A rapid and sensitive neomycin phosphotransferase II assay suitable for optimizing cell transfection protocols.
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Biomedical subjects
Publications and source records attributed to K S Miller.
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The lungs are frequently affected in systemic sclerosis, and pulmonary disease may significantly influence morbidity and mortality. The clinical, radiographic, and physiologic features of scleroderma lung disease are discussed in this article, as are new approaches to the detection and study of interstitial pneumonitis. The pathogenesis of pulmonary fibrosis is discussed in the context of data derived from bronchoalveolar lavage studies. Pulmonary vascular disease and less common pulmonary features of systemic sclerosis are also discussed.
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Interstitial pulmonary fibrosis is a common manifestation of systemic sclerosis (SSc) and is a pathologic feature shared by a variety of other diseases. In these other disease processes, the glycoprotein fibronectin (FN) has been shown to be released by the alveolar macrophage, and is thus implicated in the development of fibrosis. We therefore studied the release of FN by alveolar macrophages obtained by bronchoalveolar lavage of 17 patients with SSc and 14 controls. We found that SSc alveolar macrophages released significantly more FN than did those of controls. Furthermore, the level of FN correlated positively with the level of inflammation determined by cellular analysis of lavage fluid and negatively with carbon monoxide diffusing capacity. FN may therefore play a role in the development of lung fibrosis in SSc and may be a marker of alveolitis.
Models of pleural injury were established with intrapleural tetracycline, intrapleural carrageenan, and empyema in New Zealand White rabbits to evaluate histologically the pleural inflammatory response from 3 to 90 days. Both tetracycline and empyema models produced increases in the pleural connective tissue layers both above and below the fibroelastic membrane associated with angiogenesis and lymphangiogenesis. The influx of fibroblasts from the pleural surface into acellular fibrin strands formed adhesions between the visceral and the parietal pleurae. Injury to the mesothelial cell ranged from a cuboidal transition to total desquamation with the degree of mesothelial injury associated with the amount of fibrin adherence and the propensity toward fibrosis at 90 days. Intervention to promote the resolution of pleural inflammation without fibrosis should be directed toward preservation of the mesothelial surface, removal of pleural fibrin, and inhibition of fibroblast growth and chemotaxis.
Traditional thinking suggests that pleural fluid develops on the basis of systemic venous hypertension or a primary pleural process. Recent investigations, however, indicate that both acute lung injury and pulmonary venous hypertension can be important in the pathogenesis of pleural effusions. To evaluate the role of acute lung injury in the formation of pleural effusions, we developed a model of acute, reversible lung injury in NZW rabbits. Intravenous ethchlorvynol (ECV), known to produce permeability edema in humans, was used to produce permeability pulmonary edema in rabbits. The injury was examined over 14 days with bronchoalveolar lavage, pleural fluid analysis, and morphologic analysis. Ethchlorvynol injection (40 mg/kg) produced a PMN-predominant, exudative alveolitis (2 h), alveolar hemorrhage (6 to 10 h), and pleural effusions by 2 h (peak, 10 h). Pathologic findings included a patchy, subpleural, hemorrhagic PMN inflammatory response, which peaked by 24 h, and an acute PMN vasculitis of small arterioles and capillaries; these changes resolved in 5 to 7 days. No parietal pleural abnormalities were observed. We conclude that ECV induces an acute, reversible parenchymal lung injury resulting in a capillary leak and that fluid moves from the interstitium of the lung into the pleural space along a pressure gradient through a relatively permeable mesothelium. The data support the concept that diffuse or localized lung injury can result in pleural effusions.
A 26-year-old man had bilateral alveolar infiltrates and exudative pleural effusions following self-administration of intravenous ethchlorvynol (ECV). The effusions and pulmonary edema resolved by 72 h with supportive therapy only. As no other etiology was established, we concluded that the pathogenesis of the pleural fluid was the transvisceral pleural leak of the increased extravascular lung water induced by ECV. Current experimental and clinical evidence support the concept that pleural effusions probably develop in most states of permeability pulmonary edema.
Two hundred (200) consecutive medical and surgical patients requiring mechanical ventilation were entered into a prospective randomized trial of weaning by either intermittent mandatory ventilation (IMV) or T-piece. Patients in these groups were of similar age and sex and had the same total ventilation time (TVT). The study design provided equal time for each weaning mode after specific criteria for oxygenation and ventilation were satisfied (PaO2 greater than 55 mm Hg on FIO2 less than 0.5; VE less than 12 L/min and two of the following four parameters: MVV greater than 2 VE, VT greater than 5 ml/kg, FVC greater than 10 ml/kg, NIF less than or equal to -20 cm H2O). Of the original 200 patients 165 were entered into the weaning phase; 35 patients were withdrawn prior to weaning due to the discretion of the attending physician or protocol error. Weaning time was not different between the IMV (5.3 +/- 1.2 h, mean +/- SEM) and T-piece groups (5.9 +/- 1.4 h, p = NS). Of the 165 patients, 155 (93 percent) were weaned successfully by protocol, 79 in the IMV and 76 in the T-piece group. Of 155 patients, 136 (88 percent) were weaned on the first attempt by protocol. Of the 19 who were not weaned, 11 were weaned successfully on the second and five on the third trial; three patients required three-day weans. We conclude that clinically stable patients who require short-term mechanical ventilation and meet standard bedside weaning criteria can be weaned efficiently by protocol using either IMV or T-piece techniques.
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Levels of circulating progesterone (P) were significantly reduced in socially subordinate female golden hamsters following brief exposures to another female. Reduced P levels were accompanied by an increased incidence of implantation failure when social interactions occurred on days 2-4 after mating and by increased fetal mortality when interactions occurred later during pregnancy (days 5-7 or 10-12). P levels, the incidence of implantation failure and rate of fetal resorption were highly correlated with the number of attacks and chases sustained by subordinate females. Smaller reductions in plasma P levels and marginally significant decreases in fecundity were also noted among dominant animals and among females paired with unfamiliar males later in pregnancy. The fact that these effects occurred even with relatively brief exposure periods suggests that they could occur in the wild.
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Pneumothorax (PTX) is the most common complication associated with percutaneous needle aspiration (PNA) of the lung. Age, sex, cooperation, and lesion size, location, and depth, as well as needle size, number of passes, and radiographic calculation of total lung capacity all have been implicated in influencing the rate of PTX. Pulmonary function testing to assess PTX risk in PNA has not been previously examined. We retrospectively reviewed 159 patients undergoing PNA who had preprocedure spirometry (PFT) and chest roentgenogram (CXR) interpreted for changes of obstruction or restriction to determine if these classifications could stratify patients at high risk for PTX. We also examined single variables to determine their predictive power. Patients with normal PFT and CXR had a 10 percent risk of PTX, and only one such patient needed intervention to treat the PTX. Obstruction by PFT, regardless of CXR findings, predicted a 50 percent PTX rate. Among single variables, FEV1 proved to be the most significant predictor of PTX. Preprocedure spirometric testing can enhance the assessment of PTX risk and should be routinely performed prior to needle aspiration.
Pulmonary function tests and chest radiographs of 160 patients who had had percutaneous needle biopsy of lung lesions were reviewed to determine the value of these examinations in estimating the risk of postbiopsy pneumothorax. Chest radiographs were evaluated subjectively for changes of obstructive and restrictive airway disease and for size and depth of lesion. Pulmonary function tests, consisting of simple spirometry (forced vital capacity, percentage of predicted forced vital capacity, forced expiratory volume in 1 sec, percentage of predicted forced expiratory volume in 1 sec, and [forced expiratory in 1 sec/forced vital capacity] X 100), and the pulmonologist's interpretation were evaluated. Pneumothorax developed in 46% (31/67) of patients who had obstructive airway disease according to the results of pulmonary function tests and in 42% (34/81) of those who had obstructive airway disease according to changes on chest radiographs, compared with 19% (10/53) and 25% (17/67) of those who had normal pulmonary function tests and chest radiographs, respectively. Pneumothorax developed in 46% (23/50) of patients who had findings of obstructive airway disease on both pulmonary function tests and on chest radiographs, compared with 7% (2/28) of patients who were classified as normal by both criteria. None of the patients who had normal pulmonary function tests required placement of a chest tube, whereas 19% (13/67) of those who had obstructive airway disease required chest tubes. Decreasing size of lesion and increasing depth of lesion were associated with a significant increase in the risk of pneumothorax. We conclude that the results of chest radiographs and pulmonary function tests are useful parameters for estimating the risk of postbiopsy pneumothorax.
Protected transbronchial needle aspiration (PTBNA) of pneumonic lung theoretically could bypass dislodged upper respiratory tract flora, a potential source of contamination of protected specimen brush (PSB) cultures. To evaluate the usefulness of PSB and PTBNA in establishing the etiology of pneumonia, we prospectively studied 20 patients with acute bacterial pneumonia not receiving antibiotics. After informed consent, patients had fiberoptic bronchoscopy under fluoroscopy to localize the pneumonia, and specimens were obtained by the PSB. The protective plug of a specially devised needle for PTBNA was pneumatically dislodged and aspiration was performed within the infiltrate under fluoroscopy. Quantitative cultures were plated immediately for aerobes, anaerobes, and Legionella. Greater than 4 X 10(3) organisms/brush or 1 X 10(4) organisms/ml needle aspirate were considered to be consistent with infection. The results using PSB and PTBNA were compared in 15 of 20 patients in whom a definitive diagnosis (positive blood or pleural fluid culture) or presumptive diagnosis (expectorated sputum culture, clinical characteristics, and response to specific therapy) was established. The PSB and PTBNA cultures on uninfected control subjects (n = 5) being bronchoscoped for other reasons were negative. The PSB and PTBNA were each diagnostic in 2 of the 5 patients with definitive diagnoses. In the group with a presumptive diagnosis (n = 10), PSB was diagnostic in 7 of 10 and PTBNA in 9 of 10. The overall (definitive plus presumptive) diagnostic yield was 60% for PSB and 73% for PTBNA. Multiple organisms were isolated in high concentrations in 53% of the patients. The most common organisms recovered in addition to the primary pathogen was alpha hemolytic streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)
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A patient with mycosis fungoides involving the lung, presenting with ARDS, and diagnosed by bronchoalveolar lavage, is described. A review and correlation of chest radiographic manifestations and pathologic observations are presented. We stress the importance of obtaining a specific diagnosis in light of the tenuous radiographic-pathologic correlation and discuss procedures for diagnosis and the inclusion of bronchoalveolar lavage as a previously undescribed diagnostic modality. The dismal prognosis of these patients, once pulmonary involvement is diagnosed, is noted.
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