Modifier le comportement alimentaire : mission impossibles ?

Is it possible to modify intake behaviors for body weight control purposes? Over the last 40 years, dozens of international, peer-reviewed articles have described behavior modification approaches aiming at body weight reduction. The present article first presents a historical account of behavioral methods and their results. From the early therapies exclusively addressing behaviors (excluding restrictive diets) until the recent cognitive-behavioral treatments, published studies have reported modest weight losses associated with numerous metabolic, nutritional and psychological benefits whose maintenance, beyond the treatment duration, appear reasonably good. Recent studies specifically address the conditions of long-term maintenance. The main elements of behavioral-cognitive treatments are described briefly. Finally, the particular problems associated with these approaches in the French context are underlined.     

Les onze propositions issues des 3es États généraux des malades du cancer et de leurs proches de la Ligue contre le cancer

Sans résumé     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.     

Découverte d’une nouvelle cellule tueuse de tumeurs*

Une équipe labellisée par la Ligue vient de démasquer une cellule aux propriétés extraordinaires: elle se faufile auprès des tumeurs et les détruit en un temps record. Une première mondiale. *Article publié dans le magazine Vivre n˚ 329 écrit par la journaliste S. Delage/Sequoia ETC. Pour vous abonner, téléphoner au 0 810 111 101 (prix d’un appel local)     

Is backward disequilibrium in the elderly caused by an abnormal perception of verticality? A pilot study

OBJECTIVE: We hypothesised that backward disequilibrium (BD), defined by a posterior position of the centre of mass with respect to the base of support, could be caused by a backward tilt in the perception of verticality. METHODS: The relationship between BD, the perception of verticality, and the history of falls in 25 subjects aged 84.5+/-7.4 years was analysed. An original ordinal scale, the BD scale (BDS), was used to quantify BD. Postural (PV) and haptic verticals (HV) were measured in sagittal plane. RESULTS: BDS scores closely correlated with the number of falls (r = 0.81, p =10(-5)). The more the PV was tilted backward, the greater the BDS scores (r = -0.95, p<10(-6)), with a huge backward tilt of about 15 degrees in 4 subjects with severe BD. In these subjects, the tilt in perception of verticality was transmodal since a severe backward HV tilt was also found. CONCLUSIONS: This transmodality suggested high-order cognitive disruption in the construction of the subjective vertical used in postural control by subjects showing BD, which confirmed our hypothesis. SIGNIFICANCE: This study clearly shows that perception and action with respect to gravity are closely related and brings a new insight about fall mechanisms in the elderly.     

An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3.

A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients.