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1.
Artigo em Inglês | MEDLINE | ID: mdl-31351134

RESUMO

The incidence of colorectal cancer (CRC) and cancer-related mortality has increased in patients <55 years old.1 Consensus on optimal intervals for post-CRC surveillance colonoscopy in young patients is lacking. The primary endpoint of this study was comparison of rates of metachronous advanced neoplasia (AN) in patients diagnosed with CRC at <50 and 50-75 years. The secondary aim was to evaluate risk factors of metachronous AN.

2.
Clin Liver Dis ; 23(2): 345-361, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947881

RESUMO

Liver diseases during pregnancy pose a unique clinical challenge because they can affect the lives of both the mother and unborn child. Although severe liver disease is rare, pregnancy-related liver disease affects approximately 3% of pregnancies and can be fatal. Timely recognition and diagnosis are essential in order to institute appropriate management strategies. This article provides an overview of liver diseases during pregnancy and is divided into 2 sections: (1) liver diseases specific to pregnancy, and (2) preexisting or coincident liver diseases during pregnancy.

3.
Dig Dis Sci ; 64(9): 2505-2513, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30874988

RESUMO

OBJECTIVES: Efforts to improve colorectal cancer (CRC) screening rates include recognizing predictors of colonoscopy non-adherence and identifying these high-risk patient populations. Past studies have focused on individual-level factors but few have evaluated the influence of neighborhood-level predictors. We sought to assess the effect of census tract-based neighborhood poverty rates on scheduled screening colonoscopy non-adherence. METHODS: In this prospective observational cohort study, data from electronic medical records and appointment tracking software were collected in 599 patients scheduled to undergo outpatient CRC screening colonoscopy at two academic endoscopy centers between January 2011 and December 2012. Non-adherence was defined as failure to attend a colonoscopy appointment within 1 year of the date it was electronically scheduled. Neighborhood poverty rate was determined by matching patients' self-reported home address with their corresponding US census tract. Individual factors including medical comorbidities and prior appointment adherence behavior were also collected. RESULTS: Overall, 17% (65/383) of patients were non-adherent to scheduled colonoscopy at 1-year follow-up. Neighborhood poverty rate was a significant predictor of non-adherence to scheduled screening colonoscopy in multivariate modeling (OR 1.53 per 10% increase in neighborhood poverty rate, 95% CI 1.21-1.95, p < 0.001). By incorporating the neighborhood poverty rate, screening colonoscopy non-adherence was 31% at the highest quartile compared to 14% at the lowest quartile of neighborhood poverty rates (p = 0.006). CONCLUSIONS: Census tract-based neighborhood poverty rates can be used to predict non-adherence to scheduled screening colonoscopy. Targeted efforts to increase CRC screening efficiency and completion among patients living in high-poverty geographic regions could reduce screening disparities and improve utilization of endoscopy unit resources.

4.
J Neurol Neurosurg Psychiatry ; 90(4): 428-435, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30554138

RESUMO

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs. METHODS: In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs. RESULTS: A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH. CONCLUSIONS: In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

5.
J Cereb Blood Flow Metab ; : 271678X18805209, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30351176

RESUMO

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR ( p < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale ( p = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

7.
Cogn Neuropsychol ; 35(8): 403-414, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30145937

RESUMO

This study investigated the sublexical route in writing Chinese characters. Using a writing-to-dictation task, we compared neurotypical participants' performance on writing a set of 40 characters with homophones sharing different phonetic radicals and another set of 40 characters with homophones sharing the same phonetic radicals. The first set of stimuli was regarded as both syllable-to-character and syllable-to-radical inconsistent, while the second set of stimuli was considered syllable-to-radical consistent but syllable-to-character inconsistent. The results of the error analysis showed that the control participants demonstrated a greater tendency to make errors with preserved phonetic radicals in the second set of stimuli. Furthermore, we conducted the same task with a Chinese brain-injured patient, WCY, who had mild dyslexia and severe dysgraphia associated with mild impairment to the lexical semantic route as shown by the patient's character writing. The results showed that WCY demonstrated similar error patterns as those of the control participants and a shorter writing time in the second set of stimuli. Altogether, the observations were taken as evidence that supported our claim that a syllable-to-phonetic radical route governs the sublexical route in Chinese character writing.

8.
Mult Scler J Exp Transl Clin ; 4(3): 2055217318788699, 2018 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30038791

RESUMO

We performed a cross-sectional study in 123 Chinese multiple sclerosis patients residing in Hong Kong to evaluate their anti-John Cunningham virus status using STRATIFY JCV DxSelect assays. Anti-John Cunningham virus antibody was present in 98/123 (80%) subjects, among which 75/98 (77%) had an anti-John Cunningham virus index ≥1.5. Anti-John Cunningham virus antibody seropositivity was not correlated with age, disease duration, Expanded Disability Status Scale scores, types of multiple sclerosis (relapsing vs progressive), or disease-modifying treatments used. We found a very high seroprevalence and index of anti-John Cunningham virus antibodies in Chinese multiple sclerosis patients, which may impact the risk assessment and recommendation of disease-modifying treatments in this population.

9.
J Neurol Neurosurg Psychiatry ; 89(7): 680-686, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29599284

RESUMO

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF. METHODS: We prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group. RESULTS: A total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs. CONCLUSIONS: In Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.

11.
Gastrointest Endosc ; 87(6): 1518-1526, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29337039

RESUMO

BACKGROUND AND AIMS: The association of proximal small and diminutive hyperplastic polyps (HPs) with synchronous advanced neoplasia is not well-defined. However, sessile serrated polyps (SSPs), even when small, are known to portend a risk of synchronous neoplasia. Currently, the U.S. Multi-Society Task Force on Colorectal Cancer does not recommend a change in the surveillance interval when proximal small HPs are detected. We aimed to compare the rates of synchronous advanced neoplasia in a screening colonoscopy cohort of patients with small and then diminutive proximal HPs in comparison, first to a cohort absent any serrated or proximal HPs and then in comparison with a cohort with small proximal SSPs. METHODS: Consecutive screening colonoscopies were recorded between 2005 and 2010 at an academic medical center. Patients were divided into 3 mutually exclusive groups. Group 1 consisted of patients with at least 1 HP that was proximal to the sigmoid colon, <1 cm in endoscopic size, and up to 3 total HPs in number. Group 2 included patients without any proximal HPs or SSPs. Group 3 consisted of patients with 1 to 2 SSPs, with at least 1 being proximal to the sigmoid colon, that were <1 cm in endoscopic size and without dysplasia. Rates of synchronous advanced neoplasia in patients with small (<1 cm) and diminutive (≤5 mm) proximal HPs were compared with the rates for the other 2 groups. RESULTS: There were 482 of 2569 patients (18.8%) with a small proximal HP who met the criteria for Group 1. The rate of synchronous advanced neoplasia in patients with a small proximal HP (61/482, 12.7%) was significantly greater compared with the average risk in the non-serrated cohort (Group 2, 133/1878, 7.1%; P < .001). There was no significant difference in the rate of synchronous advanced neoplasia when the small proximal HP group was subdivided by size (≤5 mm, 51/404, 12.6% vs 6-9 mm, 10/78, 12.8%; P = 1.00). The rate of synchronous advanced neoplasia in patients with diminutive (≤5 mm) proximal HPs (51/404, 12.6%) was not significantly different from the rate observed with proximal SSPs of similar size (17/113, 15.0%; P = .529). CONCLUSION: Patients with small and diminutive proximal HPs tend to harbor higher rates of synchronous advanced neoplasia compared with those without any serrated lesions detected on screening colonoscopy. Surveillance outcomes for metachronous advanced neoplasia for patients with small proximal HPs deserves further study. The synchronous advanced neoplasia rate in patients with proximal diminutive HPs is similar to that of proximal diminutive SSPs and could have implications in a resect and discard strategy.


Assuntos
Adenoma/epidemiologia , Colo/patologia , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Pólipos do Colo/patologia , Colonoscopia , Detecção Precoce de Câncer , Feminino , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade
12.
World J Gastroenterol ; 22(28): 6484-500, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27605883

RESUMO

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Ativação Viral , Tirosina Quinase da Agamaglobulinemia , Linfócitos B/imunologia , DNA Viral/sangue , Gerenciamento Clínico , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/prevenção & controle , Humanos , Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Rituximab/uso terapêutico
13.
Gastrointest Endosc ; 84(2): 307-14, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26855297

RESUMO

BACKGROUND AND AIMS: The U.S. Multi-Society Task Force (USMSTF) stratifies patients with sessile serrated polyps (SSPs) without cytologic dysplasia of <10 mm in size as at low risk for metachronous advanced neoplasia and recommends management similar to low-risk conventional tubular adenomas. Evidence supporting the recommended surveillance interval for these low-risk SSPs is limited. We aimed to assess rates of metachronous advanced neoplasia based on the presence of an initial low-risk SSP compared with isolated low-risk tubular adenomas. METHODS: Colonoscopy data were retrieved for 2260 patients found to have an adenoma or SSP on pathology records between 2005 and 2011 at an academic medical center. The 788 patients who met study design criteria were stratified into 4 groups based on the presence of a high- or low-risk adenoma (HRA or LRA) and of a synchronous SSP on initial colonoscopy. The rates of advanced neoplasia at surveillance colonoscopy were then compared between groups. RESULTS: The rate of advanced neoplasia at surveillance in the LRA inclusive of SSP group (12/66, 18.2%) was greater than in the LRA without any SSP group (29/370, 7.8%; P = .019). The rate of advanced neoplasia at surveillance in patients with isolated low-risk SSP (10/56, 17.9%) remained significantly greater than those with isolated low-risk tubular adenomas (29/370, 7.8%; P = .024). The rate of advanced neoplasia upon surveillance in the LRA inclusive of SSP group (18.2%) was comparable with the rate observed in the index HRA without any SSP group (15.9%) (40/252, P = .709). CONCLUSIONS: The rate of advanced neoplasia upon surveillance in patients with initial low-risk SSPs is higher than in patients with initial isolated low-risk tubular adenomas and more similar to patients with initial high-risk tubular adenomas. These findings suggest that the rate of metachronous advanced neoplasia in patients with what are considered by USMSTF as "low-risk" SSPs is higher than in those without SSPs. Therefore, a surveillance interval that accounts for the presence of SSPs even in small lesions without cytologic dysplasia should be considered.


Assuntos
Adenoma/epidemiologia , Carcinoma/epidemiologia , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Centros Médicos Acadêmicos , Adenoma/patologia , Idoso , Carcinoma/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , Estudos Retrospectivos , Fatores de Risco
14.
Gastrointest Endosc ; 82(3): 497-502, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25910667

RESUMO

BACKGROUND: Since 2008, multiple guidelines have endorsed incorporation of chest CT in the radiographic staging assessment of newly diagnosed colorectal cancer (CRC). Radiographic staging practices performed after CRC is detected have not been studied. OBJECTIVE: To evaluate radiographic staging practices for newly diagnosed CRC between gastroenterologists versus non-gastroenterologists. DESIGN: Observational cohort study. SETTING: Single, tertiary-care referral center. PATIENTS: Patients newly diagnosed with a T1 or higher stage CRC at time of colonoscopy between 2008 and 2013. INTERVENTIONS: Radiographic staging. MAIN OUTCOME MEASUREMENTS: Radiographic preoperative staging examinations ordered by gastroenterologists in comparison to those ordered by non-gastroenterology specialists. RESULTS: This study included 277 patients with CRC newly diagnosed by colonoscopy. There were 141 total ordering physicians (68 gastroenterologists and 73 non-gastroenterologists). The majority of preoperative radiographic staging was performed by gastroenterologists (59.2% of patients, n = 164). Colorectal surgeons managed staging in 28.7% of patients (n = 47). Gastroenterologists were more likely to omit a staging chest CT than were non-gastroenterologists (64.6% vs 46.9%; P < .001). Physician practice setting, rectal location of tumor, and advanced endoscopic appearance of tumors were predictors of chest CT inclusion. LIMITATIONS: Single center, moderate sample size of both providers and patients. CONCLUSION: Gastroenterologists more frequently ordered the initial radiographic staging studies in newly diagnosed CRC patients. However, gastroenterologists were less likely to include chest CT in the initial staging of CRC despite current guideline recommendations to do so. If confirmed with further studies, educational efforts to improve compliance and standardization may be needed.


Assuntos
Neoplasias Colorretais/patologia , Cirurgia Colorretal/normas , Gastroenterologia/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Radiografia Torácica/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Estudos de Coortes , Colonoscopia , Neoplasias Colorretais/diagnóstico , Feminino , Hospitais Comunitários/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
Brain ; 137(Pt 12): 3142-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25367027

RESUMO

Based on accumulating post-mortem evidence of abnormalities in Purkinje cell biology in essential tremor, we hypothesized that regressive changes in dendritic morphology would be apparent in the Purkinje cell population in essential tremor cases versus age-matched controls. Cerebellar cortical tissue from 27 cases with essential tremor and 27 age-matched control subjects was processed by the Golgi-Kopsch method. Purkinje cell dendritic anatomy was quantified using a Neurolucida microscopic system interfaced with a motorized stage. In all measures, essential tremor cases demonstrated significant reductions in dendritic complexity compared with controls. Median values in essential tremor cases versus controls were: 5712.1 versus 10 403.2 µm (total dendrite length, P=0.01), 465.9 versus 592.5 µm (branch length, P=0.01), 22.5 versus 29.0 (maximum branch order, P=0.001), and 165.3 versus 311.7 (number of terminations, P=0.008). Furthermore, the dendritic spine density was reduced in essential tremor cases (medians=0.82 versus 1.02 µm(-1), P=0.03). Our demonstration of regressive changes in Purkinje cell dendritic architecture and spines in essential tremor relative to control brains provides additional evidence of a pervasive abnormality of Purkinje cell biology in this disease, which affects multiple neuronal cellular compartments including their axon, cell body, dendrites and spines.


Assuntos
Cerebelo/patologia , Espinhas Dendríticas/patologia , Tremor Essencial/patologia , Células de Purkinje/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Axônios/patologia , Feminino , Humanos , Masculino , Neurônios/citologia
16.
Acta Neuropathol ; 125(6): 879-89, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23543187

RESUMO

The Lingo-1 sequence variant has been associated with essential tremor (ET) in several genome-wide association studies. However, the role that Lingo-1 might play in pathogenesis of ET is not understood. Since Lingo-1 protein is a negative regulator of axonal regeneration and neurite outgrowth, it could contribute to Purkinje cell (PC) or basket cell axonal pathology observed in postmortem studies of ET brains. In this study, we used Western blotting and immunohistochemistry to examine Lingo-1 protein in ET vs. control brains. In Western blots, Lingo-1 protein expression level was significantly increased in cerebellar cortex (1.56 ± 0.46 in ET cases vs. 0.99 ± 0.20 in controls, p = 0.002), but was similar in the occipital cortex (p = 1.00) of ET cases vs. controls. Lingo-1 immunohistochemistry in cerebellum revealed that Lingo-1 was enriched in the distal axonal processes of basket cells, which formed a "pinceau" structure around the PC axon initial segment (AIS). We found that some Lingo-1-positive pinceau had abnormally elongated processes, targeting PC axon segments distal to the AIS. In ET cases, the percentage of Lingo-1-positive pinceau that were ≥30 or ≥40 µm in length was increased 2.4- to 4.1-fold, respectively, vs. pinceau seen in control brains (p < 0.0001). Elongated Lingo-1-positive pinceau strongly correlated with number of PC axonal torpedoes and a rating of basket cell axonal pathology. The increased cerebellar Lingo-1 expression and elongated Lingo-1-positive pinceau processes could contribute to the abnormal PC and basket cell axonal pathology and cerebellar dysfunction observed in ET.


Assuntos
Axônios/metabolismo , Cerebelo/metabolismo , Tremor Essencial/metabolismo , Tremor Essencial/patologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/patologia , Estudos de Casos e Controles , Cerebelo/patologia , Tremor Essencial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/metabolismo , Lobo Occipital/patologia
17.
J Neuropathol Exp Neurol ; 72(1): 8-17, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23242279

RESUMO

For many years, clinicians have commented on the development of signs of parkinsonism among their essential tremor (ET) patients, but the links between ET and parkinsonism are not well understood. We report 11 (12.4%) of 89 ET patients who were prospectively collected at the Essential Tremor Centralized Brain Repository during the course of its first 9 years. All patients had long-standing ET (median duration, 38 years); there was a 5- to 49-year latency from the onset of ET to the development of either parkinsonism or dementia.Despite the presence of parkinsonism or dementia during life, none had been diagnosed clinically with progressive supranuclear palsy(PSP). All 11 received the postmortem diagnosis of PSP. The prevalence of PSP in this ET sample (12.4%) is clearly larger than the population prevalence of PSP (0.001%-0.0065%). It is also 2 to 5 times the proportion of normal cases with incidental PSP in 2 previous autopsy series. This case series raises the questions of an association between ET and PSP, whether ET patients are at an increased risk of developing PSP, and what the proportion of ET patients who develop presumed Parkinson disease or Alzheimer disease in life actually have PSP (i.e. ET + PSP).


Assuntos
Tremor Essencial/complicações , Tremor Essencial/patologia , Paralisia Supranuclear Progressiva/etiologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários
18.
Neurosci Lett ; 518(1): 49-54, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22561033

RESUMO

Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28±0.47 vs. 1.06±0.32, p=0.02; and 1.38±0.75 vs. 1.00±0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET.


Assuntos
Córtex Cerebelar/metabolismo , Tremor Essencial/metabolismo , Tremor Essencial/patologia , Proteínas de Neurofilamentos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Transporte Axonal/fisiologia , Córtex Cerebelar/química , Córtex Cerebelar/patologia , Feminino , Humanos , Filamentos Intermediários/metabolismo , Masculino , Proteínas de Neurofilamentos/análise , Fosforilação , Células de Purkinje/metabolismo , Células de Purkinje/patologia
19.
Clin Neuropathol ; 31(3): 119-26, 2012 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22551915

RESUMO

BACKGROUND: Essential tremor (ET), a progressive, age-associated disease, is one of the most common neurological disorders. Yet until recently, there had been few postmortem examinations so that the full range of pathological changes associated with this disease has not been catalogued. OBJECTIVES: We report a patient with ET who had a pattern of pathological change which to our knowledge has not previously been reported in ET or another neurological disease. METHODS: Clinical-pathological case report. RESULTS: The patient had adult-onset, non-familial, kinetic arm tremor that gradually worsened. Voice and head tremors were also present. The clinical diagnosis was ET. She died at age 102. On postmortem examination, there was severe segmental loss of Purkinje cells, Bergmann gliosis and numerous torpedoes in the cerebellum. The other outstanding change was the presence of neurons in the cerebral cortex and hippocampus that contained an ubiquitinated, nuclear inclusion. These inclusions were not detected in Luxol fast blue/hematoxylin and eosin-stained sections. CONCLUSIONS: This ET patient had a pattern of pathological change that has not been reported previously. This case further reinforces the view that ET is likely to be a heterogeneous family of degenerative diseases whose underlying pathological anatomy involves the cerebellum.


Assuntos
Cerebelo/patologia , Tremor Essencial/patologia , Corpos de Inclusão/patologia , Degeneração Neural/patologia , Idoso de 80 Anos ou mais , Encéfalo/patologia , Tremor Essencial/metabolismo , Feminino , Humanos , Corpos de Inclusão/metabolismo , Ubiquitinação
20.
PLoS One ; 7(12): e53040, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300858

RESUMO

Macroautophagy is a cellular mechanism for the clearance of protein aggregates and damaged organelles. Impaired macroautophagy has been observed in neurodegenerative disorders. We investigated the macroautophagy pathway in essential tremor (ET) cases compared to age-matched controls. We analyzed microtubule-associated protein light chain 3-II (LC3-II), S6K, phosphorylated S6K, beclin-1, and mitochondrial membrane proteins levels by Western blot in the post-mortem cerebellum of 10 ET cases and 11 controls. We also performed immunohistochemistry in 12 ET cases and 13 controls to quantify LC3 clustering in Purkinje cells (PCs). LC3-II protein levels were significantly lower in ET cases vs. controls on Western blot (0.84 ± 0.14 vs. 1.00 ± 0.14, p = 0.02), and LC3-II clustering in PCs by immunohistochemistry was significantly lower in ET cases vs. controls (2.03 ± 3.45 vs. 8.80 ± 9.81, p = 0.03). In ET cases, disease duration was inversely correlated with LC3-II protein level (r = -0.64, p = 0.046). We found that mitochondrial membrane proteins were accumulated in ET (TIM23: 1.36 ± 0.11 in ET cases vs. 1.00 ± 0.08 in controls, p = 0.02; TOMM20: 1.63 ± 0.87 in ET cases vs. 1.00 ± 0.14 in controls, p = 0.03). Beclin-1, which is involved in macroautophagy, was strikingly deficient in ET (0.42 ± 0.13 vs. 1.00 ± 0.35, p<0.001). Decreased macroautophagy was observed in the ET cerebellum, and this could be due to a decrease in beclin-1 levels, which subsequently lead to mitochondrial accumulation as a result of autophagic failure. This provides a possible means by which perturbed macroautophagy could contribute to PC pathology in ET.


Assuntos
Autofagia/fisiologia , Cerebelo/metabolismo , Tremor Essencial/metabolismo , Células de Purkinje/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Estudos de Casos e Controles , Cerebelo/patologia , Tremor Essencial/patologia , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Fosforilação , Células de Purkinje/patologia
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