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Death after burn injury is usually due to complications, of which bacterial causes are dominant. We treated a patient with a burn injury who had the unusual complication of multiple brain abscesses, which were caused by methicillin-resistant Staphylococcus aureus (MRSA). The patient, a 27-year-old man, had MRSA septicemia on day 9 and pneumonia on day 18. Hemiparesis, which was the first manifestation of brain abscesses, occurred on day 27. Although antibiotics were administered aggressively, the infection was never resolved, and the patient died on day 50. Brain abscesses and MRSA infection are still major problems in the treatment of burns. This is the first report of (metastatic) multiple brain abscesses complicating treatment of a burn injury. (J BURN CARE REHABIL 1992;13:446–50)

The ABCA3 gene, of the ABCA subclass of ATP-binding cassette (ABC) transporters, is expressed exclusively in lung. We report here the cloning, molecular characterization, and distribution of human ABCA3 in the lung. Immunoblot analysis using the specific antibody reveals a 150-kDa protein in the crude membrane fraction of human lung. Immunohistochemical analyses of alveoli show that ABCA3 is expressed only in the type II cells expressing surfactant protein A. At the ultrastructural level, ABCA3 immunoreactivity was detected mostly at the limiting membrane of the lamellar bodies. Since members of the ABCA transporter family are known to be involved in transmembrane transport of endogenous lipids, our findings suggest that ABCA3 plays an important role in the formation of pulmonary surfactant in type II cells.

We studied 5 patients with acute eosinophilic pneumonia. Radiologic findings were Kerley's lines and pleural effusion on chest X-ray films, and interlobular septa on chest CT scans. Examination of transbronchial lung biopsy specimens revealed infiltration of eosinophils and lymphocytes into alveolar walls and edema of alveolar walls, interlobular septa, and perivascular connective tissue. The findings of interstitial edema were consistent with the radiological findings. Epithelial damage and bud-type intraluminal fibrosis were also seen, but residual alveolar structure was maintained. Bronchoalveolar lavage fluid contained abnormally high percentages of eosinophils and lympocytes. It also contained basophils and mast cells, which were not seen in fluid from normal subjects. Fluid from patients with chronic eosinophilic pneumonia had significantly fewer basophils than did fluid from those with acute eosinophilic pneumonia (p0.01). These findings suggest that release of chemical mediators from basophils plays a key role in interstitial edema in acute eosinophilic pneumonia.

We made histochemical and ultrastructural studies of mast cells of the skin and airways in human fetuses (7 to 40 weeks' gestation) and newborn infants. Epithelial differentiation of the skin and bronchial airways was assessed of immunohistochemical characteristics, especially on their basal cells. Histological phenotype and the characteristics to anti-total keratin antibody became identical with the phenotype in the adult by the 11th and 36th week of gestation, respectively. Interstitial fibroblastoid cells appeared oval in shape and remained relatively immature to the termination. Mast cells were first recognized by electron microscopy in the fetal skin of 18-week-old fetuses and histochemically detected in both skin and airways of 24-week-old fetuses. Mast cell counts under high power magnification (40X optical lens) light microscopy gradually increased and made a relatively dramatic rise in the early postnatal periods. The cytoplasm of mast cells showed irregular pseudopod-like elongations which gradually developed microvillous protrusions. It contained immature granules composed of varieties of morphology such as amorphous dense bodies, vesicles with dense cores, particulates and their compound forms. They were located in a corner of the cytoplasm surrounded by lamellated rough-surfaced endoplasmic reticulum. These granules became scattered widely in the cytoplasm showing distinct particulate type. Granules typical of the scroll type became dominant in the process of maturation, and the transformation of crystal-substructures occasionally took place. Prior to birth, mast cell granules fully developed as mature as those in the adult. This process of granule maturation is indicative of a reversed proceeding of slow degranulation, which is commonly seen in the so-called mucosal mast cells.

Morphologic studies of normal anterior parietal pericardium from seven patients revealed this tissue to be composed of three layers: (1) the serosa, consisting of a surface layer of mesothelial cells and a narrow submesothellal space, (2) the fibrosa, containing variously oriented layers of collagen fibrils and small elastic fibers, and (3) the epipericardial connective tissue layer, containing mainly large coarse bundles of collagen and forming part of the pericardiosternal ligament. Scanning electron microscopic examination is most useful for study of the surface features of pericardial mesothelial cells, which have single cilia and are covered with microvilli. The latter bear friction and increase the surface area for fluid transport. Junctional complexes between adjacent mesothelial cells consist of desmosomes, which reinforce intercellular adhesion and zonulae occludentes, which form permeability barriers. Actin-like filaments (50 A in diameter) are present in microvilli and in immediately subjacent regions of the cells; these filaments mediate changes in cell shape. Intermediate filaments (100 A in diameter) are associated with desmosomes and form bundles in the perinuclear regions; these filaments provide structural support to the cytoplasm.

Idiopathic pulmonary fibrosis (IPF) is a usually fatal disorder of lung with clearly defined clinical, roentgenographic, physiologic, morphologic, scintigraphic and bronchoalveolar lavage features. Current concepts of the pathogenesis of this disorder suggest a central role for a chronic alveolitis in causing changes in parenchymal cell populations and derangements in interstitial collagen. Of the many inflammatory and immune effector cells comprising the alveolitis of IPF, it is likely that the neutrophil is the most important mediator of parenchymal damage. To follow the status of lung neutrophils in patients with this disease, two methods have been utilized. Both gallium-67 scanning and bronchoalveolar lavage quantitate the extent of the alveolitis and can be used to stage and follow these patients. The treatment of IPF remains controversial, but it is likely that corticosteroids reduce the alveolitis and prolong the lifespan of these patients.

Langerhans' cells were found in lung biopsies in one of nine control patients and in 20 of 160 patients with fibrotic lung disorders, including 13 of 56 patients with idiopathic pulmonary fibrosis, two of nine patients with collagen vascular diseases, two of seven patients with hypersensitivity pneumonitis, and each of three patients with end stage fibrosis of uncertain cause. Langerhans' cells were not found in any of the 41 patients with sarcoidosis, the 35 patients with interstitial lung diseases associated with inhalation of inorganic dusts, the seven patients with pulmonary lymphangioleiomyomatosis, or the two patients with chronic eosinophilic pneumonia. In the control patient, Langerhans' cells were found between epithelial cells in bronchioles. In patients with fibrotic lung disorders, Langerhans' cells were found in the epithelial layer of bronchioles and alveoli containing proliferating epithelial cells, i.e., either cuboidal epithelial cells of bronchiolar origin or type II alveolar epithelial cells. Severe fibrosis or squamous metaplasia were not prerequisites for the presence of Langerhans' cells. The motility of Langerhans' cells apparently was restricted, as they were not found in the air spaces in any of the biopsies, and they were not recovered from bronchoalveolar lavage fluid of any of the 97 patients studied, even though some of these patients had relatively numerous Langerhans' cells in lung biopsies. These observations are in sharp contrast to those in pulmonary histiocytosis X, in which histiocytosis X cells (HX cells) occur in granulomas, in alveolar interstitium, and between epithelial cells of the lower respiratory system. HX cells also migrate into air spaces, as shown by their occurrence in bronchoalveolar lavage fluid. The HX bodies in HX cells are morphologically similar to Langerhans' cell granules, but are more numerous and pleomorphic. HX cells are considered to be reactive or activated Langerhans' cells.

The topographic distribution, population density, and ultrastructural features of metachromatic cells (mast cells and basophilic leukocytes) were studied in lung biopsies from five control patients and 17 patients with fibrotic lung disorders. The great majority of metachromatic cells were mast cells. The average number of metachromatic cells per square millimeter of tissue section was much larger in patients with fibrotic lung disorders (45.8 +/- 6.5) than in control patients (2.6 +/- 1.6). In control patients, mast cells were most frequently seen in subpleural and perivascular connective tissue. In contrast, the vast majority of mast cells in patients with fibrotic lung disorders was present in thickened, fibrous alveolar septa; mast cells also were found within the alveolar epithelial layer and alveolar lumina. The quantitative distribution of different types of mast cell granules differed in the two groups of patients: granules composed of scrolls were more frequent in control patients, and granules of the combined type (containing mixtures of different components within the same granule) were more frequent in patients with fibrotic lung disorders. Mast cells in the latter patients appeared to migrate through defects in the basement membrane into the epithelial layer and alveolar lumina; mast cells in these areas often showed reduced numbers of granules and disorganized granule content. These changes suggest that pulmonary parenchymal mast cells in fibrotic lung disorders undergo a chronic process of partial degranulation which differs from that found in anaphylaxis; this chronic release of mast cell products may contribute to the continuing alveolar injury and the ventilation-perfusion inequalities observed in the fibrotic lung disorders.

Ultrastructural studies were made of the types of alveolar epithelial cells in fibrotic lungs from 34 patients, including 20 with idiopathic pulmonary fibrosis, five with collagen-vascular diseases, six with sarcoidosis, one with lymphangioleiomyomatosis, one with histiocytosis X, and one with chronic eosinophilic pneumonia. In 28 patients, proliferation of type II alveolar epithelial cells was recognized on the basis of lamellar bodies in the cytoplasm, microvilli in the luminal surface, focal microfoldings of the basal plasma membrane, close interaction with underlying mesenchymal cells, and unilayered arrangement. Two types of cuboidal epithelial cells were recognized and were considered to be derived from bronchiolar basal cells (type A cuboidal cells) and from cuboidal cells in respiratory bronchioles (type B cuboidal cells). Type A cuboidal cells frequently contained large numbers of cytoskeletal filaments, and their basal plasma membranes possessed hemidesmosomes in close association with anchoring fibrils. Type B cells lacked hemidesmosomes and anchoring fibrils, Proliferation of either or both types of cuboidal cells was found in 30 patients. In 10 patients (average degree of fibrosis = 3.5 on a scale of 0 to +4), the proliferation involved type A cells; in 10 other patients (average degree of fibrosis = 2.5), type B cells in nine patients (average degree of fibrosis = 3.4), both type A and type B cells; in one patient cuboidal cells were identified only by light microscopy. In 17 patients, proliferating cuboidal cells formed foci of epithelial pseudostratification. Type II alveolar epithelial cells did not participate in the process of multilayering. Thus, type II alveolar epithelial cells and two types of cuboidal epithelial cells are sources of epithelial renewal in damaged alveoli in fibrotic lungs. Type II cells proliferate mainly in areas of less severe degrees of fibrosis; cuboidal cells become the main source of epithelial renewal in areas of very severe lung damage.

Ultrastructural study of pulmonary biopsy specimens from patients with fibrotic lung disease disclosed the presence of nuclear inclusions in 1% or less of cuboidal alveolar epithelial cells in 9 of 19 patients, including 6 of 12 patients with idiopathic pulmonary fibrosis, 2 of 3 patients with collagen-vascular disease, and 1 of 3 patients with sarcoidosis. Nuclear inclusions were not observed by ultrastructural study in 5 control patients. The inclusions consisted of masses or aggregates of tubules which probably were derived from the inner nuclear membranes. These tubules were smooth-walled, showed branchings and bifurcations, were composed of single trilaminar membranes, usually had a clear content, and ranged from 500 to 1000 Å in diameter. They resembled nuclear tubules which occur in other cell types under conditions of rapid growth or specific hormonal stimulation. Statistically significant differences between the groups of patients with and without nuclear inclusions in cuboidal alveolar epithelial cells were not found with respect to smoking history, degree of fibrosis in the lung biopsy specimen, or the degree of pulmonary physiologic impairment. However, the average age of the patients having nuclear inclusions was significantly greater than that of patients not having nuclear inclusions. In addition, the frequency of indentations in the nuclei of cuboidal alveolar epithelial cells was greater in patients with nuclear inclusions than in patients without nuclear inclusions. Highly significant correlations were observed between the presence of nuclear inclusions and the presence of a) anchoring fibrils and hemidesmosomes along the basal surfaces of alveolar epithelial cells and b) multilayering of the alveolar epithelium.

A 35-year-old primigravida was admitted to the Department of obstetrics complaining of dyspnea and left back pain at 21 weeks' gestation. Chest roentgenogram revealed diffuse reticulonodular shadows predominantly in both lower lung fields and arterial hypoxemia was present. Pulmonary function tests showed restrictive impairment and decreased carbon monoxide diffuse capacity. From these results, interstitial pneumonia was suspected and she was first treated with prednisolone. However during her pregnancy, spontaneous pneumothorax occurred. Following spontaneous delivery of healthy infant at 37 weeks, left chylothorax occurred, and pleurodesis was performed with OK432. Thereafter the histological diagnosis of pulmonary lymphangiomyomatosis was made by transbronchial lung biopsy and treatment of prednisolone was stopped. She was treated with tamoxifen. In addition, progesterone-receptor was detected in the pulmonary tissue obtained at open lung biopsy. She was treated with cyclophosphamide in addition to tamoxifen. At present, shortness of breath has decreased slightly in comparison with one year previously, but no improvement has been seen in lung function tests or chest roentgenogram.

Electron microscopic studies of lung were made and compared in 17 patients with lung disease (10 with idiopathic pulmonary fibrosis, 3 with collagen--vascular diseases, 3 with sarcoidosis, and 1 with chronic eosinophilic pneumonia) and in 5 control patients. In control patients, the alveolar epithelial cells were normal, and no hemidesmosomes were present between the plasma membranes and the basal laminae. In comparison, cuboidal alveolar epithelial cells were present in 15 of the patients with fibrotic lung disease; in 9 of these the alveolar epithelial cells were multilayered. In 7 of the latter 9 patients (5 with idiopathic pulmonary fibrosis and 2 with collagen-vascular diseases), the basal laminae of the alveolar epithelial cells were attached to the plasma membranes by hemidesmosomes and to the underlying interstitial connective tissue by "anchoring fibrils." These fibrils measured from 4000 to 6000 A in length and from 200 to 600 A in width. One or both ends of the anchoring fibrils inserted into thebasal lamina, often forming arcs through which collagen fibrils and connective tissue microfibrils penetrated. Anchoring fibrils showed a complex pattern of transverse banding, which differed from that of collagen and appeared to be symmetric about the center of the fibril. These anchoring fibrils, which resemble those in normal skin and other tissues, were not found in lungs of control patients. In addition, there was a significant correlation between the severity of the pulmonary fibrosis and the presence of anchoring fibrils. These observations suggest that in severe fibrotic lung disease, anchoring fibrils reinforce the attachment of the basal lamina of multilayered alveolar epithelial cells to interstitial connective tissue.

Bronchiolar findings in B8 and 9 of the right lung were taken with a BF-1. 8T bronchiolo-fiberscope in a total of 11 patients with bronchial asthma (6 male, 5 female, average age 59 years). In these patients air pollution was considered responsible for bronchial asthma. Approximately one month after the bronchoscopic examination, transbronchial lung biopsies were performed in the same portion of the lung. Histological and electron microscopic findings were correlated with the above results. Abundant secretion of a serous nature was constantly noted in the peripheral airways of each patient, which was consistent with the histological finding of goblet cell hyperplasia. Dark greenish pigmentation over the edematous mucosa was identified as anthracotic pigments, with or without iron deposit in the tissues. All patients showed occasional aggregates of alveolar macrophages with various amounts of carbon-mixed mineral dusts in their cytoplasm. Six of them formed in the alveolar interstitium micro-granuloma which consisted of epithelioid cells and multinucleated giant cells. These monocyte-derived cells were obviously adherent to one another by development of paired or unpaired subplasmallemmal linear densities along their cell membranes. Nine patients showed regeneration of bronchiolar cuboidal and type II alveolar epithelial cells along the proximal alveolar sacs. They frequently showed nuclear inclusions. This proliferative tendency is suggestive of previous bronchiolo-alveolar damage due possibly to the air pollutants in these patients.