Search PubMed⌕ Search

Biomedical subjects

D Lamb

Publications and source records attributed to D Lamb.

At least 73 records · Page 4Linked to original sources
PubMed1992

Intra-alveolar macrophage numbers in current smokers and non-smokers: a morphometric study of tissue sections.

BACKGROUND: The alveolar macrophage is believed to be important in the defence of the lung and possibly in the pathogenesis of lung disease. Cell counts in bronchoalveolar lavage fluid have suggested that smokers have an increased number of alveolar macrophages but have not enabled the number to be related to a measure of lung structure. METHODS: The number of alveolar macrophages was counted in histological sections from lung resection specimens from a group of smokers and non-smokers. The results were related to a measurement of lung structure obtained by means of an automated morphometric technique and expressed in terms of units of lung volume or of lung surface area. RESULTS: The smokers had a significantly increased number of alveolar macrophages per unit lung volume and per unit surface area, through the relative increase was less than has appeared from bronchoalveolar lavage studies. When smokers and non-smokers with similar lung structure were compared the smokers had more alveolar macrophages, indicating that smoking and not loss of lung structure is responsible for the increase. CONCLUSIONS: Smokers had more alveolar macrophages than non-smokers when the number was expressed quantitatively with respect to the underlying architecture. Changes in cell populations postulated to be important in the pathogenesis of disease within the lung should be related to lung architecture because this may vary considerably between individuals.

Adult↗
PubMed1992

Clinicopathological correlations in cor pulmonale.

BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease.

Blood Pressure↗
PubMed1992

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung.

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Carcinoma, Small Cell↗
PubMed1992

Changes in neutrophil morphology and morphometry following exposure to cigarette smoke.

Acute cigarette smoking delays neutrophils within the pulmonary circulation in some smokers. Evidence from an in-vitro Micropore filter model of the pulmonary capillaries indicates that this may be due to a smoke induced decrease in cell deformability. In order to determine whether changes in cell shape are associated with the observed decrease in neutrophil deformability following smoke exposure, cell morphology, using scanning electron microscopy, and morphometric measurements, made using transmission electron microscopy, were performed on aliquots of neutrophils harvested from whole blood in non-smoking subjects before and after exposure in vitro to cigarette smoke. Smoke exposure increased the maximum diameter and circumference of neutrophils, without changing their area. There was also a change in the maximum to minimum cell diameter ratio, which indicated that the cells had become less spherical. Scanning electron microscopy showed that smoke exposed cells had developed blebbing of their surface membranes, suggestive of an oxidative injury to the cell membrane rather than the shape changes associated with cell activation. These changes in the morphology and morphometry of smoke exposed neutrophils may contribute to the reduction in cell deformability induced by cigarette smoke.

Anthropometry↗
PubMed1991

Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump.

To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time.

Animals↗
PubMed1991

Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos.

We have previously reported that normal pleural leukocytes secrete a urokinase-type plasminogen activator inhibitor (PAI) in culture. In view of the pathogenic effects of asbestos on the pleura, in particular pleural fibrosis, we have extended these observations to crocidolite asbestos-exposed rats. Pleural leukocytes from rats exposed to crocidolite asbestos were found to secrete more PAI in culture than controls. The activity of PAI in pleural leukocyte-conditioned medium increased in a dose-dependent manner in relation to the quantity of asbestos injected into the lung. However, with increasing time post asbestos instillation, there was no significant change in the secretion of PAI by pleural leukocytes in culture compared with earlier time points of crocidolite-exposed rats. Plasminogen activator was not detectable in the conditioned medium at any time point. The data derived from this study may help to elucidate the pathogenesis of some pleural disorders caused by exposure to fibrous dusts in the lungs.

Animals↗
PubMed1991

Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse after the use of at least one other standard anti-cancer agent. The patient was to have received no prior radiotherapy or intravesical therapy for at least 4 weeks prior to entry. Patients also did not suffer significant cardiac dysfunction, such as angina, congestive heart failure, or uncompensated cardiomyopathy. All patients were given 4-6 doses of intravesical novantrone at the same dose level at weekly dosing interval. Patients were required to retain the drugs in the bladder for 2 h. Baseline study included history/physical, hematology, blood chemistry, cystoscopy, bladder barbotage, urine cytology, cystometrogram to assess the bladder capacity, and finally, chest X-ray, EKG, and MUGA scan, if indicated. Weekly assessment involved toxicity notation, blood chemistry, hematology and urinalysis. Monthly assessment included physical examination, toxicity notation, hematology, urinalysis and blood chemistry. Within 4 weeks of completion of the last dose, patients underwent repeat cystoscopy to assess disease status. Patients who responded to the 4-6 week induction phase were entered in a monthly dose regimen for up to 5 months. A total of 23 patients were enrolled: 22 males and 1 female. One patient dropped out before receiving medication because of a protocol violation for entry criteria. Twenty-two patients were eligible for assessment of safety and 20 were eligible for assessment of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

New automated technique for assessing emphysema on histological sections.

The assessment of emphysema in human lungs has traditionally been based on observations made on whole lung slices. These methods are inappropriate for the study of early emphysema, because as much as 75% of the alveolar wall surface area may have been lost by the time airspaces are visible to the naked eye. A new, automated image analysis system, the Fast Interval Processor (FIP), was used to measure airspace wall surface area per unit volume of lung tissue (AWUV). AWUV was measured on histological sections of lung tissue and expressed in mm2/mm3. The study sample consisted of resection specimens from 40 patients (32 men and 8 women whose ages ranged from 23-74 years). Histological sections from the inflated specimens were scanned using the FIP, and a mean AWUV value was calculated for each. The intra- and interobserver reproducibility of this method of measuring AWUV were examined. The results obtained using the FIP were also compared with those from an established image analysis system. The FIP is a fast, efficient technique which gave highly reproducible results comparable with those obtained with an established and much more time consuming measuring technique.

Histological Techniques↗
PubMed1991

Death in Denmark: a reply.

This reply to Martyn Evans's support for a cardiac-centered concept of death attempts to meet some objections to the brainstem definition of death. Evans's appeal to Wittgenstein's philosophy is also criticised.

Attitude to Health↗
PubMed1991

Lung cancer in lifelong non-smokers. Edinburgh Lung Cancer Group.

The Edinburgh Lung Cancer Group registered 3070 new patients with lung cancer in the five years 1981-5 from a catchment population of 950,000. After review only 74 (2%) were classified as lifelong non-smokers. They differed significantly from the 2996 smokers with lung cancer in that far more were female (77% v 26%) and their mean age was higher (75.4 v 68.0 years). More were in the worst Karnofsky performance categories and fewer patients underwent surgery. The stages of disease were similarly distributed in the two groups and the five year survival was equally poor (5%). Histological cell type was determined in 59 of the 74 patients. All histological cell types were present. More non-smokers had adenocarcinoma than smokers (42% v 13%) and fewer had squamous cell carcinoma (32% v 49%) or small cell carcinoma (15% v 24%). Lung cancer in lifelong non-smokers is uncommon and the diagnosis should therefore always be questioned.

Adenocarcinoma↗
PubMed1990

Intratumoral heterogeneity of DNA content in lung cancer.

Heterogeneity of DNA content was analyzed in 208 samples from 20 resected lung tumors. Only one carcinoma was homogeneously diploid, but the others had DNA aneuploidy in at least some tissue samples. Eighteen tumors (90%) had varying degrees of heterogeneity of DNA content. Over half of these could have been mislabeled as diploid if the tumors had not been widely sampled. The importance of adequate sampling in assessing ploidy status of lung tumors is emphasized.

Adenocarcinoma↗
PubMed1990

Secretion of plasminogen activator inhibitor by normal rat pleural leukocytes in culture.

The normal balance between coagulation and fibrinolysis in the pleural cavity is poorly understood despite the critical role of the pleura in the movement of the lungs. To determine the fibrinolytic activity and the interaction between plasminogen activators and their inhibitors in the normal pleural space, we tested normal rat pleural leukocytes, principally macrophages and mast cells, and their supernatants, for activity in an [125I]fibrin degradation assay. It was found that pleural leukocytes did not release plasminogen activator, but the leukocytes and their supernatants inhibited the plasminogen-dependent fibrinolysis caused by both alveolar leukocytes and mesothelial cells. Further experiments demonstrated that pleural leukocytes produce a protein inhibitor primarily against urokinase-induced fibrinolysis in culture and that macrophages are the main source of the inhibitor. The lysate of mast cell-enriched population exhibited high plasminogen activator activity while no such activity could be determined in macrophage-enriched lysate. These data show that normal rat pleural leukocytes contain plasminogen activator inside the cells and synthesize a urokinase-type plasminogen activator inhibitor in culture that may be important in the fibrinolysis/coagulation balance in the pleural space.

Animals↗
PubMed1990

An investigation into the role of human papillomavirus in endobronchial papillary squamous tumours.

Tissue specimens from 15 patients with endobronchial papillary squamous tumours were probed for the presence of human papillomavirus DNA using the technique of in situ hybridization with probes to human papillomavirus genotypes 4, 5, 6b, 8, 11, 16 and 18. Despite the histological similarity of these lesions to known human papillomavirus-associated tumours no evidence of hybridization was detected in any of the cases analysed. It is thus unlikely that human papillomavirus has a significant role in the genesis of these tumours.

Aged↗
PubMed1990

Importance of sampling method in DNA analysis of lung cancer.

Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out.

Adenocarcinoma↗