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A morning lymphocytosis has been observed in patients under methylprednisolone (mPDN) treatment. We here determine prospectively the timing and magnitude of mPDN-induced lymphocytosis and study the effects of concomitant beta-blockers administration on lymphocyte count (L). L was measured before and 24 to 72 hours after initiating mPDN treatment in 20 patients with immune-mediated inflammatory disorders (IMID). After one week, patients with increased L were divided in two groups receiving, in addition to mPDN, either propranolol or a placebo; L was determined 4 days later. Lymphocyte subpopulations and mPDN plasma levels were determined in subsets of the patients. Values are expressed as median with 25%-75% interquartile range. A 73.4 % (37-305) increase of L was observed in 18/20 patients as soon as 48 (48-72) hours after initiating mPDN (32 mg; 16-32). Lymphocytosis (L ≥4,000/µL) was observed in 7 patients and hyperlymphocytosis (L ≥ 5,000/µL) in 4 of them. No significant changes in L variation were shown under propranolol. In conclusion, the morning lymphocytosis observed during mPDN treatment occurs in the very first days of mPDN administration. The lack of effect of propranolol does not support the role of an increased adrenergic tone.

Background Treatment options for chronic SIADH include water restriction (WR) and urea. The usefulness of urine osmolality to guide the choice of the treatment option is not clearly defined. We hypothesized that urine osmolality can indicate whether treatment with mild water restriction alone could be successful. Methods Retrospective Review of clinical and biochemical (blood and urine) data of patients with chronic SIADH treated for at least one year with mild WR (1.5–2 l/day) either with or without urea. Results Twenty nine patients were included. Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were 129 ± 2 mEq/l and 274 ± 78 mOsm/kgH2O respectively before WR, and increased to 138.5 ± 3 mEq/l and 505 ± 87 mOsm/kgH 2 O ( P 2 O respectively and increased to 136.5 ± 1 mEq/l and 490 ± 151 mOsm/kgH 2 O ( P 2 O and increased to 136.5 ± 2 mEq/l and 698 ± 157 mOsm/kgH 2 O ( P Conclusions About 30% of patients could be treated by moderate WR alone. All these patients presented an initial urine osmolality lower than 400 mOsm/kgH 2 O.

Hypercalcemia is a common pathological condition in clinical practice. The two most common causes are primary hyperparathyroidism and cancer. SIADH is often encountered in cancer cases and is the most common cause of hyponatremia. The aim of this study is to evaluate serum sodium levels in a cohort of patients with hypercalcemia and consider its predictive value in determining the origin of this hypercalcemia.We performed a retrospective study on a series of 15.284 blood tests among adult patients with hypercalcemia. After selection, the study population had 151 patients. We studied mainly serum sodium and etiology of hypercalcemia in our population.We observed a statistically significant association between the presence of hyponatremia and the neoplastic etiology of hypercalcemia. This association persisted after exclusion of patients under treatment with loop diuretics. Conversely, there was no association between hypernatremia and cancer-related hypercalcemia. Among 151 patients with hypercalcemia, 16 presented hyponatremia and 7 with hypernatremia. SIADH was the main cause of hyponatremia. We performed univariate and multivariate logistic regression showing the association between the presence of cancer and the presence of hyponatremia.Our study shows that there is an association between the presence of hyponatremia and neoplastic origin of hypercalcemia. Besides, the association described between hyponatremia and cancer is not faulted by the presence of hypercalcemia, a potential cause of acquired nephrogenic diabetes insipidus.L’hypercalcémie est une condition pathologique courante en pratique clinique. Les deux causes les plus fréquentes sont l’hyperparathyroïdie primaire et le cancer. Le syndrome de sécrétion inappropriée de l’hormone antidiurétique (SIADH) est souvent rencontré dans les cas de cancer, et constitue la cause la plus fréquente d’hyponatrémie. Le but de cette étude est d’évaluer la natrémie dans une cohorte de patients atteints d’hypercalcémie et d’apprécier sa valeur prédictive dans la détermination de l’origine de cette hypercalcémie. Matériel et méthode : Nous avons réalisé une étude rétrospective sur une série de 15.284 analyses sanguines chez des patients adultes hypercalcémiques. Après sélection, la population de l’étude comptait 151 patients. Nous avons étudié principalement la natrémie et l’étiologie de l’hypercalcémie au sein de notre population. Résultats : Nous avons observé une association statistiquement significative entre la présence d’une hyponatrémie et l’étiologie néoplasique de l’hypercalcémie. Cette association persistait après l’exclusion des patients sous traitement par diurétiques de l’anse. Par contre, il n’existait pas d’association entre l’hypernatrémie et l’origine cancéreuse de l’hypercalcémie. Sur 151 patients hypercalcémiques, 16 étaient hyponatrémiques et 7 étaient hypernatrémiques. Un SIADH représentait la cause principale des cas d’hyponatrémie. Nous avons réalisé une régression logistique uni- et multivariée montrant l’association entre l’existence d’un cancer et la présence d’une hyponatrémie.Notre étude montre qu’il existe une association entre la présence d’une hyponatrémie et l’étiologie néoplasique de l’hypercalcémie. Par ailleurs, l’association classiquement décrite entre hyponatrémie et cancer n’est pas prise en défaut par la présence d’une hypercalcémie, cause potentielle de diabète insipide néphrogénique acquis.

The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood–brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS., SCOPUS: ar.j, info:eu-repo/semantics/published

We report the case of a 74-year-old woman admitted to the emergency unit for resting dyspnea. Clinical presentation, cardiac MRI and echocardiography were consistent with cardiac tamponade requiring emergency pericardiocentesis. Cytologic examination of the pericardial fluid revealed the presence of CD68pos CD1aneg S100neg foamy histiocytes (Fig. 1). Additional investigations complied with the diagnosis of Erdheim-Chester histiocytosis. Treatment with αIFN was initiated but the patient developed severe neutropenia that contraindicated further administration. The detection of BRAFV600E mutation on histiocytes isolated from the pericardial liquid and CNS involvement (cerebral masses) prompted the administration of vemurafenib, a selective BRAFV600E kinase inhibitor. Four months after the initiation of low-dose vemurafenib, pericarditis almost resolved and cerebral masses decreased by 50% (Fig. 2). To our knowledge, analysis of pericardial fluid allowing the diagnosis of Erdheim-Chester disease and the detection of the BRAFV600E mutation has in fact been rarely described in the literature. This case report and the successful evolution under vemurafenib also support the use of BRAFV600E inhibitors in αIFN-intolerant patients with BRAFV600E mutation, particularly in case of heart and central nervous system involvement.

Adequate protein folding is necessary for normal cell function and a tightly regulated process that requires proper intracellular ionic strength. In many cell types, imbalance between protein synthesis and degradation can induce endoplasmic reticulum (ER) stress, which if sustained, can in turn lead to cell death. In nematodes, osmotic stress induces massive protein aggregation coupled with unfolded protein response and ER stress. In clinical practice, patients sustaining rapid correction of chronic hyponatremia are at risk of osmotic demyelination syndrome. The intense osmotic stress sustained by brain cells is believed to be the major risk factor for demyelination resulting from astrocyte death, which leads to microglial activation, blood-brain barrier opening, and later, myelin damage. Here, using a rat model of osmotic demyelination, we showed that rapid correction of chronic hyponatremia induces severe alterations in proteostasis characterized by diffuse protein aggregation and ubiquitination. Abrupt correction of hyponatremia resulted in vigorous activation of both the unfolded protein response and ER stress accompanied by increased autophagic activity and apoptosis. Immunofluorescence revealed that most of these processes occurred in astrocytes within regions previously shown to be demyelinated in later stages of this syndrome. These results identify osmotic stress as a potent protein aggregation stimuli in mammalian brain and further suggest that osmotic demyelination might be a consequence of proteostasis failure on severe osmotic stress., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction Au cours de l’infection aigue par le Parvovirus B19, des lesions de vascularite ont ete parfois signalees se limitant generalement a une poussee de purpura vasculaire predominant aux membres inferieurs, mais des signes systemiques plus graves peuvent parfois simuler en tout point une vascularite necrosante (manifestations neurologiques, digestives ou rhumatologiques). Des associations entre purpura rhumatoide et infection a Parvovirus B19 ont ete decrites. Le Parvovirus B19 est suspecte sans que cela soit demontre dans la genese du purpura rhumatoide. Observation Nous decrivons le cas d’un patient âge de 27 ans sans antecedents particuliers, qui a ete hospitalise pour purpura des membres inferieurs, associe a des douleurs abdominales diffuses crampoides et des douleurs neuropathiques en decharges electriques fulgurantes. Le patient se plaignait egalement d’arthralgies invalidantes touchant petites et moyennes articulations. Ce tableau rappelait fortement un purpura rhumatoide. Une biopsie des lesions purpuriques au niveau des membres inferieurs a atteste de la presence d’une vascularite leucocytoclasique touchant les petits vaisseaux, mais l’immunofluorescence est revenue negative. Le taux d’IgA dans le sang etait normal. Une etiologie virale pouvant expliquer le tableau a ete recherchee. Le bilan a confirme la presence d’une infection recente a Parvovirus B19 (serologie positive en IgM). La PCR revient positive dans le sang. Une PCR n’a pas pu etre faite sur la biopsie cutanee vue la fixation prealable des lames. Le patient a ete mis sous corticoides pendant 3 jours en attendant les resultats de la biopsie. Quand le diagnostic fut etabli, l’abstention therapeutique a ete choisie pour la suite de la prise en charge. L’evolution a ete vite favorable avec la disparition des douleurs abdominales suivie de l’effacement progressif du purpura, l’amelioration des douleurs neuropathiques et la disparition du syndrome inflammatoire. Conclusion Le diagnostic d’une infection a Parvovirus B19 responsable d’une vascularite avec atteinte systemique a ete retenu sans que l’association a un purpura rhumatoide ne soit etablie. Mais une surveillance reguliere du patient est necessaire afin de guetter une nouvelle poussee voir l’apparition d’une veritable vasculite a IgA. L’association entre infection a Parvovirus B19 et l’induction d’une veritable vascularite a ete decrite et pose des questions sur le caractere viro-induit des vascularites et sur la physiopathologie de ces maladies qui reste encore mal comprise.

Une femme, âgee de 73 ans, ancienne documentaliste, consultait a veille de Noel. Ses antecedents comportaient une constipation hronique, une hepatite virale guerie, une hypertension arterielle, ne insuffisance veineuse, un syndrome de Raynaud, une presyacousie, une depression severe avec beaucoup d’insomnies, un ancer du sein droit en remission et une keratoconjonctivite bilaerale recidivante. Son pere et sa sœur avaient deja fait plusieurs entatives de suicide. Un de ses fils, geriatre de profession, avait fait n burn-out et l’autre etait depressif. Elle avait rec u 20 ans auparavant une anticoagulation curative et ne corticotherapie generale pour une nevrite optique anterieure roite et des arthralgies etiquetees « maladie de Horton ». Elle avait te hospitalisee quelques mois apres cet episode pour une aggraation de la nevrite optique qui semblait d’allure inflammatoire. es lesions cutanees erythemato-papuleuses non prurigineuses

info:eu-repo/semantics/published

Summary Background and objectives Vaptans (vasopressin V2-receptor antagonists) are a new approach for the treatment of hyponatremia. However, their indications remain to be determined, and their benefit compared with that of the usual treatments for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not been evaluated. This prospective, long-term study compared the efficacy, tolerability, and safety of two oral vaptans with those of oral urea in patients with SIADH. Design, setting, participants, & measurements Patients with chronic SIADH of various origins were treated first with vaptans for 1 year. After an 8-day holiday period, they received oral urea for an additional 1-year follow-up. Serum sodium was measured every 2 months, and drug doses were adjusted accordingly. Results Thirteen participants were initially included in the study (serum sodium, 125±3 mEq/L); 12 completed the 2-year treatment period. Treatment with vaptans (satavaptan, 5–50 mg/d, n=10; tolvaptan, 30–60 mg/day, n=2) increased natremia (serum sodium, 135±3 mEq/L) during the 1-year vaptan period without escape. Hyponatremia recurred in the 12 participants when vaptans were stopped (holiday period). Urea improved the natremia with the same efficacy (serum sodium, 135±2 mEq/L) as vaptans during the 1-year urea treatment period. One participant treated with tolvaptan withdrew from the study early because of excessive thirst. Another patient receiving urea developed hypernatremia without complications. Conclusions Urea has efficacy similar to that of vaptans for treatment of chronic SIADH. Tolerance is generally good for both agents.

Introduction Il existe de multiples medicaments susceptibles de causer une hyperprolactinemie. Cette elevation ne depasse generalement pas 100 ng/mL sauf pour certains neuroleptiques, comme la risperidone, ou cette elevation peut atteindre 200 ng/mL. Au-dela de cette valeur, le diagnostic de prolactinome est le plus probable. Observations Une patiente de 48 ans est admise pour mise au point d’une inappetence associee a des nausees, une perte de poids et une fatigue extreme. L’examen clinique revele un IMC a 17,6 kg/m2 et une legere hypertension arterielle. La patiente ne presente ni gynecomastie, ni galactorrhee. Son traitement a domicile consiste en amitriptyline, L-thyroxine, pantoprazole, pilule œstro-progestative en continu (Yasmin), zolpidem, et domperidone ou metoclopramide en alternance depuis plusieurs semaines. Une gastroscopie montre une oesophagite associee a une hernie hiatale. Le scanner abdominal est sans particularite. La biologie montre une hyperprolactinemie severe (694 ng/mL). Une IRM hypophysaire decrit un microadenome de 5 mm de plus grand axe. Un rythme hormonal de 24 h realise apres l’arret de sa pilule œstro-progestative et des anti-nauseeux montre une nette diminution des taux de prolactine (49 a 71 ng/mL). L’arret ulterieur de l’amitriptyline n’entraine qu’une diminution marginale de la prolactinemie (49 a 56 ng/mL). Discussion Le cas de cette patiente decrit une hyperprolactinemie d’origine medicamenteuse inhabituellement severe (pres de 700 ng/mL), associee principalement a la prise d’anti-nauseeux. Il est en outre probable qu’un microprolactinome et/ou l’anxiodepression severe presentee par la patiente aient aggrave l’elevation observee, comme en temoigne l’hyperprolactinemie moderee persistante malgre l’arret des medicaments incrimines.

Cadarache, the European site for ITER, is located at around 50 km as the crow flies from the sea. The feasibility of the transport of large and heavy ITER components has thus been thoroughly studied. These studies have covered the following items: • possible itineraries between the most convenient harbour (Fos) and Cadarache; • packaging (in particular for the largest and heaviest components); • means of transport (two types of trailers allowing to avoid lifting and load transfers); • logistics (analysis of transfer kinematics, including temporary storage); • administrative procedures and planning for the road adaptation, taking benefit of the recent successful implementation in the south-west of France of an itinerary for the Airbus A380 components. These studies, performed between 2001 and 2003, led to a viable solution, with a reasonable cost, fully supported by the French authorities. The planning necessary to implement the road modifications is also fully compatible with the expected dates of ITER components delivery.

Introduction L’enteropathie associee a l’Olmesartan est une entite recemment decrite. Cela a ete decrit pour la premiere fois en 2012 par la Mayo Clinic qui ont rapporte une serie de 22 cas. Puis il s’en suivit quelques cas rapportes dans la litterature. Le but de ce travail est de rapporter un nouveau cas severe d’une sprue associee a l’Olmesartan, pour rappeler l’importance de rechercher une cause medicamenteuse lors de diarrhee chronique et severe. Observation Nous rapportons le cas d’un patient de 80 ans, suivi pour une hypertension arterielle traitee par l’olmesartan. Il s’est presente avec une diarrhee chronique et un amaigrissement depuis 4 mois. L’evolution a ete marquee par l’apparition d’une confusion et une deshydratation importante ayant entraine une insuffisance renale aigue associee a une acidose metabolique. Notre patient a ete admis aux soins intensifs ou il a ete stabilise et a eu une hemofiltration. Il fut transfere en medecine interne pour le bilan etiologique de cette diarrhee chronique. Multiples hemocultures et coprocultures se sont averees negatives, une endoscopie digestive totale etait normale. Le patient presentait un syndrome de malabsorption tres important et une atropie villositaire diffuse. Les serologies pour la maladie cœliaques etaient negatives et les autres causes de sprue ont ete exclues. Devant la suspicion d’une cause medicamenteuse, l’olmesartan a ete stoppe, une semaine apres le patient commencait a s’ameliorer jusqu’a amendement total des symptomes apres 4 semaines de l’arret. Conclusion Les praticiens ne doivent pas omettre de reviser la liste des medicaments de leurs patients devant des symptomes digestifs associes ou non a une atrophie villositaire, surtout chez les sujets âges polymediques ou une atteinte digestive severe peut engager le pronostic vital. Les sartans doivent etre stoppes devant l’apparition de tout symptome digestif notamment une diarrhee inexpliquee.

Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done., SCOPUS: ar.j, info:eu-repo/semantics/published

Large vessels vasculitis and more specifically, Giant cell arteritis, is characterized by increased inflammatory markers, headaches and altered clinical status. Diagnosis is confirmed by biopsy of temporal arteries showing the presence of granuloma and vasculitis. We hereby report the case of a patient presenting initially as pericarditis and revealing large vessel vasculitis using FDG-PET., Journal Article, info:eu-repo/semantics/published