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Biomedical subjects

E F Winton

Publications and source records attributed to E F Winton.

82 records · Page 5Linked to original sources

Colony stimulating activity and continuous flow centrifugation leukapheresis induced proteinuria.

Urinary granulocyte colony stimulating activity (CSA) was studied in normal individulas donating granulocytes. Donors were given corticosteroids 2 h prior to a 4-h leukapheresis using an Aminco celltrifuge in which hydroxyethyl starch was introduced into the donor line. Urine was collected 12-24 h prior to the procedure and 12-24 h beginning at the time of administration of corticosteroids. Colony stimulating activity was measured using mouse marrow cells grown in soft agar. After leukapheresis a significant increase in protein excretion was noted (139.94 +/- 28.1 to 288.69 +/- 63.8 mg per gram of creatinine) and the bulk of the protein was albumin. CSA isolated from G-75 Sephadex columns was increased in five donors, decreased in five donors and undetectable in nine donors. No CSA inhibitors were detectable. There was a significant correlation between the quantity of protein recovered from G-75 Sephadex column and CSA.

Adrenal Cortex Hormones↗

Development of a practical oral dexamethasone premedication schedule leading to improved granulocyte yields with the continuous-flow centrifugal blood cell separator.

Studies were conducted to improve the yield of granulocytes collected for transfusion from normal donors by means of the continuous-flow centrifugal blood cell separator. Nonleukapheresed donors were medicated with varying schedules of corticosteroids to learn the magnitude and duration of granulocytosis. Normal donors were medicated with varying schedules of corticosteroids prior to a 4-hr leukapheresis and the granulocyte yields determined. It was found that maximum yields (32.2 x 10(9) granulocytes) were obtained by use of dexamethasone given orally 12 and 3 hr prior to leukapheresis. There was a good correlation between the yields and the circulating granulocyte count at the start and during the procedure.

Administration, Oral↗

A controlled study of the efficacy of granulocyte transfusions in patients with neutropenia.

A randomized clinical trial to determine the efficacy of granulocyte transfusions in neutropenic patients with infection was conducted. Criteria for patient selection included a proved infection, a granulocyte count of less than 300/mm3, availability of a suitable donor and failure to respond to at least 72 horus of appropriate antibiotic therapy. Thirty patients were assigned at random to receive either granulocyte transfusions or to serve as a control group. Antibiotic therapy was continued in both groups. Responses were judged by the degree of diminution of infectious episodes and survival. The results showed that 11 of 13 control patients failed to respond during the period of observation, whereas 10 of 17 patients given transfusions responded. The results were statistically significantly different (p less than 0.05). The median survival was 22.5 days in the group given transfusions (group 2) and 7.7 in the control group (group 1) (p less than 0.01). The granulocyte transfusions were most effective in patients with hypocellular marrows who failed to recover during the period of observation. These results indicate that granulocyte transfusions are effective in the short-term control of infections in neutropenic patients.

Adult↗

Slide chamber culture system for the in vitro study of humoral regulation of granulocyte and monocyte-macrophage proliferation and differentiation.

A liquid culture system employing slide chambers was developed to facilitate the study of proliferation and differentiation of mouse neutrophilic granulocytes and cells of the monocyte-macrophage series. Cultures were initiated with 1-2.5 X 10(4) light density marrow cells which had been fractionated on Ficoll-Hypaque. In the presence of colony-stimulating activity (CSAHU), two types of clusters were observed. One was tight, spheroidal, and composed of neutrophilic granulocytes, while the other was a loose grouping of flattened cells of the monocyte-macrophage series. The slide chamber culture is adaptable to microscopic assay techniques (e.g., cluster size, autoradiography, immunofluorescence) as well as quantitative biochemical methods (e.g., rate of 3H-thymidine incorporation, DNA quantitation). We have demonstrated both a shortening of the generation time of granulocytes in tight clusters and increasing rates of 3H-thymidine incorporation into DNA, with a corresponding increase in total culture DNA as a function of CSAHU concentration. Granulocytic differentiation in the tight spheroidal clusters has been demonstrated by histochemical stains and immunofluorescence of an antibody to a marker protein specific for the secondary granule of the neutrophil (lactoferrin).

Animals↗

Phase I trial of dianhydrogalactitol administered Iv in a weekly schedule.

Dianhydrogalactitol was given to 28 patients with a variety of advanced solid tumors on a weekly schedule in iv doses ranging from 2 to 80 mg/m2. No significant toxicity was encountered at doses up to 40 mg/m2/week for 4 weeks. At higher doses mild-to-moderate nausea and vomiting and hematologic toxicity were noted. Thrombocytopenia was more common than granulocytopenia and frequently resolved more slowly. No adverse drug-realted effects on liver, renal, coagulation, or cardiac function were seen. Although no patient had significant antitumor response (as strictly defined), objective improvement was noted in two patients, one with hypernephroma and the other with malignant melanoma. for phase II studies, a weekly dose of 70 mg/m2 is recommended for patients with normal hematopoiesis, with reduction by 25% (55 mg/m2) in patients with extensive prior radiation therapy, prior chemotherapy, and/or widespread metastasis to the bone.

Adult↗

Hemoglobin Atlanta or alpha 2 beta 2 75 Leu-Pro (E19): an unstable variant found in several members of a Caucasian family.

Hemoglobin Atlanta, alpha 2 beta 2 75 Leu-Pro (E19), has been found in several members of three generations of a Caucasian family living in metropolitan Atlanta. The abnormal hemoglobin is one of the nine unstable variants in which either a leucyl or an alanyl residue is replaced by a prolyl residue. These substitutions have been observed in the B, E, F, and G helixes of the beta chain and in the H helix of the alpha-chain. Hemoglobin Atlanta heterozygotes are mildly affected by the presence of this unstable hemoglobin.

Alanine↗

Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group.

The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial. Of 128 patients entered, 102 (80%) were evaluable for response. Remission was achieved in 13 of 80 evaluable patients with acute myeloid leukemia, in one of 12 evaluable patients with acute lymphoid leukemia, and in none of 11 patients with blastic transformation of chronic granulocytic leukemia. Three remissions occurred in patients with acute myeloid leukemia who were refractory to initial induction chemotherapy with cytarabine and anthracycline combination chemotherapy. Remissions were relatively durable, lasting a median of 28 weeks in the 13 patients with refractory acute myeloid leukemia (range, 14-54 weeks). Toxic effects included universal severe myelosuppression, hyperbilirubinemia at a frequency and severity similar to those seen with amsacrine used as a single agent, moderately severe stomatitis and diarrhea, three incidents of amsacrine-related cardiac dysrhythmia, and a single case of probable drug-related cardiomyopathy. This combination has activity in the treatment of myeloid leukemia, which is primarily resistant to cytarabine and anthracyclines, and could have a role in primary management.

Adolescent↗

Intensive chemotherapy with daunorubicin, 5-azacytidine, 6-thioguanine, and cytarabine (DATA) for the blastic transformation of chronic granulocytic leukemia.

Thirty patients with blastic transformation of chronic granulocytic leukemia were treated with a combination of daunorubicin, 5-azacytidine, 6-thioguanine, and cytarabine. Hematopoietic toxic effects were substantial and eight of 23 patients developed hepatic dysfunction (bilirubin greater than 5.5 mg/dl). Although the regimen resulted in marked decrease in peripheral blood blast cells and produced marrow hypoplasia in most of the patients (20 of 23), there was little therapeutic benefit. Seven patients died while aplastic, nine had recurrence of blastic leukemia, and only four had partial improvement in marrow function.

Adolescent↗