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Biomedical subjects

M Beer

Publications and source records attributed to M Beer.

At least 37 records · Page 2Linked to original sources

[(23)sodium MRI for infarct imaging of the human heart].

PURPOSE: Sodium is elevated in acute/subacute myocardial infarction due to three distinct mechanisms: Breakdown of ion homeostasis with accumulation of intracellular sodium, extracellular edema formation and, during scar formation, increase of extracellular vs. intracellular space as cardiomyocytes are replaced by connective tissue. 23Na MRI has previously been shown to have the potential to demonstrate myocardial infarction in an animal model. Aim of this study was, therefore, to demonstrate myocardial infarction with the use of 23Na-MRI in patients. MATERIAL AND METHODS: 10 patients were examined 14 +/- 7 days after first myocardial infarction using a 23Na surface coil at 1.5 T. Double angulated short axis images of the entire heart were imaged using an ECG-triggered 3d-FLASH-sequence (FOV, 450 mm; matrix, 64 x 128; spatial resolution, 3.5 x 7 mm2; slice thickness, 16 mm; 32 acquisitions). Areas of elevated sodium signal intensity were correlated with infarct-related wall motion abnormalities imaged by Cine MRI in breathhold-technique. RESULTS: All patients showed an area of elevated sodium signal intensity that correlated well with the clinically determined localization of myocardial infarction as well as with regional wall motion abnormalities detected by Cine MRI. CONCLUSIONS: Elevated 23Na MR image signal intensity demonstrates subacute myocardial infarction in patients.

Aged↗

A simple method to check the dynamic performance of electrical impedance tomography systems.

The test concept as well as the design of a simple resistor phantom suitable for the evaluation of the properties of electrical impedance tomographic (EIT) systems is presented. Input and transfer impedance of the phantom are matched with those of the human thorax. Amplitude of the local impedance variations similar to in vivo conditions (ventilation) can be intentionally set to perform measurements on different states. The theoretical potential differences between the electrodes are calculated. The evaluation procedure is performed in terms of the local amplitude of the relative impedance change as well as the local distribution of noise. The whole procedure can be applied either to compare quantitatively the performance of different EIT data acquisition systems or to determine the amount of measurement disturbance caused by the external electrical environment in clinical settings.

Cardiography, Impedance↗

An occupational therapy Internet school.

Four centres in the UK, Belgium, the Netherlands and Sweden have collaborated to provide Internet-based courses for student and professional occupational therapists. The basis of the occupational Therapy Internet School (OTIS) is the concept of the 'virtual college'. This comprises the design and implementation of a sophisticated Internet-based system through which courses can be managed, prepared and delivered on line, and through which students can communicate both with the staff and their peers. The aim is to support and facilitate the whole range of educational activities within a remote electronic environment.

Education, Distance↗

Analysis of first-pass and delayed contrast-enhancement patterns of dysfunctional myocardium on MR imaging: use in the prediction of myocardial viability.

OBJECTIVE: The purpose of the study was to analyze first-pass and delayed contrast-enhancement patterns of dysfunctional myocardial regions on MR imaging after injection of gadopentetate dimeglumine to predict myocardial viability in patients with coronary artery disease. SUBJECTS AND METHODS: Twelve patients with wall motion abnormalities and related coronary artery disease revealed by conventional coronary angiography underwent MR imaging at 1.5-T before and 3 months after revascularization therapy. Short-axis images were acquired using a cine gradient-echo sequence. Each slice was divided into eight segments. Overall, 73 segments with impaired contractility were imaged during the first-pass and 14 +/- 2 min after injection of 0.05-mmol/kg gadopentetate dimeglumine at a flow of 3 ml/sec using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as the criterion of viability. RESULTS: At study entry, 26 dysfunctional segments showed delayed hyperenhancement compared with the adjacent functional segments within the same slice, and 47 did not reveal hyperenhancement. After revascularization, 25 (96%) of the 26 hyperenhanced segments did not recover function, whereas 39 (83%) of the 47 segments without hyperenhancement showed mechanical improvement. Segment-related sensitivity and specificity for the correlation of lack of delayed hyperenhancement with myocardial viability were 39 (98%) of 40 and 25 (76%) of 33, respectively. Hypoenhancement during first-pass did not serve as a reliable criterion of viability. CONCLUSION: Evidence of delayed hyperenhancement of dysfunctional myocardium may be used to predict lack of mechanical improvement or nonviability, whereas the lack of hyperenhancement can be correlated with improvement of regional contractility or viability after revascularization.

Aged↗

Pentostatin (Nipent) and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with previously untreated, treated, and fludarabine-refractory B-cell chronic lymphocytic leukemia.

Renewed interest in chronic lymphocytic leukemia (CLL) has led to an unprecedented number of investigators contributing to all aspects of research in this disease. In fact, the evolution of research in the area of molecular aberrations in CLL and their impact on treatment resistance alone is striking. These data, along with the advent of the purine analogs, have been central to this paradigm shift. The inferior response rate, the abbreviated response duration, and the inability to prolong survival with alkylating agents such as chlorambucil have resulted in purine analogs being used as first- and second-line therapy for patients with CLL. In fact, patients treated with fludarabine have a higher overall and complete response rate as well as a disease-free survival advantage compared with patients treated with alkylator-based therapy. Pentostatin, the first purine analog to enter clinical trials, was never subjected to extensive schedule optimization despite its demonstrated efficacy and its paucity of significant myelosuppression compared with the other purine analogs. However, pentostatin induced a 25% to 30% response rate in heavily pretreated CLL patients, including some who had received prior fludarabine, suggesting possible non-cross-resistance. Based on preclinical data demonstrating synergistic activity when a DNA damaging agent (eg, an alkylating agent) is followed by an inhibitor of DNA repair (a purine analog), a number of purine analog/alkylator combinations have been and are presently being examined in a variety of lymphoid neoplasms. While the clinical data conflict, at least two phase II studies examining a combination of a purine analog and an alkylator in untreated patients with CLL have generated promising data. This report describes the scientific justification and the design of a new phase II study examining the combination of pentostatin and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with untreated, treated, and fludarabine-refractory B-cell CLL.

Antibiotics, Antineoplastic↗

1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.

After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1, 3-dihydroimidazol-2-yl)piperidine 8. Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot" procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1, 3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or 5-position of the 1, 3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater selectivity (>1000-fold) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has >1000-fold selectivity over all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D(4) receptor.

Animals↗

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↗

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 MR imaging after myocardial infarction--assessment and follow-up of regional and global left ventricular function.

Myocardial infarction often leads to regional wall motion defects and in case of large defects to remodeling of the left ventricle. With this study, changes in regional and global myocardial function of 12 patients 3 weeks after myocardial infarction and after revascularization therapy were determined using MRI. Cine MRI was performed at study entry at rest and during low-dose dobutamine stimulation. All patients were re-examined at rest 3 and 6 months after the revascularization, including analysis of wall thickening and of left ventricular end-diastolic volume index (LVEDVI), end-systolic volume index (LVESVI), ejection fraction (LVEF), and mass index. After revascularization. 6 patients with stress-induced improvement of regional wall thickening recovered, 4 patients without improvement did not, but 2 patients without stress-induced improvement of wall thickening also recovered. Concerning global cardiac function, patients with mainly improved regional wall motion also showed a lower LVESVI and a higher LVEF than patients without improvement of regional contractility 6 months after revascularization in comparison to study entry. In conclusion, improvement of global myocardial function after revascularization is higher in patients with improved contractility in the infarcted region. The extent of the response of regions with wall motion defects to dobutamine stress correlates with the actual improvement after revascularization, and, therefore, dobutamine stress MRI may be helpful in selecting patients that will have a higher benefit from a revascularization therapy.

Adult↗

Cyclosporine-induced autologous graft-versus-host disease in patients with acute myeloid leukemia undergoing non-myeloablative chemotherapy without progenitor cell reinfusion.

To determine the incidence and severity of cyclosporine-induced graft-versus-host disease following non-myeloablative chemotherapy without progenitor cell reinfusion in patients with acute leukemia, 17 adults with refractory acute myeloid leukemia (14) or blastic phase of chronic myeloid leukemia (3) were treated with etoposide 2400 mg/m2 and cyclophosphamide 120 mg/kg followed by cyclosporine (CsA) 2.5 mg/kg i.v. daily and interferon gamma 0.025 mg/m2 subcutaneously every other day until day 28. Skin biopsies were obtained on days 14 and 28, or on the appearance of a skin rash, and graded for GVHD. Blood samples were examined at baseline and weekly starting on day 14 for natural killer (NK) cell and T cell lymphocytic changes. Post-treatment lymphocytes from select patients were assessed for allogeneic NK cell and autologous leukemic cell cytolytic activity. Four patients developed pathologic grade 2 cutaneous acute GVHD. Of the three patients who achieved a complete remission, two had evidence of GVHD. Post-treatment, three patients (two with GVHD) in whom adequate numbers of lymphocytes could be obtained showed NK cell cytolytic activity against allogeneic tumor cells (K562), but none had cytolytic activity against their own cryopreserved leukemic cells. These data suggest that in patients with AML treated with subablative doses of chemotherapy without autotransplant, autologous GVHD can be induced, although at an incidence lower than that reported for CsA-induced GVHD following marrow transplantation. An enhancement of T cell and NK cell activity levels similar to experiences in syngeneic models of autologous GVHD was seen, but no direct autologous leukemic cell cytotoxicity could be demonstrated.

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↗

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↗

[Selection of BVDV genotype II isolates using a monoclonal antibody and FACS analysis].

The infection of cattle with the bovine viral diarrhea virus (BVDV) in Germany is gaining attention and guidelines for the "protection of cattle farms against BVDV infections" were passed in 1997. New investigations about the damages induced by BVDV infections as well as the new occurrence of so-called BVDV genotypes (BVDV I and II) made the problems to become aware. The newly described BVDV genotype considerably differs both genetically and antigenetically from the up to now known BVD-viruses (BVDV I). The subdivision in BVDV genotypes I and II is based on genomic differences, which are determined by sequence analyses of different parts of the viral genome. Here, we describe the classification of BVDV in genotypes using a monoclonal antibody and indirect immunofluorescence with flow cytometry (FACS) based analysis. The suitability of the mab WB160 (Central Veterinary Laboratory, Weybridge; UK) for the classification of both BVDV-genotypes was first checked using genetically defined BVDV isolates. While all BVDV I isolates (n = 20) reacted with high fluorescence signals, the mab WB160 could not detect any of the defined BVDV II isolates (n = 20). Subsequently, 505 BVDV field strains isolated between 1993-1997 were screened for both genotypes using the mab WB160 and FACS analysis. 33 (6.5%) of the BVDV isolates were classified as BVDV II.

Animals↗

Laparoscopic nephrectomy: the experience of the laparoscopy working group of the German Urologic Association.

PURPOSE: The centers of the laparoscopy working group of the German Urologic Association collected data to prove the efficacy, safety and reproducibility of laparoscopic nephrectomy. MATERIALS AND METHODS: At 14 centers 482 laparoscopic nephrectomies have been performed until December 1996 via a transperitoneal approach in 344 (71%) and a retroperitoneal approach in 138 (29%). All 482 laparoscopic nephrectomies were performed by a total of 20 surgeons with an average of 24 procedures per surgeon (range 4 to 105). The indications for nephrectomy were benign renal pathology in 444 patients (92%), including renovascular disease in 28%, hydronephrosis in 20%, reflux nephropathy in 15%, chronic pyelonephritis in 12%, end stage nephrolithiasis in 11%, renal dysplasia in 4% and renal tuberculosis in 1%. Of the remaining 38 patients (8%) laparoscopic radical nephrectomy was performed for renal cell carcinoma in 5% and for upper tract transitional cell carcinoma in 3%. RESULTS: Operating time depended mainly on the pathology of the kidney (that is small dysplastic organ versus large hydronephrosis) and the learning curve of the surgeon. However, the average operating time did not vary significantly among the different centers (maximum 277.6 and minimum 81.9 minutes). Intraoperative or perioperative complications were noted in 29 patients (6.0%), including bleeding in 22 (4.6%), bowel injury in 3, hypercarbia in 2 and pleura lesion in 1 and pulmonary embolism in 1. The conversion rate was 10.3% (bleeding, bowel injury, difficult dissection), including 4 patients with renal tuberculosis, 2 with xanthogranulomatous nephritis, and 1 each following renal trauma and embolization. The re-intervention rate was 3.4% due to bleeding in 6 cases, abscess formation in 3, intestinal stenosis in 2 and a pancreatic fistula and port hernia in 1. Mean hospital stay was 5.4 days. CONCLUSIONS: Laparoscopic nephrectomy has become a well established procedure in those urology departments focusing on laparoscopy. The indications and results are reproducible at these centers. However, for patients with severe perinephritis (that is renal tuberculosis, xanthogranulomatous nephritis, posttraumatic atrophy) a higher likelihood of open conversion must be considered.

Adolescent↗

In vitro effects and clinical evaluation of a human chorionic gonadotrophin preparation in acute leukemia.

Commercial human chorionic gonadotrophin (HCG) preparations decrease the tumorigenicity of human tumors in immunodeficient mice and induce apoptotic cell death in animal tumor models. Preliminary studies in humans have demonstrated tumor regression in patients with Kaposi's sarcoma given intralesional injections of HCG. To further evaluate HCG's antitumor activity we conducted in vitro and clinical evaluations of HCG in acute myeloid leukemia (AML). In HL-60 leukemic cell lines, a 20-40% inhibition of cell density was demonstrated by trypan blue exclusion method at low concentrations of an HCG preparation (2 x 10(-3)-2 x 10(-2)). Similar concentrations also resulted in a reduction in the proportion of cells in G2M phase of the cell cycle, as well as enhanced differentiation compared to control cells. Fifteen patients with advanced AML with marrow blast counts >30%, and five with marrow blast counts between 10 and 26% were given daily subcutaneous injections of HCG 2-4 IU and oral levamisole 50 mg weekly. Five patients with absolute blast counts in the blood ranging from 0 to 3500/microl and percent blasts in the marrow ranging from 16 to 81% were observed to have no progressive increase in either marrow or peripheral blast counts for 70-121 days. One patient with a pretreatment blast count of 10% in the marrow, no circulating blasts and minor cytopenias had a decrease in marrow blasts to less than 5% which has persisted at 550 days. No significant improvement from baseline levels of neutrophils, hemoglobin or platelets were observed in any nl the patients treated. Increases in apoptotic cell death were observed in over 50% of patients' cells with some demonstrating peak levels similar to experiences in patients treated with DNA-damaging chemotherapy. A decreased expression of bcl-2 was seen in the majority of patients ranging from 6 to 62%. These new observations suggest that HCG preparations may inhibit leukemic cell growth through enhancement of cell death mechanisms and could be used in judicious combinations with other approaches. The results confirm the pro-apoptotic effects of HCG preparations reported in patients with Kaposi's sarcoma. Identification of the active component of HCG preparations and further understanding of its growth modulatory action will be important in its development as a clinically useful agent.

Acute Disease↗