Biomedical subjects
Publications and source records attributed to M H Cullen.
In a double-blind, cross-over study of twenty male volunteers intravenous injection of 0.4 mg naloxone prevented the impairment of psychomotor performance induced by low levels of blood alcohol. The possibility that alcohol produces intoxication by stimulating the release of endogenous opioid peptides should be investigated.
Forty-three lymph node biopsies were performed prior to retreatment in 30 unselected patients who had relapsed following chemotherapy for advanced non-Hodgkin's lymphoma of low grade histological type. Eight patients (27%) showed unequivocal evidence of transformation to a high grade variety of lymphoma. These included 4 out of 21 cases originally having had follicular lymphoma and 4 out of 9 cases having had diffuse lymphoma. In 2 further patients with follicular lymphoma, relapse was diagnosed following examination of the bone marrow and in one the tumor had clearly transformed. In 5 of the transformed lymphomas the cell type was predominantly centroblastic, in 2 immunoblastic and in the remaining 2 centrocytic (anaplastic). Five of the 9 cases developing high grade lymphoma have died after a median interval of 5 months from transformation, whereas only 3 of 23 cases showing no change are dead. In 4 patients low grade lymphoma persisted in the bone marrow at the time of nodal transformation. The clinical circumstances at the time of rebiopsy were unhelpful in predicting transformation.
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The effect of 24 h exposure to nitrous oxide on the cell division cycle in human bone marrow has been studied in vivo using the technique of DNA flow microfluorimetry. All patients who received nitrous oxide showed a significant increase in the proportion of early S-phase cells with a decrease in late S, G2 and mitotic cells. These changes resemble those seen following the use of S-phase-specific cytotoxic drugs. Control patients showed no such effect. Parallel studies have suggested that interference with the function of vitamin B12 underlies this response. Nitrous oxide may provide a convenient method for studying the cell kinetic aspects of acute B12 deficiency and the possibility of using it to increase the therapeutic index of antitumour drugs is discussed.
A study of seven patients with AILD has confirmed previously reported cytological and immunological changes in the peripheral blood. In themselves these changes should not be considered as specific. Histological examination of the bone marrow may show more characteristic lesions which involve haemopoietic, lymphoid, and stromal cells. Three patients had bone marrow features similar to myelofibrosis, which are considered to be diagnostic of AILD.
A case is reported of cytomegalovirus (CMV) infection with radiological, gastroscopic and histological appearances which led to a mistaken diagnosis of carcinoma of the stomach.
Angio-immunoblastic lymphadenopathy (AIL) is a disease of unknown aetiology and pathogenesis. It has features of hyperimmunity, immune deficiency and can behave like a malignant lymphoma. An underlying abnormality of T-cell regulatory function has been proposed. We report ten patients with AIL followed prospectively and review 200 cases from the literature. As well as showing the typical features described in previous retrospective series namely: constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, skin eruptions, hypergammaglobulinaemia and characteristic lymph node histology; four patients had oedema with ascites or pleural effusions associated with hyponatraemia and hypoalbuminaemia. We have also observed low free thyroxine indices in three patients with elevated TSH levels in two, but without clinical features of hypothyroidism. Seven of the patients in this study were treated with prednisone and cyclophosphamide. Three achieved complete remission but only one patient has survived longer than two years. Failure to achieve complete remission has been associated with a 90 per cent mortality within one year of the onset of disease in the reports reviewed. Corticosteroids alone have produced only a 40 per cent rate of remission. The management of poor responders, non-responders and many relapse cases in unsatisfactory. More instensive chemotherapy is very hazardous, increasing the already high risk of severe infections, and is often unsuccessful. Histological features recently reported to represent co-existent immunoblastic lymphoma at diagnosis were recognized in three of our patients, two of which went on to develop definite lymphoma.
Sixty-six untreated patients with advanced non-Hodgkin's lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide, vincristine, and prednisolone or with chlorambucil. The complete remission rate was higher in the group receiving combination chemotherapy, but the overall response rate was the same for both groups. The mean duration of complete remission was the same as that of good partial remission, and was the same for both treatments. The duration of remission was influenced by histological type and extent of disease at presentation, but not age. Those who responded to the initial treatment (whether with complete or with good partial remission) survived significantly longer than did non-responders. It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis, especially young patients with extensive disease.
Thirty previously untreated adults with diffuse histiocytic and diffuse undifferentiated lymphoma were treated with a combination of adriamycin, vincristine, prednisolone, and L-asparaginase. Complete remission was achieved in 11 out of 12 cases with stage III and 7 out of 18 cases with stage IV disease (P less than 0.005). Bone marrow infiltration, clinical central nervous system involvement, and massive intra-abdominal disease all influenced the prognosis adversely. Complete remission was followed by cranial irradiation and intrathecal methotrexate, and maintained with weekly cyclophosphamide and methotrexate and daily 6-mercaptopurine. The duration of remission was significantly longer for patients with stage III disease (the median of which has not been reached), than for patients with stage IV disease (P = 0.007). Survival was significantly longer for patients in whom complete remission was achieved than for those in whom it was not (P = 0.001), and also for patients with stage III than for those with stage IV disease (P = 0.02).
A case of fatal graft-versus-host disease was seen in an adult with acute leukaemia, after transfusion of leucocytes from normal donors. This is the first reported case of graft-versus-host disease following transfusion of normal blood-products to a patient with a disease not usually associated with severe immunoincompetence. The number of lymphocytes transfused was no higher than that given when platelet concentrates are prepared from a single donor.
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