M W Beckmann

Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Bavaria, Germany

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Publications (416)717.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa.Methods:Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival.Results:FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94).Conclusions:FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.British Journal of Cancer advance online publication, 30 October 2014; doi:10.1038/bjc.2014.567 www.bjcancer.com.
    British journal of cancer. 10/2014;
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    ABSTRACT: GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
    Nature Communications 09/2014; · 10.74 Impact Factor
  • Geburtshilfe und Frauenheilkunde 09/2014; 74(S 01). · 0.85 Impact Factor
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    ABSTRACT: Gynaecological cancer centres have been established nationwide in Germany since 2008 according to the certification system of the German Cancer Society (Deutsche Krebsgesellschaft e. V. [DKG]) and the German Society for Gynaecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V. [DGGG]). However, patient access to the certified gynaecological cancer centres is currently only possible through direct referrals. A longitudinal structure with the corresponding long-term documentation of both the high-grade precursors as well as the cancers does not exist as yet. According to the aims of the National Cancer Plan, a corresponding structure for the cancer entity "cervix carcinoma" should be established. The foundations for such a structure are appropriate diagnostic units that are responsible, after nationwide screening, for clarification according to guideline-conform principles. On the basis of the vote of the certification commission for gynaecological cancer centres under the chairmanship of the DKG, the Working Group for Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V. [AGO]), the Committee on Cervical Pathology and Colposcopy (Arbeitsgemeinschaft Zervixpathologie & Kolposkopie [AG-CPC]) and the DGGG the certification system for gynaecological dysplasia has been established. As a general principle, a distinction is made between the certification of a consulting practice for gynaecological dysplasia and a gynaecological dysplasia facility in order to integrate both outpatient and inpatient health-care facilities into the certification system. In analogy to the further catalogue of requirements from the DKG, quantitative and qualitative minimum numbers are demanded. Furthermore, the requirements of the certification process include a summary of patient information, the applied guidelines, continuing and further training, interdisciplinary cooperation in tumour boards, contents or, respectively, procedure descriptions for consulting practices and the trial participations. Central components of the questionnaire are quality indicators that can be used as specific and measurable elements to evaluate the quality of treatment. After successful pilot certification, finalisation of the updated version of the questionnaire and a completed specialist auditor training course for the certification of gynaecological dysplasia, it will be possible to establish a nationwide treatment system for dysplasia within certified structures.
    Geburtshilfe und Frauenheilkunde 09/2014; 74(9):860-867. · 0.85 Impact Factor
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    Human Molecular Genetics 08/2014; · 7.69 Impact Factor
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    ABSTRACT: Aim: Certification of breast centers helps improve the quality of care but requires additional resources, particularly for documentation. There are currently no published data on the actual staff costs and financial resources required for such documentation. The aim of this study was to determine the time and resources required to document a patient with primary breast cancer from diagnosis to the end of follow-up, to establish a database for future strategic decisions. Material and Methods: All diagnostic and therapeutic procedures of patients with primary breast cancer were recorded at the University Breast Center of Franconia. All time points for documentation were evaluated using structured interviews. The times required to document a representative number of patients were determined and combined with the staff costs of the different professional groups, to calculate the financial resources required for documentation. Results: A total of 494 time points for documentation were identified. The study also identified 21 departments and 20 different professional groups involved in the documentation. The majority (54 %) of documentation was done by physicians. 62 % of all documentation involved outpatients. The results of different scenarios for the diagnosis, therapy and follow-up of breast cancer patients in a certified breast center showed that the time required for documentation can be as much as 105 hours, costing € 4135. Conclusion: This analysis shows the substantial staffing and financial costs required for documentation in certified centers. A multi-center study will be carried out to compare the costs for certified breast centers of varying sizes with the costs of non-certified care facilities.
    Geburtshilfe und Frauenheilkunde 08/2014; 74(8):743-751. · 0.85 Impact Factor
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    ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
    Nature 07/2014; 514(7520):92-7. · 38.60 Impact Factor
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    ABSTRACT: Purpose: To determine the accuracy of sonographic weight estimation (WE) for small-for-gestational-age (SGA) fetuses, and to further differentiate the evaluation between symmetric and asymmetric SGA fetuses. Materials and Methods: The accuracy of WE in SGA fetuses (n = 898) was evaluated using 14 sonographic models and was further differentiated between symmetric (n = 750) and asymmetric (n = 148) SGA fetuses. SGA fetuses were considered to be asymmetric with a head circumference to abdominal circumference ratio above the 95th percentile. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. Results: Results for the subgroup of asymmetric SGA fetuses differed significantly from the subgroup of symmetric SGA fetuses. MPE values were closer to zero with most of the formulas in the asymmetric SGA group. Apart from the Siemer, Shepard, Merz and Warsof equations, all formulas showed an underestimation of fetal weight in asymmetric SGA fetuses. In contrast, in the symmetric SGA group, all of the formulas commonly used for fetuses in a normal weight range showed a systematic overestimation of fetal weight. Overall the best accuracy was achieved by using the Sabbagha equation (MPE 1.7 %; SD 9.0 %; MAPE: 6.0). Conclusion: An accurate WE in SGA fetuses is feasible using the Sabbagha formula. However, one has to be aware of the significant differences in WE between symmetric and asymmetric SGA fetuses.
    Ultraschall in der Medizin 07/2014; · 4.65 Impact Factor
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    ABSTRACT: Aim: Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. Material and Methods: In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. Results: A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). Conclusion: Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives.
    Geburtshilfe und Frauenheilkunde 07/2014; 74(7):656-660. · 0.85 Impact Factor
  • A M Boos, M W Beckmann, R E Horch, J P Beier
    Geburtshilfe und Frauenheilkunde 06/2014; 74(6):574-578. · 0.85 Impact Factor
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    ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    BioMed Research International 04/2014; · 2.71 Impact Factor
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    Human Molecular Genetics 04/2014; Hum Mol Genet.(23(7)):1934-46.. · 7.69 Impact Factor
  • M W Beckmann, I Linde, C Bütof, R Kreienberg, P Gass
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    ABSTRACT: The Guidelines programme of the German Society of Gynaecology and Obstetrics (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in-house planning and organisation of all guidelines as well as representation outside of the DGGG. This article does not concern the development of the guidelines as much as it concerns the planning, organisation, registration, editing and publication of the guidelines in context of the DGGG Guidelines programme. It targets interested parties, especially authors and coordinators of guidelines.
    Geburtshilfe und Frauenheilkunde 03/2014; 74(3):251-259. · 0.85 Impact Factor
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    ABSTRACT: Mammography is the central diagnostic method for clinical diagnostics of breast cancer and the breast cancer screening program. In the clinical routine complementary methods, such as ultrasound, tomosynthesis and optional magnetic resonance imaging (MRI) are already combined for the diagnostic procedure. Future developments will utilize investigative procedures either as a hybrid (combination of several different imaging modalities in one instrument) or as a fusion method (the technical fusion of two or more of these methods) to implement fusion imaging into diagnostic algorithms. For screening there are reasonable hypotheses to aim for studies that individualize the diagnostic process within the screening procedure. Individual breast cancer risk prediction and individualized knowledge about sensitivity and specificity for certain diagnostic methods could be tested. The clinical implementation of these algorithms is not yet in sight.
    Der Radiologe 02/2014; · 0.47 Impact Factor
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    ABSTRACT: BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
    British Journal of Cancer 02/2014; 110(4):1088-100. · 5.08 Impact Factor
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    ABSTRACT: Background: The aim of this study was to evaluate how many embryos will develop if more than 3 2-pronuclei-stage oocytes (2-PNOs) are cultured at the patient's request and in accordance with the Germany Embryo Protection Law. Methods: A total of 106 cycles of patients undergoing their 1st, 2nd or 3rd cycle of IVF or ICSI treatment in 2010 were prospectively included in the study. In each individual case, a decision was taken prior to treatment about the number of 2-PNOs to be cultured after each cycle. Results: Ninety female patients were treated for a total of 106 cycles. A mean of two to six 2-PNOs were cultivated for a period of between 3 and 6 days for each patient. After culture, no viable embryo was identified for 5 patients (4.7 %), a single viable embryo was identified for 37 cycles (34.7 %), and 2 viable embryos were identified for 52 cycles (48.8 %). Eleven patients (10.3 %) had 3 viable embryos after a further 11 cycles and 1 patient had 4 viable embryos in a single cycle. Ten of the patients with 3 embryos each opted to have all 3 embryos transferred in the same cycle. This meant that a single embryo from one patient with 3 viable embryos and a single embryo of the patient with 4 viable embryos were cryopreserved after culture. The pregnancy rate was 19 % per embryo transfer and 25 % per blastocyst transfer (20 pregnancies in total). All cryopreserved embryos were transferred in a subsequent cycle. Discussion: Based on this study it is possible to make a statement about the number of viable embryos which should be cultivated to obtain, at best, two embryos for transfer without running an unacceptably high risk of producing too many embryos which would then need to be cryopreserved. Only 12 patients (13.3 %) had more than 2 viable embryos. The number of supernumerary pre-implantation-stage embryos was acceptably low (only 2 patients had additional viable embryos, 2.2 %). This means that it is possible to fulfil the wishes of individual patients while complying with the German Embryo Protection Law.
    Geburtshilfe und Frauenheilkunde 02/2014; 74(2):157-160. · 0.85 Impact Factor
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    ABSTRACT: Purpose: The aim of the present study was to compare the safety and efficacy of the Kiwi OmniCup system with conventional vacuum delivery. Methods: A retrospective study of operative vaginal deliveries was done for 4682 births. The procedures included 217 operative vaginal deliveries (4.6 %), 79 of which were done using conventional vacuum extraction (37 %) and 138 using the Kiwi system (63 %). Results: Use of the Kiwi system was associated with a significant reduction in episiotomies (61 vs. 76 % in the control group; p < 0.05). The rates of successful completion of birth were comparable for the two systems (94 % with the Kiwi system and 99 % with conventional vacuum delivery). Cup detachment occurred significantly more often in the Kiwi group (p < 0.005), requiring a change to a different method of birth significantly more often. It was necessary to change the procedure significantly more often from the mid-pelvis (p < 0.05). The incidence of maternal and foetal injuries was similar for the two systems. Conclusions: With regard to obstetric efficacy and safety and foetal and maternal injuries, the Kiwi system is an acceptable alternative to the conventional vacuum cup. The advantages of the Kiwi system are its significantly lower episiotomy rate and its ease and rapidity of use.
    Geburtshilfe und Frauenheilkunde 02/2014; 74(2):146-151. · 0.85 Impact Factor
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    ABSTRACT: We report on a case of sebaceous carcinoma of the breast as a rare histological special subtype of breast cancer. Because these tumors are uncommon, differential diagnostic considerations and the exclusion of Muir-Torre syndrome are emphasized. Finally possible mechanisms of development and therapeutic strategies for this carcinoma are discussed.
    Der Pathologe 01/2014; · 0.62 Impact Factor
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    ABSTRACT: Die Mammographie ist die zentrale diagnostische Methode der klinischen symptombezogenen Abklärung von Brusterkrankungen und des Brustkrebsscreenings. In der klinischen Diagnostik wird sie heute schon oft durch zusätzliche Untersuchungsmethoden wie dem Ultraschall, der Tomosynthese und ggf. auch der MRT-Bildgebung unterstützt. Zukünftige Entwicklungen gehen in die Richtung, dass diese Kombination aus 2 oder mehr Untersuchungsverfahren entweder in Hybrid- (Aufnahme mehrerer unterschiedlicher Bildmodalitäten in einem einzigen Gerät) oder in Fusionsmethoden (Zusammenführung und Registrierung von Bilddaten aus verschiedenen Modalitäten) technisch professionalisiert werden. Des Weiteren könnten an subgruppenbezogene Erkrankungsrisiken und individuelle Sensitivitäten und Spezifitäten angepasste Diagnostikkombinationen für eine Screeningdiagnostik Gegenstand künftiger Studien sein. Wir stellen die aktuellen Entwicklungen auf diesen Gebieten und deren momentane Relevanz für die klinische Praxis und Entwicklungspotenzial für die Zukunft dar.
    Der Radiologe 01/2014; 54(3). · 0.47 Impact Factor
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    ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    BioMed research international. 01/2014; 2014:491459.

Publication Stats

2k Citations
717.48 Total Impact Points

Institutions

  • 2001–2014
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • • Department of Obstetrics and Gynaecology, School of Midwifery
      • • Department of Diagnostic Radiology
      Erlangen, Bavaria, Germany
  • 1999–2014
    • Universitätsklinikum Erlangen
      • Department of Obstetrics and Gynaecology
      Erlangen, Bavaria, Germany
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
  • 1994–2012
    • Heinrich-Heine-Universität Düsseldorf
      • Frauenklinik
      Düsseldorf, North Rhine-Westphalia, Germany
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2011
    • HELIOS Klinikum Berlin-Buch
      Berlín, Berlin, Germany
  • 2001–2002
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1996–2000
    • University of Cologne
      • Institute for Genetics
      Köln, North Rhine-Westphalia, Germany
    • RWTH Aachen University
      • Department of Gynaecology and Obstetrics
      Aachen, North Rhine-Westphalia, Germany
  • 1991–1995
    • University of Chicago
      • Department of Obstetrics & Gynecology
      Chicago, IL, United States
  • 1993
    • The University of Chicago Medical Center
      • Department of Obstetrics and Gynecology
      Chicago, Illinois, United States
    • University of Freiburg
      • Institute of Medical Biometry and Medical Informatics
      Freiburg, Baden-Württemberg, Germany
  • 1992
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 1991–1992
    • University of Illinois at Chicago
      • Department of Obstetrics and Gynecology (Chicago)
      Chicago, IL, United States