Search PubMed⌕ Search

Biomedical subjects

M R Cooper

Publications and source records attributed to M R Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1983

T-lymphocytes escape membrane defect in paroxysmal nocturnal haemoglobinuria.

Erythrocytes, granulocytes and platelets from patients with paroxysmal nocturnal haemoglobinuria (PNH) are abnormally sensitive to lysis by complement. We studied T-lymphocytes from PNH patients for abnormal complement lysis sensitivity. T-lymphocytes free of other contaminating blood cells were prepared by sedimentation, nylon wool filtration, and density gradient centrifugation. The lymphocytes were then labelled with 51Cr and lysis induced by antithymocyte globulin and rabbit complement. PNH lymphocytes were no more susceptible to complement-mediated lysis than lymphocytes from normal individuals. The unusual sensitivity of PNH erythrocytes could still be demonstrated when rabbit serum was a source of complement so the lack of any difference in the sensitivity of normal and PNH lymphocytes was probably not attributable to the inability of rabbit serum to elicit the membrane defect. PNH erythrocytes and granulocytes also acquire more membrane-bound C3 when human complement is activated. Therefore we also searched for increased membrane C3 binding on PNH lymphocytes using anti-I antibody and human serum as a complement source. C3 binding was measured using 125I labelled monoclonal mouse anti-human C3. While we verified increased membrane C3 binding on PNH granulocytes during complement activation we were unable to show similar differences between PNH and normal T-lymphocytes. Thus PNH T-lymphocytes do not share the membrane abnormalities of PNH-erythrocytes and granulocytes.

Aged↗
PubMed1983

Vincristine by continuous infusion in refractory breast cancer: a phase II study.

Eighteen patients with advanced refractory breast carcinoma were treated with vincristine (VCR), 0.5 mg I.V. bolus followed by continuous I.V. infusions of 0.25 mg/m2/day for 5 days every 3 weeks. The daily dose of VCR was infused in 1000 ml D5W to which was added hydrocortisone 50 mg and heparin 3000 U. Patients received from one to six courses (mean 2.3 courses). No objective responses were observed. Stable disease was noted in five patients who had skeletal metastases only. Disease progression occurred in the remaining 13 patients, 10 of whom had received prior VCR by bolus injection. The principal toxicity consisted of constipation without ileus and hyporeflexia-paresthesias. Vincristine, administered by continuous I.V. infusion according to this dose and schedule does not appear to be effective in the treatment of patients with advanced refractory breast cancer.

Breast Neoplasms↗
PubMed1982

Vincristine, doxorubicin, and cyclophosphamide versus low-dose intravenous cyclophosphamide, methotrexate, and 5-fluorouracil in advanced breast cancer: a randomized trial of the Piedmont Oncology Association.

Eighty-one evaluable patients with recurrent or metastatic breast cancer were randomized to receive either vincristine 1 mg/m2, doxorubicin 40 mg/m2 on day one and cyclophosphamide 200 mg/m2 orally days 3-6 (VAC); or cyclophosphamide 350 mg/m2, methotrexate 20 mg/m2, and 5-fluorouracil 350 mg/m2 (CMF) intravenously, all on day 1. Courses of each of the above regimens were repeated every three weeks. Twenty-one of 45 patients (47%) on VAC and seven of 44 patients (16%) on CMF had complete or partial response (P less than 0.05). The duration of response was six months for CMF and nine months for VAC. Hematologic toxicity was minimal for both groups but three patients receiving VAC developed cardiac toxicity. Overall survival projections at this time indicate no differences between the VAC or CMF treated patients.

Antineoplastic Agents↗
PubMed1982

Comparison of oral melphalan, CCNU, and BCNU with and without vincristine and prednisone in the treatment of multiple myeloma. Cancer and Leukemia Group B experience.

A total of 361 evaluable patients with previously untreated multiple myeloma were randomized to receive oral melphalan (0.15 mg/kg/day for seven days, followed by 0.05 mg/kg/day after recovery from the nadir of the leukocytes), BCNU (150 mg/m2 intravenously every six weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-week course of prednisone starting at 0.8 mg/kg for the first two weeks. At week 22, one-half of the patients were randomized to receive vincristine (1 mg/m2) and prednisone (0.6 mg/kg for seven days) every two months in addition to previous therapy. The melphalan treated patients showed a significantly higher overall objective response frequency (59%), according to Myeloma Task Force criteria, when compared to those treated with BCNU (40%) or CCNU (42%). The survivals for all patients were not statistically different for the three treatment programs. However, the good-risk patients treated with melphalan had significantly longer survival (P = 0.02) than the equivalent patients who received BCNU or CCNU. The addition of vincristine and prednisone at week 2 did not significantly increase the percentage of subsequent objective responses or prolong the subsequent survival of any treatment group. It is concluded that oral melphalan is superior to BCNU and CCNU in producing objective responses and in prolonging survival in good risk patients.

Antineoplastic Agents↗
PubMed1982

Nonseminomatous germ cell cancer of the testis. Reducing treatment-related morbidity in patients with disseminated disease.

Fourteen previously untreated patients with metastatic nonseminomatous germ cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimen which was designed to reduce treatment-related morbidity. Nine of 10 patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs have relapsed (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without adversely affecting complete response rates.

Antineoplastic Agents↗
PubMed1982

Nonseminomatous germ-cell cancer of the testis.

Fourteen previously untreated patients with metastatic nonseminomatous germ-cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimens that was designed to reduce treatment-related morbidity. Nine of ten patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs has had a relapse (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without the complete response rates being adversely affected.

Antineoplastic Agents↗
PubMed1982

Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of Bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association.

The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (P greater than 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

Adult↗
PubMed1982

Effect of methanol extraction residue of Bacillus Calmette-Guerin in advanced Hodgkin's disease.

One-hundred-ninety-six patients with Stage III and IV Hodgkin's disease were prospectively randomized to receive either treatment with the methanol extraction residue of Bacillus Calmette-Guerin (MER/BCG) or no immunotherapy. Prior to the MER/BCG randomization, patients received six courses of induction and two years of maintenance chemotherapy so that a group with a presumptively low tumor burden could be established. Only patients achieving a complete remission were evaluated. During the first two years of immunotherapy, the MER/BCG group had a relapse frequency twice that of controls. The overall crude relapse frequency and disease-free survival were similar between the two treatment groups. The MER/BCG dose schedule used in this study was associated with a high frequency of unacceptable toxicity. Ulcerations of greater than 1 cm occurred in one-third of the patients with associated pain, fever, and occasional lymphadenopathy. A high degree of patient noncompliance (36%) was observed. Age (P = 0.002), prior radiotherapy (P = 0.032), and chemotherapy (P = 0.044) were prognostic factors found to significantly influence remission duration. These factors were balanced between patients treated with immunotherapy and those who were not. MER/BCG therapy did not significantly delay or prevent relapse.

Adult↗
PubMed1982

Does tuftsin alter phagocytosis by human polymorphonuclear neutrophils?

The physiological significance of the putative phagocytosis-promoting peptide, tuftsin, was investigated by measurement of chemiluminescence generated during phagocytosis and by assay of the uptake of radiolabeled bacteria. We found no differences in either assay when we compared serum from splenectomized patients (which purportedly lacks tuftsin) with normal serum. Further, there was no difference when serum from splenectomized patients was employed in the presence of absence of exogenous tuftsin. Similar results were obtained under a variety of conditions, utilizing three different challenge particles with varying particle-cell ratios and serum from 20 different splenectomized patients. These results do not agree with the hypothesis that tuftsin plays a major role in promoting phagocytosis.

Blood↗
PubMed1982

Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.

A randomized comparison of the relative efficacy and toxicity of daunorubicin (DNR) at 30 or 45 mg/sq m or adriamycin (ADM) at 30 mg/sq m, given on the first 3 days of a 7-day continuous infusion of cytosine arabinoside (ara-C) at 100 mg/sq m/day, shows the outcome to be dependent on anthracycline, dose, and patient age. DNR 45 is significantly better than DNR 30 or ADM 30 for inducing complete remissions (CR) in patients younger than 60 yr, (72%, 59%, 58% CRs, respectively). DNR 30 is better than DNR 45 or ADM 30 for inducing CR in patients older than 60 yr (47%, 31%, 35%, respectively). There was a corresponding shift in the induction mortality for the age, dose, and anthracycline groups. Adriamycin was significantly more toxic to the gastrointestinal tract than daunorubicin. The duration of complete remission, with cyclic courses of maintenance therapy, was independent of the patient's age, the dose, or choice of anthracycline used in induction, and of whether the maintenance courses were given every 4 wk or every 8 wk.

Adolescent↗
PubMed1982

Effect of age on therapeutic response and survival in advanced Hodgkin's disease.

Although age is a recognized prognostic factor in advanced Hodgkin's disease, there are few data concerning the use of combination chemotherapy in patients greater than 60 years. In two phase III trials of the Cancer and Leukemia Group B, 385 previously untreated patients with stage III or IV Hodgkin's disease received multidrug chemotherapy. All patients received a combination of either mechlorethamine or a nitrosourea, as well as a vinca alkaloid, procarbazine, and prednisone. Two hundred and five patients were less than 40 years of age, 107 were 40-59 years, and 73 were greater than or equal to 60 years. The overall response rates in these three age groups were 70%, 66%, and 40%, respectively. Age at the time of diagnosis was the predominant factor affecting response, and the response rate was not significantly higher in those older patients who received full doses of chemotherapy. Age was also associated with an increased frequency of serious leukopenia and thrombocytopenia. The group of patients greater than or equal to 60 years of age experienced the shortest median time to recurrence, 33 months. The intermediate age group also had a shorter time to recurrence (median, 44 months) than patients less than 40 years (median not yet reached). The low complete response rate and the short duration of response in the patients greater than or equal to 60 years of age resulted in a median survival time of 18 months. Even when the analysis of restricted to just the older patients who received greater than or equal to 90% of the projected drug doses, the complete remission rate, the median time to recurrence (20 months), and the duration of survival (27 months) are still much shorter than in younger patients.

Adult↗
PubMed1981

Intravenous vincristine infusion: phase I trial.

In an attempt to sustain potentially cytotoxic concentrations of vincristine in man, a five-day continuous infusion of vincristine after an initial intravenous bolus injection was administered to 30 patients with refractory malignancies. Three dosage levels were explored (0.5 mg/m2, 0.75 mg/m2, and 1.0 mg/m2 daily for five days). Neurologic and hematologic toxicity were severe at the high dose level, whereas mild to moderate toxicity occurred at the 0.5 and 0.75 mg/m2 dose levels. Objective responses were noted in 11 patients (37%) with the following malignancies: non-Hodgkin's lymphoma (4), acute non-lymphoblastic leukemia (2), chronic granulocytic leukemia in blast crisis (1), carcinoma of the breast (3), and small cell carcinoma of the lung (1). Responses were observed at each infusion dose level. Nine of the 11 responders had previously progressed while receiving conventional intravenous bolus injection of vincristine. These data suggest that the clinical usefulness of vincristine may be enhanced by the use of infusion techniques. A maximum daily dose of 0.5 mg/m2 given for five days is recommended for future trials of intravenous vincristine infusion.

Aged↗
PubMed1981

Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association.

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.

Adenocarcinoma↗
PubMed1981

A randomized comparative trial of chemotherapy and irradiation therapy for stage II breast cancer.

One hundred fifty-eight evaluable patients with Stage II carcinoma of the breast with positive lymph nodes were treated either with adjuvant chemotherapy or irradiation therapy followed by chemotherapy. Patients were randomized to test the effectiveness of L-phenylalanine mustard (L-PAM) with and without postoperative irradiation therapy (R.T.) against cyclophosphamide, 5-fluorouracil, and methotrexate (CMF) with and without postoperative irradiation therapy in decreasing the frequency of recurrence. No significant difference was observed between L-PAM as compared with R.T. plus L-PAM (P = 0.85). The difference between CMF and R.T. plus CMF was significant in support of CMF alone (P = 0.04). The frequency of recurrence between R.T. plus L-PAM and R.T. plus CMF showed no difference. A comparison of the chemotherapy only regimens showed an advantage of CMF over L-PAM (P = 0.05). Both the delay in starting chemotherapy and the significant decrease in percent optimal drug dosage during the first six cycles of therapy are factors that may influence the high frequency of relapse observed in the R.T. plus chemotherapy groups. Of the four treatments, CMF has the lowest frequency of recurrence.

Adult↗