Brain death and brainstem death.
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Biomedical subjects
Publications and source records attributed to D Lamb.
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The study objectives were to determine the effect of several factors related to tissue preparation on the relationship between medial area and size of the muscular pulmonary artery (defined in terms of total length of internal elastic lamina). This relationship took the form y = Axb that was linearized by plotting the square root of medial area against artery size. Complete distention of pulmonary arteries by an injection medium caused the internal elastic lamina to stretch by a factor of approximately 1.5. The relationship between medial area and artery size was unaffected by either the pressure method used for lung inflation/fixation or the tissue-embedding medium. Tissue shrinkage was considerable with paraffin embedding and negligible with glycol methacrylate. More arteries were considered measurable in glycol methacrylate-embedded tissue.
Current methods for quantitating the media of pulmonary arteries are inadequate in that either they produce measurements of the media and artery size that are affected by vasoconstriction, or they are complicated to use. We developed a method that overcomes these problems. It produces measurements of medial area and the artery size is expressed in terms of the total length of the internal elastic lamina. The measurements are obtained directly from histologic sections using a light microscope with a camera lucida attachment in conjunction with a microcomputer linked to a digitizing board. Repeatability of the measurements is excellent but it is essential to digitize at a magnification at which crinkles in the internal elastic lamina are clearly visible. Arteries that are considered to be digitizable are representative of the total muscular pulmonary artery population.
Eleven patients with peripheral bronchial carcinoma had computerised tomographic (CT) scans before operation. The resected specimens from six of these patients showed mild centri-acinar emphysema. Preoperatively the two groups had not differed significantly in spirometric findings or lung volumes. The frequency distribution curves of EMI numbers within the lung fields of patients who proved to have centri-acinar emphysema differed significantly from those of the group who did not, there being more pixels in the EMI range -450 to -500 in the emphysematous group (p less than 0.001). Detailed assessment of lung density by CT scanning may be useful in the diagnosis of emphysema in life.
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Measurement of the Doubling Times [DT] for 27 human pulmonary neoplasms have been made. Squamous and large cell tumours had a wide range of values for DT whereas for small cell undifferentiated carcinoma, and possibly large cell undifferentiated carcinomata without stratification, the range was narrower. Mean DT for different primary bronchogenic carcinoma groups were: Squamous cell 146 days, Adenocarcinoma 72 days, Small cell 66 days, and Large Cell 111 days. The number of adenocarcinomata is very small in number and our value of 72 days is probably not representative of this group of tumours. Relationship between DT and tumour differentiation was difficult to identify in our series. Of these 27 a unique series of 17 have parallel data on DT and Potential Doubling Time (DTpot) and the Cell Loss Factor [0] calculated. Great discrepancy between DT and DTpot existed in each case and cell loss was high, ranging from 54% to 99%. All primary bronchogenic carcinomata had cell loss of greater than 70%; in almost two thirds of these cases the value was 90% or more. All undifferentiated tumours and a majority of poorly differentiated tumours had cell loss of 90% or more. As cell loss increased, tumour thymidine labelling index (TLI) increased and the tumours tended to be less well differentiated. The relationship, if any, between cell loss and DT was unclear.
The pathology and dust content of lungs from 261 coalminers in relation to the appearances of their chest radiographs taken within four years of death were examined. Radiological opacities of coalworkers' pneumoconiosis were more profuse the more dust was retained in lungs. Among the men who had mined low rank coal--that is, with a relatively high proportion of ash--the increase in profusion was most closely related to the ash component of the dust, whereas in men who had mined high rank coal both coal and ash increased in the lungs in relation to radiological profusion. The fine p type of opacity was found to be associated with more dust and a higher proportion of coal and less ash than the nodular r opacity, and was also more likely to be associated with emphysema. The pathological basis of the different types of opacity found on the radiographs of coalminers related to the number, size, and nodularity of the dust lesions. Larger fibrotic lesions were likely to appear as r opacities, whereas fine reticular dust deposition was most likely to present as p opacities, q opacities showing a mixture of appearances. The study has shown that the composition of dust retained in the lung, as well as its amount, makes an important contribution to the radiographic appearances of pneumoconiosis. In particular, the r type of lesion on the radiograph of a low rank coalminer indicates the possibility of a silicotic like lesion.
The goblet cell and Clara cell populations of human distal airway epithelium were examined. The bronchioles, terminal bronchioles, and respiratory bronchioles of 16 smokers and four non-smokers were studied by both light and electron microscopy in surgically resected specimens. A very significantly (p less than 0.001) greater number of goblet cells were found in the bronchioles of smokers compared than in those of non-smokers but no such difference was evident in terminal/respiratory bronchioles. Clara cell numbers in contrast were lower in the bronchioles (p less than 0.01) and terminal and respiratory bronchioles of smokers (p less than 0.01). Both of these alterations in cell frequency may adversely affect small airway function in smokers.
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The lungs of 450 coal miners who had been studied previously in a long-term epidemiologic project at 24 British mines have been examined post-mortem for signs of dust-related fibrosis and emphysema. Reliable estimates of cumulative (working-life) exposures to respirable mine dust were available for 342 of the men. The relative frequency of emphysema increased with age at death, and both panacinar and centriacinar emphysema occurred more frequently in smokers than in nonsmokers. The proportion of subjects with any emphysema was 47% in 92 men with no palpable dust lesions, 65% in 183 with small, simple pneumoconiotic lesions, and 83% in 175 miners with massive fibrosis (PMF). The chance of finding centriacinar emphysema in those with PMF increased significantly with increasing exposure to coal dust in life (p less than 0.025). A similar but less convincing relationship was found in those with simple pneumoconiosis (p less than 0.11), but in both groups, increasing amounts of ash with a given exposure to coal reduced the probability of finding centriacinar emphysema. The occurrence of centriacinar emphysema was associated also with increasing amounts of dust retained in the lungs. A preliminary exploration of this association did not support the hypothesis that emphysematous lungs clear dust less efficiently. We conclude that the association observed between exposure to respirable coal dust and emphysema in coal miners indicates a causal relationship. However, because it can be demonstrated only for men whose lungs show some dust-related fibrosis, it is suggested that the extent and nature of such fibrosis may be a crucial factor in determining the presence of centriacinar emphysema.
The in vitro thymidine labelling indices (TLI) of 58 human lung tumours were assessed using autoradiography. The labelling technique involved incubation of 1 mm3 tumour fragments with 3H-thymidine (5 muCi ml-1) under conditions of hyperbaric oxygenation at a pressure of 3 atmospheres. Only a rim of labelling was achieved along the edges of fragments and the depth of this rim varied from tumour to tumour. A technique for counting TLIs was therefore devised to take this into account. In general, those tumours showing low TLI values of less than 5.0% showed a greater depth of labelling. The common malignant tumours of the bronchus showed a wide range of values (2.2-30.4%) though the adenocarcinomata had a lower average value than the other groups. With the squamous carcinomata a relationship with differentiation was shown. The mean value for small cell carcinomata (16.9%)--a highly aggressive tumour--was no higher than for the other groups. The low grade malignant tumours showed TLIs of less than 3.0% and these values correlate with their less aggressive clinical behaviour. Labelling of stromal cells and inflammatory cells varied greatly from tumour to tumour; however, no correlation was found with the TLIs of tumour cells.
The prevalence of right ventricular hypertrophy was studied in necropsy material from 215 coalworkers, a group which consisted of 115 men with simple or no pneumoconiosis and 100 with progressive massive fibrosis. Right ventricular hypertrophy was considered to be present if the ratio of the weight of the left ventricle plus septum to that of the right ventricle was less than 2:1. The prevalence of right ventricular hypertrophy was low (15%) in the absence of progressive massive fibrosis and appeared to be related to emphysema or airways disease or both, and not to simple pneumoconiosis. It was evident only in subjects who had smoked. In subjects with progressive massive fibrosis the prevalence of right ventricular hypertrophy was higher (34%) and it was occasionally seen in non-smokers. The prevalence increased with increasing size of lesion, and for any given size of lesion subjects with right ventricular hypertrophy had more panacinar emphysema than those without right ventricular hypertrophy. There was no relationship, however, between the extent of massive lesions or amount and type of emphysema and the degree of right ventricular hypertrophy.
The lungs of 490 British coal miners were examined for comparisons of the lesions of coal workers' pneumoconiosis with lung dust content and dust exposure. Variations were found in histological appearances that formed a range, the extremes of which indicated two separate patterns of disease. In men from high rank collieries, whose lung dust had a high carbon content and little ash, most of the nodules of simple pneumoconiosis were evenly pigmented with dust, and where progressive massive fibrosis (lesions greater than 1 cm in diameter) had developed, this appeared to be by the enlargement of a single lesion. In men from low rank collieries where the ash content of lung dust was high, the centers of the nodules were often free of dust particles and in extreme cases these lesions were very similar to silicotic nodules. If PMF developed in these cases, it often appeared to be by the fusion of closely spaced groups of smaller nodules. While there appeared to be little difference between the lung dust composition of men from high rank collieries and the dust to which they had been exposed, in men from low rank collieries the proportion of the noncoal minerals in the lungs was usually higher than it had been in the mine dust. This indicated some form of differential retention of these components, which was progressively more marked in men with the more serious grades of pneumoconiosis.
Thirty-seven consecutive patients, referred to a respiratory unit with a histological diagnosis of small cell carcinoma of the bronchus, were treated with a combined chemotherapy regime of adriamycin, vincristine and cyclophosphamide. Palliative radiotherapy was given for the control of symptoms. Thirty of 37 patients responded to treatment, 11/37 having a complete and 19/37 a partial response. The median survival of those patients with a complete response was 55 weeks, significantly higher (P less than 0.01) than either those with partial or no response to treatment. Those patients with limited disease survived longer. A high proportion of patients relapsed at the primary site of the tumour in the lungs. The relationship between the therapeutic response and the histological subtype of small cell carcinoma suffered from the limitations of the available pathological material. However, more of the patients with a complete response were of the lymphocytic-like pattern of small cell carcinoma. Useful survival in these patients with inoperable small cell carcinoma was achieved using this regime of chemotherapy, even in those patients with extensive disease, five of whom had survived for over one year.
Bronchocentric granulomatosis has no specific clinical, radiological or immunological features, the diagnosis remains that of morphology on biopsy or resected lung tissue. The morphological features of bronchocentric granulomatosis can occur in a variety of situations and we believe this pathology reflects one of the limited ways in which bronchi can respond to injury, the essential requirement for its development being a sustained and/or intense inflammatory insult within the bronchial lumen.
Respiratory, renal, and hepatic insufficiency developed in five patients who had been admitted to hospital for a variety of reasons. Although in four cases Aspergillus had been isolated from tracheal secretions before death, the significance of this finding was not fully appreciated, and in all five the diagnosis of aspergillosis was made at necropsy. Since treatment has to be started early if it is to be effective, patients with any combination of respiratory, renal, and hepatic failure should have their tracheal secretions examined daily. If Aspergillus is cultured, and hyphae are present in a fresh smear, and the patient has features of a generalised infection without an obvious site of infection, treatment for aspergillosis should be considered.
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Bronchi from 94 coalminers were examined for enlargement of the mucous glands. The measurements used were the mean and maximum ratios of gland thickness to wall thickness, the mean acinar diameter, and the ratio of the gland area to the area of the non-cartilaginous portion of the bronchial wall. The relationships between these measurements and the subjects' smoking habits and their past exposure to dust in the coal mines were analysed. Smoking was found to be significantly related to mean and maximum gland-to-wall ratios. In addition, coalmine dust exposure was found to be significantly related to maximum gland:wall ratio. No significant relationships were found between gland dimensions and pneumoconiosis or dust retained in the lung. These results lend support to the view that irritants encountered in an occupational environment may play an important part in the development of hypersecretion of mucus.