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Demmert M.,University of Lübeck | Schaper A.,University of Lübeck | Pagel J.,University of Lübeck | Gebauer C.,University of Leipzig | And 11 more authors.
Pediatric Research | Year: 2015

Background:To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants.Methods:We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death.Results:Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model.Conclusion:This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants. © 2015 International Pediatric Research Foundation, Inc.


Fiegl M.,Ludwig Maximilians University of Munich | Unterhalt M.,Ludwig Maximilians University of Munich | Kern W.,MLL Munich Leukemia Laboratory | Braess J.,Klinikum Barmherzige Bruder | And 15 more authors.
Leukemia | Year: 2014

Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m 2 bid, days 1-2 and 8-9 (3 g/m 2 for patients ≤60 years with refractory AML or ≥2nd relapse); idarubicin 10 mg/m 2 daily, days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine, 15 mg/m 2, 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic stem cell transplantation, with a significantly higher number of patients in CR or incomplete remission in the F-SHAI group (22 vs 10%, P<0.01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML. © 2014 Macmillan Publishers Limited. All rights reserved.


Burkhardt R.,Kassenarztliche Vereinigung Niedersachen | Pankow W.,Vivantes Klinikum Berlin Neukolln
Pneumologie | Year: 2016

In general chronic obstructive pulmonary disease (COPD) can be diagnosed in family practice from history and spirometry. Inconclusive spirometry findings have to be assessed further by techniques available in a pulmonologist's office. Further testing is done for differential diagnostic reasons and for prognostic appraisal. Successful smoking cessation importantly alters the natural downhill course of the disease. Patient education and rehabilitative interventions (e. g. participation in lung sport groups) help to improve life quality. Medical therapies with bronchospasmolytics applied by inhalation as monotherapies, free and fixed combinations have symptomatic benefit. Considering the increase of pneumonia risk from inhaled corticosteroids their use should be restricted to patients with a straightforward indication, e. g. coexisting asthma. © Georg Thieme Verlag KG Stuttgart. New York.


Ciarimboli G.,Universitatsklinikum Munster | Holle S.K.,Universitatsklinikum Munster | Vollenbrocker B.,Universitatsklinikum Munster | Hagos Y.,University of Gottingen | And 8 more authors.
Molecular Pharmaceutics | Year: 2011

Anticancer treatment with ifosfamide but not with its structural isomer cyclophosphamide is associated with development of renal Fanconi syndrome leading to diminished growth in children and bone problems in adults. Since both cytotoxics share the same principal metabolites, we investigated whether a specific renal uptake of ifosfamide is the basis for this differential effect. First we studied the interaction of these cytotoxics using cells transfected with organic anion or cation transporters and freshly isolated murine and human proximal tubules with appropriate tracers. Next we determined changes in membrane voltage in proximal tubular cells to understand their differentiated nephrotoxicity. Ifosfamide but not cyclophosphamide was significantly transported into cells expressing human organic cation transporter 2 (hOCT2) while both did not interact with organic anion transporters. This points toward a specific interaction of ifosfamide with hOCT2, which is the main OCT isoform in human kidney. In isolated human proximal tubules ifosfamide also interacted with organic cation transport. This interaction was also seen in isolated mouse proximal tubules; however, it was absent in tubules from OCT-deficient mice, illustrating the biological importance of this selective transport. Ifosfamide decreased the viability of cells expressing hOCT2, but not that of control cells. Coadministration of cimetidine, a known competitive substrate of hOCT2, completely prevented this ifosfamide-induced toxicity. Finally, ifosfamide but not cyclophosphamide depolarized proximal tubular cells. We propose that the nephrotoxicity of ifosfamide is due to its selective uptake by hOCT2 into renal proximal tubular cells, and that coadministration of cimetidine may be used to prevent ifosfamide-induced nephrotoxicity. © 2011 American Chemical Society.


Reichert J.,Universitatsklinikum Carl Gustav Carus | Eulerich-Gyamerah S.,University Hospital of Tuebingen | Poets C.,University Hospital of Tuebingen | Kribs A.,Universitatsklinikum Cologne | And 6 more authors.
Monatsschrift fur Kinderheilkunde | Year: 2014

Approximately 8.8 % of all newborn infants are born before 37 weeks of gestational age and are defined as preterm infants. For preterm infants the length of the initial stay in the neonatal intensive care unit (NICU) can last from weeks to months. Nowadays, medical treatment is focused on the neurological development which is affected not only by the physiological extrauterine environment but also by separation of mother and child during NICU treatment. Therefore, new care concepts encompass the optimal medical care of the infant as well as the best support for the whole family. The parents become the primary caregivers of their infant and are responsible for the development from the very beginning. Moreover, they need consultation, training and individualized discharge planning. Characteristics of structure and process of psychological sociomedical care for families of premature and ill, mature newborn children are described by a complex care model. © 2014, Springer-Verlag Berlin Heidelberg.


PubMed | University of Leipzig, University of Cologne, Klinikum Kassel, Krankenhaus Barmherzige Bruder St. Hedwig and 6 more.
Type: Journal Article | Journal: Pediatric research | Year: 2015

To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants.We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death.Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs.14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model.This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants.


PubMed | Vivantes Klinikum Berlin Neukolln and Kassenarztliche Vereinigung Niedersachen
Type: Journal Article | Journal: Pneumologie (Stuttgart, Germany) | Year: 2016

In general chronic obstructive pulmonary disease (COPD) can be diagnosed in family practice from history and spirometry. Inconclusive spirometry findings have to be assessed further by techniques available in a pulmonologists office. Further testing is done for differential diagnostic reasons and for prognostic appraisal. Successful smoking cessation importantly alters the natural downhill course of the disease. Patient education and rehabilitative interventions (e. g. participation in lung sport groups) help to improve life quality. Medical therapies with bronchospasmolytics applied by inhalation as monotherapies, free and fixed combinations have symptomatic benefit. Considering the increase of pneumonia risk from inhaled corticosteroids their use should be restricted to patients with a straightforward indication, e.g. coexisting asthma.

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