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Biomedical subjects

S Brunet

Publications and source records attributed to S Brunet.

At least 163 records · Page 9Linked to original sources

Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases.

Patients with previous invasive fungal infections (IFI) are at high risk of reactivation of the infection during BMT, even after an apparently curative antifungal treatment. We report four patients who suffered an IFI after intensive chemotherapy for acute leukemia and were later submitted for BMT. One patient had developed a chronic systemic candidiasis during consolidation chemotherapy and received prophylactic oral or iv fluconazole (200 mg daily) throughout BMT. Two patients developed an invasive pulmonary aspergillosis after intensive chemotherapy, one of them after salvage therapy for post-allogeneic BMT relapse and the other after consolidation therapy. The former patient underwent partial lobectomy after treatment with amphotericin B before a second allogeneic BMT was performed. Both patients received prophylactic itraconazole (400 mg daily by mouth) throughout the BMT procedure. The fourth patient had pneumonia caused by Scedosporium apiospermum (the anamorph form of the fungus Pseudallescheria boydii) during consolidation chemotherapy which was successfully treated with itraconazole. During BMT he also received oral itraconazole (400 mg daily) as prophylaxis against reactivation of the infection. All four patients had successful BMT and none had clinical, radiological or microbiological evidence of reactivation of IFI during BMT.

Administration, Oral↗

Frozen vs. nonfrozen bone marrow for autologous transplantation in lymphomas: a report from the Spanish GEL/TAMO Cooperative Group.

To investigate the impact of frozen and non-frozen bone marrow on engraftment kinetics and disease outcome, 94 patients with non-Hodgkin's lymphoma (NHL) autografted with frozen marrow (F group) were retrospectively compared with 38 who received marrow stored at 4 degrees C or 10 degrees C (NF group). The major end points of this study were time to hematopoietic recovery and early toxicity; disease response, disease-free survival (DFS), and relapse rate were also analyzed. Upon comparison of the NF and F groups, no significant differences were found in the period of time required to achieve a granulocyte count higher than 0.5 x 10(9)/l (20 and 22 days, respectively, p = 0.47) or a platelet count higher than 20 x 10(9)/l (28 and 27 days, respectively, p = 0.54). In addition, both groups behaved similarly in respect to toxic death (NF group 13%, F group 22%, p = 0.36), response rate (complete remission rate 78% in both groups), DFS (NF group 48%, F group 49%, p = 0.66), and relapse rate (NF group 30, F group 19%, p = 0.37). This study confirms that nonfrozen bone marrow is useful to support patients with NHL treated with myeloablative therapies.

Adolescent↗

Cytometric profiles of bone marrow and spleen lymphoid cells after mercury exposure in mice.

The potential immunotoxic effects of mercury chloride on murine bone marrow (bm) cell subpopulations, including analysis of maturation patterns for B-cells, were evaluated by flow cytometric analysis. CD-1 outbred mice were exposed for 28 days to relatively low doses of 25-100 ppm HgCl2 in drinking water and the mercury-related functional cellular changes were validated in a macrophage phagocytosis assay. Lymphocyte subsets from the bone marrow population were stained with PNA lectin and a panel of monoclonal antibodies against cell surface antigens. The incidence of subset-specific staining was also monitored in spleens and thymuses. A dose-effect correlation was noted for the mercury-related activation of macrophage phagocytosis. Subchronic exposure to mercuric chloride resulted in a transient (7-14 day) decrease of the lymphoid/total bm cell ratio and affected the incidence of splenic T-cell subsets, however, without a clear dose-response correlation. The B-cell population in spleen and maturation patterns of B-cells in bm appeared to be unaffected by the mercury exposure. Overall, cytometric analysis of lymphoid cell subsets in murine bone marrow revealed transient and subset-non-specific cell fluctuations after subchronic exposure to inorganic mercury.

Animals↗

Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.

Acute Disease↗

The role of alcohol providers in prevention: an evaluation of a server intervention programme.

Server intervention is a relatively new approach in the attempt to reduce the incidence of drinking and driving. Although a number of evaluations have suggested that the approach may be effective, there have been few comprehensive evaluations of such programmes. The present study utilized process evaluation techniques to assess reactions to a programme developed by the Addiction Research Foundation, and a quasi-experimental design to determine the impact of the programme on the serving practices of servers. Actors portrayed behaviours often faced by servers, and observers rated the reactions of the servers, who were unaware of the simulations, to these situations. The programme appears to have been effective in changing behaviour, in that trained servers exhibited less inappropriate responses than did untrained servers. In addition the results suggested that the programme increased servers' knowledge about their obligations and potential strategies for dealing with these situations. The implications of these findings for future implementations of such programmes are discussed.

Accidents, Traffic↗

Treatment of refractory and relapsed adult acute leukemia using a uniform chemotherapy protocol.

Twenty-nine adult patients with relapsed (21) or refractory (8) de novo acute leukemia (12 ALL and 17 ANLL) were treated with a remission-induction salvage chemotherapeutic protocol including vindesine, mitoxantrone, cyclophosphamide, intermediate-dose cytosine arabinoside, prednisolone and methotrexate. Ten of seventeen (59%) ANLL and 8/12 ALL (67%) achieved complete remission (CR). Seven of eight (86%) cases refractory to first-line remission-induction therapy (3/4 ANLL and 4/4 ALL) entered complete remission. The most frequent non-hematologic side effects were gastrointestinal. All patients experienced severe pancytopenia, with median times to recovery of granulocyte and platelet counts of 28 and 29 days, respectively. Nine of twenty-nine (31%) patients suffered febrile episodes of unknown origin and 13/29 (45%) suffered documented infections. Five patients (17%) died while aplastic, four from infection and one from cardiotoxicity. Four patients who entered CR were submitted to a bone marrow transplantation (BMT), two autologous and two allogeneic BMT. Sixteen of the 18 patients who entered CR relapsed, with a median remission duration of 3.5 +/- 2.9 months. Two patients remain in remission at 5+ and 17+ months. These results suggest that this protocol is an effective remission-induction salvage therapy for adult acute leukemias.

Adolescent↗

[Rheumatologic manifestations of chronic myelomonocytic leukemia. Presentation of 2 cases].

We describe two patients with chronic myelomonocytic leukemia (CMML) and associated rheumatic manifestations. The first patient presented an acute seronegative arthritis one month before the diagnosis of CMML and another bout one month after the diagnosis had been made. No specific cause was found after complete laboratory and roentgenographic studies. The second patient was diagnosed of Sjögren's Syndrome two years before the CMML became apparent. Although immunologic abnormalities are frequently observed in CMML, after a thorough bibliographic research we have found scarce reports describing associated rheumatic conditions.

Acute Disease↗

Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group.

Data on 49 allogeneic bone marrow transplant (BMT) recipients who developed interstitial pneumonia due to cytomegalovirus (CMV) were collected retrospectively. All patients were treated with ganciclovir and high doses of intravenous immune globulin, although types of immune globulins and schedules of treatment varied. Seventeen (35%) of 49 patients responded to treatment. Thirty days after the diagnosis of interstitial pneumonia, the survival rate among patients was 31%. CMV was detected in 81% of patients on whom autopsies were performed. The survival rate among patients who received total body irradiation (TBI) was significantly lower (11 [27%] of 41) than that among patients who did not receive TBI (six [75%] of eight; odds ratio = 12.3; P = .009). No other factor, including age, grade of graft-versus-host disease, types and dose of immune globulin used, or dose of ganciclovir, was correlated to survival. These results show that although survival of allogeneic BMT recipients with CMV interstitial pneumonia has improved, more than one-half of the patients still died of pneumonia. Thus, both prophylaxis for and treatment of CMV infection must be improved.

Adolescent↗

High-dose chemotherapy with bone marrow rescue for treatment of Hodgkin's disease.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Adolescent↗

Evaluation of direct effects of enoximone on systemic and pulmonary vascular bed in animals with a Jarvik total artificial heart.

Enoximone, a phosphodiesterase inhibitor, has positive inotropic and vasodilating actions. To evaluate specific effects of this drug on the systemic and pulmonary vascular bed, we administered enoximone as a 10-minute intravenous bolus at two different doses of 2 and 3 mg/kg of body weight, at different days, to five Holstein calves with a Jarvik 7-70 ml total artificial heart (Symbion, Inc., Salt Lake City, Utah). The calves were monitored for aortic pressure, right atrial pressure, pulmonary arterial pressure, and left atrial pressure. For each experiment cardiac output was maintained constant, and systemic and pulmonary vascular resistances were calculated at 0, 15, 30, and 60 minutes and every hour for 8 hours after infusion. Statistical analysis used analysis of variance and the paired t test with Bonferroni's correction. Data showed the following: (1) a marked systemic vasodilating action of enoximone at peak effect at 30 minutes with a 20% decrease in systemic vascular resistance from baseline value under constant cardiac output, returning progressively to normal values throughout the 8 hours; (2) a comparable effect for the two separate doses tested; (3) no specific action on the pulmonary vascular bed with "nonunidirectional" changes in pulmonary vascular resistance. This model was validated by the infusion of prostaglandin I2 in the same animals, at different days, which significantly decreased pulmonary vascular resistance of 50% at peak effect, under constant cardiac output. In summary, enoximone showed a proper systemic vasodilating effect with no specific action on the pulmonary vascular bed in an animal model of the total artificial heart. Decrease in pulmonary vascular resistances obtained with enoximone in clinical practice seems more related to the inotropic properties of the drug. Enoximone should not be administered in pulmonary hypertension, as suggested before.

Animals↗

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG.

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.

Adult↗

[Treatment of resistant or relapsing Hodgkin's disease with high doses of chemotherapy followed by autologous bone marrow transplant].

Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno-occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower.

Adolescent↗