Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy.

Recent evidence suggests that lactate could be a preferential energy substrate transferred from astrocytes to neurons. This would imply the presence of specific transporters for lactate on both cell types. We have investigated the immunohistochemical localization of two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Using specific antibodies raised against MCT1 and MCT2, we found strong immunoreactivity for each transporter in glia limitans, ependymocytes and several microvessel-like elements. In addition, small processes distributed throughout the cerebral parenchyma were immunolabeled for monocarboxylate transporters. Double immunofluorescent labeling and confocal microscopy examination of these small processes revealed no co-localization between glial fibrillary acidic protein and monocarboxylate transporters, although many glial fibrillary acidic protein-positive processes were often in close apposition to elements labeled for monocarboxylate transporters. In contrast, several elements expressing the S100beta protein, another astrocytic marker found to be located in distinct parts of the same cell when compared with glial fibrillary acidic protein, were also strongly immunoreactive for MCT1, suggesting expression of this transporter by astrocytes. In contrast, MCT2 was expressed in a small subset of microtubule-associated protein-2-positive elements, indicating a neuronal localization. In conclusion, these observations are consistent with the possibility that lactate, produced and released by astrocytes (via MCT1), could be taken up (via MCT2) and used by neurons as an energy substrate.

Diagnostic accuracy of G-CSF, IL-8, and IL-1ra in critically ill children with suspected infection.

OBJECTIVE: To elucidate the diagnostic accuracy of granulocyte colony-stimulating factor (G-CSF), interleukin-8 (IL-8), and interleukin-1 receptor antagonist (IL-1ra) in identifying patients with sepsis among critically ill pediatric patients with suspected infection. DESIGN AND SETTING: Nested case-control study in a multidisciplinary neonatal and pediatric intensive care unit (PICU) PATIENTS: PICU patients during a 12-month period with suspected infection, and plasma available from the time of clinical suspicion (254 episodes, 190 patients). MEASUREMENTS AND RESULTS: Plasma levels of G-CSF, IL-8, and IL-1ra. Episodes classified on the basis of clinical and bacteriological findings into: culture-confirmed sepsis, probable sepsis, localized infection, viral infection, and no infection. Plasma levels were significantly higher in episodes of culture-confirmed sepsis than in episodes with ruled-out infection. The area under the receiver operating characteristic curve was higher for IL-8 and G-CSF than for IL-1ra. Combining IL-8 and G-CSF improved the diagnostic performance, particularly as to the detection of Gram-negative sepsis. Sensitivity was low (<50%) in detecting Staphylococcus epidermidis bacteremia or localized infections. CONCLUSIONS: In this heterogeneous population of critically ill children with suspected infection, a model combining plasma levels of IL-8 and G-CSF identified patients with sepsis. Negative results do not rule out S. epidermidis bacteremia or locally confined infectious processes. The model requires validation in an independent data-set.

Diagnostic approach to pupillary abnormalities.

PURPOSE OF REVIEW: This article presents an overview of the common and various kinds of pupillary disorders that can be encountered in an outpatient setting. RECENT FINDINGS: The dorsal midbrain is a site where lesions may produce either an afferent or an efferent pupillary defect. The classic pupillary syndrome secondary to a dorsal midbrain lesion is bilateral light-near dissociation. Another recognized deficit is bilateral mydriasis. Recent reports have documented unilateral mydriasis, unilateral light-near dissociation, and a relative afferent pupillary defect without visual loss in association with lesions of the dorsal midbrain. These are rare syndromes. SUMMARY: Careful history and examination can often identify and localize the pupillary disorder, as well as guide appropriate evaluation.

Juridical double taxation by cross border transactions: the Block Case (C-67/08)

Treaty Establishing the European Community, operative until December 1st 2009, had already established in its article 2 the mission of the up until then European Community and actual European Union is to promote an harmonious, equilibrated and sustainable development of the economic activities of the whole Community. This Mission must be achieved by establishing a Common Market, an Economic and Monetary Union and the realization of Common Policies. One of the instruments to obtain these objectives is the use of free circulation of people, services and capitals inside the Common and Interior Market of the European Union. The European Union is characterized by the confirmation of the total movement of capitals, services and individuals and legal peoples’ freedom; freedom that was already predicated by the Maastricht Treaty, through the suppression of whatever obstacles which are in the way of the objectives before exposed. The old TEC in its Title III, now Title IV of the Treaty on the Functioning of the European Union, covered the free circulation of people, services and capitals. Consequently, the inclusion of this mechanism inside one of the regulating texts of the European Union indicates the importance this freedom supposes for the European Union objectives’ development. Once stood up the relevance of the free movement of people, services and capitals, we must mention that in this paper we are going to centre our study in one of these freedoms of movement: the free movement of capital. In order to analyze in detail the free movement of capital within the European framework, we are going to depart from the analysis of the existent case law of the Court of Justice of the European Union. The use of jurisprudence is basic to know how Community legislation is interpreted. For this reason, we are going to develop this work through judgements dictated by the European Union Court. This way we can observe how Member States’ regulating laws and the European Common Law affect the free movement of capital. The starting point of this paper will be the Judgement C-67/08 European Court of Justice of February 12th 2009, known as Block case. So, following the argumentation the Luxemburg Court did about the mentioned case, we are going to develop how free movement of capital could be affected by the current disparity of Member States’ legislation. This disparity can produce double taxation cases due to the lack of tax harmonized legislation within the interior market and the lack of treaties to avoid double taxation within the European Union. Developing this idea we are going to see how double taxation, at least indirectly, can infringe free movement of capital.

Standardization and evaluation of ELISA for the serodiagnosis of amoebic liver abscess

An ELISA test for the serological diagnosisof amoebic liver abscess (ALA) was standardized and evaluated in sera from three groups of patients: (1) three patients with diagnosis confirmed by isolation of the parasite,(2) thirty seven patients with diagnosis established by clinical findings and ultrasound studies and (3) seven patients whose diagnosis were established by clinical findings and a positive double immunodifusion test. Ninety one serum samples from healthy subjects and 22 from patients with other liver or parasitic diseases were also included in the study. the optimum concentration of Entamoeba histolytica antigen was 1.25 µg/ml and optimum dilutions of serum and anti-human IgG-alkaline phosphatase conjugate were 1:400 and 1:4000 respectively. The cut-off point of the ELISA test in this study was an absorbance value of 0.34. The test parameters were: sensitivity = 95.7 per cent, specificty = 100 per cent, positive predictive value = 100 per cent and negative predictive value = 98.2 per cent.The ELISA test was found to be of great use as a diagnostic tool for the establishment of amoebic etiology in patients with clinical supposition of ALA. The test could also be used for seroepidemiological surveys of the prevalence of invasive amoebiasis in a given population, since it allows the processing of a greater number of samples at a lower cost tahn other serological tests.

Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?

BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

Knowledge of Catalan, public/private sector choice and earnings: Evidence from a double sample selection model

This paper explores the earnings return to Catalan knowledge for public and private workers in Catalonia. In doing so, we allow for a double simultaneous selection process. We consider, on the one hand, the non-random allocation of workers into one sector or another, and on the other, the potential self-selection into Catalan proficiency. In addition, when correcting the earnings equations, we take into account the correlation between the two selectivity rules. Our findings suggest that the apparent higher language return for public sector workers is entirely accounted for by selection effects, whereas knowledge of Catalan has a significant positive return in the private sector, which is somewhat higher when the selection processes are taken into account.

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: Application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

ABSTRACT: BACKGROUND: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. METHODS: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. RESULTS: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. CONCLUSION: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

Personal experience with diagnostic and therapeutic aspects of human Leishmania (Viannia) braziliensis in Três Braços

Diagnostic and therapeutic aspects of human infection with Leishmania (Viannia) braziliensis found in the littoral forest of the state of Bahia are reviewed. There is pressing need for alternative cheap oral drug therapy.

Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial.

OBJECTIVE: To determine the subjective response to iron therapy in non-anaemic women with unexplained fatigue. DESIGN: Double blind randomised placebo controlled trial. SETTING: Academic primary care centre and eight general practices in western Switzerland. PARTICIPANTS: 144 women aged 18 to 55, assigned to either oral ferrous sulphate (80 mg/day of elemental iron daily; n=75) or placebo (n=69) for four weeks. MAIN OUTCOME MEASURES: Level of fatigue, measured by a 10 point visual analogue scale. RESULTS: 136 (94%) women completed the study. Most had a low serum ferritin concentration; <or= 20 microg/l in 69 (51%) women. Mean age, haemoglobin concentration, serum ferritin concentration, level of fatigue, depression, and anxiety were similar in both groups at baseline. Both groups were also similar for compliance and dropout rates. The level of fatigue after one month decreased by -1.82/6.37 points (29%) in the iron group compared with -0.85/6.46 points (13%) in the placebo group (difference 0.95 points, 95% confidence interval 0.32 to 1.62; P=0.004). Subgroups analysis showed that only women with ferritin concentrations <or= 50 microg/l improved with oral supplementation. CONCLUSION: Non-anaemic women with unexplained fatigue may benefit from iron supplementation. The effect may be restricted to women with low or borderline serum ferritin concentrations.

Estimation of the radiation risks in diagnostic procedures to populations and patients

Since 1895, when X-rays were discovered, ionizing radiation became part of our life. Its use in medicine has brought significant health benefits to the population globally. The benefit of any diagnostic procedure is to reduce the uncertainty about the patient's health. However, there are potential detrimental effects of radiation exposure. Therefore, radiation protection authorities have become strict regarding the control of radiation risks.¦There are various situations where the radiation risk needs to be evaluated. International authority bodies point to the increasing number of radiologic procedures and recommend population surveys. These surveys provide valuable data to public health authorities which helps them to prioritize and focus on patient groups in the population that are most highly exposed. On the other hand, physicians need to be aware of radiation risks from diagnostic procedures in order to justify and optimize the procedure and inform the patient.¦The aim of this work was to examine the different aspects of radiation protection and investigate a new method to estimate patient radiation risks.¦The first part of this work concerned radiation risk assessment from the regulatory authority point of view. To do so, a population dose survey was performed to evaluate the annual population exposure. This survey determined the contribution of different imaging modalities to the total collective dose as well as the annual effective dose per caput. It was revealed that although interventional procedures are not so frequent, they significantly contribute to the collective dose. Among the main results of this work, it was shown that interventional cardiological procedures are dose-intensive and therefore more attention should be paid to optimize the exposure.¦The second part of the project was related to the patient and physician oriented risk assessment. In this part, interventional cardiology procedures were studied by means of Monte Carlo simulations. The organ radiation doses as well as effective doses were estimated. Cancer incidence risks for different organs were calculated for different sex and age-at-exposure using the lifetime attributable risks provided by the Biological Effects of Ionizing Radiations Report VII. Advantages and disadvantages of the latter results were examined as an alternative method to estimate radiation risks. The results show that this method is the most accurate, currently available, to estimate radiation risks. The conclusions of this work may guide future studies in the field of radiation protection in medicine.¦-¦Depuis la découverte des rayons X en 1895, ce type de rayonnement a joué un rôle important dans de nombreux domaines. Son utilisation en médecine a bénéficié à la population mondiale puisque l'avantage d'un examen diagnostique est de réduire les incertitudes sur l'état de santé du patient. Cependant, leur utilisation peut conduire à l'apparition de cancers radio-induits. Par conséquent, les autorités sanitaires sont strictes quant au contrôle du risque radiologique.¦Le risque lié aux radiations doit être estimé dans différentes situations pratiques, dont l'utilisation médicale des rayons X. Les autorités internationales de radioprotection indiquent que le nombre d'examens et de procédures radiologiques augmente et elles recommandent des enquêtes visant à déterminer les doses de radiation délivrées à la population. Ces enquêtes assurent que les groupes de patients les plus à risque soient prioritaires. D'un autre côté, les médecins ont également besoin de connaître le risque lié aux radiations afin de justifier et optimiser les procédures et informer les patients.¦Le présent travail a pour objectif d'examiner les différents aspects de la radioprotection et de proposer une manière efficace pour estimer le risque radiologique au patient.¦Premièrement, le risque a été évalué du point de vue des autorités sanitaires. Une enquête nationale a été réalisée pour déterminer la contribution des différentes modalités radiologiques et des divers types d'examens à la dose efficace collective due à l'application médicale des rayons X. Bien que les procédures interventionnelles soient rares, elles contribuent de façon significative à la dose délivrée à la population. Parmi les principaux résultats de ce travail, il a été montré que les procédures de cardiologie interventionnelle délivrent des doses élevées et devraient donc être optimisées en priorité.¦La seconde approche concerne l'évaluation du risque du point de vue du patient et du médecin. Dans cette partie, des procédures interventionnelles cardiaques ont été étudiées au moyen de simulations Monte Carlo. La dose délivrée aux organes ainsi que la dose efficace ont été estimées. Les risques de développer des cancers dans plusieurs organes ont été calculés en fonction du sexe et de l'âge en utilisant la méthode établie dans Biological Effects of Ionizing Radiations Report VII. Les avantages et inconvénients de cette nouvelle technique ont été examinés et comparés à ceux de la dose efficace. Les résultats ont montré que cette méthode est la plus précise actuellement disponible pour estimer le risque lié aux radiations. Les conclusions de ce travail pourront guider de futures études dans le domaine de la radioprotection en médicine.

Monads in double categories

We extend the basic concepts of Street's formal theory of monads from the setting of 2-categories to that of double categories. In particular, we introduce the double category Mnd(C) of monads in a double category C and dene what it means for a double category to admit the construction of free monads. Our main theorem shows that, under some mild conditions, a double category that is a framed bicategory admits the construction of free monads if its horizontal 2-category does. We apply this result to obtain double adjunctions which extend the adjunction between graphs and categories and the adjunction between polynomial endofunctors and polynomial monads.

Lévy area for Gaussian processes: A double Wiener--Itô integral approach

"Vegeu el resum a l'inici del document del fitxer adjunt."