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Biomedical subjects

A Wilke

Publications and source records attributed to A Wilke.

At least 19 recordsLinked to original sources
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↗
PubMed1990

[Lung function diagnosis using multi-frequency oscillometry with reference to lung volume].

The ranking of various oscillometry parameters was to be tested in patients with a broad spectrum of disturbances of pulmonary function, objectified by body plethysmographic and technical oesophageal pressure measurement of the respiratory resistance, lung volumes and lung elasticity. For this purpose the oscillatory resistance Rfo and the phase angle phi were measured at 8, 12 and 16Hz and phi was measured as it changed, depending on the lung volume V. It was found that enhanced respiratory resistance values are satisfactorily represented by Rfo for the purposes of preliminary and basic diagnostics. Besides, enhanced Rfo values are markedly dependent on the frequency, phi being shifted to negative values. Difference between Rfo values at 8 and 16 Hz (delta R8-16) less than 0.7 hPa/l/s phi greater than or equal to -10 degrees can be considered as being still normal with the employed measuring principle and are a valuable supplement for assessing the degree of obstruction. The difference between phi in the medium respiratory position and at 90 or 100% total capacity (delta phi) is less than 5 degrees during slow inspiration in 80% of the patients suffering from emphysema. In 80% of the persons with healthy lungs and those suffering from fibrosis there is an inspiratory negativation of phi (delta phi greater than 5 degrees) so that the phi-V relationship appear suitable for distinguishing patients with restricted vital capacity in respect of emphysema and fibrosis. Patients suffering fron fibrosis differ from healthy subjects by slightly more negative phi values. The borderline values for delta R8-16, phi and delta phi were confirmed in two further series of examinations on children and adolescents.

Adult↗
PubMed1990

[Ergo-oxytensiometry--recommendations on methodology and evaluation].

The purpose of this review is to provide recommendations for measurement and interpretation of ergooxymetry relevant to performance in out-patient departments. Ergooxymetry is the most suitable method for assessment of physical work capacity. The examination demands a distinct indication and knowledge of contraindications. On the basis of a standardized 3-step loading (VO2 = 1,050 ml/min, VO2 = 1,350 ml/min, VO2 = 1,650 ml/min; incremental loading without breaks; 6 min for each loading step) criteria for interpretation are given for PaO2, heart rate, arterial blood pressure and FEV1 respectively ROS.

Adult↗
PubMed1989

Role of Ca2+ and Mg2+ for endothelial permeability of water and albumin in vitro.

The permeability of endothelial monolayers grown on a polycarbonate filter membrane and continuously exposed to a hydrostatic pressure of 10 cm H2O was studied. The ionophores A23187 and ionomycin dose dependently (0.1-10 microM) enhanced the hydraulic conductivity of sealed endothelial cell monolayers 10 to 15-fold, at the same time the reflection coefficient of albumin dropped from 0.75 to 0.2. The effects of A23187 were dependent on extracellular Ca2+. In the absence of Ca2+, however, Mg2+ could substitute for Ca2+. Phase contrast- and scanning electron-microscopy showed that the A23187-induced effects were accompanied by gap-formation in the intercellular clefts. These gaps probably are the sites which allowed enhanced fluid exchange. Ionophore-induced effects on permeability could be modified by antagonists of calmodulin function and of arachidonate liberation and metabolism. The data suggest that alterations of endothelial Ca2+-homeostasis induce metabolic events which result in an increased permeability of an endothelial monolayer.

Albumins↗
PubMed1989

[Theoretical and experimental studies of the diagnostic relevance and comparability of mechanical oscillation parameters].

The practical application of the forced oscillation technique for the analysis of the mechanics of respiration is hampered by the fact that the measured frequency-dependent impedance values R(f) and X(f) cannot be related directly to the parameters airway resistance Raw and pulmonary compliance CL. Furthermore, various derived oscillatory parameters are employed which are not directly comparable even with one another. In order to be able to estimate the diagnostic relevance and comparability of the impedance curves R(f) and X(f), their form-specific characteristics R = R(5)-R(20) and X(5), as also the equipment-specific parameters Ros (Siregnost FD5) and Rfo (custo vit), the relationships of these oscillatory parameters to Raw and CL were simulated in a structural model of the respiratory system, and tested in the real system. It was shown that already from frequencies of f greater than 10Hz upwards, R(f) no longer reacts to an increase in resistance in the peripheral region of the lung, and at 20 Hz indicates only the upper airway component of a global obstruction demonstrated body-plethysmographically with Raw. The diagnostic information on peripheral airway obstruction is contained in both components R(f) and X(f) of the respiratory impedance; with increasing obstruction and increasing frequency, it progressively reverts to the X(f) curve. Therefore, by including X(f) in the resistance evaluation for the parameters Ros and Rfo, the underevaluation of R(f) as compared with Raw can in part be compensated for, although an overe stimation at low Raw values with Ros and a large scatter of the Rfo values in the case of large Raw figures has to be accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1989

[Practical experiences with 2 oscillatory measuring procedures, Siregnost FD 5 and custo vit, in the assessment of chronic airway obstruction].

In patients with chronic obstructive airway disease, comparative examinations using body plethysmography were performed with a view to evaluating the effectiveness of two forced oscillation techniques, fixed-frequency and poly-frequency techniques in estimating disorders of respiration mechanics. At slight and moderate elevations in bronchial flow resistance, a better agreement was found between the custo vit resistance figure and body plethysmography. A differentiation of healthy subjects from patients with low-grade obstruction by means of the FD 5, requires the establishment of the phase angle (phi), too, while in the case of the custo vit unit, this is possible by demonstrating the frequency dependence of the impedance. Patients with more severe disease with secondary emphysematous changes, reveal a clear difference between the phase signal (psi) primarily measured on the FD 5, and the phase angle. Forced oscillation usefully supplements spirometery in the respiratory basic diagnostic work-up employed through-out treatment. Fixed-frequency techniques require the determination of the phase angle for assessment of peripheral obstructions; the advantage of the poly-frequency technique can be seen in the largely specific demonstration of the frequency dependency of the resistance.

Airway Resistance↗
PubMed1989

[Oscillometric differentiation of lung fibrosis and lung emphysema].

In three groups of healthy subjects and patients with pulmonary fibrosis or pulmonary emphysema, the secondary periodical oscillatory phenomena observed under conditions of normal breathing and a slow VC manoeuvre on the Siregnost FD 5 were broken down into a volume- and a flow-synchronous component, as also a third component with no correlation with either volume or flow, and which can be observed in the primary parameters Ros and psi, as also the secondary parameters Rre and phi. While both fibrotic patients and healthy subjects revealed a volume-inverse phase behaviour, patients with pulmonary emphysema revealed a volume-proportional phase behaviour. This difference in volume dependence is explained by the difference in elastic recoil in patients with fibrosis as compared with those suffering from emphysema, and the associated different influence on the filling of the lungs with air and blood.

Adult↗
PubMed1989

[Report of a trial of polyfrequent oscillo-resistometry with the custo vit equipment].

With the aim of determining the significance of the principle of the multi-frequency forced oscillation technique employed by the custo vit to determine the airway resistance, measurements were performed on a number of test subjects, employing a unit available with three different software modifications. A comparison with the resistance values obtained with other equipment (whole-body plethysmograph, Siregnost FD5), revealed the diagnostic usefulness of the technique of frequency-dependent resistance. It was also confirmed that the phase angles, also obtainable with the custo vit, play a considerable role in the significant differentiation of the degree of obstruction. The differences in comparison with other methods are critically examined, and proposals made for a further improvement of the forced oscillation technique employed by the custo vit.

Airway Resistance↗