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Biomedical subjects

C Bevan

Publications and source records attributed to C Bevan.

50 records · Page 3Linked to original sources

Lung function of office workers exposed to humidifier fever antigen.

Office workers who became sensitised to antigens derived from humidifier sludge developed episodes of fever, malaise, and other symptoms, including polyuria and mild chest tightness. The episodes usually occurred on a Monday evening and were to some extent dose-related. Lung function was assessed over a day shift on two occasions, including one after which almost all the susceptible subjects developed symptoms. The symptoms were preceded by a 6% reduction in forced expiratory volume and vital capacity, a corresponding increase in residual volume, and a reduction in flow rate after 75% vital capacity had been expired. There were no changes in peak expiratory flow, forced expiratory flow at 50% of vital capacity, or transfer factor. In some subjects the transfer factor was apparently reduced 36 hours later, but for this there may have been another explanation. The physiological features were considered to reflect narrowing of small airways in the lung. The changes, however, were minimal and not the main cause of the symptoms. A feature of the episode was the severity of the constitutional symptoms despite the low airborne dust levels.

Adult↗

An investigation of operating theatre staff exposed to humidifier fever antigens.

Sixty staff working in a hospital operating theatre, where a case of humidifier fever had been identified, were studied together with 49 subjects working in other parts of the hospital. They each had a blood test for serology, a skin test, and a chest radiograph and completed a questionnaire. The theatre staff also had pulmonary function tests. The theatre humidifier was found to contain several organisms including amoebae and antigens cross-reacting highly with those implicated in previous outbreaks of humidifier fever. Of the 60 exposed subjects, 25 had developed antibodies, nine had probable symptoms of humidifier fever, and six possible symptoms. There was a strong association between symptoms and antibodies (p = 6 x 10(-5) by Fisher's exact test). The development of antibodies was also related to duration of exposure in the theatre (p less than 0.01 by X2 test for trend) and inversely to smoking (p = 0.0073 by Fisher's exact test) but not to history of atopy. Because of the presence of antigens and because certain biocides added were ineffective in controlling antigenic build-up the humidifier was switched off. Eight months later specific IgG levels in the theatre staff sera, estimated by an enzyme-linked immunosorbent assay technique, had fallen on average by 25%. Inhalation challenge with humidifier water was performed in eight subjects. Four subjects reacted to the challenge, including both those with antibodies and previous symptoms.

Air Conditioning↗

Relationship between type of simple coalworkers' pneumoconiosis and lung function. A nine-year follow-up study of subjects with small rounded opacities.

One hundred and twenty-five men who were identified in 1968 as having the simple pneumoconiosis of coalworkers were re-examined nine years later when their mean age was 59.6 years. On both occasions the lung function and response to exercise were assessed. There was no evidence for progression of simple pneumoconiosis between the surveys, but 14 had developed small irregular opacities on their chest radiographs and 28 showed early changes of progressive massive fibrosis (PMF). After allowing for the effects of smoking and of exposure to coal dust, subjects with both p and r types of simple pneumoconiosis exhibited a reduced transfer factor compared with subjects having q-type opacities; subjects with r-type opacities also showed an increased pulmonary elastic recoil pressure. The presence of irregular opacities, independent of rounded opacities, was associated with a low transfer factor and decreased slope of phase III of the single breath oxygen test. Subjects who developed PMF between 1968 and 1978 had p or r opacities more often than q opacities: these subjects had an increase pulmonary elastic recoil pressure. The development of PMF was also associated with physiological evidence of airways obstruction. The changes in subjects with r opacities are consistent with the presence of space occupying lesions that may progress to PMF. Subjects with p opacities have physiological evidence of emphysema as do some subjects with established PMF. Irregular opacities may reflect the presence of both emphysema and diffuse fibrosis. There is need for more morbid anatomical evidence on the underlying pathology.

Coal Mining↗

H2 receptor blockade and bronchial hyperreactivity to histamine in asthma.

The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration of metiamide or burimamide but not of cimetidine. These findings suggest the possible deleterious effect of H2 receptor antagonists in asthmatic subjects. The effects of H2 receptor blockade with cimetidine on bronchial hyperreactivity to histamine were studied in 10 asthmatic volunteers by whole body plethysmography. Cimetidine 800 mg and placebo were administered orally on two separate days, eight hours and two hours before study. No significant difference in baseline levels of airways obstruction was seen with the two agents. Inhalational challenge with increasing concentrations of histamine revealed no significant difference in bronchial hyperreactivity to histamine between cimetidine and placebo treatment days. H2 receptor blockade with cimetidine does not appear to affect ventilatory function or bronchial hyperreactivity to histamine in asthmatic subjects. It has been suggested that cimetidine may have H1 as well as H2 receptor blocking properties which prevent this effect.

Adult↗

Induction of bronchial hypersensitivity: evidence for a role for prostaglandins.

Bronchial hyper-responsiveness is a particular feature of asthma, but also occurs in normal subjects after a viral upper respiratory tract infection or ozone inhalation. Such stimuli would be expected to result in the release of chemical mediators of inflammation. In this study, the effects of one of these, prostaglandin F2 alpha (PGF2 alpha), on the response of normal subjects to inhaled histamine has been investigated. Nine normal volunteers took 10 inhalations of increasing concentrations of PGF2 alpha at 15-minute intervals from a Wright's nebuliser under standard conditions until a change in sGaw could be detected. The next lowest serial dilution of PGF2 alpha was subsequently inhaled by each subject every 15 min for 90 min to ensure the absence of a cumulative effect. Inhalation dose-response curves to histamine diphosphate were constructed on two separate occasions using the same standardised technique. Doses were administered every 15 min and sGaw determined five minutes after each. On one occasion each dose of histamine was immediately preceded by the non-active test dose of PGF2 alpha and on the second by saline as placebo. The study was performed double-blind and in random order. After pretreatment with PGF2 alpha the histamine dose-response curve was significantly shifted to the left in a parallel fashion (p less than 0.001). There was a significant decrease in the doses of histamine required to cause a 20% fall in sGaw (p less than 0.0015) but no significant change in the slopes of the dose-response regression lines, indicating that bronchial muscle sensitivity rather than reactivity had been predominantly affected.

Adult↗

Effects of exposure to slate dust in North Wales.

In a study of slate workers in four areas in North Wales 725 workers and ex-workers who had been exposed to slate and to no other dust were seen, together with 530 men from the same area who had never been exposed to any dust. Evidence of pneumoconiosis was found in one-third of the slate workers, and 10% had degrees of pneumoconiosis that would attract compensation (category 2 or higher). The prevalence of respiratory symptoms was high, and there was evidence of an effect of both simple and complicated pneumoconiosis on lung function additional to that of age. There was a high prevalence (40-50%) of radiological lesions suggestive of healed tuberculosis in men aged over 55. Either pneumoconiosis or old tubercular lesions (or both together) could account for the current symptomatology and disability of the men.

Adolescent↗

Inhaled antihistamines--bronchodilatation and effects on histamine- and methacholine-induced bronchoconstriction.

To assess further the bronchodilator activity of inhaled antihistamines ten stable asthmatic subjects inhaled aerosols of clemastine, 1 mg/ml, and saline placebo administered double blind. Subjects underwent bronchial challenge with increasing concentrations of histamine and methacholine, and specific airways conductance was measured by whole body plethysmography at each concentration. There was a significant 21.9% increase in specific airways conductance after inhalation of clemastine. Subjects could tolerate significantly higher mean concentrations of histamine when treated with clemastine than with saline. The shift of the cumulative log histamine dose-reponse curve suggests that such protection is due to competitive antagonism to the inhaled clemastine. Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action.

Adult↗

A community survey of asthmatic characteristics.

A survey was undertaken among adults aged 20-44 years in a South Wales town. Persons with a history of wheezing with breathlessness and in the absence of a cold were identified by postal questionnaires and seen at a clinic, together with a sample of subjects without these symptoms. The response rates for the first and second stages of the survey were 99.6% and 91.0% respectively, and 574 subjects were ultimately seen. Asthmatic patients (those receiving treatment within the previous year) had some airways obstruction at rest, which increased after exercise. They also had strong allergic tendencies, as shown by personal and family history, skin tests, and serum IgE levels. The ex-asthmatics (those not receiving treatment within the previous year) showed these tendencies to a lesser extent. A larger group gave a history of wheezing but stated that they had never had asthma; in their response to exercise and allergic traits they resembled the control group rather than the asthmatics, and appeared to have the features of chronic bronchitis. Asthma and chronic bronchitis would therefore seem to be distinct entities within the population studied.

Adult↗

Motor activity effects in female Fischer 344 rats exposed to isopropanol for 90 days.

In a previous subchronic neurotoxicity study, increases in motor activity were observed for female rats after 9 and 13 weeks of exposure to 5000 ppm of isopropanol vapor. The present study was conducted to evaluate the reproducibility of these effects and, if reproducible, to assess the potential for reversibility following cessation of exposure. Two groups, each containing 30 female Fischer 344 rats, were exposed to concentrations of zero (control) and 5000 ppm of isopropanol vapor for 6 h per day, 5 days per week. Fifteen of the animals in the control and 5000 ppm groups were exposed for 9 weeks (designated as the 9-week subgroup), while the other 15 animals in each group were exposed for 13 weeks (designated as the 13-week subgroup). Motor activity was assessed for both subgroups prior to exposure and following 4, 7 and 9 weeks of exposure. Motor activity was also measured for rats in the 13-week subgroup following 11 and 13 weeks of exposure. These motor activity measurements were made 18-20 h following the end of the last exposure for that week. In addition, to evaluate the reversibility of motor activity effects, measurements were made on three occasions during the week following the final exposure for rats in both the 9-week and 13-week subgroups and weekly thereafter for five additional weeks for rats in the 13-week subgroup. Increases in cumulative test session motor activity counts were observed following 4, 7 and 9 weeks of exposure for rats in the 9-week subgroup. Increases in cumulative test session motor activity counts were also observed following 4, 7, 9, 11 and 13 weeks of exposure for rats in the 13-week subgroup. Reversibility of this effect was observed for rats in the 9-week subgroup within 2 days following the last exposure. Reversibility was also noted for rats in the 13-week subgroup but not until Study Week 15 (2 weeks following the last exposure). Minor changes were observed in the shape of the motor activity habituation curves for isopropanol-exposed animals in the 9-week and 13-week subgroups at ca. 50% of the measurement intervals beginning at Study Week 4. While most of these statistical changes were observed in conjunction with increases in cumulative test session motor activity, some were observed following time points where recovery of the cumulative test session motor activity counts had occurred. No change in the shape of the motor activity habituation curve was observed at 42 days following the last exposure, indicating that complete recovery of motor activity effects had occurred. Thus, repeated exposure of female rats to 5000 ppm of isopropanol produced reversible increases in motor activity.

2-Propanol↗

Two-generation reproduction toxicity study with isopropanol in rats.

A two-generation reproduction toxicity study was conducted in rats with isopropanol. Thirty rats of each sex per group (P1) were dosed once daily by oral gavage with 0, 100, 500 or 1000 mg isopropanol kg-1 for at least 10 weeks prior to mating. Parental animals were mated within groups for up to 3 weeks. Parental females were dosed during mating, gestation and lactation; parental males were dosed during mating through delivery of their last litter sired. The P2 adults were selected from the F1 litters and were dosed for 10-13 weeks before mating to produce a single litter. Findings in the parental animals included increased lactation body weight gain in the mid- and high-dose females, increased liver and kidney weights in the mid- and high-dose groups of both sexes and centrilobular hepatocyte hypertrophy in some P2 males. There was also accumulation of hyaline droplets and other microscopic findings in the kidneys from the mid- and high-dose P1 males and from all treated groups of the P2 males. Increased mortality was observed in the high-dose F1 offspring during the early postnatal period, although no other clinical signs of toxicity were observed in the offspring of either generation. In addition, offspring body weight was reduced during the early postnatal period in the high-dose F1 males and in the high-dose F2 pups of both sexes. Eighteen out of 70 F1 weanlings in the 1000 mg kg-1 group died or were euthanized prior to P2 selection. No treatment-related post-mortem findings were observed in the offspring from either generation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Propanol↗

Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice.

Administration, Inhalation↗

Subchronic toxicity study of dicyclopentadiene vapor in rats.

Fischer 344 rats were exposed by inhalation to 0, 1, 5 or 50 ppm dicyclopentadiene (DCPD) vapor 6 hr/day, 5 days/week for 13 weeks, followed by a 13-week recovery period. Animals were euthanized following completion of exposure at 2, 6, or 13 weeks and at postexposure weeks 4 or 13. No mortality, overt signs, body weight changes, hematologic or clinical chemistry values were related to DCPD exposure. In the high-exposure male rats, relative liver weights were significantly increased but with no accompanying histopathologic changes. Exposure to DCPD produced adverse kidney effects in male, but not female, rats as evidenced by the excretion of epithelial cells in the urine. Histologic changes were localized to the proximal tubules of the kidney and included increased accumulation of protein droplets, regenerative epithelium, and the presence of intraluminal proteinaceous material. In addition, several alterations in renal function were observed. Urinary Na+ excretion rates were decreased and urinary K+ excretion rates were increased throughout the exposure period; however, glucose was not present in the urine, and creatinine clearance was normal. The ability of the kidney to concentrate urine was also impaired. After the recovery period, many of the treatment-related kidney effects were not observed, including the presence of hyaline droplets in the proximal tubules and epithelial cells in the urine. These findings indicate an overall low degree of systemic toxicity following subchronic inhalation exposure of dicyclopentadiene at exposure levels up to 50 ppm. The only effect that was observed was a male rat-specific nephropathy that is characteristic of the hyaline droplet nephropathy produced by a diverse group of compounds.

Administration, Inhalation↗