Chylothorax and respiratory failure in Kaposi's sarcoma.
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Biomedical subjects
Publications and source records attributed to M L Warnock.
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To determine the histologic changes occurring during a pulmonary immune response, the lungs of antigen-primed C57BL/6 mice were examined on various days after intratracheal challenge with 10(8) sheep erythrocytes. The response was characterized by 1) dense perivascular aggregates composed largely of mononuclear cells; 2) endothelial cell hypertrophy and subendothelial inflammatory cell collections in vessels of a variety of sizes; 3) variable degrees of focal, reversible vascular injury (angiopathy) of both muscular arteries and small veins; and 4) increased cellularity of alveolar walls. Inflammatory cells appeared to emanate from small veins and venules and from minute thin-walled vessels adjacent to large arteries. The reaction peaked at 3 to 4 days and then gradually declined over a period of 6 weeks, never quite reaching baseline. We believe that this experimental model will be an important means of further defining both the mechanisms of lymphocyte entry to the lungs in response to antigen and the factors controlling the pathogenesis of related angiopathies.
Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.
A 2-yr-old child developed massive hepatic necrosis caused by an unusual hypersensitivity response to phenobarbital that was prescribed for presumed febrile seizures. Despite discontinuation of the barbiturate, this child experienced fulminant hepatic failure and died. Review of the literature indicates that phenobarbital-induced hepatic injury is uncommon and usually mild. Prompt and permanent cessation of the drug results in resolution of symptoms in most patients.
We cultured bronchoalveolar lavage fluid for the human immunodeficiency virus (HIV) from 23 consecutive patients with acquired immunodeficiency syndrome (AIDS) and pulmonary symptoms. We also included a nonconsecutive AIDS patient with recent worsening of respiratory symptoms who had had lymphocytic interstitial pneumonitis (LIP) diagnosed six months earlier. Infectious HIV was present in the cellular fraction from two of the 23 consecutive patients and in the patient with LIP. No virus was isolated from the cell-free portion of the centrifuged fluids. The patients from whom HIV was cultured were not distinguishable from other patients by clinical, radiographic, or laboratory data, and their subsequent course did not appear to differ. One patient with a positive HIV culture had organizing pneumonia without evidence of LIP at autopsy three weeks after lavage. This study demonstrates that HIV can be cultured from cells obtained by bronchoalveolar lavage and suggests that its presence is not associated with a single specific pulmonary histologic pattern.
The immunohistochemical reactivity of 38 mesotheliomas and 44 adeno-carcinomas or large cell carcinomas of the lung with monoclonal antibodies (MAb) B72.3 and Leu M1 was compared with their reactivity with the routine histochemic stains periodic acid-Schiff with diastase digestion (PAS-D) and alcian blue +/- hyaluronidase. Both MAbs reacted selectively with carcinomas when a positive test was set at greater than or equal to 10% reactive tumor cells. However, MAb B72.3 reacted with significantly more of the carcinomas (86%, chi-square test, P less than 0.01) and bound to a greater percentage of tumor cells (47 +/- 28%; mean +/- SD, t-test, P less than 0.001) than Leu M1 (57% and 25 +/- 28%, respectively). The similar reactivities of surgically resected tumor specimens and post mortem tissues with both antibodies confirmed antigen stability and suggested broad clinical utility. PAS-D stained 61% of the carcinomas. Using the markers for carcinomas (PAS-D, B72.3, and Leu M1), the tumors were classified into the correct group in 80 of 82 (98%) cases (95% confidence level: greater than 92% accuracy). The alcian blue stain was useful to confirm a diagnosis of dimorphic or epithelial mesothelioma (48% were positive).
A committee of the College of American Pathologists has proposed that the diagnosis of asbestosis requires fibrosis in respiratory bronchiolar walls and the presence of asbestos bodies (ABs) in tissue sections. To determine whether histologic ABs reliably reflect asbestos fiber concentrations in asbestosis, we compared the concentration of ABs in histologic sections to concentrations of ABs and fibers in tissue extracts of 14 asbestos workers with nonspecific interstitial fibrosis. ABs in histologic sections and extracts correlated well, r = 0.95. Counted and classified by electron microscopy, electron diffraction, and X-ray spectroscopy, commercial amphibole fibers (r = 0.94) also correlated well with ABs, but noncommercial amphiboles (r = -0.02) or chrysotile (r = 0.29) did not. In five subjects with a high percentage of noncommerical amphibole fibers, fewer than 0.5 histologic ABs/cm2 were present despite a total amphibole concentration that was similar to that in subjects with more histologic ABs. We conclude that ABs will be scarce or absent in histologic sections from some subjects with asbestosis, and that for such subjects, extracts of asbestos fibers should yield over 500,000 total amphibole fibers/g dry lung to signify that interstitial fibrosis may be caused by asbestos.
To determine whether the cytochemical localization of peroxidase activity could be used as a marker of monocyte influx into the lung during an inflammatory response, the authors studied the peroxidase phenotypes of lavaged alveolar macrophages from rats with bacille Calmette-Guérin (BCG)-induced pulmonary inflammation. Rats were immunized subcutaneously and 2 weeks later intravenously with BCG. During the early phase of pulmonary inflammation, an increase was observed in the numbers of alveolar macrophages with no peroxidase activity in the endoplasmic reticulum. These cells appeared to reflect monocyte influx into the injured lung. The later stages of inflammation were characterized by increased numbers of alveolar macrophages with peroxidase-positive endoplasmic reticulum, probably due to activation of enzymatic activity in situ. During the early phase, peroxidase activity was also observed within macrophage cytoplasmic inclusions, probably representing both primary monocyte lysosomes and internalized myeloperoxidase from inflammatory neutrophils. Serial observations indicated that the peroxidase-positive cytoplasmic inclusions became negative with time. It is concluded that inflammation-induced modulation of peroxidase activity in the endoplasmic reticulum and in cytoplasmic inclusions makes the alveolar macrophage peroxidase phenotype no more than a rough marker of monocyte influx into the inflamed lung.
To determine whether we could distinguish asbestos-related lung cancers from unrelated ones, we typed and quantified by electron-optical methods the asbestos fibers in the lungs of 75 men with lung cancer. All but eight men had some history of asbestos exposure. On the basis of combined amosite and crocidolite (AC) concentrations, we divided the subjects into three groups (AC fibers per gram of dry lung): low (less than 10(5)); intermediate (10(5) to 10(6)); and high (greater than 10(6)). Age, smoking history, latent period, and type and location of tumors were similar in all three groups. Of 62 evaluated subjects, zero of 14 in the low group, seven of 29 in the intermediate group, and five of 19 in the high group had asbestosis. Epidemiologic studies suggest that persons exposed to concentrations of asbestos that can cause asbestosis are at increased risk for lung cancer. Thus, the subjects in our intermediate and high concentration groups may have been at increased risk for cancer, even when they did not have asbestosis. Because large burdens of asbestos do not always cause pulmonary fibrosis, asbestosis may be a poor marker of fiber-related lung cancer.
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A laborer who worked in a steel mill and in a shipyard developed a nonspecific pulmonary interstitial fibrosis. Postmortem samples of his lung were digested, and the inorganic material present was extracted and examined using transmission electron microscopy, electron diffraction, and electron microprobe analysis. Uncoated asbestos fibers were present (1.4 X 10(5)/g wet lung), but the surprising finding was the presence of a large number of fly ash particles (6 X 10(6)/g wet lung). Fly ash, the particulate material produced during coal combustion, has not previously been reported to be present in human lung tissue. Although the contribution of the asbestos to this man's lung disease is uncertain, we believe, based on previous studies implicating aluminum silicates in pneumoconiosis, that the fly ash, an aluminum silicate, may be a contributing factor.
We compared the numbers of asbestos bodies in 2 histologic sections of lung from 25 subjects showing a wide range of total asbestos burden with the numbers of asbestos bodies and fibers (analyzed by electron diffraction and x-ray spectroscopy) extracted from the lung. We also compared the numbers of extracted asbestos bodies with the numbers of fibers in 24 other subjects. Histologic and extracted asbestos bodies were correlated best with total asbestos fibers and with amosite and crocidolite fibers, and not at all with chrysotile fibers. Nevertheless, the total fiber count could not be reliably estimated from the count of either histologic or extracted bodies. Although asbestos bodies appeared to be fairly uniformly distributed in these lungs, detection of early fibrosis or asbestosis required careful examination of all portions of the parenchyma. When we defined asbestos histologically as clusters of 3 or more asbestos bodies adjacent to areas of fibrosis, we found that subjects with asbestosis had more than 240,000 asbestos fibers/g of wet lung. The nature of the disease in lungs showing fibrosis and more than 240,000 fibers/g, but only isolated asbestos bodies, is uncertain.
The authors analyzed asbestos fibers in lung samples from 20 subjects with pleural plaques discovered on autopsy and compared the findings to their previous analyses of lungs from subjects with little or no asbestos exposure and no plaques. Sixteen of the subjects with plaques had a history of exposure to asbestos. The authors used electron-optical methods and energy-dispersive x-ray spectroscopy to investigate the structure, diffraction patterns, and chemical composition of the asbestos fibers. The subjects with plaques had significantly higher median concentrations than the control subjects for amosite and crocidolite fibers (P less than 0.01) but not for the other fiber types. Minimal microscopic asbestosis was present in the 3 subjects who had the highest amosite concentrations. In the subjects with typical plaques, a history of asbestos exposure, and more fibers than in the control population, the relation of the plaques to asbestos was confirmed; for others, it was uncertain.
Pulmonary involvement in mixed connective tissue disease has been considered a benign manifestation that is easily treated with corticosteroids. We followed 5 patients who had mixed connective tissue disease and severe, rapidly progressive, lung disease. Two types of lung disease were found, interstitial lung disease and pulmonary hypertension. Histologic sections from our patients were compared with sections from patients who had interstitial lung disease and systemic lupus erythematosus or pulmonary hypertension and scleroderma. Although clinical presentations were similar, the immunofluorescent and electron microscopic findings for interstitial lung disease were somewhat different in patients with systemic lupus erythematosus. Histologic findings for pulmonary hypertension appeared different in patients with mixed connective tissue disease and patients with scleroderma. For patients with either type of lung disease, corticosteroid therapy proved inadequate, but nearly cytotoxic therapy may be beneficial.
Analyses of asbestos bodies from the general population have confirmed that these structures, like asbestos bodies from the lungs of asbestos workers, contain an asbestos core. In members of the general population this core is almost always an amphibole, whereas asbestos workers may have bodies formed on either amphibole or chrysotile. Most adults have a few bodies, and increasing numbers are seen in blue collar workers and others who handle small amounts of the fiber, with the highest levels being seen in asbestos workers. In men with minimal or extensive occupational exposure, asbestos bodies are formed on the commercial fibers, amosite and crocidolite, whereas women also form a significant number of bodies on the noncommercial fibers, anthophyllite and tremolite. These findings suggest that women may be exposed to specific asbestos-containing products, eg, cosmetic talc. The commercial fibers found in women and white collar men probably reflect atmospheric pollution with asbestos. At the highest levels of exposure, numbers of asbestos bodies correlate in a general way with the presence of asbestosis, although no precise value has been determined above which asbestosis is always found. In persons with much lower or environmental exposure, there does not appear to be any correlation between numbers of bodies and disease, in particular between numbers of bodies and carcinoma of the lung or gastrointestinal tract. The situation for mesothelioma is uncertain.
Cytoplasmic hyaline material resembling Mallory's alcoholic hyaline has previously been described in pulmonary alveolar cells of patients with asbestosis. We present 14 new cases of cytoplasmic hyaline found in patients with a variety of processes causing damage to the alveolar lining; these include cases of radiation pneumonia, diffuse interstitial fibrosis, organizing bacterial pneumonia, as well as asbestosis. Hyaline was found only in the setting of an unusual type II cell change, which ultrastructurally appeared to represent squamous metaplasia. We conclude that pulmonary cytoplasmic hyaline is not specific for asbestosis but rather is a nonspecific reaction to injury;
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