Simulation des caractéristiques ECG du syndrome de Brugada à l'aide d'un programme de modélisation 3D

Introduction : Le syndrome de Brugada, décrit en 1992 par Pedro et Josep Brugada, est un syndrome cardiaque caractérisé par un sus-décalage particulier du segment ST associé à un bloc de branche droit atypique au niveau des dérivations ECG V1 à V3. Les altérations ECG du syndrome de Brugada sont classifiées en 3 types dont seul le type 1 est diagnostique. Les mécanismes physiopathologiques exacts de ce syndrome sont pour le moment encore controversés. Plusieurs hypothèses sont proposées dans la littérature dont deux principales retiennent l'attention : 1) le modèle du trouble de repolarisation stipule des potentiels d'action réduits en durée et en amplitude liés à un changement de répartition de canaux potassiques 2) le modèle du trouble de dépolarisation spécifie un retard de conduction se traduisant par une dépolarisation retardée. Dans le STEMI, un sus-décalage ST ressemblant à celui du syndrome de Brugada est expliqué par deux théories : 1) le courant de lésion diastolique suggère une élévation du potentiel diastolique transformé artificiellement en sus-décalage ST par les filtres utilisés dans tous les appareils ECG.¦Objectif : Recréer les manifestations ECG du syndrome de Brugada en appliquant les modifications du potentiel d'action des cardiomyocytes rapportées dans la littérature.¦Méthode : Pour ce travail, nous avons utilisé "ECGsim", un simulateur informatique réaliste d'ECG disponible gratuitement sur www.ecgsim.org. Ce programme est basé sur une reconstruction de l'ECG de surface à l'aide de 1500 noeuds représentant chacun les potentiels d'action des ventricules droit et gauche, épicardiques et endocardiques. L'ECG simulé peut être donc vu comme l'intégration de l'ensemble de ces potentiels d'action en tenant compte des propriétés de conductivité des tissus s'interposant entre les électrodes de surface et le coeur. Dans ce programme, nous avons définit trois zones, de taille différente, comprenant la chambre de chasse du ventricule droit. Pour chaque zone, nous avons reproduit les modifications des potentiels d'action citées dans les modèles du trouble de repolarisation et de dépolarisation et des théories de courant de lésion systolique et diastolique. Nous avons utilisé, en plus des douze dérivations habituelles, une électrode positionnée en V2IC3 (i.e. 3ème espace intercostal) sur le thorax virtuel du programme ECGsim.¦Résultats : Pour des raisons techniques, le modèle du trouble de repolarisation n'a pas pu être entièrement réalisée dans ce travail. Le modèle du trouble de dépolarisation ne reproduit pas d'altération de type Brugada mais un bloc de branche droit plus ou moins complet. Le courant de lésion diastolique permet d'obtenir un sus-décalage ST en augmentant le potentiel diastolique épicardique des cardiomyocytes de la chambre de chasse du ventricule droit. Une inversion de l'onde T apparaît lorsque la durée du potentiel d'action est prolongée. L'amplitude du sus-décalage ST dépend de la valeur du potentiel diastolique, de la taille de la lésion et de sa localisation épicardique ou transmurale. Le courant de lésion systolique n'entraîne pas de sus-décalage ST mais accentue l'amplitude de l'onde T.¦Discussion et conclusion : Dans ce travail, l'élévation du potentiel diastolique avec un prolongement de la durée du potentiel d'action est la combinaison qui reproduit le mieux les altérations ECG du Brugada. Une persistance de cellules de type nodal au niveau de la chambre de chasse du ventricule droit pourrait être une explication à ces modifications particulières du potentiel d'action. Le risque d'arythmie dans la Brugada pourrait également être expliqué par une automaticité anormale des cellules de type nodal. Ainsi, des altérations des mécanismes cellulaires impliqués dans le maintien du potentiel diastolique pourraient être présentes dans le syndrome de Brugada, ce qui, à notre connaissance, n'a jamais été rapporté dans la littérature.

Atypical Mucocutaneous Leishmaniasis Caused by Leishmania braziliensis in an Acquired Immunodeficiency Syndrome Patient: T-cell Responses and Remission of Lesions Associated with Antigen Immunotherapy

An atypical case of acquired immunodeficiency syndrome-associated mucocutaneous lesions due to Leishmania braziliensis is described. Many vacuolated macrophages laden with amastigote forms of the parasite were found in the lesions. Leishmanin skin test and serology for leishmaniasis were both negative. The patient was resistant to therapy with conventional drugs (antimonial and amphotericin B). Interestingly, remission of lesions was achieved after an alternative combined therapy of antimonial associated with immunotherapy (whole promastigote antigens). Peripheral blood mononuclear cells were separated and stimulated in vitro with Leishmania antigens to test the lymphoproliferative responses (LPR). Before the combined immunochemotherapy, the LPR to leishmanial antigens was negligible (stimulation index - SI=1.4). After the first course of combined therapy it became positive (SI=4.17). The antigen responding cells were predominantly T-cells (47.5%) most of them with CD8+ phenotype (33%). Very low CD4+ cells (2.2%) percentages were detected. The increased T-cell responsiveness to leishmanial antigens after combined therapy was accompanied by interferon-g (IFN-g) production as observed in the cell culture supernatants. In this patient, healing of the leishmaniasis lesions was associated with the induction of a specific T-cell immune response, characterized by the production of IFN-g and the predominance of the CD8+ phenotype among the Leishmania-reactive T-cells.

Syndrome métabolique, diabète sucré et vulnérabilité: une approche "syndémique" de la maladie chronique [Metabolic syndrome, diabetes mellitus and vulnerability: a syndemic approach of chronic diseases].

The pandemic metabolic syndrome is generally attributed to our lifestyle. The current therapeutic strategies are centered on the behavioral changes and pharmacotherapy. A deeply analysis reveals the importance of the socio-cultural determinants with a "dose-responses effect according to the socio-economic level. The "syndemic" theory, which puts at the same level the socio-cultural environment, the behaviors and biomedecine, suggests a more holistic approach. This theory suggests introducing other partners of care, such cultural-mediators and welfare workers trained in the care, to have finally an approach centered on the roots of the causes. The healthcare networks centered on the management of the costs of health should not forget the socio-cultural dimension, unless wanting to select the good cases.

Cutaneous plasmacytosis: an unusual presentation sharing features with POEMS syndrome?

Cutaneous plasmacytosis is a recently described skin disorder consisting of brown to red papules and nodules containing polyclonal plasmacytes. In this particular case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting with a primary hypothyroidisim. The last two signs have only been described to date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation, and might suggest an overlap between these two entities.

Narcolepsy and familial advanced sleep-phase syndrome: molecular genetics of sleep disorders.

Sleep disorders are very prevalent and represent an emerging worldwide epidemic. However, research into the molecular genetics of sleep disorders remains surprisingly one of the least active fields. Nevertheless, rapid progress is being made in several prototypical disorders, leading recently to the identification of the molecular pathways underlying narcolepsy and familial advanced sleep-phase syndrome. Since the first reports of spontaneous and induced loss-of-function mutations leading to hypocretin deficiency in human and animal models of narcolepsy, the role of this novel neurotransmission pathway in sleep and several other behaviors has gained extensive interest. Also, very recent studies using an animal model of familial advanced sleep-phase syndrome shed new light on the regulation of circadian rhythms.

Ocular involvement in idiopathic hypereosinophilic syndrome: a rare finding [Augenbeteiligung beim idiopathischen Hypereosinophilen Syndrom: ein seltener Befund]

Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterised by persistent eosinophilia associated with multiple organ damage. The three criteria required for the diagnosis of the disease are: a sustained absolute eosinophilic count in the serum greater than 1500/μl present for longer than 6 months, no aetiology for secondary eosinophilia present and identification of signs and symptoms of end-organ involvement [1][2]. Despite significant progress in our understanding of the pathogenesis of some forms of hypereosinophilic syndrome, the current state of knowledge is still insufficient to formulate a new comprehensive etiologic definition of HES [3]. Very few reports can be retrieved describing ocular involvement in HES. Retinal arteriolar occlusions were observed in the pre-equatorial region and documented by angiography in one report [4], while the principal defects noted in a second report were occlusions of major retinal vessels, choroidal infarct, and patchy or delayed choroidal filling [5]. We present a case of extensive bilateral choroidal infiltrates in a patient suffering from idiopathic hypereosinophilia, potentially attributable to her disease.

Outcome of patients with acute coronary syndrome in hospitals of different sizes. A report from the AMIS Plus Registry.

To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.

Microsporidia and acquired immunodeficiency syndrome

Microsporidia is a common term that has been used to refer to a group of eukaryotic, obligate intracellular protozoan parasites belonging to the phylum Microspora. They are important agricultural parasites, contaminating commercial insects; they are also important by infecting laboratory rodents, rabbits and primates. Ever since the early cases found by Magarino Torres, who reported the presence of Encephalitozoon in a patient suffering of a meningoencephalomyelitis, some human pathology caused by microsporidia has been described. However, only after the acquired immunodeficiency syndrome outbreak have these organisms appeared as significant etiological agents in different pathologies. Even so, they remain underestimated. In the present article, the importance of microsporidia for the human pathology in immunocompromised host has been stressed.

Immunocompromised host: from the early events until the impact of acquired immunodeficiency syndrome

The concept that microorganisms can modulate the host resistance was historically reviewed in the present article. The importance of African trypanosomiasis in the development of the research on immunosuppression as well as the impact of human immunodeficiency virus infection are discussed. Each day new opportunistic organisms establish a constant challenge for the correct diagnosis of concomitant infections in acquired immunodeficiency syndrome. The importance of parasite infection in the balance of host resistance in the third world was emphasized. Finally, some aspects of Leishmania as opportunistic organisms were presented.

Human immunodeficiency virus/acquired immunodeficiency syndrome and tropical diseases: a Brazilian perspective

The paper summarizes recent findings on the epidemiology and pathogenesis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/Aids), highlighting the role of co-infections with major tropical diseases. Such co-infections have been studied in the Brazilian context since the beginning of the Aids epidemic and are expected to be more frequent and relevant as the Aids epidemic in Brazil proceeds towards smaller municipalities and the countryside, where tropical diseases are endemic. Unlike opportunistic diseases that affect basically the immunocompromised host, most tropical diseases, as well as tuberculosis, are pathogenic on their own, and can affect subjects with mild or no immunossuppression. In the era of highly active anti-retroviral therapies (HAART), opportunistic diseases seem to be on decrease in Brazil, where such medicines are fully available. Benefiting from HAART in terms of restoration of the immune function, putative milder clinical courses are expected in the future for most co-infections, including tropical diseases. On the other hand, from an ecological perspective, the progressive geographic diffusion of Aids makes tropical diseases and tuberculosis a renewed challenge for Brazilian researchers and practitioners dealing with HIV/Aids in the coming years.

Inferior vena cava syndrome due to Echinococcus multilocularis.

Alveolar echinococcosis is an invasive, tumor-like zoonosis, accidentally transmitted to humans. We present a case of recurrent inferior vena cava (IVC) syndrome due to alveolar echinococcosis and strongly suspected on transthoracic echocardiographic examination.

The cuticle : not only a barrier for plant defence: A novel defence syndrome in plants with cuticular defects.

The cuticle is a physical barrier that prevents water loss and protects against irradiation, xenobiotics and pathogens. This classic textbook statement has recently been revisited and several observations were made showing that this dogma falls short of being universally true. Both transgenic Arabidopsis thaliana lines expressing cell wall-targeted fungal cutinase (so-called CUTE plants) or lipase as well as several A. thaliana mutants with altered cuticular structure remained free of symptoms after an inoculation with Botrytis cinerea. The alterations in cuticular structure lead to the release of fungitoxic substances and changes in gene expression that form a multifactorial defence response. Several models to explain this syndrome are discussed.