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Biomedical subjects

F Oberling

Publications and source records attributed to F Oberling.

At least 19 recordsLinked to original sources
PubMed1992

Hemostatic changes in human adoptive immunotherapy with activated blood monocytes or derived macrophages.

Human blood monocytes (Mo) and monocyte-derived macrophages (M psi) possess cytotoxic effects against tumor cell lines when appropriately stimulated by various biological response modifiers, e.g., gamma interferon (gamma IFN) and muramyltripeptide (MTP). Activated Mo/M psi represent a new tool for the treatment of human malignancies, termed "adoptive cellular immunotherapy". Activated Mo/M psi express tissue factor procoagulant activity (PCA), which is a physiological trigger of blood coagulation. PCA was evaluated in vitro using a modification of the one-stage recalcification clotting time, and hemostatic changes were studied in vivo in cancer patients. Nine patients with peritoneal carcinomatosis were injected intraperitoneally with activated Mo and 11 patients with non-small cell lung carcinomas were infused intravenously with activated M psi. Hemostatic changes were followed using activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen level, antithrombin III (ATIII) and protein C (PC) activities. Fibrinolytic activity was estimated by euglobulin lysis time and assays for plasminogen and fibrin/fibrinogen degradation products (FDP). These assays were performed before and after each autologous infusion and on days 2 and 3. Activated Mo and M psi expressed potent PCA (85.5 +/- 7.5 U/ml for MTP activated Mo and 50 +/- 5.3 U/ml for gamma IFN activated M psi suspensions). In both groups of patients, APTT, PT, and TT underwent no significant variations. There was no significant consumption of ATIII or PC, and fibrinolysis was not activated during the study period. In the group injected intraperitoneally with MTP-activated Mo, fibrinogen showed a significant and progressive increase in relation to the development of an inflammatory reaction, reaching a maximum average value of 6.1 g/l at the end of the therapy with a concomitant increase in FDP levels. This increase was not observed after intravenous therapy with gamma IFN-activated M psi. No patient suffered from hemorrhagic or thrombotic events. In our experience, repeated injections of activated Mo or M psi expressing potent tissue factor PCA did not induce significant in vivo activation of the coagulation system in cancer patients.

Aged↗
PubMed1992

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.

Adult↗
PubMed1992

Immunophenotypic characterisation of human peritoneal and alveolar macrophages and of human blood monocytes differentiated in the presence of either GM-CSF or M-CSF or a combination of GM-CSF/M-CSF.

In vivo, circulating blood monocytes (Mo) migrate into the various tissues where they undergo terminal maturation into macrophages (M phi) with morphological and sometimes functional properties that are characteristic for the tissue in which they reside. This tissue-specific M phi heterogeneity results from the immediate microenvironment, but may also originate from genetically distinct Mo subpopulations. The in vitro transformation of Mo to M phi is thought to reflect the events of the in vivo maturation and thus is widely used as a model to analyse M phi development. To study the heterogeneity within the mononuclear phagocyte system, we have investigated the phenotypic characterisation of mature tissue M phi, blood Mo and Mo-derived M phi cultured in medium with either GM-CSF, M-CSF or a combination of both cytokines. Tissue peritoneal and alveolar M phi showed different antigenic specificities, particularly concerning the transferrin receptor and CD68 and CD14 antigens. M-CSF-derived M phi when compared to the other M ø populations also exhibited a significantly increased expression of transferrin receptor and CD68 antigen. In contrast, GM-CSF treated cells which exhibited a better long term survival, showed notably more positivity for CD11b and CD32 antigens. These results show that the phenotypic heterogeneity of the different M phi populations is limited and appears to result from discrepancies in the differentiation and/or activation of the cells. The location of the CD68 antigen, which is generally considered to be an intracellular protein, was investigated at the ultrastructural level and found to be exclusively situated at the outer cell membrane.

Antibodies, Monoclonal↗
PubMed1992

[Rare opportunistic fungal diseases in patients with organ or bone marrow transplantation].

Candidiasis, aspergillosis and cryptococcosis are the most common fungal infections in transplant recipients. However other fungal infections have been reported. Mucormycosis, Scedosporium infections, fusariosis and trichosporonosis represent the largest part of these rare mycosis. The clinical and mycological features are described here. In addition, cases of very uncommon mycosis, most of them only once reported, have been reviewed. Overall the diagnosis is difficult as mycological examinations are often negative till the disease is disseminated. Amphotericin B remains the reference treatment except in Scedosporium infections which respond more likely to azole antifungal agents. Despite the treatment the outcome is usually fatal.

Bone Marrow Transplantation↗
PubMed1992

Etoposide, ifosfamide, and methotrexate combination chemotherapy for aggressive non-Hodgkin's lymphomas after failure of the LNH 84 regimen.

We assessed the efficacy and tolerability of VIM (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study. Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a partial response (PR). The six remaining patients attained complete response (CR) after LNH 84 induction, but relapsed either during consolidation therapy or after completing the whole program. Twenty-three patients are evaluable for response. The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed in nine cases (39%). The CR rate was particularly high (67%) in the group of patients who had PR with LNH 84 induction treatment. Of the ten who had attained CR, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101 VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or 4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes recorded, one was fatal. This study demonstrates that CR and long disease-free survival are obtainable with the VIM regimen in a small number of patients failing a high-dose doxorubicin-containing first-line treatment.

Adult↗
PubMed1992

Hairy cell leukemia and factor VIII inhibitor: a case report.

Acquired factor VIII inhibitors are usually described in hemophilia A, although some cases have been documented in chronic inflammatory diseases and malignant tumors. We report here the first case of a factor VIII inhibitor appearing in the course of hairy cell leukemia. Interferon therapy over a 5 month period led to complete remission of leukemia with parallel disappearance of the acquired factor VIII inhibitor.

Factor VIII↗
PubMed1992

Malignant thymic lymphoblastic lymphoma and myasthenia gravis: an exceptional association.

Thymic lymphoblastic lymphoma and myasthenia gravis rarely coexist. Only two cases have been reported and we describe here a third case. A 60 year old man presented a typical history of myasthenia gravis, confirmed by neurological investigations including electromyography. Chest X-ray revealed an anterior mediastinal tumor. At thoracotomy, a 60 mm mass adherent to the pericardium was excised and a lymphoblastic lymphoma was diagnosed. The lymphogram showed enlarged pelvic and abdominal lymph nodes consistent with lymphoma. A m-BACOD chemotherapy regimen gave rapid and complete remission of both lymphoma and myasthenia gravis and the patient is now alive 25 months after the start of chemotherapy with no evidence of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Human blood-derived macrophages: differentiation in vitro of a large quantity of cells in serum-free medium.

Large quantities of human blood-derived monocytes have been cultured in suspension in nonadherent cell culture bags and maintained for up to 3 weeks in a serum-free medium. This serum-free medium contained Iscove's modified Dulbecco's medium (IMDM) supplemented with human albumin, alpha-phosphatidylcholine, transferrin, and insulin. Morphology, cell surface antigens, and functional properties of these in vitro maturing macrophages were studied in comparison with macrophages cultured in a standard medium containing 10% fetal calf serum. In this report we demonstrate that this serum-free medium allows a better yield of cell survival than the standard medium; it also allows the differentiation of blood monocytes into fully functional macrophagic cells that express the different antigens found in mature macrophages. The results indicate that the use of serum-free defined medium offers good conditions in which to culture large numbers of human monocytes and allows an accurate analysis of the effect of supplementation with growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on the differentiation and survival of monocytes and macrophages. Serum-free cultures could also be helpful for the precise analysis of the cell secretion activity and for determining the factors that are responsible for monocyte maturation into macrophages.

Antigens, Surface↗
PubMed1979

[Persisting deficiency of cell mediated immunity in Hodgkin's disease in complete remission (author's transl)].

There is increasing evidence in the literature for persistent deficiency in cell-mediated immunity (CMI) in Hodgkin's diseases during apparent remissions after discontinuation of the treatment. Patients were followed for 6 months to 2 years after all treatments were stopped. There was a high percentage (41.6) of subjects with skin anergy to seven recall antigens, a highly significant (p less than 0,0001) decrease, as compared with controls, in total and active E rosettes independently from the number of lymphocytes, and a highly significant diminution of T-lymphocyte in vitro reactivity to various doses of phyto haemagglutinine (PHA). There was no difference between the patients tested between 6 months and 1 year and those tested more than 2 years after treatment. No correlation between skin tests and active rosettes was found in this series. Finally, the CMI deficiency is some what different in patients on remission and in untreated patients.

Female↗
PubMed1979

[Fluorocarbons as blood substitutes. Toxicity in the rat].

Liquid fluorocarbons, having high solubility for gases (O2, CO2...) have been used as artificial blood substitutes in animals with variable results. The great diversity of these products and the lack of reproductiveness in their composition have not permitted, up to now, a standardization of their utilisation norms. Our work was to study the toxicity, in the rat, of a new kind of fluorocarbon emulsion (E-66, Ugine-Kuhlmann, France) used as an artificial blood substitute during exchange-perfusion. The short survival of the rats is in opposition to the good in vitro results obtained in other experiments (high solubilities of oxygen and dioxide carbon). The toxicity of this fluorinated emulsion is demonstrated by histologic lesions in lungs, liver and kidneys and the great amount of fluor stored in these organs. The mechanism of this toxicity is still to be demonstrated. Hepatic lesions (hyperhemia with dilatation of central veins and sinusoids) and pulmonary lesions (vascular congestion, alveolar oedema) prove a circulatory disturbance leading to right-sided cardiac failure. However, cellular degenerescence lesions, observed in hepatocytes and renal tubular cells, do not permit to exclude formally a cellular toxicity of the E-66 emulsion.

Animals↗
PubMed1979

Combination chemotherapy of malignant histiocytosis.

Three patients with malignant histiocytosis treated with combination chemotherapy are reported. Induction treatment included bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone (BACOP). Complete response was obtained in one patient who is alive and well 32 months after diagnosis. A partial response was obtained in the second patient, who is alive and well 35 months after diagnosis. The third patient died with drug-induced agranulocytosis and sepsis.

Adolescent↗
PubMed1979

Acquired C1 inhibitor deficiency in a case of lymphosarcoma of the spleen. Reversal of complement abnormalities after splenectomy.

A patient with an extensive lymphosarcoma of the spleen without involvement of other lymphoid organs and hypogammaglobulinaemia showed the characteristic complement profile of an acquired C1-inhibitor deficiency. Both functional and immunochemical studies revealed extremely low levels of the inhibitor of C1-esterase. Correction of the low levels of early acting complement components and of the low C1-inhibitor level followed the splenectomy. In vitro tests showed that lymphosarcoma tissue pieces or cells were able to interact with complement, resulting in a depletion of the haemolytic activity. These findings provide evidence that tumour cells were responsible for the abnormalities of the complement system.

Aged↗