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Biomedical subjects

G Tricot

Publications and source records attributed to G Tricot.

At least 235 records · Page 13Linked to original sources

[Sarcomatous and leukemic forms of Waldenström's macroglobulinemia].

Four cases of sarcomatous or leukaemic types of Waldenström's macroglobulinemia are presented. They are characterized by tumoral and compressive localizations of lymph node or spleen, or by a hyper-leukocytosis with many circulating abnormal cells. These cells are different from the lympho-plasma cells regularly observed in Waldenström's macroglobulinemia, and can be assimilated to malignant immunoblasts. They have a proliferative aspect and seem to produce less macroglobulin and to recover some beta-glucuronidase activity. The sarcomatous and leukemic types of Waldenström's macroglobullinemia have a poor prognosis and may appear as terminal transformation of the disease.

Aged↗

Ketoconazole vs. itraconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results of two nonrandomized studies.

The efficacies of antifungal prophylaxis with ketoconazole and itraconazole, a new triazole, in patients with prolonged granulocytopenia were evaluated in two nonrandomized studies. The conditions other than the drug administered for prophylaxis were equivalent in the two studies. The incidence of fatal fungal infections was significantly higher among patients given ketoconazole than among those given itraconazole (P = .02); this trend was especially evident with fatal infections due to Aspergillus (P = .0045). The level of protection from fatal fungal infection afforded by itraconazole was highly significant among patients who were granulocytopenic for more than 25 days (P less than .0001) and among patients with acute lymphoblastic leukemia (P = .008). Failures of prophylaxis with itraconazole may have been due to inadequate levels of drug in plasma. Although these results must be interpreted with caution because they were obtained in consecutive nonrandomized studies, the use of itraconazole for antifungal prophylaxis in granulocytopenic patients seems to be a major advance and to be especially advantageous in hospitals, where the incidence of fatal aspergillosis in these patients is high.

Adolescent↗

Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.

Tamoxifen has been shown to induce apoptosis in multiple myeloma cell lines and primary myeloma cells. Daily tamoxifen was given to 12 consecutive multiple myeloma patients who either relapsed following autologous stem cell transplantation (11) or had progressive disease on conventional chemotherapy (1). Methotrexate was also given biweekly to enhance the antiangiogenetic effect. Two patients achieved complete remission lasting 8 and 18 months. Two additional patients had stable disease (SD) for 7 and 11 months. All responders were men and the earliest signs of response were seen after approximately 6-8 weeks of treatment. The regimen was very well tolerated. Speculations about a possible mechanism of action of tamoxifen in multiple myeloma are discussed.

Adult↗

[Demonstration by direct immunofluorescence of intracellular immunoglobulins on sections of tissues fixed in Bouin's fluid and embedded in paraplast].

Sections obtained from lymphoid tissues fixed immediately after biopsy in Bouin's fluid and embedded in paraplast may be used to visualize the immunosecretory cells with classical direct immunofluorescence. A comparative study of the same fragments processed according to the frozen section method followed by acetone fixation or according to Sainte-Marie's method confirms the value and the advantages of the proposed technique. Early fixation of thin fragments seems to be the main point.

Animals↗

[Lymphadenopathy caused by hemophagocytic sinus histiocytosis (Destombes-Rosai-Dorfman syndrome). Immunologic and histopathologic study of a new case].

The case reported is one of lymphadenopathy due to haemophagocytic sinusal histiocytosis which had progressed for more than 10 years before resulting in death at the age of 58 years. In this advanced form, all superficial and deep nodes were involved. In addition to histiocytic hyperplasia, with haemophagocytosis and lipid overload, there was plasmocytic hyperplasia, i.e. B-lymphocytes, with polyclonal hypergamma-globulinaemia and an increase in the levels of many antibodies, in particular against rubella and the Epstein-Barr virus. The aetiopathological significance is discussed, in particular the role of an infection due to the EB virus.

B-Lymphocytes↗

[Angiofollicular lymphoid hyperplasia (Castelman's tumor) in the mediastinum. Apropos of 2 cases].

The authors report two new cases of angiofollicular hyperplasia of the mediastinum (Castelman's tumour). The only clinical peculiarity was a rapid increase in volume. The authors then review about 200 published cases. Emphasising the existence of 3 different histological types (plasma cell form, vascular hyaline form and intermediate form) and on the association in certain cases of hematological disorders such as anemia and hypergamma globulinemia. The significance of this lesion is discussed. An inflammatory theory with reactional hyperplasia of the beta-lymphocytes is proposed. It was supported by a direct immunofluorescent study of two cases (first study of this type carried out on such lesions) which showed polyclonal plasma cell hyperplasia predominating on the IgG.

Adolescent↗

[Splenic lympho-plasmocytic sarcomas discovered by exploratory laparotomy in 2 cases of cold agglutinin disease].

The 2 patients have cold agglutinin disease with lymphoid nodules in the bone marrow. A splenectomy was done because of the severity of the hemolytic anemia and because of the increasing splenomegaly. Tumoral nodules with the aspect of lymphoplasmocytic sarcoma or immunocytoma were discovered in the spleen. Those tumors can be considered either as a morphologic aspect of the cold agglutinin disease which is yet considered as a kind of chronic lymphoproliferative syndrom or as the proliferation of an other clone. In this hypothesis, the lymphoplasmocytic sarcoma habe the same signification that the Richter's syndrome in chronic lymphoid leukemia and that the sarcoma appearing in Waldenström's macroglobulinemia or in alpha heavy chain disease.

Abdomen↗

[Pseudolymphoma and lymphoproliferative syndromes in Gougerot-Sjögren syndrome (author's transl)].

Five cases of pseudolymphoma in Sjögren's syndrome were reported. Pseudolymphoma's pathological aspects described by Rothman then Talal are discussed. After recognition of the Sjögren's syndrome and a pseudolymphoma appearance, the risk of lymphomatous evolution enjoin a clinical close attention. Among our five cases, three had a peculiar evolution: one has presented and immunoblastic lymphoma (case 2). In an other case (case 3) the pathological aspect was very near to the angioimmunoblastic lymphadenopathy features. Waldenström's macroglobulinemia was cause of death of the last one (case 5).

Aged↗

A subpopulation of lymph node B-CLL cells expresses the common acute lymphoblastic leukemia antigen.

Tumoral lymph nodes (LN) from 7 B-CLL patients were studied with a panel of monoclonal antibodies and in situ immunohistochemical technique. The large majority of LN B-CLL cells carried the phenotype slg+ BA-1+OKIal+ and was admixed with variable numbers of helper/inducer and suppressor/cytotoxic T-cells. In each of the LN studied, regularly distributed, scattered J5+TdT-BA-3- small lumphoid cells were observed, showing no topographical predilection, nor tendency to cluster. J5+ small lymphoid cells may represent pre-B cells which have entered the LN and proliferate and mature in situ, giving rise to a leukemic sIg+OKIal+BA-1+J5- population. This would explain the early generalized LN involvement in B-CLL, and is in agreement with cell-kinetic and compartment in B-CLL LN. Alternatively, J5+ small lymphoid cells may represent a subset of LN B-CLL cells which have acquired the common acute lymphoblastic leukemia antigen during some transformation.

Antibodies, Monoclonal↗

Tiazofurin: molecular and clinical action.

UNLABELLED: The purpose is to provide an overview of the molecular and clinical impact of tiazofurin. METHOD: The biochemical and clinical techniques were reported (1, 2). RESULTS: IMP DH activity increased in various animal and human tumors and was particularly high in leukemic blast cells. The increased activity was due to an elevation in the mRNA concentration of type II isozyme. Tiazofurin, a C-nucleoside, was converted in sensitive cells to the active metabolite, TAD, which tightly bound at the NADH site inhibited IMP DH activity. The inhibition led to decreased GTP concentration, down-regulation of ras and myc oncogenes and induced maturation of blast cells. New evidence shows that tiazofurin injection downregulated signal transduction activity due to a reduction of the activities of PI and PIP kinases leading to a decrease in the concentration of the second messenger, IP3. In patients; tiazofurin infusion and allopurinol administration led to reduction of IMP DH activity and GTP concentration. Allopurinol inhibited xanthine oxidase activity leading to a marked rise in hypoxanthine concentration which inhibited the increased guanine salvage pathway. In the clinic, the increase in serum hypoxanthine concentration is essential for the success of tiazofurin treatment. Tiazofurin showed additivity or synergism with ribavirin, retinoic acid, taxol, quercetin, gemcitabin, dipyridamole and brefeldin. Ribavirin which inhibits IMP DH at the IMP site has been shown to prolong the IMP depressing action of tiazofurin in rat bone marrow cells. CONCLUSION: Tiazofurin and allopurinol achieve reduction of GTP concentration in leukemic blast cells through inhibition of IMP DH and GPRT activities. As a result, induced maturation occurs with down-regulation of ras and myc oncogenes and probably reduced signal transduction capacity. Tiazofurin in leukemic patients provides over 75% therapeutic responses and patients can be treated with this combination for many months with good quality of life. These clinical and biochemical results were recently confirmed independently (3).

Allopurinol↗

Biochemically targeted therapy of refractory leukemia and myeloid blast crisis of chronic granulocytic leukemia with Tiazofurin, a selective blocker of inosine 5'-phosphate dehydrogenase activity.

Conventional antileukemic chemotherapy in relapsed or refractory acute leukemia or myeloid blast crisis of chronic granulocytic leukemia (CGL) is not curative and remissions, if attained, are usually of short duration. The primary goal of antileukemic therapy in these patients should be the identification of agents that are more selective and better targeted in their action. Tiazofurin is known to inhibit inosine 5'-phosphate dehydrogenase (IMPDH), the rate limiting enzyme of de novo guanine ribonucleotide synthesis. The activity of this enzyme is markedly increased in leukemic cells. To prevent de novo GTP synthesis, it is also necessary to block the guanine-salvaging activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This was achieved by increasing the plasma levels of hypoxanthine through the administration of allopurinol. Twenty-seven patients with end stage leukemia or myeloid blast crisis of CGL were treated with tiazofurin. Assays of IMPDH activity and GTP concentrations in leukemic cells, as well as hypoxanthine levels in the serum, provided a method to monitor the impact of tiazofurin/allopurinol therapy and to adjust drug doses. In these poor prognosis patients seven attained a complete response (CR), 3 had a hematologic improvement and an antileukemic effect was seen in 4. An excellent correlation was observed between biochemical and clinical activity of tiazofurin/allopurinol, with biochemical responses preceding clinical results. However, clinical responses were usually short-lived with IMPDH activity starting to increase soon after discontinuation of therapy, but patients responding again after reinstitution. Tiazofurin therapy was generally well tolerated in patients with less than 15 days of treatment and no other major medical complications. Although an antiproliferative effect was observed in some patients, bone marrows remained cellular in most cases with a marked shift from blasts to granulocytes. Severe neutropenia was absent in the majority of cases and patients could be discharged in good clinical condition immediately after completion of therapy. Tiazofurin/allopurinol therapy provided a rational, biochemically targeted and biochemically monitored approach to the treatment of poor prognosis leukemia and should serve as a paradigm in enzyme pattern-targeted chemotherapy.

Adult↗