[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.

[Seventeen years of haemovigilance in France: assessment and outlook]. / Dix-sept ans d'hémovigilance en France: bilan, perspectives.

Since 1994, the French haemovigilance network has not stopped evolving. Based initially on the reporting of informations and incidents related to recipients, it quickly became interested in the procedures and other activities related to blood component transfusion, in order to improve blood safety. Despite some failures (under reporting, heavy declarative management), the French haemovigilance network is going to continue working on improving blood safety, both at the level of the recipients and the donors, and participate to the global improvement of quality of care.

Prognostic value of E-cadherin, beta-catenin, CD44v6, and HER2/neu in metastatic cutaneous adenocarcinoma.

CONTEXT: Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases. OBJECTIVE: To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade. DESIGN: E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%). RESULTS: Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin--a member of the cadherin family functioning as an invasion suppressor molecule. CONCLUSIONS: These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.

[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.

[Transfusion incidents reports of grade zero: a national and descriptive analysis upon two years of practical survey]. / Les incidents transfusionnels de grade zéro: analyse descriptive nationale sur deux ans de pratique.

A grade zero transfusion incident is defined as an inappropriate transfusion of blood component due to one or several failures without immediate clinical or biological consequences for the recipient. Two years after the setting up of the mandatory notification of these incidents, Afssaps haemovigilance unit performed a first descriptive national analysis of the data collected in years 2003 and 2004 at the national level. This analysis was based on one part on computarised e-Fit national database and on the other part on investigation results documents and additional surveys set up by the network professionals. From a quantitative point of view, this study reveals differences in notification as well as in the type of analysis from one region to another. Quantitatively, 45% of grade zero transfusion incidents correspond to attribution errors. The site of origin of grade zero incidents is for almost 73% linked to health establishment, clinical unit or hospital blood bank, and for almost 23% linked to blood establishment. Complete analysis has notably shown that 9% of the incidents are due to errors in blood component prescription. This descriptive analysis, which identifies recurrent failure and critical points originating from non-appropriated transfusions, should constitute the starting point of a reflection aiming at optimising and standardising methods of analysis of grade zero transfusion incidents and at elaborating suggestions to better control critical points.

The French haemovigilance system.

Haemovigilance is a national system of surveillance and alarm, from blood collection to the follow-up of the recipients, gathering and analysing all untoward effects of blood transfusion in order to correct their cause and prevent recurrence. In France haemovigilance was created by law and notification of transfusion incidents is a legal obligation. The haemovigilance network associates local correspondents in each hospital and blood centre with regional co-ordinators and is centralised by the Agence Française du Sang. After 4 years the incident reporting rate is 2.3 per 1,000 allogeneic blood components transfused, justifying for example increased efforts in the prevention of bacteria-associated transfusion reactions, haemolytic transfusion reactions or vascular overload. However, haemovigilance still has to be strenghtened by improved information management or further progress in standardisation from one region to the other. The most important factor of success is collaboration between blood centres and hospitals. Haemovigilance clearly is the ultimate quality indicator of a transfusion service.

Effect of pentacaine and its derivatives on the contractile responses of smooth muscle in the guinea-pig stomach.

The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic acid] and some of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyclopentyl ester of 3(n)-pentyloxyphenyl-carbanilic acid], K-2002 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], K-2006 [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], and carbanilates P2 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4-methoxy-carbonylphenyl-carbanilic acid], P3 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 3-methoxy-phenyl-carbanilic acid], and PeJ, the quaternized derivative of pentacaine), as well as that of oxethazaine was studied on longitudinal antral and circular fundic smooth muscle strips of the guinea-pig stomach. All the carbanilates studied relaxed the smooth muscle, attenuated the spontaneous smooth muscle contractions and shifted the acetylcholine, histamine, and BaCl2 cumulative concentration effect curves to the right, reducing their maximum. There was no direct relationship between their relaxing potency and the ability to reduce the action of different stimulants. For the effectiveness of the carbanilates studied, substitution in the lipophilic part of the molecule was more important than in the hydrophilic part and the meta position was more advantageous than the para position. Pentyloxy-derivatives (pentacaine, K-1905, K-2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy (P3)-derivatives. Opening of the heterocyclic ring (K-1905) in the hydrophilic part of the molecule did not affect significantly the potency of the derivative studied, while quaternization (PeJ) significantly reduced the potency. It is suggested that the carbanilates studied may affect the smooth muscle responses via changes in the membrane fluidity and Ca2+ availability, and that these effects might be partly responsible also for their antiulcer activity.

Antiulcer activity of pentacaine and some of its derivatives: effect on experimentally induced gastric and duodenal lesions and on gastric acid secretion in rats.

The antiulcer, gastroprotective, and antisecretory effects of selected carbanilates were tested in rats. The compounds K-1905 and K-2002 were found to have beneficial effects similar to those of pentacaine in phenylbutazone- and ethanol-induced gastric injury and in cysteamine-induced duodenal lesions; their antisecretory activity was also comparable to pentacaine in pylorus-ligated rats. Compounds P2 and P3 were generally less effective than pentacaine, and compound P1 was gastrotoxic. Thus pentyloxy-substitution on the benzene ring of the parent structure (K-1905 and K-2002) is more suitable for antiulcer and gastroprotective activity than methoxy-substitution on the meta-position (P3) or alkyloxy-substitution on the para-position (P2, P1). The results indicate that the two carbanilates K-1905 and K-2002 can be considered prospective antiulcer drugs.