Raimund Stein

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (143)334.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In 30% of children with urinary tract anomalies, urinary tract infection (UTI) can be the first sign. Failure to identify patients at risk can result in damage to the upper urinary tract. To provide recommendations for the diagnosis, treatment, and imaging of children presenting with UTI. The recommendations were developed after a review of the literature and a search of PubMed and Embase. A consensus decision was adopted when evidence was low. UTIs are classified according to site, episode, symptoms, and complicating factors. For acute treatment, site and severity are the most important. Urine sampling by suprapubic aspiration or catheterisation has a low contamination rate and confirms UTI. Using a plastic bag to collect urine, a UTI can only be excluded if the dipstick is negative for both leukocyte esterase and nitrite or microscopic analysis is negative for both pyuria and bacteriuria. A clean voided midstream urine sample after cleaning the external genitalia has good diagnostic accuracy in toilet-trained children. In children with febrile UTI, antibiotic treatment should be initiated as soon as possible to eradicate infection, prevent bacteraemia, improve outcome, and reduce the likelihood of renal involvement. Ultrasound of the urinary tract is advised to exclude obstructive uropathy. Depending on sex, age, and clinical presentation, vesicoureteral reflux should be excluded. Antibacterial prophylaxis is beneficial. In toilet-trained children, bladder and bowel dysfunction needs to be excluded. The level of evidence is high for the diagnosis of UTI and treatment in children but not for imaging to identify patients at risk for upper urinary tract damage. In these guidelines, we looked at the diagnosis, treatment, and imaging of children with urinary tract infection. There are strong recommendations on diagnosis and treatment; we also advise exclusion of obstructive uropathy within 24h and later vesicoureteral reflux, if indicated. Copyright © 2014. Published by Elsevier B.V.
    European Urology 12/2014; · 12.48 Impact Factor
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    ABSTRACT: Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed dis- covery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P 5 8.88 3 1025; follow- up: P 5 0.0025; combined: 1.09 3 1026) in a highly conserved 32 kb intergenic region containing regulatory ele- ments between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the geni- tal region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P 5 0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify asso- ciation of common variation with CBE.
    Human Molecular Genetics 10/2014; 23(29). · 6.68 Impact Factor
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    ABSTRACT: Background and purposeTo investigate resource use and burden associated with spina bifida (SB) in Germany.MethodsA questionnaire was used to obtain information on SB-related healthcare resource use and assistive technologies used for the last 1 and 10 years. Individuals with SB were recruited at a tertiary specialist clinic. To participate, persons with SB required the cognitive ability to respond or a caregiver to answer questions on their behalf. They could use personal medical charts or other records to answer. The analyses included assessment of frequency and extent of resource use for both time frames.ResultsData on 88 persons with a diagnosis of SB were collected (44% female). During the last year, 88.6% (N = 78) reported at least one visit to a general practitioner's (GP's) office, 77.3% (N = 68) to a urologist and 69.3% (N = 61) to a physiotherapist. The annual average number of visits was 7.6 GP, 3.6 urologist and 65.3 physiotherapist visits. Amongst those hospitalized, a single hospitalization lasted 7.3 days on average, whereas the average annual number of hospital days was 14.8 days. During the previous 10 years, 67.0% (N = 59) of responders used a wheelchair, 64.7% (N = 57) used glasses and 59.1% (N = 52) used orthopaedic shoes, with an average of 2.5, 2.8 and 6.1 new items used, respectively.Conclusions The results indicate that persons with SB require a substantial amount of interaction with healthcare providers, as well as other healthcare-related resource use, both in the shorter and longer terms.
    European Journal of Neurology 08/2014; · 3.85 Impact Factor
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    ABSTRACT: Background Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients.Methods Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls.ResultsNew duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24–1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes.Conclusion Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 04/2014; · 2.27 Impact Factor
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    Raimund Stein, Peter Rubenwolf
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    ABSTRACT: Metabolic disturbances are well-known, but sometimes neglected immediate consequences or late sequelae following urinary diversion (UD) using bowel segments. Whereas subclinical disturbances appear to be quite common, clinically relevant metabolic complications, however, are rare. Exclusion of bowel segments for UD results in loss of absorptive surface for its physiological function. Previous studies demonstrated that at least some of the absorptive and secreting properties of the bowel are preserved when exposed to urine. For each bowel segment typical consequences and complications have been reported. The use of ileal and/or colonic segments may result in hyperchloremic metabolic acidosis, which can be prevented if prophylactic treatment with alkali supplementation is started early. The resection of ileal segments may be responsible for malabsorption of vitamin B12 and bile acids with subsequent neurological and hematological late sequelae as well as potential worsening of the patient's bowel habits. Hence, careful patient and procedure selection, meticulous long-term follow-up, and prophylactic treatment of subclinical acidosis is of paramount importance in the prevention of true metabolic complications.
    Frontiers in Pediatrics 03/2014; 2:15.
  • P Rubenwolf, R Stein
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    ABSTRACT: Cryptorchidism, or undescended testis (UDT), occurs in 1-3% of male term infant births. At least two-thirds of UDTs will descend spontaneously, typically during the first 6 months of life. UDTs are associated with loss of spermatogenic potential and testicular malignancy in the long term. Orchiopexy performed prior to puberty may significantly reduce the malignant potential by up to 4-fold. Neoadjuvant hormonal therapy starting at 6 months of life has been shown to potentially improve the testicle's fertility index and should be part of the therapeutic concept. However, the use of hormonal treatment and HCG beyond the first year of life is to be challenged given a potentially negative impact on testicular function. Laparoscopic exploration and therapy is the method of choice for non-palpable testes. Ideally, surgical repair of the UDT should be completed by the age of 1 year.
    Aktuelle Urologie 11/2013; 44(6):445-451. · 0.47 Impact Factor
  • Raimund Stein, Peter Rubenwolf
    Journal of pediatric urology 10/2013; · 1.38 Impact Factor
  • BJU International 07/2013; 112(1):137-55. · 3.13 Impact Factor
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    ABSTRACT: PURPOSE: To investigate the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. MATERIAL AND METHODS: Open-label, randomized, three period change-over clinical study including 20 healthy adult subjects. In period 1 and 2, subjects received single doses of either 10 mg oxybutynin-HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeated intravesical applications (7 doses) of 10 mg oxybutynin-HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin (NDO) were quantified by LC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. RESULTS: Systemic exposure to racemic oxybutynin following intravesical administration was significantly higher, yielding 294% (90%-CI: 211-408%) of that after oral intake of immediate-release preparations, as measured by dose-normalized AUC. By contrast, systemic exposure to racemic NDO reached only 21% (90%-CI: 15%-29%). The AUC-ratio of NDO/oxybutynin was 14-fold reduced for intravesical administration. Following intravesical multi-dose administration, cumulation of oxybutynin (1.3-fold) and NDO (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated, with a third of participants reporting anticholinergic adverse effects. CONCLUSION: The present study provides evidence of a significantly higher bioavailability of intravesical versus oral oxybutynin administration by circumvention of the intestinal first-pass metabolism. Given the high efficacy and reduced rate of adverse effects, intravesical oxybutynin should be considered in patients with NLUTD who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.
    The Journal of urology 05/2013; · 3.75 Impact Factor
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    ABSTRACT: Vom 10. bis zum 12. November 2011 fand in Mainz die 19. Jahrestagung des Arbeitskreises Nierentransplantation (NTX) der Akademie der Deutschen Urologen statt. Diesjährige Schwerpunkte waren operativ-technische Aspekte, die immunsuppressive Therapie, Transplantatabstoßung, Schwangerschaft, Sexualität und psychologische Konflikte von Nierentransplantierten. Die Vortragenden dokumentierten die Relevanz der Interdisziplinarität für die NTX und kamen außer aus der Urologie aus den Fachbereichen Anästhesie, Gynäkologie, Chirurgie, Dermatologie, Nephrologie, Radiologie und der psychosomatischen Medizin. Zum Abschluss der Veranstaltung wurde der Bernd-Schönberger-Preis 2011 verliehen.
    Der Urologe 04/2013; 51(4). · 0.44 Impact Factor
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    ABSTRACT: PURPOSE: In a retrospective study we analyzed the outcome of patients treated for rhabdomyosarcoma (RMS) of the bladder/prostate with special attention to radical surgery. METHODS: In 25 patients with genitourinary RMS (15 bladder/10 prostate) the median age at diagnosis was 4 years [1-18], and 8 patients had a stage II RMS, 12 stage III and 5 stage IV. In 19/25 (12 bladder/7 prostate), radical surgery and urinary diversion were performed. Urinary diversion comprised 2 continent anal diversions, 11 continent cutaneous diversions, 4 colon conduits and 2 urethral diversions (2 + 3 years of age). In the younger child with urethral diversion, a cutaneous appendix stoma was additionally constructed in case of inability to void spontaneously. RESULTS: 4/19 patients who underwent radical surgery died of metastatic RMS; 1 patient with neurofibromatosis died of a secondary tumor. After median follow-up of 132 months (14-420), 14 patients currently have no evidence of disease. 8/14 patients who survived developed 17 complications requiring operative revision. All patients with a continent diversion are continent. The patients with orthotopic bladder substitution are continent day & night and void spontaneously. CONCLUSION: For RMS confined to the bladder or bladder neck, radical cystoprostatectomy and orthotopic bladder substitution are an option. Urethral diversion using the ileocecal segment (Mainz-pouch I) offers the advantage of utilizing the appendix as an additional continent cutaneous stoma, which enables parents to evacuate residual urine in young boys, until able to empty the pouch completely themselves. For all other patients with vital tumor after primary chemotherapy, cutaneous urinary diversion is an option. Long-term complication rates in this complex group of patients are acceptable.
    Journal of pediatric urology 02/2013; · 1.38 Impact Factor
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    ABSTRACT: BACKGROUND: The exstrophy-epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC. METHODS Array-based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high-penetrance mutations involving small sequence changes. RESULTS A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ. CONCLUSIONS The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples. 19p13.12, microduplication, bladder exstrophy-epispadias complex, array-based molecular karyotyping, in situ hybridization analysis, copy number variations, WIZ Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 01/2013; · 2.27 Impact Factor
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    ABSTRACT: The never ending discussion about the diagnostics and treatment of vesicoureteral reflux (VUR) now includes arguments for diagnostic nihilism as well as invasive diagnostics and therapy, which is reminiscent of the debate on prostate cancer in adulthood. The common goal of all currently competing diagnostic strategies and approaches is the prevention of renal scars by the most effective and least burdensome approach. There is a difference between acquired pyelonephritic scars with VUR (acquired reflux nephropathy) and congenital reflux nephropathy (primary dysplasia) which cannot be influenced by any therapy.The VUR can be verified by conventional radiological voiding cystourethrography (VCUG), by urosonography, radionuclide cystography or even by magnetic resonance imaging (MRI). The guidelines of the European Association of Urology/European Society for Paediatric Urology (EAU/ESPU) recommend radiological screening for VUR after the first febrile urinary tract infection. Significant risk factors in patients with VUR are recurrent urinary tract infections (UTI) and parenchymal scarring and the patients should undergo patient and risk-adapted therapy. Infants with dilating reflux have a higher risk of renal scarring than those without dilatation of the renal pelvis. Bladder dysfunction or dysfunctional elimination syndrome represents a well-known but previously neglected risk factor in combination with VUR and should be treated prior to any surgical intervention as far as is possible.Certainly not every patient with VUR needs therapy. The current treatment strategies take into account age and gender, the presence of dysplastic or pyelonephritic renal scars, the clinical symptoms, bladder dysfunction and frequency and severity of recurrent UTI as criteria for the therapy decision. The use of an antibacterial prophylaxis as well as the duration is controversially discussed. Endoscopic therapy can be a good alternative to antibacterial prophylaxis or a surveillance strategy in patients with low grade VUR. In patients with dilating VUR and given indications for surgery, endoscopic treatment can be offered. However, parents should be completely informed about the significantly lower success rate of endoscopic therapy compared to open surgical procedures. The open surgical techniques guarantee the highest success rates and should be used in patients with a dilating VUR and high risk of renal damage.
    Der Urologe 01/2013; · 0.44 Impact Factor
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    Raimund Stein
    Central European journal of urology. 01/2013; 66(1):10-1.
  • BJU International 12/2012; 110(11):1843-7. · 3.13 Impact Factor
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    ABSTRACT: PURPOSE: To assess the risk for the exstrophy-epispadias-complex (EEC) following treatment for infertility with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), two assisted reproductive techniques (ART). MATERIALS AND METHODS: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (OR) (95% confidence intervals [CI]) were determined to quantify associations using logistic regression. RESULTS: In total, 123 EEC patients born between 1997 and 2011 in Germany, who were recruited through participating departments of paediatric urology and paediatric surgery throughout Germany and the German self-help organisations Blasenekstrophie/Epispadie e.V. and Kloakenekstrophie, were included. Controls were all German live-births (n=10,069,986) born between 1997 and 2010. Overall, 12 cases (10%) and 129,982 controls (1%) were born after treatment with IVF or ICSI. Conception by ART was associated with an over eight times higher risk of EEC compared to spontaneous conception (OR, 8.3; 95% CI, 4.6-15.0; P<0.001). Separate analyses showed a significantly increased risk for EEC after treatment with IVF (OR, 14.0; 95% CI, 6.5-30.0; P<0.0001) as well as after treatment with ICSI (OR, 5.3; 95% CI, 2.2-12.9; P<0.0001). CONCLUSIONS: The present study provides evidence that assisted reproductive techniques such as IVF and ICSI go along with a strongly increased risk of having a child with EEC. However, it remains unclear whether our finding may be due to ART per se and/or due to underlying infertility/subfertility aetiology or characteristics of the parents.
    The Journal of urology 11/2012; · 3.75 Impact Factor
  • BJU International 10/2012; 110(7):1078-94. · 3.13 Impact Factor
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    ABSTRACT: Bladder cancer is not a rare disease: In 2010, there were more than 70 000 affected patients in the United States. Radical cystectomy for the treatment of muscle invasive bladder cancer necessitates urinary diversion. We present the current options for urinary diversion and their different indications on the basis of a selective search for pertinent literature in PubMed and our own clinical experience. When bladder cancer is treated with curative intent, continence-preserving orthotopic urinary bladder replacement is preferred. For heterotopic urinary bladder replacement, a reservoir is fashioned from an ileal or ileocecal segment. Urine is diverted to the rectum by way of the sigmoid colon. When bladder cancer is treated with palliative intent, non-continence-preserving cutaneous urinary diversion is usually performed: The creation either of a renal-cutaneous fistula or a self-retaining ureteral stent is a purely palliative procedure. In these interventions, the resorptive surface of the bowel segment used can no longer play its original physiological role in the gastrointestinal tract, even though its absorptive and secretory functions are still intact. This has metabolic consequences, because the diverted urine here comes into contact with a large area of bowel epithelium. Early preventive treatment must be provided against potentially serious complications such as metabolic acidosis and loss of bone density. The resection of ileal segments can also lead to malabsorption. The risk of secondary malignancy is elevated after either continence-preserving anal urinary diversion (>2%) or bladder augmentation (>1%). There are four options for urinary diversion after cystectomy that can be performed when surgery is performed with either curative or palliative intent. There are also a number of purely palliative interventions.
    Deutsches Ärzteblatt International 09/2012; 109(38):617-22. · 3.61 Impact Factor
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    ABSTRACT: CONTEXT: A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. OBJECTIVE: To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). EVIDENCE ACQUISITION: An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS: Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS: RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.
    European Urology 08/2012; · 10.48 Impact Factor
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    ABSTRACT: Epispadias is the mildest phenotype of the human bladder exstrophy-epispadias complex (BEEC), and presents with varying degrees of severity. This urogenital birth defect results from a disturbance in the septation process, during which separate urogenital and anorectal components are formed through division of the cloaca. This process is reported to be influenced by androgen signaling. The human PARM1 gene encodes the prostate androgen-regulated mucin-like protein 1, which is expressed in heart, kidney, and placenta. We performed whole mount in situ hybridization analysis of Parm1 expression in mouse embryos between gestational days (GD) 9.5 and 12.5, which are equivalent to human gestational weeks 4-6. Since the spatio-temporal localization of Parm1 corresponded to tissues which are affected in human epispadias, we sequenced PARM1 in 24 affected patients. We found Parm1 specifically expressed in the region of the developing cloaca, the umbilical cord, bladder anlage, and the urethral component of the genital tubercle. Additionally, Parm1 expression was detected in the muscle progenitor cells of the somites and head mesenchyme. PARM1 gene analysis revealed no alterations in the coding region of any of the investigated patients. These findings suggest that PARM1 does not play a major role in the development of human epispadias. However, we cannot rule out the possibility that a larger sample size would enable detection of rare mutations in this gene.
    Gene 07/2012; 506(2):392-5. · 2.20 Impact Factor

Publication Stats

878 Citations
334.88 Total Impact Points

Institutions

  • 2012–2014
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
    • Max Planck Institute for Molecular Genetics
      • Department of Developmental Genetics
      Berlín, Berlin, Germany
  • 1991–2014
    • Johannes Gutenberg-Universität Mainz
      • • Abteilung Kinderurologie
      • • Department of Urology
      • • III. Department of Medicine
      Mayence, Rheinland-Pfalz, Germany
  • 2013
    • Telekom Germany GmbH
      Bonn, North Rhine-Westphalia, Germany
  • 2010–2013
    • University of Bonn
      • Institute of Human Genetics
      Bonn, North Rhine-Westphalia, Germany
  • 2008
    • Mater Misericordiae University Hospital
      Dublin, Leinster, Ireland
  • 1997
    • St. Mary's Hospital Gelsenkirchen
      Gelsenkirchen, North Rhine-Westphalia, Germany
  • 1996
    • Universität Witten/Herdecke
      Witten, North Rhine-Westphalia, Germany