Biomedical subjects

D G Frazer

Publications and source records attributed to D G Frazer.

At least 55 records · Page 3Linked to original sources

PubMed1992

Risks of keratitis and patterns of use with disposable contact lenses.

Disposable soft contact lenses have been marketed as a safer alternative to conventional soft lenses. We undertook a case-control study of patients attending the casualty unit of an eye hospital to quantify the relative risk of keratitis in disposable lens wear and to establish associated patterns of use. All eligible contact lens users were identified and asked to complete a questionnaire (n=242). Keratitis, microbial or sterile, was the most common complication in disposable lens users, occurring in 16 of 41 subjects. The relative risks for all lens types were estimated by comparison with rigid lenses (the referent). Both extended- and daily-wear disposable lenses were associated with higher risks of keratitis than other lens types including conventional extended-wear lenses. Poor hygiene, disinfectant system failure, and lens type may all account for these statistically significant trends.

Acanthamoeba Keratitis↗

PubMed1992

Influence of epithelium on the reactivity of guinea pig isolated, perfused trachea to bronchoactive drugs.

The mechanisms by which the epithelium affects reactivity of guinea pig trachealis to agonists were examined using the isolated, perfused trachea preparation. Contractile agonists (acetylcholine, methacholine, carbachol or histamine) were more potent when applied to the serosal (extraluminal, EL) surface compared to the mucosal (intraluminal, IL) surface, and the IL maximum responses to these agents were smaller. In epithelium-denuded tracheae, IL reactivity to the agonists was increased to the EL level. Physostigmine (10(-7) M) increased the EL and IL potency of acetylcholine to that of carbachol (+/- epithelium), and elevated the IL acetylcholine maximum response (+ epithelium); the relative role of epithelial acetylcholinesterase could not be defined. Indomethacin (3 x 10(-6) M) increased, in an epithelium-dependent manner, the IL acetylcholine, carbachol and histamine maximum responses to the EL level. Phentolamine plus propranolol (both 10(-6) M) potentiated the IL maximum response to methacholine, Isoproterenol also was more potent extraluminally than intraluminally, and the EL and IL maximum responses were similar. IL isoproterenol reactivity was elevated to the EL level in rubbed tracheae. Corticosterone (5 x 10(-5) M) potentiated EL and IL responses to isoproterenol (+/- epithelium); the relative role of epithelial extraneuronal uptake could not be delineated. The epithelium reduces reactivity to mucosally applied drugs by acting as a diffusion barrier. In addition, responses to mucosally administered contractile agonists are inhibited by a physiological antagonism caused by modulatory prostanoids, catecholamines and, possibly, epithelium-derived relaxing factor.

Animals↗

PubMed1991

Inhibition of stimulant-induced activation of phagocytic cells with tetrandrine.

Tetrandrine is an alkaloid obtained from the root of a medicinal herb which is employed in China as a treatment for silicosis. One proposed mechanism for the development of silica-induced fibrosis is lung damage resulting from particle-induced inflammation and secretion of reactive compounds from alveolar phagocytes. Therefore, the objective of the present study was to determine if tetrandrine exhibited the ability to inhibit respiratory burst activity of pulmonary phagocytes. The data indicate that although tetrandrine is not cytotoxic to phagocytic cells, it is a potent inhibitor in vitro of zymosan-stimulated oxygen consumption, superoxide anion release, and hydrogen peroxide secretion by alveolar macrophages. Tetrandrine is also effective in vivo in preventing activation of alveolar macrophages after inhalation or intratracheal instillation of silica. Tetrandrine also inhibits stimulant-induced chemiluminescence by polymorphonuclear leukocytes. Since tetrandrine does not alter stimulant-induced depolarization of phagocytic cells, its inhibitory action is not via interference with receptor-ligand binding but rather must occur elsewhere in the stimulus-secretion coupling scheme.

Alkaloids↗

PubMed1990

Reactivity of guinea-pig isolated trachea to methacholine, histamine and isoproterenol applied serosally versus mucosally.

Guinea-pig tracheas were perfused with recirculating modified Krebs-Henseleit solution while monitoring changes in inflow-outflow pressure difference, which is an index of trachealis muscle tone. The reactivities of the trachealis muscle to methacholine, histamine and isoproterenol applied separately to the mucosal (intraluminal, IL) or serosal (extraluminal, EL) compartments were compared, and evidence for the agonist-induced release of epithelium-derived relaxing factor (EpDRF) was sought. All agents were more potent when added to the EL compartment, but the IL/EL EC50 ratios were different: 100 for methacholine, 41 for histamine and 25 for isoproterenol. Methacholine or histamine added to the IL compartment, after the preparations were pre-contracted with the same concentration of the agonist or 30 mM KCl added EL, did not result in relaxation. Likewise, IL isoproterenol did not evoke contraction. IL KCl evoked relaxation. The results indicate that the epithelium reduces access of bronchoactive agents to the muscle, while an immediate relaxant effect of EpDRF released by agonists could not be demonstrated.

Animals↗

PubMed1987

Ghost cell glaucoma in phakic eyes.

We report 3 cases of ghost cell glaucoma all of which occurred in phakic patients with onset between 18 months and 4 years after vitreous haemorrhage. There appears to have been spontaneous disruption of the anterior hyaloid face in all 3 cases. Control of the glaucoma was achieved by medical treatment in one case and by trabeculectomy in two.

Glaucoma↗

PubMed1987

Trichothecene mycotoxins in aerosolized conidia of Stachybotrys atra.

Stachybotrys atra is the etiologic agent of stachybotryotoxicosis, and this fungus and its trichothecene mycotoxins were recently implicated in an outbreak of unexplained illness in homes. S. atra was grown on sterile rice, autoclaved, dried, and then aerosolized by acoustic vibration. The distribution of particles (mass and number) was monitored on an aerodynamic particle sizer interfaced with a computer. Dust was collected on preweighed glass-fiber filters and extracted with 90% aqueous methanol. Extracts were tested for the ability to inhibit protein synthesis in rat alveolar macrophages, the ability to inhibit the proliferation of mouse thymocytes, and the presence of specific trichothecene mycotoxins. Virtually all of the particles were less than 15 micron in aerodynamic diameter, and the mass median diameter was 5 micron. Thus, most of the particles were respirable. Microscopic analysis of the generated dust revealed that ca. 85% of the dust particles were conidia of S. atra, another 6% were hyphal fragments, and the remainder of the particles were unidentifiable. Thus, greater than 90% of the particles were of fungal origin. The extracts strongly inhibited protein synthesis and thymocyte proliferation. Purified satratoxin H was also highly toxic in the same systems. Each of the individual filters contained satratoxin H (average, 9.5 ng/mg of dust). Satratoxin G and trichoverrols A and B were found in lesser amounts in some, but not all, of the filters. The limit of analysis is ca. 50 ng. These results establish that the conidia of S. atra contain trichothecene mycotoxins. In view of the potent toxicity of the trichothecenes, the inhalation of aerosols containing high concentrations of these conidia could be a potential hazard to health.

Aerosols↗

PubMed1986

Compression keratopathy.

A 31-year-old man developed a localized corneal epithelial lesion after exposure to a high-pressure fire extinguisher jet. Visual acuity was temporarily decreased from 20/20 to 20/40 and intraocular pressure was increased to 28 mm Hg. Both values returned to normal within 18 hours after treatment. This represents an extreme form of anterior corneal mosaic associated with microsplits of the corneal epithelium.

Adult↗

PubMed1986

Comparison of lung sounds and gas trapping in the study of airway mechanics.

We have previously shown that gas is trapped in isolated animal lungs and have proposed that this gas-trapping process is related to meniscus formation in the small airways of the lung. The purpose of this investigation was to compare how the lung sound-generation process and the gas-trapping process are related to airway mechanics and each other. Rats were anesthetized, the heart and lungs were removed en bloc and placed in a liquid-filled plethysmograph. Lung sounds were recorded by using a microphone acoustically coupled to the tracheal cannula. The results show that discontinuous lung sounds in the form of crackles occur during lung inflation at the same time gas trapping takes place.

Animals↗

PubMed1985

Evidence of sequential opening and closing of lung units during inflation-deflation of excised rat lungs.

In this study we propose a descriptive model of the events occurring in an excised lung during an inflation-deflation cycle. The model was developed by observing changes in small pressure-volume loops superimposed on quasistatic pressure volume curves. It was found that the shape of the small loops during lung inflation was a function of the previous end-expiratory pressure. These experimental results could most easily be explained by a model of the lung in which individual lung units open sequentially as the lung is inflated. During sequential recruitment, individual lung units open quickly to a volume determined by the transpulmonary pressure. The units then homogeneously increase and decrease in size according to pressure-volume curves similar to the deflation curve of the entire lung. Once lung units have been recruited, they remain open until the lung has been deflated to end-expiratory pressures below 3-4 cm H2O. Reducing the end-expiratory pressure to lower values causes additional derecruitment of lung units until a transpulmonary pressure of 0.0 to -1.0 cm H2O has been reached.

Animals↗

PubMed1985

Effects of a two-year inhalation exposure of rats to coal dust and/or diesel exhaust on tension responses of isolated airway smooth muscle.

This study was performed to determine whether chronic inhalation exposure of rats to levels of coal dust (CD) and/or diesel exhaust (DE) similar to those experienced by underground miners affects the pharmacologic characteristics of the animal's airway smooth muscle. Animals were exposed for 2 yr to CD alone (2 mg/m3 of respirable particulates), DE alone (2 mg/m3 of respirable particulates), or CD and DE (CD + DE) in combination (1 mg/m3 CD plus 1 mg/m3 DE). Concentration-response relationships for tension changes induced with acetylcholine, 5-hydroxytryptamine, potassium chloride, and isoproterenol were assessed in vitro on isolated preparations of rat airway smooth muscle (trachealis). Compared with control animals, the maximal contractile responses to acetylcholine of tissues from CD-, DE-, and CD + DE-exposed animals were significantly increased; the effects of CD and DE exposure were additive. The CD + DE exposure, but not the individual treatments, resulted in a significant increase in the maximal relaxation response elicited by isoproterenol; this interaction may have resulted from the addition of, or the synergism between, the nonsignificant effects of CD and DE alone. No treatment altered the sensitivity (EC50 values) of the muscles to the agonists used. The results indicate that chronic exposure to CD, DE, and CD + DE produces differential modifications in the behavior of rat airway smooth muscle. These findings may have some bearing on humans exposed to these substances.

Administration, Intranasal↗

PubMed1984

Regional differences in gas trapping (airway closure) between apex and base of excised rat lungs.

Excised rat lungs were ventilated with air under three conditions: (a) while suspended by the trachea and surrounded by air, (b) while inverted and surrounded by saline, and (c) while upright and surrounded by saline. The distribution of transpulmonary pressures over which gas trapping occurred in the lung for each of the three conditions was found by a method previously described by Frazer et al. (1979). A distribution having a small standard deviation (SD) indicates more uniform gas trapping in the lung while a larger SD indicates less uniform gas trapping. Results showed that the SD was 0.63 for the inverted lung in saline, 1.10 for the lung in air, and 1.57 for the upright lung in saline. We conclude that gas trapping in lungs inverted in saline occurs more uniformly than gas trapping in lungs in air or upright in saline. The results obtained in saline in the upright and inverted position also imply that as the lung is deflated surrounded by air, gas trapping initially occurs in the base of the lung before it occurs in the apex. Since gas trapping and airway closure are related, there could also be intrinsic dissimilarities in airway closure between the apex and base of excised rat lungs suspended by the trachea in air.

Animals↗

PubMed1982

The effect of temperature on gas trapping in excised lungs.

In this study the effect of temperature on gas trapping in excised lungs was examined with two types of experiments in rats. In the first, changes in gas trapping following ten successive inflation-deflation cycles at the same constant ventilation rate were examined at 17, 27, 37 and 42 degrees C. In the second, the effects of five different ventilation rates at temperatures of 17, 27 and 37 degrees C were determined. The fraction of gas trapped in lungs repeatedly ventilated for ten inflation-deflation cycles at constant ventilation rates remained nearly constant with time at 17 and 27 degrees C but decreased with time at 37 and 42 degrees C. The amount of gas trapped in the lung at 27 degrees C fell with the logarithm of increasing ventilation rate. Lowering the temperature shifted this relationship toward lower ventilation rates while increasing the temperatures caused an apparent shift toward higher ventilation rates.

Animals↗

PubMed1981

Trapped gas and lung hysteresis.

The amount of gas trapped in excised rat lungs was determined after four inflation-deflation cycles between total lung capacity (TLC) and several end-expiratory volumes or end-expiratory pressures. Lungs ventilated in this way exhibited pressure-volume curves that formed closed loops with varying degrees of hysteresis. The area of these loops was highly correlated with the amount of gas trapped in the lungs. Trapped gas volume and hysteresis increased with deflation to increasingly lower end-expiratory volumes or pressures. The processes responsible for lung hysteresis, however, seem to be primarily dependent upon end-expiratory pressure and only slightly dependent upon end-expiratory volume. A possible explanation of these findings is that menisci, formed in the small airways of the lung during deflation at low lung volumes, are responsible for both the trapped gas and the pressure-volume hysteresis of the lung.

Airway Resistance↗

PubMed1980

The effects of several gases (He, N2, N2O, and SF6) on gas trapping in excised lungs.

Rat lungs were ventilated in a saline filled plethysmograph with the trachea attached to a cannula extending through the chamber base. Because it was possible to connect the cannula to an anesthesia bag, the gases used to ventilate the lungs could easily be controlled. During the first part of the study, lungs were inflated-deflated at different rates for 10 cycles with one of four different gases (SF6, N2, He, or N2O). It was found that all gases were trapped at very slow ventilation rates. As the rates were increased, however, the amount of gas trapped in the lungs decreased at ventilation rates which were characteristic of each particular gas. Gas trapping decreased first in lungs ventilated with SF6, then N2, He, and finally N2O. The amount of gas trapped in the lungs at a given inflation-deflation rate was related to the solubility of the gas divided by the square root of its molecular weight. During the second part of the study the effect of different mixtures of SF6 and O2 on the amount of gas trapped was examined. All the results indicated that diffusion of gases through liquid walls of menisci or bubbles that occlude the airways is responsible for trapped gas in excised lungs.

Animals↗

PubMed1980

Lung degassing: an evaluation of two methods.

This study compares the effectiveness of the oxygen absorption and vacuum degassing methods for removing trapped gas from lungs. In addition, the effects of changing vacuum pressure, number of times to degas, and lung orientation during the vacuum degassing procedure were evaluated. To evaluate the two methods, a capacitance spirometer was designed and constructed to record lung volume as lungs were vacuum degassed. When lungs containing trapped gas were degassed in a vacuum chamber, they initially expanded, then slightly decreased in volume until the vacuum was released. Lung volume rapidly decreased as the pressure in the vacuum chamber returned to ambient pressure. The results showed that oxygen absorption atelectasis was more effective in removing gas from the lungs than vacuum degassing the lungs. When vacuum degassing was use, it was found to be most effective when the pressure in the chamber was reduced to the vaporization pressure of H2O and when the lungs were degassed twice. Degassing the lungs more than twice did not significantly remove more gas from the lungs. Lung orientation did not affect the removal of gas during vacuum degassing.

Animals↗

PubMed1979

Meniscus formation in airways of excised rat lungs.

The object of this study was to determine the transpulmonary pressure at which menisci form in the airways of excised rat lungs. The necessary geometric requirements for meniscus formation are normally met in the airways, but a meniscus is presumably prevented from forming at large lung volumes because too little fluid is present. At lower lung volumes a meniscus could form easier since airway caliber is reduced and less fluid is required. A series of pressure-volume curves were recorded for lungs in which meniscus formation was inhibited by increasing the end expiratory pressure. Assuming the number of airways containing at least one meniscus was proportional to the amount of gas trapped in the excised rat lung, it was found that the menisci were formed in 68% of the airways between positive transpulmonary pressures of 1.4 and 3.0 cm H2O during deflation.

Airway Obstruction↗

PubMed1979

The effect of pulmonary edema on gas trapping in excised rat lungs.

The object of this study was to determine how pulmonary edema affects the volume of gas trapped in excised lungs as they are slowly ventilated. In this study trapped gas is defined as the volume of gas that cannot be removed from the lungs with a negative transpulmonary pressure of -5 cm H2O (Frazer and Weber, 1976). Experimental pulmonary edema was produced by ventilating rats using high inspiratory positive pressure breathing (HIPPB) as described by Webb and Tierney (1974). The amount of gas trapped in both edematous and control lungs was then compared as the lungs were inflated-deflated under identical conditions in 6 different 4 cycle sequences. During each sequence the lungs were deflated to an end expiratory pressure of either +6, +4, +3, +2, 0.0, or -5 cm H2O. It was found, that gas became trapped at more positive values of end expiratory pressure in lungs having pulmonary edema than in control lungs. These results were interpreted as evidence that the airways close sooner, at more positive transpulmonary pressures, in edematous lungs than in control lungs.

Animals↗

PubMed1979

Trapped gas at maximum lung volume in intact isolated rat lungs.

Excised rat lungs were ventilated with air in a liquid filled plethysmograph that was enclosed in a large pressure chamber, C(B). The lungs were inflated then deflated by removing or adding saline to the plethysmograph while the trachea was attached to a cannula extending through the plethysmograph base. In this system, tracheal pressure, Pao, was equal to gas pressure inside C(B). The gas pressure was held constant at either ambient pressure (Pamb), Pamb + 350 Torr, or Pamb - 350 Torr. When excised lungs were ventilated slowly from their atelectatic state for 10 inflation-deflation cycles with Pao equal to any one of the three pressures, an equivalent amount of gas was trapped in the lungs. If after 10 cycles, however, lungs containing trapped gas were inflated and held at maximum lung volume, the trapped gas spaces could be made to expand in response to rarefaction or compression of the tracheal gas. The amount of expansion and contraction of the trapped gas spaces demonstrates that trapped gas is likely trapped between menisci of a foam that occlude the alveoli or small airways.

Animals↗