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Biomedical subjects

M S Dunnill

Publications and source records attributed to M S Dunnill.

13 recordsLinked to original sources

Effect of ventilation with positive end-expiratory pressure on the development of lung damage in experimental acid aspiration pneumonia in the rabbit.

Sixteen anaesthetized rabbits were subjected to tracheostomy and lung damage produced by the instillation of 4.5 ml/kg hydrochloric acid (pH 1.5) into the trachea. Half of the animals were ventilated with a positive end-expiratory pressure (PEEP) of 3 cmH2O and half with a PEEP of 10 cmH2O for 5 h, the mean airway pressure being kept at 12 cmH2O by adjustment of the end-inspiratory pause time. Pressure-volume curves were recorded every hour. Although the arterial PO2 values and compliance above the inflection point on the pressure-volume curve were greater in the group submitted to 10 cmH2O PEEP, there were no significant differences between the groups in terms of survival and histological findings.

Animals

Interleukin 4 receptor expression on human lung tumors and normal lung.

Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the IL-4 receptor-positive tumors also expressed epidermal growth factor receptors. Positive labeling for IL-4 receptors was also obtained on nonneoplastic bronchial epithelium and on lymphocytes and macrophages infiltrating the tumor stroma. The role of IL-4 and its receptor in normal human lung is unknown, but the expression of IL-4 receptors on particular subtypes of lung tumors suggests that they may have a role in differentiation or proliferation of squamous and adenocarcinomas.

Adenocarcinoma

Pulmonary granulomatosis and angiitis.

A wide variety of disease processes, each requiring different therapy, may give rise to granulomatous and vasculitic pulmonary lesions, making accurate aetiological diagnosis essential. For this, adequate sampling of tissue is necessary, and this usually requires open lung biopsy in order to obtain sufficient material for microbiological, immunocytochemical and ultrastructural as well as histopathological investigation. Many cases diagnosed as lymphomatoid granulomatosis are examples of extranodal lymphoma. It is suggested that this is an inappropriate name and that such cases should be referred to as pulmonary lymphomas and the phenotype specified.

Churg-Strauss Syndrome

Ki-67 immunostaining and survival in operable lung cancer.

One hundred and eighty-seven operable lung tumours were immunostained with the monoclonal antibody Ki-67 and divided into groups of high, moderate or low proliferation. Patients have been followed clinically for up to 7 years to ascertain whether this immunocytochemical measurement reflected tumour behaviour in terms of survival. The majority of the tumours were squamous cell carcinomas (104 cases) and adenocarcinomas (60 cases). These were divided into three groups of low, intermediate and high growth fraction, in which survival was better for tumours of lower proliferative rate up to approximately 2 years after operation. By 5 years these differences had largely disappeared and all tumours of a particular type showed a similar survival curve. Small cell carcinomas (13 cases) had high Ki-67 labelling indices, with more than 60% of patients deal in the first year, whereas carcinoid tumours (10 cases) had low labelling rates and all but one are still alive. We conclude that measurement of lung tumour growth rate with the monoclonal antibody Ki-67 shows promise as a possible indicator of short-term survival and perhaps as a means of choosing a group of patients with adenocarcinomas and squamous cell carcinomas for post-operative chemotherapy.

Adenocarcinoma

Pulmonary fibrosis.

Diffuse interstitial pulmonary fibrosis is the end result of alveolar damage which may occur as a sudden acute incident or as a slowly developing process. Potentiating factors include release of enzymes and generation of oxygen radicals by granulocytes. Evidence from studies on broncho-alveolar lavage fluid and from immunocytochemistry indicate that an autoimmune process has an important but, as yet, not clearly defined role in initiating the disease. The fibrosis is probably due to proliferation of small clones of fast growing fibroblasts of a specific phenotype. Bronchiolitis obliterans, organizing pneumonia, idiopathic pulmonary fibrosis, usual interstitial pneumonia and desquamative interstitial pneumonia represent different aspects of the same condition. Their varied morphological appearances probably reflect the fact that tissue has been taken at different stages in the development of the disease.

Bronchoalveolar Lavage Fluid

Renal transplantation and a positive serological cross-match.

A renal transplant involving a recipient with a positive serological cross-match against donor lymphocytes generally results in hyperacute rejection of the graft. 13 cadaveric renal transplants were performed in recipients with a known positive serologic cross-match against donor B lymphocytes. 12 of these serological cross-matches were positive against donor blood, node, or spleen lymphocytes, but the reactivity was directed against donor B lymphocytes only. 3 transplants failed, 2 because of rejection and 1 because of renal-artery thrombosis. 10 transplants are functioning, 6 to 42 weeks after the operation. Of these 10 successful grafts, 3 had no acute rejection episodes, while 7 had an early acute rejection episode which responded to treatment. Histologically, the grafts showed a cellular rejection, similar to that in enhanced renal allografts in the rat. It is possible to transplant a kidney in a high-risk patient with a positive B lymphocyte cross-match with a low risk of failure. In addition active enhancement of the graft might sometimes occur.

Acute Disease

Acquired cystic disease of the kidneys: a hazard of long-term intermittent maintenance haemodialysis.

In the period 1968-76, necropsies were carried out on 30 patients who had been treated by long-term intermittent maintenance haemodialysis. Fourteen of these patients developed bilateral cystic disease of the kidney. Clinical, pathological, and radiological investigation of these patients when they first presented did not reveal any evidence of renal cystic change. The main complications of this condition are haemorrhage and tumour formation. Six patients developed renal tumours, and in five cases these were multiple. The histological appearance of these neoplasms gave no indication as to whether they would behave in an aggressive manner. One patient died of metastatic carcinomatosis from a renal primary. The condition of acquired cystic disease of the kidney should be suspected if patients on maintenance haemodialysis suffer from recurrent haematuria or are found to have enlarging kidneys.

Adult

The significance of vesicoureteric reflux in non-pyelonephritic patients supported by long term hemodialysis.

Vesicoureteric reflux was found unexpectedly during routine investigations before renal transplantation in 12 patients with chronic glomerulonephritis and in one with hypertensive nephrosclerosis. They had all received long term hemodialysis treatment for nine to 106 months (mean 47 months) at the time of micturating cystourethrography (MCU). Four of the patients had previously had a normal MCU indicating that reflux developed after onset of end stage renal failure. The cause of reflux is obscure. It was not related directly to defunctioning of the urinary tract as several patients had daily urine volumes in excess of 300 ml. Infection, another potential cause, was uncommon in patients with reflux. Histology of the excised ureters showed abnormality in most cases with loss of the normal mucosal folds and submucosal cellular infiltrate and fibrosis. These changes are also unexplained. In this group of patients nephroureterectomy for reflux in anticipation of renal transplantation was associated with considerable morbidity. A minimal estimate of the incidence of reflux in chronic glomerulonephritis was 11%. We suggest that in this group and in patients with renal diseases other than chronic pyelonephritis reflux alone does not constitute sufficient indication for nephroureterectomy before transplantation to warrant the risks of major surgery.

Adolescent

Renal tubular necrosis due to shock: light and electron-microscope observations.

The renal biopsy findings in a 76 yr-old woman suffering grom anuria due to acute tubular necrosis are described. The glomeruli were normal on light- and electron microscopy. Immunofluorescent studies failed to reveal any fibrin or immunoglobulins in the glomerular capillaries. Extensive focal areas of necrosis were seen in the tubular epithelium often exposing the lumen of the tubule directly to the tubular basement-membrane. In some areas necrotic cells lay adjacent to normal or near normal cells. The proximity of the necrotic tubular epithelium to the oedematous interstitial tissue and the peritubular capillaries, together with the finding of normal glomeruli is compatible with the theory of back diffusion as a mechanism for the oliguria.

Acute Kidney Injury

Segmental glomerulonephritis.

The renal biopsy findings in 40 patients with segmental glomerulonephritis are reported. The term is used to describe a condition in which one or more segments of the glomerular tuft is involved by disease when other segments appear unaffected on light microscopy. The word 'focal' is not used as it may be taken to imply that the changes affect some glomeruli but not others and the evidence for this is not convincing. Segmental glomerulonephritis was a relatively common finding in cases of proteinuria with or without the nephrotic syndrome. The severity of the glomerular changes did not correlate with the ultimate prognosis. On the other hand the tubular and interstitial changes, as assessed by a grading procedure and by point counting, were significantly less severe in those patients who showed clinical recovery than in those who did not.

Adolescent

Aetiology of emphysema.

There is now overwhelming evidence that lung destruction resulting in emphysema is largely due to enzymatic action on pulmonary connective tissues, mainly elastin. These enzymes are probably derived from neutrophil polymorphonuclear leucocytes and alveolar macrophages. Arguments are advanced to show that release of these enzymes is related to cigarette smoking. This explanation for the pathogenesis of emphysema is compatible with the distribution of the disease within the lung noted in epidemiological studies. If this conclusion with regard to the role of cigarette smoking is correct it must follow that, apart from patients with alpha 1-antitrypsin deficiency, emphysems is a disease which could be almost entirely eliminated if the smoking habit was abandoned.

Adult