L'examen neuropsychologique en pratique quotidienne [Neuropsychological test in daily practice]

Neuropsychology is a scientific discipline, born in the XIX century, and bridges the fields of neurology and psychology. Neuropsychologists apply scientific knowledge about the relationship between brain function and mental performances. The major clinical role of a neuropsychological evaluation is to help to establish medical and functional diagnosis in patients (adults or infants) with different neurological pathologies such as stroke, traumatic brain injury, dementia, epilepsy.... Such analysis necessitates accurate observation of behaviour and administration of tests of mental abilities (e.g. language, memory...). Test results can also help to clarify the nature of cognitive difficulties and to support the formulation of plans for neuropsychological therapy and functional adjustment in every day life.

A comparative study of the TF-Test®, Kato-Katz, Hoffman-Pons-Janer, Willis and Baermann-Moraes coprologic methods for the detection of human parasitosis

This study compares the diagnostic accuracy of the TF-Test® (TFT) for human parasitosis with results obtained using the traditional Kato-Katz (KK), Hoffman-Pons-Janer (HPJ), Willis and Baermann-Moraes (BM) techniques. Overall, four stool samples were taken from each individual; three alternate-day TFT stool samples and another sample that was collected in a universal container. Stool samples were taken from 331 inhabitants of the community of Quilombola Santa Cruz. The gold standard (GS) for protozoa detection was defined as the combined results for TFT, HPJ and Willis coproscopic techniques; for helminth detection, GS was defined as the combined results for all five coproscopic techniques (TFT, KK, HPJ, Willis and BM). The positivity rate of each method was compared using the McNemar test. While the TFT exhibited similar positivity rates to the GS for Entamoeba histolytica/dispar (82.4%) and Giardia duodenalis (90%), HPJ and Willis techniques exhibited significantly lower positivity rates for these protozoa. All tests exhibited significantly lower positivity rates compared with GS for the diagnosis of helminths. The KK technique had the highest positivity rate for diagnosing Schistosoma mansoni (74.6%), while the TFT had the highest positivity rates for Ascaris lumbricoides (58.1%) and hookworm (75%); HPJ technique had the highest positivity rate for Strongyloides stercoralis (50%). Although a combination of tests is the most accurate method for the diagnosis of enteral parasites, the TFT reliably estimates the prevalence of protozoa and selected helminths, such as A. lumbricoides and hookworm. Further studies are needed to evaluate the detection accuracy of the TFT in samples with varying numbers of parasites.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

An evaluation of the dot-ELISA procedure as a diagnostic test in an area with a high prevalence of human Toxocara canis infection

The aim of this work was to evaluate a dot-enzyme-linked immunosorbent assay (dot-ELISA) using excretory-secretory antigens from the larval stages of Toxocara canis for the diagnosis of toxocariasis. A secondary aim was to establish the optimal conditions for its use in an area with a high prevalence of human T. canis infection. The dot-ELISA test was standardised using different concentrations of the antigen fixed on nitrocellulose paper strips and increasing dilutions of the serum and conjugate. Both the dot-ELISA and standard ELISA methods were tested in parallel with the same batch of sera from controls and from individuals living in the problem area. The best results were obtained with 1.33 µg/mL of antigen, dilutions of 1/80 for the samples and controls and a dilution of 1/5,000 for the anti-human IgG-peroxidase conjugate. All steps of the procedure were performed at room temperature. The coincidence between ELISA and dot-ELISA was 85% and the kappa index was 0.72. The dot-ELISA test described here is rapid, easy to perform and does not require expensive equipment. Thus, this test is suitable for the serological diagnosis of human T. canis infection in field surveys and in the primary health care centres of endemic regions.

Effect of serum sample inactivation on the performance of latex agglutination test for paracoccidioidomycosis serodiagnosis

Paracoccidioidomycosis is diagnosed from the direct observation of the causative agent, but serology can facilitate and decrease the time required for diagnosis. The objective of this study was to determine the influence of serum sample inactivation on the performance of the latex agglutination test (LAT) for detecting antibodies against Paracoccidioides brasiliensis. The sensitivity of LAT from inactivated or non-inactivated samples was 73% and 83%, respectively and the LAT selectivity was 79% and 90%, respectively. The LAT evaluated here was no more specific than the double-immunodiffusion assay. We suggest the investigation of other methods for improving the LAT, such as the use of deglycosylated antigen.

Association between HIV status and HIV knowledge in the population attending Non-Governmental Organizations to perform the rapid HIV test in Catalonia

Human Immunodeficiency Virus continues to be a pandemic. Spain is one of the European countries with the highest incidence of HIV. Within Catalonia, Spain many projects have been implemented with the intention of improving HIV knowledge and lowering the incidence. HIV knowledge is also known to have a positive effect on lowering stigma and discrimination of the people living with HIV. However, few studies study the distribution of HIV knowledge and its association to HIV status, age, sex, geographical zone of origin and level of education within the same study. Objectives: To identify if HIV knowledge is associated with HIV status, age, sex, geographical zone of origin and level of education. Method: Quantitative, cross-sectional, centre-based study comprising of people receiving an HIV test in Catalonia, Spain. Data will be collected from the 11 HIV Non-Governmental Organisations in Catalonia, Spain. The Brief HIV Knowledge Scale will be used to assess HIV knowledge; information from the HIV test session will be used to assess HIV status, age, sex, geographic zone of origin and level of education. The association between HIV knowledge and the afore mentioned variables will then be calculated.

Incongruence between test statistics and P values in medical papers

Given an observed test statistic and its degrees of freedom, one may compute the observed P value with most statistical packages. It is unknown to what extent test statistics and P values are congruent in published medical papers. Methods:We checked the congruence of statistical results reported in all the papers of volumes 409–412 of Nature (2001) and a random sample of 63 results from volumes 322–323 of BMJ (2001). We also tested whether the frequencies of the last digit of a sample of 610 test statistics deviated from a uniform distribution (i.e., equally probable digits).Results: 11.6% (21 of 181) and 11.1% (7 of 63) of the statistical results published in Nature and BMJ respectively during 2001 were incongruent, probably mostly due to rounding, transcription, or type-setting errors. At least one such error appeared in 38% and 25% of the papers of Nature and BMJ, respectively. In 12% of the cases, the significance level might change one or more orders of magnitude. The frequencies of the last digit of statistics deviated from the uniform distribution and suggested digit preference in rounding and reporting.Conclusions: this incongruence of test statistics and P values is another example that statistical practice is generally poor, even in the most renowned scientific journals, and that quality of papers should be more controlled and valued

A system to test the toxicity of brake wear particles

Fine particulate matter from traffic increases mortality and morbidity. An important source of traffic particles is brake wear. American studies reported cars to emit break wear particles at a rate of about 11mg/km to 20mg/km of driven distance. A German study estimated that break wear contributes about 12.5% to 21% of the total traffic particle emissions. The goal of this study was to build a system that allows the study of brake wear particle emissions during different braking behaviours of different car and brake types. The particles should be characterize in terms of size, number, metal, and elemental and organic carbon composition. In addition, the influence of different deceleration schemes on the particle composition and size distribution should be studied. Finally, this system should allow exposing human cell cultures to these particles. An exposure-box (0.25 cubic-m volume) was built that can be mounted around a car's braking system. This allows exposing cells to fresh brake wear particles. Concentrations of particle numbers, mass and surface, metals, and carbon compounds were quantified. Tests were conducted with A549 lung epithelial cells. Five different cars and two typical braking behaviours (full stop and normal deceleration) were tested. Particle number and size distribution was analysed for the first six minutes. In this time, two braking events occurred. Full stop produced significantly higher particle concentrations than normal deceleration (average of 23'000 vs. 10'400 #/cm3, p= 0.016). The particle number distribution was bi-modal with one peak at 60 to 100 nm (depending on the tested car and braking behaviour) and a second peak at 200 to 400 nm. Metal concentrations varied depending on the tested car type. Iron (range of 163 to 15'600 μg/m3) and Manganese (range of 0.9 to 135 μg/m3) were present in all samples, while Copper was absent in some samples (<6 to 1220 μg/m3). The overall "fleet" metal ratio was Fe:Cu:Mn = 128:14:1. Temperature and humidity varied little. A549-cells were successfully exposed in the various experimental settings and retained their viability. Culture supernatant was stored and cell culture samples were fixated to test for inflammatory response. Analysis of these samples is ongoing. The established system allowed testing brake wear particle emissions from real-world cars. The large variability of chemical composition and emitted amounts of brake wear particles between car models seems to be related to differences between brake pad compositions of different producers. Initial results suggest that the conditions inside the exposure box allow exposing human lung epithelial cells to freshly produced brake wear particles.

Fast test for assessing the susceptibility of Mycobacterium tuberculosis to isoniazid and rifampin by real-time PCR

Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB), a leading cause of death from infectious disease worldwide. Rapid diagnosis of resistant strains is important for the control of TB. Real-time polymerase chain reaction (RT-PCR) assays may detect all of the mutations that occur in the M. tuberculosis 81-bp core region of the rpoB gene, which is responsible for resistance to rifampin (RIF) and codon 315 of the katG gene and the inhA ribosomal binding site, which are responsible for isoniazid (INH). The goal of this study was to assess the performance of RT-PCR compared to traditional culture-based methods for determining the drug susceptibility of M. tuberculosis. BACTEC TM MGIT TM 960 was used as the gold standard method for phenotypic drug susceptibility testing. Susceptibilities to INH and RIF were also determined by genotyping of katG, inhA and rpoB genes. RT-PCR based on molecular beacons probes was used to detect specific point mutations associated with resistance. The sensitivities of RT-PCR in detecting INH resistance using katG and inhA targets individually were 55% and 25%, respectively and 73% when combined. The sensitivity of the RT-PCR assay in detecting RIF resistance was 99%. The median time to complete the RT-PCR assay was three-four hours. The specificities for tests were both 100%. Our results confirm that RT-PCR can detect INH and RIF resistance in less than four hours with high sensitivity.

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4+ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4+ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8+ and human leukocyte antigen-DR expression on CD3+ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.

CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells.

BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.

INTRODUCTION CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. METHODS A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. RESULTS Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). CONCLUSION Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.

Influence of Bacille Calmette-Guérin vaccination on size of tuberculin skin test reaction : to what size ?

RESUME Le diagnostic d'infection tuberculeuse repose essentiellement sur le test tuberculinique (test de Mantoux). Cependant, le résultat de ce dernier est également influencé par d'autres facteurs, le plus important étant la vaccination par le Bacille Calmette-Guérin (BCG), interaction connue depuis de nombreuses années. Il est généralement admis que l'effet de la vaccination peut entraîner des réactions positives jusqu'à un diamètre d'induration de 15 mm. Au-delà, la positivité du test est en général attribuée à une primo-infection tuberculeuse. Peu d'études se sont réellement penchées sur le sujet. Chez le personnel de soins soumis à des Mantoux répétés, cette notion revêt une importance particulière pour interpréter correctement une réaction fortement positive en l'absence de facteurs de risque tuberculeux, dans un pays à faible endémie tuberculeuse. Notre étude a cherché à déterminer si le diamètre transversal de l'induration du Mantoux était un critère fiable pour distinguer une positivité associée à une infection tuberculeuse de celle associée à une ancienne vaccination. Elle s'est attachée à rechercher un seuil au-delà duquel l'infection tuberculeuse pourrait être considérée comme probable. Entre janvier 1991 et mars 1998, tous les nouveaux employés du CHUV ont été invités à recevoir un test tuberculinique à l'occasion de leur visite d'entrée à la Médecine du personnel. En cas de réponse négative, un deuxième test a été pratiqué une semaine plus tard, pour détecter un éventuel effet booster. Lors de la première visite, l'infirmière a rempli un questionnaire comprenant les données démographiques usuelles, des informations concernant les facteurs pouvant influencer la positivité du test, notamment les antécédents de vaccination par le BCG, les expositions à la tuberculose et l'existence d'antécédents d'infection tuberculeuse. Parmi les 5117 sujets inclus dans l'étude, nous avons trouvé que l'influence de la vaccination variait en fonction de l'âge. Chez les sujets de moins de 40 ans, la vaccination par le BCG était le prédicteur le plus important d'un Mantoux positif inférieur à 18 mm, de loin supérieur aux facteurs de risque habituels pour une infection tuberculeuse, eux aussi significatifs. L'effet du BCG était présent pour des réactions allant jusqu'à 20 mm. Pour les Mantoux supérieurs à 20 mm, l'odds ratio (OR) relatif au BCG demeure clairement élevé (supérieur à 3,4) bien que non significatif. Par contre, pour les employés âgés de plus de 40 ans, le BCG est un facteur prédictif pour les tests supérieurs à 10 mm (OR 2.4) mais n'est plus un facteur significatif pour une taille supérieure à 15 mm. Ces résultats montrent que l'interprétation d'un test tuberculinique même fortement positif, doit être faite avec prudence et discernement. En effet, notre étude démontre que chez les sujets vaccinés de moins de 40 ans, dans les zones de faible endémie tuberculeuse particulièrement en l'absence de facteurs de risque pour une infection tuberculeuse, un Mantoux positif jusqu'à 18 mm est dû, le plus probablement, à une ancienne vaccination par le BCG, plutôt qu'à une infection par M tuberczilosis. L'interprétation des Mantoux de taille inférieure à 18 mm et les Mantoux effectués chez des sujets de moins de 40 ans, doit prendre en compte l'existence d'un BCG antérieur. En conséquence, la mise en évidence d'une réaction de Mantoux fortement positive ne devrait pas conduire systématiquement à un traitement préventif. L'absence de spécificité du test Mantoux, utilisé pour le dépistage de la tuberculose depuis bientôt une centaine d'année, est un problème connu. Nous démontrons que la taille de l'induration ne peut pas être utilisée de façon fiable comme critère pour identifier une infection tuberculeuse chez une personne vaccinée avec le BCG, avec le risque de sui-traiter un nombre important de sujets. Dans notre étude, 21% des sujets avaient un Mantoux supérieur ou égal à 15 mm et auraient dû être traités selon les recommandations en vigueur en Suisse si l'on ne tenait pas compte du BCG antérieur. Des tests plus spécifiques sont actuellement à l'étude et permettront vraisemblablement, à l'avenir, de palier au problème de l'absence de spécificité du test de Mantoux. Abstract : Background. Previous bacillus Calmette-Guerin (BCG) vaccination can confound the results of a tuberculin skin test (TST). We sought to determine a cutoff diameter of TST induration beyond which the influence of BCG vaccination was negligible in evaluating potential Mycobacterium tuberculosis infection in a population of health care workers with a high vaccination rate and low incidence of tuberculosis. Methods. From 1991 through 1998, all new employees at the University Hospital of Lausanne, Switzerland, underwent a 2-step TST at entry visit. We also gathered information on demographic characteristics, along with factors commonly associated with tuberculin positivity, including previous BCG vaccination, history of latent M. tuberculosis infection, and predictors for M. tuberculosis infection. Results. Among the 5117 investigated subjects, we found that influence of BCG vaccination on TST results varied across categories of age (likelihood ratio test, 0.0001). Prior BCG vaccination had a strong influence on skin test results of mm in diameter among persons <40 years old, compared with the influence of factors predictive of M. tuberculosis infection. Prior latent M. tuberculosis infection and travel or employment in a country in which tuberculosis is endemic also had significant influences. Conclusions. Interpretation of TST reactions of mm among BCG-vaccinated persons <40 years of age must be done with caution in areas with a low incidence of tuberculosis. In such a population, except for persons who have never been vaccinated, TST reactions of ---518 mm are more likely to be the result of prior vaccination than infection and should not systematically lead to preventive treatment.