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Biomedical subjects

M Attal

Publications and source records attributed to M Attal.

At least 109 records · Page 6Linked to original sources

Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.

Adolescent↗

Hairy cell transformation of a B-cell chronic lymphocytic leukemia: a morphological, cytochemical, phenotypic and molecular study.

The normal counterparts of the B cells found in hairy cell leukemia (HCL) are not known. We report here a detailed morphological, cytochemical, immunological and molecular analysis of a patient with B-cell chronic lymphocytic leukemia (B-CLL) who later in the course of his disease developed hairy cell leukemia. We speculate that hairy cell transformation of B-CLL might be related to an in vivo protein kinase C mediated cellular activation of B-CLL cells.

Blotting, Southern↗

Intravenous interleukin-2 just after high dose BCNU and autologous bone marrow transplantation. Report of a multicentric French pilot study.

This multicentric pilot study was conducted in order to evaluate the feasibility of early interleukin-2 (IL2) after high dose chemotherapy requiring autologous bone marrow transplantation (ABMT). BCNU at 800 mg/m2 was followed, 3 days later, by the reinjection of the bone marrow cells. At day 4, IL2 at 18 x 10(6) i.u./m2/day was given as a continuous infusion during a minimum of 6 days (first phase of study) or for 6 more days after 1 day break (second phase of the study). Twenty patients were included. Toxicity was not negligible, with one toxic death, but IL2 therapy does not damage the haematological recovery of most patients. However, a 6-day IL2 treatment period only appears tolerable. In 18 evaluable patients, three responses were observed: one complete response (CR) of short duration in a non-Hodgkin's lymphoma, one CR (24 months +) and one partial response (PR) (6 months) in two patients with metastatic gastric adenocarcinoma. This study confirms that IL2, restricted to a 6-day treatment period, is feasible immediately after high-dose chemotherapy requiring ABMT without haematological problem in most patients. The response rate was unexpected for a pilot study and this combined therapy obviously requires further study.

Adult↗

[Magnetic resonance imaging in the bone sites of malignant non-Hodgkin's lymphoma. Apropos of 16 cases].

The primordial role of MRI in the staging of primary or secondary bone tumors has been clearly established. The authors report a study of 16 patients with NHL with suspected bone involvement, investigated by conventional radiography, bone scan, CT, bone marrow biopsy and MRI. The authors believe that, in the future, MRI will have an important role in the staging and follow-up of treatment of bone lymphomas. Better than any other techniques, MRI provides a precise assessment of tumor extension. It also represents a valuable method for monitoring patients during treatment by visualising the course of the disease.

Adult↗

Prevention of acute GVHD by in vivo use of anti-interleukin-2 receptor monoclonal antibody (33B3.1): a feasibility trial in 15 patients.

Results of allogeneic bone marrow transplantation (BMT) are still impaired due mainly to acute graft-versus-host disease (GVHD). Successful T cell depletion may abolish GVHD but causes increased rates of rejection and relapse. In vivo blocking of the CD25 receptor on T cells induces efficient and selective immunosuppression. We present results of a pilot trial studying the use of a CD25 MoAb (33B3.1) to prevent acute GVHD after allogeneic BMT. Fifteen patients were included in the study; 14 had a fully HLA matched sibling donor. In association with short methotrexate and cyclosporin A post-graft immunosuppression, the patients received 10 mg of 33B3.1 monoclonal antibody daily according to three successive schedules to study toxicity on marrow graft. No major adverse clinical experiences occurred. Engraftment was not delayed; after 4 months, full chimerism was documented in 14/15 studied patients. No human anti-rat antibody was detected during treatment period. No GVHD occurred during the period of antibody administration. Two patients relapsed; seven are alive and well with a median follow-up of 650 days. This study justifies a prospective controlled study to determine the real impact of 33B3.1 on GVHD prophylaxis.

Acute Disease↗

Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy.

Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma.

Adult↗

[Diagnosis of early complications of the transplanted kidney by pulsed Doppler].

Thirty four patients with advanced renal insufficiency and after kidney transplantation have been prospectively studied using pulsed wave doppler. The doppler flows were evaluated using an index of resistance. The index of resistance varies proportionally with the peripheral resistances. This study showed in 14 patients without symptoms a mean index of resistance equal to 0.71 +/- 0.087. During acute rejection, the mean index of resistance increases to 0.91 +/- 0.12 (p less than 0.01). Seven patients with acute tubular necrosis and an index of resistance equal to 1 (p less than 0.01). There is no increase of the indices of resistance in patients with cytomegalovirus infection or with overdosed cyclosporin treatment. The pulsed wave doppler has a very good sensitivity to diagnose the acute rejection (90%) and acute tubular necrosis (100%) but cannot differentiate them. However, the repetition of systematic examinations allows the early diagnosis of acute rejection and the follow-up of the vascularization of anuric kidneys related to tubulopathy.

Female↗

The CD24 antigen discriminates between pre-B and B cells in human bone marrow.

When bone marrow (BM) lymphoid cells from 12 adult healthy donors were labeled by CD24 antibodies and analyzed by flow cytometry, two positive populations of cells were demonstrated in each sample (by a separated bimodal specific immunofluorescence). One population had intermediate CD24-Ag density (termed CD24+ cells) whereas the other had high CD24-Ag density (termed CD24(2+) cells). CD24+ cells represented 5.8 +/- 2.7% of the total lymphoid BM cells and CD24(2+) cells 5.6 +/- 2.5%. Using dual fluorescence analysis on eight samples, all CD24+ cells expressed the CD21 and CD37 mature B cell Ag and also surface IgM (sIgM), but this population lacked CD10 Ag. These cells also expressed CD19 Ag, and at a higher density than CD24(2+) cells. They were also positive for HLA-DR Ag. Conversely, CD24(2+) cells were shown to be early cells of the B cell lineage. While all the CD24(2+) cells were HLA-DR+ and CD19+, 64 +/- 16% of them expressed CD20 Ag (at a lower density than CD24+ cells), 65 +/- 21% CD10 Ag, and 22 +/- 8% were positive for cytoplasmic mu-chains (c mu). None of these cells expressed the CD21 and CD37 mature B cell Ag or sIgM. Additional experiments on four different healthy donors demonstrated that 30 +/- 9% of the CD24(2+) cells expressed the CD34 Ag and that the CD24+ cells did not express it. Thus, the CD24 Ag permits discrimination between two populations of the B cell lineage present in adult BM: 1) A CD24(2+) cell population including "pre" pre-B cells (HLA-DR+, CD19+, CD10+/-, CD20-, CD21-, CD34+, CD37-, c mu-), "intermediate" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu-), and "true" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu+). 2) A CD24+ cell population including B cells of the standard phenotype (HLA-DR+, CD19+, CD10-, CD20+, CD21+, CD34-, CD37+, c mu-, sIgM+).

Adult↗

Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation.

T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL-2 after autologous BMT leading to a major immune activation 2.5 months after BMT.

Adolescent↗

Immunohistochemical detection of multidrug resistance associated P-glycoprotein in stromal cells of malignant lymphomas.

We examined the distribution of the P-glycoprotein by immunohistochemistry in 25 malignant lymphomas (15 CHOP-derived regimen resistant non-Hodgkin's lymphomas and 10 Hodgkin's diseases). The study was performed on both cryostat and ModAMeX sections; the latter method preserves fixation-sensitive antigens and allows a more precise morphologic identification of neoplastic and non-neoplastic cell populations in contrast to cryostat sections. In both non-Hodgkin's lymphomas and Hodgkin's diseases, cells that were stained on cryostat sections were identified as macrophages and endothelial cells and not neoplastic lymphoid cells, by the ModAMeX technique. These findings suggest that the quantitative assessment of the multidrug resistance gene RNA by Northern blotting performed on fresh homogenates may overestimate the RNA content of neoplastic cells in a number of lymphoid tumors. In addition, the mechanism of chemoresistance in non-Hodgin's lymphomas is less likely to be associated with the P-glycoprotein expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The value of pulsed Doppler for the follow-up of the transplanted kidney in the first 3 months of transplantation].

This prospective study was conducted in 34 consecutive renal transplant patients. Pulsed doppler was used to evaluate the peripheral resistance (PR) in the transplant vessels. Under normal conditions, the PR of the graft is low, resulting in a continuous diastolic blood flow. The intensity of this blood flow was evaluated by means of a resistance index (RI), Pourcelot's index, calculated as follows: RI = systolic peak - end-diastolic peak/systolic peak This study demonstrated values for RI of 0.71 +/- 0.087 in 14 totally asymptomatic patients. In 10 cases of acute rejection, the RI increased to 0.91 +/- 0.12. The 7 patients with acute tubular necrosis had an RI equal to 1. In patients with cytomegalovirus infection of suffering from cyclosporin overdose, the RI was not modified in relation to asymptomatic subjects. This study demonstrates the existence of a rise in the PR in cases of acute rejection and acute tubular necrosis with a sensitivity of 90% and 100% respectively for these two diagnoses. However, this method cannot be used to distinguish between acute rejection and acute tubular necrosis.

Cyclosporins↗