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Biomedical subjects

J Staiger

Publications and source records attributed to J Staiger.

At least 19 recordsLinked to original sources

CoCoDat: a database system for organizing and selecting quantitative data on single neurons and neuronal microcircuitry.

We present a novel database system for organizing and selecting quantitative experimental data on single neurons and neuronal microcircuitry that has proven useful for reference-keeping, experimental planning and computational modelling. Building on our previous experience with large neuroscientific databases, the system takes into account the diversity and method-dependence of single cell and microcircuitry data and provides tools for entering and retrieving published data without a priori interpretation or summarizing. Data representation is based on the framework suggested by biophysical theory and enables flexible combinations of data on membrane conductances, ionic and synaptic currents, morphology, connectivity and firing patterns. Innovative tools have been implemented for data retrieval with optional relaxation of search criteria along the conceptual dimensions of brain region, cortical layer, cell type and subcellular compartment. The relaxation procedures help to overcome the traditional trade-off between exact, non-interpreted data representation in the original nomenclature and convenient data retrieval. We demonstrate the use of these tools for the construction, tuning and validation of a multicompartmental model of a layer V pyramidal cell from the rat barrel cortex. CoCoDat is freely available at . Its application is scalable from offline use by individual researchers via local laboratory networks to a federation of distributed web sites in platform-independent XML format using Axiope tools.

Action Potentials↗

Specific stimulation of peripheral blood mononuclear cells from patients with acute myocarditis by peptide-bound flavin adenine dinucleotide (FAD), a naturally occurring autologous hapten.

The tryptic FAD-peptide carrying the flavin in 8alpha-(N3)histidyl linkage as natural hapten was isolated by HPLC from the bacterial enzyme 6-hydroxy-d-nicotine oxidase. The same flavin protein linkage is found in the mitochondrial succinate dehydrogenase flavoprotein subunit, the predominant flavoprotein with covalently bound FAD in mitochondria of cardiomyocytes. Peripheral blood mononuclear cells (PBMC) were isolated from four patients with acute myocarditis, seven patients with dilated cardiomyopathy (DCM) and from four healthy control individuals. The response of PBMC to the FAD-peptide was evaluated by measuring proliferation ([3H]-dThd incorporation) and cytokine secretion [interferon (IFN)-gamma]. PBMC from all patients with acute myocarditis showed positive responses to the FAD-peptide, in contrast to PBMC from patients with DCM or control individuals. Following the recovery of the patients from the acute inflammation of the heart, PBMC no longer exhibited a proliferation response to the FAD-peptide. A chemically synthesized FAD-free peptide with identical amino acid sequence induced no response of PBMC. The results are consistent with a recall response by activated T cells, specific for the normally cryptic mitochondrial flavin-hapten, which may be liberated following cardiomyocyte destruction during the inflammation of the heart.

Acute Disease↗

Analysis of mitochondrial antigens reveals inner membrane succinate dehydrogenase flavoprotein subunit as autoantigen to antibodies in anti-M7 sera.

The role of mitochondrial proteins as antigens to antibodies of anti-M7 sera was analysed by flavin fluorescence, one- and two-dimensional Western blots and blue native gel electrophoresis. Flavin fluorescence of succinate dehydrogenase (SucDH, complex II of the respiratory chain) of rat liver inner mitochondrial membranes correlated with the immunoreactivity of a representative anti-M7 myocarditis serum. Antigens of isolated bovine heart mitochondria reacting with antibodies of myocarditis serum on two-dimensional Western blots were identified by MALDI-TOF and NanoESI mass spectrometry as myosin heavy chain beta and as dihydrolipoamide dehydrogenase of the mitochondrial 2-oxoacid dehydrogenase complexes. The SucDH-flavoprotein was not resolved as a discrete protein spot on two-dimensional polyacrylamide gels. However, separation of the rat liver inner mitochondrial membrane complexes by blue native gel electrophoresis followed by Western blotting, and Western blots of purified Escherichia coli SucDH complex revealed that anti-M7 sera contained antibodies directed against the SucDH-flavoprotein subunit.

Animals↗

Effectiveness of digitoxin versus trichlormethiazide/amiloride in congestive heart failure NYHA class II/III and sinus rhythm.

The effects of digitoxin and/or diuretic agents were investigated in patients with congestive heart failure (CHF) in sinus rhythm with respect to changes in hemodynamic parameters, cardiac dimensions, and bicycle ergometric exercise capacity. In a randomized, double-blind study 16 male patients with CHF NYHA class II and III received a placebo for 1 week (baseline) and then were randomly allocated, double blind, to take either digitoxin (digitalis group, DI: N = 8) or trichlormethiazide/amiloride (diuretic group, DG: N = 8) for 3 weeks (VP I). The patients who were first treated with digitoxin received the diuretic agent for a further 3 weeks and vice versa (VP II). At baseline and after VP I and II, a physical examination, two-dimensional echocardiography, and bicycle ergometry were performed. Heart rate (HR), systolic (BPs), and diastolic (BPd) blood pressure at rest, and BPs and 50 watts, were not significantly changed during the observation period. HR at 50 watts was decreased in DI (11.5 +/- 10.1 beats/min.) after VP I and II, but not in DG. BPd was significantly reduced after VP II in DI (8.2 +/- 4.6 mmHg) and in DG (9.3 +/- 8.9 mmHg). DI presents at baseline significantly higher end-diastolic (LVEDV) and end-systolic (LVESV) left ventricular dimensions, whereas left atrial diameter (LA) and stroke volume (SV) and ejection fraction (LVEF) were not significantly different. After VP I, a significantly decreased LA was found in DI, but not in DG. After VP II, all cardiac dimensions were significantly reduced compared with the baseline in DI, whereas in DG only a decrease in LVESV was found. SV was significantly increased in DI, but not in DG after VP I, SV and LVEF were significantly improved in DI and in DG after VP II. Exercise capacity did not change significantly in DI and DG. Digitoxin in combination with trichlormethiazide/amiloride is effective in reducing primarily enlarged left atrial and left ventricular dimensions, and is sufficient to improve the impaired systolic left ventricular function in CHF of NYHA class II and III in sinus rhythm. However, a significant increase in exercise capacity was not found. Treatment with digitoxin seems to be more relevant as a monotherapy with trichlormethiazide/amiloride.

Aged↗

The long-term involution of physiological cardiomegaly and cardiac hypertrophy.

The long-term involution of physiological cardiomegaly and cardiac hypertrophy. Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 244-249, 1989. Forty-five former athletes in endurance disciplines, primarily Olympic medalists and World Cup, European Cup, and German champions, for whom results of an exercise ECG and radiological heart volume measurement were available from their active competitive phase, were examined. The study protocol included clinical examination, laboratory controls, resting and exercise ECG, determination of cardiac volume, and one- and two-dimensional echocardiographic examination. Of the 45 former athletes contacted, 38 appeared for examination. Of these, four presented with heart disease (two with infarction, one with aortic stenosis, and one with arrhythmia). The remaining 34 were divided into groups of still active (more than 300 kcal.wk-1) and inactive (less than 300 kcal.wk-1) athletes. The interval between the first and second examination averaged 23 yr. The active former athletes showed a weight increase of 5.2% (P less than 0.01) and a reduction of 14% in ergometric performance (P less than 0.02). The inactive group had a marked weight increase of 17.4% (P less than 0.001); the ergometric performance was lowered by 20% (P less than 0.001). The absolute heart size had decreased in the active group by 6.1% (NS) and the relative heart size by 10.7% (P less than 0.005); the corresponding values in the inactive group were 4.5% (NS) and 18% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Influence of symptom-limited stress on blood lactate behaviour in coronary heart disease (CHD) patients.

In order to document the possible influence of stress limiting factors (STLF: chest pain, ST-segment depression) on exercise-induced blood lactate increase in CHD patients (post myocardial infarction) 88 males were examined in a stepwise bicycle stress test. Blood lactate samples were drawn at the end of each stress step. The patients were divided into 2 groups without (n = 45) and with (n = 43) STLF, higher blood lactate concentrations, however, were only observed in relation to the exercise intensity reached at the end of the stress test. Neither the symptom chest pain nor the degree of ST-depression showed a significant influence on the physical performance capacity and the lactate concentration at the anaerobic threshold. Nevertheless, a physical performance capacity above 1 W/kg seems to be necessary to reach the anaerobic threshold level. When the lactate measurement is used in CHD patients, the influence of age on the maximum lactate concentrations must be considered.

Aged↗

[Echocardiographic contractility reserve and invasive hemodynamics in physical stress in probands with healthy hearts and patients with dilated cardiomyopathy].

In the present study, 17 patients with angiographically proven dilative cardiomyopathy (CM) were investigated simultaneously by both invasive right heart catheter and 1D/2D echocardiography at rest (R) and during bicycle exercise (E) stress test. They were compared with 14 normal subjects (N). The echocardiographic contractility reserve was determined as an increase in the systolic pump function (shortening fraction-SF, ejection fraction - EF) and compared with pulmonary capillary wedge pressure during exercise. 14/17 echocardiograms of dilative cardiomyopathy and all echocardiograms of normal subjects at rest as well as during exercise could be accepted. In N, echocardiographic parameters of systolic function significantly increased during exercise, whereas dilative cardiomyopathy showed decreased contractility reserve with no increase in pump function (for CM patients, at rest SF: 21.3% +/- 8%; EF: 41.6% +/- 14%; exercise SF: 21.3 +/- 9%; EF: 40.7% +/- 15%). Hemodynamic investigation in CM showed no increase in stroke volume accompanied by a pathologic increase in pulmonary wedge pressure, ranging from x = 16.4 mmHg at rest, up to 30.0 mm Hg in exercise (p less than 0.001), whereas in normal subjects, no pathologic increase in pressure was present (from 10.3 mm Hg at rest to 13.7 mm Hg during exercise). There were closed relations between invasive and non-invasive data. The relative alteration of stroke volume during E showed in N and in CM good correlation with echocardiography (N + 19%, CM -2%) and invasive data (N + 18%, CM + 2%). FSe during stress and PCPm showed a closed inverse correlation during exercise (p less than 0.001; r = 0.8). The lower the contractility in echocardiogram, the higher PCPm was in exercise.

Cardiac Output↗

Two-dimensional echocardiographic measurements of left ventricular volume and stroke volume of endurance-trained athletes and untrained subjects.

The left ventricular volume (EDV), the left ventricular total volume (TDV), and the stroke volume (SV) of 40 male untrained subjects and 68 endurance athletes were determined using one-dimensional echocardiography, two-dimensional echocardiography, and a combined method. The accuracy of the volume and stroke volume measurements was checked by comparing them to ergometrically determined maximum oxygen pulse (max O2-P) and to radiographic heart volume (HV). There was clear improvement in the EDV, TDV, and SV measurements when using two-dimensional echocardiography and the combined method in comparison to one-dimensional echocardiography. The best correlation to the max-O2-P was reached by TDV2 (combined method, r = 0.8738). This method includes the myocardium of the left ventricle similar to heart volume measurements. The relationship is as close as between HV and max O2-P (r = 0.8665). The method suggested here is sufficiently accurate to be used in performance diagnosis to determine the size of the left ventricular volume and to classify pathological size changes or those due to training.

Adolescent↗

[Ventricle function in low-dose digitoxin in patients with chronic heart failure (stage II/III)].

Using one- and two-dimensional echocardiographic parameters, left ventricular function and dimensions were investigated in 11 patients with chronic heart failure (NYHA stages II-III) and in 10 normal subjects after administration of low-dose digitoxin (0.07 mg). Tests were performed before the begin of therapy, on the 3rd day following rapid saturation, and on the 15th day under maintenance therapy. There was no significant decrease either of heart volume as assessed by X-ray or of enddiastolic volume measured echocardiographically. However--predominantly in patients--a marked decrease in endsystolic diameter (p less than 0.01) and an increase in posterior wall motion amplitude (p less than 0.05) was observed resulting in increased stroke volume, shortening fraction (p less than 0.001). Early diastolic left ventricular filling speed also increased significantly in both groups (p less than 0.01). Changes in these parameters were more pronounced in patients than in normal subjects. In both groups the effects were achieved soon after rapid saturation, increasing slightly during the period of chronic administration of low-dose digitoxin. Parallel to the changes in echocardiographic parameters, a noticeable clinical improvement occurred among patients. No side effects were observed as serum digitoxin levels were in the therapeutic range. It may be concluded that low-dose digitoxin can be employed to increase cardiac contractility in patients with heart failure.

Adult↗

[Echocardiographic septal motion in 50 patients with coronary artery disease. A correlative study with coronary angiographic findings (author's transl)].

The literature about pathological septal motion in coronary artery disease is contradictory. Purpose of this study was to reveal the sensitivity and specificity of the echocardiography for diagnosis of stenoses and occlusions (S/O) of the left anterior descending artery (LAD). 50 patients with CAD were studied using coronary angiography and echocardiography. In 32 of the cases a critical stenosis (over 70% narrowing) of the LAD was present. History of old infarction was found in 80% of the patients. Angina pectoris was absent at the time of the investigation. It was proven that the sensitivity of the echocardiography for the diagnosis of coronary stenoses and for proximal and peripheral LAD-S/O is not high (44%-61%). 50 percent of all LAD-S/O and 61% of the proximal LAD-S/O have a pathological septal movement. In presence of a pathological septal motion, however, it may be concluded that there is a critical stenosis in one or more of the three main coronary arteries (predictive value 91%). The diagnosis of the localization of the occlusion by echocardiography is not possible. 1/3 of peripheral LAD-S/O also lead to a dyscinetic septum which mostly is found in proximal LAD-S/O. The number of false positive (pathological) echocardiographic septal dyscinetic motion is low (12%). The sensitivity of echocardiographic method for diagnose of coronary alteration is increased when using the differentiation between stenosis and occlusion of LAD. By that it can be revealed that full occlusions of the LAD lead in 80% to septal dyscinetic motion, whereas stenoses are only rarely combined with pathological septum (36%). It is concluded that not only the localization but predominantly the degree of the vessel-narrowing influences the septal movement. Perhaps these findings may help to declare the contradictory results in literature.

Adult↗

[Percutaneous transluminal dilatation of the subclavian artery (author's transl)].

Percutaneous transluminal balloon-catheter dilatation successfully removed the stenosis in three out of four patients with obstruction of a subclavian artery. The arm oscillogram became normal and after an average of four months later the three patients remain without symptoms. The method is particularly suitable, as an alternative to operative intervention, if the stenosis is in the proximal part of the subclavian artery.

Aged↗

Postmortem angiographic and pathologic-anatomic findings in coronary heart disease: a comparative study using planimetry.

Comparisons of the results of angiographic and pathologic-anatomic estimations of the degree of coronary artery stenosis are rare and the findings contradictory. In the present study, postmortem examinations were carried out on 26 hearts with coronary artery disease. Quantitative planimetric measurements of 203 coronary artery cross-sections were performed and compared with the results of postmortem coronary angiograms. Using a score rating scale, a highly significant difference (P < 0.001) between the angiographic and morphologic findings was detected, with the degree of stenosis and underestimated angiographically in 96 of the 203 sections (47%), overestimated in 18 (9%), and correctly estimated in 89 (44%). The tendency to underestimation was equal in all of the coronary arteries (left anterior descending, circumflex, and right coronary arteries); there were no statistically significant differences (P < 0.20, P < 0.30, P < 0.10). The frequency of angiographic underestimation of the degree of morphologic stenosis--especially in critical stenoses of more than 60%)--has important implications in the assessment of whether coronary artery surgery is warranted.

Coronary Angiography↗