Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.

IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Stroke Aphasia: 1,500 Consecutive Cases.

Background: To study the characteristics of vascular aphasia in a cohort of patients with a first-ever stroke. Methods: All patients admitted to the Lausanne neurology department for a first-ever stroke between 1979 and 2004 were included. Neurological examination including language was performed on admission. Stroke risk factors, stroke origin and location, associated symptoms and Rankin scale scores were recorded for each patient. The influence of these factors on aphasia frequency and subtypes was analyzed using logistic regression models. Results: 1,541 (26%) of patients included in this study had aphasia. The more frequent clinical presentations were expressive-receptive aphasia (38%) and mainly expressive aphasia (37%), whereas mainly receptive aphasia was less frequently observed (25%). In ischemic stroke, the frequency of aphasia increased with age (55% of nonaphasic vs. 61% of aphasic patients were more than 65 years old), female sex (40% of women in the nonaphasia group vs. 44% in the aphasia group) and risk factors for cardioembolic origin (coronary heart disease 20 vs. 26% and atrial fibrillation 15 vs. 24%). Stroke aphasia was more likely associated with superficial middle cerebral artery (MCA) stroke and leads to relevant disability. Clinical subtypes depended on stroke location and associated symptoms. Exceptions to the classic clinical-topographic correlations were not rare (26%). Finally, significant differences were found for patients with crossed aphasia in terms of stroke origin and aphasia subtypes. Conclusions: Risk factors for stroke aphasia are age, cardioembolic origin and superficial MCA stroke. Exceptions to classic clinical-topographic correlations are not rare. Stroke aphasia is associated with relevant disability. Stroke location and associated symptoms strongly influence aphasia subtypes.

Stable isotope geochemistry and formation mechanisms of quartz veins; Extreme paleoaltitudes of the Central Alps in the Neogene

Quartz veins ranging in size from less than 50 cm length and 5 cm width to greater than 10 m in length and 5 m in width are found throughout the Central Swiss Alps. In some cases, the veins are completely filled with milky quartz, while in others, sometimes spectacular void-filling quartz crystals are found. The style of vein filling and size is controlled by host rock composition and deformation history. Temperatures of vein formation, estimated using stable isotope thermometry and mineral equilibria, cover a range of 450 degrees C down to 150 degrees C. Vein formation started at 18 to 20 Ma and continued for over 10 My. The oxygen isotope values of quartz veins range from 10 to 20 permil, and in almost all cases are equal to those of the hosting lithology. The strongly rock-buffered veins imply a low fluid/rock ratio and minimal fluid flow. In order to explain massive, nearly morromineralic quartz formation without exceptionally large fluid fluxes, a mechanism of differential pressure and silica diffusion, combined with pressure solution, is proposed for early vein formation. Fluid inclusions and hydrous minerals in late-formed veins have extremely low delta D values, consistent with meteoric water infiltration. The change from rock-buffered, static fluid to infiltration from above can be explained in terms of changes in the large-scale deformation style occurring between 20 and 15 Ma. The rapid cooling of the Central Alps identified in previous studies may be explained in part, by infiltration of cold meteoric waters along fracture systems down to depths of 10 km or more. An average water flux of 0.15 cm 3 cm(-2)yr(-1) entering the rock and reemerging heated by 40 degrees C is sufficient to cool rock at 10 km depth by 100 degrees C in 5 million years. The very negative delta D values of < -130 permil for the late stage fluids are well below the annual average values measured in meteoric water in the region today. The low fossil delta D values indicate that the Central Alps were at a higher elevation in the Neogene. Such a conclusion is supported by an earlier work, where a paleoaltitude of 5000 meters was proposed on the basis of large erratic boulders found at low elevations far from their origin.

French version of the addiction severity index (5th Edition): validity and reliability among Swiss opiate-dependent patients. French validation of the Addiction Severity Index.

OBJECTIVE: The aim of the study was to validate a French adaptation of the 5th version of the Addiction Severity Index (ASI) instrument in a Swiss sample of illicit drug users. PARTICIPANTS AND SETTING: The participants in the study were 54 French-speaking dependent patients, most of them with opiates as the drug of first choice. Procedure: Analyses of internal consistency (convergent and discriminant validity) and reliability, including measures of test-retest and inter-observer correlations, were conducted. RESULTS: Besides good applicability of the test, the results on composite scores (CSs) indicate comparable results to those obtained in a sample of American opiate-dependent patients. Across the seven dimensions of the ASI, Cronbach's alpha ranged from 0.42 to 0.76, test-retest correlations coefficients ranged from 0.48 to 0.98, while for CSs, inter-observer correlations ranged from 0.76 to 0.99. CONCLUSIONS: Despite several limitations, the French version of the ASI presents acceptable criteria of applicability, validity and reliability in a sample of drug-dependent patients.

c-Jun N-terminal kinase pathway inhibition in intracerebral hemorrhage.

Background: Inhibition of the c-Jun N-terminal kinase (JNK) pathway by the TAT-coupled peptide XG-102 (formerly D-JNKI1) induces strong neuroprotection in ischemic stroke in rodents. We investigated the effect of JNK inhibition in intracerebral hemorrhage (ICH). Methods: Three hours after induction of ICH by intrastriatal collagenase injection in mice, the animals received an intravenous injection of 100 mu g/kg of XG-102. The neurological outcome was assessed daily and the mice were sacrificed at 6 h, 1, 2 or 5 days after ICH. Results: XG-102 administration significantly improved the neurological outcome at 1 day (p < 0.01). The lesion volume was significantly decreased after 2 days (29 +/- 11 vs. 39 +/- 5 mm(3) in vehicle-treated animals, p < 0.05). There was also a decreased hemispheric swelling (14 +/- 13 vs. 26 +/- 9% in vehicle-treated animals, p < 0.05) correlating with increased aquaporin 4 expression. Conclusions: XG-102 attenuates cerebral edema in ICH and functional impairment at early time points. The beneficial effects observed with XG-102 in ICH, as well as in ischemic stroke, open the possibility to rapidly treat stroke patients before imaging, thereby saving precious time.

Treatment of extraintestinal manifestations in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.

VEGF is required for growth and survival in neonatal mice.

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.

Insuffisance veineuse chronique stade III: Prise en charge physio- thérapeutique [3rd degree chronic venous insufficiency: physiotherapy treatment]

A venous ulcer is the end result of a long pathological process where venous hypertension represents the principal cause of a number of complications. The physiotherapist by adapting various different therapeutic approaches improves the vascular, joint and respiratory problems of these patients.

Etat de mal épileptique : traitements et facteurs pronostics

L'état de mal épileptique est une condition médicale sévère fréquemment rencontrée dont la mortalité est importante. Son traitement représente donc une urgence médicale. Il a déjà été démontré par des études bien conduites (Treiman et al., 1998) que l'administration de benzodiazépines est efficace en première intention. Or, 35-45% des états de mal échappent à ce traitement et malheureusement, les données scientifiques concernant le traitement de deuxième ligne sont nettement moins consistantes. Par ailleurs, si le rôle pronostique des caractéristiques de l'état de mal (type de crise, étiologie, état de conscience, âge du patient) sont connues (Rossetti et al., 2006), (Neligan and Shorvon, 2011), le rôle des comorbidités n'a reçu que peu d'attention à ce Dans la première partie de ce travail publiée dans Epilepsia (Alvarez et al., 2011) nous nous sommes intéressé au traitement de deuxième ligne et principalement aux trois substances les plus prescrites : la phénytoine (PHT), le valproate (VPA) et plus récemment le lévétiracetam (LEV). A ce jour, aucune étude n'avait comparé l'efficacité de ces substances pourtant largement utilisées. Ainsi, afin de savoir lequel ces anti-épileptiques utilisés en 2ème ligne est le plus efficace, nous avons extrait de notre base de données regroupant tout les états de mal épileptiques traités au Centre Hospitalier Universitaire Vaudois, tous les épisodes durant lesquelles le traitement par benzodiazépines à échoué (187 épisodes). Nous avons ensuite comparé les différentes caractéristiques cliniques et les différents outcomes de trois groupes de patients (ceux qui ont reçu de la PHT, du VPA ou du LEV). Nous avons pu mettre ainsi en évidence certaines différences d'efficacité inconnues jusqu'alors entre le VPA et le LEV, impliquant une certaine prudence face à l'emploi grandissant de ce dernier. La seconde partie de notre publiée dans Epilepsia (Alvarez et al., 2012) s'est portée sur les facteurs pronostiques de l'état de mal et plus précisément sur le rôle joué par les comorbidités. En utilisant la même base de données, nous avons pu démontrer que le pronostique d'un état de mal est très majoritairement influencé par l'étiologie et l'âge et que les comorbidités ne jouent qu'un rôle marginal. La présence de comorbidités n'impliquant pas forcément une mauvaise issue, la fragilité de certains patients ne doit pas dissuader les cliniciens à traiter adéquatement ces patients souffrant d'une condition aussi sévère qu'un état de mal épileptique.

Cutaneous plasmacytosis: an unusual presentation sharing features with POEMS syndrome?

Cutaneous plasmacytosis is a recently described skin disorder consisting of brown to red papules and nodules containing polyclonal plasmacytes. In this particular case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting with a primary hypothyroidisim. The last two signs have only been described to date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation, and might suggest an overlap between these two entities.

The dermatologists' role in managing psoriatic arthritis: results of a swiss delphi exercise intended to improve collaboration with rheumatologists.

BACKGROUND: Psoriatic arthritis (PsA) substantially impacts the management of psoriatic disease. OBJECTIVE: This study aimed to generate an interdisciplinary national consensus on recommendations of how PsA should be managed. METHODS: Based on a systematic literature search, an interdisciplinary expert group identified important domains and went through 3 rounds of a Delphi exercise, followed by a nominal group discussion to generate specific recommendations. RESULTS: A strong consensus was reached on numerous central messages regarding the impact of PsA, screening procedures, organization of the interaction between dermatologists and rheumatologists, and treatment goals. CONCLUSION: These recommendations can serve as a template for similar initiatives in other countries. At the same time, they highlight the need to take into account the impact of the respective national health care system. © 2015 S. Karger AG, Basel.