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Biomedical subjects

A A Dawson

Publications and source records attributed to A A Dawson.

At least 19 recordsLinked to original sources

p53 mutation and expression in lymphoma.

Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.

Adult

Non-Hodgkins lymphoma of the head and neck: experience in the Grampian area.

The records of 44 cases of non-Hodgkins lymphoma (NHL) presenting to the ear, nose and throat department in the Grampian area from 1980-1988 were examined in relation to site of occurrence, histology, age at presentation, clinical stage, treatment and survival. The median age was 67 years and there was a preponderance of high grade histology, especially in disease affecting the tonsil. Most deaths occurred in the first year; patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year. The site of disease had no influence on survival.

Adolescent

Obscure anaemia and hepatic dysfunction in Castleman's disease.

A case is reported illustrating a rare and puzzling cause of long standing anaemia and abnormal liver function tests. The diagnosis of Castleman's disease came to light only after an adrenal mass was noted during ultrasound examination. Removal of the mass led to a rapid reversal of all the abnormalities.

Adolescent

The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination.

Three consecutive patients with acute promyelocytic leukaemia who presented with severe haemorrhagic syndromes were studied and the findings contrasted with those of two patients with classical defibrination after electroshock or complicated labour. The leukaemic patients showed no depletion of fibrinogen. There was no evidence of disordered thrombin generation by either intrinsic or extrinsic pathway sufficient to account for their haemorrhage. All, however, showed strikingly enhanced fibrinolytic activity, which could have accounted for bleeding. This fibrinolytic disorder was characterized by free u-PA in the plasma and differed from that seen after classical defibrination, where free t-PA was observed. U-PA was found also in malignant promyelocytes, which may be the source of u-PA activity in the patients' plasma. Bleeding in promyelocytic leukaemia may be primarily a fibrinolytic disorder.

Electrophoresis, Polyacrylamide Gel

Accelerated increase in aortic diameter in patients treated for lymphoma.

Cytotoxic chemotherapeutic agents, particularly the anthracyclines, are known to be cardiotoxic, but toxic effects on the aorta have not previously been documented. In this study, diameters of ascending and descending thoracic aortae were measured by computerized tomography in 69 patients with lymphoma, before and after first-line treatment with one of 7 different regimes. Minor increases in aortic diameter over the study period due to the aging process were expected. These increases were greater than anticipated in both the ascending and the descending aortae after chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and CVP (cyclophosphamide, vincristine, and prednisolone) regimes. Smaller changes, or changes which were not statistically significant, were noted after MVPP (mustine, vinblastine, procarbazine, and prednisolone), ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone), ChlVP (chlorambucil, vincristine and prednisolone), mediastinal radiotherapy, and radiotherapy plus MVPP (MVPP/XRT). Cardiovascular damage associated with certain forms of cytotoxic therapy is not confined to the heart, but also affects the aorta.

Antineoplastic Combined Chemotherapy Protocols

The effects of four drug regimens on sister chromatid exchange frequency in patients with lymphomas.

Patients undergoing first-line chemotherapy after diagnosis of lymphoma have considerable DNA damage in their peripheral blood lymphocytes, using sister chromatid exchange (SCE) frequency as a sensitive indicator. Different drug regimens produce different patterns of changes in SCE frequency. These may be related to their potential to induce second malignancies.

Antineoplastic Combined Chemotherapy Protocols

Methylprednisolone, etoposide, vindesine, and chlorambucil (PEEC) alone or alternating with CHOP as initial or salvage therapy for non-Hodgkin's lymphoma.

A novel cytotoxic drug combination, PEEC, has been tested in the initial or salvage treatment of lymphomas. The PEEC combination alone is active in high grade or intermediate grade NHL with two complete and two partial remissions out of four patients so treated. When combined with standard CHOP therapy using an alternating regime, seven out of 11 patients obtained a complete remission and four partial remission. Ten patients were well, off treatment, beyond one year from presentation. The combination was less impressive, however, as salvage therapy with two partial responses in a heavily pre-treated group of nine patients.

Adult

Obstructive jaundice. An unusual presentation of granulocytic sarcoma.

A 36-year-old woman presented with obstructive jaundice, found at laparotomy to be due to a granulocytic sarcoma in the head of the pancreas. Six months later she developed lymphadenopathy in the left supraclavicular fossa. In spite of chemotherapy containing cytarabine and vincristine, she developed acute myeloid leukaemia (French-American-British [FAB] type M4) 16 months after the onset of her illness.

Adult

Splenectomy in the management of haematological disease.

Patients, both adults and children, with various haematological disorders who had splenectomy electively in the diagnosis, staging or treatment of their condition during a 15-year period in the Aberdeen hospitals were reviewed. The outcome regarding the disease and the immediate and long-term complications of splenectomy in this group of 185 patients are presented. Splenectomy has an acceptably low morbidity, even in patients with serious haematological disease, in the hands of an experienced surgical team, where there is close co-operation between surgeon and haematologist. Occasionally, late overwhelming infections may occur, despite prophylaxis with penicillin and pneumococcal vaccination. It seems likely that, in their zeal to report such hazards, authors may allow the pendulum against splenectomy to swing too far, in the direction of leaving patients, especially adults, with considerable symptoms and poor health, rather than risk the occasional consequences of the asplenic state.

Adolescent

Non-cytotoxic antibodies in chronic lymphocytic leukaemia.

Non-cytotoxic Fc receptor blocking antibodies against autologous B lymphocytes were sought in sera from patients with chronic lymphocytic leukaemia (CLL), using a rosette inhibition assay. They were found in 11 of 52 (21%) of patients with CLL, but were not associated with previous blood transfusion or pregnancy, suggesting that they were unlikely to have resulted from allogeneic stimulation. Fc receptor blockade was more commonly detected in sera from patients with stage B rather than stage A CLL (Binet classification), though this did not achieve significance beyond the 90% level, and it was noted in 62.5% of those with lymphocyte doubling times of less than one year, compared with 36.3% of those whose lymphocyte doubling time was more than one year. The results indicate that autologous Fc receptor blocking antibody activity occurs in sera from patients with CLL, is more likely to be generated by the tumour itself than by allogeneic stimulation, and is associated with increased tumour load. Such antibodies may permit tolerance of tumour by the host.

Autoantibodies