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Biomedical subjects

R M Cherniack

Publications and source records attributed to R M Cherniack.

At least 73 records · Page 4Linked to original sources

Structure-function correlation of early stages of lung injury induced by intratracheal bleomycin in the rabbit.

After measurement of lung volume, pressure-volume relationship of the lungs, flow-volume relationship, and single-breath diffusing capacity, the effect of endotracheal injection of bleomycin (10 micrograms/kg) on structural and functional changes was assessed in 21 rabbits and compared with 8 rabbits who received endotracheal injection of saline. Lung function was reassessed in the control rabbits at 1, 3, and 5 wk, and they were then killed. The bleomycin-treated rabbits were divided into 3 groups and retested at 1 (n = 7), 3 (n = 6), and 5 (n = 8) wk. Each group of animals was killed after the functional assessment, and after fixation the lungs were examined morphometrically. The degree of fibrosis in the bleomycin-treated animals was small even at 5 wk. Volume densities of pulmonary structures, alveolar wall thickness, airway diameters, airway inflammation scores, and fibrosis scores were determined and their correlation with the functional measurements was assessed. Lung volume subdivisions, pressure-volume characteristics, and diffusing capacity for carbon monoxide were significantly reduced, and the resistance of the upstream segment of airways was significantly increased after the bleomycin injection. Changes in lung volume correlated significantly with the volume densities of free alveolar cells, nonparenchymal tissue, and alveolar wall thickness. The exponent K, derived by fitting an exponential function to the pressure-volume data, which is indicative of lung elastic behavior, did not correlate with any morphometric index of interstitial disease. The diffusing capacity for CO was significantly correlated with the volume densities of alveolar wall, nonparenchymal tissue, and alveolar wall thickness, but these correlations became nonsignificant when the diffusing capacity was corrected for alveolar volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bleomycin-induced lung injury in the rabbit. Analysis and correlation of bronchoalveolar lavage, morphometrics, and fibroblast stimulating activity.

We have used a rabbit model of bleomycin-induced lung injury to evaluate the chronological changes in the bronchoalveolar lavage fluid (BALF) constituents. The correlation of these changes with morphologic alterations and measured soluble mediators of fibrosis has also been assessed. Three groups of 8 treated and 8 control New Zealand white rabbits received 10 U/kg bleomycin in normal saline, or equal volumes of saline intratracheally. The animals underwent bronchoalveolar lavage with a balloon tipped catheter localized to the right lower lobe at 3, 8, or 12 wk. Total cell counts and differentials were performed on the BALF. The lungs were examined histologically for inflammatory cells in the interstitium, alveoli, and airways by morphometric techniques. The lungs were also assayed for total hydroxyproline content. Bronchoalveolar lavage fluid supernatants and supernatants from lavaged macrophages cultured for 24 h were assayed for fibroblast stimulating activity (FSA) by 3H-thymidine incorporation into rabbit lung fibroblasts. There was a significant increase in macrophages and neutrophils in the BALF at 3 wk only, although the elevation of macrophages was sustained for longer than that of neutrophils. The numbers of BALF macrophages correlated with the morphometric assessment of the number of intra-alveolar macrophages (p less than 0.001) and interstitial mononuclear cells (p less than 0.001), as well as the extent of airway inflammation (p less than 0.001). The numbers of BALF neutrophils correlated with morphometrically assessed alveolar (p less than 0.01) and interstitial neutrophils (p less than 0.01) but not with any airway inflammation scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of pulmonary function tests in the assessment and treatment of patients with airway hyperreactivity.

Simple spirometry at each office visit (and if feasible, determination of lung volume) along with regular assessment of peak flow by the patient are important determinations that facilitate assessment of the progress of the disorder, as well as the impact of therapy. When there is a trend towards falling air flow rates, determination of the arterial blood gas tensions and calculation of the P(A-a)O2 will foster early recognition of the development of increased flow resistance in the peripheral lung units, so that intervention can be instituted. In the early stages of peripheral airway obstruction, the arterial PO2 and the P(A-a)O2 are sensitive indicators of the severity of the disturbance, whereas changes in FEV1 may be minimal. If intervention is not instituted early enough, the work of breathing may increase significantly and reach a stage where hypoxemia is associated with a rising PaCO2, which is indicative of serious deterioration.

Airway Resistance↗

Chronic and acute asthma. Keys to successful management.

The goal of chronic asthma management is to maintain maximal bronchodilation, which is achieved by regular monitoring of ventilatory function and by use of bronchodilators. A trial of corticosteroid is justified if symptoms are not controlled and marked improvement in forced expiratory volume in one second is not achieved by appropriate use of bronchodilating agents. Corticosteroids should also be used if symptoms exacerbate. If hospitalization is required, a more rigorous therapeutic program, which may involve oxygenation, aminophylline and/or corticosteroid administration, fluid therapy, and ventilatory support, should be instituted.

Administration, Oral↗

Relationship between serum theophylline levels and pulmonary function before and after inhaled beta-agonist in "stable" asthmatics.

In 9 "stable" adult asthmatics, the relationship between serum theophylline level and pulmonary function, as well as the interaction of aminophylline and inhaled beta2-agonist on pulmonary function, were studied. At varying levels of serum theophylline between 6 and 25 micrograms/ml, which were brought about by increasing oral doses of a slow-release theophylline preparation, the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), airway resistance (Raw), and lung volume were assessed before and after inhalation of a B2-sympathicomimetic (isoetharine). In those subjects in whom it was possible to obtain blood levels within all 3 ranges of less than 10, 11 to 15, and greater than 15 micrograms/ml, there was a significant (p less than 0.05) increase in FEV1 between a mean level of 6.4 +/- 0.9 micrograms/ml and one of 12.8 +/- 0.2 micrograms/ml, but there was no further significant improvement at a mean value of 19.2 micrograms/ml +/- micrograms/ml. Specific airways conductance (SGaw) showed no change at increasing serum theophylline levels. In addition, inhaled beta-agonist increased FEV1 and SGaw maximally at all times, irrespective of the serum theophylline level, and there was no relationship between the response to inhaled bronchodilator and the serum theophylline level. The data indicate that unlike the patient in serious difficulty, ventilatory function was not improved by maximizing serum theophylline levels in this population of stable asthmatics. This suggests that theophylline may be less useful for the stable asthmatic patient than for the acutely ill patient.

Administration, Intranasal↗

Respiratory abnormalities in employees of the hard rock mining industry.

Respiratory symptoms, forced vital capacity, and the single breath N2 test were assessed in male employees (25 to 54 yr of age) who had been employed for more than 5 yr in the mining industry in Manitoba. The results were compared with those in a similar group of men selected from the general population. The prevalence of cough and/or phlegm in both nonsmoking and smoking mining employees was significantly greater than that in the sample of the general population (p less than 0.05). In both nonsmokers and ex-smokers amongst the mining employees, the parameters derived from the single breath N2 test tended to be lower and maximal expiratory flow rates tended to be higher than in comparable groups in the general population sample. In smokers, FVC, FEV1, FEV1/FVC, maximal expiratory flow rates, RV/TLC, and the slope of phase III were significantly worse in smelter workers than in underground workers. Alterations in lung function in those who worked underground, but not in those who worked in the smelter, was related to the duration of employment in the industry. The data suggest that exposure to mining irritants may result in disorders of lung function, and that this effect is greater in cigarette smokers.

Adult↗

Evidence for a sodium electrogenic pump in airway smooth muscle.

We tested the hypothesis that the resting membrane potential (Em) of guinea pig and bovine airway smooth muscle (ASM) (m. trachealis transversus) might be influenced by a Na+ electrogenic pump. To determine the Em of ASM, glass microelectrodes filled with 3 M KCI and offering an impedance between 40 and 80 M omega were used. After incubation a normal oxygenated physiological salt solution (PSS) [pH, 7.38 +/- 0.02 (SD); temp, 37 +/- 0.5 degrees C (SD)] for 60 min, the Em of guinea pig ASM was -62.5 +/- 1.25 (SE) mV (successful impalement of 437 cells of 37 tracheal preparations from 37 different animals) and that of bovine ASM was -60.0 +/- 1.5 mV (successful impalement of 306 cells of 26 tracheal preparations from 26 different animals). Tracheal preparation consisted of 10-mm-long segments of cervical or intrathoracic portions of the trachea. Approximately 30% of the cells of both species exhibited spontaneous electrical activity (slow waves). Studies to determine whether an electrogenic pump was present revealed that a) ouabain (10(-5) M), a specific inhibitor of the Na+ pump, causes depolarization of ASM in both species; b) exposure of ASM to a K+-free solution resulted in a similar depolarization followed by a hyperpolarization; c) exposure to normal PSS after "Na+ loading" resulted in significant hyperpolarization of ASM when these preparations were returned to normal PSS; and d) Em of ASM decreased on exposure to a low temperature (21, 25, and 29 degrees C) and increased at a high temperature (40 degrees C). It is concluded that an active electrogenic pump is present in guinea pig and bovine airway smooth muscle.

Animals↗

Physical therapy.

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Drainage↗

Relationship between the single-breath N test and age, sex, and smoking habit in three North American cities.

This report describes a collaborative study conducted in Montreal, Canada, Portland, Ore., and Winnipeg, Canada, to establish the relationship between the single-breath N2 test and age, sex, and smoking and to determine the prevalence of functional abnormalities in these populations. In nonsmokers, age-related regressions for closing volume, closing capacity, and the slope of phase III obtained from the single-breath N2 test, plus the ratio of the I-s forced expiratory volume to the forced vital capacity had very similar slopes, suggesting that differences in geographic location, climate, air pollution, and occupation had no effect on lung function detectable by these tests. Among the 6 city/six groups there was no systematic difference in the prevalence of functional abnormalities between the cities, but closing capacity expressed as a percentage of total lung capacity was abnormal most often in men and the slope of the alveolar plateau was abnormal most often in women. The prevalence of respiratory symptoms within different smoking categories was similar in the 3 cities. Although the number of cigarettes smoked had a significant effect on every test except the ratio of the I-s forced expiratory volume to forced vital capacity in men, the effect of age was considerably greater than the effect of smoking, and the dose-response relationship was weak. We conclude that additional factors may interact with smoking to place a smoker at risk of developing chronic airflow limitation.

Adult↗

Alpha1-antitrypsin phenotypes and lung function in a moderately polluted northern Ontario community.

To determine whether persons with intermediate value alpha1-antitrypsin phenotypes living in a polluted environment manifest significant abnormalities in lung function, a study was undertaken of an age-, sex- and smoking-stratified sample of 391 persons from the town of Fort Frances, Ont., which has elevated values of total dustfall, suspended particulates and hydrogen sulfide. Indices of pulmonary function were derived from the maximum expiratory flow and the single breath expiratory flow and the single breath expiratory nitrogen washout curves. The percentage frequency of the M, MS and MZ pheontypes was 91.7, 7.3 and 0.8, respectively. There was no significant difference between the M and MS groups as indicated by the nitrogen washout curve and maximum expiratory flow curve. There was no significant difference between the three MZ subjects and the M group. In both M and MS groups smokers displayed evidence of airflow obstruction when compared with nonsmokers. It would appear that, when compared with M subjects, persons with the MS phenotype living in a moderately polluted area show no changes in indicators of pulmonary function, including tests of early airway disease, that cannot be attributed to their smoking habit.

Adult↗

Mechanical properties of the lung in extrinsic allergic alveolitis.

The lung function of 14 patients with extrinsic allergic alveolitis caused by exposure to mouldy hay (farmer's lung) or to birds (bird fancier's lung) was studied one week and four to six weeks after the last exposure to antigen. These data, together with lung mechanics measured four weeks after antigen exposure, were compared with measurements in 34 healthy non-smoking control subjects. Shortly after exposure to antigen there were reduction in lung volumes, increased elastic recoil (reduced compliance), and varied effects on expiratory flow and reduced gas transfer. With time, lung volumes and gas transfer improved, but expiratory flow often remained decreased. The data on lung mechanics showed that reduced compliance was often found, but this increased recoil did not always produce high airflow indicating increased upstream airways resistance. Patients with a longer duration of the illness tended to have increased compliance (reduced recoil) and low airflow. These results show that the described pathological changes of airway involvement, fibrosis, and emphysema in allergic alveolitis are manifest in the lung function of patients with the disease.

Adult↗

Prevalence of respiratory abnormalities in a rural and an urban community.

Population samples stratified on sex, age and smoking habits were studied in a rural and an urban community with a low level of air pollution to establish "normal" values of parameters derived from the single-breath N2 curve, the effect of smoking on these parameters, and any differences related to an urban or rural environment. Respiratory symptoms and past illnesses, smoking habits, and residential as well as occupational history were obtained by a respiratory questionnair. Pulmonary function was assessed by the single-breath N2 test and the forced vital capacity maneuver. In "healthy" nonsmokers, residual volume/total lung capacity, closing volume/vital capacity on expiration, and closing capacity/total lung capacity were significantly related to age. The slope of phase III was related to neither height nor age. There was no significant difference in prediction equations between the 2 communities for any of these parameters. Multiple regression analysis indicated that smoking had an effect on residual volume/total lung capacity, closing volume/vital capacity on expiration, closing capacity/total lung capacity, and the slope of phase III in both sexes. Abnormal values were more prevalent among male than female smokers in both communities, the highest prevalence being found in the slope of phase III in both sexes (35 to 40 per cent). The slope of phase III and closing capacity/total lung capacity were consistently related to the current number of cigarettes smoked per day.

Adult↗

Extrinsic allergic alveolitis from bird exposure. Studies on the immediate hypersensitivity reaction.

Six patients with extrinsic allergic alveolitis had weak immediate and strong late reactions of intracutaneous injection of bird serum. Biopsy of the late reaction revealed vasculitis and immunoglobulin and complement deposition in one. The antibody responsible for the immediate hypersensitivity could be transferred in serum. It was short lasting (4 hr) and resistant to heat and 2-mercaptoethanol. No evidence of an immediate reaction in the lungs could be detected following inhalation challenge as judged by examination of spirometry, flow volume loops and single breath nitrogen washout curves.

Adolescent↗

Measurement of 'closing volume' initiated from functional residual capacity.

Comparison of the nitrogen method closing volume (CV) test, with oxygen inspiration initiated at residual volume (RV method) and functional residual capacity (FRC method), was made in 91 seated normal subjects. For RV and FRC methods, respectively CV%VC (mean+/-SD) was 14.4% (+/-6.2) and 17.5%(+/-7.5) (P=0.005); slope of Phase III of CV trace was 0.99% N2/1 (+/-0.76) and 1.66% N2/1(+/-1.07) (P=0.005); size of cardiogenic oscillations was 1.05% N2(+/-0.42) and 1.21% N2(+/-0.40) (P=0.001). These data confirm earlier predictions, based on a calculated increased lung top to bottom N2 gradient in the FRC method. Support for this mechanism was obtained in 5 additional normal subjects in whom the increased CV%VC, slope of Phase III and size of cardiogenic oscillations with the FRC method were eliminated when the top-to-bottom N2 gradient was reduced by breathing a reduced FIN2. Measurements made using the classical RV method cannot be directly compared to those using the FRC method.

Adult↗

The effect of acute, intensive cigarette smoking on maximal expiratory flows and the single-breath nitrogen washout trace.

The effect of acute, intensive cigarette smoking on forced vital capacity and the single-breath expired N2 trace was studied in 82 smokers. There were significant decreases in the "effort-dependent" tests, such as peak flow and 1-sec forced expiratory volume, but no change in the more "effort-independent" tests, such as maximal mid-expiratory flow and maximal expiratory flow at 25 per cent of the vital capacity. Closing volume was unchanged in absolute terms and as a percentage of vital capacity. Closing capacity was unchanged in absolute terms and as a percentage of total lung capacity, but there was a significant increase in the slope of Phase III of the N2 washout curve after the acute smoking session. The tests of function that changed significantly after acute, intensive smoking were the ones that improved in 52 subjects who modified their smoking habits. The data suggest that acute, intensive cigarette smoking may be associated with an increase in resistance to air flow in the larger airways or a reduction in effort, and with increased nonuniformity of intraregional distribution of ventilation.

Adult↗