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  1. Siar CH, Tan BH
    J Oral Sci, 2000 Dec;42(4):205-10.
    PMID: 11269378
    The turnaround time (TAT) for oral biopsies received for histological examination by the Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya, for the years 1978, 1988 and 1998 was evaluated. For the three years studied, TATs for 61, 233 and 463 specimens were retrospectively analysed. Testing intervals, that is, from the dates the surgeons procured the specimens, the laboratories accessioned them and until the pathologists signed off the diagnoses, were used to calculate TAT. The performance level of the respective pathologists, the growth of tissue diagnostic services and the possible variables that influence TAT were also evaluated. As prompt diagnosis means prompt treatment, which in turn has a bearing on prognosis, the TAT pertinent to oral malignant tumors was emphasized. The mean TAT, its mode and median fell significantly in 1998 compared with the previous 2 years; it was lower for soft tissue than for hard tissue specimens, and lower for malignant, than for non-malignant specimens. The progression of tissue diagnostic services is up to a satisfactory level, as 88.89 % of biopsies could render diagnoses within a fair period of time in 1998.
  2. Saha N, Tan PY, Tan BH
    Z Morphol Anthropol, 1980;71(1):107-9.
    PMID: 6969497
    1829 school-boys of Singapore comprised of 849 Chinese, 469 Malays and 511 Indians were investigated for the incidence of red-green colour-blindness with Ishihara's plates. The incidence of red-green colour-blindness was found to be 3.8%, 4.5% and 4.5%, respectively in Chinese, Malay and Indian boys. The incidence among the different dialect groups was variable with the highest incidence of red-green colour-blindness among Mandarin speaking group (14.3%), followed by Hainanese speaking (6.7%) and other dialect groups of Chinese (2.8% to 4.5%). The incidence of red-green colour-blindness was higher in the older boys compared with the younger boys when all the three ethnic groups are combined.
  3. Tan BH, Sockalingam S, Ganesan D
    Br J Neurosurg, 2023 Jun 22.
    PMID: 37345453 DOI: 10.1080/02688697.2023.2225611
    OBJECTIVES: Posterior cervical foraminotomy is a surgical procedure used to treat unilateral cervical radiculopathy. It provides direct decompression of the nerve root without the necessity of fusion while maintaining cervical mobility. With the advancement in image-guidance technology and minimal access techniques, intra-operative CT has provided a safer, more accurate instrumentation placement with less radiation exposure to operative staff and provides better anatomical visualization quality compared to traditional intra-operative imaging techniques. This case series aims to address the applications of advanced image guidance in posterior cervical foraminotomy and describe the nuances.

    METHOD: A technical report on a series of seven cases on intraoperative CT navigation for posterior cervical foraminotomy surgery. Posterior cervical foraminotomy was performed in all patients under CT guided navigation system without an image intensifier. In one case after the foraminotomy, the extruded disc was carefully removed by gentle retraction.

    RESULT: From 1 January 2020 to 31 December 2021, a total of seven patients with nine cervical foraminotomy procedures were performed using the aid of CT-guided navigation. The series comprised five women and two men whose mean age was 50.6 years. In all cases, the radiculopathy symptoms were diminished significantly. There were no cases of instability on the dynamic cervical radiograph. There were no complications during the surgical procedure.

    CONCLUSION: The navigation also allows the surgeon to localise the index level accurately and appraise the adequacy of the intended decompression in three planes of the CT scan image. The ability to perform accurate spine navigation would be the precursor for robotic spinal surgery.

  4. Tan BH, Chor Leow T, Foo HL, Abdul Rahim R
    Biomed Res Int, 2014;2014:469298.
    PMID: 24592392 DOI: 10.1155/2014/469298
    A superoxide dismutase (SOD) gene of Lactococcus lactis M4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression of sodA under T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD of L. lactis IL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172).
  5. Ho CK, Yip KT, Eng JB, Rajan L, Tan BH
    Med J Malaysia, 2001 Sep;56(3):374-7.
    PMID: 11732086
    A 16 year-old man presented with fracture of both his femurs after a road traffic accident. Chest radiograph revealed mediastinal widening. Subsequent CT scan and arch aortogram confirmed the findings of traumatic aortic arch transection at the isthmus. He underwent successful surgical repair. High index of suspicion and prompt actions are important in managing this potentially fatal but treatable condition.
  6. Ho TM, Tan BH, Ismail S, Bujang MK
    Asian Pac J Allergy Immunol, 1995 Jun;13(1):17-22.
    PMID: 7488339
    Aerosampling using Rotorod samplers was conducted in the Institute for Medical Research, Kuala Lumpur, Malaysia, from December 1991 to November 1993. Samples were collected twice a week between 10.00 hours to 12.00 hours. Rods were stained and examined microscopically. A total of 8 and 20 types of pollens and mold spores were collected, respectively. More mold spores were collected than pollens. Grass pollen constituted more than 40 percent of total pollen counts. Gramineae pollen counts peaked in March and September. The most abundant mold spore was Cladosporium followed by Rust, Nigrospora, Curvularia and Smut. Cladosporium counts peaked in February and August. Rust counts peaked in June and December whereas counts for Nigrospora peaked in February and October. Highest counts of Smut were recorded in March and October. Curvularia counts peaked in January, June and September.
  7. Dong AN, Tan BH, Pan Y, Ong CE
    Clin Exp Pharmacol Physiol, 2018 10;45(10):991-1001.
    PMID: 29858511 DOI: 10.1111/1440-1681.12978
    Over the past 2 decades, knowledge of the role and clinical value of pharmacogenetic markers has expanded so that individualized pre-emptive therapy based on genetic background of patients could be within reach for clinical implementation. This is evidenced from the frequent updating of drug labels that incorporates pharmacogenetic information (where compelling data become available) by the regulatory agencies (such as the US FDA), and the periodical publication of guidelines of specific therapeutic recommendations based on the results of pharmacogenetic tests by the pharmacogenetics working groups or consortiums of professional bodies. Clinical relevance of the cytochrome P450 (CYP) polymorphism related to dose, effectiveness and/or toxicity of key drugs are presented in this review, including that of warfarin, clopidogrel, tricyclic antidepressants, and proton pump inhibitors. Prospect for routine clinical application of CYP genotyping before prescribing drugs is still currently unclear due to challenges and barriers associated with availability of well-defined and validated pharmacogenetic studies, the interpretation, result reporting and potential error of genotype testing, involvement of non-genetic factors, and other patient's demographic and disease conditions. Further studies to provide additional supporting clinical data and acceleration of pharmacogenetic testing standards and techniques should help improve the evidence base needed for clinical utility and hence move the implementation of genotype-guided therapy in clinical practice a step closer to reality.
  8. Dong AN, Tan BH, Pan Y, Ong CE
    J Pharm Pharm Sci, 2021;24:94-112.
    PMID: 33626316 DOI: 10.18433/jpps31305
    Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein. Overall, CYP2R1 structure adopts a closed conformation with the B' helix serving as a gate covering the substrate access channel, with the substrate vitamin D3 occupying a position with the side chain pointing toward the heme group. In liver, CYP2R1 25-hydroxylates vitamin D and serves as an important determinant of 25(OH)D level in the tissue and in circulation. While substrate profile has been well studied, inhibitor specificity for CYP2R1 requires further investigation. Both exonic and non-exonic single nucleotide polymorphisms (SNPs) have been reported in CYP2R1, including the CYP2R1*2 carrying Leu99Pro exchange, and a number of non-exonic SNPs with variable functional consequences in gene regulation. A non-exonic SNP, rs10741657, has its causal relationship with diseases established, including that of rickets, ovarian cancer, and multiple sclerosis. The role of other CYP2R1 SNPs in vitamin D deficiency and their causal link to other traits however remain uncertain currently and more studies are warranted to help identify possible physiological mechanisms underlying those complex traits.
  9. Tan BH, Pan Y, Dong AN, Ong CE
    J Pharm Pharm Sci, 2017;20(1):319-328.
    PMID: 29145931 DOI: 10.18433/J3434R
    In vitro and in silico models of drug metabolism are utilized regularly in the drug research and development as tools for assessing pharmacokinetic variability and drug-drug interaction risk. The use of in vitro and in silico predictive approaches offers advantages including guiding rational design of clinical drug-drug interaction studies, minimization of human risk in the clinical trials, as well as cost and time savings due to lesser attrition during compound development process. This article gives a review of some of the current in vitro and in silico methods used to characterize cytochrome P450(CYP)-mediated drug metabolism for estimating pharmacokinetic variability and the magnitude of drug-drug interactions. Examples demonstrating the predictive applicability of specific in vitro and in silico approaches are described. Commonly encountered confounding factors and sources of bias and error in these approaches are presented. With the advent of technological advancement in high throughput screening and computer power, the in vitro and in silico methods are becoming more efficient and reliable and will continue to contribute to the process of drug discovery, development and ultimately safer and more effective pharmacotherapy. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
  10. Khairul Azhar J, Jacqueline HSG, Tony LKH, Tan BH, Steven JM
    Med J Malaysia, 2011 Dec;66(5):504-6.
    PMID: 22390113
    We report a case of a healthy 78-year-old indonesian man who presented with chronic weight loss, poor appetite and lethargy. CT abdomen showed bilateral adrenal masses. EUS-guided FNA was performed on the left adrenal gland. Histopathology report was Histoplasma Capsulatum. He recovered well with antifungal treatment without any complication. In this case, we found that the role of EUS -guided FNA was not only limited to diagnosis but also helped in the prognosis of the disease since the method was able to assess the general anatomy of the adrenal gland better than other imaging modalities due to its close proximity and direct visualization.
  11. Ho K, Ang LW, Tan BH, Tang CS, Ooi PL, James L, et al.
    J Infect, 2011 Apr;62(4):263-70.
    PMID: 21315108 DOI: 10.1016/j.jinf.2011.02.001
    OBJECTIVES: We conducted an epidemiological review of the chikungunya fever situation in Singapore and described the measures taken to prevent the chikungunya virus from becoming entrenched in the tropical city-state.
    METHODS: All laboratory-confirmed cases and outbreak investigation reports maintained by the Communicable Diseases Division, Ministry of Health, and Aedes mosquito surveillance data obtained by the National Environment Agency during the period 2006 and 2009 were reviewed and analysed.
    RESULTS: Sporadic cases were imported into Singapore until the first local transmission occurred in an urban area where Aedes aegypti was the predominant vector. Subsequent introduction of a mutant viral strain (A226V) in early 2008 resulted in the rapid spread to suburban and rural areas where Aedes albopictus was the primary vector. 1072 cases including 812 (75.7%) indigenous cases were reported. The main sources of importation were India and Malaysia. Foreign contract workers were identified as high-risk for indigenous infections.
    CONCLUSIONS: The disease was successfully brought under control through aggressive vector control measures directed at A. albopictus. Although the incidence has sharply declined since January 2009, a high degree of vigilance is maintained to prevent a recurrence of epidemic transmission which can occur even with a well-established nationwide mosquito control programme.
  12. Tan AT, Emmanuel SC, Tan BY, Teo WS, Chua TS, Tan BH
    Ann Acad Med Singap, 2002 Jul;31(4):479-86.
    PMID: 12161884
    INTRODUCTION AND METHODS: Cardiovascular diseases have progressively increased in importance as a major contributor of morbidity and mortality in Asia. However, many countries in Asia do not have nationwide systematically-collected and standardised data on myocardial infarction (MI). To accurately document the extent of atherosclerotic coronary heart disease in Singapore, a nationwide myocardial infarct registry was established in the mid-1986. Possible myocardial infarct events were identified through daily national lists of cardiac enzymes, hospital discharge codes, mortuary records and the national death registry. Data obtained from clinical history, cardiac enzymes and 12-lead electrocardiogram Minnesota codes were entered into an algorithm based on the WHO MONICA study. Cases identified as "definite" MI were included in the decade's review for this study.

    RESULTS: From 1988 to 1997, 13,048 myocardial infarct events were diagnosed with 3367 deaths. There was a 39.1% decline in mortality, with an average decline of 6.5% per year [95% confidence intervals (CI), -3.9% to -9.1%]. However, the decline in incidence was only 20.8% with an average decline of 2.4% per year (95% CI, -6.6% to -1.2%). The highest incidence and mortality rates for both genders were seen in the Indians, followed by the Malays and the Chinese.

    CONCLUSION: Over 10 years, from 1988 to 1997, we documented a significant fall in mortality from MI in Singapore. There was a smaller decline in the incidence of infarction. Singapore implemented a National Healthy Lifestyle Programme in 1992 as a 10-year effort. The disparity in the incidence and mortality may suggest that a more dramatic and immediate impact has taken place in mortality through therapeutic programmes; primary preventive programmes would be more difficult to evaluate and have a more gradual impact. Only with continual accurate data collection through the whole country, over a much longer period, can the relative value of preventive and therapeutic programmes in coronary heart disease be assessed.

  13. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Ong CE
    Drug Metab Pers Ther, 2021 Apr 09;36(4):259-270.
    PMID: 34821124 DOI: 10.1515/dmpt-2020-0182
    OBJECTIVES: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6.

    METHODS: CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6-antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking.

    RESULTS: The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro-in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition.

    CONCLUSIONS: Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

  14. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, et al.
    Biopharm Drug Dispos, 2018 Apr;39(4):205-217.
    PMID: 29488228 DOI: 10.1002/bdd.2127
    Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.
  15. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Ong CE
    Drug Metab Pers Ther, 2021 Apr 08.
    PMID: 33831979 DOI: 10.1515/dmdi-2020-0182
    OBJECTIVES: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6.

    METHODS: CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6-antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking.

    RESULTS: The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro-in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition.

    CONCLUSIONS: Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

  16. Chen YC, Chayakulkeeree M, Chakrabarti A, Gan GG, Kwong YL, Liu WL, et al.
    J Antimicrob Chemother, 2022 09 30;77(10):2579-2585.
    PMID: 35904002 DOI: 10.1093/jac/dkac251
    Management of invasive mould infections (IMIs) is challenging in Asia, as awareness among medical practitioners can be low and resources are limited. Timely diagnosis and appropriate treatment of IMIs can mitigate the impact on morbidity and mortality, but diagnostic methods, as well as access to preferred antifungal medications, may vary throughout the region. Knowledge of local epidemiology and accurate diagnosis and identification of causal pathogens would facilitate optimal treatment but data in Asia are lacking. To address these unmet needs in the management of IMIs, this paper is a call for urgent action in the following areas: improving awareness of the threat of IMIs; providing education to frontline clinicians across a broad range of specialties on 'red flags' for suspicion of IMIs; prioritizing cost-effective rapid diagnostic testing; improving access to preferred antifungal medications; and closing the gaps in local epidemiological data on IMIs to inform local treatment guidelines.
  17. Apisarnthanarak A, Kwa AL, Chiu CH, Kumar S, Thu LTA, Tan BH, et al.
    Infect Control Hosp Epidemiol, 2018 10;39(10):1237-1245.
    PMID: 30227898 DOI: 10.1017/ice.2018.188
    Inappropriate use of antibiotics is contributing to a serious antimicrobial resistance problem in Asian hospitals. Despite resource constraints in the region, all Asian hospitals should implement antimicrobial stewardship (AMS) programs to optimize antibiotic treatment, improve patient outcomes, and minimize antimicrobial resistance. This document describes a consensus statement from a panel of regional experts to help multidisciplinary AMS teams design programs that suit the needs and resources of their hospitals. In general, AMS teams must decide on appropriate interventions (eg, prospective audit and/or formulary restriction) for their hospital, focusing on the most misused antibiotics and problematic multidrug-resistant organisms. This focus is likely to include carbapenem use with the goal to reduce carbapenem-resistant gram-negative bacteria. Rather than initially trying to introduce a comprehensive, hospital-wide AMS program, it would be practical to begin by pilot testing a simple program based on 1 achievable core intervention for the hospital. AMS team members must work together to determine the most suitable AMS interventions to implement in their hospitals and how best to put them into practice. Continuous monitoring and feedback of outcomes to the AMS teams, hospital administration, and prescribers will enhance sustainability of the AMS programs.
  18. Thung TY, Radu S, Mahyudin NA, Rukayadi Y, Zakaria Z, Mazlan N, et al.
    Front Microbiol, 2017;8:2697.
    PMID: 29379488 DOI: 10.3389/fmicb.2017.02697
    The aim of the present study was to investigate the prevalence of Salmonella spp., Salmonella Enteritidis and Salmonella Typhimurium in retail beef from different retail markets of Selangor area, as well as, to assess their pathogenic potential and antimicrobial resistance. A total of 240 retail beef meat samples (chuck = 60; rib = 60; round = 60; sirloin = 60) were randomly collected. The multiplex polymerase chain reaction (mPCR) in combination with the most probable number (MPN) method was employed to detect Salmonella spp., S. Enteritidis and S. Typhimurium in the meat samples. The prevalence of Salmonella spp., S. Enteritidis and S. Typhimurium in 240 beef meat samples were 7.50, 1.25, and 0.83%, respectively. The microbial loads of total Salmonella was found in the range of <3 to 15 MPN/g. Eight different serovars of Salmonella were identified among the 23 isolates, and S. Agona was the predominant serovar (26.09%). Interestingly, all the Salmonella isolates were resistant to penicillin, erythromycin and vancomycin, but the sensitivity was observed for tetracycline, gentamicin and amoxicillin/clavulanic acid. All 23 isolates were resistant to at least three antibiotics. Two S. Typhimurium isolates (8.70%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.56 which shown resistance to nine antibiotics. PCR analysis of virulence genes showed that all Salmonella isolates (100%) were positive for the invA gene. Meanwhile, pefA was only identified in S. Enteritidis and S. Typhimurium. The findings in this study indicate that retail beef products tested were widely contaminated with multi-drug resistant (MDR) Salmonella and various virulence genes are present among the isolated Salmonella serovars.
  19. Ng OT, Thoon KC, Chua HY, Tan NW, Chong CY, Tee NW, et al.
    Emerg Infect Dis, 2015 Jul;21(7):1192-6.
    PMID: 26079293 DOI: 10.3201/eid2107.141443
    During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.
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