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Biomedical subjects

M F D'Agay

Publications and source records attributed to M F D'Agay.

At least 19 recordsLinked to original sources

CD8 lymphocytosis and pseudotumoral splenomegaly in HIV infection.

Three patients infected with human immunodeficiency virus (HIV) presented with pseudotumoral splenomegaly, CD8 lymphocytosis (3.5-5.1 x 10(9)/l), and hypergammaglobulinaemia. Spleen and bone marrow showed diffuse CD8 lymphocyte and plasma-cell infiltration. Amplification of the T-cell-receptor gamma chain gene did not reveal any clonal T-cell population. Phenotypic analysis showed a predominance of CD8/CD57 suppressor T cells with expression of activation markers (DR and CD38). No cytotoxic T lymphocytes specific for HIV could be detected. The three patients shared the HLA haplotype A1, B8, DR3. The association with this haplotype suggests a genetically determined host immune response to HIV.

Acquired Immunodeficiency Syndrome

Production of cytokines in sarcoid lymph nodes: preferential expression of interleukin-1 beta and interferon-gamma genes.

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-2, and interferon-gamma (IFN-gamma) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1 beta gene was preferentially expressed. The distribution of cells containing IL-1 beta mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-alpha gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1 alpha gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1 beta gene was significantly higher than that of cells expressing TNF-alpha gene (P = .001), IL-6 gene (P = .007), or IL-1 alpha gene (P less than .001). Of the cells expressing lymphokine genes, those expressing the IFN-gamma gene were 31.9 (+/- 7.6) times more frequent than those expressing the IL-2 gene (P less than .001). Cells containing IFN-gamma mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1 beta gene and the IFN-gamma gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.

Cytokines

Hypersensitivity systemic reaction following intravesical bacillus Calmette-Guerin: successful treatment with steroids.

Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder carcinoma. Serious complications, including disseminated BCG infection, are infrequent. We report a case of granulomatous hepatitis with pneumonitis following intravesical administration of BCG. Cultures for mycobacteria were negative in sputum, bronchoalveolar lavage, liver and blood specimens. All symptoms disappeared within days after steroid therapy. Hypersensitivity reaction should be considered in patients with systemic symptoms after immunotherapy with BCG.

Administration, Intravesical

Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients.

PURPOSE: We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. RESULTS: Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. CONCLUSION: Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue.

Adolescent

Hodgkin's disease, clinical stages I, II A-B and IIIA. Results of brief chemotherapy followed by irradiation.

From October 1980 to September 1985, 152 patients with Hodgkin's disease (HD) in clinical stages (CS) I, II A-B and IIIA were treated with combined modality therapy (CMT): brief chemotherapy (CT) followed by radiotherapy (RT). CS IA and IIA cases received 3 cycles of MOP, while CS IB, IIB and IIIA cases were randomly assigned to receive MOP or MOP alternating with ABVD (4 cycles). Irradiation was delivered according to the areas initially involved and response to CT. CS I and II subjects in complete remission (CR) received localized fields, whereas CS I, II and IIIA subjects in partial remission (PR) received extended fields, with subtotal nodal RT for CS I and II and CS IIIA without pelvic involvement and total nodal RT for CS I and II below diaphragm and CS IIIA with pelvic involvement. Following CT, CR was 60% (IA-IIA: 71.5%, IB-IIB: 37%, IIIA: 55.5%), PR 35.5% and failure 4.5%. After CT and RT, CR was 98% (IA-IIA: 100%, IB-IIB: 95.5%, IIIA: 94.5%). Responses were similar using MOP and MOP/ABVD regimens. Fifteen patients relapsed (10%) and 15 died, 11 due to HD and 4 due to other causes, while after 7 years overall survival and relapse free survival were respectively 87% and 82% (IA-IIA 90% and 85%, IB-IIB: 80% and 80%, IIIA: 87% and 62%). Results were equivalent irrespective of CT regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers.

Veno occlusive disease (VOD) is a frequent complication of allogenic bone marrow transplantation (BMT) for which no predictive blood markers are available. 39 patients grafted for severe aplastic anemia (18), and leukemia (21) were prospectively studied. Of the 39 patients, 5 leukemic patients, but no aplastic patients developed VOD. In all the 5 patients with VOD complications we demonstrated a decrease in factor VII and in protein C before the clinical onset of the disease and before any changes in hepatic enzymes were observed. This decrease is the earliest sign of hepatic involvement by the VOD suggesting that the determination of Factor VII and protein C can be used as a prediction test to identify the patients who are at risk of developing VOD after transplantation. In addition, a toxicity of the endothelial cells was suggested by the observed increase in von Willebrand factor and in Serum Angiotensin Converting Enzyme. Signs of endothelial toxicity was more pronounced in leukemic than in aplastic patients.

Biomarkers

Interleukin-2 and interferon-gamma production in follicular lymphomas.

In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low-grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine-synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T-cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction.

Humans

Primary thrombocythaemia associated with systemic mastocytosis: a report of five cases.

Mastocytosis is an uncommon disease characterized by a proliferation of tissue mast cells involving various organs, particularly the bone marrow. Though rare, the association of mastocytosis and haematological malignancies is well established. However, the frequency of mastocytosis reported in patients with essential thrombocythaemia is relatively low. We report five cases of such an association. Our five patients were undergoing evaluation for thrombocyte when the bone marrow biopsy revealed the presence of mastocytosis. The pathogenetic significance of this association is poorly understood. The different hypotheses are discussed.

Adult

Surgical restaging of advanced Hodgkin's disease after first line chemotherapy.

47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first-line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.

Adult

Autoimmune hemolytic anemia disclosing Hodgkin's disease associated with Castleman's disease.

A man was admitted for severe autoimmune hemolytic anemia with a mediastinal mass. He required corticosteroid treatment, which altered the first histological examination. Laparosplenectomy was performed and all histological sections were negative, but the hemolytic anemia was not improved. Finally, thoracotomy was performed when the mediastinal mass increased after reducing the corticosteroid treatment. Pathological examination revealed Hodgkin's disease associated with Castleman's disease. After chemotherapy and radiotherapy, the patient remains in complete remission.

Adult

[Non-Hodgkin's lymphoma in HIV infection. A multicenter retrospective study of 21 cases].

The incidence of non-Hodgkin's malignant lymphoma is known to be increased in patients who are seropositive for the human immunodeficiency virus (HIV). We report here a multicentre retrospective study of 21 HIV-positive patients with non-Hodgkin's lymphoma seen between 1985 and 1987. All phenotype B lymphomas of intermediate or high malignancy grade according to the Working Formulation are difficult to classify histologically. Because of this problem, reexamination of the specimens by several pathologists and perhaps also the use of other morphological prognostic criteria, such as mitotic index, seem to be desirable. In more than one-third of our patients the presence of a lymphoma led to the finding of HIV seropositivity in subjects who were all issued from populations at risk. Median age was 39 years. Spread evaluation showed stage III or IV in most cases with, in 4 out of 5 patients, extranodal sites, notably the neuromeningeal system, liver, gastrointestinal tract and bone marrow. The median overall survival was 5 months, but in April 1989 2 patients had survived for more than 30 months. Obtaining complete remission (11/21 cases) was imperative for a 10 months' survival. Eight of the 11 patients in whom complete remission was obtained had received the heavy induction chemotherapy required by the degree of malignancy, but no death due to drug toxicity was recorded. 17 patients died, with active lymphoma (12 cases) and/or infection (8 cases) being documented at the time of death. The finding of more than 500/sq. mm CD4 lymphocytes in peripheral blood in 10 cases while the lymphoma was developing, and the heterogeneity of the Epstein-Barr virus (EBV) profile in serum raise the question of the role played by T-cell immunodeficiency and by EBV infection in the physiopathogenesis of these lymphomas.

Adult

Cutaneous type of adult T cell leukemia/lymphoma in a French West Indian woman. Clonal rearrangement of T-cell receptor beta and gamma genes and monoclonal integration of HTLV-I proviral DNA in the skin infiltrate.

A 45-year-old woman, a native of the French West Indies who had lived in France since 1973, developed multiple cutaneous plaques and nodules in 1987. Histopathologic studies revealed dermal infiltration with mature activated T cells (CD4+, CD25+, DR+) with nuclear convolutions and epidermatotropisim. High titers of specific human T lymphotropic virus (HTLV)-I antibodies were detected in the serum. Molecular analysis of DNA extracted from the skin tumor biopsy specimen showed a clonal integration of an HTLV-I provirus and a T-cell clonal population as demonstrated by T-cell receptor beta and gamma gene rearrangement studies. Neither HTLV-I provirus nor T-cell receptor rearrangements were detected in peripheral blood mononuclear cells DNA despite the presence of rare adult T cell leukemia cells (less than 1%) and a small excess of DR-expressing cells, and detection of HTLV-I Pol and Px sequences by in vitro gene amplification. In this case only gene analysis of the skin lesions made possible an early diagnosis of a cutaneous adult T cell leukemia. This illustrates the need for such molecular studies to differentiate, in HTLV-I seropositive patients from endemic areas, a HTLV-I-induced T cell lymphoma from HTLV-I-nonrelated cutaneous T cell lymphomas.

Antigens, CD

[Mycotic infection in immunosuppressed patients. An anatomopathologic study].

Mycotic infections are a frequent and often severe complication in the immunosuppressed patient. A review of autopsy findings in 54 cases with gross, histologic and mycologic studies was undertaken among immunocompromised patients after chemotherapy or allogenic bone marrow transplantation: fungal infections were either localized especially in lungs and gastrointestinal tract, or disseminated. Fungi were various: principally Candida and Aspergillus, but also Fusarium, Torulopsis and Trichosporon. In acquired immunodeficiency syndrome (11 autopsy cases), mycotic infections appeared different. Oral and esophageal candidiasis could be found, but cryptococcosis and histoplasmosis were the major generalized mycosis. This study suggests that fungal infections are not the same in patients treated by chemotherapy or bone marrow transplantation, and in acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome