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1.
Cardiovasc Intervent Radiol ; 47(7): 863-874, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898146

RESUMO

PURPOSE: The aim of PRISTINE was to evaluate the 6 and 12 months safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon for treatment of complex lower limb occlusive lesions (TASC II C & D) in patients with chronic limb threatening ischemia (CLTI) from Singapore. METHODS: PRISTINE was a prospective, non-randomized, single arm, observational, multi-investigator, single-center clinical study. Complication-free survival at 30 days was the safety clinical endpoint. Immediate technical success (ability to cross and dilate the lesion and achieve residual angiographic stenosis < 30%), 6-month primary vessel patency, limb salvage, clinically driven target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. RESULTS: Seventy five patients were included. There were 50 (68.0%) males; mean age, 69.0 ± 10.7 years. CLTI severity was based on the Rutherford Scale (R5 = 51; R6 = 17). Significant co-morbidities included diabetes mellitus (n = 68; 91.0%) and end-stage renal failure (n = 28; 37.0%). 112 atherosclerotic lesions were treated (TASC II D = 58 (52%); 76 (67%) de novo). There was 100% technical success. Mean lesion length treated was 22.4 ± 13.9 cm. Primary vessel patencies at 6 and 12 months were 64/86 (74%) and 43/74 (58%) and freedom from clinically driven TLR were 72/86 (84%) and 55/74 (74%) respectively. AFS was 61/73 (84.0%; five deaths and seven major lower extremity amputation) at 6-months. Mean Rutherford score improved from 5.1 ± 0.55 at baseline to 1.1 ± 2.05 (p < 0.05) at one year and there was a wound healing rate of 38/48 (79%) at the same timepoint. CONCLUSIONS: The Selution SLR™ drug eluting balloon is safe and efficacious in treating highly complex infra-inguinal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients with a high incidence of diabetes and end-stage renal failure. It is associated with highly satisfactory acute technical and clinical success, 12-month target lesion patency and AFS. LEVEL OF EVIDENCE: Level 2b, Individual Cohort Study.


Assuntos
Sistema de Registros , Sirolimo , Humanos , Masculino , Feminino , Idoso , Singapura , Estudos Prospectivos , Sirolimo/administração & dosagem , Resultado do Tratamento , Angioplastia com Balão/métodos , Pessoa de Meia-Idade , Salvamento de Membro/métodos , Isquemia Crônica Crítica de Membro , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea
2.
Hong Kong Med J ; 30(2): 147-162, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590158

RESUMO

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

3.
Ann Oncol ; 35(5): 448-457, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38382875

RESUMO

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Idoso , Sorafenibe/administração & dosagem , Sorafenibe/uso terapêutico , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Adulto
4.
Hong Kong Med J ; 29(5): 396-403, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37789507

RESUMO

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.


Assuntos
Neoplasias Pancreáticas , Tromboembolia , Humanos , Estudos Retrospectivos , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/diagnóstico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Fatores de Risco , Neoplasias Pancreáticas
5.
ESMO Open ; 8(4): 101586, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37356359

RESUMO

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Carcinoma Pulmonar de Células não Pequenas , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Neoplasias Ovarianas , Neoplasias da Próstata , Masculino , Feminino , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Ovarianas/genética , Neoplasias da Mama/genética , Oncologia , Sequenciamento de Nucleotídeos em Larga Escala
6.
Phlebology ; 36(10): 816-826, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34152882

RESUMO

BACKGROUND: The Venablock© Venous Closure System (Invamed, Ankara, Turkey) is a novel cyanoacrylate-based non-thermal non-tumescent embolization device to block refluxing truncal veins for chronic venous insufficiency and varicose veins. The aim was to prospectively evaluate the safety and 6 months efficacy of Venablock© for the treatment of primary great saphenous vein (GSV) and small saphenous vein (SSV) incompetency in a multi-ethnic cohort from Singapore. METHODS: This was a single arm, single investigator prospective study of 29 patients (39 limbs, 39 truncal veins) recruited over a 5-month period (August 2019 to February 2020), who were treated with the Venablock© device at a tertiary vascular unit in Singapore. Patients with symptomatic varicose veins (C2-6) and had truncal reflux > 0.5 second on venous Duplex ultrasound were included. Follow-up occurred at 2 weeks, 3 and 6 months with dedicated quality of life questionnaires and a targeted Duplex ultrasound performed to check for continued venous occlusion. RESULT: Mean age was 61.4 (±11.0) years and mean BMI was 26.2 (±5.7) kg/m2. 11/29 (37.9%) were males. Most common CEAP class treated was 2 (12/29, 41.3%). Mean diameter of treated GSV was 5.7 (±2.0) mm, 4.8 (±1.7) mm and 4.2 (±1.3) mm for the proximal, mid and distal above knee segments respectively. Mean time from access puncture to sheath removal was 23.4 (±10.0) mins. Vein occlusion at 2 weeks, 3 and 6 months was 39/39 (100%), 39/39 (100%) and 36/37 (97.2%) respectively. 5/29 (17.2%) developed puncture site infections, of which 3/29 (7.7%) required formal surgical drainage. 3/29 (7.7%) developed phlebitis. At 6 months, revised Venous Clinical Severity Score improved from 5.2 (±3.5) to 2.1 (±2.9; p < .001); EuroQol-5 Dimension score, from 7.4 (±2.1) to 5.7 (±1.4; p < .001); Aberdeen Varicose Vein Questionnaire score, from 18.1 (±15.5) to 7.9 (±8.9; p = .007); and Chronic Venous Insufficiency Questionnaire, from 18.6 (±16.2) to 4.5 (±6.3; p < .001). CONCLUSION: Venablock© is a safe and efficacious option of treating truncal venous insufficiency in a multi-ethnic Asian cohort from Singapore in the short term. There is a significant improvement in QoL. Longer follow-up is required to assess the durability of this technique, in particular the higher puncture site infection rates observed compared to other glue-based therapies.


Assuntos
Varizes , Insuficiência Venosa , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros , Veia Safena , Singapura , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/terapia
7.
Nurse Educ Today ; 104: 104985, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34058645

RESUMO

BACKGROUND: Previous studies suggest that increased learning satisfaction may encourage learning engagement in an online learning environment. OBJECTIVES: To evaluate the level of learning engagement and its relationship with students' perceived learning satisfaction in an online clinical nursing elective course. DESIGN: A prospective interventional study. SETTINGS: A nursing course was converted to an online format because of the coronavirus disease COVID pandemic. PARTICIPANTS: Part-time post-registration nursing undergraduates enrolled in an elective online clinical course. METHODS: Related teaching and learning strategies were deployed in the course using the Community of Inquiry framework. All students who completed the course were invited to complete an online survey that included a validated Online Student Engagement questionnaire (OSE). Pearson's correlations were used to determine the association between perceived learning satisfaction and learning engagement. A logistic regression model was used to explore the associations of gender, age, working experience and perceived learning satisfaction with higher learning engagement. RESULTS: The questionnaires were completed by 56 of 68 students (82%). The Pearson's correlation coefficient between the mean perceived learning satisfaction and OSE scores was 0.75 (p < .001). Twenty-five students (45%) were identified as highly engaged, using a cut-off of ≥3.5 for the mean OSE score. The mean perceived learning satisfaction (SD) score differed significantly between highly engaged and not highly engaged students [4.02 (0.49) vs. 3.27 (0.62), p < .001]. The logistic regression model showed that a greater perceived learning satisfaction [adjusted odds ratio (OR): 17.2, 95% C.I.: 3.46-86.0, p = .001] was associated with an increased likelihood of higher learning engagement, and >1 year of working experience (adjusted OR: 0.11, 95% C.I.: 0.01-0.89, p = .0039) was associated with a decreased likelihood of higher learning engagement. CONCLUSIONS: The study findings suggest that perceived learning satisfaction predicts learning engagement among nursing students in this online learning course.


Assuntos
COVID-19 , Educação a Distância , Estudantes de Enfermagem , Humanos , Estudos Prospectivos , SARS-CoV-2
10.
Clin Pharmacol Ther ; 101(5): 667-674, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27706800

RESUMO

The purpose of this study was to develop and validate sensitive algorithms to detect hospitalized statin-induced myopathy (SIM) cases from electronic medical records (EMRs). We developed four algorithms on a training set of 31,211 patient records from a large tertiary hospital. We determined the performance of these algorithms against manually curated records. The best algorithm used a combination of elevated creatine kinase (>4× the upper limit of normal (ULN)), discharge summary, diagnosis, and absence of statin in discharge medications. This algorithm achieved a positive predictive value of 52-71% and a sensitivity of 72-78% on two validation sets of >30,000 records each. Using this algorithm, the incidence of SIM was estimated at 0.18%. This algorithm captured three times more rhabdomyolysis cases than spontaneous reports (95% vs. 30% of manually curated gold standard cases). Our results show the potential power of utilizing data and text mining of EMRs to enhance pharmacovigilance activities.


Assuntos
Algoritmos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Doenças Musculares/epidemiologia , Creatina Quinase/sangue , Mineração de Dados , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Valor Preditivo dos Testes , Rabdomiólise/induzido quimicamente , Rabdomiólise/epidemiologia
11.
Ann Oncol ; 26(12): 2457-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26386123

RESUMO

BACKGROUND: The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). RESULTS: The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. CONCLUSIONS: Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01210495.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Cuidados Paliativos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Cuidados Paliativos/tendências , Taxa de Sobrevida/tendências , Resultado do Tratamento
13.
Pharmacogenomics J ; 14(6): 555-63, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24861855

RESUMO

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Variação Genética/genética , Biotransformação , Europa (Continente) , Humanos , Singapura
14.
Purinergic Signal ; 10(2): 241-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24310605

RESUMO

Receptors for purines and pyrimidines are expressed throughout the cardiovascular system. This study investigated their functional expression in porcine isolated pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were prepared for isometric tension recording and preconstricted with U46619, a thromboxane A(2) mimetic; adenosine-5'-diphosphate (ADP), uridine-5'-triphosphate (UTP) and MRS2768, a selective P2Y(2) agonist, were applied cumulatively, while adenosine-5'-triphosphate (ATP) and αß-methylene-ATP (αß-meATP) response curves were generated from single concentrations per tissue segment. Antagonists/enzyme inhibitors were applied prior to U46619 addition. ATP, αß-meATP, UTP and MRS2768 induced vasoconstriction, with a potency order of αß-meATP > MRS2768 > ATP ≥ UTP. Contractions to ATP and αß-meATP were blocked by NF449, a selective P2X(1) receptor antagonist. The contraction induced by ATP, but not UTP, was followed by vasorelaxation. Endothelium removal and DUP 697, a cyclooxygenase-2 inhibitor, had no significant effect on contraction to ATP but attenuated that to UTP, indicating actions at distinct receptors. MRS2578, a selective P2Y(6) receptor antagonist, had no effect on contractions to UTP. ADP induced endothelium-dependent vasorelaxation which was inhibited by MRS2179, a selective P2Y(1) receptor antagonist, or SCH58261, a selective adenosine A(2A) receptor antagonist. The contractions to ATP and αß-meATP were attributed to actions at P2X(1) receptors on the vascular smooth muscle, whereas it was shown for the first time that UTP induced an endothelium-dependent vasoconstriction which may involve P2Y(2) and/or P2Y(4) receptors. The relaxation induced by ADP is mediated by P2Y(1) and A(2A) adenosine receptors. Porcine pancreatic arteries appear to lack vasorelaxant P2Y(2) and P2Y(4) receptors.


Assuntos
Artérias/metabolismo , Endotélio Vascular/metabolismo , Pâncreas/metabolismo , Nucleotídeos de Pirimidina/metabolismo , Receptores Purinérgicos/metabolismo , Animais , Endotélio Vascular/efeitos dos fármacos , Pâncreas/irrigação sanguínea , Suínos , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/farmacologia
15.
Br J Pharmacol ; 171(3): 701-13, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24138077

RESUMO

BACKGROUND AND PURPOSE: The P2Y14 receptor is the newest member of the P2Y receptor family; it is G(i/o) protein-coupled and is activated by UDP and selectively by UDP-glucose and MRS2690 (2-thiouridine-5'-diphosphoglucose) (7-10-fold more potent than UDP-glucose). This study investigated whether P2Y14 receptors were functionally expressed in porcine isolated pancreatic arteries. EXPERIMENTAL APPROACH: Pancreatic arteries were prepared for isometric tension recording and UDP-glucose, UDP and MRS2690 were applied cumulatively after preconstriction with U46619, a TxA2 mimetic. Levels of phosphorylated myosin light chain 2 (MLC2) were assessed with Western blotting. cAMP concentrations were assessed using a competitive enzyme immunoassay kit. KEY RESULTS: Concentration-dependent contractions with a rank order of potency of MRS2690 (10-fold) > UDP-glucose ≥ UDP were recorded. These contractions were reduced by PPTN {4-[4-(piperidin-4-yl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid}, a selective antagonist of P2Y14 receptors, which did not affect responses to UTP. Contraction to UDP-glucose was not affected by MRS2578, a P2Y6 receptor selective antagonist. Raising cAMP levels and forskolin, in the presence of U46619, enhanced contractions to UDP-glucose. In addition, UDP-glucose and MRS2690 inhibited forskolin-stimulated cAMP levels. Removal of the endothelium and inhibition of endothelium-derived contractile agents (TxA2, PGF(2α) and endothelin-1) inhibited contractions to UDP glucose. Y-27632, nifedipine and thapsigargin also reduced contractions to the agonists. UDP-glucose and MRS2690 increased MLC2 phosphorylation, which was blocked by PPTN. CONCLUSIONS AND IMPLICATIONS: P2Y14 receptors play a novel vasocontractile role in porcine pancreatic arteries, mediating contraction via cAMP-dependent mechanisms, elevation of intracellular Ca²âº levels, activation of RhoA/ROCK signalling and MLC2, along with release of TxA2, PGF(2α) and endothelin-1.


Assuntos
Artérias/inervação , Músculo Liso Vascular/inervação , Pâncreas/irrigação sanguínea , Receptores Purinérgicos P2Y/metabolismo , Sistemas do Segundo Mensageiro , Vasoconstrição , Sistema Vasomotor/metabolismo , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , AMP Cíclico/agonistas , AMP Cíclico/antagonistas & inibidores , AMP Cíclico/metabolismo , Endotélio Vascular/fisiologia , Feminino , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Agonistas do Receptor Purinérgico P2Y/química , Agonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y/química , Receptores Purinérgicos P2Y/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Sus scrofa , Uridina Difosfato Glucose/agonistas , Uridina Difosfato Glucose/análogos & derivados , Uridina Difosfato Glucose/antagonistas & inibidores , Uridina Difosfato Glucose/metabolismo , Uridina Difosfato Glucose/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/antagonistas & inibidores , Vasoconstritores/farmacologia , Sistema Vasomotor/efeitos dos fármacos
17.
Hong Kong Med J ; 19(5): 407-15, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23784530

RESUMO

OBJECTIVE: To report the treatment efficacy and toxicity profile of intensitymodulated radiation therapy in Chinese patients with clinically localised prostate cancer. DESIGN: Historical cohort study. SETTING: Oncology unit in a university teaching hospital in Hong Kong. PATIENTS: Patients with clinically localised prostate cancer undergoing intensity-modulated radiation therapy in our institution between May 2001 and November 2009 were reviewed. MAIN OUTCOME MEASURES: The 5-year biochemical failure­free survival, 5-year overall survival, as well as acute/late gastro-intestinal toxicities and genito-urinary toxicities. RESULTS: A total of 182 patients were treated with prostate intensitymodulated radiation therapy with or without whole-pelvic radiotherapy. The median follow-up was 44 months. The median patient age was 72 years. Overall survival of the cohort was 92% after 5 years. The favourable, intermediate, and unfavourable risk category distributions of the National Comprehensive Cancer Network were 21 (12%), 42 (23%), and 119 (65%), respectively. The 5-year actuarial biochemical failure­free survival rates for patients in these categories were 95%, 82%, and 80%, respectively. Multivariate analysis identified early tumour stage, low pre-treatment prostate-specific antigen levels, and the use of adjuvant androgen deprivation as independent prognostic factors for better biochemical failure­free survival. Grade 2 and 3 late gastro-intestinal/genito-urinary toxicities occurred in 8%/3% and 4%/3% of the patients, respectively. CONCLUSION: Intensity-modulated radiation therapy for prostate cancer is feasible and safe in the Chinese population. These data are consistent with the results of other series in Caucasian populations.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Estudos de Viabilidade , Seguimentos , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Hong Kong , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias da Próstata/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Sistema Urogenital/efeitos da radiação
18.
Hong Kong Med J ; 19(3): 214-21, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23568938

RESUMO

OBJECTIVES. To identify the prevalence of anaemia in Chinese type 2 diabetic patients managed in a primary care setting and to explore its associations with cardiovascular complications and kidney disease. DESIGN. Retrospective case series study. SETTING. General Out-patient Clinic of Hospital Authority, Hong Kong. PATIENTS. Chinese type 2 diabetic patients who had annual assessments between 1 January 2010 and 31 December 2011 were recruited. Their complete blood picture, serum creatinine, estimated glomerular filtration rate (calculated by Modification of Diet in Renal Disease method), haemoglobin A1c, and urine albumin-creatinine ratio were retrieved. Anaemia was defined as a haemoglobin level of <130 g/L in men and <120 g/L in women (World Health Organization criteria). Student's t test and analysis of variance were used to analyse continuous variables and the Chi squared test for categorical data. Pearson's correlation coefficient and multivariate logistic regression were used to examine associations between haemoglobin level and different variables including age, gender, serum creatinine level, estimated glomerular filtration rate, and urine albumin-creatinine ratio. All statistical tests were two-sided, and a P value of <0.05 was considered significant. RESULTS. Among 6325 Chinese type 2 diabetic patients fulfilling the inclusion criteria, 1441 were found to have anaemia with a period prevalence of 22.8%. The prevalence of anaemia increased significantly with deterioration of renal function. Compared with diabetic patients with normal haemoglobin levels, anaemic diabetic patients had a higher co-morbidity rate for stroke, ischaemic heart disease, hypertension, and chronic kidney disease (P<0.001). Independent predictors for haemoglobin level among diabetic patients were age, gender, serum creatinine level, estimated glomerular filtration rate, haemoglobin A1c, and urine albumin-creatinine ratio (P<0.001). Multivariate analysis showed that male gender, old age, increased serum creatinine level, decreased estimated glomerular filtration rate, elevated urine albumin-creatinine ratio, and co-morbidity with stroke or ischaemic heart disease were associated with greater odds for the presence of anaemia. CONCLUSION. Anaemia is common among Chinese type 2 diabetic patients, particularly those with impaired renal function or established cardiovascular disease. Early detection of anaemia and prompt referral to specialist care for optimal treatment, if associated with severe renal impairment or high-risk proteinuria at the primary care settings, is recommended.


Assuntos
Anemia/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Renal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Hong Kong/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Atenção Primária à Saúde , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
19.
Br J Pharmacol ; 170(8): 1449-58, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24528237

RESUMO

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Terapia de Alvo Molecular , Farmacologia , Humanos , Ligantes , Preparações Farmacêuticas/química
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