Post-operative erythropoiesis is limited by the inflammatory effect of surgery on iron metabolism.
; ; Beguin, Yves et al
in European Journal of Clinical Investigation (1995), 25(6), 383-9
The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood-transmissible ... [more ▼]
The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood-transmissible diseases has led to the restrictive use of homologous blood and to interest in alternatives for correcting anaemia. We investigated the pathophysiology of postoperative anaemia by studying variables of erythropoiesis, iron metabolism, and inflammation in 48 consecutive patients who underwent total hip replacement. Haemoglobin concentration remained low during 14 days after surgery with only a mild increase in erythropoietin concentration and reticulocyte count. No increase in serum transferrin receptor concentration was observed during the first 2 weeks after surgery. Postoperative serum ferritin increased, whereas serum iron, transferrin and transferrin saturation decreased significantly. There was a marked increase in interleukin-6 and C-reactive protein with maximal values on the 1st and 4th post-operative day, respectively. At 6 weeks after surgery, haemoglobin concentration and variables of iron metabolism were almost at the preoperative level and serum transferrin receptor concentration was significantly increased, indicating increased erythropoietic activity. These changes were preceded by the normalization of interleukin-6 and C-reactive protein levels. Haemoglobin, iron, transferrin, and ferritin concentrations were not influenced by iron therapy during the postoperative period and no differences of erythropoietic and iron variables were observed between transfused and non-transfused patients. In conclusion, post-operative erythropoiesis is associated with an inflammatory effect of surgery on iron metabolism, which can explain, despite a slightly increased production of erythropoietin, the persistence of anaemia and the lack of effect of iron supplementation after surgery. [less ▲]Detailed reference viewed: 17 (2 ULg)
Serum erythropoietin during autologous bone marrow transplantation: relationship to measures of erythroid activity.
; ; et al
in Clinical & Laboratory Haematology (1995), 17(2), 139-44
Marked elevation of serum erythropoietin (sEPO) occurs following high dose chemotherapy for malignant disease. It has been proposed that the subsequent fall in sEPO constitutes a relative erythropoietin ... [more ▼]
Marked elevation of serum erythropoietin (sEPO) occurs following high dose chemotherapy for malignant disease. It has been proposed that the subsequent fall in sEPO constitutes a relative erythropoietin (EPO) deficiency, prompting trials of recombinant EPO to reduce red cell transfusion during chemotherapy. We have investigated these phenomena by serial estimations of reticulocytes and sEPO in 11 autologous marrow transplant recipients. sEPO reached two to five times baseline 0 to 5 days after transplant but the inverse relationship between sEPO and haematocrit was maintained. Observed to expected log sEPO (Epo ratio) rose and fell in parallel with sEPO, remaining greater than 1.0 throughout. A progressive fall in reticulocyte count during chemotherapy was followed by an increase during engraftment. The strong inverse relationships between reticulocytes and Epo ratio in the 10 days after initiating chemotherapy support the hypothesis that loss of EPO-receptor bearing erythroid precursors allows a rise in sEPO during chemotherapy. The elevation of Epo ratio levels during engraftment indicates that it is the availability of EPO-sensitive progenitors, rather than the supply of EPO, that limits the rate of resumption of erythropoiesis after high-dose chemotherapy. [less ▲]Detailed reference viewed: 9 (1 ULg)
Pure red cell aplasia following peripheral stem cell transplantation: complete response to a short course of high-dose recombinant human erythropoietin.
; ; Beguin, Yves et al
in Haematologica (1994), 79(5), 456-9
We studied a patient who developed pure red cell aplasia (PRCA) following peripheral stem cell transplantation for non-Hodgkin lymphoma. Serum erythropoietin was appropriate for the degree of anemia ... [more ▼]
We studied a patient who developed pure red cell aplasia (PRCA) following peripheral stem cell transplantation for non-Hodgkin lymphoma. Serum erythropoietin was appropriate for the degree of anemia. Corticosteroid treatment was ineffective. Four months after transplantation rHuEpo was administered subcutaneously at a dose of 150 U/Kg per day, five days a week for 8 weeks. Treatment induced an erythropoietic response and corrected anemia. Response was maintained following discontinuation of rHuEpo. This study and previous reports indicate that high doses of rHuEpo given over a short time can resolve PRCA following autologous or allogeneic stem cell transplantation. [less ▲]Detailed reference viewed: 18 (0 ULg)
Defective Epo production contributes to anemia persistent after ARF in nephropathia epidemica (NE)
; ; Beguin, Yves
in Papadimitriou & Alexopoulos (Ed.) Proceedings of the 3rd International Satellite Symposium on Acute Renal Failure (1994)Detailed reference viewed: 14 (1 ULg)
Estimation of effective and total erythropoiesis in myelodysplasia using serum transferrin receptor and erythropoietin concentrations, with automated reticulocyte parameters.
; ; Beguin, Yves et al
in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (1994), 8(1), 151-5
The erythroid abnormality in patients with myelodysplasia (MDS) is multifactorial, with ineffective erythropoiesis and poor in vitro progenitor response to erythropoietin (EPO). Serum EPO concentration is ... [more ▼]
The erythroid abnormality in patients with myelodysplasia (MDS) is multifactorial, with ineffective erythropoiesis and poor in vitro progenitor response to erythropoietin (EPO). Serum EPO concentration is variable among patients for a given haemoglobin concentration. We studied 19 non-transfusion-dependent patients with MDS, and 13 healthy elderly control subjects in an attempt to define the factors governing variability in serum EPO and to further characterise the anaemia of MDS. Serum EPO concentration was appropriate for the degree of anaemia in 15/19 MDS patients, and was positively related to mean cell volume (MCV), mean cell haemoglobin (MCH), and percentage highly fluorescent reticulocytes (% HFR), but not to absolute or percentage reticulocyte count. Although the observed/predicted ratio for serum transferrin receptor (TfR) concentration was low in 12 of 19 MDS subjects, no relationship to haemoglobin concentration, reticulocytes or serum EPO was seen. Serum TfR was positively correlated with WBC and platelet counts. Serum TfR was higher in patients with sideroblastic anaemia than refractory anaemia. Standardized in vivo p50 was positively correlated to red cell 2,3 diphosphoglycerate concentration, although this was not the only factor influencing the oxygen dissociation curve. We conclude that effective erythroid output responsive to endogenous EPO drive in MDS is positively related to MCV, MCH and % HFR. Serum TfR may not represent effective output as precisely as % HFR, but may be proportional to total marrow erythropoietic activity. [less ▲]Detailed reference viewed: 37 (1 ULg)
Use of recombinant human erythropoietin after bone marrow transplantation in pediatric patients with acute leukemia: effect on erythroid repopulation in autologous versus allogeneic transplants.
; ; et al
in Bone Marrow Transplantation (1994), 13(4), 403-10
We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) in children undergoing allogeneic or mafosfamide-purged autologous BMT for ALL or AML. rHuEPO was administered ... [more ▼]
We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) in children undergoing allogeneic or mafosfamide-purged autologous BMT for ALL or AML. rHuEPO was administered intravenously at a dose of 75 U/kg/day for 30 days after transplant. Ten rHuEPO-treated patients receiving allogeneic BMT and 10 given autologous BMT were compared with 15 allogeneic and 10 autologous historical controls. Endogenous EPO production was appropriate for the degree of anemia after autologous BMT. In these patients, rHuEPO did not accelerate erythroid repopulation and did not modify transfusion requirements. With allogeneic BMT, erythroid marrow activity increased faster in patients given rHuEPO than in controls and resulted in higher red cell production, the mean reticulocyte count on day +30 being 187 +/- 51 x 10(9)/l in treated patients versus 107 +/- 63 x 10(9)/l in controls (p < 0.01). The total number of RBC units administered was 1.7 +/- 1.3 in the rHuEPO group versus 5.1 +/- 3.0 in the control group (p < 0.001). The total number of platelet transfusions was 4.0 +/- 2.3 for patients given allogeneic BMT and receiving rHuEPO versus 8.4 +/- 6.8 for historical controls (p < 0.05) whereas it was similar in rHuEPO-treated and control autologous BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 11 (1 ULg)
Erythropoietic activity and iron metabolism in autologous blood donors during recombinant human erythropoietin therapy.
; ; Beguin, Yves et al
in European Journal of Clinical Investigation (1994), 24(6), 426-32
The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 ... [more ▼]
The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 U kg-1 body weight twice weekly during a 3 week period) on variables of erythropoiesis and iron metabolism in 62 autologous blood donors, of whom 32 received rhEPO (epo group) and 30 did not (control group). Patients donated only 2 units of blood and received oral iron in order to restrict phlebotomy-induced decrease of iron stores. Pre-phlebotomy haemoglobin concentration (14.0 +/- 0.8 g dl-1) was completely regenerated in the epo group at surgery (13.7 +/- 1.3 g dl-1); haemoglobin concentration in the control group fell from 13.5 +/- 1.4 g dl-1 to 11.6 +/- 1.4 g dl-1 after the phlebotomies and did not improve during the pre-operative phase. Total erythropoietic activity expressed as serum transferrin receptor concentration (sTfR) showed a 4-fold increase from 3.8 +/- 0.9 micrograms ml-1 to 14.9 +/- 4.8 micrograms ml-1 in the epo group. Effective erythropoietic activity measured by absolute reticulocyte count, however, declined after the fourth rhEPO injection in the epo group. Serum ferritin was lower in the epo group, but no differences in serum iron, transferrin concentration and transferrin saturation were observed between the groups. A marked increase in free erythrocyte protoporphyrin (FEP) was observed in the epo group, whereas FEP levels in the controls remained within normal ranges. Despite oral iron supplementation and the limited number of phlebotomies, the effect of rhEPO therapy in autologous donors is restricted by iron depletion. [less ▲]Detailed reference viewed: 33 (3 ULg)
Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation.
; ; et al
in Bone Marrow Transplantation (1994), 14(6), 929-35
We carried out a pilot study to evaluate the combined use of recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children ... [more ▼]
We carried out a pilot study to evaluate the combined use of recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children given allogeneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Using analysis of variance, laboratory and clinical data referring to these children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid repopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receiving rhEpo alone and in those receiving combined treatment. These latter, however, showed a further reduction in the total number of red blood cell units required to reach transfusion independence (1.1 +/- 0.7 in the study population vs 2.7 +/- 1.2 in rhEpo group vs 4.2 +/- 2.3 in historical controls; values are mean +/- 1 SD; p < 0.001). Neutrophil engraftment, i.e. time for neutrophils to reach 0.5 x 10(9)/l, was 11 +/- 3 days in children receiving combined treatment, significantly shorter than that of the control groups (16 +/- 3 and 18 +/- 5, respectively; p < 0.001). Acceleration of neutrophil recovery translated into fewer infections: days of fever were significantly reduced in the study population (4 +/- 2 vs 11 +/- 8 vs 15 +/- 6, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 14 (1 ULg)
Effect of recombinant human erythropoietin on platelets in patients with anemia of renal failure: correlation of platelet count with erythropoietic activity and iron parameters.
Beguin, Yves ; ; R'Zik, Samir et al
in European Journal of Haematology (1994), 53(5), 265-70
We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1 ... [more ▼]
We examined the effect of treatment with rHuEpo on platelet counts in 61 hemodialysis patients and correlated them with changes in erythropoietic activity, iron status and inflammation. Platelets (10(9)/1) increased from 220 +/- 80 to 245 +/- 102 after 14 days and stabilized at that level up to day 90 (p < 0.0001). The increment was similar in complete or partial responders but was not observed in failures. Serum transferrin receptor (sTfR, a measure of total erythropoiesis) and Het rose much more progressively, but relative platelet increments correlated with relative increases in sTfR and Hct. Relative platelet increments correlated inversely with relative changes of SeFe or transferrin saturation, but not with their absolute values, nor with baseline ferritin or its progressive decrease. Although baseline platelet count was 12% higher in patients with inflammation and correlated with serum haptoglobin, relative increases were similar in patients with or without inflammation. In conclusion, rHuEpo produced a clinically minor but consistent elevation of platelet counts. These modifications were not related primarily to modifications in iron stores, functional iron deficiency, or inflammation, but paralleled the expansion of erythropoietic activity. The results suggest that rHuEpo has a small positive effect on platelet production, but it cannot be ruled out that this could be partially mediated through functional iron deficiency. [less ▲]Detailed reference viewed: 12 (2 ULg)
Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with chronic lymphocytic leukemia.
Beguin, Yves ; ; et al
in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (1993), 7(12), 2019-2025
We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL ... [more ▼]
We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL) and evaluated them in relation to clinical and biological parameters of the disease, as well as serum immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001), sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/- 11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234 +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic), Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma, or solid tumors. Advancing Rai clinical stage was associated with a progressive elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis confirmed the value of soluble receptor determinations in the clinical evaluation of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS) and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001), sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001) and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced consistent reductions of sCD23 levels in two responding patients. We conclude that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass and clinical stage, and could be helpful in monitoring these patients; and (ii) sIL-2R, sCD8, and sTfR levels are less specifically increased and could be influenced by other factors such as immune activation and erythropoiesis. [less ▲]Detailed reference viewed: 86 (3 ULg)
Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin.
Beguin, Yves ; ; et al
in Blood (1993), 81(4), 1067-76
We evaluated the quantitative value of a simple model of erythropoiesis, based on the basic assumptions that the red blood cell (RBC) mass determines erythropoietin (Epo) production, which in turn ... [more ▼]
We evaluated the quantitative value of a simple model of erythropoiesis, based on the basic assumptions that the red blood cell (RBC) mass determines erythropoietin (Epo) production, which in turn stimulates erythropoietic activity. The RBC mass was quantitated by direct isotopic measurement (RCM), Epo production by serum Epo levels, and erythropoiesis by the ferrokinetic measurement of the erythron transferrin uptake (ETU), the serum transferrin receptor (TfR) level, and the reticulocyte (retic) index, and was completed by an evaluation of overall marrow erythron cellularity. We studied a total of 195 subjects, including 31 normal individuals, 38 patients with polycythemia, and 126 patients with various forms of anemia. Instead of only quantitating Epo and erythropoiesis in absolute terms, we also evaluated them in relation to the degree of anemia or polycythemia, and expressed the results as a ratio of observed values to values predicted from the regression equations between hematocrit (Hct) on the one hand, and Epo, TfR, and ETU on the other, obtained in a carefully selected subpopulation. The slope of the regression of TfR (as well as ETU) versus Hct was very similar to the slope of the regression of Epo versus Hct. Average EPO and TfR (as well as ETU) values predicted from the regression equations were quite comparable to observed values in most groups of subjects, with exceptions predictable from knowledge of the pathophysiology of these hematologic disorders. We identified four major patterns of erythropoiesis, ie, normal, hyperdestruction (with variants of hemolysis or ineffective erythropoiesis), intrinsic marrow hypoproliferation, and defective Epo production. Dissecting out groups of patients showed much greater heterogeneity than when patients were analyzed by group. This was particularly true in the case of a hypoproliferative component being combined with hyperdestruction, giving what we called a "mixed disorder of erythropoiesis." We conclude that the pathophysiology of anemia can be assessed by a simple measurement of Hct, retic index, Epo, and TfR levels, with Epo and TfR being more informative when expressed in relation to the degree of anemia. The model is particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient. However, it has limitations inherent to the relative invalidity of TfR in iron deficiency, the imprecision of a retic count, and the difficulty in distinguishing hemolysis from ineffective erythropoiesis in some patients and in recognizing a component of hyperdestruction in hypoproliferative anemia. [less ▲]Detailed reference viewed: 31 (1 ULg)
Dynamics of erythropoietic recovery following bone marrow transplantation: role of marrow proliferative capacity and erythropoietin production in autologous versus allogeneic transplants.
Beguin, Yves ; Oris, Renée ; Fillet, Georges
in Bone Marrow Transplantation (1993), 11(4), 285-92
The mechanisms of erythrocyte recovery after BMT are not known. We investigated the respective role of marrow function and erythropoietin production in 31 ABMT and 47 allogeneic BMT by analysing ... [more ▼]
The mechanisms of erythrocyte recovery after BMT are not known. We investigated the respective role of marrow function and erythropoietin production in 31 ABMT and 47 allogeneic BMT by analysing peripheral counts, serum erythropoietin levels, and serum transferrin receptor (TfR) levels which have been shown to be a quantitative measurement of erythropoiesis. Median times to complete neutrophil (25 vs 48 days, p < 0.0001) and platelet (45 vs 263 days, p < 0.001) recovery were faster after allogeneic BMT than ABMT, but complete erythrocyte recovery was slower (218 vs 101 days, p < 0.001). After ABMT, erythrocyte recovery paralleled that of neutrophils and platelets, and erythropoietin levels remained appropriate for the degree of anemia. After allogeneic BMT, erythrocytes developed independently of the other cell lines and defective erythropoietin production delayed recovery of adequate erythropoietic activity. This correlated with an alteration of renal function only in those patients remaining erythropoietin deficient beyond day 180. However, supranormal erythropoietin levels in interstitial pneumonia suggests that erythropoietin response to hypoxia is not abrogated. CMV infection could also affect erythropoiesis through erythropoietin production after ABMT as well as allogeneic BMT. It is concluded that after ABMT the development of erythropoiesis is determined by the overall marrow proliferative activity and erythropoietin plays only a facilitating role. After allogeneic BMT, erythropoiesis depends on erythropoietin levels which remain inadequate for prolonged periods of time. The results suggest that the administration of recombinant human erythropoietin could reduce transfusion requirements after BMT. [less ▲]Detailed reference viewed: 29 (2 ULg)
Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation.
; ; Beguin, Yves et al
in British Journal of Haematology (1993), 84(4), 752-4
We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered ... [more ▼]
We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect. [less ▲]Detailed reference viewed: 14 (1 ULg)
Mesures quantitatives de l'erythropoiese. Le recepteur soluble de la transferrine.
in Bulletin et Mémoires de l'Académie Royale de Médecine de Belgique (1993), 148(1-2), 100-4105-7
Iron transport in plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor. The soluble form of the transferrin receptor has been ... [more ▼]
Iron transport in plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor. The soluble form of the transferrin receptor has been identified in plasma. Dosage of the soluble receptor represents a simple, reliable, quantitative assay of erythropoiesis, which should replace the standard ferrokinetic measurement. Using this dosage, it is now possible to investigate the pathophysiology of anemia in many conditions, and to analyze the erythropoietic response to treatment with recombinant erythropoietin. [less ▲]Detailed reference viewed: 50 (1 ULg)
Purification, expansion, and multiple fluorochrome labeling of cord blood hemopoietic precursors: preliminary results.
; Gothot, André ; Grosdent, Jean-Claude et al
in Journal of Hematotherapy (1993), 2(2), 259-61
CD34-positive cells were isolated from a total of 23 cords using CellPro Ceprate columns. AIS MicroCellector flasks, and panning. The cells were (1) expanded in serum-free culture supplemented with a ... [more ▼]
CD34-positive cells were isolated from a total of 23 cords using CellPro Ceprate columns. AIS MicroCellector flasks, and panning. The cells were (1) expanded in serum-free culture supplemented with a variety of combinations of cytokines and (2) immunophenotyped using multiple fluorochrome labeling. The results indicated that the avidin column produced the highest purity of CD34-positive cells, and that immature blast cells could be expanded in serum-free culture. Preliminary results suggested that the four fluorochrome labeling technique may provide useful information on the lineage commitment of cord blood precursor and blast cells. [less ▲]Detailed reference viewed: 22 (1 ULg)