Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. METHODS AND RESULTS: One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years). CONCLUSIONS: Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.

Périartérite noueuse et hépatite C: association fortuite [Periarteritis nodosa and hepatitis C: a fortuitous association?]

Polyarteritis nodosa is a vasculitis of unknown origin which can be rarely associated with hepatitis B. A exceptional clinical situation of a polyarteritis nodosa associated with hepatitis C is described. This case is also the occasion to review the clinical manifestations, the diagnostic strategy und the therapeutic options of this rare vasculitis.

Speech and oromotor deficits of epileptic origin in benign partial epilepsy of childhood with rolandic spikes (BPERS). Relationship to the acquired aphasia-epilepsy syndrome.

The authors report three children who suffered temporary oromotor or speech disturbances as focal epileptic manifestations within the frame of benign partial epilepsy of childhood with rolandic spikes and review similar cases described in the literature. The deficit can occur as an initial symptom of the disorder without visible epileptic seizures and interferes in a variable way with simple voluntary oromotor functions or complex movements including speech production, depending on the exact location and spread of the discharging epileptic focus around the perisylvian region. The most severe deficit produces the anterior operculum syndrome. More subtle non-linguistic deficits such as intermittent drooling, oromotor apraxia or dysfluency, as well as linguistic ones involving phonologic production, can occur. The rapidity of onset, progression and recovery of the deficit is very variable as well as its duration and presumably reflects the degree of epileptic activity. In some cases, rapid improvement with antiepileptic medication occurs and coincidence between the paroxysmal EEG activity (which is usually bilateral) and the functional deficit is seen. The clinical and EEG profile of the seizures disorder and the dynamic of the deficit in these cases bear a strong resemblance to what is seen in the acquired epilepsy-aphasia syndrome (Landau and Kleffner). The variations in clinical symptoms appear more related to the main site, local extension and bilaterality of the epileptic foci rather than a basic difference in physiopathology.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging

Les maladies cardiovasculaires restent la cause de mortalité la plus élevée dans le monde occidental. Il s'agit d'un processus long et complexe, dont l'infarctus du myocarde et la mort cardiaque ne sont que la fin d'un spectrum. La perfusion myocardique joue un rôle central dans l'évolution de la maladie et survient chronologiquement en amont de la dysfonction diastolique et systolique, ainsi que de l'infarctus du myocarde. Une meilleure compréhension de la Physiopathologie sous-jacente est cruciale dans le diagnostique et la prise en charge du patient. Dans ce sens, ce travail tente d'évaluer l'apport de l'évaluation de la perfusion myocardique évaluée par la tomographic à émission de positron (PET/CT) quant à la prédiction d'événements cardiovasculaires. De plus, l'apport de l'évaluation quantitative par rapport à l'évaluation qualitative a été démontré dans ce travail. Nous avons utilisé un radiotraceur unique au regard de ses caractéristiques. En effet, Le Rubidium-82 est un traceur qui ne nécessite pas d'un cyclotron pour sa fabrication, dès lors qu'il est produit par un générateur, rendant ainsi sa disponibilité un atout et un avantage potentiel lors de futurs implémentations à plus grande échelle. Ce travail démontre la supériorité de l'analyse de perfusion myocardique quantitative par rapport à l'analyse traditionnelle qualitative, ce qui n'était pas encore confirmé avec le Rubidium-82. Les résultats montrent une démarcation significative entre les différentes valeurs de perfusion quantitative/absolue, permettant de distinguer différentes populations plus ou moins à risque en terme de prédiction d'événements cardiaques futurs. Il est intéressant de noter que dans un modèle combinant l'analyse qualitative et quantitative proposé dans ce travail, l'inclusion des résultats les plus ischémiques obtenus par l'analyse qualitative avec les résultats de perfusion les plus bas en terme de flux myocardique absolu (analyse quantitative) démarque une population à très bas risque d'événements cardiovasculaires majeurs, une prédiction pouvant être observée surplus de 1'000 jours. Ces résultats forment un ajout significatif quant à l'évaluation de la perfusion myocardique par la médecine nucléaire, notamment par ce model intégratif proposé, lequel permet une prédiction précise et contributive dans le cadre de futurs événements cardiovasculaires majeurs.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Hypertension portate et infection par le VIH [Portal hypertension and HIV infection]

In the era of antiretroviral therapies, the outcome of patients with chronic HIV infection has considerably changed and their prolonged survival allows the development of chronic liver diseases as a major cause of mortality. Although viral hepatitis, alcoholic and non alcoholic steatohepatitis account forthe majority of chronic liver damage in these patients, there is a growing number of cases with unexplained liver disease, many of which are associated with clinical manifestations of portal hypertension. Inthissituation, nodularregenerative hyperplasia is a frequent finding, characterized at histology by the presence of a nodular architecture in the absence of significant fibrosis, resulting from progressive obliteration of small portal veins. This article describes the clinical presentation, diagnostic aspects, pathogenic mechanisms, as well as the management of this emergent non cirrhotic liver disease in HIV-infected patients.

Idiopathic desquamative interstitial pneumonia in a child: a case report.

BACKGROUND: Desquamative interstitial pneumonia is a rare form of interstitial lung disease in children. Respiratory symptoms appear progressively, are often subtle, and diagnosis is often delayed by a mean of 6 months after onset. High resolution chest computed tomography is the most sensitive imaging technique for demonstrating and identifying interstitial pneumonia. The typical histologic pattern of desquamative interstitial pneumonia, with prominent clustered alveolar macrophages, diffuse reactive alveolar epithelial hyperplasia and globular proteinaceous material, is diagnostic. Desquamative interstitial pneumonia in children can be idiopathic, though it is mostly related to an inborn error of surfactant metabolism. CASE PRESENTATION: We present the complex clinical course and pathologic findings of a 30-months-old Mauritian and Senegalese girl with idiopathic desquamative interstitial pneumonia and multiple extrapulmonary manifestations. To our knowledge, this is the first case report of desquamative interstitial pneumonia to occur as part of a syndrome with multiple organ involvement. CONCLUSION: We believe that desquamative interstitial pneumonia is not always associated with mutations of the surfactant proteins, and can still be idiopathic, especially when occurring as part of a syndrome with multiple organ involvement, as described in other interstitial lung diseases.

Probable metabolic interaction between methadone and fluvoxamine in addict patients.

We report five cases where fluvoxamine (FLVX) was added to maintenance treatment with methadone (MTD) in addict patients with affective disorders. In view of the implication of FLVX in several metabolic drug interactions, MTD plasma levels were measured before and after treatment with FLVX. A slight increase (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In the remaining three patients, the interaction was more pronounced (40-100% increase of the MTD plasma level/dose ratio), with clinical manifestations of opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when starting or stopping treatment with FLVX in patients receiving maintenance treatment with methadone.

La maladie de Wilson: un caméléon clinique auquel il faut penser [A primer on Wilson disease for the general practitioner].

Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.

Respiratory surveillance of patients with Duchenne and Becker muscular dystrophy.

Duchenne muscular dystrophy is is the most common form of the childhood muscular dystrophies. It follows a predictable clinical course marked by progressive skeletal muscle weakness, lost of ambulation before teen-age and death in early adulthood secondary to respiratory or cardiac failure. Becker muscular dystrophy is less common and has a milder clinical course but also results in respiratory and cardiac failure.Altough recent advances in respiratory care and new technologies have improved the outlook many patients already received only a traditional non-interventional approach. The aims of this work are: to analyse the pathophysiology and natural history of respiratory function in these diseases, to descript their clinical manifestations, to present the diagnostics tools and to provide recommendations for an adequated respiratory care in this particular population based on the updated literature referenced.

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy.

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

THE ADULA NAPPE: STRATIGRAPHY, STRUCTURE AND KINEMATICS OF AN EXHUMED HIGH-PRESSURE NAPPE

This study analyses the stratigraphy, structure and kinematics of the northern part of the Adula nappe of the Central Alps. The Adula nappe is one of the highest basement nappes in the Lower Penninic nappe stack of the Lepontine Dome. This structural position makes possible the investigation of the transition between the Helvetic and North Penninic paleogeographic domains. The Adula nappe is principally composed of crystalline basement rocks. The investigation of the pre-Triassic basement shows that it contains several Palaeozoic detrital metasedimentary formations dated from the Cambrian to the Ordovician. These formations contain also some volcanic or intrusive magmatic rocks. Ordovician metagranites dated at ~450 Ma are also a common rock-type of the Adula basement. These formations underwent Alpine and Variscan deformation and metamorphism. Permian granites (Zervreila orthogneiss, dated at ~290 Ma) have intruded this pre-structured basement in a post-orogenic geodynamic context. Due to their age, the Zervreila orthogneiss are good markers for alpine deformation. The stratigraphy of the Mesozoic and Paleogene sedimentary cover of the Adula nappe is essential to unraveling its pre- orogenic history. The autochthonous cover is assigned to a North Penninic Triassic series that testifies for a transition between the Helvetic and Briançonnais Triassic domains. The Adula domain goes through an emersion during the Middle Jurassic, and is part of a topographic high during the first phase of the Alpine rift. The sediments of the late Middle Jurassic show a drowning phase associated with a tectonic activity and a breccia formation. In the neighbouring domains, coeval with the drowning phase in the Adula domain, a strong extensional crustal delamination and a scattered magmatic activity is associated with the main opening of the North Penninic domain. The Upper Jurassic of the Adula nappe is characterized by a carbonate formation comparable with those in the Helvetic or Subbriaçonnais domains. Flysch s.l. deposition starts probably at the end of the Cretaceous. These sediments are deposited on a large unconformity testifying for a Cretaceous sedimentary gap. The Adula nappe exhibits a very complex structure. This structure is formed by several deformation phases. Two ductile deformations are responsible for the nappe emplacement. The first deformation phase is associated with a folding compatible with a top-to-south movement at the top of the nappe. The second phase is dominant and pervasive throughout the whole nappe. It goes with a strong north vergent folding and the main nappe emplacement. These two phases cause the exhumation and emplacement of a coherent, although pre-structured, piece of continental crust. Two further deformation phases postdate the nappe emplacement. - Ce travail concerne l'étude géologique de la partie nord de la nappe de l'Adula dans les Alpes centrales. La nappe de l'Adula est l'une des nappes cristallines la plus élevée dans la pile des nappes du Pennique inférieur des Alpes lepontines. Cette position particulière permet d'étudier la transition entre les nappes des domaines helvétique et pennique inférieur. La nappe de l'Adula est principalement composée de socle cristallin : l'étude de l'histoire géologique du socle est donc l'un des thèmes de cette recherche. Ce socle contient plusieurs formations métasédimentaires paléozoïques du Cambrien à I'Ordovicien. Ces métasédiments sont issus de formations clastiques comprenant souvent des roches magmatiques volcaniques et intrusives. Ces métasédiments ont subi les cycles orogéniques varisque et alpin. La nappe de l'Adula contient plusieurs corps magmatiques granitiques métamorphisés. Les premiers métagranites sont Ordovicien et témoignent d'un environnement de marge active. Ces granites sont aussi polymétamorphiques. Les deuxièmes métagranites sont représentés par les orthogneiss de type Zervreila. Ce métagranite est d'âge permien (-290 Ma). Il est mis en place dans un contexte tectonique post-orogénique. Ce granite est un maqueur de la déformation alpine car il n'est pas affecté par les orogenèses précédentes, flippy Le contenu stratigraphique des roches mésozoïques et cénozoiques de la couverture sédimentaire de la nappe de l'Adula est'important pour en étudier son histoire pré-alpine. La couverture autochtone est composée d'une série d'âge triasique d'affinité nord-pennique, un faciès qui marque la transition entre les domaines helvétiques et briançonnais au Trias. Le domaine paléogéographique représenté dans la nappe de l'Adula connaît une émersion pendant le Jurassique moyen. Cette émersion marque le commencement du rift dans le domaine alpin. La sédimentation de la fin du Jurassique moyen est marquée par une transgression marine accompagnée par des mouvements tectoniques et la formation d'une brèche. Cette transgression est contemporaine des importants mouvements tectoniques et des manifestations magmatiques dans les unités voisines qui marquent la phase principale d'ouverture du bassin nord-pennique. Le Jurassique supérieur est caractérisé par l'instauration d'une sédimentation carbonatée comparable à celle du domaine helvétique ou subbriançonnais. Une sédimentation flyschoïde, probablement du Crétacé à Tertiaire, est déposée sur une importante discordance qui témoigne d'une lacune au Crétacé. La structure complexe de la nappe de l'Adula témoigne de nombreuses phases de déformation. Ces phases de déformation sont en partie issues de la mise en place de la nappe et de déformations plus tardives. La mise en place de la nappe produit deux phases de déformation ductile : la première produit un plissement compatible avec un cisaillement top-vers-le sud dans la partie supérieure de la nappe; la deuxième produit un intense plissement qui accompagne la mise en place de la nappe vers le nord. Ces deux phases de déformation témoignent d'un mécanisme d'exhumation par déformation ductile d'un bloc cohérent.

Bloodstream and endovascular infections due to Abiotrophia defectiva and Granulicatella species.

BACKGROUND: Abiotrophia and Granulicatella species, previously referred to as nutritionally variant streptococci (NVS), are significant causative agents of endocarditis and bacteraemia. In this study, we reviewed the clinical manifestations of infections due to A. defectiva and Granulicatella species that occurred at our institution between 1998 and 2004. METHODS: The analysis included all strains of NVS that were isolated from blood cultures or vascular graft specimens. All strains were identified by 16S rRNA sequence analysis. Patients' medical charts were reviewed for each case of infection. RESULTS: Eleven strains of NVS were isolated during the 6-year period. Identification of the strains by 16S rRNA showed 2 genogroups: Abiotrophia defectiva (3) and Granulicatella adiacens (6) or "para-adiacens" (2). The three A. defectiva strains were isolated from immunocompetent patients with endovascular infections, whereas 7 of 8 Granulicatella spp. strains were isolated from immunosuppressed patients, mainly febrile neutropenic patients. We report the first case of "G. para-adiacens" bacteraemia in the setting of febrile neutropenia. CONCLUSION: We propose that Granulicatella spp. be considered as a possible agent of bacteraemia in neutropenic patients.