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Biomedical subjects

H Wilkens

Publications and source records attributed to H Wilkens.

At least 55 records · Page 3Linked to original sources

[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↗

[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↗

[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↗

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↗

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↗