure to prevent preterm birth. In the sense of evidence-based medicine, long-standing, scientifically proven therapeutic success should be incorporated into the meta-analysis as well. © Georg Thieme Verlag KG.

Bruckner M.,University of Konstanz | Dickel D.,University of Konstanz | Singer E.,Klinikum Konstanz | Legler D.F.,University of Konstanz
European Journal of Immunology | Year: 2012

Migration and homing of DCs to lymphoid organs is pivotal for inducing adaptive immunity and tolerance. DC homing depends on the chemokine receptor CCR7. However, expression of CCR7 alone is not sufficient for effective DC migration. A second signal, mediated by prostaglandin E2 (PGE2), is critical for the development of a migratory DC phenotype. PGE2 is important for inducing efficient immune responses, but, if deregulated, contributes to chronic inflammation, autoimmune diseases through Th17-cell development and tumorigenesis. In contrast, activation of liver X receptor (LXR)α has recently been shown to interfere with CCR7 expression and migration of DCs resulting in a reduced immune response. Here, we demonstrate that PGE2 downregulates LXRα expression in human monocyte derived as well as ex vivo DCs. Moreover, PGE2 stimulation dampens LXR activation, auto-regulation and LXR-mediated gene transcription. Consequently, we show that PGE2 enhances CCR7 expression and migration of LXR-activated DCs. Furthermore, we provide evidence that PGE2 signaling and LXR activation specifically elicit converse effects on CCR7 expression and DC migration. In contrast, production of MMP9, CCL4, COX-2, and IL-23 is solely regulated by PGE2, but not by LXR activation, offering new perspectives for therapeutic interventions. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hauser M.A.,University of Konstanz | Kindinger I.,University of Konstanz | Laufer J.M.,University of Konstanz | Spate A.-K.,University of Konstanz | And 5 more authors.
Journal of Leukocyte Biology | Year: 2016

The homeostatic chemokines CCL19 and CCL21 and their common cognate chemokine receptor CCR7 orchestrate immune cell trafficking by eliciting distinct signaling pathways. Here, we demonstrate that human CCR7 is N-glycosylated on 2 specific residues in the N terminus and the third extracellular loop. Conceptually, CCR7 glycosylation adds steric hindrance to the receptor N terminus and extracellular loop 3, acting as a "swinging door" to regulate receptor sensitivity and cell migration. We found that freshly isolated human B cells, as well as expanded T cells, but not naïve T cells, express highly sialylated CCR7. Moreover, we identified that human dendritic cells imprint T cell migration toward CCR7 ligands by secreting enzymes that deglycosylate CCR7, thereby boosting CCR7 signaling on T cells, permitting enhanced T cell locomotion, while simultaneously decreasing receptor endocytosis. In addition, dendritic cells proteolytically convert immobilized CCL21 to a soluble form that is more potent in triggering chemotactic movement and does not desensitize the receptor. Furthermore, we demonstrate that soluble CCL21 functionally resembles neither the CCL19 nor the CCL21 phenotype but acts as a chemokine with unique features. Thus, we advance the concept of dendritic celldependent generation of micromilieus and lymph node conditioning by demonstrating a novel layer of CCR7 regulation through CCR7 sialylation. In summary, we demonstrate that leukocyte subsets express distinct patterns of CCR7 sialylation that contribute to receptor signaling and fine-tuning chemotactic responses. © Society for Leukocyte Biology.

Karges B.,RWTH Aachen | Rosenbauer J.,Heinrich Heine University Dusseldorf | Holterhus P.-M.,University of Kiel | Beyer P.,Evangelisches Krankenhaus Oberhausen | And 7 more authors.
European Journal of Endocrinology | Year: 2015

Objective: To investigate rates and risk factors of hospital admission for diabetic ketoacidosis (DKA) or severe hypoglycemia in young patients with established type 1 diabetes. Design: In total, 31 330 patients with type 1 diabetes (median age 12.7 years) from the Diabetes Patienten Verlaufsdokumentation (DPV) Prospective Diabetes Registry treated between 2011 and 2013 in Germany were included. Methods: Admission rates for DKA (pH<7.3 or bicarbonate <15 mmol/l) and severe hypoglycemia (requiring assistance from another person) were calculated by negative binomial regression analysis. Associations of DKA or hypoglycemia with patient and treatment characteristics were assessed by multivariable regression analysis. Results: The mean admission rate for DKA was 4.81/100 patient-years (95% CI, 4.51-5.14). The highest DKA rates were observed in patients with HbA1c ≥9.0% (15.83 (14.44-17.36)), age 15-20 years (6.21 (5.61-6.88)) and diabetes duration of 2-4.9 years (5.60 (5.00-6.27)). DKA rate was higher in girls than in boys (5.35 (4.88-5.86) vs 4.34 (3.95-4.77), PZ0.002), and more frequent in migrants than in non-migrants (5.65 (4.92-6.49) vs 4.57 (4.23-4.93), PZ0.008). The mean admission rate for severe hypoglycemia was 1.45/100 patient-years (1.30-1.61). Rates were higher in migrants compared to non-migrants (2.13 (1.72-2.65) vs 1.28 (1.12-1.47), P<0.001), and highest in individuals with severe hypoglycemia within the preceding year (17.69 (15.63-20.03) vs patients without preceding hypoglycemia 0.42 (0.35-0.52), P<0.001). Differences remained significant after multivariable adjustment. Conclusions: The identification of at-risk individuals for DKA (patients with high HbA1c, longer diabetes duration, adolescents, girls) and for severe hypoglycemia (patients with preceding severe hypoglycemia, migrants) may facilitate targeted diabetes counselling in order to prevent these complications. © 2015 The authors.

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