Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells, primarily in the bone marrow (BM). The role of the BM microenvironment in the pathogenesis of the ...disease has been demonstrated, especially for the survival and growth of the myeloma plasma cells. Functional characterization of the major component of the BM microenvironment, namely the recently characterized mesenchymal stem cells (MSCs), was never performed in MM. Based on a series of 61 consecutive patients, we evaluated the ability of MSCs derived from myeloma patients to differentiate into adipocytes and osteocytes, inhibit T-cell functions, and support normal hematopoiesis. MSCs phenotypic characterization and quantification of interleukin-6 (IL-6) secretion were also performed. As compared to normal MSCs, MSCs from MM patients exhibited normal phenotype, differentiation capacity and long-term hematopoietic support, but showed reduced efficiency to inhibit T-cell proliferation and produced abnormally high amounts of IL-6. Importantly, these characteristics were observed in the absence of any detectable tumor plasma cell. Chromosomal analysis revealed that MM patients MSCs were devoid of chromosomal clonal markers identified in plasma cells. MM MSCs present abnormal features that may participate in the pathogenesis of MM.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
La nécessité d’adapter les pratiques de gestion des concentrés érythrocytaires en blocs opératoires et réanimations à l’évolution du cadre législatif réglementaire a généré une démarche collective ...d’amélioration des pratiques. Réunis sous l’impulsion des coordonnateurs régionaux d’hémovigilance de la Drass Île-de-France, des représentants de prescripteurs de transfusions, correspondants d’hémovigilance de huit hôpitaux de l’Assistance publique–Hôpitaux de Paris et représentants de l’EFS Île-de-France, en présence de représentants de l’Agence française de sécurité sanitaire des produits de santé (Afssaps), ont coordonné une évaluation des pratiques locales des activités transfusionnelles des blocs opératoires et services de réanimation devant se mettre en conformité. Chaque hôpital a ensuite proposé des actions d’amélioration locales, validées par les instances régionale et nationale. Nous présentons cette démarche originale de travail collectif d’évaluation des pratiques aboutissant à des propositions d’amélioration pour répondre à une mise en conformité réglementaire tout en gérant au mieux les flux de produits sanguins sans mettre en jeu la sécurité transfusionnelle.
The need to adapt red blood cells concentrates management in surgery blocs and resuscitation to the changes of the legal framework has lead to a collective approach to improve practices. Gathered by the regional hemovigilance coordinators of the Drass Île-de-France (regional office of health and social actions), representatives of doctors’ ordering transfusions and hemovigilance correspondents of the Assistance publique–Hôpitaux de Paris and representatives of the EFS (French blood establishment) Île-de-France, together with representatives of the Afssaps (French health products safety agency), have coordinated an assessment of local transfusion practices in surgery blocs and resuscitation that have to be compliant. Each hospital then offered local improvement actions, approved by regional and national instances. We present this original and collective approach of assessing practices leading to offers that both respond to a legal framework and improve blood products flows without damaging transfusion security.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and ...infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9+/-18.6 and 98.0+/-36.5%, respectively. Mean cell viability was 68.25+/-18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This phase I trial was designed to assess the feasibility and safety of autologous skeletal myoblast transplantation in patients with severe ischemic cardiomyopathy.
Experimentally, myoblast grafting ...into postinfarction myocardial scars improves left ventricular function.
Ten patients were included on the basis of the following criteria: 1) severe left ventricular dysfunction (ejection fraction ≤35%); 2) the presence of a postinfarction akinetic and nonviable scar, as assessed by dobutamine echocardiography and 18-fluorodeoxyglucose positron emission tomography; and 3) an indication of coronary bypass in remote areas. Skeletal myoblasts were grown from a biopsy taken at the thigh.
An average of 871 × 106cells (86% of myoblasts) were obtained after a mean period of 16 days and implanted uneventfully across the scar at the time of bypass. Except for one patient whose early death was unrelated to the cell transplantation, all patients had an uncomplicated postoperative course. Four patients showed delayed episodes of sustained ventricular tachycardia and were implanted with an internal defibrillator. At an average follow-up of 10.9 months, the mean New York Heart Association functional class improved from 2.7 ± 0.2 preoperatively to 1.6 ± 0.1 postoperatively (p < 0.0001), and the ejection fraction increased from 24 ± 1% to 32 ± 1% (p < 0.02). A blinded echocardiographic analysis showed that 63% of the cell-implanted scars (14 of 22) demonstrated improved systolic thickening. One noncardiac death occurred 17.5 months after transplantation.
These preliminary data suggest the feasibility and safety of autologous skeletal myoblast transplantation in severe ischemic cardiomyopathy, with the caveat of an arrhythmogenic potential. New-onset contraction of akinetic and nonviable segments suggests a functional efficacy that requires confirmation by randomized studies.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
L'évolution des caractéristiques hématologiques et biochimiques des hématies prélevées chez deux patients
sickle cell (SC) a été comparée á celle de témoins normaux, en vue d'évaluer la faisabilité ...d'une transfusion autologue chez un patient poly-immunisé, drépanocytaire hétérozygote composite SC. Les concentrés érythrocytaires ont été conservés sur SAG Mannitol á + 4 °C. La conservation par congélation et des épreuves isotopiques de recirculation ont été réalisées chez un des patients. Les paramètres hématologiques et biochimiques des globules rouges SC et des témoins AA ont une évolution comparable au cours de la conservation á + 4 °C. Les épreuves de recirculation d'un des patients, réalisées respectivement sur les hématies fraîches, conservées 42 jours á + 4 °C et décongelées, montrent une demi-vie nettement diminuée par rapport á la demi-vie moyenne des globules rouges normaux: 11,6 jours pour les hématies fraîches, 20 heures et 13 jours pour les deux populations des hématies conservées á + 4 °C, 12 heures et 14 jours pour les hématies décongelées. Avant toute mise en pratique, nos résultats doivent être confirmés par d'autres essais chez des patients hétérozygotes composites SC.
In order to evaluate the feasibility of the autologous transfusion in an alloimmunized sickle cell patient, changes in the hematologic and biochemical characteristics of erythrocytes stored for 42 days from two patients with sickle cell SC anemia were compared with control subjects' (Hb A) red blood cells. Erythrocytes were stored in Saline Adenosine Dextrose Mannitol at + 4° C. The cryopreservation storage was made and
51Cr red cell survival was measured in one patient. No significant difference in the hematologic and biochemical parameters of the SC red blood cells and the control subjects was observed during the storage at + 4°C. Red cell survivals determined in fresh cells, cells stored for 42 days at + 4°C and thawed cells from one patient demonstrate much shorter half-life values than those of normal red blood cells. Before application, our results need to be confirmed by the same protocol with another patient with sickle cell SC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background The incidence and potential clinical consequences of bacterial contamination of autologous and allogeneic BM products remains open to question. We report our experience of bacterial ...contamination of BM grafts and adverse events that occurred after transplantation. Methods From January 2003 to February 2006, 257 BM harvests were processed and infused at our institution. Analysis of microbial contamination incidence before and after processing, sensitivity spectra of isolated bacteria and adverse events after graft infusion were analyzed. Results Nineteen of 257 BM (7.4%) were contaminated. Coagulase-negative Staphylococcus ( n = 9) and Propionibacterium acnes ( n = 6) were the most frequently isolated microorganisms. Two of nine coagulase-negative staphylococci were found to be resistant to erythromycin and two of six P. acnes to fosfomycin and gentamycin. The frequency and severity of immediate adverse events reported in patients receiving a contaminated graft were similar to those observed in patients receiving a non-contaminated product. No major adverse sequelae occurred after infusion of contaminated grafts. Finally, none of the patients transplanted with a contaminated graft developed bacteriemia that could have been related to the isolated microorganism. Discussion Microbial contamination of BM progenitor cell grafts does not induce severe clinical complications or infectious diseases after infusion. The vast majority of isolated pathogens were skin contaminants.
Full text
Available for:
DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UKNU, UL, UM, UPCLJ, UPUK
Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic ...venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.
This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.
Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (
P = .94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.
Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The need to adapt red blood cells concentrates management in surgery blocs and resuscitation to the changes of the legal framework has lead to a collective approach to improve practices. Gathered by ...the regional hemovigilance coordinators of the Drass Ile-de-France (regional office of health and social actions), representatives of doctors' ordering transfusions and hemovigilance correspondents of the Assistance publique-Hôpitaux de Paris and representatives of the EFS (French blood establishment) Ile-de-France, together with representatives of the Afssaps (French health products safety agency), have coordinated an assessment of local transfusion practices in surgery blocs and resuscitation that have to be compliant. Each hospital then offered local improvement actions, approved by regional and national instances. We present this original and collective approach of assessing practices leading to offers that both respond to a legal framework and improve blood products flows without damaging transfusion security.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND: Recently, cases of chronic hepatitis were linked to the presence of genomic sequences of a newly described RNA virus termed hepatitis G virus (HGV) and belonging to the Flaviviridae ...family. STUDY DESIGN AND METHODS: The presence of HGV RNA was searched for by polymerase chain reaction in a population of blood donors and in patients who had received multiple blood component transfusions and/or intravenous immunoglobulin (IVIG) infusions. RESULTS: Twenty‐one (4.2%) of 500 donors were positive for HGV RNA as were 21 (10.7%) of 196 nonimmunosuppressed patients who had received multiple transfusions of packed red cells, 4 (8.7%) of 46 common variable immune deficiency (CVID) patients who had received only IVIG, and 22 (24.7%) of 89 bone marrow transplant (BMT) patients who had received IVIG and cellular components. The proportion of HGV‐positive individuals was significantly higher in the immunosuppressed recipients (CVID and BMT patients) than in the nonimmunosuppressed patients who were multiply transfused with packed red cells (p < 0.03). The proportion of HGV‐ positive individuals was significantly higher in the BMT patients who had received IVIG and cellular components than in the CVID patients who had received IVIG only (p < 0.03). Eight (17.0%) of the 47 HGV‐positive recipients and 48 (16.9%) of the 284 HGV‐negative recipients had a serum alanine aminotransferase level higher than the upper limit of normal (nonsignificant difference). The medical history of HGV‐positive donors failed to reveal a particular at‐risk event. The large majority of HGV‐infected patients had a normal serum alanine aminotransferase level, and the proportion of patients with elevated alanine aminotransferase was the same in HGV‐positive and in HGV‐negative recipients. CONCLUSION: The pathological significance of HGV infection remains unelucidated, and the classification of HGV as a new hepatitis virus was perhaps premature.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Our aim was to obtain a viable and easily available dermal substitute (DS) for the definitive coverage of full-thickness burns. A DS composed of a collagen–glycosaminoglycan–chitosan dermal matrix ...(DM) colonized with foreskin fibroblasts (FF) is described. FF-colonized DS were compared to the DM seeded with adult dermal fibroblasts (DF). FF-colonized DS expressed more fibrillin and tropoelastin than that with DF. Reconstructed skin obtained with both FF- and DF-colonized DS similarly expressed laminin-5 and collagen VII at the dermal–epidermal junction. Both FF- and DF-colonized DS produced cutaneous wound healing mediators in a dose-dependent manner in the presence of platelet lysate. After freeze-thawing, the FF-colonized DS were recovered in culture and retained their ability to produce vascular endothelial growth factor. Grafting of DS into nude rats achieved a complete healing of a dermal–epidermal lesion with a good epidermalization.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
