RESUMO
BACKGROUND: Poor medication adherence is a major factor in the secondary prevention of cardiovascular diseases (CVD) and contributes to increased morbidity, mortality, and costs. Interventions for improving medication adherence may have limited effects as a consequence of self selection of already highly adherent participants into clinical trials. METHODS: In this retrospective cohort study, existing levels of medication adherence were examined in self-decided participants and non-participants prior to inclusion in a randomized controlled study (RCT), evaluating the effect of an intervention to improve adherence. In addition, the non-participants were further divided into 'responders' and 'non responders'. All individuals had manifest cardiovascular disease and completed a questionnaire with baseline characteristics, the Beliefs about Medicines Questionnaire (BMQ) and the Modified Morisky Scale® (MMS®) as part of a regular screening program. A logistic regression was conducted to examine the relationship between study participation willingness, adherence level and the beliefs about medication. RESULTS: According to the MMS® the adherence level was comparable in all groups. In both (non)-participants groups, 36% was classified as high adherent; 46% participants versus 44% non-participants were classified as medium adherent and 19% of the participants versus 20% of the non-participants were low adherent (p = 0.91. The necessity concern differential (NCD) from the BMQ was 3.8 for participants and 3.4 for non-participants (p = 0.32). CONCLUSION: This study shows that adherence to medication and beliefs about medication do not differ between participants and non-participants before consenting to participate in an RCT. The study design seems not to have led to greater adherence in the study group.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Comportamento de Redução do Risco , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária/métodos , Inquéritos e QuestionáriosRESUMO
Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (P<0.05) most likely explained by an association of methylation state of the 5' flanking CpG island and expansion size in blood (P<0.0001) and brain (P<0.05). In several informative C9orf72 parent-child transmissions, we identified earlier onset ages, increasing expansion sizes and/or increasing methylation states (P=0.0034) of the 5' CpG island, reminiscent of disease anticipation. Also, intermediate repeats (7-24 units) showed a slightly higher methylation degree (P<0.0001) and a decrease of C9orf72 promoter activity (P<0.0001) compared with normal short repeats (2-6 units). Decrease of transcriptional activity was even more prominent in the presence of small deletions flanking G4C2 (P<0.0001). Here we showed that increased methylation of CpGs in the C9orf72 promoter may explain how an increasing G4C2 size lead to loss-of-function without excluding repeat length-dependent toxic gain-of-function. These data provide insights into disease mechanisms and have important implications for diagnostic counseling and potential therapeutic approaches.
Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas/genética , Adulto , Idade de Início , Esclerose Lateral Amiotrófica/metabolismo , Bélgica , Proteína C9orf72 , Ilhas de CpG/genética , Metilação de DNA/genética , Regulação para Baixo , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/metabolismo , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Proteínas/metabolismoRESUMO
Alzheimer's disease (AD) is the most common cause of dementia, characterized by the progressive impairment of cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % of the AD cases and is induced by a complex interplay between genetic and environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) and pesticides (e.g. fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects of Alzheimerogens. We compared transcriptomics changes in sAD induced pluripotent stem cell (iPSC) derived cortical neurons to differentially expressed genes (DEGs) identified in post-mortem AD brain tissue. These analyses showed that many AD-related processes could be identified in the sAD iPSC-derived neurons, and furthermore, could even identify more DEGs functioning in these processes than post-mortem AD-brain tissue. Thereafter, we exposed the iPSCs to AD-inducing factors (copper(II)chloride, fipronil sulfone and an inflammatory cytokine cocktail). Cytokine exposure induced expression of immune related genes while copper-exposure affected genes involved in lipid and cholesterol metabolism, which are known AD-related processes. Fipronil-exposure did not result in significant transcriptomic changes, although prolonged exposures or higher doses may be necessary. Overall, we show that iPSC-derived cortical neurons can be beneficial in vitro models to identify Alzheimerogens and AD-related molecular mechanisms.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Neurônios/fisiologia , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/genética , Diferenciação Celular , Cobre/toxicidade , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica , Humanos , Masculino , Metais Pesados/toxicidade , Neurônios/efeitos dos fármacos , Praguicidas/toxicidade , Transcriptoma , Proteínas tau/genéticaRESUMO
OBJECTIVES: Anti-Hu antibodies (Hu-Abs) are the most frequent onconeural antibodies associated with paraneoplastic neurologic syndromes (PNS). PNS include a variety of neurological syndromes, affecting less than 1/10,000 patients with cancer. In the majority of cases, PNS will manifest before the malignancy is diagnosed. We found a case in which PNS was diagnosed without finding a primary malignancy after extensive work-up and even post-mortem autopsy. PATIENT AND METHODS: We present a case report of a 58-year-old man. This article includes extensive clinical work-up, full-body autopsy and brain autopsy with classical histochemical and myelin stainings and immunohistochemistry was performed. RESULTS: The patient developed a progressive trigeminal neuropathy over a period of 5 years, in combination with cerebellar degeneration, asymmetrical brainstem and limbic encephalitis. Serum showed repeatedly high anti-Hu antibodies. Comprehensive cancer screening could not demonstrate any primary malignancy. Therapy with corticosteroids, plasma exchange, cyclophosphamide and rituximab showed no beneficial effect. He died from the complications of enteric ganglionitis 5 years after onset of the first symptoms. A postmortem autopsy could not detect a primary malignancy either. Brain morphology is described in detail. CONCLUSION: Paraneoplastic anti-Hu encephalitis cases associated with SCLC or other primary neoplasms are well known. An adult with a progressive multifocal neurological syndrome in the presence of positive anti-Hu antibodies, but without any primary neoplasm after a follow-up over 5 years is unusual.
Assuntos
Dor Abdominal/etiologia , Doenças Autoimunes/complicações , Encefalite Límbica/etiologia , Doenças do Nervo Trigêmeo/etiologia , Anticorpos Antinucleares , Autopsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND/AIM: Although most late-onset seizures (LS) appear within 2 years after stroke, some of them occur later and their characteristics are unknown. The aim of this study was to compare the characteristics of patients with very-late-onset seizures (VLS) to those with early-onset seizures (ES) and those with LS. PATIENTS: The study group consisted of 204 patients with stroke-related seizures (29 ES, 128 LS and 47 VLS). RESULTS: Intracranial haemorrhage was a more frequent cause of ES than of LS and no cause at all of VLS. On the other hand, 25% of the VLS were related to lacunar strokes. Status epilepticus occurred in 20.7% of the ES, in 11.7% of the LS and in 2.1% of the VLS patients. Seizure recurrences were 13.8% in the ES, 54.7% in the LS and 34.0% in the VLS group. Neurological impairment, at stroke onset, and the degree of disability were more severe in patients with ES compared to those with LS and were very mild in the VLS group. The EEG findings as a whole did not show significant differences between the three groups, although a normal EEG was more frequent in the VLS group. CONCLUSION: VLS occur in patients with minor ischaemic strokes with good recovery and benign disease course.
Assuntos
Convulsões/epidemiologia , Convulsões/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Encéfalo/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Masculino , Recuperação de Função Fisiológica , TempoRESUMO
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, and Nasu Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy are both underrecognized progressive degenerative white matter diseases that can present with young dementia, leukoencephalopathy and brain calcifications. We report and compare three cases in terms of clinical phenotype, imaging and neuropathological findings. Both cases have led to the identification of two novel causal mutations.
Assuntos
Encéfalo/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Demência/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Leucoencefalopatias/diagnóstico por imagem , Lipodistrofia/diagnóstico por imagem , Osteocondrodisplasias/diagnóstico por imagem , Panencefalite Esclerosante Subaguda/diagnóstico por imagem , Adulto , Encéfalo/patologia , Calcinose/patologia , Demência/patologia , Epilepsia/patologia , Feminino , Humanos , Leucoencefalopatias/patologia , Lipodistrofia/patologia , Masculino , Pessoa de Meia-Idade , Osteocondrodisplasias/patologia , Panencefalite Esclerosante Subaguda/patologiaRESUMO
In this report, we describe the peculiar eye movements of a young man who became comatose after a head injury. The eyes moved rhythmically from one side to another, without pausing in the lateral positions. This phenomenon has been described as "ping pong gaze" (PPG), referring to short-cycling periodic alternating gaze with smooth eye deviations. In the present patient, however, a saccadic type of PPG could be confirmed by oculography. Possible clinical and pathophysiological implications are discussed.
Assuntos
Coma/etiologia , Traumatismos Craniocerebrais/complicações , Transtornos da Motilidade Ocular/etiologia , Movimentos Sacádicos/fisiologia , Adulto , Coma/patologia , Nervo Facial/fisiopatologia , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Condução Nervosa/fisiologiaRESUMO
Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.
Assuntos
Doença de Alzheimer/prevenção & controle , Apolipoproteínas E/genética , Terapia de Reposição de Estrogênios , Estrogênios/uso terapêutico , Menopausa , Fármacos Neuroprotetores/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Feminino , Humanos , Incidência , PrevalênciaRESUMO
The aim of this study was to evaluate the impact of a structured screening and nurse-based intervention on cardiovascular risk factors. In patients with established cardiovascular disease, a cardiovascular risk profile was assessed, and lifestyle was evaluated by using an automated questionnaire. A multidisciplinary team proposed an integral individualized plan of care on the basis of these assessments. During follow-up, a nurse-led lifestyle intervention program and the best medical treatment were offered. A total of 328 outpatients were included. After screening, a follow-up term of at least 1 year was reached in 176 patients (59.9%). Low-density lipoprotein cholesterol and systolic blood pressure were significantly reduced. A reduction in the amount of smoking, alcohol consumption, and unhealthy eating habits was observed. However, the amount of physical activity was unaffected, and body mass was increased. A structural evaluation of cardiovascular risk factors and an integrated nurse-led approach can successfully reduce risk in cardiovascular patients.