[Profiles of people who return unused medicine to pharmacies in Puy-de-Dôme, and their motivations for doing so]. / Profils et motivations des personnes déposant des Médicaments Non Utilisés (MNU) dans les officines du Puy-de-Dôme (France).

An unused drug (U.D.) is described as a drug which is purchased, whether according to a prescription or not, but which is not taken. In the past few years, French people have acquired the habit of returning U.D.s to pharmacies. Nevertheless, few studies have been performed to define their typical features and the motivations of these individuals. A descriptive study was carried out in 1/5 of the pharmacies in Puy de Dôme (France) over three 1 week periods between February and June 1998. 377 people (that is, 82% of those who bring U.D. back to the pharmacies) accepted to participate in this study. The main results are as follows: 1. the U.D. are primarily brought back by women (of all ages); 2. these women mainly return U.D. from the family medicine cabinet; 3. the donations result essentially from "the force of habit", "cleaning out the family medicine cabinet" and also, although in lesser proportion, for "humanitarian reasons". This behaviour is contradictory with the communication messages of Cyclamed, the official French association whose mission is to collect drug waste and unused drugs in order to preserve the environment and to promote energy development and valorisation.

Drinking water and cardiovascular disease.

A link between cardiovascular disease (CVD) mortality and the hardness of drinking water (DW) is suggested by about 30 epidemiological studies performed worldwide in the general population since 1957. This review examines the main ecological studies, case-control studies and cohort studies, published between 1960 and 2000. Attention is paid to the problem of interpretation of this typical result of environmental epidemiology. Some studies focused on the role played by inorganic elements known as DW contaminants (mainly, As, Pb) and above all on the role of the magnesium content of DW and its cardioprotective effects. To date, it would be impossible to understand this environmental findings without large intervention studies performed in well-controlled public health programs.

[Comparison of plasma total homocysteine determinations in 9 French hospital laboratories by using 6 different methods]. / Comparaison du dosage de l'homocystéine plasmatique totale dans neuf laboratoires par six techniques différentes.

A lot of methods are now available for total plasma homocysteine (tHcy) determination. Commercial kits using immunoassay, easier to use, begin to supplant in-house laboratory methods. Our aim is to evaluate the interchangeability of tHcy measurements in 9 French hospital laboratories. Six different method types were used: 2 gas chromatography-mass spectrometry (GC-MS), 2 HPLC with fluorescence detection subdivided in one in-house method and one commercial kit (Bio-Rad ), 3 fluorescence polarization immunoassays (FPIA), 1 enzyme immunoassay, 1 amino acid analyser, 1 capillary electrophoresis coupled with laser-induced fluorescence detection (EC-LIF). Each laboratory analysed 41 patient's plasma samples in which 8 samples contained added homocystine. Results were analysed for imprecision, recovery, and methodological differences. The mean among-laboratory imprecision (CV) ranged from 12.5 to 18% in function of plasma sample type and was identical to the mean among-method variation. In terms of recovery, we obtained underestimated results with immunoassays. The bias relative to the GC-MS method was less than 12.5% except for two laboratories, one using FPIA assay and the other EC-LIF. In conclusion, the interchangeability of tHcy results between laboratories is not satisfactory and does not allow us to evaluate cardiovascular risk linked to moderate increases of tHcy.

[Plasma homocysteine measurement: a study of pre-analytical variation factors for conditions for total plasma homocysteine concentration]. / Dosage de l'homocystéine plasmatique: étude des facteurs de variation préanalytiques sur la concentration en homocystéine plasmatique totale.

An increase in homocysteine, a sulphur amino acid, is nowdays considered as a risk factor for cardiovascular diseases, and is independent of other risk factors. Reference range for total plasma homocysteine level in adults is usually 5-15 mmol/l. Hyperhomocysteinemia is defined as a fasting total plasma homocysteine level > 15 mmol/l. There may be also graded increased risks for subjects with homocysteinemia from 10 to 15 mmol/l. However, no threshold has been defined, partly because of the lack of standardization in pre-analytical and analytical steps. The aim of the present work was to evaluate three pre-analytical parameters on plasma homocysteine levels: i) the influence of three anticoagulants (EDTA, sodium citrate and lithium heparin); ii) the delay period of blood sample on ice before centrifugation; and iii) the advantages of strong acidic citrate at room temperature. The mean concentrations of total plasma homocysteine were different in function of the anticoagulant. These differences (EDTA minus lithium heparin or EDTA minus sodium citrate) were less than 10% however the used methods and could explain the good correlation between the results. However we recommend to keep the anticoagulant constant in the same study. When EDTA blood samples were immediately put on crushed ice, the maximum delay period before centrifugation could reach 4 hours. If ice is unavailable, strong acidic citrate at room temperature is a good alternative until for 4 hours.

[The community pharmacist and the problem of excessive drinkers]. / Le pharmacien d'officine face au problème des buveurs excessifs.

On a daily basis, the community pharmacist is just as concerned with alcohol (when detecting the interactions between alcohol and medication, or the use of alcohol as an excipient or active ingredient), as with alcoholism (when filling prescriptions, providing advice and guidance to patients, or undertaking other health education actions). In order to define the pharmacist's perception of the problem of alcoholism, an opinion poll was conducted by direct interrogation using a standardised questionnaire. The poll surveyed the owners of 101 randomly selected pharmacies in Puy de Dome. All of the pharmacists questioned are sensitive to and aware of the problem of interactions resulting from mixing alcohol and medication at the time of filling prescriptions. On the other hand, their perception of alcoholism and their behavior towards alcoholic patients vary. They frequently stressed the difficulty of establishing a dialogue. In spite of receiving information and training on alcoholism, perceived as insufficient, pharmacists claim to be really concerned by this problem. As field workers, community pharmacists think that they have a major role to play in carrying out health education campaigns and alcoholism prevention. In fact, the pharmacy is a privileged setting for facilitating encounters and discussions, where alcoholism, like all public health problems, can be addressed.

[Description of unused drugs collected in pharmacies in the Puy-de-Dôme region in France]. / Description des Médicaments Non Utilisés (MNU) collectés dans les pharmacies du Puy-de-Dôme.

BACKGROUND: An unused drug (UD) is defined as a drug which is purchased, after prescription or not, but which is not taken. Public health campaigns in France have requested people to return these drugs to their pharmacy. To data, few data have been available concerning the quantity of collected UD and their potential re-use. A study was performed in the pharmacies of the Puy-de-Dôme region in France to describe the UD circuit. METHODS: A random sample of 1 out of 5 pharmacies in the Puy-de-Dôme region (France) were defined by single level stratified sampling from the list of all pharmacies operating in the region. An exhaustive record of all UD people brought back to these pharmacies was made in 1998 during three 1-week periods. The following data were recorded for each UD: the name of the drug, the pharmaceutical industry code (CIP), the price, the rate of social Security refunding, the mention of "free specimen" on the package, the inscription on the list of poisonous substances and on the list of essential drugs defined by the World Health Organization (WHO), the registration on the list of drugs reserved for hospital use, the packaging notice (opened or not), the therapeutic class, and the formulation. RESULTS: 10,254 US (717kg) were collected during the study period. The therapeutic classes of the UD were similar to those of drugs purchased in France. According to the selling price, these UD had an economic value of 405,845FF (i.e. 3.6% of Social Security refundings paid in the Puy-de-Dôme region during this same period). Only 20% of the UD were potentially reusable for humanitarian purposes. Their estimated economic value was 87,456FF (i.e. 0.78% of the annual Puy-de-Dôme Social Security refunding). Moreover, 43.4% of the reusable drugs were on the WHO list of essential drugs. CONCLUSION: Although the volume of collected UD is high, use by humanitarian associations is on the decline because of the cost of collection and low economic yield. Furthermore, UD must be collected in a systematic manner to preserve the environment and prevent domestic accidents.

[Required procedure for nominal data files processing in biomedical research]. / Procédure à mettre en aeuvre pour le traitement informatique des données nominatives dans le cadre de la recherche biomédicale.

To date, biomedical research using nominal data files for the data collection, data acquisition or data processing has had to comply with 2 French laws (Law of December, 20, 1988, modified, relating to the protection of patients participating in biomedical research, and the Law of January, 6, 1978, completed by the Law of July 1, 1994 n degrees 94-548, chapter V bis). This later law dictates rules not only for the establishment of nominal data files, but also confer individual rights to filed persons. These regulations concern epidemiological research, clinical trials, drug watch studies and economic health research. In this note, we describe the obligations and specific general and simplified procedure required for conducting biomedical research. Included in the requirements are an information and authorization procedure with the local and national consultative committees on data processing in biomedical research (CCTIRS, Comité Consultatif sur le Traitement de l'Information en Recherche Biomédicale, and CNIL, Commission Nationale Informatique et Libertés).

Geographic variation of the mortality from cardiovascular disease and drinking water in a French small area (Puy de Dome).

Cardiovascular disease (CVD) has been the first cause of mortality in the population of Puy de Dôme (PDD) (France) between 1988 and 1992. The mortality rates are significantly higher than those observed in the whole population of France (for the female population, 354.8 versus 327.3 per 100,000 persons/year and for the male population, 335.7 versus 287.9 per 100,000 persons/year). Moreover, an ecological study, which used the Standardized Mortality Ratios (SMR) and performed at the canton level, has allowed a special variation of mortality from CVD in PDD to be described. A decreased gradient of mortality (especially, "Ischemic Heart diseases" [ICM-9, codes 410-414] and "Cerebro-vascular Diseases" [ICM-9, codes 430-438]) has been observed from the periphery (rural area) to the middle (urban area) of PDD. Moreover, a statistically significant negative relationship has been observed between the hardness of the drinking water supplies in PDD and the CVD mortality data (i.e., the lower the hardness of drinking water, the higher the SMR). Although, the low hardness of drinking water can contribute to the high CVD mortality observed among the PDD population, the role of other risk factors (i.e., biological, nutritional) must also be taken into consideration in further prospective studies.

Effects of humic substances and phenolic compounds on the in vitro toxicity of aluminium.

The effects of natural chelators [humic acids (HA), caffeic acid (CFA), p-coumaric acid (PCA), protocatechuic acid (PA), vanillic acid (VA), salicylic acid (SA), and 4-hydroxyacetophenone (HY)] and effects of well-known chelators [EDTA and citric acid (CA)] on the in vitro toxicity of aluminium (Al) were investigated with the L-929 murine, Vero simian, and MRC-5 human cell lines. Moderate in vitro cytotoxic effects were induced by Al on the three cell lines (IC(50) values ranking from 5.6 to 7.6 mM). Furthermore, an increased toxicity was observed when Al was concurrently administered with CA, SA, VA, PCA, and HY. Inversely, significant cytoprotective effects were noted with EDTA, HA, CFA, and PA. The role of chelators, and especially the position and the number of reactive moieties of the phenolic compounds tested, can be highlighted to explain the different toxicological Al behavior observed.

Tetrahymena pyriformis: a tool for toxicological studies. A review.

Among protozoa, Tetrahymena pyriformis is the most commonly ciliated model used for laboratory research. After a brief description of the morphology and biology of Tetrahymena pyriformis, this article focuses on the most important and recent investigations performed with this species in toxicology and ecotoxicology. The methodological features of its culture, and main tests, based on cell growth rate, biochemical markers, behavioral changes and motility, are discussed. Examples of xenobiotics (organic and inorganic substances, pharmaceutical drugs, water pollutants) tested with Tetrahymena pyriformis are also given.

Toxicity assessment of 16 inorganic environmental pollutants by six bioassays.

The relative toxicity of 16 environmental pollutants, such as inorganic elements (Ba, Cd, Co, Cr, Cu, Fe, Ge, Hg, Mn, Nb, Pb, Sb, Sn, Ti, V, and Zn), is evaluated on the L-929 established cell line of murine fibroblasts, with five bioassays [RNA synthesis rate assay (RNA), MTT reduction assay (MTT), neutral red incorporation assay (NRI), Coomassie blue assay, and cellular growth rate assay], and on the ciliated protozoa Tetrahymena pyriformis GL [doubling time of T. pyriformis GL population assay (DTP)]. For each inorganic substance, the six bioassays allowed the toxicological index IC50 ("inhibitory concentration 50%") to be calculated. The IC50 values are useful to rank the tested elements and to compare the features of the six bioassays. The most sensitive assays were the RNA, MTT, NRI, and DTP assays. Moreover, the in vitro IC50 values correlated with the in vivo LD50 values; these results were close to those obtained with established lines of human, murine, or fish cells. The sensitivity and the complementarity of these bioassays would be in favor of their incorporation in a "battery" of tests used for toxicological screening studies of xenobiotics.

Microplate technique for screening and assessing cytotoxicity of xenobiotics with Tetrahymena pyriformis.

The microplate technique (MT) is developed and compared to the usual flask technique (FT) of Tetrahymena pyriformis GL cultures for assessing toxic effects of organic and inorganic substances on this ciliated protozoa model. Applied to the IC50 determination of 29 xenobiotics, the MT demonstrated good correlation with the FT (Y = 0.991X + 0.012, r = 0.94, P < 0.0001). The MT is rapid, easy-to-handle, inexpensive, and statistically reliable and, so, may be helpful for screening investigations of water-soluble xenobiotics.

Chemical and in vitro toxicological evaluations of water packaged in polyvinyl chloride and polyethylene terephthalate bottles.

This study proposed a new strategy assessing the health risks of mineral water packaging and compared the chemical analytical techniques and some in vitro cytotoxicological assays for the study of PVC and PET materials at the main stages of the manufacturing process of bottles. These evaluations were carried out with food simulant (deionized-endotoxin-tested water) and with natural mineral water in real conditions of packaging and storage (from 0 to 24 months). The complementarity of these two approaches is discussed. Some analytical and cytotoxic abnormalities were detected in the food simulant after contact with the batches of powdered PVC compound, PET resin and their intermediate steps of transformation (PVC-'paraison', PET-'perform'). But these results did not reflect the actual behaviour of the finished PVC and PET bottles, for which no major abnormality was detected in the natural mineral water.

Comparative study of two in vitro models (L-929 fibroblasts and Tetrahymena pyriformis GL) for the cytotoxicological evaluation of packaged water.

The preservation of 234 samples of water packaged in polychloride vinyl (PVC), polyethylene terephthalate (PET) and glass-bottles was concurrently evaluated using both classical chemical analysis oriented to finding organic and inorganic substances which could have been leached by the packaging and in vitro toxicological bioassays using two models: the L-929 established cell line of fibroblasts and the ciliated protozoa Tetrahymena pyriformis GL. Although no significant abnormality was detected with the chemical analysis, cytotoxicity was detected with both models in some samples of water bottled for > 18 months, for either PVC, PET or glass-packaging. However, statistical analysis did not allow a mathematical relationship between the cytotoxic effects, the length of storage and the packaging to be demonstrated.

Prospective survey of colonization and infection caused by expanded-spectrum-beta-lactamase-producing members of the family Enterobacteriaceae in an intensive care unit.

The occurrence of expanded-spectrum-beta-lactamase-producing strains was prospectively studied in 56 patients in an intensive care unit. Ten patients were infected or colonized; some of these patients had asymptomatic intestinal colonization. Four different expanded-spectrum beta-lactamases were identified and used as epidemiological markers to survey nosocomial infections.