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Biomedical subjects

A Wilke

Publications and source records attributed to A Wilke.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Alcohol and myocarditis].

The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic findings in endomyocardial biopsy in about 30% of all cases was myocarditis with a lymphocytic infiltrate in association with myocyte degeneration or focal necrosis. In myocarditis, the network of microtubules and intermediate filaments is also disrupted by the inflammatory reaction which involves resident cells (myocytes, fibroblasts, endothel cells) and systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. After all, in patients with alcohol abuse and myocarditis the immune functioning appears to be compromised. Several studies suggest that heavy drinking alters both lymphocyte and granulocyte production and function. Alcohol consumption per se might harm the immune system. Furthermore, the myocardial damage due to alcohol consumption could initiate autoreactive mechanisms comparable to those in viral or idiopathic myocarditis. Patients with alcohol abuse and myocarditis have a poor prognosis: signs of biventricular failure including tachycardia, hepatomegaly, and peripheral and lung edema are observed. These symptoms are as nonspecific as are various echocardiographic and electrocardiographic changes such as atrial and ventricular arrhythmias which may be associated both with myocarditis, alcoholic cardiomyopathy and acute effects of drinking without hemodynamic alterations. For the management of patients with alcohol abuse the prevention of further alcohol intake is mandatory to reverse the myocardial damage and the unfavorable predisposition for infection. Specific treatment of myocarditis is the second important option, and treatment of heart failure by reducing the size of the dilated heart and alleviating the signs and symptoms of heart failure is a logical third step.

Acetaldehyde↗
PubMed1995

[Cardiac structure-function relationship and the renin-angiotensin-aldosterone system in hypertensive heart disease].

Based on the epidemiologic data of the Framingham heart study, arterial hypertension and coronary artery disease are the most frequent etiologic factors for the development of heart failure. In the pressure overloaded heart, hypertrophic growth of the myocardium includes the enlargement of cardiac myocytes stimulated by ventricular loading. Non-myocyte cell growth involving cardiac fibroblasts may also occur but is not primarily regulated by the hemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium while vascular smooth muscle cell growth accounts for the medial thickening of resistance vessels. This remodeling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness and impaired coronary vasodilator reserve, leading to ventricular diastolic and systolic dysfunction and ultimately to the appearance of symptomatic heart failure. Several lines of evidence suggest that the renin-angiotensin-aldosterone system is involved in regulating the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In rats with genetic hypertension, established left ventricular hypertrophy, abnormal diastolic stiffness due to interstitial fibrosis, and reduced coronary vasodilator reserve associated with medial wall thickening of intramyocardial resistance vessels, the ACE inhibitor lisinopril was able to restore myocardial structure and function to normal. These cardioreparative properties of ACE inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.

Animals↗
PubMed1995

[The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction].

The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoantibodies↗
PubMed1994

Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures.

In an experimental study with 18 minipigs, we have tried to establish a model for the standardized evaluation of mechanical, histological and radiological phenomena of degenerative and reparative processes within the lumbar motion segment. Comparing different operative techniques revealed that the intradiscal application of hyaluronic acid into the nuclear defect is likely to enhance the regeneration process. Using the measurement of disc compliance, a semiautomatic picture analyzer and a new semiquantitative disc score could make future studies more comparable. From this basis, the intradiscal application of hyaluronic acid deserves further evaluation.

Animals↗
PubMed1993

Near ultraviolet light inactivation of dihydroxyacid dehydratase in Escherichia coli.

The effects of near ultraviolet (NUV) light on a NUV chromophore-containing oxidant-sensitive enzyme, dihydroxyacid dehydratase (DHAD), were measured in seven strains of Escherichia coli. The strains differed in production of the oxidant-defense enzymes, superoxide dismutases (Fe-SOD and Mn-SOD), and catalases HPI and HPII. With the stress of aerobic growth but without NUV exposure, the strains lacking either Fe or Mn SOD or both SODs had 57%, 25%, and 12%, respectively, of the DHAD-specific activity of the parent (K12) strain. Under the same conditions, the catalase strains that were wild type, overproducing, and deficient had comparable DHAD-specific activities. When aerobic cultures were exposed for 30 min to NUV with a fluence of 216 J/m2/s at 310-400 nm, the percentage decreases in DHAD-specific activities were similar (ranging from 75% to 89%) in strains with none, either, or both SODs missing, and in the catalase-overproducing strain. However, the decreases were only 58% and 52% in the strain with catalase missing and in its parent, respectively. The NUV-induced loss of DHAD enzyme activity was not accompanied by any detectable loss of the DHAD protein as measured by polyclonal antibody to DHAD.

Catalase↗
PubMed1993

[Evaluation of the biocompatibility of implant materials with human bone marrow cell cultures].

A cell culture biocompatibility test for implant materials is described. For the first time, the human bone marrow cells that actually come into direct contact with the implanted biomaterial can be employed. The usefulness of this method is shown for materials which have long been used in the clinical situation (hydroxyapatite, commercially pure titanium and ultra-high molecular weight polyethylene). After two weeks in culture, light- and fluorescence-microscopic and SEM studies revealed significant differences in cell growth. Maximum compatibility was shown by the hydroxyapatite specimen. In the case of commercially pure titanium we found somewhat decreased biocompatibility. Polyethylene was associated with distinct signs of cytotoxicity. These results are compatible with those of animal experiments and clinical experience. Our system would thus appear to be a useful screening test for some implantation materials, and may help reduce the need for animal tests.

Biocompatible Materials↗
PubMed1993

Human neutrophil elastase increases permeability of cultured pulmonary endothelial cell monolayers.

Polymorphonuclear leukocytes (PMN) contribute to increased pulmonary vascular permeability in inflammatory lung injury, but the mechanism of their action is complex. In the present study we examined possible effects of PMN-derived proteases on the permeability of pulmonary endothelial cell monolayers grown on polycarbonate filter membranes and exposed continuously to a hydrostatic pressure of 10 cm H2O. Cell- and serum free PMN-supernatants (human PMN, stimulated with 30 ng/ml phorbol-myristate acetate for 30 min, presence of catalase, were centrifuged, the supernatants were passed through a 0.45 micron filter) dose-dependently (calculated PMN: endothelial cell ratio of 2:1 and more) increased hydraulic conductivity of endothelial cell monolayers ten- to twentyfold within 20-70 min. At the same time the dextran reflection coefficient decreased from 0.8 to 0.1. Phase contrast and scanning electronmicroscopy showed a widening of intercellular gaps. The effects of the postsecretory PMN-supernatant were blocked dose-dependently by inhibitors of human neutrophil elastase (HNE) but not of cathepsin G. On quantitative grounds highly purified HNE was similarly active as postsecretory PMN supernatant. The effects of HNE were inhibited by pretreatment with eglin-c or heat, but not with heparin. The data suggest that HNE is an effective and sufficient neutrophil-derived mediator to increase endothelial permeability. HNE appears to act primarily enzymatically and not as a cationic protein.

Amino Acid Sequence↗
PubMed1992

Bioavailability of metronidazole formulations (Vagimid).

The bioavailability of metronidazole (0.5 g) from Vagimid tablets and dragées were compared with tablets of a reference formulation in 12 male healthy volunteers (age 20-32 years, body weight 61-77 kg). Metronidazole and its two main oxidized metabolites in serum were determined quantitatively with an hplc method. Metronidazole from Vagimid tablets was absorbed more rapidly than from the reference but at the same extent of absorption. The pharmacokinetic profile of Vagimid dragées was similar to the behaviour of the reference but AUC of dragées was slightly but significantly lower. All elimination parameters of metronidazole as well as the formation of the two metabolites were not different after administration of the oral formulations.

Adult↗
PubMed1992

[Use of multi-frequency oscillation method in the respiratory mechanics perimeter diagnosis].

Oscillatory resistance Rrs and reactance Xrs curves were measured in the frequency range 4-25 Hz at FRC-level and at the course of vital capacity manoeuvres. The 55 subjects investigated were separated into the three groups healthy subjects and patients with restrictive and obstructive lung diseases by means of the parameters airway resistance Raw and lung compliance CL estimated by body-plethysmography and esophageal pressure technique, respectively. In accordance with the Raw- and CL-values in each group the parameters Rrs and Xrs demonstrate at FRC-level a different frequency dependent behaviour. An enhancement of Raw in patients with COLD causes a drop of Rrs(f) and a displacement of the whole Xrs-curve into the negative direction. Conversely, the reduction of CL in patients with fibrosis leads to a significant decrease of Xrs-values at lower frequencies without marked changes in the Rrs-curves. An additional enhancement of Raw and a further reduction of CL can be induced by decrease and increase of lung volume VL in comparison with the FRC-level. These alterations can be detected also in the frequency dependent shape of the Rrs- and Xrs-curves. Because of this inverse influence of VL on Raw and CL the diagnostic differentiation between patients with mild obstructive and restrictive lung diseases can be improved by a simultaneous evaluation of the volume and frequency dependence of oscillatory parameters.

Airway Resistance↗
PubMed1992

Screening of pulmonary hypertension in chronic obstructive pulmonary disease and silicosis by discriminant functions.

The aim of our prospective multicentric study was to develop a screening method for pulmonary hypertension in patients with chronic lung diseases. We investigated 710 patients in 10 hospitals: 315 males and 109 females with chronic obstructive pulmonary disease, and 286 males with silicosis. Manifest pulmonary hypertension was defined as pulmonary artery pressure greater than 20 mmHg (2.7 kPa) at rest. The multivariate statistical method used was a stepwise discriminant analysis. In males with chronic obstructive pulmonary disease, the diameter of the right descending pulmonary artery, forced expiratory volume in one second (FEV1) arterial oxygen tension (PaO2) at rest, and age turned out to be relevant for discrimination of groups with and without manifest pulmonary hypertension. For females the FEV1/FVC (forced vital capacity) ratio replaced the absolute value of FEV1 in the calculated discriminant function. In females, sensitivity and specificity were below 80%. In males, both were distinctly above 80%. In silicosis, the diameter of the right descending pulmonary artery was much less important, since it could frequently not be measured precisely. In these cases, precision of the prediction of about 80% could only be obtained by combined evaluation of spirometry, PaO2 during exercise, and body plethysmography. The calculated discriminant functions are appropriate for screening patients with risk of pulmonary hypertension. For different chronic lung diseases, and for both sexes, different combinations of parameters are relevant. The method is recommended to select patients who should undergo an invasive examination of pulmonary haemodynamics.

Discriminant Analysis↗
PubMed1991

Bone marrow obtained during hip surgery: a novel source for studies of hemopoiesis in human long-term bone marrow culture (LTBMC).

Studies with human bone marrow cells are often impaired by the poor quality of sternal aspirates due to varying numbers of contaminating blood cells before enrichment procedures and insufficient progenitor cell yields. In this study we report on experiments performed with human bone marrow cells isolated from a) spongiose bone fragments collected during hip surgery in patients with osteoarthritis or b) sternal aspirates. After Ficoll-Histopaque density gradient centrifugation absolute cell numbers were always lower in the samples obtained from sternal aspirates. However, both sources proved to yield the same proportions of the respective myeloid cell populations. Human long-term bone marrow cultures (LTBMC), semi-solid agar assays (CFU-GM day 14), and 3H-thymidine incorporation assays proved the comparability of the two bone marrow sources.

Adult↗
PubMed1991

Pharmacokinetics of almitrine in healthy volunteers and patients with essential hypertension.

Pharmacokinetic studies with the arterial chemoreceptor stimulant almitrine (100 mg per os) were performed in 12 healthy volunteers and 8 patients with essential hypertension stage I in order to evaluate the suitability of the drug for physiological tests. The parent compound was determined gas-chromatographically. Almitrine was absorbed with maximal serum levels after 1.8 +/- 0.4 h in healthy volunteers and 1.5 +/- 0.3 h in patients. The elimination proceeded biexponentially with terminal half-lives from 14.6 to 43.4 h in volunteers and 12.5-45.0 h in patients. Further characteristics were large distribution volumes (16.1 +/- 4.5 ml/g in healthy volunteers, 13.9 +/- 4.7 ml/g in patients) and large interindividual variations of all pharmacokinetic parameters by a factor of 2 to 6. Significant differences between healthy individuals and patients were not observed. The drug was well tolerated. The pharmacokinetic properties of almitrine should be included into its evaluation as a test compound.

Administration, Oral↗
PubMed1991

[Inspiratory phase angle behavior in oscilloresistometry].

Oscillatory measurement of resistance can get more practical relevance including the phase angle (PSI) and the volume dependence. Different findings during deep inspiration in patients with pulmonary emphysema (PSI unchanged) and with pulmonary fibrosis (PSI-Negativation) are known. To explain these findings transpulmonary pressure (Ptp) was measured parallel to PSI in 85 subjects. PSI-negativation was found in 31 of 43 patients with pulmonary fibrosis and in 10 of 19 healthy subjects. Patients with pulmonary emphysema have nearly constant or slight positive phase angles. Subjects with negativation of phase angle have significantly higher Ptp-levels at 100% TLC. This high pressure is reached by an in comparison to volume overproportional increase of pressure in the end part of the lung expansion curve. It is proposed to estimate the PSI-V-dependence in ranges from middle level of breathing to 75% of vital capacity VC and from 75% to 100% VC separately. By this modification the qualitative noninvasive assessment of lung compliance could be more efficient. Several findings indicate, that the observed secondary periodic of PSI are dependent from heart rhythm and therefore from intrathoracic blood volume.

Adult↗
PubMed1990

Role of actin and myosin in the control of paracellular permeability in pig, rat and human vascular endothelium.

1. We have investigated the endothelial actomyosin system with particular emphasis on its possible role in actively opening a paracellular route for permeability. 2. Actin and myosin comprised 16% of total endothelial protein with a molar actin/myosin ratio of 16.2 which is close to the actin/myosin ratio of muscle (studies on freshly isolated pig pulmonary arterial endothelial cells, PAEC). 3. By immunocytochemistry at the light and electron microscope levels the bulk of actin and myosin was colocalized in close vicinity to the intercellular clefts of both micro- and macrovascular endothelial cells in situ and in vitro. 4. Calcium-ionophore-induced rise in permeability of human umbilical venous endothelial cells (HUVEC) and PAEC monolayers grown on filters in a two-chamber permeability system was caused by opening of intercellular gaps. Gap formation depended on the rise in intracellular Ca2+ and could be blocked by the calmodulin-binding drugs trifluperazine (TFP) and W7. 5. In skinned monolayers of cultured PAEC and in isolated sheets of HUVEC gap formation was shown to require ATP and occurred only when free myosin binding sites were available on endothelial actin filaments (experiments with myosin subfragment 1 modified by N-ethylmaleimide, S1-NEM). 6. These experiments suggest that actin and myosin in endothelial cells play a central role in regulating the width of the intercellular clefts, thereby controlling the paracellular pathway of vascular permeability.

Actins↗
PubMed1990

Attitudes toward autopsy refusal by young adults.

A survey of 158 18- to 24-yr. old college and 119 noncollege adults indicated that the latter were more reluctant to approve autopsies for spouses, children and distant relatives. Nonstudents also expressed more objections to autopsies than did students.

Adolescent↗
PubMed1990

N-acetylation and debrisoquine type oxidation polymorphism in Caucasians--with reference to age and sex.

Phenotypes of the N-acetylation and debrisoquine type oxidation polymorphism were determined with sulfamethazine and debrisoquine in 145 healthy volunteers (31-80 years, 64 males, 81 females) of a North-East German area. Seventeen (11.7%) were poor metabolizers of debrisoquine and 81 (55.9%) slow acetylators of sulfamethazine. No significant correlations between the frequencies of oxidation and acetylation phenotypes, age, and sex were found. Only a tendency of rapid acetylators to accumulate among individuals above 60 years was noticed. Parameters of phenotyping were not influenced by sex. With age, metabolic ratios of N-acetylation but not of oxidation phenotyping increased. The urinary excretion (0-8 hours) of debrisoquine, sulfamethazine and their metabolites was strikingly reduced in the elderly. Misclassifications of acetylation phenotyping cannot be excluded because of the age dependent kinetics of the test drug.

Acetylation↗
PubMed1990

Oxidation phenotyping with debrisoquine in Germany (East).

An hplc method is described which determines debrisoquine and its metabolite, 4-hydroxydebrisoquine, quantitatively after conversion of the guanidine moieties into the corresponding pyrimidines. Sensitivity, precision, and accuracy have been sufficient enough for the reliable hydroxylation phenotyping of 145 non-related healthy volunteers (64 males, 81 females, 31-80 years). 17 (11%) were poor metabolizers of debrisoquine (gene frequency: 34.2%).

Adult↗