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2.
Hong Kong Med J ; 29(5): 383-395, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37766463

RESUMO

INTRODUCTION: In 2020, patients with critical coronavirus disease 2019 (COVID-19) had a 28-day mortality rate of 30% to 50% worldwide; outcomes among such patients in Hong Kong were unknown. This study investigated 28-day mortality and corresponding risk factors among patients with severe or critical COVID-19 in Hong Kong. METHODS: This retrospective cohort study included adult patients with severe or critical COVID-19 who were admitted to three public hospitals in Hong Kong from 22 January to 30 September 2020. Demographics, comorbidities, symptoms, treatment, and outcomes were examined. RESULTS: Among 125 patients with severe or critical COVID-19, 15 (12.0%) died within 28 days. Overall, the median patient age was 64 years; 48.0% and 54.4% of patients had hypertension and obesity, respectively. Respiratory samples were confirmed severe acute respiratory syndrome coronavirus 2 RNA-positive after a median of 3 days. The most common presenting symptom was fever (80.0% of patients); 45.6% and 32.8% of patients received care in intensive care unit and required mechanical ventilation, respectively. In logistic regression analysis comparing 28-day survivors and non-survivors, factors associated with greater 28-day mortality were older age (odds ratio [OR] per 1-year increase in age=1.12, 95% confidence interval [CI]=1.04-1.21; P=0.002), history of stroke (OR=15.96, 95% CI=1.65-154.66; P=0.017), use of renal replacement therapy (OR=15.32, 95% CI=2.67-87.83; P=0.002), and shorter duration of lopinavir-ritonavir treatment (OR per 1-day increase=0.82, 95% CI=0.68-0.98; P=0.034). CONCLUSION: The 28-day mortality rate among patients with severe or critical COVID-19 in Hong Kong was 12.0%. Older age, history of stroke, use of renal replacement therapy, and shorter duration of lopinavir-ritonavir treatment were independent predictors of 28-day mortality.


Assuntos
COVID-19 , Acidente Vascular Cerebral , Adulto , Humanos , Pessoa de Meia-Idade , Lactente , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Hong Kong/epidemiologia , Estudos Retrospectivos , Pandemias
4.
Clin Radiol ; 76(2): 158.e1-158.e12, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33008621

RESUMO

AIM: To describe and test a new method that increases the conspicuity of a Hill-Sachs lesion on internal rotation (IR) radiographs. MATERIALS AND METHODS: This study had institutional review board approval. A retrospective search for patients with a prior shoulder dislocation and a Hill-Sachs lesion documented on magnetic resonance imaging (MRI) was performed over a 10-year period identifying 256 test patients. In Part 1, the IR radiographs from test cases were randomised with controls, and three readers scored them independently for the defect. The readers were then taught the Broken Circle (BC) method and re-scored the radiographs. In Part 2, 15 cases of Hill-Sachs lesions that were missed by all readers in Part 1 were randomised with controls, and were shown to 25 radiology residents before (pre-test) and after (post-test) learning the BC method. A paired t-test was used to compare the differences in sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In Part 1, the sensitivity increased 19.7% (54.1%-73.8%; p<0.05) and NPV increased 10.8% (62.5%-73.3%; p<0.01). In Part 2, post-test sensitivity for residents increased 16.3% (55.2%-71.5%; p<0.0001), accuracy increased 13.4% (64%-77.4%; p<0.0001), and NPV increased 13.3% (40.8%-54.1%; p<0.0001) independent of the level of training. The change in accuracy was also statistically significant for every individual class. CONCLUSION: The BC method was an effective technique that facilitated detection of a Hill-Sachs lesion at all levels of training, and was useful as a teaching tool.


Assuntos
Lesões de Bankart/diagnóstico por imagem , Radiografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Ombro/diagnóstico por imagem , Adulto Jovem
5.
Hong Kong Med J ; 26(5): 372-381, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32641539

RESUMO

PURPOSE: Streptococcus pneumoniae is a common pathogen involved in community-acquired pneumonia. Invasive pneumococcal disease is often associated with higher co-morbidity rates, but mortality-related findings have been inconclusive. This study investigated predictors of 30-day mortality and invasive pneumococcal disease. METHODS: This retrospective analysis included adults with pneumococcal disease who were admitted to Pamela Youde Nethersole Eastern Hospital from 1 January 2011 to 31 December 2018. Demographics, microbiological characteristics, and outcomes were compared between 30-day survivors and non-survivors, and between patients with invasive disease and those with non-invasive disease. Intensive care unit (ICU) subgroup analysis was performed. The primary outcome was 30-day all-cause mortality; secondary outcomes were ICU and hospital mortalities, and ICU and hospital lengths of stay. RESULTS: In total, 792 patients had pneumococcal disease; 701 survived and 91 (11.5%) died within 30 days. Notably, 106 (13.4%) patients had invasive pneumococcal disease and 170 (21.5%) patients received intensive care. Vasopressor use (odds ratio [OR]=4.96, P<0.001), chronic kidney disease (OR=3.62, P<0.001), positive urinary antigen test results (OR=2.57, P=0.001), and advanced age (OR=2.19, P=0.010) were independent predictors for 30-day mortality by logistic regression analysis. Among critically ill patients, chronic kidney disease (OR=4.64, P<0.001), higher APACHE IV score (OR=3.73, P=0.016), and positive urinary antigen test results (OR=2.94, P=0.008) were predictors for 30-day mortality. Logistic regression analysis revealed that chronic kidney disease (OR=3.10, P<0.001) was a risk factor for invasive pneumococcal disease. CONCLUSION: Advanced age, vasopressor use, chronic kidney disease, and positive urinary antigen test results were independent predictors for 30-day mortality in patients with pneumococcal disease.


Assuntos
Infecções Comunitárias Adquiridas/mortalidade , Mortalidade Hospitalar , Infecções Pneumocócicas/mortalidade , Streptococcus pneumoniae , APACHE , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/microbiologia , Cuidados Críticos/estatística & dados numéricos , Resultados de Cuidados Críticos , Estado Terminal/mortalidade , Feminino , Hong Kong/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Estudos Retrospectivos , Fatores de Risco
7.
Clin Radiol ; 75(3): 237.e1-237.e9, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31787211

RESUMO

AIM: To investigate the feasibility of applying a deep convolutional neural network (CNN) for detection/localisation of acute proximal femoral fractures (APFFs) on hip radiographs. MATERIALS AND METHODS: This study had institutional review board approval. Radiographs of 307 patients with APFFs and 310 normal patients were identified. A split ratio of 3/1/1 was used to create training, validation, and test datasets. To test the validity of the proposed model, a 20-fold cross-validation was performed. The anonymised images from the test cohort were shown to two groups of radiologists: musculoskeletal radiologists and diagnostic radiology residents. Each reader was asked to assess if there was a fracture and localise it if one was detected. The area under the receiver operator characteristics curve (AUC), sensitivity, and specificity were calculated for the CNN and readers. RESULTS: The mean AUC was 0.9944 with a standard deviation of 0.0036. Mean sensitivity and specificity for fracture detection was 97.1% (81.5/84) and 96.7% (118/122), respectively. There was good concordance with saliency maps for lesion identification, but sensitivity was lower for characterising location (subcapital/transcervical, 84.1%; basicervical/intertrochanteric, 77%; subtrochanteric, 20%). Musculoskeletal radiologists showed a sensitivity and specificity for fracture detection of 100% and 100% respectively, while residents showed 100% and 96.8%, respectively. For fracture localisation, the performance decreased slightly for human readers. CONCLUSION: The proposed CNN algorithm showed high accuracy for detection of APFFs, but the performance was lower for fracture localisation. Overall performance of the CNN was lower than that of radiologists, especially in localizing fracture location.


Assuntos
Inteligência Artificial , Fraturas do Quadril/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
Clin Radiol ; 74(9): 735.e15-735.e22, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256908

RESUMO

AIM: To investigate the effect of peri-ampullary duodenal diverticula (PAD) on extrahepatic bile duct (EHBD) dilatation before and after cholecystectomy. MATERIALS AND METHODS: During a 5-year period, a total of 860 consecutive patients with prior cholecystectomy were examined using abdominal computed tomography (CT). After exclusion of those with other obstructive EHBD lesions, 61 patients with PAD were recruited for evaluation of EHBD dilatation before and after cholecystectomy and were compared with a randomly sampled control group (n=113) without PAD. EHBD diameter was measured on coronal reconstruction CT using electronic callipers on the picture archiving and communication system monitors by two reviewers in consensus. RESULTS: There was no significant difference in EHBD diameter between PAD and non-PAD groups (8.2±2.8 versus 7.8±2.3 mm; p=0.276) before cholecystectomy. Compared with preoperative diameter, EHBD was significantly dilated after cholecystectomy (7.9±2.5 versus 9.8±3.4 mm, p<0.001), regardless of the presence of PAD; the degree of change was more prominent in the PAD group than in the non-PAD group (3.3±2.4 versus 1.1±1.6 mm; p<0.001) after surgery. The size of PAD did not affect the degree of EHBD dilatation after cholecystectomy (p=0.522). In the non-PAD group, the degree of EHBD dilatation was positively correlated with the follow-up interval after cholecystectomy (r=0.298; p=0.002), while the PAD group showed no significant correlation (r=-0.036; p=0.797). In patients with ≥2 mm postoperative EHBD dilatation, PAD incidence was higher than that in other patients (odds ratio, 8.739; p<0.001). CONCLUSION: Regardless of their size or postoperative follow-up duration, PAD induce marked post-cholecystectomy biliary dilatation.


Assuntos
Ductos Biliares/patologia , Colecistectomia , Divertículo/complicações , Divertículo/diagnóstico por imagem , Duodenopatias/complicações , Duodenopatias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares/diagnóstico por imagem , Dilatação Patológica/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem
9.
Contraception ; 96(3): 175-182, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28596122

RESUMO

OBJECTIVES: Three measures to assess the provision of effective contraception methods among reproductive-aged women have recently been endorsed for national public reporting. Based on these measures, this study examined real-world trends and regional variations of contraceptive provision in a commercially insured population in the United States. STUDY DESIGN: Women 15-44years old with continuous enrollment in each year from 2005 to 2014 were identified from a commercial claims database. In accordance with the proposed measures, percentages of women (a) provided most effective or moderately effective (MEME) methods of contraception and (b) provided a long-acting reversible contraceptive (LARC) method were calculated in two populations: women at risk for unintended pregnancy and women who had a live birth within 3 and 60days of delivery. RESULTS: During the 10-year period, the percentages of women at risk for unintended pregnancy provided MEME contraceptive methods increased among 15-20-year-olds (24.5%-35.9%) and 21-44-year-olds (26.2%-31.5%), and those provided a LARC method also increased among 15-20-year-olds (0.1%-2.4%) and 21-44-year-olds (0.8%-3.9%). Provision of LARC methods increased most in the North Central and West among both age groups of women. Provision of MEME contraceptives and LARC methods to women who had a live birth within 60days postpartum also increased across age groups and regions. CONCLUSIONS: This assessment indicates an overall trend of increasing provision of MEME contraceptive methods in the commercial sector, albeit with age group and regional variations. If implemented, these proposed measures may have impacts on health plan contraceptive access policy.


Assuntos
Anticoncepção/tendências , Acessibilidade aos Serviços de Saúde/tendências , Adolescente , Adulto , Anticoncepção/métodos , Feminino , Humanos , Seguro Saúde , Período Pós-Parto , Gravidez , Gravidez não Planejada , Estados Unidos , Adulto Jovem
10.
Clin Radiol ; 72(3): 247-254, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27789027

RESUMO

AIM: To validate the usefulness of diffusion-weighted imaging (DWI) in the differentiation of high-flow haemangiomas showing pseudo-washout appearance on gadoxetic acid-enhanced hepatic MRI from small hypervascular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: DWI (b=50, 800 s/mm2) with apparent diffusion coefficient (ADC) maps for 50 haemangiomas (6.4±2.9 mm) showing intense enhancement on arterial dominant phase imaging and hypointensity on transitional and/or hepatobiliary phase imaging during gadoxetic acid-enhanced MRI were retrospectively analysed and compared with that of 113 hypervascular HCCs (12.8±3.7 mm). In addition to measurement of mean ADC values on DWI and contrast-to-noise ratio (CNR) on corresponding T2-weighted imaging, qualitative analysis of DWI was performed for each lesion by two independent observers using a five-point scale. RESULTS: Both of mean ADC value (1.902 versus 0.997×10-3 mm2/s) and mean CNR (119.2 versus 36.9) for haemangioma were significantly larger than for HCC (p<0.001). On receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.995 for ADC values was significantly larger than 0.915 for CNRs (p=0.002). When the ADC value of 1.327×10-3 mm2/s was used as the threshold for the diagnosis of haemangioma, the sensitivity and specificity were 98% and 97.3%, respectively. The mean sensitivity and specificity of qualitative analysis for the differentiation of haemangioma from HCC were 92% and 99.1%, respectively. CONCLUSION: For high-flow small haemangiomas showing pseudo-washout appearance during gadoxetic acid-enhanced hepatic MRI, high b-factor DWI including an ADC map may provide additional information to enhance the confidence to exclude small hypervascular HCCs.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Gadolínio DTPA , Hemangioma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Meios de Contraste , Feminino , Hemangioma/patologia , Humanos , Aumento da Imagem/métodos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 51(12): 728-733, 2016 Dec 09.
Artigo em Chinês | MEDLINE | ID: mdl-27978913

RESUMO

Objective: To establish a digital workflow in the treatment of mandibular condylar osteochondroma with secondary dentofacial deformities using navigation and endoscope combined with orthognathic surgery. Methods: Thirty-six patients with unilateral condylar osteochondroma were analyzed retrospectively. Preoperative planning and simulation were carried out on the digital three-dimansional (3D) model in all patients. With the aid of image-guided endoscopic navigation, osteochondroma resection and condylectomy were accurately performed. Secondary dentofacial deformities were simultaneously corrected using orthognathic surgery. All patients were followed up regularly and received postoperative CT scans. The preoperative simulated model and the postoperative actual model were matched using ProPlan CMF 2.0 software. Four corresponding points were marked in the virtual and actual ostectomy plane, respectively. The intersections of mandibular sigmoid notch and posterior ramusrim with condylectomy plane were marked as the anterior point and the posterior point, respectively. The perpendicular bisector of the line from the anterior point to the posterior point was intersected with the lateral and medial margin of condylectomy plane to form the lateral point and the medial point, respectively. The straight-line distances between the corresponding points in the virtual and actual ostectomy plane were respectively measured to analyze the ostectomy discrepancy. Results: All of 36 patients obtained satisfactory clinical effects. Facial symmetry and morphology were greatly improved. Postoperative CT showed that condylar tumors were completely removed. The preoperative simulated model and the postoperative actual model were matched. The average discrepancy between the planned and actual surgical resection was minimal on the anterior points ([0.24 ± 0.17] mm) and the mean error was maximal on the posterior points ([3.86±1.03] mm). The patients showed no signs of tumor recurrence in the 6 to 12 months of follow-up. Conclusions: Endoscope-assisted and navigation-guided tumor resection and condylectomy combined with simultaneous orthognathic surgery has satisfactory clinical effects in the treatment of condylar osteochondroma and secondary dentofacial deformities. The digital management workflow reported in this paper provides us a valuable option for this potentially complicated procedure.


Assuntos
Deformidades Dentofaciais , Neoplasias Mandibulares , Osteocondroma , Endoscopia , Humanos , Mandíbula , Côndilo Mandibular , Recidiva Local de Neoplasia , Cirurgia Ortognática , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Fluxo de Trabalho
12.
Transl Psychiatry ; 6(10): e931, 2016 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-27779627

RESUMO

Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost of hundreds of billions of dollars each year, necessitating more effective treatment strategies and novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification of the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels of a panel of markers would provide an invaluable tool for MDD as the infrastructure-including equipment, trained personnel, billing, and governmental approval-for similar tests is well established in clinics worldwide. Here we present a supervised classification model utilizing support vector machines (SVMs) for the analysis of transcriptomic data readily obtained from a peripheral blood specimen. The model was trained on data from subjects with MDD (n=32) and age- and gender-matched controls (n=32). This SVM model provides a cross-validated sensitivity and specificity of 90.6% for the diagnosis of MDD using a panel of 10 transcripts. We applied a logistic equation on the SVM model and quantified a likelihood of depression score. This score gives the probability of a MDD diagnosis and allows the tuning of specificity and sensitivity for individual patients to bring personalized medicine closer in psychiatry.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Marcadores Genéticos/genética , Modelos Psicológicos , Máquina de Vetores de Suporte , Adulto , Estudos de Casos e Controles , Transtorno Depressivo Maior/psicologia , Feminino , Perfilação da Expressão Gênica , Humanos , Funções Verossimilhança , Masculino , Medicina de Precisão , Valor Preditivo dos Testes , Probabilidade
13.
Br J Radiol ; 87(1035): 20130513, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24472726

RESUMO

OBJECTIVE: To describe multidetector CT imaging features of solid pseudopapillary tumours (SPTs) in male patients and to compare these imaging features with those found in female patients. METHODS: The institutional review board approved this retrospective study. We included the CT images of 72 patients (M:F = 12:60; mean age, 35.0 years) diagnosed with SPT by histology. CT images were reviewed on the following: location of the tumour, maximal diameter, shape, margin and the fraction of the tumour composition. Statistical differences in CT imaging features were analysed. RESULTS: Male patients with SPTs were significantly older than female patients (42.4 years vs 33.4 years, p = 0.0408) and the mean size of the SPTs in male patients was larger (6.3 cm vs 4.6 cm, p = 0.0413) than that of SPTs in female patients. Lobulated shape of the SPTs was most frequent in male patients, whereas oval shape was most frequent in female patients (p = 0.0133). SPTs in male patients tended to have a solid component (p = 0.0434). Progressive enhancement in the solid portion of the tumour was seen in 9 (81.8%) of 11 SPTs in male patients and in 30 (79.0%) of 38 SPTs in female patients on multiphasic CT. CONCLUSION: The imaging features of SPTs in male patients usually appeared as a somewhat large-sized solid mass with a lobulated margin and progressive enhancement. These imaging features may help to differentiate SPTs from other pancreatic tumours for their proper management. ADVANCES IN KNOWLEDGE: SPTs in male patients appear as somewhat large-sized solid masses with lobulated margins, and this form occurs more frequently in older male patients than in female patients.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Neoplasias Pancreáticas/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
14.
Eur Rev Med Pharmacol Sci ; 17(11): 1427-37, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23771531

RESUMO

BACKGROUND AND OBJECTIVES: Recently, type II collagen (CII) was found to be effective clinically for treatment of rheumatoid arthritis (RA). However, the molecular properties of CII could be changed during the preparation process. In the present study, we isolated CII from chick sternal cartilage and studied the structural characteristics of purified CII. MATERIALS AND METHODS: Pepsin-solubilized CII was purified from sternal cartilage of the chick using a combination of pepsin digestion, NaCl precipitation and DEAE-Sepharose CL 6B ion exchange chromatography. Then, the molecular structure and physicochemical properties of pepsin-solubilized CII were investigated. RESULTS: According to the electrophoretic patterns, the purified preparation consisted of a single band (α chain) and dimmers (ß chains) with a subunit Mr of 110 kDa, were characterized to type II, and contained imino acid of 232 residues/1000 residues. The maximum transition temperature (Tmax) of the pepsin-solubilized CII measured by DSC was 45.60°C. Circular dichroism (CD) spectra analysis revealed that pepsin-solubilized CII retained more intermolecular crosslinks during the preparation process. Investigation results of atomic force microscope (AFM) indicated that the collagen fibrils from chick cartilage were about 146 nm in width and highly periodic with a banding pattern of -68.3 nm spacing. Analysis of physical properties indicated that pepsin-solubilized CII were highly solubilized in the pH range of 1-3.5 and the optimal NaCl concentration was 0.6 mol/L. CONCLUSIONS: Chick sternal cartilage can be used as an alternative CII source.


Assuntos
Cartilagem/química , Colágeno Tipo II/química , Aminoácidos/análise , Animais , Galinhas , Dicroísmo Circular , Colágeno Tipo II/ultraestrutura , Microscopia de Força Atômica , Pepsina A/metabolismo , Estabilidade Proteica , Esterno
15.
Cell Death Dis ; 3: e347, 2012 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-22785533

RESUMO

Diverse death phenotypes of cancer cells can be induced by Photofrin-mediated photodynamic therapy (PDT), which has a decisive role in eliciting a tumor-specific immunity for long-term tumor control. However, the mechanism(s) underlying this diversity remain elusive. Caspase-3 is a critical factor in determining cell death phenotypes in many physiological settings. Here, we report that Photofrin-PDT can modify and inactivate procaspase-3 in cancer cells. In cells exposed to an external apoptotic trigger, high-dose Photofrin-PDT pretreatment blocked the proteolytic activation of procaspase-3 by its upstream caspase. We generated and purified recombinant procaspase-3-D(3)A (a mutant without autolysis/autoactivation activity) to explore the underlying mechanism(s). Photofrin could bind directly to procaspase-3-D(3)A, and Photofrin-PDT-triggered inactivation and modification of procaspase-3-D(3)A was seen in vitro. Mass spectrometry-based quantitative analysis for post-translational modifications using both (16)O/(18)O- and (14)N/(15)N-labeling strategies revealed that Photofrin-PDT triggered a significant oxidation of procaspase-3-D(3)A (mainly on Met-27, -39 and -44) in a Photofrin dose-dependent manner, whereas the active site Cys-163 remained largely unmodified. Site-directed mutagenesis experiments further showed that Met-44 has an important role in procaspase-3 activation. Collectively, our results reveal that Met oxidation is a novel mechanism for the Photofrin-PDT-mediated inactivation of procaspase-3, potentially explaining at least some of the complicated cell death phenotypes triggered by PDT.


Assuntos
Caspase 3/metabolismo , Éter de Diematoporfirina/farmacologia , Metionina/química , Fármacos Fotossensibilizantes/farmacologia , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Caspase 3/genética , Domínio Catalítico , Linhagem Celular Tumoral , Éter de Diematoporfirina/uso terapêutico , Humanos , Células Jurkat , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Isótopos de Nitrogênio/química , Oxirredução , Isótopos de Oxigênio/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Ligação Proteica , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espectrometria de Massas em Tandem , Raios Ultravioleta
16.
Br J Radiol ; 85(1018): e879-86, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22573299

RESUMO

OBJECTIVE: To compare the value of diffusion-weighted MRI (DWI) with the venous "washout" appearance during dynamic MRI for the assessment of small arterial hypervascular lesions in cirrhotic liver. METHODS: After exclusion of benign hypervascular lesions, including haemangiomas and subcapsular non-tumorous arterioportal shunts, indicated by typical imaging features, a total of 109 small arterial hypervascular lesions (0.5-3.0 cm in the longest diameter) in 65 patients with cirrhosis who underwent gadopentetate dimeglumine-enhanced dynamic MRI and DWI (b=50, 400, 800 s mm(-2)) at 1.5 T during a 16-month period were retrospectively analysed to determine the presence of venous washout during dynamic imaging or sustained hyperintensity upon increasing the b factor size on DWI. RESULTS: Among the 99 hypervascular hepatocellular carcinomas (HCCs), sustained hyperintensity on DWI (92/99, 93%) was more prevalent than the washout appearance (72/99, 72%) on dynamic MRI (p<0.001). Depending on the lesion size, subcentimetre-sized HCCs had a significantly lower prevalence of venous washout (13/30, 43%) than the sustained hyperintensity on DWI (27/30, 90%) (p=0.001). In all 10 hypervascular benign conditions, there was no venous washout on dynamic MRI and no sustained hyperintensity on DWI. Sensitivity and specificity for diagnosis of hypervascular HCCs were 92.9% and 100% in DWI and 72% and 100% in dynamic MRI, respectively. CONCLUSION: Compared with the venous washout during dynamic imaging, DWI provides more reliable information in the MRI assessment of small hypervascular HCCs, distinguishing them from atypical hypervascular benign or pseudolesions. DWI could complement the early diagnosis of small hypervascular HCCs that do not display venous washout during dynamic imaging.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/irrigação sanguínea , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Br J Radiol ; 85(1013): 571-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21304008

RESUMO

OBJECTIVES: The purpose of this study was to describe the MRI features of the benign pancreatic neoplasm serous oligocystic adenoma (SOA) that differ from those of mucinous cystic neoplasm (MCN), a neoplasm with the potential for malignant degeneration. METHODS: Seven patients with SOA (seven women; mean age 36.6 years) and eight patients with MCN (eight women: mean age 39.9 years) were included. Several imaging features were reviewed: mass size, location, shape, wall thickness, cyst configuration (Type I, unilocular; Type II, multiple clustered cyst; Type III, cyst with internal septation) and signal intensity of the lesion with heterogeneity. RESULTS: SOA lesions were smaller (3.4 cm) than those of MCN (9.3 cm) (p=0.023). The commonest lesion shape was lobulated (85.7%) for SOA, but oval (50.0%) or lobulated (37.5%) for MCN (p=0.015). The most common cyst configuration was Type II (85.7%) for SOA and Type III (75.0%) for MCN (p=0.008). Heterogeneity of each locule in T(1) weighted images was visible in all cases of MCN, but in no case for SOA (p=0.004). CONCLUSION: SOA could be differentiated from MCN by identifying the imaging features of lobulated contour with multiple clustered cyst configurations and homogeneity of each locule in T(1) weighted MR images.


Assuntos
Cistadenoma Mucinoso/diagnóstico , Cistadenoma Seroso/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico , Adulto , Cistadenoma Mucinoso/patologia , Cistadenoma Seroso/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/patologia , Adulto Jovem
18.
Clin Genet ; 82(5): 460-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21848650

RESUMO

This study explored the role of TCOF1 insertion mutations in Taiwanese patients with craniofacial anomalies. Twelve patients with single or multiple, asymmetrical congenital craniofacial anomalies were enrolled. Genomic DNA was prepared from leukocytes; the coding regions of TCOF1 were analyzed by polymerase chain reaction and direct sequencing. Clinical manifestations were correlated to the TCOF1 mutation. Six of 12 patients diagnosed with hemifacial microsomia exhibited a novel insertion mutation 4127 ins G (frameshift) in exon 24 in the TCOF1 gene. All six patients were diagnosed with anomalies on the left side. In addition, four of these six patients had hearing impairment; three had other major anomalies; and two had developmental delay. The insertion caused a frameshift, an early truncation, the loss of two putative nuclear localization signals (residues 1404-1420 and 1424-1440), and the loss of coiled coil domain (1406-1426) in treacle protein. These findings support the existence of two regulators of growth of the mandibular condyles.


Assuntos
Assimetria Facial/genética , Mutagênese Insercional , Proteínas Nucleares/genética , Fosfoproteínas/genética , Adulto , Criança , Pré-Escolar , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Éxons , Feminino , Mutação da Fase de Leitura , Genoma Humano/genética , Humanos , Lactente , Recém-Nascido , Masculino , Sinais de Localização Nuclear/genética , Proteínas Nucleares/metabolismo , Fenótipo , Fosfoproteínas/metabolismo , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Taiwan
19.
Br J Radiol ; 83(985): 71-81, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19581309

RESUMO

Following transcatheter arterial chemoembolisation (TACE), the appearances on CT or MR images are largely related to the chemical and ischaemic insults to the portal tract. Understanding the mechanism of TACE-induced changes is essential for radiologists in order to determine the therapeutic effect as well as to distinguish these changes from recurrent tumours. This pictorial review illustrates the haemodynamic and substantial parenchymal changes related to TACE for hepatic malignancy.


Assuntos
Quimioembolização Terapêutica , Hemodinâmica , Neoplasias Hepáticas/terapia , Idoso , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/etiologia , Atrofia/diagnóstico por imagem , Atrofia/etiologia , Doenças dos Ductos Biliares/diagnóstico por imagem , Doenças dos Ductos Biliares/epidemiologia , Doenças dos Ductos Biliares/etiologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Infarto/diagnóstico por imagem , Infarto/etiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Circulação Hepática/fisiologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Br J Radiol ; 83(987): 212-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19505965

RESUMO

The purpose of this study was to evaluate the diagnostic ability of the expanded gallbladder fossa and right posterior hepatic notch signs for hepatic fibrosis determined by double contrast-enhanced MRI. For patients with chronic viral hepatitis B (n = 96) or hepatitis C (n = 13) who underwent gadopentate dimeglumine-enhanced dynamic MRI followed by ferucarbotran-enhanced gradient-echo imaging, the degree of parenchymal fibrosis was categorised into three groups based on the extent of reticulation and nodularity: (1) pre-cirrhotic or minimal fibrosis; (2) mild to moderate fibrosis; (3) advanced cirrhosis. Each group was evaluated for the presence of a sharp notch in the posterior-medial surface of the right lobe of the liver and expanded gallbladder fossa. The expanded gallbladder fossa sign gradually increased with an increasing degree of fibrosis (Group 1, 50%; Group 2, 61%; Group 3, 78%), and there was no significant difference (p>0.5) between hepatitis B (67%) and C (73%). In the case of the right posterior hepatic notch sign, only 6% of Group 1 and Group 2 patients were positive; 27% of hepatitis B patients and 90% of hepatitis C patients in Group 3 exhibited the sign (p<0.05). Owing to its low prevalence, even in advanced cirrhosis, the right posterior hepatic notch sign is of little value in the diagnosis of cirrhosis due to chronic hepatitis B virus infection, whereas an expanded gallbladder fossa could be used as a non-specific indicator of early fibrosis before the gross appearance of advanced hepatic fibrosis.


Assuntos
Vesícula Biliar/patologia , Cirrose Hepática/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Meios de Contraste , Dextranos , Estudos de Viabilidade , Feminino , Óxido Ferroso-Férrico , Gadolínio DTPA , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
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