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Biomedical subjects

D Bron

Publications and source records attributed to D Bron.

At least 109 records · Page 6Linked to original sources

Phase I-II evaluation of carminomycin in adults with acute leukemia.

Twenty courses of carminomycin were administered to 18 evaluable adult patients with acute leukemia (14 ANLL, 2 ALL, 2 CGL-BC). All but one received daily doses of 6-14 mg/m2 for 5 consecutive days. Two patients older than 60 yr had not prior chemotherapy and the others had refractory or relapsed disease. The median age was 60 yr. Three ANLL patients achieved complete remission for 8, 9 and 9 months respectively, with no maintenance therapy. None of these had proven clinical resistance to daunomycin and/or doxorubicin. Mucositis was dose-related and dose-limiting. Nausea and vomiting were rare. Alopecia was constant. Cardiac arrythmia was ascribed to carminomycin in two patients. One episode of cardiac failure seemed clearly drug-related and recovered with symptomatic treatment. In conclusion, encouraging antileukemic activity was observed with carminomycin in poor-risk patients. At doses up to 12 mg/m2 day X 5, extramedullary toxicity remained acceptable.

Acute Disease↗

Production of human monoclonal IgG antibodies against Rhesus (D) antigen.

An Epstein-Barr virus (EBV)-transformed human B-cell line ( LB4r ) producing anti-Rhesus [Rho(D) antigen] antibody was fused with a non-immunoglobulin-producing mouse-human heteromyeloma ( SHM - D33 ) and selected in hypoxanthine/aminopterin/thymidine medium containing 0.5 microM ouabain. Surviving hybrids found to secrete specific anti-Rho(D) antibody were cloned by limiting dilution. Two clones (D4-B2 and E10-C1) producing high levels (12 and 20 micrograms/ml per 10(6) cells per 24 hr, respectively) of monospecific antibody (IgG3, lambda chain) were selected for expansion and further characterization. Compared to the parental cell line ( LB4r ), these hybridoma cell lines presented several advantages: antibody production was increased 10-fold, cloning efficiency was improved, and the EBV genome was not retained. Antibody production has been stable for greater than 8 months. These human monoclonal anti-Rho(D) antibodies have demonstrated utility in routine blood-group typing. They may also prove useful in the biochemical and genetic characterization of the Rh antigen system. Most important, they offer a source of Rh-immune globulin for the prevention of Rh immunization and alloimmune hemolytic disease of the newborn.

Animals↗

[Monitoring amiodarone].

Serum levels of amiodarone (A) and desethylamiodarone (D) were determined by HPLC in 34 adults receiving loading (2 g) or maintenance doses (200 mg daily) of amiodarone. Serum levels of A after i.v. loading doses were much higher (1.35 micrograms/ml) than after equivalent oral doses (0.51 microgram/ml), suggesting low bioavailability. During maintenance therapy, very low levels of A were measured during the first 3 months of treatment (0.31 microgram/ml), after which they tended to rise (0.53 microgram/ml), as did the ratio of D/A. Among 4 children under maintenance therapy, one had high serum levels of A (1.50 micrograms/ml) and D (2.50 micrograms/ml) and showed nervous and cutaneous signs of toxicity.

Aged↗

Total parenteral nutrition-induced cholestasis mimicking large bile duct obstruction.

The authors present a case of cholestatic jaundice which developed during total parenteral nutrition. The histology of the liver mimicked the picture of large bile duct obstruction. However, there was no duct obstruction and the symptoms regressed after the caloric input was reduced. At postmortem examination, the portal inflammatory infiltrate had cleared and was replaced by fibrosis. Alterations in bile chemistry could be responsible for the similarity between the lesions induced by parenteral feeding and those classically described in large bile duct obstruction.

Biopsy↗

Scientific basis and criticism of current therapy of acute leukemia.

The factors which are thought to determine the response of acute leukemia (AL) to therapy are: 1) tumor size 2) drug dose 3) sensitivity to drug, 4) scheduling of drugs and 5) suppression of normal hemopoiesis. Each of these factors is considered in terms of the scientific data supporting their importance. Inability to measure the size of the tumor mass during all phases of treated AL continues to weaken rational strategies for therapy especially maintenance chemotherapy. Increasing the drug dose improves cell kill and potentially the cure rate up to the limits of toxicity. These limits may be extended by bone marrow transplantation. Various systems to study the drug sensitivity of leukemic cells are in experimental use, including stem cell assays but as yet they do not give a guide to altering therapy. The scheduling of multiple drugs is designed to increase cell kill by recruitment into the cycle, but "sanctuaries" appear to exist for resting cells. The suppression of normal hemopoiesis apparently due to leukemia-associated inhibitors is associated with favorable prognosis in childhood ALL but use of this information to improve treatment protocols is still unclear.

Acute Disease↗

Suppressor cell induction and reticuloendothelial cells activation produced in the mouse by beta 1-3 glucan.

We made a sequential study of the proliferative and functional changes occurring in RE cells after beta 1-3 glucan administration in BDF1, and C57BL mouse. beta 1-3 glucan was administered by single i.v. 50 mg/kg or i.p. 15 mg/kg injection. This successively induced changes in RE cells as follows: on day 3 a rise of acid phosphatase activity in peritoneal macrophages; on day 6 an increase of 3H-TdR incorporation in spleen and peritoneal lymphocytes together with an intense suppression of PHA and LPS responses by spleen cells; on day 10 a 5-fold increase of the percentage of peroxidase rich monocytes in the peritoneum. Thereafter all the values went back to or below control. Our results indicate that beta 1-3 glucan is an in vivo mitogen and a macrophage activator.

Animals↗

Clinical studies with a THC analog (BRL-4664) in the prevention of cisplatin-induced vomiting.

BRL-4664, a THC analog, has been administered to 23 patients at a dose of 10 or 15 mg repeated twice. All patients were on cisplatin therapy, and 16 of them had experienced severe vomiting during the previous course of cisplatin. There was a statistically significant difference between the group with prior cisplatin therapy and without prior therapy in terms of number of vomiting episodes, emphasizing the role of conditioned reflexes. The dose of 15 mg administered before and twice after the infusion of cisplatin was well tolerated. Only minor side effects were observed.

Antiemetics↗

Growth factors and DLI in adult haploidentical transplant: a three-step pilot study towards patient and disease status adjusted management.

Haploidentical transplant is now established as a procedure of choice for patients who lack a compatible donor. However, they are still referred too late, heavily pretreated, at very advanced stages. We initiated a three-step phase I study trying improve transplant-related mortality, relapse rate, and immunity: G-CSF + DLI, GM-CSF + DLI, patient- and disease-adapted strategy. Thirty-three consecutive leukemia patients, aged 18-55, were investigated (20 very poor risk, 11 poor risk, and 2 better risk). GvH type NK alloreactivity was chosen when possible (18/33) and balanced across the three groups. In the first nine patients, G-CSF was used and escalated prophylactic DLI started at month 1. Thus, G-CSF and 1-3 DLI (10(4) CD3/kg) is safe. It results in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (10(4) CD3/kg) at day 30 unless aGVHD (3 patients). The comparison between the two first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD: 0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD > 1: 9/12, price to pay: GVHD resulting in five deaths in total. Step 3 (13 patients) consists of a patient-adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK alloreactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mug) is given the follow-up of these 13 patients, although promising is currently short (median 5 months). Overall, TRM at day 100 is 3/29, reflecting the good tolerance of the conditioning in a heavily pretreated population (median age: 43). NRR mortality (8/26) at 1 year is greater in the GM-CSF + DLI group, reflecting the impact of severe aGVHD. We conclude that the third strategy might improve the outcome without exposing patients to unnecessary severe GVHD.

Adolescent↗

The effect of Epoetin alfa on quality of life in anemic cancer patients.

OBJECTIVES: The purpose of this paper is to review evidence on the use of Epoetin alfa in the treatment of anemia associated with cancer treatment through a discussion of clinical and quality-of-life considerations. MATERIALS AND METHODS: Cancer patients often experience fatigue, which leads to reduced quality of life. There are few effective treatments available to manage this potentially debilitating symptom, which can lead clinicians to become discouraged about treating fatigue. When cancer-related fatigue is due to anemia, there are viable treatment options. This paper reviews the current management of anemia in cancer patients, with an emphasis on the use of recombinant human erythropoietin (Epoetin alfa). CONCLUSIONS: Anemia can contribute to the reduced quality of life experienced by cancer patients. Blood transfusion, the traditional method of treating anemia, is effective and relatively inexpensive, but is associated with certain risks and is subject to limitations in blood supply. Epoetin alfa therapy provides healthcare providers with an effective alternative to blood transfusion, and trial results suggest that this intervention has a positive effect on patients' quality of life. The optimal starting and stopping points for therapy have not yet been determined. In practice, many physicians begin treatment when hemoglobin levels drop below 10 g/dL and stop when they rise above 13 g/dL, with a 75% dose reduction until completion of chemotherapy if hemoglobin again drops below 12 g/dL. Nonresponse (< 1 g/dL rise in hemoglobin) is met with dose increase at 4 weeks and discontinuation after 8 weeks. Controlled studies comparing anemia management via transfusion to the use of Epoetin alfa have not been done to date. Therefore, the relative cost-effectiveness of Epoetin alfa, an effective but expensive intervention, remains unknown.

Anemia↗