The renin-angiotensin system and arterial wall behavior.

To assess the behavior of the arterial wall in hypertensive patients, we developed a noninvasive ultrasonic device. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Blood pressure, which is a co-determinant of compliance, is thus taken into account. This method allows one to compare arteries from patients with different blood pressures. Arterial compliance and distensibility were first investigated in healthy young volunteers administered either lisinopril (20 mg), atenolol (100 mg) or nitrendipine (20 mg) once a day. After 8 days of treatment, only lisinopril was found to increase arterial compliance. Subsequently, we compared arterial diameter- and distensibility-pressure curves from newly diagnosed and untreated hypertensive patients with those of matched normotensive control patients. Diameter-pressure curves did not differ significantly between the groups and distensibility was not reduced. Similar findings were later obtained in an animal model, when mechanical properties of carotid arteries were compared between spontaneously hypertensive rats and normotensive counterparts (Wistar-Kyoto rats). These results, although interesting by providing noninvasive information on the elastic response of the wall, call for further development of the technique to be able to measure arterial wall thickness. Stress-strain relationship could ultimately be established to thoroughly characterize physical properties of blood vessel walls.

Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?

The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the "drug addiction circuitry," an increasing amount of evidence demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.

Patients presenting with somatic complaints in general practice : dépression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors

RAPPORT DE SYNTHÈSE Introduction En médecine de premier recours, les plaintes physiques sont fréquemment associées à des troubles dépressifs, anxieux et somatoformes et peuvent les masquer. Il est fréquemment reporté que ces troubles mentaux ont tendance à être insuffisamment diagnostiqués. Par ailleurs, peu d'études ont été conduites en médecine de premier recours concernant la possible association entre facteurs de stress psychosociaux et troubles dépressifs, anxieux et somatoformes. Objectifs Les objectifs étaient de déterminer la prévalence des troubles dépressifs, anxieux et somatoformes chez des patients consultant avec une plainte physique en médecine de premier recours, ainsi que d'explorer la possible association entre ces troubles mentaux et des facteurs de stress psychosociaux. Méthodes Nous avons conduit une étude transversale, multicentrique parmi vingt et un cabinets médicaux en Suisse Romande et la Policlinique Médicale Universitaire de Lausanne. Les sujets étaient sélectionnés aléatoirement parmi des patients qui avaient présenté spontanément au moins une plainte physique et qui avaient consulté lors d'une demi- journée de consultation considérée pour l'étude. Les patients inclus ont rempli l'auto- questionnaire Patient Health Questionnaire (PHQ) entre novembre 2004 et juillet 2005. Nous avons utilisé la version française et validée du PHQ qui permet le diagnostic des principaux troubles mentaux selon les critères du DSM-IV et l'analyse de l'exposition aux facteurs de stress psychosociaux. Résultats Neuf cent dix-sept patients se présentant avec au moins une plainte physique ont été inclus. Le taux de troubles dépressifs, anxieux et somatoformes a été de 20,0% (intervalle de confiance [IC] à 95% = 17,4%-22,7%), 15,5% (IC 95% = 13,2%- 18,0%) et 15,1% (IC 95% = 12,8%~17,5%), respectivement. Les facteurs de stress psychosociaux ont été significativement associés aux troubles mentaux. Les patients avec une accumulation de facteurs de stress psychosociaux ont été le plus souvent déprimés, anxieux ou ont manifesté des troubles somatoformes, avec une augmentation par un facteur 2,2 (IC 95% = 2,0-2,5) pour chaque facteur additionnel. Conclusions Bien que la relation entre facteurs de stress psychosociaux et trouble dépressif soit bien établie, cette étude montre qu'il existe un lien entre ces facteurs de stress et les troubles dépressifs, anxieux et somatoformes. L'investigation de ces troubles mentaux chez des patients consultant avec un symptôme physique en médecine de premier recours est pertinente. D'autres explorations sont nécessaires pour investiguer le bénéfice potentiel d'une prise en charge intégrée des facteurs de stress psychosociaux sur la diminution des plaintes physiques et des troubles mentaux chez les patients que suivent les médecins de premier recours.

Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.

Personality disorders and the Five-Factor Model among French speakers in Africa and Europe

Objective: Several authors have suggested that Personality Disorders (PDs) might be more accurately described using a dimensional model instead of a categorical one. The aim of this study was to describe the relationship between PDs and the Five-Factor Model (FFM)-a dimensional model describing normal personality traits known for its invariance across cultures-in two different cultural settings. Method: Subjects from nine French-speaking African countries (n = 2,014) and from Switzerland (n = 697) completed both the French-version of the IPDE screening questionnaire, assessing the ten DSM-IV PDs, and the French-version of the NEO-PI-R, assessing the five domains and thirty facets of the FFM. Results: Correlations between PDs and the five domains of the FFM were similar in both samples. For example, Neuroticism was highly correlated with Borderline, Avoidant, and Dependent PDs in both Africa and Switzerland. The total rank-order correlation (rho) between the two correlation matrices was very high (rho = 0.93) and significant (P < 0.001), as were the rhos for all domains of the FFM and all PDs, except Paranoid and Dependent PDs. However, the rhos for PDs across facet-scales were all highly significant (P < 0.001). Moreover, 80% of Widiger and colleagues' predictions and 70 % of Lynam and Widiger's prototypes, concerning the relationship between PDs and the FFM, were confirmed in both samples. Conclusions: The relationship between PDs and the FFM was stable in two samples separated by a great cultural distance. These results suggest that a dimensional approach and in particular the FFM might be useful for describing PDs in a variety of cultural settings.

From Leadership to Citizenship Behavior in Public Organizations: When Values Matter

After decades of management reforms in the public sector, questions on the impact of leader-ship behavior in public organizations have been attracting increasing attention. This paper investigates the relationship between transformational leadership behavior and organizational citizenship behavior as one major extra-role outcome of transformational leadership. Refer-ring to a growing body of research that shows the importance of public service values and employee identification in public administration research, we include public service motiva-tion and organizational goal clarification as mediating variables in our analysis. Structural equation modeling is applied as the method of analysis for a sample of 569 public managers at the local level of Switzerland. The findings of our study support the assumed indirect relation-ship between leadership and employee behavior and emphasize the relevance of public ser-vice values when analyzing leadership behavior in public sector organizations.

Intrinsically photosensitive retinal ganglion cells.

The recent discovery of melanopsin-expressing retinal ganglion cells that mediate the pupil light reflex has provided new insights into how the pupil responds to different properties of light. These ganglion cells are unique in their ability to transduce light into electrical energy. There are parallels between the electrophysiologic behavior of these cells in primates and the clinical pupil response to chromatic stimuli. Under photopic conditions, a red light stimulus produces a pupil constriction mediated predominantly by cone input via trans-synaptic activation of melanopsin-expressing retinal ganglion cells, whereas a blue light stimulus at high intensity produces a steady-state pupil constriction mediated primarily by direct intrinsic photoactivation of the melanopsin-expressing ganglion cells. Preliminary data in humans suggest that under photopic conditions, cones primarily drive the transient phase of the pupil light reflex, whereas intrinsic activation of the melanopsin-expressing ganglion cells contributes heavily to sustained pupil constriction. The use of chromatic light stimuli to elicit transient and sustained pupil light reflexes may become a clinical pupil test that allows differentiation between disorders affecting photoreceptors and those affecting retinal ganglion cells.

Le concept de test relationnel en psychothérapie: origine, développements et applications aux troubles de la personnalité = The test concept in psychotherapy: origins, developments and application to personality disorders

Le concept de test relationnel (test, en anglais ; Weiss et Sampson, 1986 [16]) est présenté. Ses origines dans les écrits de Freud sont brièvement retracées et son inscription dans la théorie des croyances pathogènes de Weiss présentée. Par ailleurs, les autres éléments de la théorie psychanalytique de Weiss sont présentés (buts thérapeutiques, obstacles, traumas, insight, test relationnel). Toutes ces étapes sont illustrées par des exemples tirés de la littérature. Un développement récent du concept de test relationnel est présenté et appliqué à la psychothérapie des troubles de la personnalité (Sachse, 2003 [14]). Finalement, les auteurs donnent deux brefs exemples de tests relationnels tirés de leur propre pratique de psychothérapeute et discutent des modèles en les comparant entre eux. Des conclusions concernant l'utilité du concept de test relationnel pour la pratique psychothérapeutique et la recherche en psychothérapie sont proposées. The test concept (Weiss and Sampson, 1986 [16]) is presented. Its origins in Freud's works are briefly evoked and its place within the theory of pathogenic beliefs by Weiss presented. We present also the remaining elements of Weiss' psychoanalytic theory which are objectives, obstacles, traumas and insight. Every step of the reflection is illustrated with case examples, drawn from the literature. A recent development of the test concept is presented and applied to the psychotherapy of personality disorders (Sachse, 2003 [14]). Finally, the authors give brief examples of tests having occurred in their own practice as psychotherapists and discuss the models by comparing them among each other. Conclusions are drawn concerning the usefulness of the test concept for psychotherapy practice and research.

Community introduction of practice parameters for autistic spectrum disorders: Advancing early recognition.

OBJECTIVES: Within a strong interdisciplinary framework, improvement in the quality of care for children with autistic spectrum disorders through a 2 year implementation program of Practice Parameters, aimed principally at improving early detection and intervention. METHOD: We developed Practice Parameters (PPs) for Pervasive Developmental Disorders and circulated the PPs to all child and adolescent psychiatrists practicing in the region. RESULTS: PP development and parallel information strategies resulted in a significant decrease of 1.5 years in the mean-age-at-diagnosis. However, further analysis indicated that improvement was only transient. CONCLUSION: Despite the encouraging improvement in mean-age-at-diagnosis 2 years after PP implementation, other indicators showed a failure to maintain the improvements. A systematic screening program would be the most reliable method to reinforce the PPs.

Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior.

The dynamic properties of helix 12 in the ligand binding domain of nuclear receptors are a major determinant of AF-2 domain activity. We investigated the molecular and structural basis of helix 12 mobility, as well as the involvement of individual residues with regard to peroxisome proliferator-activated receptor alpha (PPARalpha) constitutive and ligand-dependent transcriptional activity. Functional assays of the activity of PPARalpha helix 12 mutants were combined with free energy molecular dynamics simulations. The agreement between the results from these approaches allows us to make robust claims concerning the mechanisms that govern helix 12 functions. Our data support a model in which PPARalpha helix 12 transiently adopts a relatively stable active conformation even in the absence of a ligand. This conformation provides the interface for the recruitment of a coactivator and results in constitutive activity. The receptor agonists stabilize this conformation and increase PPARalpha transcription activation potential. Finally, we disclose important functions of residues in PPARalpha AF-2, which determine the positioning of helix 12 in the active conformation in the absence of a ligand. Substitution of these residues suppresses PPARalpha constitutive activity, without changing PPARalpha ligand-dependent activation potential.

The adolescent with a chronic condition. Part I: developmental issues.

The prevalence of chronic conditions among adolescents is difficult to assess due to the lack of quality data focusing specifically on this age group, as well as the diversity in methodology and definitions used. However, surveys carried out by self administered questionnaires among in-school adolescent populations indicate that around 10% of adolescents suffer from such a condition. The aim of this paper is to analyse the reciprocal effects of chronic conditions and adolescent development by reviewing the effect of chronic disease on growth and puberty and on psychosocial development, and the effect of developmental issues on the course and management of chronic disease.

Histological behavior of glutaraldehyde cross-linked bovine collagen injected into the human bladder for the treatment of vesicoureteral reflux

Endoscopic subureteral collagen injection has become an accepted means for the treatment of vesicoureteral reflux in children. The aim of this study was to evaluate the histological behavior of glutaraldehyde cross-linked bovine collagen implants. The specimens were harvested from 29 patients who underwent reimplant surgery 2 to 30 months (mean 9.5) after unsuccessful subureteral injection therapy. In addition to routine hematoxylin and eosin staining, a new staining method (solophenyl red 3BL) able to demonstrate selectively neoformation of types I and III human collagen, was applied. Invasion of host fibroblasts into the bovine implant and the formation of endogenous types I and III collagen were demonstrated in all 29 cases. Adverse histological reactions were rare and, if present, they were predominantly of an inflammatory nature.

Neuroprotection for optic nerve disorders.

The concept that optic nerve fiber loss might be reduced by neuroprotection arose in the mid 1990s. The subsequent research effort, focused mainly on rodent models, has not yet transformed into a successful clinical trial, but provides mechanistic understanding of retinal ganglion cell death and points to potential therapeutic strategies. This review highlights advances made over the last year. In excitotoxicity and axotomy models retinal ganglion cell death has been shown to result from a complex interaction between retinal neurons and Müller glia, which release toxic molecules including tumor necrosis factor alpha. This counteracts neuroprotection by neurotrophins such as nerve growth factor, which bind to p75NTR receptors on Müller glia stimulating the toxic release. Another negative effect against neurotrophin-mediated protection involves the action of LINGO-1 at trkB brain-derived neurotrophic factor (BDNF) receptors, and BDNF neuroprotection is enhanced by an antagonist to LINGO-1. As an alternative to pharmacotherapy, retinal defences can be stimulated by exposure to infrared radiation. The mechanisms involved in glaucoma and other optic nerve disorders are being clarified in rodent models, focusing on retrograde degeneration following axonal damage, excitotoxicity and inflammatory/autoimmune mechanisms. Neuroprotective strategies are being refined in the light of the mechanistic understanding.