Rolf Fimmers

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V., Bonn, North Rhine-Westphalia, Germany

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Publications (291)1120.45 Total impact

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    ABSTRACT: There is evidence of a probable key role of the activator protein-2 γ (AP-2γ) in placental development. It is still an open question whether AP-2γ expression may be influenced by preeclampsia, which is a serious pregnancy complication, or by smoking, which has deleterious effects on trophoblastic development.
    Archives of Gynecology and Obstetrics 10/2014; · 1.33 Impact Factor
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    ABSTRACT: Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5 %). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 08/2014;
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    ABSTRACT: To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders.
    European radiology. 07/2014;
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    ABSTRACT: Purpose To evaluate the diagnostic value of cardiac magnetic resonance (MR) imaging at 3 T in patients suspected of having acute myocarditis by using a multiparametric cardiac MR imaging approach including T1 relaxation time as an additional tool for tissue characterization. Materials and Methods Ethics commission approval was obtained for this prospective study, and written informed consent was obtained from all subjects. Twenty four patients with acute myocarditis (mean age ± standard deviation, 34.7 years ± 15.1; 75% men) and 42 control subjects (mean age, 38.7 years ± 10.2; 64% men) were included. Cardiac MR imaging approaches included relative T2 short tau inversion-recovery signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late gadolinium enhancement, native T1 relaxation times, and extracellular volume fraction. Receiver operating characteristic analysis was performed to compare diagnostic performance. The reference standard was the clinical evidence for acute myocarditis. Results Native T1 relaxation times were significantly longer in patients with acute myocarditis than in control subjects (1185.3 msec ± 49.3 vs 1089.1 msec ± 44.9, respectively; P < .001). Areas under the curve of native T1 relaxation times (0.94) were higher compared with those of other cardiac MR parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018, .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were equivalent compared with those of the established combined Lake Louise criteria (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%). Conclusion Diagnostic performance with native T1 mapping was superior to that with T2 ratio and early gadolinium enhancement ratio, and specificity was higher with native T1 mapping than that with Lake Louise criteria. This study underlines the potential of native T1 relaxation times to complement current cardiac MR approaches in patients suspected of having acute myocarditis. © RSNA, 2014 Online supplemental material is available for this article .
    Radiology 06/2014; · 6.34 Impact Factor
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    ABSTRACT: To investigate the impact of Bruch Membrane pathology on the choroid in Pseudoxanthoma elacticum (PXE) DESIGN: Monocenter cross sectional prospective case series. The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy and/or genetic analysis. Eyes with PXE were subdivided into 3 groups: Eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (group 1), eyes with active or fibrotic CNV (group 2) and eyes with chorioretinal atrophy only (group 3). Choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Compared to controls (331μm±24; mean±95%CI), mean subfoveal choroidal thickness in eyes of PXE patients was significantly reduced within all three groups (group 1: 243μm±29; group 2: 184μm±28; group 3: 104μm±28; p<0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was most obvious close to the optic disc and approximated the level of controls towards the periphery. Within the PXE subgroups eyes without CNV or chorioretinal atrophy (group 1) showed the least reduction of choroidal thickness, while it was most pronounced within group 3. The results indicate that changes of Bruch Membrane can be associated with choroidal alterations, which are most pronounced in presence of advanced disease. A role of Bruch Membrane for choroidal homeostasis may reflect a possible contribution of Bruch Membrane alterations to CNV and geographic atrophy development in age-related macular degeneration.
    American Journal of Ophthalmology 04/2014; · 4.02 Impact Factor
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    ABSTRACT: Purpose: To further characterize a subgroup of patients exhibiting the fundus autofluorescence (FAF) "diffuse-trickling" phenotype associated with geographic atrophy (GA). Methods: In the context of the Fundus Autofluorescence in Age related Macular Degeneration (FAM) Study, patients with "diffuse-trickling" GA were examined and characterized by FAF and spectral-domain optical coherence tomography imaging (HRA, Spectralis HRA+OCT, Heidelberg Engineering). Age, gender distribution, and medical history were compared to FAM study patients (n=288, 60.1% female) with other GA phenotypes ("non-diffuse-trickling"). In a subset of patients, subfoveal choroidal thickness (SCT) was analyzed. Results: Patients with "diffuse-trickling" (n=61) - compared to patients with "non-diffuse-trickling" GA - had a significantly younger age at first presentation (68.2±11.6 vs.75.4±8.1 years, p<0.001), a shift in the proportion of men from 55% in the age group <65 to 19% in the age group ≥65, and a significantly higher rate of myocardial infarction (MI) in the age group <65 (24% vs. 0%,p=0.011); all but one patient with MI were male. Further evaluation revealed that in the age group <65, 54% of patients with "diffuse-trickling" had been hospitalized due to cardiovascular diseases including hypertensive crisis, angina, and MI. Analysis of choroidal thickness revealed a significantly thinner SCT in "diffuse-trickling" compared to "non-diffuse-trickling" GA (135.2±56.4 vs. 191.4±77.8µm,p<0.001). Conclusions: The results indicate an association of "diffuse-trickling" GA with systemic cardiovascular disorders in the younger study population. Together with the ocular morphological characteristics including a lobular appearance and a thin choroid, a vascular insufficiency at the level of the choroid may play a pathogenetic role in this distinct GA phenotype.
    Investigative ophthalmology & visual science 04/2014; · 3.43 Impact Factor
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    ABSTRACT: This study investigated the efficacy of 131iodine-labeled lipiodol (131I-lipiodol) as a palliative therapy, evaluated overall survival (OS) across Barcelona Clinic Liver Cancer (BCLC) stages, and determined the main prognostic factors influencing OS in patients with hepatocellular carcinoma (HCC). Patients, methods: We retrospectively analyzed 57 (44 men; mean age, 65.7 years; mean activity per session, 1.6 GBq; mean cumulative activity in patients with >1 sessions, 3.9 GBq) HCC patients who underwent 131I-lipiodol therapy. A majority of patients exhibited Child-Pugh class B (53.6%) disease and a good Eastern Cooperative Oncology Group performance status (0-1; 72%). Multinodular disease was observed in 87.7% patients, bilobar disease in 73%, and portal vein occlusion (PVO) in 54%. Furthermore, 21.1% patients were staged as BCLC B and 59.6 % as BCLC C. All patients were followed until death. Results: The median OS was 6.4 months, which varied significantly with disease stage (median OS for BCLC A, B, C, and D was 29.4, 12.0, 4.6, and 2.7 months, respectively; p = 0.009); Child-Pugh score and class; presence of ascites, PVO, or extrahepatic disease; largest lesion size; favourable treatment response; international normalized ratio, baseline albumin and alpha-fetoprotein levels. Patients with a Child-Pugh A liver disease had a longer OS. Conclusion: Currently, different treatment modalities for HCC include radioembolization, transarterial chemoembolization, and systemic therapy with sorafenib; however, 131I-lipiodol therapy remains a feasible alternative for patients without a favourable response to other therapies, particularly for patients with Child-Pugh A liver cirrhosis.
    Nuklearmedizin 01/2014; 53(3). · 1.67 Impact Factor
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    ABSTRACT: Introduction The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Materials and Methods Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. Results APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. Conclusions This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: The German Version of the Manchester Triage System (MTS) has found widespread use in EDs across German-speaking Europe. Studies about the quality criteria validity and reliability of the MTS currently only exist for the English-language version. Most importantly, the content of the German version differs from the English version with respect to presentation diagrams and change indicators, which have a significant impact on the category assigned. This investigation offers a preliminary assessment in terms of validity and inter-rater reliability of the German MTS. Construct validity of assigned MTS level was assessed based on comparisons to hospitalization (general / intensive care), mortality, ED and hospital length of stay, level of prehospital care and number of invasive diagnostics. A sample of 45,469 patients was used. Inter-rater agreement between an expert and triage nurses (reliability) was calculated separately for a subset group of 167 emergency patients. For general hospital admission the area under the curve (AUC) of the receiver operating characteristic was 0.749; for admission to ICU it was 0.871. An examination of MTS-level and number of deceased patients showed that the higher the priority derived from MTS, the higher the number of deaths (p<0.0001 / χ(2) Test). There was a substantial difference in the 30-day survival among the 5 MTS categories (p<0.0001 / log-rank test).The AUC for the predict 30-day mortality was 0.613. Categories orange and red had the highest numbers of heart catheter and endoscopy. Category red and orange were mostly accompanied by an emergency physician, whereas categories blue and green were walk-in patients. Inter-rater agreement between expert triage nurses was almost perfect (κ = 0.954). The German version of the MTS is a reliable and valid instrument for a first assessment of emergency patients in the emergency department.
    PLoS ONE 01/2014; 9(2):e88995. · 3.53 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.
    Journal of Clinical Hypertension 01/2014; 16(1):41-6. · 2.36 Impact Factor
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    ABSTRACT: The actual number of resin microspheres is approximately 30-60 times higher than glass microspheres per 3 GBq vial. Thus, radioembolization (RE) with resin microspheres exerts an embolization effect besides the radiation effect. This embolization effect can occasionally cause early back flow of the microspheres before application of the entire calculated dose. To avoid these adverse side effects, RE has to be terminated at an earlier time point. Measurement of the residual activity in the delivery box, which includes the v-vial, tube and catheter, to calculate the achieved target dose is often challenging. The aim of the current study was to establish a post-RE measurement method comparable to the glass microspheres method without unnecessary radiation exposure to the staff and risk of contamination. Methods: Two different measurements were performed. First, total radioactivity in the shipping vial was measured in an ion chamber and then it was put in the delivery box and the radiation was measured from a 30 cm distance from the centre of the box with a dosimeter. The required radioactivity was then transferred to the v-vial, and the shipping vial was measured again. After that, the v-vial was measured from the same distance from the centre of the box with dosimeter. Results: Altogether 62 times the shipping vial with different activities were measured with a significant positive correlation between the amount of the activity measured in the iron chamber and the radiation dose, measured with dosimeter (r² = 0.98; p< 0.001). There was also a strong positive correlation between these measurements of the v-vial (r² = 0.98; p< 0.001). Conclusion:With measurement of the residual activity in the delivery box using a dosimeter the percentage of the whole injected activity can be easily calculated. This facilitates the calculation of the actual, achieved target and non-target dose in those cases, where therapy had to be stopped because of eminent flow reversal or obstruction.
    Nuklearmedizin 10/2013; 53(1). · 1.67 Impact Factor
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    ABSTRACT: Glioblastoma is a highly malignant, invariably fatal brain tumor for which effective pharmacotherapy remains an unmet medical need. Screening of a compound library of 160 synthetic and natural toxic substances identified the antihelmintic niclosamide as a previously unrecognized candidate for clinical development. Considering the cellular and interindividual heterogeneity of glioblastoma, a portfolio of short-term expanded primary human glioblastoma cells (pGBM; n = 21), common glioma lines (n = 5), and noncancer human control cells (n = 3) was applied as a discovery platform and for preclinical validation. Pharmacodynamic analysis, study of cell-cycle progression, apoptosis, cell migration, proliferation, and on the frequency of multipotent/self-renewing pGBM cells were conducted in vitro, and orthotopic xenotransplantation was used to confirm anticancer effects in vivo. Niclosamide led to cytostatic, cytotoxic, and antimigratory effects, strongly reduced the frequencies of multipotent/self-renewing cells in vitro, and after exposure significantly diminished the pGBMs' malignant potential in vivo. Mechanism of action analysis revealed that niclosamide simultaneously inhibited intracellular WNT/CTNNB1-, NOTCH-, mTOR-, and NF-κB signaling cascades. Furthermore, combinatorial drug testing established that a heterozygous deletion of the NFKBIA locus in glioblastoma samples could serve as a genomic biomarker for predicting a synergistic activity of niclosamide with temozolomide, the current standard in glioblastoma therapy. Together, our data advocate the use of pGBMs for exploration of compound libraries to reveal unexpected leads, for example, niclosamide that might be suited for further development toward personalized clinical application. Clin Cancer Res; 19(15); 4124-36. ©2013 AACR.
    Clinical Cancer Research 08/2013; 19(15):4124-36. · 7.84 Impact Factor
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    ABSTRACT: PURPOSE: To assess tight junction integrity in cultured human foetal retinal pigment epithelium (RPE) after exposure to clinically relevant indocyanine green (ICG) concentrations. METHODS: Human foetal RPE was cultured with the Hu & Bok method. The apical compartments of well-differentiated cultures were exposed to 0.125, 0.05 and 0.025 mg/ml ICG with or without 10-min illumination. Vehicle and trypsin/EDTA or EDTA alone served as controls. Three minutes was chosen to mimic surgical exposure time, while 3 h was used for toxicity assays, with subsequent wash out. Cell-cell junctions were studied before and after exposure by phase contrast microscopy and immunofluorescence (ZO-1). Blood-retinal barrier function was measured through transepithelial electrical resistance (TER). RESULTS: At 6-8 weeks postconfluence, RPE had grown into pigmented hexagonal monolayers with stable TER (435-1227 Ω*cm2 ). After 3 min ICG exposure, cell morphology remained unchanged, with patchy cell-cell dissociation in positive controls. A continuous ZO-1 signal was detected in ICG groups, whereas trypsin controls showed patchy loss of the tight junction stain. TER had dropped at 1.5 h after 3 min exposure to 22.8 ± 3.1%, compared with 10.2 ± 3.9% in positive controls. Surgical light illumination did not affect TER. After 3 h exposure to 0.05 mg/ml ICG, TER decreased to 58.1 ± 8.3%, while vehicle controls maintained similar levels as prior to exposure (92.7 ± 2.4%). TER recovered in all ICG groups to prior levels within 3 days. CONCLUSION: Indocyanine green (ICG) exposure induced a transient decrease in transepithelial electrical resistance, despite unaltered tight junction structure.
    Acta ophthalmologica 07/2013; · 2.44 Impact Factor
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    ABSTRACT: Mastocytosis is a rare heterogeneous disease characterized by increase of mast cells (MCs) in different organs. Neurotrophins have been shown to promote differentiation and survival of MCs, which in turn represent a major source of neurotrophins. Thus, a contribution of neurotrophins to mastocytosis seems highly conceivable, but has not yet been investigated. We could demonstrate expression of high-affinity neurotrophin receptors TrkA for nerve growth factor (NGF)-β, TrkB for brain-derived neurotrophic factor (BDNF) and NT-4 and TrkC for NT-3 on skin MCs and of TrkA and TrkC on intestinal MCs of patients with mastocytosis. Moreover increased expression of NGF-β, NT-3, TrkA, B, C and isoforms truncated TrkB-T1 and truncated TrkC were observed on skin mast cells. Patients with mastocytosis featured elevated serum levels of NGF, NT-3 and NT-4. Levels of NGF-β and NT-4 correlated with tryptase levels, suggesting a link between mast cell load and blood levels of NGF and NT-4. Migration of CD117(+) progenitor cells from the blood was enhanced towards NGF-β gradient in both mastocytosis and controls. Together with enhanced neurotrophin levels, the elevated expression of modified Trk receptors on skin and gut mast cells might contribute to the pathophysiology of mastocytosis in autocrine and paracrine loops.
    Blood 07/2013; · 9.78 Impact Factor
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    ABSTRACT: Identification of reliable risk factors for recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) has important implications. Left atrial (LA) pressure is a largely observator-independent parameter that can easily be determined after transseptal puncture. The purpose of this study was to investigate the predictive value of LA pressure for AF recurrence after PVI. Two hundred five consecutive patients with paroxysmal or persistent AF scheduled for first PVI were included. Baseline clinical data were collected. During PVI, LA pressure was determined invasively after transseptal puncture. PVI was performed with radiofrequency or cryoenergy, and patients were followed for 25 ± 7 months. One hundred five (51 %) patients had AF recurrence. Patients with persistent AF prior to ablation had significantly more recurrences than patients with paroxysmal AF (70.1 vs. 42.0 %, p < 0.001). Mean LA pressure was significantly higher in patients with recurrence of AF (13.4 ± 7.1 vs. 11.0 ± 5.2 mmHg, p = 0.007), as was mean LA volume index (40.1 ± 18.5 vs. 33.0 ± 11.2 mL/m(2), p < 0.001). In the multivariate analysis, mean LA pressure was predictive in patients with normal or mildly enlarged LA, while AF type was not predictive. For each 1-mmHg increase in LA pressure, the risk of AF recurrence increased by 11 % in this subgroup. In patients with moderately or severely enlarged LA, AF type was predictive whereas LA pressure was not. LA pressure, AF type, and LA volume index are independent predictors for recurrence of AF after PVI. LA pressure may be helpful especially in patients with small atria, where AF type is not predictive.
    Journal of Interventional Cardiac Electrophysiology 06/2013; · 1.39 Impact Factor
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    ABSTRACT: PURPOSE:: To evaluate different therapies for choroidal neovascularization (CNV) due to angioid streaks (AS). METHODS:: Studies were identified by a systematic literature search and were included in the analysis based on predefined criteria. Primary outcome measure was change in best-corrected visual acuity (BCVA). RESULTS:: Fifty-four relevant studies were identified and included mostly uncontrolled case series. No randomized controlled trials were available. Treatment with vascular endothelial growth factor inhibitors improved or stabilized BCVA in all case series. Photodynamic therapy slowed down disease progression with stabilization or decrease of BCVA. Individual BCVA and follow-up data for each treated eye were reported in >160 cases for both treatments, vascular endothelial growth factor inhibitors and photodynamic therapy. In a pooled analysis of those studies, the difference of mean change in BCVA between both treatment groups was estimated as approximately 6 (0.59 logMAR [95% confidence interval, 0.8-0.38; P < 0.0001]). A better baseline BCVA was associated with a better BCVA outcome (P < 0.0001). Laser photocoagulation yielded comparable results as photodynamic therapy but application was mostly restricted to extrafoveal lesions, was complicated by frequent recurrences, and led to more retinal damage with subsequent absolute scotomas. Combination therapies seem to be not superior to monotherapy. CONCLUSION:: Intravitreal vascular endothelial growth factor inhibitors are currently the most effective treatment of CNV due to angioid streaks.
    Retina (Philadelphia, Pa.) 05/2013; · 2.93 Impact Factor
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    ABSTRACT: Purpose: Preferential streaming of the ductus venosus (DV) toward the right atrium has been observed in fetuses with left diaphragmatic hernia (LDH). The purpose of this retrospective study was to compare survival rates to discharge between a group with preferential streaming of the DV toward the right heart and a group in which this abnormal flow pattern was not present.Materials and Methods: We retrospectively searched our patient records for fetuses with LDH in whom liver position, DV streaming and postnatal outcome information was available. 55 cases were found and divided into two groups: Group I fetuses exhibited abnormal DV streaming toward the right side of the heart; group II fetuses did not. Various prognostic and outcome parameters were compared.Results: 62 % of group I fetuses and 88 % of group II fetuses survived to discharge (p = 0.032). Fetoscopic tracheal balloon occlusion (FETO) was performed in 66 % of group I fetuses and 23 % of group II fetuses (p = 0.003). Postnatal ECMO therapy was performed in 55 % of group I fetuses and 23 % of group II infants (p = 0.025). Moderate to severe chronic lung disease in survivors was observed in 56 % of the survivors of group I and 9 % of the survivors of group II (p = 0.002).Conclusion:Preferential streaming of the DV toward the right heart in human fetuses with left-sided diaphragmatic hernia was associated with a poorer postnatal outcome despite a higher rate of invasive pre- and postnatal procedures compared to fetuses without this flow abnormality. Specifically, abnormal DV streaming was found to be an independent predictor for FETO.
    Ultraschall in der Medizin 05/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: Previous studies have proven that long-lasting success in the therapy of neovascular age-related macular degeneration (AMD) and other neovascular retinal diseases depends on monthly follow-up examinations to assess visual acuity and retinal morphology. MATERIALS AND METHODS: The interactive database Bonn ophthalmology online network (BOON) offers a platform for patient monitoring, increasing control reliability and providing a tool for permanent communication between treating centers and referring ophthalmologists. The BOON data-based project started in 2009 at the department of ophthalmology at Bonn University and ten referring ophthalmology practices. It was programmed to communicate diagnostic findings, images and patient appointments online. In order to react promptly the system gave immediate notice if patients had missed a follow-up appointment or the condition had worsened. Patients were recruited in 2009 and 2010 and were followed for 1 year. Each patient had an electronic master file with several registers in which, besides personal data, precise diagnostic findings, imaging and reports were quickly and easily entered by means of detailed check box and drop-down menus. Each follow-up was registered and an alert email was sent to the referring physician in cases of missed appointments or disease progression. RESULTS AND CONCLUSIONS: The BOON database supports the requirements for a fast and detailed communication between treating and referring physicians in the treatment of patients with AMD as well as other retinal diseases. It was programmed to support data exchange and monthly control visits and thus a better patient management. Results will show whether this helps to enhance long-term treatment success in neovascular diseases.
    Der Ophthalmologe 05/2013; · 0.53 Impact Factor
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    ABSTRACT: BACKGROUND: Gingival invaginations are a common side effect of orthodontic therapy involving tooth extraction and subsequent space closure. Consequences of gingival invaginations are a jeopardized stability of the space closure and hampered oral hygiene. In a retrospective study, the factor time until initiation of orthodontic space closure after tooth extraction has been identified as a potential risk factor for the development of gingival invaginations. The aim of this pilot study is to proof this hypothesis and to enable a caseload calculation for further clinical trials. The referring question is: is it possible to reduce the number of developing gingival invaginations by initiation of orthodontic space closure after tooth extraction at an early point of time? DESIGN: The intended pilot study is designed as a multicenter randomized controlled clinical trial, comparing the impact of two different time intervals from tooth extraction to initiation of orthodontic space closure on the development of gingival invaginations.Forty participants, men and women in the age range of 11 to 30 years with orthodontically related indication for tooth extraction in the lower jaw, will be randomized 1:1 in one of two treatment groups. In group A the orthodontic tooth movement into the extraction area will be initiated in a time interval 2 to 4 weeks after tooth extraction. In group B the tooth movement will be initiated in a time interval >12 weeks after extraction. A possible effect of these treatment modalities on the development of gingival invaginations will be documented at the moment of space closure or 10 months +/- 14 days after initiation of space closure respectively, by clinical documentation of the primary (reduced number of gingival invagination) and the secondary endpoint (reduction of the severity of gingival invaginations).Trial registration: Trial Number U1111-1132-6655; German Clinical Trials Register DRKS00004248.
    Trials 04/2013; 14(1):108. · 2.21 Impact Factor
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    ABSTRACT: BACKGROUND: Epidermal Langerhans cells (LC) expressing the high-affinity receptor for IgE (FcεRI) play a key role in atopic dermatitis (AD). AD skin is highly colonized with Staphylococcus aureus (S.a.), which are sensed by Toll-like receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of FcεRI on LC. OBJECTIVES: To study a putative impact of TLR2 signaling on FcεRI, we analyzed FcεRI and known transcription factors of the receptor after ligand binding to TLR2. METHODS: We generated LC from CD34(+) progenitors in vitro (CD34LC) expressing FcεRI and TLR2 as well as its partners TLR1 and TLR6. The expression of FcεRI and known transcription factors of the receptor was analyzed on the protein and RNA level by flow cytometry, Western blotting, and real-time PCR. RESULTS: For CD34LC from 123 donors, we observed a high heterogeneity in FcεRI surface expression correlating with mRNA level of its α-chain. Stimulation of TLR1/2 or TLR2/6 dramatically down-regulated FcεRI on protein and mRNA level of both α- and γ-chain. Further analysis of putative transcription factors for FCER1A revealed the lack of GATA1 in CD34LC, weak expression of ELF1 and YY1, and high expression of PU.1. While ELF1 and YY1 appeared to be little affected by TLR2 engagement, PU.1 was significantly down-regulated. CONCLUSIONS: Taken together, our findings show that in human, LC ligation of TLR2 by S.a.-derived products down-regulates FcεRI and its transcription factor PU.1, thus suggesting that FcεRI is controlled by PU.1 in these cells.
    Allergy 03/2013; · 5.88 Impact Factor

Publication Stats

6k Citations
1,120.45 Total Impact Points


  • 2006–2014
    • Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.
      Bonn, North Rhine-Westphalia, Germany
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
    • University of Antwerp
      • Medische Genetica (MEDGEN)
      Antwerpen, VLG, Belgium
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 1994–2014
    • University of Bonn - Medical Center
      • Institute for Clinical Chemistry and Clinical Pharmacology
      Bonn, North Rhine-Westphalia, Germany
  • 1988–2014
    • University of Bonn
      • • Institutes of Molecular Medicine and Experimental Immunology
      • • Department of Neurobiology
      • • Klinik und Poliklinik für Dermatologie und Allergologie
      • • Klinik und Poliklinik für Nuklearmedizin
      • • Institute of Human Genetics
      • • Medizinische Klinik und Poliklinik II
      Bonn, North Rhine-Westphalia, Germany
  • 2010
    • Clinic for Minimally Invasive Surgery
      Berlín, Berlin, Germany
  • 2008–2010
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • Universitätsklinikum Jena
      Jena, Thuringia, Germany
  • 2005–2007
    • University of Münster
      • Department of Psychiatry
      Münster, North Rhine-Westphalia, Germany
  • 2004–2005
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Obstetrics and Gynaecology, School of Midwifery
      Erlangen, Bavaria, Germany
  • 1996–2002
    • Johannes Gutenberg-Universität Mainz
      • I. Department of Medicine
      Mainz, Rhineland-Palatinate, Germany
  • 2001
    • University of Washington Seattle
      • Department of Obstetrics and Gynecology
      Seattle, WA, United States
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine I
      München, Bavaria, Germany
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
  • 2000
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1998
    • Sigmund-Freud-Institut
      Frankfurt, Hesse, Germany