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International audience; ObjectivesTo assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).MethodsWe conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score).ResultsForty-six patients with TA were included, with a median age of 43 years [29–54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2–3] at baseline to 0 [0–1] and 0 at 3 and 6 months, respectively; p

Background Objectives We report the long term outcome of 46 TA patients treated with tocilizumab, describe the factors of response and compare the vascular event free survival to DMARDs. Methods retrospective nationwide french study Results We observed a decrease in the NIH scale; in C-reactive protein levels and in daily prednisone dose at 3 and 6 months, respectively; p Conclusions This nationwide study shows that tocilizumab may reduce the incidence of vascular complications in TA. Disclosure of Interest None declared

Resume Propos La cryofibrinogenemie est meconnue et les etudes peu nombreuses. L’objectif de notre etude etait de decrire la frequence, les manifestations cliniques et les pathologies associees chez les patients ayant une cryofibrinogenemie isolee. Methodes Il s’agit d’une etude monocentrique retrospective. Ont ete inclus, a partir de la base de donnees du laboratoire d’immunologie, les patients ayant eu une cryofibrinogenemie isolee entre le 1er janvier 2011 et le 31 decembre 2012. Resultats Deux cent quatre-vingt-une recherches consecutives de cryofibrinogenemie ont ete repertoriees. Soixante-treize patients avaient une recherche de cryofibrinogenemie positive : 12 patients avaient une cryofibrinogenemie isolee et 61 (soit 84 %) avaient simultanement une cryofibrinogenemie et une cryoglobulinemie. L’âge moyen etait de 59 ± 19 ans, et 7 patients etaient des femmes (58 %). Les manifestations cutanees etaient presentes chez la moitie des patients. Une atteinte renale etait presente chez 7 patients (58 %), une neuropathie peripherique dans 5 cas (42 %) et une manifestation rhumatologique chez 4 patients (33 %). La survenue d’une manifestation thrombotique etait signalee chez 7 patients (58 %). La concentration mediane de cryofibrinogene etait de 254 ± 304 mg/L. Cinq patients avaient une cryofibrinogenemie secondaire. Le traitement le plus souvent utilise etait la corticotherapie. Conclusion La cryofibrinogenemie est une entite meconnue des cliniciens. La recherche de cryofibrinogenemie est moins frequente que la recherche de cryoglobulinemie alors que les manifestations cliniques sont proches. La recherche est souvent positive, avec une forte prevalence des evenements thrombotiques dans cette population. Ceci souligne l’importance de realiser des etudes prospectives concernant les cryofibrinogenemies.

Le reseau quebecois de la sante et des services sociaux, a l’exemple de celui de nombreux pays industrialises, doit trouver des facons de repondre a la demande grandissante tout en controlant la hausse des couts. De plus en plus de directions d’etablissements voient dans les activites de logistique hospitaliere un reservoir d’economies potentielles de meme qu’une facon de mieux soutenir la performance clinique. Depuis une dizaine d’annees, on trouve differentes etudes qui tracent le portrait des activites logistiques dans les etablissements de sante de la province de Quebec. Cet article permet d’etablir un pont entre ce passe et le present afin de mieux comprendre les enjeux logistiques actuels. L’article propose ensuite des axes de developpement possibles pour les activites de logistique hospitaliere. Il se conclut par des observations sur les competences que doivent posseder les gestionnaires de la logistique pour faciliter la mise en œuvre des axes de developpement suggeres.

Introduction Pour evaluer l’efficacite du tocilizumab chez les patients atteints d’arterite de Takayasu (TA). Patients et methodes Nous avons realise une etude retrospective multicentrique de 46 patients avec TA traites par tocilizumab. Nous avons analyse les facteurs associes a la reponse au tocilizumab et l’incidence des complications vasculaires dans TA les patients traites avec le tocilizumab en comparaison avec ceux sous DMARDs. Resultats Quarante-six patients avec TA ont ete inclus, avec un âge mediane de 43 ans [29–54], et 35 de sexe feminin (76 %). Nous avons observe une diminution de NIH median (de 3 [2–3] au depart a 0 [0–1] et de 0 a 3 et 6 mois, respectivement ; p Conclusion Cette etude a l’echelle nationale montre que le tocilizumab est une alternative therapeutique interessante et pourrais reduire les complications vasculaires dans TA.

Introduction Le Tocilizumab (TCZ) est un anticorps monoclonal dirige contre le recepteur de l’Interleukine 6. Il a l’AMM pour le traitement de la polyarthrite rhumatoide et de l’arterite a cellules geantes mais est utilise de plus en plus frequemment au cours de nombreuses maladies autoimmunes refractaires. L’objectif de cette etude etait de decrire l’efficacite et tolerance du TCZ utilise hors AMM en medecine interne. Materiels et methodes Il s’agit d’une etude retrospective, descriptive et multicentrique realise dans 9 services de medecine interne. Les donnees ont ete colligees en janvier 2019. Resultats Cinquante et un patients ont ete inclus (19 hommes et 32 femmes). L’age moyen etait de 55,6 ± 17 ans (intervalle 23–80). Un traitement par TCZ a ete utilise : – au cours de 12 connectivites (23,5 %) : polychondrite atrophiante (n = 6), sclerodermie systemique (n = 3), syndrome des anti-synthetase (n = 1), connectivite inclassee (n = 3) ; – au cours de 10 vascularites (19 %) : arterite de Takayasu (n = 7), maladie de Cogan (n = 1), panarterite noueuse (n = 1), vascularite inclassee (n = 1) ; – au cours de 10 pathologies ophthalmologiques (19 %) : uveite posterieure non infectieuse (n = 8), ophtalmie sympathique (n = 1), orbitopathie de Basedow (n = 1) ; – au cours de 8 maladies de Still de l’adulte (16 %) ; – au cours de 5 pseudo polyarthrite rhizomelique (10 %) ; – au cours de 3 pathologies diverses (6 %) : amylose AA idiopathique, maladie de Castelmann multicentrique non liee a HHV8, Erdheim Chester (1 cas chacun). La duree moyenne d’evolution de la maladie a l’initiation du TCZ etait de 7,5 ± 6,4 ans. Dans 44 cas (86 %) le TCZ a ete instaure en cas de maladie refractaire a un traitement par corticoides et immunosuppresseurs. Les traitements anterieurs incluaient : corticotherapie (83 %), methotrexate (66 %), anti-TNF (44 %), azathioprine (20,8 %), mycophenolate mofetil (12 %), cyclophosphamide (8 %), rituximab (10 %), hydroxychloroquine (6 %), anakinra chez 2 patients, interferon, dapsone, etoposide, leflunomide, abatacept, salazopyrine ou immunoglobulines intra veineuses dans 1 cas. Le traitement par TCZ etait utilise en premiere ligne (15,5 %), deuxieme ligne (17,5 %), troizieme ligne (31 %), quatrieme ligne (19 %), cinquieme ligne (14 %), sixieme ligne (12 %) ou en septieme ligne therapeutique dans un cas. Le traitement par TCZ etait associe au methotrexate dans 3 cas (6 %) et en monotherapie chez les autres patients. La voie d’administration initiale etait majoritairement intraveineuse (96 %). Au cours du suivi 3 patients ont eu un relai de la forme intra-veineuse a sous cutanee. A la fin du suivi, 41 patients (80 %) etaient encore sous TCZ, avec une periode moyenne de suivi de 22 ± 23 mois (intervalle 1–90). Chez ces patients, la dose moyenne quotidienne de corticoides a baisse significativement de 16,5 ± 18 mg a 5,7 ± 13,7 mg (p Le traitement par TCZ a ete interrompu chez 10 patients (19 %) : du fait d’un echec therapeutique (n = 2), d’un echappement therapeutique (n = 2) ou d’un evenement indesirable (=6). Les evenements indesirables, survenus chez 12 patients, etaient infectieux (2 pneumonies bacteriennes, zona, sinusite), prurite (n = 1), urticaire (n = 1), dyslipidemie (n = 1), apparition d’une HTA (n = 2), reaction a la perfusion (n = 1), dermatite bulleuse (n = 1), insuffisance renale aigue (n = 1), angioedeme (n = 1), ulcerations buccales (n = 1). Conclusion Le TCZ est utilise hors AMM en pratique clinique au cours de nombreuses pathologies autoimmunes. Il permet une diminution significative de la prise de corticoide. Son efficacite a court terme est evaluee a 93 % chez les patients sous TCZ depuis au moins 6 mois. Neanmoins, le traitement a du etre interrompu chez 19 % des patients, du fait d’un evenement indesirable dans 12 % des cas. Dans le futur le TCZ sera probablement mis en place plus souvent et plus precocement au cours des maladies autoimmunes mais d’autres etudes, prospective ou comparatives sont necessaires pour preciser la place du TCZ dans l’arsenal therapeutique de ces pathologies.

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual-site transcranial magnetic stimulation with a 10-millisecond (short IHI) and a 40-millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia. © 2013 International Parkinson and Movement Disorder Society

Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging.

Introduction: The most prevalent etiologies of splenomegaly (SM) easily detected by routine clinical practice are hematological malignancies, portal hypertensions (PH), and hemolytic anemias. However, after these first line diagnoses are ruled out, many cases of SM can remain unexplained. At this point, diagnosis becomes challenging due to the fact that many signs and symptoms can be non-specific, and SM could also be associated to rarer etiologies, such as lysosomal storage diseases (LSD) (e.g. Gaucher disease, acid sphingomyelinase deficiency (Niemann Pick Diseases)). The SplenoMegaly Study (SMS) is a prospective, observational, multi-center, and longitudinal study ongoing in France, which aims to estimate the prevalence of the different etiologies of unexplained SM. We present here preliminary descriptive data on the patients' characteristics and their established diagnosis at follow-up. Methods: Since 2015, all patients aged ≥15 years and referred to the hematology or internal medicine department in 117 French hospitals, with an unexplained SM diagnosis (confirmed by echography or CT-scan with a craniocaudal length ≥13 cm) have been invited to participate. Unexplained cause of SM was defined as a first negative clinical workup based on patient's interview and physical examination, and biological routine tests (including complete blood and reticulocytes count, clotting test, liver enzymes, bilirubin, protein electrophoresis, ESR and CRP). A total of 500 patients will be enrolled. For each patient, last visit takes place at the moment an etiology is identified or up to 12 months after the inclusion. All exams and tests conducted for diagnostic purposes are under each physician's responsibility. Since there is no clinical gold standard for the precise definition of SM, Splenocalc application, adjusting for gender and patient height [Chow and al., 2016], is used to confirm the SM. Results: As of May 2018, 190 consecutive patients (58% male) have been included with a median age of 53 years (16-94 years), a median spleen length of 15 cm (range: 13-30 cm), and 88.6% showed an homogeneous spleen structure. Three patients presented with an obvious diagnosis following the initial workup (n=2, chronic lymphocytic leukemia with lymphocytosis; n=1, sarcoidosis with adenopathies) should not have been included. A total of 129 patients (68%) were considered to have completed the study. Of them, 72 patients (56%) had an established diagnosis. Five categories were identified: lymphoproliferative malignancies (n=20; 27.8%; median age: 66); autoimmune disorders (n=15; 20.8%; median age: 48); myeloproliferative malignancies (n=10; 13.9%; median age: 72); PH (n=10; 13.9%; median age: 62) and other diagnoses, including LSDs (n=17; 23.6%; median age: 40). PH was mainly of nonalcoholic origin. Patients with an established diagnosis were significantly older (median age: 61.5 years vs. 45.0 years; p=0.002) and the SM was significantly greater (mean length: 16.7±3.2 vs. 15.6±2.3 cm; p=0.05) than those with no diagnosis. Hematological malignancies were more common in the oldest patients compared to other diagnostic categories (median age: 66.5; p= Conclusions: Patients who finally have an established diagnosis were older and had a significantly larger spleen than those with no diagnosis. The spleen length cut-off of 13 cm or more seems reliable since almost 9 out 10 cases were confirmed by Splenocalc application. Furthermore, after 12 months of regular medical evaluations, 44% of patients remained with an unexplained SM. This proportion seems to be higher than percentages reported in the literature, but our 12-month follow up period might be too short. The final analysis planned on a total population of 500 patients will estimate the prevalence of each etiology of unexplained SM as well as the exams and tests conducted for diagnosis purpose. Disclosures Denis: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sanhes:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ziza:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bauduer:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Berger:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Costello:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mehdi:Sanofi: Employment. Michaud:Sanofi: Honoraria, Research Funding. Urbanski:Sanofi: Honoraria, Research Funding. Rose:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

The interhemispheric interactions between homologous wrist extensor and flexor muscles representations in the right and left primary cortex (M1) were studied using a paired-pulse transcranial magnetic stimulation in healthy subjects. The magnitude of interhemispheric inhibition (IHI) was studied in 9 right-handed subjects at short (10 ms, SIHI) and long (40 ms, LIHI) interstimulus intervals between the magnetic conditioning (CS) and test stimulus in the motor dominant to non-dominant cortex and vice versa, while the right or left hand was at rest or performing a unimanual sustained tonic contraction (holding a pen with the hand contralateral to the CS). A bidirectional powerful interhemispheric inhibition could be elicited at the short and long IHI phases (SIHI and LIHI) in wrist extensor and flexor muscles in most of the subjects at rest. SIHI but not LIHI was significantly bidirectionally reduced during unimanual contraction of the hand contralateral to the CS stimulation in comparison with rest. The amount of IHI after the stimulation of the "non-dominant" right hemisphere was not reduced in comparison with IHI after stimulation of the "dominant" left hemisphere whatever the active or resting condition. IHI directed to the wrist muscles had a similar level than IHI directed to digit muscles (FDI) at rest. Our data indicate that contralateral wrist muscles activity evokes a global, bidirectional reduction in IHI which was more pronounced for SIHI. These results provide additional evidence that changes in interhemispheric interactions between the M1s are involved in the control of unimanual movements including suppression of unwanted motor activity in the opposite limb during unilateral movements.

Introduction La cholecystite aigue et l’arterite temporale sont rares au cours de la granulomatose eosinophilique avec polyangeite (EGPA). Observation Un patient de 64 ans aux antecedents d’appendicectomie, hernie hiatale et polypectomie presente une toux chronique avec une tracheo-broncho-malacie a l’endoscopie bronchique. La toux cede initialement sous corticoides et antibiotherapie. Trois mois plus tard, il est hospitalise pour toux, arthromyalgies diffuses, oedemes prurigineux et petechies des membres inferieurs. Il existe une hypereosinophilie a 7250/mm 3 . Les serologies parasitaires sont negatives. Le traitement par corticotherapie a 1 mg/kg/j pendant 15 jours et antiparasitaire d’epreuve est inefficace. Il est adresse en medecine interne pour toux et dysesthesies des pieds. L’examen retrouve une douleur en hypochondre droit, des arthromyalgies, des crepitants des bases. Il decrit des cephalees avec claudication de la mâchoire. Est apparue une multinevrite avec atteinte des nerfs median droit et sciatique poplite interne gauche confirmee par l’electromyographie. Il persiste une hypereosinophilie a 2880 elements/mm 3 et CRP a 134 mg/L malgre la corticotherapie. L’echographie montre une vesicule biliaire alithiasique avec un epaississement et un dedoublement parietal. Le bilan hepatique est normal. Un traitement medical initial par antibiotherapie est decide. Une biopsie cutanee des lesions purpuriques montre une necrose fibrinoide de la paroi capillaire avec infiltrats eosinophiles. Les ANCA sont positifs au titre de 800, de type cANCA, anti-MPO a 3,7 AI. La biopsie d’artere temporale montre une arterite necrosante segmentaire et focale sans cellule geante et nombreux polynucleaires eosinophiles. Il n’y a pas d’atteinte renale ni cardiaque. Une EGPA est diagnostiquee. Un traitement par bolus de prednisone a 500 mg/j et cyclophosphamide a 600 mg/kg sont realises, permettant la disparition rapide de la toux, des cephalees avec claudication des mâchoires, des douleurs abdominales, de l’hypereosinophilie et du syndrome inflammatoire. L’etat du patient s’aggrave brutalement avec recidive violente de la douleur abdominale et defense generalisee. Le scanner abdominal et la cœlioscopie confirment une peritonite par perforation de la vesicule biliaire. L’anatomopathologie revele une cholecystite aigue necrosante a eosinophiles avec images de vascularite. Les suites operatoires sont simples, le traitement par corticoides et cyclophosphamide est maintenu. Discussion Ce patient presente une EGPA a atteintes pulmonaire, neurologique peripherique, cutanee et digestive et une arterite temporale necrosante symptomatique. Il s’agit d’une forme severe avec un Five-Factor Score a 1, resistante a la corticotherapie a 2 mg/kg/j. Il existe plusieurs cas decrits d’arterite temporale necrosante sans cellules geantes dans l’EGPA. Serrano-Castro PJ et al. decrivent 5 cas [1] . Il s’agit souvent de patients ayant des symptomes de maladie de Horton et une hypereosinophilie, avec decouverte d’EGPA a l’anatomopathologie. Endo T et al. evoquent l’existence d’une entite clinique distincte d’EGPA avec atteinte des vaisseaux de moyen calibre [2] . Mais cette atteinte pourrait aussi constituer un facteur pronostique d’EGPA. La cholecystite aigue dans l’EGPA est rarement decrite, de diagnostic souvent echographique, sans consensus therapeutique medical ou chirurgical. L’atteinte digestive fait partie des facteurs pronostiques de Five-Factor Score avec indication a une immunosuppression par cyclophosphamide ou rituximab [3] . Dans notre cas, cette complication digestive etait grave avec peritonite biliaire, survenue sous fortes doses de corticoides et cyclophosphamide. On peut se demander si la corticotherapie a favorise la perforation ou si le traitement n’a pas ete suffisant pour stopper le processus de necrose fibrinoide de la paroi vesiculaire. La cholecystectomie precoce, qui avait ete discutee, aurait evite la perforation vesiculaire et pourrait etre proposee aux patients symptomatiques. Inversement, le risque de complication peroperatoire en phase aigue d’une vascularite n’est pas connu, notamment sur le plan infectieux. Conclusion Nous rapportons un cas d’EGPA avec deux atteintes rares : l’arterite temporale necrosante symptomatique et la cholecystite necrosante perforee. L’existence d’une arterite temporale dans l’EGPA traduit une atteinte des vaisseaux de moyen calibre qui ne fait pas partie des criteres pronostiques classiques. Elle etait neanmoins associee ici a des atteintes graves. La prise en charge des cholecystites de l’EGPA par chirurgie precoce ou apres traitement medical doit etre discutee au cas par cas au regard du risque de perforation avec complications potentiellement severes.

Introduction L’acces aux soins est une problematique majeure du systeme de sante actuel. Dans une region en pleine expansion demographique, l’Hopital Joseph Ducuing a Toulouse a mis en place en 2016 une ligne telephonique d’astreinte destinee aux medecins generalistes de la region. Materiels et methodes Il s’agit d’une etude quantitative, retrospective, descriptive, observationnelle et monocentrique. L’objectif principal est de decrire les motifs d’appel des medecins ayant utilise la ligne directe d’avis de medecine interne durant sa premiere annee de mise en place. Les objectifs secondaires consistent en la description du type de prise en charge apres l’appel. Resultats Trois cent quatre-vingt-deux appels ont ete recenses. On retrouve une augmentation de 64 % des appels en un an. Deux tiers des patients etaient des femmes. Les deux pics d’âge se situaient chez les 41–50 ans et les plus de 71 ans. Il s’agissait dans 85,5 % des cas de situations diagnostiques complexes. Les premiers motifs retrouves etaient les affections rhumatologiques, les syndromes inflammatoires, l’asthenie et les affections dermatologiques. Un patient sur 5 a beneficie d’une reponse telephonique seule. Quarante-quatre pour cent ont ete vus en consultation et 30 % ont ete hospitalises. Le pourcentage d’hospitalisations augmente avec l’âge. Le delai de prise en charge moyen etait de 5,8 jours pour les situations urgentes et 24,7 jours pour les cas non urgents. Apres la premiere consultation, le suivi etait assure par les internistes dans 55 % des cas, d’autres specialistes dans 18 % des cas et le medecin generaliste seul dans 21 % des cas. Discussion L’incertitude diagnostique est une part essentielle de la pratique de la medecine. Il est de la responsabilite du medecin generaliste de faire appel aux autres professionnels lorsqu’il se trouve dans une situation qu’il ne peut resoudre. Plusieurs etudes mettent en evidence les difficultes d’acces des generalistes aux specialites hospitalieres, qui aboutissent souvent a des passages aux urgences non justifies. Cette ligne d’astreinte s’inscrit dans la continuite d’autres dispositifs qui ont une volonte de faciliter l’acces aux soins hospitaliers. Sa facilite d’utilisation et ses delais de prise en charge courts apportent une vraie reponse aux obstacles decrits par les generalistes. Si l’on peut en theorie la considerer comme un outil de tele-expertise, il s’agit surtout d’un ticket d’entree vers l’hopital, sans denaturer la relation medecin-patient. Le Projet de Loi de Financement de la Securite Sociale pour 2018 a pour objectif d’encadrer et de remunerer les actes de tele-expertise, afin d’en faciliter le developpement. Conclusion La ligne d’astreinte de medecine interne de l’hopital Joseph Ducuing apporte une solution aux obstacles rencontres par les generalistes pour obtenir une expertise dans les situations diagnostiques complexes. Une etude de la satisfaction de ces derniers serait enrichissante pour en ameliorer le fonctionnement.

Introduction Les pericardites virales sont frequentes. Le virus en cause est rarement identifie. Le Bocavirus, de decouverte recente, n’a jamais ete rapporte, a notre connaissance, au cours d’une pericardite. Observation Une patiente de 25 ans consulte aux urgences pour l’apparition de douleurs thoraciques anterieures associees a des vomissements depuis 48 heures. Elle n’a pas d’ATCD notable en dehors de la consommation de cannabis. Son traitement habituel comporte une pilule estro-progestative microdosee (desogestrel 75 μg). A l’examen clinique, l’auscultation cardiopulmonaire est normale, l’hemodynamique est stable, la saturation a 99 % de sp02 en air ambiant, la frequence cardiaque a 84 bpm. L’abdomen est souple. Le bilan biologique montre un syndrome inflammatoire modere, avec une CRP a 40 mg/L. L’hemogramme est normal avec 6600 GB/mm3. Une cytolyse hepatique sur les TGP a 3 N est presente. La lipase est normale. L’ECG initial montre un rythme sinusal et regulier, sans trouble de la repolarisation. Un angioscanner thoracique est realise aux urgences, eliminant une embolie pulmonaire. Il retrouve par ailleurs des micronodules flous branches bilateraux predominant au lobe inferieur gauche. Les serologies Parvovirus B 19, EBV et CMV positives en IgG, les serologies VIH et VHC negatives et la serologie VHB retrouve une protection post-vaccinale. Sur le prelevement nasopharyngee la recherche de virus respiratoire retrouve la positivite de la PCR Bocavirus. Devant la recidive de la douleur thoracique, associee a des nausees et l’absence d’amelioration, un nouvel ECG realise montre des ondes T amples et diffuses non systematisees a un territoire coronaire, compatible avec le diagnostic de pericardite. Une ETT est realisee montrant l’absence d’epanchement pleural, compatible avec le diagnostic de pericardite seche. L’evolution est finalement favorable apres la mise en place d’un traitement par acide acetylsalicylique a la posologie de 3 g par jour. Discussion Le Bocavirus est un Parvovirus identifie en 2005. Il est retrouve habituellement sur des prelevements nasopharynges lors d’infection respiratoires aigues et sur des echantillons de selles lors de gastro-enterites chez les jeunes enfants [1] , [2] . Il a aussi ete decrit dans un cas d’infection du systeme nerveux central [3] . Conclusion Nous rapportons ici un cas de pneumo-pericardite chez une femme jeune dont le bilan etiologique met en evidence un Bocavirus par PCR sur prelevement nasopharynge. Les autres prelevements infectiologiques sont negatifs. C’est a notre connaissance la premiere observation decrite de pericardite a Bocavirus.

Introduction Il est recommande d’effectuer un bilan annuel chez les personnes porteuses du VIH afin de depister les comorbidites et de reevaluer le traitement. Un parcours en hospitalisation de jour pour ces patients a ete mise en place en 2016 a l’hopital Joseph-Ducuing (Toulouse). Patients et methodes Nous avons realise une etude quantitative, retrospective, descriptive, observationnelle et monocentrique dont l’objectif principal etait de decrire les complications depistees lors du bilan annuel VIH sur un an du 01/01/2017 au 31/12/2017. Les donnees ont ete recueillies grâce a une fiche standardisee de renseignement completee lors de la venue de chaque patient. Resultats Cent vingt-neuf dossiers ont pu etre analyses. Parmi les patients 86 etaient des hommes (67 %). La moyenne d’âge etait de 49,1 ans. Dix-sept pour cent des patients etaient un stade sida et 36 % avaient un Nadir de CD4 Cent vingt-six patients (98 %) etaient traites, 88 % par tritherapie, 8 % par bitherapie (10 patients) et 4 % (5 patients) par monotherapie d’inhibiteur de protease. L’evaluation numerique globale moyenne donnee par le patient (tolerance, simplicite, nombre de comprimes et de prise) etait de 9,3/10. La couverture vaccinale etait insuffisante dans 68 % des cas. La couverture etait de 46 % pour le DTP, 25 % la grippe, 19 % pour le pneumocoque. Concernant le niveau de risque cardiovasculaire, celui ci etait tres faible pour 23 % patients, faible pour 22 % des patients, intermediaire pour 22 % des patients, eleve pour 27 % des patients et tres eleve pour 6 % des patients. En outre, 13 % des patients repondaient aux criteres de syndrome metabolique. Selon les recommandations, un bilan cardiologique complementaire etait donc indique dans 46 % des cas, dont une epreuve d’effort dans 19 %. Concernant la cible de LDL cholesterol, une statine etait indiquee alors que le patient n’en avait pas dans 7 % des cas. Concernant la fonction renale, 37 % des patients avaient une clairance CKD-EPI 300 mg/g. Concernant le depistage de lesions anales, 71 % des patients avaient une indication a avoir une consultation proctologique. Quarante-huit pour cent des patients en ont beneficie le jour meme de l’HDJ et une anomalie a ete depistee lors de cet examen chez 14 % d’entre eux. Une consultation de gynecologie a ete effectuee chez 27 femmes (62 %) et une complication genitale ou mammaire mise en evidence chez 55 % d’entre elles. Une recherche de sang dans les selles etait indiquee pour 29 % des patients, et n’a ete realisee que chez 32 % des patients. La recherche etait positive dans 5 % des cas. Concernant la reevaluation du traitement anti-retroviral une proposition de modification therapeutique etait proposee dans 20 % des cas (complication, effet secondaire, prevention de toxicite…). Conclusion La prise en charge avec un bilan de synthese annuelle est recommandee pour le suivi des personnes vivant avec le VIH. Sa realisation lors d’une hospitalisation de jour et l’utilisation d’une fiche de recueil standardisee permet d’aborder tous les points. Au sein d’une population suivie medicalement la couverture vaccinale est insuffisante. Le risque cardiovasculaire est certainement sous-evalue en consultation et le depistage proctologique sous effectue en externe. Le fait que le patient soit interroge et examine par un autre medecin que son medecin habituel est egalement un element interessant dans la critique constructive de la prise en charge. L’etude de l’impact des recommandations donnees a l’issue de la synthese de l’evaluation annuelle et leur realisation ou non serait un travail complementaire interessant a realiser.

The aim of the present study was to look at the long-term efficacy and side effects profiles of pramipexole in a large cohort of drug naïve patients with regard to dopaminergic medications. In all, 195 consecutive restless legs syndrome (RLS) patients who were prescribed pramipexole more than 1 year previously, agreed to undergo a telephone interview to assess both the efficacy and side effects of pramipexole. Forty-three patients had discontinued pramipexole: 20 because of side effects, six because of a lack of efficacy, six for both and 11 for other reasons. Patients who continued pramipexole for more than 1 year (n = 152) reported a mean decrease in RLS symptoms severity of 80.9% (SD = 19.6%). At the onset of treatment, the most common side effects were nausea (30%), tiredness (9%), dizziness (8%), headache (4%), insomnia (3%), dry mouth (2%), difficulty to concentrate (1.3%) and sleepiness (0.7%), At 30 months, most patients (n = 124/152; 81.6%) reported an absence of side effects of pramipexole. None of the adverse effects occurred in more than 5% of patients at follow-up. The present study confirms, in a large cohort of unselected patients, that pramipexole is effective and safe in the long-term treatment of RLS.

Objective: To investigate the regional cerebral perfusion in patients with idiopathic REM behavior disorder (RBD) in order to establish the topography of networks involved. Methods: We performed cerebral blood flow evaluation using 99m Tc-Ethylene Cysteinate Dimer (ECD) SPECT on eight patients with polysomnographically confirmed RBD and nine age-matched controls. Comparisons were made using SPM2. Results: We found increased perfusion in the pons and putamen bilaterally and in the right hippocampus. In addition, we observed a decreased perfusion in frontal (Brodmann area [BA] 4, 6, 10, 43, 44, 47 bilaterally and left BA 9, 46) and temporo-parietal (BA 13, 22, 43 bilaterally and left BA 7, 19, 20, 21, 39, 40, 41, 42) cortices. Conclusion: Perfusional abnormalities in patients with REM behavior disorder were located in the brainstem, striatum, and cortex. These abnormalities are consistent with the anatomic metabolic profile of Parkinson disease.

Resume Introduction Une pathologie thymique, benigne ou maligne, peut accompagner les pathologies auto-immunes. Si elle est plus frequente en cas de myasthenie, de neuromyotonie ou encore d’erythroblastopenie, elle peut se rencontrer dans presque toutes les maladies auto-immunes. Observation Nous rapportons la premiere description, a notre connaissance, d’une association entre un thymome malin et un syndrome de Reynolds (definie par la presence d’une cirrhose biliaire primitive et d’une sclerodermie). Conclusion L’hypothese physiopathologique avancee est un echappement thymique de lymphocytes T autoreactifs a l’origine de la pathologie auto-immune dans ce contexte de syndrome auto-immun multiple.

Recently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28-hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night.

Objective : Periodic leg movements during sleep (PLMS) are often associated with electroencephalographic (EEG) changes, such as microarousals (MA), and with heart rate (HR) variations. The aim of the present study was to evaluate the effects of age and gender on HR changes associated with PLMS in restless legs syndrome (RLS) patients. Methods : Forty-two RLS patients underwent one night of polysomnographic recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men) according to age, i.e. young (25–40 years), middle-aged (41–55 years) and elderly (56–71 years) patients. The RR interval was calculated for 5 intervals before and 15 intervals after the onset of 50 PLMS in each patient. Results : PLMS were associated with HR changes characterized by a tachycardia followed by a bradycardia. However, a reduction in the tachycardia and the bradycardia was observed with age. Moreover, women showed a higher amplitude in the bradycardia than men. No age or gender difference was found for MA index and duration. Conclusions : This study showed age and gender differences in the magnitude of the HR changes associated with PLMS. The knowledge of HR variations during sleep, including rapid HR changes associated with sleep events such as PLMS or MA, may be helpful in understanding the potential mechanisms involved in the increased cardiac risk observed in elderly.

Restless legs syndrome (RLS) is a common sleep-related disorder principally characterised by leg paresthesia associated with an irresistible urge to move. A majority of RLS patients experience periodic leg movements during sleep (PLMS) and wakefulness. Pharmacological evidence suggests that RLS-PLMS may be caused by a central nervous system dopaminergic (DA) dysfunction. The aim of the present study was to evaluate the striatal pre- and postsynaptic DA status in patients suffering from both RLS and PLMS, by means of [123I] beta-CIT and [123I]IBZM SPECT respectively. Ten drug-naïve patients and ten age-matched controls participated in this study. All participants were recorded for at least one night of polysomnography before the SPECT studies. No difference was seen in DA transporter ([123I] beta-CIT) binding between RLS-PLMS patients (MD=4.89) and controls (MD=4.81; p=0.81). The study of the striatal D2-receptor binding ([123I]IBZM) revealed a significantly lower binding in patients (MD= 1.72) compared with controls (MD=1.85; p=0.006). These results support the hypothesis that a central DA dysfunction is involved in the physiopathology of RLS-PLMS. Several mechanisms may be responsible for the decrease of the D2-receptor binding. However, since [123I] beta-CIT binding is normal, a decreased number of D2-receptors or a decreased affinity of D2-receptors for [123I]IBZM is more likely than an increased level of synaptic DA with attendant downregulation of D2-receptors.

Background Cryofibrinogenemia is frequently associated with cryoglobulinemia. The aim of this study was to determine the characteristics associated with the presence of cryofibrinogenemia in patients with cryoglobulinemic vasculitis. Methods This was a single-center retrospective study that included patients with cryoglobulinemic vasculitis who were tested for cryofibrinogen at a tertiary referral center between January 1, 2011 and December 31, 2012. Twenty-nine patients fulfilled the CryoVas (cryoglobulinemic vasculitis) Survey criteria for cryoglobulinemic vasculitis. Eighteen patients had a detectable cryofibrinogen (CF-positive) and 11 had no detectable cryofibrinogen (CF-negative). Median cryoglobulin levels were 89 ± 129 mg/L in the CF-positive group and 68 ± 82 mg/L in the CF-negative group ( P = .32). Median cryofibrinogen level was 70 ± 174 mg/L. Clinical manifestations were similar in both groups. Cancers and hematological disorders were more frequent among CF-positive patients (39% vs 0%, P = .026). Levels of alpha-1 and alpha-2 globulinemia were higher in the CF-positive group. Cryofibrinogenemia ≥ 100 mg/L was associated with cryoglobulinemic vasculitis (odds ratio [OR] 2.86; 95% confidence interval [CI], 1.06-7.73) in cryoglobulinemic patients. Presence of cryofibrinogenemia was associated with use of corticosteroids, immunosuppressants, or plasmapheresis in cryoglobulinemic vasculitis patients (OR 22.7; 95% CI, 2.02-256.44). Conclusions Our results strongly suggest that presence of cryofibrinogenemia is associated with a more severe phenotype among patients with cryoglobulinemic vasculitis.

Restless legs syndrome (RLS) is defined by an irresistible need to move associated with leg paresthesia. Two additional features are essential for diagnosis: (1) worsening of symptoms at rest with temporary relief by activity, and (2) worsening of symptoms during the evening and/or during the night. The suggested immobilization test (SIT) has been developed to evaluate the presence of these criteria. This test quantifies leg movements and leg discomfort during a 1-hour period of immobility prior to bedtime. We used the SIT to evaluate the effects of immobility on leg discomfort and leg movements experienced by 19 patients with RLS and 19 control subjects. Results show that immobility significantly worsens both leg discomfort and periodic leg movements (PLM) in patients with RLS but not in controls. Patients with RLS showed a higher leg discomfort score (32.6 +/- 15.1 mm vs. 5.7 +/- 7.9 mm; P < 0.00001), a greater maximum leg discomfort value (63.4 +/- 27.4 mm vs. 13.7 +/- 23.0 mm; P < 0.00001) and a greater PLM index (88.4 +/- 62.6 vs. 10.4 +/- 20.6; P < 0.00004) than control subjects. These results further validate the use of the SIT as a diagnostic and research tool for RLS and confirm the contention of the International RLS study group that RLS symptoms worsen at rest.

Objective: To evaluate the characteristics of leg movements experienced by patients with the restless legs syndrome (RLS) during wakefulness using the suggested immobilization test (SIT).Methods: Forty patients with primary RLS who showed an index of leg movements greater than 40 during the SIT were selected for these analyses.Results: In general, Coleman's criteria for scoring PLMS were appropriate for scoring leg movements during the SIT. However, a substantial number of leg movements lasted between 5 and 10 s, exceeding Coleman's maximum duration criterion. The other criteria used to score PLMS (i.e. movements separated by 4-90 s and occurring in series of four consecutive movements) allowed detection of more than 90% of all leg movements recorded during the SIT. The distribution of inter-movement intervals (IMI) suggests that a great majority of leg movements recorded during the SIT are periodic, with a modal value of IMI between 11-12 s.Conclusion: Considering that leg movements recorded during the SIT last longer than those occurring during sleep, we recommend using a duration criterion of 0.5-10 s for scoring the former. We also recommend using the same periodicity criteria for the SIT as those used for scoring PLMS.

Restless legs syndrome (RLS) is a neurologic disorder characterized principally by leg paresthesia and motor restlessness. Several clinical reports indicated that many patients with RLS also have arm paresthesia and restlessness. In the present study, the incidence of arm restlessness was assessed by questionnaire in 230 patients diagnosed with idiopathic RLS. Arm restlessness was reported by 48.7% of the patients. Patients with and without arm restlessness were compared with regard to clinical and polysomnographic parameters. No between-group differences were found for age at onset of RLS, duration of illness, gender, presence of a family history of RLS, sleep latency, total sleep time, sleep efficiency, and periodic leg movements index during sleep. However, arm restlessness was more frequent in patients with severe RLS. Interestingly, the polysomnographic data failed to differentiate the patients with arm restlessness from those without arm restlessness, except for sleep efficiency, which tended to be lower in patients with arm restlessness. In conclusion, the results of the present study are in agreement with clinical observations that a large proportion of patients with RLS have arm restlessness.

A high proportion of patients with restless legs syndrome (RLS) also complain of arm paresthesia but the presence of periodic arm movements (PAM) has never been documented in a sleep laboratory in these patients. We investigated the prevalence of PAM during nocturnal sleep and awakenings in 22 RLS patients. Fifteen patients had a PAM index >5 movements per hour during wakefulness and among them only 3 had a PAM index >5 during sleep. Twenty patients had a periodic leg movement (PLM) index >5 during wakefulness and 17 had a PLM index >5 during sleep. In 42.8% of cases, PAM showed temporal relationship with PLM during wakefulness. These results show that PAM is frequent in RLS and suggest that the basic neurological dysfunction responsible for RLS is probably not located exclusively at the level of the lumbar spinal cord but involves neuronal systems located at upper levels.

Restless legs syndrome (RLS) patients experience periodic stereotyped leg movements while awake and during sleep. The aim of the present study was to measure the effects of sex, age and the sleep/wake state on several characteristics (frequency, duration and periodicity) of these periodic leg movements (PLM). One hundred unrelated patients diagnosed with primary RLS were studied. During wakefulness, frequency of PLM increased and the mean inter-movement interval decreased with advancing age. The modal value of inter-movement interval distribution was also altered suggesting that aging influences rhythm-generation mechanisms. Sleep/wake states had a profound effect on leg movement characteristics. Movements of longer duration were seen during wakefulness, while REM sleep was characterized by the shorter duration and the lowest frequency of PLM, due most likely to the inhibition of spinal motoneurons that prevails in REM sleep. States of vigilance also modulated the periodicity of PLM. Intervals were shorter during wakefulness and increased progressively from stage 1 to stage 2 sleep, and to slow wave sleep (SWS). During REM, the duration of sleep intervals returned to values obtained in stage 1 sleep; these two stages sharing similar patterns of EEG activity. These results indicate that a single state dependent mechanism may be responsible for the periodicity of PLM noted both during sleep and wakefulness.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 4 juin 2015

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual-site transcranial magnetic stimulation with a 10-millisecond (short IHI) and a 40-millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia.

Cryofibrinogenemia is a cryoprotein that was first identified in 1955 by Korst and Kratochvil. Unlike cryoglobulin, the precipitate forms only in plasma and not in the serum. The presence of cryofibrinogen in plasma can be asymptomatic. Cryofibrinogenemia is considered a rare disorder: its prevalence varies from 0% to 7% in healthy subjects and from 8% to 13% in hospitalized patients. Nevertheless, cryofibrinogenemia, when a cryopathy is clinically suspected, has been reported in 12% to 51% of patients. Skin manifestations are usually the first signs and are usually moderate; in addition, cold intolerance, Raynaud phenomenon, purpura, or livedo reticularis often occurs. Skin necrosis, acral ulcers, and gangrene can lead to surgery and amputation. Systemic manifestations are common, and arterial or venous thrombotic events are frequent. Cryofibrinogenemia may be primary (essential) or secondary to other underlying disorders, such as carcinoma, infection, vasculitis, collagen disease, or associated with cryoglobulinemia. The histological features of cryofibrinogenemia can confirm the presence of cryofibrinogen within small and medium arteries, plus occlusive thrombotic diathesis composed of eosinophilic refractile deposits within vessel lumina. Cryofibrinogenemia is a treatable and potentially reversible disease.In moderate forms, it can be treated by simply avoiding cold temperatures. The use of corticosteroids in association with low-dose aspirin is the treatment of choice for moderate forms, although stanozolol is an alternative maintenance therapy. Immunosuppressive therapies, plasmapheresis, and/or intravenous fibrinolysis are useful at treating severe forms of cryofibrinogenemia. The use of anticoagulants is limited to the management of thrombotic events. Treatment of secondary cryofibrinogenemia involves the management of associated diseases. Regular follow-ups are needed because of the high risk of recurrence. Moreover, up to half of patients with cryofibrinogenemia considered as essential may develop lymphomas in the following years. Compared with cryoglobulinemia, less is known about cryofibrinogenemia. Its diagnosis should be considered when suggestive clinical manifestations are present and when there are specific biopsy findings. Although identification of cryofibrinogen in blood samples is simple and inexpensive, cryofibrinogenemia can be asymptomatic, and a lack of diagnosis criteria can make diagnosis difficult to confirm. This review describes the clinical manifestations and the biological and pathological features and discusses the criteria used to diagnose and manage cryofibrinogenemia.

We have estimated the time for the last common ancestor of extant seed plants by using molecular clocks constructed from the sequences of the chloroplastic gene coding for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL) and the nuclear gene coding for the small subunit of rRNA (Rrn18). Phylogenetic analyses of nucleotide sequences indicated that the earliest divergence of extant seed plants is likely represented by a split between conifer-cycad and angiosperm lineages. Relative-rate tests were used to assess homogeneity of substitution rates among lineages, and annual angiosperms were found to evolve at a faster rate than other taxa for rbcL and, thus, these sequences were excluded from construction of molecular clocks. Five distinct molecular clocks were calibrated using substitution rates for the two genes and four divergence times based on fossil and published molecular clock estimates. The five estimated times for the last common ancestor of extant seed plants were in agreement with one another, with an average of 285 million years and a range of 275-290 million years. This implies a substantially more recent ancestor of all extant seed plants than suggested by some theories of plant evolution.

The Betuleae is one of the two Betulaceae tribes and contains two genera, the actinorhizal genus Alnus and the nonactinorhizal genus Betula. To elucidate the phylogenetic relationships within the tribe and compare the relative amounts of genetic diversity between the genera Alnus and Betula, rbcL and 18S rRNA gene sequences as well as rDNA internal transcribed spacer (ITS1 and ITS2) sequences were obtained and compared. In rbcL and 18S rRNA, several substitutions were detected between Alnus and Betula but no variation was observed within Alnus. Minimal length variation was observed among ITS sequences. The numbers of substitutions per site for ITS were, on average, close to 10 times those estimated for 18S between Alnus and Betula. In ITS, numbers of substitutions were, on average, more than twice as large between genera than within genera. Phylogenies from ITS sequences were estimated using neighbor-joining analysis of substitution rates, maximum likelihood and parsimony methods. Each of the two genera appeared monophyletic, which was supported by high bootstrap estimates. Relationships among the three sections of Betula analyzed were also better resolved than those among the three subgenera of Alnus analyzed. Phylogenies estimated from ITS sequences suggested a relatively recent diversification of each genus, in agreement with fossil data.

The immunosuppressive and carcinogenic effects of aryl hydrocarbons such as 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and 3-methylcholanthrene (MC) on B lymphocytes of adult rodents and the induction of cytochrome P450IA1 and aryl hydrocarbon hydroxylase (AHH) in human mitogenactivated lymphocytes and B-lymphoblastoid cell lines are believed to be mediated by the Ah receptor. However, there has not been a direct demonstration or characterization of the Ah receptor in denned populations of any of these cells. We report here the detection and characterization of an abundant, high-affinity B lymphocyte Ah receptor in the AHH-inducible human B lymphoblastoid cell line BCR-5. Our results represent the first characterization of a human lymphocyte receptor in a well-defined lymphocyte population. Sucrose density gradient analysis of BCR-5 cytosols incubated with [ 3 H]TCDD revealed a characteristic 9 S specific binding peak. The maximum concentration of Ah receptor was about 200 fmol/mg protein. Specific binding to the Ah receptor was also detected with [ 3 H]MC and, to a lesser extent, with [ 3 H]benzolalpyrene. The apparent binding affinity ( K d ) for [ 3 H]TCDD (determined by saturation analyses) was about 5 nM. A specific [ 3 H ] TCDD-Ah receptor complex which sedimented at 5 S was extracted from nuclei of BCR-5 cells incubated at 37° with [ 3 H]TCDD. The Ah receptor of BCR-5 cells is thus similar in characteristics to that identified in other cell lines. When BCR-5 cells were exposed in culture for 24 hr to increasing concentrations of benz[ a ]anthracene there was a concentrationdependent increase in induction and a good correlation ( r = 0.98) between the level of induced AHH activity and the relative abundance of cytochrome P450IA1 mRNA. The human B lymphoblastoid cell line BCR-5, therefore, has a complete regulatory mechanism for Ah receptor-mediated induction of cytochrome P450IA1 that is essentially the same as that which has been well established in many rodent species. The accessibility of human blood lymphocytes and the ease of establishment of B lymphoblastoid cell lines from any donor provide a source of pure cultures of human B lymphocytes which can be grown continuously in vitro for the study of mechanisms related to Ah receptor-mediated cytochrome P450IA1 induction, immunosuppression and carcinogenesis.

Study Objectives: It is now well established that symptoms of restless legs syndrome (RLS) are worsened by immobility and that their severity fluctuates according to a circadian pattern with a maximum occurring in the late evening or during the night. However, no study has ever attempted to dissociate these two effects. The objective of this study was to evaluate the nycthemeral variations in the effects of duration of immobility on symptoms of RLS. Design: A 28-hour modified constant routine protocol. Setting: Sleep Disorders Center, Montreal Sacre-Cœur Hospital. Participants: Seven patients with primary RLS (3 men, 4 women; mean age: 43.9 years) and seven controls matched for age (42.4 years) and gender. Intervention: None. Measurements and Results: A 40-minute Suggested Immobilization Test (SIT) was repeated every 2 hours during the 28-hour protocol in order to quantify both subjective leg discomfort and periodic leg movements (PLM). Regarding leg discomfort, a two-way ANOVA performed on patients' data revealed a significant interaction (p=0.037) between Time within the SIT and Time of day. Simple effect analyses performed to decompose the interaction showed that the increase in leg discomfort with duration of immobility was found only on SIT 7, 8, 9, 10 and 12, which corresponds to the period between 21:20 and 08:00. In addition, in patients, a significant circadian variation (p

Mr. B. was hospitalized for repeated falls and a painful syndrome of his right leg evolving since several weeks. The symptoms began with paroxysmal painful contractures in the lower back and in the right leg. Progressively, a hypertonia of the lower limb has settled, leading to falls, loss of independence and use of a rolling chair. On the clinical examination, we noticed a global contraction of the right leg, with an ankle in equinovarus and a quasi-irreducible flexion at 20 degrees of the knee. Muscle spasms were very painful, triggered by muscle contractions and by emotion. An electrophysiological study was performed. The needle electromyography objectived abnormal muscular activities at rest with a continue muscle activity on the right adductor, quadriceps, anterior tibialis and on muscles of the feet (Fig. 1). Motor and sensory nerve conduction variables, including: motor nerve conduction velocities, distal latencies and amplitudes were within normal. Analysis of the cerebro-spinal fluid was normal. On the immunological findings, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies and onco-neural antibodies were negative. Glutamic Acid Decarboxylase antibodies (GAD) were positive at 111 U/ml (N: 0–1). The clinical examination, electrophysiological and immunological findings led to the diagnosis of a limited form of Stiff-man syndrome: a Stiff-leg syndrome.