Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics: AVASTIN OUEST cohort of the Observatory of Cancer of the Brittany and Pays de la Loire Areas (Observatoire dédié au Cancer Bretagne / Pays de la Loire).

BACKGROUND: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer. METHODS/RESULTS: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks. CONCLUSION: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.

En 2006, bevacizumab-FOLFIRI représente la thérapie ciblée administrable dès la première ligne chez les patients porteurs d'un cancer colorectal métastatique non opérable. Une série homogène de 111 patients colligés en région Bretagne et Pays de la Loire ayant reçu du bevacizumab- FOLFIRI en première ligne en 2006 révèle les résultats suivants: 51 réponses, 29 stabilités, 21 progressions et 10 toxicités avant évaluation. La médiane de survie globale (OS) est de 25,1 mois et la médiane de survie sans progression (PFS) de 10,2 mois. Dans le cas d'une chirurgie secondaire, l'OS médian triple de 18,8 mois chez les patients non réséqués versus 59,2 mois ceux réséqués. En comparant les sujets âgés de plus et de moins de 70 ans, aucune différence n'a été mise en évidence en termes de bénéfice ou de risque. Bevacizumab-FOLFIRI pourrait être administré en pratique courante chez les personnes âgées sous couvert d'une évaluation gériatrique et d'une approche multidisciplinaire.

Comparison between the biofilm initiation of Campylobacter jejuni and Campylobacter coli strains to an inert surface using BioFilm Ring Test.

AIMS: The adhesion to an inert surface (the first step of biofilm formation) of the two main pathogenic Campylobacter species, Campylobacter jejuni and Campylobacter coli, isolated from diverse origins, was compared. METHODS AND RESULTS: Adhesion assays were conducted in 96-well, polystyrene microtiter plates using the BioFilm Ring Test method. This new technique, based on magnetic bead entrapment, was shown to be suitable for analysing the adhesion of Campylobacter sp. strains by comparing the adhesion of four C. jejuni strains as revealed by the BioFilm Ring Test and immunodetection. Among the 46 strains tested, C. jejuni and C. coli displayed different adhesion capabilities ranging from no adhesion to strong adhesion. However, no strain of C. coli was strongly adherent, and statistically, C. coli adhered less to an inert surface than C. jejuni. In addition, strains isolated from animals or carcasses were less adherent than those isolated from food-processing and clinical cases. CONCLUSIONS: These observations suggest that the food environment and the human body could have selected strains with greater adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: The adhesion capability of strains could partly explain the cross-contamination or re-contamination of food products by Campylobacter. This property could provide a mode of survival for Campylobacter in the food chain.

Effect of the new imidazoline derivative S-22068 (PMS 847) on insulin secretion in vitro and glucose turnover in vivo in rats.

We have investigated the possible mechanisms underlying the antihyperglycaemic effect of the imidazoline derivative S-22068. In vitro, in the presence of 5 mmol/l glucose, S-22068 (100 micromol/l) induced a significant and sustained increase in insulin secretion from isolated, perifused, rat islets and a marked sensitization to a subsequent glucose challenge (10 mmol/l). S-22068 (100 micromol/l was able to antagonize the stimulatory effect of diazoxide on 86Rb efflux from preloaded islets incubated in the presence of 20 mmol/l glucose. Experiments were also performed to investigate whether S-22068 can alter glucose turnover and peripheral insulin sensitivity in vivo in mildly diabetic rats and obese, insulin resistant, Zucker rats. Neither glucose production nor individual tissue glucose utilization was modified by S-22068 in either group of rats. Similar results were obtained whether the studies were performed under basal conditions or during euglycaemic/hyperinsulinemic clamps. The results suggest that S-22068 exerts part of its antihyperglycaemic effect by promoting insulin secretion without alteration of peripheral insulin sensitivity.

Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline.

Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2', 4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of alpha2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4', 5'-dihydro-1'H-imidazol-2'-yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 micromol/kg) as after ip administration and appears as a good candidate for clinical investigations.

[Food habits, consumption, and knowledge of a low-income French population]. / Habitudes, consommations et connaissances alimentaires des Français en situation de précarité financière.

Behaviors related to nutrition as well as the eating habits of low-income French people are analyzed from data collected by the Nutrition and Health Barometer of the CFES in 1996. French people with monthly incomes of less than 4000 francs appear to go to fast-food restaurants more often than to other types of restaurant (for leisure or work). They appear to eat their three main meals alone more often, to spend less time over the evening meal, to watch television during their noon and evening meals, to have cheese or another dairy product rather than a main dish, and to limit their evening meal to a single dish. They are less numerous than higher-income people to have the "ideal" breakfast. These economically disavantaged French people do their shopping more often in large of medium-sized supermarkets and more often plan their meals according to the family budget. In terms of food they are more numerous to eat neither fruit nor vegetables; they consume less pork, fish and shellfish, dairy products, alcoholic beverages and especially before-dinner drinks. This study shows that the eating behavior of low-income French people is less in conformity with commonly accepted nutritional recommendations. Likewise, the rate of obesity observed among the women from this households appears high.

Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 1. Synthesis and biological activities of N-benzyl-N'-(arylalkyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines .

The physiopathology of non-insulin-dependent diabetes mellitus is associated with a dysfunction in the regulation of insulin secretion. The alpha 2-adrenoceptors have been reported to be involved in this alteration, although alpha 2-antagonists containing an imidazoline ring may stimulate insulin secretion independently of alpha 2-adrenoceptor blockage. Recently, a new "imidazoline-binding site" involved in the control of K(+)-ATP channels in the B cell has been proposed. In the course of searching for new antidiabetic agents, 1-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-benzylpiperazines, 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-alkylpiperazines, and 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-benzylpiperazines have been designed and evaluated as potential adrenoceptor antagonists. Pharmacological evaluation was performed in vivo using glucose tolerance tests performed on a rat model of type II diabetes obtained by injection of a low dose (35 mg/kg) of streptozotocin (STZ). For some compounds, binding experiments were performed on alpha 2 adrenoceptors and I1 and I2 imidazoline-binding sites. The biological and physicochemical data have been combined with molecular modeling studies to establish structure-activity relationships. The most active compound was 1-(2',4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl)- 4-methylpiperazine (7f); intraperitoneal administration (100 mumol/kg) of 7f strongly improved glucose tolerance in STZ diabetic rats. This effect seemed at least partly mediated by a significant increase of insulin secretion. Other compounds of the same family (7b, 16f, 23b) have also shown potent activity. We found no correlation between in vivo antihyperglycemic properties and in vitro affinities for alpha 2-adrenoceptors or I1, and I2 binding sites. These compounds can be considered as antihyperglycemic agents potentially useful for treatment of type II diabetes and are currently under complementary investigation.

[School lunch and nutrition of pupils ended in disadvantaged environments: reports, stakes, assistance with the decision]. / Restauration scolaire et alimentation des élèves issus des milieux défavorisés: constats, enjeux, aide à la décision.

Because of a growing poverty in France, the most disadvantaged families are having to give up school lunches for their children, with negative consequences from the point of view of nutrition. The data collected and worked by the authors calls for a more qualified interpretation. A drop in school meal attendance is a reality in some establishments and in some departments. Falling incomes in families experiencing the greatest difficulties undoubtedly influence the choice of expenditure, but it is not possible to generalise it at national level or to confirm any downward trend in attendance. Beside socio-economic factors, it is wide to consider also the food supply, school catering conditions and others factors bound up with changes in eating habits among young and their families. In any case, there is no proof for the moment of any repercussions on pupil's nutritional health, even though this will have to be structurally monitored. Neither has it been proved that pupils who do not take school meals are any the less well fed.

[Diet and health of deprived population in developed countries : What is the link.]. / Alimentation et santé des populations défavorisées dans les pays développés : quelle relation ?

The diet is often unbalanced and deficient in poverty situations and deprived populations are becoming larger and larger in developed countries. Negative effects on the health of poor populations are expected in the short or long term. The link between diet and health is well investigated in many epidemiological studies ; however they seldom analyse the link between infectious diseases and diet in western countries and rarely include poverty indicators that could help to provide more information about the situation among poor populations.

A multicenter double-blind comparative study of rilmenidine and clonidine in 333 hypertensive patients.

The efficacy and acceptability of rilmenidine were studied in a double-blind clonidine-controlled multicenter trial; after a 4-week placebo run-in period, patients with supine diastolic blood pressure (BP) between 95 and 115 mm Hg received as monotherapy either rilmenidine or clonidine over 6 weeks. The initial dose (rilmenidine 1 mg/day or clonidine 0.15 mg/day) was doubled (1 mg or 0.15 mg twice a day, respectively) after 2 weeks if diastolic BP remained greater than or equal to 90 mm Hg. Three hundred and thirty-three patients (mean age 57.8 +/- 0.7 years) with a systolic BP of 170.53 +/- 0.92 mm Hg and a diastolic BP of 101.57 +/- 0.30 mm Hg were randomly divided into 2 homogenous groups (rilmenidine, n = 162 and clonidine, n = 171). All patients taking rilmenidine completed the trial. Seventeen patients taking clonidine (10%, p less than 0.01 vs rilmenidine) were withdrawn because of severe side effects. Systolic and diastolic BP were significantly reduced in both groups at every examination (at 2, 4 and 6 weeks). The mean decreases in supine and erect BP were identical in both groups: systolic BP 19 mm Hg and diastolic BP 12 mm Hg after 6 weeks. BP was normalized (systolic BP less than 160 and diastolic BP less than or equal to 90 mm Hg) in 57% of patients taking rilmenidine and 56% of patients taking clonidine (60% of normalized patients had been taking the single dose in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)