Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.

Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.

L'état des communes dans le canton de Vaud

Les communes vaudoises ne sont pas épargnées par les profonds changements que subissent les communes suisses depuis les années 90. Le nombre de réformes a augmenté de manière considérable et les causes de ces changements sont multiples: une complexité croissante des prestations à fournir, la recherche de formes organisationnelles plus efficaces, la difficulté de trouver des personnes s'engageant en politique. Vu ces défis, la fusion de communes a été fréquente dans certains cantons. Quant à lui, le canton de Vaud reste un canton avec un grand nombre de communes de petite taille. C'est entre autre sous l'aspect de la différente taille des communes que cette étude aborde des thèmes concernant les communes vaudoises, comme par exemple les limites de performances des communes, la politique et l'administration communale, les relations et la répartition des tâches entre les communes et le canton, la collaboration intercommunale où encore les fusions de communes. L'analyse se base sur les données de l'enquête auprès des secrétaires communaux suisses qui a lieu régulièrement depuis 1988.

Ultrasound Biomicroscopy Evaluation of Anterior Extension of Retinoblastomas : A Clinico-Pathological Study

Purpose: Extension of retinoblastoma cells anterior to the vitreous surface is a criteria used to categorize retinoblastomas in Group E. In some cases, the assessment of anterior chamber invasion is readily visible by slit lamp examination, but in other cases, invasion of the posterior chamber is clinically difficult to determinate. Ultrasound biomicroscopy (UBM) allows high-resolution images of the anterior segment and structures normally hidden from clinical visualization such as ciliary body, zonule or posterior chamber. This prompted us to evaluate the value of UBM in the assessment of posterior and anterior chamber involvement in patients with peripheral extending retinoblastomas. Methods: We retrospectively reviewed all retinoblastoma cases that underwent enucleation in our institution from 1.1996 till 12.2009 in which UBM ( 35-MHz or 50-MHz) evaluation was available. The UBM results were compared with the histopathological data. Results: From 1.1996 till 12.2009, 146 enucleations were performed in our institution. UBM information was available in 18 cases. There were 8 males and 10 females. The mean age was 4 years old. UBM allowed correct assessement of posterior chamber invasion in 15 cases (13 cases with retinoblastoma in the posterior chamber and 2 cases without retinoblastoma in the posterior chamber). There was a significant correlation between the presence of retinoblastoma cells in the posterior chamber detected by UBM and the histopathological confirmation of posterior chamber involvement (p=0,0008). The sensitivity of UBM in the assessment of posterior chamber invasion by retinoblastoma was 81% and the specificity 100%. UBM allowed correct assessment of anterior chamber invasion in 13 cases. The sensitivity of UBM for this purpose was 50% and the specificity 60 %. Conclusions: In selected cases of advanced retinoblastoma, UBM appears to represent a valuable tool in the evaluation of the precise extension of the disease. Although our series encompasses only a limited number of cases, the sensitivity and specificity of UBM in the assessment of retinoblastoma anterior extension is interesting. Further prospective multi-centered clinical studies would be necessary to better delineate the utility of this method in the precise categorization of retinoblastoma anterior extension

Cerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury.

Growing evidence suggests that endogenous lactate is an important substrate for neurons. This study aimed to examine cerebral lactate metabolism and its relationship with brain perfusion in patients with severe traumatic brain injury (TBI). A prospective cohort of 24 patients with severe TBI monitored with cerebral microdialysis (CMD) and brain tissue oxygen tension (PbtO2) was studied. Brain lactate metabolism was assessed by quantification of elevated CMD lactate samples (>4 mmol/L); these were matched to CMD pyruvate and PbtO2 values and dichotomized as glycolytic (CMD pyruvate >119 μmol/L vs. low pyruvate) and hypoxic (PbtO2 <20 mm Hg vs. nonhypoxic). Using perfusion computed tomography (CT), brain perfusion was categorized as oligemic, normal, or hyperemic, and was compared with CMD and PbtO2 data. Samples with elevated CMD lactate were frequently observed (41±8%), and we found that brain lactate elevations were predominantly associated with glycolysis and normal PbtO2 (73±8%) rather than brain hypoxia (14±6%). Furthermore, glycolytic lactate was always associated with normal or hyperemic brain perfusion, whereas all episodes with hypoxic lactate were associated with diffuse oligemia. Our findings suggest predominant nonischemic cerebral extracellular lactate release after TBI and support the concept that lactate may be used as an energy substrate by the injured human brain.

Immunocytochemical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. II. Electron microscopic study.

Following a former immunohistochemical study in the rat brain [Arluison, M., Quignon, M., Nguyen, P., Thorens, B., Leloup, C., Penicaud, L. Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. I. Immunohistochemical study. J. Chem. Neuroanat., in press], we have analyzed the ultrastructural localization of GLUT2 in representative and/or critical areas of the forebrain and hindbrain. In agreement with previous results, we observe few oligodendrocyte and astrocyte cell bodies discretely labeled for GLUT2 in large myelinated fibre bundles and most brain areas examined, whereas the reactive glial processes are more numerous and often localized in the vicinity of nerve terminals and/or dendrites or dendritic spines forming synaptic contacts. Only some of them appear closely bound to unlabeled nerve cell bodies and dendrites. Furthermore, the nerve cell bodies prominently immunostained for GLUT2 are scarce in the brain nuclei examined, whereas the labeled dendrites and dendritic spines are relatively numerous and frequently engaged in synaptic junctions. In conformity with the observation of GLUT2-immunoreactive rings at the periphery of numerous nerve cell bodies in various brain areas (see previous paper), we report here that some neuronal perikarya of the dorsal endopiriform nucleus/perirhinal cortex exhibit some patches of immunostaining just below the plasma membrane. However, the presence of many GLUT2-immunoreactive nerve terminals and/or astrocyte processes, some of them being occasionally attached to nerve cell bodies and dendrites, could also explain the pericellular labeling observed. The results here reported support the idea that GLUT2 may be expressed by some cerebral neurones possibly involved in glucose sensing, as previously discussed. However, it is also possible that this transporter participate in the regulation of neurotransmitter release and, perhaps, in the release of glucose by glial cells.

Fièvre à répétition chez l'enfant: penser au syndrome de PFAPA [Periodic fever in children: keep in mind the PFAPA syndrome]

Les maladies autoinflammatoires font partie du diagnostic différentiel de l'état fébrile à répétition chez l’enfant. Ces maladies sont caractérisées par des poussées inflammatoires sans cause évidente. Certaines de ces maladies, comme la Fièvre méditerranéenne familiale, ont une origine génétique et nécessitent un traitement régulier pour éviter des conséquences graves à long terme. Le syndrome de PFAPA est la plus fréquente des fièvres récurrentes et son diagnostic se base sur des critères diagnostiques peu précis. Son traitement reste controversé. La prednisone en dose unique permet d'interrompre la poussée et l'amygdalectomie peut induire une rémission dans une majorité des cas. The autoinflammatory diseases should be considered in the differential diagnosis of recurrent fever in childhood. These diseases are characterized by inflammatory episodes without an evident cause. Some of these diseases, like the Familial Mediterranean Fever, have a genetic origin and need a chronic treatment to avoid severe complications on the long term. PFAPA syndrome is the most frequent cause of recurrent fever and is diagnosed based on unspecific criteria. The treatment is still controversial. One dose of Prednisone is able to interrupt the flare and tonsillectomy may induce a remission in the majority of the cases

Le taux de détresse respiratoire du nouveau-né augmente, celui des césariennes aussi: et si ce n'était pas un hasard? [Respiratory distress of the neonate and the rate of caesarean section have increased over the last 30 years. Is there a link?]

Ces trente dernières années, on note en Suisse une augmentation significative de l'incidence du syndrome de détresse respiratoire (SDR) chez le nouveau-né (NN), touchant particulièrement les enfants avec un poids de naissance >2500 g. En même temps, le taux des césariennes (CS) s'est aussi accru. Une explication pour une éventuelle corrélation entre les deux évolutions est une augmentation en particulier des CS électives qui ont tendance à être planifiées à un terme précoce pour éviter la mise en travail spontanée. Suite à cela, le foetus est privé de différents mécanismes qui favorisent l'adaptation pulmonaire périnatale. Les bénéfices réels de la CS sur la morbidité tant foetale que maternelle ne doivent pas faire oublier que la CS est un facteur de risque pour le SDR du NN. Ce risque peut être diminué efficacement en planifiant une CS élective après 39 semaines révolues. In Switzerland, the rate of respiratory distress in neonates needing hospitalization has doubled over the last thirty years, concerning in particular babies weighing more than 2500 g. In the same time, the rate of Caesarean section (CS) has also multiplied. We suppose that a link between the two evolutions might be the increase of elective CS. They tend to be planned early at term to avoid the onset of spontaneous labour As a consequence, the foetus is deprived of different mechanisms helping pulmonary transition around birth. The potential benefits of CS regarding morbidity of foetus and mother should not overshadow that CS is a significant risk factor for respiratory problems of the neonate. This risk could be dramatically decreased by planning elective CS only after completed 39 weeks of gestation

Adolescents' beliefs about marijuana use: a comparison of regular users, past users and never/occasional users.

A questionnaire investigating adolescents' opinions and experiences regarding marijuana use was administered to 163 adolescents and young adults (96 boys and 67 girls) aged 13 to 20 (mean age = 16.8, s.d. = 1.5). Items referred to marijuana and other substances' dangerousness, representations regarding the positive and negative consequences of marijuana use. Responses were compared according to marijuana use status (classified into never/occasional use, current regular use and past regular use). Results show that adolescents' opinions differ according to their experience with marijuana use. Current regular users evaluate marijuana as less dangerous, but alcohol and heroin as more dangerous in comparison with never/occasional and past users. Current and past users are more likely to define marijuana as a medical drug and a plant used in agriculture, and less likely to define it as an illegal drug. Current and past users evaluate marijuana use as a way to cope with stress, to relax to a greater extent than do never/occasional users do. The latter attribute more negative consequences to marijuana use such as diminished driving ability and school performance and a pathway to hard drugs.

Existential values transformation in all organ transplantation: A qualitative prospective study.

Organ transplantation offers a treatment of choice for patients suffering from end stage illnesses. The aim of this IRB approved prospective qualitative study was to analyze patients’ psychological concerns from their inclusion on the waiting list for first organ transplantation (TX) (T1; N=71; kidney, K=30; liver, Li=11; lung, Lu=15; heart, H=15) and six months after TX (T2; N=49; K=15; Li=10; Lu=14; H=10). Semi-structured interviews were conducted at home or in a place selected by patients. Qualitative pattern analysis (QUAPA) of the verbatim transcriptions was applied. T1 (K) Patients maintained an apparent normality (87%), building emotional protection (23%), and developing a fatalist attitude towards life (43%). (Li) Physical limits were set to spare energy until TX (73%). Illness led to reevaluation of life values (66%). (Lu) Physical and psychological self-protection was prioritized when health declined (67%). Modified life values, fatalism (33%) and spirituality (27 %) were mentioned. (H) Patients husbanded physical (80%) and psychological (67%) resources and self-protection. Modified life values and fatalist attitude towards life were reported (40%). T2 (K) New perspective on life was described, with increase of empathy towards others (20%). (Li) Positive identity and life values modifications (60%), greater openness towards others, closeness to significant ones (30%) and a more self-centered attitude (30%) prioritizing the essential (20%) were reported. Lack of respect of life values generated anger (40%). (Lu) Setting existential priorities and increase in spirituality (64%), along with the development of new life values, greater openness to others (57%) and closeness to significant ones (21%) were underlined. Lack of respect of human values induced negative feelings (36%). Self-centered attitudes, setting limits to other people were mentioned (29%). (H) Change in life values with setting life priorities was reported (70%) with increase in spirituality, and the lack of respect of life values generated anger (50%). Self-centered attitudes were reported (60%). TX not only comes with positive physical benefits, but also with positive existential values and psychological transformation, and the development of a more altruistic attitude and humanistic values.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

OBJECTIVE: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. METHODS: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). RESULTS: Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. CONCLUSION: In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.