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Biomedical subjects

D Caillot

Publications and source records attributed to D Caillot.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Altered peripheral nerve conduction in HIV-patients.

An electrophysiological study on peripheral nerves conduction was performed on HIV-seropositive patients without neurological signs on clinical examination. Eight of the 28 patients (28%) had an infraclinical neuropathy, which was myelinic or axonal and rather distal than proximal. The mechanism of these involvements is not known, but their early existence could justify an early treatment even for asymptomatic patients.

AIDS-Related Complex↗

[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↗

[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↗

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↗