Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro.

AIMS: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis. METHODS: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators. RESULTS: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC. CONCLUSIONS: Conflicting results of SPARCL-1's differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level.

[Delayed adverse reactions to blood donation: From haemovigilance data to specific studies]. / Les effets indésirables retardés chez les donneurs de sang : des données de l'hémovigilance aux études spécifiques.

OBJECTIVES: Delayed adverse reactions to blood donation occur after the donor left donation site. Their intrinsic gravity and possible complications can be increased by the fact the donor is alone. This can also increase bad memories, leading to a donation giving up. Blood transfusion centre is only aware in case of donor feedback, hence an event underrating. We choose to compare our data upon delayed adverse donor reactions with those we could find in past studies. METHODS: A first data level comes from French haemovigilance data while serious adverse reactions declaration is mandatory. But a second level can be reached using blood transfusion centre computerized data because all the donation reactions are saved whatever the gravity is. In both cases, delayed reactions are only those reported by donors. We try to make an exhaustive search of specific studies upon the real delayed reactions incidence so as to compare with our data. RESULTS: There were 1957 serious adverse reactions declared in our regional haemovigilance database between 2011 and 2015: 49 % occurring during donation, 40 % after it but before donor departure, and 11 % delayed events. There were 16,050 adverse reactions recorded during the first trimester of 2016 in mainland France, with 2.7 % delayed ones. Proportion of delayed events rises when gravity rises, until 27.6 % for the most serious ones. It varies between 2.2 % and 2.7 % for vasovagal reactions, haematomas, and other local reactions, and reaches 16.2 % for other general reactions. Data found in other studies with a spontaneous donor notification are of the same kind. But four studies soliciting specifically donor notification give a dramatically higher delayed reactions incidence, with an understatement greater than three out of four. Moreover, these studies found a majority of delayed reactions, which are not included in haemovigilance like fatigue or bruising. CONCLUSIONS: Occurrence of a delayed donor reaction is clearly underrated in standard haemovigilance. It remains to be seen whether it have the same impact on donor return as immediate reactions. Considering that delayed reactions are much larger, it might be interesting to take them into account in the evaluation of strategies dedicated to lower immediate reactions.

[Managing diversity in Swiss Health care]. / Gérer la diversité en milieu clinique: compte rendu de la première Conference nationale des Migrant Friendly Hospitals.

The development of Migrant Friendly Hospitals is an important first step towards eliminating health care disparities in Switzerland and an important reminder to health policy makers and practitioners across the health care system of their responsibility to provide non-discriminatory quality health care to all patients.

Characteristics of patients with rheumatoid arthritis in France: a study of 1109 patients managed by hospital based rheumatologists.

OBJECTIVE: To describe the characteristics of rheumatoid arthritis in patients managed by hospital based rheumatologists in France. METHODS: All public and non-profit private hospitals in France were invited to participate in a cross sectional study. Clinical data on the day of inclusion and health resources used for rheumatoid arthritis over the previous 12 months (treatments, medical devices, physician visits, examinations, hospital admissions, and other health professional care) were recorded. RESULTS: 1109 patients from 75 centres located throughout the country were included (846 female; mean disease duration, 10.6 years; mean age, 56.7 years). Active disease (swollen joint count > or =6, tender joint count > or =6, and two of: morning stiffness > or =45 min, C reactive protein > or =20 mg/l, erythrocyte sedimentation rate >28 mm/h) was observed in 146 patients (13.2%). Mean (SD) DAS(28) was 4.51 (1.55). Severe extra-articular manifestations were reported in 8.4%. ACR functional status was: class I, 19%; class II, 28%; class III, 31%; class IV, 22%. Comorbidity was observed in 44.9% of cases, particularly chronic pulmonary disease and coronary or peripheral vascular disease. Average AIMS2-SF dimension scores were between 4.56 and 6.18, and mean HAQ was 1.32 (0.77). Disease modifying antirheumatic drugs (DMARDs) were prescribed for 82.1% of the patients. During the previous four weeks, one DMARD was used in 62.5%, and two or more in 19.5%. Corticosteroids were prescribed in 72%. CONCLUSIONS: In a rheumatoid arthritis population managed by hospital based rheumatologists, the disease was active in 13% and severe in more than one third of cases.

Cyclophilin B binding to platelets supports calcium-dependent adhesion to collagen.

We have recently reported that cyclophilin B (CyPB), a secreted cyclosporine-binding protein, could bind to T lymphocytes through interactions with two types of binding sites. The first ones, referred to as type I, involve interactions with the conserved domain of CyPB and promote the endocytosis of surface-bound ligand, while the second type of binding sites, termed type II, are represented by glycosaminoglycans (GAG). Here, we further investigated the interactions of CyPB with blood cell populations. In addition to lymphocytes, CyPB was found to interact mainly with platelets. The binding is specific, with a dissociation constant (kd) of 9 +/- 3 nmol/L and the number of sites estimated at 960 +/- 60 per cell. Platelet glycosaminoglycans are not required for the interactions, but the binding is dramatically reduced by active cyclosporine derivatives. We then analyzed the biologic effects of CyPB and found a significant increase in platelet adhesion to collagen. Concurrently, CyPB initiates a transmembranous influx of Ca(2+) and induces the phosphorylation of the P-20 light chains of myosin. Taken together, the present results demonstrate for the first time that extracellular CyPB specifically interacts with platelets through a functional receptor related to the lymphocyte type I binding sites and might act by regulating the activity of a receptor-operated membrane Ca(2+) channel.

Receptor-mediated transcytosis of cyclophilin B through the blood-brain barrier.

Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein mainly located in intracellular vesicles and secreted in biological fluids. In previous works, we demonstrated that CyPB interacts with T lymphocytes and enhances in vitro cellular incorporation and activity of CsA. In addition to its immunosuppressive activity, CsA is able to promote regeneration of damaged peripheral nerves. However, the crossing of the drug from plasma to neural tissue is restricted by the relative impermeability of the blood-brain barrier. To know whether CyPB might also participate in the delivery of CsA into the brain, we have analyzed the interactions of CyPB with brain capillary endothelial cells. First, we demonstrated that CyPB binds to two types of binding sites present at the surface of capillary endothelial cells from various species of tissues. The first type of binding sites (K(D) = 300 nM; number of sites = 3 x 10(6)) is related to interactions with negatively charged compounds such as proteoglycans. The second type of binding sites, approximately 50,000 per cell, exhibits a higher affinity for CyPB (K(D) = 15 nM) and is involved in an endocytosis process, indicating it might correspond to a functional receptor. Finally, the use of an in vitro model of blood-brain barrier allowed us to demonstrate that CyPB is transcytosed by a receptor-mediated pathway (flux = 16.5 fmol/cm2/h). In these conditions, CyPB did not significantly modify the passage of CsA, indicating that it is unlikely to provide a pathway for CsA brain delivery.

[Complications of colonic diverticular disease during rheumatoid polyarthritis: 7 cases]. / Complications de la maladie diverticulaire colique au cours de la polyarthrite rhumatoïde: sept observations.

INTRODUCTION: Among the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAID) and corticoids are mentioned complications of colonic diverticular disease. However, very few studies have described their consequences in rheumatoid arthritis. EXEGESIS: We report on seven patients who were admitted in our department between 1984 and 1997. All patients received corticoids and another antirheumatic drug (gold salts, hydroxychloroquine, immunosuppressive drugs); treatment also included NSAID in four cases. Two patients had a necrotizing vasculitis accompanying rheumatoid arthritis. Intestinal accompanying diseases were the following: one diverticulitis, three colonic perforations with pelviperitonitis, one colovesical fistula, one pelvic abscess, and one diverticular hemorrhage. All patients underwent surgery with positive results. CONCLUSION: Combination of the four following symptoms: fever, abdominal pain, diarrhea, and hemorrhage, can uncover a complication of colónic diverticular disease occurring in the course of rheumatoid arthritis. It should be investigated, even if no history of diverculosis may be evidenced.

[Educational strategies and tools in a public health program at the University of Geneva]. / Stratégies et outils pédagogiques dans le cadre d'un Diplôme de Santé publique: une expérience à l'Université de Genève.

In the Swiss context, the newly developed MPH programme at the University of Geneva is experimental in educational matters. Indeed the programme is fully learner-centered and community-oriented. Throughout the curriculum students plan, implement and evaluate intervention programmes or/and research projects related to health problems of the communities they are in charge of. In this article, we describe the educational strategies and tools used in this MPH curriculum (professional profile, mind-mapping procedures, field-work either on research projects or on intervention programmes, group work and evaluation procedures). These strategies and tools might assist some educational experimentation in MPH programmes in search of public health relevance and pedagogic efficacy.

[An innovative program for public health training at the University of Geneva. Program during employment centered on the student and oriented to the population's health needs]. / Un programme innovateur de formation en santé publique à l'université de Genève. Programme en cours d'emploi centré sur l'étudiant et orienté vers les besoins de santé de la population.

Switzerland's first Master degree course in public health was launched in the autumn of 1990 at the Geneva University School of Medicine. It is a 3 year, part-time course, which is learner-centred and community-oriented. The aim of the course is to prepare students to use a multi-disciplinary approach to plan, implement and evaluate activities intended to solve public health problems. Throughout the course, studies plan, implement and evaluate projects concerning health problems they have encountered in their work as health professionals. The curriculum includes individual and group work, discussions and seminars with teachers and students, and brainstorming sessions with specially trained facilitators. The students can thus identify and fulfil individual educational objectives while working on community-related health projects. Priority health needs of individuals and communities are thus the pivotal points of the novel approach to public health training.

[Bone metastases in epidural invasion of gastrinoma]. / Métastases osseuses avec extension épidurale d'un gastrinome.

Malignant gastrinoma is a nonbeta islet cell tumor which rarely disseminates to the bone. However, in the case reported herein, diffuse metastatic bone disease with symptomatic epidural spread developed. Somatostatin and 99mTc-HDP bone scans demonstrated hot spots in the same sites, establishing that the bone lesions contained somatostatin receptor. Irradiation was effective in relieving pain.