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See detailLow T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.
Baron, Frédéric ULg; Baudoux, Etienne ULg; Frere, Pascale ULg et al

in Bone Marrow Transplantation (2003), 32(8), 829-34

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen ... [more ▼]

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]

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See detailTransmission of chronic myeloid leukemia through peripheral-blood stem-cell transplantation.
Baron, Frédéric ULg; Dresse, Marie-Françoise; Beguin, Yves ULg

in New England Journal of Medicine [=NEJM] (2003), 349(9), 913-4

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See detailRecombinant human erythropoietin therapy is very effective after an autologous peripheral blood stem cell transplant when started soon after engraftment.
Baron, Frédéric ULg; Frere, Pascale ULg; Fillet, Georges ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2003), 9(15), 5566-72

PURPOSE: Previous trials of recombinant human erythropoietin (rHuEpo) therapy after autologous hematopoietic stem cell transplantation have administered very high doses of i.v. rHuEpo starting on day 1 ... [more ▼]

PURPOSE: Previous trials of recombinant human erythropoietin (rHuEpo) therapy after autologous hematopoietic stem cell transplantation have administered very high doses of i.v. rHuEpo starting on day 1 and continuing for 1-2 months until erythroid engraftment and have shown no benefit of rHuEpo therapy. We sought to establish a more effective use of rHuEpo in this setting. EXPERIMENTAL DESIGN: In this report, we show in a first cohort of 45 lymphoma or myeloma patients undergoing peripheral blood stem cell transplant (control group) that endogenous erythropoietin levels are high for the degree of anemia during the first 3 weeks after transplant but become adequate or slightly decreased thereafter. We thus enrolled 41 consecutive similar patients in a trial of rHuEpo therapy at a dose of 500 units/kg/week started on day 30 after the transplant. RESULTS: The 12-week probability of achieving hemoglobin (Hb) levels of 13 g/dl was 87% in rHuEpo-treated patients versus 14% in controls (P = 0.0001). Mean Hb levels were significantly higher in the rHuEpo group than in the control group from day 42 through day 150 after transplant (Ps of <0.05 to <0.001). Two of 41 patients in the rHuEpo group versus 12 of 45 patients in the control group had Hb levels of <9 g/dl between day 42 and day 100 after the transplant (P = 0.0078). CONCLUSIONS: Anemia after autologous peripheral blood stem cell transplant is exquisitely sensitive to rHuEpo when therapy is started soon after engraftment. This is the first convincing report showing that rHuEpo is effective in this setting. Our data set the stage for a more rational use of rHuEpo after autologous hematopoietic stem cell transplantation and should renew interest in erythropoietin therapy in this setting. Prospective, randomized trials should investigate the impact of rHuEpo therapy on transfusion requirements and quality of life. [less ▲]

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See detailLong-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
Schetelig, Johannes; Fetscher, Sebastian; Reichle, Albrecht et al

in Haematologica (2003), 88(11), 1272-8

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the ... [more ▼]

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms. RESULTS: The median age at transplantation was 53 years. HDCT was given as part of 1st-line therapy (N=14; 48%) or 2nd/3rd-line therapy (N=15; 52%). Regimens for the mobilization of peripheral blood stem cells (PBSC) included VIPE (N=7; 26%), DexaBEAM (N=6; 22%), CHOP-like regimens (N=6; 22%), other regimens (N=5; 19%) or alternatively growth factor alone (N=3; 11%). The median yield of PBSC was 3.8x106 CD34+cells/kg. Two patients received autologous bone marrow. The HDCT consisted of BEAM-type regimens in 16 patients, ICE-type regimens in 7, and other regimens in 6 patients. There was one treatment-related death. The rate of complete remissions increased from 45% before HDCT to 76% after HDCT. As of January 2003, after a median observation time of living patients of 5 years (range 2.5 to 10 years), 14 patients have died (13 from progressive disease), and 15 patients are alive. The probability of 5-year overall and event-free survival was 44% (95% CI, 22% to 66%) and 37% (95% CI, 17% to 57%), respectively. Long-term disease-free survival was observed in patients transplanted during 1st-line treatment as well as in the context of 2nd/3rd-line therapy. INTERPRETATION AND CONCLUSIONS: There is evidence that AIL is susceptible to high-dose chemotherapy. HDCT and autologous stem cell transplantation should be considered in selected patients with AIL. [less ▲]

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See detailComment je traite ... la leucemie myeloide chronique (LMC).
Hafraoui, Kaoutar ULg; Humblet-Baron, Stéphanie ULg; Baron, Frédéric ULg et al

in Revue Médicale de Liège (2003), 58(1), 7-12

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine ... [more ▼]

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). The authors discuss the results of a phase I and three phase II trials reporting the efficacy of STI571 as treatment for CML patients and propose two simplified algorithms that may help to guide decision-making for the individual patient. [less ▲]

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See detailSoluble transferrin receptor for the evaluation of erythropoiesis and iron status.
Beguin, Yves ULg

in Clinica Chimica Acta (2003), 329(1-2), 9-22

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR ... [more ▼]

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency. [less ▲]

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See detailCell cycle duration at the time of maternal zygotic transition for in vitro produced bovine embryos: effect of oxygen tension and transcription inhibition.
Lequarré, Anne-Sophie ULg; Marchandise, J.; Massip, A. et al

in Biology of Reproduction (2003), 69(5), 1707-13

Early embryonic cleavages are mostly regulated by maternal components then control of development progressively depends on newly synthesized zygotic products. The timing of the first cleavages is a way to ... [more ▼]

Early embryonic cleavages are mostly regulated by maternal components then control of development progressively depends on newly synthesized zygotic products. The timing of the first cleavages is a way to assess embryo quality. The goal of this study was to evaluate the duration of the fourth cell cycle, at the time of maternal-to-zygotic transition (MZT) in in vitro-produced bovine embryos by means of cinematographic analysis. We found that 75% of the embryos displayed a long fourth cycle (43.5 +/- 5.4 h) whereas the remaining embryos had a very short fourth cell cycle (8.9 +/- 2.9 h). Both groups did not differ in cleavage rhythm up to the eight-cell stage and timing of cavitation and blastocyst expansion was identical. However, embryos with a short fourth cell cycle had a better blastocyst rate than embryos with a long cycle (59% versus 38%, P < 0.01). Total cell number, inner cell mass (ICM):total cell ratio, and hatching rate were identical for blastocysts produced from embryos with either a long or a short fourth cell cycle. In a second experiment, we showed that increasing the oxygen tension, from 5% to 20%, decreased the percentage of embryos with a short fourth cell cycle, from 25% to 11% (P < 0.01), indicating that suboptimal culture conditions can influence the length of this cycle. Finally, we investigated whether fourth cell cycle duration could be influenced by transcription inhibition. With alpha-amanitin added at 18 h postinsemination (HPI), cleavage was reduced (66% versus 79%) and, at 70 HPI, the 9- to 16-cell rate increased (50% versus 25%) concomitantly with a 5- to 8-cell rate decrease (16% versus 47%). A similar pattern was observed when the drug was added at 6 HPI or 42 HPI but not at 0 HPI. Cinematographic analysis revealed that alpha-amanitin increased the first cell cycle duration whereas the second and third cell cycles were not affected. With the drug, one third of the embryos could develop up to the 9- to 16-cell stage and they all had a short fourth cell cycle (11.2 +/- 3.7 h) with a good synchrony of cleavage between blastomeres. These results suggest that duration of the fourth cell cycle of bovine embryo, during the MZT, is under a zygotic transcriptional control that can be affected by oxidative conditions. [less ▲]

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See detailLa géographie appliquée à l’université de Liège
Binard, Marc ULg; Devillet, Guénaël ULg; Erpicum, Michel ULg

in Bulletin de la Société Géographique de Liège (2003), 43

Historic of the applied geography within the various units of the Geographic Department of the University of Liège (Belgium)

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See detailAutocrine/paracrine activation of the GABA(A) receptor inhibits the proliferation of neurogenic polysialylated neural cell adhesion molecule-positive (PSA-NCAM+) precursor cells from postnatal striatum.
Nguyen, Laurent ULg; Malgrange, Brigitte ULg; Breuskin, Ingrid ULg et al

in Journal of Neuroscience (2003), 23(8), 3278-94

GABA and its type A receptor (GABA(A)R) are present in the immature CNS and may function as growth-regulatory signals during the development of embryonic neural precursor cells. In the present study, on ... [more ▼]

GABA and its type A receptor (GABA(A)R) are present in the immature CNS and may function as growth-regulatory signals during the development of embryonic neural precursor cells. In the present study, on the basis of their isopycnic properties in a buoyant density gradient, we developed an isolation procedure that allowed us to purify proliferative neural precursor cells from early postnatal rat striatum, which expressed the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). These postnatal striatal PSA-NCAM+ cells were shown to proliferate in the presence of epidermal growth factor (EGF) and formed spheres that preferentially generated neurons in vitro. We demonstrated that PSA-NCAM+ neuronal precursors from postnatal striatum expressed GABA(A)R subunits in vitro and in situ. GABA elicited chloride currents in PSA-NCAM+ cells by activation of functional GABA(A)R that displayed a typical pharmacological profile. GABA(A)R activation in PSA-NCAM+ cells triggered a complex intracellular signaling combining a tonic inhibition of the mitogen-activated protein kinase cascade and an increase of intracellular calcium concentration by opening of voltage-gated calcium channels. We observed that the activation of GABA(A)R in PSA-NCAM+ neuronal precursors from postnatal striatum inhibited cell cycle progression both in neurospheres and in organotypic slices. Furthermore, postnatal PSA-NCAM+ striatal cells synthesized and released GABA, thus creating an autocrine/paracrine mechanism that controls their proliferation. We showed that EGF modulated this autocrine/paracrine loop by decreasing GABA production in PSA-NCAM+ cells. This demonstration of GABA synthesis and GABA(A)R function in striatal PSA-NCAM+ cells may shed new light on the understanding of key extrinsic cues that regulate the developmental potential of postnatal neuronal precursors in the CNS. [less ▲]

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See detailSentence processing strategies in French-speaking children with SLI: a study of morphosyntactic cues
Maillart, Christelle ULg; Schelstraete, Marie-Anne

in Journal of Multilingual Communication Disorders (2003), 1

The sentence comprehension strategies used by children with speci®c language impairments (SLI) were examined within the framework of the Competition Model (Bates and MacWhinney, 1989). The experiment was ... [more ▼]

The sentence comprehension strategies used by children with speci®c language impairments (SLI) were examined within the framework of the Competition Model (Bates and MacWhinney, 1989). The experiment was a replication of Kail and Charvillat'experiment (1988) designed to investigate the use of different morphosyntactic cues (i.e. word order, clitic pronoun, verbal agreement) in sentence comprehension by children (4;6 ± 6;6) with normal language development. They found that French speaking children used mainly information on word order with a lesser reliance on the other cues (word order4clitic pronoun4verbal agreement). In the present study, the same experiment was replicated with 25 French speaking children with SLI. The results suggested that children with SLI had speci®c di culties in processing clitic pronouns, while verbal agreement could be processed (word order4verbal agreement4clitic pronoun). This pattern seems to be a speci®c strategy and not simply a delayed pro®le. In addition, our results were compatible with a theoretical account in terms of limitation in processing capacities. [less ▲]

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See detailCompetition Policy and the Euromed Partnership
Petit, Nicolas ULg; Geradin, Damien

in European Foreign Affairs Review (2003)

This paper seeks to provide a critical assessment of the efforts made by the EC to stimulate the development of competition laws in the Mediterranean countries with which it is engaged in partnership ... [more ▼]

This paper seeks to provide a critical assessment of the efforts made by the EC to stimulate the development of competition laws in the Mediterranean countries with which it is engaged in partnership agreements. It reviews the content of the competition provisions of the association agreements, as well as their effectiveness. In then examines the regular calls for convergence on the EC competition law model to which Mediterranean countries are object. There is indeed room for debate regarding the opportunity, as well as the nature of such convergence. The paper concludes that a deep convergence approach, whereby the non-candidate Partner countries would transpose EC competition rules in their domestic legal order, would provide many benefits for both the EC and these countries. [less ▲]

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See detailDecidability of invariant validation for paramaterized systems
Fontaine, Pascal; Gribomont, Pascal ULg

in Lecture Notes in Computer Science (2003), 2619

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See detailIsokinetic profile of javelin throwers and relationship to field tests
Forthomme, Bénédicte ULg; Croisier, Jean-Louis ULg; Forthomme, L. et al

in Vlaams Tijdschrift voor Sport Geneeskunde & Sport Wetenschappen (2003), 95

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See detailComment j'explore ... un trouble de la magnésémie
Boman, Xavier ULg; Guillaume, Thierry; Krzesinski, Jean-Marie ULg

in Revue Médicale de Liège (2003), 58(2), 104-108

Magnesium (Mg) therapy is often proposed against stress and to correct asthenia. Thus our aim has been to review the role of Mg, the mechanisms of its homeostasis before detailing the clinical ... [more ▼]

Magnesium (Mg) therapy is often proposed against stress and to correct asthenia. Thus our aim has been to review the role of Mg, the mechanisms of its homeostasis before detailing the clinical presentations and etiologies of hypo- and hypermagnesemia and their exploration. Hypomagnesemia frequently occurs but is clinically rarely recognized without biological serum ionic determinations because causing atypical signs miming those of other ion deficiencies. Hypermagnesemia is uncommon but often occurs in the presence of renal insufficiency especially with excess of Mg administration. [less ▲]

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See detailComment je traite ... les troubles de la magnésémie
Guillaume, Thierry; Krzesinski, Jean-Marie ULg

in Revue Médicale de Liège (2003), 58(7-8), 465-467

Because symptoms associated with hypomagnesia are highly aspecific, this ionic abnormality is rarely searched for although it could be present in as much as 20 % of the population. The mode of correction ... [more ▼]

Because symptoms associated with hypomagnesia are highly aspecific, this ionic abnormality is rarely searched for although it could be present in as much as 20 % of the population. The mode of correction (oral or intravenous) depends on the etiology, severity and clinical consequences of hypomagnesemia. Significant hypermagnesemia only occurs in the presence of renal insufficiency and/or acute excess administration, mainly by the intravenous route. If interruption of administration does not suffice, renal dialysis might become necessary to quickly correct the magnesemium serum levels. [less ▲]

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