Intervenciones de enfermería promotoras de la vinculación con los recién nacidos hospitalizados - revisión scoping / Intervenções de enfermagem promotoras da vinculação ao recém-nascido hospitalizado -revisão scoping / Nursing interventions concerning the bonding of hospitalized newborns - scoping review

Introducción: El proceso de vinculación consiste en un vínculo emocional entre el recién nacido y los padres o cuidador. El apego del recién nacido a su cuidador es la base de todas las relaciones posteriores que desarrollará a lo largo de la vida. Objetivo: Mapear las intervenciones de enfermería que promueven el vínculo afectivo en recién nacidos con necesidad de hospitalización. Método: Esta revisión de alcance se realizó según el método del Instituto Joanna Briggs, siendo las principales fuentes de información las bases de datos: PubMed, MEDLINE, CINAHL vía EBSCO, LILACS, Cochrane Library, Academic Search Complete, en portugués e inglés, sin límite de tiempo. Resultados: Se incluyeron 53 estudios en esta revisión. Las intervenciones de enfermería identificadas en la literatura se dividen en dos grupos: en la promoción de la interacción entre los padres y el recién nacido, es decir, la proximidad física, la promoción de la lactancia materna, la inclusión de los padres en el cuidado del recién nacido y en la interacción entre los padres y el equipo de enfermería, a través de la comunicación y el apoyo emocional. Conclusión: El enfermero juega un papel fundamental en el resTablecimiento del proceso de vinculación entre el recién nacido hospitalizado y los padres, para que sean capaces de pasar de un rol en el que son meros espectadores a convertirse en los principales cuidadores del recién nacido, formados y vinculados. (AU)

Introdução: O processo de vinculação consiste numa ligação emocional entre o recém-nascido e os pais ou o cuidador. A vinculação do recém-nascido ao seu cuidador é a base de todas as relações posteriores que este desenvolverá ao longo da vida e em particular em contexto de internamento hospitalar. Objetivo: Mapear na literatura as intervenções de enfermagem promotoras de vinculação em recém--nascidos em internamento hospitalar. Método: Revisão de literaturascoping nas normas do Joanna Briggs Institute, sendo as principais fontes de informação as bases de dados: PubMed, MEDLINE, CINAHL via EBSCO, LILACS, Cochrane Library, Academic Search Complete, em português e inglês. A seleção dos estudos e extração dos dados foram realizados por dois revisores independentes. Resultados: Foram incluídos 53 estudos. As intervenções de enfermagem identificadas na literatura como promotoras da vinculação organizam-se em dois grupos: na promoção da interação entre os pais e o recém-nascido, a proximidade física ou presença, a promoção da amamentação, a inclusão dos pais nos cuidados ao recém-nascido, e na interação entre os pais e a equipa de enfermagem (através da comunicação e o apoio emocional). Conclusão: Os enfermeiros desempenham um papel fundamental para o restabelecimento do processo vinculativo entre o recém-nascido internado e os pais, seja na facilitação da relação pais-filho, seja enquanto interlocutores da relação. Esta scoping eleva intervenções de natureza relacional, que merecem ser testadas em relação à sua efetividade na vinculação. (AU)

Introduction: The bonding process consists of an emotional bond between the newborn and the parents or caregiver. The newborn's attachment to his caregiver is the basis of all subsequent relationships that he will develop throughout life. Objective: To map nursing interventions that promote bonding in newborns in need of hospitalization. Method: This scoping review was carried out according to the method of the Joanna Briggs Institute, the main sources of information being the databases: PubMed, MEDLINE, CINAHL via EBSCO, LILACS, Cochrane Library, Academic Search Complete, in portuguese and english, without time limit. Results: 53 studies were included in this review. The nursing interventions identified in the literature are divided into two groups: in promoting interaction between parents and the newborn, namely physical proximity, the promotion of breastfeeding, the inclusion of parents in the care of the newborn, and in interaction between parents and the nursing team, through communication and emotional support. Conclusion: Nurses play a fundamental role in reestablishing the binding process between the hospitalized newborn and the parents, so that they are able to move from a role in which they are mere spectators to become the main caregivers of the newborn, trained and linked. (AU)

Parenting of Children with Autism Spectrum Disorder: A Grounded Theory Study.

BACKGROUND: Parenting a child with an autism spectrum disorder (ASD) involves several processes and emotions during this transition. In addition to the family's natural transition when a child is born, the family of a child with ASD has to deal with the particularities of the disability, its characteristics, and its evolution. METHODS: This is a qualitative grounded theory study aiming to deepen the knowledge about the process of parenting children with ASD. Data were collected using interviews and observations of nine couples and one single mother. RESULTS: Coding and analysis led to the main theme, which is as follows: parenting of children with ASD as representative of the parents' transformation while caring for the child, also based on adaptation throughout this experience. CONCLUSIONS: Parenting is a dynamic process, grounded on the interaction of different contexts, such as family, education, health, and society, and on the co-construction of different times and episodes. These characteristics underline the complex and individual nature of parenting children with autism, which requires specific assessments and interventions by nurses when caring for these families, whether in a family nursing context, community nursing, and pediatric nursing or midwifery.

Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?

INTRODUCTION: AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively. METHODS: Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis. RESULTS: Multivariate analysis showed shorter PFS for T carriers [HR=2.0, 95% CI, 1.4-3.0, p<0.0001] and shorter OS [HR=1.8, 95% CI, 1.1-3.0, p=0.017] globally, as well as in a subgroup of patients (n=144) treated with first line platinum-based chemotherapy [HR=2.0, 95% CI, 1.3-3.1, p=0.001] and [HR=1.8, 95% CI, 1.1-3.1, p=0.026], respectively. CONCLUSION: This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.

Intervenciones de enfermería promotoras de la adaptación del niño / joven / familia a la hospitalización: una scoping review / Intervenções de enfermagem promotoras da adaptação da criança / jovem / família à hospitalização: uma scoping review / Nursing interventions promoting child /youth /family adaptation to hospitalization: a scoping review

OBJETIVO: Identificar el proceso de adaptación del niño y la familia a la hospitalización y mapear las intervenciones de enfermería que promueven la adaptación a la hospitalización del niño/joven/familia. MÉTODO: Elaboración de Scoping Review basado en Joanna Briggs Institute (2014). Criterios de inclusión para Población: Niño, Joven (0-18 años) y Familia; Concepto: Intervenciones promotoras hacia la adaptación y Contexto: Hospitalización. Los estudios considerados fueron estudios cuantitativos, cualitativos y revisiones sistemáticas. Búsqueda de artículos en tres bases de datos electrónicas - PUBMED, MEDLINE y CINAHL. Criterio de selección: datados entre 2012 y 2019 y en régimen full text. Idiomas: inglés y portugués. RESULTADOS: Se analizaron un total de 14 artículos, destacando que el diseño del estudio incluye 2 revisiones sistemáticas de la literatura, 7 estudios cualitativos y 5 cuantitativos. Los resultados del análisis se organizaron por temas: adaptación del niño a la hospitalización, adaptación de los padres y estrategias que promueven la adaptación a la hospitalización. Las intervenciones dirigidas a los niños se centran en el fortalecimiento de los mecanismos para hacer frente a los problemas y en el aumento de la seguridad, y se han clasificado en estrategias de comunicación; actividades recreativas y de relajación; promoción de la esperanza y estrategias de coping. CONCLUSIÓN: Las intervenciones de enfermería promotoras de la adaptación a la hospitalización mapeadas pretenden disminuir la ansiedad y el estrés del niño / familia, aumentando la capacidad para recibir información, participar en el cuidado y en las decisiones. Se destacan el juego terapéutico, informaciones anticipatorias, técnicas de relajación, distracción, humor, musicoterapia, kits de adaptación, grupos terapéuticos y estrategias promotoras de esperanza

OBJETIVO: Identificar o processo de adaptação da criança e família à hospitalização e mapear as intervenções de enfermagem promotoras da adaptação à hospitalização da criança/jovem/família. MÉTODO: Elaboração de uma Scoping Review com base no Joanna Briggs Institute (2014). Critérios de inclusão - População: Criança, Jovem (0-18 anos); Conceito: Intervenções promotoras da adaptação e Contexto: Hospitalização. Os estudos considerados foram estudos quantitativos, qualitativos e revisões sistemáticas. Pesquisa de artigos em três bases de dados eletrónicas - PUBMED, MEDLINE e CINAHL. Critério de selecção: datados entre 2012 e 2019 e em regime full text. Línguas de inclusão: Português e Inglês. RESULTADOS: Foram analisados 14 artigos, salientando-se que o desenho de estudo incluem 2 revisões sistemáticas da literatura, 7 estudos qualitativos e 5 quantitativos. Os resultados da análise foram organizados por temas: adaptação da criança à hospitalização, adaptação dos pais à hospitalização e estratégias promotoras de adaptação à hospitalização. As intervenções dirigidas à criança centram-se no fortalecimento dos mecanismos de enfrentamento e no aumento da segurança, tendo estas sido categorizadas em estratégias comunicacionais; atividades lúdicas/brincar e atividades de relaxamento; promoção da esperança e estratégias de coping. CONCLUSÃO: As intervenções de Enfermagem promotoras da adaptação à hospitalização mapeadas visam diminuir a ansiedade e stress da criança/família, aumentando a capacidade para receber informação, participar nos cuidados e em decisões. Destacam-se a brincadeira terapêutica, informações antecipatórias, técnicas de relaxamento, distração, humor, musicoterapia, kits de adaptação, grupos terapêuticos e estratégias promotoras de esperança

OBJECTIVE: Identify the adaptation process of the child and family to hospitalization and map the nursing interventions that promote the child/youth/family's adaptation to hospitalization. METHOD: Elaboration of a Scoping Review based on the Joanna Briggs Institute (2014). Inclusion criteria - Population: Child, Young (0-18 years old); Concept: Interventions promoting adaptation and Context: Hospitalization. The studies considered were quantitative, qualitative and systematic reviews. Electronic databases used for article search - PUBMED, MEDLINE and CINAHL. Selection criteria: full text articles dated between 2012 and 2019. Languages of inclusion: Portuguese and English. RESULTS: A total of 14 articles were analyzed, including 2 systematic reviews of the literature, 7 qualitative studies and 5 quantitative studies. The results of the analysis were organized by themes: the child's adaptation to hospitalization, the parent's adaptation to hospitalization and strategies promoting adaptation to hospitalization. The interventions aimed at children are focused on strengthening coping mechanisms and on increasing the sense of security. These have been categorized into communication strategies; playful activities and relaxation activities; and promotion of hope and coping strategies. CONCLUSION: The mapped Nursing interventions that promote adaptation to hospitalization intend to decrease the child / family's anxiety and stress, increasing the ability to receive information and to participate in care and decisions. Intervention such as therapeutic play, anticipatory information, relaxation techniques, distraction, humor, music therapy, adaptation kits, therapeutic groups and hope-promoting strategies are emphasized

Promoción del sueño en unidades de cuidados intensivos neonatales: scoping review / Promoção do sono em unidades de cuidados intensivos neonatais: scoping review / Sleep promotion in neonatal intensive care units: scoping review

El sueño desempeña un papel fundamental en el crecimiento y desarrollo de los recién nacidos, su privación presenta numerosos efectos negativos. El ambiente de las unidades de cuidados intensivos neonatales (UCIN) se presenta como perturbador y nocivo del sueño neonatal. OBJETIVO: Mapear la evidencia científica existente en cuanto a las estrategias promotoras del sueño de los recién nacidos en contexto de UCIN. Metodología: Scoping review basada en la metodología propuesta por el Joanna Briggs Institute, utilizando los siguientes motores de búsqueda y bases de datos: MEDLINE via PubMed, CINHAL Plus with Full Text e Nursing & Allied Health Collection: Comprehensive via EBSCO-HOST, Academic Search Complete, ScienceDirect e Directory of Open Access Journals via B-ON, LILACS, RCAAP e SciELO. Definido como limitadores artículos publicados en los últimos 5 años (hasta febrero de 2019), disponibles en portugués o inglés y en texto completo. RESULTADOS: Se localizaron 186 registros, y la muestra final incluyó 9 estudios que respondieron al objetivo de la revisión sobre la base de los criterios de inclusión definidos. Las estrategias promotoras del sueño identificadas remiten a la gestión del ambiente en la UCIN, concentración de los cuidados de enfermería respetando el ciclo de sueño / vigilia de los recién nacidos, posicionamiento adecuado, contención, succión no nutritiva, técnica de Yakson, toque humano suave, canguro materno, masaje, estímulos auditivos tranquilos y colchón modelador. Conclusión: Dada la importancia del sueño en el desarrollo de los recién nacidos, es fundamental el papel del Enfermero a través de la adopción de estrategias protectoras y promotoras de éste, especialmente en contexto de UCIN

O sono tem um papel fundamental no crescimento e desenvolvimento dos recém-nascidos, com a sua privação a apresentar inúmeros efeitos negativos. O ambiente das unidades de cuidados intensivos neonatais (UCIN) apresenta-se como perturbador e nocivo do sono neonatal. OBJETIVO: Mapear a evidência científica existente quanto às estratégias promotoras do sono do recém-nascido em contexto de UCIN. Método: Scoping review baseada na metodologia proposta pelo Joanna Briggs Institute, com recurso aos seguintes motores de busca e bases de dados: MEDLINE via PubMed, CINHAL Plus with Full Text e Nursing & Allied Health Collection: Comprehensive via EBSCO-HOST, Academic Search Complete, ScienceDirect e Directory of Open Access Journals via B-ON, LILACS, RCAAP e SciELO. Definidos como limitadores artigos publicados nos últimos 5 anos (até fevereiro de 2019), disponíveis em português ou inglês e em texto integral. RESULTADOS: Foram localizados 186 registos, tendo a amostra final incluído 9 estudos que responderam ao objetivo da revisão com base nos critérios de inclusão definidos. As estratégias promotoras do sono identificadas remetem para a gestão do ambiente na UCIN, concentração dos cuidados de Enfermagem respeitando o ciclo de sono-vigília dos recém-nascidos, posicionamento adequado, contenção, sucção não-nutritiva, técnica de Yakson, toque humano suave, canguru materno, massagem, estímulos auditivos calmos e colchão modelador. Conclusão: Dada a importância do sono no desenvolvimento dos recém-nascidos, é fulcral o papel do Enfermeiro através da adoção de estratégias protetoras e promotoras deste, especialmente em contexto de UCIN

Sleep plays a fundamental role in the growth and development of newborns, with their deprivation having many negative effects. The environment of the neonatal intensive care units (NICU) presents itself as disturbing and harmful for the neonatal sleep. OBJECTIVE: Map the existing scientific evidence regarding the strategies promoting newborn's sleep in the NICU setting. Methodology: Scoping review based on the methodology proposed by the Joanna Briggs Institute, using the following search engines and databases: MEDLINE via PubMed, CINHAL Plus with Full Text and Nursing & Allied Health Collection: Comprehensive via EBSCO-HOST, Academic Search Complete, ScienceDirect and Directory of Open Access Journals via B-ON, LILACS, RCAAP and SciELO. As search limiters, there were defined articles published in the last 5 years (until February 2019), available in Portuguese or in English and in full text. RESULTS: A total of 186 results were listed, and the final sample included 9 studies that responded to the review objective based on the selected inclusion criteria. The sleep-promoting strategies identified refer to the management of the environment in the NICU, the concentration of Nursing care respecting the newborn's sleep-wake cycle, and non-pharmacological interventions such as proper positioning, physical restraint, non-nutritive sucking, Yakson technique, gentle human touch, kangaroo mother care, massage, calm auditory stimuli and remolding mattress. Conclusion: Given the importance of sleep in the newborn's development, the nurse's role is crucial through the implementation of protective and promoting sleep strategies, especially in the NICU

Intervenciones promotoras de esperanza en padres de niños con necesidades especiales de salud: una revisión scoping / Intervenções promotoras de esperança em pais de crianças com necessidades especiais de saúde: uma revisão scoping / Hope promoting interventions in parents of children with special health needs: a scoping review

El concepto de esperanza ha sido identificado como central para la enfermería, ganando visibilidad en el ámbito de la atención al niño con necesidades especiales de salud y sus familias. Surgiendo nuevos desafíos en la enfermería pediátrica y constatando las necesidades de los padres ante las adversidades que enfrentan, las intervenciones promotoras de esperanza deberán ser vistas en destaque.Objetivo: Mapear las intervenciones que se han implementado y evaluado para promover la esperanza en los padres de los niños con necesidades especiales de salud.Método: Se llevó a cabo una revisión scoping, siguiendo la metodología propuesta por el Joanna Briggs Institute, en las bases de datos PubMed, CINHAL completa y SciELO, en portugués, inglés y español y en el marco de tiempo 2008-2018.Resultados: Fueron incluidos en esta revisión 7 estudios. La investigación encontrada es mayoritariamente cualitativa, dispersa en términos temporales y diferenciados en el marco conceptual. En la mayoría de los casos, los estudios engloban intervenciones de carácter grupal e individual, con variabilidad de contextos y características de intervención.Conclusión: Se mantiene la discusión sobre intervenciones promotoras de esperanza en los cuidados de enfermería pediátrica, existiendo necesidad de más investigación para la validación de intervenciones que promuevan la esperanza en los padres de niños con necesidades especiales de salud

O conceito de esperança tem sido identificado como central para a enfermagem, ganhando visibilidade no âmbito da prestação de cuidados à criança com necessidades especiais de saúde e suas famílias. Surgindo novos desafios na enfermagem pediátrica e constatando as necessidades dos pais diante as adversidades que enfrentam, as intervenções promotoras de esperança deverão ser vistas em destaque. Objetivo: Mapear as intervenções que foram implementadas e avaliadas para promover a esperança em pais de crianças com necessidades especiais de saúde. Método: realizou-se uma revisão scoping, seguindo a metodologia proposta pelo Joanna Briggs Institute, nas bases de dados Pubmed, CINHAL complete e SciELO, nos idiomas português, inglês e espanhol e na janela temporal de 2008 a 2018. Resultados: Foram incluídos nesta revisão 7 estudos. A investigação encontrada é maioritariamente qualitativa, dispersa em termos temporais e diferenciada no quadro conceptual. Maioritariamente avaliada em indivíduos, os estudos englobam intervenções de carater grupal e individual, com variabilidade de contextos e características de intervenção. Conclusão: mantém-se a discussão sobre intervenções promotoras de esperança nos cuidados de enfermagem pediátrica, existindo necessidade de mais investigação para a validação de intervenções que promovam a esperança em pais de crianças com necessidades especiais de saúde

The concept of hope has been identified as central to nursing and have gained visibility in the caring of children with special health needs and their families. With the emergence of new challenges in pediatric nursing and knowing the needs and adversities parents are facing in their daily life, interventions that promote hope should be highlighted.Objective: to map the interventions that have been implemented and evaluated to promote hope in parents of children with special health needs.Method: a scoping review was held, following Joanna Briggs Institute methodology, in the databases Pubmed, CINHAL complete and SciELO, in portuguese, english and spanish and in the time window from 2008 to 2018.Results: Seven studies were included in this review. The research that was found is mostly qualitative, dispersed in time and differentiated in terms of conceptual framework. Mostly evaluated in individuals, the studies encompass either group and individual interventions, with a large variability of contexts and intervention characteristics. Conclusion: discussions about hope promoting interventions in pediatric nursing care are currently occurring, the need for more research persists for the validation of hope promotion interventions in parents of children with special health needs

Platelet aggregation at discharge: a useful tool in acute coronary syndromes?

INTRODUCTION: Inhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention. OBJECTIVE: To stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation. METHODS: We performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate(®) analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0-188.0) days. RESULTS: The median value of platelet aggregation was 16.0U (11.0-22.5U) with a maximum of 41.0U and a minimum of 4.0U (normal value according to the manufacturer: 53-122U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A - platelet aggregation <18.5U, n=44; and group B - platelet aggregation ≥18.5U, n=26. The groups were similar with respect to demographic data (age 60.5 [49.0-65.0] vs. 62.0 [49.0-65.0] years, p=0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p=0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p<0.01). Platelet aggregation higher than 18.5U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38-32.90, p=0.02). CONCLUSION: In our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.

CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a Portuguese center.

BACKGROUND: Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. OBJECTIVE: To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. METHODS: We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days. RESULTS: The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group. CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.

Genetic characterization of warfarin sensitivity in a population of cardiovascular patients on chronic anticoagulation.

BACKGROUND: Genetic factors account for 35-40% of the interindividual variation observed in response to warfarin. The most important genes involved are CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex subunit 1). OBJECTIVES: To determine the prevalence of the different genotypes influencing response to oral anticoagulants in a population of cardiovascular patients on chronic anticoagulation and to investigate the correlation between genotype and the warfarin dose required for optimal anticoagulation. METHODS: A total of 91 chronically anticoagulated consecutive patients were genotyped for CYP2C9 and VKORC1, using PCR and reverse hybridization. RESULTS: Of the 91 patients, 57.1% were male and mean age was 67.4 +/- 13.1 years. most frequent indication for warf was atrial fibrillation (56.8%). We analyzed the prevalence of the different CYP2C9 and VKORC1 genotypes in this population and found that the warfarin doses required to maintain patients at their desired anticoagulation target were significantly different among carriers of the different genotypes. CONCLUSIONS: Our study highlights the importance of genetic study in the clinical management of patients on chronic anticoagulation, increasing the safety and efficacy of warfarin therapy.

Platelet hyperactivation in maintained growth hormone-deficient childhood patients after therapy withdrawal as a putative earlier marker of increased cardiovascular risk.

GH deficiency (GHD) is associated with a higher risk of vascular disease, whose pathophysiological mechanisms remains not yet fully elucidated. This study aimed to assess the main cardiovascular risk indexes, plasma catecholamines content, and the platelet function in childhood-onset GHD patients. Some of the main clinical examinations related with cardiovascular risk, plasma catecholamines content, as well as platelet intracellular free calcium concentration ([Ca(2+)](i)), whole-blood aggregation, and morphology were evaluated in childhood-onset GHD patients treated with GH for a variable period and off GH therapy for at least 2 yr before entry into study and in sex-, age-, and body mass index-matched control groups. Among the patients, group 1 (GHD-1) has recovered GH levels after withdrawal, whereas group 2 (GHD-2) has remained GH deficient. Minor differences on the cardiovascular risk indexes were observed between the groups. Plasma catecholamine concentrations in the GHD groups did not statistically differ from the control group, but higher adrenaline content was observed in the GHD-2 group when compared with the GHD-1 one. Basal and thrombin-evoked [Ca(2+)](i) and platelet aggregation were identical between the GHD-1 group and the matched control. However, the GHD-2 group has increased thrombin-evoked [Ca(2+)](i) (297.0 +/- 15.7 Deltanmol/liter; P < 0.01), collagen, and ADP-induced platelet aggregation (33.3 +/- 4.3 and 12.5 +/- 2.1 Omega, respectively; P < 0.05) vs. the control-2 group (Delta[Ca(2+)](i): 102.1 +/- 13.6 Deltanmol/liter; aggregation: 19.6 +/- 2.9 and 6.2 +/- 0.8 Omega). The platelet hyperreactivity state in the GHD-2 was reinforced by morphologic studies of electron microscopy. In conclusion, there were minor differences between the GHD-1 group and the controls, which might be due to the recovery of GH levels after therapy withdrawal. However, the maintained GHD group, despite minor cardiovascular risk index differences, has increased [Ca(2+)](i) and aggregation, which could indicate a hyperactivation state that might be viewed as an earlier marker of cardiovascular disturbances.

Isosorbide-5-mononitrate treatment prevents cyclosporin A-induced platelet hyperactivation and the underlying nitric oxide-cyclic guanosine-3',5'-monophosphate disturbances.

INTRODUCTION: The clinical use of cyclosporin A (CsA) is commonly associated with the development of hypertension and increased risk of thromboembolic events. Decreased endothelium-dependent relaxation and increased platelet activation seems to be involved on those side effects, but the underlying mechanisms are not yet elucidated. The present study aimed to evaluate the CsA effect on the platelet NO-cyclic guanosine-3',5'-monophosphate (cGMP) pathway and the putative benefits of concomitant isosorbide-5-mononitrate (IS-5-MN) administration on CsA-induced hypertension and on platelet hyperactivation. MATERIALS AND METHODS: Blood pressures, platelet NO synthase activity and cGMP content, intracellular free calcium concentration ([Ca2+]i) and whole blood platelet aggregation were assessed in three rat groups orally treated, during 7 weeks, with the following diets: orange juice (control group), 5 mg/kg/day of CsA (CsA group) and 150 mg/kg/day, b.i.d., of IS-5-MN for 2 weeks and IS-5-MN plus 5 mg/kg/day of CsA for 7 weeks (IS-5-MN+CsA group). RESULTS: IS-5-MN treatment has prevented hypertension development obtained in the solely CsA-treated rats. CsA treatment has inhibited NOS activity, which was reverted by the concomitant IS-5-MN and CsA administration. On the contrary, platelets from CsA-treated rats had cGMP content increased when compared with the control rats. The variation obtained when ISMN was present was less predominant. Therefore, the organic nitrate treatment has prevented platelet hyperactivation, namely, by decreasing thrombin-evoked [Ca2+]i and collagen-evoked platelet aggregation, when compared with the solely CsA-treated group. The preventive effect of IS-5-MN was reinforced by electron microscopy studies of platelet activation. CONCLUSIONS: By increasing [Ca2+]i and aggregation, CsA induces platelet hyperactivation and simultaneously increases cGMP content, which might represent a compensatory inhibitory mechanism. The concomitant IS-5-MN treatment prevents the above-mentioned platelet hyperreactivity and tends to normalize the NO-cGMP pathway as well as the development of hypertension.