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S Brunet

Publications and source records attributed to S Brunet.

At least 127 records · Page 7Linked to original sources

[Isolated thrombocytopenia in pregnancy. Etiopathogenic study and therapeutic approach in 60 patients].

BACKGROUND: We analyze the etiopathogenesis and clinical and immunohematological characteristics of 60 pregnant women with isolated thrombocytopenia (TP) (platelet count < 150 x 10(9)/l); and the frequency of TP and hemorrhagic complications in their newborn. We suggest the therapeutic approach for each maternal TP type. PATIENTS AND METHODS: We performed: clinical history, platelet count (EDTA K3, sodium citrate, microscopic exam) and investigation of antiplatelet antibodies (immunofluorescence) in all pregnant women. A familial history and ultrastructure of platelets were studied when hereditary macrothrombocytopenia (HM) was suspected. A Levine's test of homogenicity of variances was applied to compare the mean platelet count in each diagnostic group. A linear regression between maternal and newborn platelet counts was performed. RESULTS: In 37 thrombocytopenic women (62%) no antiplatelet antibodies were found, and the clinical history was negative for previous TP or abnormal bleeding. Four patients (7%) were diagnosed as pseudothrombocytopenia EDTA-mediated, and eight (13%) of HM. Finally, an autoimmune etiology was suspected in 11 women (18%) and antiplatelet antibodies were detected in 9. Mean platelet counts of mother with immune TP did not show statistically significant differences with other diagnostic groups. Abnormal bleeding was not observed in any patient or newborn. There was no correlation between platelet counts of mothers and newborns. Platelet count obtained by skull bone punction led to unnecessary caesarians in four cases. CONCLUSIONS: The frequency of immune thrombocytopenia in pregnant women is low (18%). There is a high prevalence of benign TP (62%). The pseudothrombocytopenias and HM are frequent findings (20%), and special care is advisable in these cases to avoid unnecessary therapeutic procedures.

Female↗

Assembly and immunogenicity of chimeric Gag-Env proteins derived from the human immunodeficiency virus type 1.

We evaluated the potential of the precursor Gag protein (Pr55) of the human immunodeficiency virus type 1 (HIV-1) as a carrier for the presentation of envelope epitopes. Recombinant chimeric core-envelope protein-expressing constructs were derived by deletion of regions within the gag gene, especially of regions encoding p24 capsid epitopes. Sequences encoding either the principal neutralization determinant (PND) and/or the CD4-binding domains (CD4BS) were then inserted. Deletion of residues 196-226 within the p24 capsid protein did not prevent self-assembly into virus-like particles (VLPs) whereas deletion of residues 299-328 completely abolished VLP formation. Thus the major homology region (MHR) and proximal sequences are required for capsid assembly. An immunization study in mice showed that assembled chimeric proteins elicited strong anti-Gag, weak anti-envelope, and no neutralizing humoral responses. Nonassembled chimeric proteins were poor immunogens. Mapping of Pr55 antigenic sites using sera from immunized mice and peptides overlapping the entire Gag precursor showed that p24 capsid and p17 matrix epitopes presented to the immune system differed from the mature form (p24 or p17) and the multimeric immature form (Pr55).

Amino Acid Sequence↗

Bacteremia due to glucose non-fermenting gram-negative bacilli in patients with hematological neoplasias and solid tumors.

Twenty-six patients with hematological or solid tumors who developed bacteremia caused by Stenotrophomonas maltophilia (n = 10), Pseudomonas putida (n = 6), Sphingomonas paucimobilis complex (n = 4) or Alcaligenes xylosoxidans (n = 6) in the period between 1993 and 1995 were studied. Seventeen patients were neutropenic during the infection, and 13 were undergoing bone marrow or peripheral blood stem cell transplantation. Twenty-three patients had catheter-related infections; only 3 of the 26 patients developed septic complications (all due to Stenotrophomonas maltophilia). Twenty patients were cured following catheter removal, either as primary measure (n = 8) or salvage measure (n = 12). Four responded to antibiotic therapy only, and two died of septic complications. Such infections in hematological and oncological patients have increased in this hospital from no cases in 1975 to 11 cases in 1995.

Adolescent↗

Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation.

PURPOSE: To evaluate prospectively the feasibility and results of bone marrow transplantation (BMT) after induction and intensification chemotherapy (CT) in patients with de novo acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 159 patients less than 51 years of age were treated. Induction CT consisted of daunorubicin 60 mg/m2 for 3 days, cytarabine (ARA-C) 100mg/m2 for 7 days, and etoposide 100 mg/m2 for 3 days. The first intensification therapy included mitoxantrone 10 mg/m2 for 3 days and ARA-C 1.2 g/m2 every 12 hours for 4 days. Amsacrine (100 or 150 mg/m2 for 3 days) and ARA-C (1.2 g/m2 every 12 hours for 2 or 4 days) were given as the second intensification therapy. Depending on the availability of a human leukocyte antigen (HLA)-identical sibling, the intention of treatment after CT was allogeneic BMT (allo-BMT) or autologous BMT (ABMT). RESULTS: Complete remission (CR) was obtained in 120 patients (75%) and partial remission (PR) in 11 (7%), while 15 patients (10%) were refractory and 13 (8%) died during induction. There was a trend for better leukemia-free survival (LFS) at 4 years for patients assigned to the ABMT group (50% +/- 6%) compared with the allo-BMT group (31% +/- 7%) (P = .08). This difference in LFS reached statistical significance when considering only transplanted patients (63% +/- 3% at 4 years after ABMT and 38% +/- 11% after allo-BMT, P = .02). The favorable results in patients who received ABMT (no toxic deaths and 37% +/- 7% probability of relapse at 4 years) contrast with the poor outcome of allografted patients (11 patients with transplant-related mortality). CONCLUSION: Our study reflects the difficulties in the completion of a therapeutic strategy that include BMT and suggests that intensification before BMT may be useful in the setting of ABMT, but this approach was associated with a high mortality rate in allo-BMT patients.

Acute Disease↗

Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia.

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 micrograms/kg) or granulocyte-macrophage colony-stimulating factor (10 micrograms/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 X 10(9)/l for three consecutive days. Eleven patients (58%, 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 X 10(9)/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.

Acute Disease↗

Mobilization of peripheral blood progenitor cells by cyclophosphamide and rhGM-CSF in multiple myeloma.

Fifteen consecutive patients with multiple myeloma (MM) scheduled for peripheral blood progenitor cell (PBPC) transplantation, were randomly selected to receive cyclophosphamide (CY) (4 g/m2) alone (group I) or associated with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (5 micrograms/kg/day) (group II). The mean time of neutropenia after CY administration was 9.8 +/- 4.3 days in group I and 6.4 +/- 1.2 days in group II (P = 0.0228). One hundred and eight aphereses were performed (7.1 +/- 1.8 aphereses per patient in group I and 6.4 +/- 2.8 aphereses per patient in group II). rhGM-CSF administration after CY allowed a higher collection of CD34+ cells in apheresis products (1.42 +/- 1.68 x 10(6) CD34+ cells/kg) in comparison to without factor administration (0.47 +/- 0.52 x 10(6) CD34+ cells/kg) (P = 0.0165). The mean number of cells infused per patient was 6.56 +/- 4.02 x 10(8) MNC/kg and 7.64 +/- 3.00 x 10(4) CFU-GM/kg in group I and 6.25 +/- 4.03 x 10(8) MNC/kg and 8.16 +/- 9.73 x 10(4) CFU-GM/kg in group II. The mean time to recover 0.5 x 10(9) granulocytes/I, 20 and 50 x 10(9) platelets/I in peripheral blood (PB) was 17.2 +/- 7.4, 13.4 +/- 3.7 and 16.5 +/- 6.9 days respectively, in group I and 13.3 +/- 1.7, 11.6 +/- 1.6 and 15 +/- 6.3 days, in group II. rhGM-CSF administration after CY treatment for PBPC mobilization in MM patients reduces the neutropenic period after CY and enhances apheresis CD34+ cell collection.

Adult↗

Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group.

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).

Actuarial Analysis↗

Tuberculosis in bone marrow transplant recipients: report of two cases and review of the literature.

Over a 6 year period we have seen two cases of tuberculosis among 118 allogeneic and 237 autologous bone marrow (BMT) or peripheral blood transplants. Both patients had received an HLA-identical related allogeneic BMT. The first case suffered from extensive chronic graft-versus-host disease (GVHD) and developed pulmonary tuberculosis 19 months after BMT. An open-lung biopsy was required to establish the diagnosis, and response to antituberculosis agents was complete, with no relapse at 49 months post-BMT. The second patient received a CD4+ T lymphocyte-depleted BMT, was receiving steroids for acute GVHD and developed rapid-onset meningeal tuberculosis on day +107 post-BMT. Despite initial severe neurologic deterioration, response to antituberculosis agents was good, and she remains alive and well 11 months from BMT. Review of the scant literature on this topic reveals that this is a relatively rare infection in BMT recipients despite their often severely immunosuppressed condition, occurring mainly in recipients of T cell-depleted allogeneic grafts or those who develop GVHD.

Adult↗

Malondialdehyde-modified HDL leads to accumulation of cholesterol in rat liver endothelial cells.

In order to study in vivo the effect of modified high density lipoprotein (HDL) on the movement of free cholesterol to liver cells and bile, we injected i.v. into rats, native or malondialdehyde modified HDL labelled with [14C]cholesterol. Bile analysis indicated that the contribution of labelled cholesterol to bile acid secretion was diminished in the group receiving MDA-modified HDL when compared to control group. On the other hand, the liver analysis revealed higher radioactivity in the treated group. A separation of liver cells into parenchymal, endothelial, and kupffer at 90 min after the injection of MDA-modified HDL or native HDL indicated that the endothelial cell uptake of labelled free cholesterol from MDA-modified HDL was 2.6-fold higher than for native HDL. It is suggested that liver endothelial cells may be involved in the protection against atherogenoic oxidized lipoprotein. However, with regard to our finding, the uptake of cholesterol from modified HDL was detrimental to bile acid secretion.

Animals↗

[Minimal residual disease in chronic myeloid leukemia in patients with long survival after allogeneic bone marrow transplantation].

BACKGROUND: The study of the minimum residual disease in a series of patients diagnosed with chronic myeloid leukemia (CML) treated with non manipulated allogeneic bone marrow transplantation (BMT) reporting a survival longer than 6 months is presented. METHODS: The positivity of the chimeric transcription bcr-abl was studied in 18 long surviving BMT patients. The complementary DNA (cDNA) corresponding to this transcription was amplified by the polymerase chain reaction (PCR) technique. Double internal PCR (PCR nested) was performed to increase the sensitivity of the determination. RESULTS: The first determination was performed in different post BMT stages with a median of 27 months (4-97). Fourteen out the 18 patients were positive for the bcr-abl transcription. On the second determination carried out in 11 cases with a sample obtained 24 months after the first 7 out of the 10 positive cases evaluated presented an identical pattern while the patient who originally was negative, remained so. The original transcription became negative in three patients. Only one of the positive cases developed hematologic relapse during the study period. CONCLUSIONS: Aggressive chemo-radiotherapy does not eradicate the leukemic clone in all patients with chronic myeloid leukemia. The persistence of positive results in a high number of patients with chronic myeloid leukemia in remission for over 6 months after bone marrow transplantation is not predictive of imminent relapse.

Adult↗

Rapid chiral separation methods development by cyclodextrin-mediated capillary electrophoresis for acidic and basic compounds.

Chiral separation methods development using conventional techniques such as GC or HPLC requires a lot of experience, effort, and expense, due to the wide diversity of the optically active solutes and their possible chiral selectors. Capillary electrophoresis has received increased attention as an alternative technique for chiral separation due to its inherent high efficiencies and ease of methods development. However, due to the wide variety of chiral selectors available in CE, the benefits of this technique might be diminished without an appropriate methods development scheme. In this paper detailed examples are shown for fast, efficient, and predictable chiral capillary electrophoresis separation methods development based on a new and systematic theory. Optimized separations and their parameters are presented for several enantiomeric acids and bases. All the three possible cases, such as the use of low and high pH, as well as pH = pK buffer systems are thoroughly discussed.

Acids↗

Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation.

Autologous hematopoietic stem cell transplantation was used for treatment of 384 patients with multiple myeloma in 37 centers during the years 1986-1994. An analysis of prognostic factors was performed in 207 of these patients. One hundred forty one were males and 66 females, and median age was 49 years (range, 24-68). Actuarial survival at 78 months is 45%. Factors associated with a good prognosis were: response on chemotherapy immediately pretransplant, administration of only one treatment regimen, a low serum-beta 2-Microglobulin value at diagnosis and the use of a conditioning regimen including melphalan. In a multivariate analysis, response status pretransplant, age < 45 years, melphalan conditioning and non-TBI conditioning were independently predictive for longer survival, while transplantation after only one line of primary treatment and isotype other than light-chain were of borderline significance. Post-transplant alpha-interferon treatment was associated with improved survival in responsive patients. Eighteen patients treated in one center (Huddinge) passed a double autograft program, and 14 are in continuous complete remission ([CR]; n = 10) or good partial remission (n = 4) at a median time of 17 months after the first transplant (range, 2-38). In five CR patients, polymerase chain reaction (PCR)-analysis of the clone-specific immunoglobulin-rearrangement was performed, and four are PCR-negative up to 33+ months after the first transplantation. We conclude that autografting in myeloma is most effective when applied early in the course of disease in younger, chemotherapy-reponsive patients. Alpha-interferon maintaince treatment seems to be beneficial with respect to improved survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Viridans streptococcal shock syndrome during bone marrow transplantation.

Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.

Acute Disease↗