Publications by authors named "Petra Degenhardt"

12 Publications

  • Page 1 of 1

Human exome and mouse embryonic expression data implicate ZFHX3, TRPS1, and CHD7 in human esophageal atresia.

PLoS One 2020 5;15(6):e0234246. Epub 2020 Jun 5.

Institute of Human Genetics, Medical Faculty of Bonn, University of Bonn, Bonn, Germany.

Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.

Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.

Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.

Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234246PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274392PMC
August 2020

Pulmonary outcome of esophageal atresia patients and its potential causes in early childhood.

J Pediatr Surg 2017 Aug 3;52(8):1255-1259. Epub 2017 Jan 3.

Charité Universitaetsmedizin Berlin, Department of Pediatric Surgery, Augustenburger Platz 1, 13353 Berlin; Klinikum Ernst von Bergmann, Department of Pediatric Surgery, Charlottenstrasse 72, 14467 Potsdam.

Introduction: The aim of this study was to illustrate the pulmonary long term outcome of patients with repaired esophageal atresia and to further examine causes and correlations that might have led to this outcome.

Methods: Twenty-seven of 62 possible patients (43%) aged 5-20years, with repaired esophageal atresia were recruited. Body plethysmography and spirometry were performed to evaluate lung function, and the Bruce protocol treadmill exercise test to assess physical fitness. Results were correlated to conditions such as interpouch distance, gastroesophageal reflux or duration of post-operative mechanical ventilation.

Results: Seventeen participants (63%) showed abnormal lung function at rest or after exercise. Restrictive ventilatory defects (solely restrictive or combined) were found in 11 participants (41%), and obstructive ventilatory defects (solely obstructive or combined) in 13 subjects (48%). Twenty-two participants (81%) performed the Bruce protocol treadmill exercise test to standard. The treadmill exercise results were expressed in z-score and revealed to be significantly below the standard population mean (z-score=-1.40). Moreover, significant correlations between restrictive ventilatory defects and the interpouch distance; duration of post-operative ventilation; gastroesophageal reflux disease; plus recurrent aspiration pneumonia during infancy; were described.

Conclusion: It was shown that esophageal atresia and associated early complications have significant impact on pulmonary long term outcomes such as abnormal lung function and, in particular restrictive ventilatory defects. Long-running and regular follow-ups of patients with congenital esophageal atresia are necessary in order to detect and react to the development and progression of associated complications such as ventilation disorders or gastroesophageal reflux disease.

Level Of Evidence: Prognosis study, Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.12.025DOI Listing
August 2017

Reduced Microvascular Density in Omental Biopsies of Children with Chronic Kidney Disease.

PLoS One 2016 15;11(11):e0166050. Epub 2016 Nov 15.

Department of Pediatric Nephrology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.

Patients And Methods: Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.

Results: Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).

Conclusions: Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166050PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113061PMC
June 2017

Postnatal lung function in congenital cystic adenomatoid malformation of the lung.

Ann Thorac Surg 2015 Apr 14;99(4):1164-9. Epub 2015 Feb 14.

Department of Neonatology, Charité University Medical Centre, Berlin, Germany.

Background: Management of prenatally diagnosed but postnatal asymptomatic pulmonary lesions remains controversial. The aim of this study was to investigate the effect of congenital cystic adenomatoid malformation of the lung (CCAM) on postnatal lung function tests (LFT) and to elucidate whether LFTs help identify infants who would benefit from early surgery.

Methods: The LFTs were performed in 26 CCAM infants at a median (interquartile range) postmenstrual age of 42.4 (39.6 to 44.0) weeks and compared with LFT from 30 healthy controls. The LFT included the measurement of tidal breathing, functional residual capacity by body plethysmography, respiratory mechanics (respiratory compliance), and respiratory resistance by occlusion test and blood gas analysis.

Results: The CCAM infants showed a restrictive ventilation disorder with increased respiratory rates (p = 0.006) and marginally decreased tidal volumes (p = 0.043). Furthermore, respiratory compliance was significantly reduced as compared with controls (p < 0.001). No statistically significant differences were seen in the respiratory resistance, functional residual capacity, and capillary blood gases. Particularly in CCAM infants who had surgery in the first 2 years of life, a marked reduction of respiratory compliance (p < 0.001) was seen preoperatively.

Conclusions: Congenital cystic adenomatoid malformation can cause restrictive ventilation disorders, which can be detected and monitored by postnatal LFT. Thus, LFT represents an additional tool to support the decision for or against surgical intervention.
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http://dx.doi.org/10.1016/j.athoracsur.2014.11.018DOI Listing
April 2015

The expression of vascular endothelial growth factor and its receptors in congenital bronchopulmonary cystic malformations.

Eur J Pediatr Surg 2012 Apr 19;22(2):127-32. Epub 2012 Apr 19.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) represent rare hamartomatous abnormalities of the lung. Dysregulation of cytokines that influence pulmonary vasculogenesis and epithelial growth, both known to be altered in BPS and CCAM, may play a role in their pathogenesis.

Objective: We hypothesized that expression of vascular endothelial growth factor (VEGF) or its receptors might be altered in CCAM and BPS, possibly distinguishing CCAM from BPS, or from controls.

Methods: Lung biopsy specimens obtained from infants who had undergone surgery for BPS (n = 4) or CCAM (n = 5) within the first month of life and normal lung autopsy samples (n = 4) serving as controls were investigated immunohistochemically for the protein expression levels of VEGF and its corresponding receptors.

Results: VEGF, vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor receptor 3 (VEGFR3) staining was detected in CCAM and BPS specimens, as well as in control samples. VEGFR2 expression increased from controls to CCAM and from CCAM to BPS, the difference between controls and BPS being significant. The expression of VEGF, VEGFR1, and VEGFR3 was similar among the three groups. Consistent with a possible involvement of VEGFR2 in altered vasculogenesis-bronchiogenesis interaction, its expression was predominantly found in bronchial but not alveolar regions.

Conclusions: The data suggest a possible role of VEGF-VEGFR2 interaction in the pathogenesis of congenital bronchopulmonary cystic malformations. However, VEGFR2 does not represent a suitable histochemical marker to distinguish between BPS and CCAM.
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http://dx.doi.org/10.1055/s-0032-1308692DOI Listing
April 2012

Prenatal two- and three-dimensional imaging in two cases of severe penoscrotal hypospadias.

J Clin Ultrasound 2011 Nov-Dec;39(9):539-43. Epub 2011 May 2.

Department of Obstetrics, Charité University Hospital, Berlin, Germany.

We present the prenatal two- and three-dimensional (3D) ultrasound (US) findings in two cases of severe penoscrotal hypospadias. 3D sonography was used for better definition of ambiguous genitalia. The images were compared with postnatal clinical features. Despite hypospadias being the most common urogenital anomaly of male neonates, the diagnosis is often missed before birth. Performing prenatal ultrasound should include the study of genitals, not only determining the sex.
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http://dx.doi.org/10.1002/jcu.20832DOI Listing
February 2012

Resolution of opioid-induced postoperative ileus in a newborn infant after methylnaltrexone.

J Pediatr Surg 2011 Mar;46(3):e13-5

Department of Neonatology, Charité University Medical Center, Berlin, Germany.

Transient impairment of bowel function is a frequent and distressing problem in neonates on opioid-induced analgesia. Methylnaltrexone, a peripheral-acting μ-opioid receptor antagonist, has been studied in adults for the treatment of opioid-induced constipation in advanced illness and has been suggested as a promising therapeutic concept for reducing postoperative ileus. Here, we report on a newborn infant on fentanyl analgesia after major abdominal surgery with aggravated ileus. After 8 days of quiescent bowel, the patient's intestinal dysmotility resolved within 15 minutes after intravenous administration of methylnaltrexone (0.15 mg/kg body weight). Methylnatrexone was repeated daily until cessation of fentanyl administration. There were no signs of pain or opioid withdrawal.
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http://dx.doi.org/10.1016/j.jpedsurg.2010.10.015DOI Listing
March 2011

Impaired somatic growth and delayed lung development in infants with congenital diaphragmatic hernia--evidence from a 10-year, single center prospective follow-up study.

J Pediatr Surg 2009 Jul;44(7):1309-14

Department of Neonatology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.

Purpose: In infants with congenital diaphragmatic hernia (CDH), somatic growth and pulmonary development are key issues beyond the time of intensive care treatment. The aim of the study was to investigate the somatic growth and pulmonary function after discharge and to compare CDH patients with a group of matched controls.

Methods: Anthropometric measurements and lung function tests were performed in 26 infants after surgical repair of CDH and 26 non-CDH intensive care patients, matched for gestational age and birth weight. Spontaneously breathing infants were tested at a mean of 44 weeks postconceptional age (range, 36-58 weeks). Body weight, body length, respiratory rate (RR), tidal volume (V(T)), functional residual capacity by body plethysmography (FRC(pleth)), respiratory compliance (C(rs)), and respiratory resistance (R(rs)) were measured.

Results: The mean (SD) weight gain per week in the CDH infants was significantly lower compared to non-CDH infants (89 [39] g vs 141 [49] g; P = .002). The breathing pattern between both groups differed considerably. In CDH infants, V(T) was significantly lower (P < .001) and RR significantly higher (P = .005). The respiratory compliance was also significantly (P < .001) reduced, whereas R(rs) did not differ significantly. No statistically significant differences were seen in FRC(pleth) related to the body weight between CDH and non-CDH infants (20.3 [4.4] mL/kg vs 21.5 [4.9] mL/kg).

Conclusion: Despite apparently well-inflated lungs after surgery, evidence of early and significantly reduced weight gain and impaired lung function in CHD patients should prompt careful dietary monitoring and regular lung function testing.
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http://dx.doi.org/10.1016/j.jpedsurg.2008.10.047DOI Listing
July 2009

[Emergencies in pediatric traumatology--fractures in the growing age and pediatric polytrauma].

Anasthesiol Intensivmed Notfallmed Schmerzther 2009 Jun 12;44(6):445-9; quiz 450. Epub 2009 Jun 12.

Klinik und Poliklinik für Kinderchirurgie, Charité - Universitätsmedizin Berlin.

Deep knowledge of characteristic features of the growing skeleton is necessary for effective treatment of fractures in the pediatric population. The first part of emergency treatment of pediatric fractures involves immobilisation and appropriate pain management. In addition reduction of the fracture, either open or closed, with or without internal or external fixation are further treatment options used by the experienced pediatric surgeon. Generally, the principles of therapy of pediatric polytrauma are similar to the management of trauma in adults (ATLS). Nonetheless, attention must be paid to anatomical and physiological differences especially between young children and adults.
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http://dx.doi.org/10.1055/s-0029-1225754DOI Listing
June 2009

A complex congenital anomaly: liver eventration because of intrathoracic rib and vertebral segmentation disorder--a case report.

J Pediatr Surg 2008 Jun;43(6):E5-7

Clinic of Pediatric Surgery, Charité-Campus Virchow-Hospital, Humboldt-University, Berlin 13353, Germany.

The complicated processes of chest development and differentiation frequently lead to malformations of the ribs and vertebrae. An intrathoracic rib is a rare anomaly. We report here, for the first time, a complex congenital malformation with liver eventration because of a right intrathoracic rib and vertebral segmentation disorder of the spine in a 7-year-old girl without respiratory impairment. Diagnostic features and therapy for congenital rib anomalies are described.
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http://dx.doi.org/10.1016/j.jpedsurg.2008.01.062DOI Listing
June 2008

Clinical efficacy and compatibility of allogeneic avital tissue transplants sterilized with a peracetic acid/ethanol mixture.

Cell Tissue Bank 2002 ;3(4):235-43

Institute for Transfusion Medicine (Tissue Bank) (Tel.: 0049/30/450 525161; Fax: 0049/30/450 525976; e-mail:

In the course of the past 20 years a quantity of approximately 60,000 allogeneic avital tissue grafts sterilized with the peracetic acid-ethanol method (PES) were transplanted successfully. Based on a retrospective report of clinical experience of the years 1997-2001 on the overall scope of tissue grafts manufactured by the Tissue Banks of the University Hospital Charité and the German Institute for Cell and Tissue Replacement, the clinical efficacy and side effects of 18.3% (3.087/16.823) of all transplants were studied. Cancellous (1.601/3.087) and cortical (291/3.087) bone transplants as well as amnion (1.027/3.087) constituted the greatest part. In 91% of the examined patients (2.369/2.592) tissue integration ratios ranging from good up to very well could be observed. The transplant function of defect replacement or of a spacer respectively could be obtained for all types of tissue. The clinical effect caused by the transplant resulted in more than 99% of the transplants in primary integration or in the desired aim of the therapy (defect replacement, stabilization in case of palliative operations, etc.). In less than 1% (9/2.592) of cases a secondary healing occurred for cancellous bone transplantations or, revisional operations became necessary. In all cases severe side effects, in particular transmission of infectious diseases or transplant rejections, were not observed.
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http://dx.doi.org/10.1023/A:1024697515420DOI Listing
January 2002

Prenatal diagnosis of congenital mesoblastic nephroma in 2 siblings.

J Ultrasound Med 2003 Aug;22(8):823-7; quiz 828-9

Department of Obstetrics, Charité, Campus Virchow-Clinic Berlin, Berlin, Germany.

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http://dx.doi.org/10.7863/jum.2003.22.8.823DOI Listing
August 2003