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1.
Artigo em Inglês | MEDLINE | ID: mdl-31963654

RESUMO

Ischemic stroke is the most common type of stroke, and early interventional treatment is associated with favorable outcomes. In the guidelines, thrombolytic therapy using recombinant tissue-type plasminogen activator (rt-PA) is recommended for eligible patients with acute ischemic stroke. However, the risk of hemorrhagic complications limits the use of rt-PA, and the risk factors for poor treatment outcomes need to be identified. To identify the risk factors associated with in-hospital poor outcomes in patients treated with rt-PA, we analyzed the electronic medical records of patients who were diagnosed with acute ischemic stroke and treated for rt-PA at Chang Gung Memorial Hospitals from 2006 to 2016. In-hospital death, intensive care unit (ICU) stay, or prolonged hospitalization were defined as unfavorable treatment outcomes. Medical history variables and laboratory test results were considered variables of interest to determine risk factors. Among 643 eligible patients, 537 (83.5%) and 106 (16.5%) patients had favorable and poor outcomes, respectively. In the multivariable analysis, risk factors associated with poor outcomes were female gender, higher stroke severity index (SSI), higher serum glucose levels, lower mean corpuscular hemoglobin concentration (MCHC), lower platelet counts, and anemia. The risk factors found in this research could help us study the treatment strategy for ischemic stroke.

2.
Int J Stroke ; 14(7): 670-677, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31226919

RESUMO

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

3.
J Pineal Res ; 66(1): e12538, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30415481

RESUMO

Cyclic 3-hydroxymelatonin (C3-OHM) and N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) are two major cascade metabolites of melatonin. We previously showed melatonin provides multiple levels of mitochondria-targeted protection beyond as a mitochondrial antioxidant during ionomycin-induced mitochondrial Ca2+ (mCa2+ ) stress in RBA1 astrocytes. Using noninvasive laser scanning fluorescence coupled time-lapse digital imaging microscopy, this study investigated whether C3-OHM and AFMK also provide mitochondrial levels of protection during ionomycin-induced mCa2+ stress in RBA1 astrocytes. Interestingly, precise temporal and spatial dynamic live mitochondrial images revealed that C3-OHM and AFMK prevented specifically mCa2+ -mediated mitochondrial reactive oxygen species (mROS) formation and hence mROS-mediated depolarization of mitochondrial membrane potential (△Ψm ) and permanent lethal opening of the MPT (p-MPT). The antioxidative effects of AFMK, however, were less potent than that of C3-OHM. Whether C3-OHM and AFMK targeted directly the MPT was investigated under a condition of "oxidation free-Ca2+ stress" using a classic antioxidant vitamin E to remove mCa2+ -mediated mROS stress and the potential antioxidative effects of C3-OHM and AFMK. Intriguingly, two compounds still effectively postponed "oxidation free-Ca2+ stress"-mediated depolarization of △Ψm and p-MPT. Measurements using a MPT pore-specific indicator Calcein further identified that C3-OHM and AFMK, rather than inhibiting, stabilized the MPT in its transient protective opening mode (t-MPT), a critical mechanism to reduce overloaded mROS and mCa2+ . These multiple layers of mitochondrial protection provided by C3-OHM and AFMK thus crucially allow melatonin to extend its metabolic cascades of mitochondrial protection during mROS- and mCa2+ -mediated MPT-associated apoptotic stresses and may provide therapeutic benefits against astrocyte-mediated neurodegeneration in the CNS.


Assuntos
Astrócitos/efeitos dos fármacos , Melatonina/farmacologia , Mitocôndrias/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Astrócitos/citologia , Cálcio/metabolismo , Células Cultivadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
4.
Ther Adv Neurol Disord ; 11: 1756286418802688, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30283500

RESUMO

Background: To compare the long-term clinical outcomes of different antihypertensive drugs in stable patients after acute hemorrhagic stroke (HS). Methods: From January 2001 to December 2013, patients with first-ever primary HS were identified in the National Health Insurance Research Database, Taiwan. Patients with traumatic intracerebral hemorrhage and secondary HS were excluded. Those with first-ever HS were recruited and classified into three groups: (1) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB); (2) calcium channel blocker (CCB); and (3) other antihypertensive drugs (comparison) groups. Propensity score matching was used to balance the distribution of baseline characteristics, stroke severity, and medications between any two of the three groups. A validation study was performed using the databank of the Stroke Registry in Chang-Gung Healthcare System to reduce the bias. Primary outcomes were recurrent HS, ischemic stroke, any stroke, and all-cause mortality. Results: Compared to the comparison group, the ACEI/ARB group [35.4% versus 39.3%; hazard ratio (HR), 0.84; 95% confidence interval (CI), 0.74-0.95] and CCB group (33.0% versus 41.9%; HR, 0.72; 95% CI, 0.64-0.81) had a lower risk of all-cause mortality during long-term follow up. The CCB group had a similar risk of all-cause mortality to the ACEI/ARB group. Risks of recurrent HS, ischemic stroke, or any stroke were not different between the study groups. Conclusions: Antihypertensive drug class could be important to long-term outcomes in HS patients in addition to the target control of blood pressure. Both ACEIs/ARBs and CCBs are associated with lower risks of all-cause mortality. Our results may be applied to inform future research on hypertensive control in HS patients.

5.
Int J Geriatr Psychiatry ; 33(8): 1019-1027, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29726588

RESUMO

OBJECTIVE: Few studies have investigated the relationship between specific body measures and dementia. METHODS: Three-dimensional anthropometric body surface scanning data containing 38 body measures were collected from 6831 participants from the health examination department of a medical center in Taiwan during 2000 to 2008, and 236 dementia cases were identified during the 10-year follow-up. A multiple Cox regression analysis was performed. RESULTS: Specific body measures, namely chest width (hazard ratio [HR] = 0.90; 95% confidence interval [CI] = 0.83-0.98), and right thigh circumference (HR = 0.93; 95% CI = 0.90-0.96), were protective predictors to dementia occurrence. Waist circumference (HR = 1.03; 95% CI = 1.02-1.05) was a risk factor in dementia occurrence. Among the combinations, dementia risk was higher in participants with a larger waist circumference and a smaller right thigh circumference, with the highest HR of 2.49 (95% CI = 1.54-4.03). CONCLUSION: The body measures provide clues for future applications and scientific merits in both clinical and preventive medicine.


Assuntos
Demência/diagnóstico , Coxa da Perna/anatomia & histologia , Tórax/anatomia & histologia , Circunferência da Cintura , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan
6.
Angiology ; 69(7): 582-590, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29105494

RESUMO

Causes of death in both ischemic stroke (IS) and hemorrhagic stroke (HS) subtypes are not comprehensively studied. Between 2008 and 2011, we enrolled 11 215 first-ever stroke patients from the Stroke Registry of Chang-Gung Healthcare System and linked these data to the national death registry. The main causes of death in each stroke subtype were assessed. Patients with HS had higher overall mortality than IS (32.0% vs 18.1%, P < .001). In IS subtypes, large-artery atherosclerosis plus cardioembolism had the worst mortality (40.7%, P < .001). Stroke was the leading cause of death in both IS and HS within the first year. Stroke remained the major cause of death in HS, but cancer was the leading cause of death in IS after the first year. After excluding the patients with previous cancer history, cancer was still an important cause of death in IS and HS, particularly in the IS subtypes of small vessel occlusion, stroke of undetermined etiology, and transient ischemic attack.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Isquemia Encefálica/mortalidade , Causas de Morte , Hemorragias Intracranianas/mortalidade , Sistema de Registros , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/etnologia , Feminino , Humanos , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/etnologia , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida , Taiwan
7.
BMC Cardiovasc Disord ; 17(1): 154, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28610565

RESUMO

BACKGROUND: Many studies have determined that dehydration is an independent predictor of outcome after ischemic stroke (IS); however, none have determined if the use of thrombolytic therapy modifies the negative impact of poor hydration. To inform the stroke registry established at our institution, we conducted a retrospective study to determine if dehydration remains a negative prognostic factor after IS patients treated with tissue plasminogen activator (tPA). METHODS: Between 2007 and 2012, we recruited 382 subjects; 346 had data available and were divided into 2 groups on the basis of their blood urea nitrogen/creatinine (BUN/Cr) ratio. Dehydrated subjects had a BUN/Cr ratio ≥ 15; hydrated subjects had a BUN/Cr < 15. The primary outcome was impairment at discharge as graded by the Barthel Index (BI) and the modified Rankin Scale (mRS). RESULTS: The dehydration group had a greater mean age; more women; lower mean levels of hemoglobin, triglycerides, and sodium; and higher mean potassium and glucose levels. A favorable outcome as assessed by the mRS (≤2) was significantly less frequent among dehydrated subjects, but a favorable outcome by the BI (≥60) was not. Logistic regression and multivariate models confirmed that dehydration is an independent predictor of poor outcome by both the mRS and the BI; however, it was not predictive when patients were stratified by Trial of Org 10,172 in Acute Stroke Treatment subtype. CONCLUSIONS: Our findings indicate that use of thrombolytic therapy does not eliminate the need to closely monitor hydration status in patients with IS.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Desidratação/complicações , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Equilíbrio Hidroeletrolítico , Idoso , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Distribuição de Qui-Quadrado , Creatinina/sangue , Desidratação/diagnóstico , Desidratação/fisiopatologia , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
8.
J Clin Neurosci ; 43: 192-195, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28511974

RESUMO

Recognizing the cause is essential for the management of meralgia paresthetica (MP), also known as lateral femoral cutaneous neuropathy. The aim of this study was to investigate the etiologies of MP and their influence on each other. This retrospective study enrolled referral patients with electromyographic studies who fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to December 2013. Data including age, gender, body weight, body height, occupation, and relevant medical history were collected. The etiological analysis was based on age and gender. A total of 50 patients (30 males and 20 females) were enrolled. The average age (±standard deviation) at diagnosis was 49.8±12.8years. Risk factors were identified in 29 cases (58.0%). More patients younger than 50years of age were male (73.1%, p=0.049). Peaks of age occurred between 41-50years in men and 51-60years in women. More males had a body mass index≥24kg/m2 (69.2% vs. 31.6%, p=0.012) and ≥27kg/m2 (34.6% vs. 0.0%, p=0.006). Overweight and obese patients were more vulnerable to occupational factors (50.0% vs. 19.0%, p=0.030). Only one case had diabetes mellitus (2%). Male middle-aged patients with a higher body mass index and certain occupations had an increased risk of MP. In contrast to the peak age distribution of the male patients, the frequency of developing MP was relatively even among the women at all ages. The cause was often obscure.


Assuntos
Síndromes de Compressão Nervosa/epidemiologia , Adulto , Feminino , Neuropatia Femoral , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
9.
J Stroke Cerebrovasc Dis ; 26(8): 1695-1703, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28408066

RESUMO

BACKGROUND AND PURPOSE: As Chinese Asian populations have an increased risk of intracerebral hemorrhage (ICH) after intravenous tissue plasminogen activator (IV tPA), we aimed to design a rapid, clinically applicable risk scoring system to predict ICH and functional outcomes after IV tPA treatment in Asian ischemic stroke patients. METHODS: From January 2009 to December 2012, consecutive acute ischemic stroke patients treated with IV tPA recruited from the Stroke Registry in Chang Gung Healthcare System (SRICHS) in Taiwan and the National University Hospital of Singapore (NUHS) acute stroke database were used to create and validate a scoring system. Nomogram was created for ICH and 3-month mortality. RESULTS: In total, 932 patients were included in the study: 386 from SRICHS for the derivation of scoring system and 546 from NUHS to validate it. We used nomograms to assign weightage to the scoring system. The presence of atrial fibrillation, glucose level, and the National Institutes of Health Stroke Scale (NIHSS) score were significantly associated with the risk of ICH. Age, NIHSS score, hyperlipidemia, and the presence of post-tPA ICH were significantly associated with mortality. The areas under the curve of derivation and validation cohorts were .663 and .662 for ICH, and .808 and .790 for mortality, respectively. CONCLUSIONS: The scoring system using nomograms can provide a fast, practical, and user-friendly tool that allows physicians to predict the risk of ICH and functional outcomes with IV tPA treatment in a clinical setting.


Assuntos
Grupo com Ancestrais do Continente Asiático , Técnicas de Apoio para a Decisão , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Seleção de Pacientes , Valor Preditivo dos Testes , Sistema de Registros , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Singapura/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Taiwan/epidemiologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
10.
Clin Appl Thromb Hemost ; 23(7): 814-820, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27443695

RESUMO

BACKGROUND: The risk of symptomatic infarct swelling has been reported to be higher in patients treated with recombinant tissue plasminogen activator (rt-PA). The aim of this study was to evaluate the timing of symptomatic infarct swelling after rt-PA treatment. METHODS: We retrospectively analyzed 14 868 patients with acute ischemic stroke from a stroke registry databank. We recruited patients with massive middle cerebral artery (MCA) infarction and symptomatic infarct swelling and excluded those with parenchymal or symptomatic hemorrhage. Multiple linear regression and multivariate logistic regression analyses were used to estimate the impact of rt-PA on the timing of symptomatic infarct swelling. RESULTS: A total of 23 patients with rt-PA treatment and 117 patients without rt-PA treatment were included. The rt-PA treatment group had a lower rate of coronary artery disease (8.7% vs 32.5%; P = .023), lower severity of baseline National Institutes of Health Stroke Scale score (19 vs 23; P = .014), shorter duration of infarct swelling (27.6 vs 45.4 hours; P < .001), and higher rate of hemicraniectomy surgery (65.2% vs 28.2%; P =.001) than those without rt-PA treatment. After adjusting for variables in multiple linear regression analysis, rt-PA treatment and an elevated C-reactive protein level were associated with early symptomatic infarct swelling ( P = .014 and P = .041, respectively). The rt-PA treatment was an independent factor related to early symptomatic infarct swelling within 36 hours ( P = .005; odds ratio [OR]: 5.3; confidence interval [CI]: 1.65-17.0) or 48 hours ( P = .009; OR: 16.4; CI: 2.00-134). CONCLUSION: Intravenous rt-PA treatment may hasten the onset of cerebral edema and subsequent cerebral herniation in large MCA territory infarction.


Assuntos
Infarto da Artéria Cerebral Média/patologia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Edema Encefálico , Proteína C-Reativa/análise , Estudos de Casos e Controles , Doença da Artéria Coronariana , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia , Ativador de Plasminogênio Tecidual/uso terapêutico
11.
J Stroke Cerebrovasc Dis ; 25(11): 2660-2667, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27480821

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a risk factor for atrial fibrillation (AF) and is known to be an important risk factor for death from stroke. The influence of AF on long-term outcomes in patients with ischemic stroke remains controversial. To clarify the exact influence of AF on stroke outcome and exclude the effect from DM, we investigated the influence of AF on the 3-year outcomes of nondiabetic patients with acute first-ever ischemic stroke. METHODS: Five-hundred seventy-four nondiabetic patients with acute first-ever ischemic stroke were enrolled and had been followed for 3 years. Patients were divided into 2 groups according to whether AF was diagnosed or not. Clinical presentations, risk factors for stroke, laboratory data, comorbidities, and outcomes were recorded. RESULTS: A total of 107 patients (18.6%) had AF. The age was significantly older in patients with AF. Total anterior circulation syndrome occurred more frequently among patients with AF (P < .001). The mean length of stay in the acute ward was significantly higher in patients with AF (P < .001). Furthermore, dependent functional status following discharge was higher in patients with AF (P < .001). Multivariate Cox regression revealed that AF is a significant predictor of 3-year all-cause mortality (hazard ratio = 1.98, 95% confidence interval = 1.07-3.67, P = .022). CONCLUSIONS: AF is associated with increased risk of 3-year mortality in nondiabetic patients with acute first-ever ischemic stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.


Assuntos
Fibrilação Atrial/mortalidade , Isquemia Encefálica/mortalidade , Acidente Vascular Cerebral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Taiwan/epidemiologia , Fatores de Tempo
12.
J Clin Neurosci ; 33: 124-128, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27436765

RESUMO

The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P<0.001 and P=0.009, respectively). Multivariate Cox regression revealed that pneumonia in acute stroke stage is a significant predictor of 3-year mortality (hazard ratio=6.39, 95% confidence interval=4.03-10.11, P<0.001). In conclusion, pneumonia during the acute stroke stage is associated with increased risk of 3-year mortality. Interventions to prevent pneumonia in acute stroke stage might improve ischemic stroke outcome.


Assuntos
Isquemia Encefálica/complicações , Isquemia Encefálica/mortalidade , Pneumonia/complicações , Pneumonia/mortalidade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
13.
Clin Neurol Neurosurg ; 137: 15-21, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26117593

RESUMO

OBJECTIVE: The influence of renal dysfunction on the clinical presentation and outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of renal dysfunction on the outcomes of patients with acute first-ever ischemic stroke. METHODS: Nine-hundred thirty-four patients with acute first-ever ischemic stroke were enrolled and followed for 3 years. Renal function was assessed using the equation of the Modification Diet for Renal Disease for estimated glomerular filtration rate (eGFR). Serum creatinine levels were obtained within 3 days of acute stroke onset. Reduced eGFR was defined as eGFR<60ml/min/1.73m(2). Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. RESULTS: Total 264 patients (28.3%) had a reduced eGFR. The prevalence of older age, hypertension, and atrial fibrillation was significantly higher in patients with a reduced eGFR. Total anterior circulation syndrome occurred more frequently among patients with a reduced eGFR (P=0.010). Multivariate Cox regression revealed that a reduced eGFR is a significant predictor of 3-year mortality (HR=1.67, 95% CI=1.06-2.62, P=0.026). CONCLUSION: Reduced eGFR during the acute stroke stage is associated with increased risk of 3-year mortality. Furthermore, risk of acute complications and poor functional outcomes following discharge was significantly higher in patients with a reduced eGFR.


Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/complicações , Taxa de Filtração Glomerular/fisiologia , Nefropatias/complicações , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Feminino , Humanos , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
14.
J Stroke Cerebrovasc Dis ; 23(6): 1344-50, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24468071

RESUMO

BACKGROUND: Several coexisting diseases have been reported in patients with moyamoya vasculopathy (MMV), but studies of quasi-moyamoya disease (quasi-MMD) are rare. This study aims to investigate the frequency of known coexisting diseases in patients with quasi-MMD and to compare quasi-MMD with moyamoya disease (MMD). METHODS: Between 2000 and 2011, we retrospectively screened patients with International Classification of Diseases, Ninth Revision, code of 4375 (MMD) in the Health Information System of our hospital. The vascular images of each patient were confirmed by 2 neurologists and 1 neuroradiologist based on the diagnostic criteria of Japan Ministry of Health and Welfare. We excluded the patients with missing images and erroneous diagnosis. Demographics, coexisting diseases, laboratory data, treatment, and recurrent strokes were recorded. The eligible patients were divided into quasi-MMD and MMD groups according to the presence or absence of coexisting diseases. RESULTS: MMV was found in 90 patients including 37 (41.1%) quasi-MMD and 53 (58.9%) MMD. Atherosclerosis (32.4%) and thyroid disease (29.7%) were the leading coexisting diseases in quasi-MMD. Patients with MMD became symptomatic in a bimodal age distribution, whereas patients with quasi-MMD became symptomatic in a single-peak distribution. The prognosis of recurrent strokes was similar between quasi-MMD and MMD based on Kaplan-Meier analysis. CONCLUSIONS: A bimodal distribution of onset age was noted in MMD, whereas a single-peak distribution was found in quasi-MMD. Coexisting diseases were usually underevaluated but were more common than expected in patients with MMV. Atherosclerosis and thyroid diseases were the leading coexisting diseases in different preferential age.


Assuntos
Aterosclerose/epidemiologia , Doença de Moyamoya/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Free Radic Biol Med ; 67: 314-29, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24291231

RESUMO

Transient opening of the mitochondrial permeability transition pore plays a crucial role in hypoxic preconditioning-induced protection. Recently, the cyclophilin-D component of the mitochondrial permeability transition pore has been shown to interact with and regulate the F1F0-ATP synthase. However, the precise role of the F1F0-ATP synthase and the interaction between cyclophilin-D and F1F0-ATP synthase in the mitochondrial permeability transition pore and hypoxic preconditioning remain uncertain. Here we found that a 1-h hypoxic preconditioning delayed apoptosis and improved cell survival after stimulation with various apoptotic inducers including H2O2, ionomycin, and arachidonic acid in mitochondrial DNA T8993G mutation (NARP) osteosarcoma 143B cybrids, an F1F0-ATP synthase defect cell model. This hypoxic preconditioning protected NARP cybrid cells against focal laser irradiation-induced oxidative stress by suppressing reactive oxygen species formation and preventing the depletion of cardiolipin. Furthermore, the protective functions of transient opening of the mitochondrial permeability transition pore in both NARP cybrids and wild-type 143B cells can be augmented by hypoxic preconditioning. Disruption of the interaction between cyclophilin-D and F1F0-ATP synthase by cyclosporin A attenuated the mitochondrial protection induced by hypoxic preconditioning in both NARP cybrids and wild-type 143B cells. Our results demonstrate that the interaction between cyclophilin-D and F1F0-ATP synthase is important in the hypoxic preconditioning-induced cell protection. This finding improves our understanding of the mechanism of mitochondrial permeability transition pore opening in cells in response to hypoxic preconditioning, and will be helpful in further developing new pharmacological agents targeting hypoxia-reoxygenation injury and mitochondria-mediated cell death.


Assuntos
DNA Mitocondrial/genética , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Ácido Araquidônico/farmacologia , Cardiolipinas/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Quimera , Ciclofilinas/genética , Ciclofilinas/metabolismo , DNA Mitocondrial/metabolismo , Expressão Gênica , Humanos , Peróxido de Hidrogênio/farmacologia , Ionomicina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Mutação , Espécies Reativas de Oxigênio/metabolismo
16.
PLoS One ; 8(11): e81546, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24312318

RESUMO

BACKGROUND: F1F0-ATP synthase (F1F0-ATPase) plays important roles in regulating mitochondrial function during hypoxia, but the effect of F1F0-ATPase defect on hypoxia/reoxygenation (H/RO) is unknown. The aim of this study was to investigate how mtDNA T8993G mutation (NARP)-induced inhibition of F1F0-ATPase modulates the H/RO-induced mitochondrial dysfunction. In addition, the potential for melatonin, a potent antioxidant with multiple mitochondrial protective properties, to protect NARP cells exposed to H/RO was assessed. METHODS AND FINDINGS: NARP cybrids harboring 98% of mtDNA T8993G genes were established as an in vitro model for cells with F1F0-ATPase defect; their parental osteosarcoma 143B cells were studied for comparison. Treating the cells with H/RO using a hypoxic chamber resembles ischemia/reperfusion in vivo. NARP significantly enhanced apoptotic death upon H/RO detected by MTT assay and the trypan blue exclusion test of cell viability. Based on fluorescence probe-coupled laser scanning imaging microscopy, NARP significantly enhanced mitochondrial reactive oxygen species (mROS) formation and mitochondrial Ca(2+) (mCa(2+)) accumulation in response to H/RO, which augmented the depletion of cardiolipin, resulting in the retardation of mitochondrial movement. With stronger H/RO stress (either with longer reoxygenation duration, longer hypoxia duration, or administrating secondary oxidative stress following H/RO), NARP augmented H/RO-induced mROS formation to significantly depolarize mitochondrial membrane potential (ΔΨm), and enhance mCa(2+) accumulation and nitric oxide formation. Also, NARP augmented H/RO-induced mROS oxidized and depleted cardiolipin, thereby promoting permanent mitochondrial permeability transition, retarded mitochondrial movement, and enhanced apoptosis. Melatonin markedly reduced NARP-augmented H/RO-induced mROS formation and therefore significantly reduced mROS-mediated depolarization of ΔΨm and accumulation of mCa(2+), stabilized cardiolipin, and then improved mitochondrial movement and cell survival. CONCLUSION: NARP-induced inhibition of F1F0-ATPase enhances mROS formation upon H/RO, which augments the depletion of cardiolipin and retardation of mitochondrial movement. Melatonin may have the potential to rescue patients with ischemia/reperfusion insults, even those associated with NARP symptoms.


Assuntos
DNA Mitocondrial/genética , Melatonina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Mutação , Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Cálcio/metabolismo , Cardiolipinas/metabolismo , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo
17.
J Neuroimmunol ; 261(1-2): 129-33, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23796872

RESUMO

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis that is rarely reported. Our study evaluated the first known patient who developed anti-AMPA receptor encephalitis during pregnancy. Initial brain MRI revealed bilateral limbic encephalitis. However, rapid brain atrophy on MRI with extensive hypometabolism of cerebral cortices, caudate nuclei and brain stem hypoperfusion on (18)F-FDG PET developed when clinically progressed. IgG index of serial CSF studies reflected the clinical improvements after plasmapheresis and plasma exchange. The clinical spectrum of anti-AMPA receptor encephalitis may be expanded from limited limbic involvement to extended central nervous system.


Assuntos
Autoanticorpos/sangue , Encefalopatias/metabolismo , Encéfalo/patologia , Progressão da Doença , Doença de Hashimoto/metabolismo , Complicações na Gravidez/imunologia , Complicações na Gravidez/metabolismo , Receptores de AMPA/antagonistas & inibidores , Receptores de AMPA/imunologia , Adulto , Atrofia/imunologia , Atrofia/patologia , Encéfalo/imunologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalite , Feminino , Doença de Hashimoto/imunologia , Doença de Hashimoto/patologia , Humanos , Gravidez , Complicações na Gravidez/patologia , Fatores de Tempo
18.
J Stroke Cerebrovasc Dis ; 22(8): e455-62, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23800497

RESUMO

BACKGROUND: We aimed to assess whether intracranial carotid artery calcification (ICAC) evident on head computed tomography is a risk factor for symptomatic intracerebral hemorrhage (sICH) following tissue plasminogen activator (tPA) treatment for acute stroke. METHODS: We classified 297 consecutive patients into 2 groups (no to mild ICAC and moderate to severe ICAC) according to ICAC severity. Outcome measures included detection of intracerebral hemorrhage and assessment using a modified Rankin scale (mRS) at 1 month and 1 year after stroke. RESULTS: ICH (any type) was significantly more common in patients with moderate to severe ICAC than in patients with no to mild ICAC (22.5% versus 12%; relative risk [RR], 1.67; 95% confidence interval [CI], 1.1-2.5; P<.05). The moderate to severe ICAC group tended to have a higher percentage of sICH, but this association was not statistically significant (RR, 1.57; 95% CI, .75-3.3, P>.05). Multivariate adjusted regression analysis revealed that moderate to severe ICAC was an independent risk factor for ICH following tPA treatment (odds ratio, 2.52; 95% CI, 1.07-5.94; P=.04). Dependent functional outcome (mRS score 3-6) at 1-month and 1-year follow-up was significantly associated with moderate to severe ICAC (RR, 1.56; 95% CI, 1.06-2.27; and RR, 1.56; 95% CI, 1.06-2.33; P<.05). However, ICAC was not an independent factor of functional dependency at 1-month and 1-year follow-up in the final multivariate regression model. CONCLUSION: A significantly higher percentage of patients with moderate to severe ICAC developed ICH following tPA administration for stroke. ICAC severity is an independent risk factor for ICH events. ICAC severity can help predict short-term and long-term functional dependency in tPA-treated patients, although this can be confounded by other cardiovascular risk factors and stroke severity.


Assuntos
Doenças das Artérias Carótidas/complicações , Hemorragia Cerebral/induzido quimicamente , Fibrinolíticos/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Calcificação Vascular/complicações , Idoso , Doenças das Artérias Carótidas/diagnóstico , Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico , Distribuição de Qui-Quadrado , Avaliação da Deficiência , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Taiwan , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Calcificação Vascular/diagnóstico
19.
Oxid Med Cell Longev ; 2013: 159567, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23533684

RESUMO

Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ (0)) lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa(2+)) were compared between two different astrocyte cell lines, control and ρ (0) astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 and ρ (0) astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, ρ (0) astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa(2+) elevation in control showed higher levels than ρ (0) at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa(2+) stress during severe oxidative insult.


Assuntos
Cálcio/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Astrócitos/citologia , Astrócitos/metabolismo , Benzoxazóis/química , Linhagem Celular , DNA Mitocondrial , Transporte de Elétrons/efeitos dos fármacos , Corantes Fluorescentes/química , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Compostos de Quinolínio/química , Ratos , Imagem com Lapso de Tempo
20.
Clin Neurol Neurosurg ; 115(8): 1446-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23419407

RESUMO

OBJECTIVES: We aimed to investigate the effect of hypercholesterolemia on recovery after acute ischemic stroke. METHODS: Data of 3048 patients admitted for acute ischemic stroke from January to December 2009 were collected from the Stroke Registry in the Chang Gung Healthcare System. Baseline characteristics of patients with and without hypercholesterolemia were compared. The association of hypercholesterolemia with neurological severity and recovery was analyzed using multivariate logistic regression. The patients were then divided on the basis of age for subgroup analysis. RESULTS: The number of patients with and without a history of hypercholesterolemia was 474 (15.6%) and 2574 (84.4%), respectively. Univariate analysis showed that patients with hypercholesterolemia had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (p=0.004). However, during hospitalization, these patients displayed less improvement in their NIHSS score (p=0.002). These results remained significant in multivariate logistic regression analysis (p<0.001 and p=0.002, respectively). Subgroup analysis showed a similar association for hypercholesterolemia in both younger (age<70) and older (age≥70) age groups. CONCLUSIONS: Acute ischemic stroke in patients with hypercholesterolemia was correlated with reduced severity on admission and less favorable recovery during hospitalization, regardless of age.


Assuntos
Hipercolesterolemia/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipercolesterolemia/complicações , Lipídeos/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Prognóstico , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Adulto Jovem
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