Displaying publications 1 - 20 of 41 in total

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  1. Loh GOK, Wong EYL, Goh CZ, Tan YTF, Lee YL, Pang LH, et al.
    Ann Med, 2023;55(2):2270502.
    PMID: 37857359 DOI: 10.1080/07853890.2023.2270502
    The study aimed to develop a sensitive and high-throughput liquid chromatography coupled with tandem mass spectrometry method to quantify concentrations of tramadol and paracetamol simultaneously in human plasma. Sample preparation involved single-step protein precipitation using methanol and two deuterated internal standards, tramadol D6 and paracetamol D4. Agilent Poroshell 120 EC-C18 (100 × 2.1 mm, 2.1 µm) analytical column was employed to achieve chromatographic separation. Detection was in positive ion multiple reaction monitoring mode. A tailing factor (Tf) of <1.2, separation factor (K prime) of >1.5 from the column dead time and signal-to-noise (S/N) ratio >10, were obtained for analytes and internal standards. The standard curve was linear over the concentration range of 2.5-500.00 ng/mL for tramadol and 0.025-20.00 μg/mL for paracetamol. A small injection volume of 1 µL, low flow rate of 440 µL/min and short analysis time of 3.5 min reduced the solvent consumption, analysis cost and system contamination. The results of method validation parameters fulfilled the acceptance criteria of bioanalytical guidelines. The method was successfully applied to a bioequivalence study of fixed-dose combination products of tramadol and paracetamol in Malaysian healthy subjects.
  2. Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    BMC Infect Dis, 2021 Nov 17;21(1):1162.
    PMID: 34789179 DOI: 10.1186/s12879-021-06876-0
    BACKGROUND: Current assays for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on time consuming, costly and laboratory based methods for virus isolation, purification and removing inhibitors. To address this limitation, we propose a simple method for testing RNA from nasopharyngeal swab samples that bypasses the RNA purification step.

    METHODS: In the current project, we have described two extraction-free reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for the detection of SARS-CoV-2 by using E gene and RdRp gene as the targets.

    RESULTS: Here, results showed that reverse transcription loop-mediated isothermal amplification assays with 88.4% sensitive (95% CI: 74.9-96.1%) and 67.4% sensitive (95% CI: 51.5-80.9%) for E gene and RdRp gene, respectively.

    CONCLUSION: Without the need of RNA purification, our developed RT-LAMP assays for direct detection of SARS-CoV-2 from nasopharyngeal swab samples could be turned into alternatives to qRT-PCR for rapid screening.

  3. Low SF, Ngiu CS, Sridharan R, Lee YL
    BMJ Case Rep, 2014;2014.
    PMID: 24717859 DOI: 10.1136/bcr-2013-202690
    Midgut malrotation commonly presents in the neonatal period, and rarely manifests its symptoms in adulthood with an estimated incidence of 0.2-0.5%. Nevertheless, the symptoms are non-specific with no strong pointers towards the clinical diagnosis. Consequently, the diagnosis is usually disclosed with imaging or surgery. We report a case of small bowel obstruction secondary to a congenital peritoneal band with underlying midgut malrotation in a 48-year-old man.
  4. Kit Loh GO, Ling Wong EY, Fung Tan YT, Lee YL, Chew CK, Mohd Sali ND, et al.
    Bioanalysis, 2021 Nov 08.
    PMID: 34743613 DOI: 10.4155/bio-2021-0185
    Aim: To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to investigate the potential back-conversion of 4HDG to duloxetine using stability study. Materials & methods: The LC-MS/MS method was validated according to the EMA and USFDA Bioanalytical Method Validation Guidelines and applied to pilot bioequivalence study. Results & conclusion: The method validation results were within the acceptance limits. The stability study and incurred sample reanalysis results ruled out the occurrence of back-conversion. The study highlighted the conduct of back-conversion test and the advantages of LC-MS/MS method in terms of sensitivity, specificity and low consumption of organic solvents.
  5. Liam CCK, Boo YL, Lee YL, Law KB, Ho KW, Shahnaz SAKS, et al.
    Blood Cell Ther, 2021 Feb 25;4(1):1-8.
    PMID: 36712843 DOI: 10.31547/bct-2020-009
    BACKGROUND: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.

    PURPOSE: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.

    MATERIALS AND METHODS: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.

    RESULTS: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n=78). The most common subtype is IgG Kappa (n=67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n=31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n=119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.

    DISCUSSION AND CONCLUSIONS: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.

  6. Liam CCK, Tiao JY, Yap YY, Lee YL, Sathar J, McRae S, et al.
    Blood Res, 2023 Mar 31;58(1):36-41.
    PMID: 36632683 DOI: 10.5045/br.2023.2022133
    BACKGROUND: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.

    METHODS: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.

    RESULTS: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.

    CONCLUSION: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

  7. Muhammad Ismail HI, Teh CM, Lee YL, National Paediatric H1N1 Study Group
    Brain Dev, 2015 Jan;37(1):120-9.
    PMID: 24746706 DOI: 10.1016/j.braindev.2014.03.008
    In 2009, pandemic influenza A H1N1 emerged in Mexico and subsequently spread worldwide. In Malaysia, there were more than a thousand of confirmed cases among children. The general clinical characteristics of these children have been well-published. However, the description of neurologic complications is scarce.
  8. Lee YL, Nasir FFWA, Selveindran NM, Zaini AA, Lim PG, Jalaludin MY
    Diabetes Res Clin Pract, 2023 Nov;205:110981.
    PMID: 37890700 DOI: 10.1016/j.diabres.2023.110981
    AIMS: Despite emerging evidence of increased paediatric diabetes mellitus (DM) and diabetic ketoacidosis (DKA) worldwide following the COVID-19 pandemic, studies in Asia are lacking. We aimed to determine the frequency, demographics, and clinical characteristics of new onset type 1 DM (T1DM) during the pandemic in Malaysia.

    METHODS: This is a retrospective multicenter study involving new onset T1DM paediatric patients in Klang Valley, Malaysia during two time periods ie 18th September 2017-17th March 2020 (pre-pandemic) and 18th March 2020-17th September 2022 (pandemic).

    RESULTS: There was a total of 180 patients with new onset T1DM during the 5-year study period (71 pre-pandemic, 109 pandemic). An increase in frequency of T1DM was observed during the pandemic (52 in 2021, 38 in 2020, 27 in 2019 and 30 in 2018). A significantly greater proportion of patients presented with DKA (79.8 % vs 64.8 %), especially severe DKA (46.8 % vs 28.2 %) during the pandemic. Serum glucose was significantly higher (28.2 mmol vs 25.9 mmol/L) with lower venous pH (7.10 vs 7.16), but HbA1c was unchanged.

    CONCLUSIONS: New onset T1DM increased during the pandemic, with a greater proportion having severe DKA. Further studies are required to evaluate the mechanism leading to this rise to guide intervention measures.

  9. Muhammad Ismail HI, Tan KK, Lee YL, Pau WS, Razali KA, Mohamed T, et al.
    Emerg Infect Dis, 2011 Apr;17(4):708-10.
    PMID: 21470467 DOI: 10.3201/eid1704.101212
    To determine effects of pandemic (H1N1) 2009 on children in the tropics, we examined characteristics of children hospitalized for this disease in Malaysia. Of 1,362 children, 51 (3.7%) died, 46 of whom were in an intensive care unit. Although disease was usually mild, ≥ 1 concurrent conditions were associated with higher death rates.
  10. Lee YL, Verma RK, Yadav H, Barua A
    Eur J Dent Educ, 2016 Nov;20(4):218-228.
    PMID: 26277860 DOI: 10.1111/eje.12164
    BACKGROUND: Facebook and mobile texting are prevalent in the lives of almost every student. However, little is known about the relationship between Facebook usage or mobile texting and their impacts on health amongst undergraduate dental students. In this study, excessive Facebook use and excessive mobile texting were studied as they relate to impacts on health.

    MATERIALS AND METHODS: A cross-sectional study was conducted at a private university in Malaysia. A total of 188 undergraduate dental students were interviewed using a pre-tested and self-rated questionnaire. Data collected from participants were analysed using SPSS version 18.0. Chi-square test, Fisher's exact test and multiple logistic regression analyses were applied to study the relationship between explanatory variables and excessive Facebook use and excessive mobile texting.

    RESULTS: The prevalence of excessive Facebook use and excessive mobile texting amongst undergraduate dental students was found to be 33.2% and 33.0%, respectively. According to a multivariate analysis, texting habits, such as the presence of daytime sleepiness after texting late at night (aOR = 2.682, 95% CI = 1.142-6.301) and the presence of anxious feelings if students failed to receive a timely response (aOR = 3.819, 95% CI = 1.580-9.230), were determined to be significant predictors of excessive mobile texting. Excessive Facebook use was found to be significantly related to three variables as follows: fewer numbers of close friends (aOR = 2.275, 95% CI = 1.057-4.898), the checking of updates on the Facebook walls of their friends (aOR = 2.582, 95% CI = 1.189-5.605) and the absence of active and vigorous feelings during Facebook use (aOR = 3.401, 95% CI = 1.233-9.434).

    CONCLUSIONS: Approximately one-third of undergraduate dental students in this study experienced excessive Facebook use and/or excessive mobile texting. Health education and promotion should be instituted to create awareness, whilst students should be advised to practise self-control with respect to both mobile texting and Facebook usage.

  11. Chong CW, Alkatheeri AHS, Ali N, Tay ZH, Lee YL, Paramasivam SJ, et al.
    Gut Pathog, 2020;12:14.
    PMID: 32175011 DOI: 10.1186/s13099-020-00352-x
    Background: The rise of nature-based ecotourism in the past decade has introduced unprecedented challenges in managing the increasing interaction between humans and animals. The potential transmission of antibiotic resistant microbes between humans and non-human primate populations is a concern due to their genetic similarity. Malaysia is well known for hotspots of wildlife diversity where non-human primates like monkeys and orangutans have become popular tourist attractions. In this study, we assessed the prevalence of antimicrobial resistant Staphylococcus aureus, Enterococcus species, and other Enterobacteriaceae in the faeces of human (HS) and two non-human primates (NHP) in Malaysia, the Long-tailed macaque (Macaca fascicularis, MF) and Silvered leaf monkey (Trachypithecus cristatus, TC). In addition, the faecal bacterial composition was profiled to evaluate the potential association between antibiotic resistant profiles and composition of gut microbiota.

    Results: We tested the isolated bacteria using a selection of antibiotics. The results showed that both the number of antibiotic resistant strains and resistance level were higher in humans than NHPs. Overall, the composition of gut microbiome and pattern of antibiotic resistance showed that there was higher similarity between MF and TC, the two NHPs, than with HS. In addition, samples with higher levels of antibiotic resistance showed lower bacterial richness. Homo sapiens had the lowest bacterial diversity and yet it had higher abundance of Bacteroides. In contrast, NHPs displayed higher bacterial richness and greater prevalence of Firmicutes such as Ruminococceae and Oscillospira.

    Conclusion: Higher antibiotic susceptibility in NHPs is likely related to low direct exposure to antibiotics. The lack of resistance may also suggest limited antimicrobial resistance transmission between humans and NHP. Nonetheless, continued monitoring over a long period will help mitigate the risk of anthropozoonosis and zooanthroponosis.

  12. Chong PP, Abdul Hadi SR, Lee YL, Phan CL, Tan BC, Ng KP, et al.
    Infect Genet Evol, 2007 Jul;7(4):449-56.
    PMID: 17324639
    Recurrent vulvovaginal candidiasis affects women worldwide and the resistance to azole drugs may be an important factor. The extent of strain-to-strain variation within a species and its relationship to the ability of the organism to colonize the vulvovaginal mucosa is not well established. The aims of this study were to compare: (i) the genotypes of Candida strains in sequential infections in patients with recurrent vaginitis, (ii) the genotypes of strains in patients with only one episode of infection in a period of 1 year and (iii) determine the in vitro antifungal susceptibilities of strains that cause recurrent vaginitis. Fifty-one cultured specimens from six distinct Candida species were genotyped via random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) method using the ERIC1 and ERIC2 primers (ERIC, enterobacterial repetitive intergenic consensus). Statistical analyses allowed three different scenarios to be discerned for recurrent cases: (i) strain maintenance without genetic variation, (ii) strain maintenance with minor genetic variation and (iii) outright strain replacement. The genetic relatedness between strains from patients with recurrent vaginitis and patients with single episode of vaginitis were demonstrated by the dendogramme and the mean pairwise similarity coefficient S(AB) for the intergroup comparison was 0.223. However, intragroup genetic relatedness was slightly higher than intergroup comparison, with mean S(AB) of 0.261 and 0.331 for Groups I and II, respectively. A high proportion of Group I isolates (87.5%) causing recurrent infections were resistant to ketoconazole, whereas 41.7% of these isolates were cross-resistant to both clotrimazole and ketoconazole as shown by the in vitro antifungal susceptibility test, especially for C. glabrata isolates. Pregnancy status of patients displayed a highly significant association with C. albicans species whereas non-albicans species had a markedly higher prevalence in non-pregnant patients (p<0.001). These results may have a profound impact on the management of vaginal candidiasis, especially in recurrent cases.
  13. Lim MT, Lim YMF, Teh XR, Lee YL, Ismail SA, Sivasampu S
    Int J Qual Health Care, 2019 Aug 01;31(7):37-43.
    PMID: 30608582 DOI: 10.1093/intqhc/mzy252
    OBJECTIVE: To determine the extent of self-management support (SMS) provided to primary care patients with type 2 diabetes (T2D) and hypertension and its associated factors.

    DESIGN: Cross-sectional survey conducted between April and May 2017.

    SETTING: Forty public clinics in Malaysia.

    PARTICIPANTS: A total of 956 adult patients with T2D and/or hypertension were interviewed.

    MAIN OUTCOME MEASURES: Patient experience on SMS was evaluated using a structured questionnaire of the short version Patient Assessment of Chronic Illness Care instrument, PACIC-M11. Linear regression analysis adjusting for complex survey design was used to determine the association of patient and clinic factors with PACIC-M11 scores.

    RESULTS: The overall PACIC-M11 mean was 2.3(SD,0.8) out of maximum of 5. The subscales' mean scores were lowest for patient activation (2.1(SD,1.1)) and highest for delivery system design/decision support (2.9(SD,0.9)). Overall PACIC-M11 score was associated with age, educational level and ethnicity. Higher overall PACIC-M11 ratings was observed with increasing difference between actual and expected consultation duration [β = 0.01; 95% CI (0.001, 0.03)]. Better scores were also observed among patients who would recommend the clinic to friends and family [β = 0.19; 95% CI (0.03, 0.36)], when health providers were able to explain things in ways that were easy to understand [β = 0.34; 95% CI (0.10, 0.59)] and knew about patients' living conditions [β = 0.31; 95% CI (0.15, 0.47)].

    CONCLUSIONS: Our findings indicated patients received low levels of SMS. PACIC-M11 ratings were associated with age, ethnicity, educational level, difference between actual and expected consultation length, willingness to recommend the clinic and provider communication skills.

  14. Lee YL, Jaafar NR, Ling JG, Huyop F, Abu Bakar FD, Rahman RA, et al.
    Int J Biol Macromol, 2024 Apr;263(Pt 1):130284.
    PMID: 38382786 DOI: 10.1016/j.ijbiomac.2024.130284
    Polyethylene terephthalate (PET) is one of the most produced plastics globally and its accumulation in the environment causes harm to the ecosystem. Polyethylene terephthalate hydrolyse (PETase) is an enzyme that can degrade PET into its monomers. However, free PETase lacks operational stabilities and is not reusable. In this study, development of cross-linked enzyme aggregate (CLEA) of PETase using amylopectin (Amy) as cross-linker was introduced to solve the limitations of free PETase. PETase-Amy-CLEA exhibited activity recovery of 81.9 % at its best immobilization condition. Furthermore, PETase-Amy-CLEA exhibited 1.37-, 2.75-, 2.28- and 1.36-fold higher half-lives than free PETase at 50 °C, 45 °C, 40 °C and 35 °C respectively. Moreover, PETase-Amy-CLEA showed broader pH stability from pH 5 to 10 and could be reused up to 5 cycles. PETase-Amy-CLEA retained >70 % of initial activity after 40 days of storage at 4 °C. In addition, lower Km of PETase-Amy-CLEA indicated better substrate affinity than free enzyme. PETase-Amy-CLEA corroded PET better and products yielded was 66.7 % higher than free PETase after 32 h of treatment. Hence, the enhanced operational stabilities, storage stability, reusability and plastic degradation ability are believed to make PETase-Amy-CLEA a promising biocatalyst in plastic degradation.
  15. Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    Int J Infect Dis, 2022 Jul;120:132-134.
    PMID: 35472524 DOI: 10.1016/j.ijid.2022.04.036
    OBJECTIVES: Preventing reverse transcription loop-mediated isothermal amplification (RT-LAMP) carryover contamination could be solved by adding deoxyuridine triphosphate (dUTP) and uracil-DNA glycosylase (UDG) into the reaction master mix.

    METHODS: RNA was extracted from nasopharyngeal swab samples by a simple RNA extraction method.

    RESULTS: Testing of 77 samples demonstrated 91.2% sensitivity (95% confidence interval [CI]: 78-98.2%) and 100% specificity (95% confidence interval: 92-100%) using UDG RT-LAMP.

    CONCLUSION: This colorimetric UDG RT-LAMP is a simple-to-use, fast, and easy-to-interpret method, which could serve as an alternative for diagnosis of SARS-CoV-2 infection, especially in remote hospitals and laboratories with under-equipped medical facilities.

  16. Loh GOK, Wong EYL, Tan YTF, Lee YL, Pang LH, Chin MC, et al.
    PMID: 32905988 DOI: 10.1016/j.jchromb.2020.122337
    A simple, rapid, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method was developed to determine sitagliptin in human plasma. Diphenhydramine HCl was used as internal standard (IS). The chromatographic separation was achieved using Agilent Poroshell 120 EC-C18 - Fast LC column (100 × 2.1mmID, 2.7) fitted with UHPLC Guard Poroshell 120 EC-C18 (5 × 2.1mmID, 2.7 µm). The mobile phase consisted of 0.1% v/v formic acid and methanol (45:55, v/v) run at a flow rate of 0.45 mL/min at 30 °C. Methanol produced relatively cleaner plasma sample as deproteinization agent. Polytetrafluoroethylene membrane was preferred over nylon membrane as the former produced clear plasma samples. The standard calibration curve was linear over the concentration range of 5-500.03 ng/mL. The within-run precision was 0.53-7.12% and accuracy 87.09-105.05%. The between-run precision was 4.74-11.68% and accuracy 95.02-97.36%. The extended run precision was 3.60-6.88% and accuracy 93.18-95.82%. The recovery of analyte and IS was consistent. Sitagliptin in plasma was stable at benchtop (short term) for 24 h, in autosampler tray for 48 h, in instrumentation room for 48 h (post-preparative), after 7 freeze-thaw cycles (-20 ± 10 °C), and 62 days in the freezer (-20 ± 10 °C). Both sitagliptin (analyte) and IS stock solutions were stable for 62 days when kept at room temperature (25 ± 4 °C) and in chiller (2-8 °C). The validated method was successfully applied to a bioequivalence study of two sitagliptin formulations involving 26 healthy Malaysian volunteers.
  17. Lee YL, Ting TH, Lim CT, Thilakavathy K, Musa NH, Ling KH
    PMID: 38647408 DOI: 10.4274/jcrpe.galenos.2024.2023-12-1
    IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.
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