Search PubMed⌕ Search

Biomedical subjects

M S Dunnill

Publications and source records attributed to M S Dunnill.

At least 19 recordsLinked to original sources
PubMed1995

A new cyclosporin derivative, SDZ-IMM-125, prolongs renal allograft survival in dogs.

Previous studies in vitro and in rodent transplantation models have suggested that an analogue of cyclosporin, SDZ-IMM-125, has immunosuppressive properties at least equivalent to that of cyclosporin. As the bioavailability of the drug was considered to be greater than that of cyclosporin, it was hoped that lower doses could be used with the avoidance of nephrotoxicity. Renal allografts were undertaken between beagle dogs from two partially inbred breeding colonies. After transplantation, SDZ-IMM-125 was given orally at a dosage of 5, 7.5, 10 or 20 mg/kg/day, and graft survival compared to that in dogs given cyclosporin 10 mg/kg or in untreated animals. The results showed that SDZ-IMM-125 is immunosuppressive in dogs and prolongs graft survival up to 50 days at a dosage of 20 mg/kg/day. However, at this dose histological changes suggestive of liver toxicity were observed in one dog, and mild anaemia was produced,but there was no evidence of nephrotoxicity. Absorption profiles suggested that the drug is rapidly absorbed and metabolized, and that a more frequent daily dosage may be appropriate. Overall, there appeared to be no significant advantage for the analogue SDZ-IMM-125 over cyclosporin. The transplant model was associated with a high spontaneous renovascular thrombosis rate, particularly after cyclosporin administration, which was prevented by the daily administration of aspirin.

Animals↗
PubMed1993

bcl-2 protein in non-small-cell lung carcinoma.

BACKGROUND: The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival. METHODS: Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals. RESULTS: We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P < 0.1) and in the group with squamous-cell carcinoma (P < 0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P < 0.02) and in the group with squamous-cell carcinoma (P < 0.01). CONCLUSIONS: The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.

Adenocarcinoma↗
PubMed1993

International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology.

A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

Graft Rejection↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Spontaneous rupture of renal allografts: the importance of renal vein thrombosis in the cyclosporin era.

Spontaneous renal allograft rupture occurring within 14 days of transplantation occurred in 15 patients from 791 consecutive transplants. In each of eight patients treated with azathioprine and prednisolone there was pathological evidence of rejection and only two patients had thrombosis of the renal vein. Of the seven cases occurring in patients treated with triple therapy regimen (low dose cyclosporin, prednisolone and azathioprine), histological evidence of rejection was present in only three cases, but renal vein thrombosis was found in all seven. Spontaneous rupture of a transplanted kidney, a relatively uncommon complication, is more likely to be due to renal vein thrombosis than to rejection in the cyclosporin era.

Adult↗
PubMed1990

Immunosuppression and thrombosis in renal transplantation: an immunohistological study.

Renal biopsies were taken from 42 patients at seven and 21 days after renal transplantation. Paraffin sections from these specimens were examined immunocytochemically for the presence of platelet microthrombi in glomerular capillaries using the monoclonal antibody Y2/51. Patients were treated by one of four different immunosuppressive regimes, three of which included cyclosporin A, either alone or in combination with steroids and azathioprine. Microthrombi were detected in approximately 30% of biopsies and were much commoner in patients receiving multi-drug therapy. We conclude that, contrary to previous suggestions, glomerular capillary thromboses are not frequent in patients on cyclosporin A alone. They are found mainly in patients on multiple drug therapy, particularly when steroids are included. The detection of microthrombi is unlikely to be of assistance in the earlier detection of cyclosporin toxicity.

Azathioprine↗
PubMed1990

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↗
PubMed1989

A randomized comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease.

Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.

Animals↗
PubMed1989

Comparison of the effects of high frequency oscillation and controlled mechanical ventilation on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome.

Saline lavage of the lungs of eight anaesthetized New Zealand White rabbits was performed to produce a surfactant-depletion model of the neonatal respiratory distress syndrome. A characteristic change in the shape of the pressure-volume curve occurred, with the appearance of an inflection point on the inspiratory limb. The animals were treated with high frequency oscillation (HFO) at 15 Hz and the results compared with those of a previously studied group of eight similar rabbits treated with controlled mechanical ventilation (CMV) with end-expiratory pressure equal to the pressure at the inflection point, but with the same mean airway pressure of 15 mm Hg. The animals treated with HFO had significantly higher arterial oxygen tensions and end-expiratory lung volumes than those treated with CMV, but there was no significant difference between hyaline membrane scores. Although there was no significant difference in mean survival times, five of the HFO treated animals showed reversion of the shape of their pressure-volume curves towards the prelavage configuration, suggesting a recovery of surfactant function.

Animals↗
PubMed1989

Langerhans cells in human lung tumours: an immunohistological study.

In an immunocytochemical study of 41 human lung tumours we have shown that Langerhans cells can be reliably identified using the anti-CD1 monoclonal antibody NA1/34. Langerhans cells are present in all the main varieties of human lung tumour although they are infrequent in both small cell carcinoma and carcinoid tumour. There is considerable variation in numbers of Langerhans cells in both adenocarcinomas and squamous cell carcinomas. In this study tumours were divided into those with high numbers of Langerhans cells (greater than 2 per high power field) and those with low numbers (less than 2 per high power field). Analysing these results against patient survival showed a markedly worse survival in those tumours with a high number of Langerhans cells for all the tumours as a single group and for squamous cell carcinoma as a single entity.

Adenocarcinoma↗
PubMed1989

In situ hybridization studies of adenoviral infections of the lung and their relationship to follicular bronchiectasis.

We have used a probe against the adenovirus genome to study cultured epithelial cells specifically infected with various types of adenovirus and Graham 293 cells, which contain few copy numbers of a fraction of the adenovirus genome. We have also examined lung tissue obtained from three cases of acute adenovirus pneumonia, two cases of adenovirus pneumonia that had passed through the acute phase, and nine cases of follicular bronchiectasis. Our purpose was to determine whether the probe was effective in detecting a wide variety of adenovirus types, to determine whether it could detect adenovirus in lung tissue that had been fixed and stored in paraffin blocks for several years, and to test the hypothesis that adenovirus was an important cause of follicular bronchiectasis. The results show that the probe was able to detect adenovirus from Genera B1, B2, C, D, and E with a sensitivity of 5 to 10 copies/cell. The probe also detected adenovirus in 14 of 14 slides from three cases of acute disease, but failed to obtain a positive result in the cases examined after an acute infection or in any of the cases of follicular bronchiectasis. We conclude that the in situ hybridization technique is useful in the investigation of active adenovirus infection of the lung. The failure to show that the virus persisted in the chronic respiratory disease that follows adenovirus infection, or that it was present in cases of follicular bronchiectasis could be due to either a true absence, or to its presence in a latent form that is below the level of sensitivity of this technique.

Adenoviridae Infections↗
PubMed1989

Immunocytochemical analysis of cytocentrifuged fine needle aspirates. A study based on lung tumors aspirated in vitro.

The value of Cytospin preparations of fine needle aspiration (FNA) biopsy material for immunocytochemical analysis was investigated using aspirates obtained from 23 resected human lung tumors. The results were compared with those on cryostat sections from the same tumors. The Cytospin preparations of the FNA biopsies gave the best immunostaining reactions and enabled a comprehensive range of monoclonal antibodies (MAbs) to be utilized. The quality of the Cytospin immunostaining compared favorably with that on cryostat sections of the same tumors and generally yielded a similar immunophenotype. However, the Cytospin preparations were not suitable for staining with MAb Ki67, which detects an antigen associated with cellular proliferation. With Ki67, conventionally prepared smears were much superior and enabled an assessment of tumor growth fraction that concurred with the growth fraction calculated from cryostat sections in most cases.

Antibodies, Monoclonal↗
PubMed1988

Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome.

Sixteen rabbits were anaesthetized and subjected to saline lavage of the lungs to produce surfactant deficiency. This resulted in an arterial oxygen tension of less than 12 kPa on 100% inspired oxygen and an inflection point on the pressure-volume curve at a pressure of 8-12 mmHg. After lavage the animals were randomly assigned to receive either conventional mechanical ventilation (CMV) with a positive end-expiratory pressure (PEEP) of 1-2 mmHg (group I - low PEEP) or CMV with PEEP equal to the inflection point pressure (group II - high PEEP). Mean airway pressures were kept at 14-16 mmHg in both groups by increasing the inspiratory:expiratory time ratios in the low PEEP group. The 5-h protocol was completed by 4 animals in group I and 6 animals in group II, early death usually being associated with a metabolic acidosis. On 100% oxygen, the mean PaO2 at 2-h post-lavage was 15.2 +/- 8.3 kPa in group I and 39.6 +/- 21.8 kPa in group II. Group I had much lower end-expiratory lung volumes (3.0 +/- 1.5 ml above FRC) than group II (34.9 +/- 12.2 ml above FRC). Histological examination of the lungs revealed significantly less hyaline membrane formation in group II (p = 0.001). Thus, the prevention of alveolar collapse by the use of high PEEP levels appears to reduce lung damage in this preparation.

Animals↗