RESUMEN
Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.
Asunto(s)
Proteínas Reguladoras de la Apoptosis , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos , Receptores Depuradores , Sepsis , Animales , Ratones , Ciego/cirugía , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Modelos Animales de Enfermedad , Ligadura , Lipopolisacáridos , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fagocitosis , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Sepsis/inmunología , Sepsis/tratamiento farmacológico , Choque Séptico/inmunología , Proteínas Reguladoras de la Apoptosis/uso terapéutico , Receptores Depuradores/uso terapéuticoRESUMEN
BACKGROUND: Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology. SUMMARY: Our objective was to assess the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies. The MEDLINE, ISI Web of Science and Scopus databases were searched (1983-2013) for studies performed in well-defined populations and geographical regions. Two independent reviewers assessed the studies and extracted data and predefined methodological parameters. Overall, 22 studies were included, reporting on 14,539 patients from 16 countries. Multisource population-based studies yielded higher prevalence values than studies based primarily on hospitals or genetic centres. The prevalence range of dominant HCA was 0.0-5.6/10(5), with an average of 2.7/10(5) (1.5-4.0/10(5)). Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease was the most common dominant ataxia, followed by SCA2 and SCA6. The autosomal recessive (AR) HCA (AR-HCA) prevalence range was 0.0-7.2/10(5), the average being 3.3/10(5) (1.8-4.9/10(5)). Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. The prevalence of autosomal dominant (AD) HSP (AD-HSP) ranged from 0.5 to 5.5/10(5) and that of AR-HSP from 0.0 to 5.3/10(5), with pooled averages of 1.8/10(5) (95% CI: 1.0-2.7/10(5)) and 1.8/10(5) (95% CI: 1.0-2.6/10(5)), respectively. The most common AD-HSP form in every population was spastic paraplegia, autosomal dominant, type 4 (SPG4), followed by SPG3A, while SPG11 was the most frequent AR-HSP, followed by SPG15. In population-based studies, the number of families without genetic diagnosis after systematic testing ranged from 33 to 92% in the AD-HCA group, and was 40-46% in the AR-HCA, 45-67% in the AD-HSP and 71-82% in the AR-HSP groups. KEY MESSAGES: Highly variable prevalence values for HCA and HSP are reported across the world. This variation reflects the different genetic make-up of the populations, but also methodological heterogeneity. Large areas of the world remain without prevalence studies. From the available data, we estimated that around 1:10,000 people are affected by HCA or HSP. In spite of advances in genetic research, most families in population-based series remain without identified genetic mutation after extensive testing. © 2014 S. Karger AG, Basel.
Asunto(s)
Ataxia Cerebelosa/epidemiología , Paraplejía/epidemiología , Degeneraciones Espinocerebelosas/epidemiología , Estudios Transversales , Humanos , Prevalencia , Paraplejía Espástica Hereditaria/epidemiologíaRESUMEN
INTRODUCTION: By 2002 Portugal had one of the highest mortality rates due to cerebrovascular diseases among the European Countries. Meanwhile, several strategies have been adopted to improve prevention and treatment in the acute phase, amongst which the Stroke Code. The purpose of this study is to describe how this measure has been used and its outcome as part of a prospective community based study of stroke/TIA incidence in Northern Portugal. MATERIALS AND METHODS: Between 1st October 2009 and 30th September 2010 all strokes occurred in patients registered at Western Porto, Mirandela and Vila Pouca de Aguiar health centres have been recorded. For cases ascertainment multiple sources of information were used, including the WEB, letter, e-mail and Alert P1, as well as systematic searches on databases provided by the entities involved in this study: hospital emergency, discharge records, diagnosis procedures, death certificates, Stroke Code admissions and health centre emergency records. RESULTS: Six hundred strokes were recorded in a population of 241 000 (incidence rate of 250 / 100 000 person-years) and 434 were first-ever-in-the-lifetime (180 / 100 000). There were 72 Stroke Code calls and in 66.7% of them a stroke was confirmed. Considering the criteria for Stroke Code call (age = 80 years, functional independency, the stroke signs/symptoms, and time after episode = 3 hours), only 15.9% patients "could" have access to it. Of those who used the Stroke Code, only 56.3% fulfilled the criteria. Considering all patients fulfilling Stroke Code criteria, 96.3% that used prehospital Stroke Code were inpatients, as well as 83.3% that used intra/interhospital Stroke Code and 64.0% of the remainder; this trend is also present in patients with ischaemic stroke submitted to fibrinolysis, 77.3%, 36.4% and 17.4%, respectively. A high post-stroke Rankin was more frequent among Stroke Code users (70.3% vs. 35.3%), but they exhibit more often the three stroke signs/symptoms (44.0% vs. 16.2%). After adjusting for age, sex and number of signs, the risk of a more severe post-stroke Rankin is not significantly different among patients using the prehospital Stroke Code (OR = 2.9, 95% CI: 0.8 - 10.2). CONCLUSIONS: The criteria for accessing the Stroke Code are currently restrictive. Though the Stroke Code is accessed in case of more severe patient's conditions, the proportion of patients treated with fibrinolysis is relatively high in comparison with other studies.
Introdução: Em 2002 Portugal detinha uma das mais altas taxas de mortalidade por doenças cerebrovasculares entre os países europeus. Várias estratégias foram adoptadas para melhorar a prevenção da doença e o seu tratamento na fase aguda, entre as quais a criação da Via Verde do Acidente Vascular Cerebral. O objectivo deste trabalho é descrever a utilização e resultados desta estratégia no contexto de um registo prospectivo comunitário na Região Norte de Portugal. Material e Métodos: Foram registados todos os AVCs ocorridos entre 1 de Outubro de 2009 e 30 de Setembro de 2010 nos utentes inscritos no agrupamento de centros de saúde do Porto Ocidental e nos de Mirandela e Vila Pouca de Aguiar. Para a detecção de casos utilizaram-se múltiplas fontes de informação: notificação via WEB, e-mail, Alerta P1 e pesquisas sistemáticas em registos disponibilizados pelas entidades envolvidas - urgências hospitalares, listas de altas, procedimentos de diagnóstico, óbitos, Via Verde do Acidente Vascular Cerebral e serviço de atendimento de situações urgentes. Resultados: Ocorreram 600 AVCs em 241 000 habitantes (taxa de incidência de 250 / 100 000), dos quais 434 foram primeiros na vida (180 / 100 000). Foram registados 72 acessos à Via Verde do Acidente Vascular Cerebral, dos quais 66,7% foram diagnosticados como AVC. Considerando os quatro critérios de activação (idade ≤ 80 anos, independência funcional, sinais/sintomas do AVC e tempo após episódio ≤ 3 horas), só 15,9% dos doentes a poderiam utilizar e, dos utilizadores, apenas 56,3% satisfaziam esses critérios. Dos doentes com critérios de activação, foram internados 96,3% pela VV pré-hospitalar, 83,3% pela VV intra/inter-hospitalar e 64,0% dos restantes; a fibrinólise foi realizada em 77,3%, 36,4% e 17,4% dos doentes com enfarte cerebral, respectivamente. O Rankin pós- AVC é mais grave nos utilizadores da VV pré-hospitalar (70,3% vs. 35,3%), mas estes apresentam mais assiduamente os três sinais/ sintomas de AVC (44,4% vs. 16,2%). Ajustando para a idade, sexo e número de sinais, o risco de incapacidade grave pós-AVC não é significativamente diferente no acesso pela VV pré-hospitalar (RP = 2,9; IC 95%: 0,8 - 10,2), bem como a taxa de letalidade. Conclusões: Os critérios para activação da Via Verde do Acidente Vascular Cerebral são muito restritivos. Embora esta seja mais vezes accionada em situações clínicas graves, a proporção de doentes que realizou fibrinólise é relativamente alta em comparação com outros estudos.
Asunto(s)
Accidente Cerebrovascular/clasificación , Accidente Cerebrovascular/diagnóstico , Anciano , Femenino , Humanos , Masculino , Portugal , Estudios ProspectivosRESUMEN
IMPORTANCE: Epidemiological data on hereditary cerebellar ataxia (HCA) and hereditary spastic paraplegia (HSP) are scarce. OBJECTIVE: To present the prevalence and distribution of HCA and HSP in Portugal. DESIGN AND SETTING: Population-based, nationwide, systematic survey, from January 1, 1994, through April 15, 2004, in Portugal. PARTICIPANTS: Multiple sources of information were used (review of clinical files, active collaboration of neurologists and geneticists, and investigation of affected families), but the main source was active collaboration of general practitioners. Patients were examined by the same team of neurologists, using homogeneous inclusion criteria. The clinical data were registered, and all families were genetically tested. RESULTS: Overall, 1336 patients from a population of 10,322 million were diagnosed as having HCA or HSP, a prevalence of 12.9 per 100,000 population. Hereditary cerebellar ataxia was more prevalent (prevalence, 8.9 per 100,000 population; 5.6 for dominant and 3.3 for recessive ataxias) than HSP (prevalence, 4.1 per 100,000 population; 2.4 for dominant and 1.6 for recessive). Machado-Joseph disease (spinocerebellar ataxia type 3) (prevalence, 3.1 per 100,000 population), Friedreich ataxia (prevalence, 1.0 per 100,000 population), and ataxia with oculomotor apraxia (prevalence, 0.4 per 100,000 population) were the most frequent HCAs. Spastic paraplegia types 4 (prevalence, 0.91 per 100,000 population), 3 (prevalence, 0.14 per 100,000 population), and 11 (prevalence, 0.26 per 100,000 population) were the most prevalent HSPs. CONCLUSIONS AND RELEVANCE: This population-based survey covered all the Portuguese territory and mobilized most general practitioners and health centers. To our best knowledge, this survey was the largest ever performed for HCA and HSP. Prevalence of autosomal dominant ataxias was high, particularly for Machado-Joseph disease (spinocerebellar ataxia type 3). The genetic cause has not been identified in 39.7% of the patients studied.
Asunto(s)
Paraplejía/epidemiología , Paraplejía/genética , Vigilancia de la Población/métodos , Degeneraciones Espinocerebelosas/epidemiología , Degeneraciones Espinocerebelosas/genética , Estudios Transversales , Humanos , Paraplejía/diagnóstico , Portugal/epidemiología , Prevalencia , Degeneraciones Espinocerebelosas/diagnósticoRESUMEN
Objetivo. Nos proponemos estimar la prevalencia del hipotiroidismo tratado en nuestra Área de Salud a partir de la prescripción de hormona tiroidea. Describimos asimismo sus características y diferencias en base a diversos factores sociodemográficos. Diseño. Estudio descriptivo de corte transversal. Emplazamiento. Área Sanitaria de Guadalajara (España). Participantes. Sujetos en tratamiento con levotiroxina por hipotiroidismo incluidos en tarjeta sanitaria durante el año 2009. Mediciones Principales. Se evaluaron la distribución por sexo, edad y lugar de residencia, previo ajuste de tasas. Otras variables analizadas fueron el tipo de hipotiroidismo, última dosis prescrita y niveles de TSH, comparando en función de variables sociodemográficas. Resultados. Un 3,3% de la población (IC 95%: 3,3-3,4) recibió tratamiento con levotiroxina (5,8% mujeres y 1,0% varones), observando la tasa más elevada en mujeres mayores de 65 años (11,9%). La tasa ajustada fue 38,8/1000 (IC 95%: 37,7-40,0) para el medio urbano y 34,6/1000 (IC 95%: 33,4-35,8) para el rural. Edad media de 56,6 años (DE: 18,2). Se asume origen autoinmune en el 76% de los casos con causa reconocible, utilizando una dosis media de 76,84mcg/día. Un 76,2% de los pacientes presentaron un rango correcto de TSH. Conclusiones. El hipotiroidismo subclínico es un proceso frecuente entre los usuarios de un Centro de Salud y mayoritariamente tiene origen autoinmune. El diagnóstico es más frecuente en el sexo femenino y en población mayor. Existe habitualmente un buen control de las cifras de TSH. Las diferencias geográficas son poco relevantes(AU)
Objective. It is our aim to estimate the prevalence of hypothyroidism treated in our health care area from the prescription of thyroid hormone. Likewise, we describe its characteristics and differences on the basis of various socio-demographic factors. Design. Cross sectional descriptive-type study. Location. Guadalajara (Spain) health care area. Participants. Subjects under treatment with levothyroxine for hypothyroidism included on health card throughout the year 2009. Main Measures. Distribution by gender, age and place of residence, after rate adjustment. Other analyzed variables were the type of hypothyroidism, last prescribed dosage and TSH levels, compared according to socio-demographic variables. Results. 3,3% of the population (IC 95%: 3,3-3,4) were treated with levothyroxine (5,8% female y 1,0% male), with the highest rate being seen in women over 65 years old (11,9%). The adjusted rate was 38,8/1000 (IC 95%: 37,7-40,0) for urban areas and 34,6/1000 (IC 95%: 33,4-35,8) for rural areas. Average age 56,6 years (DE: 18,2). An autoimmune origin is assumed in 76% of cases with a recognizable cause, using an average dose of 76,84mcg/day. 76,2% of the patients showed a correct level TSH. Conclusions. Subclinical hypothyroidism is a frequent complaint among Health Centre users and has a chiefly autoimmune origin. Diagnosis is more frequent in females and in older members of the population. TSH figures are usually closely checked. Geographical differences of little significance(AU)
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hipotiroidismo/epidemiología , Hipotiroidismo/prevención & control , Triyodotironina/uso terapéutico , Tiroxina/metabolismo , Tiroxina/uso terapéutico , Estudios Transversales/métodos , Estudios Transversales/normas , Estudios Transversales , Atención Primaria de Salud/métodos , Atención Primaria de Salud/tendencias , Atención Primaria de Salud , Hipotiroidismo/etiologíaRESUMEN
BACKGROUND: Changes in meteorological parameters have been associated with cardiovascular mortality and stroke. The high incidence of stroke in Portugal may be modelled by short- or long-term weather changes whose effect may be different across stroke types and severity. METHODS: Data include all patients with a first-ever-in-a-lifetime stroke registered in a population of 86,023 residents in the city of Porto from October 1998 to September 2000. Specific stroke types were considered and ischaemic stroke (IS) subtype was defined according to the Oxfordshire Community Stroke Projet classification and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Information on daily temperature, humidity and air pressure was obtained from the National Meteorological Office. The Poisson distribution was used to model the daily number of events as a function of each weather parameter measured over different hazard periods, and the binomial model to contrast effects across subgroups. Differential effects of meteorological parameters and hazard periods upon stroke occurrence and outcome were analysed in a stepwise model. RESULTS: Among the 462 patients registered, 19.6% had a primary intracerebral haemorrhage (PICH) and 75.3% an IS. Among patients with IS, 21.6% were total anterior circulation infarcts (TACIs), 19.8% partial anterior circulation infarcts (PACIs), 19.5% posterior circulation infarcts (POCIs) and 39.1% were lacunar infarcts (LACIs). The aetiology of IS was large artery atherosclerosis in 6.9%, cardioembolism in 23.3% and small artery occlusion in 35.6%. The incidence of PICH increased by 11.8% (95% CI: 3.8-20.4%) for each degree drop in the diurnal temperature range in the preceding day. The incidence of IS increased by 3.9% (95% CI: 1.6-6.3%) and cardioembolic IS by 5.0% (95% CI: 0.2-10.1%) for a 1°C drop in minimum temperature in the same hazard period. The incidence of TACIs followed the IS pattern while for PACIs and POCIs there were stronger effects of longer hazard periods and no association was found for LACIs. The relative risk of a fatal versus a non-fatal stroke increased by 15.5% (95% CI: 6.1-25.4%) for a 1°C drop in maximum temperature over the previous day. CONCLUSIONS: Outdoor temperature and related meteorological parameters are associated with stroke occurrence and severity. The different hazard periods for temperature effects and the absence of association with LACIs may explain the heterogeneous effects of weather on stroke occurrence found in community-based and hospital admission studies. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.
Asunto(s)
Accidente Cerebrovascular/epidemiología , Tiempo (Meteorología) , Anciano , Presión Atmosférica , Intervalos de Confianza , Embolia/complicaciones , Embolia/epidemiología , Femenino , Humanos , Humedad , Infarto de la Arteria Cerebral Posterior/complicaciones , Hemorragias Intracraneales/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Distribución de Poisson , Población , Portugal/epidemiología , Factores de Riesgo , Estaciones del Año , Factores Sexuales , Accidente Cerebrovascular/mortalidad , Accidente Vascular Cerebral Lacunar/epidemiología , Accidente Vascular Cerebral Lacunar/mortalidad , Accidente Vascular Cerebral Lacunar/terapia , Temperatura , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Several studies conducted in hospital emergency departments have shown that most patients delay in responding to stroke symptoms. In the general population, recognition of stroke and the appropriate reactions are important for prevention and acute treatment, particularly in areas with a high stroke incidence. The objective of this study was to compare general knowledge about stroke/TIA and prompt action in urban and rural populations. METHODS: In the first half of 2007, a cross-sectional study on stroke knowledge was undertaken in rural and urban populations from the Viana do Castelo district. About 1% of people aged at least 18 years registered at three community health centers were asked to check a list of vascular risk factors (VRF), stroke/TIA warning signs, and other non-specific signs, as well as indicate how they would react in the presence of warning signs or stroke/TIA. RESULTS: The 347 urban participants were on average younger than the 316 rural participants (46 vs. 51 years) and fewer had a low educational level (44 vs. 62% had less than 5 years of full education). About 50% identified at least 8 out of 13 VRF and indicated the brain as the body location; 39.7% recognized simultaneously the three key warning signs of the FAST campaign - irrespective of gender, educational level, and residential area. Education and urban environment increased the odds of calling the emergency medical services (EMS), while age had the opposite effect. After adjustment, recognition of brain location and calling EMS in case of paralysis/weakness or dizziness/vertigo increased the odds of calling the EMS in case of stroke, while recognition of the warning signs was not associated with an EMS call. CONCLUSIONS: People's reaction to stroke depends mostly on their sociodemographic profile and their reaction to specific warning signs, independently of recognizing them as 'originating from stroke'.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Población Rural/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Escolaridad , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
La infección por citomegalovirus (CMV) debe ser investigada en pacientes sanos con cuadro pseudogripal consistente en fiebre, astenia, aumento inexplicado de los niveles de transaminasas y linfomonocitosis periférica. Es un cuadro relativamente frecuente, por lo que puede pasar totalmente desapercibido o con escasas manifestaciones clínicas, sobre todo en el paciente inmunocompetente. Los síntomas faríngeos y adenomegalias son menos frecuentes que en la infección mononucleósica por virus de Epstein-Barr. Presentamos el caso de un paciente sin factores de riesgo que presenta un cuadro febril prolongado y alteraciones hepáticas, con evolución espontánea a la normalización y serología compatible con infección por CMV(AU)
Cytomegalovirus (CMV) infection should be investigated in healthy patients who have flu-like symptoms consisting of fever, fatigue, unexplained increase of transaminases and peripheral lymphomonocytosis. These are relatively common symptoms so they may pass completely unnoticed or with few clinical manifestations, especially in immunocompetent patients. Pharyngeal symptoms and swollen lymph nodes are less frequent than in mononucleosis infection caused by Epstein-Barr virus. We report a case of a patient with no risk factors who presented with persistent fever and liver alterations, which resolved spontaneously and with serological findings compatible with a recent CMV infection(AU)
Asunto(s)
Humanos , Masculino , Adulto , Fiebre/complicaciones , Fiebre/diagnóstico , Fiebre/etiología , Citomegalovirus/aislamiento & purificación , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/etiología , Hepatitis/complicaciones , Inmunocompetencia , Tos/complicaciones , Tos/etiologíaRESUMEN
The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2-2.4 versus HR for men = 0.9, 95% CI 0.7-1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1-2.8) and current smokers (HR = 3.1, 95% CI 1.4-7.1), but not in former smokers (HR = 1.3, 95% CI 0.7-2.4). HFE mutations are associated with increased risk of incident CHD in women.
Asunto(s)
Enfermedad Coronaria/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana/genética , Anciano , Presión Sanguínea , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Enfermedad Coronaria/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Proteína de la Hemocromatosis , Humanos , Incidencia , Lípidos/sangre , Masculino , Persona de Mediana Edad , Mutación , Factores Sexuales , FumarRESUMEN
OBJECTIVE: To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals. METHODS AND RESULTS: In a population-based study of 7,983 individuals aged 55 years and older, we compared the risks of all-cause and coronary heart disease (CHD) mortality by APOE genotype, both overall and in subgroups defined by body mass index (BMI). We found significant evidence for interaction between APOE and BMI in relation to total cholesterol (p=0.04) and HDL cholesterol (p<0.001). Overall, APOE*2 carriers showed a decreased risk of all-cause mortality. Analyses within BMI strata showed a beneficial effect of APOE*2 only in normal weight persons (adjusted hazard ratio (HR) 0.7[95% CI 0.5-0.9]). APOE*2 was not associated with a lower risk of all-cause mortality in overweight or obese persons. The effect of APOE*2 in normal weight individuals tended to be due to the risk of CHD mortality (adjusted HR 0.5 [95% CI 0.2-1.2]). CONCLUSION: The APOE*2 allele confers a lower risk of all-cause mortality only to normal weight individuals.
Asunto(s)
Apolipoproteínas E/genética , Peso Corporal , Predisposición Genética a la Enfermedad/genética , Mortalidad , Anciano , Índice de Masa Corporal , Enfermedad Coronaria/mortalidad , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Incidencia , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Riesgo , Administración de la SeguridadAsunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/genética , Enfermedad Coronaria/mortalidad , ADN/genética , Polimorfismo Genético , Anciano , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Enfermedad Coronaria/genética , Enfermedad Coronaria/metabolismo , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Tasa de Supervivencia/tendenciasRESUMEN
In recent years there has been growing use of methamphetamine (METH) by pregnant women, resulting in an increasing number of children exposed prenatally to this drug of abuse. METH is known to be potentially neurotoxic to human adults, but there is minimal information with respect to the consequences of such exposure to the fetus. The purpose of this study was to ascertain external parameters of animal development, as well as neurochemical and immunohistochemical alterations at three key points of retinal development (postnatal day [PND] 7, 14, and 30). Rats of the Wistar strain were used in this experimental model. Pregnant females received a dose of 5 mg/kg body weight per day of METH-HCl in 0.9% saline, from gestational day (GD) 8 to 22. The control group to be used was pair fed and saline injected. Litters were randomly culled at PND 1 to 8 pups. Analysis of maternal body weight gain during pregnancy showed that females treated with METH had lower body weights than control-treated females. The body weight on PND 1, showed that animals treated with METH prenatally had smaller body weights than the control-treated animals and also that females weighed less than males. Prenatal exposure to METH did not alter the retinal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the male group and the level of dopamine (DA) in both female and male groups when compared with their respective pair fed control groups during the first month of life. Correlating with the neurochemical data, no obvious changes on the localization of TH immunoreactivity in the rat retina at PND 7, 14, and 30 could be detected between control and METH-treated animals. Thus, exposure to METH disrupted this pattern in a gender-dependent manner. These data confirm previous observation that developing rats are protected against the adult type of METH-induced neurotoxicity. Therefore, conventional markers used for adult animals appear to be unsatisfactory to demarcate boundaries of the PND 1 to 30 critical periods.
Asunto(s)
Intercambio Materno-Fetal , Metanfetamina/toxicidad , Preñez , Retina/efectos de los fármacos , Retina/embriología , Animales , Peso Corporal , Modelos Animales de Enfermedad , Dopaminérgicos/farmacología , Femenino , Inmunohistoquímica , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Retina/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Since the development of different cell types in the retina occurs at different rates, it is possible that exposure to an exogenous substance may produce effects during one time period, but not during another. This study aims to analyze the effects of methamphetamine (METH) in the growth pattern of an experimental model as well as neurochemical and immunohistochemical parameters of the dopaminergic system of the rat retina. The three development stages chosen in this study are key markers in rat eye development. Rats were given 15 mg/kg body weight per day of METH as subcutaneous injections in 0.9% saline (3 mL/kg weight/day) from the day after birth PND 1 to PND 6, PND 13, and PND 29. Each daily dose was split into two. The control group was injected subcutaneously with saline. Both the schedule and volume for injecting saline in the control group were the same as for the METH-treated group. There were no significant differences in the total number of offspring per litter among treatment groups. All offspring had similar body weight at birth. Analysis of body weight on PND 1, showed that animals treated with METH had similar body weights to control-treated animals and females had smaller weights than males. For growth evolution, only litters with a sex ratio of four males and four females were used. Animals treated with METH had smaller body weights than the control-treated animals for all ages studied (PND 7, 14, and 30). Within the control group at PND 30, a significant difference was found in the body weight of females, which was lower when compared with males. For the postnatal model, 7 deaths occurred for the METH-exposed group. No deaths occurred in the control group in a total of 16 saline-injected litters comprising 186 pups. Although the levels of dopamine (DA) was within normal values for the postnatally exposed METH group when compared with its respective control group at PND 7 and 30, at PND 14 this was not the case: in this experimental group, the level of DA was lower than in the control group for both females and males. Support for this result was not evident from the TH immunoreactivity studies, probably because the methodology lacks the sensitivity to distinguish any mild effects, such as that observed in the postnatal model at PND 14. The level of the DA metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) remained unaffected at all ages studied, for both females and males. The results obtained in this study support the view that, during the critical periods in which the catecholamines can influence the development of neurones, METH transiently affects the pattern of the dopaminergic system in the developing retina.
Asunto(s)
Dopamina/metabolismo , Metanfetamina/toxicidad , Retina/crecimiento & desarrollo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Tamaño Corporal , Modelos Animales de Enfermedad , Femenino , Masculino , Atención Posnatal , Ratas , Ratas Endogámicas BB , Retina/efectos de los fármacos , Retina/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
OBJECTIVE: To determine the differences in number of years lived free of cardiovascular disease (CVD) and number of years lived with CVD between men and women who were obese, pre-obese, or normal weight at 45 years of age. RESEARCH METHODS AND PROCEDURES: We constructed multistate life tables for CVD, myocardial infarction, and stroke, using data from 2551 enrollees (1130 men) in the Framingham Heart Study who were 45 years of age. RESULTS: Obesity and pre-obesity were associated with fewer number of years free of CVD, myocardial infarction, and stroke and an increase in the number of years lived with these diseases. Forty-five-year-old obese men with no CVD survived 6.0 years [95% confidence interval (CI), 4.1; 8.1] fewer than their normal weight counterparts, whereas, for women, the difference between obese and normal weight subjects was 8.4 years (95% CI: 6.2; 10.8). Obese men and women lived with CVD 2.7 (95% CI: 1.0; 4.4) and 1.4 years (95% CI: -0.3; 3.2) longer, respectively, than normal weight individuals. DISCUSSION: In addition to reducing life expectancy, obesity before middle age is associated with a reduction in the number of years lived free of CVD and an increase in the number of years lived with CVD. Such information is paramount for preventive and therapeutic decision-making by individuals and practitioners alike.
Asunto(s)
Envejecimiento , Enfermedades Cardiovasculares/epidemiología , Infarto del Miocardio/epidemiología , Obesidad/complicaciones , Accidente Cerebrovascular/epidemiología , Índice de Masa Corporal , Enfermedades Cardiovasculares/mortalidad , Costo de Enfermedad , Femenino , Humanos , Esperanza de Vida , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Obesidad/epidemiología , Obesidad/mortalidad , Sobrepeso/fisiología , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: There are no community-based studies on the incidence of transient ischemic attacks (TIAs) in Portugal. This study was designed to determine TIA incidence and the risk of stroke occurrence in rural and urban populations in northern Portugal. METHODS: All suspected first-ever TIAs occurring between October 1998 and September 2000 in 18,677 residents in a rural municipality and 86,023 living in the city of Porto were entered into a population-based registry. Standard definitions and comprehensive sources of information were used for identification of patients who were followed up at 3 and 12 months after the TIA. RESULTS: During a 24-month period, 141 patients with a first-ever TIA were registered, 36 in rural and 104 in urban areas. The vascular territory was carotid in 66.7% of the patients, vertebrobasilar in 29.1%, and undetermined in 4.3%. The overall crude annual incidence rate per 1000 was 0.67 (95% CI, 0.45 to 1.04), 0.61 (95% CI, 0.38 to 1.01) for rural, and 0.96 (95% CI, 0.43 to 2.33) for urban populations. The risk of stroke within the first 7 days of the index event was 12.8% (95% CI, 7.3 to 18.3), reaching 21.4% (95% CI, 14.6 to 28.1) at 1 year. Three factors were associated with stroke occurrence within 120 days after TIA: patients' age > or =65 years and an episode in the carotid distribution lasting > or =3 hours. CONCLUSIONS: The incidence of TIA in northern Portugal, particularly in rural populations, ranks among the highest reported in community-based studies, following closely the stroke incidence trend (ACINrpc). Early recognition of TIA by patients and physicians is crucial for effective stroke prevention.
Asunto(s)
Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Factores de Edad , Anciano , Arterias Carótidas/patología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Proyectos Piloto , Portugal , Pronóstico , Riesgo , Factores de Riesgo , Población Rural , Accidente Cerebrovascular , Factores de Tiempo , Población UrbanaRESUMEN
BACKGROUND AND PURPOSE: Mortality statistics indicate that Portugal has the highest stroke mortality in Western Europe. Data on stroke incidence in Northern Portugal, the region with the highest mortality, are lacking. This study was designed to determine stroke incidence and case fatality in rural and urban populations in Northern Portugal. METHODS: All suspected first-ever-in-a-lifetime strokes occurring between October 1998 and September 2000 in 37,290 residents in rural municipalities and 86,023 living in the city of Porto were entered in a population-based registry. Standard definitions and comprehensive sources of information were used for identification of patients who were followed-up at 3 and 12 months after onset of symptoms. RESULTS: During a 24-month period, 688 patients with a first-ever stroke were registered, 226 in rural and 462 in urban areas. The crude annual incidence was 3.05 (95% CI, 2.65 to 3.44) and 2.69 per 1000 (95% CI, 2.44 to 2.93) for rural and urban populations, respectively; the corresponding rates adjusted to the European standard population were 2.02 (95% CI, 1.69 to 2.34) and 1.73 (95% CI, 1.53 to 1.92). Age-specific incidence followed different patterns in rural and urban populations, reaching major discrepancy for those 75 to 84 years old, 20.2 (95% CI, 16.1 to 25.0) and 10.9 (95% CI, 9.0 to 12.8), respectively. Case fatality at 28 days was 14.6% (95% CI, 10.2 to 19.3) in rural and 16.9% (95% CI, 13.7 to 20.6) in urban areas. CONCLUSIONS: Stroke incidence in rural and urban Northern Portugal is high compared to that reported in other Western Europe regions. The high official mortality in our country, which could be explained by a relatively high incidence, was not because of a high case fatality rate.
Asunto(s)
Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Estudios Prospectivos , Población Rural , Accidente Cerebrovascular/mortalidad , Población UrbanaRESUMEN
BACKGROUND: Neurological and cognitive sequelae resulting from cardiac arrest (CA), despite their potential personal and social impact, are usually not considered as major outcome measures in long-term analysis of survivors. The aim of this study is to analyze the contribution of neuropsychological testing and cerebral imaging to the development of a long-term classification of neurological impairment. PATIENTS AND METHODS: A total of 19 patients admitted over a 3 years period in an eight-bed intensive care unit of a tertiary care hospital with a diagnosis of CA were alive and attended a 6-month follow-up consultation. Eleven of these patients agreed to participate in this study carried out between 1 and 3 years after CA. Patients were classified using the Cerebral Performance Categories (CPC), neurological examination, detailed cognitive testing and computerized tomography (CT) scan with qualitative and quantitative imaging analysis. RESULTS: Six of the 11 patients had good cerebral performance. Verbal and visuo-spatial short-term memory scores were associated with CPC. All patients with at least moderate cerebral disability had abnormal verbal memory test results compared with only one survivor with CPC 1; visuo-spatial short-term memory was abnormal in four moderately affected survivors and normal in those with CPC 1. The bicaudate ratio evaluated in the CT scan was correlated with the verbal memory score while the III ventricle diameter correlated with the executive functions score, suggesting involvement of different brain areas in these functions. CONCLUSIONS: Neuropsychological and CT scan measurements are proxy measures of long-term impairment of CA survivors, providing a dichotomized global evaluation of CA survivors in close agreement with CPC.
Asunto(s)
Reanimación Cardiopulmonar/métodos , Trastornos del Conocimiento/diagnóstico , Paro Cardíaco/complicaciones , Trastornos de la Memoria/diagnóstico , Calidad de Vida , Adulto , Distribución por Edad , Anciano , Reanimación Cardiopulmonar/efectos adversos , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/etiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Paro Cardíaco/terapia , Humanos , Incidencia , Unidades de Cuidados Intensivos , Masculino , Trastornos de la Memoria/epidemiología , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Variaciones Dependientes del Observador , Portugal/epidemiología , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Sobrevivientes , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodosRESUMEN
Methamphetamine (Meth) is an illicit substance known to interfere with catecholaminergic systems and a popular recreational drug among young adult women, that is, in gestational age. Tyrosine hydroxylase (TH), the rate-limiting enzyme of the synthetic pathway of catecholamines, is a good marker to assess potential effects of Meth in catecholaminergic (particularly in dopaminergic) systems. In the rat, prolonged neonatal Meth exposure altered several dopaminergic markers (TH activity and gene expression) in substantia nigra pars compacta (SN) and in caudate-putamen (TH activity) when animals matured. However, it was never verified whether gestational exposure to Meth might compromise TH enzyme in the pups during the neonatal immature periods. The present study was designed to address this issue by analyzing TH gene expression, measured by in situ hybridization in SN and ventral tegmental area (VTA), dopaminergic areas that are well characterized as target areas for Meth, and in rats prenatally exposed to this psychostimulant. To this end, dated pregnant Wistar rat dams received 5 mg Meth hydrochloride/kg body weight/day. It was administered subcutaneously from gestational day 8 until 22. The control group was pair-fed and saline injected, using the same experimental protocol as for Meth-treated dams. On the day of birth (postnatal day 0, PND 0), litters were culled to 8 pups, sex-balanced whenever possible, and were followed until the day of sacrifice (PND 7, 14, or 30). Meth treatment differentially affected TH mRNA levels in VTA and SN, in an age- and gender-dependent manner. Thus, TH mRNA levels were decreased in the VTA of PND 7 and PND 14 females gestationally exposed to Meth; this effect was not evident in males or on PND 30. TH mRNA levels also tend to decrease in SN of PND 14 females gestationally exposed to Meth. Collectively, the present results indicated that gestational Meth exposure affects TH gene expression in the postnatal life, a phenomenon that appears to be transient, since it is no longer evident by the end of the first month of life in the rat.