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  1. Fulltext Antiphospholipid syndrome presenting as mesenteric vein thrombosis and gangrenous small bowel
    Wan Ali WASR, Mohd Shahrir MS, Hussein H
    International Medical Journal Malaysia, 2011;10(2):0-0.
    MyJurnal
    A 35-year-old Jordanian gentleman presented with worsening right iliac fossa pain of three-day durations with vomiting, loose stool and intermittent fever. He later underwent laparoscopic surgery, which was subsequently converted to open laparotomy. Intraoperatively, there was thickened bowel with multiple mesenteric lymph nodes, and also thrombosis of the small bowel vein supplying the affected bowel lesion, the diagnosis which was later confi rmed with the histopathological report. Resection with end-to-end anastomosis was done during the surgery. Within one-week post laparotomy, he developed another progressive abdominal pain and distension, vomiting and no bowel opening. He was sent for another exploratory laparotomy. Intraoperatively, there was a gangrenous small bowel segment measuring 130 cm, with an intact large bowel and previous anastomotic site. Resection of 150 cm of the small bowel was subsequently done.
  2. Fulltext Beyond the joints in rheumatoid arthritis: Effects of adalimumab on hematologic and lipid indices
    Sakthiswary R, Syahrul Sazliyana S, Mohd Shahrir MS, Shahril NS, Hussein H
    EXCLI J, 2012;11:142-9.
    PMID: 27385955
    Tumor necrosis factor alpha (TNFα) is a multifunctional cytokine which plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Apart from its well recognized proinflammatory properties, it is known to interfere with lipid metabolism and erythropoiesis. We evaluated the effects of adalimumab on hematologic, lipid and inflammatory parameters using data from patients on adalimumab 40 mg fortnightly from 2 centers in Malaysia. Mean changes in laboratory values from baseline to Weeks 4, 12 and 24 were compared using paired T test and Wilcoxon signed-rank test. We studied 18 patients with RA who were on adalimumab 40 mg fortnightly. The inflammatory markers i.e. erythrocyte sedimentation rate and C reactive protein showed significant changes as early as at week 4 compared to baseline with p values of 0.003 and 0.005, respectively. From a baseline of high disease activity with a mean Disease Activity Score using 28 joint counts (DAS 28) of 5.3, there was a steady improvement in the disease activity and remission was achieved at week 24 with a DAS 28 of 2.4. The hemoglobin level improved at week 12 (p=0.013) and this was sustained till week 24. As opposed to previous studies, the LDL level significantly decreased at week 12 (p=0.015) and this change persisted till week 24 (p=0.001). The total cholesterol showed a similar pattern as the LDL. The pharmacodynamics of adalimumab therapy in rheumatoid arthritis extend beyond the joints with favorable effects on haemoglobin and lipid profile.

    Study site: Putrajaya Hospital and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  3. Thickened carotid intima media thickness and carotid atherosclerosis among lupus nephritis patients: the role of traditional and lupus-specific factors
    Sazliyana S, Mohd Shahrir MS, Kong NC, Tan HJ, Hamidon BB, Azmi MT
    Int J Rheum Dis, 2011 Aug;14(3):267-75.
    PMID: 21816023 DOI: 10.1111/j.1756-185X.2011.01638.x
    AIM: The objectives of this study were to investigate the frequency of thickened carotid intima media thickness (CIMT) and atherosclerosis among lupus nephritis (LN) patients and to study their associated risk factors.
    METHOD: In this cross-sectional study, carotid ultrasonography was performed on consecutive LN patients to determine CIMT and presence of carotid plaques. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex from the 'Carotid Atherosclerosis Progression Study'. The association between thickened CIMT with traditional cardiovascular risk factors and lupus characteristics were examined. A total of 83 patients with the mean age of 33.6 ± 10 years were recruited.
    RESULTS: Fourteen patients (16.9%) had thickened CIMT and three (3.6%) had carotid plaques. On univariate analysis, traditional risk factors significantly associated with thickened CIMT (P < 0.05) were patient's current age, diabetes mellitus and waist circumference. Meanwhile, a lower serum C4 levels and higher serum C-reactive protein levels were the lupus-specific factors associated with thickened CIMT (P < 0.05, P < 0.05 and P < 0.01, respectively). In logistic regression analysis, the independent predictors of thickened CIMT were age of diagnosis, lower serum C4 levels and waist circumference (P < 0.05).
    CONCLUSION: More lupus specific factors were independently associated with thickened CIMT, suggesting that a multi-targeted approach of treatment addressing both the lupus and traditional cardiovascular risks are very important. Larger prospective studies of these special risk factors are indicated.
  4. Clinical and high resolution computed tomography characteristics of patients with rheumatoid arthritis lung disease
    Mohd Noor N, Mohd Shahrir MS, Shahid MS, Abdul Manap R, Shahizon Azura AM, Azhar Shah S
    Int J Rheum Dis, 2009 Jul;12(2):136-44.
    PMID: 20374331 DOI: 10.1111/j.1756-185X.2009.01376.x
    Introduction: Rheumatoid arthritis (RA) is a systemic disease of unknown cause. A variety of pulmonary disorders have been described in association with RA. Among the most common are interstitial lung disease
    (ILD) and bronchiectasis.
    Objectives: This study aims to determine the characteristics of RA patients with lung disease in relation to clinical characteristics, pulmonary function test (PFT) and high resolution computed tomography (HRCT) thorax.
    Method: This is a 6-months cross-sectional study involving 63 consecutive RA patients in an outpatient rheumatology clinic. Patients had a mean disease duration of 5 years and above. Disease activity and severity
    was assessed by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Articular Damage (RAAD) score. Full pulmonary function test (PFT) and HRCT of thorax were performed.
    Conclusions: The prevalence of RA-ILD is 44% and 67% of patients are asymptomatic. There was significant higher proportion (68%) in patients of Chinese ethnicity who have ILD. Diffusion capacity of carbon monoxide
    was abnormal in all patients and forced expiratory flow (FEF)25–75% was low in 16%. Restrictive pattern was 66.7% by PFT. The most common HRCT findings were reticulation (46%) followed by ground glass opacities
    (38.1%) and bronchiectasis (28.6%). There was no association between ILD and male gender, duration of the disease, smoking, rheumatoid factor, extra-articular manifestations, disease activity or severity.
    Key words: high resolution computed tomography, interstitial lung disease, lung function test, rheumatoid arthritis.
    Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  5. A cross-sectional study of diastolic dysfunction in rheumatoid arthritis and its association with disease activity
    Abdul Muizz AM, Mohd Shahrir MS, Sazliyana S, Oteh M, Shamsul AS, Hussein H
    Int J Rheum Dis, 2011 Feb;14(1):18-30.
    PMID: 21303478 DOI: 10.1111/j.1756-185X.2010.01593.x
    AIMS: The aim of this study was to evaluate the left ventricular (LV) diastolic dysfunction in rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations and to estimate whether there is any correlation between RA disease severity and disability and LV diastolic dysfunction.
    METHODS: The study was a cross-sectional study involving 53 patients (47 female and 6 male) with RA without clinically evident heart disease and 53 healthy subjects (47 female and 6 male) who served as a control group. Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects.
    RESULTS: Of 17 cardiac parameters assessed, only two were abnormal. None of the specific cardiac diastolic dysfunction parameters were significantly different in RA patients compared to the control group. There was no significant correlation between diastolic function values in RA patients and value of Disease Activity Score 28 (DAS-28) and value of Health Assessment Questionnaires Disability Index (HAQDI). Atrial (A) wave velocity was greater in RA patients compared to the control group (0.71 [0.58-0.83] vs. 0.61 [0.51-0.71]; P < 0.04). However, interventricular relaxation time (IVRT) ([73.08 ± 9.92 vs. 70.74 ± 9.02], P = 0.207), lower E/A ratio (1.27 [1.02-1.56] vs. 1.42 [1.20-1.68], P = 0.102), diastolic dysfunction parameters according to Redfield Classification (25 [47.2%] vs. 27 [50.9%] P = 0.56), diastolic dysfunction using E/A (P = 0.321) and tissue doppler imaging (E/E') (P = 0.148) were not different.
    CONCLUSION: Prevalence of diastolic dysfunction in the rheumatoid arthritis group (47.2%) was not different from controls (50.9%). LV diastolic function had no significant correlation with RA disease severity and duration of disease.
  6. Fulltext The association between serum prolactin levels and interleukin-6 and systemic lupus erythematosus activity
    Wan Asyraf WA, Mohd Shahrir MS, Asrul W, Norasyikin AW, Hanita O, Kong WY, et al.
    Reumatismo, 2018 Dec 20;70(4):241-250.
    PMID: 30570242 DOI: 10.4081/reumatismo.2018.1075
    Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.
  7. Diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis
    Syed Mohamed Suhail SM, Nur Atiqah I, Nur Salimi Zakirah ZA, Lailatul Syazwani Z, Batis WW, Md Monoto EM, et al.
    Malays J Pathol, 2019 Dec;41(3):259-265.
    PMID: 31901910
    INTRODUCTION: Rheumatoid arthritis is diagnosed based on the 2010 Rheumatoid Arthritis Classification Criteria whereby rheumatoid factor and anti-citrullinated protein antibody are the serological markers included in these criteria. Anti-RA33 antibody has the potential to provide additional diagnostic value in rheumatoid arthritis. The aim of this study is to determine the diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis.

    MATERIAL AND METHODS: Thirtyfour patients with rheumatoid arthritis and 34 non-rheumatoid arthritis individuals were included in this cross-sectional study. Anti-RA33 antibody and rheumatoid factor were performed on all samples.

    RESULTS: The sensitivity, specificity, positive and negative predictive value for anti-RA33 antibody and rheumatoid factor were 41.1%, 97.1%, 93.3%, 62.3% and 64.7%, 79.4%, 75.9%, 69.2% respectively. The overall sensitivity and specificity if either anti-RA33 antibody or rheumatoid factor are positive were 79.4% and 76.47% respectively.

    CONCLUSION: Anti-RA33 antibody showed good specificity and positive predictive value and could be considered as a potential serological marker for rheumatoid arthritis diagnosis.

  8. HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 194 Southeast Asia Chinese from Peninsular Malaysia
    Too CL, Tan LK, Heselynn H, Nor-Shuhaila S, Eashwary M, Wahinuddin S, et al.
    Hum Immunol, 2019 Nov;80(11):906-907.
    PMID: 31558331 DOI: 10.1016/j.humimm.2019.09.005
    A total of 194 Southeast Asia Chinese from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, the HLA-B, HLA-DRB1 and HLA-DQB1 were in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from HWEP in HLA-A (p 
  9. Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors
    Buji RI, Abdul Murad NA, Chan LF, Maniam T, Mohd Shahrir MS, Rozita M, et al.
    Lupus, 2018 Apr;27(5):744-752.
    PMID: 29161964 DOI: 10.1177/0961203317742711
    Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p 
  10. HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 951 Southeast Asia Malays from Peninsular Malaysia
    Tan LK, Mohd-Farid B, Salsabil S, Heselynn H, Wahinuddin S, Lau IS, et al.
    Hum Immunol, 2016 Oct;77(10):818-819.
    PMID: 27370684 DOI: 10.1016/j.humimm.2016.06.022
    A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), -B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).
  11. Fulltext The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study
    Tan LK, Too CL, Diaz-Gallo LM, Wahinuddin S, Lau IS, Heselynn H, et al.
    Arthritis Res Ther, 2021 01 30;23(1):46.
    PMID: 33514426 DOI: 10.1186/s13075-021-02431-z
    BACKGROUND: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy.

    METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.

    RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.

    CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.

  12. HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 271 Southeast Asia Indians from Peninsular Malaysia
    Nurul-Aain AF, Tan LK, Heselynn H, Nor-Shuhaila S, Eashwary M, Wahinuddin S, et al.
    Hum Immunol, 2020 Jun;81(6):263-264.
    PMID: 32312605 DOI: 10.1016/j.humimm.2020.04.004
    A total of 271 Southeast Asia Indians from Peninsular Malaysia were genotyped for HLA-A, -B, -C, -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, HLA-B and HLA-DQB1 was in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from the HWEP for HLA-A (p 
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