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Biomedical subjects

A Dewar

Publications and source records attributed to A Dewar.

At least 73 records · Page 4Linked to original sources

Lipoprotein macroaggregates in bronchoalveolar lavage fluid from patients with diffuse interstitial lung disease: comparison with idiopathic alveolar lipoproteinosis.

Lipoprotein macroaggregates were present in cytocentrifuge preparations of bronchoalveolar lavage fluid from four patients with diffuse lung diseases other than idiopathic alveolar lipoproteinosis. In three patients the primary diagnosis was cryptogenic fibrosing alveolitis and in one sarcoidosis. We confirmed the presence of large multilamellar aggregates of lipoprotein by ultrastructural examination in patients with both interstitial lung disease and idiopathic alveolar lipoproteinosis. The small lamellar bodies and amorphous debris found in idiopathic alveolar lipoproteinosis were rare in the patients with interstitial lung disease. The lavage fluid from patient with interstitial lung disease did not show the substantial alterations in phospholipid composition that were seen in lavage fluid in idiopathic alveolar lipoproteinosis. These ultrastructural and biochemical features may help to distinguish idiopathic from other causes of alveolar lipoproteinosis, particularly at an early stage, when differential diagnosis may be difficult.

Adult↗

Primary ciliary dyskinesia: cytological and clinical features.

Thirty patients with functional and/or morphological abnormalities of respiratory tract cilia were identified. The diagnosis of primary ciliary dyskinesia was based on observed abnormalities of ciliary ultrastructure or beating in vitro (beat pattern, beat frequency or percentage of motile cilia). Beat frequency and motility indices approached the normal range in some cases and suggests that the term 'immotile cilia syndrome' is not appropriate. Morphological abnormalities were most commonly due to deficiency of dynein arms, affecting the outer arms (n = 7), inner arms (n = 3) or both (n = 10). Examples of radial spoke and microtubular defects were also identified but in seven subjects ciliary ultrastructure was normal. In six patients paired samples of nasal and bronchial cilia were obtained and showed consistent abnormalities of motility and ultrastructure. Adenosine triphosphate and adenosine triphosphatase did not restore in vitro motility when added to dynein deficient cilia. The clinical picture was of life-long sinusitis and recurrent bronchial infection but the spectrum was broader than that encompassed by Kartagener's triad (dextrocardia, sinusitis and bronchiectasis). Fourteen patients had normal cardiac situs and definite or highly suggestive evidence of bronchiectasis was present in only 17 patients. Radiological evidence of sinusitis was common but absence of frontal sinuses was not universal. Chronic serous otitis media was a frequent finding but deafness was rarely profound. Fertility problems were common but were not universal in female subjects. Lung function testing revealed evidence of airflow obstruction but this was mild in most cases.

Adenosine Triphosphatases↗

Pleural mesothelioma of epithelial type and pulmonary adenocarcinoma: an ultrastructural and cytochemical comparison.

Twelve diffuse pleural mesotheliomas of epithelial type have been compared with 20 intrapulmonary adenocarcinomas. All mesotheliomas were negative for epithelial mucin by diastase periodic acid Schiff staining and for carcinoembryonic antigen by immunoperoxidase staining, whereas 17/20 carcinomas stained for epithelial mucin and 15/20 for carcinoembryonic antigen. Hyaluronidase-sensitive alcian blue positive material was present in 6/10 mesotheliomas and 0/20 carcinomas. Previously described electron microscopic differences were validated, including one which has so far received insufficient emphasis: microvilli making direct contact through basement membrane deficiencies with collagen fibres on the abluminal side of tumour cells were identified in 10/12 mesotheliomas and in 0/20 carcinomas.

Adenocarcinoma↗

Fine structural changes in idiopathic pulmonary haemosiderosis.

Lung biopsies from four children and two adults with idiopathic pulmonary haemosiderosis have been examined by transmission electron microscopy. No qualitative differences were identified between the children and the adults but the changes were more severe in the children. In each case the major damage involved the capillary endothelium and its basement membrane. Capillary endothelial swelling was very noticeable and in one case the endothelium was attenuated but gaps between endothelial cells were very difficult to find. Capillary narrowing and platelet aggregation were common. The capillary endothelial basement membrane showed focal thickening, particularly on the thick side of the air/blood barrier, but no electron dense deposits were identified. Degenerative changes in the alveolar epithelium were not so marked as those in the capillary endothelium and the epithelial basement membrane was normal except for haemosiderin deposition. Haemosiderin was also noted on elastin and within intra-alveolar macrophages. Other secondary changes included mild interstitial oedema and fibrosis. These findings indicate that the major site of damage is the alveolar capillary, but provide no evidence of the cause of the disease.

Adolescent↗

Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum.

Animals↗

Mast cells, atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases.

Bronchoalveolar lavage (BAL) samples from exposed patients with extrinsic allergic alveolitis (EAA) contained mast cells in increased numbers in addition to lymphocytes. The counts rarely exceeded 0.5% in sarcoidosis, cryptogenic fibrosing alveolitis, or asbestosis or in control samples, but they were as much as 10-fold higher in EAA (p less than 0.001). Higher concentrations of histamine were demonstrated in EAA BAL-cell lysates, and histamine was released from cells challenged with anti-IgE. Electron microscopic examination confirmed that the cells were mast cells that differed from mast cells in dermal connective tissue and alveolar interstitial tissue but resembled bronchial subepithelial tissue mast cells in showing more features suggestive of activation. However, they showed more marked degranulation, and many were young. By light microscopy, they also resembled "mucosal" rather than "connective" tissue mast cells since granule staining was prevented by formaldehyde. Mast cell counts fell to normal after removal of patients from exposure, but lymphocyte increases, including atypical "blast" forms, persisted despite clinical recovery. Neutrophils were also increased before, but rarely after, removal. We suggest that EAA may provide an example of a human disease to support recent evidence that some delayed hypersensitivity disorders involve mast cells as well as lymphocytes.

Alveolitis, Extrinsic Allergic↗

Fine structural changes in cryptogenic fibrosing alveolitis and asbestosis.

Lung biopsies from 17 patients with cryptogenic fibrosing alveolitis of a cellular rather than fibrotic pattern were examined by transmission electron microscopy in the hope that such cases would show features of pathogenetic significance. Further selection was made by choosing minimally affected areas. There was no ultrastructural evidence of immune complex deposition but alveolar epithelial and capillary damage was frequently found (17 and 14 of the 17 cases respectively). Alveolar epithelial injury consisted of patchy necrosis and regenerative hyperplasia. Alveolar capillary injury consisted of cytoplasmic swelling and basement membrane thickening and reduplication. Many of these features have not been emphasized in previous reports and their prominence in early stages of the disease suggest that they may have pathogenetic significance, possible mechanisms of which are discussed. Similar findings identified during the course of this study in 8 asbestos workers suggest that similar pathogenetic mechanisms may operate in asbestosis.

Asbestosis↗

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↗

Cutaneous and pulmonary histopathological responses to platelet activating factor (Paf-acether) in the guinea-pig.

The effect of synthetic Paf-acether has been studied in guinea-pig skin, following intradermal injection, and in guinea-pig lung, following intravenous administration. Histopathological responses to Paf-acether were assessed by both light microscopy and electron microscopy. In addition, plasma protein extravasation and platelet accumulation were quantitatively assessed using radiolabelling techniques. Intradermal injection of Paf-acether, but not lyso-Paf, elicited acute increased vascular permeability, accompanied by intravascular accumulation of platelets and neutrophils. There was evidence, 2-8 h after intradermal injection of Paf-acether, of perivascular infiltration with neutrophils. At 24 h there was a mixed cellular infiltrate comprising mononuclear cells in addition to neutrophils. Following systemic administration of Paf-acether, aggregates of platelets in close association with neutrophils were evident within the pulmonary vasculature. Intravenous injection of Paf-acether, but not lyso-Paf, caused intrathoracic accumulation of radiolabelled platelets. These results suggest that Paf-acether has properties consistent with those of a mediator of inflammation.

Animals↗

Hydrocephalus and primary ciliary dyskinesia.

Primary ciliary dyskinesia was shown in a 12 year old boy with bronchiectasis who had developed hydrocephalus in the neonatal period. The possible relevance of his ciliary abnormality is discussed.

Child↗

Peripheral blood cell changes in response to acute hypoglycaemia in man.

Peripheral white and red blood cell changes were studied in response to acute insulin-induced hypoglycaemia in six normal, six splenectomized and five sympathectomized (tetraplegic) subjects. The normal subjects were restudied during beta (propranolol) and beta 1-selective (metoprolol) adrenergic blockade. In the normal subjects a lymphocytosis immediately followed the acute hypoglycaemic reaction (R) with a neutrophilia 2 h later. The early lymphocytosis was absent in sympathectomized subjects (P less than 0.001) and reduced under beta blockade (P less than 0.02) in normal subjects, indicating mediation via an adrenergic mechanism. The later neutrophilia from R + 60 min was not abolished by adrenergic blockade or preceding sympathectomy; the enhanced response with propranolol was associated with an elevated plasma cortisol. Haemoglobin, packed cell volume and total erythrocyte count rose maximally at R in all groups except the sympathectomized subjects in whom all parameters declined progressively from basal values. These peripheral erythrocytes changes appear to be mediated via an adrenergic mechanism which is unaffected by beta adrenergic blockade and which does not involve splenic contraction.

Acute Disease↗

Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.

Adult↗

Screening for ciliary dyskinesia - a spectrum of defects of motility and structure.

Ciliary motility and ultrastructure were studied in cystic fibrosis, bronchiectasis and Kartagener's syndrome and normal control subjects. In cilia from patients with Kartagener's syndrome, beat frequency was slower and there were more microtubular abnormalities and fewer dynein arms than for each of the other groups. In Kartagener's syndrome, ciliary motility and outer dynein arm numbers were positively correlated and there was a wide variation in each. Cystic fibrosis ciliary beat frequency and ultrastructure were normal.

Adolescent↗