Displaying publications 1 - 20 of 34 in total

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  1. Abdullah JM, Husin A
    Acta Neurochir. Suppl., 2011;111:421-4.
    PMID: 21725794 DOI: 10.1007/978-3-7091-0693-8_72
    The use of intravascular hypothermia in the treatment of hemorrhagic stroke is currently still being researched. The exact therapeutic properties and effect of hypothermia on the natural progression of the disease are not known, and a only small number of papers has been published with results from these studies. Mild hypothermia at 34°C was induced in six patients with hemorrhagic stroke in the first 48 h after presentation, using an intravascular catheter placed in the inferior vena cava. The hypothermia was induced and maintained for 24 h followed by gradual rewarming. Another 18 patients with hemorrhagic stroke but not receiving hypothermia were then taken as the control group, and all patients were treated with standard stroke management. The patients were then followed up using the modified Rankin Scale (mRS) for 6 months and 1 year. There was a statistically significant improvement at 6 months and 1 year follow-up using the mRS score in the hypothermia group, indicating a possible beneficial effect of early therapeutic hypothermia in the management of acute hemorrhagic stroke. However, a larger study is needed in order to confirm our finding.
  2. Yamin D, Husin A, Harun A
    Trop Biomed, 2020 Dec 01;37(4):903-910.
    PMID: 33612744 DOI: 10.47665/tb.37.4.903
    Candida parapsilosis is an important pathogen of healthcare-associated bloodstream infections (BSI) causing high mortality and morbidity in immunocompromised patients in addition to other Candida species including C. albicans, C. tropicalis, C. glabrata, and C. krusei. Knowledge on recent local species distribution and trend is essential. An increase in the proportion of C. parapsilosis candidemia has been recently observed as a result of many risk factors. The distribution of candidemia has been changing in the last three decades. To determine the proportion of different Candida species causing candidemia in a tertiary-care hospital during January 2001 - December 2018, a retrospective study performed in a 853-bedded tertiary-care hospital in north-eastern Malaysia. All cases of candidemia from January-2001 to December-2018 were included, and the review was performed based on patients' medical records and laboratory database. The frequency of different Candida species was determined. This study showed that out of 1175 patients with candidemia, C. parapsilosis was the most common species contributing to 29.2% (343/1175) of candidemia, followed by C. albicans 20.1% (236/1175), C. tropicalis 18.7% (220/1175), C. glabrata 6.0% (71/1175), C. guilliermondii 3.7% (43/1175), C. rugosa 1.9% (22/1175), C. famata 1.7% (20/1175), C. krusei 1.4% (16/1175), C. dubliniensis 0.8% (9/1175), C. lusitaniae 0.7% (8/1175), C. lipolytica 0.3% (4/1175), C. pelliculosa 0.3% (4/1175), C. haemulonii, C. kefyr, C. utilis and C. inconspicua (1/1175 each). In addition, 14.9% (175/1175) belonged to Candida spp. which were not identified to species level. In conclusion, a different scenario for the proportion of Candida species with C. parapsilosis predominates over C. albicans as a nosocomial pathogen leading to candidemia has been shown in this study.
  3. Win TT, Kamaludin Z, Husin A
    Malays J Pathol, 2016 Aug;38(2):153-7.
    PMID: 27568673 MyJurnal
    Primary mediastinal large B-cell lymphoma (PMLBL) is an uncommon non-Hodgkin lymphoma with a distinct clinicopathological entity in the WHO classification of lymphoid malignancies. It is known to originate from B-cells of the thymus. It mimics thymic neoplasms and other lymphomas clinically and histopathologically. We reported a 33-year-old obese man who presented with shortness of breath off and on for 4 years. Radiologically, there was a huge anterior mediastinal mass. Tru-cut biopsy was initially diagnosed as type-A thymoma. Histopathological examination of the excised specimen revealed PMLBL with stromal fibrosis and sclerosis which created a diagnostic difficulty. The neoplastic cells varied from medium-sized to large pleomorphic cells, including mononuclear cells with centroblastic and immunoblastic features as well as bi-lobed Reed Sternberg (RS)-like cells and horse-shoe like hallmark cells. Some interlacing spindle cells and epithelioid cells were also present. Immunohistochemically, tumour cells expressed diffuse positivity for LCA, CD20, CD79a, CD23, Bcl2, MUM-1 and heterogenous positivity for CD30 and EMA, and were negative for CD10, CD15 and ALK. Ki67 scoring was very high. Tumour cells infiltrated into peri-thymic fat and pericardium. No malignant cells were detected in the pleural fluid and there was no bone marrow infiltration. The patient showed partial response to 6 cycles of RICE chemotherapy, and was planned for second line chemotherapy using hyper-CVAD regimen followed by autologous stem cell transplantation. This case illustrates the importance of thorough sampling and immunohistochemistry in differentiating PMLBL from its differential diagnoses.
  4. Yamin DH, Husin A, Harun A
    Front Public Health, 2021;9:631865.
    PMID: 34458217 DOI: 10.3389/fpubh.2021.631865
    Catheter-related bloodstream infection (CRBSI) is an important healthcare-associated infection caused by various nosocomial pathogens. Candida parapsilosis has emerged as a crucial causative agent for the CRBSI in the last two decades. Many factors have been associated with the development of CRBSI including, demography, pre-maturity, comorbidities (diabetes mellitus, hypertension, heart diseases, neuropathy, respiratory diseases, renal dysfunction, hematological and solid organ malignancies, and intestinal dysfunction), intensive care unit (ICU) admission, mechanical ventilation (MV), total parenteral nutrition (TPN), prior antibiotic and/or antifungal therapy, neutropenia, prior surgery, immunosuppressant, and type, site, number, and duration of catheters. This study aims to determine C. parapsilosis CRBSI risk factors. A retrospective study has been performed in an 853-bedded tertiary-care hospital in north-eastern Malaysia. All inpatients with C. parapsilosis positive blood cultures from January 2006 to December 2018 were included, and their medical records were reviewed using a standardized checklist. Out of 208 candidemia episodes, 177 had at least one catheter during admission, and 31 cases had not been catheterized and were excluded. Among the 177 cases, 30 CRBSI cases were compared to 147 non-CRBSI cases [81 bloodstream infections (BSIs), 66 catheter colonizers]. The significance of different risk factors was calculated using multivariate analysis. Multivariate analysis of potential risk factors shows that ICU admission was significantly associated with non-CRBSI as compared to CRBSI [OR, 0.242; 95% CI (0.080-0.734); p = 0.012], and TPN was significantly positively associated with CRBSI than non-CRBSI [OR, 3.079; 95%CI (1.125-8.429); p = 0.029], while other risk factors were not associated significantly. Patients admitted in ICU were less likely to develop C. parapsilosis CRBSI while patients receiving TPN were more likely to have C. parapsilosis CRBSI when compared to the non-CRBSI group.
  5. Alyousifi Y, Othman M, Husin A, Rathnayake U
    Ecotoxicol Environ Saf, 2021 Dec 20;227:112875.
    PMID: 34717219 DOI: 10.1016/j.ecoenv.2021.112875
    Fuzzy time series (FTS) forecasting models show a great performance in predicting time series, such as air pollution time series. However, they have caused major issues by utilizing random partitioning of the universe of discourse and ignoring repeated fuzzy sets. In this study, a novel hybrid forecasting model by integrating fuzzy time series to Markov chain and C-Means clustering techniques with an optimal number of clusters is presented. This hybridization contributes to generating effective lengths of intervals and thus, improving the model accuracy. The proposed model was verified and validated with real time series data sets, which are the benchmark data of actual trading of Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) and PM10 concentration data from Melaka, Malaysia. In addition, a comparison was made with some existing fuzzy time series models. Furthermore, the mean absolute percentage error, mean squared error and Theil's U statistic were calculated as evaluation criteria to illustrate the performance of the proposed model. The empirical analysis shows that the proposed model handles the time series data sets more efficiently and provides better overall forecasting results than existing FTS models. The results prove that the proposed model has greatly improved the prediction accuracy, for which it outperforms several fuzzy time series models. Therefore, it can be concluded that the proposed model is a better option for forecasting air pollution parameters and any kind of random parameters.
  6. Abdullah J, Saffie N, Sjasri FA, Husin A, Abdul-Rahman Z, Ismail A, et al.
    Braz J Microbiol, 2014;45(4):1385-91.
    PMID: 25763045
    An in-house loop-mediated isothermal amplification (LAMP) reaction was established and evaluated for sensitivity and specificity in detecting the presence of Salmonella Typhi (S. Typhi) isolates from Kelantan, Malaysia. Three sets of primers consisting of two outer and 4 inner were designed based on locus STBHUCCB_38510 of chaperone PapD of S. Typhi genes. The reaction was optimised using genomic DNA of S. Typhi ATCC7251 as the template. The products were visualised directly by colour changes of the reaction. Positive results were indicated by green fluorescence and negative by orange colour. The test was further evaluated for specificity, sensitivity and application on field samples. The results were compared with those obtained by gold standard culture method and Polymerase Chain Reaction (PCR). This method was highly specific and -10 times more sensitive in detecting S. Typhi compared to the optimised conventional polymerase chain reaction (PCR) method.
  7. Leong MC, Kandavello G, Husin A, Perumal D, Kaur Khelae S
    Pacing Clin Electrophysiol, 2020 11;43(11):1252-1257.
    PMID: 32845014 DOI: 10.1111/pace.14049
    BACKGROUND: Elderly patients with atrial septal defect (ASD) often present with chronic atrial fibrillation and large left to right shunt. This study reports the experience of left atrial appendage (LAA) and ASD closure in patients with significant ASD and chronic atrial fibrillation.

    METHODS: We report six consecutive elderly patients with chronic atrial fibrillation and significant ASD who underwent LAA and fenestrated ASD closure from January 1, 2014 until December 31, 2019. All periprocedural and long-term (>1 year) outcomes were reported.

    RESULTS: Six patients (male: 33.3%; mean age: 66.8 ± 3.3 years) were included. Mean CHADS2 , CHA2 DS2 -VASc , and HAS-BLED scores were 2.33 ± 0.82, 3.83 ± 0.75, and 1.83 ± 0.75. Four patients underwent simultaneous procedure, while two patients underwent a staged procedure. Procedural success was achieved in all patients. Total occlusion was achieved during LAA occlusion without device embolization prior to ASD closure. Patients who underwent simultaneous procedure had a shorter total hospital stay and lower total hospital stay. During a follow-up period of 32.8 ± 19.4 months, both the devices were well seated. No device-related thrombosis or erosion reported. All patients remained in atrial fibrillation. No patients experienced any thromboembolic stroke or transient ischemic attack.

    CONCLUSIONS: LAA and ASD closure is feasible and can be safely performed in the same seating in elderly patients with a significant ASD.

  8. Nik Ramli NN, Omar N, Husin A, Ismail Z, Siran R
    Neurosci Lett, 2015 Feb 19;588:137-41.
    PMID: 25562631 DOI: 10.1016/j.neulet.2014.12.062
    Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100μM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10μM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10μM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.
  9. Makhtar SM, Husin A, Baba AA, Ankathil R
    J Genet, 2017 Sep;96(4):633-639.
    PMID: 28947711
    The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.
  10. Makhtar SM, Husin A, Baba AA, Ankathil R
    J Genet, 2018 Sep;97(4):835-842.
    PMID: 30262695
    Imatinib mesylate (IM), a well-established gold standard drug in the treatment of chronic myeloid leukaemia (CML), is a synthetic tyrosine kinase inhibitor. Despite excellent efficacy, a significant number of patients on IM therapy develop resistance to IM. Currently, great focus has been laid on the effect of interindividual pharmacogenetic variability on IM treatment responses. IM uptake is mediated by the hOCT1 protein encoded by the solute carrier 22 gene (SLC22A1). The current study investigated the impact of few single-nucleotide polymorphisms (SNPs) of SLC22A1 on mediating resistance and/or good response to IM among 278 Malaysian CML patients (146 IM-resistant group and 132 IM good response group) undergoing IM therapy on 400 mg daily. Our results showed that the allelic frequencies of heterozygous (CG) and homozygous variant (GG) genotypes of SLC22A1 C480G were significantly higher in the IM-resistant group compared with the IM good response group (41.8% versus 30.3% and 10.9% versus 4.5% with P values of 0.047 and 0.048, respectively). On evaluating the association of genotypes with risk of IM resistance development, heterozygous (CG) and homozygous (GG) variant genotypes showed significantly higher risk for developing resistance to IM treatment with odds ratio (OR): 1.901 (95% confidence interval (CI): 1.142-3.163, P = 0.013) and 3.324 (95% CI: 1.235-8.947, P = 0.017), respectively. Two SNPs and two insertions/deletions were detected in exon 7 of SLC22A1. For exon 7, 1222AA carriers together with the presence of both the 8-bp insertion and 3-bp deletion, and M420del alleles showed higher possibility of developing resistance towards IMtreatment. Our results warrant the need of genotyping this SNP in terms of modulating IM treatment in CML patients.
  11. Ankathil R, Ismail SM, Mohd Yunus N, Sulong S, Husin A, Abdullah AD, et al.
    Malays J Pathol, 2020 Dec;42(3):307-321.
    PMID: 33361712
    Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.
  12. Mohamad A, Hassan R, Husin A, Johan MF, Sulong S
    Asian Pac J Cancer Prev, 2021 Jan 01;22(1):85-91.
    PMID: 33507683 DOI: 10.31557/APJCP.2021.22.1.85
    OBJECTIVE: Chronic Lymphocytic Leukemia (CLL) is a common leukemia among Caucasians but rare in Asians population. We postulated that aberrant methylation either hypermethylation or partial methylation might be one of the silencing mechanisms that inactivates the tumour suppressor genes in CLL. This study aimed to compare the methylation status of tumour suppressor gene, ADAM12, among CLL patients and normal individuals. We also evaluated the association between methylation of ADAM12 and clinical and demographic characteristics of the participants.

    METHODS: A total of 25 CLL patients and 25 normal individuals were recruited in this study. The methylation status of ADAM12 was determined using Methylation-Specific PCR (MSP); whereas, DNA sequencing method was applied for validation of the MSP results.

    RESULTS: Among CLL patients, 12 (48%) were partially methylated and 13 (52%) were unmethylated. Meanwhile, 5 (20%) and 20 (80.6%) of healthy individuals were partially methylated and unmethylated, respectively. There was a statistically significant association between the status of methylation at ADAM12 and the presence of CLL (p=0.037).

    CONCLUSION: The aberrant methylation of ADAM12 found in this study using MSP assay may provide new exposure to CLL that may improve the gaps involved in genetic epigenetic study in CLL.

  13. Maddin N, Husin A, Gan SH, Aziz BA, Ankathil R
    Oncol Ther, 2016;4(2):303-314.
    PMID: 28261657 DOI: 10.1007/s40487-016-0035-x
    INTRODUCTION: Imatinib mesylate (IM), a selective inhibitor of the BCR-ABL tyrosine kinase, is a well-established first-line treatment for chronic myeloid leukemia (CML). IM is metabolized mainly by cytochrome P450 (CYP) in the liver, specifically the CYP3A4 and CYP3A5 enzymes. Polymorphisms in these genes can alter the enzyme activity of IM and may affect its response. In this study, the impact of two single-nucleotide polymorphisms (SNPs), CYP3A5*3 (6986A>G) and CYP3A4*18 (878T>C), on IM treatment response in CML patients (n = 270; 139 IM resistant and 131 IM good responders) was investigated.

    METHODS: Genotyping of CYP3A4*18 and CYP3A5*3 was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic variants and treatment response was assessed by means of odds ratio (OR) with 95% confidence intervals calculated by logistic regression.

    RESULTS: Our results indicated that CML patients carrying the heterozygous (AG) and homozygous variant (GG) genotype of CYP3A5*3 were associated with a significantly lower risk of acquiring resistance with OR 0.171; 95% CI: 0.090-0.324, p 

  14. Awis Qarni F, Tai E, Wh WH, Husin A
    Cureus, 2018 May 29;10(5):e2708.
    PMID: 30062082 DOI: 10.7759/cureus.2708
    Neurolymphomatosis is an atypical complication of non-Hodgkin lymphoma and leukaemia involving infiltration of neurotropic neoplastic cells in the central or peripheral nervous system. A 28-year-old Malay lady with background diffuse large B-cell lymphoma stage IV presented with left homonymous hemianopia associated with cognitive function deterioration. Her best corrected visual acuity was 6/9 in both eyes. Magnetic resonance imaging (MRI) of the brain showed a lesion suggestive of secondary lymphomatous infiltration of the splenium of corpus callosum. The patient underwent chemotherapy, after which repeated MRI showed a reduction in the lesion size. Homonymous hemianopia is a rare presentation of secondary central nervous system neurolymphomatosis. A comprehensive history, physical examination, and radiological imaging are essential to establish the diagnosis in patients presenting with visual field defects.
  15. Nayan NM, Kadir SHSA, Husin A, Siran R
    Physiol Behav, 2024 Apr 06;280:114546.
    PMID: 38583549 DOI: 10.1016/j.physbeh.2024.114546
    Maternal bisphenol A (BPA) exposure has been reported to cause learning and memory deficits in born offspring. However, little is known that this impairment is potentially caused by epigenetic modulation on the development of NMDA receptor subunits. This study investigates the effect of prenatal BPA exposure on the hippocampal miR-19a and miR-539, which are responsible for regulating NMDA receptor subunits as well as learning and memory functions. Pregnant Sprague Dawley rats were orally administered with 5 mg/kg/day of BPA from pregnancy day 1 (PD1) until gestation day 21 (GD21), while control mothers received no BPA. The mothers were observed daily until GD21 for either a cesarean section or spontaneous delivery. The male offspring were sacrificed when reaching GD21 (fetus), postnatal days 7, 14, 21 (PND7, 14, 21) and adolescent age 35 (AD35) where their hippocampi were dissected from the brain. The expression of targeted miR-19a, miR-539, GRIN2A, and GRIN2B were determined by qRT-PCR while the level of GluN2A and GluN2B were estimated by western blot. At AD35, the rats were assessed with neurobehavioral tests to evaluate their learning and memory function. The findings showed that prenatal BPA exposure at 5 mg/kg/day significantly reduces the expression of miR-19a, miR-539, GRIN2A, and GRIN2B genes in the male rat hippocampus at all ages. The level of GluN2A and GluN2B proteins is also significantly reduced when reaching adolescent age. Consequently, the rats showed spatial and fear memory impairments when reaching AD35. In conclusion, prenatal BPA exposure disrupts the role of miR-19a and miR-539 in regulating the NMDA receptor subunit in the hippocampus which may be one of the causes of memory and learning impairment in adolescent rats.
  16. Mohamad Ashari ZS, Sulong S, Hassan R, Husin A, Sim GA, Abdul Wahid SF
    Asian Pac J Cancer Prev, 2014;15(4):1863-9.
    PMID: 24641422
    The amplification of telomerase component (TERC) gene could play an important role in generation and treatment of haematological malignancies. This present study was aimed to investigate copy number amplification status of TERC gene in chronic myeloid leukaemia (CML) patients who were being treated with imatinib mesylate (IM). Genomic DNA was extracted from peripheral blood of CML-IM Resistant (n=63), CML-IM Respond (n=63) and healthy individuals (n=30). TERC gene copy number predicted (CNP) and copy number calculated (CNC) were determined based on Taqman® Copy Number Assay. Fluorescence in situ hybridization (FISH) analysis was performed to confirm the normal signal pattern in C4 (calibrator) for TERC gene. Nine of CML patients showed TERC gene amplification (CNP=3), others had 2 CNP. A total of 17 CML patients expressed CNC>2.31 and the rest had 2.31>CNC>1.5. TERC gene CNP value in healthy individuals was 2 and their CNC value showed in range 1.59-2.31. The average CNC TERC gene copy number was 2.07, 1.99 and 1.94 in CML- IM Resistant patients, CML-IM Respond and healthy groups, respectively. No significant difference of TERC gene amplification observed between CML-IM Resistant and CML-IM Respond patients. Low levels of TERC gene amplification might not have a huge impact in haematological disorders especially in terms of resistance towards IM treatment.
  17. Ab Rahman WS, Abdullah WZ, Mustaffa R, Ahmed SA, Hassan MN, Husin A
    PMID: 24093001 DOI: 10.4137/CCRep.S12122
    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria.
  18. Yunus NM, Johan MF, Ali Nagi Al-Jamal H, Husin A, Hussein AR, Hassan R
    Asian Pac J Cancer Prev, 2015;16(12):4869-72.
    PMID: 26163606
    BACKGROUND: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis.

    MATERIALS AND METHODS: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia.

    RESULTS: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374).

    CONCLUSIONS: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

  19. Wan Ab Rahman WS, Abdullah WZ, Husin A, Nik Mohd Hassan NFF, Hassan MN, Zulkafli Z
    Malays J Pathol, 2019 Aug;41(2):185-189.
    PMID: 31427554
    INTRODUCTION: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder caused by polyclonal immunoglobulin G autoantibodies against clotting factor VIII (FVIII). The incidence was reported to be rare occurring in 0.2- 4 cases/million/year. Patients may present with different clinical manifestations to various specialties. Early recognition of the disease contributes to favourable clinical outcome.

    CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention.

    DISCUSSION: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.

  20. Hassan MN, Fauzi HM, Husin A, Mustaffa R, Hassan R, Ibrahim MI, et al.
    Oman Med J, 2019 Jan;34(1):34-43.
    PMID: 30671182 DOI: 10.5001/omj.2019.06
    Objectives: Autologous peripheral blood stem cells transplantation (APBSCT) is a therapeutic option which can be used in various hematological, neoplastic disorders including lymphoproliferative disease (LPD). Differences in patient populations and treatment modalities in different transplant centers mean it is important to improve the knowledge of the different factors affecting engraftment after APBSCT for the success of this procedure. We sought to determine the factors influencing neutrophil and platelet engraftment after APBSCT in patients with LPD.

    Methods: We conducted a retrospective review of 70 patients with LPD (35 with lymphoma and 35 with multiple myeloma) who had undergone APBSCT between January 2008 and December 2016. Data obtained included disease type, treatment, and stem cell characteristics. Kaplan-Meier analysis was performed for probabilities of neutrophil and platelet engraftment occurred and was compared by the log-rank test. The multivariate Cox proportional hazards regression model was used for the analysis of potential independent factors influencing engraftment. A p-value < 0.050 was considered statistically significant.

    Results: Most patients were ethnic Malay, the median age at transplantation was 49.5 years. Neutrophil and platelet engraftment occurred in a median time of 18 (range 4-65) and 17 (range 6-66) days, respectively. The majority of patients showed engraftment with 65 (92.9%) and 63 (90.0%) showing neutrophil and platelet engraftment, respectively. We observed significant differences between neutrophil engraftment and patient's weight (< 60/≥ 60 kg), stage of disease at diagnosis, number of previous chemotherapy cycles (< 8/≥ 8), and pre-transplant radiotherapy. While for platelet engraftment, we found significant differences with gender, patient's weight (< 60/≥ 60 kg), pre-transplant radiotherapy, and CD34+ dosage (< 5.0/≥ 5.0 × 106/kg and < 7.0/≥ 7.0 × 106/kg). The stage of disease at diagnosis (p = 0.012) and pre-transplant radiotherapy (p = 0.025) were found to be independent factors for neutrophil engraftment whereas patient's weight (< 60/≥ 60 kg, p = 0.017), age at transplantation (< 50/≥ 50 years, p = 0.038), and CD34+ dosage (< 7.0/≥ 7.0 × 106/kg, p = 0.002) were found to be independent factors for platelet engraftment.

    Conclusions: Patients with LPD who presented at an early stage and with no history of radiotherapy had faster neutrophil engraftment after APBSCT, while a younger age at transplantation with a higher dose of CD34+ cells may predict faster platelet engraftment. However, additional studies are necessary for better understanding of engraftment kinetics to improve the success of APBSCT.

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