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Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 217 records · Page 12Linked to original sources
PubMed1984

In vivo acute hematotoxicity of N,N'-bis[N-(2-chloroethyl)-N-nitrosocarbamoyl]cystamine (CNCC), a new nitrosourea analog.

The in vivo hematotoxic effects on different hemopoietic cell compartments of a new nitrosourea analog CNCC were compared to another glycosidyl derivative, RFCNU. Bone marrow microenvironment in liquid culture, bone marrow and splenic colony-forming units in agar culture (GM-CFUc), relative spleen index, and spleen and bone marrow cellularity were evaluated in young adult (DBA/2 X C57B1/6)F1 mice. The drugs, dissolved in olive oil, were injected ip at either the minimal or the median or the maximal dose of the "maximally efficient dose range." A single administration of CNCC induced a dramatic depopulation of bone marrow and spleen within 12 and 24 hr and significantly reduced the GM-CFUc in both organs. A rapid recovery of both the total cell number and GM-CFUc was observed between Days 2 and 5 (kinetic experiment). The comparison of toxicity of 20 to 50 mg/kg CNCC and 15 to 30 mg/kg (2-chloroethyl)ribopyranosyl-3-nitrosourea RFCNU at Day 1 and Day 5 showed that the bone marrow microenvironment was modified by the effect of oil and was further impaired by CNCC in a concentration-dependent fashion. In contrast RFCNU had less effect on the microenvironment. Similarly, the bone marrow GM-CFUc population was reversibly impaired by CNCC in a dose-dependent fashion, and again RFCNU had less effect. In the spleen both drugs provoked a higher toxic effect than in the bone marrow; on Day 1 they decreased the GM-CFUc population by 1 to 2 log. On Day 5 a compensatory regeneration was obtained in all cases except the highest tolerable CNCC dose, whose effect was more delayed.

Acute Disease↗
PubMed1984

[An analog of gonadoliberin in the treatment of prostatic carcinoma].

Twenty-five patients with prostatic carcinoma were involved in a Gehan's oriented phase II trial of D-Trp6-LH-RH in daily doses of 500 mcg for 7 days and 100 mcg for 3 months, this lapse of time being considered optimal for evaluation of the short-term response to treatment in this disease. Serum levels of LH and testosterone decreased rapidly. After 3 months of treatment, pain had disappeared in 14/21 patients; urinary symptoms had completely regressed in 10/22 patients and partially regressed in 9. A more than 50% reduction in prostatic enlargement was detected by ultrasonography in 7/19 patients, and the overall proportion of regression at scintigraphy was 43%. Prostatic acid phosphatases decreased by more than 50% in 10/15 patients. The results obtained with this LH-RH agonist were equivalent to those of orchidectomy and oestrogen therapy. The new drug was well tolerated. Although some of the patients treated are still responding after more than 15 months of treatment, further studies are required to evaluate the duration of response.

Adenocarcinoma↗
PubMed1984

An oriented phase-II trial of D-Trp6-LH-RH in patients with prostatic carcinoma.

An oriented phase II trial of D-Trp6-LH-RH was conducted according to Gehan's statistical method on 25 patients suffering from prostatic carcinoma. LH and testosterone serum levels decreased rapidly. Pain disappeared during the third month in 14 out of the 21 patients and markedly decreased in 5. Prostatism completely regressed in 10 out of the 22 subjects presenting it and markedly decreased in 9. Prostate hypertrophy regressed, as shown by ultrasonography, in 84% and by more than 50% in 37% of the patients. The overall regression rate of bone scintigraphy images was 43%; a regression of more than 50% was only registered in 12.5% of the patients; this may be explained by the long time which is necessary before bone image disappearance occurs. Prostatic acid phosphatase levels regressed in 75% and by more than 50% in 66.7% of the patients.

Acid Phosphatase↗
PubMed1984

Cytological and immunological study of 139 patients with acute leukemia.

Sixty-six children with acute lymphatic leukemia (ALL), 26 adults with ALL and 47 adults with acute myeloid leukemia (AML) were subclassified according to the classifications French-American-British (FAB) and World-Health-Organization (WHO). Nine immunological markers and 6 cytochemical stains were also used. The reproducibility of the WHO classification of the smears performed independently twice by one observer was 93%, but that between two observers only 78%. Three patients considered ALL by A were called AML by B, but all three had the common acute leukemia antigen, CALLA. In the group of 87 patients considered ALL by B, only 74 were classified ALL by A, but of the 13 non-ALL B, none had the CALLA. Ten of these thirteen patients had myeloid markers such as Philadelphia chromosomes, peroxidase or Sudan Black B positive reactions, or Fc and C3 receptors. The remaining 3 patients were non-Hodgkin lymphoma with B-cell markers. None of the 47 cases classified as AML had CALLA. Seventeen of nineteen myeloblastic leukemias (M2, FAB) had a myeloid antigen (Mag) and 13 of 15 myelomonocytic leukemias (M4, FAB) had, in addition, Fc and C3 receptors.

Acute Disease↗
PubMed1984

Aclacinomycin A.

Explore the source record for details and available documents.

Aclarubicin↗
PubMed1984

In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses.

The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.

Aclarubicin↗
PubMed1984

Immunoelectron microscopy with immunogold staining method and monoclonal antibodies. A promising tool in ultrastructural study of lymphatic subpopulations.

The immunogold staining method has been recently introduced and proved to be of interest in immunoelectron microscopy as a tracer for detection of cell surface antigens defined by monoclonal antibodies in leukocytes. As variations in sample manipulations and different distribution patterns of gold particles in positive cells are reported, the authors described the experimental conditions which permit them to obtain a good and well interpretable labelling in peripheral blood lymphatic cells. In order to verify the sensitivity and the specificity of this labelling and the interpretation of positivity, a comparison between the percentages of positive cells obtained in electron microscopy and immunofluorescence has been reported. The correlation is acceptable and since the ultrastructural details are also well preserved, this method seems promising for the comparison of molecular phenotypic characteristics and submicroscopic appearance of lymphatic cells.

Antibodies, Monoclonal↗
PubMed1984

Zinc and immunity.

The ubiquitous trace metal zinc has been discovered since a long time as an intrinsic element in all biological systems. However, its role other than structural or catalytic in enzymes is poorly defined. Zinc plays a determinative role both in primary and secondary T lymphocyte production. Experimental data support the notion that during intrathymic maturation, non-autoreactive, immunocompetent T cell clones are selected from the excess of immature thymocytes as a result of expansion of bone marrow derived prothymocytes in response to pleiotropically acting alarmon (s) and a subsequent escape via the thymic stroma cells from nucleotide-mediated "biochemical suicide". The activity of alarmon (Ap4A), nucleotide metabolizing enzymes (TdT, DNA polymerase, thymidine kinase, 5'-nucleotidase) and some of the soluble stromal cell products (FTS) require constitutive zinc. In the peripheral lymphoid organs the magnitude and duration of antigen induced, T cell mediated immunoreactions are regulated by T-cell growth factor (IL-2). Using receptor specific monoclonal antibody probes, it has been established recently that the intracellular role of IL-2 is probably to induce the phenotypic expression of high affinity transferrin receptors, known to be the main zinc transporter system in T-lymphocytes. The coordinative role of zinc in T lymphocyte development via the inducible metallothionein system is emphasized. Some clinical aspects of zinc metabolism are discussed.

Animals↗
PubMed1984

Comparative microscopic study of cardiotoxicity and skin toxicity of anthracycline analogs.

Golden hamsters were submitted, three times a week during 4 weeks, to i.p. administration of an antracenedione, mitoxantrone (MTX), and 12 different anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (e-ADM), rubidazone (RBZ), aclacinomycin (ACM), N-trifluoroacetyladriamycin-14-valerate (AD-32), tetrahydropyranyl-adriamycin (THP-ADM), N-L-leucyl-daunorubicin (l-DNR), carminomycin (CAM), rubicyclamin (RBC) and N-trifluoroacetyl-adriamycin-14-9-hemiadipate (AD-143), at doses equivalent to 3/4 those which are optimally oncostatic on murine L1210 leukemia. The electron microscopic (EM) study of the myocardium showed that all studied drugs are cardiotoxic, but with different degree of cardiotoxicity. The histopathological study of the skin detect degenerative lesions with different degree of alopecia. According to the degree of their cardiotoxicity, skin toxicity, and general toxicity or mortality, all drugs studied are classified into 3 groups: 1st group, ADM, DNR, 1-DNR and RBZ, causing very severe cardiac alterations and alopecia (grade 2-3), and very high mortality, 2nd group, e-ADM, DTR, CAM RBC and MTX, with less severe cardiac alterations, and alopecia (grade 1-2), and always high mortality, and 3rd group, ACM, THP-ADM, AD-32 and AD-143, causing less severe myocardial alterations (grade 1-2), without alopecia (grade 0), and extremely low mortality and general toxicity.

Alopecia↗
PubMed1984

[Protocols for the treatment of leukemia and lymphoma: toward escalation or toward reduction of degree?].

The present AML protocol which only applies one anthracycline associated with arabinosyl-cytosine gives a first remission plateau of 65% and a 75% survival plateau at five years. Contrary to other teams, we do not apply the allogenic bone marrow graft at the first remission but at the second one. The new protocol comprises application of two anthracyclines, adriamycin and aclacinomycin, a possible autologous bone marrow graft at first remission upon reinforcement, a combination of methotrexate and thioguanine as maintenance chemotherapy and immunotherapy with bestatine. The two protocols respectively applied to the ALL good prognosis and reserved prognosis, give 85% global survival. The autologous bone marrow graft is added at first remission to B or T forms or voluminous CALLA + types. The advantage of CNS radiotherapy is compared with its disadvantages. Bestatine is employed in immunotherapy. The immunoprevention protocol applied to CML blastic crisis (vaccination with a pool of CB blasts) from the second year has prolonged survival of patients suffering from this affection and also treated by splenectomy and hydroxyurea. Allogeneic or autologous bone marrow graft is added to the protocol. The same protocol is applied to not very aggressive LLC and LNH (lymphocytic and centrofollicular with small cleaved nucleus cells) and includes maximum remission induced by chemotherapy followed by immunotherapy (by thymuline and then, if immunity disorders are not corrected, by zinc, then bestatine and finally tuftsin). A similar sequence was applied to the myeloma, comprising MLP-PDN-CPM chemotherapy to induce remission, combination of MLP-PDN and CPM and, if there is resistance, CLB, 6-TG, PDN and TNP. Interferon is appropriate with certain cytopenic forms. A protocol comprising VCR, ADM, PDN, CPM and TNP is applied to centrofollicular NHL with small non cleaved nucleus cells or large cells. As Hoerni and Jones have obtained significant benefits with BCG, its terminal application is compared with that of bestatine. Finally a less mutagenic protocol than MOPP and/or ABVD is proposed for Hodgkin's disease. In this protocol, two cycles alternate, and they combine: a) firstly VCR, PDN, THP-ADM and VPS, and b) secondly VLB, DXM, ACM and TNP with alternatively BLM and PPM between the cycles. This chemotherapy is followed by the same immunorestoration protocol as that applied to LLC and myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

[Delta agent].

Delta agent was found in subjects carrying B hepatitis or its. It is detectable with radio-immuno-assays and the anti-delta agent antibody. It could have a pathogenic effect on chronic hepatitis exacerbation and was found in cases of liver adenocarcinomas in marmots. It seems to be acting through a direct cytopathogenic process. Its genome is made of very low molecules weight ARN which actually is a possible intermediary between animal ARN viruses and the vegetal viroïds.

Adenocarcinoma↗
PubMed1984

Hematological toxicity of repeated injections of (chloro-2-ethyl)-ribofuranosyl-3-nitrosourea.

A previous study using a single injection of (chloro-2-ethyl)ribofuranosyl-3-nitrosourea has indicated the low acute hematotoxicity of this nitrosourea. However, because the hematotoxicity of nitrosourea is usually cumulative, we have studied the effect of injecting (chloro-2-ethyl)ribofuranosyl-3-nitrosourea (15 mg/kg) dissolved in 0.2 ml sterile oil C57BL X i.p. into DBA/2F1 mice for 5 consecutive weeks. The dose per injection represents the minimal dose necessary to show the maximal therapeutic efficacy on L1210 leukemia. Bone marrow cellularity and histology, spleen weight, bone marrow and splenic pluripotent stem cells, and colony-forming units committed to granulocyte-macrophage differentiation were measured 1, 2, 4, 7, and 14 days after the last injection in treated and control mice receiving oil only. No morphological or histological changes were found in the spleen and bone marrow of treated mice. In both organs, the number of splenic pluripotent hematopoietic stem cells decreased by about 1 log 1 day after the last injection but rapidly returned to normal values on Days 4 to 14. Granulocyte-macrophage-committed precursors were affected in both organs, at 20% of control values for bone marrow and 5% of control values for spleen on Day 1, with a transient and partial recovery on Day 4 followed by a second drop to 20 and 25% on Day 14. This effect on granulocyte-macrophage precursors contrasts with the absence of significant effect when the same treatment is used on peripheral white blood cell counts. Our results demonstrate that (chloro-2-ethyl)ribofuranosyl-3-nitrosourea belongs to the class of new nitrosoureas with low cumulative hematotoxicity.

Animals↗
PubMed1984

A four-day subrenal capsule assay for testing the effectiveness of anticancer drugs against human tumors.

The subrenal capsule assay may predict to which anticancer drug a given patient's tumor is sensitive and may also be used to screen new anticancer drugs. The present study documents that the use of this model requires a histological assessment of both the exploitability of a subrenal capsule assay and the extent of drug-induced antitumor lesions. Thirty-five tumors from 34 patients with solid tumor were submitted to a subrenal capsule assay in a total of 1130 male B6D2F1 mice. After being biopsied, each tumor was dissected by a pathologist and cut into 50 pieces (1.5 X 1.5 X 1.5 cu mm), and one piece was implanted under the renal capsule of 35 mice; the mean tumor diameter was measured on Day 0. Mice were randomized into groups of 6 to 10 animals each. On Days 1, 2, and 3, mice were treated either with placebo (control group) or with various anticancer agents. On Days 4 or 6, mice were sacrificed, the mean tumor diameter measured, and the tumor-bearing kidney fixed in Bouin's picroformol solution and processed for histological analysis after staining with hematein -eosin. Seven histological parameters were blindly rated in a semiquantitative fashion yielding a compound score ( PAPAN ) which estimated the overall quality of each xenograft between -3 and +11. On Day 4, as opposed to Day 6, mean lymphocytic infiltration was 3-fold lower (p less than 0.01), and the rate of xenografts containing well-preserved cancer cells was 2-fold larger (p less than 0.01) in three different tumor specimens. Twenty-two of 31 (71%) assays were evaluable, as defined by a histological quality control test. In those, drug effects were demonstrable by statistically significant differences among groups in 2 assays (9%) by using the relative variation in tumor size as an index of drug effectiveness and in 12 assays (54%) by PAPAN histological score. This suggests the higher sensitivity of histological scoring over tumor size measurements. Moreover, no correlation between relative variation in tumor size and PAPAN was demonstrable with statistical significance indicating the poor reliability of tumor size measurements as an index of the antitumor effectiveness of cytostatic drugs.

Adenocarcinoma↗
PubMed1984

[The model of French medicine and its structural requirements for the year 2000].

The authors review the quality and defects of the French medicine model regarding its structural, hygienic, human, budgetary, geographic, educational and scientific aspects. They suggest several solutions concerning the necessary separation between hospitals, which should be reserved for patients, and institutions for healthy subjects, because of microbial infection dangers. They recommend the division of the latter into centers for family planning and maternity, centers for the detection, prevention and health education and centers for medical adaptation and education. They stress the advantages and the necessity of maintaining two structures, public and private, and the need for a European health policy to produce medical appliances in the field of imaging and automation, which France lacks so much that the short and long term future of its medicine is threatened.

Budgets↗