Douleurs et travail : aider le patient à garder un emploi

Introduction.— A significant part of the workers suffer from musculoskeletal pain (back pain,upper limb). Some of them are at risk to ose their job due to their health condition. Objective. — The aim of the article is to describe synthetically what actors and measure can be used in order to help a patient keep his/her job in spite of the pain. Results.— First place measures include a visit with the occupational physician before work resumption, part-time return to work and workplace accommodation.Second place measures require that a professional project is built by the patient supported by a knowledgeable person. These measures depend on the funding agency.They are devoted to compensate the work disability situation, and/or to provide the training required by the patient’s project. Discussion and conclusion. — Work disability prevention faces many challenges due to barriers between the stakeholders, scattering of the knowledge and the complexity of legislative issues.However, it remains possible provided the patient is committed and supported by a case manager in charge of coordinating the information and the stakeholders. Confidence and collaboration are key issues in the process.

SMARCB1/INI1 inactivation in renal medullary carcinoma

Aims: Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Methods and results: Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. Conclusions: The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities

Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment

Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting

Effects of glucagon and PTH on the loop of Henle of rat juxtamedullary nephrons

Effects of glucagon on the loop of Henle of rat juxtamedullary nephrons. We investigated by micropuncture the effects of glucagon and parathyroid hormone (PTH) on thin limbs of juxtamedullary nephrons of rats with reduced plasma concentration of endogenous glucagon, PTH, antidiuretic hormone (ADH) and calcitonin, all four hormones enhancing the adenylate-cyclase activity in the thick ascending limbs and the distal nephron. Such a hormonal depletion suppresses the corticomedullary concentration gradient, making favourable conditions for studying the influence of these hormones on the renal concentrating mechanism. Administration of glucagon (4.4 ng/min/1) or PTH (5mU/min-1) to these hormone-deprived rats elicited the expected decrease in urinary Mg and Ca fractional excretion without modifying either fractional or absolute excretion of water. At the tip of the loop, glucagon enhanced the loop fluid osmolality by 20%, but left the delivery of water unchanged. The Na and Cl concentrations increased significantly with the osmolality, resulting in a positive correlation between the fractional delivery of either ion and the loop fluid osmolality. PTH increased the fraction of filtered phosphate delivered to the thin limbs, as expected, but, in contrast to glucagon, did not alter either the Na, Cl, or total solute fractional deliveries. The Mg, Ca and K deliveries were unaffected by glucagon and PTH. In conclusion, glucagon, which activates the cyclase system of both the medullary and cortical portion of the thick ascending limb, enhances the delivery of salt to the tip of the loop by net sodium chloride addition to the descending limb. PTH which activates the adenyl-cyclase system only in the cortical thick ascending limb cannot enhance such NaCl delivery. NaCl, when added, might therefore originate from the medullary thick ascending limb

Rapport du groupe de travail "Alimentation animale et sécurité sanitaire des aliments"

L'Agence française de sécurité sanitaire des aliments (AFSSA) a lancé, depuis juillet 1999, comme l'ont souhaité les Ministres à l'occasion de l'installation du Conseil d'administration de l'AFSSA, un travail général d'évaluation scientifique des risques liés à l'alimentation animale. A la suite des deux grandes crises, dont l'origine provient de l'alimentation animale (crise de l'encéphalopathie spongiforme subaiguë (ESB) et crise dioxines), il est apparu important de procéder à un recensement de l'ensemble des questions liées à l'alimentation animale en relation avec la sécurité des aliments et à une analyse des risques dans ce domaine. Le Directeur général de l'Agence française de sécurité sanitaire des aliments a institué un groupe de travail nommé "Alimentation animale et sécurité des aliments" et présidé par le Professeur Dominique Dormont chargé de réaliser cette analyse générale. Ce groupe de travail pourra en outre être saisi pour répondre rapidement à toute demande d'expertise relevant de sa mission, et proposer des projets d'avis ou de recommandations. Le travail de ce groupe doit couvrir l'ensemble des problématiques liées à l'alimentation animale, hors organismes génétiquement modifiés (OGM) et hors alimentation des espèces non destinées à la consommation humaine (animaux de compagnie)