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Biomedical subjects

F E Cotter

Publications and source records attributed to F E Cotter.

69 records · Page 4Linked to original sources
PubMed1989

Co-incident N and K ras gene mutations in a case of AML, restricted to differing cell lineages.

Peripheral blood from a patient with acute myeloid leukaemia (AML) of M5 FAB classification, was shown to have mutations to both the N and K ras genes. Leucophoresed blood was separated on a discontinuous Percoll density gradient to provide fractions enriched for different cell lineages. DNA extracted from these fractions was amplified using the polymerase chain reaction (PCR) technique, and hybridized with oligonucleotide probes specific for the single base mutations previously demonstrated. The N-ras mutation was shown to be restricted to the blast and monocytic cell fractions, concordant with the FAB subtype of M5. The K-ras mutation, however, was present in all fractions, suggesting it had occurred in a multi-potential stem cell representing an earlier stage in the generation of the leukaemia, or possibly an incidental background phenomenon.

Adult↗
PubMed1989

An immunohistological and genotypic study of the plasma cell form of Castleman's disease.

The plasma cell variant of Castleman's disease (angiofollicular hyperplasia) is an uncommon and poorly understood lymphoproliferative disorder which may be associated with a wide variety of systemic features. The clinical, pathological, immunophenotypic and genotypic features of a series of five cases are presented. The clinical manifestations were variable but systemic features were present in four cases. Histologically, all five cases were similar. The characteristic follicle-like structures are composed of concentric rings of B-lymphocytes with a mantle zone phenotype, surrounding an inner core of dendritic reticulum cells. The central regions are composed of plump cells that express Factor VIII related antigen, stain with Ulex europaeus I and are associated with laminin immunoreactivity. Many of these cells stain with Ki67 indicating cellular proliferation. Between these 'follicles', plasma cells are present interspersed between high endothelial venules. Using immunohistochemical techniques two cases were polyclonal, whilst in two others unequivocal lambda/IgA restriction was present; in the other case an intermediate picture of lambda/IgA predominance was apparent. Genotypic studies in three cases indicated immunoglobulin gene rearrangements but germ line T-cell receptor genes. The significance of the apparent clonal proliferation of plasma cells is discussed and a unifying model of Castleman's disease is proposed.

Adult↗
PubMed1988

Extraction of DNA from small sections of frozen tissue with simultaneous histological examination.

Though analysis of small sections of biopsy material by molecular techniques permits increased sensitivity, it also requires accurate histological examination of the tissue in order to reduce sampling error. A technique for the extraction of DNA from small sections of frozen biopsy material with simultaneous histological examination from adjacent sections is described that may enhance the accuracy of characterisation of the tissue, particularly where there is focal variation. The quality of the DNA obtained enables a full range of molecular studies to be carried out.

Biopsy↗
PubMed1988

Platelet size in patients with chronic airflow obstruction with and without hypoxaemia.

Platelet size, expressed as mean platelet volume, was estimated in 35 patients with chronic airflow obstruction and a wide range of arterial oxygen tension (PaO2) values. In these patients there was a negative correlation between MPV and PaO2 (r = -0.70). Mean platelet volume was greater (9.41 (0.86) fl) in 20 patients with an arterial PaO2 of 8 kPa (60 mm Hg) or less than in 18 normal subjects (8.21 (0.63) fl; p less than 0.001). After 24 hours of supplemental oxygen treatment there was a small fall in mean platelet volume, from 9.47 (1.06) to 8.96 (0.8) fl (p less than 0.05) in 12 hypoxaemic patients (PaO2 breathing air less than or equal to 8 kPa) but no change in nine non-hypoxaemic patients. Larger platelets are considered to be haemostatically more active, leading to abnormal platelet function, which may contribute to the development of pulmonary vascular damage in chronic hypoxaemia. Supplemental oxygen may partially reverse these changes by modifying platelet size and activity.

Aged↗
PubMed1985

Gas transfer for carbon monoxide in polycythaemia secondary to hypoxic lung disease.

The transfer factor for carbon monoxide and its subdivisions, the membrane diffusing capacity (Dm) and the pulmonary capillary blood volume (Vc), were measured in 16 patients with polycythaemia secondary to chronic hypoxic lung disease and in ten hypoxic non-polycythaemic control subjects. The mean pulmonary capillary blood volume was significantly lower in the polycythaemic patients (31.6 ml, SD 11.2) compared with the control group (65.2 ml, SD 22.5) (P less than 0.001). Erythrapheresis, as a method of isovolaemic haemodilution, was performed in 15 of the polycythaemic patients. The mean packed cell volume fell from 58 (SD 5)% to 47 (SD 5)% after treatment, with significant reductions in blood viscosity at both high and lower shear rates (P less than 0.001). The mean pulmonary capillary blood volume increased from 32.3 ml (SD 11.3) before treatment to 48.7 ml (SD 18.7) after erythrapheresis (P less than 0.01), with no significant change in membrane diffusing capacity. The rise in pulmonary capillary blood volume is another potential physiological advantage of the reduction of packed cell volume in patients with polycythaemia secondary to hypoxic lung disease.

Adult↗
PubMed1984

Erythrapheresis compared with placebo apheresis in patients with polycythaemia secondary to hypoxic lung disease.

We have assessed the effects of erythrapheresis, a method of isovolaemic haemodilution, and placebo apheresis in 10 patients with polycythaemia secondary to chronic hypoxic lung disease (Mean PaO2 7.2kPa (54 mm Hg]. The mean packed cell volume decreased from 0.60 to 0.48, with significant decreases in blood viscosity at both high and low shear rates (p less than 0.001). The 6-min walking distance improved after erythrapheresis with no significant placebo effect of the procedure compared to control subjects (p less than 0.01). Erythrapheresis is a safe procedure for packed cell volume reduction. It is associated with clinical improvement and there is no demonstrable placebo effect on exercise tolerance.

Blood Viscosity↗
PubMed1983

Erythrapheresis in patients with polycythaemia secondary to hypoxic lung disease.

Erythrapheresis was performed in 10 patients with polycythaemia secondary to hypoxic lung disease (mean PaO2, 6.8 kPa (51 mm Hg)). The mean packed cell volume decreased from 0.64 to 0.48 in men and from 0.56 to 0.42 in women, with significant decreases in blood viscosity at both high and low shear rates (p less than 0.001). Patients showed significant improvement in six-minute walking distances (p less than 0.001) and in tests of mental alertness (p less than 0.01) compared to control subjects. Visual analogue scales confirmed symptomatic improvement after erythrapheresis. Erythrapheresis significantly improved symptoms, mental function, and work performance in patients with polycythaemia secondary to hypoxic lung disease. The procedure was well tolerated by all patients and no complications occurred.

Aged↗
PubMed1983

Plasma exchange in autoimmune thrombocytopenic purpura.

We present data on 5 cases with autoimmune thrombocytopenic purpura treated with plasma exchange in whom conventional drug therapy had been ineffective. In 3, preparation for splenectomy allowed the operation to be performed without bleeding problems. 1 patient who was unfit for splenectomy underwent successful coronary artery vein grafting following preparation with plasma exchange. 2 patients were maintained for variable periods with intermittent exchanges, 1 prior to splenectomy and 1 post-splenectomy. In summary we had no prolonged response to plasma exchange but found it a useful technique as preparation for or adjunctive to more conventional therapy. It was also helpful in patients unresponsive to other forms of therapy who required a brief increase in platelet count to cover surgery or spontaneous haemorrhage.

Adolescent↗
PubMedDate not supplied

Phase 2 study of mitozantrone in combination with chlorambucil and prednisolone for relapsed and refractory non-Hodgkins lymphoma.

Thirty-six patients with non-Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out-patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well-tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3-year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived disease-free, between 28 and 38 months from entry. This study indicates that mitozantrone-based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first-line option for elderly patients.

Adult↗