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Biomedical subjects

B G Simonsson

Publications and source records attributed to B G Simonsson.

At least 19 recordsLinked to original sources

Capsaicin-induced cough in humans.

We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.

Administration, Inhalation

Bronchial reactivity in patients with recent pulmonary sarcoidosis.

Non-specific bronchial reactivity was assessed in 17 consecutive non-smoking and non-steroid treated patients with recently diagnosed pulmonary sarcoidosis, 11 with stage I disease and six with stage II disease. Bronchial reactivity was measured by recording the FEV1 after increasing doses of methacholine. Three subjects with asthma were hyperreactive. The 14 subjects with no asthma had a mean FEV1 of 96% predicted. Only one was hyperreactive, with a fall in FEV1 of over 15% after 0.1% methacholine. The median provocative concentration causing a 15% fall in FEV1 did not differ from that in a normal population studied previously. It is concluded that sarcoidosis seldom induces airway hyperreactivity within one year of diagnosis in patients with normal spirometric values.

Adult

Acute and long-term airway hyperreactivity in aluminium-salt exposed workers with nocturnal asthma.

Nineteen young male workers exposed occupationally from 1975-1977 to inhaled particles of aluminium fluoride or sulphate at 2 plants, developed nocturnal wheezing and breathlessness with reversible airways obstruction after an average of 4 months employment. At standardized methacholine provocation tests (MPT), 17 of 19 workers with normal spirometry showed airway hyperreactivity with a fall of FEV1 of greater than or equal to 15% after 0.1% methacholine. We followed 15 initially asthmatic workers for 2-5 years with MPT. Mean TD 15% FEV1 in 11 workers did not change significantly after an average of 41 months of non-exposure. Six workers continuously exposed for 48 months also failed to change their TD 15% FEV1 MCh. In 1983, only one subject had returned to normal airway reactivity. We have no reason to suspect inducing agents other than aluminium salts.

Adult

Aryl hydrocarbon hydroxylase induction levels in patients with malignant tumors associated with smoking.

The levels of aryl hydrocarbon hydroxylase (AHH) inducibility were assessed in 173 patients with cancers statistically associated with smoking, i.e., squamous cell and transitional cell carcinomas, at various sites. In 34 patients with carcinomas of the oral cavity, 41 patients with laryngeal carcinomas, and 22 patients with pulmonary carcinomas there was a highly significant overrepresentation of high inducers, whereas 30 patients with carcinomas of the renal pelvis and ureter and 46 patients with urinary bladder carcinomas did not differ significantly in this respect from a control population comprising 92 subjects with no history of neoplastic disease. The results add further support to the concept of AHH as a major activator of carcinogens belonging to the group of polycyclic aromatic hydrocarbons (PAH) when these affect the oral cavity and/or the respiratory tract. The role of AHH in urothelial carcinogenesis seems to be less explicit.

Adult

Non-specific bronchial hyperreactivity: correlation to asthma and modifying factors.

Bronchial hyperreactivity can be induced and modified by allergic and non-allergic factors affecting the airways. Bronchospasm can also be induced by small amounts of many of these agents and by other factors as well. Allergic and non-allergic subjects can be affected. Bronchial obstruction in asthma due to allergic reactions is to a large extent dependent on the degree of nonspecific bronchial reactivity. This can be influenced by different modes of treatment.

Airway Resistance

Propagation of a poorly differentiated human pulmonary adenocarcinoma in nude athymic rats.

Nude athymic rats of Rowett genetic background were injected subcutaneously with cells from a poorly differentiated human pulmonary adenocarcinoma, following propagation in nude mice. The tumour cells were obtained by thoracentesis and by pleural biopsy during thoracoscopy. So far, we have heterotransplanted 13 different malignant human tumours including malignant mesothelioma, pulmonary adenocarcinoma, malignant melanoma and malignant lymphoma. Subcutaneous tumour growth was seen in all inoculated animals, with an exponential tumour growth pattern and with tumour volume doubling times of approximately 8 days. After two initial passages in nude athymic mice of BALB/c genetic background, the human tumour so far has undergone 9 passages in athymic rats, i.e. collection of tumour material by biopsy from the preceding tumour-bearing rat generation, processing and inoculation of tumour brei with subsequent tumour growth have been repeated 8 times. Four-to-8-week-old rats of both sexes were used throughout and tumour growth was controlled by palpation twice a week. Routine histopathological sections were prepared from the tumour at various passages to assess similarity to the original tumour in the patient. The growth pattern of the xenografts remained similar at all passages just as the remarkable similarity of the heterotransplanted tumours to the original adenocarcinoma was retained at all passages. No spontaneous regressions of heterotransplanted tumours could be demonstrated. Electron microscopical analysis revealed numerous blunt microvilli and lumina partly filled with conglomerates of mucigen granules and small glycocalyceal bodies associated with external superficial microvilli. Scantiness of dark secretory granules together with free and membrane-bound polyribosomes were seen in the cytoplasm. We believe that the nude athymic rat is a valuable research tool and that the permanently transplantable human tumour reported here could be of value in delineating further the mechanisms for tumour take, growth and control.

Adenocarcinoma

Lung function and bronchial reactivity in six patients with immotile cilia syndrome.

Previous studies of immotile cilia syndrome have shown airway obstruction. The aim of this study was to analyse lung function in such patients before severe chronic obstruction had occurred. Spirometry, lung volumes, pulmonary resistance and static pressure volume diagram were studied in six patients (ages 21-43 years). Closing capacity, the volume of trapped gas and the slope of the alveolar plateau were determined with N2 wash-out tests. Regional ventilation was studied with a gamma camera after inhalation of 99Tcm-tagged dry aerosol. Arterial blood gases were determined at rest and during exercise. Bronchial reactivity was studied with FEV1 before and after inhalation of methacholine aerosol. Five of six patients showed a rather uniform pattern, dominated by signs of "small airway disease" seen in e.g. volumes of trapped gas and closing capacity. Those five patients had uneven ventilation scintiscans and bronchial hyperreactivity. Spirometric findings and lung mechanics were influenced by lung resection, scoliosis and by the lability of bronchial tone. Five patients had normal arterial blood gases at maximum work load. Working capacity was essentially normal in all but one patient, who had a high degree of obstruction. Immotile cilia syndrome is thus compatible with a comparatively well preserved lung function and a normal working capacity far into adult life.

Adult

Does atropine block antigen-induced contraction in canine bronchial rings? A preliminary report.

Isometric contractions recorded with a strain gauge, were elicited with cumulative doses of ascaris suum antigen on fresh canine bronchial rings from 8 dogs. Fifteen rings from 2 spontaneously sensitized dogs reacted with contractions to the antigen, while 11 rings from other dogs did not react. Seven sensitized rings were re-challenged after atropine, which significantly prevented the antigen from contracting these rings at a time when antigen contracted 3 non-atropinized, simultaneously tested rings from the same bronchi. Acetylcholine may play a part in the smooth-muscle contraction induced by antigen, or atropine may inhibit early activation of the "arachidonic acid cascade". The findings may be of interest in the interpretation of anti-muscarinic drugs as inhibitors of reflex cholinergic activity versus local anti-allergic effect.

Animals

Bronchial reactivity, smoking, and alpha1-antitrypsin. A population-based study of middle-aged men.

We assessed bronchial reactivity to increasing doses of inhaled methacholine (MCH) in a population-based study on alpha1-antitrypsin. We compared 34 consecutive 48- to 50-yr-old heterozygous (Pi-MZ) men with 31 men of the same age with normal Pi phenotype (Pi-M) matched for smoking habits. There was no significant difference between control FEV1 or in MCH reactivity between the Pi-MZ and the Pi-M group. Twelve Pi-MZ subjects and 11 Pi-M subjects showed a fall of greater than or equal to 15% of FEV1 (PC 15%). Smokers showed increased sensitivity to MCH in both phenotype groups, although there was no significant difference in control FEV1 between the smoking and nonsmoking groups. Eleven smokers and ex-smokers, 5 with histories of asthma or sputum production, showed bronchial hyperreactivity, i.e., PC 15% FEV1, to 0.1% MCH or lower concentrations. Among nonsmokers there was 1 reactor and 1 hyperreactor. We conclude that heterozygous alpha1-antitrypsin deficiency (Pi-MZ) does not increase bronchial reactivity and that smoking does.

Bronchi