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Biomedical subjects

B E Heard

Publications and source records attributed to B E Heard.

At least 19 recordsLinked to original sources

Apposition of fibroblasts to mast cells and lymphocytes in normal human lung and in cryptogenic fibrosing alveolitis. Ultrastructure and cell perimeter measurements.

The perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (-19.6, 25.1); P = 0.65). The PPAF range overall was 3.8-94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung. The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung.

Adult

Heterogeneous ultrastructure of human bronchial mast cells: morphometric subdivision of cell types and evidence for a degranulation gradient.

Structural heterogeneity of mast cells in human bronchial mucosa was investigated by examining 100 cells by electron microscopy and morphometry. Differential counts of secretory granules allowed subdivision of mast cells into three groups: (1) 49 cells with greater than 65% mixed granules; (2) 30 cells with greater than 30% scrolled granules; (3) 12 cells with greater than 30% particulate granules. Nine cells showed borderline characteristics. Records of depths of cells in the mucosa showed that most mixed-granule cells occupied middle levels, whereas most scrolled granule cells lay higher up, near the basement membrane. This raised the possibility that scrolled-granule cells may represent partly degranulated mixed-granule cells. Nineteen mast cells were filled with very dense mixed granules, and appeared to correspond to those staining with safranin in paraffin sections. However, morphometry did not produce any criteria for distinguishing these cells sharply from paler mixed-granule cells, which were therefore regarded as degranulating forms of the same type of cell. Evidence was found of a gradient of mast cell degranulation which appeared to increase in magnitude upward from deep submucosa to superficial mucosa. This evidence included finding a significant upward reduction in total granule area per cell, total granule numbers, numbers of mixed granules, and numbers of dense-cored granules. It was concluded that although bronchial mucosal mast cells could be subdivided ultrastructurally into three apparently heterogeneous groups, degranulation was found to produce a wide range of different cell appearances, and could, conceivably, even be responsible for the above grouping, rather than intrinsic mast cell heterogeneity.

Bronchi

Mast cells in human lungs.

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.

Alveolitis, Extrinsic Allergic

Pathology of seven mucous cell adenomas of the bronchial glands with particular reference to ultrastructure.

The pathology, including ultrastructure, of seven mucous cell adenomas of the bronchial glands is described. They occurred as polypoid intraluminal lesions in both male and female patients between the ages of 7 and 55 years (mean 26 years). Histologically they were all benign and consisted of predominantly mucus-secreting cells arranged in acini or ducts or in solid groups. A little squamous differentiation was evident in four cases, insufficient in our opinion, to justify the term mucoepidermoid tumour. By electron microscopy, many tumour cells resembled mucous cells of the bronchial glands, containing typical large mucous granules of finely granular, reticular or fibrillated material, and sometimes small electron-dense bodies. In four cases some cells showed both secretory granules and features of squamous differentiation such as numerous tonofilaments and desmosomes. Oncocytic differentiation was seen occasionally.

Adenoma

Quantitation of types I and III collagen in biopsy lung samples from patients with cryptogenic fibrosing alveolitis.

The role of changes in the relative amounts of types I and III collagen in cryptogenic fibrosing alveolitis was investigated using a biochemical method adapted for small amounts of human lung tissue. Measurements were performed in 18 biopsy and seven post-mortem lung samples from patients with cryptogenic fibrosing alveolitis and the results were compared with clinical, physiological, radiological and histological data. The mean percentage type III collagen, compared with type I collagen, was significantly lower in post-mortem lung samples from patients with cryptogenic fibrosing alveolitis who died from the disease compared with the biopsy lung samples (p less than 0.01) and with the control lung samples (p less than 0.05). There was a positive correlation between the percentage of type III collagen and response to treatment at six months as shown by the improvement in the percentage predicted Kco (p less than 0.005) and FVC (p less than 0.01) and with the radiological changes (p less than 0.05). These changes remained significant at one year (p less than 0.05 in all cases). These results suggest that patients with a higher proportion of type III collagen have earlier disease and show a better response to treatment than those with a lower proportion of type III collagen. The potential advantages of measuring collagen types for staging cryptogenic fibrosing alveolitis are discussed.

Aged

Evidence for longer survival of patients with pleural mesothelioma without asbestos exposure.

In a group of 23 patients with histologically confirmed malignant mesothelioma of the pleura who could not recall exposure to asbestos dust, survival was significantly longer than in a group of 83 patients with known exposure. Asbestos bodies were found by a quantitative method significantly less frequently in the unexposed than in the exposed group. The longer survival of patients without known exposure could not be correlated with any significant difference in the histological cell types of the tumours from those of exposed patients. In the 83 patients with known exposure survival did not relate to duration of exposure. Consequently, although the tumours of patients unable to recall exposure may be caused by unrecognised environmental contamination with asbestos dust, the longer survival of these patients would suggest a different aetiology.

Adult

Cryptogenic organizing pneumonitis.

Eight patients with histological intra-alveolar organization, but no evidence of an infective or other aetiological agent, are reported. They characteristically presented with a short history of severe dyspnoea, cough, malaise, weight loss, bilateral radiographic shadowing and a raised ESR. There was a dramatic response clinically and radiologically to prednisolone but relapse occurred quickly as the dose was reduced. Control was re-established with an increased dose of prednisolone. In order to avoid confusion with post-infective organizing pneumonia the term cryptogenic organizing pneumonitis is suggested.

Aged

Malignant mesothelioma of the pleura: relation between histological type and clinical behaviour.

The differing clinical behaviour of malignant mesothelioma of different cell types was studied in 115 cases of pleural mesothelioma, classified histologically into epithelial (60), sarcomatous (25), and mixed (30). Epithelial mesotheliomas were associated with clinical features characteristic of carcinomas rather than sarcomas, including spread of tumour by direct extension, large pleural effusions, contralateral pleural effusions, ascites, metastases in regional lymph nodes, and occasional response to radiotherapy. Sarcomatous mesotheliomas were associated with clinical features more characteristic of sarcomas, with more frequent distant metastases, little or no effusion, and shorter survival. Mixed tumours had features of both, large pleural effusions occurring as frequently as with epithelial tumours, but survival being almost as poor as in sarcomatous cases. Despite these differences there is evidence from published reports that epithelial, sarcomatous, and mixed mesotheliomas have a common origin from mesothelial cells or their precursor cells.

Humans

One very rare and one new tracheal tumour found by electron microscopy: glomus tumour and acinic cell tumour resembling carcinoid tumours by light microscopy.

Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract.

Carcinoid Tumor

Congenital lobar emphysema: a case with bronchial atresia and abnormal bronchial cartilages.

An infant with congenital left upper lobe emphysema presenting with respiratory distress and failure to thrive, which necessitated lobectomy, is described. Careful pathological examination revealed two defects in association with the emphysema: bronchial atresia and defective bronchial cartilage in the affected lobe. Whilst congenital lobar emphysema is the term usually employed to describe this clinical presentation of respiratory distress in infancy, 'panlobular emphysema of infancy' would be a more accurate description. Congenital defects in the airways may account for the development of emphysema, but there may be a more fundamental congenital tissue abnormality at alveolar level.

Bronchi

Diagnostic accuracy of cytology and biopsy in primary bronchial carcinoma.

The accuracy of diagnosis in 656 patients with the four common histopathological types of primary lung cancer has been assessed by comparing the cell type diagnosis made on cytological and histological investigation with that determined by examination of the surgically resected or necroscopy specimen. The accuracy of diagnosis achieved by cytological examination of sputum and bronchial aspirate, and by bronchial biopsy histology was over 85%. The least accurate diagnostic procedure was percutaneous needle biopsy (62%). Squamous and small cell tumours were accurately diagnosed by all four investigations but errors were made in the diagnosis of large cell and adenocarcinomas. Nearly half the number of patients (43%) with large cell carcinoma were later reclassified as having squamous carcinoma and of the patients with adenocarcinoma 32% had been predicted to be squamous and 18% large cell carcinoma. We consider such quality control of pretreatment diagnosis mandatory in management of individual patients and before enrollment in clinical trials.

Adenocarcinoma

A pathological study following bronchial artery embolization for haemoptysis in cystic fibrosis.

A detailed post-mortem study is reported on an adult with cystic fibrosis who died in respiratory failure three weeks after selective bronchial artery embolization with gelatin sponge to treat severe haemoptysis. Bronchial arteriography during the procedure showed complete occlusion of the vessel supplying the righ upper lobe and following this the bleeding stopped. However, post-mortem angiography of the same vessel demonstrated disappearance of much of the injected material with contrast bypassing the remaining gelatin to fill the peripheral bronchial arterial bed. This report therefore adds pathological evidence to previous clinical reports which have suggested that this procedure may not produce permanent occlusion of the embolised bronchial artery.

Adult