1000 resultados para Neonatal diseases
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This report provides information on selected summary results of the National Survey of Noncommunicable Diseases in Seychelles in 2013‐2014 (Seychelles Heart Study IV). The survey is also referred shortly as the "2013 Survey" in this report. Overall crude results were reported in a comprehensive report in November 2014. Further detailed analyses and recommendations on particular topics will be performed separately.
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Les traités scientifiques ne font que depuis peu d'années l'objet d'études en histoire des sciences. Pourtant, ces traités ont énormément à apporter car ils renseignent sur la manière de raisonner des auteurs, ainsi que sur le développement d'une discipline. Dans ce travail de doctorat, différents traités des maladies du système nerveux ont été dépouillés, notamment le traité de Sémiologie des affections du système nerveux (1914) de Jules Dejerine (1849-1917). Ce traité a été analysé de trois manières différentes. Il a tout d'abord été comparé à une édition précédente publiée sous forme de chapitre (1901), révélant un large remodelage du contenu du traité, suggérant une évolution rapide de la discipline neurologique en l'espace de quelques années. Deuxièmement, l'analyse de la Sémiologie a permis de recréer un réseau de professionnels avec qui Jules Dejerine était en contact et, en parcourant les livres publiés par ces auteurs, il a été possible de décrire de quelle manière ces auteurs se citent mutuellement. Finalement, ces livres contiennent de nombreuses illustrations, qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui illustrent des patients ou des pièces anatomiques pour « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la lésion, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Grâce à ces trois axes de recherche, un traité devient un outil de travail dynamique, qui évolue au fil des rééditions, influencé par les critiques et commentaires retrouvés dans d'autres traités et articles, et par les progrès accomplis dans la discipline traitée. Des, passages et certaines images de l'ouvrage circulent également de traité en traité et véhiculent l'autorité de l'auteur de ces passages et images qui en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Au début du XXe siècle, la neurologie est une jeune spécialité médicale qui se développe rapidement. Les différents médecins publient des traités, communiquent entre eux et échangent leurs données. Un traité scientifique est un outil de travail dynamique qui évolue avec les rééditions et le développement d'une discipline. Ces ouvrages recèlent toutes sortes d'informations et leur analyse ne fait que depuis peu de temps l'objet d'études en histoire des sciences. Ces traités regorgent notamment d'illustrations qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui représentent des patients ou des pièces anatomiques afin de « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la pathologie, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Les auteurs des traités, qui viennent d'Europe et d'Amérique du Nord, se citent mutuellement, permettant au lecteur de recréer leur réseau de professionnels au niveau international. De plus, comme ces auteurs réutilisent les observations et les illustrations des autres, celles-ci circulent de traité en traité et en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Until recently, the study of textbooks has been neglected in the history of the sciences. However, textbooks can provide fruitful sources of information regarding the way authors work and the development of a particular discipline. This dissertation reviews editions of a single textbook, the Sémiologie des affections du système nerveux (1914) by Jules Dejerine (1849-1917). This textbook enabled the description of three axes of research. Firstly, by comparing the book to a first edition published as a chapter, one can acknowledge an extensive remodeling of the content of the book, suggesting a vast increase in knowledge over time. Secondly, by looking at the authors that Dejerine quotes repeatedly, it becomes possible to recreate his professional network, to review the works of these authors and to determine how they cross-reference each other. Thirdly, these textbooks contain numerous medical illustrations, which are linked with the concept of "proof;" the authors demonstrate a willingness to "show" the lesion or the pathology by publishing an image. Drawings, schematic representations, radiographies, or photographs of patients or of anatomical preparations all have their own purpose in describing the lesion and the progression of the disease. They assist in the diagnosis of the pathology. By looking at all of these aspects, it is therefore possible to conclude that a neurological textbook is a dynamic object that evolves through re-editions, comments and references found in other textbooks and by the circulations of parts of these books, such as the images. The illustrations also carry the author's authority, since their ongoing use claims that the work by the owner of the image has been endorsed by others. At the same time, it validates the borrowers' arguments. By using medical illustrations from different authors worldwide, the authors are also making a claim to a common language, to a similar way of examining patients, and about how much they depend on medical imagery to prove their points. In that sense, by focusing upon these textbooks, one can affirm that neurology already existed as a worldwide specialty at the turn of the twentieth century. Much more than mere accompaniments to the text, images were of paramount importance to the unification of neurology.
Retroviral infection of the neonatal Peyer's Patch lymphocytes : the mouse mammary tumor virus model
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Glutaric aciduria type-I (GA-I) and methylmalonic aciduria (MMA-uria) are two neurometabolic diseases manifesting in neonatal period and early childhood. They belong to the group of organic acidurias and are caused by defects in the catabolism of amino acids, leading to massive accumulation of toxic metabolites in the body and severe brain injury. Therapeutic strategies are mainly based on reversing catabolic state during metabolic crisis and dietary protein restriction that both aim to prevent extra production of toxic metabolites. Specific and neuroprotective treatments are missing because the mechanisms of brain damage in these diseases are only poorly understood. The principal objective of my work was to develop in vitro models for both diseases aiming at elucidation of toxic effects of the main metabolites accumulating in GA-I (glutaric acid (GA) and 3-hydroxy glutaric acid (3-OHGA)) and MMA-uria (methylmalonic acid (MMA), propionic acid (PA) and 2-methylcitric acid (2-MCA)) on developing brain cells, and to study the cellular pathways targeted by these deleterious effects in order to find new therapeutic potentials. We used re-aggregated embryonic rat brain cells in organotypic 3D cultures, which were exposed to toxic metabolites at different developing stages of the cultures. In parallel, we studied the cellular localization of the defected enzyme in GA-I, glutaryl-CoA dehydrogenase (GCDH), in the brain and peripheral tissues of rats in adulthood and during embryonic development. GCDH expression: GCDH showed a strong neuronal expression in embryonic central and peripheral nervous system. In the adult brain, GCDH expression was exclusively neuronal with the strongest signal in cerebral cortex and Purkinje cells. GCDH expression was homogenous in embryonic peripheral organs with high levels in intestinal mucosa at late stages. Strong GCDH expression was also observed in liver and intestinal mucosa and with lower intensity in muscles, convoluted renal tubules and renal collecting tubes in adult peripheral organs. GA-I and MMA-uria in vitro models: 3-OHGA (for GA-I) and 2-MCA (for MMA-uria) showed the most deleterious effects at early stages of the cultures with morphological and biochemical alterations and induction of cell death. 3-OHGA and 2-MCA caused astrocytic cell suffering reflected by astrocytic fiber loss and swelling and retardation in oligodendrocytic maturation and/or differentiation. High ammonium increase concomitant with glutamine decrease was observed in these cultures. Neurons were not substantially affected. Our studies revealed that brain-cell generated ammonia may play a role in the neuropathogenesis of these diseases. Thus, developing neuroprotective strategies that target ammonium toxicity in the brain of GA-I and MMA-uria patients might be important according to our findings. -- L'acidurie glutarique de type I (GA-I) et l'acidurie méthylmalonique (MMA-urie) sont deux maladies neurométaboliques se manifestant durant la période néonatale ou la petite enfance, et qui appartiennent aux aciduries organiques. Elles sont causées par des défauts dans le catabolisme des acides aminés, conduisant à une accumulation des métabolites toxiques dans le corps et aussi des lésions cérébrales sévères. Le traitement est limité à une prise en charge d'urgence pendant la crise métabolique et à une diète restreinte en protéines naturelles. Des traitements spécifiques, neuroprotecteurs manquent principalement parce que les mécanismes conduisant aux lésions cérébrales dans ces maladies sont peu connus. L'objectif principal de mon travail était d'élucider les effets toxiques des métabolites accumulés dans GA-I (l'acide glutarique (GA) et l'acide 3-hydroxyglutarique (3-OHGA)) et MMA-uria (l'acide méthylmalonique (MMA), l'acide propionique (PA) et l'acide 2-méthylcitrique(2-MCA) sur les cellules du cerveau ainsi que les voies cellulaires impliquées, dans le but de trouver de potentielles nouvelles stratégies thérapeutiques. Nous avons utilisé un modèle in vitro de cultures 3D de cellules de cerveau d'embryons de rat (en développement) en les exposant aux métabolites toxiques à différents stades de développement des cultures. En parallèle, nous avons étudié la localisation cellulaire de l'enzyme déficiente dans GA-I, la CoA-glutarly déshydrogénase (GCDH), dans le cerveau et les organes périphériques des rats adultes et pendant le développement embryonnaire. L'expression de GCDH: GCDH a montré une expression neuronale forte dans le système nerveux chez l'embryon et le cerveau adulte. L'expression était homogène dans les organes périphériques avec une forte expression dans l'intestin. Les modèles in vitro de GA-I et MMA-uria : 3-OHGA en modèle GA-I et 2-MCA en modèle MMA-uria ont montré les effets délétères les plus importants avec des altérations morphologiques des cellules et biochimiques dans le milieu de culture et l'induction de mort cellulaire non-apoptotique (3-OHGA) ou apoptotique (2-MCA). 3-OHGA et 2-MCA ont provoqué une souffrance astrocytaire avec perte des fibres et gonflement et un retard de maturation et/ou de différentiation des oligodendrocytes. Une augmentation importante d'ammonium avec une diminution concomitante de glutamine a été observée dans les cultures. Les neurones n'étaient pas vraiment affectés. Nos études ont révélé que l'ammonium généré par les cellules cérébrales pourrait jouer un rôle dans la neuropathogenèse de ces deux maladies. Par conséquent, développer des stratégies neuroprotectrices ciblant la toxicité de l'ammonium dans le cerveau des patients atteints de GA-I ou MMA-urie pourrait être très important selon nos résultats.
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We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.
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BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.
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The thoracolumbar junctional region (T10-L1) of the spine is a transitional zone, where more than half of the thoracic and lumbar fractures occur. In this presentation the origin of the pathoanatomical changes in the thoracolumbar junctional region of the spine is discussed in view of the previous studies. These studies refer to a torsional force contributing to the formation of the degenerative changes, especially in the facet joints. Degenerative changes anteriorly and posteriorly do not concur in the thoracolumbar junctional region. Only a weak concurrence is found between disc degeneration and spondylosis, which refer to differences in their pathomechanisms. A strong concurrence between the degenerative changes at different levels, especially anteriorly, reflects factors causing overall degeneration in the thoracolumbar junctional region.
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INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections.
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BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.
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The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.
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Notch is a membrane inserted protein activated by the membrane-inserted γ-secretase proteolytic complex. The Notch pathway is a potential therapeutic target for the treatment of renal diseases but also controls the function of other cells, requiring cell-targeting of Notch antagonists. Toward selective targeting, we have developed the γ-secretase inhibitor-based prodrugs 13a and 15a as substrates for γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransferase (γ-GCT) as well as aminopeptidase A (APA), which are overexpressed in renal diseases, and have evaluated them in experimental in vitro and in vivo models. In nondiseased mice, the cleavage product from Ac-γ-Glu-γ-secretase inhibitor prodrug 13a (γ-GT-targeting and γ-GCT-targeting) but not from Ac-α-Glu-γ-secretase inhibitor prodrug 15a (APA-targeting) accumulated in kidneys when compared to blood and liver. Potential nephroprotective effects of the γ-secretase inhibitor targeted prodrugs were investigated in vivo in a mouse model of acute kidney injury, demonstrating that the expression of Notch1 and cleaved Notch1 could be selectively down-regulated upon treatment with the Ac-γ-Glu-γ-secretase-inhibitor 13a.
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OBJETIVO: Descrever repercussões da ração suplementada com óleo de soja ou óleo de canola, por meio da tomografia computadorizada, na distribuição do tecido adiposo abdominal, após desmame de ratos desnutridos durante a lactação. MATERIAIS E MÉTODOS: Ratas lactantes submetidas a restrição alimentar (RA) em 50%, de acordo com o consumo das lactantes controles (C). Após o desmame, filhotes desnutridos receberam ração contendo 19% de óleo de soja (RA-soja 19%) ou óleo de canola (RA-canola 19%). Os filhotes do grupo controle receberam ração contendo 7% de óleo de soja (C-soja 7%). Aos 60 dias de idade, foram realizadas medidas corporais e das áreas de tecido adiposo abdominal por meio de tomografia computadorizada. Após sacrifício, tecido adiposo abdominal foi excisado e pesado. Os dados foram expressos como média ± erro-padrão da média, considerando o nível de significância de p < 0,05. RESULTADOS: Os grupos RA 19% desenvolveram similares comprimento, massa corporal e depósito de tecido adiposo visceral. Todas as avaliações realizadas foram significantemente menores em relação ao grupo C-soja 7%. Entretanto, na tomografia computadorizada, os grupos RA-soja 19% e RA-canola 19% apresentaram diferenças significativas da distribuição do tecido adiposo abdominal. CONCLUSÃO: A tomografia computadorizada mostrou que a distribuição de tecido adiposo, na cavidade abdominal, pode ser dependente do tipo de óleo vegetal na dieta.
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Inflammatory bowel diseases (IBD) are relatively frequent in developed countries. Physiopathological events involved in the etiology of IBDs include activation of immune, mesenchymal and epithelial cells. This review gives an overview of the currently applied proteomics technologies. It describes metabolic changes and goes into the approaches using this methodology to understand the molecular mechanisms implicated in the development of the disease.
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Every year, a considerable number of clinical guidelines for the management of cardiovascular risk factors are issued. It may give the idea that this area is constantly evolving with regular changes for ambulatory clinical practice, including family medicine. Sometimes important differences between the various recommendations are observed. This led us to wonder about the evolution of recommendations for the management of diabetes, dyslipidemia and high blood pressure over time. This article presents a historical review of US and European recommendations between 1999 and 2014 to highlight what has actually changed.