[Prevention of graft-versus-host disease. Elimination of T-lymphocytes from bone marrow cells by complement-dependent cytolysis with a combination of pan-T monoclonal antibodies].
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Biomedical subjects
Publications and source records attributed to P Herve.
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Many therapeutic aspects of venous thromboembolism continue to generate controversy so that the general therapeutic guidelines given below are only indicative. The first step is the diagnosis of venous thromboembolism; this is done in the vast majority of patients by visualization of blood clots using either pulmonary angiography or phlebography. The second step is to arrest the thrombotic process; the best means of doing this is to administer IV heparin. In the case of contra-indication or documented inefficacy of heparin therapy, the only therapeutic solution is to interrupt the inferior vena cava either with a clip, an umbrella or a filter. The blood clot lysis, which represents the third step, is effected by the natural fibrinolytic system. Thrombolytics , administered as a bolus of urokinase (15000 CTA U/kg), are indicated in cases of life-threatening pulmonary emboli, i.e. those with a pulmonary vascular obstruction of more than 50% and with hypotension, shock, or acute right ventricular failure. The use of thrombolytics is more questionable when they are administered to improve the quality of vascular patency. The only indication for pulmonary embolectomy is a contra-indication or inefficacy of thrombolytics . Due to the diagnostic and therapeutic difficulties, the first and most important part of the treatment of pulmonary emboli must be the broad application of prophylaxis treatment in patients with a high risk of venous thromboembolism.
High-dose melphalan followed by "rescue" with autologous marrow stored for 12-24 hours at room temperature was used in the treatment of 14 patients with advanced tumors refractory to conventional treatment. Twelve patients were evaluable, with three complete responses (25%), five partial responses (42%), and two minimal responses (16%). Response durations ranged from 4 to 38 weeks (median, 7). There were two treatment-related deaths and one patient developed acute nonlymphocytic leukemia 3 months after a second course of high-dose melphalan.
Using the method of Capella and Kaufman, the authors propose an original cryopreservation technique of human corneas. Sixty biomicroscopically normal corneas were obtained from cadavers (50-70 years) within six hours after death. Initial protocol involves four phases: 1) cryoprotection is carried out in three baths of three minutes each with human plasma and DMSO (dimethylsulfoxide) at 2-4-7%; 2) freezing is performed with 10 ml of the final cryoprotective fluid in a controlled rate freezer, the "Minicool" (CFPO). The cornea is cooled at a rate of 2 degrees C/min from + 6 degrees C down - 40 degrees C then at 5 degrees C/min down - 140 degrees C; 3) a tank containing liquid nitrogen at - 150 degrees C is used for a long term storage; 4) thawing is carried out in a water-bath at 37 degrees C for one minute, then in serum albumin 25% for three minutes and in M-K medium for thirty minutes. Effects of three cryobiological parameters are studied: cryoprotection: DMSO is diluted with human plasma at the following increasing concentrations: 2-4-7% or 4-6-10%; freezing medium: the cornea is frozen with or without the final cryoprotective bath. Thus freezing is carried out either in dry or liquid phase; thawing: initial temperature and the osmolar decrease of the dilution are modified in order to obtain four protocols: n degrees 1, initial protocol; n degree 2, an additional step using Hanks 5% - SA 25% for three minutes (1 000 mosm); n degree 3, after initial step reheating the cornea is directly placed in M-K medium; n degree 4, temperature of 50 degrees C for ten seconds precedes the initial protocol. For each protocol change, the endothelial viability is controlled by histological and/or SEM studies results: For each protocol change, the endothelial viability is controlled by histological and/or SEM studies results: cellular osmotic lesions are greater for DMSO concentrations of 10%; dry phase freezing induces more intense and more diffuse nuclear damage than in liquid phase; thawing under protocols 4 and 2 cause a high degree of nuclear damage associated with diffuse cytoplasmic vacuole formation. Histological and SEM studies clearly show endothelial cell lesions due to the cryoconservation. The human cornea endothelium is affected by any modification of the cryobiological parameters.(ABSTRACT TRUNCATED AT 400 WORDS)
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We report ten cases of acute myeloid leukemia treated by intensive therapy followed by autologous bone marrow transplantation. Seven patients were in first relapse, and three were in complete remission. The conditioning regimen consisted of either chemotherapy alone (6-thioguanine, cytarabine, lomustine, and cyclophosphamide [TACC; eight patients]) or cyclophosphamide and total-body irradiation (two patients). All the patients in first relapse achieved complete remission (CR). The median remission duration was 9.9 months (range, 5-14), and the median survival was 14.4 months (range, 9-23.8). Of the three patients autografted during CR, one relapsed at Month 5 and two others remain in CR and are well at 18+ and 18.3+ months. High-dose chemotherapy followed by autologous bone marrow transplantation seems to be a valuable treatment for acute myeloid leukemia, if it is used immediately after the CR to consolidate the remission.
Autologous bone marrow transplantation represents a new approach to the treatment of malignant diseases when conventional therapy has failed. For this reason, the authors have collected bone marrow from 46 patients, including 24 with acute leukaemia, 7 with chronic myeloid leukaemia, 10 with lymphosarcoma and 5 with solid tumours. The mean of total cryopreserved CFU-c was 8.5 X 10(6) (range: 0.2-25). Ten cases of autologous bone marrow transplantation are reported. Seven patients had been prepared with high dosage chemotherapy alone (TACC) and three with chemotherapy combined with total body irradiation. Haematopoiesis restarted within 9 to 15 days in 5 patients and within 22 to 34 days in the other 5. Complete remission was obtained in all 5 patients with acute myeloid leukaemia grafted during their first relapse, the longest remission up to now being 390 days. One patient with chronic granulocytic leukaemia is still in second chronic phase after 360 days. Stem cells were transplanted early in the course of a T-lymphosarcoma, during complete remission; maintenance chemotherapy was withdrawn, and the chances of success of this treatment alone are being evaluated. The kinetics of blood and bone marrow CFU-c populations after transplantation were studied in 4 cases and were found to correlate closely with haematopoietic recovery following ablative bone marrow therapy. Stem cell transplantation can only be justified in acute leukaemia if it is carried out immediately after complete remission to consolidate the results and, hopefully, to prolong the remission.
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Red blood cells (RBC) were collected with citrate-phosphate-dextrose (CPD) in a blood-pack optimal additive system. After concentration to 90% hematocrit they were diluted with saline-adenine-glucose medium (SAG-RBC), and stored for 35 days. In this work the RBC were stored in the presence of leukocytes. The SAG medium allows RBC conservation during 35 days at +4 degrees C. The adenosine triphosphate (ATP) level of RBC is compatible with their survival. During the first 2 weeks, hemolysis of SAG-RBC was not greater than in CPD blood. Nevertheless, hemolysis reached 1.49% on day 35, and there was a marked increase in RBC osmotic fragility. Scanning electron-microscopic studies of 35-day RBC showed that the majority of them became echinocytes. After incubation in fresh frozen plasma, the RBC recovered satisfactory osmotic resistance and normal disc shape. The post-transfusion viability was normal with greater than 70% recovery after 48 h. The in vivo restoration of 2,3-diphosphoglycerate (2,3-DPG) was rapid in the transfused SAG-RBC, 50% of the initial 2,3-DPG level being restored in 1 h. The in vivo studies proved that the functional quality of these RBC was compatible with their use in transfusion. The most important problem concerns the supernatant hemoglobin level of the SAG-RBC to be used for massive transfusion.
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