Global and regional cerebral blood flow measurements using NMR of injected hyperpolarized xenon-129.
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Biomedical subjects
Publications and source records attributed to G Duhamel.
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The purpose of this study was to evaluate the recently proposed technique of 3He prepolarization at low temperature and high field (Kober et al. Magn Reson Med 1999; 41:1084-1087) for fast imaging of the lung. Helium-3 was cooled to 2.4 K in a magnetic field of 8 Tesla to obtain a polarization of 0.26%. The polarized 3He was warmed up to room temperature and transferred to a rat, with a final polarization of about 0.1%, large enough for acquiring a 3D image of the rat lung in 30 s.
Hyperpolarized (129)Xe dissolved in a lipid emulsion constitutes an NMR tracer that can be injected into the blood stream, enabling blood-flow measurement and perfusion imaging. A small volume (0.15 ml) of this tracer was injected in 1.5 s in rat carotid and (129)Xe MR spectra and images were acquired at 2.35 T to evaluate the potential of this approach for cerebral studies. Xenon spectra consistently showed two resonances, at 194.5 ppm and 199.0 ppm relative to the gas peak. The signal-to-noise ratio (SNR) obtained for the two peaks was sufficient (ranging from 12 to 90) to follow their time courses. 2D transverse-projection xenon images were obtained with an in-plane resolution of 900 microm per pixel (SNR range 8-15). Histological analysis revealed no brain damage except in two rats that had received three injections.
Hyperpolarized 129Xe was dissolved in a lipid emulsion and administered to anaesthetized rats by manual injections into the carotid (approximately 1-1.5 mL in a maximum time of 30 s). During injection, 129Xe NMR brain spectra at 2.35 T were recorded over 51 s, with a repetition time of 253 ms. Two peaks assigned to dissolved 129Xe were observed (the larger at 194 +/- 1 ppm assigned to intravascular xenon and the smaller at 199 +/- 1 ppm to xenon dissolved in the brain tissue). Their kinetics revealed a rapid intensity increase, followed by a plateau (approximately 15 s duration) and then a decrease over 5 s. This behaviour was attributed to combined influences of the T1 relaxation of the tracer, of radiofrequency sampling, and of the tracer perfusion rate in rat brain. Similar kinetics were observed in experiments carried out on a simple micro-vessel phantom. An identical experimental set-up was used to acquire a series of 2D projection 129Xe images on the phantom and the rat brain.
The first 3He nuclear magnetic resonance (NMR) experiments using low-temperature prepolarization are presented. 3He cells were polarized at 4.2 K and 4.7 T, transported to another magnet, heated to room temperature, and used for NMR experiments at 2.35 T. Cells with and without a rubidium coating were tested. In both cases, the NMR signal was greater than 100 times the thermal equilibrium signal. No evidence of a rubidium coating effect on the longitudinal relaxation time T1 of 3He (500 mbar) at 4.2 K could be demonstrated. NMR gradient-echo images of the cells were acquired.
The purpose of this study was to assess the relevance of a medico-economic evaluation of gallstones. In other words, would it be possible to define economic criteria that would permit to select the best therapeutic method whilst respecting medical ethics? The frequency of gallstones, the high consumption of goods and medical services they require and the important loss of productivity that ensues justify this approach. The medical literature and a number of experts have made it possible to evaluate the advantages and drawbacks of each therapeutic method by defining its indications according to criteria of effectiveness such as duration of survival, quality of life of asymptomatic patients, gallbladder clearance, etc. We have tried to find out whether the introduction of medico-economic criteria in this pathology was likely to modify the various therapeutic methods available at present. We give here three examples. The first one is that of asymptomatic gallstones where the introduction of a cost/effectiveness ratio let to the conclusion that abstention is better than surgical treatment. The second example is a comparison of costs between cholecystectomy and medical treatment in high risk patients; the result was that surgery is preferable at the age of 50 years and medical treatment from 70 years onward. Finally, a comparison between surgery and lithotrity including the cost/effectiveness ratio concluded in favour of surgery. However, ethical, methodological and conceptual problems taking into account the value of human life, the difficulty to evaluate the quality of life and exterior incitations make it necessary to moderate the practical applications of these results.
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Eight children with acquired immunodeficiency syndrome (AIDS), aged four months to 12 years, were treated with zidovudine (azidothymidine) 100 mg/m2 intravenously every six hours for 14 days, followed by oral zidovudine at the same dose for a total of six months. Of the eight, six were infected at birth and two were contaminated by blood transfusion at ages eight and nine years, respectively; seven of the eight showed specific neurologic impairment consisting of encephalopathy (six children) and myelopathy (one child). In two children, a dramatic improvement of clinical status occurred, including neurologic progress in one; in three, the improvement was dissociate or transient and in the other three, no modification was observed. A marked increase of total lymphocyte and CD4(+) cell counts occurred in four children but was transient without modification of in vitro antigen-induced lymphocyte proliferation; p24 human immunodeficiency virus serum antigens were detected in seven of eight children, then transiently disappeared in all children during intravenous therapy but reappeared progressively during the oral regimen in all but one. Progressive modification of human immunodeficiency virus serology was noted in five children, mainly characterized by the finding of anti-core antibodies. The hematologic toxicity of zidovudine was comparable with that observed in adults. These preliminary results support the need for further studies in order to delineate the optimal regimen of zidovudine in children with AIDS.
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In order to specify the factors responsible for the hepatic changes occurring during total parenteral nutrition (TPN) and to propose a preventive treatment, 30 infants treated for severe protracted diarrhea were prospectively distributed into 4 groups: I (n = 10): controls; II (n = 7): oral administration of human milk since the 15th day of TPN; III (n = 5): oral metronidazole since the 15th day; IV (n = 8): parenteral antibiotic therapy for septicemia since the 1st day. Contrary to group IV, the first 3 groups were randomly constituted on the 15th day. Liver function tests, bile and serum biliary acids, duodenal flora, hepato-biliary ultrasonography and, in 12 cases, liver histology were sequentially studied. Liver function changes were observed on the 15th day in all groups. An improvement occurred 15 days later in the infants treated, when the control group worsened (p less than 0.02). A significant increase of bile chenodeoxycholic acid levels was observed in the control group only (p less than 0.01), without change in lithocholic acid levels. These results lead the authors to recommend the preventive use of metronidazole or human milk during prolonged TPN in infants.
Although B cells reside in the bone marrow, little is known concerning their functional role in hematopoiesis. We have measured the effects of surface membrane factors released from unstimulated, circulating B cells of normal donors and patients with chronic lymphocytic leukemia on human hematopoiesis in vitro. Leukemic cells augment erythroid burst formation by allogeneic blood cells (p less than 0.05). The stimulatory effect is increased in cultures containing a high B-cell seeding density, and is decreased in those with a high peripheral blood mononuclear cell seeding density. Medium conditioned by B cells (CM) from the circulation or bone marrow stimulates the formation of erythroid bursts, granulocyte-macrophage colonies, and mixed colonies containing granulocytes, erythroblasts, monocytes, and megakaryocytes (GEMM) in serum-free cultures of allogeneic and autologous marrow (p less than 0.05). This effect is localized primarily to surface membrane vesicle-rich pellets of CM. Screening of several hematopoietic and nonhematopoietic cell types reveals that membrane vesicle-associated activity is released from B cells and mitogen-stimulated, circulating T cells. In contrast, vesicles shed from freshly isolated, resting T cells, continuous T-cell leukemia cell lines, erythrocytes, and endothelial cells do not express the activity (p greater than 0.10). The stimulatory activity is augmented in cultures of marrow cells that are depleted of B4 antigen-positive lymphocytes but not of T-lymphocytes, suggesting that endogenous release of the factor(s) occurs during incubation. Furthermore, membranes partially purified from leukemic B cells also express the activity. Together with our findings that (1) the growth enhancing factor(s) is solubilized by octylglucoside, and that (2) the factor can be immunoprecipitated with BPA-neutralizing, antimembrane IgG, our results suggest that the erythropoietic activity is an integral membrane protein that may be immunologically related to BPA. The relationship of the erythroid burst stimulatory factor to other hematopoietic activities found in CM pellets is unknown.
To examine mechanisms of cytopenia in acute nonlymphoblastic leukemia (ANLL), we determined whether leukemic plasma (LP) contains growth-promoting factors that support mammalian erythroid progenitor and pluripotential stem cell proliferation in vitro. When added to serum-free cultures of human bone marrow and peripheral blood cells, LP from anemic patients with ANLL stimulated erythroid burst formation to greater levels than did normal human plasma (p less than 0.05 for each). While LP also enhanced erythroid burst development in murine bone marrow cells, preincubation of marrow cells with LP did not alter the formation of splenic colonies (CFU-S-derived colonies) in irradiated mice (p greater than 0.10). To determine whether erythropoietin or other growth factors (functionally similar to burst-promoting activity, BPA) are important in mediating the erythropoietic effects observed in vitro, LP was preabsorbed with monospecific IgG raised against human erythropoietin or human BPA. Although elevated erythropoietin levels were found in each LP, preabsorption with antierythropoietin IgG did not alter its capacity to enhance human burst formation. In contrast, preabsorption with antimembrane IgG capable of recognizing human BPA abrogated the stimulatory effects of LP (p less than 0.05). In addition, LP was found to increase the percentage of murine CFU-S that are synthesizing DNA by the (3H) Tdr suicide technique, an effect which was not abrogated by preabsorption of LP with monospecific IgG raised against human BPA. We conclude that both erythropoietin and BPA are appropriately increased in ANLL. In addition, a factor is present in LP which induces DNA replication in murine pluripotential stem cells.
A 1 1/2-year-old Holstein heifer was examined because of a rostral mandibular mass. On the basis of radiographic and histopathologic findings, a diagnosis of compound odontoma was made. The heifer was successfully treated with surgery and irradiation.
Cardiac complications related to bone marrow grafting were investigated in a group of 63 patients undergoing bone marrow transplantation (57 autologous, 6 allogeneic) in the transplant unit of Hôpital Saint-Antoine (Paris, France) between February 1977 and October 1983. The pregraft regimen was cyclophosphamide, 6-thioguanine, cytosine arabinoside, and CCNU (TACC) in 39 cases, cyclophosphamide (CY) associated with whole-body irradiation in 16 cases, and multiple chemotherapeutic agents in 8 cases. The study was retrospective in 49 patients, and prospective in 14. The morbidity was 43% and the mortality 9%. There were 6 fatal cases of cardiomyopathies and/or pericarditis, 14 nonfatal cases of heart failure, 7 nonfatal cases of pure pericarditis, and 32 arythmias including 14 bradycardias, diversely associated on a total of 27 patients. Cyclophosphamide and/or TACC/cyclophosphamide, 6-thioguanine, cytosine arabinoside, and BCNU (BACT) were the factors basically responsible for the cardiac toxicity. The best-defined entity was an acute fatal cardiomyopathy with associated pericarditis of which we report three additional cases. The best predictors of CY toxicity were the daily weight (a gain of more than 2 kg for more than 48 hours) and the electrocardiogram (a decrease of more than 14% in the sum of the QRS complexes in the standard leads on the fourth day of chemotherapy). Routine echocardiography confirmed the high incidence of subclinical cardiac abnormalities and their reversibility. It would seem that radiotherapy and anthracyclines play a secondary role. Currently, we consider that cardiac toxicity is one of the most important limiting factors for bone marrow transplantation. We suggest, therefore, that the transplantation should be done as early as possible and preference should be given whenever possible to whole-body irradiation over high-dose chemotherapy combinations such as TACC.
Autologous bone marrow transplantation (ABMT) in chronic granulocytic leukemia (CGL) aims at reversing the acute or acceleration phases by injection of stem cells collected during the chronic phase. This study was designed to explain an unusual rate of delayed engraftment (50%) in our experience of ABMT in CGL patients. We investigated all the factors possibly responsible for abnormal perpetuation of aplasia following infusion of cryopreserved marrow stem cells. The study of CFU-gm recovery in 41 bags of frozen marrow from 25 patients revealed an overall deficiency with a mean CFU-gm recovery of 55 +/- 38% in CGL patients versus 73 +/- 15% in the control group (p less than 0.001). Our data also showed an inverse linear relation (r = -0.40, p less than 0.05) between CFU-gm concentration and recovery after freezing. A good CFU-gm recovery (greater than or equal to = 50%) was observed in 70% of cases when the concentration was less than 3700 CFU-gm/ml as compared to 30% of cases when the concentration was over 3700 CFU-gm/ml (p less than 0.001). The lack of improvement by diluting rich CFU-gm marrows to reduce CFU-gm concentration/ml, as well as the absence of relationship between CFU-gm recovery after freezing and nucleated cells concentration, suggest a particular fragility of CGL stem cells to freezing, probably related to their excessive amplification. At the present time, we strongly recommend that the highest possible dose of progenitor cells be cryopreserved, preferably at a low concentration, in patients with CGL, and particular attention devoted to the freezing procedure in each individual patient, with numerous appropriate efficiency tests.