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S Neubauer

Publications and source records attributed to S Neubauer.

At least 73 records · Page 4Linked to original sources

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.

Adenosine Triphosphate↗

Functional and energetic consequences of chronic myocardial creatine depletion by beta-guanidinopropionate in perfused hearts and in intact rats.

Oral feeding with the creatine analogue beta-guanidinopropionate (beta-GP) reduces myocardial phosphocreatine and creatine concentrations by about 80%in vitro, this is accompanied by reduced contractile performance. We hypothesized, thus, that beta-GP feeding leads to hemodynamic changes in vivo characteristic of heart failure. beta-GP was fed to Wistar rats for up to 8 weeks. In isolated hearts, function was measured isovolumically, myocardial energetics were followed with (31)P-NMR spectroscopy. In vivo hemodynamics were measured with Millar-Tip-catheters and an electromagnetic flow probe. Beta-GP feeding did not alter heart weight. In vitro, diastolic pressure-volume curves indicated structural left ventricular dilatation, and a 36% reduction of left ventricular developed pressure was found; phosphocreatine was reduced by approximately 80%, ATP unchanged and creatine kinase reaction velocity ((31)P-MR saturation transfer) decreased by approximately 90%. The total creatine pool (high-pressure liquid chromatography) was reduced by up to approximately 70%. In contrast to in vitro findings, in vivo cardiac hemodynamics (including left ventricular developed pressure, d P/d t(max), cardiac output and peripheral vascular resistance) at rest and during acute volume loading showed no alterations after beta-GP feeding. The only functional impairment observed in vivo was a 14% reduction of maximum left ventricular developed pressure during brief aortic occlusion. In the intact rat, cardiac and/or humoral compensatory mechanisms are sufficient to maintain normal hemodynamics in spite of a 90% reduction of creatine kinase reaction velocity. However, chronic beta-GP feeding leads to structural left ventricular dilatation.

Adenosine Diphosphate↗

[Bilateral testicular tumors. Contralateral benign lesions in germ cell tumors of the testis].

Bilateral testicular tumors account for approximately 3.5% of all testicular malignancies and to our knowledge about 800 cases are reported in the literature. An even more seldom event is the appearance of a testicular germ cell tumor with a contralateral benign non-germ cell tumor. We report the 6th case of such a coincidence. The dignity of a contralateral tumor should be assured by frozen section and in case of benign histology organ preserving therapy is indicated. Even in cases of bilateral testis cancer tumor enucleation may be considered, if the strict conditions for resection and follow-up are respected.

Diagnostic Imaging↗

Chronic high-dose creatine feeding does not attenuate left ventricular remodeling in rat hearts post-myocardial infarction.

OBJECTIVE: In heart failure, cardiac energy metabolism is compromised. The failing myocardium is characterized by reduced contents of both phosphorylated (phosphocreatine) and non-phosphorylated (free) creatine content as well as decreased energy reserve via creatine kinase (creatine kinase reaction velocity). These changes may contribute to cardiac dysfunction. The purpose of the present study was to determine whether chronic feeding with high-dose dietary creatine prevents the derangement of energy metabolism and the development of left ventricular remodeling in a rat model of heart failure, i.e. post-myocardial infarction (MI). METHODS AND RESULTS: Rats were subjected to sham operation or left coronary artery ligation. Surviving rats were fed with 0% (untreated) or 3% creatine (related to weight of diet) for 8 weeks. Creatine feeding increased serum creatine levels significantly approximately 2-fold. Thereafter, hearts were isolated, perfused and left ventricular pressure-volume curves obtained. Steady state and dynamic (CK reaction velocity) high-energy phosphate metabolism was determined with 31P NMR spectroscopy. In both MI groups (treated n = 8, untreated n = 7), pressure-volume curves were shifted right- and downward compared to both sham groups (treated n = 5, untreated n = 7), i.e. creatine had no effect on left ventricular remodeling. Likewise, similar reductions of phosphocreatine, free creatine and creatine kinase reaction velocity (untreated sham 12.0 +/- 0.7 mmol/lxs; untreated MI 7.8 +/- 0.7*; treated sham 13.6 +/- 1.0; treated MI 7.2 +/- 1.1*; *p < 0.025 sham vs. MI) were found in both MI groups. CONCLUSIONS: Chronic creatine feeding of post-MI rats is ineffective in preventing the functional and energetic derangements occurring post-MI. Inspite of increased serum creatine levels, neither the normal nor the failing heart accumulates additional creatine.

Adenosine Triphosphate↗

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Adult↗

[CINE-MRT for the study of the effects of regional left ventricular wall motion disorders on global heart function after a myocardial infarct and revascularization].

PURPOSE: To determine changes in global cardiac function and mass caused by infarct-associated regional wall motion abnormalities and to compare the changes after revascularization in patients with and without improvement of regional contractility. MATERIALS AND METHODS: 21 patients with regional left ventricular wall motion abnormalities and associated coronary artery stenoses requiring revascularization were examined with a Cine FLASH-2D sequence 26 +/- 12 days after their first myocardial infarction and re-examined three months after revascularization. Regional contractility and volumes and masses of both ventricles were determined. RESULTS: After revascularization, regional wall motion improvement led to decreased left ventricular volumes and improved ejection fractions, whereas patients with persisting wall motion defects showed unchanged left ventricular functional parameters. Comparing both groups of patients, the patients with improvement of regional contractility revealed lower end-systolic volumes and higher ejection fractions at follow-up. Cardiac masses and right ventricular parameters were not different, patients with a depressed right ventricular ejection fraction showed improvement at follow-up. DISCUSSION: After myocardial infarction, revascularization of the infarct-related coronary artery leads to an improvement of left ventricular function only if there is also an improvement of regional contractility. An effect on right ventricular function was not observed three months after the first small- or middle-sized myocardial infarction.

Adult↗

[The quantification of energy-rich phosphates in healthy and damaged heart muscle by SLOOP 31P-MR spectroscopy. Spatial localization with optimal pointspread function].

PURPOSE: A quantitative 31P-MR-spectroscopic technique was used to assess the energy metabolism in healthy and diseased myocardium. METHODS: 31P spectra were acquired on a 1.5 T scanner using a 3D-chemical shift imaging technique. Based on the anatomical information provided by 1H images, SLOOP (Spatial Localization with Optimal Pointspread Function) allows to obtain spectra from defined compartments. With SLOOP a free voxel shape with adaption to anatomic structures, e.g. the myocardium, is possible. Absolute values for phosphocreatine (PCr) and adenosine triphosphate (ATP) were determined using an external standard. RESULTS: 31P-spectra showed only minimal contamination by surrounding tissue. The standard deviation for the determined values of healthy volunteers was low. Compared to healthy volunteers, reduced PCr and ATP concentrations were seen for dilative cardiomyopathies and coronary artery disease and unchanged concentrations were observed for hypertensive heart disease. CONCLUSION: 31P-MR spectroscopy with SLOOP allows a non-invasive, quantitative analysis of cardiac energy metabolism.

Adenosine Triphosphate↗

[3-dimensional MR coronary angiography in the navigator technic for the primary diagnosis of coronary heart disease: a comparison with conventional coronary angiography].

PURPOSE: Evaluation of three-dimensional MR coronary angiography with the navigator technique for the primary diagnosis of coronary artery disease (CAD) in patients with chest pain. MATERIALS AND METHODS: In this prospective study 20 patients with chest pain were examined with MR coronary angiography and conventional angiography. The three-dimensional MR coronary angiography was performed using a 1.5 T scanner with an ECG-triggered 3D-FLASH-sequence and retrospective respiratory gating in the navigator technique. The MR coronary angiography was evaluated by two radiologists blinded to the results of the conventional coronary angiography. RESULTS: One patient was excluded from further evaluation due to reduced image quality. Conventional coronary angiography excluded CAD in 8/19 patients, 11/19 patients overall showed 20 stenoses (> 50%) or occlusions. With MR coronary angiography, CAD was correctly excluded in 7 patients, one patient was false positive, one patient was false negative. 14/20 stenoses (> 50%) or occlusions were detected, 5 stenoses were diagnosed false positive. Sensitivity and specificity for primary diagnosis of CAD or detection of coronary artery stenoses were 91% and 88% or 70% and 91%, respectively. DISCUSSION: Using MR coronary angiography with the navigator technique in the primary evaluation of CAD, the diagnosis of stenoses or occlusions of the main coronary arteries is feasible.

Adult↗

Multiple mechanisms are involved in the acute vasodilatory effect of 17beta-estradiol in the isolated perfused rat heart.

The purpose of this study was to define the dose-dependent effects of 17beta-estradiol on coronary flow and cardiac function in isolated rat hearts and to identify the mechanisms involved in its vasodilator action. Hearts from female and male Wistar rats were perfused at constant pressure (100 mm Hg). Stereoisomer specificity and the mechanism of vasodilation by 17beta-estradiol were examined in female rat hearts. Function was measured by a left ventricular (LV) balloon and coronary flow (CF) with an ultrasonic flowmeter. 17Beta-estradiol at 10(-6), 5 x 10(-6), and 10(-5) M increased CF in female hearts by 5 +/- 2, 27 +/- 4 (p < 0.05 vs. baseline), and 40 +/- 4% (p < 0.05 vs. baseline), respectively. The effect of 17beta-estradiol in hearts from male rats was similar but less pronounced compared with females [deltaCF 8 +/- 3, 19 +/- 3 (p < 0.05 vs. baseline)] and 25 +/- 7% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol). Maximum vasodilation by the stereoisomer 17alpha-estradiol was significantly smaller [deltaCF 5 +/- 3, 4 +/- 3 (p < 0.05 vs. female 17beta-estradiol) and 14 +/- 1% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol)] for 10(-6), 5 x 10(-6), and 10(-5) M. Pretreatment with the NO-synthesis inhibitor Nomega-methyl-L-arginine (10(-4) M) had no effect on the maximal vasodilator response to 17beta-estradiol (10(-5) M) [deltaCF 36 +/- 6% (p < 0.05 vs. baseline)]. When hearts were pretreated with the prostaglandin-synthesis inhibitor diclofenac (10(-6) M), the maximal vasodilator effect of 17beta-estradiol was partially attenuated [deltaCF 12 +/- 7% (p < 0.05 vs. female 17beta-estradiol)]. Similarly, pretreatment with the K+ATP-blocker glibenclamide (10(-6) M) partially inhibited the maximal vasodilator effect of 17beta-estradiol [deltaCF 22 +/- 6% (p < 0.05 vs. baseline; p < 0.05 vs. female 17beta-estradiol)]. Pretreatment with the Ca2+ channel antagonist nifedipine (7.2 x 10(-8) M) completely blocked the vasodilator effect. In isolated perfused rat hearts, 17beta-estradiol induced marked acute coronary vasodilation; this effect is in part gender specific, and in female hearts, largely stereoisomer specific. The dilator effect is mediated predominantly by calcium channel blockade, but prostaglandin release and K+ATP channel activation also are involved. In the isolated perfused rat heart, NO production does not contribute to the acute vasodilator effect of 17beta-estradiol.

Animals↗

Effects of ACE inhibition and beta-receptor blockade on energy metabolism in rats postmyocardial infarction.

Chronic treatment with beta-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial action remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myocardial infarction (MI) or sham operation. Thereafter, animals were treated with bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine kinase (CK) activity, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reaction velocity) of high-energy phosphates (31P nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 15%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcted hearts. Thus the favorable functional effects of beta-receptor blockers and ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.

Adenine Nucleotides↗

Giant retroperitoneal hemangiopericytoma with paraneoplastic gynecomastia. Case report and literature review.

We report on a 38-year-old patient with a giant retroperitoneal hemangiopericytoma associated with bilateral paraneoplastic gynecomastia, which led to an almost uncontrollable hemorrhage on initial surgery due to the extreme hypervascularity of the process. After angiographic evaluation and superselective embolization, a complete surgical excision of a hemangiopericytoma weighing almost 1,000 g could be achieved. To reduce the risk of recurrence adjuvant radiotherapy with 49 Gy followed. Follow-up of 24 months showed no sign of recurrence on CT scans. To our knowledge this is the first reported case of hemangiopericytoma associated with a paraneoplastic syndrome. The literature and the therapeutic concepts are presented and discussed.

Adult↗

Results and 10-year follow-up in patients with squamous cell carcinoma of the penis.

Penile malignancies are infrequent but represent a diagnostic and therapeutic challenge as patients tend to disregard early asymptomatic lesions of the disease. Due to the lack of studies involving large patient numbers, the therapeutic concepts for different stages of the disease could not be defined by prospective studies. Long-term results are rare. We present the therapeutic concepts and the 10-year results of our experience with 42 cases of penile carcinoma treated at our institution between 1973 and 1986. Therapy included radical circumcision in 10 cases, local excision of the tumor in 4, partial or total glandular resection in 6 patients, partial penectomy in 20, and total penectomy in 2 cases. Inguinal lymphadenectomy was performed initially in 14 cases with positive histology in 7 patients (50%). Complications included meatal stenosis in 8 cases (19%), urethral stricture in 1 case, death due to fulminant pulmonary embolism in 1 case and local infections in 2 cases. Follow-up of patients with initially nonmetastatic disease showed a progression to death in 4 of 35 patients (11.6%) with a mean survival of 30 (range 11.5-56) months, in patients with initial lymph node metastases progression to death occurred in 5 of 7 patients (71.4%) with a mean survival of 9.76 months (range 9 days to 24 months). Stage-related disease-specific 10-year survival rates are 100% for stages 0 and 1, 90.9% for stage 2, and 20% for stage 3, while no patient in stage 4 survived for 5 years. From our data we conclude that the single most important prognostic factor in the treatment of carcinoma of the penis is lymph node involvement. Therefore increased attention has to be paid to the recognition of early stages of this potentially curable disease.

Carcinoma, Squamous Cell↗

Three-dimensional MR coronary angiography using the navigator technique compared with conventional coronary angiography.

OBJECTIVE: We evaluated the diagnostic accuracy of three-dimensional (3D) MR coronary angiography with the navigator technique for the detection of coronary artery stenoses in comparison with that of conventional radiographic angiography. SUBJECTS AND METHODS: Thirty patients with coronary artery disease were examined with an ECG-triggered 3D fast low-angle shot sequence using retrospective respiratory gating and the navigator technique on a 1.5-T MR scanner. The data set was evaluated as a 3D view with a surface rendering technique. RESULTS: Imaging of the proximal coronary arteries was possible in all patients. The average visualized lengths of the left main, left anterior descending, left circumflex, and right coronary arteries were 1.9+/-0.5 cm (mean +/- SD), 5.2+/-2.3 cm, 4.2+/-1.9 cm, and 5.2+/-2.5 cm, respectively. Irregular breathing reduced image quality in seven of the 30 patients, making diagnosis of stenoses impossible. In the 77% of patients whose examinations resulted in high-quality images, the sensitivity and specificity for detection of significant stenoses and occlusions in all four main coronary arteries were 81% and 89%, respectively. CONCLUSION: The navigator technique allows reproducible imaging of the proximal course of coronary arteries. This technique obviates breath-hold studies, thus allowing more patients to be examined. In patients whose examinations resulted in high-quality images, significant coronary artery lesions could be seen. However, for widespread clinical use, further technical improvement is necessary to increase sensitivity and specificity.

Adult↗

Differentiation between Spitz nevi and malignant melanomas by interphase fluorescence in situ hybridization.

Spitz nevi are benign melanocytic neoplasias which have distinct pathological features that make the pathological differential diagnosis from malignant melanomas extremely difficult. The Spitz nevi may be misdiagnosed as malignant melanoma and vice versa. Therefore, interphase fluorescence in situ hybridization (I-FISH) was used for a possible discrimination between Spitz nevi and malignant melanomas on the basis of numerical aberrations of the chromosome complement in interphase nuclei of thin sections. Previous studies had shown changes in malignant melanomas which were not found at the same level in normal tissue or benign tumors. Thin sections of archival paraffin material from 42 Spitz nevi with different histological type and grade of anomaly were subjected to FISH-analyses using commercially available biotinylated and/or digoxigenated alphoid DNA probes of chromosomes 1, 6, 7, 9, 17 and 18, which were applied in combinations in a two- or three-color-FISH. Unaffected epithelial areas from the same sections served as. The obtained data were compared with those collected previously from thin sections of malignant melanomas prepared in the same way. Due to the sometimes limited nevus area investigated, the number of evaluable nuclei was lower than expected from previous experiences with malignant melanomas. Therefore, only 20 nevi could be reliably evaluated. The comparison of the group of Spitz nevi with the group of controls did not show any significant difference regarding chromosomes 1, 6, 7, 9 and 17 (Wilcoxon test). The method used to detect chromosomal loss or gain in the individual Spitz nevi demonstrated only two nevi (one of the spindle cell type with a low to middle grade of anomaly, the other of the epitheloid cell type with a middle grade of anomaly) with a gain of chromosome 7 and chromosome 17, respectively. So, with respect to the histological type and grade of anomaly, no numerical aberrations could be detected in Spitz nevi. The comparison of the group of Spitz nevi with subgroups of malignant melanomas (metastatic, non-metastatic, melanomas with a thickness <1.5 mm and melanomas with a thickness >2. 0 mm) and with the whole group of malignant melanomas showed significant differences concerning chromosome 9 (Mann-Whitney U test), signal indices, which were higher in the melanomas than in the Spitz nevi. Regarding chromosomes 6, 7 and 17 no significant differences could be shown, although a trend of gain in melanomas and of loss in Spitz nevi was observed of these chromosomes.

Adolescent↗

Three-dimensional 31P magnetic resonance spectroscopic imaging of regional high-energy phosphate metabolism in injured rat heart.

The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.

Adenosine Triphosphate↗

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↗

Changes of myocardial high-energy phosphates with the cardiac cycle during acute or chronic myocardial stress.

Whether changes of cardiac high-energy phosphate concentrations occur over the cardiac cycle remains controversial. The hypothesis was that such cyclical changes are accentuated during acute or chronic myocardial stress. Isolated rat hearts were perfused under four conditions: (1) control, (2) inotropic stimulation by doubling of perfusate [Ca2+], (3) acute hypoxia (buffer PO2 approximately 150 torr), and (4) failing, chronically infarcted hearts. 31P-MR spectra were obtained at seven time points of the cardiac cycle. Under control conditions, cyclical changes ("cycling") of ATP (11+/-3%*, *P < 0.05) and phosphocreatine (9+/-2%*) were detected, inorganic phosphate cycling did not reach statistical significance. At high [Ca2+] perfusion, cycling of phosphocreatine (9+/-5%*) was not accentuated, cycling of ATP and inorganic phosphate did not reach significance. During acute hypoxia, cycling of ATP (10+/-4%*) and inorganic phosphate (11+/-4%*) occurred, but cyclical changes of phosphocreatine were not significant. In chronically infarcted hearts, the extent of cyclical changes of ATP, phosphocreatine, and inorganic phosphate was not accentuated. Thus, in perfused rat heart, small oscillations of high-energy phosphates during the cardiac cycle are detectable, but such changes are not accentuated during acute or chronic stress. The concentrations of high-energy phosphates over the cardiac cycle are tightly regulated.

Acute Disease↗