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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 217 records · Page 12Linked to original sources
PubMed1979

The disposition of cyclophosphamide in a group of myeloma patients.

The disposition of cyclophosphamide and its alkylating metabolites was investigated in a group of myeloma patients with varying degrees of renal function impairment. No correlation between renal function and clearance of cyclophosphamide or its alkylating metabolites was found. No evidence of accumulation of cyclophosphamide or alkylating activity was found in four patients receiving radiolabelled cyclophosphamide. Renal function was found to be related to the reciprocal of the area under curve of alkylating activity, indicating that this area increased as renal function decreased. In view of the large nonrenal component of alkylating activity elimination and the large inter-subject variability, it is recommended that dose of cyclophosphamide is not altered in moderate impairment of renal function.

Alkylating Agents↗
PubMed1979

Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma. A sequential study over 28 days. II. Changes in non-specific (NK, K and T cell) lymphocytoxicity and delayed hypersensitivity skin reactions.

C. parvum and BCG produced significant changes in NK, K and T cell lymphocytotoxicity using a Chang liver target cell. A consistent temporal pattern over 28 days of early depression, recovery, overshoot and then decline was described. This was particularly marked for C. parvum and 'K' cell activity. Skin test reactivity to recall antigens at 28 days was not appreciably different from the pre-immunization reactivity. The importance of using lymphocyte concentration-cytotoxicity titration curves and the linearization of such curves is discussed. An immunotherapy schedule with 3 weekly immunization intervals is proposed as the optimum schedule in patients receiving C. parvum at a dose of 2.0 mg/m2 i.v.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1979

Effects of repeated Corynebacterium parvum and BCG therapy on immune parameters: a weekly sequential study of melanoma patients. I. Changes in non-specific (NK, K and T cell) lymphocytotoxicity, peripheral blood counts and delayed hypersensitivity reactions.

Increased lymphocyte cytotoxicity, particularly of 'killer' K cell type was recorded with repeated immunizations of either C. parvum or BCG. A 3 week interval between immunizations was capable of maintaining the increase in cytotoxicity. No marked alterations of 'recall' skin hypersensitivity reactions nor of peripheral blood counts were noted. Expression of cytotoxicity results as percentage 51Cr release, lytic units/ml and cytotoxic capacity (after logit transformation of the cytotoxicity-lymphocyte curves) are described. A 3 week immunization schedule is suggested where BCG and C. parvum are used as immunotherapeutic agents, in the doses quoted.

Adult↗
PubMed1979

Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma a sequential study over 28 days. I. Changes in blood counts, serum immunoglobulins and lymphoid cell populations.

The effects of a single immunization of melanoma patients with BCG or C. parvum on the blood counts, serum immunoglobulin levels and lymphoid subpopulations were followed by multiple assays over 28 days. C. parvum produced a decrease in the white cell count, lymphocyte count and lymphoid T and sIg+ cell numbers, which recovered within 1 week; BCG did not produce such a marked depression. Both agents were associated with increases in T cell numbers and lymphocyte PHA blastogenesis after the first week; these declined to pre-immunization values by 3-4 weeks. The sIg-bearing cell subpopulation also increased after BCG. Different methods of expression the results were compared and the difficulties of immunological monitoring are discussed.

Adult↗
PubMed1979

Effects of repeated Corynebacterium parvum and BCG therapy on immune parameters: a weekly study of melanoma patients II. Changes in serum immunoglobulins and lymphoid cell subpopulations.

Two groups, each of eight patients, with metastatic melanoma were immunized with either C. parvum or BCG at 3-weekly intervals. The serum IgG, IgA, IgM levels, E-rosettes, EA-rosetts, sIg-bearing cells, 'null cells' and lymphocyte blastogenesis at four PHA concentrations were assayed, before immunization and weekly thereafter for 8 weeks. The pre-immunization E-rosette values were significantly reduced, with a significant increase in 'null cell' values and EA-rosette percentages, when compared with healthy controls. Following C. parvum immunization, significant increases occurred in E-rosette percentages with decreases in EA-rosette and 'null cell' counts. A significant reduction in 'null cell' values also occurred with BCG. Other parameters including PHA blastogenesis did not exhibit statistically significant changes. Different methods of expressing the results (particularly of blastogenesis data) were compared, as were the similarities between the present investigation and a study of the effects of a single immunization. The relationship between the subpopulation changes and lymphocyte cytotoxicity described in an earlier article (Thatcher, Swindell & Crowther, 1979a) is discussed.

BCG Vaccine↗
PubMed1978

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin's disease and 138 with non-Hodgkin's lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin's lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin's disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin's disease.

Abdominal Neoplasms↗
PubMed1978

MVPP chemotherapy regimen for advanced Hodgkin's disease.

During January 1968 to December 1972, 133 patients with advanced Hodgkin's disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.

Adolescent↗
PubMed1978

Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type.

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.

Adult↗
PubMed1978

Combination chemotherapy for acute lymphoblastic leukaemia in adults.

Fifty-one adults with acute lymphoblastic leukaemia were entered into a trial of intense initial chemotherapy and early "prophylaxis" of the central nervous system (CNS). Initial treatment with OPAL (Oncovin (vincristine), prednisolone, adriamycin (doxorubicin), and L-asparaginase (colaspase)) followed by craniospinal or cranial irradiation and intrathecal methotrexate produced remission in 36 patients (71%). Seventeen of these patients relapsed three to 18 months after the start of remission; the remainder had been in remission for 12 to 52 months by the end of the study. The predicted median duration of complete remission was 18.5 months. None of the four patients who initially had clinical evidence of CNS disease, three of whom also had leukaemic cells identical to those found in Burkitt's lymphoma, achieved remission. Those patients who initially had hepatomegaly or splenomegaly had a shorter remission than those without. The predicted median survival was 27 months in those who achieved complete remission, one month in those who did not, and 21 months overall. The addition of colaspase and doxorubicin to vincristine and prednisolone and the use of early CNS treatment clearly improved the remission rate among adults with acute lymphoblastic leukaemia, though the presence and length of remission was affected by the extent of disease at presentation. Burkitt-like leukaemia, which had a poor prognosis, is probably a separate disease and may benefit from a different therapeutic approach.

Adolescent↗
PubMed1978

Lymphocyte function related to survival curves in patients with metastatic melanoma treated by chemoimmunotherapy.

Thirty-eight patients with metastatic melanoma were evaluated immunologically prior to chemoimmunotherapy. The assays used included recall antigen skin hypersensitivity; lymphocyte count; nonspecific T, non-T, and K cell lymphocytotoxicity; and T and B cell rosette enumeration. Survival curves were computed for each of four ranges of values of a given immunologic test. The higher ranges of positive skin tests, lymphocyte count, cytotoxicity, and T and B subpopulation numbers were consistently associated with the longer survivals. The differences reached statistical significance for non-T cell cytotoxicity and B and T cell peripheral blood counts. Pretreatment immune reactivity, particularly that involvingg non-T cell function, appears related to length of survival.

Antineoplastic Agents↗
PubMed1978

Combination chemotherapy for advanced non-Hodgkin's lymphoma of unfavourable histology.

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).

Adolescent↗
PubMed1977

Lymphocyte function in the blood of patients with untreated non-Hodgkin lymphoma: influence of stage and pathology.

Lymphocytotoxicity of T, non-T and K cells was found to be diminished in a proportion of 30 patients with untreated non-Hodgkin lymphoma; T cell number as enumerated by E sheep cell rosettes was also reduced. The reduction was greatest in patients with disease of unfavorable pathology; the effect of stage on these tests was not marked. Decreased skin reactivity was found in the same group of patients with unfavorable pathology. The reduction of direct and antibody dependent lymphocytotoxicity was not related to an obvious reduction in non-T cell numbers, as assessed by rosetting tests. There was, however, a decrease in phytohemagglutinin cytotoxicity in those groups with reduced T cell number. The influence of unfavorable pathology on lymphocyte effector function is emphasized by this study.

Adult↗