Displaying publications 81 - 100 of 138 in total

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  1. HanafI S, Abdullah WZ, Adnan RA, Bahar R, Johan MF, Azman NF, et al.
    MyJurnal
    HbE/β-thalassemia is the most common severe form of thalassemia particularly in SEA region including Malaysia and globally, it comprised of a significant severe form of β-thalassemia disorder. It has various clinical manifestations ranging from very mild anemia to severe manifestation similar to beta thalassemia major. Many different syndromes are observed in HbE/β-thalassemia. Several genetic modifiers have been reported to play important role in contributing to phenotypic variability. The true reasons underlying this phenotypic variability remain unknown. The most reliable predictive factor of the disease phenotype is the nature of the beta globin gene mutation itself. However, the degree of severity is also believed to be affected by other genetic modifiers. For instance, high HbF level ameliorates the clinical severity of β thalassemia patients. Therefore, identification of these genetic modifiers is very important. The association of severe clinical manifestation and the specific β-globin gene mutation has been known. But the wide scope and other potential predictors have been only recently appreciated. This review therefore aimed to reveal the potential genetic modifiers of HbE/βthalassemia patients based on the previous reported studies. A better understanding on the mechanisms underlying the variety of phenotypes of this disease may lead to the direction for a better future management plans. This also promotes “personalized medicine” in patient care.
  2. Ambayya A, Razali R, Sulong S, Zulkefli ES, Yap YY, Sathar J, et al.
    Cancers (Basel), 2023 Feb 22;15(5).
    PMID: 36900179 DOI: 10.3390/cancers15051386
    Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients' samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.
  3. Azman NF, Abdullah WZ, Hanafi S, Diana R, Bahar R, Johan MF, et al.
    Ann Hematol, 2020 Apr;99(4):729-735.
    PMID: 32078010 DOI: 10.1007/s00277-020-03927-5
    HbE/Beta thalassemia (HbE/β-thalassemia) is one of the common genetic disorders in South East Asia. It is heterogeneous in its clinical presentation and molecular defects. There are genetic modifiers which have been reported to influence the disease severity of this disorder. The aim of this study was to determine the genetic polymorphisms which were responsible for the disease clinical diversity. A case-control study was conducted among Malay transfusion-dependent HbE/β-thalassemia patients. Patients who were confirmed HbE/β-thalassemia were recruited and genotyping study was performed on these subjects. Ninety-eight patients were selected and divided into moderate and severe groups based on clinical parameters using Sripichai scoring system (based on hemoglobin level, spleen size, growth development, the age of first transfusion and age of disease presentation). Forty-three (44.9%) and 55 (56.1%) patients were found to have moderate and severe clinical presentation, respectively. Genotyping analysis was performed using Affymetrix 6.0 microarray platform. The SNPs were filtered using PLINK and Manhattan plot by R software. From the GWAS results, 20 most significant SNPs were selected based on disease severity when compared between moderate and severe groups. The significant SNPs found in this study were mostly related to thalassemia complications such as rs7372408, associated with KCNMB2-AS1 and SNPs associated with disease severity. These findings could be used as genetic predictors in managing patients with HbE/β-thalassemia and served as platform for future study.
  4. Yusoff Z, Maqbool M, George E, Hassan R, Ramasamy R
    Med J Malaysia, 2016 Jun;71(3):105-10.
    PMID: 27495882 MyJurnal
    Mesenchymal stem cells (MSCs) derived from human umbilical cord (UC) have been considered as an important tool for treating various malignancies, tissue repair and organ regeneration. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are better alternative to MSCs that derived from bone marrow (BM-MSCs) as they are regarded as medical waste with little ethical concern for research and easily culture-expanded. In this present study, the foetal distal end of human UC was utilised to generate MSC by explant method. Upon in vitro culture, adherent cells with fibroblastic morphology were generated with rapid growth kinetics. Under the respective inductive conditions, these cells were capable of differentiating into adipocytes and osteocytes; express an array of standard MSC's surface markers CD29, CD73, CD90, CD106 and MHC-class I. Further assessment of immunosuppression activity revealed that MSCs generated from UC had profoundly inhibited the proliferation of mitogen-activated T lymphocytes in a dosedependent manner. The current laboratory findings have reinforced the application of explant method to generate UCMSCs thus, exploring an ideal platform to fulfil the increasing demand of MSCs for research and potential clinical use.
  5. Islam MA, Kundu S, Hassan R
    Curr Gene Ther, 2020;19(6):376-385.
    PMID: 32141417 DOI: 10.2174/1566523220666200306092556
    Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.
  6. Elnager A, Hassan R, Idris Z, Mustafa Z, Wan-Arfah N, Sulaiman SA, et al.
    Biomed Res Int, 2015;2015:627471.
    PMID: 25664321 DOI: 10.1155/2015/627471
    Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.
  7. Hassan R, Mohd Yusof M, Kamarudin NA
    Malays J Med Sci, 2010 Oct;17(4):67-70.
    PMID: 22135564 MyJurnal
    An atlanto-occipital dislocation is a rare airbag-induced injury in trauma patients. We report a case of an atlanto-occipital dislocation in a 6-year-old patient who was an unrestrained passenger in the front seat of a vehicle involved in a low-speed motor vehicle accident. This case illustrates the fatal threat of airbag deployment to the child passenger travelling in the vehicle front seat even in a low-speed collision, and supports the recommendation that children under 12 years of age travelling in vehicles with dual airbag systems should be seated in the back.
  8. Jeffree SM, Ahmed K, Safian N, Hassan R, Mihat O, Lukman KA, et al.
    Am J Trop Med Hyg, 2018 Jan;98(1):45-50.
    PMID: 29141714 DOI: 10.4269/ajtmh.17-0081
    Sabah is a Malaysian state situated in the northern part of Borneo, and it is endemic for malaria. The incidence of malaria is the lowest (0.05/1,000 population) in Penampang districts of Sabah. In June 26, 2012, two Plasmodium falciparum malaria cases were notified to public health department from a village in Penampang. Immediate investigation was initiated to identify the risk factors and to institute control measures. We performed active case finding by asking household members of all houses in the village regarding malaria symptoms and by examining blood smears. Environmental investigation was performed by collecting samples to detect mosquito breeding sites and to identify malaria transmitting vector mosquitoes. A case-control study with a ratio of 1:4 (11 cases and 44 controls) was conducted using self-administered questionnaire. The microscopic examination of blood smear for malarial parasite and entomology sampling was carried out. The malarial attack rate was 2.3%, 6/11 smears have gametocyte, and the case fatality rate was 9.1%. One case was a migrant rubber tapper from Indonesia which happened to be the first case with gametocyte positive. Overall, the incidence of malaria was higher (6/11) among rubber tappers. The odds of cases for those living nearby stagnant water were 7.3 [95% confidence interval: 1.2-43.5] times higher. In conclusion, an outbreak of P. falciparum malaria was introduced into a malaria-free village by a migrant rubber tapper, by whom the imported parasite was introduced to the community via vector Anopheles balabacensis. Living near stagnant water bodies was the risk factor in this outbreak.
  9. Zreaqat M, Hassan R, Halim AS
    Int J Oral Maxillofac Surg, 2012 Jun;41(6):783-8.
    PMID: 22424709 DOI: 10.1016/j.ijom.2012.02.003
    This comparative cross-sectional study assessed the facial surface dimensions of a group of Malay children with unilateral cleft lip and palate (UCLP) and compared them with a control group. 30 Malay children with UCLP aged 8-10 years and 30 unaffected age-matched children were voluntarily recruited from the Orthodontic Specialist Clinic in Hospital Universiti Sains Malaysia (HUSM). For the cleft group, lip and palate were repaired and assessment was performed prior to alveolar bone grafting and orthodontic treatment. The investigation was carried out using 3D digital stereophotogrammetry. 23 variables and two ratios were compared three-dimensionally between both groups. Statistically significant dimensional differences (P<0.05) were found between the UCLP Malay group and the control group mainly in the nasolabial region. These include increased alar base and alar base root width, shorter upper lip length, and increased nose base/mouth width ratio in the UCLP group. There were significant differences between the facial surface morphology of UCLP Malay children and control subjects. Particular surgical procedures performed during primary surgeries may contribute to these differences and negatively affect the surgical outcome.
  10. Ho SF, Tan SJ, Mazlan MZ, Iberahim S, Lee YX, Hassan R
    Diagnostics (Basel), 2023 Jul 21;13(14).
    PMID: 37510189 DOI: 10.3390/diagnostics13142445
    Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.
  11. Ali WN, Ahmad R, Nor ZM, Ismail Z, Ibrahim MN, Hadi AA, et al.
    PMID: 23413702
    Many of the most widely spread vector-borne diseases are water related, in that the mosquito vectors concerned breed or pass part of their lifecycle in or close to water. A major reason for the study of mosquito larval ecology is to gather information on environmental variables that may determine the species of mosquitoes and the distribution of larvae in the breeding habitats. Larval surveillance studies were conducted six times between May 2008 and October 2009 in Pos Lenjang, Kuala Lipis, Pahang. Twelve environmental variables were recorded for each sampling site, and samples of mosquito larvae were collected. Larval survey studies showed that anopheline and culicine larvae were collected from 79 and 67 breeding sites, respectively. All breeding sites were classified into nine habitat groups. Culicine larvae were found in all habitat groups, suggesting that they are very versatile and highly adaptable to different types of environment. Rock pools or water pockets with clear water formed on the bank of rivers and waterfalls were the most common habitats associated with An. maculatus. Environmental variables influence the suitability of aquatic habitats for anopheline and culicine larvae, but not significantly associated with the occurrence of both larvae genera (p>0.05). This study provides information on mosquito ecology in relation to breeding habitats that will be useful in designing and implementing larval control operations.
  12. Al-Jamal HA, Mat Jusoh SA, Hassan R, Johan MF
    BMC Cancer, 2015;15:869.
    PMID: 26547689 DOI: 10.1186/s12885-015-1695-x
    Tumor-suppressor genes are inactivated by methylation in several cancers including acute myeloid leukemia (AML). Src homology-2 (SH2)-containing protein-tyrosine phosphatase 1 (SHP-1) is a negative regulator of the JAK/STAT pathway. Transcriptional silencing of SHP-1 plays a critical role in the development and progression of cancers through STAT3 activation. 5-Azacytidine (5-Aza) is a DNA methyltransferase inhibitor that causes DNA demethylation resulting in re-expression of silenced SHP-1. Lestaurtinib (CEP-701) is a multi-targeted tyrosine kinase inhibitor that potently inhibits FLT3 tyrosine kinase and induces hematological remission in AML patients harboring the internal tandem duplication of the FLT3 gene (FLT3-ITD). However, the majority of patients in clinical trials developed resistance to CEP-701. Therefore, the aim of this study, was to assess the effect of re-expression of SHP-1 on sensitivity to CEP-701 in resistant AML cells.
  13. Hassan R, Johari M, Nijhar JS, Sharifah BSA, Low LL, Amri N
    Med J Malaysia, 2021 03;76(2):254-257.
    PMID: 33742640
    We describe here the first laparotomy involving a COVID-19 patient in Malaysia. A 60-year-old man screened positive for SARS-CoV-2 in March 2020 and developed acute abdomen in the ward in Hospital Sultanah Bahiyah, Kedah. He underwent laparotomy and cholecystectomy for gangrenous cholecystitis. All personnel adhered to infectious control precautions, donning full personal protective equipment (PPE) throughout the surgery. Post-operatively, due to raised septic parameters, he was carefully diagnosed with and treated empirically for superimposed bacterial sepsis instead of cytokine release syndrome, with confirmed blood culture of Klebsiella pneumoniae. Patient was discharged well later. None of the staff involved in his care developed COVID-19 infection.
  14. Ahmad S, Lambuk L, Ahmed N, Mussa A, Tee V, Mohd Idris RA, et al.
    Nanomedicine (Lond), 2023 Oct;18(24):1733-1744.
    PMID: 37982749 DOI: 10.2217/nnm-2022-0300
    Background: Nab-paclitaxel is formulated to address several limitations of paclitaxel. Methods: A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Results: Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Conclusion: Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.
  15. Zreaqat M, Hassan R, Samsudin AR, Alforaidi S
    Eur J Pediatr, 2023 Dec;182(12):5501-5510.
    PMID: 37777602 DOI: 10.1007/s00431-023-05226-3
    Twin-block appliance had been advocated as a potential treatment option in paediatric obstructive sleep apnoea (OSA) due to their favourable effect in enhancing upper airway parameters and improving OSA symptoms. The aim of this study was to evaluate the effect of twin-block appliance therapy on upper airway parameters/dimensions and the apnoea-hypopnea indexes (AHIs) in OSA children with class II mandibular retrognathic skeletal malocclusion using cone-beam computed tomography. This prospective longitudinal study comprised 34 polysomnography-proven OSA growing children with class II mandibular retrognathic skeletal malocclusion between the ages of 8 and 12 years who had completed myofunctional twin-block therapy and matched corresponding controls. The upper airway was segmented into the nasopharynx, oropharynx, and hypopharynx, and the effect of twin-bock treatment on upper airway parameters/dimensions was assessed pre- and posttreatment using CBCT analysis, while a second standard overnight PSG was performed to determine changes in the AHI. At the nasopharynx level, minimal (nonsignificant) increases in all variables were observed within the twin-block group and between the groups (P > 0.05). At the level of the oropharynx, all variables increased significantly in the treatment group and between groups (P 
  16. Shahzad A, Hassan R, Aremu AY, Hussain A, Lodhi RN
    Qual Quant, 2020 Aug 04.
    PMID: 32836471 DOI: 10.1007/s11135-020-01028-z
    In response to the emerging and ever solution to the COVID-19 outbreak. This study proposes a theoretical framework based on literature and model to determined E-learning portal success. The study compared males and females to E-learning portal usage. The study objective is to check the difference between male and female E-learning portals' accessibility among the students' perspective. The study included service quality, system quality, information quality, user satisfaction, system use, and E-learning portal success. The empirical data of 280 students participated from the different universities of Malaysia through google surveys analyzed using the Partial Least Squares Structural Equation Modelling. The study further divided the full model into two domains, which are female and male. In the male model, information quality and system quality have direct relationships with user satisfaction. Information quality also supported the relationship with system use. At the same time, there is a positive relationship between user satisfaction and E-learning portals. Likewise, in the female model, E-service quality and Information quality both are supported by system use and user satisfaction. Similarly, system quality has a positive relationship with user satisfaction, and user satisfaction has a positive relationship with E-learning portals. The study will be further helpful for the Malaysian universities policy-makers such as top management, ministry of higher education, Malaysian universities union in designing the policies and programs on E-learning Portal Success in the country. The findings of the study reveal that males and females have a different level of in terms of usage of towards E-learning portals in Malaysian Universities.
  17. Alazzawi MMJ, Husein A, Alam MK, Hassan R, Shaari R, Azlina A, et al.
    Prog Orthod, 2018 Apr 16;19(1):10.
    PMID: 29658096 DOI: 10.1186/s40510-018-0208-2
    BACKGROUND: Quality bone regeneration, which leads to the improvement of bone remodeling, is essential for orthodontic treatment. In order to improve bone regeneration and increase the amount of tooth movement, different techniques have been implemented. The object of this study is to compare the effects of low-level laser therapy (LLLT), low-intensity pulsed ultrasound (LIPUS), and their combination on bone remodeling during orthodontic tooth movement.

    METHODS: Eighty (80) male, 6-week-old Sprague Dawley rats were grouped in to four groups, the first group was irradiated with (940 nm) diode laser, second group with LIPUS, and third group with combination of both LLLT and LIPUS. A forth group used was a control group in an incomplete block split-mouth design. The LLLT and LIPUS were used to treat the area around the moving tooth once a day on days 0-7, then the experiment was ended in each experimental endpoint (1, 3, 7, 14, and 21 days). For amount of tooth movement, models were imaged and analyzed. Histological examination was performed after staining with (hematoxylin and eosin) and (alizarin red and Alcian Blue) stain. One step reverse transcription-polymerase chain reaction RT-PCR was also performed to elucidate the gene expression of RANK, RANKL, OPG, and RUNX-2.

    RESULTS: The amount of tooth movement, the histological bone remodeling, and the RT-PCR were significantly greater in the treatment groups than that in the control group. Among the treatment groups, the combination group was the highest and the LIPUS group was the lowest.

    CONCLUSION: These findings suggest that LLLT and LIPUS can enhance the velocity of tooth movement and improve the quality of bone remodeling during orthodontic tooth movement.

  18. Jawad MM, Husein A, Azlina A, Alam MK, Hassan R, Shaari R
    J Biomed Opt, 2013 Dec;18(12):128001.
    PMID: 24337495 DOI: 10.1117/1.JBO.18.12.128001
    Bone regeneration is essential in medical treatment, such as in surgical bone healing and orthodontics. The aim of this study is to examine the effect of different powers of 940 nm diode low-level laser treatment (LLLT) on osteoblast cells during their proliferation and differentiation stages. A human fetal osteoblast cell line was cultured and treated with LLLT. The cells were divided into experimental groups according to the power delivered and periods of exposure per day for each laser power. The (3-(4,5-dimethylthiazol-2yl)-2,5 diphenyl tetrazolium bromide) (MTT) assay was used to determine cell proliferation. Both alkaline phosphatase and osteocalcin activity assays were assessed for cell differentiation. All treatment groups showed a significant increase in cell proliferation and differentiation compared to the control group. Regarding the exposure time, the subgroups treated with the LLLT for 6 min showed higher proliferation and differentiation rates for the powers delivered, the 300-mW LLLT group significantly increased the amount of cell proliferation. By contrast, the 100 and 200 mW groups showed significantly greater amounts of cell differentiation. These results suggest that the use of LLLT may play an important role in stimulating osteoblast cells for improved bone formation.
  19. Abdullah WZ, Ismail R, Nasir A, Mohamad N, Hassan R
    Fetal Pediatr Pathol, 2013 Apr;32(2):77-81.
    PMID: 22536947 DOI: 10.3109/15513815.2012.671447
    Combined factor V and VIII deficiency is a rare bleeding disorder. Diagnosis of congenital coagulation factor deficiency in a neonate is challenging due to "immaturity" of the hemostatic system. A 2-day-old baby girl presented with spontaneous cephalhematoma. She was found to have persistent abnormal coagulation tests and finally diagnosed as combined factor V and VIII deficiency. Interestingly, factor V and factor VIII in developmental hemostasis are quite similar with adult levels in newborn, and hence early diagnosis is possible. An investigation to detect underlying hemostatic defects is recommended in newborns with spontaneous cephalhematoma.
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