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Biomedical subjects

M S Morgan

Publications and source records attributed to M S Morgan.

At least 73 records · Page 4Linked to original sources

The effects of ozone and nitrogen dioxide on lung function in healthy and asthmatic adolescents.

The aim of this project was to investigate whether or not well characterized groups of healthy adolescents and adolescents with asthma differed in their sensitivity to ozone and nitrogen dioxide at near ambient concentrations of these pollutants. The project was divided into three phases. In each phase, ten healthy and ten asthmatic adolescents were exposed via a mouthpiece to three different atmospheres (filtered air, ozone, and nitrogen dioxide, at either 0.12 or 0.18 ppm) on separate days at least one week apart. During Phase I, subjects at rest inhaled the test atmospheres at 0.12 ppm for two 30-minute periods. The following pulmonary functional values were measured before, during, and after exposure: peak flow, total respiratory resistance, thoracic gas volume at functional residual capacity, maximal flow at 50 and 75 percent of expired vital capacity (performed with both room air and a helium-oxygen mixture), and forced expiratory volume in one second. Pulmonary function was not consistently altered in either the asthmatic or the healthy nonasthmatic adolescents as a result of the exposures. As a result, the study was repeated with the addition of ten minutes of exercise to the 30-minute rest exposure period (Phase II). In Phase II, small but significant increases in total respiratory resistance to all test atmospheres were seen after exposure at 0.12 ppm during exercise in both healthy and asthmatic adolescents. However, the increase in resistance between the groups of subjects was not statistically different. On the basis of these results, Phase III was conducted at higher concentrations of the pollutants (0.18 ppm). In Phase III, statistically significant changes were seen in average total respiratory resistance values in both healthy and asthmatic adolescents exposed to 0.18 ppm ozone while exercising. Again, the difference between the groups was not significant. Small decreases in average forced expiratory volume were found in healthy subjects exposed to ozone and filtered air. After exposure to nitrogen dioxide there was a 3 percent decrease in the forced expiratory volume in one second in asthmatic subjects. This change was not significant. It is concluded that there were no differences in pulmonary function responses between asymptomatic, allergic asthmatic adolescents and healthy adolescents exposed to either ozone or nitrogen dioxide under the conditions of these studies. However, an increase in total respiratory resistance was observed in both asthmatic and healthy adolescent subjects after their exercise exposure to 0.18 ppm ozone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Overall and regional lung function in dogs exposed acutely to ozone.

Regional distribution of ventilation and overall function of the lungs were compared in anesthetized, paralyzed, mechanically ventilated dogs exposed to ozone. Three animals were exposed at each concentration (0,0.13,0.22, and 0.45 ppm ozone) for 3 hr. There were no significant changes in pulmonary flow resistance, dynamic compliance, or flow rates derived from maximum forced expiratory maneuvers. The distribution of inspired gas was determined using air containing 13N and a positron camera to follow wash-in in each of 80 or more regions of the lung. The mean wash-in time (T) and its standard deviation did not change in sham-treated dogs, but T increased by 40 to 100% in exposed animals. Dogs showing increases in T also had increased frequency dependence of compliance (correlation significant at P less than 0.05). The changes in 13N wash-in reflected less uniform distribution of ventilation, with the greatest disparity occurring between central and marginal regions. Altered regional mechanical function, in the absence of overall changes, suggested that the initial effect of ozone was on the small airways. The measurement may be a sensitive indicator of acute irritation in the lung periphery.

Animals↗

Upper respiratory irritation from controlled exposure to vapor from carbonless copy forms.

Exposure to carbonless copy forms has been associated with subjective reports of respiratory and skin irritation, but objective measurements of human reactions to exposure are lacking. Thirty workers with complaints of prior sensitivity to the forms were given brief, controlled exposure to vapors from carbonless forms and from bond paper in random, single-blind fashion. Nasal impedance increased 34% after exposure to carbonless forms (P less than .025) and rose 8% after exposure to plain paper (P greater than .10). However, frequency of symptoms did not differ between the two exposure modes, and was not correlated with the nasal measurements. Quantitation of nasal congestion by this technique may be a sensitive measure of short-term reaction to inhalation of irritants.

Adult↗

Role of membranes and energy-producing reactions in cellular processing of insulin in primary cultures of rat hepatocytes.

Incubation of primary cultures of rat hepatocytes with the local anesthetics, procaine or lidocaine, had little or no effect on insulin uptake or degradation but caused an inhibition of insulin-stimulated glycogenesis. While exposure of cultures to the amines, monodansylcadaverine or CH3NH2, resulted in significant dose-dependent decreases in glycogenesis, only monodansylcadaverine (an inhibitor of receptor clustering) decreased uptake whereas CH3NH2 (a lysosomotropic agent) caused increases in both insulin uptake and degradation. When cells were treated with agents which inhibit glycolysis (NaF, 2-deoxy-D-glucose) or oxidative metabolism (2,4-dinitrophenol, carbonyl cyanide m-chlorophenyl hydrazone, NaN3, antimycin A), pronounced inhibitions of each of the bioactivities studied (syntheses of glycogen, protein, lipid) were observed, but only the glycolytic inhibitors decreased insulin uptake. These results suggest that insulin is internalized by an endocytotic process involving receptor clustering and requiring metabolic energy derived from glycolysis. The post-receptor biosynthetic processes involved in the expression of the biological activities of insulin (syntheses of glycogen, protein, lipid) require energy produced by oxidative metabolism while the degradation of insulin is carried out by nonlysosomal mechanisms which are not energy-requiring.

Amines↗

Participation of cellular thiol/disulphide groups in the uptake, degradation and bioactivity of insulin in primary cultures of rat hepatocytes.

The effects on the uptake (cell-associated 125I) and degradation (125I-labelled products released into the medium) of 125I-insulin and bioactivity (protein, glycogen and lipid synthesis) of insulin caused by altering the cellular thiol/disulphide status in primary cultures of rat hepatocytes were studied. Incubation of hepatocyte cultures with various exogenous thiol compounds (reduced glutathione, 2-mercaptoethanol, cysteamine, dithiothreitol) resulted in increased insulin binding, but markedly decreased degradation and bioactivity. These effects could be reversed by washing or by the addition of oxidized glutathione, which alone had no effect. When cultures were exposed to certain thiol-modifying reagents (N-ethylmaleimide, p-chloromercuribenzoate, p-chloromercuribenzenesulphonate, iodoacetamide, iodoacetate), some decreases in bioactivity were evident, but the pronounced decrease in insulin degradation observed with the thiol-containing compounds was not observed with this class of compounds. None of the thiol-containing or -modifying agents tested had any significant effect on cellular ATP concentrations, indicating that the effects observed were due to perturbation of the thiol/disulphide status. Depletion of intracellular glutathione by DL-buthionine SR-sulphoximine (a specific inhibitor of glutathionine biosynthesis) decreased the syntheses of glycogen and lipid by about one-half, while having essentially no effect on protein synthesis, ATP concentrations or on the binding and degradation of insulin. The data presented here indicate that although intracellular thiol (glutathione) concentrations may be important for the maintenance of full expression of certain biological activities (glycogen and lipid synthesis), the thiol/disulphide groups on the cell surface and those immediately inside the cell membrane may be more critical in the mediation of insulin action, including the degradation and bioactivity of insulin in primary cultures of rat hepatocytes.

Animals↗

Induction of eustachian tube dysfunction with histamine nasal provocation.

This study assessed changes in nasal airway resistance and nasal airway power as well as eustachian tube function after histamine nasal provocation in 12 atopic subjects and 10 nonatopic subjects. Results demonstrated that subjects could not be placed in the atopic or nonatopic group on the basis of prechallenge nasal resistance and power measurements. Atopic subjects demonstrated a statistically significant difference in nasal airway power after histamine provocation (p less than 0.05). Nine of 12 atopic subjects demonstrated tympanometric changes indicative of eustachian tube dysfunction, whereas none of 10 nonatopic subjects had these changes (p less than 0.001). These results suggest a differential sensitivity of nonatopic and atopic individuals to histamine, which may be an important pathogenetic mechanism leading to the development of eustachian tube dysfunction and possible subsequent development of otitis media with effusion in the atopic group.

Adult↗

The effects of sulfur oxides on nasal and lung function in adolescents with extrinsic asthma.

Ten adolescent subjects with extrinsic asthma were exposed during intermittent exercise to filtered air, 0.5 ppm of sulfur dioxide (SO2), or 100 micrograms/m3 of sulfuric acid (H2SO4) on 5 separate days. The purpose of the study was to compare changes in nasal power (the work of nose breathing) with pulmonary functional changes depending on the route of inhalation of the sulfur oxide pollutants, oral inhalation through a rubber mouthpiece or oronasal inhalation via a face mask. Nasal power was measured with a modified skin diving mask equipped with two differential pressure transducers. Statistically significant changes in total respiratory resistance, FEV1, and maximum flow calculated at 50% and 75% vital capacity were observed after all exposures to SO2 and H2SO4. The magnitude of change in FEV1 and maximum flow calculated at 50% vital capacity was higher after oral compared to oronasal inhalation of SO2. The nasal work of breathing increased 32% after SO2 exposure by mouthpiece and 30% after SO2 exposure via face mask (p less than 0.05). The nasal power changes after the H2SO4 exposures were not different from the sham exposures. We conclude that oronasal inhalation of 0.5 ppm of SO2 produces a significant increase in the nasal work of breathing and that the route of exposure reduces but does not eliminate the lower airway reactions observed on oral exposure.

Adolescent↗

Acute effects of 0.12 ppm ozone or 0.12 ppm nitrogen dioxide on pulmonary function in healthy and asthmatic adolescents.

Adolescent asthmatic subjects have been shown to be much more sensitive than healthy adolescents to the inhaled effects of sulfur dioxide. To test whether similar adolescent asthmatics are more sensitive to other common ambient air pollutants, 10 healthy and 10 asthmatic adolescent subjects were exposed for 60 min to filtered air, 0.12 ppm ozone (O3), and 0.12 ppm nitrogen dioxide (NO2) on separate days at rest. The following pulmonary functional values were measured before, at 30 min, and after 60 min of exposure: peak flow, total pulmonary resistance (RT), thoracic gas volume at functional residual capacity (FRC), maximal flow at 50 and 75% of expired vital capacity (Vmax50 and Vmax75), and forced expiratory volume in one second (FEV1). Following 60 min of exposure at rest to low concentrations of O3 or NO2, there were no consistent significant functional changes in either healthy or asthmatic adolescent subjects. There also were no measurable differences between the 2 groups.

Adolescent↗

Standard threshold shift criteria. An investigation of the most reliable indicator of noise-induced hearing loss.

Definition of a standard threshold shift (STS) and its use as an early indicator to identify those employees with deteriorating hearing are necessary aspects of hearing conservation programs in industry. STS criteria were evaluated using techniques borrowed from decision theory and signal detection theory to separate audiometric threshold shifts into true-positive and false-positive shifts. The current Occupational Safety and Health Administration definition of a "change in hearing threshold relative to the baseline audiogram of an average of 10 dB or more at 2, 3 or 4 kHz in either ear" and the American Academy of Otolaryngology-Head and Neck Surgery recommendation of a "10 dB or greater change for the worse for either the 0.5, 1, 2 kHz pure tone average or the 3, 4, 6 kHz pure tone average, in either ear" were supported. Revision of baselines after an STS occurs is recommended.

Audiometry↗

Some observations on frequency of respirator fit tests.

Quantitative respirator fit tests were repeated with workers who had demonstrated adequate fit initially. As the interval between first and second tests increased, it was expected that the rate of failure (penetration of test aerosol greater than 1%) on the second test also would increase. No significant time relationship was demonstrated, but the results suggest that the opposite of our expectation occurred: failure rates decreased with longer time intervals. If confirmed, the results suggest a simple strategy for repeat fit testing.

Humans↗

Permeation through five commercially available glove materials by two pentachlorophenol formulations.

Five glove materials were tested for permeation by two commonly used formulations of pentachlorophenol (PCP). Permeation was conducted using the method used in two prior studies by NIOSH. The lower limit of PCP quantitation in the receiving side of the permeation cell was 70 parts per billion (ppb). When challenged with a 4.3% PCP in diesel oil solution, both the Dayton Flexible Products Triflex (PVC) and the Best 64 NFW (natural rubber) gloves exhibited breakthrough times thirty seconds after exposure. The Playtex #835 (latex/neoprene) glove exhibited breakthrough after sixty minutes, but showed a five fold greater rate of permeation than the Dayton and the Best glove. Neither the Edmont Sol-Vex (nitrile rubber) nor the Granet Glo-Gluv (PVC) gloves had been permeated after testing for 8 and 16 hours respectively. Following challenge with a 4.2% sodium pentachlorophenate solution, only the Best (natural rubber) glove allowed breakthrough; this only thirty seconds after exposure. Neither the Dayton (5 hours), Playtex (7.5 hours), Edmont (15.5 hours), nor Granet (15.5 hours) gloves had been permeated following completion of testing after the listed duration. This study has shown that different gloves offer differing resistance to permeation by PCP based upon the composition of the glove and the PCP formulation tested.

Chlorophenols↗

Measurements of respiratory ammonia and the chemical neutralization of inhaled sulfuric acid aerosol in anesthetized dogs.

The extent of neutralization of inhaled H2SO4 aerosol by endogenous NH3 has been measured in the surgically isolated upper airways of anesthetized dogs. Neutralization was observed to be inversely proportional to particle size. The H2SO4 particles with initial dry diameters of 0.5 micrometer and 1.0 micrometer underwent 0.28 (+/- 0.08) and 0.06 (+/- 0.06)% neutralization per ppb of laryngeal NH3, respectively, during passage through the mouth and out of the larynx at a flow of 0.1 L/s. At either particle size, neutralization is related to the route of entry, being greater for entry via the mouth than the nose. Limited measurements for entry via the mouth show more neutralization of 0.7 micrometer particles at 0.1 L/s than at 0.2 L/s. These results are consistent with a reaction that is limited by the rate of NH4 diffusion to the particle's surface.

Aerosols↗

Relationship of central and peripheral airway resistance to lung volume in dogs.

We could not reconcile reported relationships between lung resistance measurements and lung volume with bronchographic and anatomic studies showing that airway diameters change monotonically with lung volume and that small airways change diameter proportionately at least as much as large ones. Accordingly we measured central and peripheral airways resistances with a new technique. The relevant pressures were measured with a tracheal cannula, a wedged retrograde catheter, and two parenchymal needles in seven open-chested dogs while pleural pressure was oscillated at 1 Hz. In contrast to previous studies, the volume dependency of peripheral resistance was at least as great as that of central resistance with vagi intact, the volume dependencies of central and peripheral resistances were not abolished by vagotomy, and neither resistance increased systematically at high volumes. Volume dependency of central resistance resembled predictions for isotropic expansion of airways with vagi cut but increased with bronchomotor tone. These results fit generally with bronchographic data. Previous studies may have been affected by volume dependency due to "tissue resistance" and catheter phase lags.

Airway Resistance↗

In vivo tissue reactivity of radiation-cured silicone rubber implants.

Silicone rubber implants are clinically used in large numbers and elicit a milk tissue reaction. An occasional patient develops an accentuated reaction, an observation which has stimulated clinicians to try to understand this process more fully. The chemistry of medical silicone implants, including quantitative composition, is reviewed. This in vitro laboratory study show less tissue reaction-cured silicone with SiO2 filler. A proposed system for fabrication and curing of a silicone implant, with the qualities of strength and diminished tissue reactivity, is discussed.

Animals↗