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Biomedical subjects

Y Carcassonne

Publications and source records attributed to Y Carcassonne.

At least 19 recordsLinked to original sources

Effect of tetrahydrouridine on metabolism and transport of 1-beta-D-arabinofuranosylcytosine in human cells.

Deamination of cytosine arabinoside (ara-C) by cytidine deaminase is the main mode of inactivation of this drug which can be responsible for ara-C resistance. The present study was undertaken to determine the effect of tetrahydrouridine (THU; a potent inhibitor of cytidine deaminase) on ara-C transport and metabolism in human cells. A rapid transport of ara-C into freshly isolated hepatocytes and an increased intracellular accumulation of the unchanged drug were observed in the presence of 50 micrograms/ml THU. THU inhibited the intracellular deamination of ara-C by 80% and slowed elimination of the compound extracellularly. The intracellular ara-C concentrations achieved after incubation with 1 micrograms/ml ara-C plus 50 micrograms/ml THU are similar to those attained with ara-C (10 micrograms/ml) alone. Treatment of leukemic K562 cells with the combination of THU (50 micrograms/ml) and ara-C (1 micrograms/ml) led to an augmentation of intracellular ara-C triphosphate formation up to twofold.

Cells, Cultured

Histological evolution of peripheral T-cell lymphomas. Study of six cases.

The authors report 6 cases of histological transformation in peripheral T-cell lymphomas of low grade of malignancy. The transformation occurs in 75% of the cases, in extra-nodal sites and corresponds to a monomorphic of pleiomorphic large cell type. There is no discordance in the immunologic results between the two phases. The transformation seems to occur earlier than in B lymphomas, with a relative frequency of hematological manifestations and no therapeutic response.

Aged

[Cytoplasmic immunoglobulins in chronic B-lymphoid leukemia].

Chronic lymphocytic leukemia B-cells (B-CLL cells) have surface immunoglobulin (Smlg). In addition, cytoplasmic immunoglobulins (Clg) have been reported in chronic lymphocytic leukemia B-cells and are useful for ascertaining monoclonality of the disease. In a study of 60 cases of chronic lymphocytic leukemia B-cells, surface immunoglobulin determinations alone demonstrated monoclonality in 38% of cases, versus 65% of cases with combined surface immunoglobulin and cytoplasmic immunoglobulins determinations. Membrane markers were studied using a panel of monoclonal antibodies. Thirty-six per cent of patients were positive for CD 10. No correlations were seen between immunologic markers and clinical stage.

B-Lymphocytes

Inoperable nonmetastatic squamous cell carcinoma of the esophagus managed by concomitant chemotherapy (5-fluorouracil and cisplatin) and radiation therapy.

Thirty-five patients with nonmetastatic squamous cell carcinoma of the esophagus were treated with chemotherapy (5-fluorouracil, cisplatin) and concomitant split-course radiation therapy. All of the patients presented with dysphagia. Treatment consisted of two courses of chemotherapy with 5-FU (1 g/m2/day in continuous infusion for 5 days [days 1 to 5 and days 29 to 33] ) and cisplatin (70 mg/m2 intravenous bolus at days 2 and 30). Radiation therapy was concomitant in two courses delivering 20 Gy in 5 days (days 1 to 5 and days 29 to 33). On the first day of treatment, endoscopic peroral dilation or Nd-YAG laser therapy was usually carried out. At the end of the treatment, all of the patients were capable of oral nutrition. Histoendoscopic confirmation was made 8 weeks after the beginning of the therapy. Twenty-five of the 35 patients had a complete response with negative biopsy findings. There was only one serious complication (fatal myelosuppression) in the only patient who received more than two courses of chemotherapy. Sixteen patients died and 19 were still alive at 3 to 42 months after the beginning of treatment. Overall median survival for the 35 patients is 17 months. Actuarial survival was 55 +/- 18% at 1 year and 41 +/- 21% at 2 years. The median survival of the Stage I and II patients is 28 months. These results confirm that concomitant chemoradiotherapy is capable of producing a very high histoendoscopic complete response rate and improved 1-year and 2-year survival. The use of concentrated split-course radiotherapy enabled the authors to reduce the total length of the treatment to two periods of 5 days, with results that are similar to previous studies using classic radiotherapy for a 5-week to 7-week period.

Adult

Splenectomy for hypersplenism in chronic lymphocytic leukaemia and malignant non-Hodgkin's lymphoma.

Between 1 January 1980 and 31 July 1988, 62 patients with chronic lymphocytic leukaemia (CLL) or malignant non-Hodgkin's lymphoma (NHL) were splenectomized for splenomegaly and presumed hypersplenism. All patients except one had splenomegaly (mean (s.d.) weight 1585(872) g, range 150-4300 g) and 34 had massive splenomegaly (greater than 1500 g). Forty-nine patients had platelet counts less than 100 x 10(9)/l and 16 patients had anaemia with haemoglobin levels less than 10 g/dl. White cell counts were less than 3 x 10(9)/l in six NHL patients. Fifteen patients had bicytopenia, and three NHL patients had tricytopenia. The selected group of 62 patients underwent splenectomy largely because of failure to respond to medical therapy (39 patients) or inability to tolerate or start adequate chemotherapy because of very low blood counts (11 patients). There was one postoperative death, and a 29 per cent morbidity rate. The response rate was 89 per cent in the first month after splenectomy and 39 patients (63 per cent) had a continuing complete response with a median follow-up of 26 months (range 3-96 months). Twelve patients (10 with CLL) received no further therapy after splenectomy. Seven patients failed to respond and 15 relapsed after splenectomy. These 22 patients could be distinguished on the basis of: (1) lower average preoperative platelet counts (P less than 0.007), postoperative platelet counts (P less than 0.001), and postoperative rise in platelets (P less than 0.004); (2) lower average spleen weight (P less than 0.052); (3) preoperative chemotherapy (P less than 0.044). However preoperative and postoperative platelet counts were the only two variables selected by stepwise regression analysis (P less than 0.05 and P less than 0.01, respectively). Bone marrow failure did not preclude complete response after splenectomy. Long-term survivors emerged from the group of patients with continuing complete response. Of the seven patients who failed to respond, five died with a median survival of 4 months, and of the 15 patients who relapsed after splenectomy, 13 died, with a median survival of 6 months after relapse and 18 months after splenectomy. Thus, splenectomy may be an effective palliation for both CLL and NHL patients with splenomegaly and hypersplenism.

Adult

Results of fractionated TBI prior to bone marrow transplantation in standard risk leukaemia at Marseille.

One hundred and six patients with standard risk leukaemia were given fractionated TBI prior to allogeneic (72 cases, 27 of whom were T-depleted) or autologous (34 cases) bone marrow transplantation (BMT). Disease free survival at 5 years is 68% for allogeneic non T-depleted BMT and 33% for T-depleted BMT. Deaths are related to relapse, GVHD, infections, pneumonitis, encephalitis, VOD, AIDS, rejection.

Adolescent

Fractionated total body irradiation and bone marrow transplantation in acute lymphoblastic leukemia.

From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic (57 patients of whom 16 T-depleted) or before autologous (51 patients) bone marrow transplantation (BMT). BMT was realized in 66 patients (31 allogeneic and 35 autologous) in first complete remission (CR) and in 42 patients (26 allogeneic and 16 autologous) in second CR or greater or in relapse. All patients received high doses of alkylating agents prior to a low-dose fractionated total body irradiation of 11 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the three BMT types, allogeneic non T-depleted, allogeneic T-depleted, and autologous, and to the status of the patient at the time of the transplantation. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. For the allogeneic population, the 4-year disease-free survival (DFS) is 47%; it is 68.5% in first CR patients, 23.5% in second or subsequent CR patients, and 50% in T-depleted BMT. For the autologous population, 4-year DFS is 35.7%; it is 52% in first CR patients and 30% in patients in second CR or greater. The conditioning regimen appears to be efficient in terms of disease control with a low rate of complications for the non T-depleted population, transplanted in first CR, but has to be improved for the other patients.

Adolescent

Genotypic analysis in large cell lymphomas expressing a restricted set of differentiation antigens.

Immunophenotyping and immunogenotyping were performed in a series of 8 large cell lymphomas exhibiting anaplastic or "histiocytic" morphology and displaying an uncertain phenotype due to a restricted number of differentiation antigens. 6 cases expressed the Ki-1 antigen. 4 cases expressed one or two B-cell markers and contained rearrangements of the immunoglobulin genes. One of them also exhibited a T-cell receptor (TCR) beta gene rearrangement. 3 cases expressed a single T-cell differentiation antigen. Among them, only 1 displayed both gamma and beta TCR gene rearrangement; 1 only contained a gamma TCR gene rearrangement and 1 completely lacked clonal rearrangements. The eight cases expressed an inconclusive immunophenotype due to an abundant population of reactive cells but showed an immunoglobulin gene rearrangement. In conclusion, 5 out of the 8 unusual lymphomas studied here could be characterized by immunogenotyping. This approach was, however, inconclusive in the 3 remaining cases, whose lineage and differentiation stage remain poorly defined.

Adult

High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients.

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.

Adolescent

Rearrangement of the beta T-cell receptor gene in a monocytoid B-cell lymphoma.

We describe an unusual case of monocytoid lymphoma displaying a rearrangement of the T-cell receptor beta-chain gene associated with a rearrangement of the immunoglobulin heavy-chain gene, and of the lambda light-chain gene. This lymphoma was morphologically similar to previous cases in the literature, and was clinically of low grade. The lymphoma expressed the lambda light chain, HLA-DR, CD21, and CD22. Though the B-cell lineage of this lymphoma seems very likely, the genotypic profile raises a cautionary note regarding the supposed high stage of differentiation of monocytoid lymphomas.

B-Lymphocytes

[Value of upper digestive fibroscopy in the evaluation of initial spread of malignant extradigestive non-Hodgkin's lymphomas. Results in 101 patients].

The aim of this prospective study was to assess the frequency of gastroduodenal involvement during initial staging of extradigestive non Hodgkin's lymphoma. One hundred and one patients (64 men and 37 women; mean age 57.7; range 22-77 years) underwent an upper digestive endoscopy with multiple biopsies before any treatment. The origin of lymphoma was nodal in 76 cases and extranodal in 25 cases. Biopsy specimens were taken from all gross lesions; when the mucosa was considered as normal, biopsy specimens were obtained from the corpus, the antrum, and the duodenum. Endoscopy was normal in 37 patients; nevertheless in 4/37 patients, biopsies revealed lymphoma infiltration. In 64 patients, endoscopy showed macroscopic anomalies: biopsies were negative in 47 patients and showed lymphoma involvement in 17 patients. The involvement site was the corpus of the stomach (11 cases), the antrum (9 cases), and the duodenum (9 cases); lesions were multifocal in 10/21 patients. The association of several types of lesions was noticed in 5 patients. Lesions included volcano-like craters (8 cases), large folds of brain-like appearance (4 cases), tumors greater than 3 cm (3 cases), gastric ulcers (3 cases), erosive gastritis (3 cases), and erythematous duodenitis (2 cases). Overall, 21 of 101 patients (20.8 percent) had positive biopsies, 17 with endoscopic lesions and 4 without. Only 5/21 patients presented upper gastrointestinal symptoms. Staging of the lymphoma changed to Stage IV in 11 patients (4 stage I, 4 stage II and 3 stage III) (10.9 percent) after gastrointestinal involvement was documented. Gastroduodenal involvement is not related to initial site (nodal or extranodal), stage of extension or grade of malignancy of the lymphoma.

Adult

[Contribution of the analysis of genotype to the diagnosis of malignant lymphoma with abundant epithelioid reaction. Apropos of a case].

The authors describe the case of a 67 year-old woman bearing a malignant lymphoma displaying two different histological patterns: a Lennert's lymphoma pattern in a cervical lymph node and a diffuse centroblastic lymphoma pattern in an axillary node. Immunophenotyping on frozen and paraffin sections showed a predominant positivity of T-cell markers in the cervical node, while the axillary lymphadenopathy exhibited a major positivity of B-cell markers and a restricted expression of the lambda light chain. However, genotyping provided the evidence of a single neoplastic B-cell clone proliferating in both cervical and axillary nodes. These findings suggest that histological pattern of Lennert's lymphoma is devoid of absolute specificity. Thus, genotypic analysis is a useful tool for the diagnosis of so-called "lymphoepithelioid lymphomas".

Aged

Detection of residual bcr/abl translocation by polymerase chain reaction in chronic myeloid leukaemia patients after bone-marrow transplantation.

The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/abl hybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abl transcript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

Adolescent

Fractionated total body irradiation and allogeneic bone marrow transplantation for standard risk leukemia.

From March 1982 to December 1986, 32 patients with standard risk leukaemia were conditioned for allogeneic bone marrow transplantation (BMT) with low dose fractionated total body irradiation (TBI) after infusion of alkylating agents. This series includes six children and 26 adults. Minimal follow-up was 24 months. The total dose of 11 Gy, given in 5 daily fractions of 2.20 Gy, was given in the lateral position, following chemotherapy with either melphalan or cyclophosphamide. Lungs were shielded for 2 out of the 5 fractions. All patients had in vivo dosimetry. The death rate is 25% without relapse or rejection. Disease-free survival is 73% at 5 years. Toxic deaths are detailed: 2 from sepsis and veino-occlusive disease of the liver, 3 from severe graft versus host disease (GVHD), 2 from GVHD associated with virus pneumonitis and one from HIV infection. Fractionated low dose rate TBI is discussed regarding its decreased toxicity and its efficiency for disease control.

Adult

Liquid culture and cryopreservation of marrow cells of leukaemic patients prior to autologous bone marrow transplantation.

The feasibility of marrow cryopreservation for autologous bone marrow transplantation after 7 d in liquid culture was assessed in 10 leukaemic patients. A median of 0.17 x 10(8) nucleated cells/kg and 0.4 x 10(4) CFU-GM/kg could be collected after the complete procedure, with overall a consistent cell loss. Long-term cultures could be established from these cultured and frozen marrows, showing the persistance of precursors of haematopoietic and stromal cells. In vitro a significant decrease in the proportion of leukaemic cells could be observed in only one out of nine evaluable patients. This patient, with refractory AML, received an autologous transplant and is alive in continuous complete remission after 600 d. One patient with chronic myeloid leukaemia in acute phase underwent an autologous BMT with a marrow collected and cultured while in chronic phase and failed to engraft. These results show the feasibility of cryopreservation of cultured marrow cells for autologous bone marrow transplantation. The procedure is associated with poor cell recovery and must be improved to have a more general clinical application. This technology may have a major application with the emergence of modulators of growth and differentiation of haematopoietic cell lines.

Adolescent

[Modification of the relative plasma concentrations of methyl and methylene groups in cancer: a study using proton NMR spectroscopy].

Fossel et al. have recently proposed the proton NMR examination of plasmatic lipoproteins--and more precisely the determination of an index obtained from the averaged linewidth of the CH2 and CH3 resonances--as a possible tool for detection of cancer. Many evaluations conducted on an international basis have demonstrated that initial expectations were not met and that the test lacked sensitivity, specificity, and predictive value to be accepted as a screening and diagnostic tool. In our evaluation we have collected plasma from healthy subjects, from patients with various kinds of cancer at different stages of evolution and therapy, and from patients suffering from a variety of pathologies, including benign tumors. In accordance with Chmurny et al., we observed that the linewidth index (LWI) is precise and reproducible when care is taken in the handling and storage of samples and in the fasting of subjects. After finding no predictive value to the test, we have reanalyzed the spectra and studied the variations of the ratio defined by the methylene signal area over the methyl signal area. This ratio is significantly increased in cancer. Furthermore, it offers a better separation of statistical populations permitting a more precise discrimination between cancer, other pathologies and controls. We have also found that malignant tumors arising from mesenchyma (sarcoma, leukemia, lymphoma) induce less important variations in the CH2/CH3 ratio than adenocarcinoma or glioma, when such differences cannot be documented using the LWI. These observations are particularly interesting since they might bring new information on the metabolic modifications of the LWI and the CH2/CH3 ratio might reflect the embryologic origin of the tumors and raise the issue of the heterogeneity of cancer disease.

Humans