Hospitals are the target, not the cause.
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Biomedical subjects
Publications and source records attributed to J R Castle.
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Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.
In the past, preoperative pulmonary function abnormalities have identified a group of patients in danger of postoperative cardiorespiratory morbidity and mortality. We selected a group of 56 patients, each of whom had a lung mass and had demonstrated significant abnormalities in screening pulmonary function. By using temporary unilateral pulmonary artery occlusion and quantitative macroaggregate lung scanning, we then studied these patients for split pulmonary function. Those patients whose noncancerous lung had a calculated forced expiratory volume in 1 sec greater than 800 ml and a circulation that could accommodate all of the cardiac output without producing hypertension or arterial hypoxemia were offered thoracotomy. Of the 56 patients, we judged 6 to be physiologically inoperable and did not offer surgery. Another 4 patients were not offered surgery, and 4 refused surgery. Forty-two patients underwent surgical exploration-of these, 17 then had a pneumonectomy and 13, a lobectomy. Of the 30 patients resected, 6 died in surgery (4 from respiratory insufficiency). These cardiorespiratory mortality rates (neumonectomy, 17.6 per cent; lobectomy, 7.7 per cent) are lower than those reported previously when patients had equivalent pulmonary function abnormality. A follow-up of 49 of 56 patients revealed that 59 per cent of the patients undergoing either pneumonectomy or lobectomy were still living 1 to 3 years after the resection. Our results suggested that the preoperative testing of split pulmonary function permitted an attempt at surgery in patients who might otherwise be considered inoperable by history, physical examination, screening pulmonary function tests alone.
Proteolysis (or more specifically, elastolysis) of the lung may be involved in the pathogenesis of pulmonary emphysema. To investigate the human alveolar macrophage as a potential mediator of lung damage, elastase-like esterase and protease activity was determined in these cells as well as in alveolar lavage fluid and in peripheral blood leukocytes. Bronchoalveolar lavage was used to obtain alveolar cells and fluid in normal volunteers who were divided into two groups according to cigarette smoking history, nonsmokers and smokers. Results of these studies revealed that human alveolar macrophages possess a high activity of both elastase-like esterase and protease. Furthermore, the alveolar macrophages of cigarette smokers has a significantly greater elastase-like esterase and protease activity than those of nonsmokers. When the 4- to 5-fold increase in the number of macrophages found cigaretts smokers is taken into account there was approximately 10 times more elastase-like esterase activity and 18 times more protease activity within macrophages in the alveolar spaces of cigarette smokers' lungs. This makes the alveolar macrophage a poten potential source of proteolytic enzymes in man.
The content of alpha-1-antitrypsin in the serum, alveolar lavage fluid, and alveolar macrophages of smokers and nonsmokers was studied. Bronchoalveolar lavage was used to obtain alveolar fluid and macrophages from normal volunteers, and alpha-1-antitrypsin and albumin were measured using the electroimmunodiffusion technique. The serum level of inhibitor was not different between the two groups, while the total lavage fliud content of alpha-1-antitrypsin was increased in the smokers. The level of alpha-1-antitrypsin was also significantly greater (P less than 0.001) in the alveolar macrophages of the smokers suggesting the possibility of chronically increased alveolar levels in the cigarette smoker as a possible protective mechanism against proteolysis.
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