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1.
Neoplasma ; 67(1): 119-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31829024

RESUMO

Previously, we identified that sortilin related VPS10 domain containing receptor 1 (SorCS1) was hypermethylated in colorectal cancer (CRC) tissues. Here, we aimed to investigate the association between CRC and SorCS1. DNA methylation was determined by methylation-specific polymerase chain reaction (MSP) or quantitative real-time methylation analysis (MethyLight). Colorectal cancer tissue specimens from 239 patients that had undergone surgical treatment were evaluated using immunohistochemistry (IHC) analysis for the expression of SorCS1 and correlated with clinicopathological variables and prognosis. We found that SorCS1 was hypermethylated in CRC cell lines and 67.5% (27/40) CRC tumor tissues. The loss of SorCS1 mRNA (p<0.001) and protein expression (p=0.033) were highly correlated with promoter methylation. In addition, SorCS1 expression was significantly increased in younger patients (p=0.006), low CEA level (p<0.001) and pT1-2 stage (p=0.005). Survival analysis revealed that decreased expression of SorCS1 was an independent factor for predicting the increased risk of recurrence (p=0.024) and poor overall survival (p=0.006). Subgroup analysis for CEA level, pT and pN classifications showed that SorCS1 retained its stratified significance only in patients with low CEA level, pT3-4 tumors and pN1-2 lymph node status. Our findings suggest that SorCS1 is epigenetically inactivated in a substantial fraction of CRC, and its expression may be a promising prognostic factor in CRC patients.


Assuntos
Neoplasias Colorretais/genética , Receptores de Superfície Celular/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Metilação de DNA , Humanos , Imuno-Histoquímica , Recidiva Local de Neoplasia , Prognóstico
2.
Eur J Gynaecol Oncol ; 34(2): 183-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23781595

RESUMO

A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumor do Seio Endodérmico/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Adulto , Feminino , Humanos , Transplante de Células-Tronco , Transplante Autólogo
3.
J Prev Alzheimers Dis ; 10(2): 178-185, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36946444

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease affecting mostly elderly adults. Recent diagnostic criteria for AD recommend the use of imaging and/or cerebrospinal fluid (CSF) biomarkers together with clinical presentation for a more persuasive diagnosis. The invasiveness and expense of such examinations have led to the search for blood-based biomarkers. The plasma levels of amyloid-ß (Aß) protein and tau peptides have been found to correlate with CSF levels and imaging findings in patients with AD. This study was conducted to explore the predictive utility of plasma Aß1-42 and total tau (t-tau) levels for cognitive decline in healthy adults. METHODS: In this prospective longitudinal study, we enrolled adults aged ≥ 50 years with normal cognition at Taipei Veterans General Hospital from November 2016 to April 2019. Blood samples were collected on recruitment, and plasma Aß1-42 and t-tau levels were quantified through immunomagnetic reduction. Thorough neurophysiological assessment was performed at baseline and at the annual follow-up visit. The participants were divided into two groups according to cognitive decline. The predictive utility of Aß1-42 and t-tau levels was evaluated by receiver operating characteristic curve analysis. RESULTS: Of 60 participants recruited, seven participants progressed to mild cognitive impairment and 53 retained normal cognition on follow-up (average 1.07 ± 0.2 years). The baseline levels of plasma biomarkers (Aß1-42, t-tau, and Aß1-42 × t-tau) were significantly higher in the progressive than in the stable group (p = 0.005, p = 0.007, and p = 0.005, respectively). Higher plasma biomarker levels (Aß1-42 ≥ 16.96 pg/ml and Aß1-42 × t-tau ≥ 382 pg2/ml2) predicted more cognitive decline on annual follow-up visits. CONCLUSION: Plasma Aß1-42 and t-tau levels have predictive utility for cognitive decline, even in subjects with normal cognition. Higher baseline plasma Aß1-42 and t-tau levels may indicate a higher risk of cognitive decline in cognitively normal adults.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Idoso , Humanos , Adulto , Estudos Longitudinais , Estudos Prospectivos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano
4.
J Prev Alzheimers Dis ; 10(3): 562-570, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357298

RESUMO

BACKGROUND: Subjective cognitive decline is proposed to be associated with future mild cognitive impairment and dementia. A better understanding of the roles of self-reported and informant-reported subjective cognitive complaints can provide a more delicate picture in dementia recognition and early diagnosis. OBJECTIVES: To evaluate the accuracy of self-reported and informant-reported subjective cognitive complaints and the relation of subjective cognitive complaints and neuropsychological function in cognitively unimpaired, mild cognitive impairment and populations with dementia. DESIGN: We conducted a cross-sectional survey and evaluate the relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups. SETTING: We recruited individuals diagnosed with cognitively unimpaired or mild cognitive impairment or dementia with Alzheimer's clinical syndrome from a memory clinic in a tertiary medical center in Taiwan. PARTICIPANTS: Participants, age greater than 50 years old, were enrolled in this study. Participants' informants were also enrolled for the cognitive questionnaire assessment. MEASUREMENTS: Participants' and informants' subjective cognitive complaint scores were collected based on a 12-item questionnaire. Neuropsychological assessments of global cognitive function, memory, language, executive function, visuospatial function and calculation were performed. The relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups were assessed by linear regression model. RESULTS: There were 1536 individuals and 1028 informants enrolled in this study. Self-reported subjective cognitive complaint scores from early and late mild cognitive impairment and dementia with Alzheimer's clinical syndrome participants showed no significant differences, but informants' subjective cognitive complaint scores showed a significant increase. Informant-reported subjective cognitive complaint scores related to neuropsychological tests in population with dementia. Neither self-reported nor informant-reported subjective cognitive complaint scores related to neuropsychological tests in cognitively unimpaired and mild cognitive impairment populations. CONCLUSIONS: Self-reported subjective cognitive complaints alone may not be sufficient to demonstrate clinical significance in different stages of cognitive impairment. Incorporating informant-reported subjective cognitive complaints, along with considering individual's anxiety and depressive status, are crucial in assessing cognitive statuses in clinical practice.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Pessoa de Meia-Idade , Autorrelato , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Estudos Transversais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Cognição
5.
Benef Microbes ; 12(3): 283-293, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34030609

RESUMO

Escherichia coli Nissle (EcN), a probiotic bacterium protects against several disorders. Multiple reports have studied the pathways involved in cardiac hypertrophy. However, the effects of probiotic EcN against diabetes-induced cardiac hypertrophy remain to be understood. We administered five weeks old Wistar male (271±19.4 g body weight) streptozotocin-induced diabetic rats with 109 cfu of EcN via oral gavage every day for 24 days followed by subjecting the rats to echocardiography to analyse the cardiac parameters. Overexpressed interleukin (IL)-6 induced the MEK5/ERK5, JAK2/STAT3, and MAPK signalling cascades in streptozotocin-induced diabetic rats. Further, the upregulation of calcineurin, NFATc3, and p-GATA4 led to the elevation of hypertrophy markers, such as atrial and B-type natriuretic peptides. In contrast, diabetic rats supplemented with probiotic EcN exhibited significant downregulated IL-6. Moreover, the MEK5/ERK5 and JAK2/STAT3 cascades involved during eccentric hypertrophy and MAPK signalling, including phosphorylated MEK, ERK, JNK, and p-38, were significantly attenuated in diabetic rats after supplementation of EcN. Western blotting and immunofluorescence revealed the significant downregulation of NFATc3 and downstream mediators, thereby resulting in the impairment of cardiac hypertrophy. Taken together, the findings demonstrate that supplementing probiotic EcN has the potential to show cardioprotective effects by inhibiting diabetes-induced cardiomyopathies.


Assuntos
Cardiomegalia/terapia , Diabetes Mellitus Experimental/terapia , Cardiomiopatias Diabéticas/terapia , Escherichia coli/fisiologia , Interleucina-6/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Probióticos/uso terapêutico , Animais , Calcineurina/metabolismo , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , MAP Quinase Quinase 5/metabolismo , Masculino , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Ratos , Ratos Wistar , Fator de Transcrição STAT3/metabolismo , Estreptozocina
6.
J Microsc ; 237(2): 200-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20096050

RESUMO

Two-photon fluorescence microscopy and confocal reflectance microscopy were compared to detect intracellular gold nanorods in rat basophilic leukaemia cells. The two-photon photoluminescence images of gold nanorods were acquired by an 800 nm fs laser with the power of milliwatts. The advantages of the obtained two-photon photoluminescence images are high spatial resolution and reduced background. However, a remarkable photothermal effect on cells was seen after 30 times continuous scanning of the femto-second laser, potentially affecting the subcellular localization pattern of the nanorods. In the case of confocal reflectance microscopy the images of gold nanorods can be obtained with the power of light source as low as microwatts, thus avoiding the photothermal effect, but the resolution of such images is reduced. We have noted that confocal reflectance images of cellular gold nanorods achieved with 50 microW 800 nm fs have a relatively poor resolution, whereas the 50 microW 488 nm CW laser can acquire reasonably satisfactory 3D reflectance images with improved resolution because of its shorter wavelength. Therefore, confocal reflectance microscopy may also be a suitable means to image intracellular gold nanorods with the advantage of reduced photothermal effect.


Assuntos
Basófilos/química , Citosol/química , Ouro/análise , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanotubos/análise , Animais , Linhagem Celular Tumoral , Ratos
7.
J Neurol Sci ; 277(1-2): 174-5, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19033078

RESUMO

A 55-year-old man developed ischemic stroke after three episodes of transient dysarthria and left hemiplegia, a typical manifestation of capsular warning syndrome. Magnetic resonance imaging of the brain showed bilateral basal ganglionic infarction. The patient had no significant risk of stroke. However, the systemic manifestations, an elevated titer of perinuclear anti-neutrophilic cytoplasmic antibody and a skin biopsy revealing leukocytoclastic venulitis confirmed the undrlying microscopic polyangiitis.


Assuntos
Doenças dos Gânglios da Base/etiologia , Isquemia Encefálica/etiologia , Acidente Vascular Cerebral/etiologia , Vasculite do Sistema Nervoso Central/complicações , Vasculite Leucocitoclástica Cutânea/complicações , Doenças dos Gânglios da Base/patologia , Isquemia Encefálica/patologia , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologia , Vasculite do Sistema Nervoso Central/patologia , Vasculite Leucocitoclástica Cutânea/patologia
8.
J Nutr Health Aging ; 23(9): 904-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641743

RESUMO

OBJECTIVES: Reciprocal age-related impairments in physical and cognitive functioning have been termed 'cognitive frailty', which is associated with adverse health outcomes and is a potential target for preventing or delaying the onset of disability in older people. However, cognitive frailty as currently defined is challenging to diagnose. To facilitate earlier diagnosis and intervention, we conducted this study to develop and validate a simple evidence-based instrument to identify community-dwelling elders at risk of cognitive frailty. DESIGN: Retrospective analyses of data from the I-Lan Longitudinal Aging Study (ILAS) to develop a prediction model, and from the Longitudinal Aging Study of Taipei (LAST) for external validation. SETTING: Community-dwelling adults from Taipei City, New Taipei City and Yilan (I-Lan) County, Taiwan. PARTICIPANTS: 1271 community residents ≥65 years old, without impaired global cognition or dependency for activities of daily living/instrumental activities of daily living. MEASUREMENTS: Demographic characteristics, anthropometric measurements, medical history, Mini-Mental State Examination, Montreal Cognitive Assessment, Functional Autonomy Measuring System, Functional Assessment Staging Test, Center for Epidemiologic Studies Depression Scale, handgrip strength, 6-metre walk speed. METHODS: Baseline characteristics of groups with/without cognitive frailty were analyzed and factors differing significantly in univariate analysis input to binary logistic regression to develop a cognitive frailty risk (CFR) score. RESULTS: The prevalence of cognitive frailty was 15.8% overall; ILAS 21.4%, LAST 8.4%. Predictors of CFR comprised: age ≥75 years; female sex; waist circumference ≥90 cm (male), ≥80 cm (female); calf circumference <33 cm (male), <32 cm (female); memory deficits; and diabetes mellitus. CFR ≥5/14 had sensitivity of 70%, specificity of 60%, and predictive accuracy of 72%. CONCLUSIONS: A CFR score based on simple history-taking and anthropometric measurements integrates age, sex, cardiometabolic risk, memory deficits, sarcopenia, and nutrition, with validated predictive accuracy, and could be performed easily in community settings to identify seniors with cognitive frailty for appropriate interventions.


Assuntos
Envelhecimento/psicologia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Idoso Fragilizado/psicologia , Avaliação Geriátrica/métodos , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Feminino , Fragilidade , Força da Mão/fisiologia , Humanos , Vida Independente , Estudos Longitudinais , Masculino , Prevalência , Estudos Retrospectivos , Sarcopenia/psicologia , Taiwan
9.
Leukemia ; 20(4): 604-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16453003

RESUMO

The roles of CEBPalpha mutations and its cooperating mutations in the relapse of acute myeloid leukemia (AML) are not clear. CEBPalpha mutations were analyzed on 149 patients with de novo AML at both diagnosis and relapse. Twenty-two patients (14.8%) had the mutations at diagnosis, two patients had N-terminal nonsense mutations alone, one had homozygous inframe duplication at the bZIP domain, and 19 patients had both N-terminal and bZIP mutations. Twenty patients relapsed with identical mutant patterns, two lost CEBPalpha mutations and none acquired the mutations at relapse. Cloning analysis showed that the N-terminal and C-terminal mutations occurred on separate cloned alleles and also on the same alleles in most of the diagnosis and relapse samples. Losing one of the two or more mutations on the same allele or acquiring the other mutation on the allele original carrying single mutation were observed not infrequently in the paired samples analyzed. Seven patients with CEBPalpha mutations had cooperating mutations with FLT3/ITD, FLT3/TKD or N-ras but not K-ras mutations. Our study showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis retained the identical mutant patterns but frequently changed in the allelic distribution at relapse.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Adolescente , Adulto , Idoso , Alelos , Medula Óssea/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Feminino , Genes ras/genética , Humanos , Lactente , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Tirosina Quinase 3 Semelhante a fms/genética
10.
Leukemia ; 20(2): 218-23, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16341046

RESUMO

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.


Assuntos
Leucemia Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Translocação Genética/genética , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Duplicação Gênica , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
J Prev Alzheimers Dis ; 4(1): 37-43, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29188858

RESUMO

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.


Assuntos
Demência/epidemiologia , Dieta Saudável , Sobrepeso/epidemiologia , Animais , Índice de Massa Corporal , Café , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Comportamento Alimentar , Peixes , Taiwan/epidemiologia , Chá , Verduras
12.
Phys Med Biol ; 51(20): N371-9, 2006 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-17019025

RESUMO

The refractive index of biological tissue is a fundamental parameter in applications of optical diagnosis and laser treatments. In the present work, the refractive indices and thermo-optic coefficients of some basic biomaterials, such as blood plasma, haemoglobin solution and lipid membrane, were studied by the method of total internal reflection at the wavelengths of 532 and 632.8 nm that are the most frequently used laser wavelengths in the biomedical field. The effects of the sample concentration and the temperature on refractive index were measured, and empirical relationships were summarized, accompanied by a theoretical explanation based on molecular polarization theory. The results provide some fundamental data for the refractive indices of these biomaterials under variant conditions, and also demonstrate that the total internal reflection method is a feasible and reliable way to measure the refractive indices of biological samples.


Assuntos
Materiais Biocompatíveis/química , Biopolímeros/química , Tecido Conjuntivo/fisiologia , Teste de Materiais/métodos , Refratometria/métodos , Humanos , Luz , Espalhamento de Radiação
13.
AJNR Am J Neuroradiol ; 37(10): 1889-1897, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27127004

RESUMO

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

14.
Leukemia ; 18(3): 466-75, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14737077

RESUMO

The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, P<0.001). FLT3/ITD(+) patients progressed to AML more rapidly than FLT3/ITD(-) patients (2.5+/-0.5 vs 11.9+/-1.5 months, P=0.114). FLT3/ITD(+) patients had a significantly shorter survival than FLT3/ITD(-) patients (5.6+/-1.3 vs 18.0+/-1.7 months, P=0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (P<0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.


Assuntos
Genes ras/genética , Leucemia Mieloide/genética , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Doença Aguda , Medula Óssea/patologia , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Humanos , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , Tirosina Quinase 3 Semelhante a fms
15.
Exp Hematol ; 29(2): 202-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11166459

RESUMO

OBJECTIVE: Analysis of X-chromosome inactivation patterns (XCIPs) is a useful tool in the diagnosis of clonal disorders. The human androgen receptor (HUMARA) locus is especially useful for clonality study. The present study was conducted 1) to determine the heterozygosity rate for HUMARA locus in Taiwanese women, 2) to determine the frequency of excessive skewing in different cell types, and 3) to determine the utility of XCIPs in the differential diagnosis of thrombocytosis. PATIENTS AND METHODS: XCIPs by HUMARA-PCR assay were performed on purified granulocytes and T cells from 73 female patients presenting with idiopathic persistent thrombocytosis (IT), 10 patients with reactive thrombocytosis (RT), and 46 bone marrow samples from female controls. XCIPs of buccal mucosa cells were also compared with those of T cells in 57 patients with IT. The percentage of clonal granulocytes was calculated after correcting for the degree of Lyonization in T cells. RESULTS: The heterozygosity rate for the HUMARA gene was 89.1% in Taiwanese females. The median age of informative IT patients and controls was 59 (18-92) and 58 (19-89), respectively. Excessive skewing (allele ratio <0.33) was more frequent in granulocytes than in T cells in both controls (12/43 vs 9/43, p = 0.080) and IT patients (56/64 vs 25/64, p < 0.001). XCIPs were the same for both buccal mucosa and T cells in 43 patients but were different in 14 patients. Of the 43 informative controls, 31 had a polyclonal pattern; an ambiguous pattern was found in nine; and the remaining three, aged 71, 73, and 80, respectively, had a clonal pattern. A clonal pattern was found in 42 IT patients, a polyclonal pattern in 12, and an ambiguous pattern in 10 of the 64 IT patients. The frequency of clonal, polyclonal, and ambiguous patterns in the 40 IT patients with age < or = 65 was 55.0%, 30.0%, and 15.0%, respectively. None of the IT patients aged >65 had a polyclonal disease. IT patients aged >65 had a significantly higher frequency of clonal pattern (p = 0.030) and a significantly lower frequency of polyclonal pattern (p = 0.002) than those with age <65. Of the eight heterozygous patients with RT, one aged 80 exhibited a clonal pattern, and the remaining seven had a polyclonal pattern. CONCLUSIONS: The present study on Taiwanese females showed a heterozygosity rate of 89.1% for the HUMARA gene. Our results confirmed that IT is a heterogeneous disorder in terms of clonality. Twenty-three percent of IT patients exhibited a greater than 20% difference in allele expression for buccal mucosa and T cells. Presence of a clonal XCIP in young patients with IT can serve as a positive marker for the diagnosis of clonal thrombocytosis, and elderly patients with polyclonal XCIPs are unlikely to have essential thrombocythemia.


Assuntos
Mecanismo Genético de Compensação de Dose , Reação em Cadeia da Polimerase/métodos , Receptores Androgênicos/genética , Trombocitose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Medula Óssea/química , Células Clonais , DNA/análise , Feminino , Granulócitos/química , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mucosa Bucal/química , Linfócitos T/química , Taiwan
16.
Arch Neurol ; 53(1): 66-71, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8599561

RESUMO

BACKGROUND: Most published studies have shown lower prevalence rates of Parkinson's disease (PD) in Asian and black African than in Western countries, leading to the hypothesis that Asians and blacks might be protected from PD. OBJECTIVE: To investigate the prevalence of PD in a Chinese population. DESIGN: Community-based survey. SETTING: Registered residents 50 years of age or older (N = 5061) on the islet of Kinmen located off the southeastern coast of China [corrected]. METHOD: Single-phase door-to-door survey by neurologists. All participants were administered a questionnaire and received motor examinations of the Unified Parkinson's Disease Rating Scale. RESULTS: The participation rate was 96% (N = 3915) among 4158 contacted individuals. Twenty-three cases of PD were identified, including three cases with dementia. The crude prevalence rate of PD was 587 (95% confidence interval (CI), 373 to 884) per 100,000 persons 50 years of age or older. Assuming no case of PD among individuals under 50 years of age, the prevalence rate was 119 (95% CI, 80 to 169) per 100,000 for the total population. CONCLUSIONS: The prevalence rates of PD in Kinmen were much higher than those reported from mainland China, but slightly lower than those reported from more developed countries. The present findings suggest that, instead of genetic factors, differences in case-ascertainment, life expectancy, and the length of survival with PD may be more important contributors to the variations in observed PD prevalence rates.


Assuntos
Etnicidade , Inquéritos Epidemiológicos , Doença de Parkinson/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/etnologia , Prevalência
17.
Neurology ; 54(2): 314-9, 2000 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-10668689

RESUMO

OBJECTIVE: To investigate the prevalence, risk factors, and prognosis of chronic daily headache (CDH) in a population of elderly Chinese subjects. METHODS: A community-based survey of registered residents > or =65 years old (n = 2,003) in two townships of Kinmen Island in 1993. A neurologist used a structured questionnaire and clinical interview to make the diagnosis of headache. Subjects who had headaches > or =15 days/month for > or =6 months in the previous year were considered to have CDH. CDH was further classified into chronic tension-type headache (CTTH), CDH with migrainous features (CDH/MF), and other CDH. Person-to-person biannual follow-up of the subjects with CDH was done in June 1995 and August 1997. RESULTS: A total of 1,533 people (77%) participated in our prevalence study. Sixty subjects (3.9%) fulfilled the criteria for CDH, with a higher prevalence in women (F/M: 5.6%/1.8%, p < 0.001). Of these subjects, 42 (70%) had CTTH, 15 (25%) had CDH/MF, and 3 (5%) had other CDH. Only 23% of those with CDH had consulted physicians for their headaches in the previous year. Multivariate logistic regression revealed the significant risk factors for CDH to be analgesic overuse (OR = 79), a history of migraine (OR = 6.6), and a Geriatric Depression Scale-Short Form score of > or =8 (OR = 2.6). The follow-up results in 1995 and 1997 showed that about two-thirds of the subjects still had CDH. Analgesic overuse (relative risk = 1.6) in 1993 was a significant predictor of persistent CDH at follow-up. CONCLUSIONS: A total of 3.9% of this elderly population had CDH, with CTTH being the most common subtype. Almost two-thirds of those with CDH had persistent frequent headaches at follow-up. Analgesic overuse was a significant predictor of a poor outcome.


Assuntos
Idoso/estatística & dados numéricos , Transtornos de Enxaqueca/epidemiologia , Cefaleia do Tipo Tensional/epidemiologia , Analgésicos/administração & dosagem , Povo Asiático , Doença Crônica , Depressão/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Transtornos de Enxaqueca/tratamento farmacológico , Prevalência , Prognóstico , Fatores de Risco , Distribuição por Sexo , Taiwan/epidemiologia , Cefaleia do Tipo Tensional/tratamento farmacológico
18.
Neurology ; 53(5): 962-6, 1999 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-10496253

RESUMO

OBJECTIVE: To calculate the frequencies of apolipoprotein E (apoE) alleles in a large Chinese community sample and to compare the serum cholesterol levels of epsilon2, epsilon3, and epsilon4 carriers. BACKGROUND: In comparison with Western populations, a lower frequency of the apoE epsilon4 allele among the Chinese has been proposed as one factor for the lower prevalence of AD found in Chinese populations, but there are insufficient Chinese data on epsilon4 frequency that are based on large community samples. In addition, although Western studies have repeatedly found a lower cholesterol level in epsilon2 carriers and a higher cholesterol level in epsilon4 carriers in comparison with epsilon3 homozygotes, two Chinese studies have yielded inconsistent findings between them. METHODS: During the incidence phase of an epidemiologic survey of several neurologic disorders in a Chinese community, the authors took blood samples from 2,326 participants to determine the apoE genotypes and to measure cholesterol levels. RESULTS: The allelic frequencies of epsilon2, epsilon3, and epsilon4 were 11.8%, 76.4%, and 11.8% among 17 AD patients, and 7.8%, 84.1%, and 8.1% for the entire sample. The mean cholesterol level of the epsilon2 carriers was significantly lower, and that of the epsilon4 carriers significantly higher, than that of the epsilon3 homozygotes. CONCLUSIONS: The obtained epsilon4 rate of 8.1% is lower than most of the Western findings, and this may account in part for the lower prevalence of AD found among the Chinese. The associations between the apoE genotype and serum cholesterol level are similar between Chinese and white populations.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Colesterol/sangue , Idoso , Idoso de 80 Anos ou mais , Alelos , China , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
19.
Neurology ; 49(1): 195-200, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9222190

RESUMO

OBJECTIVE: To investigate the prevalence of headaches in a Chinese elderly population. BACKGROUND: There are few headache surveys in the elderly. Previous studies have shown a low headache prevalence in Chinese. TARGET POPULATION: eligible registered residents > or = 65 years old (N = 2,003) in two townships of Kinmen Island on August 1, 1993. All participants completed a headache questionnaire and underwent clinical evaluation and examination by a neurologist. Headache diagnoses were made according to the International Headache Society, 1988. RESULTS: 1,533 persons (77%) participated in the study, of whom 584 (38%) had at least one episode of headache in the previous year. One-year prevalence of migraine was 3.0%, and tension-type headache, 35%. The prevalence of migraine, but not tension-type headaches, continued to decline with age in the elderly. Life-time prevalence of "incapacitating headache" was 10%, and that of migraine, 5.2%. Forty-two percent of migraineurs stopped having migraine before this survey. In comparison with "10 years ago" 8% participants felt their current headaches were worse, 25% better, and 67%, no change, with a net improvement of 17%. CONCLUSIONS: We have reported the highest headache prevalence among different Chinese elderly populations, but these were still lower than those reported from Western series. More than half of the elderly life-time migraineurs still had attacks of migraine. Severe headaches, including migraine but not tension-type headaches, declined with age.


Assuntos
Envelhecimento/fisiologia , Cefaleia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Prevalência
20.
Neurology ; 54(11): 2061-6, 2000 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-10851363

RESUMO

OBJECTIVE: To examine the effects of estrogen therapy on cognition, mood, and cerebral blood flow in patients with AD. BACKGROUND: Some studies have suggested estrogen may be effective in the treatment of AD. However, most of these studies were not controlled adequately. METHODS: Fifty female AD patients were recruited in a randomized, double-blind, placebo-controlled 12-week trial. Each member of the estrogen-treated group received conjugated estrogen (Premarin) 1.25 mg/day. The primary outcome measures were the Cognitive Ability Screening Instrument (CASI), Clinical Dementia Rating (CDR), and Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary outcome measures were Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), and 99mTc hexamethylpropylene amine oxime SPECT of the brain. RESULTS: No meaningful differences were found between the outcome measures (CASI, CDR, CIBIC-plus, BEHAVE-AD, HARS, HDRS, and cerebral blood flow) taken from the estrogen-treated group and those from the control group. CONCLUSION: A 1.25-mg/day dose of Premarin administered for 12 consecutive weeks does not produce a meaningful effect on cognitive performance, dementia severity, behavior, mood, and cerebral perfusion in female AD patients. Because estrogen therapy has been suspected of yielding adverse effects, and its therapeutic effectiveness is in doubt, additional evaluation of its role in AD treatment ought to be conducted.


Assuntos
Afeto/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Distribuição de Qui-Quadrado , Método Duplo-Cego , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade
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