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Handgretinger R.,University Hospital of Tuebingen
Blood | Year: 2014

In this issue of Blood, Wang et al suggest an algorithm for the selection of the best donor in HLA haplotype-mismatched transplantation of T-replete granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow and peripheral blood stem cells.1 © 2014 by The American Society of Hematology. Source


Poets C.F.,University Hospital of Tuebingen
Sleep Medicine | Year: 2010

Apnea of prematurity (AOP) is a developmental sleep disorder which is yet to be completely understood. Although there is some evidence of brainstem immaturity, there is nothing to suggest that infants with AOP have gross deficits in respiratory control. It appears, however, that the early (and frequent) occurrence of hypoxemia during apnea in preterm infants is related to their low expiratory lung volume, which falls even further during apnea, while the accompanying bradycardia results from this combination of apnea and hypoxemia. Feeding is an important trigger for AOP. While hypoxemia during feeding is most likely related to an immature coordination between sucking, swallowing and breathing and potentially also to an immature laryngeal chemoreflex, hypoxemia after feeding may be caused by diaphragmatic fatigue; gastro-esophageal reflux only rarely plays a role. The time course of AOP, i.e., its increased occurrence during the second and third rather than the first week of life, together with data from physiological studies, also suggests a role for diaphragmatic fatigue. Additional factors include upper airway obstruction, persistence of the fetal response to hypoxia, i.e., ventilatory depression, and the close proximity between the eupneic and apneic CO2 thresholds in neonates. Observational data cannot provide definite answers on cause-and-effect issues but may provide a starting point for further studies into mechanisms involved in AOP and for the development of new therapeutic interventions. First, however, we need to better define how much AOP can be tolerated in an infant without endangering neurodevelopment. © 2010 Elsevier B.V. Source


Handgretinger R.,University Hospital of Tuebingen
Seminars in Oncology | Year: 2012

Haploidentical transplantation opens the possibility to offer this treatment to a large number of patients with an otherwise incurable disease, such as some hematologic or oncologic malignancies, inborn or acquired bone marrow failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Initial attempts at haploidentical transplantation using unmanipulated bone marrow were associated with a high transplant-related mortality. However, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes compared to previous decades. Methods for the in vitro depletion of T lymphocytes from mobilized peripheral blood stem cells (PBSC) to prevent graft-versus-host disease (GvHD) have facilitated the wider use and acceptance of haploidentical transplantation in children and adult patients. Besides in vitro T-cell depletion techniques, other methods, such as the isolation of alloreactive natural killer (NK) cells, virus-specific T lymphocytes, and other effector or regulatory cells are nowadays available to rapidly rebuild the immune system after haploidentical transplantation for the prevention of severe infections or relapses of the underlying diseases. © 2012 Elsevier Inc. All rights reserved. Source


Kuemmerle-Deschner J.B.,University Hospital of Tuebingen
Seminars in Immunopathology | Year: 2015

The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare diseases. CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID), also known as chronic infantile neurologic, cutaneous, and articular (CINCA) syndrome. The clinical phenotype of CAPS is characterized by systemic inflammation. General symptoms are fatigue and fever. Local manifestations affect multiple tissues such as skin, joints, muscles, eyes, and the central nervous system. Distinct clinical features are characteristic for each subphenotype. In FCAS, these are cold-induced urticaria and fever, inMWS systemic amyloidosis and hearing loss and in NOMID/CINCA central nervous system inflammation and bone deformities. CAPS is caused by single heterozygous germline or somatic gain of function mutations in the NLRP3 gene encoding the protein cryopyrin. Cryopyrin nucleates an NLRP3 inflammasome, which regulates the activation and cleavage of caspase-1 that cleaves the pro-inflammatory cytokines, IL-1β and IL-18. IL-1β plays the key role in the induction of inflammation in CAPS. This has been confirmed by the application of IL-1 blocking agents, which lead not only to a rapid and sustained reversal of daily symptoms but also to some extent of long-term disease sequelae. To prevent CAPS-induced organ damage, early diagnosis and swift initiation of effective treatment are mandatory. ©Springer-Verlag Berlin Heidelberg 2015. Source


Rupp F.,University Hospital of Tuebingen
The International journal of oral & maxillofacial implants | Year: 2011

Hydrophilicity is gaining increasing interest as a factor that might influence the osseointegration of dental implants. Therefore, in this study the dynamic wetting behavior of currently marketed dental titanium implants was analyzed by tensiometry, and its relationship to surface topography was examined. Nine screw-type implant systems from eight manufacturers were evaluated. Dynamic water contact angles were analyzed by tensiometric multiloop Wilhelmy experiments (10 loops, 10 mm/min immersion speed). The wetted length (perimeter) of the immersed samples was estimated by three-dimensional picture profile measurement of the thread height of the respective implant screws. Wettability was quantified by first advancing contact angles. Additionally, static contact angles were determined using the sessile drop technique. All implant surfaces were characterized by scanning electron microscopy (SEM). Contact angle data were subjected to one-way analysis of variance followed by the Student t test. SEM revealed different types of surface morphology resulting from the different manufacturing processes. The first advancing mean contact angles of all implants ranged from 0 degrees (SLActive) to 138 degrees (OsseoSpeed), demonstrating statistically significant differences between implants. Because of kinetic hysteresis, initially hydrophobic implants became hydrophilic during following immersion loops. The tensiometric method was used to compare wettability of dental implants. A range from fully wettable/superhydrophilic to virtually unwettable/hydrophobic was observed on the implant surfaces examined. Source

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