Organization and results of drug vigilance in France

Pharmacovigilance represents all methods of detection, assessment, information and prevention of adverse drug reactions (ADRs). It mainly involves the post-marketing phase because of the low probability of detecting all possible adverse effects of a drug during pre-marketing development. The most widely used method for pharmacovigilance is spontaneous reporting which is an excellent signal generator but precludes satisfactory calculation of incidence rates. The French Pharmacovigilance System has been set up in 1973; reporting of ADRs has been made mandatory in 1984 for prescribers. This system consists in a network of 30 regional centres under supervision of a coordinating committee at the French Drug Agency. The number of ADR cases received, assessed and recorded by the regional centres is around 10,000 per year; a similar number of cases are reported to the Drug Agency by the pharmaceutical industry. Moreover, Regional Centres work as Drug Information Centres answering more than 23,000 inquiries per year.     

The molecular biology of bladder carcinoma

OBJECTIVE: The clinical course of transitional cell carcinoma of the bladder can be difficult to predict due to its potential to invade the muscle layer and/or develop to a high grade lesion. Bladder carcinoma can arise from genetic changes that may activate the oncogenes (-c-erbB2, c-erbB1, c-myc, ras, etc.) and/or inactivate the suppressor genes (p53, Rb). The aim of the present study is to continue a study protocol on the molecular biology of bladder tumors. METHODS/RESULTS: From January, 1993 to January, 1995, 85 patients were studied. These patients were divided into two groups: the first group comprised 14 controls of urothelial tissue and the second comprised 65 cases of transitional cell carcinoma of the bladder. p53 expression was determined by an immunohistochemical method (NCL-p53-DO7 monoclonal antibody). Quantification of the p8 oncoprotein in cytosol and EGFR (epidermal growth factor receptor) in membrane was performed by ELISA (Oncogene Science) and RIA (Vienna Lab), respectively. A statistically significant relationship between the expression of p53 and EGFR with tumor stage and grade was found. Quantification of p185 and EGFR showed higher values in the tumor tissue than in the control samples, but a worse survival could not be determined. CONCLUSIONS: The present study shows that p53 expression can be considered to be a prognostic factor. It provides useful information on the aggressive behaviour of the tumor and has a direct relation with the survival rates.     

The use of direct tension tests for the assessment of low temperature properties of bituminous binders

In France, tensile tests on bituminous binders are usually performed on vertical electromechanical loading frames, the test samples being placed in an insulated temperature control chamber and the deformations determined from the displacement of the cross-head. The paper presents the results of an inter-laboratory study of which the objective was to evaluate the suitability of this kind of equipment for the performance of direct tension tests at low temperatures. Most of the test parameters, used for this study complied with the procedure proposed by SHRP as from 1995 (AASHTO TP3). The various operating factors, and more particularly those affecting the determination of true sample elongation (mechanical plays, deformation of the gripping systems, ....), are discussed and a number of correcting procedures are proposed. Nevertheless, the results remained scattered. Considering the “flat” evolution of strain at failure with temperature in the domain of brittle behaviour, this makes it rather difficult to accurately define the temperature for failure at 1% elongation (T_ε=1%). This is also the case when this temperature is located in the zone of transition between brittle and ductile behaviour. The authors suggest that, together with the corresponding tensile strain, this “transition temperature” could be used as an alternative criterion which has the advantage of being linked to a physical behaviour of the material.     

L'impact des sympt?mes somatiques dans l'évaluation de la dépression chez une population gériatrique.

Studied the relationship among age, physical health status, and psychic and somatic symptoms of depression among elderly adults. Human Ss: 318 male and female Canadian older adults (aged 65–102 yrs). Information on sociodemographic factors and health status was obtained using the Older American Research Scale, French version, by R. Lefran?ois et al (1988). A French version by P. Bourque and D. Beaudette (1982) of the Beck Depression Inventory was also used. The results were evaluated according to each S's sex, age, institutionalized residence status, and health status. Statistical tests were used. (English abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA

The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.