Biomedical subjects
Publications and source records attributed to G Joos.
26 months after the onset of alcohol-induced pain, a diagnosis of primary pulmonary Hodgkin's (PPHD) disease could be made in a 34-year-old woman. Standard radiology of the thorax remains normal up to 18 months after the onset of symptoms. A short review of the literature concerning PPHD is given.
Explore the source record for details and available documents.
Tracheobronchomegaly (TBM) is a rare disorder of uncertain aetiology, characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent lower respiratory tract infections. Two patients with TBM are presented. In one case, a marked decrease of elastic and smooth muscle tissue was present in the bronchial biopsy specimens, obtained by rigid bronchoscopy. The airways of the second patient were visualized using computed tomography. The dimensions of the airways of our patients are compared with the normal values supplied in the literature.
Asthma is characterized by the presence of airway inflammation and an increased responsiveness to many different stimuli. The hyperresponsiveness to indirect stimuli such as adenosine, bradykinin, neuropeptides, sulphur dioxide suggest that the hyperresponsiveness in asthma results from the complex interaction between inflammatory cells, neurons and smooth muscle cells. Several mechanisms may be involved in the influence of airway inflammation on airway responsiveness: increased mucosa permeability: enhanced exposure of irritant receptors, modulation of airway smooth muscle behavior by inflammatory mediators, mucosal edema, enhanced release of neurotransmitters, increased local reflex activity, decreased breakdown of neurotransmitters, etc. We have investigated the interaction between airway inflammation and responsiveness in two animal models: acute exposure to endotoxin and chronic exposure to aerosolized antigen. Both models demonstrate the complexity of interaction between inflammatory processes and demonstrate positive controlling mechanisms that inhibit the increase in airway responsiveness due to airway inflammation. The lack of such controlling mechanisms may be involved in the development of the asthmatic airway hyperresponsiveness.
Neuropeptides and purines are possible autonomic neurotransmitters. Both tachykinins (neurokinin A, substance P) and adenosine cause acute airway narrowing by synergistic activation of airway mast cells and postganglionic vagal nerve endings.
Purines and neuropeptides may act as neurotransmitters of the local axon reflex in the airways. Nedocromil sodium has been shown to inhibit adenosine- and neurokinin A-induced bronchoconstriction both in the rat and in man. In this study we used the rat model for further investigation of the mechanism of action of nedocromil sodium in the adenosine- and neurokinin A-challenge. The animals were challenged intravenously, and immediately after maximal bronchoconstriction a bronchoalveolar lavage was performed and histamine was assayed in the supernatant of the lavage fluid. Nedocromil sodium significantly inhibited the adenosine- and the neurokinin A-induced increase in histamine concentration in the lavage fluid. Nedocromil sodium had no influence on the airway responsiveness to serotonin or carbachol. We therefore concluded that the inhibitory effect of nedocromil sodium on adenosine- and neurokinin A-induced bronchoconstriction can be explained by its activity on airway mast cells.
In some animal species substance P and neurokinin A (NKA) cause bronchoconstriction by the release of acetylcholine from postganglionic cholinergic nerve endings. The aim of the present study was to investigate the effect of an anticholinergic drug, oxitropium bromide, on bronchoprovocation with NKA in asthmatics. Eleven mild asthmatics (mean % predicted FEV1 85.5) received on 2 separate days, double blind, in a randomised order, 400 mcg oxitropium bromide or placebo, 90 min before challenge with NKA. NKA was inhaled at 3 concentrations (10(-4), 3.10(-4) and 10(-3) M). Specific airways conductance (sGaw) and forced expiratory volume in 1 s (FEV1) were used as parameters of airway calibre. Compared to the placebo-aerosol, oxitropium bromide caused a significant increase in sGaw and FEV1. On the placebo-treatment day, NKA caused a concentration-dependent decrease in sGaw and FEV1. The percentage changes in sGaw and FEV1 on the oxitropium day were not statistically different from those occurring on the placebo day. We conclude that oxitropium bromide caused a significant bronchodilation but offered no significant protection against NKA-induced bronchoconstriction in mild asthmatic subjects.
Explore the source record for details and available documents.
The neuropeptides substance P and neurokinin A are present in sensory airway nerves. Their effect on airway calibre was compared in six healthy non-smoking subjects and six asthmatic subjects. On separate days increasing concentrations (from 10(-9) to 10(-6) mol/ml) of each neuropeptide were administered by nebuliser and the airway response measured as change in specific airway conductance (sGaw). Substance P and neurokinin A caused no change in sGaw in the healthy subjects. Inhalation of substance P up to the highest concentration of 10(-6) mol/ml caused no change in sGaw in the asthmatic subjects. Neurokinin A, however, caused bronchoconstriction with a mean fall in sGaw of 48% (SEM 12%) after 5 x 10(-7) mol/ml. The onset of bronchoconstriction was rapid, but sGaw had returned to baseline values within one hour in all but one patient.
We studied the bronchial effects of intravenously administered tachykinins in inbred rats. Substance P and related tachykinins caused a dose-dependent bronchoconstriction. The bronchial reactivity to substance P differed significantly between different inbred rat strains. Substance K, eledoisin and kassinin were more potent than substance P in causing bronchoconstriction. This suggests a predominance in the bronchi of SP-E receptors. The bronchial effects of substance P and eledoisin were largely inhibited by atropine and slightly enhanced by hexamethonium. In addition to a direct effect on airway smooth muscle, tachykinins interfere with the cholinergic airway innervation of the rat at the ganglionic and postganglionic level.
Several peptides have been localised to pulmonary nerves and endocrine cells. The neuropeptides vasoactive intestinal polypeptide (VIP) and substance P have potent effects on the airway smooth muscle, bronchial glands and blood vessels. There is increasing evidence that VIP and substance P are neurotransmitters of the non-adrenergic, non-cholinergic nervous (NANC) system. Non-adrenergic inhibitory nerves are the predominant inhibitory nervous system of the human airways. The presence of VIP in the innervation of the airways and the demonstration that it can mimick the effect of NANC nerve stimulation supports the hypothesis that it could be a mediator of the NANC system in the lungs. Sensory nerve fibers containing substance P can contribute to the smooth muscle contraction and mucosal oedema seen in asthma, by local axon reflexes that are initiated by noxious stimuli, such as for example cigarette smoke. A rat model for study of the bronchial reaction to substance P and related tachykinins, is described. In addition to a direct effect on airway smooth muscle, a large part of the broncho-constrictory actions of tachykinins in the rat is mediated by interaction with cholinergic nerves.
Neuropeptides and purines are possible neurotransmitters of the nonadrenergic noncholinergic nervous system of the airways. We investigated possible synergistic mechanisms between these two bronchoconstricting agents in a rat model. We observed that both adenosine and tachykinins enhance histamine release in the airways and that adenosine and neurokinin A act synergistically both on airway narrowing and histamine release.