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Biomedical subjects

D J Riley

Publications and source records attributed to D J Riley.

At least 91 records · Page 5Linked to original sources
PubMed1982

beta-Aminopropionitrile prevents bleomycin-induced pulmonary fibrosis in the hamster.

beta-Aminopropionitrile (beta APN), an agent that prevents collagen accumulation in tissues, was evaluated for its ability to prevent excess collagen formation in bleomycin-induced pulmonary fibrosis in the hamster. Two groups of animals received a single endotracheal dose of bleomycin; one of these was injected with beta APN twice daily for 30 days. A third group received endotracheal saline and a fourth group received saline and beta APN. After 30 days, we measured pressure-volume curves of saline-filled lungs, collagen content, and degree of fibrosis. Endotracheal bleomycin increased collagen content, decreased lung volume, and produced fibrosis and a mortality rate of 51%. The administration of beta APN to bleomycin-treated animals prevented excess collagen accumulation and diminished total protein, reversed volume diminution, produced less fibrosis, and improved the mortality rate to 24%; beta APN alone had no effect on lung mechanics or collagen content. The biochemical, functional, and structural features of bleomycin-induced lung fibrosis are amenable to control with beta APN.

Aminopropionitrile↗
PubMed1981

Prevention of bleomycin-induced pulmonary fibrosis in the hamster by cis-4-hydroxy-l-proline.

We investigated the effect of the proline analogue cis-hydroxyproline on pulmonary fibrosis produced by intratracheal administration of bleomycin in hamsters. Two groups of animals received a single dose of bleomycin; one of these groups was also injected with cis-hydroxyproline twice daily for 30 days. Control animals received intratracheal saline. Lungs were examined on day 30. In the bleomycin group, the collagen content of lungs was 131% of the control value (p less than 0.05). Administration of cis-hydroxyproline decreased collagen accumulation to 114% of the control value (p less than 0.05). Pressure-volume curves were significantly shifted downward and to the right of control in the bleomycin group; this shift was partially prevented by cis-hydroxyproline. Morphometric studies showed that alveolar walls comprised 15% of the lung parenchyma in the control group and 19% in the bleomycin group (p less than 0.05). Administration of cis-hydroxyproline significantly decreased alveolar walls to 16% of the lung parenchyma (p less than 0.05). We conclude that cis-hydroxyproline partially prevents the chemical, structural, and functional changes of bleomycin-induced pulmonary fibrosis in the hamster.

Animals↗
PubMed1980

Prevention of collagen deposition following pulmonary oxygen toxicity in the rat by cis-4-hydroxy-L-proline.

Exposure of rats to high oxygen tensions causes increased collagen content of lungs and alveolar enlargement in 3-6 wk. We tested whether cis-hydroxyproline, a proline analogue that inhibits collagen synthesis, could prevent the collagen accumulation and alveolar enlargement. Rats were exposed to hyperoxia for 60 h and then to room air and hyperoxia for alternate 24-h periods for 11.5 d. Treated oxygen-exposed rats received 200 mg/kg cis-hydroxyproline twice daily over the 14-d exposure period. Control rats breathed room air. Examination of lungs on day 14 showed collagen content of oxygen-exposed lungs to be 48% greater than control (P < 0.05). The collagen content of the treated oxygen-exposed lungs was -12% of control (NS). Total lung volume was 16% greater than control in oxygen-exposed rats (P < 0.05) and 8% greater than control in treated oxygen-exposed rats (NS). Morphometric studies showed alveolar size was greater than control in oxygen-exposed rats (188+/-11 [SE] vs. 143+/-6 mumul [P < 0.05]). Oxygen-exposed, treated rats had a mean alveolar volume of 150+/-7 mumul. Lung pressure-volume curves were significantly shifted to the left of control in the oxygen-exposed rats, whereas the curves of the oxygen-exposed, treated group were identical to control. These data suggest that cis-hydroxyproline prevented the accumulation of collagen in the lungs in pulmonary oxygen toxicity. In addition, there was apparent protection from airspace dilatation and decreased lung elasticity, suggesting that alveolar enlargement after oxygen toxicity is linked to the deposition in lung tissue of new connective tissue fibers.

Animals↗
PubMed1979

Effects of morphine on ventilatory response to exercise.

The effects of analgesic doses of morphine on ventilation, arterial blood gas tensions, chemical control of breathing, and the ventilatory response to exercise were studied in six normal subjects. After administration of 0.2 mg/kg morphine, resting ventilation decreased primarily because of a reduction of tidal volume. Ventilatory responses to carbon dioxide and hypoxia were significantly reduced to one-half and one-third of control, respectively. Ventilatory responses at any given level of exercise were significantly reduced after morphine. However, since oxygen consumption during exercise was similarly reduced after morphine, the relationship between ventilation and metabolic rate during steady-state exercise was not altered by the drug. In addition, morphine prolonged the attainment of steady-state ventilation in four of the six subjects, similar to that reported for chemodenervated subjects. The findings suggest that blunting of chemoreception for hypoxia and hypercapnia has no effect upon the link between metabolic rate and ventilation during steady-state exercise, but the hypoxia chemoreflex may be involved in determining the dynamic characteristics of the response.

Acid-Base Equilibrium↗
PubMed1979

Enhanced responses to aerosolized bronchodilator therapy in asthma using respiratory maneuvers.

To determine if respiratory maneuvers may enhance the response to inhaled bronchodilator drugs, we evaluated the bronchodilator responses when isoproterenol was: inhaled as a bolus high (80 percent VC) compared to low (20 percent VC) lung volumes, and inhaled as a single 800 microgram dose compared to four 200 microgram doses given 20 min apart. Nine asthmatic subjects inhaled isoproterenol sequentially at high and low lung volumes on two separate days; 15 others inhaled single doses of 200, 400, 600, and 800 microgram isoproterenol on four separate days. FEV1, specific conductance (Gaw/VL), Vmax50%, and the slope of phase 3 of the single-breath nitrogen test (deltaN2/L) were measured 10 min after each dose. FEV1 and Gaw/VL increased and deltaN2/L decreased more following inhalation at high compared to low lung volume (P less than 0.05). Gaw/VL increased more in the group given 800 microgram in divided doses than the group given a single dose (P less than 0.05). These findings suggest that the bronchodilator response to isoproterenol may be enhanced by inhaling the drug in divided doses sequentially and by delivering the drug near maximal inspiration. An enhanced response after the latter maneuver may be due to more uniform distribution of the drug to airway receptor sites.

Adult↗
PubMed1977

Blunted respiratory drive in congenital myopathy.

Two patients with clinically mild congenital myopathies presented with chronic respiratory failure. Muscle weakness alone could not account for the respiratory insufficiency since static respiratory pressures were not markedly impaired, ventilation during exercise was normal, and daytime ventilation was normal if ventilatory assistance was provided at night. The ventilatory responses to inhaled carbon dioxide were very low, suggesting that impairment of the central nervous respiratory chemoreceptor contributed to hypoventilation. These patients and others described in the literature suggest that central depression of ventilation may occur more frequently than previously recognized in patients with muscular disorders. Patients with chronic respiratory failure due to central depression of respiratory drive can be effectively managed by assisted ventilation at night.

Adult↗
PubMed1977

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion.

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.

Adult↗
PubMed1976

Complications of obesity-hypoventilation syndrome in childhood.

The obesity-hypoventilation syndrome is rare in children, but it leads to serious complications and is associated with a high mortality. We report a child with this syndrome whose condition improved after intestinal bypass surgery. Review of the literature indicates that vigorous treatment of this disorder is necessary to prevent fatalities.

Adolescent↗
PubMed1976

The response of asthmatic subjects to isoproterenol inhaled at differing lung volumes.

Asthmatics are usually instructed to use pressurized bronchodilator aerosols by delivering a bolus of drug at the beginning of a full inspiration. Because airways are better dilated near total lung capacity, the delivery of the drug near the end of a full breath might allow better penetration of particles into the lung and greater bronchodilatation. To test this hypothesis, 13 asthmatic subjects inhaled 400 mug of isoproterenol at 20 per cent (low) and at 80 per cent (high) vital capacity. The studies were done on 2 separate days when the severity of asthma was the same. Forced vital capacity, 1-sec forced expiratory volume, specific airway conductance and maximal flow at 50 per cent of viral capacity were measured at frequent intervals after drug administration. Ten min after drug delivery, there was a significantly greater (P less than 0.05) improvement in 1-sec forced expiratory volume after the drug was inhaled at the high lung volume compared to the response after delivery at the low lung volume. The differences in forced vital capacity, specific conductance, and maximal flow at 50 per cent of vital capacity were not significant. We concluded that inhaling a bronchodilator drug at the end of a full inspiration causes relatively greater bronchodilatation than inhaling the same dose at the beginning of inspiration.

Adolescent↗
PubMed1976

Regional bronchoconstriction in asthma. 133Xenon washout scans following parenteral methacholine.

To determine the influence of bronchoconstriction on the distribution of ventilation during an asthma attack, pulmonary clearance of 133xenon was evaluated in four normal and eight asthmatic subjects within three to five minutes after intramuscular injection of methacholine. In asthmatics, administration of 4-10 mg methacholine resulted in a decrease of forced vital capacity of 28.5 +/- 5.1 (SE) percent and a decrease in expiratory flow at 60 percent vital capacity of 44.2 +/- 6.9 percent (P less than 0.001). The cumulative ventilation required to reach 50 percent of the pre-washout radioactivity increased from 3.6 +/- 0.8 to 9.9 +/- 1.6 L after administration of the drug (P less than 0.05). The normal subjects showed no ventilatory effects after receiving 10 mg methacholine. Comparison of clearance of 133xenon from ten areas of lung (each representing approximately 6 percent of the surface area of one lung) showed that all areas were affected to approximately the same extent during drug-induced asthma. These findings suggest that parenteral methacholine is an effective way to demonstrate airway hyperreactivity and that the airway response to methacholine in asthmatics is relatively generalized throughout the lung.

Adult↗
PubMed1975

Allergic bronchopulmonary aspergillosis: evidence of limited tissue invasion.

The cause of granulomatous parenchymal reaction in allergic bronchopulmonary aspergillosis has been attributed to a hypersensitivity reaction. A case is reported with Aspergillus fumigatus identified in lung tissue, suggesting that the pathologic changes in some cases can be due to limited parenchymal colonization.

Aspergillosis↗