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Acute effects of routine firefighting on lung function.

We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Respiratory disease in a photographer.

Reversible airways obstruction occurred in a photographer after long-term exposure (over many years) to sulfuric and acetic acid fixers. Air-exchange recommendations for darkrooms by the Building Officials Code Administration [1981] differ markedly from those recommended by the American Society of Heating, Refrigerating, and Airconditioning Engineers [1977] and the fixer manufacturer (Eastman Kodak). Use of fume hoods or rates of air-exchange higher than are required by law may be necessary to prevent symptoms and disease in certain workers.

Adult↗

Fisher's syndrome: a pharmacological study of the pupils.

A pharmacological study was performed in the involved pupils to demonstrate the site of lesion in a patient with Fisher's syndrome who showed marked ptosis, complete external ophthalmoplegia, pupillary involvement with anisocoria, facial paresis, ataxia, areflexia, and albuminocytological dissociation in the cerebrospinal fluid. The instillation of 2.5% methacholine produced mild constriction of one pupil. This response was not detectable in the recovery stage. The instillation of 1.25% l-epinephrine produced marked bilateral dilation of the pupils, in both the early and recovery stages. Instillation of 5% tyramine produced pupillary dilation as in the normal pupil. The response to 5% cocaine, tested only in the recovery stage, was weak in one pupil. These results imply that the pupillary involvement was due to peripheral involvement of the sympathetic and parasympathetic nervous systems. The lesion in the sympathetic nervous system was preganglionic, but in the parasympathetic nervous system the precise localization could not be determined.

Aged↗

Pharmacological studies of the pupils in familial amyloid polyneuropathy.

Pharmacological studies of the pupils of 7 patients with familial amyloid polyneuropathy (FAP) were performed in order to demonstrate the site of the lesion. Supersensitivity to 1.25% epinephrine was observed frequently, but not to 2.5% methacholine. The lesions of the sympathetic nervous system, judging from the epinephrine and tyramine tests, were regarded as preganglionic in 2 patients and postganglionic in 4. Among 3 patients reexamined six months later, 1 had developed signs of sympathetic postganglionic disturbance and another showed a peripheral parasympathetic disturbance associated with progress of a sympathetic preganglionic disturbance. From these results it was suggested that in FAP, sympathetic abnormalities involve the pupils more often than parasympathetic disturbances, and pharmacological studies can detect the autonomic dysfunction before it becomes clinically apparent.

Adult↗

Extracellular sodium is required for methacholine-induced secretion of mucus glycoconjugates from canine tracheal explants.

Extracellular sodium is known to influence secretion by certain secretory cells, possibly by mobilizing calcium from cellular stores or by altering intracellular pH via regulation of a Na(+)-H+ antiport system. Using canine tracheal explants, we determined whether agents which alter sodium fluxes are capable of modulating basal or cholinergically-induced secretion of mucus glycoconjugates. Methacholine, a cholinergic agonist, increased mucus secretion from explants incubated in the presence or absence of calcium, but had no effect on secretion when incubated in sodium-deficient media, indicating (a) that cholinergically-induced secretion can be mediated by mobilization of cellular calcium and (b) that extracellular sodium was required for this stimulatory effect. Several agents which increase intracellular sodium were tested for their effect on mucus secretion. Ouabain, a sodium pump inhibitor, and veratridine, a sodium channel activator, did not significantly affect control or methacholine-induced secretion; gramicidin, a sodium ionophore, also had no effect on basal release. Tetrodotoxin, a sodium channel inhibitor, was also without effect on basal or methacholine-stimulated mucus release. Agents which alter intracellular pH were also examined for their effects on basal or methacholine-induced glycoconjugate secretion. Amiloride, which decreases intracellular pH by inhibiting Na(+)-H+ exchange, produced a 19 per cent increase in basal secretion (not statistically significant), but had no effect on methacholine-induced secretion. An agent, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which decreases intracellular pH by inhibiting HCO3(-)-Cl- exchange, elicited decreases in both basal and methacholine-induced secretion, but the inhibition did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Methacholine provocation of Prinzmetal's variant angina pectoris: a revised perspective.

We report 13 patient with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicated a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.

Adult↗

Duration of effect of gallopamil, a calcium channel blocker, on methacholine-induced bronchoconstriction.

We previously demonstrated a modest but significant protective effect of inhaled gallopamil (D600), the methoxy derivative of verapamil, against methacholine-induced bronchoconstriction; however, the duration of the protective effect of this and other calcium channel blockers is unknown. We therefore evaluated the duration of this protective effect in 15 asthmatic subjects in a prospective, placebo-controlled trial. Methacholine challenges (Cockcroft method) were performed 2 hours before and 30 minutes after the administration of placebo, and 1 mg and 10 mg of inhaled gallopamil. Gallopamil did not alter resting airway caliber, but significantly increased the concentration of methacholine required to decrease the FEV1 20% 30 minutes after the dose. Results with both the 10-mg and 1-mg doses were significantly different from placebo, but not from each other. The duration of this protective effect was transient in the group as a whole; the mean drug activity ratios were not significantly different with this sample 2.5 hours after the dose. Thus the short duration of effect limits the potential clinical usefulness of gallopamil in suppressing the signs and symptoms of chronic asthma.

Adolescent↗

In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat.

The current study was designed to assess the methacholine dose-response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155-250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg-1 i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (p(aw)) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml-1) through the breathing circuit. Baseline p(aw) and pA mean (+/- SD) values (6.44 +/- 2.06 and 8.25 +/- 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose-response study (P = 0.001), whereas p(aw) was not increased. The increase in pA was significantly higher than that of p(aw) (P less than 0.001). The relationship between the mean (+/- SE) values of ptr and pA could be well described by a straight line (r = 0.990, P less than 0.001). There were also significant correlations based on regression equations between ptr and p(aw) (r = 0.947, P less than 0.001) and pA and p(aw) (r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats.

Administration, Inhalation↗

Differentiation-associated decrease in muscarinic receptor sensitivity in human neuroblastoma cells.

Muscarinic receptor-linked increases in intracellular free Ca2+ as measured with quin-2 and Ca2+ release from monolayers of cells have been measured in the human neuroblastoma cell line SH-SY5Y. Induction of differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a decrease in the sensitivity of the cells to low concentrations of agonists with respect to the induced increase in cytosolic free Ca2+ and stimulation of Ca2+ efflux. No decrease in agonist binding affinity was observed when the displacement of a labelled antagonist, 3H-NMS, by a non-labelled agonist was studied.

Calcium↗

Mechanism of methacholine-induced rise in intraocular pressure in the dog.

The mechanism of the methacholine-induced rise in intraocular pressure in the dog was studied to determine the basis of the relationship, if any, between lens thickness and intraocular pressure. The results rule out a vasodilator component in methacholine intraocular pressure elevation, and the tonometric recording of the elevation makes unlikely the involvement of methacholine stimulation of the rectus muscles of the eye. Thus, indirect evidence points to methacholine stimulation of ciliary muscle contraction with consequent thickening of the lens as responsible for its intraocular pressure-elevating effect and, hence, the ability of the response under investigation to specify the cycloplegic liability of a neurotropic antispasmodic agent.

Animals↗

Cardiorespiratory status in long-term survivors of prematurity, with and without hyaline membrane disease.

Forty-eight children, born at less than 33 weeks' gestation and without bronchopulmonary dysplasia (BPD) or Wilson-Mikity syndrome (WM) were studied at a mean age of 9.1 years, to identify the incidence and possible factors contributing to the development of long-term abnormalities in pulmonary function. As neonates, 30 children had hyaline membrane disease (HMD) of whom 21 required ventilation. Eighteen did not have HMD, of whom 9 required ventilation for nonrespiratory reasons. All patients had grown normally. Four of the 48 (8.3%) had clinical asthma, 5 had persisting chest x-ray abnormalities (10.6% of 47 chest x-rays performed), each having been ventilated for HMD. There was a close association between duration of ventilation, oxygen administration, and subsequent abnormal chest x-ray. Electrocardiogram and M-mode echocardiograms were normal in all but 2 patients. Only 3 patients had significant restrictive lung disease, 3 had evidence of significant airways obstruction, and 13 (27.7%) had signs of air trapping. Methacholine challenge was positive in 30 of 46 patients (65.2%). The incidence of a positive methacholine challenge did not correlate with history of HMD, duration of ventilation, or high oxygen administration. There is an increased incidence of airway hyperreactivity in survivors of prematurity, not associated with any identified therapeutic maneuver during the neonatal period.

Female↗