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Fulltext The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway in spontaneously breathing anaesthetised adults

Hui MT, Subash S, Wang CY

Anaesthesia, 2011 Apr;66(4):274-7.
PMID: 21401540 DOI: 10.1111/j.1365-2044.2011.06620.x

The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway after suction of the upper airway, in anaesthetised spontaneously breathing adult patients, are not known. To determine these, we studied 38 healthy patients, aged between 18 and 44 years. The target desflurane concentration in each individual patient was determined by the Dixon up-and-down method. When the predetermined target end-tidal desflurane concentration reached steady state, we kept a constant end-expiratory partial pressure between the alveolus and the brain for 10 min before attempting to remove the classic laryngeal mask airway after suctioning the upper airway. The initial desflurane target concentration was set at 6% and up-down desflurane increments were 0.1%. This continued until there were at least six crossover pairs. From the probit analysis, the 50% effective dose of desflurane was 5.29% (95% CI 5.132-5.379%) and the 95% effective dose was 5.55% (95% CI 5.429-6.394%).
Fulltext Blockade of Eosinophil-Induced Bronchial Epithelial-Mesenchymal Transition with a Geranyl Acetophenone in a Coculture Model

Lee YZ, Yap HM, Shaari K, Tham CL, Sulaiman MR, Israf DA

Front Pharmacol, 2017;8:837.
PMID: 29201006 DOI: 10.3389/fphar.2017.00837

Epithelial-mesenchymal transition (EMT) is currently recognized as the main cellular event that contributes to airway remodeling. Eosinophils can induce EMT in airway epithelial cells via increased transforming growth factor (TGF)-β production. We assessed the effect of synthetic 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) upon eosinophil-induced EMT in a cellular model. The human eosinophil cell line EoL-1 was used to induce EMT in BEAS-2B human bronchial epithelial cells. The induction of EMT was dose-dependently suppressed following tHGA treatment in which the epithelial morphology and E-cadherin expression were not altered. Protein and mRNA expression of vimentin, collagen I and fibronectin in eosinophil-induced epithelial cells were also significantly suppressed by tHGA treatment. Following pathway analysis, we showed that tHGA suppressed eosinophil-induced activator protein-1-mediated TGF-β production by targeting c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways. These findings corroborated previous findings on the ability of tHGA to inhibit experimental murine airway remodeling.
Fulltext Factors Associated With Falls Among Urban-Dwellers Aged 55 Years and Over in the Malaysian Elders Longitudinal Research (MELoR) Study

Alex D, Khor HM, Chin AV, Hairi NN, Cumming RG, Othman S, et al.

Front Public Health, 2020;8:506238.
PMID: 33304870 DOI: 10.3389/fpubh.2020.506238

Falls are major issues affecting the older population with potentially serious complications, including fractures, head injury, institutionalization, fear of falling and depression. While risk factors for falls have been established across Western Europe and North America, geographical differences in falls risk have not been well researched. We aim to examine the clinical and physical risk factors for falls in a middle-income South East Asian country. Cross-sectional data from the Malaysian Elders Longitudinal Research (MELoR) study involving 1,362 community dwelling individuals aged 55 years and above was utilized. Information on sociodemographic and medical history was obtained by computer-assisted questionnaires completed during home visits and hospital-based detailed health checks. Univariate and multivariate analyses compared non-fallers and fallers in the previous 12 months. Urinary incontinence, hearing impairment, depression, arthritis and cognitive impairment were risk factors for falls in the past 12 months after adjustment for age in our study population. Awareness about the risk factors in a population helps the design of fall prevention strategies that target specific or multiple risk factors.
Kojic Acid and Kojic Acid Ester: Review on Nanotechnology-based Approach for Enhancing the Delivery Efficacy

Lokman Hakim NYD, A/P Joginder Singh HK, Kang Nien H, Siau Hui M, Zee Wei L

Recent Adv Drug Deliv Formul, 2023 Apr 06.
PMID: 37038680 DOI: 10.2174/2667387817666230406091232

Kojic acid (KA), a fungal secondary metabolite, is commonly used in the cosmetic industry as a skin-whitening agent because of its ability to inhibit tyrosinase, the enzyme involved in melanin production. However, KA has shown poor depigmenting effects and becomes unstable after prolonged storage. Its use in cosmetics products has also been restricted due to its hydrophilic nature. To overcome these limitations, the structure of KA can be altered to form KA derivatives, such as KA ester (KAE), with improved chemical and biological properties. For instance, multiple studies have shown that KAE is more effective at inhibiting tyrosinase, is less toxic and more stable than KA, thus making it more beneficial. Aside from structural modification, nanotechnology applications such as nanoemulsion, and others have shown the ability to strengthen the efficacy of both KA and KAE by increasing skin permeability and delivering the drug more precisely to the targeted site with better controlled release rate. Therefore, the aim of this review article is to discuss the importance of modifying KA's chemical structure as well as the role of nanoemulsion, solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), liposomes and ethosomes in improving topical delivery of KA and KAE for cosmetic and pharmaceutical applications.
Erratum to: recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history

Kang PC, Phuah SY, Sivanandan K, Kang IN, Thirthagiri E, Liu JJ, et al.

Breast Cancer Res Treat, 2015 Apr;150(3):699-700.
PMID: 25833212 DOI: 10.1007/s10549-015-3360-0
Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history

Kang PC, Phuah SY, Sivanandan K, Kang IN, Thirthagiri E, Liu JJ, et al.

Breast Cancer Res Treat, 2014 Apr;144(3):635-42.
PMID: 24578176 DOI: 10.1007/s10549-014-2894-x

Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.
Fulltext Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group

Loong HH, Shimizu T, Prawira A, Tan AC, Tran B, Day D, et al.

ESMO Open, 2023 Aug;8(4):101586.
PMID: 37356359 DOI: 10.1016/j.esmoop.2023.101586

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.
Fulltext Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Milne RL, Burwinkel B, Michailidou K, Arias-Perez JI, Zamora MP, Menéndez-Rodríguez P, et al.

Hum Mol Genet, 2014 Nov 15;23(22):6096-111.
PMID: 24943594 DOI: 10.1093/hmg/ddu311

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.