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Fulltext Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?

Tan EC, Aziz NA, Ahmad S

BMJ Case Rep, 2012;2012.
PMID: 22907854 DOI: 10.1136/bcr-2012-006518

A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding neuropsychiatric symptoms because they can adversely affect the patient's quality of life as well as impede rehabilitation efforts.
Singapore Human Mutation/Polymorphism Database: a country-specific database for mutations and polymorphisms in inherited disorders and candidate gene association studies

Tan EC, Loh M, Chuon D, Lim YP

Hum Mutat, 2006 Mar;27(3):232-5.
PMID: 16429432

There is a need for country/population-specific databases because the existence of population-specific mutations for single gene disorders is well documented, and there is also good evidence for ethnic differences in the frequencies of genetic variations involved in complex disorders. Thus the Singapore Human Mutation/Polymorphism Database (SHMPD) was created to provide clinicians and scientists access to a central genetic database for the Singapore population. The data catalogued in the database include mutations identified in Singapore for Mendelian diseases, and frequencies of polymorphisms that have been investigated in either healthy controls or samples associated with specific phenotypes. Data from journal articles identified by searches in PubMed and other online resources, and via personal communications with researchers were compiled and assembled into a single database. Genes are categorized alphabetically and are also searchable by name and disease. The information provided for each variant of the gene includes the protein encoded, phenotype association, gender, size, and ethnic origin of the sample, as well as the reported genotype and allele frequencies, and direct links to the corresponding abstracts on PubMed. Our database will facilitate molecular diagnosis of Mendelian disorders and improve study designs for complex traits. It will be useful not only for researchers in Singapore, but also for those in countries with similar ethnic backgrounds, such as China, Taiwan, Hong Kong, Indonesia, and Malaysia.
Fulltext Association between non-alcoholic fatty liver disease evaluated by transient elastography with extracranial carotid atherosclerosis in a multiethnic Asian community

Tan EC, Tai MS, Chan WK, Mahadeva S

JGH Open, 2019 Apr;3(2):117-125.
PMID: 31061886 DOI: 10.1002/jgh3.12114

Background and Aim: There is not much data on the association between non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis assessed using Fibroscan with carotid intima-media thickness (CIMT) in the general population. The objective of this study was to evaluate the association between NAFLD and advanced fibrosis, as diagnosed by Fibroscan, with an increased CIMT in the Malaysian population.
Methods: A cross-sectional study of government officers and their family members attending a health screening at a public healthcare facility was conducted. All subjects underwent clinical evaluation, biochemical testing, anthropometry, ultrasound carotid Doppler, and Fibroscan examination.
Results: Data for 251 subjects were analyzed (mean age 47.1 ± 12.4 years, 74.1% male). Prevalence of NAFLD and advanced fibrosis were 57.4 and 17.5%, respectively. Independent factors associated with NAFLD were waist circumference (odds ratio [OR] = 1.077, 95% confidence interval [CI] 1.038-1.118, P < 0.001) and serum alanine aminotransferase (ALT) (OR = 1.039, 95% CI 1.005-1.074, P = 0.024). Independent factors associated with advanced fibrosis were male gender (OR = 4.847, 95% CI 1.369-17.155, P = 0.014) and serum aspartate aminotransferase (AST) (OR = 1.057, 95% CI 1.003-1.113, P = 0.036). Prevalence of increased CIMT was 29.0%. Independent factor associated with increased CIMT was older age (OR = 1.146, 95% CI 1.067-1.231, P < 0.001). Of the subjects, 34.5% with NAFLD had increased CIMT compared to 19.1% of the subjects without NAFLD (P = 0.063). Advanced fibrosis was not associated with increased CIMT.
Conclusions: Prevalence of NAFLD, advanced liver fibrosis, and increased CIMT were high. NAFLD and advanced liver fibrosis appeared not to be associated with increased CIMT. However, a larger sample size is needed to demonstrate whether there is any association.
Innate Immune and Neuronal Genetic Markers Are Highly Predictive of Postoperative Pain and Morphine Patient-Controlled Analgesia Requirements in Indian but Not Chinese or Malay Hysterectomy Patients

Barratt DT, Sia AT, Tan EC, Somogyi AA

Pain Med, 2021 Nov 26;22(11):2648-2660.
PMID: 34015137 DOI: 10.1093/pm/pnab172

OBJECTIVE: Pain severity and opioid requirements in the postoperative period show substantial and clinically significant inter-patient variation due mainly to factors such as age, surgery type, and duration. Genetic factors have not been adequately assessed except for the neuronal OPRM1 rs1799971 and COMT rs4680, whereas the contribution of innate immune signaling pathway genetics has seldom been investigated.
SETTING: Hospital surgical ward.
SUBJECTS: Women (107 Indian, 184 Malay, and 750 Han Chinese) undergoing total hysterectomy surgery.
METHODS: Morphine consumption, preoperative pain, and postoperative pain were evaluated in relation to genetic variability comprising 19 single-nucleotide polymorphisms (SNPs) in 14 genes involved in glial activation, inflammatory signaling, and neuronal regulation, plus OPRM1 (1 SNP) and COMT (3 SNPs).
RESULTS: Pre- and postoperative pain and age were associated with increased and decreased morphine consumption, respectively. In Chinese patients, only 8% of the variability in consumption could be explained by these nongenetic and genetic (BDNF, IL1B, IL6R, CRP, OPRM1, COMT, MYD88) factors. However, in Indian patients, 41% of morphine consumption variability could be explained by age (explaining <3%) and variants in OPRM1 rs1799971, CRP rs2794521, TLR4 rs4986790, IL2 rs2069762, COMT rs4818, TGFB1 rs1800469, and IL6R rs8192284 without controlling for postoperative pain.
CONCLUSIONS: This is the highest known value reported for genetic contributions (38%) to morphine use in the acute postoperative pain setting. Our findings highlight the need to incorporate both genetic and nongenetic factors and consider ethnicity-dependent and nonadditive genotypic models in the assessment of factors that contribute to variability in opioid use.
Fulltext Recurrent cerebral infarcts secondary to marantic endocarditis in a patient with adenocarcinoma of the lung

Tai ML, Tan EC, Ang CC, Liam CK

Singapore Med J, 2016 Sep;57(9):524-5.
PMID: 27663211 DOI: 10.11622/smedj.2016157
Asthma and TNF variants in Chinese and Malays

Tan EC, Lee BW, Tay AW, Chew FT, Tay AH

Allergy, 1999 Apr;54(4):402-3.
PMID: 10371104
Ethnic differences in pain perception and patient-controlled analgesia usage for postoperative pain

Tan EC, Lim Y, Teo YY, Goh R, Law HY, Sia AT

J Pain, 2008 Sep;9(9):849-55.
PMID: 18550441 DOI: 10.1016/j.jpain.2008.04.004

There are reports suggesting that sensitivity to and tolerance of both clinical and experimental pain differ among ethnic groups. We examined self-rated pain score and morphine usage in 1034 women who underwent elective lower cesarian section (LSCS) for their deliveries. Data on pain scores and amount of total morphine use according to patient-controlled analgesia were collected every 4 hours. Overall, lowest pain scores were recorded 12 hours after surgery and highest at 24 hours. Morphine consumption was highest within the first 4 hours and lowest between 12 and 16 hours. There were statistically significant ethnic group differences in pain scores (P = 1.7 x 10(-7)) and morphine usage (P = 2.8 x 10(-15)) between ethnic groups, with Indians having the highest mean pain score and using the highest amount of morphine. The ethnic differences in pain score and morphine self-administration persisted after controlling for age, body mass index, and duration of operation.
Fulltext Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay

Rothan HA, Zulqarnain M, Ammar YA, Tan EC, Rahman NA, Yusof R

Trop Biomed, 2014 Jun;31(2):286-96.
PMID: 25134897 MyJurnal

Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.
Fulltext Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel

Brett M, McPherson J, Zang ZJ, Lai A, Tan ES, Ng I, et al.

PLoS One, 2014;9(4):e93409.
PMID: 24690944 DOI: 10.1371/journal.pone.0093409

Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.
Fulltext The impact of dyspepsia on symptom severity and quality of life in adults with headache

Tai ML, Norhatta N, Goh KJ, Moy FM, Sujarita R, Asraff AA, et al.

PLoS One, 2015;10(1):e0115838.
PMID: 25629323 DOI: 10.1371/journal.pone.0115838

BACKGROUND: Dyspepsia and headache frequently co-exist, but the clinical implication of this association is uncertain. We planned to examine the prevalence and impact of dyspepsia in adults with headache.
METHODS: A cross-sectional study was conducted in a secondary care setting. Clinical, psychological and health-related quality of life (HRQOL) data were compared between subjects with headache and controls (non-headache subjects). The impact of dyspepsia was analysed further in subjects with headache alone.
RESULTS: 280 subjects (93 cases with headache and 187 matched controls) were recruited. The following baseline characteristics of subjects were as follows: mean age 45.0 ± 17.3 years, 57.0% females and ethnic distribution-Malaysian = 45 (48.4%), Chinese n = 24 (25.8%) and Indians n = 24 (25.8%). Headache sub-types among cases with headache were as follows: tension-type headache (TTH) n = 53 (57.0%) and migraine n = 40 (43.0%). Dyspepsia was more prevalent in cases with headache compared to controls (25.8% vs 12.8%, p = 0.011), and headache was independently associated with dyspepsia (OR 2.75, 95% CI 1.39-5.43). Among cases with headache, there was a trend towards a higher prevalence of dyspepsia in those with migraine (27.5%) compared to TTH (24.5%). Subjects with headache and dyspepsia, compared to those with headache alone, had a greater severity of headache symptoms (63.67 ± 22.85 mm vs 51.20 ± 24.0 mm VAS, p = 0.029). Overall HRQOL scores were lower in headache subjects with dyspepsia (EQ-5D summary score 0.82 ± 0.18 vs 0.90 ± 0.16, p = 0.037 and EQ-5D VAS 62.08 ± 17.50 mm vs 72.62 ± 18.85 mm, p = 0.018), compared to those without dyspepsia.
CONCLUSION: Dyspepsia is associated with more severe headache symptoms and results in a lower HRQOL in patients with headache.
Self-improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia

Bishnoi P, Ng YZ, Wei H, Tan EC, Lunny DP, Wong XFCC, et al.

Am J Med Genet A, 2021 02;185(2):625-630.
PMID: 33258232 DOI: 10.1002/ajmg.a.61975

Self-improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral-distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization.