Biomedical subjects
Publications and source records attributed to P S Hasleton.
Giant cell arteritis (GCA) may present as pyrexia of unknown origin with profuse night sweats, pain on mastication, headache, pain in the region of the temporal arteries, polymyalgia rheumatica, myocardial infarction or dissecting aortic aneurysm. Few cases with pulmonary involvement have been described. We report a patient with temporal arteritis preceded by pulmonary vascular disease.
The presence of a number of regulatory peptides (bombesin, gastrin, glucagon, somatostatin, calcitonin and ACTH) was compared in 30 typical carcinoid tumours and 27 well differentiated neuroendocrine carcinomas (atypical carcinoids) using conventional immunocytochemistry. Strong immunostaining for one or more peptide was observed in 97% of the typical carcinoids (29/30) whereas only 67% of the neuroendocrine carcinomas showed immunoreactivity. The peptide most frequently detected in typical carcinoids was bombesin (67%), while gastrin was more common in neuroendocrine carcinomas (44%). Immunoreactivity for more than one peptide was present in 33 tumours and in three cases, six different peptides were detected. The study shows that immunoreactivity to various peptides is more common in typical carcinoids than well differentiated neuroendocrine carcinomas. The significance of these findings is discussed.
The pre-treatment serum levels of neuron-specific enolase (NSE), phosphohexose isomerase (PHI) and circulating immune complexes (CC) as tumour markers were compared to measurements of standard haematology and biochemical indices in 73 patients with lung cancer, as an aid to differentiation of tumour type, estimating disease extent, predicting response to therapy and prognosis. Elevated NSE greater than or equal to 12.5 ng ml-1, PHI greater than or equal to 55 mgl-1 levels were observed in 55% of cases for NSE, 90% for PHI and 49% for CC. NSE was significantly elevated in 61% (25/41) of patients with SCLC (P less than 0.005) compared to 41% (13/32) with NSCLC. CC levels were significantly raised in 72% (23/32) of patients with NSCLC (P less than 0.05) compared to 32% with SCLC. The levels of NSE and PHI were not related to tumour stage but CC was significantly raised in limited compared to extensive disease in SCLC (P less than 0.05). Serum albumin was significantly lower in NSCLC compared to SCLC, and median values of alkaline phosphatase, gamma-glutamyltranspeptidase and aminoaspartate transferase were significantly higher in patients with extensive disease. The pre-treatment serum values of NSE, PHI, and CC did not predict the response to therapy or prognosis in the 73 patients with lung cancer. The most important prognostic factor was the number of abnormal routine laboratory parameters (greater than 4) in this group of patients.
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Fifty three bronchopulmonary carcinoid tumours were studied to assess the significance of DNA ploidy, determined by flow cytometry of paraffin embedded tissue. Twenty eight were typical carcinoid tumours and 25 well differentiated neuroendocrine carcinomas. Twenty seven were DNA diploid and 26 DNA aneuploid. DNA aneuploidy was significantly associated with histological features of increased malignant potential. Survival data were available for 43 patients. Of the 19 with DNA diploid tumours, 16 survived five years, compared with 14 of 24 with DNA aneuploid tumours--the difference being at the borderline of statistical significance. In a Cox multivariate regression analysis with other histological variables, DNA ploidy did not confer independent prognostic information. It is concluded that, although DNA aneuploidy as determined by flow cytometry is an indicator of increased malignant potential in bronchopulmonary carcinoid tumours, it does not provide clinically useful information additional to the results of routine histological examination.
The present paper examines the results of quantitative assessment of intimal longitudinal smooth muscle (ILSM) in small arteries from normal mesentery in man. 212 vessels from 24 patients who underwent colectomy for colorectal carcinoma were studied. The mean amount of ILSM in these vessels was found to be 1.42% (range 0.00-8.90%) of external vessel diameter. A statistically significant (p = 0.018) positive correlation was demonstrated between the mean amount of ILSM in vessels from any individual patient and the level of diastolic blood pressure. It is concluded that increased intravascular tension is one factor which influences the development of ILSM in human small mesenteric arteries.
DNA ploidy patterns of 107 colorectal adenocarcinomas were retrospectively analyzed by flow cytometry (FCM) and correlated with clinicopathological and immunohistological parameters as grade, vascular and serosal invasion, carcinoembryonic antigen, secretory component (SC) and expression of HLA-DR antigens. Using the classical division into DNA diploid and DNA aneuploid tumors, a correlation with SC expression was observed. Subdivision of aneuploid tumors according to the discussed hypothetical functional criteria into hyperdiploid, hypotetraploid, tetraploid and hypertetraploid groups led to statistically significant correlation with serosal invasion. Among the immunohistological parameters the interdependence of SC and HLA-DR expression may be also of interest. The need for subdivision of DNA aneuploidy is broadly discussed so as to permit the analysis of different properties, cellular origins and kinetic parameters. Ultimately this may lead to more clinically meaningful interpretation of DNA histograms.
Pyridinoline, a collagen specific covalent crosslink, was quantified in acid hydrolysates of human aorta using a non-equilibrium inhibition ELISA. The study was based on specimens from seven cases of aortic dissection and from seven control subjects whose death was unrelated to thoracic aortic dissection. There were no significant differences in the amounts or concentrations of pyridinoline in aortas with dissecting aneurysms compared with normal tissue, thus excluding the possibility of a causative relation between the degree of pyridinoline crosslinking of collagen molecules and dissection of the thoracic aorta. In all cases, however, the number of pyridinoline crosslinks per molecule of collagen in the ascending aorta and arch approached the theoretical maximum for lysyl derivatives and was as high as that present in cartilage. Thus in this region of the vessel pyridinoline represents the major stabilising crosslink of collagen. In contrast, the number of pyridinoline crosslinks per collagen molecule decreased maximally by a factor of 10 between the arch and the proximal regions of the descending thoracic aorta. This suggests a possible correlation between the rigidity of collagen fibres and the forces exerted on the aortic wall during diastole and systole.
A clinico-pathological study of 35 bronchial carcinoid tumours was undertaken. Age, T stage, N stage, lymph node involvement, number of lymph nodes involved and number of cigarettes smoked per day were the clinical variables affecting survival. The histological variables related to survival were; mitotic count, necrosis, nuclear pleomorphism, vascular and lymphatic permeation and an undifferentiated growth pattern. All these features could be detected with routine histological stains, whereas immunocytochemical methods for demonstrating neuron specific enolase were of no help in assessing the prognosis. However there was a tendency for a well differentiated neuroendocrine carcinoma to stain strongly in some areas with carcinoembryonic antigen.
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The influence of polymorphic variants of the human c-Ha-ras gene on predisposition to lung cancer has been investigated. The human c-Ha-ras gene has been shown to reside on a polymorphic BamH1 restriction fragment. This restriction fragment length polymorphism (RFLP) results from variation in the size of a region of repetitive DNA 3' to the gene. An attempt has been made to characterise and compare the c-Ha-ras RFLP's in a normal population and in a group of cancer patients. DNA was extracted from the white blood cells of 101 normal donors and four common Ha-ras alleles identified, with occasional rare alleles of various sizes. The allele frequencies were examined in 132 lung cancer patients, comprising 66 individuals with small cell carcinoma of the lung (SCCL) and 66 with non-small cell carcinoma of the lung (non-SCCL). An abnormal allele distribution was found in individuals with non-SCCL compared to both control and SCCL values suggesting a degree of genetic pre-position to non-SCCL. In addition, analysis of the Ha-ras RFLP's in solid samples inferred a deletion of material from the short arm of chromosome 11 in two of 16 informative samples.
A case of diffuse leiomyomatosis of the oesophagus is described. This condition is rare and has been confused with diffuse leiomyomata in the past. The aetiology is obscure.
Four cases of pulmonary veno-occlusive disease are described. Two patients, who were brothers, had respiratory tract infections. The third patient had chronic active hepatitis and coeliac disease suggesting an abnormality of the immune system; the fourth patient had no obvious cause but presented initially with systemic hypertension. Three of the cases had been diagnosed initially as primary pulmonary hypertension either on open lung biopsy or clinically. In all cases the pulmonary arteries were abnormal with medial hypertrophy, intimal fibrosis and, in some cases, thrombosis in elastic pulmonary arteries. These findings suggest that pulmonary veno-occlusive disease is not confined to veins and should be considered as a widespread pulmonary vascular disease. The range of aetiological factors indicate that it should not be considered as a single disease entity.
Probable progesterone production was identified by an immunoperoxidase assay in a case of an ovarian sex cord tumour with annular tubules. The tumour was associated with a serous cystadenofibroma in the opposite ovary and with adenoma malignum (adenocarcinoma) of the cervix.
This study reports the results of serial observations of simple haematological indices (haemoglobin concentration, white cell count and platelet count) in 25 patients who developed radiation bowel disease as a late complication of pelvic radiotherapy for malignancy. It is compared with a control group of 25 women patients who received pelvic radiotherapy but did not develop radiation bowel disease. There is a highly significant elevation in the platelet count (P less than 0.0001) at a time when the patients develop radiation bowel disease. The platelet count returns to normal after successful excision of the disease but the elevation recurs if further radiation disease develops in the urinary or gastrointestinal tracts. It is suggested that the platelet count may have a useful role in the diagnosis of radiation bowel disease.
Tumour cords have been measured in 33 cases of squamous cell carcinoma (SCC) of the bronchus and 19 cases of SCC of the uterine cervix. The overall mean cord radius for SCC in both sites was 104 microns, similar to the overall mean for various tumours in rodents. For tumour cells adjacent to blood vessels in cords of SCC, the mean Mitotic Index was 2.1% and from this value a rapid potential doubling time could be inferred (approximately 31 to 66 h). The proportion of dead cells within cords of cervical SCC was higher than in animal tumours. Using measured values for cord radius and published equations that describe the diffusion and consumption of oxygen in metabolising tissue, an attempt was made to calculate the oxygen partial pressure in vessels of cords of these SCC.
A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage.
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