Hypersensitivity reactions to blood components: document issued by the allergy committee of the French medicines and healthcare products regulatory agency.

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.

[Operational qualification of the computer-based information system and electronic data interchanges in a hospital blood bank]. / Qualification opérationnelle du système informatique d'un dépôt de sang et de ses échanges de données.

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.

[Pulmonary complications of transfusion (TACO-TRALI)]. / Complications pulmonaires de la transfusion (TACO-TRALI).

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.

[Supplying surgery blocs in red cell concentrates: a collective approach to improve practices]. / Approvisionnement des blocs opératoires en concentrés érythrocytaires: une démarche collective d'amélioration des pratiques.

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.

Inherent radiosensitivity and split-dose recovery in plateau-phase cultures of 10 human tumour cell lines.

The radiation response of 10 human tumour cell lines, eight of them established in our Institute, was analysed. Single dose acute survival curves were constructed and fitted with the linear-quadratic (LQ) model. The mean inactivation dose (D) was also calculated, together with D(o) and n. In order to measure both split-dose recovery and delayed plating recovery of plateau-phase cells, confluent cultures were subjected to two doses of 2 Gy 24 h apart, and plated 24 h later, simulating clinical fractionation. Survival of these cells (S2 x 2) was compared to that following 4 Gy given to cells plated at low density and an overall recovery factor (RF) was derived, including both types of recovery. S2 x 2 and RF were compared to the intrinsic radiosensitivity parameters. The three melanoma cell lines differed in radiation response, and the three squamous cell carcinoma cell lines were rather radioresistant. The neuroblastoma cell line was highly sensitive, yet it expressed the highest beta and the highest RF. Using a non-parametric correlation test, S2 x 2 was found to be related to D, whereas RF was not related to the radiosensitivity parameters. However, the two cell lines with the lowest D and the lowest S2 expressed the highest RF. These results suggest that radiosensitive cell lines may have a considerable capacity to recover if confluent cultures are exposed to fractionated irradiation. The overall recovery factor (RF) used here is proposed as a useful measure of cellular recovery.

Pseudomonas aeruginosa O-11 folliculitis. Development into ecthyma gangrenosum in immunosuppressed patients.

Six immunocompromised patients were shown to exhibit Pseudomonas aeruginosa folliculitis in apocrine regions similar to "swimming pool" folliculitis. The lesions evolved within 24 hours as severe ecthyma gangrenosum. The source of the P aeruginosa, serotype O-11, was found in the water system of the hospital. Clinical identification of the lesions and early treatment is important to prevent severe manifestations.

Detection of rare circulating breast cancer cells by filtration cytometry and identification by DNA content: sensitivity in an experimental model.

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.

Effects of tamoxifen on potential doubling time of human breast cancer cell line determined by image cytometry of double fluorescent BrdU and DNA labeling.

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.

Cell growth inhibitory effects of caulerpenyne, a sesquiterpenoid from the marine algae Caulerpa taxifolia.

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.

Assessment of nutritional proteins during the parenteral nutrition of cancer patients.

Albumin, prealbumin, retinol-binding protein, and transferrin were all measured on the sera of 39 cancer patients before and during parenteral nutrition (PN). At the outset of PN, the concentrations of all of these proteins were low, as compared to reference values, and thus quantitatively reflected the degree of malnutrition. Prealbumin proved to be the most interesting parameter during PN: (1) during an initial period it rapidly reflects the nutritional input, and (2) after two weeks of PN it allows differentiation of patients whose prealbumin level rises regularly during PN and will survive from those patients whose prealbumin level drops after the initial period and will die during or within the month following PN. Prealbumin thus offers a means for biochemical monitoring of PN as well as having a prognostic value.

A new epithelial membrane antigen (Calam 27) as a marker of carcinoma in serous effusions.

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.

Toxicity of a combination of ABVD chemotherapy and mediastinal irradiation for Hodgkin's disease patients with massive initial mediastinal involvement.

The authors report on 5 Hodgkin's disease (HD) patients with a mediastinothoracic ratio greater than or equal to 0.35 treated by ABVD chemotherapy (adriamycin, bleomycin, vindesine, DTIC) and irradiation. All 5 patients developed complications and there was 1 death. Administration of adriamycin and bleomycin in combination with irradiation may have been responsible for this poor treatment tolerance. Use of such protocols, and especially use of ABVD after mediastinal irradiation, should probably be avoided in the management of patients with massive mediastinal involvement.

[Host-tumor relationship as a function of the orosomucoid-prealbumin ratio]. / Etude de la relation hôte-tumeur par le rapport orosomucoïde sur préalbumine.

Of the various prognostic factors for cancer, biological parameters of the Host/Tumour relationship allow objective evaluation of the conflict between the organism and the disease. Alpha 1-acid glycoprotein (Orosomucoïd), which belongs to the Acute Phase Reactant's Proteins, and prealbumin, a highly sensitive nutritional protein, are two compounds whose blood levels vary in inverse proportion during perceptible-stage cancers: alpha 1-acid glycoprotein concentrations increase while prealbumin values drop. The ratio of the blood levels of these two parameters provides a more sensitive index than either parameter taken alone. Study of the orosomucoïd/prealbumin ratio (ROP) in a population of 132 patients and 63 controls revealed a good association between the ratio values and the different stages of the disease. The highest values corresponded to patients with active disease; normal levels were obtained for patients in partial or complete remission. During the course of disease, the orosomucoïd/prealbumin ratio is more reliable than the sedimentation rate. Furthermore, when measured at the onset of the disease, this ratio is an undeniable prognostic element, independent of the stage of disease extension.

[CAL 54, a new cell line derived from a human renal carcinoma: characterization and radiosensitivity]. / CAL 54, une nouvelle lignée cellulaire dérivée d'un carcinome rénal humain: caractérisation et radiosensibilité.

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.

[Initial treatment of infiltrating tumors of the bladder. Combined transurethral resection and systemic chemotherapy]. / Traitement initial des tumeurs infiltrantes de vessie. Association résection transurétrale-chimiothérapie systémique.

From September 1983 to September 1986, 20 patients (mean age 65 years) with a muscle-infiltrating tumour of the bladder would normally have been treated by total cystectomy. Instead, they were staged by intravenous urography, pelvic and abdominal computerized tomography, physical examination under general anaesthesia and deep transurethral resection, then given neoadjuvant chemotherapy consisting of cisplatinum and 5-fluorouracil, six courses at intervals of 28 days. Results were evaluated after the 3rd and 6th courses by computerized tomography, intravenous pyelography and transurethral resection. Nine patients had a clinical complete response (6 pT2, 2 pT3, 1 pT4). The median follow-up in january, 1988 was 30 months (range 17-52 months). This protocol was objectively active and well tolerated, even by elderly subjects. Two problems remain concerning patients with complete response: the respective roles of chemotherapy and transurethral resection in the outcome, and the prevention of recurrence (5/9 complete response patients).

[Transfusion-associated circulatory overload]. / Œdèmes aigus pulmonaires de surcharge post-transfusionnels.

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.

[Factsheets: support in the analysis of recipients' adverse reactions]. / Fiches techniques: aide à l'analyse des effets indésirables receveurs.

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.

[Hospital blood bank: information system and immuno-hematology]. / Dépôt de sang: apport d'un système informatique dans la sécurité immuno-hématologique.

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.

[Post-transfusion pulmonary oedema: the French hemovigilance network classification method]. / Œdèmes pulmonaires transfusionnels: classification des cas notifiés en hémovigilance.

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.

[Patient safety and root cause analysis]. / Sécurité des patients et analyse des causes racines.

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.