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Fulltext Perspectives on the Application of Cytogenomic Approaches in Chronic Lymphocytic Leukaemia

Wan Mohamad Zamri WN, Mohd Yunus N, Abdul Aziz AA, Zulkipli NN, Sulong S

Diagnostics (Basel), 2023 Mar 03;13(5).
PMID: 36900108 DOI: 10.3390/diagnostics13050964

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy characterised by the accumulation of monoclonal mature B lymphocytes (positive for CD5+ and CD23+) in peripheral blood, bone marrow, and lymph nodes. Although CLL is reported to be rare in Asian countries compared to Western countries, the disease course is more aggressive in Asian countries than in their Western counterparts. It has been postulated that this is due to genetic variants between populations. Various cytogenomic methods, either of the traditional type (conventional cytogenetics or fluorescence in situ hybridisation (FISH)) or using more advanced technology such as DNA microarrays, next generation sequencing (NGS), or genome wide association studies (GWAS), were used to detect chromosomal aberrations in CLL. Up until now, conventional cytogenetic analysis remained the gold standard in diagnosing chromosomal abnormality in haematological malignancy including CLL, even though it is tedious and time-consuming. In concordance with technological advancement, DNA microarrays are gaining popularity among clinicians as they are faster and better able to accurately diagnose the presence of chromosomal abnormalities. However, every technology has challenges to overcome. In this review, CLL and its genetic abnormalities will be discussed, as well as the application of microarray technology as a diagnostic platform.
Fulltext Profile and outcome of post stroke patients managed at selected public primary care health centres in Peninsular Malaysia: A retrospective observational study

Abdul Aziz AF, Ali MF, Yusof MF, Che' Man Z, Sulong S, Aljunid SM

Sci Rep, 2018 12 19;8(1):17965.
PMID: 30568180 DOI: 10.1038/s41598-018-36154-0

Data on post stroke outcomes in developing countries are scarce due to uncoordinated healthcare delivery systems. In Malaysia, the national stroke clinical practice guideline does not address transfer of care and longer term post stroke care beyond tertiary care. Hence, post stroke care delivery may be delivered at either tertiary or primary care facilities. This study aimed at describing patients' characteristics and outcomes of post stroke care delivered by the primary care teams at public primary care healthcentres across Peninsular Malaysia. Multi staged sampling was done to select public primary care health centres to recruit post stroke patients. At each health centre, convenience sampling was done to recruit adult patients (≥18 years) who received post stroke care between July-December 2012. Baseline measurements were recorded at recruitment and retrospective medical record review was done simultaneously, for details on medical and / or rehabilitation treatment at health centre. Changes in the measurements for post stroke care were compared using paired t-tests and Wilcoxon Rank test where appropriate. Total of 151 patients were recruited from ten public primary care healthcentres. The mean age at stroke presentation was 55.8 ± 9.8 years. Median duration of follow up was 2.3 (IQR 5.1) years. Majority co-resided with a relative (80.8%), and a family member was primary caregiver (75.%). Eleven percent were current smokers. Almost 71.0% of patients achieved BP ≤ 140/90 mmHg. Only 68.9% of the patients had been referred for neurorehabilitation. Percentage of recorded data was highest for blood pressure (88.1%) while lowest was HbA1c (43.0%). For clinical outcomes, systolic and diastolic blood pressure, triglyceride level and calculated GFR (eGFR) showed statistically significant changes during follow up (p
Fulltext Profiles and Factors Associated with Poor Glycemic Control Among Inpatients with Diabetes Mellitus Type 2 as a Primary Diagnosis in a Teaching Hospital

Ismail A, Suddin LS, Sulong S, Ahmed Z, Kamaruddin NA, Sukor N

Indian J Community Med, 2016 7 8;41(3):208-12.
PMID: 27385874 DOI: 10.4103/0970-0218.183590

CONTEXT: Diabetes mellitus is a growing health problem in most countries. In Malaysia, there was an increase in prevalence over the years. This makes diabetes also a growing concern in Malaysia, which warrants strengthening of the prevention and control programme.
AIMS: This paper aims to describe the profiles of diabetes mellitus type 2 in tertiary setting and to identify the risk factors for high level of HbA1c among the study population. The findings will give a glimpse on current status of diabetes in our country and may reflect the achievement of the country in combating this disease.
SETTINGS AND DESIGN: A cross-sectional study was conducted in UKM Medical Centre.
METHODS AND MATERIAL: Medical records of patient with E11 ICD-10 code were collected using Case Report Form.
STATISTICAL ANALYSIS USED: Descriptive analysis done of mean and median while test of association were done using Spearman correlation and logistic regression.
RESULTS: The results showed that majority of inpatients of DMT2 showed mean age of 58.8 + 12.6 years and most were males (56.7%) with secondary level of education (41.7%). Median duration of disease was 12.0 + 11.0 years with median HbA1c level of 8.9 ± 4.4%. Only small proportion of patients achieved the desired level of HbA1c <6.5% (21.3%) and significant association was found with tertiary level of education [AOR = 0.10, 95%CI = 0.01-0.96] and with type of anti-diabetic therapy [AOR = 15.90, 95%CI=1;2.03-124.30].
CONCLUSIONS: In conclusion, diabetes mellitus type 2 inpatients still showed unsatisfactory glycemic control and holistic approach using health education should be advocated continuously in the future in view of education being one of the predictors for the good HbA1c outcome.
Quality of life in Malaysian colorectal cancer patients

Wan Puteh SE, Saad NM, Aljunid SM, Abdul Manaf MR, Sulong S, Sagap I, et al.

Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:110-7.
PMID: 23857846 DOI: 10.1111/appy.12055

The rapidly increasing of incidence colorectal cancer (CRC) in Malaysia and the introduction of new treatments that prolong survival advocating treatment outcome measures such as patients' quality of life (QOL) are evaluated in this study. The study aims to determine QOL in CRC patients according to cancer stage and age.
Tannic acid enhances cisplatin effect on cell proliferation and apoptosis of human osteosarcoma cell line (U2OS)

Kasiram MZ, Hapidin H, Abdullah H, Hashim NM, Azlina A, Sulong S

Pharmacol Rep, 2022 Feb;74(1):175-188.
PMID: 34652600 DOI: 10.1007/s43440-021-00330-3

BACKGROUND: The increase in cases of chemoresistance of cisplatin for osteosarcoma treatment has called for the need to establish a new treatment regime. Tannic acid (TA) possesses a potent antiproliferative effect against various cancers. Therefore, this study investigated the effect of TA combined with cisplatin on human osteosarcoma cell lines (U2OS).
METHODS: MTT assay was used to determine the half-maximal inhibitory concentration (IC50), while the combination index (CI) value was utilized to analyze the interaction within each combination. The antiproliferative effect of the treatment was evaluated by trypan blue exclusion assay. The morphological changes of cells were observed under a phase-contrast inverted microscope. The nuclear morphology and percentage of apoptosis cells were evaluated by using the Hoechst 33258 staining and annexin V/PI assay, respectively.
RESULTS: The U2OS cells showed cytotoxic effect when treated with TA and cisplatin, with IC50 at 4.47 µg/mL and 16.25 µg/mL, respectively. The TA demonstrated no significant inhibition effect on the normal human fetal osteoblast cells (hFOB 1.19); yet, interestingly, a potent proliferative effect was indicated. Synergistic interaction was triggered when TA was combined with cisplatin at percentage ratios of 90:10 and 85:15. Meanwhile, antagonistic interaction was induced in the combination at percentage ratios of 75:25 and 50:50. On the other hand, a significant antiproliferative effect with prominent morphological alteration was detected in the cells treated with a combination of TA and cisplatin at the percentage ratio of 90:10. Additionally, combination-treated cells demonstrated the highest percentage of apoptosis cells, with distinct chromosomal condensation, nuclear fragmentation, reduction of nuclear volume, and notable apoptotic body.
CONCLUSION: Therefore, there is a high potential for the inclusion of TA in the cisplatin-based chemotherapeutic regimen of osteosarcoma.
Telomerase activity in Malaysian patients with central nervous system tumors

Isa MN, Sulong S, Sidek MR, George PJ, Abdullah JM

Southeast Asian J. Trop. Med. Public Health, 2003 Dec;34(4):872-6.
PMID: 15115103

Telomerase, the enzyme that stabilizes telomere length is reactivated with almost all cancer types, and may be a useful diagnostic marker for malignancy. Telomerase activity has been detected in germ line cells and most cancer cells, whereas most normal somatic cells have no clearly detectable telomerase activity. In our study, we aim to detect telomerase activity in 20 human central nervous system tumors from Malaysian patients. Telomerase activity was detected based on a highly sensitive procedure consisting of a CHAPS detergent-based extraction from frozen tissues and a PCR-based telomeric repeat amplification protocol (TRAP) using a TRAPEZE Telomerase Detection Kit (Intergen, Co). Telomerase activity was considered positive when a ladder of products was observed starting at 50bp, with 6bp increments. The activity was detected in 30% of the samples analysed, included glioblastoma multiforme, meduloblastoma, paraganglioma and oligodendroglioma. The result of Fisher's exact test indicated that there was a significant association between telomerase activity status with tumor grade (p=0.003). These results suggest that telomerase activity may be an important marker for tumor malignancy.
Telomerase reverse transcriptase downregulation by RNA interference modulates endoplasmic reticulum stress and mitochondrial energy production

Mohd Zain MZ, Ismail NH, Ahmad N, Sulong S, Karsani SA, Abdul Majid N

Mol Biol Rep, 2020 Oct;47(10):7735-7743.
PMID: 32959195 DOI: 10.1007/s11033-020-05848-y

Telomerase is a cancer promoting ribonucleoprotein complex and is a potential therapeutic target for cancer. In this study, the effects of telomerase downregulation on the whole cell proteome were investigated. Understanding how the effect of downregulation on the whole proteome profile will generate a greater understanding of the possible roles played by telomerase in cancer. Downregulation was achieved by RNA interference (RNAi), targeting the telomerase reverse transcriptase (TERT) subunits of telomerase. Transfection of TERT siRNA downregulates TERT gene expression and induced downregulation of telomerase activity. Investigation of the effect of silencing TERT in telomerase was further validated through proteomic analysis by performing 2-dimension electrophoresis (2DE) coupled with MALDI-TOF/TOF. 12 protein spots in HeLa cells were reported to be significantly differentially expressed with 11 of them were upregulated and 1 downregulated. Through STRING analysis, differentially expressed proteins demonstrated strong associations with endoplasmic reticulum stress marker and mitochondrial energy production marker. In conclusions, the result exhibited novel integrated proteomic response involving endoplasmic reticulum stress and mitochondrial energy production in response to the TERT downregulation in cervical cancer cells.
The Epigenesis of Salivary Glands Carcinoma: From Field Cancerization to Carcinogenesis

Mat Lazim N, Yousaf A, Abusalah MAH, Sulong S, Mohd Ismail ZI, Mohamud R, et al.

Cancers (Basel), 2023 Mar 31;15(7).
PMID: 37046772 DOI: 10.3390/cancers15072111

Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications may also contribute to the genesis and progression of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is now widely accepted that epigenetics plays an important role in SGCs development. A basic epigenetic process that has been linked to a variety of pathological as well as physiological conditions including cancer formation, is DNA methylation. Transcriptional repression is caused by CpG islands hypermethylation at gene promoters, whereas hypomethylation causes overexpression of a gene. Epigenetic changes in SGCs have been identified, and they have been linked to the genesis, progression as well as prognosis of these neoplasms. Thus, we conduct a thorough evaluation of the currently known evidence on the involvement of epigenetic processes in SGCs.
Fulltext The Integrated Care Pathway for Managing Post Stroke (ICAPPS) Patients in the Community: A Cost -Effectiveness Analysis

Abdul AA, Muhammad Nur A, Sulong S, Aljunid S

Value Health, 2014 Nov;17(7):A761.
PMID: 27202786 DOI: 10.1016/j.jval.2014.08.259
Fulltext The Unique Biology behind the Early Onset of Breast Cancer

Siddig A, Tengku Din TADA, Mohd Nafi SN, Yahya MM, Sulong S, Wan Abdul Rahman WF

Genes (Basel), 2021 03 05;12(3).
PMID: 33807872 DOI: 10.3390/genes12030372

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
Fulltext The integrated care pathway for managing post stroke patients (iCaPPS©) in public primary care Healthcentres in Malaysia: impact on quality adjusted life years (QALYs) and cost effectiveness analysis

Abdul Aziz AF, Mohd Nordin NA, Muhd Nur A, Sulong S, Aljunid SM

BMC Geriatr, 2020 02 18;20(1):70.
PMID: 32070291 DOI: 10.1186/s12877-020-1453-z

BACKGROUND: The delivery of post stroke care is fragmented even in advanced public healthcare systems, globally. Primary care teams are entrusted to provide longer term care for stroke survivors in most developing countries. The integrated Care Pathway for Post Stroke patients (iCaPPS©) was designed to guide primary care teams to incorporate further rehabilitation and regular screening for post stroke complications among patients residing at home in communities, using the shared-care approach, especially in areas with limited access to specialist stroke care services. The iCaPPS© addressed coordination of rehabilitation and screening for post stroke complications which were absent in the current conventional care of patients managed at public primary care healthcentres. This study aimed to evaluate the cost effectiveness and impact of iCaPPS© on quality-adjusted- life-years (QALY) compared with current conventional monitoring at public primary care healthcentres.
METHODS: A pragmatic healthcentre-based cluster randomised controlled trial-within trial on 151 post stroke patients from 10 public primary care facilities in Peninsular Malaysia was conducted to evaluate QALY of patients managed with iCaPPS© (n = 86) vs conventional care (n = 65) for 6 months. Costs from societal perspective were calculated, using combination of top down and activity-based costing methods. The 5-level EQ5D (EQ-5D-5 L) was used to calculate health state utility scores. Cost per QALY and incremental cost effectiveness ratio (ICER) were determined. Differences within groups were determined using Mann-Whitney tests.
RESULTS: Total costs for 6 months treatment with iCaPPS© was MYR790.34, while conventional care cost MYR527.22. Median QALY for iCaPPS© was 0.55 (0,1.65) compared to conventional care 0.32 (0, 0.73) (z = - 0.21, p = 0.84). Cost per QALY for iCaPPS© was MYR1436.98, conventional care was MYR1647.56. The ICER was MYR1144.00, equivalent to 3.7% of per capita GDP (2012 prices).
CONCLUSIONS: Management of post stroke patients in the community using iCaPPS© costs less per QALY compared to current conventional care and is very cost effective.
TRIAL REGISTRATION: Trial Registration number ACTRN12616001322426. Registered 21 September 2016. (Retrospectively registered).
Fulltext The integrated care pathway for post stroke patients (iCaPPS): a shared care approach between stakeholders in areas with limited access to specialist stroke care services

Abdul Aziz AF, Mohd Nordin NA, Ali MF, Abd Aziz NA, Sulong S, Aljunid SM

BMC Health Serv Res, 2017 Jan 13;17(1):35.
PMID: 28086871 DOI: 10.1186/s12913-016-1963-8

BACKGROUND: Lack of intersectoral collaboration within public health sectors compound efforts to promote effective multidisciplinary post stroke care after discharge following acute phase. A coordinated, primary care-led care pathway to manage post stroke patients residing at home in the community was designed by an expert panel of specialist stroke care providers to help overcome fragmented post stroke care in areas where access is limited or lacking.

METHODS: Expert panel discussions comprising Family Medicine Specialists, Neurologists, Rehabilitation Physicians and Therapists, and Nurse Managers from Ministry of Health and acadaemia were conducted. In Phase One, experts chartered current care processes in public healthcare facilities, from acute stroke till discharge and also patients who presented late with stroke symptoms to public primary care health centres. In Phase Two, modified Delphi technique was employed to obtain consensus on recommendations, based on current evidence and best care practices. Care algorithms were designed around existing work schedules at public health centres.

RESULTS: Indication for patients eligible for monitoring by primary care at public health centres were identified. Gaps in transfer of care occurred either at post discharge from acute care or primary care patients diagnosed at or beyond subacute phase at health centres. Essential information required during transfer of care from tertiary care to primary care providers was identified. Care algorithms including appropriate tools were summarised to guide primary care teams to identify patients requiring further multidisciplinary interventions. Shared care approaches with Specialist Stroke care team were outlined. Components of the iCaPPS were developed simultaneously: (i) iCaPPS-Rehab© for rehabilitation of stroke patients at community level (ii) iCaPPS-Swallow© guided the primary care team to screen and manage stroke related swallowing problems.

CONCLUSION: Coordinated post stroke care monitoring service for patients at community level is achievable using the iCaPPS and its components as a guide. The iCaPPS may be used for post stroke care monitoring of patients in similar fragmented healthcare delivery systems or areas with limited access to specialist stroke care services.

TRIAL REGISTRATION: No.: ACTRN12616001322426 (Registration Date: 21st September 2016).
The role of social media in primary care

Abdul Rashid A, Kamarulzaman A, Sulong S, Abdullah S

Malays Fam Physician, 2021 Jul 22;16(2):14-18.
PMID: 34386159 DOI: 10.51866/rv1048

Online activities have become the norm. From searching for new information to conducting business meetings, social media's role in daily life continues to grow in prominence. It is estimated that the majority of the population uses social media, and users include doctors and other healthcare professionals. It is critical for primary care doctors to note how social media can substantially influence one's healthcare behaviour and decision making. Because primary care doctors are usually the first line of contact for patients, they are the most easily accessible and most instrumental in using social media to steer the public toward proper information on healthcare.
Fulltext Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate

Mohamad Shah NS, Sulong S, Wan Sulaiman WA, Halim AS

Mol Genet Genomic Med, 2019 May;7(5):e635.
PMID: 30924295 DOI: 10.1002/mgg3.635

BACKGROUND: Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.
METHODS: Genome-wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.
RESULTS: Genome-wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2-p16.1, 6p11.2-p12.3, 14q13-q21, and 16q12.1. There was significant decreased, p
Fulltext What We Know about the Molecular Genetics of Central Nervous System (CNS) Tumours in Malaysia

Sulong S, Yusoff AA, Zainuddin N, Abdullah JM, Pannatil JG, Jaafar H, et al.

Malays J Med Sci, 2004 Jan;11(1):37-43.
PMID: 22977358 MyJurnal

The new millennium has been regarded as a genomic era. A lot of researchers and pathologists are beginning to understand the scientific basis of molecular genetics and relates with the progression of the diseases. Central nervous system (CNS) tumours are among the most rapidly fatal of all cancers. It has been proposed that the progression of malignant tumours may result from multi-step of genetic alterations, including activation of oncogenes, inactivation of tumour suppressor genes and also the presence of certain molecular marker such as telomerase activity. In this paper, we review some recent data from the literature, including our own studies, on the molecular genetics analysis in CNS tumours. Our studies have shown that two types of tumour suppressor genes, p53 and PTEN were involved in the development of these tumours but not in p16 gene among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase activity also has been detected in various types of CNS tumours. Thus, it is important to assemble all data which related to this study and may provide as a vital information in a new approach to neuro-oncology studies in Malaysia.
Fulltext What is next after transfer of care from hospital to home for stroke patients? Evaluation of a community stroke care service based in a primary care clinic

Aziz AF, Aziz NA, Nordin NA, Ali MF, Sulong S, Aljunid SM

J Neurosci Rural Pract, 2013 Oct;4(4):413-20.
PMID: 24347948 DOI: 10.4103/0976-3147.120243

CONTEXT: Poststroke care in developing countries is inundated with poor concordance and scarce specialist stroke care providers. A primary care-driven health service is an option to ensure optimal care to poststroke patients residing at home in the community.
AIMS: We assessed outcomes of a pilot long-term stroke care clinic which combined secondary prevention and rehabilitation at community level.
SETTINGS AND DESIGN: A prospective observational study of stroke patients treated between 2008 and 2010 at a primary care teaching facility.
SUBJECTS AND METHODS: Analysis of patients was done at initial contact and at 1-year post treatment. Clinical outcomes included stroke risk factor(s) control, depression according to Patient Health Questionnaire (PHQ9), and level of independence using Barthel Index (BI).
STATISTICAL ANALYSIS USED: Differences in means between baseline and post treatment were compared using paired t-tests or Wilcoxon-signed rank test. Significance level was set at 0.05.
RESULTS: Ninety-one patients were analyzed. Their mean age was 62.9 [standard deviation (SD) 10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between acute stroke and first contact with the clinic 4.0 (interquartile range 9.0) months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007), while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P = 0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median BI increased from 81 (range: 2-100) to 90.5 (range: 27-100) (Z = 2.34, P = 0.01). Median PHQ9 scores decreased from 4.0 (range: 0-22) to 3.0 (range: 0-19) though the change was not significant (Z= -0.744, P = 0.457).
CONCLUSIONS: Primary care-driven long-term stroke care services yield favorable outcomes for blood pressure control and functional level.

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