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Biomedical subjects

C Bevan

Publications and source records attributed to C Bevan.

At least 37 records · Page 2Linked to original sources

A study of Spanish sepiolite workers.

BACKGROUND: Sepiolite is an absorbent clay that is used as pet litter. It forms thin crystals, which are a transition between chain and layered silicates. Inhalation studies in animals have shown no evidence of pulmonary damage. This paper reports a cross sectional study of the total work force of the largest sepiolite production plant in the world. METHODS: Two hundred and eighteen workers (210 men and eight women) were studied. Height, age, and smoking history were recorded. Chest radiographs were read according to the International Labour Office (ILO) classification by two readers. Readings were used to construct a numerical score, which was then used in statistical analyses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were divided by the square of the height. Casella size selective personal samplers were used in randomly selected operatives to collect dust eight years before the rest of the study was carried out. These samples were evaluated gravimetrically. Total dust samples were examined by optical and electron microscopes. Results were analysed by bivariate linear regression, chi 2 tests, and analysis of variance. RESULTS: When allowance was made for smoking habit workers exposed to dry dust showed a significantly greater decline in FEV1 with age than workers with little exposure to dry dust. A similar pattern applied to FVC. Radiographic score showed deterioration with age but no clear differences from other variables. High concentrations of dust were found in the bagging department and also in the classifier shed. CONCLUSIONS: The major finding was that lung function deteriorated more rapidly in those who had had more exposure to dust, but there was no evidence of any accompanying radiographic change.

Adult↗

Contamination of bronchoscopes with Mycobacterium tuberculosis.

Difficulties with disinfection of endoscopes and reports of cross-contamination of bronchoscopy specimens have previously been described. A recent episode of mycobacterial cross-contamination of bronchoscopy specimens was identified in a tertiary care referral centre. Two of eight bronchoscope suction valves cultured positive for Mycobacterium tuberculosis and the cause of the outbreak was traced to a faulty wash/disinfect switch in an automatic washer. The situation was resolved following autoclaving of all suction valves and repair of the endoscope washer. This report highlights the problems with instrument design and supports previous recommendations to autoclave suction valves routinely after each use.

Bronchoscopes↗

An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

Abnormalities, Drug-Induced↗

Sensory irritation response in mice to sulfur dust.

The potential of sulfur dust to produce sensory irritation was evaluated in mice. Male Swiss--Webster mice were exposed by head-only inhalation to 106, 263, or 451 mg/m3 sulfur dust aerosol at room temperature. Breathing frequency and patterns were monitored before, during, and after exposure to evaluate the animal's sensory irritation response to the test atmosphere. Group average breathing rates were decreased 7 and 17% below pretest values in mice exposed to 106 and 263 mg/m3, respectively; however, breathing patterns appeared normal, indicating that there was no sensory irritation. Mice exposed to 451 mg/m3 showed an increase in breathing frequency of 7%, with 1/4 mice displaying very slight signs of pulmonary (deep lung) irritation. Some of the mice in the low- and high-dose groups exhibited signs of slight eye irritation immediately after exposure, but all mice were normal 1 day later. On the basis of these findings, exposure to sulfur dust up to 451 mg/m3 did not produce any sensory or upper airway irritation in mice.

Aerosols↗

Role of Ca2+ in sorbitol release from rat inner medullary collecting duct (IMCD) cells under hypoosmotic stress.

The role of Ca2+ was studied in the release of the organic osmolyte sorbitol from rat IMCD cells in response to hypoosmotic stress. When cells were exposed to hypoosmotic media, sorbitol release was greatly reduced in Ca-free media which, on readmission of Ca2+, returned to control values. Under isoosmotic conditions, the ionophore A23187 stimulated sorbitol release without any effect on cell volume. Addition of trifluoperazine, a calmodulin inhibitor, but not the protein kinase C inhibitor H-7, inhibited the osmotically-activated sorbitol release. These results suggest that sorbitol release is a calmodulin-dependent event, possibly activated by a rise in intracellular calcium as a result of cell swelling.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Choline transport in collecting duct cells isolated from the rat renal inner medulla.

Glycerophosphorylcholine (GPC) plays an important role in the osmoregulation of the renal inner medulla. Under hyperosmotic conditions, a striking increase in cellular GPC content is observed. In order to characterize the cellular events involved in GPC metabolism, we have studied the uptake of choline, a precursor of GPC, by freshly isolated rat inner medullary collecting duct (IMCD) cells at 300 mosmol/l. Choline uptake occurred by a single transport system with an apparent affinity (Km) of 80 microM and a maximal velocity (Vmax) of 120 pmol/microliter cell water/min. Hemicholinium-3, ethanolamine and N,N-dimethylethanolamine were potent inhibitors, but betaine had no effect. Choline uptake was not altered by the replacement of Na+ with N-methylglucamine+, suggesting a sodium-independent process. Addition of 50 mM KCl to the incubation medium to reduce the cell membrane potential inhibited choline uptake by 19 +/- 4% after 10 min. Increasing the extracellular osmolarity to 600 or 900 mosmol/l had no effect on the kinetic parameters of choline uptake. These results suggest that choline uptake into IMCD cells occurs by a sodium-independent transport system driven by the inside negative cell membrane potential. Furthermore, the increase in the GPC content under hyperosmotic conditions is not associated with increased activity of the transport systems of biosynthetic precursors.

Animals↗

Cadmium inhibition of L-alanine transport into renal brush border membrane vesicles isolated from the winter flounder (Pseudopleuronectes americanus).

Using isolated brush border membrane vesicles from the kidney of the winter flounder (Pseudopleuronectes americanus), we have studied the effect of cadmium on L-alanine transport. Pretreatment of vesicles with 0.1 mM Cd2+ resulted in inhibition of L-alanine uptake in the presence of a NaCl (but not KCl) gradient. Inhibition was due to a specific interaction with the sodium-alanine cotransport system and not a change in the driving forces for alanine transport, since Cd2+ did not affect sodium-dependent D-glucose uptake. The effect of Cd2+ on Na+-alanine cotransport showed mixed-type inhibition which is only partially reversible by EDTA. Cd2+ uptake itself was shown to be time and temperature dependent, resulting in binding to both sides of the membrane. No direct correlation was possible between inhibition of L-alanine transport and the amount of Cd2+ taken up by the membranes. Nevertheless, the striking time dependence of the effect of Cd2+ on sodium-dependent L-alanine uptake and the inability of EDTA to reverse the inhibitory action of Cd2+ suggest that Cd2+ inhibits Na+-alanine cotransport at the cytoplasmic side of the membrane.

Alanine↗

Interaction of cadmium with brush border membrane vesicles from the rat small intestine.

Cd2+ uptake by brush border membrane vesicles isolated from rat small intestine was investigated by a rapid filtration technique. Cd2+ uptake showed time- and temperature-dependence. Changes in medium osmolarity had no effect on Cd2+ uptake, indicating that the process involves primarily binding of Cd2+ to membrane component(s). Membrane-impermeable chelating agents removed only about 60-65% of the bound cadmium from intact vesicles preincubated with Cd; almost all Cd was removed by chelators when membrane permeability was increased by 1-butanol. Thus Cd uptake by membrane vesicles results in binding to both sides of the membrane. Pretreatment of vesicles with cadmium resulted in a time-dependent inhibition of D-glucose uptake in the presence of a sodium (but no potassium) gradient. This inhibition is correlated with Cd binding to external sites on the D-glucose transporter, and not the driving force for D-glucose transport.

Animals↗

A study of evening primrose seed oil in atopic asthma.

It has shown recently that Evening Primrose Oil (Efamol) produces a significant clinical improvement in atopic eczema. Efamol contains gamma-linolenic acid which is a precursor to PGE1 a more consistent bronchodilator than PGE2. We have conducted a double blind placebo controlled study in atopic asthmatics given Efamol for an eight week period looking at the control of asthma, including histamine challenge tests. We have found no effect on the asthma or challenge tests although Efamol produced an alteration in fatty acid profile. The patients showed an abnormal fatty acid profile. We speculate that such fatty acid abnormalities could be important in the aetiology of asthma.

Adult↗

A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells.

Lactate production and ion fluxes were measured in isolated rat papillary collecting duct cells (PCD) to gain further insight into the transport properties of the papillary collecting duct. Lactate production was found to be inhibited by bumetanide in a dose-dependent manner, a maximum inhibition of 22% was obtained at 10(-4) M bumetanide and an apparent Ki of 10(-8) M was determined. Bumetanide inhibition of lactate production was dependent on the presence of sodium and chloride. Chloride removal inhibited lactate production also by 20%. Bumetanide (10(-4) M) inhibited by 35% sodium uptake into PCD cells exposed to 10 mM ouabain and chloride uptake into ion depleted PCD cells by 40%. In addition, this bumetanide-sensitive chloride uptake was dependent on the presence of sodium and potassium in the incubation medium. Furthermore, 86Rb uptake into these cells was significantly reduced in the presence of 10(-4) M bumetanide. These data provide evidence for the operation of a Na-K-Cl cotransport system in rat papillary collecting duct cells. This transport system might be involved in active chloride transport in the papillary collecting duct and/or volume regulation of the PCD cells.

Animals↗

The effect of cigarette withdrawal on asthmatics who smoke.

Fourteen asthmatics volunteered to stop smoking. Seven managed to stop for only 24 h and seven for 1 week. There was a significant increase in peak flow and specific airways conductance as early as the first 24 h of abstention, while after 7 days of abstention there was a further increase in peak flow and specific airways conductance and a reduction in bronchial responsiveness to histamine. Two subjects felt that their symptoms were worse while abstaining and one of these showed an increase in bronchial responsiveness. After abstention for 1 week, four of the seven subjects recorded an improvement in symptoms. Asthmatics who smoke should be encouraged to stop. Despite an improvement in symptoms and objective measurements, asthmatics may find it difficult to stop smoking and will need considerable help and encouragement if they are to succeed.

Adult↗

Mortality of slate workers in north Wales.

In a study in 1975 of the mortality experienced over six years by two groups of men one group had been exposed to slate dust and the other had had no previous exposure to dust. In non-smokers there was no material excess mortality associated with past exposure to dust but in smokers there was a pronounced (26%) excess. In the slate workers the risk for smokers was on average 76% greater than for non-smokers, and increased with severity of pneumoconiosis; in those who had not been exposed to dust the risk was 50% greater for smokers than non-smokers. In ex-smokers among those who had been exposed to slate dust the risk of death was higher in those with the lower lung function initially. No such association was detected in the other groups.

Adolescent↗

Respiratory disability in ex-cotton workers.

A high proportion of textile workers handling cotton and flax complain of respiratory symptoms and show a loss in lung function. These effects are reversible in the early stages but the degree to which they lead to permanent respiratory disability is unknown. Two surveys were therefore conducted in which respiratory function and symptoms were compared in ex-textile workers and in control subjects who had never been exposed to textile dusts. One survey was of ex-flax workers in Northern Ireland. The present survey was of ex-cotton workers in Lancashire. A survey of random population samples in Oldham and Bolton, in both of which cotton had formerly been the most important source of employment, was conducted. After allowing for age, height, and smoking, lung function was about 2-8% lower in the ex-textile workers than in controls who had never been exposed to any dust. Ex-textile workers were slightly shorter than the controls, suggestive of past social and nutritional deprivation which may have contributed to the decrement in lung function. There was evidence of a small but increasing decrement in lung function with an increase in a "dust exposure" score. For men, about 15 years of heavy dust exposure was associated with a loss in FEV1 equivalent to that shown by light or ex-smokers. For women, 15 years of heavy dust exposure appeared to be associated with a decrement in FEV1 about half that of light smoking.

Adult↗

Role of airway receptors in the breathing pattern of patients with chronic obstructive lung disease.

To determine whether airway receptors are responsible for the rapid, shallow breathing pattern seen in hypercapnic chronic obstructive lung disease, 10 patients underwent upper airway anaesthesia with inhaled lignocaine in a placebo controlled study. There was a significant reduction in breathing frequency after lignocaine (p less than 0.001) that was due to an increase in expiratory time (p less than 0.001). The inspiratory time remained unchanged, but tidal volume increased significantly (p less than 0.02). It is concluded that, while airway receptors may have a role in determining the frequency of breathing in chronic obstructive lung disease, other factors are responsible for the reduced inspiratory time.

Aged↗

Association between rise in antibodies and increase in airway sensitivity after intramuscular injection of killed influenza virus in asthmatic patients.

Nineteen stable asthmatic patients were given killed influenza virus intramuscularly. In 9 patients who developed a fourfold or greater rise in haemagglutination antibodies, an increase in airway sensitivity to histamine was demonstrated 48 h later. There was no significant change in histamine sensitivity in those patients who failed to develop a fourfold rise in haemagglutination antibodies. The increased histamine sensitivity was not associated with a deterioration in asthma symptoms, peak expiratory flow, nor an increase in bronchodilator requirements.

Adolescent↗

Time-dependent effect of prostaglandin E2 inhalation on airway responses to bronchoconstrictor agents in normal subjects.

Studies were performed to investigate whether hyperresponsiveness of the airways could be induced in normal subjects by inhalation of prostaglandin E2 (PGE2). During the initial bronchodilator phase of PGE2 action the bronchoconstrictor effect of inhaled histamine was significantly antagonised. When bronchoconstrictor challenges were started shortly after the end of the bronchodilator response to PGE2, however, significant enhancement of the effects of both inhaled histamine and methacholine occurred. It was predominantly sensitivity to these agents that was increased, with a parallel shift of the dose-response curves towards increased bronchoconstriction. Thus PGE2 may be protective in the acute phase of a bronchoconstrictor challenge, but in a chronic inflammatory condition its net effect may be a balance between this beneficial action and a non-specific potentiation of the activity of bronchoconstrictor agents.

Airway Resistance↗