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1.
Hong Kong Med J ; 30(3): 218-226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38835098

RESUMO

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.


Assuntos
Líquido Amniótico , Atresia Biliar , Vesícula Biliar , Idade Gestacional , gama-Glutamiltransferase , Humanos , gama-Glutamiltransferase/sangue , Feminino , Gravidez , Estudos Retrospectivos , Valores de Referência , Líquido Amniótico/química , Atresia Biliar/diagnóstico , Atresia Biliar/sangue , Valor Preditivo dos Testes , Adulto , Diagnóstico Pré-Natal/métodos
3.
J Pers Med ; 12(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35743641

RESUMO

A number of genomic variants related to native American ancestry may be associated with an increased risk of developing Acute Lymphoblastic Leukemia (ALL), which means that Latin American and hispanic populations from the New World may be relatively susceptible to this disease. However, there has not yet been any comprehensive investigation of the variants associated with susceptibility to ALL in traditional Amerindian populations from Brazilian Amazonia. We investigated the exomes of the 18 principal genes associated with susceptibility to ALL in samples of 64 Amerindians from this region, including cancer-free individuals and patients with ALL. We compared the findings with the data on populations representing five continents available in the 1000 Genomes database. The variation in the allele frequencies found between the different groups was evaluated using Fisher's exact test. The analyses of the exomes of the Brazilian Amerindians identified 125 variants, seven of which were new. The comparison of the allele frequencies between the two Amerindian groups analyzed in the present study (ALL patients vs. cancer-free individuals) identified six variants (rs11515, rs2765997, rs1053454, rs8068981, rs3764342, and rs2304465) that may be associated with susceptibility to ALL. These findings contribute to the identification of genetic variants that represent a potential risk for ALL in Amazonian Amerindian populations and might favor precision oncology measures.

4.
Hong Kong Med J ; 27(5): 338-349, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34706984

RESUMO

INTRODUCTION: Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and to examine predictors for recreational cycling-induced intracranial haemorrhage. METHODS: This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital. RESULTS: In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital. CONCLUSIONS: The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture.


Assuntos
Traumatismos em Atletas , Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/etiologia , Dispositivos de Proteção da Cabeça , Hong Kong/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Hong Kong Med J ; 26(6): 479-485, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33284132

RESUMO

OBJECTIVES: To investigate the effects of pre-hospital stroke screening and notification on reperfusion therapy for patients with acute ischaemic stroke. METHODS: Pre-hospital stroke screening criteria were established based on a modified version of the Face Arm Speech Time (FAST) test. Screening was performed during ambulance transport by emergency medical service (EMS) personnel who completed a 2-hour training session on stroke screening. Temporal trends affecting acute ischaemic stroke investigation and intervention were compared before and after implementation of the pre-hospital screening. RESULTS: From July 2018 to October 2019, 298 patients with suspected stroke were screened by EMS personnel during ambulance transport prior to hospital arrival. Of these 298 patients, 213 fulfilled the screening criteria, 166 were diagnosed with acute stroke, and 32 received reperfusion therapy. The onset-to-door time was shortened by more than 1.5 hours (100.6 min vs 197.6 min, P<0.001). The door-to-computed tomography time (25.6 min vs 32.0 min, P=0.021), door-to-needle time (49.2 min vs 70.1 min, P=0.003), and door-to-groin puncture time for intra-arterial mechanical thrombectomy (126.7 min vs 168.6 min, P=0.04) were significantly shortened after implementation of the pre-hospital screening and notification, compared with historical control data of patients admitted from January 2018 to June 2018, before implementation of the screening system. CONCLUSION: Implementation of pre-hospital stroke screening using criteria based on a modified version of the FAST test, together with pre-arrival notification, significantly shortened the door-to-reperfusion therapy time for patients with ischaemic stroke. Pre-hospital stroke screening during ambulance transport by EMS personnel who complete a 2-hour focused training session is effective for identifying reperfusion-eligible patients with stroke.


Assuntos
Programas de Triagem Diagnóstica , Serviços Médicos de Emergência/métodos , AVC Isquêmico/diagnóstico , Reperfusão/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Auxiliares de Emergência/educação , Feminino , Implementação de Plano de Saúde , Humanos , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
6.
Am J Hosp Palliat Care ; 36(9): 760-766, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30744386

RESUMO

BACKGROUND: Noncancer patients with life-limiting diseases often receive more intensive level of care in their final days of life, with more cardiopulmonary resuscitation performed and less do-not-resuscitate (DNR) orders in place. Nevertheless, death is still often a taboo across Chinese culture, and ethnic disparities could negatively affect DNR directives completion rates. OBJECTIVES: We aim to explore whether Chinese noncancer patients are willing to sign their own DNR directives in a palliative specialist clinic, under a multidisciplinary team approach. DESIGN: Retrospective chart review of all noncancer patients with life-limiting diseases referred to palliative specialist clinic at a tertiary hospital in Hong Kong over a 4-year period. RESULTS: Over the study period, a total of 566 noncancer patients were seen, 119 of them completed their own DNR directives. Patients had a mean age of 74.9. Top 3 diagnoses were chronic renal failure (37%), congestive heart failure (16%), and motor neuron disease (11%). Forty-two percent of patients signed their DNR directives at first clinic attendance. Most Chinese patients (76.5%) invited family caregivers at DNR decision-making, especially for female gender (84.4% vs 69.1%; P = .047) and older (age >75) age group (86.2% vs 66.7%; P = .012). Of the 40 deceased patients, median time from signed directives to death was 5 months. Vast majority (95%) had their DNR directives being honored. CONCLUSION: Health-care workers should be sensitive toward the cultural influence during advance care planning. Role of family for ethnic Chinese remains crucial and professionals should respect this family oriented decision-making.


Assuntos
Diretivas Antecipadas/etnologia , Povo Asiático/psicologia , Atitude Frente a Morte/etnologia , Cuidados Paliativos/psicologia , Ordens quanto à Conduta (Ética Médica)/psicologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/psicologia , Competência Cultural , Tomada de Decisões , Família , Feminino , Hong Kong , Humanos , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/psicologia , Estudos Retrospectivos , Fatores Socioeconômicos , Assistência Terminal/psicologia , Fatores de Tempo
7.
Neuroradiology ; 60(10): 1093-1096, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30132019

RESUMO

Cerebral venous sinus thrombosis is an uncommon cause of stroke with high morbidity and mortality rates from venous infarction, intracranial hemorrhage, and extensive cerebral edema. Endovascular treatment with various devices has been proposed as a salvage treatment when standard medical treatment with systemic anticoagulation is ineffective, especially in long segment dural sinus thrombosis. We describe our technique of transvenous endovascular aspiration thrombectomy with large bore thrombectomy catheters, followed by placement of microcatheter for local thrombolytic infusion at the site of thrombosis. We report a retrospective study of angiographic and clinical outcome of six consecutive patients treated with this approach. Endovascular aspiration thrombectomy with large bore catheters followed by continuous local thrombolytic infusion appeared to be a safe and effective salvage treatment for selected patients with cerebral dural venous sinus thrombosis refractory to medical treatment.


Assuntos
Imageamento por Ressonância Magnética , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/terapia , Trombectomia/métodos , Terapia Trombolítica/métodos , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
8.
J Thromb Haemost ; 16(4): 791-801, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29442415

RESUMO

Essentials It is unclear if platelet micro-RNAs can regulate de novo protein synthesis of platelets. Platelet de novo protein synthesis of thrombospondin-1 (TSP-1) was induced by thrombin. Thrombin stimulation in vitro altered platelet microRNA profiles, including decreased miR-27b. Decreased miR-27b hampers platelet angiogenic activities via enhancing de novo TSP-1 synthesis. SUMMARY: Background Platelets can synthesize proteins upon activation. Platelets contain a number of microRNAs (miRNA) and a fully functional miRNA effector machinery. It is, however, unclear if platelet miRNAs can regulate protein synthesis of platelets, and whether the regulation may produce a physiological impact. Objectives To investigate if and how platelet miRNAs regulate de novo syntheses of angiogenic regulators and subsequently modulate platelet angiogenic activities. Methods and Results Microarray-based miRNA profiling showed that thrombin stimulation in vitro down- or up-regulated a number of platelet miRNAs, both in the total platelet miRNAs and in Ago2-associated miRNAs. Among those altered miRNAs, miR-27b was down-regulated in both the total and Ago2-immunoprecipitated miRNA profiles of platelets, which was confirmed by reverse transcription-quantitative PCR (RT-qPCR). Using western blotting assays, we showed that thrombin induced platelet de novo synthesis of thrombospondin-1, and that the level of thrombospondin-1 synthesis could reach a level of 3-5-fold higher than that before thrombin stimulation. With either the platelet precursor megakaryocyte cell line MEG-01 cells or mature platelets, we demonstrated that transfection of miR-27b mimic, but not the negative control of miRNA mimic, markedly reduced thrombospondin-1 protein levels. The latter subsequently enhanced platelet-dependent endothelial tube formation on matrigel. Conclusions Thrombin stimulation in vitro reduces platelet miR-27b levels that may markedly enhance thrombin-evoked platelet de novo synthesis of thrombospondin-1. Elevation of platelet miR-27b by transfection inhibits thrombospondin-1 synthesis, and subsequently enhances platelet pro-angiogenic activities. Hence, platelet activation-dependent reduction of miR-27b levels may represent a novel negative regulatory mechanism of platelet angiogenic activities.


Assuntos
Inibidores da Angiogênese/farmacologia , Plaquetas/efeitos dos fármacos , MicroRNAs/sangue , Neovascularização Fisiológica/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Trombina/farmacologia , Trombospondina 1/biossíntese , Adulto , Proteínas Argonautas/sangue , Plaquetas/metabolismo , Linhagem Celular , Células Progenitoras Endoteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais , Trombospondina 1/sangue , Trombospondina 1/genética , Adulto Jovem
9.
Hong Kong Med J ; 24(1): 73-80, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29424346

RESUMO

Acute ischaemic stroke due to large vessel occlusion leads to grave neurological morbidity and mortality. Conventional intravenous thrombolysis is ineffective in achieving timely reperfusion in this group of patients. The publication of five positive randomised controlled trials of emergency thrombectomy for acute ischaemic stroke in 2015 provided strong evidence to support endovascular reperfusion therapy and represented a paradigm shift in acute stroke management. In this article, we review the current evidence and international guidelines, and report on the findings of a survey study of the clinical practice and opinions of local neurologists, neurosurgeons, and interventional radiologists in emergency thrombectomy. We also discuss the controversies around thrombectomy treatment, local experience, and suggestions to incorporate thrombectomy in acute stroke treatment.


Assuntos
Isquemia Encefálica/cirurgia , Emergências , Acidente Vascular Cerebral/cirurgia , Trombectomia/normas , Isquemia Encefálica/complicações , Análise Custo-Benefício , Hong Kong , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombectomia/economia , Tempo para o Tratamento , Resultado do Tratamento
10.
Hong Kong Med J ; 22(5): 410-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562986

RESUMO

OBJECTIVES: To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. METHODS: This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. RESULTS: A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3-16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. CONCLUSIONS: This is the first Hong Kong territory-wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency.


Assuntos
Antibacterianos/administração & dosagem , Infecção da Ferida Cirúrgica/epidemiologia , Vancomicina/administração & dosagem , Derivação Ventriculoperitoneal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Falha de Equipamento , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Hong Kong Med J ; 21(5): 435-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26371158

RESUMO

OBJECTIVES: To examine the level of family satisfaction in a local intensive care unit and its performance in comparison with international standards, and to determine the factors independently associated with higher family satisfaction. DESIGN: Questionnaire survey. SETTING: A medical-surgical adult intensive care unit in a regional hospital in Hong Kong. PARTICIPANTS: Adult family members of patients admitted to the intensive care unit for 48 hours or more between 15 June 2012 and 31 January 2014, and who had visited the patient at least once during their stay. RESULTS: Of the 961 eligible families, 736 questionnaires were returned (response rate, 76.6%). The mean (± standard deviation) total satisfaction score, and subscores on satisfaction with overall intensive care unit care and with decision-making were 78.1 ± 14.3, 78.0 ± 16.8, and 78.6 ± 13.6, respectively. When compared with a Canadian multicentre database with respective mean scores of 82.9 ± 14.8, 83.5 ± 15.4, and 82.6 ± 16.0 (P<0.001), there was still room for improvement. Independent factors associated with complete satisfaction with overall care were concern for patients and families, agitation management, frequency of communication by nurses, physician skill and competence, and the intensive care unit environment. A performance-importance plot identified the intensive care unit environment and agitation management as factors that required more urgent attention. CONCLUSIONS: This is the first intensive care unit family satisfaction survey published in Hong Kong. Although comparable with published data from other parts of the world, the results indicate room for improvement when compared with a Canadian multicentre database. Future directions should focus on improving the intensive care unit environment, agitation management, and communication with families.


Assuntos
Comportamento do Consumidor , Família/psicologia , Unidades de Terapia Intensiva/normas , Adulto , Canadá , Comunicação , Tomada de Decisões , Feminino , Pesquisas sobre Atenção à Saúde , Ambiente de Instituições de Saúde , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Relações Profissional-Família , Agitação Psicomotora/terapia
12.
Br J Cancer ; 111(11): 2091-102, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25349971

RESUMO

BACKGROUND: Gastrointestinal stromal tumour (GIST) is mainly initialised by receptor tyrosine kinase gene mutations. Although the tyrosine kinase inhibitor imatinib mesylate considerably improved the outcome of patients, imatinib resistance still remains a major therapeutic challenge in GIST therapy. Herein we evaluated the clinical impact of microRNAs in imatinib-treated GISTs. METHODS: The expression levels of microRNAs were quantified using microarray and RT-qPCR in GIST specimens from patients treated with neoadjuvant imatinib. The functional roles of miR-125a-5p and PTPN18 were evaluated in GIST cells. PTPN18 expression was quantified by western blotting in GIST samples. RESULTS: We showed that overexpression levels of miR-125a-5p and miR-107 were associated with imatinib resistance in GIST specimens. Functionally, miR-125a-5p expression modulated imatinib sensitivity in GIST882 cells with a homozygous KIT mutation but not in GIST48 cells with double KIT mutations. Overexpression of miR-125a-5p suppressed PTPN18 expression, and silencing of PTPN18 expression increased cell viability in GIST882 cells upon imatinib treatment. PTPN18 protein levels were significantly lower in the imatinib-resistant GISTs and inversely correlated with miR-125a-5p. Furthermore, several microRNAs were significantly associated with metastasis, KIT mutational status and survival. CONCLUSIONS: Our findings highlight a novel functional role of miR-125a-5p on imatinib response through PTPN18 regulation in GIST.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , MicroRNAs/fisiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Mesilato de Imatinib , Mutação , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases não Receptoras/fisiologia , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
13.
Transplant Proc ; 46(2): 630-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656031

RESUMO

We report a case of 59-year-old woman who received a kidney transplant 7 years earlier without evidence of viral hepatitis history. She was asymptomatic initially and a newly developed nodule, ∼2.3 cm in size, was discovered in the right liver during routine sonographic examination. Computerized tomography-guided biopsy was inconclusive at that time. However, the lesion grew to 6.8 cm and bilobular multiple nodules developed with concomitant massive ascites and hyperbilirubinemia months later. Laparoscopy showed typical bluish-reddish-blackish nodules. Needle-biopsy histology showed severe sinusoid dilation and dropout of centrilobular hepatocytes consistent with peliosis hepatis. Reticulin staining also demonstrated disruption of sinusoidal reticulin fibers. We tried to withdraw possible offending drugs to anticipate regression of peliosis, but it failed and liver dysfunction progressed, leaving liver transplant as the last resort in such rare circumstances.


Assuntos
Transplante de Rim , Peliose Hepática/diagnóstico , Feminino , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Peliose Hepática/patologia , Peliose Hepática/fisiopatologia , Tomografia Computadorizada por Raios X
15.
Oncogene ; 33(35): 4407-17, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24469038

RESUMO

Wig-1, also known as ZMAT3, is a p53 target gene that encodes an RNA-binding zinc-finger protein involved in the regulation of mRNA stability through binding to AU-rich elements (AREs). We have used microarray analysis to identify novel Wig-1 target mRNAs. We identified 2447 transcripts with >fourfold differential expression between Wig-1 and control small interfering (si)RNA-treated HCT116 cells. Several p53 target genes were among the deregulated transcripts. We found that Wig-1 regulates FAS and 14-3-3σ mRNA independently of p53. We show that Wig-1 binds to FAS mRNA 3'-UTR and decreases its stability through an ARE in the 3'-UTR. Depletion of Wig-1 was associated with increased cell death and reduced cell cycle arrest upon DNA damage. Our results suggest a role of Wig-1 as a survival factor that directs the p53 stress response toward cell cycle arrest rather than apoptosis through the regulation of FAS and 14-3-3σ mRNA levels.


Assuntos
Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Proteínas de Transporte/metabolismo , Pontos de Checagem do Ciclo Celular , Exorribonucleases/genética , Proteínas Nucleares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Receptor fas/genética , Proteínas 14-3-3/metabolismo , Regiões 3' não Traduzidas , Elementos Ricos em Adenilato e Uridilato , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Exorribonucleases/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Análise em Microsséries , Proteínas Nucleares/genética , Proteínas de Ligação a RNA , Receptor fas/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-25570742

RESUMO

Over the last decade the changing healthcare environment has required hospitals and specifically Biomedical Engineering to critically evaluate, optimize and adapt their operations. The focus is now on new technologies, changes to the environment of care, support requirements and financial constraints. Memorial Sloan Kettering Cancer Center (MSKCC), an NIH-designated comprehensive cancer center, has been transitioning to an increasing outpatient care environment. This transition is driving an increase in-patient acuity coupled with the need for added urgency of support and response time. New technologies, regulatory requirements and financial constraints have impacted operating budgets and in some cases, resulted in a reduction in staffing. Specific initiatives, such as the Joint Commission's National Patient Safety Goals, requirements for an electronic medical record, meaningful use and ICD10 have caused institutions to reevaluate their operations and processes including requiring Biomedical Engineering to manage new technologies, integrations and changes in the electromagnetic environment, while optimizing operational workflow and resource utilization. This paper addresses the new and expanding responsibilities and approach of Biomedical Engineering organizations, specifically at MSKCC. It is suggested that our experience may be a template for other organizations facing similar problems. Increasing support is necessary for Medical Software - Medical Device Data Systems in the evolving wireless environment, including RTLS and RFID. It will be necessary to evaluate the potential impact on the growing electromagnetic environment, on connectivity resulting in the need for dynamic and interactive testing and the growing demand to establish new and needed operational synergies with Information Technology operations and other operational groups within the institution, such as nursing, facilities management, central supply, and the user departments.


Assuntos
Tecnologia Biomédica , Engenharia Biomédica , Atenção à Saúde , Sistemas de Comunicação no Hospital , Hospitais , Humanos , Serviço Hospitalar de Engenharia e Manutenção , Assistência ao Paciente , Melhoria de Qualidade , Software , Tecnologia sem Fio
17.
Blood Cancer J ; 3: e152, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-24121164

RESUMO

Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL.

18.
Hong Kong Med J ; 19(1): 69-73, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23378358

RESUMO

As a means of preventing secondary ischaemic stroke, angioplasty and stenting are considered potentially beneficial for patients with severe intracranial atherosclerotic stenosis. However, the role of stenting has been challenged since the publication of the first randomised controlled trial on Stenting versus Aggressive Medical Management for Preventing Recurrent stroke in Intracranial arterial Stenosis (SAMMPRIS). This indicated that aggressive medical management was superior to stenting using Wingspan to prevent recurrent stroke, because stenting has a high peri-procedural stroke and death rate. In this paper, we review the management of intracranial atherosclerosis, revisit the skepticism on stenting, and state our position on the topic in the form of recommendations. These are based on the prevalence of the disease in Hong Kong, the high risk of recurrent stroke despite medical therapy in the presence of haemodynamic intracranial stenosis without sufficient collaterals, an analysis of the weak points of SAMMPRIS, and results of clinical studies in Hong Kong.


Assuntos
Angioplastia/métodos , Arteriosclerose Intracraniana/cirurgia , Stents , Acidente Vascular Cerebral/prevenção & controle , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Constrição Patológica , Hong Kong , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Prevenção Secundária , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia
19.
Neuro Oncol ; 15(5): 562-77, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23444257

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor of the central nervous system, is characterized by a relentless disease recurrence despite continued advancement in surgery, radiotherapy, and chemotherapy. Resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, remains a major challenge. Understanding the mechanisms behind TMZ resistance can direct the development of novel strategies for the prevention, monitoring, and treatment of tumor relapse. METHODS AND RESULTS: Our research platform, based on the establishment of 2 pairs of TMZ-sensitive/resistant GBM cells (D54-S and D54-R; U87-S and U87-R), has successfully identified prolyl 4-hydroxylase, beta polypeptide (P4HB) over-expression to be associated with an increased IC50 of TMZ. Elevated P4HB expression was verified using in vivo xenografts developed from U87-R cells. Clinically, we found that P4HB was relatively up-regulated in the recurrent GBM specimens that were initially responsive to TMZ but later developed acquired resistance, when compared with treatment-naive tumors. Functionally, P4HB inhibition by RNAi knockdown and bacitracin inhibition could sensitize D54-R and U87-R cells to TMZ in vitro and in vivo, whereas over-expression of P4HB in vitro conferred resistance to TMZ in both D54-S and U87-S cells. Moreover, targeting P4HB blocked its protective function and sensitized glioma cells to TMZ through the PERK arm of the endoplasmic reticulum stress response. CONCLUSIONS: Our study identified a novel target together with its functional pathway in the development of TMZ resistance. P4HB inhibition may be used alone or in combination with TMZ for the treatment of TMZ-resistant GBM.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glioma/tratamento farmacológico , Pró-Colágeno-Prolina Dioxigenase/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias Encefálicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Dacarbazina/farmacologia , Citometria de Fluxo , Glioma/metabolismo , Humanos , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Temozolomida , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
20.
Clin Neuroradiol ; 22(4): 295-303, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23124329

RESUMO

INTRODUCTION: The pipeline embolization device (PED) is a new endovascular stent designed for the treatment of challenging intracranial aneurysms (IAs). Its use has been extended to nonruptured and ruptured IAs of a variety of configurations and etiologies in both the anterior and posterior circulations. METHODS: We conducted a systematic review of ten eligible reports on its clinical efficacy and safety. RESULTS: There were 414 patients with 448 IAs. The majority of the IAs were large (40.2 %), saccular or blister-like (78.3 %), and were located mostly in the anterior circulation (83.5 %). The regimens of antiplatelet therapy varied greatly between and within studies. The mean number of the PED used was 2.0 per IA. Deployment was successful in around 95 % of procedures. Aneurysm obliteration was achieved in 82.9 % of IAs at 6-month. The overall incidences of periprocedural intracranial vascular complication rate and mortality rate were 6.3 and 1.5 %, respectively. CONCLUSION: The PED is a safe and effective treatment for nonruptured IAs. Its use in the context of acute subarachnoid hemorrhage (SAH) should be cautioned. Its main limitations include the need for prolonged antiplatelet therapy, as well as the potential risks of IA rupture and non-IA-related intracerebral hemorrhages (ICH). Future studies should aim at identifying factors that predispose to incomplete obliteration, delayed rupture, and thromboembolic complications.


Assuntos
Embolização Terapêutica/instrumentação , Embolia Intracraniana/terapia , Stents , Aneurisma Roto/terapia , Desenho de Equipamento , Seguimentos , Humanos , Aneurisma Intracraniano/terapia , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/mortalidade , Assistência de Longa Duração , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento
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