Sangramento durante a anticoagulação oral: alerta sobre um mal maior

FUNDAMENTO: Sangramento é uma das grandes preocupações em pacientes sob anticoagulação oral. OBJETIVO: Investigar causas determinantes do sangramento em usuários de anticoagulante oral. MÉTODOS: Foram acompanhados prospectivamente, por 48 ± 7,2 meses, 360 pacientes com fibrilação atrial (FA), todos em uso de anticoagulante oral (ACo) com INR-alvo de 2,0-3,5, avaliados em média a cada 30 dias. Os pacientes foram investigados quanto à presença de patologia associada que levasse a sangramento. RESULTADOS: Participaram deste estudo 338 pacientes. Desses, 210 (62,13%) eram do sexo feminino. A estenose mitral estava presente em 218 pacientes (64,4%), a prótese biológica mitral em 64 (18,9%) e a insuficiência da valva mitral em 56 (16,5%). O sangramento ocorreu em 65 pacientes (19,2%) e de forma grave em 7 (10%). Em 38/65 pacientes (58,5%), identificou-se nova doença associada, facilitadora do sangramento. Em 100% dos pacientes com sangramento na faixa terapêutica, foi encontrada doença associada, contra 49,05% de diagnóstico de doenças associadas naqueles com INR > 3,5 (p = 0,001). CONCLUSÃO: O diagnóstico de doença local associada ao sangramento foi frequente entre os medicados com anticoagulante oral (58,5%). Houve associação entre sangramento com INR na faixa terapêutica (INR 2,0-3,5) e diagnóstico de patologia predisponente a sangramento (p < 0,001). Em pacientes em uso de anticoagulante oral que apresentam sangramento, é mandatória a investigação da causa, sobretudo se a INR estiver na faixa terapêutica.

Ausência de interação clopidogrel-estatina em pacientes submetidos a implante de "stent" coronário

FUNDAMENTO: Alguns estudos têm sugerido redução da atividade do clopidogrel sobre a ativação e adesão plaquetárias em pacientes em uso de estatinas. OBJETIVO: Avaliar se a ativação e agregação plaquetárias diminuem com clopidogrel, e se ocorre redução da ação do clopidogrel quando associado à atorvastatina ou à sinvastatina. MÉTODOS: Estudo prospectivo que incluiu 68 pacientes com angina estável em uso prévio de sinvastatina, atorvastatina, ou nenhuma estatina (grupo controle), com indicação prévia eletiva de realização de intervenção coronária percutânea. Foi analisada a ativação plaquetária através do número de plaquetas, níveis de P-selectina e glucoproteína IIb/IIIa (com e sem estímulo de ADP) através de citometria de fluxo. Os resultados foram analisados antes e após a intervenção coronária percutânea e da administração de clopidogrel. RESULTADOS: Observamos redução da atividade plaquetária com uso de clopidogrel. Além disso, não houve diferenças entre as variáveis analisadas que comprovassem redução da atividade do clopidogrel quando associado à estatinas. Observou-se níveis de p-selectina (pré-angioplastia: 14,23±7,52 x 11,45±8,83 x 7,65±7,09; pós angioplastia: 21,49±23,82 x 4,37±2,71 x 4,82±4,47, ρ<0,01) e glicoproteína IIb/IIIa (pré-angioplastia: 98,97±0,43 x 98,79±1,25 x 99,21±0,40; pós angioplastia: 99,37±0,29 x 98,50±1,47 x 98,92±0,88, ρ=0,52), respectivamente nos grupos controle, atorvastatina e sinvastatina. CONCLUSÃO: Concluímos que a ativação plaquetária diminui com a administração de clopidogrel, e que o clopidogrel não tem seu efeito antiplaquetário reduzido na presença de sinvastatina ou atorvastatina.

Determinants of Functional and Structural Properties of Large Arteries in Healthy Individuals

Background: Changes in the properties of large arteries correlate with higher cardiovascular risk. Recent guidelines have included the assessment of those properties to detect subclinical disease. Establishing reference values for the assessment methods as well as determinants of the arterial parameters and their correlations in healthy individuals is important to stratify patients. Objective: To assess, in healthy adults, the distribution of the values of pulse wave velocity, diameter, intima-media thickness and relative distensibility of the carotid artery, in addition to assessing the demographic and clinical determinants of those parameters and their correlations. Methods: This study evaluated 210 individuals (54% women; mean age, 44 ± 13 years) with no evidence of cardiovascular disease. The carotid-femoral pulse wave velocity was measured with a Complior® device. The functional and structural properties of the carotid artery were assessed by using radiofrequency ultrasound. Results: The means of the following parameters were: pulse wave velocity, 8.7 ± 1.5 m/s; diameter, 6,707.9 ± 861.6 μm; intima-media thickness, 601 ± 131 μm; relative distensibility, 5.3 ± 2.1%. No significant difference related to sex or ethnicity was observed. On multiple linear logistic regression, the factors independently related to the vascular parameters were: pulse wave velocity, to age (p < 0.01) and triglycerides (p = 0.02); intima-media thickness, to age (p < 0.01); diameter, to creatinine (p = 0.03) and age (p = 0.02); relative distensibility, to age (p < 0.01) and systolic and diastolic blood pressures (p = 0.02 and p = 0.01, respectively). Pulse wave velocity showed a positive correlation with intima media thickness (p < 0.01) and with relative distensibility (p < 0.01), while diameter showed a positive correlation with distensibility (p = 0.03). Conclusion: In healthy individuals, age was the major factor related to aortic stiffness, while age and diastolic blood pressure related to the carotid functional measure. The carotid artery structure was directly related to aortic stiffness, which was inversely related to the carotid artery functional property.

Carnegie Institution of Washington publication.

no. 210 (1915)

Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

AbstractBackground:Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear.Objective:To evaluate hK1-specific amidase activity in the urine of CAD patientsMethods:Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates.Results:Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity.Conclusion:CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease.

A disponibilidade do fósforo de oiversos fosfatos estudada por meio do método de Neubauer"

In order to study the phosphorus availability from various phosphates fertilizers an experiment was performed according to the biological seedling method of Neubauer. The physico-chemical properties of the soil "terra roxa-misturada", a red soil derived from basaltic rocks are given in the Portuguese text. Rice (Oryza sativa, L.) instead of rye (Secale cereale, L.) was used. Five replications of each of the following treatments were made: 1 - check, with 350 g of sand 2 - 350 g of sand plus 100 g of soil 3 - 350 g of sand and plus 100 g of soil plus 40 mg of P2O5, from superphosphate. 4 - 350 g of sand plus 100 g of soil plus 40 mg of P2O5. from Olinda (Brazil) phosphorite. 5 - 350 g of sand plus 100 g of soil plus 40 mg of P2O5 from Florida (U. S. A.) phosphorite. 6 - 350 g os sand plus 100 g of soil plus 40 mg of P2O5 from Hyperphosphate, a commertial name of a North African (Gafsa) phosphorite. 7 - 350 g of sand plus 100 g of soil plus 40 mg of P2O5 from Araxá (Brazil) apatite. After 18 days of growth, the roots and tops of rice seedlings were harvested and analysed for phosphorus, and the results are summarized in table 1. Table 1 - Milligrams of P2O5 determined in rice seedlings. Treatments Mean of 5 replications mg of P2O5 1 ..................... 24.196 2 ..................... 23.850 3 ..................... 30.724 4 ..................... 27.620 5 ..................... 27.480 6..................... 30.210 7 ..................... 26.032 The least significant difference at the 5% level by Tukey's procedure for comparisons among the treatments means is 1.365 mg of P(2)0. It is interesting to observe that rice plants did not take any phosphorus from the soil according to he data of the treatments n.° 1 and n.° 2. This can be explained by the high phosphorus fixing capacity of the soil "terra roxa misturada".

Influência de cafés de gôsto rio em ligas com cafés de bebida mole

Os autores estudam a influência do café Rio em ligas com cafés brasileiros de bebida Mole. Foram ensaiadas porcentagens crescentes de Café Rio: 0,0; 0,5; 1,0; 1,5; 2,0; 2,5; 3,0; 3,5; 4,0; 4,5; 5,0; 7,5; 10,0; 12,5; 15,0; 20,0; 25,0; 30,0; 35,0; 40,0; 50,0. Realizaram-se dois experimentos em blocos incompletos equilibrados, com t = 21 tratamentos (os mencionados acima), k = 3 parcelas por bloco, r = 10 repetições, b = 70 blocos, L = 1. Cada parcela era formada de 3 xícaras, de tipo padrão, sobre as quais cada degustador dava uma só opinião. Cada parcela era provada por 3 degustadores. Os dados coletados são, pois, 630 para cada ensaio (210 parcelas, 3 degustadores). Atribuia-se a cada parcela, para fins de análise estatística, a média das opiniões dos 3 degustadores. Os dois ensaios deram resultados bem concordantes, que levaram às seguintes conclusões: a) Faz-se necessária a transformação dos dados, pois as variâncias relativas aos diversos tratamentos são muito discrepantes. b) A transformação T = √ Y dá resultados satisfatórios. c) O café Rio prejudica sensivelmente a bebida do café Mole, para teores a partir de 2,0%. d) Para teores de 4,5% em diante a liga tem bebida Riada ou Rio. e) A regressão obtida não é estritamente linear, mas a linha reta da uma aproximação razoável. f) Consideradas as porcentagens de 0,0 a 10,0%,a equação de regressão para os dados transformados pela transformação T = √ Y é: T = 1,7045 - 0,127 X, onde X é a porcentagem de café Rio e T dá a bebida, na escala numérica adotada, transformada pela raíz quadrada. g) A equação de regressão para os tratamentos de 0,0 a 10,0% de cafe Rio é Y = 3,0997 - 0,3281 X, isto é, há uma queda de 0,3281 na escala numérica da bebida, para cada unidade de porcentagem de café Rio.

Heimerziehung : das therapeutische Milieu in der stationären Jugendhilfe ; wird die klassische Heimerziehung ihrer Zielgruppe noch gerecht?

[s.c.]

Desenvolvimento embrionário, larval e juvenil de Hemisorubim platyrhynchos (Siluriformes, Pimelodidae) da bacia do rio Paraná

O objetivo deste estudo foi descrever o desenvolvimento embrionário, larval e juvenil da jurupoca, Hemisorubim platyrhynchos (Valenciennes, 1840), bem como as mudanças nos padrões de crescimento alométrico durante a ontogenia inicial da espécie. Um total de 90 ovos, 210 larvas e 24 juvenis provenientes de reprodução induzida foram analisados quanto a variáveis morfométricas e merísticas, além do coeficiente de crescimento alométrico em relação à cabeça, tronco e cauda durante o período larval e juvenil inicial. Os ovos apresentaram diâmetro médio de 1,74 mm, espaço perivitelino amplo (21,29%), com média de 0,37 mm, e diâmetro médio do vitelo de 1,08 mm. O comprimento padrão (CP) das larvas variou de 3,47 a 11,85 mm, com a maioria das medidas apresentando aumento proporcional ao longo do desenvolvimento. O número total de miômeros variou de 40 a 46 (pré-anal=15-17 e pós-anal=24-30). As larvas iniciais de H. platyrhynchos apresentam pigmentação na cabeça e na região ântero-ventral do corpo (anterior e posterior do saco vitelino). No estágio de pós-flexão, a pigmentação se intensifica, distribuindo-se na região dorsal da cabeça, formando uma faixa longitudinal que se estende do focinho ao opérculo, assim como uma faixa transversal, de um flanco a outro, passando pela região anterior da nadadeira dorsal, com máculas distribuídas ao longo do corpo nos juvenis (CP=19,5-49,09 mm). Nos primeiros estágios de desenvolvimento larval, a cabeça e a cauda crescem muito mais rapidamente do que o tronco, o que indica prioridades relacionadas à alimentação e natação, as quais posteriormente tendem à isometria, com um crescimento rápido do tronco nos juvenis iniciais.

Manual del curso básico: la accesibilidad en el servicio público

El manual del curso está estructurado en ocho capítulos. Los seis primeros desarrollan los contenidos necesarios para conocer y aplicar las condiciones de accesibilidad adecuadamente en los servicios públicos: desde las nociones y características vinculadas con las necesidades de distintos tipos de ciudadanos, hasta el contexto normativo, institucional y conceptual que se ha venido consolidando en torno a la idea de accesibilidad universal. Los dos últimos capítulos ofrecen medidas y recomendaciones para lograr una administración pública accesible, tanto en sus servicios donde se produce la relación con los ciudadanos, como en los entornos en que los empleados trabajan.

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.

Sympatric speciation in palms on an oceanic island.

The origin of species diversity has challenged biologists for over two centuries. Allopatric speciation, the divergence of species resulting from geographical isolation, is well documented. However, sympatric speciation, divergence without geographical isolation, is highly controversial. Claims of sympatric speciation must demonstrate species sympatry, sister relationships, reproductive isolation, and that an earlier allopatric phase is highly unlikely. Here we provide clear support for sympatric speciation in a case study of two species of palm (Arecaceae) on an oceanic island. A large dated phylogenetic tree shows that the two species of Howea, endemic to the remote Lord Howe Island, are sister taxa and diverged from each other well after the island was formed 6.9 million years ago. During fieldwork, we found a substantial disjunction in flowering time that is correlated with soil preference. In addition, a genome scan indicates that few genetic loci are more divergent between the two species than expected under neutrality, a finding consistent with models of sympatric speciation involving disruptive/divergent selection. This case study of sympatric speciation in plants provides an opportunity for refining theoretical models on the origin of species, and new impetus for exploring putative plant and animal examples on oceanic islands.