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E Solary

Publications and source records attributed to E Solary.

At least 127 records · Page 7Linked to original sources
PubMed1992

Autologous bone marrow transplantation vs intensive chemotherapy in first complete remission: interim results of GOELAM study in AML.

In November 1987, the French group GOELAM initiated a randomized study comparing allogeneic bone marrow transplantation (BMT), autologous bone marrow transplantation (ABMT) and intensive consolidation chemotherapy (ICC). The induction treatment was randomized between Idarubicin plus Cytarabine and Zorubicine plus Cytarabine: 223 patients with de novo AML and aged 15-50 years are currently evaluable and 178 of them (80%) have achieved complete remission (CR) with no significant difference between both arms. Forty four patients under 40 years of age and having a HLA identical sibling were assigned to BMT and 38 were actually transplanted. Thirty of the 134 other patients did not receive the planned first course of ICC, 4 patients died during this course, and 21 were excluded before randomisation. Thus, only 64 patients have currently been randomized between the 2nd course of ICC (34 patients) and ABMT (30 patients). ABMT was prepared by the Baltimore regimen and the marrow was unpurged. With a median follow-up time of 29 months, the actuarial risk of relapse at 3 years is 29% for BMT, 38% for ABMT and 53% for ICC. The 3 year disease free survival (DFS) is 51% for BMT, 62% for ABMT and 47% for ICC. These differences are not statistically significant. When intention to treat is considered, there is no difference in the actuarial DFS between the BMT and the non BMT groups. Longer follow-up time and larger number of patients are warranted to demonstrate any significant advantage of one of these approaches.

Acute Disease↗
PubMed1991

Sufficient levels of quinine in the serum circumvent the multidrug resistance of the human leukemic cell line K562/ADM.

Reversal of multidrug drug resistance (MDR) has been achieved in vitro by a variety of agents including verapamil, quinidine, cyclosporine A, and amiodarone. The toxicity of these agents precludes the achievement of sufficient levels in the serum to circumvent efficiently the MDR in vivo. The authors previously demonstrated that quinine, the widely used antimalarial agent, is able to reverse primary resistance of rat colon cancer cells to anthracyclines. In this report, the efficiency of quinine formiate in reversing the doxorubicin (ADM) (Adriamycin, Adria Laboratories, Columbus, OH) resistance of the well-defined MDR human leukemic cell line K562/ADM was demonstrated. In culture medium, quinine is slightly less effective than verapamil in increasing the cytotoxicity and uptake of ADM when both drugs are used at the same concentration. A nontoxic dose of 5 micrograms/ml is necessary to reverse the MDR in K562/ADM cells. In patients receiving quinine formiate in a continuous intravenous infusion, a significant correlation (r = 0.84) was found between the serum levels of quinine and the ability of sera to increase ADM uptake in K562/ADM cells. When quinine is administered at a conventional dose (25 to 30 mg/kg/d), serum levels consistently reach more than 8 micrograms/ml without severe side effects; ear noises and vertigo are the dose-limiting side effects. At these concentrations, quinine induces a more than double increase in ADM uptake in K562/ADM cells. Pharmacokinetic data indicate that quinine should be administered 24 to 36 hours before anti-cancer drugs in clinical trials that test its efficiency as a modifier of MDR in human hematologic malignant neoplasms.

Doxorubicin↗
PubMed1991

P-glycoprotein expression and in vitro reversion of doxorubicin resistance by verapamil in clinical specimens from acute leukaemia and myeloma.

The expression of the P-glycoprotein which is associated with the development of multidrug resistance in various cell lines was investigated in 87 fresh acute leukaemia and multiple myeloma samples using the specific mouse monoclonal antibody MRK16 in an indirect immunofluorescence assay. Considering a 10% positive cell cut-off value, a heterogeneous expression of P-glycoprotein was observed in 5/22 (22.7%) de novo acute leukaemias, 7/22 (31.8%) relapse or secondary acute leukaemias, 14/27 (51.8%) acute transformation of myeloproliferative or myelodysplastic syndromes and 5/16 (31.2%) multiple myelomas. This expression was not associated with specific cytogenetic abnormalities, especially alterations of chromosome 7q. Verapamil, a calcium channel blocker, has been demonstrated to circumvent the multidrug resistance in cell lines, possibly by interfering with P-glycoprotein function. Using the microculture tetrazolium assay, verapamil was demonstrated to increase the sensitivity of fresh leukaemic or myeloma cells to doxorubicin in 19/43 (43.1%) samples. The doxorubicin IC50 level and the capacity of verapamil to increase the sensitivity of blast cells to doxorubicin in vitro did not correlate with the expression of P-glycoprotein. We conclude that high non-cytotoxic concentrations of verapamil were able to increase the in vitro doxorubicin sensitivity of fresh acute leukaemia and myeloma cells without detectable expression of the P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Potential usefulness of quinine to circumvent the anthracycline resistance in clinical practice.

Quinine, the widely used antimalaria agent, was found to increase the cytotoxicity of epideoxorubicin (epiDXR) in resistant DHD/K12 rat colon cancer cells in vitro. Quinine appeared as slightly less effective than quinidine or verapamil for anthracycline potentiation but its weaker cardiotoxicity could counterbalance this disadvantage in vivo. Serum from six patients treated by conventional doses of quinine (25-30 mg kg-1 day-1) was demonstrated to enhance the accumulation of epiDXR in DHD/K12 cells as judged by fluorescence microscopy and HPLC assay (1.6 to 6-fold compared with control serum). In this patients quinine concentrations in serum ranged from 4.4 to 10.1 micrograms ml-1. Our results suggest that quinine could be safely used as anthracycline resistance modifier in clinical practice.

Animals↗
PubMed1990

Quinine circumvents the doxorubicin resistance of a multidrug resistant human leukemic cell-line, K562/DXR.

Reversal of multidrug resistance (MDR) has been obtained in vitro by a variety of agents but clinical use of these resistance modifiers is hampered by their own toxicity. Quinine, the natural isomer of quinidine, is demonstrated to circumvent doxorubicin (DXR) resistance of an MDR human leukemic cell-line, K562/DXR. In culture medium, quinine (5 mu/ml or more) significantly increases cytotoxicity and accumulation of DXR in the resistant cells but not in the parental sensitive cells. When quinine is administered by continuous intravenous infusion in the doses conventionally used in chloroquino-resistant malaria (30 mg/kg/d), serum levels reach 8-11 micrograms/ml without prohibitive toxicity. Sera from quinine-treated patients enhance DXR uptake in K562/DXR cells in dose-dependent fashion. The conditions for the safe use of quinine as an MDR modifier in the treatment of refractory human hemopoietic malignancies are defined.

Doxorubicin↗
PubMed1989

Infraclinical neuropathies related to immunodeficiency virus infection associated with higher T-helper cell count.

To assess subclinical involvement of the peripheral nervous system and its relationship to the immunological status of human immunodeficiency virus (HIV)-infected patients, we prospectively studied the peripheral nerve conductions and the subsets of peripheral blood lymphocytes of HIV patients. Fifty-seven patients, aged 20-54 years, 28 homosexuals and 29 heterosexuals, classified as CDC II-III (40 patients) and CDC IV (17 patients) were studied. No neurological symptoms or signs were present on bedside examination or questioning for all of the CDC II-III patients. For each conduction measured (H-reflex, sural and sciatic velocities, sural amplitude), the geometric mean was below normal values (p less than 0.05). Among the 57 HIV-infected patients, 20 (35%) had a significant decrease of at least one electrophysiologic measurement: 10/17 CDC IV patients vs. 10/40 CDC II-III patients (p less than 0.05). Two or more simultaneous abnormalities were more often observed in the CDC IV than in the CDC II-III group (9/10 vs. 4/10) (p less than 0.01). In the CDC II-III group, patients with subclinical neuropathies had higher T-helper and lower T-suppressor cell counts and higher T-helper/T-suppressor ratios than random patients without any neurologic abnormalities (1,057 vs. 657 cells/microliters, p less than 0.05, and 757 vs. 1,304 cells/microliters, p less than 0.01, 1.55 vs. 0.68, p less than 0.01, respectively). We conclude that (a) the peripheral nervous system is precociously and subclinically involved in the HIV disease; (b) the patients with infraclinical neuropathies have a significantly higher T-helper cell count than those without any neurologic involvement. The mechanism and the prognostic value of these two findings remain to be more precisely examined, and further studies are required.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunologic analysis of a thousand cases of acute leukemia. French Groupe d'Etude Immunologique des Leucémies (GEIL).

The French Groupe d'Etude Immunologique des Leucémies (GEIL), now in its fifth year of existence, has collected extensive immunological information on more than 1,000 leukemia patients. The rationale of such multicentric group is to improve immuno-phenotyping and investigate rare phenotypes, with relevance to the clinical outcome of the patients. These aims are described and exemplified through 3 of the first studies performed.

Antigens, Differentiation↗
PubMed1987

[Combination of a 3d-generation cephalosporin (cefotaxime or ceftazidime) and a new quinolone (pefloxacine) in the treatment of febrile episodes in neutropenic diseases (37 cases)].

The combination of beta-lactam antibiotics and new quinolones is a form of broad spectrum antibiotic therapy rapidly bactericidal in vitro which could be an alternative to the classical combination of beta-lactam antibiotics and aminoglycosides in the first line treatment of febrile episodes in patients with neutropenia. The treatment of 37 initial febrile episodes (12 cases of septicemia, 7 infectious sites and 38 cases of fever of unknown origin) in 33 neutropenic patients (PMN leucocytes less than 500/mm3) using the combination of a third generation cephalosporin (cefotaxime or ceftazidime) and a new quinolone (pefloxacin) resulted in an 86% immediate success rate (32 cases/37). Results and course during treatment were similar in both groups (cefotaxime or ceftazidime). A second febrile episode occurred in 11 cases (4 superinfections, 2 chest infections, 5 fevers of unknown origin). Clinical acceptability was satisfactory in both groups. Minimal and transient changes in liver function tests were observed in 19% of the successfully treated patients. Study of quantitative aerobic stool cultures revealed the emergence of resistant bacterial strains, essentially Pseudomonas sp. (6 cases). More extensive trials should provide a better view of the role of this new combination in the first line treatment of febrile episodes in the neutropenic patient.

Agranulocytosis↗
PubMed1987

[Treatment of bacterial infections by ofloxacin. 42 cases].

Fourty-two patients with 44 infective sites were treated with ofloxacin alone (22) or associated with an other antibiotic (20). Thirty-five patients (83%) and 37 infective localisations (84%) were cured. The treatment efficacy was similar for ofloxacin alone or associated, and for treatments given with first or second intent. All non-documented infections were cured. Two of the 4 failures were pneumococcal. So, the non-documented infections, the genital and urinary tract infections, the pulmonary infections (second intent) and osteitis seem to be the best indications of ofloxacin therapy.

Adult↗
PubMed1987

Immunoglobulin phenotype in 164 B cell chronic lymphocytic leukemias: is there a relationship with initial clinical stage and survival?

In 164 B cell chronic lymphocytic leukemias, surface membrane immunoglobulin (SmIg) phenotype has been determined on lymphocytes from 158 patients (mean age = 66 years, sex ratio = 1.43) to examine the prognostic significance of cell marker phenotype. Correlation of clinical stages of the disease according to Rai and Binet and SmIg phenotype emphasized the absence of the SmIgG phenotype, suggesting more mature cells, at stage C according to Binet (11 of 13 being stage A) and at stage III or IV according to Rai. The majority of SmIg phenotypes was SmIgM +/- D. Survival curves according to SmIg heavy or light chain phenotypes did not emphasize a prognostic significance of cell marker phenotype. Peripheral lymphocytosis over 50,000/microliter correlated with a worse prognosis regardless of clinical staging and SmIg phenotype.

Aged↗