Biomedical subjects

B Paule

Publications and source records attributed to B Paule.

42 records · Page 3Linked to original sources

PubMed1985

The possible role of radiotherapy in chronic lymphocytic leukaemia: a critical review.

The few clinical studies which have utilized irradiation as a treatment modality for chronic lymphocytic leukaemia (CLL) during the last two decades have led to rather conflicting and sometimes disappointing results. Low-dose total body irradiation (TBI) and extracorporeal, or mediastinal, radiotherapy did not appear to be superior to chemotherapy in most trials. Only the fractionated low-dose (600-800 rad) splenic irradiation was found to induce a long-lasting decrease of the lymphocyte count and a decrease in bone marrow infiltration in a significant proportion of cases, without any noticeable haematological toxicity. But new data is recently emerging; stratification of CLL in various subgroups, better understanding of the role of the normal T-cell subsets, better knowledge of the interaction between irradiation and haematopoiesis, and of the radiosensitivity of the various lymphocyte subpopulations. Thus one can now reconsider the possible role radiotherapy, and particularly splenic irradiation, can play as an alternative treatment to chemotherapy for CLL. Haematological toxicity is still limiting the use of TBI. The spleen irradiation avoids this drawback. Recent data suggest that this splenic irradiation could be efficient by means of several mechanisms; the successive destruction, fraction after fraction, of the part of the malignant lymphocyte clone present in the spleen is likely to be the main therapeutic explanation, with the knowledge that the lower the differentiation of the malignant clone, the more efficacious the irradiation. But in parallel, the destruction of the large subset of T-suppressors which is constantly present in the spleen may account for the improvement of the peripheral blood count after splenic irradiation, and possibly for a direct effect towards the malignant clone. With respect to these new data, splenic irradiation clearly needs further clinical evaluation in the treatment of CLL.

Clinical Trials as Topic↗

PubMed1985

[Radiosensitivity of lymphocytes. Possible therapeutic impact].

Radiosensitivity of lymphocytes is related to the population under study: for B lymphocytes it depends on their degree of differentiation and for each subset of T lymphocyte it depends on their state of activation. Precise knowledge of lymphocyte, radiosensitivity could have interesting therapeutic consequences in all malignant proliferation of B or T lymphocytes. The most typical example seems to be BCLL in which normalisation of lymphocyte subsets could be localized irradiation in volume (the spleen) and in dose (a number of grays) allow the destruction of an important percentage of a malignant clone and the normalisation of the populations of OKT4+, OKT8+ subset which play a part in the pathogenesis of the disease, notably in the mechanism of certain anemias.

B-Lymphocytes↗

PubMed1985

Multimodal approach to the treatment of stage III ovarian carcinoma: preliminary report of a pilot study and critical review.

In an attempt to improve survival rates in Stage III, grade III-IV ovarian carcinoma (5 years survival rate less than 10%), we have tested the feasibility of a combined modality approach in 10 patients. Five of the 10 patients have been treated with surgery, chemotherapy, second look laparotomy, whole abdominopelvic irradiation and chemotherapy. Three patients are alive without evidence of disease (range 24 to 54 months) after entering the combined programme. We conclude that a combined modality therapy can be safely delivered. The acute toxic effects were not more frequent or more severe than with other therapeutic approaches. These results are compared with published reports in the literature.

Adult↗

PubMed1984

Lactate dehydrogenase isoenzyme activity in malignant haematological diseases.

The isoenzymes 1 and 2 (LDH1 and LDH2) of lactic dehydrogenase (LDH) were studied in the serum of 32 patients with malignant haematological diseases. In non-Hodgkin lymphoma (NHL) a diminution in LDH1 and an increase in LDH2 was a sign of evolution towards a more aggressive phase of the disease, or the absence of clinical remission, even when no significant variation of total LDH can be observed in the serum. In acute lymphoblastic leukaemia (ALL), the isoenzymatic variations are not an early indication of relapse. No significant variations in serum LDH or of these isoenzymes was observed in chronic lymphocytic leukaemia (CLL) or Hodgkin's disease (HD). Only in NHL did the variations of LDH1 and LDH2 appear to be a biochemical marker of the tumour process and of cellular differentiation.

Hematologic Diseases↗

PubMed1983

[Demonstration of antineutrophil antibodies using radioiodinated protein A].

The granulocyte associated IgG in normal and neutropenic subjects has been determined by a direct quantitative assay using radiolabeled staphylococcal protein A. This assay allows us to postulate an immunological mechanism to explain the neutropenia in 19 cases of neutropenias associated with malfunctions of the immune system and in 4 cases of idiopathic neutropenias. Discussed in this report is the possible interaction of immune complexes bound in vivo to the granulocytes. By an immunofluorescence test, it has been possible to detect IgG or IgM antibodies in only 52% of patients with a positive direct assay. The determination of granulocyte-associated IgG is therefore a better indicator in our study for defining an auto-immune neutropenia than the detection of free antibodies in the sera.

Adult↗

PubMedDate not supplied

[Metastatic colorectal cancer: new therapeutics].

NEED FOR NEW CHEMOTHERAPEUTIC AGENTS: The use of 5-FU in combination with leucoverin (LV) in the treatment of advanced colorectal cancer has consistently provided antitumoral response. The antitumoral activity of the 5-FU/LV combination is associated with inhibition of thymidylate synthetase, an essential enzyme in pyrimidine de novo biosynthesis of thymidilates as precursors of DNA synthesis. However, dose-limiting toxicities and the limited impact on survival point to the need to develop new drugs and approaches to improve therapeutic efficacy and survival. CLINICAL RESULTS: In advanced colorecal cancer, clinical results have confirmed the therapeutic efficacy of direct and indirect thymidylate synthetase inhibitors. Promising new agents: 5-FU prodrugs and inhibitors of dihydropyrimidine dehydrogenase (DPD) are promising chemotherapeutic agents with good oral bioavailability which can be combined with other drugs (leucoverin) with acceptable toxicity. Oxaliplatin and topoisomerase inhibitors such as irinotecan (CPT-11) have demonstrated activity in previously treated and newly diagnosed patients. COMBINATIONS: The best combination between DNA interaction drugs based on potentiation of DNA damage induced by thymidylate synthetase inhibitors and inhibition of DNA repair by DNA interactions remains to be evaluated.

Antimetabolites, Antineoplastic↗