Keks holm - 1

Sanktpeterburg 1766

Reljacija o vzjatii Gelzenforsa

Sanktpeterburg 1766

Vyborg

Sanktpeterburg 1766

Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

Nachalnoe ouchenie chelovekom hotjashchim ouchitsja knig bozhestvennago pisanija

[Moskva?] 1723

Estado actual de fruticultura colombiana y perspectivas para su desarrollo

La horticultura en Colombia comprende las áreas de floricultura, fruticultura, olerícultura, producción de plantas aromáticas y medicinales y la horticultura urbana. La promoción y desarrollo del sector frutícola representa para Colombia una importante fuente de crecimiento de la agricultura, de generación de empleo rural y de desarrollo con equidad para las distintas regiones puesto que las frutas pueden asentarse en los diversos pisos térmicos de que dispone el país, a la vez que conforma una producción administrada con criterios de eficiencia y sostenibilidad en escalas que van desde micro, pequeños y medianos productores hasta grandes productores y empresas. Durante las últimas cuatro décadas el área sembrada en frutas expresa una dinámica de constante crecimiento, consiguiendo así aumentar su participación tanto en el área dedicada a cultivos no transables, como en el total del área de la agricultura sin café. Así, mientras en 1970 la participación del área frutícola en los no transables era del 1,6%, en el 2005 ésta era del 12,6%. Las áreas plantadas en frutas en Colombia pasaron de 191.035 ha en 2003 a 225.325 ha en 2007 lo que representa un crecimiento de 17,9 %, mientras que los volúmenes de producción pasaron de 2.675.736 t a 3.279.264 t en el mismo período en 47 especies frutícolas. El Plan Frutícola Nacional - PFN, constituye una propuesta estratégica conformada por conjunto coherente de objetivos, estrategias y programas que, con base en una visión de futuro, buscan la meta inicial de duplicar el área de la producción frutícola nacional, asegurar las condiciones tecnológicas y de innovación para una producción sostenible y de calidad, agregar valor en la cadena frutícola, y lograr una vinculación plena en los mercados internacionales. Se busca que los participantes conozcan los principales desarrollos de la fruticultura Colombiana, sus retos y oportunidades para la próxima década.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Caractérisation du profil pharmacocinétique de la vancomycine chez des patients hospitalisés en médecine générale et chirurgie

Contexte & Objectifs: La vancomycine (VCM) est un antibiotique utilisé pour le traitement de certaines infections sévères. C'est un candidat idéal pour le suivi thérapeutique (TDM) car il possède une forte variabilité inter-individuelle, une marge thérapeutique étroite et une relation concentration-efficacité et -toxicité établie. L'objectif de ce travail est de quantifier la variabilité inter-individuelle des concentrations et les facteurs qui l'influencent, et d'évaluer l'adéquation des posologies pour viser les cibles thérapeutiques. Méthodes: Les données ont été récoltées dans le cadre du TDM réalisé en routine au Centre Hospitalier Universitaire Vaudois. Les données pharmacocinétiques ont été analysées par régression linéaire à effet mixte (NONMEM®). Les variables d'intérêt étaient: le sexe, l'âge, le poids, la clairance à la créatinine (CLCRT) et les co-médications. Des simulations ont été réalisées à partir du modèle final afin de déterminer le pourcentage de patients en-dehors des intervalles de concentrations cibles (10-20 mg/L), et toxiques (>30 mg/L) avant et après adaptation posologique de VCM selon la fonction rénale. Résultats: 705 concentrations de VCM ont été mesurées chez 191 patients. Un modèle monocompartimental incluant une variabilité inter-individuelle sur la clairance (CL) et le volume de distribution (Vd) décrit au mieux les données. La CLCRT et la co-administration de diurétiques influencent significativement la CL, et le Vd augmente proportionnellement avec le poids. Ces covariables expliquent 50% et 27% de la variabilité, respectivement. Les simulations ont montré que pour les stades de maladie rénale 3 et 4 le pourcentage de patients en-dehors des cibles est de 51% et 45% et diminue respectivement à 40% et 37% après adaptation posologique. De plus, 15% et 8% des patients avec insuffisance rénale de stade 3 et 4 présentent des concentrations >30 mg/L, seuil qui s'abaisse environs à 5% après adaptation posologique. Discussion: L'importante variabilité des concentrations de VCM est en grande partie expliquée par la CLCRT, la co-administration de diurétiques et le poids. L'administration des posologies recommandées pour les patients avec une maladie rénale de stades 3 et 4 pourrait exposer un nombre significatif de patients à des concentrations en dehors des cibles thérapeutiques, mais paraît corrigées par une adaptation posologique basée sur le TDM.

Implementation of bayesian therapeutic drug monitoring in modern patient care

The variability observed in drug exposure has a direct impact on the overall response to drug. The largest part of variability between dose and drug response resides in the pharmacokinetic phase, i.e. in the dose-concentration relationship. Among possibilities offered to clinicians, Therapeutic Drug Monitoring (TDM; Monitoring of drug concentration measurements) is one of the useful tool to guide pharmacotherapy. TDM aims at optimizing treatments by individualizing dosage regimens based on blood drug concentration measurement. Bayesian calculations, relying on population pharmacokinetic approach, currently represent the gold standard TDM strategy. However, it requires expertise and computational assistance, thus limiting its large implementation in routine patient care. The overall objective of this thesis was to implement robust tools to provide Bayesian TDM to clinician in modern routine patient care. To that endeavour, aims were (i) to elaborate an efficient and ergonomic computer tool for Bayesian TDM: EzeCHieL (ii) to provide algorithms for drug concentration Bayesian forecasting and software validation, relying on population pharmacokinetics (iii) to address some relevant issues encountered in clinical practice with a focus on neonates and drug adherence. First, the current stage of the existing software was reviewed and allows establishing specifications for the development of EzeCHieL. Then, in close collaboration with software engineers a fully integrated software, EzeCHieL, has been elaborated. EzeCHieL provides population-based predictions and Bayesian forecasting and an easy-to-use interface. It enables to assess the expectedness of an observed concentration in a patient compared to the whole population (via percentiles), to assess the suitability of the predicted concentration relative to the targeted concentration and to provide dosing adjustment. It allows thus a priori and a posteriori Bayesian drug dosing individualization. Implementation of Bayesian methods requires drug disposition characterisation and variability quantification trough population approach. Population pharmacokinetic analyses have been performed and Bayesian estimators have been provided for candidate drugs in population of interest: anti-infectious drugs administered to neonates (gentamicin and imipenem). Developed models were implemented in EzeCHieL and also served as validation tool in comparing EzeCHieL concentration predictions against predictions from the reference software (NONMEM®). Models used need to be adequate and reliable. For instance, extrapolation is not possible from adults or children to neonates. Therefore, this work proposes models for neonates based on the developmental pharmacokinetics concept. Patients' adherence is also an important concern for drug models development and for a successful outcome of the pharmacotherapy. A last study attempts to assess impact of routine patient adherence measurement on models definition and TDM interpretation. In conclusion, our results offer solutions to assist clinicians in interpreting blood drug concentrations and to improve the appropriateness of drug dosing in routine clinical practice.

Utilisation des céramiques biphasées dans les pertes de substance osseuse acétabulaire sévères dans les reprises de prothèse totale de hanche (PTH) : étude de 22 cas avec suivi à long terme

Management of bone loss in revision total hip replacement remains a challenge. To eliminate any immunological or infectious problem and so to try to improve the long-term results obtained with allografts, the authors used synthetic ceramics as bone substitutes since 1995. We reviewed 13 of the patients of our study, we previously reported in 2005 (Schwartz and Bordei in Eur J Orthop Surg Traumatol 15: 191 2005), which was a pro- spective cohort of thirty-two cases of acetabular revision reconstruction, with a mean follow-up of 14.4 years yet (from 9 to 16 years). Clinical results were assessed according to Oxford scale and Postel and Merle d'Aubigne (PMA) scale. Since 2005, no specific complications were noted. The average PMA functional hip score was 14.9 (vs. 9.2 before revision) at follow-up over 9 years. Nine patients still alive in 2013 were seen again by a surgeon, which was not the operator, with a mean follow-up of 15.3 years: Their Oxford average score was 40.3. Radio- logical assessment affirmed a good integration of the sub- stitutes in bone without any edging in all cases. A progressive invasion of the ceramics by bone can be seen on the X-ray. We conclude that about 15 years of average delay, which is a significant follow-up in orthopedic sur- gery, the outcomes without specific complications are satisfactory and allow one to go with these materials in total hip revision surgery.

A correlação de métodos dexa e cdexa em absortimetria mineral óssea

OBJETIVO: Estudar a intercambiabilidade dos resultados de densidade mineral óssea entre máquinas de absortimetria de raios-x em duas energias (DEXA) Hologic® e de absortimetria computadorizada de raios-x convencionais em duas energias (CDEXA) Cromox®. MATERIAIS E MÉTODOS: Para 38 casos de quadril e 31 casos de coluna lombar avaliados em 43 pacientes atendidos em um centro de diagnóstico por imagem, medidas de densidade mineral óssea foram realizadas em ambas as máquinas. A máquina Cromox® foi calibrada usando-se o phantom Cromox® de referência para absortimetria óssea. RESULTADOS: Forte correlação entre os resultados obtidos nas duas máquinas foi encontrada para cada sítio do esqueleto. O coeficiente de correlação linear medido para o colo femoral direito foi r = 0,920, p < 0,0001, e r = 0,923, p < 0,0001 para as vértebras L2-L4 da coluna lombar. Como o resultado expresso em Tscore é importante na prática clínica em densitometria óssea, a diferença média em Tscore entre as máquinas foi calculada, resultando em média aritmética de DTscore = 0,191 para o quadril e média aritmética de DTscore = 0,228 para a coluna. Estado esquelético é estabelecido de acordo com a definição da Organização Mundial da Saúde como normal, osteopenia ou osteoporose. A concordância de estado esquelético entre as máquinas foi superior a 76% para o quadril e superior a 77% para a coluna, e superior a 96% quando se considerou concordância em ao menos um dos dois sítios. CONCLUSÃO: Os coeficientes de correlação linear obtidos são muito próximos das referências internacionais entre máquinas padrão-ouro, reportados como r > 0,95. Para ambos os sítios, a diferença média aritmética em Tscore entre as máquinas é pequena, menor que a menor variação significativa.