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Biomedical subjects

P S Hasleton

Publications and source records attributed to P S Hasleton.

At least 55 records · Page 3Linked to original sources
PubMed1996

Pulmonary herpes simplex in burns patients.

In this study we aimed to determine the incidence of herpes simplex virus (HSV) in the lungs of burns patients, and its association with the presence of adult respiratory distress syndrome (ARDS) and pneumonia. Haematoxylin and eosin (H&E), and immunohistochemical (IHC) staining for HSV was performed on lung tissue from 54 patients who had died following burn injury and from nine control cases. Polymerase chain reaction (PCR) for HSV deoxyribonucleic acid (DNA) was performed on a subset both of burns cases and controls. No viral inclusions were detected in H&E sections, but 50% of the burns cases were positive for HSV by IHC staining; no control cases were positive. Nuclear and cytoplasmic immunopositivity for HSV was seen in macrophages and epithelial lining cells. HSV was strongly associated with ARDS (p=0.007), but not with pneumonia (p=0.577). The relative risk of HSV infection was higher for cases with ARDS (2.21) than for those with pneumonia (1.26). PCR for HSV DNA was positive in three out of five burns cases, and in one out of five control cases. Immunohistochemical staining is more sensitive for the detection of herpes simplex virus than haematoxylin and eosin staining for detection of viral inclusions. Burns cases have a high incidence of pulmonary herpes simplex virus infection. Polymerase chain reaction results may not be fully representative due to problems of tissue necrosis postmortem. Pulmonary herpes simplex virus is strongly associated with adult respiratory distress syndrome and the two may be causally linked. Early detection and treatment of pulmonary herpes simplex virus in burns patients may reduce pulmonary complications and mortality.

Adolescent↗
PubMed1996

TNF alpha mRNA and protein in cardiac transplant biopsies: comparison with serum TNF alpha levels.

OBJECTIVES: To examine the role of TNF alpha (TNF alpha) in cardiac transplant rejection by simultaneous analysis of protein expression and its messenger RNA within serum and grafted tissue. METHODS: 54 endomyocardial biopsy specimens were taken from 19 patients at various times after transplantation. TNF alpha messenger RNA was localised using a digoxygenin labelled complementary DNA probe. An anti-TNF alpha antibody was used to immunohistochemically label the protein product. Serum TNF alpha levels at the time of biopsy were analysed using a specific enzyme-linked immunosorbent assay. RESULTS: TNF alpha mRNA was present in 22/34 endomyocardial biopsies. Eight also contained TNF alpha protein. None had protein alone. Expression did not relate to the grade of rejection in the present or subsequent biopsies. Serum TNF alpha was undetectable (assay sensitivity 30-330 pg/ml) for the majority of specimens. In the nine cases with elevated serum levels, eight samples were from cases within the first 30 days post transplant (r = -0.379; P < 0.05). CONCLUSIONS: Neither tissue TNF alpha mRNA, tissue protein, nor serum TNF alpha relate to the grade of rejection. Furthermore, TNF alpha expression within endomyocardial biopsies is not reflected in the serum. These findings argue against the use of serum analysis as an indicator of cytokine profiles within cardiac tissue allografts. The demonstration of a trend in the early expression of TNF alpha after transplantation suggests that its release may not be specific to the process of rejection.

Adult↗
PubMed1995

Synovial sarcoma of the pharynx.

Synovial sarcoma is rarely seen in the head and neck region. A case of synovial sarcoma of the pharynx in a child is presented.

Child↗
PubMed1995

Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis.

BACKGROUND: Cryptogenic fibrosing alveolitis (synonymous with idiopathic pulmonary fibrosis) is a clinically heterogeneous condition in which the precipitating factor is unclear. Both environmental and infective factors have been implicated. An association between Epstein-Barr virus (EBV) and cryptogenic fibrosing alveolitis was suggested over a decade ago by a study based on EBV serology, but the significance of this has been unclear. METHODS: Lung tissue obtained surgically from patients (n = 20) with cryptogenic fibrosing alveolitis was investigated for evidence of EBV replication and compared with lung tissue from 21 control patients. Fourteen of the 20 patients had received no specific therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV viral capsid antigen (VCA) and gp 340/220 antigen, which are expressed during the lytic phase of the EBV life cycle, were studied. RESULTS: Fourteen (70%) of the 20 patients with cryptogenic fibrosing alveolitis were positive for both EBV VCA and gp 340/220 compared with two (9%) of the 21 controls. In the patients with cryptogenic fibrosing alveolitis viral replication was localised to pulmonary epithelial cells using epithelial cell markers, and immunohistochemical analysis confirmed the staining to be within type II alveolar cells. CONCLUSIONS: This is the first report of in vivo EBV replication within epithelial cells of the lower respiratory tract in an immunocompetent human host. Furthermore, this suggests that EBV may be an immune trigger or contribute to lung injury in cryptogenic fibrosing alveolitis, thus offering a potential new avenue of treatment.

Adult↗
PubMed1995

Necrotic, ulcerative bronchitis, the presenting feature of lymphoproliferative disease following heart-lung transplantation.

Following heart-lung transplantation two of 21 patients who survived more than 100 days developed post-transplant lymphoproliferative disease. Both presented with localised ulcerative bronchitis documented at flexible bronchoscopy four months after transplantation. Histological examination showed necrosis with acute inflammation and ulceration. Case 2 demonstrated lymphoproliferative disease from biopsies subsequently taken at rigid bronchoscopy. Case 1 later developed lung nodules and a monoclonal high grade B cell non-Hodgkin's lymphoma was confirmed by an open lung biopsy. The bronchoscopic features described should alert clinicians to post-transplant lymphoproliferative disease as an underlying diagnosis and suggest that bronchus associated lymphoid tissue is the initial site for clonal proliferation in the disease.

Adult↗
PubMed1994

Rejection in heart transplantation strongly correlates with HLA-DR antigen mismatch.

It is well established that incompatible HLA antigens presented by donor tissue readily evoke an immune response. Prospective HLA matching policies, widespread in European kidney transplant centers have reduced the level of HLA mismatching and have significantly improved graft survival. The influence of HLA incompatibility in heart transplantation remains controversial, and prospective HLA matching is seldom achieved. We examined the role of HLA antigen mismatching on transplant rejection by analyzing 2569 endomyocardial biopsies (EMB) from 157 consecutive orthotopic heart transplants performed from April 1987 to August 1993 in our own center. Biopsies were graded according to the accepted International Classification, with grade 2 and higher indicating rejection. Among 91 patients who received a 2 HLA-DR mismatch transplant 34% of 1624 biopsies analyzed were graded as > or = 2. This frequency fell to 29% of 797 biopsies for 53 patients with a one-HLA-DR mismatch and to 18% of 148 biopsies for 13 patients in the zero-HLA-DR-mismatch group (P < 0.00005). No significant effect on EMB grade frequencies was observed using the same method of analysis with transplants mismatched at the HLA-A or HLA-B loci apart from analysis of HLA-B matched transplants at 3 months posttransplant (P = 0.02). The close linkage of the HLA-B and HLA-DR loci may account for this observation. The results of this study show that heart transplants matched at the HLA-DR locus have a significantly reduced incidence of EMB grades indicative of rejection requiring augmented immunosuppressive therapy. We propose that prospective HLA-DR matching should be adopted for allocation of donor hearts for more efficient use of this precious and limited resource.

Adolescent↗
PubMed1994

Glycosaminoglycan content is increased in dissecting aneurysms of human thoracic aorta.

Ten thoracic aortas were obtained from cases of dissecting aneurysms and 10 from age-matched controls. Full wall thickness samples (1 cm diameter) were taken at 12 sites for both groups. Content, concentration and ratio to total glycosaminoglycan (GAG) were determined for chondroitin sulphate (CS), hyaluronate (HA), heparan sulphate (HS) and dermatan sulphate (DS). When compared with controls, content of CS and HS increased over the whole length of dissected aortas, whereas increased HA and DS were localised to dissected areas of affected aortas as were increased tissue mass and collagen and elastin content. Changes in concentration and ratios, significant for some GAGs and consequent upon these increases, may help to compromise the mechanical properties of the aortic wall. The localised increases in HA and DS content in areas where collagen and elastin were increased suggests that these GAGs are functionally related to these fibrous proteins in aorta, whereas CS and HS are not.

Aged↗
PubMed1993

Increased elastin content and decreased elastin concentration may be predisposing factors in dissecting aneurysms of human thoracic aorta.

OBJECTIVE: The aim was to investigate whether changes in elastin distribution in the thoracic aorta are associated with occurrence of dissecting aneurysms. METHODS: Ten thoracic aortas were obtained at necropsy from dissections (mean patient age 74.3 years, SD 7.3) and from 10 age matched controls (mean age 73.1 years, SD 6.9). Full wall thickness samples (1 cm diameter) were taken at 12 sites between heart and diaphragm from aortas of dissections and controls. Elastin content (total elastin per sample), concentration (mg.mg-1 tissue dry weight), degree of cross linking, and amino acid composition were determined. RESULTS: Comparison of areas of dissected aortas involved in dissection with corresponding areas of controls showed significant increases in content of elastin (p < 0.05), content and concentration of proteins other than elastin and collagen (p < 0.01), and a decrease in elastin concentration (p < 0.01). Comparison of areas remote from dissection with corresponding areas in controls showed no significant differences except for decreased elastin concentration (p < 0.05). There were no differences in elastin cross linking. Elastin from dissected aortas had a higher content of aspartate, threonine, serine, glutamate, and lysine and a lower content of glycine, alanine, and valine than elastin from controls (p < 0.05). CONCLUSIONS: Biochemical changes in dissections are localised to the dissected area, with increased deposition of elastin, collagen, and other proteins. The altered matrix composition is likely to change the mechanical properties, possibly increasing the tendency to rupture.

Aged↗
PubMed1993

Histological examination of peroperative frozen sections in suspected lung cancer.

BACKGROUND: Despite extensive investigations some patients with suspected lung cancer may undergo thoracotomy without preoperative histological proof of malignancy. A questionnaire on the use of histological examination of peroperative frozen sections in such patients was sent to 50 thoracic surgeons. Replies were received from 41 surgeons and indicated an absence of consensus on the usefulness of histological examination of frozen sections in this context, confirming the need for this study. METHODS: During one year 60 consecutive patients undergoing thoracotomy for suspected lung cancer without a prior histological diagnosis were studied prospectively. At thoracotomy the surgeon assessed the lesion macroscopically and a verdict on whether it was malignant was recorded. A biopsy specimen was then taken for examination of a frozen section and the result recorded. The appropriate operation was performed and the surgeon's verdict and the report on the frozen section were compared with the definitive histological diagnosis based on a paraffin section. RESULTS: Of 50 malignant lesions, 43 were identified by the surgeon and 47 by examination of the frozen section (sensitivity 86% and 94% respectively). Of 10 benign lesions, four were identified by the surgeon and nine by examination of the frozen section (specificity 40% and 90% respectively). CONCLUSIONS: Clinical and macroscopic assessment at thoracotomy are inferior to examination of frozen sections in suspected lung cancer, particularly where the lesion is benign. Lung resection should not be performed without examination of peroperative frozen sections when thoracotomy is performed for suspected but unproved lung cancer.

Biopsy↗
PubMed1993

Pulmonary diffusion abnormalities in heart transplant recipients. Relationship to cytomegalovirus infection.

Lung function of patients with heart failure is characterized by a variety of changes proposed as being due to passive congestion, secondary pulmonary fibrosis, and/or recurrent pulmonary emboli. A diffusion impairment thought to be due to cyclosporine has also been noted in patients following heart transplantation. Similar changes of unclear origin have been observed in renal transplant recipients. The objective of this study was to determine the extent to which lung function changes are reversible by cardiac transplantation and relate changes to the status of the recipients lung in the presence of possible vascular, iatrogenic, immune, or infectious injury. We analyzed the data of 22 patients who underwent lung function testing before and after heart transplantation and correlated changes to hemodynamic change, episodes of rejection, concentration of cyclosporine, and cytomegalovirus infection. Despite excellent graft function, the carbon monoxide transfer factor deteriorated to a mean of 57 percent of predicted postoperatively. The fall in diffusion factor did not correlate with episodes of cardiac rejection, cyclosporine levels, or hemodynamic status. In those patients who had serologic evidence of cytomegalovirus infection, the reduction in transfer factor was greater compared to those without infection despite a normal chest radiograph. The effects of cardiopulmonary bypass were unlikely to have been responsible for the abnormalities as lung function was assessed at a mean of 14 months after surgery. In heart transplant recipients, a change in diffusion capacity may represent an additional marker for cytomegalovirus infection and reflect infectious/immune injury late following surgery.

Cyclosporine↗
PubMed1992

Desmoplastic malignant mesothelioma: a review of 17 cases.

AIMS: To identify the histological features of desmoplastic mesothelioma, and to determine its incidence and prognosis. METHODS: Two hundred and fifty five cases of malignant mesothelioma were examined over seven years (1982-9) to identify the desmoplastic variant. Sections were cut at 5 microns and stained with haemotoxylin and eosin and with CAM 5.2 (Dakopatts). Asbestos fibre counts were carried out by light microscopy in 14 cases using the potash digestion method. RESULTS: Seventeen cases were identified as desmoplastic mesothelioma giving an incidence of 6.6%. In 11 cases the cell type in more cellular areas was sarcomatous and in six others it was biphasic. The mean survival time from onset of symptoms to death was 5.8 months for the sarcomatous variant and 6.8 months for the biphasic variant. Twelve of 16 patients had had previous occupational exposure to asbestos, ranging from five months to 43 years. The diagnosis of desmoplastic mesothelioma was only accepted if acellular connective tissue comprised 50% or more of the tumour bulk. Also seen was collagen necrosis, anastomosing bands of often hyalinised collagen with a prominent storiform pattern, and where cellular detail was present there were hyperchromatic nuclei. CONCLUSIONS: Desmoplastic mesothelioma is a rare variant of malignant mesothelioma with a storiform collagen pattern, collagen necrosis, bland acellular collagen and focal cytological features of malignancy. Though rare, it is important to recognise this variant and distinguish it from a pleural plaque, nonspecific reactive pleural fibrosis, pleurisy, rheumatoid disease, or, rarely, spindle cell sarcomas.

Adult↗
PubMed1992

Vascular invasion in non-small cell lung carcinoma.

AIMS: To determine if there is any correlation between vascular invasion and prognosis in non-small cell carcinoma of the lung; and to look specifically at invasion of vascular channels by tumour cells. METHODS: Eighty seven patients undergoing lobectomy or pneumonectomy for adenocarcinoma or squamous carcinoma were followed up for five years. The histological sections were studied for evidence of vascular invasion using an elastic van Gieson stain. The incidence of intimal fibrosis in arteries and veins was noted and the proportion with vascular invasion evaluated using a scoring system. The presence or absence of lymphatic permeation and tumour necrosis were noted. Survival data were analysed using the log rank test. RESULTS: The overall five year survival was 32%. There were 64 squamous cell carcinomas and 23 adenocarcinomas. Vascular invasion was seen in 77% of patients and lymphatic invasion in 44%. Neither the presence nor absence nor the proportion of blood vessels showing vascular invasion showed any relation to prognosis. Intimal fibrosis and tumour necrosis were unrelated to prognosis. Patients with lymphatic permeation had recurrence and died earlier than those without. CONCLUSION: The presence of arterial or venous invasion by adenocarcinoma or squamous carcinoma of the lung was unrelated to survival; lymphatic permeation was associated with poor prognosis. The two common non-small cell lung cancers behaved differently from other solid tumours, where vascular invasion was a significant factor in determination of prognosis. The presence of intimal fibrosis was unrelated to prognosis.

Adenocarcinoma↗
PubMed1991

Late BCNU lung: a light and ultrastructural study on the delayed effect of BCNU on the lung parenchyma.

We describe eight patients who developed interstitial pulmonary fibrosis following BCNU (carmustine) therapy for cerebral tumours. The fibrosis presented 12-17 (mean 14) years after exposure to the drug. A distinctive pattern of pulmonary fibrosis with involvement of the apices and subpleural areas was seen in one patient dying of the disease. Light microscopy showed interstitial elastosis and intra-alveolar fibrosis which was often focal with an associated mild lymphoplasmacytic infiltrate, intra-alveolar oedema, macrophages, and some neutrophils. Ultrastructural studies showed electron lucency of type I pneumocytes, with breaks in the cytoplasmic membranes leaving a bare basement membrane. Degenerative change was also seen in endothelial cell cytoplasm along with lipofuscin deposition. While BCNU pulmonary fibrosis has been described up to 2 years after treatment, this complication so late after therapy, though rare, has important implications for the follow-up of patients receiving this drug.

Astrocytoma↗
PubMed1991

Lack of C-erbB-2 protein expression in pulmonary carcinoid tumours.

To determine if amplification of the C-erb-B2 proto-oncogene could be correlated with prognosis in carcinoid tumours, 49 pulmonary carcinoid tumours (26 typical, 23 atypical) were examined using a polyclonal antibody to the C-terminal peptide of the C-erb-B2 protein sequence. No C-erb-B2 gene product could be shown: the demonstration of C-erb-B2 does not seem to help, therefore, in determining diagnosis or prognosis in pulmonary carcinoid tumours.

Biomarkers, Tumor↗