Burkitt's lymphoma has proved to be a very useful model for the evaluation of both massive therapy regimens and purging techniques. Results from several centres now confirm a number of general principles in relation to the use of ABMT procedures in this tumour. Patients in whom conventional chemotherapy has failed can be cured by massive therapy but this should be limited to those who have responded to salvage regimens or have only achieved first PR. Chemoresistant relapse is unlikely to be cured and the high probability of a transient response does not justify the procedure in such cases. Important ongoing clinical studies include the use of ABMT in first CR for CNS disease or B-cell ALL. Results in allogeneic grafts suggest that current massive therapy regimens are curative in only 20–50% of patients (Appelbaum and Thomas, 1983) and new combinations are, therefore, still required. Phase I and II studies in patients with ‘resistant relapse’ are investigating the use of sequential high-dose alkylating agents and role of TBI.
The effect of freezing on phytohemagglutinin-induced interferon-γ (IFN-γ) production by human peripheral blood mononuclear cells (PBMCs) was studied. The possible mechanism responsible for the observed effects were also analyzed. Fronzen PBMCs produced significantly larger quantities (if IFN-γ than fresh cells. Like the frozen cells, the monocyte- and natural killer cell-eliminated populations of fresh PBMCs also secreted significantly larger quantities of IFN-γ. In contrast, the freezing process had no enhancing effect on IFN-γ production by monocyte-depleted PBMCs. Irradiated PBMCs also secreted larger quantities of IFN-γ. The results suggest that functional inactivation, of a subset of cryosensitive suppressor monocytes is associated with an increase in IFN-γ production by the T lymphocytes. The results provide further evidence that monocytes mediate their suppressive effect through the activation of a subset of radiosensitive, immuno-down-regulatory T cells. The ability of frozen cells to produce larger quantities of IFN-γ should be of clinical importance. For instance, cancer patients receiving frozen PBMCs as stem cell support (after myeloablative radio/chemotherapy) should benefit from the increased IFN-γ secretion because of its potent immunoregulatory, microbicidal, and antitumor activities.
Many human atherosclerotic lesions, showing no evidence of fissure or ulceration, contain a large amount of fibrin which may be in the form of mural thrombus on the intact surface of the plaque, in layers within the fibrous cap, in the lipid-rich centre, or diffusely distributed throughout the plaque. Small mural thrombi are invaded by SMCs and collagen is deposited in patterns closely resembling the early proliferative gelatinous lesions. In experimental animals, thrombi are converted into lesions with all the characteristics of fibrous plaques, and in saphenous-vein bypass grafts, fibrin deposition is the main cause of wall thickening and occlusion. There seems little doubt that fibrin deposition can both initiate atherogenesis and contribute to the growth of plaques. Epidemiological studies indicate that increased levels of fibrinogen and clotting activity are associated with accelerated atherosclerosis, and although blood fibrinolytic activity has given inconsistent results, in arterial intima both fibrinolytic activity and plasminogen concentration are decreased in cardiovascular disease. Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate, and by binding fibronectin, which stimulates cell migration and adhesion. Fibrin degradation products, which are present in the intima, may stimulate mitogenesis and collagen synthesis, attract leukocytes, and alter endothelial permeability and vascular tone. In the advanced plaque fibrin may be involved in the tight binding of LDL and accumulation of lipid. Thus there is extensive evidence that enhanced blood coagulation is a risk factor not only for thrombotic occlusion, but also for atherogenesis. Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.
Oxalic acid was employed for the catalytic transfer hydrogenation of used vegetable cooking oil. Hydrogen production was achieved upon the decomposition of oxalic acid using a commercial industrially sulfided NiW/SiO2-Al2O3 catalyst. Products were analysed by attenuated infrared spectroscopy, simulated distillation and gas chromatography-flame ionisation detection/thermal conductivity detection for the produced gases. No hydrogen gas was added for these tests, which were performed in a nitrogen atmosphere at an initial pressure of 0 bar in an autoclave. Unprecedented results were obtained, with a high yield of deoxygenated hydrotreated vegetable oil hydrocarbons being achieved while avoiding the use of formic acid, which is both toxic and irritant.
Les progrès achevés en hématologie à la fin du XXe siècle et au cours des premières années du XXIe siècle ont été considérables. Elles ont été essentiellement dues au fait que les cellules sanguines chez les patients atteints d’hémopathies malignes, peuvent facilement être prélevées et étudiées. Des progrès méthodologiques majeurs ont été réalisés en cytogénétique avec l’utilisation de la fluorescence in situ, en immunophénotypage avec des cytomètres de flux à 8 et 10 couleurs, en biologie moléculaire avec la découverte de nombreux oncogènes et marqueurs moléculaires tumoraux par « Polymerase Chain reaction » (PCR) et plus récemment avec l’utilisation du séquençage (Next Generation Sequencing NGS). Les cellules tumorales sont aujourd’hui étudiées à l’échelle individuelle. Les patients sont surveillés en continu en fonction de la détection ou non de la maladie résiduelle (MRD) et l’objectif qui était hier d’obtenir des remisions complètes (RC) cytologiques est aujourd’hui remplacé par la nécessité d’obtenir des RC moléculaires sans maladie résiduelle détectable dites RC « MRD négatives ». En parallèle et en partie grâce à ces avancées technologiques, des progrès jusque-là inégalés sont survenus dans le domaine thérapeutique avec l’apparition de thérapeutiques ciblées soit agents chimiques tels les inhibiteurs de tyrosine kinase largement utilisés pour le traitement des leucémies chroniques et dans une moindre mesure leucémies aiguës myéloblastiques, soit immunothérapies (anticorps monoclonaux combinés à des toxiques antitumoraux, anticorps monoclonaux bispécifiques, CAR-T cells, etc.) pour les leucémies aiguës lymphoblastiques, lymphomes et myélomes. Les greffes de cellules souches hématopoiétiques ont également évolué dans de larges proportions. Près de 50 000 greffes sont réalisées chaque année dans le monde (60 % autogreffes, 40 % allogreffes). Les cellules souches sont aujourd’hui en majorité (80 %) prélevées par cytaphérèses dans le sang périphérique alors que la moelle osseuse était la source privilégiée au XXe siècle. Les conditionnements prégreffe sont dans la majorité des cas des conditionnements atténués et la mortalité liée à la greffe a chuté considérablement. Surtout il est devenu possible de trouver un donneur pour pratiquement chaque indication grâce au fichier international de donneurs volontaires non apparentés et surtout grâce à la possibilité récente (depuis 2005) de réaliser les greffes à partir de donneurs intrafamiliaux haploidentiques. De ce fait les greffes tendent de plus en plus à être intrafamiliales. L’avenir des greffes est en constante discussion face au développement des thérapeutiques ciblées et nul ne peut prédire avec clarté la place qu’elles auront conservé dans 5 ans.The progress achieved in hematology at the end of the 20th century and during the first years of the 21st century was considerable. This probably was mainly due to the fact that blood cells from patients with hematological malignancies can easily be collected and studied. Major methodological progress has been made in cytogenetics with the use of in situ fluorescence, in immunophenotyping with 8 and 10 color flow cytometers, in molecular biology with the discovery of numerous oncogenes and tumor molecular markers by Polymerase Chain reaction (PCR) and more recently with the use of Next Generation Sequencing (NGS). Tumor cells are now studied on an individual scale. Patients are continuously monitored according to the detection or not of minimal residual disease (MRD) and the objective which was yesterday to obtain complete cytological remissions (CR) is today replaced by the need to obtain molecular CR without detectable residual disease called “MRD negative” CRs. In parallel and in part thanks to these technological advances, hitherto unequaled progress has occurred in the therapeutic field with the appearance of targeted therapies, either chemical agents such as tyrosine kinase inhibitors, widely used for the treatment of chronic leukemia and, to a lesser extent acute myeloblastic leukemias, or immunotherapies (monoclonal antibodies combined with antitumor toxins, bispecific monoclonal antibodies, CAR-T cells, etc.) for acute lymphoblastic leukemias, lymphomas and myelomas. Hematopoietic stem cell transplants have also evolved in large proportions. Nearly 50,000 transplants are performed each year worldwide (60% autografts, 40% allografts). Stem cells are now mostly (80%) collected by cytapheresis from peripheral blood, whereas bone marrow was the preferred source in the 20th century. Pre-graft conditioning is now in most cases attenuated (Reduced intensity conditioning “RIC”) and graft-related mortality has dropped considerably. Above all, it has become possible to find a donor for practically every indication thanks to the international file of unrelated voluntary donors and above all thanks to the recent possibility (since 2005) of carrying out transplants from haploidentical intra-family donors with the use of high dose cytoxan. As a result, transplants increasingly tend to be intrafamilial. The future of transplants is under constant discussion in the face of the development of targeted therapies and no one can predict with any clarity the place they will have retained in 5 years.
The economic value of increasing the reproductive performance of a breeding-ewe flock through selecting replacement ewes that attain puberty (AP) in their first year of life was quantified using bio-economic farm system modelling. In all of the scenarios modelled, the breeding-ewes were first presented for mating as yearlings (18–19 months of age) to enable them to start lambing at 2 years of age. For a New Zealand hill country sheep farm initially weaning 1.4 lambs per ewe mated, farm profit was improved by 6% when the percentage of breeding ewes that attained puberty in their first year of life was increased from 25% to 100%. However, if current sheep-industry target liveweight recommendations for rearing ewe lambs are met then between 70 and 95% of breeding-ewes should already attain puberty in their first year of life, and under these circumstances any further gains in farm profitability through specifically using this selection policy will be small (<2%). Countering the reproductive performance benefits of this selection policy was: (1) ewe liveweight increased with a higher AP%, which increased the individual feed requirements of the ewes; and (2) ewe mortality increased as multiple-bearing ewes became increasingly prevalent. The economic cost of using additional resources to further increase the farm's feed supply outweighed the benefits, resulting in the need to reduce farm breeding ewe numbers. The methodology and farm system model used for this study can be readily applied to other sheep farming systems. This can identify components of the reproductive process which should be targeted for further research to maximise on-farm benefits, and provide information on how a farm system will need to change for this to be successfully achieved.
High-dose chemotherapy with autologous stem cell support is increasingly used in malignant disease. There are few data from randomized, controlled, clinical studies on which to base our approach, and many publications consist of retrospective analyses that do not help elucidate the overall role of high-dose therapy. There has been a rapid increase in the use of peripheral blood as a source of stem cells that may reduce the toxicity of the procedure, but this has spawned an enthusiasm for high-dose therapy particularly in conditions such as myeloma and solid tumors where, as yet, there are few clinical data to demonstrate survival benefit.
