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Biomedical subjects

R A Matthay

Publications and source records attributed to R A Matthay.

At least 91 records · Page 5Linked to original sources

New techniques for the assessment of interstitial lung disease.

The authors succinctly describe the pathogenic mechanisms of this disease and the failures of the traditional diagnostic techniques in providing data about the extent of alveolitis and thus about disease activity and prognosis. The authors then show how the new methods of bronchoalveolar lavage and gallium-67 scanning may provide such information. Next in the discussion is how these techniques are applied to the understanding and management of sarcoidosis and idiopathic pulmonary fibrosis. And finally, the authors propose an integrated approach that uses both the new and traditional methods in the diagnosis and management of interstitial lung disease.

Biopsy↗

Improvement in cardiac performance by oral long-acting theophylline in chronic obstructive pulmonary disease.

Although oral theophylline is a widely used bronchodilator in chronic obstructive pulmonary disease (COPD), its effects upon cardiac performance have not been fully established. The effect of slow release oral theophylline upon right ventricular and left ventricular ejection fraction was evaluated using first-pass quantitative radionuclide angiocardiography in 15 patients with COPD. After 72 hours of therapy, oral theophylline significantly increased right ventricular ejection fraction (42% to 48%, p less than 0.005). In 7 of 10 patients with depressed baseline right ventricular performance, including two with cor pulmonale, right ventricular ejection fraction normalized (greater than or equal to 45%). After long-term therapy, an average of 16 weeks, right ventricular fraction also increased (43% to 48%, p less than 0.005). Left ventricular ejection fraction improved significantly from 64% to 68% (p less than 0.05) at 72 hours and from 61% to 65% (p less than 0.025) after long-term therapy. These data indicate that oral theophylline produces a sustained modest enhancement of resting biventricular performance in COPD.

Administration, Oral↗

Kinetic analysis of respiratory tract proteins recovered during a sequential lavage protocol.

Although bronchoalveolar lavage (BAL) has been used as a research tool for over a decade, the technique of lavage has varied markedly between laboratories. For example, lavage instillate volumes from 50 to 300 ml have been used, and yet the influence of the variable of total lavage volume on subsequent protein recovery is uncertain. We performed sequential BAL (50 ml/aliquot; total volume, 300 ml) of the right middle lobe of 14 normal volunteers and separately processed and analyzed recovered aliquots for the absolute and relative concentrations of several protein substances. These proteins include free secretory component and secretory IgA, which emanate from airway secretions, and IgG, which is thought to transude from more distal alveolar sites. Analysis of these data showed a marked decrease in the absolute concentration of all proteins measured in serial aliquots. Analysis of protein ratios in sequential aliquots, however, revealed no significant change from the first to the fifth recovered aliquot. Finally, we analyzed the influence of the size of the first recovered aliquot on absolute and relative concentrations of proteins. Here there seemed to be a trend indicating preferential recovery of airway proteins in smaller aliquots. This was significant for the ratio of free secretory component to albumin (p less than 0.05). We conclude that lung proteins are efficiently and homogeneously sampled with 100 ml of lavage instillate. Larger volumes will add more protein but not alter protein ratios. Lavage with smaller volumes may preferentially sample airway proteins.

Adolescent↗

Lung cancer: a persistent challenge.

The most frequently diagnosed type of lung cancer now is probably adenocarcinoma. This cell type is not clearly related to smoking, but may reflect environmental and occupational factors. Staging systems assess the extent of primary and metastatic disease, aid in determining appropriate treatment, and suggest prognosis. Clinical stage correlates with survival rate, but most staging systems underestimate the extent of metastases in lung cancer.

Adenocarcinoma↗

Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure.

Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and cross-sectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data.

Acute Disease↗

Quantitation of carcinoembryonic antigen in the lung lining fluid of normal smokers and nonsmokers.

Bronchoalveolar lavage was performed in 47 volunteers: 19 nonsmokers and 28 smokers. Total protein, albumin, immunoglobulins G and A, and carcinoembryonic antigen (CEA) were measured in the concentrated lavage effluent. Although a significant increase (p < 0.001) in the ratio of CEA to total protein recovered from the group of smokers was found, this increase primarily reflected the greater increase that occurred in a subgroup of 7 smokers. However, the increases in lavage CEA correlated weakly (p = 0.096) with smoking history in pack-years, and not at all with plasma CEA concentrations. Results regarding the number of cells recovered and immunoglobulin-to-albumin concentration ratios in these subjects were similar to those reported by others. Thus, CEA was increased in the lavage fluid of a subgroup of otherwise normal young smokers. It is possible that CEA might serve as a useful indicator of future airway disease in certain young smokers.

Adult↗

Cystic fibrosis pseudomonas opsonins. Inhibitory nature in an in vitro phagocytic assay.

Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system. The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakeCF = 18 x 10(3) 14C cpm) were inhibited compared with appropriate positive controls (hyperimmune serum, HIS; [rateHIS = 399; uptakeHIS = 29 x 10(3), P less than 0.005]). The ability of such CF-derived opsonins to potentiate macrophage intracellular bactericidal processes was mildly impaired (bacterial survivalCF = 15 x 10(3) colony forming units (CFU)/min, survivalHIS = 9 x 10(3)). Further characterization of this defect, assessed with functional studies of the Fab and Fc portions of the immunoglobulin molecule, revealed an impairment in the attachment of these specific antibodies to the alveolar macrophage membrane Fc gamma receptors. Preliminary studies of the physical-chemical properties of these immunoglobulins were normal. The expression of this inhibitory activity in vivo may facilitate Pseudomonas colonization and the subsequent established infections in the respiratory tracts of CF subjects.

Antibodies, Bacterial↗

Elastase and lysozyme activities in human alveolar macrophages. Effects of cigarette smoking.

We compared the elastase and lysozyme activities of cells obtained by bronchoalveolar lavage from normal smokers and nonsmokers. After total and differential cell counts were obtained for the initial lavage cell population, we determined the enzyme activities of the total lavage cell population, the culture vessel's adherent alveolar macrophage cell fraction, and the cell culture supernatant medium. Our data indicated that macrophages, particularly from smokers, synthesized a calcium-dependent activity against a synthetic elastase substrate, succinyl-trialanine-p-nitroanilide. This activity was enhanced in smokers and was distinct from the polymorphonuclear leukocyte elastase as measured with this synthetic substrate. Measurements using insoluble elastin labeled with 3H demonstrated that smokers' macrophages also contained a serine-proteinase activity whose inhibitor profile resembled that of polymorphonuclear leukocyte elastase. Finally, macrophages from smokers secreted 5 times more lysozyme and contained more lactate dehydrogenase activity than did nonsmokers' macrophages. We suggest that pulmonary macrophages take up the polymorphonuclear leukocyte elastase and contain a synthetic substrate, "elastase". The biologic significance of this elastase activity is unclear. The enhanced lysozyme secretion by smokers' alveolar macrophages indicated increased biosynthetic activity by these cells.

Adult↗