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Background Regarding blood safety, transfusion-transmitted bacterial infection (TTBI) remains the most frequent infectious risk. The incidence of these episodes needs to be assessed and updated frequently to accurately manage this risk. Study Design and Methods TTBIs were reported by the French network of local correspondents in each hospital and blood center. The regional coordinator managed the investigation. A multidisciplinary expert group from the French National Agency of Medicine and Health Products Safety (ANSM) analyzed each TTBI according to a standardized scale of imputability and severity. Only cases with likely or certain imputability are reported in this study. Results In France, 18.0 × 106 red blood cell (RBC) products, 1.94 × 106 platelet concentrates (PCs), and 2.44 × 106 fresh-frozen plasma units were transfused throughout 2000 to 2008. The incidence of TTBI was 2.45, 24.7, and 0.39 per million blood components (BCs), PCs, and RBCs, respectively. For PCs, the incidences of severe (vital threat or death) and fatal TTBI were 13.4 and 5.14 per million, respectively. PCs were responsible for 87% of TTBIs. A total of 66.7% of the implicated bacteria were Gram positive, most of them belonging to the normal skin flora. A total of 33.3% of the other implicated bacteria were Gram negative. Conclusion The French hemovigilance system provides an accurate estimate of the TTBI incidence during a period with diversion and improving skin disinfection but without bacterial detection screening. This tool would be able to evaluate further additional safety procedures like bacterial screening and pathogen reduction technology.

In order to help the analysis of adverse effects of transfusion, factsheets have been written by working groups of the French agency for the safety of health products ANSM. Each factsheet deals with a blood transfusion side effect and is composed of five parts, including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules for filing the notification form to ANSM. Since 2006, 11 factsheets have been published on the French haemovigilance network website. The major characteristics of the two last sheets published "post-transfusion purpura" and "non erythrocyte incompatibility reaction" are presented, followed by the updated card for "allergy". These factsheets give relevant guidelines allowing better evaluation of recipients' adverse reactions, particularly their diagnosis, severity and accountability. They also could initiate studies among European and international haemovigilance networks.

A working group of the French National Hemovigilance Committee has been in charge of heightening awareness of Transfusion-Associated Circulatory Overload (TACO) among physicians and nurses. This multidisciplinary group has produced the present document that focuses on epidemiological data provided by the French haemovigilance network, physiopathology, diagnosis, treatment and specific actions that could prevent or minimize the risk of TACO.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related mortality and morbidity. Epidemiologic studies using data from national transfusion schemes can help achieve a better understanding of TRALI incidence. STUDY DESIGN AND METHODS: A multidisciplinary working group analyzed TRALI cases extracted from the French Hemovigilance Network Database (2007-2008). All notified cases were reviewed for diagnosis. Those meeting the Canadian Consensus Conference criteria for TRALI were classified according to imputability to transfusion and clinical severity. Patient data (clinical characteristics, number and types of products transfused, and serology results) were obtained. RESULTS: There were 62 TRALI cases and 23 possible TRALI cases during the 2-year period. An immune-mediated mechanism was identified in 30 of 50 TRALI cases with complete serology. TRALI was considered to be the cause of death in 7.1% of patients and might have contributed to death in an additional 9.4% of TRALI or possible TRALI patients. Occurrence ranked high in obstetrics (15%), after surgery (34%), and in hematologic malignancies (21%). Single-donor high-plasma-volume components were involved in half of the cases where the implicated blood product could be determined and carried the highest risk per component (1:31,000 for single-donor fresh-frozen plasma units and apheresis platelet [PLT] concentrates, and 1:173,000 for red blood cells). No incident could be definitively related to the transfusion of solvent/detergent-treated pooled plasma (>200,000 units transfused), nor to pooled PLT concentrates. CONCLUSION: The proportion of TRALI cases related to plasma-rich components was lower than previously described.

Safety in the field of transfusion medicine has greatly improved in France. The risk of viral transmission has decreased by a factor greater than 1500 within the last 20 years. In comparison, the risk related to ABO error has decreased only by half. The reporting of critical incidents, which occur at any step of the transfusion procedure is now mandatory in France and is subject to an in-depth analysis, using methods close to that used in aviation safety. The goal of these analyses is to better understand human factors in order to implement more adequate prevention measures.

Due to regulations, hospital blood banks have to equip them with a computer-based information system. This system facilitates the management of the blood bank and ensures the safety of the storage, issuing and traceability of the blood and blood components. It permits to create a medical file for each transfused patient, which contains the characteristics of the blood components transfused and the immunohematological status of the patient, received by electronic data interchange from the blood establishment. Thus, from the assistance to the prescription of blood transfusion to the issuing and traceability of the blood components, the computer-based information system is the guarantee of the transfusion security in a hospital blood bank.

Pulmonary oedema after transfusion of blood products may be hydrostatic (transfusion-associated circulatory overload [taco]) or exsudative (transfusion-related acute lung injury [trali]). Both conditions have been recognized as major hazards to transfusion recipients. Risk characterization is necessary to improve safety and to monitor trends in the national blood transfusion system. A collaborative multidisciplinary working group of the French National Hemovigilance Committee has proposed an analysis framework for case definitions and classification. The method relies on internationally used definitions and is adapted to the codification procedures used in the french transfusion incident reports electronic data management.

Since 1985, a Council Resolution defines a new approach to technical harmonization and standards. The directives resulting from this new approach establish the essential safety requirements with which products put on the market must conform, and which should therefore enjoy free movement throughout the European Union, owing to a presumption of conformity. However, if the manufacturer is responsible for the conformity of its product in terms of safety, it is the end-user who must make sure that its requirements for a specific use or a considered application are satisfied and that the product meets its needs. It is the objective of the procedure of validation, which calls upon protocols of qualification intended to show the aptitude of a material, a system, a device, of an installation, to meet the requirements of specified quality and safety. This concept of qualification applies to the data-processing software of the hospital blood banks. Only the stage of operational qualification will be developed here. It involves scenarios made up of test files which make it possible to check the electronic data interchanges between the hospital blood bank and the blood establishment (transmission of the results of analysis, transmission of the data of traceability), as well as the functions of assistance to the issuing of the labile blood products.

Les œdemes pulmonaires survenant pendant ou apres une transfusion figurent parmi les accidents graves les plus frequents, dans le systeme francais d'hemovigilance. Ils comportent les œdemes hemodynamiques (transfusion-associated circulatory overload [TACO]) et les œdemes lesionnels (transfusion-related acute lung injury [TPALI]). Les TACO representent actuellement une cause majeure de deces lors d'une transfusion en France. Les donnees d'hemovigilance sur le TRALI montrent qu'ils sont de plus en plus notifies. Dans la serie francaise, aucun TRALI n'est survenu apres transfusion de plasma poole SD. Un logigramme permettra de classer de maniere plus reproductible les œdemes pulmonaires dans la base e-fit.

Resume La necessite d’adapter les pratiques de gestion des concentres erythrocytaires en blocs operatoires et reanimations a l’evolution du cadre legislatif reglementaire a genere une demarche collective d’amelioration des pratiques. Reunis sous l’impulsion des coordonnateurs regionaux d’hemovigilance de la Drass Ile-de-France, des representants de prescripteurs de transfusions, correspondants d’hemovigilance de huit hopitaux de l’Assistance publique–Hopitaux de Paris et representants de l’EFS Ile-de-France, en presence de representants de l’Agence francaise de securite sanitaire des produits de sante (Afssaps), ont coordonne une evaluation des pratiques locales des activites transfusionnelles des blocs operatoires et services de reanimation devant se mettre en conformite. Chaque hopital a ensuite propose des actions d’amelioration locales, validees par les instances regionale et nationale. Nous presentons cette demarche originale de travail collectif d’evaluation des pratiques aboutissant a des propositions d’amelioration pour repondre a une mise en conformite reglementaire tout en gerant au mieux les flux de produits sanguins sans mettre en jeu la securite transfusionnelle.

SUMMARY: The French Hemovigilance Network has been established in 1994 and records all adverse events associated with the transfusion of a labile blood products (LBP) regardless of their severity. From 1994 to 2006 35,423,172 LBP were issued, 85,812 adverse transfusion reactions notified, and 139 cases of transfusion related acute lung injury (TRALI) observed. The LBP most at risk is fresh frozen plasma (FFP), followed by platelets concentrates (PC) and packed red cells (PRC). However, because the use of FFP is not frequent in France, it only accounts for about 10% of TRALI, whereas PRC and PC are involved in the remaining cases. In no case, pooled FFP treated with solvent-detergent were involved. Patients' profiles are peculiar with a high disease burden. Therefore, targeting a prevention policy only on FFP would result in a marginal reduction of TRALI in France.

Tamoxifen is the widespread anti-hormonal compound used for the treatment of human breast cancer. It is admitted that its effects are mediated via estrogen receptors (ER) but the molecular basis of its activity has yet to be clearly defined. In this work, we have developed a new image cytometry procedure in order to clarify the interactions between steroid receptors and tamoxifen at the cell cycle kinetic level. On untreated cells, an increase of ER level and a decrease of progesterone receptor (PR) level during the G0/G1 phase were demonstrated. Then, the ER and PR levels fell during the S-phase until the beginning of G2/M phase, where an increase was observed, especially for PR. These results suggest that ER is synthesized preferentially during the G0/G1 transition and PR during the S/G2 transition. After short-term tamoxifen treatment an augmentation of ER level was observed which was not dose-dependent, suggesting an increase in receptor translation rather than an augmentation of ER synthesis. PR level declined in the majority of the population leading to a selection of a subset of proliferating PR negative cells after treatment. These data demonstrate that the synthesis of steroid receptors is linked with the progression of cells through the cell cycle and indicate that tamoxifen blocks MCF-7 cells in G1 via its interactions with ER. Our multifluorescence imaging procedure appears to provide a rapid and quantitative approach which is useful for investigating alterations in steroid receptors after endocrine treatment.

In order to help the analysis of adverse effects of transfusion, factsheets have been written by working groups of the French agency for the safety of health products ANSM. Each factsheet deals with a blood transfusion side effect and is composed of five parts, including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules for filing the notification form to ANSM. Since 2006, 11 factsheets have been published on the French haemovigilance network website. The major characteristics of the two last sheets published "post-transfusion purpura" and "non erythrocyte incompatibility reaction" are presented, followed by the updated card for "allergy". These factsheets give relevant guidelines allowing better evaluation of recipients' adverse reactions, particularly their diagnosis, severity and accountability. They also could initiate studies among European and international haemovigilance networks.

A working group of the French National Hemovigilance Committee has been in charge of heightening awareness of Transfusion-Associated Circulatory Overload (TACO) among physicians and nurses. This multidisciplinary group has produced the present document that focuses on epidemiological data provided by the French haemovigilance network, physiopathology, diagnosis, treatment and specific actions that could prevent or minimize the risk of TACO.

These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.

Safety in the field of transfusion medicine has greatly improved in France. The risk of viral transmission has decreased by a factor greater than 1500 within the last 20 years. In comparison, the risk related to ABO error has decreased only by half. The reporting of critical incidents, which occur at any step of the transfusion procedure is now mandatory in France and is subject to an in-depth analysis, using methods close to that used in aviation safety. The goal of these analyses is to better understand human factors in order to implement more adequate prevention measures.

Pulmonary oedema after transfusion of blood products may be hydrostatic (transfusion-associated circulatory overload [taco]) or exsudative (transfusion-related acute lung injury [trali]). Both conditions have been recognized as major hazards to transfusion recipients. Risk characterization is necessary to improve safety and to monitor trends in the national blood transfusion system. A collaborative multidisciplinary working group of the French National Hemovigilance Committee has proposed an analysis framework for case definitions and classification. The method relies on internationally used definitions and is adapted to the codification procedures used in the french transfusion incident reports electronic data management.

Due to regulations, hospital blood banks have to equip them with a computer-based information system. This system facilitates the management of the blood bank and ensures the safety of the storage, issuing and traceability of the blood and blood components. It permits to create a medical file for each transfused patient, which contains the characteristics of the blood components transfused and the immunohematological status of the patient, received by electronic data interchange from the blood establishment. Thus, from the assistance to the prescription of blood transfusion to the issuing and traceability of the blood components, the computer-based information system is the guarantee of the transfusion security in a hospital blood bank.

Pulmonary oedemas occurring during or after a blood transfusion appear as the most frequent serious immediate incidents in the French hemovigilance database. They include transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO are a major cause of transfusion-related death in France. TRALI are more and more recognized and notified. In no case, pooled fresh frozen plasma (100 donations) treated with solvent-detergent were involved in French TRALI cases. A logigrame will allow hemovigilance officers to better classify pulmonary oedemas in e-fit, the French hemovigilance database.

Since 1985, a Council Resolution defines a new approach to technical harmonization and standards. The directives resulting from this new approach establish the essential safety requirements with which products put on the market must conform, and which should therefore enjoy free movement throughout the European Union, owing to a presumption of conformity. However, if the manufacturer is responsible for the conformity of its product in terms of safety, it is the end-user who must make sure that its requirements for a specific use or a considered application are satisfied and that the product meets its needs. It is the objective of the procedure of validation, which calls upon protocols of qualification intended to show the aptitude of a material, a system, a device, of an installation, to meet the requirements of specified quality and safety. This concept of qualification applies to the data-processing software of the hospital blood banks. Only the stage of operational qualification will be developed here. It involves scenarios made up of test files which make it possible to check the electronic data interchanges between the hospital blood bank and the blood establishment (transmission of the results of analysis, transmission of the data of traceability), as well as the functions of assistance to the issuing of the labile blood products.

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.

Partial digestion of spectrin dimers in vitro has allowed the definition of domains. For example, the portions of the dimers that are involved in spectrin self-association are represented by the alpha I and the beta I domains. The alpha I domain (80 Kd) is further cleaved into a minor 78 Kd fragment and, more substantially, into a 74 Kd fragment. The intensity of the latter, which we expressed as the 74:(80 + 78 + 74) ratio, or the 74:alpha I ratio, is variable depending on the experimental conditions, eg, in fine, on the conformation of the alpha I domain. A number of cases of hereditary elliptocytosis (HE) are associated with an increase of the 74:alpha I ratio, also referred to as the Sp alpha I/74 abnormality. Several lines of evidence have suggested that the causal mutations may lie in the alpha- or the beta- chain, a point of importance before one undertakes studies at the gene level. In order to address this question, we reconstituted spectrin dimers in vitro, combining alpha- and beta-chains of various origins, and then carried out partial digestion and assayed the Sp alpha I/74 abnormality. The patterns obtained with reconstituted dimers were nearly identical to those of native dimers. We applied the assay to three spectrin variants that cause Sp alpha I/74 HE: (1) a variant that we previously designated spectrin Nice and whose beta-chain lacks a 4 Kd fragment in its C-terminal region; and two distinct variants that we found in two unrelated white families and that we provisionally designated spectrin Lyon and spectrin Culoz. The Sp alpha I/74 abnormality appeared in all kinds of dimers that harbored the beta- chain of spectrin Nice, or the alpha-chain of spectrin Lyon or spectrin Culoz, respectively. Therefore, we confirmed that spectrin Nice is a (alpha I/74) beta-variant, and established that both spectrin Lyon and spectrin Culoz are (alpha I/74) alpha-variants. The present assay may be extended to any spectrin variant displaying the Sp alpha I/74 abnormality.

SUMMARY: The Agence Française de Securite Sanitaire des Produits de Santé (Afssaps; French Health Products Safety Agency) is responsible, through its hemovigilance unit, for the organization and the functioning of the national hemovigilance network. In accordance with the French law, it receives all data on adverse transfusion reactions regardless of their severity. With the aim of evaluating the tolerance of two kinds of labile blood products (LBP), pooled platelet concentrates (PP) and apheresis platelet concentrates (APC), we screened the French national database from January 1, 2000 to December 31, 2006. We observed that the number of transfusion incident reports is more than twice as high with APC (8.61:1,000 LBP) than with PP (4.21:1,000 LBP). The difference between these two ratios is statistically significant as shown by chi-square test (e = 21.00 with α = 5%). The risk to suffer adverse reactions of any type, except for alloimmunization, is higher with APC, and the major type of diagnosis related to APC is allergic reaction (1:200 APC issued) even if those allergic reactions are rarely serious. The new French National Hemovigilance Commission should impel a working group evaluating this topic and above all the impact of additive solutions which have been used since 2005 to put forward preventives measures.

Current methods of detecting micrometastases in breast cancer fail in a large proportion of patients. Therefore an improved method for detection of metastases in blood samples could be of great clinical interest both for prognosis and selection of patients for adjuvant systemic therapy. We have developed a new non-invasive method which associates immuno-magnetic separation and filtration cytometry. The sensitivity of our procedure was evaluated in a model system using a mixture from a human breast cancer cell line (MCF-7) and a normal human blood sample. The identification of tumoral cells was achieved by measuring DNA content in comparison with standard cells. The lowest concentration of MCF-7 detected was 1 tumoral cell in 500,000 white blood cells. In addition, filtration cytometry provides a visual control of nuclei permitting the elimination of all doubtful cases and an automatic count of tumoral cells directly per ml of blood, which may be an independent predictor of early relapse. This new method may avoid unnecessary axillary lymph node dissection in patients with negative nodes. Our procedure seems suitable for the detection of rare circulating cells in routine laboratory testing and could be used in other applications.

A new cell line (CAL 54) was isolated from a malignant pleural effusion of a patient with renal carcinoma. CAL 54 is a continuous and stable cell line. Immunochemical staining showed simultaneous expression of cytokeratin, epithelial membrane antigen and vimentin. Cytometric flow analysis of DNA content reveals one major hyperdiploid population. Histological aspect of the tumor induced in the nude mouse showed well differentiated adenocarcinoma with papillary structure. Radiation response of these cells was evaluated by the colony-forming method and the data were fitted with the linear-quadratic model. Survival at 2 Gy (SF2) was 0.28 and the mean inactivation dose (D) = 1.50 Gy, ranking this cell line among the radiation sensitive cells. CAL 54 may be an informative cell line to investigate radiation effects in the management of renal tumours.

Caulerpa taxifolia (Vahl) C. Agardh (Ulvophyceae, Caulerpales) is an algae of tropical origin that was accidentally introduced into the Mediterranean in 1984. Caulerpenyne (Cau) is the major metabolite present in Caulerpa taxifolia. This metabolite has previously been shown to be cytotoxic against cell lines in culture as in KB cells and fibroblasts from hamsters. Cau along with 6 other drugs representative of the major classes of anticancer products was tested against 8 cancer cell lines of human origin. Cau demonstrated growth-inhibitory effects in all cases with some variability between cell lines; this inter-cell variability was, however, less marked than that observed with the anticancer drug tested. Cells of colorectal cancer origin were the most sensitive to the presence of Cau with IC50 values of 6.1 and 7.7 microM. Increasing the duration of contact between Cau and the cells from 75 min to 29.5 hr did not improve the cytotoxic efficacy of this compound. When Cau was pre-incubated in the culture medium for from 7 to 83 min before being exposed to CAL 27 cells (head and neck cancer origin), there was a constant loss of cytostatic action of Cau as a function of Cau pre-incubation time. As the bovine serum albumin concentration increased in the culture medium, the concentration-response curves showed a constant shift towards the right, indicating a loss of cytostatic activity of Cau. In the presence of Cau, cells in culture clearly exhibited an early and marked shift into S phase followed by a blockade into the premitotic G2 M phase. Possible targets for CAU remain to be identified. Cau needs to be tested on tumor bearing animals to confirm this promising antiproliferative activity.

Tamoxifen is extensively used for the treatment of human breast cancer. However, the mechanisms by which antiestrogens regulate the growth of estrogen receptor positive tumors have not been totally defined. A new methodology, using automated image analysis BIOCOM 500, was developed for determining potential doubling time (Tpot) of tumors. This new method was checked on three different human breast cancer cell lines (MCF-7, CAL 85-1, CAL 148) in comparison with flow cytometry and then applied to determine the effects of short-term tamoxifen treatment on Tpot of MCF-7 cells. Using the resulting bivariate contour plot of blue fluorescence (DNA content) versus green fluorescence (Bromodeoxyuridine content), a labeling index (LI) value of 0.39 +/- 0.05 and a Tpot value of 21 +/- 2.09 hours were determined for MCF-7 cells. As expected, data demonstrated that 72 hours of 1 microM tamoxifen treatment decreased the LI to 35% by increasing the proportion of G0/G1 cells. It increased the Tpot to 35% compared to untreated cells (Tpot = 31.8 + 4 hours) by a lengthening of G0/G1 phase without changing the length of S phase (Ts = 10.2 +/- 1 hours). At suprapharmacological concentrations (5, 10 microM), an approximately 50% increase in Tpot was observed without modification in Ts. These data suggested a specific cell cycle action of tamoxifen which was probably mediated by mechanisms other than estrogen inhibition, since these experiments were performed in estrogen-deprived medium. In addition, the automated imaging procedure appears to provide a rapid and quantitative approach to determine Tpot in fine needle biopsies which is useful for investigating alterations in cell growth after endocrine treatment or chemotherapy.

We report the case of a patient with stage 2 malignant melanoma (MM), who received a specific immunotherapy consisting of intralymphatic injections of irradiated MM cells. She developed subsequently vitiligo-like leukoderma and several plaques of localized scleroderma. Simultaneously an increase in the patient’s cytotoxic activity against MM cells was detected in vitro. The responsibility of immune phenomena and specific immunotherapy for the appearance of depigmentation and morpheas is discussed.

A new monoclonal antibody (Calam 27) that reacts with a membrane antigen present on cells of epithelial origin, but not on cells of mesothelial origin, was investigated as a means of distinguishing between mesothelial cells and malignant cells in cytologic smears of serous effusions from patients with carcinoma. Immunofluorescence staining of cells in 151 effusions from 109 patients with different diseases showed a good correlation between the cytologic diagnosis on routine preparations and the staining with Calam 27. Calam 27 was also used to study the ploidy and cell cycle kinetics of carcinoma cells versus reactive mesothelial cells and normal cells by flow cytometry; these experiments confirmed that Calam 27 is not reactive with mesothelial cells. In conclusion, Calam 27 staining can help to confirm the cytodiagnoses in cases with carcinomatous effusions.

The efficacy of Cisplatin-5-FU combination has been widely demonstrated in induction chemotherapy of head and neck cancers [1, 2]. We have confirmed these results a few years ago [3–5]. After a 6 years experience, the objective of this study is to evaluate the overall results and the impact of neo-adjauvant chemotherapy on disease free interval and survival in head and neck cancer patients.

Partial digestion of spectrin dimers in vitro has allowed the definition of domains. For example, the portions of the dimers that are involved in spectrin self-association are represented by the alpha I and the beta I domains. The alpha I domain (80 Kd) is further cleaved into a minor 78 Kd fragment and, more substantially, into a 74 Kd fragment. The intensity of the latter, which we expressed as the 74:(80 + 78 + 74) ratio, or the 74:alpha I ratio, is variable depending on the experimental conditions, eg, in fine, on the conformation of the alpha I domain. A number of cases of hereditary elliptocytosis (HE) are associated with an increase of the 74:alpha I ratio, also referred to as the Sp alpha I/74 abnormality. Several lines of evidence have suggested that the causal mutations may lie in the alpha- or the beta-chain, a point of importance before one undertakes studies at the gene level. In order to address this question, we reconstituted spectrin dimers in vitro, combining alpha- and beta-chains of various origins, and then carried out partial digestion and assayed the Sp alpha I/74 abnormality. The patterns obtained with reconstituted dimers were nearly identical to those of native dimers. We applied the assay to three spectrin variants that cause Sp alpha I/74 HE: (1) a variant that we previously designated spectrin Nice and whose beta-chain lacks a 4 Kd fragment in its C-terminal region; and two distinct variants that we found in two unrelated white families and that we provisionally designated spectrin Lyon and spectrin Culoz. The Sp alpha I/74 abnormality appeared in all kinds of dimers that harbored the beta-chain of spectrin Nice, or the alpha-chain of spectrin Lyon or spectrin Culoz, respectively. Therefore, we confirmed that spectrin Nice is a (alpha I/74) beta-variant, and established that both spectrin Lyon and spectrin Culoz are (alpha I/74) alpha-variants. The present assay may be extended to any spectrin variant displaying the Sp alpha I/74 abnormality.

Background: ABO incompatibilities (ABOi) usually result from the failure to comply with Standard Operating Procedures (SOP). Continuous training (CT) is the main way to ensure their proper use in ultra-high security systems like civil aviation but little is known for transfusion. In France, SOP include a Beth-Vincent test at the bedside before the transfusion of Packed Red Cells (PRC). At the hospitals, Hemovigilance Officers (HO) are in charge of transfusion safety along with the settlement of traceability and the notification of all Adverse Effects (AE). If SOP and CT are requested by Law since 1993 for blood banks, they are only advised for hospitals even though the bedside Beth-Vincent test requires a special training. However, HO have more and more transposed the model of blood banks in hospitals especially since 2000. Objective: to describe time-trends of ABOi observed in e-fit, the French Hemovigilance database. Population and methods: All AE with “acute ABOi” as the final diagnostic were considered. Time-trends were studied according to the Box and Jenkins model (ARMA). Results: From 07/01/1994 to 12/31/2005, 79 106 AE were registered in e-fit, corresponding to about 30,000,000 Labile Blood Products (LBP) transfused. 304 (0.4%) were ABOi (1/107,850 LBP transfused). There were 183 men and 121 women with 81.3% of whom more than 40 years old. 205 patients (67.4%) received only PRC, 73 (24.0%) Platelet Concentrates (PC), 22 (7.2%) Fresh Frozen Plasma (FFP) and 4 (1.3%) more than a single LBP. 18 ABOi were fatal, possibly (4 cases) probably (4 cases) or definitely (9 cases) associated with a PRC, and 1 doubtfully with a FFP. Time-trends displayed 3 periods: (1) from 1994 to 1997 ABOi increased concurrently with the frequency of all AE notifications, (2) from 1997 to 2000 they reached a steady-state with 35 ABOi/year on average (1/70,000 LBP), (3) since 2001 they regularly decreased of 14%/year on average (13 ABOi for 2005 = 1/198,450 LBP). The localization of the failure to comply with SOP (i.e. hospital, blood bank or both) was studied for PRC. From 1997 to 2005, the liability of blood banks alone or along with hospitals remained stable (resp 0.42 and 2.58/year on average) whereas those of hospitals dramatically decreased (16.25/year from 1997 to 2000 and 8.6/year from 2001 to 2005). Conclusion: (1) ABOi are now 3 times less frequent than in 2000 ; (2) a notification bias is unlikely because both hospitals and blood banks are aware of traceability data that include the ABO phenotype for both the recipient and the LBP issued ; (3) CT applied on a nationwide basis seems to be the main factor to reduce ABOi in hospitals ; (4) a residual risk related to human errors seems to exist ; (5) the way to overcome that risk remains a matter of debate.

Background: Transfusion Related Acute Lung Injury (TRALI) is a life-threatening complication of allogenic blood transfusion, manifested typically by a non-cardiogenic pulmonary edema. However, the magnitude of the risk of TRALI remains unknown at this time, all the more so as a variety of other clinically similar respiratory complications can be associated with transfusion. Hemovigilance had been implemented in France since 1994. All adverse effects (AE) regardless of their severity should be notified on a normalized form to AFSSaPS, the French health products safety agency, as required by the French law. Objective : to describe TRALI observed in e-FIT, the French hemovigilance database. Population and methods: AE possibly, probably or definitely associated with transfusion were considered for inclusion. As the item “ TRALI” was explicitly present since 09/01/2001, we screened the database from 07/01/1994 to 09/01/2001 with “ pulmonary edema AND fluid overload excluded” , or with free comments including the words “TRALI ” , “ anti-granulocyte antibodies ”, “ non-cardiogenic pulmonary edema ” , “ white lung syndrome ” . The subsequent AE were considered for inclusion only if TRALI was the final diagnostic. Results: From 07/01/1994 to 06/01/2006, 82,436 AE were registered in e-FIT, corresponding to about 30,000,000 labile blood products (LBP) transfused. 117 AE fulfilled the above criteria (3.9/1,000,000 LBP transfused). There were 59 men and 58 women, age = 0 to 86 (median 58); 34 men and 21 women were 60 years old or more. 107 patients presented with pulmonary symptoms, 93 with dyspnea, 63 with chills and/or hyperthermia and 53 with a typical pulmonary edema. 13 TRALI were fatal, 85 were life-threatening and 19 were benign. 42 patients received only packed red cells, 4 only fresh frozen plasma and 40 only platelet concentrates ; among the 31 remainders, 14 received platelets concentrates associated with an other LBP. Conclusion: Although the initial French database was not adapted to detect TRALI cases until 2001, the dynamics of notification is of interest ; TRALI is more frequent in elderly patients, as noted in other reports ; Platelets concentrates remains the more frequently LBP involved, but packed red cells also contribute to nearly half of the TRALI reported ; Besides the classical life-threatening presentation, a benign form of TRALI seems to exist ; A national working party is implementing new ways to define and investigate TRALI, which will provide more accurate information on TRALI in France.

The urinary polyamines putrescine (PU) and spermidine (SPD) were measured for 67 patients with lymphomas: 49 non-Hodgkin (NHL) and 18 Hodgkin's disease (HD). Monthly repeat measurements were obtained over an average follow-up period of 12.5 months. For NHL, a good association was observed between polyamine levels and the severity of the stage; the distribution of values between nodular and diffuse forms was also significantly different. No such correlations were seen for HD. The evolution of PU values in time has been shown to reflect disease activity for NHL. Non-specific fluctuating PU values were found in the case of HD. In the case of 20 patients with NHL undergoing chemotherapy, comparison of polyamine levels before and after chemotherapy allowed differentiation between the population of complete responders to treatment and those with only partial or no response.

The OPR was studied in 203 patients with squamous cell carcinoma of the head and neck at the time of diagnosis, before any specific treatment. The mean initial OPR value was significantly higher in cancer patients than in 63 healthy controls: 5.29 +/- 3.09 vs. 2.63 +/- 1.07; P less than 0.001. There was no significant difference by anatomic site, but the OPR was significantly lower in stage I-II disease than in stage III-IV: 5.10 +/- 3.85 vs. 3.23 +/- 1.99, P less than 0.001. An initial OPR under or over 6 seems to be an important prognostic factor: at 2 years, 51% of patients with an OPR less than 6 were alive vs. only 24.5% of those with an OPR greater than 6, P less than 0.001. The difference was also noted in patients with stage III-IV disease (mean survival: 16 months vs. 7 months, P less than 0.001) and in 89 of the patients who received chemotherapy (mean survival 16 months vs. 6 months, P less than 0.001) whatever the response to chemotherapy. The OPR index, which explores nutritional and acute phase reactant proteins, seems to reflect the host-tumor relationship. Its initial value is strongly related to prognosis at 2 years.

We describe a new spectrin variant with a truncated beta-chain. It was discovered in a 17-year-old white boy presenting with intermittent jaundice and spleen enlargement. He also displayed numerous smooth elliptocytes. On sodium dodecyl sulfate-polyacrylamide gel, the truncated beta-chain (beta'-chain) appeared as an additional band of approximately 216 kilodaltons, migrating between spectrin beta-chain and ankyrin. It represented 30% of total beta-chain. The beta'-chain reacted with an antispectrin beta-chain monoclonal antibody. It failed to become phosphorylated when ghosts were incubated in the presence of [gamma-32P] adenosine triphosphate. Whole spectrin tetramerization was defective since the amount of spectrin dimer was increased in spectrin crude extract and the association constant of the spectrin dimer self- association was decreased. Spectrin whole tetramer isolated from spectrin crude extracts contained small quantities of beta'-chain. Spectrin tryptic peptides showed an increase of the 74,000-dalton fragment at the expense of the 80,000-dalton fragment. So far, the latter abnormality has been used to characterize a number of cases of hereditary elliptocytosis or pyropoikilocytosis with no other apparent change. In the present case, we consider that the abnormality is a consequence of the beta-chain alteration. The parents seemed asymptomatic. As a result, we regard this new spectrin variant as deriving from a de novo mutation.