77 results on '"Frank Wiesmann"'
Search Results
2. Contrast enhancement and artifact reduction in magnetization-prepared MR angiography.
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R. Deichmann, Frank Wiesmann, C. Hillenbrand, D. Hahn, and Axel Haase
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- 1999
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3. Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTi m e HIV-1 Reference Assay
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Carsten Tiemann, Jörg Fuhrmann, Robert Ehret, Gunnar Schalasta, Martin Daumer, Heribert Knechten, Christian Noah, Martin Obermeier, Frank Wiesmann, Patrick Braun, Eva Wolf, Gudrun Naeth, and Rolf Kaiser
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0301 basic medicine ,Microbiology (medical) ,Abbott ,Aptima ,Serial dilution ,Concordance ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Context (language use) ,Cobas 6800 ,Hologic ,medicine.disease_cause ,Sensitivity and Specificity ,viral load monitoring ,03 medical and health sciences ,Virology ,Humans ,Medicine ,Volume concentration ,Roche ,Retrospective Studies ,Automation, Laboratory ,Chromatography ,Plasma samples ,business.industry ,virus diseases ,HIV ,Viral Load ,Clinical routine ,RealTime ,Molecular Diagnostic Techniques ,HIV-1 ,RNA ,RNA, Viral ,Reagent Kits, Diagnostic ,business ,Viral load - Abstract
High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTime m2000 assay., High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTime m2000 assay. Assay precision and accuracy were evaluated in a retrospective evaluation out of excess plasma material from four HIV-1+ individuals (subtypes B, C, CRF01_AE, and CRF02_AG). Native plasma samples were diluted to nominal concentrations at 50 and 200 copies/ml (according to the RealTime m2000 assay). All dilutions were tested in triplicate in five independent runs over 5 days and in three labs per system. Assay concordance was determined using 1,011 surplus clinical routine samples, as well as selected retrospective longitudinal samples from 7 patients on treatment. The three assays yielded highly concordant results for individual clinical samples (R2 > 0.98; average difference, ≤0.2 log copies/ml) and retrospective longitudinal samples from patients on treatment. The Aptima and RealTime assays showed similar high precision, meeting the 5σ criterion for the majority of samples across all labs and subtypes. The Cobas assay was less precise, missing the 5σ criterion for the majority of samples at low concentrations. In this analysis, results from the Cobas assay appeared less reliable near the clinically relevant cutoff and should be interpreted with more caution in this context. Due to high precision, full automation, and high concordance with the RealTime assay, the Aptima assay represents a good alternative in routine VL monitoring.
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- 2018
4. Präzisionsanalyse zweier voll-automatisierter HIV-Viruslast-Assays, Aptima HIV-1 Quant Dx und Cobas 6800 HIV-1 im Vergleich zu RealTime HIV-1 im niedrig virämischen Bereich
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Patrick Braun and Frank Wiesmann
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- 2018
5. Multicentric performance analysis of HCV quantification assays and its potential relevance for HCV treatment
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Gudrun Naeth, Annemarie Berger, Patrick Braun, Heribert Knechten, Hans H. Hirsch, H. Wedemeyer, R. S. Ross, Stephan Regenass, Frank Wiesmann, Christoph Sarrazin, University of Zurich, and Wiesmann, F
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0301 basic medicine ,Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Cobas taqman ,030106 microbiology ,Single measurement ,Immunology ,Medizin ,610 Medicine & health ,Hepacivirus ,Reference laboratory ,Antiviral Agents ,2726 Microbiology (medical) ,03 medical and health sciences ,medicine ,Humans ,Immunology and Allergy ,Viral load ,ddc:610 ,Reproducibility ,2403 Immunology ,Plasma samples ,business.industry ,Reproducibility of Results ,COBAS Taqman ,General Medicine ,Hepatitis C, Chronic ,Virology ,Patient management ,RealTime ,Assay variation ,HCV ,Hcv treatment ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,RNA, Viral ,Drug Monitoring ,business ,Rapid Communication - Abstract
An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1-47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1-21.0 % and CTM v2: 15.0-32.3 %; CVs at 25 IU/ml: RealTime 17.6-34.9 % and CTM v2 28.2-54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR. CA extern
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- 2017
6. Novel insights into LV remodeling after murine myocardial infarction by in vivo magnetic resonance tissue velocity mapping
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Frank Wiesmann, Eberhard Rommel, Joerg U.G. Streiff, Matthias Nahrendorf, Volker Herold, Stefan Neubauer, and Axel Haase
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medicine.medical_specialty ,Radiography ,Myocardial Infarction ,Mice ,In vivo ,Internal medicine ,medicine ,Animals ,Myocardial infarction ,Ventricular remodeling ,Cardiac imaging ,Tissue velocity ,Ventricular Remodeling ,medicine.diagnostic_test ,business.industry ,Models, Cardiovascular ,Stroke Volume ,Magnetic resonance imaging ,Stroke volume ,medicine.disease ,Magnetic Resonance Imaging ,Mice, Inbred C57BL ,Disease Models, Animal ,Cardiology ,business ,Blood Flow Velocity - Published
- 2016
7. Differentiation of athlete's heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance
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Matthew D. Robson, Hugh Watkins, Frank Wiesmann, Ingegerd Östman-Smith, Steffen E. Petersen, Stefan Neubauer, Joseph B. Selvanayagam, Jane M. Francis, Barbara Casadei, and Saul G. Myerson
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Adult ,medicine.medical_specialty ,Systole ,Heart Ventricles ,Diastole ,Cardiomyopathy ,Magnetic Resonance Imaging, Cine ,Left ventricular hypertrophy ,Sensitivity and Specificity ,Internal medicine ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Aged ,Ejection fraction ,Radiological and Ultrasound Technology ,business.industry ,Hypertrophic cardiomyopathy ,Heart ,Stroke Volume ,Stroke volume ,Aortic Valve Stenosis ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Hypertensive heart disease ,Stenosis ,Logistic Models ,ROC Curve ,Hypertension ,cardiovascular system ,Cardiology ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,business ,Sports - Abstract
PURPOSE: Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging. METHODS: A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined. RESULTS: Left ventricular (LV) mass indices were similar for all forms of LVH (p > 0.05), which were at least 35% higher than those obtained in healthy volunteers (p < 0.05). Multiple logistic regression showed that the percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive heart disease. Using a receiver operating curve-determined cut-off value for diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes' hearts could be differentiated from all forms of pathological cardiac hypertrophy with 99% specificity. CONCLUSIONS: Athlete's heart can be reliably distinguished from all forms of pathological cardiac hypertrophy using CMR-derived LV volume and geometric indices, but pathological forms of LVH present with overlapping cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical value.
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- 2016
8. Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI
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Judith Rautenberg, Alex Frydrychowicz, Frank Wiesmann, Axel Haase, Eberhard Rommel, Ralf Illinger, and Stefan Neubauer
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Male ,Pathology ,medicine.medical_specialty ,Heart disease ,Physiology ,Cardiomyopathy ,Mice, Transgenic ,Ventricular Function, Left ,Mice ,In vivo ,Physiology (medical) ,Animals ,Medicine ,Ventricular remodeling ,Heart Failure ,Ventricular Remodeling ,medicine.diagnostic_test ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Ventricle ,Heart failure ,Circulatory system ,Ventricular Function, Right ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output ( r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes ( P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.
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- 2016
9. Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound
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Jane M. Francis, Matthew D. Robson, Stefan Neubauer, M Robinson, Frank Wiesmann, Keith M. Channon, and C P Leeson
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Adult ,Male ,medicine.medical_specialty ,Brachial Artery ,Internal medicine ,medicine.artery ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Brachial artery ,Pulse wave velocity ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Non invasive ,Ultrasound ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,Control subjects ,Magnetic Resonance Imaging ,Compliance (physiology) ,Carotid Arteries ,Echocardiography ,Cardiology ,cardiovascular system ,Female ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Vascular function ,Blood Flow Velocity ,circulatory and respiratory physiology - Abstract
Ultrasound is an established modality for quantification of vascular function in clinical studies of cardiovascular disease. We determined whether cardiovascular magnetic resonance imaging (CMR) can provide a comparable assessment of vascular function. In seventeen control subjects, we used CMR to quantify endothelium-dependent (flow mediated dilatation, FMD) and endothelium-independent dilatation of the brachial artery, brachial and carotid distensibility, aortic compliance, and pulse wave velocity. These were compared to brachial and carotid measurements obtained by established ultrasound protocols. Twelve of the volunteers then underwent repeated measurements with both modalities. There was good agreement between imaging modalities for measures of endothelial function and arterial structure in the same subjects (difference between CMR and ultrasound for FMD = 0.14 +/- 6.8%, and brachial artery area = - 0.7 +/- 2.2 mm2, correlation between modalities for FMD = 0.62, p = 0.01 and for area = 0.87, p = < 0.0001). Inter-study reproducibility was also similar (coefficient of variation (CV) for FMD: CMR = 0.3, ultrasound = 0.3, CV for brachial artery area: CMR = 0.1, ultrasound = 0.1). Comparability and reproducibility were not as strong for functional measures if repeated studies were several days apart (CV for FMD by ultrasound on the same day = 0.1 and several days apart = 0.4). CMR and ultrasound show good agreement for quantitative measures of vascular structure and function with good reproducibility for both modalities. The major advantage of CMR is that it allows one-stop integrated assessment of both peripheral and central measures of vascular function.
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- 2016
10. Multi-modal magnetic resonance imaging quantifies atherosclerosis and vascular dysfunction in patients with type 2 diabetes mellitus
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Robin P. Choudhury, Keith M. Channon, Cheerag Shirodaria, Clare E. Jackson, Stefan Neubauer, Jane M Francis, Matthew D. Robson, Frank Wiesmann, Justin M.S. Lee, and Charalambos Antoniades
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Magnetic Resonance Imaging, Cine ,030209 endocrinology & metabolism ,Type 2 diabetes ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Article ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,medicine.artery ,Internal medicine ,Internal Medicine ,Medicine ,Humans ,Brachial artery ,Pulse wave velocity ,Aged ,Aortic atherosclerosis ,Aorta ,business.industry ,Type 2 Diabetes Mellitus ,Arteries ,Middle Aged ,medicine.disease ,Atherosclerosis ,Diabetes Mellitus, Type 2 ,Cardiology ,cardiovascular system ,Cardiology and Cardiovascular Medicine ,business ,Diabetic Angiopathies - Abstract
Vascular magnetic resonance imaging (MRI) is emerging as a powerful research tool. We studied 18 patients with type 2 diabetes mellitus and 20 controls (all with coronary artery disease). MRI measured distensibility, pulse wave velocity (PWV) and atherosclerosis in the aorta, and brachial artery flow-mediated dilatation (FMD). Patients with diabetes showed lower aortic distensibility (2.1 × 10-3 vs. 3.5 × 10-3 mmHg-1, p
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- 2016
11. Therapieerfolg nrti-reduzierter Regimen mit Integrase-Inhibitoren in der deutschen Nordrhein-Kohorte
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Frank Wiesmann
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- 2016
12. Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function
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Ly-Mee Yu, Ashok Handa, I Kylintireas, Janet E. Digby, Stefan Neubauer, Paul N. Durrington, Robin P. Choudhury, Matthew D. Robson, Keith M. Channon, Colin Cunnington, Cheerag Shirodaria, Thomas Bannister, Frank Wiesmann, and Justin M.S. Lee
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medicine.medical_specialty ,030204 cardiovascular system & hematology ,Placebo ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,030212 general & internal medicine ,medicine.diagnostic_test ,Vascular disease ,business.industry ,Cholesterol ,Magnetic resonance imaging ,medicine.disease ,3. Good health ,Nicotinic agonist ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Circulatory system ,business ,Cardiology and Cardiovascular Medicine ,Blood vessel - Abstract
Objectives: Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function.Background: NA raises high-density lipopr...
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- 2009
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13. Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker
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Alfons Meindl, Frank Wiesmann, Nadia Harbeck, Beate Betz, Rita K. Schmutzler, Edgar Dahl, Takako Sasaki, Norbert Arnold, Juliane Volkmann, Dieter Niederacher, Juliane Ramser, Ariane Sadr-Nabavi, Heide Hellebrand, Rene Kreutzfeld, Marion Kiechle, Joerg Naehrig, Stefanie Engert, and Susanne Seitz
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Adult ,Cancer Research ,Pathology ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Angiogenesis ,DNA Mutational Analysis ,Gene Expression ,Loss of Heterozygosity ,Angiogenesis Inhibitors ,Breast Neoplasms ,Biology ,Epigenesis, Genetic ,Metastasis ,Extracellular matrix protein 1 ,Breast cancer ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Promoter Regions, Genetic ,education ,Aged ,Oligonucleotide Array Sequence Analysis ,Aged, 80 and over ,Extracellular Matrix Proteins ,education.field_of_study ,Neovascularization, Pathologic ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,DNA Methylation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Oncology ,Tissue Array Analysis ,DNA methylation ,Cancer research ,Female ,Breast disease ,Tamoxifen ,medicine.drug - Abstract
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was recently described as an antagonist of angiogenesis. Motivated by a strong dependence of tumor growth and metastasis on angiogenesis, we investigated the role of EFEMP1 in human breast cancer. We applied RNA microarray expression analysis and quantitative real-time PCR (QRT) in a total of 45 sporadic breast cancer tissues and found EFEMP1 down-regulation in 59% and 61% of the analyzed tissues, respectively. This down-regulation was confirmed on protein level. Immunohistochemistry in 211 breast cancer tissues resulted in reduced or even abolished EFEMP1 expression in 57-62.5% of the tumors. Bisulphite genomic sequencing in breast cancer cell lines and primary breast cancer tissues revealed promoter methylation as the major cause of this down-regulation. Furthermore, analysis of 203 clinically well characterized primary breast cancers displayed a significant correlation of reduced EFEMP1 protein expression with poor disease-free (p = 0.037) and overall survival (p = 0.032), particularly in those node-positive patients who received adjuvant anthracycline-based chemotherapy, but not in those treated by either cyclophosphamide-methotrexate-5-fluorouracil (CMF) or Tamoxifen. In summary, the presented data demonstrate for the first time the reduced EFEMP1 expression on RNA and protein level in a substantial number of sporadic breast carcinomas and its correlation with epigenetic alterations. Furthermore, these data point towards a possible predictive impact of EFEMP1 expression in primary breast cancer.
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- 2009
14. Early changes in arterial structure and function following statin initiation: Quantification by magnetic resonance imaging
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Jane M Francis, Keith M. Channon, Clare E. Jackson, Stefan Neubauer, Frank Wiesmann, Steffen E. Petersen, Justin M.S. Lee, Robin P. Choudhury, Paul Leeson, Matthew D. Robson, and Cheerag Shirodaria
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Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Magnetic resonance angiography ,Article ,Coronary artery disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Magnetic resonance imaging ,Internal medicine ,medicine.artery ,Medicine ,Humans ,Carotid Stenosis ,030212 general & internal medicine ,Aorta ,Aged ,Carotid ,medicine.diagnostic_test ,business.industry ,Vascular disease ,Statin ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,Atherosclerosis ,medicine.anatomical_structure ,Carotid Arteries ,Circulatory system ,Cardiology ,Female ,Radiology ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Cardiology and Cardiovascular Medicine ,Magnetic Resonance Angiography ,Blood vessel ,Artery - Abstract
Effective LDL-cholesterol (LDL-C) reduction improves vascular function and can bring about regression of atherosclerosis. Alterations in endothelial function can occur rapidly, but changes in atherosclerosis are generally considered to occur more slowly. Vascular magnetic resonance imaging (MRI) is a powerful technique for accurate non-invasive assessment of central and peripheral arteries at multiple anatomical sites. We report the changes in atherosclerosis burden and arterial function in response to open label statin treatment, in 24 statin-naïve newly diagnosed stable coronary artery disease patients. Patients underwent MRI before, and 3 and 12 months after commencing treatment. Mean LDL-C fell by 37% to 70.8 mg/dL (P
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- 2008
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15. How to Perform an Accurate Assessment of Cardiac Function in Mice using High-Resolution Magnetic Resonance Imaging
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Stefan Neubauer, Frank Wiesmann, Jürgen E. Schneider, and Craig A. Lygate
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medicine.medical_specialty ,Heart Ventricles ,Myocardial Infarction ,Magnetic Resonance Imaging, Cine ,Image processing ,Ventricular Function, Left ,Animals, Genetically Modified ,Electrocardiography ,Mice ,Coronary circulation ,Heart Rate ,Coronary Circulation ,Image Processing, Computer-Assisted ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Heart Failure ,Mice, Knockout ,Observer Variation ,Ejection fraction ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Orientation (computer vision) ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,Stroke volume ,Image segmentation ,Disease Models, Animal ,medicine.anatomical_structure ,Chronic Disease ,Heart Function Tests ,cardiovascular system ,Hypertrophy, Left Ventricular ,Radiology ,Artifacts ,Cardiology and Cardiovascular Medicine ,business ,Biomedical engineering - Abstract
High-resolution magnetic resonance cine imaging (cine-MRI) is a method that allows for a non-invasive assessment of left ventricular function and mass. To perform this quantitation, hearts are imaged from the base to the apex by a stack of two-dimensional images. Thus, analysis of myocardial mass and function by cine-MRI does not rely on geometric assumptions. Geometric and functional parameters, such as end-diastolic volume (EDV), end-systolic volume (ESV) or ejection fraction (EF), are obtained by subsequent image segmentation of the respective cine frames in each slice. While this technique has been well established in clinical practice, it is now rapidly becoming the reference method in experimental cardiovascular MRI for accurate quantification of cardiac parameters, thereby aiding the phenotyping of the increasing number of transgenic and surgical mouse models. However, accurate measurement of cardiac functional parameters requires the images to be acquired in short-axis orientation of the heart, which can be difficult to define, particularly in animals with diseased hearts. Furthermore, data analysis can be the source of a systematic error, mainly for myocardial mass measurement. Here, we describe a protocol that allows for a quick and reproducible approach of obtaining the relevant cardiac views for cine-MRI, and we explain how an accurate experimental image analysis can be performed.
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- 2006
16. Functional and Structural Vascular Remodeling in Elite Rowers Assessed by Cardiovascular Magnetic Resonance
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Frank Wiesmann, Matthew D. Robson, Steffen E. Petersen, Stefan Neubauer, Joseph B. Selvanayagam, Keith M. Channon, Lucy Hudsmith, and Jane M Francis
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Adult ,Male ,medicine.medical_specialty ,Brachial Artery ,Population ,Diastole ,030204 cardiovascular system & hematology ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,medicine.artery ,Internal medicine ,medicine ,Humans ,Common carotid artery ,Brachial artery ,Endothelial dysfunction ,education ,Exercise ,Aorta ,education.field_of_study ,business.industry ,030229 sport sciences ,medicine.disease ,Magnetic Resonance Imaging ,Elasticity ,medicine.anatomical_structure ,Carotid Arteries ,Regional Blood Flow ,Case-Control Studies ,Cardiology ,Arterial stiffness ,Physical Endurance ,cardiovascular system ,Female ,Radiology ,Endothelium, Vascular ,business ,Cardiology and Cardiovascular Medicine ,Artery ,Sports - Abstract
OBJECTIVES: We aimed to noninvasively quantify the effects of chronic exercise training on both peripheral and central conduit artery function and structure with high-resolution magnetic resonance imaging (MRI). BACKGROUND: Physical activity has well-known beneficial effects on vascular function in subjects with endothelial dysfunction. Exercise also leads to beneficial effects on endothelial function in elderly athletes, possibly contributing toward the reduced risk from coronary artery disease in this age group. However, conflicting data exist on the training effects in the younger population. METHODS: A total of 49 young (age 20 to 35 years) nonsmoking subjects, comprising elite rowers and age- and gender-matched sedentary control subjects, underwent MRI (1.5-T). The ascending, the proximal descending, and the distal descending aorta, and the common carotid artery and the brachial artery were assessed for diastolic and systolic area and distensibility. Endothelial-dependent and -independent brachial artery dilatation were also assessed by cine MRI. RESULTS: Rowers showed vascular remodeling with enlarged brachial (by 51%, p < 0.001) and reduced central conduit artery cross-sectional areas (by up to 28% [e.g., distal descending aorta], p < 0.001). Vessel distensibilities (mm Hg(-1)) were similar for elite rowers when compared with sedentary control subjects at all levels of the aorta and the carotid and brachial artery (p > 0.05 for all). Endothelial-dependent dilation (percentage and mm2) was similar for rowers and control subjects (p > 0.05). However, rowers showed reduced absolute (by 33%) endothelial-independent dilation (p < 0.001). CONCLUSIONS: Young elite rowers demonstrate normal endothelial-dependent but reduced endothelial-independent dilation. Chronic, whole body, combined endurance- and strength-training does not lead to changes in arterial stiffness but to vascular remodeling.
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- 2006
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17. Myocardial Tissue Phase Mapping with Cine Phase-Contrast MR Imaging: Regional Wall Motion Analysis in Healthy Volunteers
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Matthew D. Robson, Joseph B. Selvanayagam, Bernd Jung, Frank Wiesmann, Jane M Francis, Stefan Neubauer, Juergen Hennig, and Steffen E. Petersen
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Adult ,Male ,Systole ,Diastole ,Magnetic Resonance Imaging, Cine ,Imaging, Three-Dimensional ,Reference Values ,Healthy volunteers ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Phase mapping ,Wall motion ,Observer Variation ,Reproducibility ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,Magnetic resonance imaging ,Myocardial Contraction ,Mr imaging ,Female ,Nuclear medicine ,business - Abstract
PURPOSE: To establish prospectively a database of normal three-dimensional systolic and diastolic endocardial and epicardial velocity values for all myocardial segments in healthy volunteers by using cine phase-contrast velocity magnetic resonance imaging, also called tissue phase mapping (TPM). MATERIALS AND METHODS: The study was approved by the institutional ethics committee and was conducted according to principles of the Declaration of Helsinki; each subject provided informed written consent. Ninety-six healthy volunteers (57 [59%] men, 39 [41%] women; mean age, 38 years +/- 12 [standard deviation]) underwent cardiac phase-contrast imaging with a black blood segmented k-space gradient-echo sequence for the analysis of three-dimensional myocardial velocity with high spatial resolution at 1.5 T on basal, midventricular, and apical short-axis views. Eighteen consecutive volunteers were imaged twice to determine interstudy reproducibility, and intra- and interobserver variability values were analyzed. Systolic and diastolic velocity curves were analyzed for peak velocity and time to peak velocity in the radial, circumferential, and longitudinal directions, as well as for torsion rate and longitudinal strain rate. Mixed-effects models with a random intercept for volunteers were used to test differences among the three ventricular sections and the transmural, endocardial, and epicardial parameters. RESULTS: TPM enabled reproducible assessment of myocardial velocity with small intra- and interobserver variability values. Systolic peak radial velocity was lowest at the apical level (P < .001); diastolic peak radial velocity was similar at all three myocardial levels (P = .73). As viewed from the apex, a relative counterclockwise rotation during systole was followed by a relative clockwise rotation of the apex against the base. Diastolic and systolic peak longitudinal velocity values decreased from base to apex (P < .001). A gradient between endocardium and epicardium was observed for radial velocity values, with greater endocardial velocity values (P < .001). CONCLUSION: TPM is a reproducible comprehensive modality for assessment of regional wall motion, and intra- and interobserver variability values are low.
- Published
- 2006
18. Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis
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Jürgen Veeck, Oliver Galm, C Huszka, Eva Klopocki, Matthias Dürst, Edgar Dahl, O Camara, Ruth Knüchel, Frank Wiesmann, H An, Glen Kristiansen, Dieter Niederacher, and Beate Betz
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Adult ,Cancer Research ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Epigenesis, Genetic ,chemistry.chemical_compound ,Breast cancer ,Secreted frizzled-related protein 1 ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Gene Silencing ,skin and connective tissue diseases ,Molecular Biology ,Aged ,Glycoproteins ,Aged, 80 and over ,Intracellular Signaling Peptides and Proteins ,Wnt signaling pathway ,Cancer ,DNA Methylation ,Middle Aged ,medicine.disease ,Demethylating agent ,Gene Expression Regulation, Neoplastic ,Wnt Proteins ,chemistry ,DNA methylation ,Cancer research ,Female ,Ovarian cancer ,Carcinogenesis - Abstract
The canonical Wnt signalling pathway plays a key role during embryogenesis and defects in this pathway have been implicated in the pathogenesis of various types of tumours, including breast cancer. The gene for secreted frizzled-related protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a chromosomal region (8p22–p12) that is often deleted in breast cancer. In colon, lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by promoter methylation. We have previously shown that loss of SFRP1 protein expression is a common event in breast tumours that is associated with poor overall survival in patients with early breast cancer. To investigate the cause of SFRP1 loss in breast cancer, we performed mutation, methylation and expression analysis in human primary breast tumours and breast cell lines. No SFRP1 gene mutations were detected. However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP). We found a tight correlation (P
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- 2006
19. Left Ventricular Non-Compaction
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Matthew D. Robson, Steffen E. Petersen, Jane M Francis, Stefan Neubauer, Joseph B. Selvanayagam, Frank Wiesmann, Robert H. Anderson, and Hugh Watkins
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medicine.medical_specialty ,business.industry ,Diastole ,Cardiomyopathy ,Hypertrophic cardiomyopathy ,Dilated cardiomyopathy ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,medicine.disease ,Left ventricular noncompaction cardiomyopathy ,3. Good health ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Aortic valve stenosis ,Cardiology ,medicine ,cardiovascular system ,Left ventricular noncompaction ,Radiology ,business ,Cardiology and Cardiovascular Medicine - Abstract
OBJECTIVES We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction (LVNC) from lesser degrees of trabecular layering seen in healthy volunteers and, in those with cardiomyopathies and concentric left ventricular hypertrophy, potential differential diagnoses. We hypothesized that pathological trabeculation could be distinguished by determining the ratio of non-compacted to compacted myocardium (NC/C ratio). BACKGROUND Left ventricular non-compaction is characterized by a non-compacted myocardial layer in the left ventricle. Cardiovascular magnetic resonance images this layer with unprecedented quality, particularly in the ventricular apex, where echocardiography has inherent difficulties. METHODS We analyzed magnetic resonance cine images, using the 17-segment model in 45 healthy volunteers, 25 athletes, 39 patients with hypertrophic cardiomyopathy and 14 with dilated cardiomyopathy, 17 with hypertensive heart disease, and 30 with aortic stenosis, as well as images from 7 patients previously diagnosed with LVNC whose diagnoses were supported by additional features. RESULTS Areas of non-compaction were common and occurred more frequently in all groups studied in apical and lateral, rather than in basal or septal, segments. A NC/C ratio of >2.3 in diastole distinguished pathological non-compaction, with values for sensitivity, specificity, and positive and negative predictions of 86%, 99%, 75%, and 99%, respectively. CONCLUSIONS Left ventricular non-compaction is diagnosed accurately with CMR using the NC/C ratio in diastole.
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- 2005
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20. Global impairment of brachial, carotid, and aortic vascular function in young smokers
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Robin P. Choudhury, Jane M Francis, Steffen E. Petersen, Frank Wiesmann, Stefan Neubauer, Paul Leeson, Keith M. Channon, Matthew D. Robson, and Qian Wang
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Aortic arch ,medicine.medical_specialty ,Aorta ,Pathology ,business.industry ,Vascular disease ,Hemodynamics ,030204 cardiovascular system & hematology ,medicine.disease ,3. Good health ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine.artery ,Descending aorta ,Internal medicine ,Ascending aorta ,Cardiology ,cardiovascular system ,Medicine ,Endothelial dysfunction ,Brachial artery ,business ,Cardiology and Cardiovascular Medicine - Abstract
Objectives The purpose of this study was to assess vascular dysfunction in young smokers by high-resolution magnetic resonance imaging (MRI). Background Cigarette smoking is a well-known cause of endothelial dysfunction, reflected by impaired brachial artery reactivity to hyperemia. We hypothesized that smoking induces both peripheral endothelial dysfunction and altered function in central conduit arteries, and that these global changes in vascular function could be directly quantified in a single noninvasive examination using high-resolution MRI. Methods A total of 22 healthy young volunteers (mean age 31 ± 2 years; 12 nonsmokers, 10 smokers: cumulative cigarette consumption 11.9 ± 6.0 pack-years) underwent noninvasive high-resolution MRI to assess central vascular distensibility and pulse-wave velocity (PWV), and cross-sectional flow-mediated dilation (FMD) of the brachial artery. Results Brachial artery FMD was significantly reduced in smokers compared with nonsmokers (7.5 ± 2.7% vs. 15.5 ± 2.0%; p = 0.03), indicating impaired endothelium-dependant relaxation, whereas endothelium-independent responses to sublingual glyceroltrinitrate(400 μg) were identical in both groups. Impaired peripheral endothelial function in smokers was accompanied by striking decreases in central vascular distensibility in both the common carotid arteries (−45.7%; p = 0.02) and at multiple sites in the aorta (ascending aorta −26.9%, p = 0.04; thoracic descending aorta −25.0%, p = 0.01; abdominal descending aorta −25.5%, p = 0.02). Aortic arch PWV in smokers was increased by 19% (p = 0.02). Conclusions Cigarette smoking induces global changes in both peripheral and central vascular function. Direct quantification of multiple parameters of vascular function using high-resolution MRI will provide powerful new approaches to the assessment of vascular disease pathogenesis, diagnosis, and treatment.
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- 2004
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21. Value of Delayed-Enhancement Cardiovascular Magnetic Resonance Imaging in Predicting Myocardial Viability After Surgical Revascularization
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David P. Taggart, Frank Wiesmann, Attila Kardos, Joseph B. Selvanayagam, Steffen E. Petersen, Jane M Francis, and Stefan Neubauer
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Gadolinium DTPA ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Coronary Artery Bypass, Off-Pump ,Contrast Media ,Magnetic Resonance Imaging, Cine ,Myocardial Reperfusion Injury ,Delayed enhancement ,Revascularization ,Cohort Studies ,Necrosis ,Coronary artery bypass surgery ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Postoperative Period ,Coronary Artery Bypass ,Aged ,Randomized Controlled Trials as Topic ,Observer Variation ,medicine.diagnostic_test ,business.industry ,Myocardium ,Magnetic resonance imaging ,Perioperative ,Middle Aged ,Magnetic Resonance Imaging ,Myocardial Contraction ,Clinical trial ,Cardiology ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Cohort study ,Surgical revascularization - Abstract
Background— Despite the accepted utility of delayed-enhancement MRI in identifying irreversible myocardial injury, no study has yet assessed its role as a viability tool exclusively in the setting of coronary artery bypass surgery (CABG), and no study has repeated delayed-enhancement MRI late after revascularization. In a clinical trial in which patients underwent CABG by either the off-pump or on-pump surgical technique, we hypothesized that (1) preoperative delayed-enhancement MRI would have high diagnostic accuracy in predicting viability and (2) the occurrence of perioperative myocardial necrosis would affect late regional wall motion recovery. Methods and Results— Fifty-two patients undergoing multivessel CABG were studied by preoperative and early (day 6) and late (6 months) postoperative cine MRI for global and regional functional assessment and delayed-enhancement MRI for assessment of irreversible myocardial injury. Preoperatively, 611 segments (21%) had abnormal regional function, whereas 421 segments (14%) showed evidence of hyperenhancement. At 6 months after revascularization, 57% (343 of 611) of dysfunctional segments improved contraction by at least 1 grade. When all preoperative dysfunctional segments were analyzed, there was a strong correlation between the transmural extent of hyperenhancement and the recovery in regional function at 6 months ( P Conclusions— Delayed-enhancement MRI is a powerful predictor of myocardial viability after surgery, suggesting an important role for this technique in clinical viability assessment.
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- 2004
22. Fast, high-resolution in vivo cine magnetic resonance imaging in normal and failing mouse hearts on a vertical 11.7 T system
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Karen Hulbert, Craig A. Lygate, Kieran Clarke, Frank Wiesmann, Damian J. Tyler, Stefan Neubauer, Paul J. Cassidy, Jürgen E. Schneider, and Stuart M. Grieve
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Heart Failure ,Male ,Cardiac function curve ,Materials science ,medicine.diagnostic_test ,Relaxation (NMR) ,Myocardial Ischemia ,Magnetic Resonance Imaging, Cine ,Heart ,Magnetic resonance imaging ,Field strength ,Anatomy ,medicine.disease ,Mice, Inbred C57BL ,Mice ,Heart failure ,Models, Animal ,Horizontal position representation ,Vertical direction ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Image resolution ,Biomedical engineering - Abstract
PURPOSE: To establish fast, high-resolution in vivo cine magnetic resonance imaging (cine-MRI) on a vertical 11.7-T MR system and to investigate the stability of normal and failing mouse hearts in the vertical position. MATERIALS AND METHODS: To optimize the method on a high-field system, various MR-related parameters, such as relaxation times and the need for respiratory gating, were quantitatively investigated. High-resolution cine-MRI was applied to normal mice and to a murine heart failure model. Cardiac functional parameters were compared to matched mice imaged previously on a horizontal MR system. RESULTS: A T(1) of 1.10 +/- 0.27 seconds and a T(2) of 18.5 +/- 3.9 msec were measured for murine myocardial tissue. A quantitative analysis also proved respiratory gating to be essential for obtaining artifact-free cine images in the vertical position at this field strength. Cardiac functional parameters of mice, obtained within one hour, agreed well with those from previous studies of mice in the horizontal position. CONCLUSION: This work shows that MR systems with a vertical bore design can be used to accurately measure cardiac function in both normal and chronically failing mouse hearts within one hour. The increased signal-to-noise ratio (SNR) due to the higher field strength could be exploited to obtain higher temporal and spatial resolution compared to previous studies that were performed on horizontal systems with lower field strengths.
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- 2003
23. In vivo time-resolved quantitative motion mapping of the murine myocardium with phase contrast MRI
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Michael Szimtenings, Axel Haase, Volker Herold, Frank Wiesmann, Matthias Nahrendorf, Eberhard Rommel, Titus Lanz, and Jörg U. G. Streif
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Cardiac function curve ,Materials science ,Phase contrast microscopy ,Myocardial Infarction ,Magnetic Resonance Imaging, Cine ,Infarction ,computer.software_genre ,Imaging phantom ,law.invention ,Electrocardiography ,Mice ,Nuclear magnetic resonance ,law ,In vivo ,Voxel ,Image Processing, Computer-Assisted ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Image resolution ,Phantoms, Imaging ,business.industry ,medicine.disease ,Myocardial Contraction ,Mice, Inbred C57BL ,Temporal resolution ,Nuclear medicine ,business ,computer - Abstract
Myocardial motion of healthy mice and mice with myocardial infarction was assessed in vivo by phase contrast (PC) cine MRI. The imaging module was a segmented fast low angle shot (FLASH) sequence with velocity compensation in all three gradient directions. To accomplish additional motion encoding, the spin phase was prepared using bipolar gradient pulses, which resulted in a linear dependence between the voxel velocity and spin phase. This method provided accurate quantification of the velocity magnitude and direction of the murine myocardium at a spatial resolution of 234 μm and a temporal resolution of about 10 ms. The acquisition was EKG-gated and the mice were anesthetized by inhalation of 1.5–4.0 vol.% isoflurane at 1.5 l/min oxygen flow. To validate the MRI measurements, an experiment with a calibrated rotating phantom was performed. Deviations between MR velocity measurements and optical assessment by a light detector were lower than 1.6%. During our study, myocardial motion velocities between 0.4 cm/s and 1.7 cm/s were determined for the healthy murine myocardium across the heart cycle. Areas with myocardial infarction were clearly segmented and showed a motion velocity which was significantly reduced. In conclusion, the method is an accurate technique for the assessment of murine myocardial motion in vivo. Magn Reson Med 49:315–321, 2003. © 2003 Wiley-Liss, Inc.
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- 2003
24. In vivo assessment of absolute perfusion in the murine skeletal muscle with spin labeling MRI
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Jörg U. G. Streif, Wolfgang R. Bauer, Axel Haase, Matthias Nahrendorf, Frank Wiesmann, Eberhard Rommel, Karl-Heinz Hiller, and Christiane Waller
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medicine.diagnostic_test ,Chemistry ,business.industry ,Skeletal muscle ,Magnetic resonance imaging ,Vasodilation ,Site-directed spin labeling ,Microsphere ,medicine.anatomical_structure ,In vivo ,medicine ,Surface coil ,Radiology, Nuclear Medicine and imaging ,Nuclear medicine ,business ,Perfusion - Abstract
Purpose To assess absolute perfusion in the skeletal muscle of mice in vivo with spin labeling magnetic resonance imaging (MRI) under normal and stress conditions. Materials and Methods Absolute perfusion in the skeletal muscle of 27 C57BL/6 mice was assessed in vivo non-invasively by spin labeling MRI at 7.05 T. This technique was based on the acquisition of T1 maps with global and slice-selective spin inversion in separate acquisitions. T1 mapping was performed by inversion recovery snapshot fast low angle shot imaging. To guarantee proper spin inversion within the whole mouse, a dedicated radiofrequency (RF) coil combination was constructed. A birdcage resonator was used for transmission, while detection of the MRI signal was achieved by a surface coil. Results Basal perfusion in the hindlimbs was determined to be 94 ± 10 mL (100 g · minute)–1 (mean ± standard error of the mean [SEM], N = 27). This value is in good agreement with perfusion values determined by invasive techniques such as microspheres. A subgroup of six animals received a constant dose of 4 mg (kg · minute)–1 of the vasodilator adenosine by an intraperitoneal catheter. In this case, perfusion was significantly increased to 179 ± 56 mL (100 g · minute)–1 (mean ± SEM, N = 6, P < 0.02). Mean basal perfusion in this subgroup was 96 ± 26 mL (100 g · minute)–1. Conclusion Spin labeling MRI is a well-suited technique for the in vivo assessment of absolute perfusion in the murine skeletal muscle. J. Magn. Reson. Imaging 2003;17:147–152. © 2002 Wiley-Liss, Inc.
- Published
- 2002
25. Determination of regional blood volume and intra-extracapillary water exchange in human myocardium using Feruglose: First clinical results in patients with coronary artery disease
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Anja Lehning, Michael Bock, Georg Ertl, Axel Haase, Christian M. Wacker, Frank Wiesmann, Lothar R. Schad, Peter M. Jakob, Jörn Sandstede, and Wolfgang R. Bauer
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Male ,Iron ,Contrast Media ,Coronary Disease ,Blood volume ,Water exchange ,Human myocardium ,Coronary artery disease ,Coronary Circulation ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Magnetite Nanoparticles ,Aged ,medicine.diagnostic_test ,business.industry ,Myocardium ,Water ,Dextrans ,Oxides ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Ferrosoferric Oxide ,Capillaries ,medicine.anatomical_structure ,Regional Blood Flow ,Relaxation rate ,Female ,Nuclear medicine ,business ,Blood vessel - Abstract
The aim of this pilot study in humans was to investigate the effect of an intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and compared with a theoretical model which allowed determination of the intra- extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9 %). A linear response range of DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow the determination of RBV with intravascular CA.
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- 2002
26. Variation analysis of six HCV viral load assays using low viremic HCV samples in the range of the clinical decision points for HCV protease inhibitors
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Annemarie Berger, Patrick Braun, Christoph Sarrazin, Rolf Kaiser, Frank Wiesmann, Robert Ehret, Gudrun Naeth, and Heribert Knechten
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Microbiology (medical) ,Hepacivirus ,Immunology ,TaqMan ,Viremia ,Antiviral Agents ,Quantification ,medicine ,Immunology and Allergy ,Humans ,Protease Inhibitors ,Clinical decision ,COBAS ,Original Investigation ,biology ,Reproducibility of Results ,General Medicine ,Hepatitis C ,Hepatitis C, Chronic ,Viral Load ,biology.organism_classification ,medicine.disease ,Virology ,Decision points ,Blood ,RealTime ,Hcv protease ,HCV ,Viral load - Abstract
In the range of clinical decision points for response-guided therapy of HCV, there is still insufficient data concerning the conformity of quantification results obtained by different assays and their correlation with the HPS/CTM v2 assay which was used for initial clinical studies. In a head-to-head comparison, assay accuracy and detection rates of six quantitative assays [artus HCV QS-RGQ, COBAS Ampliprep/COBAS TaqMan HCV v1/v2, High Pure System/COBAS TaqMan (HPS), RealTime HCV, and Versant HCV1.0] were assessed by measuring WHO and PEI standards at dilution steps near clinical decision points. Detection rates and mean differences between assays were evaluated by analyzing twenty clinical samples at 10, 100, and 1,000 IU/mL. Ten replicates from specimens with different HCV genotypes were used to analyze pan-genotypic intra-assay variation. At ≤ 25 IU/mL, RealTime demonstrated the highest detection rates. With 0.1 log difference when testing clinical samples, results obtained from the Versant and RealTime assays matched best with results from HPS. Mean difference analysis across all assay results revealed wide differences between 0.01 and 0.75 log IU/mL. RealTime showed the lowest intra-assay variation across genotypes 1-4 (25, 100, 1,000 IU/mL). There are substantial analytical differences between viral load assays clinicians should be aware of. These variations may have impact on clinical decisions for patients on HCV triple therapy and may argue for assay-specific decision points equivalent to reference values established in studies using HPS. A comparison of quantification is recommended prior to a switch of assays during ongoing therapy.
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- 2014
27. Vascular Hypertrophy and Increased P70S6 Kinase in Mice Lacking the Angiotensin II AT 2 Receptor
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Frank Wiesmann, Martin J. Lohse, Lorenz Meinel, Jörg Peters, Lutz Hein, Andreas Simm, Kerstin Hadamek, Marc Brede, Axel Haase, and Stefan Engelhardt
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Agonist ,Angiotensin receptor ,medicine.medical_specialty ,Captopril ,medicine.drug_class ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Receptor, Angiotensin, Type 2 ,Mice ,Culture Techniques ,Physiology (medical) ,Internal medicine ,Renin–angiotensin system ,medicine ,Animals ,Vascular Diseases ,Phosphorylation ,Receptor ,Phenylephrine ,Mice, Knockout ,Receptors, Angiotensin ,Angiotensin II receptor type 1 ,business.industry ,Ribosomal Protein S6 Kinases ,Hemodynamics ,Myography ,Heart ,Hypertrophy ,Magnetic Resonance Imaging ,Angiotensin II ,Endocrinology ,Vasoconstriction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Signal Transduction ,medicine.drug - Abstract
Background Angiotensin II activates 2 distinct G protein–coupled receptors, the AT 1 and AT 2 receptors. Most of the known cardiovascular effects of angiotensin II are mediated by the AT 1 receptor subtype. The aim of the present study was to test whether deletion of the AT 2 receptor gene in mice (AT 2 -KO mice) leads to long-term functional or structural alterations in the cardiovascular system. Methods and Results In vivo pressure responses to angiotensin II or the α 1 -adrenergic receptor agonist phenylephrine were greatly enhanced in AT 2 -KO mice. Deletion of the angiotensin AT 2 receptor did not lead to a compensatory increase of the activity of the circulating renin-angiotensin system, and arterial blood pressure was identical in wild-type control mice (WT) and AT 2 -KO mice. Cardiac contractility as assessed by LV catheterization and by rapid MRI also did not differ between AT 2 -KO and WT mice. Isolated femoral arteries from AT 2 -KO mice, however, showed enhanced vasoconstriction to angiotensin II, norepinephrine, and K + depolarization compared with WT. Morphometric analysis of large and small femoral arteries revealed a significant hypertrophy of media smooth muscle cells. Phospho-P70S6 kinase levels were significantly increased in aortas from AT 2 -KO mice compared with WT mice. Treatment of mice with an ACE inhibitor for 8 weeks abolished the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in AT 2 -KO mice. Conclusions These results indicate that vascular AT 2 receptors inhibit the activity and, hence, hypertrophic signaling by the P70S6 kinase in vivo and thus are important regulators of vascular structure and function.
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- 2001
28. Can We Use Vertical Bore Magnetic Resonance Scanners for Murine Cardiovascular Phenotype Characterization? Influence of Upright Body Position on Left Ventricular Hemodynamics in Mice
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Axel Haase, Frank Wiesmann, Lutz Hein, and Stefan Neubauer
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Male ,medicine.medical_specialty ,Supine position ,Posture ,Hemodynamics ,Blood Pressure ,Ventricular Function, Left ,Hypotension, Orthostatic ,Mice ,Orthostatic vital signs ,Internal medicine ,Heart rate ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Mice, Inbred C57BL ,Blood pressure ,medicine.anatomical_structure ,Ventricle ,Cardiology ,Ventricular pressure ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
High resolution magnetic resonance (MR) imaging is uniquely suited for cardiovascular phenotype characterization in transgenic mice. Experimental MR scanners with the high magnetic field strength are commonly built with a vertical bore design. The hemodynamic consequences of a prolonged upright body position in anesthetized mice are, however, unknown. Thus, the purpose of this work was to investigate the influence of a vertical body position on murine systemic blood pressure and left ventricular (LV) hemodynamics over time. We studied six C57Bl/6 mice at 14-16 weeks of age (body weight, 24-28 g) under isoflurane anesthesia. Positioned supine on a 37 degrees C warming pad, a microtip catheter was advanced via the right carotid artery into the left ventricle. Continuous registration of LV hemodynamics was performed at rest and after tilting of the table to a 90-degree vertical position. After tilting, there was a transient decrease of LV systolic pressure to 96% of initial values immediately after tilting with return to baseline level within 6 min. Tilting to vertical position had no influence on LV end-diastolic pressure, heart rate, maximal rate of left ventricular pressure increase, and maximal rate of left ventricular pressure decrease. Over a follow-up period of 60 min in vertical position, there were no significant changes in murine hemodynamics. An acute change of body position is fully compensated by a normal orthostatic response in anesthetized mice. Prolonged upright body position exerts no significant changes in murine LV hemodynamics. Hence, high resolution MR studies for cardiovascular phenotype characterization in transgenic mice performed on vertical bore MR scanners allow measurements under physiologic conditions.
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- 2001
29. Magnetic Resonance Imaging of Coronary Arteries and Heart Valves in a Living Mouse: Techniques and Preliminary Results
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Axel Haase, Frank Wiesmann, Jan Ruff, and Titus Lanz
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Nuclear and High Energy Physics ,Short axis ,Biophysics ,Biochemistry ,Electrocardiography ,Mice ,Left coronary artery ,Heart Rate ,In vivo ,medicine.artery ,Image Interpretation, Computer-Assisted ,Cardiac valve ,Animals ,Medicine ,Isotropic resolution ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Condensed Matter Physics ,Coronary Vessels ,Heart Valves ,Magnetic Resonance Imaging ,Coronary arteries ,medicine.anatomical_structure ,Respiratory Mechanics ,business ,Algorithms ,Biomedical engineering ,Gradient echo - Abstract
New investigations in MRI of a mouse heart showed high-contrast cardiac images and thereby the possibility of doing functional cardiac studies of in vivo mice. But is MRI, in addition, capable of visualizing microstructures such as the coronary arteries and the heart valves of a living mouse? To answer this question, 2D and 3D gradient echo sequences with and without flow compensation were used to image the coronary arteries. To increase signal-to-noise ratio, a birdcage resonator was optimized for mouse heart imaging. Contrast between blood and myocardium was achieved through the inflow effect. A segmented three-dimensional FLASH sequence acquired with a multiple overlap thin slab technique showed the best results. With this technique an isotropic resolution of 100 μm was achieved. The left coronary artery could be visualized up to the apex of the heart. This is demonstrated with short axis views and 3D surface reconstructions of the mouse heart. The four cardiac valves were also visible with the 3D method.
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- 2000
30. Progressive hypertrophy and heart failure in β 1 -adrenergic receptor transgenic mice
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Frank Wiesmann, Stefan Engelhardt, Lutz Hein, and Martin J. Lohse
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Cardiac function curve ,Aging ,medicine.medical_specialty ,Gene Expression ,Cardiomegaly ,Mice, Transgenic ,Biology ,Muscle hypertrophy ,Contractility ,Mice ,Organ Culture Techniques ,Internal medicine ,Heart rate ,medicine ,Animals ,Myocyte ,Receptor ,Heart Failure ,Multidisciplinary ,Ejection fraction ,Biological Sciences ,medicine.disease ,Myocardial Contraction ,Endocrinology ,Heart failure ,Receptors, Adrenergic, beta-1 - Abstract
Stimulation of cardiac β 1 -adrenergic receptors is the main mechanism that increases heart rate and contractility. Consequently, several pharmacological and gene transfer strategies for the prevention of heart failure aim at improving the function of the cardiac β-adrenergic receptor system, whereas current clinical treatment favors a reduction of cardiac stimulation. To address this controversy, we have generated mice with heart-specific overexpression of β 1 -adrenergic receptors. Their cardiac function was investigated in organ bath experiments as well as in vivo by cardiac catheterization and by time-resolved NMR imaging. The transgenic mice had increased cardiac contractility at a young age but also developed marked myocyte hypertrophy (3.5-fold increase in myocyte area). This increase was followed by progressive heart failure with functional and histological deficits typical for humans with heart failure. Contractility was reduced by ≈50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of ≈20%. We conclude that overexpression of β 1 -adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased β 1 -adrenergic receptor signalling is ultimately detrimental.
- Published
- 1999
31. Contrast enhancement and artifact reduction in magnetization-prepared MR angiography
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Claudia M. Hillenbrand, Frank Wiesmann, Ralf Deichmann, Axel Haase, and Dietbert Hahn
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Contrast enhancement ,Materials science ,medicine.diagnostic_test ,Mr angiography ,Imaging phantom ,Artifact reduction ,Magnetic resonance angiography ,Electronic, Optical and Magnetic Materials ,symbols.namesake ,Magnetization ,Nuclear magnetic resonance ,Fourier transform ,In vivo ,symbols ,medicine ,Computer Vision and Pattern Recognition ,Electrical and Electronic Engineering ,Software - Abstract
A method for the contrast enhancement and reduction of artifacts in three-dimensional (3D) magnetization-prepared (MP) magnetic resonance angiography (MRA) sequences is presented. A common artifact in these sequences is a periodical signal loss inside the vessels at the slab-slab junctions due to progressive saturation of the blood spins. This effect may be overcome by numerical optimization of the excitation pulses in dependence on sequence-related and physiological parameters. The feasibility of this method is shown in a phantom and an in vivo experiment by visualization of the carotid arteries and intracranial vessels. Furthermore, a method for contrast enhancement in MRA by data postprocessing is proposed, based on appropriate filtering of k-space data before Fourier transformation. This method is tested in two in vivo experiments by visualization of the arteries in the head and leg of healthy volunteers. © 1999 John Wiley & Sons, Inc. Int J Imaging Syst Technol 10, 266–272, 1999
- Published
- 1999
32. Comparison of fast spiral, echo planar, and fast low-angle shot MRI for cardiac volumetry at .5T
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Frank Wiesmann, Peter D. Gatehouse, David N. Firmin, Jonathan R. Panting, Andrew M. Taylor, and Dudley J. Pennell
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Adult ,Male ,Time Factors ,Materials science ,Image quality ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Magnetic Resonance Imaging, Cine ,Both ventricles ,Flash (photography) ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Image resolution ,Spiral ,Observer Variation ,Echo-planar imaging ,Echo-Planar Imaging ,business.industry ,Reproducibility of Results ,Heart ,Magnetic Resonance Imaging ,Temporal resolution ,Feasibility Studies ,Female ,Nuclear medicine ,business ,Echo planar ,Biomedical engineering - Abstract
The application of fast imaging is necessary to reduce the scanning time for cardiac volumetric MRI. Fast spiral, echo planar imaging (EPI), and fast low-angle shot (FLASH) imaging are rapid MRI techniques that allow image acquisition within a fraction of a second. Performed as a multi-shot technique, breath-hold imaging with high temporal and spatial resolution is feasible. This study evaluated the accuracy of interleaved spiral, EPI, and FLASH imaging for measuring ventricular volume and mass at .5T. Breath-hold short-axis cines in parallel planes covering both ventricles were acquired in 16 volunteers with all three fast methods, as well as with conventional gradient-echo imaging for comparison. All fast techniques showed good agreement with conventional imaging. Despite its lower temporal resolution, FLASH imaging yielded higher image quality than EPI and spiral, making FLASH more reliable and suggesting that at .5T, it is the method of choice for rapid cardiac volumetric imaging.
- Published
- 1998
33. Hybrid ordered phase encoding (HOPE): An improved approach for respiratory artifact reduction
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Andrew M. Taylor, Guang Z. Yang, Frank Wiesmann, Jennifer Keegan, David N. Firmin, Peter D. Gatehouse, Permi Jhooti, and Dudley J. Pennell
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Male ,Artifact (error) ,Heart Diseases ,Phantoms, Imaging ,business.industry ,Image quality ,Computer science ,Respiration ,Heart ,Pattern recognition ,k-space ,Respiratory monitoring ,Magnetic Resonance Imaging ,Imaging phantom ,Position (vector) ,Encoding (memory) ,Image Processing, Computer-Assisted ,Humans ,Female ,Radiology, Nuclear Medicine and imaging ,Artificial intelligence ,Artifacts ,business ,Algorithms ,Cardiac imaging - Abstract
Respiration causes continuous change in cardiac position, which leads to image degradation. Phase-encode reordering methods are often used to reduce these artifacts. An improved method for suppressing motion artifacts by reordering the acquisition of k space has been developed that is less sensitive to change of breathing patterns and bulk movement. We describe the theory behind the new approach and compare its results with those of existing methods by use of a phantom with simulated and actual acquired breathing patterns. The comparison was also made in vivo; cardiac scans were performed in 15 subjects with image planes that are known to be particularly susceptible to respiratory artifact. A significant improvement in image quality was achieved compared with conventional nonreordered and existing reordering methods.
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- 1998
34. Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse
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Sabine Voll, Wolfgang R. Bauer, Stefan Neubauer, Jan Ruff, Axel Haase, Frank Wiesmann, Eberhard Rommel, M. von Kienlin, and Karl-Heinz Hiller
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Male ,Models, Anatomic ,Materials science ,Short axis ,Resolution (mass spectrometry) ,Systole ,Heart Ventricles ,Male mice ,Sensitivity and Specificity ,Ventricular Function, Left ,Mice ,Nuclear magnetic resonance ,Diastole ,Reference Values ,Cardiac magnetic resonance imaging ,In vivo ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Observer Variation ,medicine.diagnostic_test ,Phantoms, Imaging ,business.industry ,Magnetic resonance imaging ,Image Enhancement ,Myocardial function ,Magnetic Resonance Imaging ,Mice, Inbred C57BL ,Ventricular Function, Right ,Nuclear medicine ,business ,Ex vivo - Abstract
The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.
- Published
- 1998
35. Comparison of the Beckman Coulter DxN VERIS and Abbott RealTime assays in analyzing HCV positive plasma samples
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Frank Wiesmann, Patrick Braun, Heribert Knechten, B. Haase, and Gudrun Naeth
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Infectious Diseases ,Plasma samples ,business.industry ,Virology ,Medicine ,business ,HCV Positive - Published
- 2016
36. Comparison of HIV-1 viral load assay performance in immunological stable patients with low or undetectable viremia
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Robert Ehret, Patrick Braun, Annemarie Berger, Gudrun Naeth, Heribert Knechten, and Frank Wiesmann
- Subjects
Microbiology (medical) ,Reproducibility ,Concordance ,T-Lymphocytes ,Immunology ,Human immunodeficiency virus (HIV) ,Reproducibility of Results ,Viremia ,HIV Infections ,General Medicine ,Assay sensitivity ,Biology ,Viral Load ,medicine.disease_cause ,medicine.disease ,Lymphocyte Activation ,Virology ,Real-time polymerase chain reaction ,medicine ,HIV-1 ,Immunology and Allergy ,Humans ,Viral load ,CD8 - Abstract
The goal of antiretroviral therapy is reduction in morbidity and mortality via suppression of human immunodeficiency virus (HIV) viral load (VL) to undetectable levels. VL assay sensitivity has improved over time, but the reproducibility and clinical importance of VL results marginally higher than the limit of detection (LoD) are uncertain. We assessed the reproducibility and concordance of low VL results obtained with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 version 2.0 (CAP-CTM) and the Abbott RealTime (m2000) HIV-1 assays, using longitudinal specimens from HIV-1-infected patients with low VL (300 copies/ml) and stable CD4+ cell counts. Based on replicate testing of 3 specimens, coefficients of variation for log-transformed VL results were 5-8 % for m2000 and 9-10 % for CAP-CTM. The concordance between assays in specimens from patients with previously undetectable, detectable but not quantifiable VL, or variable (undetectable/detectable but not quantifiable VL) results over time was 90, 56, and 56 %, respectively. Correlation between results for specimens with quantifiable VL (initially 40-300 copies/ml) was moderate (R (2) = 0.48) with significantly higher results for CAP-CTM and a mean difference (CAP-CTM minus m2000) of 0.10 log(10) copies/ml. T-cell activation (CD8+/CD38+ percentage) in patients with low VL was initially higher than in patients with undetectable VL, and then decreased to equivalent levels over time. These results indicate that residual viremia at levels slightly above the LoD have no negative effect on T-cell activation.
- Published
- 2012
37. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer
- Author
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Renate Krings, Edgar Dahl, Thomas J. Fuchs, Abdelaziz En-Nia, Arndt Hartmann, Sonja Djudjaj, E. Breuer, Sandra E. Dunn, Frank Wiesmann, Peter J. Wild, Peter R. Mertens, University of Zurich, and Dahl, E
- Subjects
Cancer Research ,Blotting, Western ,610 Medicine & health ,Breast Neoplasms ,Enzyme-Linked Immunosorbent Assay ,Kaplan-Meier Estimate ,Biology ,Transfection ,lcsh:RC254-282 ,Disease-Free Survival ,Prostate cancer ,Mice ,Breast cancer ,1311 Genetics ,Antibody Specificity ,10049 Institute of Pathology and Molecular Pathology ,Progesterone receptor ,medicine ,Genetics ,Biomarkers, Tumor ,Animals ,Humans ,1306 Cancer Research ,Nuclear protein ,Cell Nucleus ,Messenger RNA ,Mice, Inbred BALB C ,Hybridomas ,Antibodies, Monoclonal ,Nuclear Proteins ,Y box binding protein 1 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Prognosis ,Immunohistochemistry ,DNA-Binding Proteins ,Cell nucleus ,medicine.anatomical_structure ,Oncology ,Tissue Array Analysis ,Monoclonal ,Immunology ,Cancer research ,2730 Oncology ,Female ,Y-Box-Binding Protein 1 ,Receptors, Progesterone ,Research Article - Abstract
Background Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Methods Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. Results YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size Cox regression models failed to demonstrate significance for nuclear YB-1 detection as independent prognostic marker. Conclusion Monoclonal YB-1 antibody F-E2G5 should be of great value for prospective studies to validate YB-1 as a novel biomarker suitable to optimize breast cancer treatment., BMC Cancer, 9 (1), ISSN:1471-2407
- Published
- 2009
38. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study
- Author
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Justin M S, Lee, Matthew D, Robson, Ly-Mee, Yu, Cheerag C, Shirodaria, Colin, Cunnington, Ilias, Kylintireas, Janet E, Digby, Thomas, Bannister, Ashok, Handa, Frank, Wiesmann, Paul N, Durrington, Keith M, Channon, Stefan, Neubauer, and Robin P, Choudhury
- Subjects
Carotid Artery Diseases ,Male ,Time Factors ,Cholesterol, HDL ,Confounding Factors, Epidemiologic ,Cholesterol, LDL ,Middle Aged ,Magnetic Resonance Imaging ,Niacin ,Drug Administration Schedule ,Treatment Outcome ,Double-Blind Method ,Delayed-Action Preparations ,Humans ,Female ,Tunica Intima ,Tunica Media ,Triglycerides ,Aged ,Hypolipidemic Agents - Abstract
Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function.NA raises high-density lipoprotein cholesterol (HDL-C) and reduces low-density lipoprotein cholesterol and is widely used as an adjunct to statin therapy in patients with coronary artery disease. Although changes in plasma lipoproteins suggest potential benefit, there is limited evidence of the effects of NA on disease progression when added to contemporary statin treatment.We performed a double-blind, randomized, placebo-controlled study of 2 g daily modified-release NA added to statin therapy in 71 patients with low HDL-C (40 mg/dl) and either: 1) type 2 diabetes with coronary heart disease; or 2) carotid/peripheral atherosclerosis. The primary end point was the change in carotid artery wall area, quantified by magnetic resonance imaging, after 1 year.NA increased HDL-C by 23% and decreased low-density lipoprotein cholesterol by 19%. At 12 months, NA significantly reduced carotid wall area compared with placebo (adjusted treatment difference: -1.64 mm(2) [95% confidence interval: -3.12 to -0.16]; p = 0.03). Mean change in carotid wall area was -1.1 +/- 2.6 mm(2) for NA versus +1.2 +/- 3.0 mm(2) for placebo. In both the treatment and placebo groups, larger plaques were more prone to changes in size (r = 0.4, p = 0.04 for placebo, and r = -0.5, p = 0.02 for NA).In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531).
- Published
- 2009
39. Abstract 2219: High Dose Modified-release Nicotinic Acid Reduces Carotid Atherosclerosis: a Randomized, Placebo-controlled Magnetic Resonance Study
- Author
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Justin M Lee, Matthew D Robson, Ly-Mee Yu, Cheerag C Shirodaria, Colin Cunnington, Ilias Kylintireas, Tom Bannister, Frank Wiesmann, Ashok Handa, Keith M Channon, Stefan E Neubauer, and Robin P Choudhury
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Large clinical outcome studies (AIM-HIGH and HPS-2THRIVE) are underway testing the strategy of adding high dose nicotinic acid (NA) to statin treatment. However, the effect of this on atherosclerosis progression is unknown. Hypothesis: Nicotinic acid 2g daily would reduce change in carotid wall area, assessed by MRI, compared to placebo. Methods: We performed a double-blind randomized placebo-controlled study of 2g once daily modified release NA added to background statin therapy in 71 patients with low HDL-C known coronary heart disease with type 2 diabetes mellitus or carotid / peripheral atherosclerosis The pre-specified primary end point was the change in carotid artery wall area, assessed by MRI, after 1 year. We compared the treatment effect using a mixed effect model adjusting for baseline covariates. Results: 22/35 NA and 29/36 placebo patients completed MRI at all time points. Baseline characteristics were similar. In the NA treated group, HDL-C increased 23% (39±6 to 48±7 mg/dL), and LDL-C decreased 19% (85±23 to 69±21 mg/dL). At 12 months, the NA group had a significantly higher reduction in carotid wall area compared to placebo (adjusted treatment difference [95% CI] = −1.64 mm 2 [−3.12, −0.16]; P=0.03). Median (IQR) change in carotid wall area was −1.42 mm 2 (−2.65, 0.79) for NA and 0.47 mm 2 (−0.97, 2.59) for placebo. At 12 months the change in carotid plaque index (calculated by the recognised method of normalising wall area to total vessel area) was also reduced compared to placebo (treatment difference −0.016 [−0.03, −0.0022]; P = 0.02). Even as early as six months, although there was no treatment difference for change in absolute carotid wall area (−0.98 mm 2 [−2.45, 0.49]; P = 0.2), change in carotid plaque index was already significantly lower in the NA treated group (−0.016 [−0.03, 0.0019]; P = 0.03). Conclusions: This is the first demonstration that addition of high dose modified-release nicotinic acid, to statin-treated patients with low HDL-C, reduces carotid atherosclerosis at 12 months compared to placebo.
- Published
- 2008
40. Phenotypic assays for the determination of coreceptor tropism in HIV-1 infected individuals
- Author
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Patrick, Braun and Frank, Wiesmann
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Receptors, CXCR4 ,Phenotype ,Receptors, CCR5 ,HIV-1 ,Humans ,Biological Assay ,HIV Infections ,HIV Envelope Protein gp120 ,Virus Internalization ,Virus Replication ,Polymerase Chain Reaction - Abstract
Coreceptor tropism antagonists represent a new class of antiretrovirals for the treatment of HIV infection. The knowledge of patients' viral population tropism before the initiation of and during therapy with such compounds may be critical in order to optimize treatment strategies. In this review we focus on the characteristics of phenotypic assays for the determination of HIV coreceptor tropism. Beside traditional phenotypic assays, there are at least four phenotypic recombinant virus assays (RVA) available to predict coreceptor usage: Trofile (Monogram Biosciences), Phenoscript (VIRalliance), XtrackC/ PhenX-R (inPheno) and a platform developed by Virco. Trofile and Phenoscript represent single-cycle assays and are able to determine coreceptor tropism without cocultivation of HIV particles in cell culture. Trofile offers the most clinically validated data with currently about 25,000 analysed samples. The detection of minority variants is a limitation of all population-based assays and varies between 1 and 10%, depending on the assay used. XtrackC/PhenX-R and Virco's platform combine genotypic and phenotypic assays to analyze a patient's sample for tropism. Although all assays are validated for the assessment of coreceptor tropism in different HIV-1 subtypes, there is still a need for further evaluations. Furthermore, the establishment of cut-offs for X4 minority species will be difficult, and is affected by many factors like patient sample quality, the input volume, viral load, the detection limits and PCR variations. Overall, RVAs confirm efficiency and accuracy thus making them suitable for the clinical management of HIV infected individuals treated with coreceptor antagonists.
- Published
- 2007
41. Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma
- Author
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Arndt Hartmann, Edgar Dahl, Stefan Denzinger, Ruth Knüchel, Christine G. Hammerschmied, Frank Wiesmann, Matthias Woenckhaus, Ronald Simon, Eva Klopocki, W.F. Wieland, Peter J. Wild, Bernhard Walter, Guido Sauter, Jürgen Veeck, and Robert Stoehr
- Subjects
Adult ,Cancer Research ,Tumor suppressor gene ,Loss of Heterozygosity ,Biology ,medicine.disease_cause ,Loss of heterozygosity ,Secreted frizzled-related protein 1 ,Renal cell carcinoma ,Neoplasms ,Genetics ,medicine ,Gene silencing ,Humans ,RNA, Messenger ,Promoter Regions, Genetic ,Molecular Biology ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Membrane Proteins ,DNA Methylation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Kidney Neoplasms ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Tissue Array Analysis ,Immunology ,DNA methylation ,Cancer research ,Intercellular Signaling Peptides and Proteins ,Carcinogenesis - Abstract
Oncogenic wingless-related mouse mammary tumour virus (Wnt) signalling, caused by epigenetic inactivation of specific pathway regulators like the putative tumour suppressor secreted frizzled-related protein 1 (SFRP1), may be causally involved in the carcinogenesis of many human solid tumours including breast, colon and kidney cancer. To evaluate the incidence of SFRP1 deficiency in human tumours, we performed a large-scale SFRP1 expression analysis using immunohistochemistry on a comprehensive tissue microarray (TMA) comprising 3448 tumours from 36 organs. This TMA contained 132 different tumour subtypes as well as 26 different normal tissues. Although tumour precursor stages of, for example kidney, colon, endometrium or adrenal gland still exhibited moderate to abundant SFRP1 expression, this expression was frequently lost in the corresponding genuine tumours. We defined nine novel tumour entities with apparent loss of SFRP1 expression, i.e., cancers of the kidney, stomach, small intestine, pancreas, parathyroid, adrenal gland, gall bladder, endometrium and testis. Renal cell carcinoma (RCC) exhibited the highest frequency of SFRP1 loss (89% on mRNA level; 75% on protein level) and was selected for further analysis to investigate the cause of SFRP1 loss in human tumours. We performed expression, mutation and methylation analysis in RCC and their matching normal kidney tissues. SFRP1 promoter methylation was frequently found in RCC (68%, n=38) and was correlated with loss of SFRP1 mRNA expression (p
- Published
- 2007
42. Functional assessment of isolated right heart failure by high resolution in-vivo cardiovascular magnetic resonance in mice
- Author
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Axel Haase, G. Ertl, M. Spindler, Frank Wiesmann, Eberhard Rommel, Alex Frydrychowicz, and Stefan Neubauer
- Subjects
medicine.medical_specialty ,Ventricular Dysfunction, Right ,Cardiovascular research ,High resolution ,Magnetic Resonance Imaging, Cine ,Mice ,Right heart failure ,In vivo ,Internal medicine ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Cardiac Output ,Heart Failure ,Ejection fraction ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Stroke Volume ,medicine.disease ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,Cardiac phenotype ,business - Abstract
Precise and noninvasive characterization of the development of the cardiac phenotype in murine models of heart failure has been widely demanded in modern cardiovascular research. High-resolution cardiovascular magnetic resonance (CMR) has been proven to be a powerful tool for the accurate and reproducible assessment of LV and RV parameters in healthy mice. Whereas changes in LV parameters in models of heart failure have been thoroughly evaluated, RV dysfunction has not. Purpose of this study was to characterize a model of isolated RV failure induced by pulmonal banding by in vivo CMR at 7T. RV parameters differed significantly from those of normal mice in terms of RV end-diastolic volume (EDV: 85 +/- 14 microL vs. control 36 +/- 3 microL, p < 0.0001), RV end-systolic volume (ESV: 121 +/- 10 microL vs. control 84 +/- 4 microL, p < 0.005) and RV ejection fraction (EF: 31 +/- 6 % vs. control 57 +/- 2 %, p < 0.001). With regard to EDV, ESV, SV and EF LV parameters, there were no significant differences between pulmonary banded and control mice indicating overt isolated RV failure.
- Published
- 2007
43. Comparison of four commercial quantitative HIV-1 assays for viral load monitoring in clinical daily routine
- Author
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Rainer Kühn, Heribert Knechten, Frank Wiesmann, Robert Ehret, Mechthild Knickmann, Sven Thamm, Gerald Warnat, Frauke Zabbai, and Patrick Braun
- Subjects
Branched DNA Signal Amplification Assay ,Cobas taqman ,Clinical Biochemistry ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Mean difference ,medicine ,Routine analysis ,Daily routine ,Diagnostic Tests, Routine ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Biochemistry (medical) ,Reproducibility of Results ,General Medicine ,Viral Load ,Virology ,Regimen ,HIV-1 ,RNA, Viral ,Biological Assay ,Reagent Kits, Diagnostic ,business ,Nucleic Acid Amplification Techniques ,Viral load - Abstract
Background: Quantification of viral load (VL) is standard for monitoring HIV-1 therapy and is crucial before deciding whether to switch or to continue a current antiretroviral regimen. Methods: We compared the performance of the four most widely used commercial viral-load assays, CO BAS Amplicor Monitor v1.5, Versant HIV-1 RNA 3.0, Abbott RealTime HIV-1 and Cobas AmpliPrep/Cobas TaqMan HIV-1 (CAP/CTM), in terms of intra- and inter-assay variability, as well as hands-on-time, specificity and ability to quantify group M subtypes. Results: Although linearity and correlation were confirmed for the assays and comparable sensitivity and specificity were verified for genetically diverse HIV-1 subtypes, demonstrating suitability for monitoring of HIV group M isolates, the viral loads obtained showed variations, with a mean difference of 0.1-0.4 log, depending on the system used. Conclusions: Although sensitivity and precision were confirmed for all the systems, differences between them should be taken into account when viral load monitoring of the same person is performed using different systems.
- Published
- 2007
44. Evaluation of two assays for the quantification of HIV and HCV in clinical routine
- Author
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Gudrun Naeth, Heribert Knechten, Patrick Braun, B. Haase, and Frank Wiesmann
- Subjects
medicine.medical_specialty ,Infectious Diseases ,business.industry ,Virology ,Internal medicine ,medicine ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,Clinical routine ,business - Published
- 2015
45. High-resolution MR imaging in mice
- Author
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Jan Ruff, Axel Haase, and Frank Wiesmann
- Subjects
Male ,Cardiac function curve ,Materials science ,Myocardial Infarction ,Biophysics ,High resolution ,Mice, Transgenic ,Electrocardiography ,Mice ,Dobutamine ,Animals ,Ventricular Function ,Radiology, Nuclear Medicine and imaging ,Wall motion ,Mouse Heart ,Image resolution ,Radiological and Ultrasound Technology ,business.industry ,Heart ,Magnetic Resonance Imaging ,Mr imaging ,Mice, Inbred C57BL ,Disease Models, Animal ,Nuclear medicine ,business ,Biomedical engineering - Abstract
Due to its high temporal and spatial resolution, the described MR technique is able to face the requirements of the small sized, fast beating mouse heart, resulting in time-resolved visualization of the cardiac morphology and function in great detail. This allows for accurate and reproducible quantification of LV performance including wall motion and contraction-relaxation dynamics. Hence, MRI offers the non-invasive investigation of physiological and pathophysiological changes of cardiac function over time, both under acute and chronic myocardial stress.
- Published
- 1998
46. Sex-specific characteristics of cardiac function, geometry, and mass in young adult elite athletes
- Author
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Stefan Neubauer, Matthew D. Robson, Lucy Hudsmith, Bernd Jung, Frank Wiesmann, Jane M. Francis, Hugh Watkins, Helen A. Doll, Steffen E. Petersen, and Juergen Hennig
- Subjects
Adult ,Male ,Cardiac function curve ,medicine.medical_specialty ,Cardiac Volume ,Athlete's heart ,Rowing ,Magnetic Resonance Imaging, Cine ,Cardiomegaly ,Physical Therapy, Sports Therapy and Rehabilitation ,Ventricular Function, Left ,Muscle hypertrophy ,Cardiovascular Physiological Phenomena ,Internal medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Elite athletes ,Orthopedics and Sports Medicine ,Young adult ,Sex Characteristics ,Ejection fraction ,medicine.diagnostic_test ,Cardiac cycle ,business.industry ,Mean age ,Magnetic resonance imaging ,Sex specific ,Case-Control Studies ,Cardiac hypertrophy ,Linear Models ,Ventricular Function, Right ,Physical therapy ,Cardiology ,Female ,business ,Sports - Abstract
PURPOSE: To study young adult elite athletes with age- and sex-matched sedentary controls to assess sex-specific differences for left ventricular (LV) and right ventricular (RV) volumes and mass as well as for LV contraction and relaxation. MATERIALS AND METHODS: A total of 23 male athletes (mean age 25 +/- 4 years, training 22 +/- 7 hours/week in rowing, swimming, or triathlon) and 20 female athletes (mean age 24 +/- 4 years, training 19 +/- 5 hours/week in rowing, swimming, or triathlon) and age- and sex-matched sedentary controls (21 male/17 female) underwent cardiovascular magnetic resonance (CMR) imaging (1.5 Tesla). Cardiac phase contrast imaging using a black-blood k-space segmented gradient echo sequence was used for analysis of cardiac contraction and relaxation and steady-state free-precession cine images were acquired for determination of cardiac volumes and mass. RESULTS: Male and female athletes showed similar increases in LV and RV volume and mass indices when compared to controls (ranging between 15% and 42%). No sex-specific differences in training effect on LV and RV volumes, mass indices, and ejection fractions, as well as LV to RV ratios of these volume and mass indices (parameters of balanced LV and RV dilatation and hypertrophy) were observed (all P for interaction >0.05). Similarly, no sex-specific differences in training effect on cardiac contraction and relaxation were found (all P for interaction >0.05). CONCLUSION: Young adult elite athletes do not show sex-specific adaptive structural and functional changes to exercise training in accordance with the benign nature of the hypertrophy associated with athlete's heart.
- Published
- 2006
47. Cardiomyocyte-restricted deletion of connexin43 during mouse development
- Author
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Harold V.M. van Rijen, Frank Wiesmann, Michael D. Schneider, Susanne Kirchhoff, Klaus Willecke, Jacques M.T. de Bakker, Martin Theis, Wouter H. Lamers, Pieter A. Doevendans, Thomas Ott, Jung-Sun Kim, Joachim Degen, Dominik Eckardt, Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biology, Amsterdam Cardiovascular Sciences, Cardiology, Cardiologie, Anatomie en Embryologie, and RS: NUTRIM School of Nutrition and Translational Research in Metabolism
- Subjects
medicine.medical_specialty ,Cell type ,Gestational Age ,Biology ,Muscle hypertrophy ,Electrocardiography ,Mice ,Fetal Heart ,Pregnancy ,Internal medicine ,medicine ,Ventricular outflow tract ,Myocyte ,Animals ,Myocytes, Cardiac ,Molecular Biology ,Mice, Knockout ,Myocardium ,Embryogenesis ,Gap junction ,Age Factors ,Gene targeting ,Heart ,Embryonic stem cell ,Mice, Inbred C57BL ,Endocrinology ,Connexin 43 ,Gene Targeting ,cardiovascular system ,Female ,sense organs ,biological phenomena, cell phenomena, and immunity ,Cardiology and Cardiovascular Medicine - Abstract
Although the gap junction protein Connexin43 (Cx43) is expressed in various cell types during embryonic development, mice with a global inactivation of Cx43 survive until birth but die perinatally due to an obstruction of the right ventricular outflow tract of the heart. To analyze the functional role of Cx43 gap junction channels in cardiomyocytes of the developing and early postnatal heart, we used alphaMyHC-Cre mice to ablate Cx43 expression selectively in cardiomyocytes during development. We found efficient ablation of Cx43 in cardiomyocytes during embryonic development starting at embryonic day (ED) 9.5 in the ventricular wall. Analyses of cardiac Cx43 protein at birth indicated complete loss of Cx43 expression in cardiomyocytes. All mice homozygously deficient for Cx43 in cardiomyocytes died until postnatal day (PD) 16. Heterozygous inactivation of Cx43 in cardiomyocytes neither altered atrial nor ventricular activation, but homozygous ablation led to changes in ventricular activation, i.e. significant decrease of the QRS-amplitude and prolonged QRS-duration already at PD 4. Cardiac morphology was similar to controls until PD 1, but subtle morphological changes were found in a subgroup of mutant mice at later stages. Besides narrowing of the ventricular outlet region at PD 6, hypertrophy of ventricular myocardium was found at PD 12. Our data indicate that complete inactivation of cardiac Cx43 during development predisposes hearts to develop postnatal morphological alterations, which differ from outflow tract obstructions described for Cx43 null mice. In addition, complete loss of cardiac Cx43 protein during development correlates with slowed ventricular activation at PD 4, impairs viability during development, and leads to death of all mutant mice until PD 16.
- Published
- 2006
48. Low level HIV viremia is more frequent under protease-inhibitor containing firstline therapy than under NNRTI-regimens
- Author
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Mechthild Knickmann, Heribert Knechten, Patrick Braun, and Frank Wiesmann
- Subjects
medicine.medical_specialty ,Pediatrics ,Efavirenz ,Nevirapine ,business.industry ,Public Health, Environmental and Occupational Health ,Lopinavir ,Raltegravir ,Gastroenterology ,Group B ,Atazanavir ,Regimen ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Internal medicine ,medicine ,Poster Sessions – Abstract P296 ,business ,Darunavir ,medicine.drug - Abstract
Introduction : An association of persistent low level viremia (LLV) below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease-inhibitor regimens than in NNRTI- / or integrase-inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50–200 copies/mL) and weak viremia (201–500 copies/mL) in firstline-treated patients according to their therapy regimen. Methods : A total of 832 and 944 patients from 23 German centres were under firstline therapy in 2012 and 2013, respectively. All patients received their therapy for more than 24 weeks. VL data was related to clinical data retrospectively including ART-composition, subdivided into NNRTIs (Efavirenz, Nevirapine), PIs (Atazanavir, Darunavir, Lopinavir) and INIs (Raltegravir). Low viremic patients were classified into two arms of 50–200 copies/mL (group A) and 201–500 copies/mL (group B). Results : Success of therapy was defined as
- Published
- 2014
49. In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging
- Author
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Jörg U. G. Streif, Frank Wiesmann, Eberhard Rommel, Christiane Waller, Matthias Nahrendorf, Axel Haase, Karl-Heinz Hiller, and Wolfgang R. Bauer
- Subjects
medicine.medical_specialty ,Contrast Media ,Blood volume ,Mice ,Internal medicine ,Heart rate ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Myocardial infarction ,Least-Squares Analysis ,Analysis of Variance ,Blood Volume ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Coronary Vessels ,Magnetic Resonance Imaging ,Capillaries ,Isoflurane ,Anesthetic ,cardiovascular system ,Cardiology ,Female ,Spin Labels ,business ,Propofol ,Artifacts ,Perfusion ,medicine.drug - Abstract
The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 × 469 μm and a slice thickness of 2 mm. The T1 imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 ± 53 mL (100 g · min)−1 for anesthesia with isoflurane (N = 11) at a mean heart rate (HR) of 455 ± 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 ± 40 mL (100 g · min)−1 (N = 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 ± 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 ± 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 ± 81 mL (100 g · min)−1 (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 ± 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N = 4, HR 233 ± 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research. Magn Reson Med 53:584–592, 2005. © 2005 Wiley-Liss, Inc.
- Published
- 2005
50. Accuracy of quantitative MR vessel wall imaging applying a semi-automated gradient detection algorithm--a validation study
- Author
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Jane M Francis, Stefan Neubauer, Keith M. Channon, Matthew D. Robson, Frank Wiesmann, Steffen E. Petersen, and Qian Wang
- Subjects
Adult ,Male ,Validation study ,Scanner ,Coronary Artery Disease ,Edge detection ,Reference Values ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Observer Variation ,Reproducibility ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Phantoms, Imaging ,Quantitative mr ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,Coronary Vessels ,Magnetic Resonance Imaging ,Research Design ,Dark blood ,Female ,Carotid imaging ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Algorithm ,Algorithms - Abstract
UNLABELLED: Magnetic resonance imaging (MRI) is uniquely suited to study the pathophysiology of arteriosclerosis. So far, magnetic resonance (MR) measurements of vessel dimensions have mainly been done by manual tracing of vessel wall contours. However, such data postprocessing is very time-consuming and has limited accuracy due to difficulties in precise tracing of the thin vessel wall. PURPOSE: To assess the accuracy and reproducibility of quantitative vascular MR imaging applying a data analysis method based on (1) vessel wall unwrapping, followed by (2) a gradient detection algorithm for MR data postprocessing. Vascular MR imaging studies were done both in vessel phantoms and in healthy volunteers (n=29) on a clinical 1.5 T MR scanner. A dark blood double-inversion turbo spin echo sequence with fat suppression was applied, with proton-density-weighted and breath-hold acquisition for aortic imaging and T2-weighted acquisition for carotid imaging. Intraobserver and interobserver variability were systematically evaluated by two independent observers. A repeat study within 10 days of the first MRI was performed in 10 of these subjects for assessment of interstudy reproducibility. RESULTS: The semiautomated edge detection software revealed a clear view of the inner and outer vessel wall boundaries both in the phantoms and in the volunteers studied. There was close agreement between MR-derived measurements and phantom dimensions (mean difference of 1.1+/-16.9 mm2, 8.0+/-19.9 mm2, 9.0+/-12.1 mm2 for vessel wall cross-sectional area, inner vessel area, and total vessel area, respectively). Quantification of vessel dimensions was feasible in all 29 healthy volunteers studied. Semiautomated quantification of cross-sectional vessel wall area (mean+/-SD, 253.6+/-208.4 mm2) revealed close correlation for repeated measurements by one or two observers (r=0.99 each). Both intraobserver and interobserver variability of vessel wall area MR measurements were low (mean difference 7.5+/-16.7 mm2 and 14.4+/-24.6 mm2 , respectively). In the repeat study of 10 volunteers, MRI with semiautomated postprocessing quantitation revealed a high correlation and agreement of vessel dimensions between the two scans (r=0.994, mean difference 2.6+/-25.1 mm2). CONCLUSION: Semiautomated analysis methods can provide approaches that benefit from the human understanding of the image and the computer's ability to measure precisely and rapidly. Thus, by combining the latest MRI methods and semiautomated image analysis methods, we are now able to reproducibly determine the geometric parameters of blood vessels.
- Published
- 2005
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