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F Wiesmann

Publications and source records attributed to F Wiesmann.

At least 19 recordsLinked to original sources
PubMed2006

Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis.

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<0.001) between methylation and loss of SFRP1 expression in primary breast cancer tissue. SFRP1 expression was restored after treatment of tumour cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Most interestingly, SFRP1 promoter methylation was an independent factor for adverse patient survival in Kaplan-Meier analysis. Our results indicate that promoter hypermethylation is the predominant mechanism of SFRP1 gene silencing in human breast cancer and that SFRP1 gene inactivation in breast cancer is associated with unfavourable prognosis.

Adult↗
PubMed2006

Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound.

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.

Adult↗
PubMed2003

[Documentation in the cardiac catheterization laboratory using electronic databases--experiences in 176 German cath labs].

Due to the introduction of a variety of new features to the German health system, such as a new reimbursement system for inpatient work based on diagnosis-related groups, an obligation to detailed documentation for total quality management, as well as due to the continuing increase in the amount of imaging and other data within invasive cardiology, the use of electronic databases for documentation in the cardiac cath lab is of significant importance. The user friendliness and robustness of the software system for daily clinical practice is crucial for the acceptance of electronic documentation systems by physicians, nurses and technicians. This survey was aimed to explore the current practice and experiences of German cardiac catheterization labs with electronic databases particularly designed for documentation in invasive cardiology, including report generation of cath studies, risk and complication management and logistics for medical material ordering for the cath lab. Of the 176 hospitals and practices having agreed in taking part in this surveillance 165, are currently using an electronic database for administration of medical data and study reports. In 64% of the cath labs, a sub-specialized software system for detailed documentation of the course and the results of an invasive procedure, the human and material resources used, generation of the cath report, and documentation of procedural and post-procedural complications for total quality management is used. The acceptance and satisfaction with the software solutions currently available reveals to be rather inhomogeneous. While user-friendliness and flexibility of a number of software products were positively mentioned, main issues, such as missing hardware of software interfaces with the hospital information system for patient administration, missing stability of several systems, image management too complex and report configuration too inconvenient for daily clinical practice, were criticized. In general, in the light of continuing increase of the amount of clinical and imaging data as well as due to the legal obligation of detailed procedural documentation in all areas of invasive cardiology, a documentation system based on electronic databases bears the potential of an enormous economization of the daily workload of a cardiac cath lab. Prerequisites for the acceptance of such a system in clinical practice is not only the stability and reliability of the system but also the ability to link such a sub-system to existing databases via suitable interfaces and the flexibility of the system for modification of its features to meet the individual requirements of each user.

Adult↗
PubMed2001

Vascular hypertrophy and increased P70S6 kinase in mice lacking the angiotensin II AT(2) receptor.

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 alpha(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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Dobutamine-stress magnetic resonance microimaging in mice : acute changes of cardiac geometry and function in normal and failing murine hearts.

The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 microgram/g IP dobutamine. There was a significant increase of heart rate, cardiac output, and ejection fraction and significant decrease of end-diastolic and end-systolic left ventricular (LV) volumes (P<0.01 each) in normal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatation. There was a significant decrease of LV ejection fraction in infarcted mice (29%) versus sham mice (58%). Mice with MI showed a significantly reduced maximum LV ejection rate (P<0.001) and LV filling rate (P<0.01) and no increase of LV dynamics during dobutamine action, indicating loss of contractile and relaxation reserve. In 4-month-old transgenic mice with cardiospecific overexpression of the beta(1)-adrenergic receptor, which at this early stage do not show abnormalities of resting cardiac function, LV filling rate failed to increase after dobutamine stress (transgenic, 0.19+/-0.03 microL/ms; wild type, 0.36+/-0.01 microL/ms; P<0.01). Thus, MRI unmasked diastolic dysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasive assessment of systolic and diastolic components of heart failure. This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.

Adrenergic beta-Agonists↗
PubMed2001

Serial cine-magnetic resonance imaging of left ventricular remodeling after myocardial infarction in rats.

The purpose of the present study was the serial investigation of morphological and functional changes after left coronary artery ligation in the intact rat using cine-magnetic resonance imaging (MRI). MRI studies were performed 4, 8, 12, and 16 weeks after myocardial infarction (MI) with an echocardiogram (ECG)-triggered cine-fast low-angle shot (FLASH)-sequence in a 7-Tesla magnet. MI-size, left ventricular (LV) mass and volumes, cardiac index, ejection fraction (EF), and remote wall and scar thickness of 11 Wistar rats were compared to four sham-operated rats. Stress MRI with dobutamine (10 microl/kg x minute) was performed at 16 weeks. In MI groups (small MI < 30%, N = 5, large MI > 30%, N = 6), there was significant increase of LV mass (small MI + 47.8% increase, large MI + 74.1%) and wall thickness (large MI 1.21 +/- 0.03 to 1.84 +/- 0.07 mm). Scar thickness declined from four to 16 weeks (large MI 0.92 +/- 0.06 to 0.38 +/- 0.02 mm, P < 0.05). End-diastolic volume of both MI groups was significantly elevated but increased further only in animals with large MI from four to 16 weeks (657.1 +/- 38.6 to 869.7 +/- 60.7 microL, P < 0.05). Compared to sham, EF was significantly depressed in MI (large MI 31.5 +/- 2.0%). Wall thickening declined from four to 16 weeks post-MI (large MI 50.9 +/- 9.9 to 28.9 +/- 4.4%, P < 0.05). During stress, sham and MI rats increased wall thickening from 66.5 +/- 8.2 to 111.2 +/- 6.7% and from 30.8 +/- 4.3 to 47.5 +/- 5.8%, respectively (P < 0.05). Hypertrophy was found in all animals with MI throughout the entire period of observation, whereas dilatation after four weeks was only detected in animals with large MI. These morphologic changes were accompanied by an early decline of EF; myocardial function characterized by wall thickening deteriorated later.

Animals↗
PubMed2001

Breath-hold 3D MR coronary angiography with a new intravascular contrast agent (feruglose)--first clinical experiences.

Demonstration of the initial results of breath-hold 3D MR coronary angiography with patients using a new intravascular contrast agent (feruglose). Contrast-enhanced 3D MR-coronary angiography was performed in 5 patients with coronary artery disease after administration of feruglose in three different doses (0.5 (n = 3), 2, 5 mg Fe/kg body weight for each patient). MR coronary angiography was performed with an ECG-triggered 3D-FLASH-sequence during breath-hold at 1.5 T (TR 6.8 ms, TE 2.5 ms, flip-angle 30 degrees ). To reduce data acquisition time, only the two anterior elements of the phased-array body coil were activated. The data acquisition window within the cardiac cycle ranged between 217-326 ms depending on the matrix. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) of the coronary arteries were analyzed, and the results for the detection of coronary artery stenoses were compared with those obtained by conventional coronary angiography. SNR and CNR revealed an improved image quality at a dose of 2 mg Fe/kg compared with the lower dose, but no further improvement was obtained by rising the dose to 5 mg Fe/kg. Except for the left circumflex artery of one patient, at minimum the proximal parts of all four main coronary arteries could be imaged for all patients. Within the visible parts of the coronary arteries, six of eight significant coronary stenoses were identified correctly. Imaging of the proximal parts of the coronary arteries including detection of stenoses is possible during breath-hold using an intravascular contrast agent.

Aged↗
PubMed2001

Can we use vertical bore magnetic resonance scanners for murine cardiovascular phenotype characterization? Influence of upright body position on left ventricular hemodynamics in mice.

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.

Animals↗
PubMed2000

Coronary artery imaging in grown up congenital heart disease: complementary role of magnetic resonance and x-ray coronary angiography.

BACKGROUND: There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease. METHODS AND RESULTS: Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (P<0.02). CONCLUSIONS: For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.

Adult↗
PubMed2000

Magnetic resonance imaging of coronary arteries and heart valves in a living mouse: techniques and preliminary results.

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 microm 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.

Algorithms↗
PubMed2000

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice.

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia. Electrocardiogram-gated cine MRI was performed with an in-plane resolution of (78-117 microm)(2). Temporal resolution per cine frame was 8.6 ms. MRI revealed cardiac anatomy in mice from all age groups with high temporal and spatial resolution. There was close correlation between MRI- and autopsy-determined left ventricular (LV) mass (r = 0.95, SE of estimate = 9.5 mg). The increase of LV mass (range 9.6-101.3 mg), cardiac output (range 1.1-14.3 ml/min), and stroke volume (range 3. 2-40.2 microl) with age could be quantified by MRI measurements. Ejection fraction and cardiac index did not change with aging. However, LV mass index decreased with increasing age (P < 0.01). High-resolution MRI allows for accurate in vivo assessment of cardiac function in neonatal, juvenile, and adult mice. This method should be useful when applied in transgenic mouse models.

Aging↗
PubMed2000

In vivo assessment of cardiac remodeling after myocardial infarction in rats by cine-magnetic resonance imaging.

The rat infarct model offers important parallels to the process of remodeling after myocardial infarction (MI) in humans. The aim of this study was to test the feasibility of cine fast low-angle shot (FLASH) magnetic resonance imaging (MRI) for assessment of the infarcted and noninfarcted rat heart and to compare the results with established methods. In group A, MRI was done 8-16 weeks after MI on a 7-T scanner using an electrocardiogram-triggered cine-FLASH sequence. We determined left ventricular (LV) volumes and mass, wall thickness, MI size, cardiac output, and ejection fraction. Afterward, MI size was histologically determined. In group B, after MRI eight controls and eight rats 16 weeks after MI underwent conventional hemodynamic measurements for determination of cardiac output, LV volumes, and ejection fraction by electromagnetic flowmeter and pressure-volume curves. LV wet weight was determined. In group A, MRI-acquired MI size (18.5 +/- 2%) was smaller than histology (22.8 +/- 2.5%, p < 0.05) with close correlation (r = 0.97). In group B, agreement in LV mass was found between MRI and wet weight (controls, 537.6 +/- 19.6 vs. 540.3 +/- 18.4 mg; MI, 865.1 +/- 39.2 vs. 865.1 +/- 41.3 mg; for the difference p = ns, r = 0.97, p < 0.05) and in the MRI and flowmeter measurements (cardiac output, controls 73.1 +/- 2.9 vs. 75.2 +/- 2.6 ml/min; MI 82.4 +/- 5.2 vs. 81.9 +/- 3.7 ml/min; for the difference p = ns, r = 0.80, p < 0.05). End-diastolic volume by MRI differed from pressure-volume curves with good correlation (controls, 343.9 +/- 8.4 vs. 262.7 +/- 12.8 microl; MI, 737.0 +/- 70.5 vs. 671.1 +/- 64.1 microl; p < 0.05 each, r = 0.96, p < 0.05). Cine-FLASH-MRI is a valuable diagnostic tool applicable to the rat model of MI. Being noninvasive and exact, it offers new insights in the remodeling process after MI because serial measurements are possible.

Animals↗
PubMed1999

Downregulation of the Na(+)-creatine cotransporter in failing human myocardium and in experimental heart failure.

BACKGROUND: The failing myocardium is characterized by depletion of phosphocreatine and of total creatine content. We hypothesized that this is due to loss of creatine transporter protein. METHODS AND RESULTS: Creatine transporter protein was quantified in nonfailing and failing human myocardium (explanted hearts with dilated cardiomyopathy [DCM; n=8] and healthy donor hearts [n=8]) as well as in experimental heart failure (residual intact left ventricular tissue, rats 2 months after left anterior descending coronary artery ligation [MI; n=8] or sham operation [sham; n=6]) by Western blotting. Total creatine content was determined by high-performance liquid chromatography. Donor and DCM hearts had total creatine contents of 136.4+/-6.1 and 68.7+/-4.6 nmol/mg protein, respectively (*P<0.05); creatine transporter protein was 25.4+/-2.2 optical density units in donor and 17.7+/-2.5 in DCM (*P<0.05). Total creatine was 87.5+/-4.2 nmol/mg protein in sham and 65.7+/-4.2 in MI rats (*P<0.05); creatine transporter protein was 139.0+/-8.7 optical density units in sham and 82.1+/-4.0 in MI (*P<0.05). CONCLUSIONS: Both in human and in experimental heart failure, creatine transporter protein content is reduced. This mechanism may contribute to the depletion of creatine compounds and thus to the reduced energy reserve in failing myocardium. This finding may have therapeutic implications, suggesting a search for treatment strategies targeted toward creatine transport.

Animals↗
PubMed1999

Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice.

Stimulation of cardiac beta1-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 beta-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 beta1-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 approximately 50% in 35-week-old mice, and ejection fraction was reduced down to a minimum of approximately 20%. We conclude that overexpression of beta1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increased beta1-adrenergic receptor signalling is ultimately detrimental.

Aging↗
PubMed1998

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

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.

Animals↗