Displaying publications 41 - 58 of 58 in total

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  1. Jayapalan JJ, Lee CS, Lee CC, Ng KL, Junit SM, Hashim OH
    Clin Biochem, 2018 Mar;53:127-131.
    PMID: 29355489 DOI: 10.1016/j.clinbiochem.2018.01.008
    BACKGROUND: Benign thyroid goiter (BTG) and papillary thyroid carcinoma (PTC) are often interchangeably misdiagnosed.

    METHODS: Pooled urine samples of patients with BTG (n=10), patients with PTC (n=9) and healthy controls (n=10) were subjected to iTRAQ analysis and immunoblotting.

    RESULTS: The ITRAQ analysis of the urine samples detected 646 proteins, 18 of which showed significant altered levels (p<0.01; fold-change>1.5) between patients and controls. Whilst four urinary proteins were commonly altered in both BTG and PTC patients, 14 were unique to either BTG or PTC. Amongst these, four proteins were further chosen for validation using immunoblotting, and the enhanced levels of osteopontin in BTG patients and increased levels of a truncated gelsolin fragment in PTC patients, relative to controls, appeared to corroborate the findings of the iTRAQ analysis.

    CONCLUSION: The data of the present study is suggestive of the potential application of urinary osteopontin and gelsolin to discriminate patients with BTG from those with PTC non-invasively. However, this needs to be further validated in studies of individual urine samples.

  2. Yii RSL, Chuah KH, Poh KS, Lau PC, Ng KL, Ho SH, et al.
    Dig Dis Sci, 2022 01;67(1):344-347.
    PMID: 33491164 DOI: 10.1007/s10620-021-06835-4
  3. Ng KL, Huan NC, Mohammad FA, Mohd Aminudin NH, Mohammad FA, Abdul Rahaman JA
    Med J Malaysia, 2022 Jan;77(1):33-40.
    PMID: 35086992
    BACKGROUND: Bronchial provocation test (BPT) is widely used internationally not only to evaluate bronchial responsiveness in conditions especially asthma, but is also utilized as a marker of control, severity and prognosis for asthma. However, the uptake of BPT in certain countries including Malaysia remains low. We aimed to explore this lack of knowledge by assessing the current level of awareness and knowledge on BPT amongst doctors in Malaysia.

    MATERIALS AND METHODS: A nationwide web-based questionnaire targeting doctors was sent through social media (Facebook, WhatsApp and Telegram) and Malaysian Medical Association (MMA) mailing lists between 1 October 2020 - 5 February 2021.

    RESULTS: In all 415 survey responses were analysed from doctors of various grades namely medical officers to consultants. A total of 404 (97.35%) encountered patients with asthma in their daily practice. According to specialty: 169 (40.72%) were from primary care, 121 (29.16%) internal medicine, 50 (12.05%) pulmonary medicine and 75 (18.07%) others. Only 163 (39.28%) were aware of BPT as a tool to diagnose asthma. 232 (55.90%) and 124 (29.88%) regarded BPT as an important test and felt confident to refer patients for BPT respectively. Of those participants who were not confident to refer: 35.17% were unsure of BPT indications, 33.21% were unsure of centres providing BPT, 8.17% cited logistic reasons, 6.04% were concerned of possible BPT side effects. 387 (93.25%) wanted more training in BPT. The median BPT knowledge score was 20% (1 out of 5). Awareness and knowledge were affected by specialty but not by: region of practice, gender, age and grade from logistic regression analysis.

    CONCLUSION: Various national level programs and targeted local interventions are much needed to increase the awareness, knowledge and uptake of BPT in Malaysia.

  4. Eng ZH, Ahmad Jefry MM, Ng KL, Abdul Aziz A, Mat Junit S
    Malays J Pathol, 2023 Dec;45(3):375-390.
    PMID: 38155379
    Thyroid malignancy status is usually confirmed through histopathological examination (HPE) following thyroidectomy. In Malaysia, the application of molecular markers in pre-operative diagnosis of thyroid cancer remains unexplored. In this study, BRAF and NRAS gene mutation panel was assessed, and the results were compared with retrospective HPE findings. Malaysian patients with benign goitre (BTG: n=33) and papillary thyroid cancer (PTC: n=25; PTCa: n=20, PTCb: n=5) were recruited at Universiti Malaya Medical Centre from September 2019 to December 2022. PCR-direct DNA sequencing of BRAFV600, NRASG12, NRASG13, and NRASQ61 was conducted on DNA extracted from the patients' thyroid tissue specimens following thyroidectomy and HPE. BRAFV600E and NRASQ61R mutations showed absolute PTC-specificity with PTC-sensitivity of 32% and 28%, respectively. NRASQ61H demonstrated lower PTC-specificity (94%) but higher PTC-sensitivity (72%) compared to the BRAFV600E and NRASQ61R mutations. Although the NRASG12 and NRASG13 variants were absent in this study, a novel NRASV14D mutation was detected in a PTCa patient. Unlike PTCb, coexistence of BRAFV600E and NRASQ61 variants was commonly observed among the PTCa patients. Notably, all PTCb patients had NRASQ61H mutation with one patient carried both the NRASQ61H and BRAFV600E mutations. Association analysis revealed potential link between gender, BRAFV600E mutation and lymph node metastasis. In conclusion, mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H did not discriminate the two PTC subtypes but replicated the retrospective HPE findings in differentiating BTG from PTC. The application of this mutation panel in pre-operative diagnosis of thyroid nodules requires further validation in a larger sample size, preferably incorporating fineneedle aspirate biopsies.
  5. Ng KL, Tan SN, Huan NC, Nasaruddin MZ, Othman N, Rahaman JAA
    Respirol Case Rep, 2024 Mar;12(3):e01333.
    PMID: 38528948 DOI: 10.1002/rcr2.1333
    Multiple myeloma (MM) is characterized by neoplastic proliferation of monoclonal antibody producing plasma cells. In clinical practice, pleural effusion is seen in up to 6% of MM patients, with many causative factors. Nevertheless, true myelomatous pleural effusion, defined as infiltration of the pleura by myeloma cells, is very rare. In this case report, we present two patients with biopsy proven myelomatous pleural effusion. The first patient developed myelomatous pleural effusion as initial presentation while the second patient's pleural effusion occurred during disease relapse. In both cases, prompt diagnosis via medical thoracoscopy (MT) followed by early commencement of myeloma specific chemotherapy led to clinical, biochemical, and radiological resolution and therefore were crucial steps in the management of myelomatous pleural effusion.
  6. Ng KL, Huan NC, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA
    Respirol Case Rep, 2021 Feb;9(2):e00704.
    PMID: 33364028 DOI: 10.1002/rcr2.704
    Pulmonary mucormycosis is a rare but rapidly progressing and life-threatening fungal infection, usually affecting immunocompromised patients. We report a case of a previously healthy young lady who presented with prolonged cough, weight loss, and haemoptysis. Imaging showed left hilar mass with infiltration into the left main bronchus and concurrent mediastinal lymphadenopathy. Flexible bronchoscopy revealed an endobronchial mass occluding the left main bronchus. Tumour debulking was performed using rigid bronchoscopy with cryoprobe and snares. Histopathological examination revealed inflamed tissue with fungal organism. Fungal polymerase chain reaction (PCR) confirmed Rhizopus microsporus. She was treated with two weeks of intravenous amphotericin-B with complete clinical and radiological resolution.
  7. Huan NC, Ng KL, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA
    Respirol Case Rep, 2020 Dec;8(9):e00684.
    PMID: 33194207 DOI: 10.1002/rcr2.684
    Tracheobronchial stenosis due to tuberculosis (TSTB) is a potentially debilitating complication of endobronchial tuberculosis (EBTB). Endobronchial interventions including silicone stent insertion is an acceptable approach to improve quality of life among patients with TSTB. However, little is known about the optimal management strategy for patients with bronchomalacia secondary to EBTB (B-EBTB) and whether stent-related complication rates are higher among this group of patients. Herein, we report two patients with B-EBTB who unfortunately developed bronchial tear related to silicone endobronchial stenting. Both patients were successfully managed conservatively without the need for emergency open surgery. We hypothesize that endobronchial intervention might be more beneficial for patients with pure TSTB and might be riskier in cases of bronchomalacia with reduced airway thickness and loss of airway cartilaginous support. More future studies are needed to bridge the current gap in knowledge regarding the optimal management and role of endobronchial interventions among patients with B-EBTB.
  8. Huan NC, Ng KL, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA
    Respirol Case Rep, 2021 Mar;9(3):e00711.
    PMID: 33532074 DOI: 10.1002/rcr2.711
    Tracheobronchial stenosis secondary to endobronchial tuberculosis (TSTB) is a rare but debilitating complication of endobronchial tuberculosis (EBTB). Topical mitomycin-C (TMC) has been successfully utilized to restore airway patency and to prevent recurrence of TSTB, although little is known about its exact efficacy. Here, we report the biggest case series to date involving seven patients who received TMC as part of multimodality endoscopic treatment for TSTB with varying levels of success. All patients presented with dyspnoea during or after treatment completion for pulmonary tuberculosis (PTB). Four patients had short-segment concentric membranous TSTB while two patients had concurrent bronchomalacia. Another one patient had a thick fibrotic band adjacent to luminal opening. We hypothesize that TMC is more efficacious in short membranous stenosis without concurrent bronchomalacia and/or thick fibrotic bands. More studies are needed to bridge the current gaps in knowledge regarding the optimal role and benefits of TMC for TSTB patients.
  9. Lim J, Bhoo-Pathy N, Sothilingam S, Malek R, Sundram M, Hisham Bahadzor B, et al.
    PLoS One, 2014;9(8):e104917.
    PMID: 25111507 DOI: 10.1371/journal.pone.0104917
    OBJECTIVES: To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.
    MATERIALS AND METHODS: We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.
    RESULTS: There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05).
    CONCLUSION: These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.
  10. Yap NY, Ng KL, Ong TA, Pailoor J, Gobe GC, Ooi CC, et al.
    Asian Pac J Cancer Prev, 2013;14(12):7497-500.
    PMID: 24460324
    BACKGROUND: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms.

    MATERIALS AND METHODS: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis.

    RESULTS: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001).

    CONCLUSIONS: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

  11. Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al.
    Br. J. Cancer, 2015 Jun 30;113(1):150-8.
    PMID: 26022929 DOI: 10.1038/bjc.2015.183
    Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
  12. Ong TA, Khong SY, Ng KL, Ting JR, Kamal N, Yeoh WS, et al.
    Urology, 2015 Sep;86(3):487-91.
    PMID: 26142713 DOI: 10.1016/j.urology.2015.06.022
    OBJECTIVE: To evaluate the effectiveness of pelvic floor muscle exercises (PFMEs) performed with the new biofeedback Vibrance Kegel Device (VKD), compared to PFMEs alone, in treating stress urinary incontinence (SUI).

    MATERIALS AND METHODS: This was a pilot prospective, randomized trial of women aged ≥18 years with SUI symptoms who underwent PFMEs at University Malaya Medical Centre from October 2011 to October 2013. The patients were randomly divided into two groups: control (PFMEs alone) and VKD (PFMEs with VKD biofeedback). The patients underwent 16 weeks of pelvic floor training, during which they were assessed using Australian pelvic floor questionnaires and modified Oxford scales for pelvic floor muscle strength at week 0, 4, and 16.

    RESULTS: Forty patients were recruited (control 19, VKD 21). Three patients in the control group dropped out during week 16 training, whereas the VKD group had no dropouts. The VKD group reported significantly earlier improvement in SUI scores, as assessed by the Australian pelvic floor questionnaires (P = .035) at week 4. However, there was no significant difference between the groups' SUI scores at week 16. Pelvic floor muscle strength was significantly better in the VKD group at week 4 (P = .025) and week 16 (P = 0.001). The subjective cure rate was similar in both groups at week 16 (62.5% for control and 61.9% for VKD) (P = 0.742).

    CONCLUSION: Using the VKD resulted in significant early improvement in SUI scores, and pelvic muscle strength had improved significantly by the end of the study. The VKD proved useful as an adjunct for pelvic floor training.

  13. Huan NC, Ng KL, Tang JT, Kua HN, Daut UN, Muhammad NA, et al.
    Ann Acad Med Singap, 2020 12;49(12):1013-1017.
    PMID: 33463660 DOI: 10.47102/annals-acadmedsg.2020364
    The ongoing pandemic of COVID-19 has presented multiple challenges to global healthcare services, dictating changes in almost every aspect of daily medical practice. Performing aerosol generating procedures (AGPs) in the field of interventional pulmonology can lead to profound formation of aerosols, leading to a high risk of infection among healthcare workers (HCWs). We share our experiences on performing AGPs in the midst of a COVID-19 pandemic by focusing on changes in AGP practices. In a pandemic, HCWs ought to adapt to the ever-changing situation and use available resources to provide the best possible healthcare to patients, ensure safety of staff, and continue medical education of future pulmonologists.
  14. Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.
    Pathology, 2018 Aug;50(5):511-518.
    PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003
    Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.
  15. Mohd Zaki F, Ng KL, Te BC, Azman MH, Nur Aifaa L, Mohd Razali N, et al.
    Med J Malaysia, 2016 Jun;71(3):122-5.
    PMID: 27495885 MyJurnal
    Detection of neuraxial abnormality in neurologically asymptomatic adolescent idiopathic scoliosis (AIS) is crucial prior to surgery. It can only be detected on magnetic resonance imaging (MRI), which was not routinely done in this group of patient. On the other hand, whole spine radiographs for measurement of Cobb angle have been routinely included during clinic follow-up. This study aimed to determine the correlation between Cobb angle progression and neuraxial abnormality finding on MRI in asymptomatic AIS.
  16. Eng ZH, Abdullah MI, Ng KL, Abdul Aziz A, Arba'ie NH, Mat Rashid N, et al.
    Front Endocrinol (Lausanne), 2022;13:1039494.
    PMID: 36686473 DOI: 10.3389/fendo.2022.1039494
    BACKGROUND: Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Concurrent presence of cytomorphological benign thyroid goitre (BTG) and PTC lesion is often detected. Aberrant protein profiles were previously reported in patients with and without BTG cytomorphological background. This study aimed to evaluate gene mutation profiles to further understand the molecular mechanism underlying BTG, PTC without BTG background and PTC with BTG background.

    METHODS: Patients were grouped according to the histopathological examination results: (i) BTG patients (n = 9), (ii) PTC patients without BTG background (PTCa, n = 8), and (iii) PTC patients with BTG background (PTCb, n = 5). Whole-exome sequencing (WES) was performed on genomic DNA extracted from thyroid tissue specimens. Nonsynonymous and splice-site variants with MAF of ≤ 1% in the 1000 Genomes Project were subjected to principal component analysis (PCA). PTC-specific SNVs were filtered against OncoKB and COSMIC while novel SNVs were screened through dbSNP and COSMIC databases. Functional impacts of the SNVs were predicted using PolyPhen-2 and SIFT. Protein-protein interaction (PPI) enrichment of the tumour-related genes was analysed using Metascape and MCODE algorithm.

    RESULTS: PCA plots showed distinctive SNV profiles among the three groups. OncoKB and COSMIC database screening identified 36 tumour-related genes including BRCA2 and FANCD2 in all groups. BRAF and 19 additional genes were found only in PTCa and PTCb. "Pathways in cancer", "DNA repair" and "Fanconi anaemia pathway" were among the top networks shared by all groups. However, signalling pathways related to tyrosine kinases were the most significantly enriched in PTCa while "Jak-STAT signalling pathway" and "Notch signalling pathway" were the only significantly enriched in PTCb. Ten SNVs were PTC-specific of which two were novel; DCTN1 c.2786C>G (p.Ala929Gly) and TRRAP c.8735G>C (p.Ser2912Thr). Four out of the ten SNVs were unique to PTCa.

    CONCLUSION: Distinctive gene mutation patterns detected in this study corroborated the previous protein profile findings. We hypothesised that the PTCa and PTCb subtypes differed in the underlying molecular mechanisms involving tyrosine kinase, Jak-STAT and Notch signalling pathways. The potential applications of the SNVs in differentiating the benign from the PTC subtypes requires further validation in a larger sample size.

  17. Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
    PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048
    Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
  18. Lim J, Bhoo-Pathy N, Sothilingam S, Malek R, Sundram M, Tan GH, et al.
    PLoS One, 2015;10(6):e0130820.
    PMID: 26098884 DOI: 10.1371/journal.pone.0130820
    To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.
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