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The central component AcrB of the Escherichia coli drug efflux complex AcrA–AcrB–TolC has been extensively investigated by X‐ray crystallography of detergent–protein 3‐D crystals. In these crystals, AcrB packs as trimers – the functional unit. We visualized the AcrB–AcrB interaction in its native environment by examining E. coli lipid reconstituted 2‐D crystals, which were overwhelmingly formed by asymmetric trimers stabilized by strongly‐interacting monomers from adjacent trimers. Most interestingly, we observed lattices formed by an arrangement of AcrB monomers distinct from that in traditional trimers. This hitherto unobserved packing, might play a role in the biogenesis of trimeric AcrB.E. coli lipid reconstituted AcrB 2D crystals show predominantly asymmetric trimers. Inter monomer–monomer interactions stabilize adjacent AcrB trimers in 2D crystal. Crystals of AcrB containing non‐trimeric arrangement of monomers were also observed. [ABSTRACT FROM AUTHOR]

Résumé: Les atteintes ophtalmologiques permanentes, à type de neuropathie optique ischémique antérieure ou plus rarement d’occlusion artérielle rétinienne, dominent de nos jours encore le pronostic de la maladie de Horton, par leur fréquence (14–20 %) et leur gravité extrême, en contraste avec la remarquable efficacité préventive de la corticothérapie sur leur apparition. Des symptômes ischémiques fugaces (amaurose fugace ou brouillard visuel, diplopie, visions colorées) les précédent une fois sur deux, ou peuvent rester isolés. Les atteintes graves sont, pour la plupart, évitables par un diagnostic plus précoce de l’artérite temporale. L’amaurose fugace, la claudication des masséters, l’absence de symptômes systémiques, et un syndrome inflammatoire modeste représentent des facteurs de risque d’amaurose permanente. L’examen ophtalmologique en urgence, complété d’une angiographie à la fluorescéine et de tests biologiques simples (vitesse de sédimentation [VS], CRP, hémogramme), doit conduire à la mise en route immédiate d’une corticothérapie intensive (1 mg/kg par jour), éventuellement précédée d’emboles intraveineux de méthylprednisolone, plus pour stabiliser l’atteinte constituée et prévenir la cécité controlatérale, que pour tenter d’obtenir une récupération visuelle significative, exceptionnelle. La durée de la corticothérapie d’une forme ophtalmologique n’est pas codifiée ; l’objectif est le contrôle parfait de la maladie, en raison notamment d’un risque élevé (8–18 %) de récidive d’amaurose en cours de décroissance cortisonique. Des études rétrospectives suggérant un effet préventif de l’aspirine à faibles doses sur l’atteinte visuelle et cérébrovasculaire de la maladie de Horton, il est logique de l’associer aux corticoïdes dans les formes avec complication visuelle initiale. [ABSTRACT FROM AUTHOR]

Résumé: L’artérite à cellules géantes (ACG) est une vascularite des gros vaisseaux touchant les trois couches de la paroi artérielle. Elle est caractérisée par un infiltrat inflammatoire composé de lymphocytes T CD4+, de macrophages, de cellules géantes multinuclées parfois organisés en granulomes. Cet infiltrat est responsable de la destruction de la paroi artérielle avec une fragmentation de la limitante élastique interne (LEI) et un remodelage vasculaire aboutissant à une hyperplasie intimale. De récents travaux portant sur les différentes étapes de la physiopathologie de cette artérite ont permis de préciser l’importance du rôle des lymphocytes Th17 dans la phase initiale de la maladie, des cytokines pro-inflammatoires et des cellules musculaires lisses vasculaires au cours du remodelage vasculaire. Cette revue a pour objectif d’actualiser les données concernant les différentes étapes de la constitution des lésions artérielles et de proposer des pistes de réflexion afin d’appréhender au mieux la pathogénie de cette vascularite. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. EXPERIMENTAL APPROACH Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. KEY RESULTS An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. CONCLUSIONS AND IMPLICATIONS RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of speci?c residues at the CLR-RAMP interface compared with RAMP1 and RAMP2. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. EXPERIMENTAL APPROACH Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. KEY RESULTS An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. CONCLUSIONS AND IMPLICATIONS RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2. [ABSTRACT FROM AUTHOR]

Abstract: Purpose. – To analyse iatrogenic events in elderly people and determine the part of unplanned admission in postemergency units directly related to thus iatrogenic events. Methods. – The authors conducted a prospective chart review on treatments and potentials adverse drug-related events of all elderly consecutively hospitalized between January and Marsh 2003 in a postemergency department. A 6 months prospective evaluation after discharge was made for all elderly with adverse drug-related event. Results. – One hundred (and) eighty-six elderly (mean age 83±5.7 years) were prospectively included. Eighty-one per cent are ambulatory with a self-medication administration in spite of a real disability (activity of daily-living: 4.5±1.8). The number of medications consumed ranged from 0 to 15 and averaged 6, with to different source of prescriptions in 34% of the cases. The treatment was recently modified in 41 cases (22%). Adverse drug related events accounted in 55 cases (29%) and hospitalization was directly related to iatrogenic event in 32 cases (17%). Adverse drug related events could be avoided in half cases. There was no death directly related with adverse drug reactions. Follow up after discharge was obtained in 47 cases and pointed out elderly disability: 34 were again hospitalized, 14 admitted in nursing home facilities and 12 died. Treatment was equivalent to our prescription only in 35% of the cases; on the other hand, we found only four elderly with medication directly related to previous adverse event. Discussion. – Theses results pointed out once again polymedication observed in frail elderly people leading to extreme difficulty to prescription due to polypathology. Prescription renewal could be related to adverse drug related events and precipitated elderly people in disability leading to institutionalization. [Copyright &y& Elsevier]

Background: Multiple hypertension guidelines recommend out-of-office measurements for the diagnosis of hypertension in non-pregnant adults, whereas pregnancy guidelines recommend in-office blood pressure measurements. The objective of our study was to determine how Canadian Obstetric Medicine and Maternal Fetal Medicine specialists measure blood pressure in pregnancy. Methods: An email survey was sent to 69 Canadian Obstetric Medicine and Maternal Fetal Medicine specialists in academic centers across Canada to explore the practice patterns of blood pressure measurement in pregnant women. Results: The response rate was 48%. The majority of respondents (63.6%) preferred office blood pressure measurement for diagnosing hypertension, but relied on home blood pressure readings for ongoing monitoring and management of hypertension during pregnancy (59.4%). The preferred method of out-of-office blood pressure measurement was home monitoring; 24-hour ambulatory blood pressure monitoring was not used due to limited availability and cost. Conclusions: There is wide practice variation in methods of measuring blood pressure among Canadian specialists managing hypertension in pregnancy. [ABSTRACT FROM AUTHOR]

Résumé Introduction Les anomalies de l'hémostase chez le patient lupique sont majoritairement de nature thrombotique mais plus rarement hémorragique. Observation Nous rapportons le cas d'un homme de 25 ans présentant un syndrome d'activation macrophagique révélateur d'un lupus érythémateux systémique et compliqué secondairement d'un syndrome hémorragique avec un allongement du temps de thrombine et du temps de céphaline activée, corrigés in vitro par l'ajout de protamine, confirmant ainsi la présence d'un anticoagulant « héparine-like ». Le bilan d'hémostase s'est normalisé après traitement spécifique du lupus. Conclusion Cette anomalie rare du bilan d'hémostase est connue dans les hémopathies et cancers solides. Il s'agit de la première description au cours d'un lupus. Après un an de recul, aucun diagnostic d'hémopathie ou de néoplasie solide n'a été porté. Abstract Introduction In systemic lupus erythematosus, hemostasis disorders are mainly thrombotic, but more rarely hemorrhagic. Case report A 25-year-old man presented with a macrophagic activation syndrome revealing a systemic lupus erythematosus, secondarily complicated by a hemorrhagic syndrome ; biological investigations revealed an increase thrombin time and an activated partial thromboplastin time, normalized by protamin neutralization in vitro, thus confirming the presence of a heparin-like anticoagulant. The hemostasis balance normalized after the specific treatment of lupus. Conclusion This rare anomaly of hemostasis balance has been described in blood cancers and solid cancers. This is the first description of a case associated with an autoimmune connective tissue disorder such as lupus. After one year of follow-up, no diagnosis of blood or solid cancer was made. [ABSTRACT FROM AUTHOR]

Introduction L’artérite à cellules géantes (ACG) est une vascularite des gros vaisseaux habituellement traitée par corticoïdes. Ce traitement est remarquablement efficace mais doit être donné à forte dose pendant 12 à 24 mois, ce qui est responsable d’une importante morbi-mortalité dans cette population âgée. Le tocilizumab (TCZ) est un anticorps monoclonal humanisé dirigé contre les récepteurs (soluble et membranaire) de l’interleukine-6 (IL-6). Son efficacité a récemment été montrée au cours du traitement de l’ACG [1] . Cependant, les données concernant l’évolution après l’arrêt du TCZ manquaient dans cet essai thérapeutique. De plus, la durée optimale de ce traitement coûteux n’est pas connue actuellement. Dans cette étude, nous avons évalué l’intérêt d’associer, au cours des 3 premiers mois de traitement de l’ACG, un traitement par TCZ à la prednisone. Patients et méthodes Vingt patients atteints d’ACG, définie selon les critères de l’ American College of Rheumatology (ACR) et une biopsie d’artère temporale (BAT) positive et/ou une aortite diagnostiquée par angioscanner ou TEP-scanner, ont été inclus dans cette étude multicentrique et prospective, menée dans 6 centres hospitaliers français. La prednisone a été débutée à la dose de 0,7 mg/kg/j et ensuite diminuée selon un protocole standardisé [2] permettant d’atteindre la dose de 0,1 mg/kg/j après 24 semaines (S24) de traitement. Tous les patients ont aussi reçu 4 perfusions de TCZ (8 mg/kg) à S0 (inclusion), S4, S8 et S12. Le critère principal de jugement était le pourcentage de patients en rémission avec une dose de prednisone ≤ 0,1 mg/kg/j à la semaine 26. Les patients ont ensuite été suivis jusqu’à la semaine 52 et les données concernant la survenue de rechute(s) et d’événement(s) indésirable(s) ont été recueillies prospectivement. La rémission était définie comme la disparition des signes d’ACG et une CRP < 10 mg/L. La rechute était définie comme la réapparition, après une période de rémission > 1 mois, de symptômes attribuables à une ACG active et/ou d’une CRP > 10 mg/L à 2 reprises à au moins une semaine d’intervalle et sans autre cause que l’ACG. Les données quantitatives sont présentées en moyenne ± écart type [extrêmes] et les données qualitatives en nombre (%). Cet essai thérapeutique a été enregistré sur ClinicalTrials.gov ( NCT01910038 ). Résultats Vingt patients (15 femmes, 5 hommes dont 19 ACG nouvellement diagnostiquées) ont été inclus entre mars 2014 et juin 2015. L’âge au diagnostic était de 72,6 ± 7,6 ans. La BAT était positive dans 17/19 (90 %) cas et 7/16 (44 %) patients présentaient une aortite. Une atteinte visuelle était notée chez 5 (25 %) patients, dont 1 NOIAA et 1 OARC. La rémission a été obtenue dans tous les cas, après 4 semaines de suivi chez 18/20 (90 %) patients et après 8 et 12 semaines pour les 2 autres patients. Un patient est décédé (mort subite) après 25 semaines de suivi et a été considéré en échec du traitement. À la semaine 26 (14 semaines après la dernière perfusion de TCZ), 15 (75 %) des patients recevaient une dose de prednisone ≤ 0,1 mg/kg/j sans signe d’ACG active. Ce pourcentage est supérieur à celui qui avait été rapporté avec le même schéma de décroissance des corticoïdes (50 % dans le groupe placebo de l’essai HECTHOR trial) [2] . À la semaine 52, 10 (50 %) patients avaient rechuté, 31,8 ± 10,8 [20–51] après l’inclusion ; 9/10 patients recevaient encore de la prednisone à la dose de 4,4 ± 3 [1–10] mg/j. Au cours de l’étude, 64 événements indésirables sont survenus chez 18 patients, dont 3 graves chez 3 patients (1 décès, 1 épisode d’ACFA et une coxopathie rapidement destructrice). Les événements indésirables en rapport avec l’étude les plus fréquents étaient la survenue d’un déséquilibre du bilan lipidique ( n = 8) ou une infection ( n = 15 dont 3 avant S16). Conclusion L’ajout de 4 perfusions de TCZ à un traitement par prednisone au cours de l’ACG permet de diminuer rapidement la dose de corticoïdes tout en maintenant la rémission après 6 mois de traitement chez 75 % des patients. Cependant, une rechute survient dans les 50 % des cas dans un délai de 9 mois après l’arrêt du TCZ. Une meilleure connaissance des mécanismes d’action du TCZ au cours de l’ACG et l’identification de facteurs prédictifs de rechute chez les patients traités par cette biothérapie sont donc nécessaires. [ABSTRACT FROM AUTHOR]

Thermal wave radar imaging (TWRI) was developed to detect manufacturing cracks in automotive powder metallurgy components (transmission sprockets) in their green (unsintered) state. The crack detection capability of the TWRI phase was validated by two sets of cracked/crack-free green and sintered sprockets which were sectioned after TWRI measurements. An automatic defect recognition (ADR) TWR image processing method was also developed to differentiate cracks from local defects. Measurement results demonstrated that TWRI is superior to conventional lock-in thermography imaging (LITI) in both flaw detection resolution and speed, and thus is a viable green-sprocket manufacturing flaw imaging technology. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: About forty percent of the patients with primary Sjögren''s syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy. Methods: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN. Résults: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n =14), prickling (n =4), dysesthesia (n =8)] with paroxystic exacerbations (n =10) and allodynia (n =13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n =13), with a distal (n =9) and leg (n =4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n =14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n =12), mean 3.5±1.7 fibers/mm (N >6.9)] and proximal site of biopsy [(n =9), mean 7.04±2.63 fibers/mm (N >9.3)]. Conclusion: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown. [Copyright &y& Elsevier]

Trypanosoma brucei is the causative agent of African sleeping sickness in humans and one of the causes of nagana in cattle. This protozoan parasite evades the host immune system by antigenic variation, a periodic switching of its variant surface glycoprotein (VSG) coat. VSG switching is spontaneous and occurs at a rate of about 10-2–10-3 per population doubling in recent isolates from nature, but at a markedly reduced rate (10-5–10-6) in laboratory-adapted strains. VSG switching is thought to occur predominantly through gene conversion, a form of homologous recombination initiated by a DNA lesion that is used by other pathogens (for example, Candida albicans, Borrelia sp. and Neisseria gonorrhoeae) to generate surface protein diversity, and by B lymphocytes of the vertebrate immune system to generate antibody diversity. Very little is known about the molecular mechanism of VSG switching in T. brucei. Here we demonstrate that the introduction of a DNA double-stranded break (DSB) adjacent to the ∼70-base-pair (bp) repeats upstream of the transcribed VSG gene increases switching in vitro ∼250-fold, producing switched clones with a frequency and features similar to those generated early in an infection. We were also able to detect spontaneous DSBs within the 70-bp repeats upstream of the actively transcribed VSG gene, indicating that a DSB is a natural intermediate of VSG gene conversion and that VSG switching is the result of the resolution of this DSB by break-induced replication. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient. Methods: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study. Results: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04). Conclusion: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Abrupt onset of papular lesions, with ulcero necrotic evolution could refers to many dermatitis. Febrile ulceronecrotic Mucha-Habermann disease is an unusual severe form of pitiriasis lichenoides and varioliform acuta (PLEVA) characterized with ulceronecrotic eruption potentially associated with high fever and systemic symptoms leading to death. Lymphomatoid papulosis is a recurrent papulonodular eruption with an initial presentation close to PLEVA. While this disorder usually has a bening course, about 10% of the patients develop lymphoproliferative disorders such as CD30+ lymphoma. Exegesis: The authors reported an acute form of PLEVA in a young man hospitalized in internal medicine unit with fever and ulcero-necrotic papulo-vesicular lesions. Treatment with tetracycline was successful. They also report a case of lymphomatoïd pustulosis that occurred in a 34 years old woman with an extensive nodulo-pustular eruption characterized by central necrosis and ulceration. Histopathological examination revealed CD30 lymphocytic infiltration leading to diagnosis. Conclusion: Theses two dermotosis, uncommun and clinically similar, are both characterized with an unpredictable evolution that to be known by internist. [Copyright &y& Elsevier]

Background: To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. Methods: Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral ("snowball") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. Results: Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. Conclusion: Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and "local cross border" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence. [ABSTRACT FROM AUTHOR]

Introduction. – Systemic lupus erythematosus is still of unknown origin. Viruses have long been postulated to play a role in its pathogenesis particularly cytomegalovirus and Epstein-Barr virus.Exegese. – We describe three patients who presented acute onset of syste´mic lupus erythematosus concurrently with recent viral infection (two with cytomegalovirus and one with Epstein-Barr virus).Conclusion. – The peculiar clinical events emphasize the difficulty of diagnosis at the onset of the disease and suggest possible role of these viruses in the pathogenesis of SLE. [Copyright &y& Elsevier]

Objective: To identify all literature regarding depression in patients with advanced cancer and among mixed hospice populations, and to summarise the prevalence of depression according to different definitions. Methods: A systematic review was performed using extensive electronic and hand searches. All studies with quantitative data on prevalence of depression were included and categorised according to their definition of depression. Results: We identified 46 eligible studies giving information on the prevalence of depression, and a further four which gave information on case finding. The most widely used assessment of depression was the Hospital Anxiety and Depression Scale (HADS), which gave a median prevalence of 'definite depression' (i.e., a score on the depression subscale of >10) of 29%, (interquartile range, IQR, 19.50-34.25%). Studies that used psychiatric interviews indicated a prevalence of major depressive disorder ranging from 5% to 26%, with a median of 15%. Studies were generally small (median sample size 88.5, IQR 50-108), had high numbers of nonresponders, and rarely gave confidence intervals for estimates of prevalence. Conclusions: Depression is a common problem in palliative care settings. The quality of much of the available research is poor, based on small samples of patients with very high nonparticipation rates. The clinical importance of depression is described in subsequent papers. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Lead colic is a rare cause of abdominal pain. The diagnosis of lead poisoning is most often mentioned in at risk populations (children, psychotic patients). Case report: We report a 21-year-old man who presented with colicky abdominal pain. Abdominal plain radiograph showed multiple intracolonic metallic bodies. Markedly elevated lead and zinc protoporphyrin serum levels confirmed the diagnosis of lead poisoning. The patient reported that he commonly chewed fishing lead sinker and may sometimes swallow them during the preparation of fishing rod. Clinical outcome was favourable with chelation therapy. Conclusion: Lead poisoning following fishing sinker ingestion is very uncommon. Diagnosis may be discussed in the presence of foreign metallic bodies on plain abdominal radiograph and confirmed by high serum level of lead. A prompt treatment with chelation therapy and digestive emptying is usually effective. [Copyright &y& Elsevier]

Introduction Rapporter l’expérience française sur l’efficacité, la tolérance et l’évolution à l’arrêt d’un traitement par tocilizumab (TCZ) chez les patients atteints d’artérite à cellules géantes (ACG). Patients et méthodes Étude rétrospective française incluant les patients traités par TCZ pour une ACG. L’efficacité était évaluée au niveau de la clinique et de la biologie. Les effets indésirables et l’évolution après traitement étaient également recueillis. Résultats Trente-quatre patients (27 femmes et 7 hommes) d’âge moyen 70,5 ± 8,2 (moyenne ± DS) ont été inclus. Le diagnostic d’ACG était basé sur les critères ACR pour 30 patients et/ou des anomalies à l’imagerie pour 8 patients. Le traitement incluait des corticoïdes chez tous les patients. Un autre immunosuppresseur avait été prescrit avant le TCZ chez 20/34 patients (59 %). Le TCZ (8 mg/kg/mois) était prescrit après une durée d’évolution de la maladie de 18 mois et les patients ont été traités pendant 6,4 ± 4,5 mois. Le traitement était efficace chez les patients exceptés 6 chez qui persistait une activité clinique modérée. La CRP diminuait de 40,4 ± 45,6 mg/L à 1,5 ± 1,8 mg/L ( p < 0,0001) et la posologie des corticoïdes était réduite de 26,3 ± 13,8 à 10,3 ± 8,3 ( p < 0,0001). Un patient est décédé de choc septique et 3 ont dû arrêter le traitement du fait d’effets indésirables graves (péricardite tuberculeuse, cytolyse hépatique, neutropénie). Parmi les 23 patients ayant interrompu le traitement (décision médicale dans 20 cas et effets indésirables pour 3 cas), huit d’entre eux ont rechuté dans un délai moyen de 3,5 ± 1,3 mois et le TCZ a été repris chez 5 d’entre eux. Conclusion Le TCZ induit une rémission rapide et persistante chez les patients ayant une ACG. Cependant, les effets indésirables sont notables et doivent être gardés en mémoire. Des questions persistent quant à l’effet suspensif de ce traitement et au positionnement de ce traitement parmi les autres thérapeutiques. [ABSTRACT FROM AUTHOR]