Qualité de vie après traitement de l'insuffisance veineuse superficielle primaire. [Quality of life in patients traited for primary superficial venous insufficiency].

Venous symptoms and quality of life (QOL) of 78 patients (54 women, mean age 49,5±13,3 years) with primary superficial venous insufficiency (PSVI) were compared at one year after treatment with crossectomy and stripping (C/S, 56 patients) or endovenous laser ablation (EVLA, 22 patients) using the VEINES-QOL questionnaire. Both treatments significantly (p<0,001) improved the scores for venous symptoms (difference 10,6±9,9 and 9,9±8,2 score points for C/S and EVLA, respectively) and QOL (difference 10,3±8,7 and 8,4±6,6 score points for C/S and EVLA, respectively). No difference was found between treatments regarding symptoms or QOL improvement (p=0,30). We conclude that C/S and EVLA are equally effective in improving symptoms and QOL in PSVI.

The primary in vivo immune response to Mls-1 (Mtv-7 sag). Route of injection determines the immune response pattern.

Injection of cells expressing the retroviral superantigen Mls-1 (Mtv-7 sag) into adult Mls-1- mice induces a strong immune response including both T- and B-cell activation. This model was used for studying qualitative aspects of the immune response in normal mice with a defined antigen-presenting cell (the B cell) and without the use of adjuvant. BALB/c mice were injected locally or systemically with Mls-1-expressing spleen cells from Mls-1-congenic BALB.D2 mice. Intravenous injection led to an initially strong expansion of Mls-1-reactive V beta 6+ CD4+ cells mainly in the spleen, to a large degree explained by the trapping of reactive cells, and a rapid down-regulation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production, consistent with the proposed tolerogenic property of B cells as antigen-presenting cells. However, these mice developed a slowly appearing but persistent B-cell response dominated by IgG1-producing cells, suggesting a shift in lymphokines produced rather than complete unresponsiveness. Subcutaneous injection into the hind footpad with the same number of cells led to a strong local response in the draining lymph node, characterized by a dramatic increase of V beta 6+ CD4+ T cells, local production of IL-2 and IFN-gamma and a strong but short-lived antibody response dominated by IgG2a-producing cells, characteristic of a T-helper type 1 (Th1) type of response. Both routes of injection led ultimately to deletion of reactive T cells and anergy, as defined by the inability to produce IL-2 upon in vitro stimulation with Mls-1. It is concluded that Mls-1 presented by B cells induces qualitatively different responses in vivo dependent on the route of injection. We propose that the different responses result from the migration of the injected cells to different micro-anatomical sites in the lymphoid tissue. Furthermore, these results suggest that B cells may function as professional antigen-presenting cells in vivo present in an appropriate environment.

Early stage primary bone lymphoma : a retrospective, multicenter rare cancer network (RCN) study

IntroductionLe lymphome primaire de l'os (LPO) représente moins de 1% de tous les lymphomes malins. Dans cette étude, nous avons évalué le profil de la maladie, les résultats thérapeutiques, et les facteurs pronostiques d'une série consécutive de patients atteints de LPO de stade I et II. Matériel et méthodeDans treize institutions du Réseau des Cancers Rares (Rare Cancer Network), 116 patients ont été traités pour un LPO entre 1987 et 2008, et sont l'objet de cette étude rétrospective. Quatre-vingt-sept patients ont subi une chimioradiothérapie (CXRT) sans (78), ou avec (9) une chirurgie, 15 ont bénéficié de radiothérapie (RT) sans (13), ou avec (2) chirurgie, 14 d'une chimiothérapie (CXT) sans (9), ou avec (5) chirurgie. La dose médiane de RT était de 40 Gy (4-60). Le nombre médian de cycles de CXT était de 6 (2-8). Le suivi médian était de 41 mois (6-242). RésultatsLe taux de réponse global à la fin du traitement était de 91% (74% de réponses complètes et 17% de réponses partielles). Une récidive locale ou une progression ont été observées chez 12 (10%) patients et une récidive systémique chez 17 (15%) patients. La survie globale, la survie spécifique, et le contrôle local à 5 ans ont été de 76%, 78% et 92%, respectivement. En analyse univariée (log-rank test), les facteurs pronostiques favorables pour la survie globale et la survie spécifique étaient: un indice pronostique international (IPI) inférieur ou égale à 1 (P = 0.009), un grade histologique élevé (P = 0.04), une CXRT (P = 0.05), une CXT (P = 0.0004), une réponse complète (P <0.0001), et une dose de supérieure à 40 Gy (p = 0.005). Concernant le contrôle local, seules la rémission complète et stade I ont été des facteurs favorables. En analyse multivariée, le score IPI, la dose de RT, la rémission complète, et la CXT ont influencé le résultat de façon indépendante en ce qui concerne la survie globale et la survie spécifique. La rémission complète a été le seul facteur prédictif pour le contrôle local. ConclusionCette étude multicentrique rétrospective confirme le bon pronostic du LPO de stade précoce traité par une combinaison de chimio-radiothérapie. Une dose de suffisant de radiothérapie et un nombre adéquat de cycles de chimiothérapie ont été suivis des résultats les plus favorables.

Use of plasma Renin activity to monitor mineralocorticoid treatment in dogs with primary hypoadrenocorticism: desoxycorticosterone versus fludrocortisone.

BACKGROUND: Measurement of plasma renin activity (PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism (PH). OBJECTIVES: To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. ANIMALS: Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2), 21 healthy dogs (group 3), 17 dogs with treated PH (group 4). METHODS: In group 1, PRA was measured before treatment and at different times after initiating treatment. In groups 2 and 3, PRA was measured at initial presentation only. In group 4, no baseline PRA was obtained but PRA was measured once or every 1-6 months during treatment. Mineralocorticoid treatment consisted of fludrocortisone acetate (FC) or desoxycorticosterone pivalate (DOCP). RESULTS: Plasma renin activity before treatment was increased in dogs with PH compared to normal dogs and dogs with diseases mimicking PH with median activity of 27, 0.8, and 1.0 ng/mL/h, respectively. In dogs with PH, PRA decreased and normalized with mineralocorticoid treatment using DOCP but not with FC. In dogs treated with DOCP, PRA was lower than in dogs treated with FC. Plasma sodium concentrations were higher and potassium concentrations were lower with DOCP treatment compared to FC treatment. CONCLUSION AND CLINICAL IMPORTANCE: Plasma renin activity is a reliable tool for monitoring mineralocorticoid treatment. DOCP treatment more effectively suppresses PRA compared to FC in dogs with PH.

Wound infection following stoma takedown: primary skin closure versus subcuticular purse-string suture.

Abstract: Background Stoma closure has been associated with a high rate of surgical site infection (SSI) and the ideal stoma-site skin closure technique is still debated. The aim of this study was to compare the rate of SSI following primary skin closure (PC) versus a skin-approximating, subcuticular purse-string closure (APS). Methods All consecutive patients undergoing stoma closure between 2002 and 2007 by two surgeons at a single tertiary-care institution were retrospectively assessed. Patients who had a new stoma created at the same site or those without wound closure were excluded. The end point was SSI, determined according to current CDC guidelines, at the stoma closure site and/or the midline laparotomy incision. Results There were 61 patients in the PC group (surgeon A: 58 of 61) and 17 in the APS group (surgeon B: 16 of 17). The two groups were similar in baseline and intraoperative characteristics, except that patients in the PC group were more often diagnosed with benign disease (p = 0.0156) and more often had a stapled anastomosis (p = 0.002). The overall SSI rate was 14 of 78 (18%). All SSIs occurred in the PC group (14 of 61 vs. 0 of 17, p = 0.03). Conclusions Our study suggests that a skin-approximating closure with a subcuticular purse-string of the stoma site leads to less SSI than a primary closure. Randomized studies are needed to confirm our findings and assess additional end points such as healing time, cost, and patient satisfaction.

Renoncement aux soins: comment appréhender cette réalité en médecine de premier recours [Patients forgoing health care for economic reasons: how to identify this in a primary care setting?].

Although the performance of the Swiss health system is high, one out of ten patients in general practitioner's (GP) office declares having foregone care in the previous twelve months for economic reasons. Reasons for foregoing care are several and include a lack of knowledge of existing social aids in getting health insurance, unavailability of GPs and long waiting lists for various types of care. Although long term knowledge of patients or a psychosocial history of deprivation or poverty may help identify individuals at risk of foregoing care, many may remain undetected. We propose then a few instruments to help GPs to identify, in a simple and structured approach, patients at risk of forgoing care for economic reasons; these patients are frequently deprived and sometimes poor.

Inflammation-induced changes in expression and glycosylation of genetic variants of alpha 1-acid glycoprotein. Studies with human sera, primary cultures of human hepatocytes and transgenic mice.

The relative occurrence of genetic variants of human alpha 1-acid glycoprotein (AGP) in relation to changes in glycosylation was studied in sera of patients with burn injury, media of cytokine-treated primary cultures of human hepatocytes and Hep 3B cells, and sera of transgenic mice expressing the human AGP-A gene. It is concluded (i) that the glycosylation of AGP was not dependent on its genetic expression and (ii) that both the variants determined by the AGP-A gene as well as by the AGP-B/B' genes are increased after inflammation or treatment with interleukins 1 and 6.

Place de l'aspirine en prévention primaire des maladies cardiovasculaires [The role of aspirin in the primary prevention of cardiovascular disease]

For persons without cardiovascular disease, the benefit of aspirin in primary prevention has been controversial until the recent publication of several major randomized controlled trials. Since then, several medical societies recommend that clinicians discuss aspirin prevention with adults at high cardiovascular risk. Patients with low cardiovascular risk are unlikely to benefit from aspirin, as potential harms (hemorrhagic strokes, gastrointestinal bleedings) may outweigh benefits. Aspirin should be recommended in primary prevention only in patients with a 10-year cardiovascular risk > or = 10% or in diabetic patients aged > or = 40 years with a concomitant cardiovascular risk factor, after assessing contraindications for aspirin and individual's preferences for the risks and benefits associated with aspirin.

Patients âgées vulnérables au cabinet: comment les identifier et quelles ressources mobiliser [Vulnerable older patients in primary care how to identify them? Which ressources to mobilize? ].

Trust is essential to foster and preserve a long-term relationship between primary care physicians and their patients suffering from chronic diseases. However, this relation remains insufficient to successfully manage more complex situations, such as those of older patients with multiple diseases and disability. For the primary care physician, a significant limitation is the time required to plan and coordinate interventions supplied by different health and social care providers. This article describes a structured approach to support primary care physicians in this difficult task and help them to identify vulnerable older patients requiring to mobilize and coordinate health and social care resources. Current and future resources available to family physicians to complete this challenging task are further described.

p53 Mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients.

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtful.

Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension.

OBJECTIVE: The basolateral Na pump drives renotubular reabsorption. In cultured renal cells, mutant adducins, as well as sub-nanomolar ouabain concentrations, stimulate the Na-K pump. METHODS: To determine whether these factors interact and affect Na handling and blood pressure (BP) in vivo, we studied 155 untreated hypertensive patients subdivided on the basis of their plasma endogenous ouabain or alpha-adducin genotype (ADD1 Gly460Trp-rs4961). RESULTS: Under basal conditions, proximal tubular reabsorption and plasma Na were higher in patients with mutated Trp ADD1 or increased endogenous ouabain (P = 0.002 and 0.05, respectively). BPs were higher in the high plasma endogenous ouabain group (P = 0.001). Following volume loading, the increment in BP (7.73 vs. 4.81 mmHg) and the slopes of the relationship between BP and Na excretion were greater [0.017 +/- 0.002 vs. 0.009 +/- 0.003 mmHg/(muEq min)] in ADD1 Trp vs. ADD1 Gly carriers (P &lt; 0.05). BP changes were similar, whereas the slopes of the relationship between BP and Na excretion were lower [0.016 +/- 0.003 vs. 0.008 +/- 0.002 mmHg/(muEq min)] in patients with low vs. high endogenous ouabain (P &lt; 0.05). In patients with high endogenous ouabain, volume loading increased the BP in the ADD1 Trp group but not in the Gly group (P &lt; 0.05). Thus, patients with ADD1 Trp alleles are sensitive to salt and tubular Na reabsorption remains elevated after volume expansion. CONCLUSION: With saline loading, BP changes are similar in high and low endogenous ouabain patients, whereas tubular Na reabsorption increases in the high endogenous ouabain group. Saline loading unmasks differences in renal Na handling in patients with mutant adducin or high endogenous ouabain and exposes an interaction of endogenous ouabain and Trp alleles on BP.

Neuroarthropathy of the foot revealing primary systemic amyloidosis: case report and literature review.

The aims of this review were to describe the case of a patient with debilitating neuroarthropathy of the ankles and feet and reveal a primary systemic (amyloid light chain, AL) amyloidosis and to review the relevant literature concerning the peripheral neuropathy and neuroarthropathy due to amyloidosis. We will emphasize the diagnostic pitfalls and discuss prognosis and treatments of both the peripheral neuropathy and the arthropathy related to AL amyloidosis. This is a descriptive case report of a patient with neuroarthropathy of the lower limbs due to AL amyloidosis. A review and discussion of relevant literature were conducted, based on a PubMed search from 1973 to December 2013. A 51-year-old female was diagnosed with AL amyloidosis after 20 months of investigation of small painful deformities of the feet. Chronic peripheral neuropathy occurs as a manifestation of AL amyloidosis in 25 % of cases. It may exceptionally be complicated by neuroarthropathy. In this case, the paucity of clinical and electrophysiological signs of the neuropathy delayed the diagnosis, leading to a severe arthropathy. The massive destruction of the joints dominated the clinical and the poor functional outcome. Diagnosis of AL amyloidosis should be considered in the presence of a mild peripheral neuropathy and a distal destructive and painless arthropathy. The two key diagnostic procedures are serum protein electrophoresis and nerve biopsy. Delay in treatment worsens the prognosis.

Regulation of dendritic development by neurotrophic factors

AbstractEstablishment of a functional nervous system occurs through an orchestrated multistep process during embryogenesis. As dendrites are the primary sites of synaptic connections, development of dendritic arborization is essential for the formation of functional neural circuits. Maturation of dendritic arbor occurs through dynamic processes that are regulated by intrinsic genetic factors and external signals, such as environmental stimuli, neuronal activity and growth factors. Among the latter, the neurotrophic factor BDNF is a key regulator of dendritic growth. However, the mechanisms by which BDNF controls dendritic development remain elusive.In this study, we first showed that activation of the MAPK signaling pathway and phosphorylation of the transcription factor CREB are required to mediate the effects of BDNF on dendritic development of cortical neurons. However, phosphorylation of CREB alone is not sufficient to induce dendritic growth in response to BDNF. Thus, by using a mutant form of CREB unable to bind its coactivator CRTC1, we demonstrated that BDNF-induced dendritic elaboration requires the functional interaction between CREB and CRTC1. Consistent with these observations, inhibition of CRTC1 expression by shRNA-mediated knockdown was found to suppress the effects of BDNF on dendritic length and branching of cortical neurons.The nuclear translocation of CRTC1, a step necessary for the interaction between CREB and CRTC1, was shown to result from the activation of NMD A receptors by glutamate, leading to the dephosphorylation of CRTC1 by the protein phosphatase calcineurin. In line with these findings, prevention of CRTC1 nuclear translocation in the absence of glutamate, or by inhibiting NMDA receptors or calcineurin suppressed the promotion of dendritic growth by BDNF.Increasing evidence supports a role for the growth factor HGF in the regulation of dendritic morphology during brain development. Despite these observations, little is known about the cellular mechanisms underlying the effects of HGF on dendritic elaboration of cortical neurons. The second part of this study was aimed at elucidating the cellular processes that mediate the effects of HGF on dendritic differentiation. We found that HGF increases cortical dendritic growth through mechanisms that involve MAPK-dependent phosphorylation of CREB, and interaction of CREB with its coactivator CRTC1. These data indicate that the mechanisms underlying the promotion of dendritic growth by HGF are similar to those that mediate the effects of BDNF, suggesting that the role of CREB and CRTC1 in the regulation of dendritic development may not be limited to HGF and BDNF, but may extend to other neurotrophic factors that control dendritic differentiation.Together, these results identify a previously unrecognized mechanism by which CREB and its coactivator CRTC1 mediate the effects of BDNF and HGF on dendritic growth of cortical neurons. Moreover, these data highlight the important role of the cooperation between BDNF/HGF and glutamate that converges on CREB to stimulate the expression of genes that contribute to the development of dendritic arborization.RésuméL'établissement d'un système nerveux fonctionnel s'accomplit grâce à des mécanismes précis, orchestrés en plusieurs étapes au cours de l'embryogenèse. Les dendrites étant les principaux sites de connexions synaptiques, le développement de l'arborisation dendritique est essentiel à la formation de circuits neuronaux fonctionnels. La maturation de l'arbre dendritique s'effectue grâce à des processus dynamiques qui sont régulés par des facteurs génétiques intrinsèques ainsi que par des facteurs externes tels que les stimuli environnementaux, l'activité neuronale ou les facteurs de croissance. Parmi ces derniers, le facteur neurotrophique BDNF est - connu pour être un régulateur clé de la croissance dendritique. Cependant, les mécanismes par lesquels BDNF contrôle le développement dendritique demeurent mal connus.Au cours de cette étude, nous avons montré dans un premier temps que l'activation de la voie de signalisation de la MAPK et la phosphorylation du facteur de transcription CREB sont nécessaires aux effets du BDNF sur le développement dendritique des neurones corticaux. Toutefois, la phosphorylation de CREB en tant que telle n'est pas sûffisante pour permettre la pousse des dendrites en réponse au BDNF. Ainsi, en utilisant une forme mutée de CREB incapable de se lier à son coactivateur CRTC1, nous avons démontré que l'élaboration des dendrites induite par le BDNF nécessite également une interaction fonctionnelle entre CREB et CRTC1. Ces résultats ont été confirmés par d'autres expériences qui ont montré que l'inhibition de l'expression de CRTC1 par l'intermédiaire de shRNA supprime les effets du BDNF sur la longueur et le branchement dendritique des neurones corticaux.Les résultats obtenus au cours de ce travail montrent également que la translocation nucléaire de CRTC1, qui est une étape nécessaire à l'interaction entre CREB et CRTC1, résulte de l'activation des récepteurs NMDA par le glutamate, entraînant la déphosphorylation de CRTC1 par la protéine phosphatase calcineurine. De plus, le blocage de la translocation nucléaire de CRTC1 en absence de glutamate, ou suite à l'inhibition des récepteurs NMDA ou de la calcineurine, supprime complètement la pousse des dendrites induite par le BDNF.De nombreuses d'évidences indiquent que le facteur de croissance HGF joue également un rôle important dans la régulation de la morphologie dendritique au cours du développement cérébral. Malgré ces observations, peu d'éléments sont connus quant aux mécanismes cellulaires qui sous-tendent les effets du HGF sur la croissance dendritique des neurones corticaux. Le but de la seconde partie de cette étude a eu pour but d'élucider les processus cellulaires responsables des effets du HGF sur la différenciation dendritique des neurones corticaux. Au cours de ces expériences, nous avons pu mettre en évidence que le HGF induit la pousse dendritique par des mécanismes qui impliquent la phosphorylation de CREB par la MAPK, et l'interaction de CREB avec son coactivateur CRTC1. Ces données indiquent que les mécanismes impliqués dans la stimulation de la croissance dendritique par le HGF sont similaires à ceux régulant les effets du BDNF, ce qui suggère que le rôle de CREB et de CRTC1 dans la régulation du développement dendritique n'est vraisemblablement pas limité aux effets du HGF ou du BDNF, mais pourrait s'étendre à d'autres facteurs neurotrophiques qui contrôlent la différenciation dendritique.En conclusion, ces résultats ont permis l'identification d'un nouveau mécanisme par lequel CREB et son coactivateur CRTC1 transmettent les effets du BDNF et du HGF sur la croissance dendritique de neurones corticaux. Ces observations mettent également en évidence le rôle important joué par la coopération entre BDNF/HGF et le glutamate, dans l'activation de CREB ainsi que dans l'expression de gènes qui participent au développement de l'arborisation dendritique des neurones corticaux.

Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency.

OBJECTIVE: To compare the prevalence of intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency (oPOI) and in controls. DESIGN: Observational study. SETTING: Division of Infertility and Service of Genetic Medicine, Geneva University Hospitals. PATIENT(S): The study group consisted of 27 infertile women with oPOI referred by infertility specialists for FMR1 testing in 2005-6 because of unexplained poor response to controlled ovarian hyperstimulation or altered hormonal profiles. The control group consisted of 32 women undergoing genetic testing for conditions unrelated to mental retardation or ovarian function. The DNA samples were anonymized. INTERVENTION(S): In the study group, data were collected concerning reproductive/family history, hormonal markers, possible fertility treatment outcomes, and results of karyotype and FMR1 testing. In the control group, FMR1 gene testing was done. The only clinical data available in controls were sex and indication for genetic testing. MAIN OUTCOME MEASURE(S): Distribution of FMR1 alleles. RESULT(S): Six (22%) of 27 women with oPOI had FMR1 alleles of >40 repeats (intermediate to premutation range), compared with one (3%) of 32 controls. CONCLUSION(S): These results suggest that women with oPOI might be at risk of carrying alleles in the intermediate and premutation range.