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Biomedical subjects

J J Seidenfeld

Publications and source records attributed to J J Seidenfeld.

7 recordsLinked to original sources
PubMed1991

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

Acute Disease↗
PubMed1989

O2- and pneumonia-induced lung injury. II. Properties of pulmonary surfactant.

Pulmonary surfactant was isolated from the lavage fluids of animals during the course of exposure to 100% O2, 80% O2, 40% O2, or 80% O2 plus 10(8) Pseudomonas aeruginosa instilled intratracheally and analyzed for its phospholipid composition. After 4-5 days of exposure to 100% O2, disaturated phophatidylcholine (DSPC) decreased to 87% of control, whereas the ratio of phosphatidylglycerol to phosphatidylinositol (PG/PI) was 37% of control. Longer periods of ventilation with 100% O2 resulted in DSPC falling to less than 40% of control. The injury was not reversed by reducing the O2 to 50%; rather, a progressive deterioration ensued. Acute respiratory failure (ARF) induced by 5 days of bacterial infection was very similar to that seen after 5 days of exposure to 100% O2. Ventilation with 80% O2 for 6 days resulted in smaller changes in DSPC but with differences in PG/PI comparable to those seen with 100% O2 or infection. We conclude that the ability of the type II cell to synthesize surfactant of normal composition is significantly impaired in these models of ARF. The earliest index of biochemical modification is the substantial change in PG/PI, which may be predictive of early lung injury. Further exacerbation of the injury could result in the reduction of DSPC content, with subsequent changes in lung mechanics and gas exchange.

Acute Disease↗
PubMed1978

Paraquat lung injury in rabbits.

An aerosol model for the study of paraquat (PQ) toxicity was developed using a 134 litre chamber and an ultrasonic nebuliser. Three groups of New Zealand white rabbits weighing 2-3 kg were studied. Group I (n = 6) was exposed to 10 g PQ/100 ml double-distilled water (DDW), Group II (n = 24) was exposed to 200 mg PQ/100 Ml DDW and a control group (n = 6) was exposed to 100 ml DDW. In a second experiment ten animals (Group III) were exposed to 10 mg PQ/100 ML DDW over a three-month period together with a control group (n = 5). Group I animals died with extensive haemorrhagic pneumonitis 38 hours after the last challenge. Most animals in Group II surviving more than three exposures had a significant reduction (P less than 0.001) in arterial oxygen tension (PaO2) and an increase (P less than 0.001) in the alveolar-arterial O2 gradient. Specific compliance decreased (P less than 0.005) and functional residual capacity and breathing frequency increased (P less than 0.05). Tissue PQ values showed even pulmonary distribution, with evidence of PQ accumulation after repeated inhalation. The lungs showed focal interstitial fibrosis, interstitial thickening, proliferation of macrophages in the alveoli, epithelioid changes in the interstitium, Type II cell hyperplasia, and foci of acute inflammation with consolidation. Controls and Group III animals were normal. This indicates that repeated inhalation of paraquat aerosol induces dose-related interstitial pneumonitis and fibrosis in rabbits.

Animals↗
PubMed1978

Chronic experimental interstitial pneumonitis in the rabbit.

The effects on the lungs of chronic aerosol and intravenous antigen challenges in preimmunized and control rabbits were studied. Soluble and particulate antigens included ovalbumin, keyhole limpet hemocyanin, antigen-adsorbed latex particles, glutaraldehyde cross-linked ovalbumin, and killed bacille Calmette-Guérin (BCG). Despite the development of acute alveolitis in sensitized animals, chronic aerosol challenge with both soluble and particulate antigens failed to produce chronic interstitial lung disease. Chronic intravenous challenge with killed BCG, but not other particulate antigens, resulted in a progressive interstitial pneumonitis, with evidence of fibrogenesis in animals that had been presensitized to tuberculin by toepad injection of complete Freund's adjuvant. Adaptive alveolar clearance mechanisms thus appear to protect rabbits from chronically inhaled antigen. Pulmonary circulatory clearance of BCG, however, results in an interstitial pneumonitis that is dependent on previous sensitization.

Aerosols↗