3.10 Department of Pediatrics

CONTACT DETAILS
3.10
Department of Pediatrics
Professor Dr. med. Christian P. Speer
FRCP (Edin.)
(Head of the Department)
Josef-Schneider-Straße 2
97080 Würzburg
Tel.: 0931/201-27830
Fax: 0931/201-27833
E-mail: [email protected].
de
www.kinderklinik.uni-wuerzburg.de
Professor Dr. med. Matthias Eyrich
Tel.: 0931/201-27620
Professor Dr. med. Helge Hebestreit
Tel.: 0931/201-27889
Professor Dr. med. Johannes Liese, MSc
Tel.: 0931/201-27731
Professor Dr. med. Martina Prelog, MSc
Tel. 0931/201-27708
Professor Dr. med. Paul-Gerhardt Schlegel
Tel.: 0931/201-27888
Mission and
Structure
The Children’s Hospital of the University
of Würzburg (staff: 64 MD’s, 163 nurses,
45 technicians / administrative staff) comprises 115 beds including a pediatric-neonatal intensive care unit and a neonatal
intensive care unit in the perinatal centre
(obstetrics and gynecology). The Children’s
Hospital is divided into the following functional sections: neonatology, pediatric intensive care, oncology / hematology / stem cell
therapy, cardiology, pulmonology / cystic fibrosis / sports medicine, gastroenterology,
nephrology, endocrinology, diabetes, neuropediatrics / social pediatrics, immunology /
infectiology, rheumatology, and others. Every year approximately 6500 patient in the
inpatient and 15000 patients in the outpatient setting are being treated. There are
many close collaborations to the other institutions of the university hospital.
Major Research
Interests
Neonatology:
Characterization of airway remodeling
in acute and chronic lung disease of
premature infants and newborns
Very premature infants are at increased
risk for acute and chronic morbidity. Likewise mortality is increased. New data indicate
that a pulmonary or systemic inflammation
may already start prior to birth and is perpetuated during the intensive care after birth.
Among other projects, studies are conducted to analyze the influence of prenatal inflammation on the development of regulatory T-lymphocytes in the fetal thymus as
well as the pathomechanisms leading to an
inflammatory or pro-fibrotic reaction in the
lungs. Other studies focus on the molecular
events leading to airway remodeling in bronchopulmonary dysplasia (BPD). Specifically we are interested in the regulation and
association of TGFß and connective tissue
growth factor in BPD.
Pediatric Oncology, Hematology and
Stem cell transplantation:
Cellular immunity and immunmodulation in patients with malignant diseases
The immune system is capable to destroy
residual tumor cells after chemotherapy or
stem cell transplantation. We analyzed the
T-cell function in patients with leukemia or
brain tumors and were able to correlate the
findings with disease outcome. For the first
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time, we were able to show an association
of a favorable cytokine profile with disease
outcome in medulloblastoma patients. Furthermore preclinical concepts are being developed to reduce the difficult phase of aplasia after allogeneic bone marrow transplantation.
Moreover requirements for efficient T-cell
priming is analyzed in a robust, antigenspecific in vitro model and the influence of
immune response modifiers is studied.
We strive to develop new immunotherapies
for patients with malignant diseases (dendritic cell vaccination, antigen-specific Tcells, Fig.1), and – in collaboration with the
Comprehensive Cancer Center Mainfranken
– aim to implement these techniques in clinical studies.
Pediatric Infectiology
Epidemiology and prevention of pediatric infectious diseases
In several studies, the effects of vaccination
programs on the epidemiology of infectious
diseases and their acceptance are evaluated in children and adolescents. Regional
surveillance programs have been established in close cooperation with pediatricians
in private practices and pediatric hospitals
( e.g. “Bavarian Varicella Project” (BaVariPro)). Other studies in close collaboration
with the institutes of virology in Jena and
Würzburg, as well as with national reference
centers (Aachen, Würzburg) aim to identify
and type certain pathogens to identify changes (e.g. pneumococcal serotype replacement) under vaccination pressure.
Osteology:
Hypophosphatasia – pathophysiology
and new treatment options
Hypophosphatasia is a rare disease of the
bone characterized by reduced phosphata-
Fig. 1: Melan-A-specific T-cells induce
apoptosis in tumor cells. Caspase-3 activation in tumor cells after T-cell contact
(4h) is beeing displayed (400 000 T-lymphocytes for 20 000 tumor cells). Such
clear activation of caspase 3 is a clear
sign for the induction of apoptotic cell
death in the tumor cells.
se. Bone mineralisation, renal function and
possibly CNS function are impaired. Our interdisciplinary team (Children’s Hospital/Orthopedic Center for musculoskeletal Research) provides patient care for the largest
patient cohort throughout Europe.
Research projects range from pathophysiology to preclinical treatment approaches (gene
transfer). An international phase II study for
enzyme replacement was initiated in 2011.
Pediatric rheumatology:
Pathogenesis of rheumatoid and chronic-inflammatory diseases
Altered T-cell homeostasis is characteristic for autoimmune diseases. We evaluate
changes in T-cell subsets, specifically proinflammatory Th17 T-cells and regulatory
T-cells in these patients. Moreover the influence of latent infections with herpes viruses, such as the cytomegalovirus, on Tcell homeostasis and effector effector functions is analyzed.
We also cooperate with the Center for musculosceletal research to study the interaction between mesenchymal stem cells and
T-cells in patients with rheumatoid arthritis.
Pediatric pulmonology, cystic fibrosis
and sports medicine:
Exercise and physical training in healthy
children and in children with chronic pulmonary diseases
Several studies evaluate the pathophysiology of the reduced exercise capacity in patients with cystic fibrosis or former BPD. In
close collaboration with the Department of
Pediatric Radiology (Prof. Dr. M. Beer), we
could describe the turnover of energy-rich
phosphates in skeletal muscle during exercise as well as the pulmonary ventilation
and perfusion using MRI techniques (Fig.
2). Another project focused on the exerciseinduced release of mesenchymal stem cells
possibly involved in pulmonary repair mechanism.
A study sponsored by the BMBF evaluated the preventive effects of a physical
activity program in a Kindergarten setting.
The program proofed to be feasible and
effective, and is now being implemented
nationwide in collaboration with the Barmer GEK. With another partner, the Deutsche Lehrerbildungsinstitut Alexander von
Humbold, the program will also be established in Chile. Other studies analyze the
influence of special outdoor equipment
(“Aktivschiff”) in two preschools on activity behavior and motor skills of preschool kids.
Teaching
The Children’s Hospital of the University
of Würzburg offers several courses for me-
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SELECTED PUBLICATIONS
Fig. 2: Colour-coded images of pulmonary T1-relaxation times (MRI, 0.2 Tesla) from
3 children at school age, a former preterm neonate with bronchopulmonary dysplasia
(BPD), a former preterm neonate without BPD (FG), and a healthy child born at term
(Kontrolle). Upper panel: Values obtained when breathing room air. Middle panels: Values with pure oxygen. Lower panel: Differences in the T1-relaxation times (∆T1) are lower in the child with former BPD than in the other children indicating impaired regional
pulmonary function. (Images provided by Prof. Dr. M. Beer).
dical students. Students have repeatedly
evaluated the main lecture in pediatrics regularly as one of the best courses in the
faculty of medicine. Prof. Dr. C. P. Speer is
authorized to fully train MDs in pediatrics,
as well as in neonatology and pediatric intensive care. The heads of the sections for
pediatric haematolog and oncology, neuropediatrics, and pediatric pulmonology are
qualified to train MDs in their respective
subspecialties. The Children’s Hospital organizes regularly clinical rounds and educational seminars for pediatricians on a regional and national level. In addition, every
year scientific meetings and symposia are
organized in Würzburg, e.g. every 3rd year
the international symposium “Recent Advances in Neonatal Medicine“ with participants from more than 50 nations. Outside
of the United States of America this symposium represents the largest scientific forum for neonatology.
Hebestreit H, Kieser S, Junge S, Ballmann
M, Hebestreit A, Schindler C, Schenk T,
Posselt HG, Kriemler S. (2010) Long-term
effects of a partially supervised conditioning programme in cystic fibrosis. Eur Respir J 35:578-83.
Kunzmann S, Collins JJ, Yang Y, Uhlig S,
Kallapur S, Speer CP, Jobe AH, Kramer
BW. (2011) Antenatal inflammation reduces Cav-1 expression and influences multiple signaling pathways in preterm fetal
lungs. Am J Respir Cell Mol Biol 45:96976.
Mentrup B, Marschall C, Barvencik F, Amling M, Jakob F, Beck C. (2011) Functional characterization of a novel mutation
localized in the start codon of the tissuenonspecific alkaline phosphatase gene.
Bone 48:1401-8.
Morbach H, Wiegering V, Richl P, Schwarz
T, Suffa N, Eichhorn EM, Eyrich M, Girschick HJ. (2011) Activated memory B
cells may function as antigen presenting
cells in the joints of children with juvenile idiopathic arthritis. Arthritis Rheum
63:3458-66.
Wölfl M, Merker K, Morbach H, Van Gool
SW, Eyrich M, Greenberg PD, Schlegel PG.
(2011) Primed tumor-reactive multifunctional CD62L+ human CD8+ T-cells for
immunotherapy. Cancer Immunol Immunother 60:173-86.