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S Neubauer

Publications and source records attributed to S Neubauer.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of chronic dietary creatine feeding on cardiac energy metabolism and on creatine content in heart, skeletal muscle, brain, liver and kidney.

Little is known about the regulation of total creatine concentration in heart, skeletal muscle, brain, liver and kidney in response to increased dietary creatine intake. The phosphorylated fraction of intracellular creatine (phosphocreatine) remain relatively constant, and therefore, higher intracellular creatine levels may increase the energy reserve of the heart [phosphocreatine and phosphoryl transfer via creatine kinase (CK)] and of other organs. To test the effect of supplying exogenous creatine on the myocardial energy reserve and on creatine content of various organs, rats were given chow containing 0 (Untreated), 1, 3, 5, or 7% (of diet weight) creatine for ;40 days. Thereafter, hearts were perfused and left ventricular developed pressure and heart rate were recorded. High-energy phosphate concentrations were determined with 31P-NMR spectroscopy, CK reaction velocity by 31P-magnetization transfer. Total creatine was determined in heart, skeletal muscle, brain, liver, kidney and serum by high-performance liquid chromatography (HPLC). Creatine feeding increased serum creatine by 73% (1% creatine), 142% (3%), 166% (5%) and 202% (7%). In the heart, increased serum creatine levels did not affect mechanical function; ATP, phosphocreatine, inorganic phosphate, CK reaction velocity and total creatine were all unchanged. Total creatine also remained constant in brain and skeletal muscle, while creatine content increased 4.6-fold in the liver and 1.9-fold in the kidney. We conclude that myocardial energy reserve via CK cannot be increased by exogenous creatine treatment.

Adenosine Triphosphate↗
PubMed1998

Changes of creatine kinase gene expression in rat heart post-myocardial infarction.

Creatine kinase (CK) plays a crucial role in cardiac energy transduction. During chronic cardiac stress conditions leading to hypertrophy and/or heart failure, the profile of CK isoenzyme activities changes towards a fetal pattern with increases of BB- and MB-CK and decreases of MM-CK and mito-CK. Changes of myocardial CK gene expression are only indirectly reflected by measurements of CK activities. The purpose of this work was, therefore, to determine myocardial expression of B-, M- and sarcomeric mito-CK genes in an animal model of heart failure where hemodynamic alterations and CK system changes are well defined, that is, in the rat heart post-myocardial infarction. Intact residual left ventricular myocardium was harvested 2 months following infarction (MI; n = 7) or sham operation (sham; n = 6) after in vivo left-ventricular end-diastolic pressure (LVEDP) was recorded. Total CK activity was measured spectrophotometrically, CK isoenzyme distribution with agarose gel electrophoresis. Steady state mRNA levels coding for B-, M- and mito-CK genes were measured with quantitative PCR and were normalized for GAPDH expression. Total CK activity tended to be reduced in MI (5.51 +/- 0.62 IU/mg protein) compared to sham (6.77 +/- 0.24; P = 0.55). CK isoenzyme distribution showed an increase of fetal BB- + MB-CK (MI 22.0 +/- 3.1%, sham 15.1 +/- 1.0%; P < 0.05), no change of MM-CK and a decrease of mito-CK (27.0 +/- 1.5% sham, 20.8 +/- 2.0% MI: P < 0.05). Relative B-CK mRNA levels increased (sham 0.46 +/- 0.06, MI 1.03 +/- 0.09; P < 0.05) and M-CK mRNA levels decreased (sham 1.06 +/- 0.08. MI 0.66 +/- 0.09; P < 0.05) significantly post-MI. The increase of B-CK mRNA (r = 0.72; P = 0.009) and the decrease of M-CK mRNA (r = 0.76; P = 0.003) correlated significantly with in vivo LVEDP. Mito-CK mRNA levels remained unchanged after MI (sham 0.94 +/- 0.16, MI 0.98 +/- 0.09). Intact residual left-ventricular myocardium post-MI is characterized by increased B-CK-mRNA and reduced M-CK-mRNA expression.

Animals↗
PubMed1998

Endothelin-1 increases susceptibility of isolated rat hearts to ischemia/reperfusion injury by reducing coronary flow.

Endothelin-1 (ET-1) is the most potent vasoconstrictor known to date, and it was proposed that this peptide plays a major role in myocardial ischemia/reperfusion injury. ET-1 could increase myocardial susceptibility to ischemia by two mechanisms: via coronary flow reduction and/or via direct, metabolic effects on the heart. In isolated, buffer-perfused rat hearts, function was measured with a left ventricular balloon, and energy metabolism (ATP, phosphocreatine, inorganic phosphate, intracellular pH) was estimated by 31NMR-spectroscopy. Under constant pressure perfusion, hearts were subjected to 15 min of control perfusion, 15 ("moderate injury") or 30 ("severe injury") min of global ischemia, followed by 30 min of reperfusion. Hearts were pre-treated with ET-1 (boluses of 0.04, 4, 40 of 400 pmol) 5 min prior to ischemia. In the control period, ET-1 reduced coronary flow, ventricular function, phosphocreatine and intracellular pH dose-dependently: during ischemia/reperfusion, coronary flow, functional recovery and high-energy phosphate metabolism were adversely affected by ET-1 in a dose-related manner. To study effects of ET-1 not related to coronary flow reduction, additional hearts were perfused under constant flow conditions (ET-1 0 or 400 pmol) during 15 min of control, 15 min of ischemia and 30 min of reperfusion. When coronary flow was held constant, functional and energetic parameters were similar for untreated and ET-1 treated hearts during the entire protocol, i.e. the adverse effects of ET-1 on function and energy metabolism during ischemia/reperfusion were completely abolished. In both constant pressure and constant flow protocols, 400 pmol ET-1 reduced the extent of ischemic intracellular acidosis. The authors conclude that ET-1 increases the susceptibility of isolated hearts to ischemia/reperfusion injury via reduction of coronary flow.

Animals↗
PubMed1998

Chromosomal in-vitro radiosensitivity of lymphocytes in radiotherapy patients and AT-homozygotes.

BACKGROUND: We investigated the in-vitro radiosensitivity of peripheral blood lymphocytes with a special FISH/CISS-technique. PATIENTS AND METHODS: From October 1993 through April 1996, a total number of 52 cancer patients was enrolled in the study. The tumor sites in these patients were: breast (n = 41), lung (n = 4), head and neck (n = 3) as well as prostate, bladder, rectal cancer and Hodgkin's disease (each n = 1). Twenty-six of them were examined prior to planned radiotherapy (prospective group) and 26 after radiotherapy (retrospective group). Three additional individuals (without cancer or radiotherapy) with proven ataxia telangiectasia (Louis-Bar syndrome, AT-homozygotes) were also investigated and their blood samples served as positive control for radiosensitivity. The clinical radiation response of normal tissue in radiotherapy patients was scored according to the WHO grading system for acute and according to the RTOG grading system for late effects. For to estimate the intrinsic radiosensitivity, blood samples were taken and irradiated in vitro with 0 (control) or 0.7 or 2 Gy with a 6 MV-linear accelerator, standard 48-hour lymphocyte cultures were prepared, chromosomes #1, #2 and #4 were simultaneously labeled with a FISH/CISS-technique and 200 to 1,000 metaphase spreads were scored for chromosomal aberrations. The radiation sensitivity of lymphocytes was expressed as the number of radiation-induced chromosomal breaks per mitosis after 0.7 Gy or 2 Gy corrected for the 0-Gy control value. RESULTS: The frequency of chromosomal breaks/mitosis in the unirradiated control lymphocytes was 0.020 +/- 0.015 in prospective patients who had not yet received radiotherapy. It was significantly higher in retrospective patients (0.264 +/- 0.164 breaks/mitosis) as a result of the previous radiation exposure. The 3 AT-homozygotes showed also an increased number of spontaneous chromosomal breaks (0.084 +/- 0.016 breaks/mitosis), probably resulting from the chromosomal instability in this disease. This figure, however, was significantly lower than in retrospective patients. The number of radiation-induced breaks after in-vitro irradiation was comparable in lymphocytes of patients who showed no normal tissue reaction (n = 11) as compared to those with mild to moderate radiation reaction (n = 32, acute reactions Grade 1 to 2, late reactions Grade 0 to 2). In 9 patients with unexpected severe plus late Grade 3 to 4 reactions, however, a significantly higher number of radiation-induced chromosomal breaks was measured; the highest number was observed in a patient with a radiation myelitis. The 3 AT-homozygotes showed, as expected, an extreme radiosensitivity of their lymphocytes. The number of breaks/mitosis after 0.7 Gy in vitro irradiation of lymphocytes was 0.103 +/- 0.059 in patients with no normal tissue radiation reaction (n = 11), 0.122 +/- 0.146 in the group with mild to moderate radiation reactions Grade 1 to 2 (n = 32), 0.359 + 0.226 in patients with unexpected Grade 3 to 4 normal tissue reactions (n = 9) and 0.550 +/- 0.243 in the 3 AT-homozygotes (p < 0.01, t-test). The difference in lymphocyte radiosensitivity between these 4 groups was also detected after in-vitro irradiation with 2 Gy (0.484 +/- 0.132 vs. 0.535 +/- 0.228 vs. 0.926 +/- 0.349 vs. 1.423 +/- 0.072). CONCLUSIONS: We found a significantly higher number of chromosomal breaks in lymphocytes of patients with severe or extreme radiation reaction of normal tissues as compared to patients with no or only mild to moderate radiation reactions. The radiosensitivity of lymphocytes in these radiosensitive patients was in the range between normal radiosensitivity and the radiosensitivity of AT-homozygotes. Detection of patients with severely enhanced intrinsic radiosensitivity might be possible with this method.

Adult↗
PubMed1998

[Transition of myocardial ischemia to heart failure].

Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.

Chronic Disease↗
PubMed1998

Influence of left ventricular pressures and heart rate on myocardial high-energy phosphate metabolism.

This review describes the effects of changes in left ventricular pressures and heart rate on myocardial high-energy phosphate metabolism. When cardiac workload is substantially increased, creatine kinase flux will increase markedly, phosphocreatine will show a small but detectable decrease, and ATP will not change. In this context, heart rate is a much weaker acute metabolic stimulus than left ventricular developed pressure. However, in heart failure, chronic reduction of heart rate has beneficial effects on alterations of high-energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1998

Estimation of DNA single-strand breaks by single cells gel electrophoresis in tumor cells.

To estimate the frequency of single-strand breaks on a single cell level the so-called comet-assay (single cell gel electrophoresis) is a well-established technique. We present a modified protocol suitable for testing primary tumors, a kind of tissue very uneasy to be analysed in former single cell gel electrophoresis assays. Tumor cells of 12 studied cases showed a typical dose-rate effect on in vitro irradiation with different X-ray doses, as observed in peripheral blood leukocytes. Interestingly, the repair capability of primary tumor cells was lower than that of peripheral blood leukocytes of the same patients.

Adenocarcinoma↗
PubMed1998

[Complications of CT guided lumbar sympathectomy: our own experiences and literature review].

AIM: To review the complications of CT guided lumbar sympathicolysis (CTLS) on the basis of our own experience and the available literature. METHODS: 241 CTLS were performed by a standard technique according to Haaga's method. Clinical follow-up revealed 4 serious complications; these were analysed and compared with published cases. RESULTS: Amongst our patients there were three fibrotic ureter stenoses and one retroperitoneal abscess. Analysis of the serious complications described in the literature indicates that introduction of CT guided lumbar sympathicolysis has reduced the severity and frequency of complications as compared with surgical and "blind" procedures. With CTLS, no deaths due to the procedure have been reported in the literature. The results indicate that damage to the ureters can be caused by substances used for the neurolysis. CONCLUSION: Provided certain safeguards are obeyed, CTLS is a very save treatment. However damage to the ureter may follow even when the procedure was technically satisfactory. Therefore, sonographic control of the kidneys after three months is recommended.

Abscess↗
PubMed1998

[3-dimensional MR coronary angiography with navigator technique: imaging of the proximal course of a coronary artery anomaly].

Congenital coronary artery anomalies are found in 0.3 to 1.3% of patients and can cause ischemic heart disease or sudden cardiac death, especially if the anomalous coronary artery courses between the aortic root and the pulmonary artery. Identification of the anatomic course of the anomalous vessel is not always feasible by conventional radiographic coronary angiography. With MR coronary angiography not only flowing blood but also the vessel anatomy can be imaged. In previous studies, a two-dimensional gradient-echo sequence during breathhold was used demanding both cooperation of the patient and operator skill. The navigator technique reduces respiratory artifacts by retrospective respiratory gating on the diaphragm's position, obviating the need for breathhold studies. Furthermore, the three-dimensional MR coronary angiography enables post-processing using the Volume Rendering Technique for evaluation of three-dimensional view. We report on the use of this technique for the identification of the course of anomalous coronary arteries in two patient cases.

Artifacts↗
PubMed1998

Cryoablation of localized prostate cancer. Experience in 48 cases, PSA and biopsy results.

OBJECTIVES: As the first German center to perform perineal cryoablation of localized prostate cancer, we present our experience in a series of 48 consecutive patients. METHODS: 7 patients staged T1, 21 with T2 disease and 20 patients with T3 tumor were treated. 62.5% of the patients received neoadjuvant hormonal downsizing. Follow-up ranged from 4 to 27 months with a median of 15 +/- 5.7 months. RESULTS: Positive control biopsies after 6 months were obtained in 0% of T1 tumors, 16.7% of T2 tumors and 26.7% of T3 tumors. Prostate-specific antigen persistence above 1 ng/ml was diagnosed in 14.3, 33.3, and 40%, respectively. Complications were acceptable. 22.9% of the patients had prolonged urinary retention, requiring transurethral resection in 5 patients (10.4%) to relieve obstruction. In 5 cases (10.4%) incontinence was found, in 2 of these patients mild urge incontinence declined over time, in 3 cases moderate to severe stress incontinence developed. Two of these patients were pretreated with radiotherapy. No fistulae were noted. CONCLUSIONS: Cryoablation of the prostate is not a substitution for radical prostatectomy but enables the surgeon to perform a radical curative procedure in patients unfit for other radical forms of treatment or unwilling to undergo these. Long-term follow-up and prospective studies are necessary to define the clinical significance of this procedure.

Aged↗
PubMed1998

Cryoablation of localized prostate cancer: neoadjuvant downsizing of prostate cancer with LH-RH analogue depot before cryosurgery.

Radical prostatovesiculectomy, radiation therapy, and complete androgen deprivation are acknowledged therapeutic concepts in the treatment of organ-confined prostate cancer. With cryoablation of the prostate, minimal invasive therapy has become available since 1991. Improvements in cryotechnique and progress in transrectal high-resolution ultrasound permit thermo-induced damage to the whole gland to be curative. Downstaging of prostate cancer by hormone ablative therapy remains a controversial issue at this time, but the use of androgen ablation decreases the size of the prostate gland which facilitates cryosurgery and improves the results. The freezing equipment has a limited capacity, and in certain instances large gland volumes prevent adequate freezing of the prostate. Since percutaneous prostate cryosurgery leaves dead tissue in situ to be resorbed over time, downsizing reduces the amount of necrotic tissue to be resorbed, reducing the potential for complications, particularly abscesses. The use of androgen ablation also increases the deposition of fat in the area of the Denonvillier's fascia, making freezing of the rectum less likely during the procedure. In our study androgen ablative therapy was completed before performing cryosurgery in 26 of 43 patients (58%). The 17 patients not given androgen ablation therapy had gland volumes < 40 ml, tumor volumes < 3 ml, and no evidence of extracapsular tumor. The neoadjuvant therapy consisted of a 3- to 10-month course of leuprolide acetate combined with an antiandrogen.

Androgen Antagonists↗
PubMed1998

Clinical cardiac magnetic resonance spectroscopy--present state and future directions.

MR spectroscopy opens a window to the non-invasive evaluation of various aspects of cardiac metabolism. Experimentally, the method has extensively been used since 1970's. 31P-MR allows the registration of cardiac high-energy phosphate metabolism to non-invasively estimate the energetic state of the heart: ATP, phosphocreatine, inorganic phosphate, monophosphate esters and intracellular pH can all be quantitated. In conjunction with extracellular shift reagents such as [DyTTHA]3- or [TmDOTP]5-, 23Na- and 39K-MR allow the measurement of intra- and extra-cellular cation pools. 1H-MR spectroscopy allows the detection of a large number of metabolites such as, e.g. creatine, lactate, or carnitine. Human cardiac spectrocsopy has so far been confined to the 31P nucleus. Localization techniques (DRESS, ISIS, 3D-CSI etc.) are required to confine the acquired signal to the heart region. Relative quantification is straightforward (phosphocreatine/ATP ratio), absolute quantification (mM) is under development. Cardiac 31P-MR spectroscopy has research application in at least three clinical areas: (1) Coronary artery disease: A biochemical stress test for non-invasive ischemia detection (decrease of phosphocreatine with exercise) and viability assessment via quantification of ATP may become feasible. (2) Heart failure: The phosphocreatine/ATP ratio may provide an independent index for grading of heart failure, allow to monitor the longterm effects of different forms of drug therapy on cardiac energy metabolism in heart failure, and may also hold prognostic information on survival. (3) Valve disease: It is possible that the decrease of phosphocreatine/ATP can be used to guide the timing for the valve replacement. At the present time, no routine clinical applications can be defined for the use of human cardiac spectroscopy in patients with cardiac disease. However, the technique holds great potential for the future as a non-invasive approach to cardiac metabolism, and in coming years routine applications may become reality.

Adenosine Triphosphate↗