Pleural effusions frequently complicate inflammatory or infectious diseases. Of patients with pneumonia, for instance, 40% develop an effusion, which can impair pulmonary function and increase morbidity. This study of the physiology of the normal and inflamed pleura will examine those factors responsible for the imbalance of filtration and clearance which cause the accumulation of liquid. A comparative approach between species with different visceral pleuras will sort out the relative contribution of the visceral and parietal pleuras to clearance of effusions. Additional studies will center on lymphatic function. Normal pleural physiology studies will include the determination of the 1) liquid volume, 2) protein filtration (by tracer kinetics), 3) rate of clearance of liquid and protein (by artificial hydrothoraces), and 4) lymphatic clearance and pathways (by particle clearance, gamma imaging). Inflamed pleural studies will include the determination of the 1) protein filtration rate (by tracer kinetics), 2) rate of liquid and protein clearance (of artificial hydrothoraces), 3) response of the visceral and parietal pleuras (vascular labeling, histology, radiolabeled microspheres), and the 4) contribution of mediators and cells in formation of the effusion (inhibitor and depletion studies). The candidate, a pulmonary fellow in Norman Staub's laboratory, is already well acquainted with most of the experiments she proposes. She has performed experiments involving tracer kinetics, clearance of artificial hydrothoraces, and measurement of volume by dilution. She has had a long interest in pulmonary research and has both the desire and the potential for a research career. The San Francisco General Hospital and the Cardiovascular Research Institute have excellent facilities and personnel and are well equipped to support this research.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001893-03
Application #
3082287
Study Section
Research Manpower Review Committee (MR)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Broaddus, V C; Feigal Jr, D W (1994) Starting an academic career. A survey of junior academic pulmonary physicians. Chest 105:1858-63
Boylan, A M; Hebert, C A; Sadick, M et al. (1994) Interleukin-8 is a major component of pleural liquid chemotactic activity in a rabbit model of endotoxin pleurisy. Am J Physiol 267:L137-44
Wiener-Kronish, J P; Broaddus, V C (1993) Interrelationship of pleural and pulmonary interstitial liquid. Annu Rev Physiol 55:209-26
Broaddus, V C; Hebert, C A; Vitangcol, R V et al. (1992) Interleukin-8 is a major neutrophil chemotactic factor in pleural liquid of patients with empyema. Am Rev Respir Dis 146:825-30
Broaddus, V C; Araya, M (1992) Liquid and protein dynamics using a new minimally invasive pleural catheter in rabbits. J Appl Physiol 72:851-7
Broaddus, V C; Wiener-Kronish, J P; Staub, N C (1990) Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep. J Appl Physiol 68:2623-30
Wiener-Kronish, J P; Broaddus, V C; Albertine, K H et al. (1988) Relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep. J Clin Invest 82:1422-9
Wood, P A; McBride, M R; Baker, H J et al. (1985) Fluorescence polarization analysis, lipid composition, and Na+, K+-ATPase kinetics of synaptosomal membranes in feline GM1 and GM2 gangliosidosis. J Neurochem 44:947-56