Dix erreurs a ne pas commettre lors de la prise en charge d'une prothèse articulaire infectée en orthopédie [Ten errors to avoid while dealing with infected total joint arthroplasties].

Infections after total joint arthroplasty are rare but come with severe consequences. Timely, adequate and standardized treatment beginning at the onset of symptoms will have a major impact on the handling of this dreaded complication. In absences of clear guidelines, errors are often committed, with occasionally severe consequences for the patient. In this article, the 10 most frequent errors starting with diagnostics till antibiotic and surgical treatment will be discussed.

Sinusite aiguë: prise en charge en médecine de premier recours [Acute sinusitis]

Les infections des voies aériennes supérieures sont parmi les motifs de consultation les plus fréquents en médecine de premier recours. Lorsque la localisation est principalement rhinosinusienne, la cause est en général virale. Nous passons en revue dans cet article les conditions permettant de suspecter une origine bactérienne avec comme question centrale les critères pour l'instauration d'un traitement antibiotique. La place des examens paracliniques dans la stratégie diagnostique est discutée et en particulier celle de la radiographie standard. Rhino-sinusitis is one of the most complaint in ambulatory clinic sitting and nasal obstruction. This diagnosis is however difficult and general practitioners might overdiagnose acute bacterial sinusitis. Most imaging is not useful in determining sinusitis. Acute sinusitis is very often a self-limiting disease. Antibiotics should be prescribed only after one week of symptoms' duration and in case of the presence of two additional criteria: pain and purulent nasal discharge with nasal obstruction

Incontinence urinaire chez la femme: prise en charge en médecine de premier recours [Urinary incontinence in women: management in primary care]

Urinary incontinence in women is a largely under-evaluated problem that affects nearly one out of two adult women. Even thouh its physiopathology is complex and its etiologies are multiple (and often intricate), urodynamic investigations are not considered necessary before starting a conservative therapy, which can be initiated by the primary care physician. Conservative management is based upon lifestyle modifications, specialized physiotherapy, and in certain cases medication. In the case of insufficient response after three months, the patient should be recommended to a specialist who can evaluate the need for a surgical procedure.

Diagnostic et prise en charge de la thrombocytopénie immune primaire

La thrombocytopénie immune primaire (ITP) est une affection auto-immune acquise avec diminution de la survie des plaquettes et perturbation de la production plaquettaire. Il n'existe aucun test clinique simple permettant de prouver la nature auto-immune de l'affection. Pour cette raison, il s'agit presque toujours d'un diagnostic par exclusion d'autres causes. Bien que les plaquettes soient souvent inférieures à 10 x 109/l lors de la présentation initiale, la tendance hémorragique est étonnamment modérée chez la majorité des patients. Le traitement initial fait toujours appel aux corticostéroïdes, combinés à des immunoglobulines intraveineuses et à des transfusions de plaquettes dans les formes compliquées avec hémorragies significatives. Chez l'enfant, la maladie est souvent induite par des infections virales et son évolution est bénigne et spontanément régressive dans la majorité des cas. Chez l'adulte, la maladie est plus souvent persistante ou chroniquement récidivante, et le taux de plaquettes se situe souvent à un taux suffisant pour prévenir des hémorragies spontanées. Seule une faible proportion de patients souffre d'une thrombocytopénie sévère prolongée accompagnée de saignements réguliers avec risque d'hémorragies potentiellement fatales. C'est probablement ce groupe de patients restreint qui tirera surtout profit des nouvelles options thérapeutiques telles que les agonistes du récepteur de la thrombopoïétine. A la lumière de ces nouvelles possibilités, un groupe d'hématologues suisses s'est réuni pour élaborer des directives concernant la prise en charge de l'ITP conformément aux besoins et aux habitudes de notre pays.

Analyse des épisodes de bactériémies chez les patients nécessitant une prise en charge aux soins intensifs

Introduction : Bacteremia are among the leading forms of severe infections requiring ICU management, and have been reported to be associated with important morbidity and mortality. Bloodstream infection (BSI) can be classified as hospital-acquired (HA), healthcare-associated (HCA) and community-acquired (CA). Each type has its own characteristics and outcome. Methods : We analyzed all consecutive episodes of bacteremia occurring in patients hospitalized in our mixed 32-bed ICU over a 12 month period (01.10.2009-30.09.2010). HA BSI were prospectively included in a multicenter study (EUROBACT). We adapted the case report form to analyze retrospectively all other cases of BSI. Chi-square tests were used for the categorical variables and ANOVA tests for the continuous variables. Results : Bacteremia occurred in 103 patients (120 bacteria) for an incidence-density of 49.3 episodes/1000 admissions. Among HA episodes, about one quarter of episodes was related to vascular accesses, including two thirds acquired outside of the ICU. Concerning HCA BSI, two-thirds originated from the urinary tract. In contrast, a respiratory origin was found in one third of CA episodes. Multiresistant microorganisms were more frequent in HA and HCA BSI. The overall mortality was 32%, as compared to 7.9% and 13.6% for the overall ICU and hospital mortality of other ICU patients over the same period, respectively. In a multivariate model, age (1.06 [1.02-1.11]), septic shock (3.11 [1.16-8.33]) and renal remplacement (7.81 [1.50, 14.93]) were significantly associated with a fatal outcome. Conclusion : Two-thirds of bacteremia documented among ICU patients were nosocomial and in contrast to those community-acquired, Gram-negatives represented the majority of them. However, CA bacteremia were associated with a higher rate of septic shock and death. The microbiological characteristics of HCA episodes were more similar to those HA, that is why it is important to individualize this category in order to adapt the antibiotics.

Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na(+) transport.

The epithelial Na(+) channel (ENaC), located in the apical membrane of renal aldosterone-responsive epithelia, plays an essential role in controlling the Na(+) balance of extracellular fluids and hence blood pressure. As of now, ENaC is the only Na(+) transport protein for which genetic evidence exists for its involvement in the genesis of both hypertension (Liddle's syndrome) and hypotension (pseudohypoaldosteronism type 1). The regulation of ENaC involves a variety of hormonal signals (aldosterone, vasopressin, insulin), but the molecular mechanisms behind this regulation are mostly unknown. Two regulatory proteins have gained interest in recent years: the ubiquitin-protein ligase neural precursor cell-expressed, developmentally downregulated gene 4 isoform Nedd4-2, which negatively controls ENaC cell surface expression, and serum glucocorticoid-inducible kinase 1 (Sgk1), which is an aldosterone- and insulin-dependent, positive regulator of ENaC density at the plasma membrane. Here, we summarize present ideas about Sgk1 and Nedd4-2 and the lines of experimental evidence, suggesting that they act sequentially in the regulatory pathways governed by aldosterone and insulin and regulate ENaC number at the plasma membrane.

Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model.

Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (G(brain)) as function of plasma glucose (G(plasma)) can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant K(t), apparent maximum rate constant T(max), glucose consumption rate CMR(glc), and the iso-inhibition constant K(ii) that suggests G(brain) as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where G(brain) was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by K(t) ranging from 1.5 to 3.5 mM, T(max)/CMR(glc) from 4.6 to 5.6, and K(ii) from 51 to 149 mM. It was noteworthy that K(t) was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by G(brain), predicting that G(brain) eventually approaches a maximum concentration. However, since K(ii) largely exceeds G(plasma), iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.

Synthesis and transport of creatine in the CNS: importance for cerebral functions.

J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06935.x Abstract Apart of its well known function of 'energetic buffer' through the creatine/phosphocreatine/creatine kinase system allowing the regeneration of ATP, creatine has been recently suggested as a potential neuromodulator of even true neurotransmitter. Moreover, the recent discovery of primary creatine deficiency syndromes, due to deficiencies in l-arginine : glycine amidinotransferase or guanidinoacetate methyltransferase (the two enzymes allowing creatine synthesis) or in the creatine transporter, has shed new light on creatine synthesis, metabolism and transport, in particular in CNS which appears as the main tissue affected by these creatine deficiencies. Recent data suggest that creatine can cross blood-brain barrier but only with a poor efficiency, and that the brain must ensure parts of its needs in creatine by its own endogenous synthesis. Finally, the recent years have demonstrated the interest to use creatine as a neuroprotective agent in a growing number of neurodegenerative diseases, including Parkinson's and Huntington's diseases. This article aims at reviewing the latest data on creatine metabolism and transport in the brain, in relation to creatine deficiencies and to the potential use of creatine as neuroprotective molecule. Emphasis is also given to the importance of creatine for cerebral function.

Recommandations pour la prise en charge de la forme systémique l'arthrite juvénile idiopathique (maladie de Still) [Guidelines for diagnosis and treatment in systemic-onset juvenile idiopathic arthritis.]

A guideline group of pediatric rheumatologist experts elaborated guidelines related to the management of idiopathic juvenile arthritis in association with the Haute Autorité de Santé (HAS). A systematic search of the literature published between 1998 and August 2008 and indexed in Pubmed was undertaken. Here, we present the guidelines for diagnosis and treatment in systemic-onset juvenile idiopathic arthritis.

The gamma subunit is a specific component of the Na,K-ATPase and modulates its transport function.

The role of small, hydrophobic peptides that are associated with ion pumps or channels is still poorly understood. By using the Xenopus oocyte as an expression system, we have characterized the structural and functional properties of the gamma peptide which co-purifies with Na,K-ATPase. Immuno-radiolabeling of epitope-tagged gamma subunits in intact oocytes and protease protection assays show that the gamma peptide is a type I membrane protein lacking a signal sequence and exposing the N-terminus to the extracytoplasmic side. Co-expression of the rat or Xenopus gamma subunit with various proteins in the oocyte reveals that it specifically associates only with isozymes of Na,K-ATPase. The gamma peptide does not influence the formation and cell surface expression of functional Na,K-ATPase alpha-beta complexes. On the other hand, the gamma peptide itself needs association with Na,K-ATPase in order to be stably expressed in the oocyte and to be transported efficiently to the plasma membrane. Gamma subunits do not associate with individual alpha or beta subunits but only interact with assembled, transport-competent alpha-beta complexes. Finally, electrophysiological measurements indicate that the gamma peptide modulates the K+ activation of Na,K pumps. These data document for the first time the membrane topology, the specificity of association and a potential functional role for the gamma subunit of Na,K-ATPase.

Abnormal apical-to-basal transport of dietary ovalbumin by secretory IgA stimulates a mucosal Th1 response.

In celiac disease, enhanced permeability to gliadin peptides can result from their apico-basal transport by secretory immunoglobulin A1 (SIgA1) binding to the CD71 receptor ectopically expressed at the gut epithelial surface. Herein, we have established a mouse model in which there is apico-basal transport of the model antigen ovalbumin (OVA) by specific SIgA1 and have analyzed local T-cell activation. Transgenic DO11.10 mice were grafted with a hybridoma-secreting OVA-specific humanized IgA1, which could bind mouse CD71 and which were released in the intestinal lumen as SIgA. CD71 expression was induced at the gut apical surface by treating the mice with tyrphostin A8. Following gavage of the mice with OVA, OVA-specific CD4(+) T cells isolated from the mesenteric lymph nodes displayed higher expression of the activation marker CD69 and produced more interferon gamma in mice bearing the hybridoma-secreting OVA-specific IgA1, than in ungrafted mice or in mice grafted with an irrelevant hybridoma. These results indicate that the protective role of SIgA1 might be jeopardized in human pathological conditions associated with ectopic expression of CD71 at the gut surface.

Principes d'evaluation et de prise en charge des patients agés polymorbides: guide a l'intention des cliniciens [Principles for the assessment and management of polymorbid elderly patients: a guide for clinicians].

Providing care to multimorbid older patients is complex, not only because of the coexistence of multiple chronic conditions, but also because of their frequent intrication with psychological and social problems. This article describes a guide for clinicians to assess and manage multimorbid older patients. This guide was adapted from the work of a group of expert US geriatricians. It proposes seven steps: identification of the main problem; identification of patients' preferences; setting of goals of care; estimation of life expectancy; identification of relevant evidence in the literature; revision of the plan of care; and discussion of the options with the patient. The use of this guide is illustrated by a clinical case.

Paralysie faciale: diagnostic et prise en charge [Diagnosis and management of facial paralysis]

Facial palsy is an unusual pathology that requires standard investigations and management. A clinical overview of the current attitudes is suggested to the general practitioners in order to help them in initiating the adequate investigations and treatment before referring the patient to a specialist.