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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.