Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Amputations du membre inférieur [Amputations of the lower extremity]

Still nowadays amputations are frequently performed in our country. In diabetic patients the incidence of an amputation is 25 times higher than in the normal population. All possibilities of revascularisation or limb salvage must be excluded by a multidisciplinary approach before choosing an amputation. Once the decision is taken the good level of amputation and the correct technique have to determined. The goal of this article is to describe which clinical and paraclinical parameters will help the surgeon to choose the best level of amputation, which techniques are to be used for the amputation and to finally give some information about re-education and the fitting of an orthesis or prosthesis.

Interpretation of array comparative genome hybridization data: a major challenge.

The advent and application of high-resolution array-based comparative genome hybridization (array CGH) has led to the detection of large numbers of copy number variants (CNVs) in patients with developmental delay and/or multiple congenital anomalies as well as in healthy individuals. The notion that CNVs are also abundantly present in the normal population challenges the interpretation of the clinical significance of detected CNVs in patients. In this review we will illustrate a general clinical workflow based on our own experience that can be used in routine diagnostics for the interpretation of CNVs.

Anti-doping testing at the 2008 European football championship.

Big sports events like the 2008 European Football Championship are a challenge for anti-doping activities, particularly when the sports event is hosted by two different countries and there are two laboratories accredited by the World Anti-Doping Agency. This challenges the logistics of sample collection as well as the chemical analyses, which must be carried out timeously. The following paper discusses the handling of whereabouts information for each athlete and the therapeutic use exemption system, experiences in sample collection and transportation of blood and urine samples, and the results of the chemical analysis in two different accredited laboratories. An overview of the analytical results of blood profiling and growth hormone testing in comparison with the distribution of the normal population is also presented.

Tetrasomy 8 in a patient with acute nonlymphocytic leukemia: a metaphase and interphase study with fluorescence in situ hybridization.

Tetrasomy 8 constitutes a relatively rare recurring chromosome defect in myeloid disorders. The patient reported here, a 71-year-old man, presented with tetrasomy 8 as the sole chromosome abnormality associated with an acute nonlymphocytic leukemia of the M2 type. He failed to respond to chemotherapy and died one year after diagnosis. Following conventional cytogenetics and fluorescence in situ hybridization (FISH) with a centromeric probe specific for chromosome 8, tetrasomy 8 was detected in 61% of the metaphases analyzed and trisomy 8 in 39%. FISH analysis of interphase nuclei confirmed the existence of tetrasomic (35%) and trisomic cells (56%) and revealed a number of cells with two chromosomes 8 (8%). This normal population may represent lymphocytes or myeloid cells that escaped conventional analysis due to their inability to divide or to the small number of metaphases available. The relatively higher proportion of tetrasomic cells in metaphase compared with interphase may be attributed to a proliferative advantage of tetrasomic cells in vitro or to the longer duration of their cell cycle. The simultaneous presence of trisomic and tetrasomic cells confirms the hypothesis of a clonal relationship between trisomy 8 and tetrasomy 8. Our case brings further evidence to the specificity of tetrasomy 8 to myeloid disorders and to the association of this chromosome abnormality with a relatively poor prognosis. However, new patients must be studied to further delineate this cytogenetic entity.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease.

OBJECTIVES: Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables. METHODS: Data from paediatric patients with IBD enrolled in the Swiss IBD Cohort Study and the results of both the parent-rated Strengths and Difficulties Questionnaire (SDQ) and the self-reported Child Depression Inventory (CDI) were analysed. Of the 148 registered patients, 126 had at least one questionnaire completed and were included. RESULTS: The mean age of 71 patients with Crohn's disease (44 males, 27 females) was 13.4 years, and 12.8 years for the 55 patients with ulcerative or indeterminate colitis. The mean duration of disease was 1.2 and 2.7 years, respectively. The total score of the SDQ was abnormal in 11.4% of cases compared to 10% in the normal population. Abnormal sub-scores were found in 20.2% of subjects for the domain of emotional problems and in 17.1% for problems with peers. The total CDI T score indicated a significantly lower prevalence of clinical depression in IBD patients than in normal youth. No correlation between the total SDQ scores or the CDI T scores and gender, type or duration of IBD, inflammatory markers or disease scores was found. CONCLUSIONS: The prevalence of problems with behavioural and emotional adjustment among Swiss paediatric IBD patients is low and comparable to that of the normal population.

Overall and cause-specific mortality in GH-deficient adults on GH replacement.

OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. DESIGN: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. METHODS: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

Opposing roles for calcineurin and ATF3 in squamous skin cancer.

Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients. Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65 to 100-fold higher risk than in the normal population. By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent. Here we report that genetic and pharmacological suppression of calcineurin/nuclear factor of activated T cells (NFAT) function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-ras(V12) (also known as Hras1)-expressing primary human keratinocytes or keratinocyte-derived SCC cells. Calcineurin/NFAT inhibition counteracts p53 (also known as TRP53)-dependent cancer cell senescence, thereby increasing tumorigenic potential. ATF3, a member of the 'enlarged' AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumorigenic potential. Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.

HLA class II antigens (DR, DQ LOCI) and peripheral arthritis in ankylosing spondylitis.

Fifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.

Early-onset Crohn's disease is a risk factor for smaller final height

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Regulation of sodium transport in the cortical collecting duct : physiological role of GILZ in vitro and in vivo : characterisation of Na+ transport in the mCCDcl1 cell line

SUMMARY Regulation of sodium excretion by the kidney is a key mechanism in the long term regulation of blood pressure, and when altered it constitutes a risk factor for the appearance of arterial hypertension. Aldosterone, which secretion depends upon salt intake in the diet, is a steroid hormone that regulates sodium reabsorption in the distal part of the nephron (functional unit of the kidney) by modulating gene transcription. It has been shown that it can act synergistically with the peptidic hormone insulin through the interaction of their signalisation pathways. Our work consisted of two distinct parts: 1) the in vitro and in vivo characterisation of Glucocorticoid-Induced Leucine Zipper (GILZ) (an aldosterone-induced gene) mechanism of action; 2) the in vitro characterisation of insulin mechanism of action and its interaction with aldosterone. GILZ mRNA, coded by the TSC22D3 gene, is strongly induced by aldosterone in the cell line of principal cells of the cortical collecting duct (CCD) mpkCCDc14, suggesting that GILZ is a mediator of aldosterone response. Co-expression of GILZ and the amiloride-sensitive epithelial sodium channel ENaC in vitro in the Xenopus oocyte expression system showed that GILZ has no direct effect on the ENaC-mediated Na+ current in basal conditions. To define the role of GILZ in the kidney and in other organs (colon, heart, skin, etc.), a conditional knock-out mouse is being produced and will allow the in vivo study of its role. Previous data showed that insulin induced a transepithelial sodium transport at supraphysiological concentrations. Insulin and the insulin-like growth factor 1 (IGF-1) are able to bind to each other receptor with an affinity 50 to 100 times lower than to their cognate receptor. Our starting hypothesis was that the insulin effect observed at these supraphysiological concentrations is actually mediated by the IGF receptor type 1 (IGF-1R). In a new cell line that presents all the characteristics of the principal cells of the CCD (mCCDc11) we have shown that both insulin and IGF-1 induce a physiologically significant increase of Na+ transport through the activation of IGF-1R. Aldosterone and insulin/IGF-1 have an additive effect on Na+ transport, through the activation of the PI3-kinase (PI3-K) pathway and the phosphorylation of the serum- and glucocorticoid-induced kinase 1 (Sgk1) by the IGF-1R, and the induction of Sgk1 expression by aldosterone. Thus, Sgk1 integrates IGF-1/insulin and aldosterone effects. We suggest that IGF-1 is physiologically relevant in the modulation of sodium balance, while insulin can only regulate Na+ transport at supraphysiological conditions. Both hormones would bind to the IGF-1R and induce Na+ transport by activating the PI3-K PDK1/2 - Sgk1 pathway. We have shown for the first time that Sgk1 is expressed and phosphorylated in principal cells of the CCD in basal conditions, although the mechanism that maintains Sgk1 phosphorylation is not known. This new role for IGF-1 suggests that it could be a salt susceptibility gene. In effect, IGF-1 stimulates Na+ and water transport in the kidney in vivo. Moreover, 35 % of the acromegalic patients (overproduction of growth hormone and IGF-1) are hypertensives (higher proportion than in normal population), and genetic analysis suggest a link between the IGF-1 gene locus and blood pressure. RÉSUMÉ La régulation de l'excrétion rénale de sodium (Na+) joue un rôle principal dans le contrôle à long terme de la pression sanguine, et ses altérations constituent un facteur de risque de l'apparition d'une hypertension artérielle. L'aldosterone, dont la sécrétion dépend de l'apport en sel dans la diète, est une hormone stéroïdienne qui régule la réabsorption de Na+ dans la partie distale du nephron (unité fonctionnelle du rein) en contrôlant la transcription de gènes. Elle peut agir de façon synergistique avec l'hormone peptidique insuline, probablement via l'interaction de leurs voies de signalisation cellulaire. Le but de notre travail comportait deux volets: 1) caractériser in vitro et in vivo le mécanisme d'action du Glucocorticoid Induced Leucine Zipper (GILZ) (un gène induit par l'aldosterone); 2) caractériser in vitro le mécanisme d'action de l'insuline et son interaction avec l'aldosterone. L'ARNm de GILZ, codé par le gène TSC22D3, est induit par l'aldosterone dans la lignée cellulaire de cellules principales du tubule collecteur cortical (CCD) mpkCCDc14, suggérant que GILZ est un médiateur potentiel de la réponse à l'aldosterone. La co-expression in vitro de GILZ et du canal à Na+ sensible à l'amiloride ENaC dans le système d'expression de l'oocyte de Xénope a montré que GILZ n'a pas d'effet sur les courants sodiques véhiculées par ENaC en conditions basales. Une souris knock-out conditionnelle de GILZ est en train d'être produite et permettra l'étude in vivo de son rôle dans le rein et d'autres organes. Des expériences préliminaires ont montré que l'insuline induit un transport transépithelial de Na+ à des concentrations supraphysiologiques. L'insuline et l'insulin-like growth factor 1 (IGF-1) peuvent se lier à leurs récepteurs réciproques avec une affinité 50 à 100 fois moindre qu'à leur propre récepteur. Nous avons donc proposé que l'effet de l'insuline soit médié par le récepteur à l'IGF type 1 (IGF-1R). Dans une nouvelle lignée cellulaire qui présente toutes les caractéristiques des cellules principales du CCD (mCCDc11) nous avons montré que les deux hormones induisent une augmentation physiologiquement significative du transport du Na+ par l'activation des IGF-1 R. Aldosterone et insuline/IGF-1 ont un effet additif sur le transport de Na+, via l'activation de la voie de la PI3-kinase et la phosphorylation de la serum- and glucocorticoid-induced kinase 1 (Sgk1) par l'IGF-1R, dont l'expression est induite par l'aldosterone. Sgk1 intègre les effets de l'insuline et l'aldosterone. Nous proposons que l'IGF-1 joue un rôle dans la modulation physiologique de la balance sodique, tandis que l'insuline régule le transport de Na+ à des concentrations supraphysiologiques. Les deux hormones agissent en se liant à l'IGF-1R et induisent le transport de Na+ en activant la cascade de signalisation PI3-K - PDK1/2 - Sgk1. Nous avons montré pour la première fois que Sgk1 est exprimée et phosphorylée dans des conditions basales dans les cellules principales du CCD, mais le mécanisme qui maintient sa phosphorylation n'est pas connu. Ce nouveau rôle pour l'IGF-1 suggère qu'il pourrait être un gène impliqué de susceptibilité au sel. Aussi, l'IGF-1 stimule le transport rénal de Na+ in vivo. De plus, 35 % des patients atteints d'acromégalie (surproduction d'hormone de croissance et d'IGF-1) sont hypertensifs (prévalence plus élevée que la population normale), et des analyses génétiques suggèrent un lien entre le locus du gène de l'IGF-1 et la pression sanguine. RÉSUMÉ GRAND PUBLIC Nos ancêtres se sont génétiquement adaptés pendant des centaines de millénaires à un environnement pauvre en sel (chlorure de sodium) dans la savane équatoriale, où ils consommaient moins de 0,1 gramme de sel par jour. On a commencé à ajouter du sel aux aliments avec l'apparition de l'agriculture (il y a 5000 à 10000 années), et aujourd'hui une diète omnivore, qui inclut des plats préparés, contient plusieurs fois la quantité de sodium nécessaire pour notre fonction physiologique normale (environ 10 grammes par jour). Le corps garde sa concentration constante dans le sang en s'adaptant à une consommation très variable de sel. Pour ceci, il module son excrétion soit directement, soit en sécrétant des hormones régulatrices. Le rein joue un rôle principal dans cette régulation puisque l'excrétion urinaire de sel change selon la diète et peut aller d'une quantité dérisoire à plus de 36 grammes par jour. L'attention qu'on prête au sel est liée à sa relation avec l'hypertension essentielle. Ainsi, le contrôle rénal de l'excrétion de sodium et d'eau est le principal mécanisme dans la régulation de la pression sanguine, et une ingestion excessive de sel pourrait être l'un des facteurs-clé déclenchant l'apparition d'un phénotype hypertensif. L'hormone aldosterone diminue l'excrétion de sodium par le rein en modulant l'expression de gènes qui pourraient être impliqués dans la sensibilité au sel. Dans une lignée cellulaire de rein l'expression du gène TSC22D3, qui se traduit en la protéine Glucocorticoid Induced Leucine Zipper (GILZ), est fortement induite par l'aldosterone. Ceci suggère que GILZ est un médiateur potentiel de l'effet de l'aldosterone, et pourrait être impliqué dans la sensibilité au sel. Pour analyser la fonction de GILZ dans le rein plusieurs approches ont été utilisées. Par exemple, une souris dans laquelle GILZ est spécifiquement inactivé dans le rein est en train d'être produite et permettra l'étude du rôle de GILZ dans l'organisme. De plus, on a montré que GILZ, en conditions basales, n'a pas d'effet direct sur la protéine transportant le sodium à travers la membrane des cellules, le canal sodique épithélial ENaC. On a aussi essayé de trouver des protéines qui interagissent directement avec GILZ utilisant une technique appelée du « double-hybride dans la levure », mais aucun candidat n'a émergé. Des études ont montré que, à de hautes concentrations, l'insuline peut aussi diminuer l'excrétion de sodium. A ces concentrations, elle peut activer son récepteur spécifique, mais aussi le récepteur d'une autre hormone, l'Insulin-Like Growth Factor 1 (IGF-1). En plus, l'infusion d'IGF-1 augmente la rétention rénale de sodium et d'eau, et des mutations du gène codant pour l'IGF-1 sont liées aux différents niveaux de pression sanguine. On a utilisé une nouvelle lignée cellulaire de rein développée dans notre laboratoire, appelée mCCDc11, pour analyser l'importance relative des deux hormones dans l'induction du transport de sodium. On a montré que les deux hormones induisent une augmentation significative du transport de sodium par l'activation de récepteurs à l'IGF-1 et non du récepteur à l'insuline. On a montré qu'à l'intérieur de la cellule leur activation induit une augmentation du transport sodique par le biais du canal ENaC en modifiant la quantité de phosphates fixés sur la protéine Serumand Glucocorticoid-induced Kinase 1 (Sgk1). On a finalement montré que l'IGF-1 et l'aldosterone ont un effet additif sur le transport de sodium en agissant toutes les deux sur Sgk1, qui intègre leurs effets dans le contrôle du transport de sodium dans le rein.

Association studies between -1185A/G von Willebrand factor gene polymorphism and coronary artery disease

High levels of von Willebrand factor (vWF) have been associated with cardiovascular disease. The A allele of the -1185A/G polymorphism in the 5'-regulatory region of the vWF gene was associated with the highest plasma vWF levels in a normal population. To examine the association between -1185A/G polymorphism and coronary artery disease (CAD), 173 Brazilian Caucasian subjects submitted to coronary angiography were studied. Of these, 57 (33%) had normal coronary arteries (control group) and 116 (67%) had CAD (patient group). Plasma vWF levels were higher in patients (145 U/dl) than in controls (130 U/dl), but the differences were significant only for O blood group subjects. Polymerase chain reaction amplification of the 864-bp vWF promoter region followed by AccII restriction digestion was used to identify the -1185A/G genotypes. The -1185A allele frequency was 43.1% in patients and 44.7% in controls. Allele and genotype frequencies were not significantly different between patients and controls. No association was observed between the -1185A/G genotypes and plasma vWF levels in patients or controls. These results suggest that -1185A/G polymorphism is not an independent risk factor for CAD.

L’utilisation de l’information visuelle en reconnaissance d’expressions faciales d’émotion

L’aptitude à reconnaitre les expressions faciales des autres est cruciale au succès des interactions sociales. L’information visuelle nécessaire à la catégorisation des expressions faciales d’émotions de base présentées de manière statique est relativement bien connue. Toutefois, l’information utilisée pour discriminer toutes les expressions faciales de base entre elle demeure encore peu connue, et ce autant pour les expressions statiques que dynamiques. Plusieurs chercheurs assument que la région des yeux est particulièrement importante pour arriver à « lire » les émotions des autres. Le premier article de cette thèse vise à caractériser l’information utilisée par le système visuel pour discriminer toutes les expressions faciales de base entre elles, et à vérifier l’hypothèse selon laquelle la région des yeux est cruciale pour cette tâche. La méthode des Bulles (Gosselin & Schyns, 2001) est utilisée avec des expressions faciales statiques (Exp. 1) et dynamiques (Exp. 2) afin de trouver quelles régions faciales sont utilisées (Exps. 1 et 2), ainsi que l’ordre temporel dans lequel elles sont utilisées (Exp. 2). Les résultats indiquent que, contrairement à la croyance susmentionnée, la région de la bouche est significativement plus utile que la région des yeux pour discriminer les expressions faciales de base. Malgré ce rôle prépondérant de la bouche, c’est toute de même la région des yeux qui est sous-utilisée chez plusieurs populations cliniques souffrant de difficultés à reconnaitre les expressions faciales. Cette observation pourrait suggérer que l’utilisation de la région des yeux varie en fonction de l’habileté pour cette tâche. Le deuxième article de cette thèse vise donc à vérifier comment les différences individuelles en reconnaissance d’expressions faciales sont reliées aux stratégies d’extraction de l’information visuelle pour cette tâche. Les résultats révèlent une corrélation positive entre l’utilisation de la région de la bouche et l’habileté, suggérant la présence de différences qualitatives entre la stratégie des patients et celle des normaux. De plus, une corrélation positive est retrouvée entre l’utilisation de l’œil gauche et l’habileté des participants, mais aucune corrélation n’est retrouvée entre l’utilisation de l’œil droit et l’habileté. Ces résultats indiquent que la stratégie des meilleurs participants ne se distingue pas de celle des moins bons participants simplement par une meilleure utilisation de l’information disponible dans le stimulus : des différences qualitatives semblent exister même au sein des stratégies des participants normaux.

Left preference for sport tasks does not necessarily indicate left-handedness

In the elite domain of interactive sports, athletes who demonstrate a left preference (e.g., holding a weapon with the left hand in fencing or boxing in a ‘southpaw’ stance) seem overrepresented. Such excess indicates a performance advantage and was also interpreted as evidence in favour of frequency-dependent selection mechanisms to explain the maintenance of left-handedness in humans. To test for an overrepresentation, the incidence of athletes’ lateral preferences is typically compared with an expected ratio of left- to right-handedness in the normal population. However, the normal population reference values did not always relate to the sport-specific tasks of interest, which may limit the validity of reports of an excess of ‘left-oriented’ athletes. Here we sought to determine lateral preferences for various sport-specific tasks (e.g., baseball batting, boxing) in the normal population and to examine the relationship between these preferences and handedness. To this end, we asked 903 participants to indicate their lateral preferences for sport-specific and common tasks using a paper-based questionnaire. Lateral preferences varied considerably across the different sport tasks and we found high variation in the relationship between those preferences and handedness. In contrast to unimanual tasks (e.g., fencing or throwing), for bimanually controlled actions such as baseball batting, shooting in ice hockey or boxing the incidence of left preferences was considerably higher than expected from the proportion of left-handedness in the normal population and the relationship with handedness was relatively low. We conclude that (i) task-specific reference values are mandatory for reliably testing for an excess of athletes with a left preference, (ii) the term ‘handedness’ should be more cautiously used within the context of sport-related laterality research and (iii) observation of lateral preferences in sports may be of limited suitability for the verification of evolutionary theories of handedness.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.