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D Lamb

Publications and source records attributed to D Lamb.

At least 55 records · Page 3Linked to original sources
PubMed1993

Production of interleukin 1 by rat pleural leucocytes in culture after intratracheal instillation of crocidolite asbestos.

This study was undertaken to investigate the production of interleukin 1 (IL-1) by pleural leucocytes in culture and to evaluate the influence of intratracheal instillation of crocidolite asbestos on this production. Normal pleural leucocytes spontaneously released IL-1 in culture and stimulation with lipopolysaccharide (LPS) dramatically increased production. Intratracheal instillation with crocidolite asbestos induced recruitment of pleural leucocytes in the longer term and changed IL-1 production by the leucocytes. Reduced production of IL-1 was found by one day after instillation of asbestos and this was correlated with the dose of asbestos. With increasing time after instillation, however, release of IL-1 by pleural leucocytes gradually recovered to normal until, one month after asbestos injection, the leucocytes produced augmented IL-1 in culture compared with control pleural leucocytes. Our data show that pleural leucocytes possess the potential to produce IL-1 in vitro and this capability is altered by intratracheal instillation of crocidolite asbestos. This may be relevant to development of pleural diseases associated with inhalation of asbestos.

Animals↗
PubMed1993

Airspace size in lungs of lifelong non-smokers: effect of age and sex.

BACKGROUND: Emphysema is defined as the abnormal enlargement of airspaces distal to the terminal bronchiole, but the limits of normality of airspace size have never been defined. The aims of the study were to examine the effects of age and sex on airspace size in non-smokers and to define the limits of normal airspace size. METHODS: Airspace size was measured in terms of airspace wall surface area per unit volume of lung tissue (AWUV). AWUV was measured on histological sections of lung tissue with an automated scanning system, the fast interval processor. Thirty eight lifelong non-smokers were studied, 15 male and 23 female, with an age range of 21-93 years. Macroscopic emphysema was assessed semi-quantitatively on the midsagittal slice of each lung specimen. RESULTS: The relation between mean AWUV and age was negative (r = -0.78). This relation was linear, and the 95% prediction limits of its regression line were used as the limits of normality of AWUV in this sample. The AWUV-age relationship was similar in the men and women studied. Localised areas of macroscopic emphysema were found in three specimens whose mean AWUV measurements were within the normal range. CONCLUSIONS: There is a normal increase in airspace size associated with advancing age in adult lungs. The limits of normal AWUV between ages 21 and 93 years have been defined, and it is proposed that lungs with a mean AWUV below the 95% prediction limit should be considered as having emphysema.

Adult↗
PubMed1993

Relation between distal airspace size, bronchiolar attachments, and lung function.

BACKGROUND--Smoking related fixed airway obstruction may be due to airway scarring and narrowing or decreased support due to loss of adjacent alveolar walls. In this study of resected specimens, preoperative pulmonary function was compared with results of a morphometric study of lung structure. METHODS--Morphometric measurements were made on 42 inflation fixed lung specimens as follows: airspace wall surface area per unit volume (AWUV) was measured on at least 25 l mm2 histological fields from each specimen, expressed as a mean, and the mean of the lowest five measurements for each case (LF5). Minimum diameter, maximum diameter, diameter ratio (ellipticality), lumen area, and lumen circumference were measured on at least 16 non-respiratory bronchioles from each lung. Peribronchiolar alveolar support was measured as mean interalveolar attachment distance (IAAD). Measurements of pulmonary function included forced expiratory volume in one second (FEV1) (absolute and % predicted values; n = 42), slope of phase III (single breath nitrogen test; n = 28), closing volume (expressed as a percentage of vital capacity (CV/VC%); n = 28). RESULTS--Bronchiolar size was not independently related to the tests of lung function used. Percentage predicted FEV1 was related to mean IAAD, ellipticality, and mean AWUV. CV/VC% showed significant relation with ellipticality, mean AWUV, and LF5 AWUV. Slope of phase III increased with increasing IAAD. Significant correlations were found between ellipticality and AWUV (mean and LF5), and between ellipticality and IAAD. Both IAAD and ellipticality were significantly increased in patients with abnormally low FEV1. CONCLUSION--Destruction of airspace walls, particularly those attached to the peripheral bronchioles, is more influential in determining airflow limitation than bronchiolar size.

Aged↗
PubMed1993

How reliable is the diagnosis of lung cancer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party.

BACKGROUND: A study was undertaken to investigate the accuracy of typing of a series of bronchial carcinomas by experienced pathologists with an interest in lung cancer from the examination of bronchoscopic biopsy specimens. METHODS: Eighty bronchial biopsy specimens showing positive results for bronchial carcinoma were circulated to five pathologists, who recorded diagnostic criteria and diagnosis for each. Diagnoses were then compared with the diagnosis agreed from the resection specimen corresponding to each biopsy specimen. A "non-small cell carcinoma, not further specified" classification group was introduced for small biopsy specimens. RESULTS: A diagnostic accuracy of 75% was achieved for squamous cell carcinomas, 66% for small cell carcinomas, and 50% for adenocarcinomas. There was diagnostic confusion between small cell and non-small cell carcinoma in less than 10% of cases. The introduction of a non-specific non-small cell classification improved diagnostic accuracy by 10-15% for each non-small cell tumour group. CONCLUSIONS: There are appreciable inaccuracies in applying the World Health Organisation's 1981 classification of lung cancer to the diagnosis of bronchial carcinoma from small biopsy specimens and these inaccuracies have been measured. They can be diminished by introducing a less specific "non-small cell" category for use with this sort of biopsy material. Care should be taken not to overinterpret small biopsy specimens in lung cancer.

Biopsy↗
PubMed1993

Synchronous primary lung cancers: prevalence in surgical material and clinical implications.

BACKGROUND: The prevalence of synchronous primary lung neoplasms in surgical resection specimens was assessed. The associated clinical features and prognostic implications were investigated. METHODS: All surgical resections for lung cancer performed during seven years were reviewed. Synchronous tumours were defined by the presence of more than one tumour mass in the lung, by differences in histological subtype, by the presence of separate bronchial origins, or by differences in DNA stemlines. Clinical data were abstracted from case notes and information from the tumour registry. RESULTS: Just under 2% of all surgical specimens in the study period contained more than one primary carcinoma. The patients did not differ clinically from the general population of patients having surgery for lung cancer. The overall prognosis was poor (mean survival 27 months) but was significantly better for patients with synchronous squamous carcinomas (mean survival 49 months). CONCLUSION: Synchronous primary lung carcinomas are associated with a poor prognosis except in patients having tumours only of squamous histological type.

Adenocarcinoma↗
PubMed1993

Microscopic emphysema in relation to age and smoking habit.

BACKGROUND: The increases in airspace size within the human lung associated with microscopic emphysema can be assessed by measuring the airspace wall surface area per unit volume of lung tissue (AWUV). In a previous study the limits of normality of AWUV with age were estimated in lifelong non-smokers by the 95% prediction limits of the regression line for these variables. The aims of this study were to study the incidence of microscopically assessed emphysema in a group of smokers and to examine the influence of smoking habit on the susceptibility to and severity of microscopically assessed emphysema. METHODS: AWUV was measured on tissue sections from 125 lung specimens obtained from tobacco smokers (mean age 61.1 (range 33-85) years) with the fast interval processor, a rapid automatic scanning device. The mean AWUV value was calculated for each specimen and this figure was plotted against the age of the subject. The limits of normal AWUV were plotted, and AWUV values below these limits were taken as indicative of microscopically assessed emphysema. Details of the number of cigarettes smoked each day were obtained for 97 of the smokers. These subjects were grouped according to smoking habit: group 1, 1-19 cigarettes/day; group 2, 20-29 cigarettes/day; group 3, at least 30 cigarettes/day. The AWUV results from each of these groups were then assessed. RESULTS: Mean AWUV decreased with age in this group of smokers, but only 26% had microscopically assessed emphysema, indicating that within the group there were two subgroups of smokers with differing susceptibility to microscopically assessed emphysema. There were no sex differences in the incidence of microscopically assessed emphysema, nor were the incidence and severity increased with increased daily cigarette consumption. CONCLUSIONS: Susceptibility to microscopically assessed emphysema was found to be similar in male and female smokers. Daily cigarette consumption did not appear to be the primary factor influencing the susceptibility to or severity of microscopically assessed emphysema. Susceptibility differences within the smoking population should be taken into consideration in studies of the pathogenesis of emphysema.

Adult↗
PubMed1993

The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos.

We have used a rat intratracheal instillation model to study the effect of crocidolite asbestos exposure on cytokine production by bronchoalveolar lavage (BAL) leucocytes. In unexposed controls, the normal BAL leucocytes were mostly macrophages which spontaneously produced interleukin 1 (IL-1)-like activity and tumour necrosis factor (TNF-alpha) in culture; these levels were enhanced by stimulation with LPS. In animals exposed to crocidolite asbestos, two new types of cell, neutrophils and eosinophils, were recruited into the bronchoalveolar space by 1-3 days after instillation. However, the BAL profile had returned to normal by 14 days. The production of IL-1-like activity was decreased considerably compared to control from 1 to 14 days after asbestos instillation, but was increased at 30 days. However, the leucocytes produced increased TNF-alpha as early as 3 days after asbestos instillation and maintained this elevated level throughout the experimental period. Crocidolite asbestos in vitro also stimulated normal BAL leucocytes to release significantly increased amounts of IL-1-like activity and TNF-alpha. We conclude that the deposition of crocidolite asbestos fibre in the lung by instillation causes reduced production of IL-1-like activity in the acute phase, but elevated production of both IL-1-like activity and TNF in the chronic phase, suggesting that enhanced activities of these cytokines may contribute to the development of lung pathological changes in the long term.

Animals↗
PubMed1993

Reactive pleural inflammation caused by intratracheal instillation of killed microbes.

To investigate the pleural leucocyte response to severe alveolar inflammation, heat-killed Corynebacterium parvum were instilled intratracheally into the lungs of PVG rats and pleural lavage was performed. Polymorphonuclear neutrophils are not normally resident in the pleural space but were found transiently after intratracheal instillation of C. parvum. Macrophages increased gradually in the pleural space following instillation, reaching a peak at day 5. The activity of plasminogen activator inhibitor in the pleural leucocyte supernatants was increased at day 1, but returned to control levels by day 5. The activities of interleukin-1 and tumour necrosis factor secreted by pleural leucocytes were decreased compared with control pleural leucocytes at day 1 and were further reduced at day 5. The analysis of particle translocation showed that intratracheally instilled C. parvum and fluorescent beads with or without C. parvum did not reach the pleural space. We hypothesize that pleural inflammation resulting from C. parvum-induced inflammation in the lung is the result of transfer of a diffusible factor from the adjacent parenchyma.

Animals↗
PubMed1993

Primary immunization series for infants: comparison of two-component acellular and standard whole-cell pertussis vaccines combined with diphtheria-tetanus toxoids.

At 2 months of age, 145 infants were randomized to receive either a two-component acellular pertussis vaccine [lymphocytosis-promoting factor (LPF)/filamentous hemagglutinin (FHA)] or standard whole-cell pertussis vaccine, each combined with diphtheria-tetanus toxoids, as their primary immunization series. Of the 132 subjects (91%) who completed the study, those receiving the acellular vaccine had significantly fewer adverse reactions: 5% vs 30% (local) and 17% vs 30% (systemic, including fever). During the first 24 hours acetaminophen usage, a general measure of adverse reactions, was lower in the test group. Overall, 35% of the acellular vaccine doses were reaction free vs 12% of the whole-cell doses. No serious reactions occurred in either group. Antibody responses to LPF and to FHA were significantly increased after the second and third immunizations with the test vaccine and were consistently higher than levels achieved with the standard vaccine. Thus the two-component acellular pertussis vaccine was associated with fewer adverse reactions and improved serologic responses to LPF and FHA as compared with the currently recommended whole-cell vaccine.

Academic Medical Centers↗
PubMed1992

Expression of proliferating cell nuclear antigen in lung cancer: a systematic study and correlation with DNA ploidy.

Heterogeneity of expression of the proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically in 156 tissue samples from 33 surgically resected pulmonary carcinomas using the monoclonal antibody 19A2. The DNA content of each of these samples was measured by flow cytometry. Mean PCNA expression was higher in squamous carcinomas than in adenocarcinomas but there was marked intra-tumour variation in PCNA index in almost all cases. Intra-tumour heterogeneity of DNA content was noted in 11 cases. The PCNA index of these cases (34.1) was higher than that of DNA homogeneous cases (19.4). The wide variation in PCNA expression between different samples within a tumour would indicate that systematic sampling and counting will be necessary in future immunohistochemical studies of cell proliferation in tumour material.

DNA, Neoplasm↗
PubMed1992

The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.

Adenocarcinoma↗
PubMed1992

Death and reductionism: a reply to John F Catherwood.

This reply to John F Catherwood's criticism of brain-related criteria for death argues that brainstem criteria are neither reductionist nor do they presuppose a materialist theory of mind. Furthermore, it is argued that brain-related criteria are compatible with the majority of religious views concerning death.

Brain Death↗
PubMed1992

B lymphocyte accumulations in human pulmonary sarcoidosis.

BACKGROUND: Although cell mediated immunity is primarily thought to mediate the pathogenesis of sarcoidosis, the presence of immunoglobulins, immune complexes and complement suggests that processes of humoral immunity may contribute to immunopathology in sarcoid lesions. To test this hypothesis, the distribution of B lymphocytes in paraffin embedded sarcoid lesions in mediastinal lymph nodes and open lung biopsy specimens was investigated. METHODS: Paraffin sections from eight open lung and 21 lymph node biopsies from sarcoid patients and five normal and five tuberculous lymph nodes from patients with tuberculosis were stained with a panel of monoclonal antibodies by means of avidin/biotin enhanced immunocytochemistry. RESULTS: Immunohistochemical analysis of the 29 biopsy specimens from the sarcoid patients revealed large numbers of B cells in the intergranulomatous regions. Further investigations in the open lung biopsy specimens indicated that these B cells were often organised into discrete circular or oval shaped aggregates with no germinal centre morphology, in which a few CD45RO memory T lymphocytes were scattered. The B cells were polyclonal, and a few plasma cells (IgM+, IgA+, IgG+) were identified. CONCLUSIONS: The finding of large numbers of B lymphocytes in sarcoid pulmonary lesions is in contrast to bronchoalveolar lavage studies, which have demonstrated proportions of 5% or less of B cells as a total of all immune cells, and therefore indicates that bronchoalveolar lavage may not correctly sample the immune cells of lung interstitial tissue in pulmonary sarcoidosis. The B cells at these sites are the possible origin of some of the humoral changes in the serum and lesions of sarcoid patients. They may also influence the pathogenesis of the disorder by presenting antigen(s) and forming immune complexes at sites of disease activity.

Antigen-Antibody Complex↗
PubMed1992

Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases.

BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1992

Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer.

BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall.

Aged↗
PubMed1992

Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging.

BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Adenocarcinoma↗