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Biomedical subjects

Y Carcassonne

Publications and source records attributed to Y Carcassonne.

At least 55 records · Page 3Linked to original sources

Etoposide and cisplatinum in resistant lymphomas.

Etoposide and cisplatinum have used separately to treat refractory lymphomas. This report describes 22 patients in whom these two agents were used in conjunction. All had been extensively treated with standard therapies previously. The combination of etoposide and cisplatinum was chosen on the basis of preclinical evidence for synergy and because these agents do not cross-react. Cisplatinum was continuously infused for 5 days at a dose of 15 mg/m2/d. As a push a 100 mg/m2/d dose of etoposide was injected on days 1 and 2 of treatment. This schedule produced good responses in 18 patients, i.e. 15 partial remissions and three complete remissions. The side effects were acceptable.

Adult↗

Treatment of acute myeloid leukemia and blastic phase of chronic myeloid leukemia with combined eflornithine (alpha difluoromethylornithine) and methylglyoxal-bis-guanyl hydrazone (methyl-GAG).

A combined eflornithine-MGBG treatment was studied in patients with acute myeloid leukemia (AML) or blastic transformation of chronic myeloid leukemia (BT CML). The first ten patients (5 AML, 5 BT CML) received i.v. or p.o. eflornithine 6 g m-2 day-1 and i.v. MGBG 500 mg/m2 once a week. The duration of treatment was 5-37 days (median 15) with one to five MGBG infusions (median 2). The results were complete response (CR) in one patient, partial response (PR) in four, minimal response (MR) in one and failure (F) in four. Pronounced side effects, including severe mucositis, gastrointestinal disturbances and skin infiltration, were observed in eight patients. As the four PRs were achieved in patients with BT CML, it was decided also to study ten patients with this indication. In attempts to decrease the incidence and severity of unwanted effects, lower doses of eflornithine-MGBG were used, i.e., eflornithine 4 g m-2 day-1 and MGBG 200 mg m-2 once a week. The duration of treatment was 9-110 days (median 46), with 2-14 MGBG infusions (median 6). Responses observed were CR in two patients (in one of whom it was only transient), transient PR in two, transient MR in four, and F in two. Treatment at lower doses was better tolerated, thus allowing a longer duration of treatment. Five of ten patients had moderate or severe gastrointestinal disturbances and one patient had a severe subjective hearing loss. The eflornithine-MGBG combination may prove to be a useful alternative treatment for AML and BT CML, but comparative trials will ultimately be necessary for a more definitive assessment of the combination.

Adult↗

Methotrexate test-dose protocol in the presence of 7-hydroxy-methotrexate.

Methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) plasma concentration-time curves (AUC) have been analyzed in 24 patients after different routes of MTX administration. After an i.v. bolus (50 mg/m2), the AUC for 7-OH-MTX is correlated with that for MTX and inversely correlated with the MTX plasma clearance. When MTX is administered with plasma steady level standardization, using the test-dose protocol, at a level of 10(-5) M over 36 hr (10(-5), 36 hr), 7-OH-MTX-AUC is still correlated with the i.v. bolus pharmacokinetic parameters. The dose prediction using the classical test-dose protocol provides a less efficient MTX dose adjustment at 5 X 10(-4) M over 8 hr (5.10(-4), 8 hr) and the hydroxylation process is no more correlated with the i.v. parameters. On the opposite, upon 6 successive infusions with 10(-5), 36 hr or 5.10(-4), 8 hr protocols, the plasma concentrations of 7-OH-MTX are not significantly modified. This suggests that the hydroxylation process is not inducible.

Adolescent↗

[Neuropathies and HIV retrovirus infections].

Neurologic complications are frequently observed during HIV-related infections and particularly in AIDS. According to the literature, these complications more often pertain to the central nervous system (CNS) than the peripheral nervous system (PNS). A prospective study was carried out in order to determine the frequency and type of PNS disorders during HIV infections, the neurotropism of which is now well established. Forty-one HIV-infected patients - 5 asymptomatic subjects, 14 ARC (AIDS-related complex) and 22 AIDS patients - were studied from a clinical and biological angle; 40 equally underwent an EMG and nervous conduction velocity tests, 26 a lumbar puncture and 25 a nervous biopsy (associated in three cases with a muscular biopsy). The study showed that a PNS-alteration is extremely frequent (36/41, or 88% of all cases), generally mild or even subclinical (17/36); most often, the aspect is that of a sensitive axonal polyneuropathy. More severe types (polyradiculoneuritis, sensorimotor polyneuropathy, etc.) are equally observed, but much rarer. Whatever their form may be, the PNS-lesions can be observed in so-called asymptomatic subjects (2/5) as well as ARC (12/14) and AIDS (22/22) patients. They are the manifestation either of a direct lesion of the nerve through HIV, or of immune mechanisms (of humoral or cellular mediation) or of both mechanisms combined.

Acquired Immunodeficiency Syndrome↗

Kinetics of methotrexate and its metabolites in red blood cells.

It has been suggested that the intra-erythrocyte levels of methotrexate (MTX) and its polyglutamized derivatives could offer a method for evaluating intracellular MTX accumulation and its metabolism in children with acute lymphoblastic leukemia. We were interested in measuring the intra-erythrocyte levels of MTX in patients with solid tumors receiving high-dose MTX treatment. After a first incorporation stage occurring during infusion, MTX concentrations subsequently increased 9-12 days after the treatment as polyglutamized derivatives. Thirty days after the infusion, MTX and its polyglutamates were still measurable in erythrocytes. The percentage of polyglutamization varied on an individual basis, but two groups of patients could be separated according to their ability to form polyglutamates. We also noted the presence of 7-hydroxy-methotrexate (7-OH-MTX) appearing 48 hours after the beginning of the infusion which was still present in 17/20 samples 30 days after the treatment.

Adult↗

[Chronic lymphoid leukemia in young subjects].

A total of 8% of chronic lymphocytic leukemias (CLL) occur in young people, before the fourth decade, and can be considered as a specific clinical form of CLL. We report 24 cases of young CLL treated since 1975. The clinical course has the same characteristics in young as in old people except for the high tumoral B stage which has a worse prognosis.

Adult↗

[Anthracyclines in the treatment of epidermoid cancers: uterine cervix, esophagus, bronchi, head and neck].

Anthracyclines certainly do not play a leading role in the treatment of squamous-cell carcinomas. Their effectiveness in these malignancies is limited. In carcinomas of the uterine cervix, variable therapeutic (partial or complete) response rates ranging from 0% to 25% have been reported with doxorubicin as single drug therapy. Using combination chemotherapy, maximum response rates of 54% with cis-platinum and 66% with methotrexate have been achieved. In esophageal carcinoma, a low response rate, fairly consistent across studies, approximating 18%, has been recorded with doxorubicin alone. More satisfactory, although still mediocre results have been recorded with combination chemotherapy, e.g. 33% with FAP (doxorubicin, fluoro-uracile, cis-platinum). Only addition of VP 16 to FAP has yielded a good response rate (66%) in one study. In carcinoma of the lung also, doxorubicin alone has yielded low response rates, approximating 18%. Widely variable results have been reported for the numerous combination chemotherapy trials, with therapeutic response rate ranging from 5% to 66% and mean survivals ranging from 3 months for the least satisfactory trials to 18 months for the few more satisfactory series. In carcinomas of the head and neck, therapeutic response rates with doxorubicin alone have been 20 to 25%. With combination chemotherapy, rates exceeding 50%, occasionally by a fairly wide margin, have been achieved. However, the clinical response may be of fairly short duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotics, Antineoplastic↗

[Lymphocyte phenotyping in the cord blood of newborn infants].

Ontogeny and development of phenotypically defined T-cell subsets in humans, are the source of controversy. Cord blood represents a relevant model for the study of the normal T-cell differentiation pathway. We identified T lymphocytes subsets with monoclonal antibodies (Mab) in human cord blood and adults controls in an indirect immunofluorescence assay and B lymphocytes in a direct immunofluorescence assay. No difference was noted between the two populations with followed Mab: CD3-CD4-CD8-HLA class II-IL2 receptor, with a normal ratio CD4-CD8. The percentage of CD2+ cells was lower in neonatal blood. Double labeling studies characterized a lymphocyte population CD4-CD8 positive. This study revealed absence of immature T cells with CD1 monoclonal antibodies.

Antibodies, Monoclonal↗

[Dysmyelopoiesis and T lymphoma. 2 cases].

The role played by T lymphocytes in myelopoiesis has been established in in vitro studies. Dysregulation of the lymphoid system results in quantitative and, more rarely, qualitative abnormalities of myelopoiesis. The authors report the clinical data of two cases of peripheral T cell lymphoma associated with an AREB type of dysmyelopoiesis. The fact that both conditions were diagnosed simultaneously and progressed in parallel is an indirect argument in favour of the regulation of myelopoiesis by the T lymphocytes.

Aged↗

[Prolonged survival in multiple myeloma. Characteristics of presentation and response to treatment of 73 patients who survived 5 years or longer].

Data concerning the presentation and response to treatment of 73 patients with multiple myeloma who survived for 5 years or more were reviewed. At the time of diagnosis, the proportion of patients with hypercalcaemia (4%), severe anaemia (9%), renal failure (10%) or high beta 2-microglobulin levels (25%) was low. Less than one-third of our patients belonged to a "high risk" group, as defined by the three classification systems adopted: the lowest percentage of such patients (18%) was observed with the Medical Research Council classification. In all patients, but even more in those with an initially aggressive disease (P less than 0.05), obtaining a plateau (70% of the cases) or even an optimal tumoral regression with complete disappearance of monoclonal immunoglobulin (26% of the cases) seems to be a highly favourable factor. The same applies, though to a lesser degree, to slow response to chemotherapy (18 months on average). In all responders whether the remission was maintained or not by chemotherapy seemed to have no influence on the frequency (70%) and delay of relapses (4 1/2 years on average from the time of diagnosis). The risk of secondary blood disease (2 AML 1, 1 AML4, 1 RAEB, 1 ASIA, four of which were directly responsible for death) after 4 years on average of chemotherapy must be taken into consideration.

Adult↗

Methotrexate-vindesine association in head and neck cancer: modification of methotrexate's hydroxylation in presence of vindesine.

High-dose methotrexate (HD-MTX) infusions associated with vindesine (VDS) have been used in the treatment of head and neck cancer. In a previous study, VDS was shown to increase the apparent plasma clearance of MTX. We have studied the MTX hydroxylation process in the presence of VDS. Different routes of administration have been tested (IV pushes and 24-h or 36-h infusions). A radioimmunoassay has been developed to measure 7-OH-MTX. The defined protocols enabled us to show that VDS influences not only the pharmacokinetic behavior of methotrexate but also its hydroxylation, which is decreased in presence of VDS.

Adult↗

6-day subrenal capsule assay (SRCA) as a predictor of the response of advanced cancers to chemotherapy.

The 6-day subrenal capsule assay (SRCA) chemosensitivity prediction test using fresh human tumor xenografts was performed in BALBc mice for 80 advanced cancer bearing patients. Among 97 SRCA, nine were non-evaluable because patients either received no chemotherapy or non-assayed drugs, and 12 were non-interpretable because of inadequate control growth. One hundred and six correlations were established between test results and clinical response, 56 retrospective (chemotherapy then test) and 50 prospective (test then chemotherapy). Among the 56 retrospective correlations there are 45 true negative (-/-) and three false positive (+/-) corresponding to 48 poor clinical responders; and eight true positive (+/+) and 0 false negative (-/+) corresponding to eight good clinical responders. Among the 50 prospective correlations there are 26 true negative (-/-) and four false positive (+/-) corresponding to 30 poor clinical responders; and 19 true positive (+/+) and one false negative (-/+) corresponding to 20 good clinical responders. In total among the 106 correlations there are 98% good negative correlations and 79% good positive correlations. The SRCA is practicable and is available for routine clinical use providing results relevant to cancer site and reflecting previous treatment status.

Animals↗

[Detection of intracytoplasmic immunoglobulins by cytofluorography].

In this report the authors describe a method of cell permeabilisation compatible with flow cytometry. To maintain cell integrity, lysolecithin is used. This method is simple, rapid, and reproducible. Control tests demonstrated no non-specific fluorescence due to lysolecithin treatment. This technique was used in several cases of chronic lymphocytic leukemia to detect intracytoplasmic immunoglobulins and monoclonality and in one case of multiple myeloma.

B-Lymphocytes↗

[Chromosome polymorphism in allogeneic bone marrow grafts. Methods and results].

Cytogenetic studies using constitutive heterochromatin variations represent one of the best method in documentation of allogeneic bone marrow transplantation (BMT). Sex mismatched transplants are evaluated by gonosomal examination. In sex matched patients, several banding techniques are performed before BMT to detect autosomal polymorphism in donor and recipient. Can be informative: chromosomes 3 and 4 centromere, acrocentric centromere and satellites, chromosomes 1, 9 and 16 secondary heterochromatic constriction. Authors describe their methodology for these studies and results about 81 patients.

Bone Marrow Transplantation↗

[Thoracoscopic talc poudrage in pleurisies of blood diseases].

A total of 20 patients aged 50.5 +/- 4.5 years with 24 chronic pleural effusions associated with lymphomas underwent 24 thoracoscopic talc poudrages. Effusions were serofibrinous (32%), hemorrhagic (41%), or chylous (27%). The mean volume of pleural liquid evacuated by repeated thoracenteses before thoracoscopy was 5.2 +/- 0.6 l. Thoracoscopic biopsies confirmed a lymphomatous infiltration of the pleura in 95.5% of cases. A definitive pleural symphysis was obtained in all cases but 2 (92% positive results): in 1 case, a further single thoracentesis of 400 ml was necessary, and in the 2nd case the patient died within 6 days from an acute evolution of her Hodgkin's disease. The mean drainage time was 4.8 +/- 0.2 days. Overall results are thus identical to those obtained in solid tumor-related pleural effusions (91% positive results).

Adolescent↗