Impact of cannabis inhalation on driving skills in occasional smokers

Objectives: Our aim was to study the brain regions involved in a divided attention tracking task related to driving in occasional cannabis smokers. In addition we assessed the relationship between THC levels in whole blood and changes in brain activity, behavioural and psychomotor performances. Methods: Twenty-one smokers participated to two independent cross-over fMRI experiments before and after smoking cannabis and a placebo. The paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. Half of the active tracking conditions included randomly presented traffic lights as distractors. Blood samples were taken at regular intervals to determine the time-profiles of the major cannabinoids. Their levels during the fMRI experiments were interpolated from concentrations measured by GCMS/ MS just before and after brain imaging. Results: Behavioural data, such as the discard between target and cursor, the time of correct tracking and the reaction time during traffic lights appearance showed a statistical significant impairment of subject s skills due to THC intoxication. Highest THC blood concentrations were measured soon after smoking and ranged between 28.8 and 167.9 ng/ml. These concentrations reached values of a few ng/ml during the fMRI. fMRI results pointed out that under the effect of THC, high order visual areas (V3d) and Intraparietal sulcus (IPS) showed an higher activation compared to the control condition. The opposite comparison showed a decrease of activation during the THC condition in the anterior cingulate gyrus and orbitofrontal areas. In these locations, the BOLD showed a negative correlation with the THC level. Conclusion: Acute cannabis smoking significantly impairs performances and brain activity during active tracking tasks, partly reorganizing the recruitment of brain areas of the attention network. Neural activity in the anterior cingulate might be responsible of the changes in the cognitive controls required in our divided attention task.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

Risk factors for positive tuberculin skin tests among migrant and resident children in Lausanne, Switzerland

Résumé en français Cadre : Policlinique pédiatrique à Lausanne en Suisse, pays rencontrant une proportion importante de tuberculose au sein de la population de migrants. But : Déterminer les facteurs de risque associés à un test tuberculinique positif (ou test de Mantoux), notamment l'influence du BCG (Bacille Calmette Guérin) et d'un contact avec un personne ayant une tuberculose active. Les patients concernés étaient des enfants examinés dans le cadre d'un contrôle de santé ou dans le cadre d'une étude d'entourage d'un cas déclaré de tuberculose. Méthode : Etude descriptive comprenant des enfants ayant eu un test tuberculinique (2 unités RT23) entre novembre 2002 et avril 2004. L'âge, le sexe, l'anamnèse de contact avec une personne ayant une tuberculose active, la vaccination par le BCG, le pays d'origine et le lieu de naissance (en Suisse ou hors de la Suisse) étaient répertoriés. Résultats : Parmi les 234 enfants de l'étude, 176 (75%) avaient une réaction tuberculinique égal à zéro et 31 (13%) avaient une réaction positive (> 10mm). Dans le modèle de régression linéaire, la taille de la réaction tuberculinique variait significativement selon l'anamnèse de contact avec une personne ayant une tuberculose active, l'âge, l'incidence de la tuberculose dans le pays d'origine et la vaccination par le BCG. Le sexe ou le lieu de naissance n'influençait pas la taille de la réaction. Dans le modèle de régression logistique incluant toutes les valeurs répertoriées, les paramètres significativement associés avec un Mantoux positif étaient l'âge (Odds Ratio = 1.21, 95% CI 1.08 ; 1.35), l'anamnèse de contact avec une personne ayant une tuberculose active (OR = 7.31, 95% CI 2.23 ; 24) et l'incidence de la tuberculose dans le pays d'origine (OR = 1.01, 95% CI 1.00 ; 1.02). Le sexe (OR = 1.18, 95% CI 0.50 ; 2.78) et la vaçcination par le BCG (OR = 2.97, 95% CI 0.91 ; 9.72) n'étaient pas associés avec une réaction tuberculinique positive. Conclusions : L'incidence de la tuberculose dans le pays d'origine, la vaccination par le BCG et l'âge influencent le test de Mantoux (taille ou proportion de réaction > 10mm). Toutefois, le facteur de risque le plus important d'avoir une réaction tuberculinique positive est l'anamnèse de contact avec. une personne ayant une tuberculose active.

Prozone effects in microscopic agglutination tests for leptospirosis in the sera of mice infected with the pathogenic Leptospira interrogans serovar Canicola

Mice experimentally infected with a pathogenic strain of Leptospira interrogans serovar Canicola produced false negative results (prozone effect) in a microscopic agglutination test (MAT). This prozone effect occurred in several serum samples collected at different post-infection times, but it was more prominent in samples collected from seven-42 days post-infection and for 1:50 and 1:100 sample dilutions. This phenomenon was correlated with increased antibody titres in the early post-infection phase. While prozone effects are often observed in serological agglutination assays for the diagnosis of animal brucellosis and human syphilis, they are not widely reported in leptospirosis MATs.

The role of hypocretin in driving arousal and goal-oriented behaviors.

The hypocretins (Hcrts), also called orexins, are two neuropeptides secreted by a few thousand neurons restricted to the lateral hypothalamus. The Hcrt peptides bind to two receptors located in nuclei associated with diverse cognitive and physiological functions. Experimental evidence has demonstrated that the physiological roles of hypocretins extend far beyond its initial role in food consumption and has emerged as a key system in the fields of sleep disorders and drug addiction. Here, we discuss recent evidence demonstrating a key role of hypocretin in the motivation for reward seeking in general, and drug taking in particular, and we delineate a physiological framework for this peptidergic system in orchestrating the appropriate levels of alertness required for the elaboration and the execution of goal-oriented behaviors. We propose a general role for hypocretins in mediating arousal, especially when an organism must respond to unexpected stressors and environmental challenges, which serve to shape survival behaviors. We also discuss the limit of the current experimental paradigms to address the question of how a system normally involved in the regulation of vigilance states and hyperarousal may promote a pathological state that elicits compulsive craving and relapse to drug seeking.

Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.

INTRODUCTION: Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests. METHODS: The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories. RESULTS: RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43μg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected. CONCLUSIONS: RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.

A new neuropsychological instrument measuring effects of age and drugs on fitness to drive: development, reliability, and validity of MedDrive

Background: Current guidelines underline the limitations of existing instruments to assess fitness to drive and the poor adaptability of batteries of neuropsychological tests in primary care settings. Aims: To provide a free, reliable, transparent computer based instrument capable of detecting effects of age or drugs on visual processing and cognitive functions. Methods: Relying on systematic reviews of neuropsychological tests and driving performances, we conceived four new computed tasks measuring: visual processing (Task1), movement attention shift (Task2), executive response, alerting and orientation gain (Task3), and spatial memory (Task4). We then planned five studies to test MedDrive's reliability and validity. Study-1 defined instructions and learning functions collecting data from 105 senior drivers attending an automobile club course. Study-2 assessed concurrent validity for detecting minor cognitive impairment (MCI) against useful field of view (UFOV) on 120 new senior drivers. Study-3 collected data from 200 healthy drivers aged 20-90 to model age related normal cognitive decline. Study-4 measured MedDrive's reliability having 21 healthy volunteers repeat tests five times. Study-5 tested MedDrive's responsiveness to alcohol in a randomised, double-blinded, placebo, crossover, dose-response validation trial including 20 young healthy volunteers. Results: Instructions were well understood and accepted by all senior drivers. Measures of visual processing (Task1) showed better performances than the UFOV in detecting MCI (ROC 0.770 vs. 0.620; p=0.048). MedDrive was capable of explaining 43.4% of changes occurring with natural cognitive decline. In young healthy drivers, learning effects became negligible from the third session onwards for all tasks except for dual tasking (ICC=0.769). All measures except alerting and orientation gain were affected by blood alcohol concentrations. Finally, MedDrive was able to explain 29.3% of potential causes of swerving on the driving simulator. Discussion and conclusions: MedDrive reveals improved performances compared to existing computed neuropsychological tasks. It shows promising results both for clinical and research purposes.

The use of rapid dengue diagnostic tests in a routine clinical setting in a dengue-endemic area of Colombia

There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.

Molecular testing for fragile X: analysis of 5062 tests from 1105 fragile X families--performed in 12 clinical laboratories in Spain.

Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P < 0.001). Furthermore, in mothers with intermediate alleles (45-54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55-59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.

Aptitude au volant: quelle conduite [Aptitude to drive: what road to take?].

Tout médecin de premier recours devrait pouvoir se prononcer sur l'aptitude à la conduite automobile de son patient. La problématique du conducteur âgé, dépendant soit de l'alcool ou de drogues, sous traitement de médicaments psychotropes, ou encore diabétique, est abordée à la lumière des dispositions légales et des récentes recommandations. Cet article aborde également les aspects relatifs aux problèmes neurologiques, cardiologiques et orthopédiques. Any primary care doctor should be able to decide on the fitness to drive of a given patient. The issue of an older driver, patients addicted to alcohol or drugs, under current psychotropic drug treatment, or diabetic, is discussed in the light of legal provisions and current recommendations. This article also discusses aspects associated with neurological, cardiac and orthopedic issues.

Cannabis et conduite automobile [Cannabis and automobile driving]

Cannabis use has increased considerably during the last 15 years. One of the major problems dealing with cannabis use is driving under the influence of drugs. With the exception of ethyl alcohol, the majority of the epidemiological studies have shown that cannabis is the most frequently detected substance in people suspected of driving under the influence of drugs. Experimental studies are therefore needed to assess cannabis effects on driving capability. Many studies indicate that cannabis impairs psychomotor performance. This impairment becomes obvious when high doses of cannabis are taken, when ethyl alcohol or other drugs are simultaneously ingested, or when sustained attention is needed. Moreover, cannabis effects are qualitatively different from those observed after ethyl alcohol consumption. In forensic practice, cannabis impairment of driving performance must be related to cannabinoids blood concentrations. To facilitate the interpretation of cannabinoids blood levels, several models were set up recently. These models must be further improved in order to fit in with all circumstances of cannabis use.

An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy.