Perioperative antiplatelet therapy.

Aspirin is recommended as a lifelong therapy that should never be interrupted for patients with cardiovascular dis- ease. Clopidogrel therapy is mandatory for six weeks after placement of bare-metal stents, three to six months after myocardial infarction, and at least 12 months after placement of drug-eluting stents. Because of the hypercoagulable state induced by surgery, early withdrawal of antiplatelet therapy for secondary prevention of cardiovascular disease increases the risk of postoperative myocardial infarction and death five- to 10-fold in stented patients who are on continuous dual antiplatelet therapy. The shorter the time between revascularization and surgery, the higher the risk of adverse cardiac events. Elective surgery should be postponed beyond these periods, whereas vital, semiurgent, or urgent operations should be performed under continued dual antiplatelet therapy. The risk of surgical hemorrhage is increased approximately 20 percent by aspirin or clopidogrel alone, and 50 percent by dual antiplatelet therapy. The present clinical data suggest that the risk of a cardiovascular event when stopping antiplatelet agents preoperatively is higher than the risk of surgical bleeding when continuing these drugs, except during surgery in a closed space (e.g., intracranial, posterior eye chamber) or surgeries associated with massive bleeding and difficult hemostasis.

Diarrhées aiguës: propositions de prise en charge ambulatoire [Acute diarrhea: proposal for outpatient management]

Dans la majorité des cas, les diarrhées aiguës sont bénignes et d'évolution spontanément favorable. Il faut cependant savoir reconnaître les situations pouvant mener à des complications, en l'occurrence identifier les diarrhées invasives, inflammatoires, caractérisées par la présence de fièvre, de douleurs abdominales, de ténesmes, de mucus et, ou de sang dans les selles. Celles-ci sont à distinguer des diarrhées sécrétoires, non invasives, non inflammatoires, sans fièvre, généralement aqueuses et volumineuses. En cas de doute diagnostique, l'identification de leucocytes par microscopie ou test à la lactoferrine dans les selles permet d'évoquer une gastroentérite invasive. Les indications à une antibiothérapie empirique dans l'attente du résultat de la coproculture sont la présence d'un syndrome dysentérique (T > 38°C, > 6 selles/24 heures, douleurs abdominales, diarrhées mucopurulentes), l'âge avancé, des comorbidités significatives, une immunosuppression et la présence d'une prothèse endovasculaire. In the majority of the cases, an acute diarrhea is mild and of spontaneously favorable evolution. It is however necessary to know how to recognize the situations being able to lead to complications, in particular to identify the invasive, inflammatory diarrheas, characterized by the presence of fever, abdominal pains, mucus and\or blood. The identification of leukocytes by microscopy or lactoferrine test is helpful. Empiric quinolones treatment is recommended in the presence of dysenteric syndrome (T > 38 degrees C, > 6 stods/24 h 00, abdominal pain muco-purulent diarrhea), advanced age, significant comorbidities, immunosuppression or presence of an endovascular prothesis

Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.

A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.

" Ich habe viele namen " : Polyphonie und Dialogizität im autobiographischen Spätwerk Max Frischs und Friedrich Dürrenmatts

Zusammenfassung: Max Frisch und Friedrich Dürrenmatt, als Dioskuren der Schweizer Literatur zeitlebens aneinandergekettet, haben auf der Suche nach ihrem Selbst immer auch den anderen im Blick. Aus ihrer pointierten, gelegentlich polemischen wechselseitigen Abgrenzung entsteht ein künstlerisch höchst produktiver, impliziter Dialog. Er wird hier erstmals explizit gemacht. Unter den Gesichtspunkten von Polyphonie und Dialogizität wird die Konstruktion und Auflösung des autobiographischen Subjekts untersucht. Diese Fallstudien an einzelnen, repräsentativen Texten der beiden Autoren stellen neue Fragen, die für die gesamte Autobiographiediskussion relevant sind: Bei Dürrenmatts großem ,,Stoffe"-Komplex wird, unter Einbezug der textgenetischen Perspektive, der autobiographische Prozess als das Anprobieren von multiplen Ichs analysiert. Das Problem des Subjekts radikalisiert sich als Problem der Sprache, der "vielen Namen", mit denen sich das Subjekt selbst tauft. Bei Frisch deckt die Studie mit ihrem neuen Ansatz die architektonischen und musikalischen Kompositionsverfahren in "Montauk" und "Holozän" auf, eine Textarchitektur in der Zeit und im Medium der Sprache. Dabei werden bisher unbekannte Entwürfe zu diesen wichtigen Spätwerken Frischs erstmals genutzt und publiziert.

Rational design of an organometallic glutathione transferase inhibitor.

Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study.

AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors. METHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals. RESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles. CONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, and both have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hour periods from a total of 50 observation days. We measured their exposure to fine particulate matter (PM2.5), ultrafine particles, noise, and the cardiopulmonary health endpoints: blood pressure, pro-inflammatory and pro-thrombotic markers in the blood, lung function and fractional exhaled nitric oxide (FeNO) measured approximately 15 hours post-work. Heart rate variability was assessed during a sleep period approximately 10 hours post-work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased HF and LF power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and non-significantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

Sommes-nous prêts à prescrire une polypill à nos patients [Are we ready to prescribe a polypill to our patients?].

The all-in-one pill combination (Polypill) of several active components used in primary prevention of cardiovascular disease was a decade ago purposed to reduce the cardiovascular burden by more than 80%. This Polypill could be approved before 2013 in United States. Although controversed, it could answer to the worried situation even observed in Switzerland: the adherence to secondary prevention treatments is clearly insufficient and the cardiovascular events remain in the first row of death's causes. This abstract summarize the results from interventional studies who tried to valid this concept as well as the main stakes to be assessed on the medical side before to consider such a similar approach in Switzerland.

Cells with neuronal characteristics differentiate and persist for one year in rat optic nerve explants cultures.

Evidence concerning the presence or absence of common neuronglia lineages in the postnatal mammalian central nervous system is still a matter of speculation. We address this problem using optic nerve explants, which show an extremely long survival in culture. Morphological, immunocytochemical and immunochemical methods were applied. The results obtained from in vitro tissue were compared with optic nerves (ONs) and whole-brain samples from animals of different ages. Newborn rat ONs represented the starting material of our tissue culture; they are composed of unmyelinated axons, astrocytes and progenitor cells but devoid of neuronal cell bodies. At this age, Western blots of ONs were positively stained by neurofilament and synapsin I specific antibodies. These bands increased in intensity during postnatal in situ development. In explant cultures, the glia cells reach a stage of functional differentiation and they maintain, together with undifferentiated cells, a complex histotypic organization. After 6 days in vitro, neurofilaments and synapsin I could not be detected on immunoblots, indicating that 1) axonal degeneration was completed, and 2) neuronal somata were absent at the time. Surprisingly, after about 4-5 weeks in culture, a new cell type appeared, which showed characteristics typical of neurons. After 406 days in vitro, neurofilaments and synapsin I were unequivocally detectable on Western blots. Furthermore, both immunocytochemical staining and light and electron microscopic examinations corroborated the presence of this earlier-observed cell type. These in vitro results clearly show the high developmental plasticity of ON progenitor cells, even late in development. The existence of a common neuron-glia precursor, which never gives rise to neurons in situ, is suggested.

3-T direct MR arthrography of the wrist: value of finger trap distraction to assess intrinsic ligament and triangular fibrocartilage complex tears.

PURPOSE: To determine the value of applying finger trap distraction during direct MR arthrography of the wrist to assess intrinsic ligament and triangular fibrocartilage complex (TFCC) tears. MATERIALS AND METHODS: Twenty consecutive patients were prospectively investigated by three-compartment wrist MR arthrography. Imaging was performed with 3-T scanners using a three-dimensional isotropic (0.4 mm) T1-weighted gradient-recalled echo sequence, with and without finger trap distraction (4 kg). In a blind and independent fashion, two musculoskeletal radiologists measured the width of the scapholunate (SL), lunotriquetral (LT) and ulna-TFC (UTFC) joint spaces. They evaluated the amount of contrast medium within these spaces using a four-point scale, and assessed SL, LT and TFCC tears, as well as the disruption of Gilula's carpal arcs. RESULTS: With finger trap distraction, both readers found a significant increase in width of the SL space (mean Δ = +0.1mm, p ≤ 0.040), and noticed more contrast medium therein (p ≤ 0.035). In contrast, the differences in width of the LT (mean Δ = +0.1 mm, p ≥ 0.057) and UTFC (mean Δ = 0mm, p ≥ 0.728) spaces, as well as the amount of contrast material within these spaces were not statistically significant (p = 0.607 and ≥ 0.157, respectively). Both readers detected more SL (Δ = +1, p = 0.157) and LT (Δ = +2, p = 0.223) tears, although statistical significance was not reached, and Gilula's carpal arcs were more frequently disrupted during finger trap distraction (Δ = +5, p = 0.025). CONCLUSION: The application of finger trap distraction during direct wrist MR arthrography may enhance both detection and characterisation of SL and LT ligament tears by widening the SL space and increasing the amount of contrast within the SL and LT joint spaces.