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Biomedical subjects

J M Andrieu

Publications and source records attributed to J M Andrieu.

At least 91 records · Page 5Linked to original sources

The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. I. Dose-response relationships and combined effects of bleomycin with thio-tepa and gamma-rays.

The effect of bleomycin (BLM) on mouse stem cells has been analysed using the spermatocyte test. The dose-response relationships after treatment with doses of 20, 40 and 60 mg/kg of the compound as well as the combined effect of BLM and gamma-rays and BLM and thio-tepa (TT) were studied. A positive, significant correlation between the dose of BLM and the frequency of translocations was found. Two different responses were found when the yields of translocations induced after combined treatments, separated by a lapse of 24 h, were compared with the sum of translocation frequencies induced after the corresponding single treatments: (1) Potentiation, in the treatments with 1 Gy plus 9 Gy and 60 mg/kg of BLM plus 9 Gy; (2) additivity, in the treatments with 60 mg/kg of BLM plus 1 Gy, 1 Gy plus 60 mg/kg of BLM, and 0.2 mg of TT plus 60 mg/kg of BLM. In mice irradiated with 1 Gy plus 9 Gy and mice treated with 60 mg/kg of BLM plus 9 Gy, similar translocation yields were found. The potentiating effect of BLM is similar to that obtained with non-radiomimetic compounds such as triethylenemelamine, cyclophosphamide and adriamycin. These results are discussed taking into account the hypothesis of germ cell selection, and the dose of radiation employed.

Animals↗

Effects of cyclosporin on T-cell subsets in human immunodeficiency virus disease.

Cyclosporin (7.5 mg/kg daily) was given to 8 AIDS patients for 17-66 days and to 25 HIV-seropositive non-AIDS patients, 15 with stage II (T4 cells/microliter greater than or equal to 300, less than 600) and 10 with stage III (T4/microliter less than 300), for 3-6 months with the hypothesis that the drug could inhibit both HIV replication and the potential autoimmune component of HIV disease. A sustained increase over 600 T4/microliter occurred in 7 patients with stage II and 1 with stage III. T8 cells significantly decreased in most patients and lymphadenopathy disappeared in 14/16. After cyclosporin withdrawal T4 and T8 cells as well as lymphadenopathy returned to pretreatment status. Cyclosporin side effects (hypertension, creatinine increase, and anemia) were moderate and reversible. These results might stimulate biological research as well as clinical trials with cyclosporin in selected groups of HIV-seropositive subjects with the aim of delaying or preventing AIDS occurrence.

Acquired Immunodeficiency Syndrome↗

Serum suppressive activity of HIV seropositive patients.

The mechanisms by which HIV induces immunosuppression are still poorly understood so far. Several pathways of CD4 cell destruction are known, including cytolysis with or without syncitium formation and killing by cytotoxic effectors of HIV infected or non-infected CD4 cells. However, a discrepancy exists between the small number of actually infected cells in vivo and the extent of HIV-related immunodeficiency. Among other possible immunosuppressive factors, serum blocking factors have been reported, but only in AIDS-related opportunistic infections (OI), i.e. in a quite specific type of full-blown HIV disease. The purpose of this work was to determine whether serum blocking activity was unique to this group of patients, or if it was also expressed in other clinical presentations and, moreover, at earlier stages of the disease. We also attempted to delineate the nature of these seric factors. In order to do so, we assessed serum suppressive activity of 50 HIV seropositive patients, seven with OI, eight with Kaposi's sarcoma (KS), and 35 with no clinical AIDS. Our results confirm the existence of serum inhibiting factors in AIDS, and demonstrate their presence at earlier stages of the disease. They also highlight the fact that the level of serum suppression does not correlate with patients clinical status, but increases with the severity of the disease. The lower the CD4 count, the higher the suppression exerted. Furthermore, we showed that the suppression was at least partly mediated by small size molecules, which are not complement-mediated or directly lymphocytotoxic. On the other hand, this activity does not correlate with the serum level of p24 HIV core protein. The possible relation with other viral components is discussed. The relevance of these data to prognosis and pathogenesis of HIV disease deserves further investigation.

Acquired Immunodeficiency Syndrome↗

The origin of the Sternberg cell.

The Sternberg cell, the malignant cell of Hodgkin's disease, remains of uncertain nature 80 years after it was first described. Numerous hypotheses have been advanced as to its origin: that it derives from the macrophages, B lymphocyte, T lymphocyte, interdigitating reticulum cell or even from an as yet unidentified cell-line. We here review these various hypotheses, as well as the different techniques used for its study. The morphologic, ultrastructural, histochemical and immunologic studies are discussed in detail.

B-Lymphocytes↗

Serum HIV antigen and anti-P24-antibodies in 200 HIV seropositive patients: correlation with CD4 and CD8 lymphocyte subsets.

Serum HIV (P24) antigen (Ag) measured by an antigen capture ELISA (Abbott) and anti-P24-antibodies (Abs) measured by a competitive ELISA (Abbott) and by Western Blot (Dupont de Nemours) analysis were correlated with lymphocyte subsets (CD4 and CD8) in 174 HIV seropositive patients without AIDS (non-AIDS) and 26 with AIDS. In the non-AIDS group, 27% of the patients were anti-P24-Ab negative and 21% were Ag positive while in the AIDS group these figures were 62% and 54% respectively (P less than 0.001). Overall, a significant correlation exists between the Ab-Ag profile and the CD4 cell count: the percentage of patients with anti-P24-Ab positive and Ag negative decreases from 90% for patients with more than 900 CD4 cells/microliter to 21% for patients with 100 and less CD4 cells/microliter; on the contrary, the percentage of patients with anti-P24-Ab negative and Ag positive increases from 0% over 800 CD4 cells to 53% under 100 CD4 cells/microliter. A weak correlation may also exist with the CD8 cell count. The subgroup of patients with 1,000 or more CD8 cells/microliter have a higher (but not significant) percentage of subjects with Ag positive and anti-P24-Ab negative than the subgroup with less than 1,000 CD8 cells/microliter. A short-term longitudinal study (mean follow-up: 1 year) was performed on 80 non-AIDS subjects: 77% (10/13) of those who had a CD4 cell decrease (greater than 30%) were initially Ag positive, while only 21% (14/67) of those without a decrease were Ag positive at the beginning (P less than 0.1). Although the relative weight and individual predictive value of each of these parameters need to be classified, they are probably the best biological markers currently available for monitoring clinical trials with experimental drugs.

Acquired Immunodeficiency Syndrome↗

Hodgkin's disease, clinical stages IA to IIIB: combined modality therapy (3 MOPP followed by curative and prophylactic radiotherapy including the spleen). Six-year results.

From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30-40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re-treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse-free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo-aortic port in CS I and II.

Combined Modality Therapy↗

[Bronchopulmonary cancers: medical approach of the last weeks of life. Study of 191 patients].

The characteristics of patients with carcinoma of the lung during their last weeks of life were reviewed in 191 patients treated in the same department and who died between September 1982 and January 1985. The main symptoms were breathlessness (112/191) which posed difficult therapeutic problems preventing domiciliary treatment, and pain (87/191) which was more easily managed in the author's experience. The modes of death were also analysed, showing a number of sudden deaths (14). Therapeutic sedatives were the immediate cause of death in 32 cases, in the first part of the study. The authors make a rapid review of the different available palliative measures. This type of study is the only way of changing medical practices and strategies in patients dying in hospital.

Adult↗

[Particles with retrovirus appearance and reverse transcriptase activity in cell cultures derived from lymph node biopsies in Hodgkin's disease].

Long term cultures of Reed-Sternberg like cells were obtained from lymph node biopsies of two patients suffering from Hodgkin's disease. As soon as the 15th day of culture, a weak magnesium-dependent reverse transcriptase activity was observed in the cell culture supernatants. Retroviral-like particles were observed in cell cultures as well as in their supernatants.

Adult↗

[Mediastinal carcinomas in young men without primary tumors. A chemosensitive entity?].

Three patients out of 99 benefited with a complete remission following chemotherapy with Cisplatinum and Vindesine. The initial characteristics of these patients were studied, they recall a characteristic type of tumour already described and for which a hypothesis of a germ origin has been raised. In spite of their rarity the existence of complete remissions should encourage the use of chemotherapy in such patients who have a "broncho-pulmonary" cancer with a tropism for the mediastinum and without a specified primary tumour.

Adenocarcinoma, Mucinous↗

[Treatment of Hodgkin's disease by chemotherapy with MOPP alone. Long-term results].

Between 1967 and 1978, 152 Algerian patients (31 children and 121 adults) with Hodgkin's disease were treated with the mechlorethamine, vincristine, procarbazine, prednisone combination (MOPP) alone and without radiotherapy. They were separated without lymphography into limited stage (n = 37) and extensive (n = 115) stage. The high initial failure rate (54%) was principally due to inadequate symptomatic treatment and to the patients' low socio-economic status. The complete remission rate was 45% (54% for limited stages; 42% for extensive stages) and significantly higher in women (58%) than in men (37%). In 20/23 cases relapses occurred during the first 4 years of complete remission; however, the final relapse was observed during the 12th year of complete remission. The actuarial relapse rate at 15 years was 48%. The long-term (10-15 years) life expectancy was 31% overall and 70% in cases with complete remission. Prognosis was significantly better in patients with limited forms and/or without systemic symptoms.

Adolescent↗

[Inoperable non-small cell bronchopulmonary cancers. Results of ambulatory polychemotherapy including cisplatin].

Between October, 1981 and October, 1983, 57 subjects with inoperable non small-cell carcinoma of the lung (localized in 37, metastatic in 20) were treated as out-patients, after oral rehydration, with a multiple chemotherapy regimen which included Cisplatinum, Doxorubicin, Vincristine and Lomustine. No severe haematological or renal reaction was observed. After 2 courses 23 patients were responders (complete, or partial, or minor response), 2 of them with complete response. Patients with localized tumour had complementary radiotherapy, while chemotherapy was pursued in responsive patients with metastasis. Median survival was 9 months in responders and 5 months in non-responders. Thus, chemotherapy including Cisplatinum in medium doses (80 ms/sq.m) can be given to out-patients without risk of renal damage. The results obtained in this study are comparable to those of studies performed with other drug combinations including Cisplatinum.

Adult↗