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J H Wilkens

Publications and source records attributed to J H Wilkens.

12 recordsLinked to original sources
PubMed1992

Bioassay of a tracheal smooth muscle-constricting factor released by respiratory epithelial cells.

Epithelium-derived factors of unknown identity have been proposed to modulate airway smooth muscle tone. We developed a novel sensitive bioassay system that allows serial perfusion of cultured respiratory epithelial cells and guinea pig trachea (GPT). GPT responses were assessed as diameter changes by computerized video microscopy (resolution, 15 microns). A permanent hamster lung epithelial cell line was grown on microcarrier beads and perfused in a cell column. When the outflow tubing from the epithelial cell column was connected to the inflow cannula, the detector GPT contracted, reaching 28 +/- 6% of the maximum methacholine (100 microM)-induced contraction (n = 12, P less than 0.001). Perfusion of the cell column with diclofenac (10 microM) or lysin-mono-acetylsalicylic acid (100 microM) abolished the GPT contraction, whereas selective perfusion of the detector GPT with either agent did not block the contraction. Analysis of the effluent of the epithelial cell column demonstrated a significant basal release of prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2) and 6-ketoprostaglandin F1 alpha, whereas only marginal amounts of thromboxane B2 were detected. When given exogenously, PGF2 alpha, PGE2, PGI2, and U-46619 all contracted the GPT. It is concluded that lung epithelial cells can contract GPT by releasing a transferable factor. This factor is likely to be a constrictor cyclooxygenase product that is not produced in epithelium-denuded GPT.

Animals↗
PubMed1990

Effects of a PAF-antagonist (BN 52063) on bronchoconstriction and platelet activation during exercise induced asthma.

1. The effects of a specific PAF acether antagonist (BN 52063) on the response to isocapnic hyperventilation with dry cold air (ISH study) and exercise (EIA study) were assessed in a single dose and short term treatment study in 10 patients with exercise induced asthma. 2. ISH challenge was performed twice within 1 h after administration of either placebo, 240 mg BN 52063 p.o. or inhalation of 2.4 mg BN 52063. Hyperventilation increased Raw from 0.30 +/- 0.02 to 0.89 kPa s l-1 (P less than 0.001) after the first challenge and from 0.28 +/- 0.04 to 0.84 +/- 0.06 kPa s l-1 (P less than 0.001) after the second challenge. Oral pretreatment with BN 52063 did not result in a reduction of bronchoconstriction during both challenges. A significant increase of Raw was noted immediately after inhalation of BN 52063. An inhibition of PAF induced platelet aggregation (by a factor of 2) occurred after oral administration of BN 52063 after both ISH challenges (P less than 0.05). No significant inhibition of PAF induced platelet aggregation was seen after inhalation of BN 52063. At concentrations up to 30 microM in vitro, BN 52063 inhibited PAF induced platelet aggregation in a dose dependent manner. The IC50 of BN 52063 against the aggregating effect of 1 microM PAF was 7.0 +/- 2.1 microM. 3. In the EIA study the patients were challenged on the third day of treatment with either placebo or 240 mg BN 52063 p.o. or 5 mg BN 52063 by inhalation. Peak expiratory flow rates (PEFR) fell by 155 +/- 37 1 min-1 after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

[Effect of the platelet-activating factor antagonist BN 52063 on exertional asthma].

In a randomised single-blind crossover study we assessed the effects of a specific PAF acether antagonist, BN 52063, on the early asthmatic response to exercise in six patients with exercise induced asthma. After a treatment period of two days an exercise challenge on the third day was preceded by administration of either placebo or BN 52063 240 mg p.o. 3 hours or 5 mg by inhalation 30 minutes before the challenge. After the oral intake of 240 mg BN 52063 there was no effect on the initial exercise induced bronchoconstriction, but the prolonged reduction of PEF was significantly attenuated expressed as a smaller AUC (p less than 0.02). In the placebo period there was a marked increase in plasma concentrations of both platelet factor 4 (PF4) and beta-thromboglobulin (beta-TBG). Intake of BN 52063 diminished the rise in plasma concentrations of PF4 and beta-TBG after the exercise challenge significantly. The results show that platelet activation after exercise induced asthma was markedly inhibited by BN 52063, indicating that PAF acts as a mediator in exercise induced asthma.

Administration, Inhalation↗
PubMed1990

[Effects of intravenous prostaglandin E1 on bronchial histamine reactivity].

The effects of infusion of different doses of prostaglandin E1 (12.5, 25, 50 ng kg-1 min-1) on airway responsiveness to inhaled histamine dichloride were observed in 16 subjects with normal and high bronchial reactivity. Subjects were randomized to receive PGE1 or placebo within an interval of three days. Normal saline was infused on one day and PGE1 on the other days. 10 minutes after starting the PGE1 infusion bronchial provocation was induced by histamine aerosol challenge. The provocation concentration of histaminedihydrochloride causing a 50% increase in bronchial resistance increased from 0.36 +/- 0.12 to 0.57 +/- 0.19 mg/ml in hyperreactive subjects (n.s.) and from 0.77 +/- 0.12 to 1.57 +/- 0.19 mg/ml in normal subjects (beta less than 0.05) after administration of 50 ng kg-1 min-1 PGE1 (p less than 0.05). Partial flow rates measured at maximal bronchoconstriction increased dose-dependently during the infusion of PGE1 (p less than 0.05). We conclude that intravenous administration of PGE1 partially protects against histamine-induced bronchoconstriction. In hyperreactive subjects PGE1 selectively increases flow at low lung volumes indicating an action on peripheral bronchial resistance.

Airway Resistance↗
PubMed1990

[The effect of bronchial epithelium on bronchial contractility].

Removal of the epithelium increases the sensitivity of mammalian airway smooth muscle to several bronchoactive agents. An epithelium derived relaxing factor (EpDRF) of unknown identity has been postulated to modulate smooth muscle tone in the airways. Rings or segments of porcine third order bronchi, from some of which the epithelium had been removed mechanically, were mounted in organ baths for isometric tension recording. Removal of the epithelium affected bronchial reactivity. Metacholine produced concentration-dependent contractions of porcine bronchi. In the absence of epithelium the concentration response curve was shifted to the left (p less than 0.01). The effect of epithelium removal was not inhibited by diclofenac (100 microM), propranolol (5 microM), the inhibitor of endothelium-derived relaxing factor gossypol (10 microM). These observations suggest that the epithelium of porcine bronchi relaxes the tone of the subjacent smooth muscle. The EpDRF probably responsible for this effect is neither a cyclooxygenase product nor a stimulator of soluble guanylate cyclase.

Airway Resistance↗
PubMed1990

[Measuring airway resistance with the oscillation method: Oscillaire and Custovit].

Measurement of airway resistance by the oscillation method was done on the one hand by means of the pseudo random noise method (Oszillaire, Jones Company) multifrequence from 6 to 26 Hz in steps of 2 Hz. In addition, the oscillatory resistance was also determined by means of the custo vit (Customed), the frequency of the pump producing the oscillation being variable so that measurements were carried out successively at different frequencies. 2 different versions were tested. In the first version the resonance frequency was measured and then monofrequently the pertaining resistance. In another version the impedance (total airway resistance) was measured at different frequencies in a frequency range between 6 and 20 Hz in steps of 2 Hz with both methods. Additionally, the airway resistance was also measured by bodyplethysmography. A clinical study was carried out in a group of 21 healthy subjects and 34 obstructed patients with asthma bronchiale and chronic obstructive lung disease. When measuring the airway resistance with the custo vit at the frequency of resonance there was poorer differentiation between normal and obstructed subjects compared to a measurement at a fixed frequencies yielded comparable values for both methods.

Airway Resistance↗
PubMed1989

[Oscillatory measurement of airway resistance with the custo vit in comparison with Oscillaire and whole body plethysmography].

The airway resistance was measured by forced oscillation technique with the pseudorandom noise method (Oscillaire, Jones) at multiple frequencies ranging from 6 to 26 Hz in steps of 2 Hz (Ros1). In addition, the oscillatory resistance was determined with the custo vit unit (Customed), the frequency of the pump generating the oscillation being selectable (Ros2), so that successive measurements were made at different frequencies. The custo vit is available in different technical versions. With the first version, a single frequency was used to measure the resonance frequency and to determine the associated resistance. By a different version, the impedance of various frequencies in the range between 6 and 16 Hz in steps of 2 Hz were determined for both methods. Finally, using 3 frequencies (8, 12 and 16 Hz) the total impedance was differentiated into resistance and reactance. In addition, the airway resistance was determined by bodyplethysmography. A clinical study was performed in a group of 21 healthy subjects and 34 patients with bronchial asthma and chronic obstructive lung disease. With both methods, the correlation of the resistance, determined by forced oscillation technique and Raw showed decreasing values with increasing frequency. In the case of the measurement of the airway resistance with the custo vit at resonance frequency, a poorer differentiation between normal subjects and patients with obstruction was obtained as compared with measurements made at a fixed frequency of 6 Hz. This is the result of a shift in the resonance frequency towards higher frequencies in the case of an obstruction, and the simultaneously occurring frequency-dependence of the resistance. A comparison of the impedance at different frequencies revealed comparable values with both methods, but in the case of the differentiation into resistance and reactance, it was seen that higher resonance frequencies were established with Ros1 as compared with Ros2 in the case of obstruction.

Airway Resistance↗
PubMed1987

Cardiac and microcirculatory effects of different doses of prostaglandin E1 in man.

A cumulative dose response to intravenous PGE1 was established in 12 healthy volunteers. Systolic time intervals, including pre-ejection period (PEP), the ventricular ejection time (VET) and the RR-interval, were continuously determined, and transcutaneous oxygen pressure (tcpO2) was recorded. RR-intervals fell in a dose dependent manner, reaching a significantly lower level at 128 ng.kg-1.min-1 of PGE1 (basal value 842 ms falling to 756 ms). PEP decreased from 89 ms to 74 ms and the ratio PEP/VET decreased from 35% to 30%, indicating increased myocardial contractility. The maximal increase in tcpO2 was 125% on the calf and 60% on the foot. The peak tcpO2 was observed at an infusion rate of 16 ng.kg-1.min-1 PGE1. A decline in tcpO2 was seen at infusion rates greater than 64 ng.kg-1.min-1 PGE1 indicating a decrease in skin perfusion. The results indicate that the effects of intravenous PGE1 on skin perfusion occur at a lower threshold than the increase in myocardial contractility. A maximal increase in skin perfusion can be achieved with doses of PGE1 devoid of systemic haemodynamic effects.

Adult↗
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↗
PubMed1985

Nocturnal asthma: effect of a once per evening dose of sustained release theophylline.

In a double-blind, multiple-dose, cross-over study the therapeutic effects of an S-R theophylline preparation given once each night (mean 11.2 mg/kg/day) were compared to standard treatment with an S-R aminophylline preparation every 12 h (mean 10.3 mg theophylline/kg/day) in 9 patients with nocturnal asthma. On Day 5 of each treatment period, serum theophylline concentrations and PEF were measured every 2 h over a 24 h period. With the twice-daily regimen peak theophylline concentrations were lower at night than during the day (mean 9.4 +/- 0.9 vs 11.3 +/- 1.0 mg/1). With the single administration, serum theophylline concentrations were considerably higher at night (mean C max 16.3 +/- 1.4 mg/1). In spite of the high theophylline peak to trough difference (mean 12.0 +/- 2.1 mg/1) during the once daily regimen, the circadian variations of PEF were significantly reduced. Thus, greater airways' stability can be obtained by appropriate timing of theophylline administration.

Adult↗
PubMed1984

Individualizing theophylline dosage: evaluation of a single-point maintenance dose prediction method.

A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0-21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2-53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8-25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.

Adolescent↗