PubMed Health⌕ Search

Biomedical subjects

M Maynadie

Publications and source records attributed to M Maynadie.

17 recordsLinked to original sources
PubMed2005

A population-based assessment of the prognostic value of the CD19 positive lymphocyte count in B-cell chronic lymphocytic leukemia using Cox and Markov models.

No population-based study has assessed the prognostic impact on survival of the CD19 positive lymphocyte count, evaluated by immunophenotyping at diagnosis, in B-cell chronic lymphocytic leukemia (B-CLL). Aiming at addressing this issue, we investigated the clinical outcome of a well-defined population of B-CLL patients. Survival of B-CLL patients, diagnosed between 1990 and 1999 and recorded by the Registry of Hematological Malignancies of the Côte d'Or, was analysed applying Cox's regression model to the 237 included cases and to the 195 Binet stage A patients. To assess simultaneously the predictive value of each parameter on the risk of disease progression and on the risk of death, we completed this analysis by applying a three-states homogeneous Markov model to the whole study population. Analysis of the entire population showed that age (p < 0.001), Binet stage (p = 0.008) and CD19 positive lymphocyte count (p = 0.038) were three independent prognostic factors. However, in stage A patients, only progression into a more advanced stage, analysed as a time-dependent variable, and age had a clear impact on survival (p < 0.001 for both). Markov model revealed that an increased CD19 positive lymphocyte count increased the risk of disease progression in stage A patients (p = 0.002) but did not have direct impact on survival of either stage A patients with stable disease or stage B or C patients. An increased CD19 positive lymphocyte count at diagnosis is a marker of an increased risk of disease progression in stage A patients. Thus, it can be a useful tool for the clinical management of these patients.

Adult↗
PubMed2001

Identification of a leukemic counterpart of the plasmacytoid dendritic cells.

This work aims to demonstrate that CD4(+)CD56(+) malignancies arise from transformed cells of the lymphoid-related plasmacytoid dendritic cell (pDC) subset. The analysis of malignant cells from 7 patients shows that in all cases, like pDCs, leukemic cells are negative for lineage markers CD3, CD19, CD13, CD33, and CD11c but express high levels of interleukin-3 receptor alpha chain (IL-3Ralpha), HLA-DR, and CD45RA. Tumor cells produce interferon-alpha in response to influenza virus, while upon maturation with IL-3 they become a powerful inducer of naive CD4(+) T-cell proliferation and promote their T-helper 2 polarization. As pDCs, leukemic cells also express pre-Talpha and lambda-like 14.1 transcripts, arguing in favor of a lymphoid origin. In addition, malignant cells express significant levels of CD56 and granzyme B. Overall, those observations suggest that CD4(+)CD56(+) leukemic cells could represent the malignant counterpart of pDCs, both of which are closely related to B, T, and NK cells.

Adolescent↗
PubMed1999

Persistent polyclonal B lymphocytosis with binucleated lymphocytes: a study of 25 cases. Groupe Français d'Hématologie Cellulaire.

Persistent and polyclonal lymphocytosis of B lymphocytes (PPBL) with binucleated lymphocytes is an entity characterized by a polyclonal lymphocytosis. The lymphocytosis is stable for years and binucleated lymphocytes are detected on peripheral blood smears. We previously described +i(3q) as a recurrent chromosomal abnormality in seven PPBL patients. In this study we report a large series of 25 PPBL patients and demonstrated that PPBL was associated with +i(3q) in 77% of cases, premature chromosome condensation (PCC) in 50% and both abnormalities in 41% of cases. Furthermore, we demonstrated that i(3q) was present in a minority of B cells, restricted to B lymphocytes independently of the kappa or lambda light Ig chain expression, and exclusively observed in non-binucleated cells. The benign clinical course of PPBL and the lack of biological evolution in the majority of cases suggest that recognition of these disorders is so important that aggressive therapy in PPBL has to be avoided. Whether this syndrome represents a premalignant or benign disease remains unclear. The persistence of cytogenetic abnormalities after stopping tobacco use suggests no association with cigarette smoking.

Adult↗
PubMed1997

[Polyclonal lymphocytosis with binucleated lymphocytes. Morphological, immunological, cytogenetic and molecular analysis in 15 cases].

OBJECTIVES: Describe the clinical, immunological, cytogenetic and molecular aspects of polyclonal lymphocytosis with binucleated peripheral lymphocytes in order to ascertain the therapeutic consequences. PATIENTS AND METHODS: Fifteen patients, 13 women, 2 men, with a total lymphocyte count persistently above 4 x 10(9)/l at successive counts and binucleated lymphocytes on blood smears were studied. RESULTS: The syndrome is easily recognized at careful examination of blood smears which show binucleated lymphocytes and lymphoid cells with heterogeneous morphology. The lymphocytosis is polyclonal. The clinical situation remains stable without treatment despite cytogenetic clonality which contrasts with molecular polyclonality. DISCUSSION: Polyclonal lymphocytosis with binucleated lymphocytes is a clinical entity characterized by 1) nearly exclusive female predominance, mainly in young smokers; 2) lymphocyte counts above 4 x 10(9)/l which persist (> 6 months), are unchanged over time and fortuitously discovered; 3) lymphocytosis with binucleated lymphocytes on blood smears; 4) polyclonal lymphocytosis; 5) increased polyclonal serum IgM; and 6) recurrent cytogenetic anomalies with an isochromosome supenumerary marker, e.g. +i (3q). The etiology remains unknown: the role of smoking genetic predisposition or viral factors remains to be determined.

Adult↗
PubMed1997

Systemic mast cell disease associated with hairy cell leukaemia.

Systemic mast cell disease (SMCD) can be regarded as a tumorous proliferation of tissue mast cells involving various organs. The frequency with which SMCD is found in patients with haematological disorders suggests that the association is non-random. The association includes primarily, myeloid disorders such as myelodysplastic syndromes and acute or chronic myeloproliferative disorders. Lymphoproliferative disorders may also occur but more rarely, mostly non-Hodgkin's low grade B cell lymphomas. In this report a case is described in which SMCD occurred in a patient with hairy cell leukaemia.

Humans↗
PubMed1996

Expression of the multidrug resistance glycoprotein 170 in the peripheral blood lymphocytes of rheumatoid arthritis patients. The percentage of lymphocytes expressing glycoprotein 170 is increased in patients treated with prednisolone.

The objective was to evaluate the expression of the multidrug resistance P-glycoprotein (P-gp) in peripheral blood lymphocytes (PBL) of patients with rheumatoid arthritis (RA). PBL from 68 RA patients and 44 controls were evaluated. RA patients had a mean disease duration of 10.7 yr, with a mean number of past resistances to DMARDs of 0.82, and were treated with NSAIDs (n = 34), DMARDs (n = 25) and prednisolone (n = 40). Fluorescence flow cytometry was used to assess P-gp membrane expression on PBL. In the RA group, the percentage of PBL expressing P-gp was higher in patients treated with prednisolone than in other patients [mean +/- S.D.: 10.7 +/- 15.8% vs 3.3 +/- 7.6%, P < 0.03, Student] and was not related to other therapies, age, sex, RA duration, number of past resistances to DMARDs, activity, ESR, CRP. The percentage of PBL expressing P-gp did not differ in RA and control groups, but was higher in the prednisolone-treated RA patients than in controls. Prednisolone could induce a rise in the percentage of PBL expressing P-gp. On the contrary, patients with a high percentage of PBL expressing P-gp could be more resistant to DMARDs and need prednisolone earlier. Further studies are needed to address this question and to evaluate the potential implication of P-gp in drug resistance in RA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Isochromosome i(3q) and premature chromosome condensation are recurrent findings in chronic B-cell lymphocytosis with binucleated lymphocytes.

Chronic B lymphocytosis with binucleated lymphocytes (LWBL) is a recently described entity. The lymphocytosis is stable over years and atypical binucleated lymphocytes are detected on peripheral blood smears. Further investigation has shown a predominance in females, a polyclonal increase in serum IgM and HLA-DR7 expression in most cases. In almost all cases cytogenetic studies with classical culture conditions have not shown any abnormality. We describe 7 patients with LWBL associated with an abnormal karyotype. An additional i(3q) was found in 6 cases. Premature chromosome condensation (PCC) was detected in all 7 cases. As both abnormalities are rarely present in other benign or malignant proliferations, we suggest a strong correlation between LWBL and i(3q) and/or PCC.

Adult↗
PubMed1995

Flow cytometry evaluation of the multidrug-resistant phenotype with functional tests involving uptake of daunorubicin, Hoechst 33342, or rhodamine 123: a comparative study.

Multidrug-resistant (MDR) cells are characterized by a defect in drug accumulation caused by overexpression of a transmembrane glycoprotein, the P-glycoprotein (P-gp). The MDR phenotype can be characterized either by use of monoclonal antibodies raised against P-gp or with functional tests based on the intracellular accumulation of fluorescent molecules. The aim of the present study was to compare the effectiveness of functional tests performed by flow cytometry including uptake of daunorubicin (DNR) (2 micrograms/ml), Hoechst 33342 (5 micrograms/ml), or rhodamine 123 (RH 123) (0.1 microgram/ml); and to evaluate the effect of cell death induced by heating at 60 degrees C for 2 h on incorporation of DNR and RH 123. Sensitive and resistant human hematopoietic K 562 cells expressing P-gp were identified by monoclonal antibodies C 219 and MRK-16. Fluorescence of the dyes was always higher in sensitive than in resistant cells. However, DNR and Hoechst 33342 produced a slight incorporation in resistant cells, while RH 123 showed lack of incorporation in resistant cells. Thus, RH 123 allows sensitive and resistant cells to be clearly distinguished. In case of cell death, accumulation of RH 123 and DNR were different. With RH 123, fluorescence intensity strongly decreased in sensitive cells. With DNR, fluorescence intensity was enhanced in resistant cells. Thus, when the MDR phenotype is defined by uptake of DNR or RH 123, artifactual results due to cell death may be avoided by using a dye such as propidium iodide to eliminate dead cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Persistent polyclonal lymphocytosis with binucleated B lymphocytes: a genetic predisposition.

Persistent lymphocytosis is usually associated with a malignant lymphoproliferative disease (MLPD). We report six female patients presenting a chronic, moderate lymphocytosis of 2-16 years duration with atypical binucleated lymphocytes on peripheral blood smears. Further investigation showed a polyclonal increase in serum IgM and HLA-DR7 phenotype in all patients. The B cells were polyclonal because Southern hybridization of DNA and polymerase chain reaction failed to demonstrate a clonal rearrangement of immunoglobulin heavy chain genes. Peripheral blood examination showed binucleated lymphocytes in a family member of two of the cases; taken together with the association with HLA-DR7 these data suggest a genetic predisposition. The identification of this benign syndrome is important in order to prevent its misdiagnosis as a MLPD.

Adult↗
PubMed1993

Celiprolol pneumonitis.

We report on a patient who developed hypersensitivity pneumonitis during treatment with the beta-blocker, celiprolol. The clinical picture was a severe alveolitis, with compromised gas exchange. Inadvertent subsequent rechallenge with celiprolol led to recurrence of the pneumonitis, 10 weeks after drug readministration. Again, the pneumonitis was fully reversible. Lymphocytes were elevated in bronchoalveolar lavage, and progressively normalized upon discontinuation of the drug. This case is reminiscent of pneumonitis to other beta-blockers, which are reviewed here.

Adrenergic beta-Antagonists↗
PubMed1992

Feasibility of using quinine, a potential multidrug resistance-reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia.

PURPOSE: We demonstrated previously that sera from quinine-treated patients reversed the multidrug resistance (MDR) of a human leukemic cell line. We now report a phase I and II clinical study that examined the toxicity of the combination of quinine with mitoxantrone and cytarabine (Ara-C). PATIENTS AND METHODS: Fifteen adult patients with relapsed or refractory acute leukemia were treated with quinine formiate (30 mg/kg/d in continuous intravenous (IV) infusion from day 1 through day 5 or 6) associated with Ara-C (1 g/m2 in 3-hour IV infusion twice a day for 5 days) and five increasing doses of mitoxantrone (from 8 mg/m2/d for 4 days to 12 mg/m2/d for 5 days). RESULTS: The main toxicity was severe myelosuppression: the mean times to leukocyte recovery (> 500/microL), granulocytes recovery (> 500/microL), and platelet count recovery (> 50,000/microL) were 23 days (range, 17 to 29 days), 30.6 days (range, 17 to 48 days), and 35.4 days (range, 14 to 75 days), respectively. The nonhematopoietic toxicity of this regimen was acceptable. Nausea and vomiting were common, but severe mucositis was observed in only two patients. Cardiotoxicity was limited to transient episodes of moderate supraventricular tachycardia and a clinically well-tolerated bradycardia. Tinnitus and vertigo were observed in 10 cases (67%), and mild hearing loss and transient increase of serum bilirubin were observed in six patients (40%). Total quinine serum levels reached a steady-state concentration between 6.4 and 18 mg/L in 24 hours. Complete remission (CR) was achieved in eight of 14 (57%) assessable patients, and partial response (PR) was achieved in two additional patients (14%). P-glycoprotein expression was detected on blast cells from five of 13 studied patients before treatment. A response was observed in all P-glycoprotein-positive cases. CONCLUSION: Quinine can be used safely as a potential reversing agent of MDR for the treatment of clinically resistant acute leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

A multicentric study of 41 cases of B-prolymphocytic leukemia: two evolutive forms.

B-prolymphocytic leukemia (B-PLL) is an infrequent disease with a poor prognosis. We present the clinical and biological features of 41 patients. Median age was 67 years [42-89] and male-female sex ratio was 2.4. The immunophenotyping revealed B-cell phenotype, with a high level expression of surface IgM and/or IgD in all cases, FMC7+ in 76 % of cases and CD5+ in 67%. Marked spontaneous in-vitro apoptosis was observed in most cases tested (n = 12). The median overall survival time was 5 years and the event-free survival time was 37 months. As detected by univariate and multivariate analysis, the only variables associated with a poor prognosis were advanced age and anemia. No significant difference was observed between de novo PLL (n = 27) and prolymphocytoid transformation of chronic lymphocytic leukemia (n = 14). Two groups of patients were individualized according to their clinical course: patients who died within one year of diagnosis (n = 14) and patients who had a prolonged survival (n = 23) without any treatment in some cases. The comparison between the 2 groups showed that they differed in age (p = 0.01) and anemia (p = 0.02). We also observed that the patients with p53 mutations had a worse clinical outcome. Taken together these data confirm that B-PLL should be regarded as a distinct form of chronic lymphoproliferative disorder and suggest the existence of two patterns of clinical evolution.

Adult↗
PubMedDate not supplied

Multidrug resistance phenotype evaluation by immunofluorescence and functional tests: comparison of two monoclonal antibodies and three fluorescent dyes in three cells lines.

Various agents have been shown to enhance drug sensitivity of multidrug resistant (MDR) cells and are thus of interest when the MDR phenotype is identified. Detection of MDR cells is of importance and can be carried out either by immunofluorescence with monoclonal antibodies or by functional tests using fluorescent dyes uptake. MDR has been analysed by flow cytometry on three sensitive and resistant cell lines, with MRK16 and C219 monoclonal antibodies directed against P-glycoprotein (P-gp) and with rhodamine 123, Hoechst 33342 and daunorubicin. Resistant cells were revealed by MRK16 and C219 but the results obtained with MRK16 gave higher both percentages of fluorescent cells and mean fluorescence. Fluorescence intensity observed with daunorubicin was lower than with rhodamine 123. With Hoechst 33342, mean fluorescence was quite identical on sensitive and on resistant cells. It was concluded that MRK16 and rhodamine 123 were well adapted to detect P-gp and evaluate its functional ability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗