Search PubMed⌕ Search

Biomedical subjects

G W Sybrecht

Publications and source records attributed to G W Sybrecht.

At least 91 records · Page 5Linked to original sources
PubMed1989

[3H]WEB 2086 labels platelet activating factor receptors in guinea pig and human lung.

The radiolabelled platelet activating factor (PAF) receptor antagonist, [3H]WEB 2086, bound to specific sites on membrane fractions from homogenised guinea pig and human lungs. The sites on guinea pig and human membranes bound [3H]WEB 2086 with dissociation constants (KD) of 16.8 and 22.6 nM and binding capacities (Bmax) of 203 and 157 fmol/mg protein, respectively. In both species, binding was displaced competitively by PAF, suggesting that the sites labelled by [3H]WEB 2086 are PAF receptors.

Animals↗
PubMed1989

[Treatment of nocturnal bronchial asthma].

To date, the pathogenesis of nocturnal bronchiale asthma has not been completely clarified. For the treatment of nocturnal asthma that fails to respond to beta-2-sympathomimetics or inhalative glucocorticosteroids, theophylline in a delayed release form or delayed-release oral beta-2-sympathomimetics are available. In a double-blind crossover study, 10 patients with nocturnal or early-morning bronchial asthma were treated for one week with theophylline 390-900 mg daily (1/3 of the total dose being given in the morning, 2/3 in the evening) and one week with terbutaline 15 mg daily (7.5 mg in the morning and 7.5 mg in the evening). No significant differences were observed with respect to the measured peak flow values in the night and early morning. However, those receiving terbutaline more frequently required the additional application of inhalative beta-2-sympathomimetics for respiratory distress. Thus, the sustained-release form of theophylline is the more suitable drug for the treatment of nocturnal bronchial asthma. As a further study revealed, the sole administration of a sustained-release form of theophylline in the evening suffices. In the future, apart from theophylline in a delayed-release form, inhalative beta-2-sympathomimetics with a long-term effect will play an important role in the treatment of nocturnal breathing disorders.

Adolescent↗
PubMed1988

Radioligand binding of antagonists of platelet-activating factor to intact human platelets.

Two new antagonists of platelet-activating factor (PAF), the pyrrolothiazole derivative 52770 RP and the triazolodiazepine WEB 2086, have been studied as radioligands in intact human platelets. [3H]52770 RP and [3H]WEB 2086 bound specifically to high-affinity sites with dissociation constants (Kd) of 14.8 and 6.1 nM, respectively. The maximal number of sites for [3H]52770 RP binding was approx. 15-fold higher than for [3H]PAF and [3H]WEB 2086. In addition, C16-PAF, lyso-PAF, WEB 2086 and 52770 RP had Ki values which were nearly identical for both [3H]PAF and [3H]WEB 2086, whereas only 52770 RP competed for [3H]52770 RP-binding sites. These results demonstrate that in human platelets the sites of [3H]WEB 2086 binding are identical to [3H]PAF-binding sites, whereas those of [3H]52770 RP are not. [3H]WEB 2086 appears, therefore, to be a suitable antagonist radioligand for labelling PAF receptors.

Azepines↗
PubMed1988

Use of aminoglycosides in critically ill patients: individualization of dosage using Bayesian statistics and pharmacokinetic principles.

Dosage prediction methods for optimization of aminoglycoside therapy were evaluated in 19 critically ill patients. Two different three-point methods and a novel Bayesian method were used. The predictive accuracy and precision of all tested methods were clinically satisfactory. The time needed for the necessary calculations was 10-15 min. After administration of predicted dosages, approximately 90% of the observed peak and trough aminoglycoside serum concentrations fell within the therapeutic range. Without systematic use of these prediction methods, only approximately 40% of tobramycin peak serum concentrations and 80% of trough serum concentrations were within the therapeutic range. Daily dosage adjustments particularly in patients with rapid changes of aminoglycoside clearance are greatly facilitated by use of these prediction methods. These findings suggest that all of the dosage prediction methods tested are well suited for optimization of aminoglycoside dosage regimens.

Adolescent↗
PubMed1988

Evaluation of a novel Bayesian method for individualizing theophylline dosage.

A novel Bayesian drug dosing program (Abbott Pharmacokinetic Systems, Theophylline Program) was evaluated. The predictive accuracy of this method was assessed in 10 healthy volunteers receiving single intravenous test doses. Estimates for clearance and distribution volume were compared with those obtained from the area under the curve. The observed prediction error depended largely on sampling time. The deviations were lowest for the distribution volume during the first 60 min and for clearance at 12 hours after theophylline administration. Furthermore the Bayesian technique was prospectively evaluated in 10 hospitalized and 22 outpatients treated with sustained-release theophylline preparations (Uniphyllin, Bronchoretard, PulmiDur). Predictive precision and accuracy were adequate, if theophylline was given twice daily. The highest predictive accuracy was achieved in outpatients, if predictions were based on trough concentrations. In 19/22 outpatients prediction errors were within a clinically acceptable range (mean prediction error +/- standard deviation; -0.6 +/- 2.1 mg/l). Moreover in hospitalized patients (n = 5) with twice-daily maintenance regimens, concentration-time curves could mainly be predicted with sufficient accuracy. Hospitalized patients (n = 5) with once-daily dosing showed large fluctuations between peak and trough theophylline concentrations in serum. In these patients a reliable prediction of the concentration-time curves was not possible apparently due to non-linearity of theophylline kinetics. Relatively large prediction errors were found in one patient with acute viral respiratory illness and 3 patients with altered absorption. Despite certain limitations the clinical application of the Bayesian forecasting method tested appears to be promising.

Adult↗
PubMed1988

Nocturnal asthma: slow-release terbutaline versus slow-release theophylline therapy.

In a double-blind cross-over study, the effects of slow release (S-R) terbutaline tablets (b.i.d. 0.25 mg/kg per day) and S-R theophylline (5.31 mg/kg morning and 10.62 mg/kg evening) were compared in eleven patients with nocturnal asthma. On day seven of each treatment period, drug serum concentrations and peak expiratory flow (PEF) were measured every 2h over a 24-h period. During daytime, terbutaline concentrations ranged from 1.6-14.1 (median 4.5) microgram/l and during the night from 2.1-18.7 (median 4.9) micron/l. Theophylline concentrations ranged from 3.9-24.3 (median 11.5) mg/l during the day and from 3.3-20.9 (median 10.4) mg/l at night. Nocturnal wheezing occurred during theophylline treatment in four patients 7 times and during terbutaline treatment in six patients 22 times. Daytime PEF values were 472 +/- 161 l/min during theophylline therapy versus 445 +/- 169 l/min during terbutaline therapy (p less than 0.05). In the night and early morning there was no significant difference between PEF values with the two treatment forms. During theophylline treatment, fewer inhalations of beta 2-sympathomimetics were used, and there were fewer side effects. One patient experienced severe asthmatic attacks during the terbutaline treatment period. The patients preferred theophylline for the treatment of nocturnal asthma.

Adult↗
PubMed1987

A three-year prospective study of systemic manifestation in rheumatoid arthritis.

Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are responsible for the extra-articular features (EAF). In the present study, we investigated firstly whether the presence of blood vessel changes in one organ--namely the skin--may indicate blood vessel pathology and, consequently, EAF in other organs. Secondly, we investigated the number of EAF in individual patients with RA, and observed whether this changed during the course of the disease. Fifty-one RA-patients (40 female, 11 male; ages had a mean of 49.5, minimum 19, maximum 73 years; mean duration of RA was 7.3, minimum 0.25, maximum 41 years) were included in the study. Punch biopsies from the posterior calf were examined immunohistologically for vessel wall immune deposits. Further, EAF were determined by means of instrumental clinical methods such as pulmonary function test, echocardiography, electromyography, and nerve conduction velocity measurement. At the first investigation 21/51 patients had skin vessel wall immune deposits (SVWID). Five patients--all showed SVWID at first investigation--died during the three-year investigation period, 10 patients could not be followed-up for unknown reasons; the skin biopsy of one patient could not be assessed. At the final investigation, we found SVWID in 11/35 patients. SVWID-positive patients had more EAF compared to SVWID-negative patients; this was true both, at the first investigation (1.85 EAF/patient vs 1.05 EAF/patient) and at the final investigation (1.91 EAF/patient vs 0.67 EAF/patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Disorders of respiration in patients before and after liver transplantation].

In 61 patients with chronic hepatic insufficiency parameters of regulation of ventilation, mechanics of breathing and gas exchange were determined pre and in 16 patients post liver transplantation. Preoperatively disturbances of control with increased central respiratory drive resulting in chronic hyperventilation and maladaptation of perfusion to ventilation were found. Successful liver transplantation resulted in regression of these disturbances to different degrees. We therefore conclude that disturbances of respiration in patients with chronic hepatic insufficiency are reversible after successful liver transplantation.

Airway Resistance↗
PubMed1987

The importance of skin vessel wall immune deposits in the course of the systemic and articular features of rheumatoid arthritis. A prospective study.

Fifty-one rheumatoid arthritis patients were examined prospectively during a 3-year investigation period by means of immunohistological, histological, and instrumental clinical methods. Skin vessel wall immune deposits (SVWID) were found in 21/51 patients at the first and in 11/35 patients at the concluding investigation. Patients with SVWID showed more extra-articular features, more rapid progress of joint damage, higher mortality frequency, higher inflammatory activity, and higher levels of circulating immune complexes, compared with patients without SVWID.

Arthritis, Rheumatoid↗
PubMed1987

Treatment of nocturnal asthma: the role of sustained-release theophylline and oral beta-2-mimetics.

In two double-blind, multiple-dose cross-over studies the therapeutic effects of SR theophylline preparations given once each night (mean 11.2 mg/kg per day) versus twice daily in equal doses (mean 10.3 mg/kg per day) (study I) and SR-terbutaline in equal doses (mean 0.25 mg/kg per day) versus SR theophylline in unequally divided daily doses (mean 5.3 mg/kg morning dose, 10.6 mg/kg evening dose) study II) were compared in 19 patients with nocturnal asthma. At the end of each treatment period drug serum concentrations and PEFR were measured every 2 hr over a 24-hr period. With the twice-daily, equally divided regimen, serum theophylline concentrations were lower at night than during the day (mean 9.4 +/- 0.9 versus 11.3 +/- 1.0 mg/l). With the single evening administration, serum theophylline concentrations were considerably higher at night (Cmax 16.3 +/- 1.4 mg/l) and the circadian variation of PEFR was significantly reduced. PEFR was higher during night and early morning (283 +/- 14 versus 217 +/- 11 l/min, P less than 0.005). During daytime in study II, PEFR values were slightly higher with theophylline than terbutaline. There was no significant difference in peak flow between either treatment during the night and early morning. However, additional use of inhaled beta-2-mimetics because of asthmatic attacks occurred more often during terbutaline (79 times in 8/10 patients) than theophylline treatment (29 times in 5/10 patients). Symptom scores, number of attacks and side-effects clearly favor the theophylline regimen. We conclude that for patients with nocturnal asthma a once-nightly dose of SR theophylline can be sufficient for stabilization of the airways.

Adult↗
PubMed1986

Enprofylline: pharmacokinetics and comparison with theophylline of acute effects on bronchial reactivity in normal subjects.

In a double blind, placebo controlled, crossover study the pharmacokinetics and acute effects of enprofylline and theophylline on airway reactivity during histamine challenge were investigated in 10 healthy volunteers. The pharmacokinetic parameters of enprofylline were (mean): elimination half-life 1.9 h, total body clearance 191.1 ml X kg-1. h-1, volume of distribution 0.481 X kg-1, and protein binding 49%. Bronchial reactivity in the histamine inhalation test was expressed as the concentration causing a 20% fall in FEV1.0 (PC20). Mean PC20 values were lowest after placebo and highest after theophylline with the enprofylline values in between. Only the difference in PC20S after placebo and theophylline was statistically significant (p less than 0.05). At the time of determination of the PC20, the serum concentration of enprofylline was between 16.5 and 11.8 mumol/l, and that of theophylline was between 78.3 and 61.1 mumol/l. Adverse actions of enprofylline were nausea (3/10) and cardiovascular reactions (2/10), whereas theophylline mainly caused restlessness (3/10) and tremor (2/10). Thus enprofylline, in one-fifth of the serum concentration of theophylline cannot be regarded as equipotent in terms of bronchoprotection.

Adult↗