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Biomedical subjects

S M Brooks

Publications and source records attributed to S M Brooks.

At least 19 recordsLinked to original sources

Occupational asthma.

Occupational asthma is an important occupational respiratory disorder, both in terms of morbidity, disability and in the total number of cases. The two types of occupational asthma are classified on the basis of their temporal relationship to onset. Occupational asthma with latency reflects allergic occupational asthma and is a condition characterized by a preceding latent period of workplace exposure during which allergic sensitization to a material present at the work site occurs. It is characterized biochemically by immunologic alterations and physiologically by variable and work-related airflow limitation with the presence of both specific and nonspecific airway hyperresponsiveness. In contrast, occupational asthma without latency is an asthmatic condition that develops suddenly and without a preceding latent period, as epitomized by the reactive airways dysfunction syndrome (RADS). RADS is distinguished physiologically by chronic, persistent nonspecific airway hyperresponsiveness and usually occurs after a single brief high-level exposure to an irritant gas, vapor of fume; new information suggests that a more prolonged irritant exposure, in certain susceptible persons with a pre-existing allergic predisposition, can also lead to the initiation of new-onset asthma. The factors that may be influential in the pathogenesis of occupational asthma include: exposure characteristics, industrial factors, job attributes, geographic and climatic conditions, economic considerations and personal or host conditions, such as atopy and cigarette smoking. Preventive measures and opportunities for intervention are essential and must address plans for reducing or eliminating accidents and spills, as well as plans for engineering control methods and proper and effective local exhaust ventilation. Medical surveillance programs are the keystone for prevention and should identify persons who are at an increased risk for developing occupational asthma, as well as detecting asthma at an early stage when intervention options are likely to be successful. For sensitized workers, the best preventive option is completed removal from the work environment.

Asthma

Occupational asthma. Serious consequences for workers and employers.

Patients affected by occupational asthma have respiratory symptoms that may persist for months, years, or even life. Hundreds of substances have been implicated in the disease, and the list is expected to grow. The authors discuss management of this sometimes life-threatening condition and emphasize the importance of environmental controls to prevent future cases.

Asthma

The FEF25-75% and the clinical diagnosis of asthma.

Nonspecific bronchial provocation testing is clinically useful in the evaluation of patients with symptoms suggestive of asthma. Testing is usually reserved for those with normal or near normal baseline spirometry. Although bronchial provocation testing is safe and widely available, the protocol is time consuming and not without expense. It has been reported that a reduced FEF25-75% in the context of an otherwise normal spirogram suggests that asthma should be considered. To evaluate this suggestion, we compared the baseline FEF25-75% (expressed as percent of predicted) with the results of the subsequent methacholine bronchial provocation test in 205 consecutive patients referred for testing. The mean baseline FEF25-75% in the 112 patients with normally responsive airways (ie, a negative bronchial provocation test) was 95.4 +/- 27.5%. In the 93 patients with a positive bronchial provocation test, the mean FEF25-75% was 77.6 +/- 27.2%. The mean FEF25-75% in those with hyperresponsive airways was significantly lower (t = 4.616, P < .0001). Of those patients with a positive bronchial provocation test, there was no significant correlation, however, between the baseline FEF25-75% and the degree of bronchial hyperresponsiveness as assessed by the PC20FEV1 (r = .154, P = .141). When a significant reduction in FEF25-75% was defined as less than 60% of predicted, the sensitivity of the prediction rule was 25.8%, the specificity was 92.0%, the positive predictive value was 72.7%, and the negative predictive value was 60.0%. From these results, we conclude that the FEF25-75% derived from simple spirometry may be useful in predicting the presence or absence, but not the degree, of bronchial hyperresponsiveness.

Adolescent

Sugarcane exposure and the risk of lung cancer and mesothelioma.

A case-control study was conducted of the risk of lung cancer and mesothelioma from environmental and occupational exposures associated with sugarcane production. A slight, not statistically significant, excess risk of lung cancer was observed among participants who reported working in the sugarcane industry (odds ratio 1.8, 95% confidence interval 0.5-7.5). No increased risk was observed among our population, associated with living near sugarcane growing areas. Little difference was observed between cases and controls in years employed in the industry or jobs performed. Only one mesothelioma case and no controls reported working in the sugarcane industry.

Aged

Advances in occupational asthma.

Clinical and research interests in occupational asthma increased dramatically in the 1980s. Advances in our knowledge base have led to improved recognition, management, and methods for preventing this disorder. An accelerated pace of basic and clinical research is anticipated in the 1990s. These efforts will likely lead to a more complete understanding of the disease (and pay dividends in understanding asthma itself). Occupational asthma is predicted to be the preeminent occupational lung disease in the next decade.

Allergens

Human fetal tracheal smooth muscle produces spontaneous electromechanical oscillations that are Ca2+ dependent and cholinergically potentiated.

Although the electromechanical properties of, and the cholinergic innervation to adult airway smooth muscle has been extensively studied, the little information is available on developing human airway smooth muscle, and the role of cholinergic mechanisms in regulating bronchomotor tone. A total of 7 tracheae obtained at the time of elective abortion and between 12-16 weeks of gestational development were used in this study. For each trachea, muscle tension and transmembrane potentials were measured simultaneously using an isometric force transducer and a standard 3-M KCl-filled glass microelectrode. All preparations showed spontaneous electrical oscillations approximately 8 mV in amplitude, which could be increased using electrical field stimulation, or exogenously applied acetylcholine. This was accompanied by a corresponding increase in muscle tension. Atropine (0.1 microM) abolished this potentiation, but had no apparent effect on the oscillations. Slow-wave activity was completely suppressed in the absence of extracellular Ca2+, or in the presence of verapamil (1 microM) or quinidine (1 microM). It appears that these oscillations of membrane potential may be potentiated by cholinergic mechanisms which regulate cell membrane ion channels, thus serving to change excitability in a rhythmic manner.

Acetylcholine

Cross-sectional study of platinum salts sensitization among precious metals refinery workers.

A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems.

Animals

Florida red-tide toxins (brevetoxins) produce depolarization of airway smooth muscle.

Crude preparations of brevetoxin (PBTX) produce airway contraction; however, it is not known if this toxin-induced mechanical response is coupled to changes in airway smooth muscle membrane potential. Membrane potentials and contractility of in vitro canine trachealis smooth muscle preparations were simultaneously measured with a microelectrode and microforce transducer before and during exposure to either the crude toxin (0.01-1.2 micrograms/ml), or the purified fractions PBTX-2 or PBTX-3 (0.01-0.07 micrograms/ml). Membrane potentials in cultured airway smooth muscle-reaggregate preparations were similarly studied. Toxins produced concentration-dependent depolarizations and contractions in in vitro preparations. These responses were not obtained in the presence of either the muscarinic blocking agent atropine, the sodium channel blocker tetrodotoxin (TTX), 0 mM extracellular Ca2+, or the Ca2+ channel blocker verapamil. The toxins were without effect in cultured cells, whereas acetylcholine produced depolarizations which were blocked in the presence of atropine, but not TTX. This suggested the presence of functional cholinergic receptors in cultured cells, and the PBTX-induced release of endogenous acetylcholine from peripheral nerve endings in the in vitro airway smooth muscle response.

Acetylcholine

Assessment of airway hyperresponsiveness in chronic stable asthma.

Airway reactivity and disease severity were investigated in 24 subjects with stable chronic bronchial asthma. Disease severity was determined by assigning a disease severity score (DSS) representing six clinical and therapeutic parameters. Airway hyperresponsiveness was assessed in two ways: airway reactivity score (ARS) based on the number of positive responses to a question concerning exposure to 22 nonspecific inhaled irritants and methacholine challenge testing and determining the cumulative dose causing a 20% reduction in FEV2 (CMD20). A significant correlation between DDS and CMD20 (r = 0.57; p less than 0.003) and DSS and ARS (r = 0.67; p less than 0.0003) attested to the important influence of airway hyperresponsiveness on disease severity. Significant correlations for ARS with CMD20 (r = -0.60; p less than 0.002) suggested the consistency with which the ARS estimated methacholine hyperresponsiveness. We found no statistically significant correlations between DSS, ARS, or CMD20 and the age of subject, duration of asthma, or other host characteristics. There was not a significant correlation between the degree of airway obstruction and DSS or ARS noted. The results of this investigation demonstrate the value of the use of clinical information for assessing airway hyperresponsiveness and disease severity in patients with chronic stable asthma. Both ARS and DSS are useful clinical tools for estimating methacholine reactivity.

Adult

Cold air challenge and platinum skin reactivity in platinum refinery workers. Bronchial reactivity precedes skin prick response.

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

Adult

Ethanol-induced bronchodilatation in TEA-treated canine tracheal smooth muscle is mediated by a beta-adrenoceptor-dependent mechanism.

The effects of moderate concentrations of ethanol (8-34 mM) on the electromechanical activity of airway smooth muscle cells of canine trachealis, stimulated by the spasmogen tetraethylammonium (TEA), are described for in vitro and cultured reaggregate preparations. Ethanol produced a concentration-dependent hyperpolarization, and suppression of action potentials in smooth muscle preparations, in vitro, whereas it was without effect in cultured airway smooth muscle cells. In the presence of the beta-adrenoceptor antagonist propranolol (1 microM), ethanol had no effect on in vitro preparations. Isoproterenol (0.1 microM) produced hyperpolarization and suppression of action potentials in airway smooth muscle of both preparations. These effects were not observed when propranolol was additionally present. This suggests that both in vitro, and cultured airway smooth muscle preparations maintained their beta-receptors, and that ethanol caused the release of endogenous catecholamine from adrenergic nerve endings which apparently remained intact in in vitro, but not in cultured airway smooth muscle preparations.

Action Potentials

A moderate concentration of ethanol alters cellular membrane potentials and decreases contractile force of human fetal heart.

The effects of ethanol, although well studied in the adult myocardium, have been little studied in fetal tissue. Experiments in pregnant animals suggest that ethanol compromises fetal myocardial performance, in utero; however, the physiological mechanism(s) remains obscure. The present report examines, in vitro, the effects of a moderate concentration of ethanol (20 mM) directly on cell membrane potentials and contractility of human fetal left ventricle as determined using intracellular microelectrodes and microforce transducers. We observed significant decreases in action potential amplitude, upstroke velocity, duration of repolarization, and the force of contractions. These effects were reversible. As ethanol crosses the placenta, our findings suggest that moderate concentrations of ethanol, as occur during 'social drinking', may temporarily compromise fetal myocardial performance in utero.

Action Potentials

Reproductive outcomes of pregnant workers employed at 36 reinforced plastics companies. II. Lowered birth weight.

The authors analyzed the birth weights of infants whose mothers worked during pregnancy in the reinforced plastics industry, where styrene monomer is a primary chemical exposure. Reproductive and work histories were taken by telephone interview from 1535 women employed between 1974 and 1981 at 36 companies. The questionnaire was based on one used by the National Institute for Occupational Safety and Health, and indices of styrene exposure were derived from an historical set of 1500 industrial hygiene samples from the study companies. There was not a significant dose-response trend in decreasing average birth weights. However, women who worked at the most highly exposed jobs--such as laminators, rollers, or spray-up operators at boat manufacturing companies--had offspring with adjusted birth weights of 4% less than the offspring of unexposed women (95% confidence interval = -7.7% to +0.6%) after adjustment for other factors.

Birth Weight

Toluene diisocyanate-induced airway hyperreactivity in guinea pigs depleted of granulocytes.

The influence of cyclophosphamide-induced granulocyte depletion on toluene diisocyanate (TDI)-related changes in airway reactivity and pathology was assessed in guinea pigs. Twelve cyclophosphamide-treated and 12 control animals comprising each group were studied physiologically before and 2 h after a single 10-min exposure to 3 ppm of TDI. Reactivity was determined in intact unanesthetized animals by measuring specific airway conductance before and during intravenous acetylcholine infusion. After testing, tracheal tissue for light microscopic examination was obtained from three hyperreactive guinea pigs in each exposed group and compared with tissue from treated and control animals (n = 3 each) that had not been TDI exposed. Cyclophosphamide treatment caused substantial decreases in both circulating and airway granulocyte counts. However, the incidence and degree of bronchial hyperreactivity that occurred 2 h post-TDI was similar in the untreated and treated groups. Our results indicate that TDI-induced bronchial hyperreactivity 1) occurs shortly after a brief high concentration exposure and 2) appears independent of circulating or airway granulocyte counts.

Acetylcholine

Delayed anaphylactoid reaction in a worker exposed to chromium.

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.

Adult