Rapamycin Prevents and Breaks the Anti-CD3–Induced Tolerance in NOD Mice

OBJECTIVE—Non–Fc-binding anti-CD3–specific antibodies represent a promising therapy for preserving C-peptide produc-tion in subjects with recent-onset type 1 diabetes. However, the mechanisms by which anti-CD3 exerts its beneficial effect are still poorly understood, and it is questionable whether this therapeutic approach will prove durable with regard to its ability to impart metabolic preservation without additional actions designed to maintain immunological tolerance. We used the NOD mouse model to test whether rapamycin, a compound well-known for its immunomodulatory activity in mice and humans, could increase the therapeutic effectiveness of anti-CD3 treat-ment in type 1 diabetes. RESEARCH DESIGN AND METHODS—Rapamycin was ad-ministered to diabetic NOD mice simultaneously with anti-CD3 or to NOD mice cured by anti-CD3 therapy. The ability of thi

Oral contraceptives and colorectal cancer risk: a meta-analysis

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69–0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72–0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74–0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30–0.71). A better understanding of this potential relation may help informed choice of contraception. © 2001 Cancer Research Campaign http://www.bjcancer.co

The decline in breast cancer mortality in Europe: An update (to 2009)

Bosetti, Cristina Bertuccio, Paola Levi, Fabio Chatenoud, Liliane Negri, Eva La Vecchia, Carlo eng Netherlands Edinburgh, Scotland 2011/09/13 06:00 Breast. 2012 Feb;21(1):77-82. doi: 10.1016/j.breast.2011.08.001. Epub 2011 Sep 8.; International audience; We updated trends in breast cancer mortality in Europe up to the late 2000's. In the EU, age-adjusted (world standard population) breast cancer mortality rates declined by 6.9% between 2002 and 2006, from 17.9 to 16.7/100,000. The largest falls were in northern European countries, but more recent declines were also observed in central and eastern Europe. In 2007, all major European countries had overall breast cancer rates between 15 and 19/100,000. In relative terms, the declines in mortality were larger at younger age (-11.6% at age 20-49 years between 2002 and 2007 in the EU), and became smaller with advancing age (-6.6% at age 50-69, -5.0% at age 70-79 years). The present report confirms and further quantifies the persisting steady fall in breast cancer mortality in Europe over the last 25-30 years, which is mainly due to advancements in the therapy

Cancer mortality in Europe, 2005-2009, and an overview of trends since 1980

Background After a peak in the late 1980s, cancer mortality in Europe has declined by ∼10% in both sexes up to the early 2000s. We provide an up-to-date picture of patterns and trends in mortality from major cancers in Europe. Methods We analyzed cancer mortality data from the World Health Organization for 25 cancer sites and 34 European countries (plus the European Union, EU) in 2005-2009. We computed age-standardized rates (per 100 000 person-years) using the world standard population and provided an overview of trends since 1980 for major European countries, using joinpoint regression. Results Cancer mortality in the EU steadily declined since the late 1980s, with reductions by 1.6% per year in 2002-2009 in men and 1% per year in 1993-2009 in women. In western Europe, rates steadily declined over the last two decades for stomach and colorectal cancer, Hodgkin lymphoma, and leukemias in both sexes, breast and (cervix) uterine cancer in women, and testicular cancer in men. In central/eastern Europe, mortality from major cancer sites has been increasing up to the late 1990s/early 2000s. In most Europe, rates have been increasing for lung cancer in women and for pancreatic cancer and soft tissue sarcomas in both sexes, while they have started to decline over recent years for multiple myeloma. In 2005-2009, there was still an over twofold difference between the highest male cancer mortality in Hungary (235.2/100 000) and the lowest one in Sweden (112.9/100 000), and a 1.7-fold one in women (from 124.4 in Denmark to 71.0/100 000 in Spain). Conclusions With the major exceptions of female lung cancer and pancreatic cancer in both sexes, in the last quinquennium, cancer mortality has moderately but steadily declined across Europe. However, substantial differences across countries persist, requiring targeted interventions on risk factor control, early diagnosis, and improved management and pharmacological treatment for selected cancer site

O poder dos pais: orientação sobre as estratégias de comunhão dos saberes de pais de crianças com transtorno do espectro autístico

Muitas pessoas se preocupam, nestes últimos anos, com a qualidade de vida dascrianças vivendo com um transtorno do espectro autístico (TSA). Os responsáveisdos serviços públicos se mostram sensibilizados com tais preocupações, colocamem prática algumas medidas visando prevenir os maus-tratos e a negligência etrabalham na atualização de condições favoráveis ao desenvolvimento de cadacriança. É nesse contexto que se impõem a valorização do papel das famílias, o fortalecimentodos saberes dos pais e a descrição de suas capacidades de ação. Assim,essa orientação marca uma grande mudança nas relações entre profissionais e paisde crianças vivendo com incapacitações. Uma experiência conduzida no Québecpermitiu iniciar pais na avaliação do desenvolvimento de seus filhos; tratava-sede prepará-los à participação das reuniões de elaboração do Plano de ServiçosIndividuais (PSI). Um protocolo de pesquisa qualitativa foi colocado em prática e aanálise das entrevistas realizadas nos encontros entre pais e profissionais mostrouque estes assumem muitas responsabilidades. Em frente aos profissionais, os paisexpõem muitas competências e seus saberes declarados focam diversas questõesem tensões, especialmente aquelas relativas ao esclarecimento do diagnóstico e àprecisão dos objetivos de intervenção.Palavras-chave: Autismo. Famílias. Poder dos pais. Saber e saber-fazer. Qualidade de vida

Trends in cancer mortality in Mexico, 1970-1999

Background: Few data on cancer mortality have been published for Mexico over the last few decades. It is therefore of interest to conduct a systematic and updated analysis of cancer mortality in this country. Patients and methods: Age-standardised (world population) mortality rates, at all ages and truncated at age 35-64 years, from major cancers and all cancers combined were computed on the basis of certified deaths derived from the World Health Organization database for the period 1970-99. Results: Mortality rates for all neoplasms showed an upward trend in men of all ages (from 58.2/100 000 in 1970-74 to 87.1/100 000 in 1995-99) and in middle-aged men (from 76.1 to 93.7/100 000, respectively). This reflects the rise until the early 1990s in lung cancer mortality (from 8.1/100 000 in 1970-74 to 15.6/100 000 in 1995-99) and prostate cancer (from 5.5 to 12.2/100 000, respectively). In women, overall mortality rates showed an increase between the early 1970s (75.4/100 000) and the late 1990s (82.3/100 000). Total cancer mortality rates remained low, however, compared with other American countries (e.g. 153.3/100 000 men and 108.6/100 000 women in 1999 in the United States). Truncated rates were stable (126.5/100 000 in 1970-74 and 125.8/100 000 in 1995-99), although they were much higher than overall rates, reflecting exceedingly high rates for uterine (mostly cervical) cancer mortality in middle-aged women (29.5/100 000 in 1995-99). Conclusions: Total cancer mortality in Mexico has remained comparably low on a worldwide scale, and the upward trends in mortality rates for lung and other tobacco-related neoplasms have tended to level off over the last decade. However, steady rises have been observed for other major cancers, including prostate and breast. Cervical cancer remains a major health problem in wome

Etude de la réponse lymphocytaire T dans l'allergie de l'enfant, au diagnostic et au cours de la désensibilisation

Les maladies allergiques sont de plus en plus fréquentent. Elles atteignent souvent l enfant jeune chez qui l allergie respiratoire et l allergie alimentaire sont les principales pathologies. L unique traitement curatif est l immunothérapie spécifique d antigène (ITA), largement développée dans l allergie respiratoire et encore à ses débuts dans l allergie alimentaire. Pour adapter au mieux la prise en charge du patient, le diagnostic précis de l allergie est indispensable et il n existe actuellement pas d examen biologique totalement fiable. Seul, la présence d IgE spécifiques permet de diagnostiquer une sensibilisation à un allergène mais pas une allergie cliniquement symptomatique. Dans une première partie, nous avons étudié l intérêt d un test fonctionnel, l ELISpot (Enzyme-linked immunosorbent spot), dans le diagnostic de l allergie aux acariens chez l enfant asthmatique. Le nombre de lymphocytes T circulants spécifiques d acariens sécréteur d interleukine (IL)-4 ou d IL-13 était associé à la présence d une allergie symptomatique, indépendamment des IgE spécifiques. Il était plus élevé dans le cas d une rhinite allergique sévère et plus faible dans le cas d une rhinite allergique légère. De plus, il variait au cours de l année en fonction des saisons avec un pic en automne et un pic en début de printemps. Dans une deuxième partie, nous avons étudié l intérêt de l ELISpot dans le diagnostic de l allergie au lait de vache chez l enfant, confirmée par un test de provocation orale en double aveugle. Nous avons décrit que le nombre de lymphocytes T spécifiques de la caséine et sécréteurs d IL-4 et d IL-13 était associé à l allergie au lait de vache avec une sensibilité de 100%. Par ailleurs, le nombre de lymphocytes T spécifiques de la caséine était également associé à la dose maximale de lait tolérée par l enfant.Enfin, dans une troisième partie, nous avons étudié la réponse lymphocytaire T au cours d une ITA sub-linguale (SLIT) d une part et sous-cutanée (SCIT) d autre part, chez des enfants asthmatiques allergiques aux acariens suivis pendant une année. Nous avons décrit une diminution des lymphocytes Th2 (sécréteurs d IL-4 et IL-13) spécifiques d acariens après 12 mois de SLIT associée à une augmentation des cellules sécrétrices d IL-10 (Tr1) spécifiques d acariens après 6 mois de SLIT. De plus, les lymphocytes T régulateurs (CD4+CD25hiCD127loFoxp3+) étaient augmentés après 12 mois de SCIT. Nous n avons pas retrouvé de production accrue d interféron g (IFNg) par les lymphocytes T spécifiques d acariens au cours de la désensibilisation.Au total, ce travail nous a permis de décrire qu un test fonctionnel, l ELISpot, permet de réaliser un diagnostic fiable de l allergie aux acariens et de l allergie au lait de vache chez l enfant. Par ailleurs, l ITA induit une diminution des cellules Th2 et une augmentation des cellules Tr1 par voie sub-linguale ainsi qu une augmentation des Treg Foxp3+ par voie sous-cutanée sans immunodéviation Th2/Th1, chez l enfant allergique aux acariens.Allergic diseases are steadily increasing steadily and especially in children. Allergen specific immunotherapy (desensitization) is the only curative treatment for which accurate diagnosis of allergy is essential. Currently, the presence of specific IgE diagnoses a sensitization to an allergen but not a clinically symptomatic allergy. In a first part, we studied the value of a functional test, the ELISpot (Enzyme-linked immunosorbent spot) in the diagnosis of allergy to house dust mites (HDM). The number of circulating HDM-specific IL-4 and IL-13 secreting T cells was associated with the presence of symptoms, regardless of specific IgE and was higher in severe rhinitis than in mild rhinitis. In addition, it varied according to the season with a peak in autumn and a peak in early spring (wet periods with greater allergen exposure). In a second part, we studied the value of ELISpot for the diagnosis of cow's milk allergy in children, confirmed by double blind placebo control food challenge. We found that the number of casein-specific IL-4 and IL -13 secreting T-cells was associated with allergy to cow's milk. It was also inversely correlated to the cow s milk tolerated cumulative dose. Receiver-operating characteristic (ROC) curve of combined IL-4 and IL-13 analysis was generated. AUC was 0,98 (95% CI 0.90-1.06). For a cut-off of 10 IL-4- and 12 IL-13 secreting T-cells, sensitivity and negative predictive value were 100%.Finally, in the third part, we monitored antigen specific T-cell response in HDM allergic children treated with sublingual ITA (SLIT) on the one hand and subcutaneous ITA (SCIT) on the other hand, during one year. We found a decrease in HDM specific Th2 cells after 12 months of SLIT associated with an increase in HDM specific IL-10 secreting T-cells after 6 months of SLIT. In addition, regulatory T cells (CD4 + CD25hiCD127loFoxp3+) were increased after 12 months of SCIT. In conclusion, this work has allowed us to describe a functional test, the ELISpot, as a reliable tool for the diagnosis of mite allergy and cow's milk allergy in children. In addition, in HDM allergic children, a decrease of Th2 cells and an increase of IL-10 secreting T-cells was found in children treated with SLIT to HDM as well as an increase in Foxp3+ Treg in children treated with SCIT.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF