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Biomedical subjects

P Hasleton

Publications and source records attributed to P Hasleton.

31 records · Page 2Linked to original sources

Hypertonic citrate solution as an alternative to modified Euro-Collins' solution for lung preservation.

In a canine model of acute ischemic lung injury, a hypertonic citrate solution (HTC) widely used for renal preservation in the United Kingdom, was compared with modified Euro-Collins' solution (ECS) currently the most widely clinically used pulmonary perfusate. Ten beagle dogs underwent left thoracotomy and exclusion of the left lung in situ. The lung was flushed with 30 ml/kg of either HTC or ECS and subjected to 60 min of warm ischemia. The circulation to the lung was then restored, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. Lung function was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain, bronchoalveolar lavage, and ultrastructural studies. Flush perfusion with HTC was associated with significantly less severe reperfusion injury, as determined by superior arterial oxygenation (PaO2 at 1 hr: HTC--152 mmHg [(95% confidence interval) CI] [122-182], ECS--59 [47-70]; PaO2 at 4 hr: HTC--124 [100-149], ECS--51 [42-61]), lower pulmonary vascular resistance index (PVRI at 4 hrs: HTC--838 dynes sec cm-5m-2 [651-1075], ECS--1233 [963-1588]); and lower lung weight (HTC--85 g [66-107], ECS--146 [114-184]). Bronchoalveolar lavage studies demonstrated an influx of neutrophils following reperfusion that was significantly less marked in the HTC group (increase in % neutrophils: HTC 24 [19-29], ECS 77 [72-82]). Lung injury assessed by electron microscopy tended to be less severe in the HTC animals. We conclude that HTC may offer an alternative superior to ECS for lung preservation.

Animals↗

Amelioration of lung ischemic injury with prostacyclin.

The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins' solution. Group 1 (n = 5) received pretreatment with 30 ng/kg/min of PGI2 by infusion and as an additive to the flush (20 micrograms/L). Group 2 (n = 5) received no PGI2 and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies. PGI2 therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2 at 1 and 4 hr, respectively; PGI2: 145 mmHg +/- 17.0 and 114 +/- 11.2; no PGI2: 59 mmHg +/- 5.8 and 51 +/- 4.5; P less than 0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2 +/- 91; no PGI2: 1239 +/- 68; P less than 0.05) and lower lung weight (PGI2: 76 g +/- 4; no PGI2: 146 +/- 10; P less than 0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2 group (increase in % neutrophils; PGI2: 50.4 +/- 6.7; no PGI2: 76.9 +/- 6.0; P less than 0.05). Lung injury score assessed by electron microscopy was lower in the PGI2 group (PGI2: 5.2 +/- 1.1; no PGI2; 8.1 +/- 0.5; P less than 0.05). It is concluded that PGI2 treatment is protective against ischemic lung injury in this model.

Animals↗

Multiple extra-adrenal paragangliomas associated with catecholamine cardiomyopathy.

We describe a patient with multiple extra-adrenal paragangliomas who presented with clinical features of a dilated cardiomyopathy. Hypertension was not a major feature of the illness despite excessive catecholamine secretion by the tumours. Following surgical resection the changes of dilated cardiomyopathy did not regress on echocardiography and the patient died of left ventricular failure.

Abdominal Neoplasms↗

Heart transplantation for Churg-Strauss syndrome.

A patient with heart failure caused by Churg-Strauss syndrome was successfully treated with transplantation. The case was unusual because there was little evidence of Churg-Strauss syndrome in the lung. The patient remains well on standard transplant immunotherapy.

Adult↗

24-hour cyclophosphamide infusion therapy for malignant mesothelioma of the pleura.

Thirteen patients with malignant mesothelioma of the pleura have been treated with 24-hour cyclophosphamide infusion (2.5 g/m2) therapy. There were no complete responders. Three patients (23%) had a partial response, and a further three patients who did not fulfil the criteria for objective response, had subjective benefit from therapy with increase in performance status. The overall median survival from the onset of therapy was 6 months (range 2-19 months). High dose cyclophosphamide offers no advantage over standard dose therapy.

Adult↗

Expression of epidermal growth factor receptor (EGF-R) in human lung tumours.

Epidermal growth factor receptor (EGF-R) expression was assessed in 63 lung tumour samples with a monoclonal antibody (EGF-R1) by indirect immunoperoxidase staining on cryostat sections. All 15 small cell lung cancer samples were negative whereas over 80% of the 48 non small lung cancer stained positively. In 30 bronchial biopsies two monoclonal antibodies against the cytoplasmic part of the EGF-R were evaluated. These antibodies showed weaker staining than EGF-R1. No additional or enhanced staining as compared with EGF-R1 was observed, suggesting a lack of enhanced expression of a truncated EGF-R analogous to the v-erb-B oncogene product. Monoclonal antibodies against the EGF-R may be helpful diagnostically in differentiating small cell from non small cell lung cancer and may also be important in elucidating biological differences in primary lung cancer.

Adenocarcinoma↗

Target-like skin lesions in primary amyloidosis.

A case of primary amyloidosis is described, during the course of which transient, purpuric haloes appeared around long-standing Campbell de Morgan spots, forming target-like lesions of the skin.

Aged↗

Effect of chlorphentermine on the lipids of rat lungs.

Chronic administration of chlorphentermine to rats resulted in a reduction of body weight compared to a normal control group. The weight of the heart, liver, kidney, and spleen was less in the treated group while the weight of the lungs was increased significantly. There was no change in the ratio of right ventricular to left ventricular weight in the rats treated with chlorphentermine, supporting the views that this drug does not cause pulmonary hypertension. Biochemical analysis showed that the increase in the weight of the lungs was due to the accumulation of phospholipid. All classes of phospholipid were affected, but particularly phosphatidyl choline, the tissue concentration of which increased nine times. Chlorphentermine also increased the proportion of palmitate present in pulmonary phosphatidyl choline. Histological examination of the lung after treatment with chlorphentermine showed evidence of this drug-induced lipidosis. No conclusion can as yet be reached as to the mechanism involved in the accumulation of phospholipid in the lung after chlorphentermine.

Animals↗

Effects of prolonged administration of chlorphentermine on the rat lung.

Prolonged administration of the anorexigen chlorphentermine hydrochloride to young male Wistar albino rats for up to one year failed to induce in them either right ventricular hypertrophy or hypertensive pulmonary vascular disease. There was, however, the development of a pronounced pulmonary histiocytosis. Studies by light and electron microscopy showed that these histiocytes disintegrated to liberate their lamellar inclusions into the alveolar spaces, producing a picture reminiscent of alveolar proteinosis. Fibrosing alveolitis occurred in only one animal and was thought to be related to inflammatory changes rather than as a development of the pulmonary histiocytosis. Attention is drawn to the fact that thick-walled large pulmonary arteries are entirely normal in rats and should not be misinterpreted as evidence of hypertensive pulmonary vascular disease in test animals.

Animals↗

Association and dissociation of a protease and its inhibitor on the surface of lung squamous cell carcinoma cells.

Squamous cell carcinoma cells possess a cell surface protease, referred to as guanidinobenzoatase (GB). GB is a plasminogen-activator-like enzyme which can be located by the fluorescent probe 9-amino acridine in frozen sections. Fluorescence microscopy has been used to study the inhibition of this GB, the displacement of inhibitor from GB, the displacement of GB from the cell surface receptor and the preparation of both active GB and inhibitor, obtained from these frozen sections of tumour tissue.

Carboxylic Ester Hydrolases↗