Displaying all 12 publications

Abstract:
Sort:
  1. 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
  2. Fulltext Case review of sarcoidosis resembling Sjogren's syndrome
    Ahmad Y, Shahril NS, Hussein H, Said MS
    J Clin Med Res, 2010 Dec 11;2(6):284-8.
    PMID: 22043264 DOI: 10.4021/jocmr482w
    We would like to report a case of a 29-year-old male patient who presented with multiple lymphadenopathy and vague symptoms of low grade fever, cough, weight loss, rashes, vomiting, dry eyes and dry mouth. Physical examination revealed submandibular lymphadenopathy, vasculitic rashes over both lower limbs, and parotid gland enlargement. Blood investigations showed mild anemia with leukocytosis, predominantly eosinophilia and high erythrocyte sedimentation rate and C-reactive protein. Computed tomography of the neck, thorax and abdomen showed bilateral submandibular, submental adenopathy, mediastinal and para-aortic lymphadenopathy with generalized reticulonodular densities in both lower lobes. There were hepatomegaly and bilateral enlarged kidneys with renal cyst. Histopathological examination from the cervical lymph node later revealed non-caseating granuloma, consistent of sarcoidosis. Patient responded well to prednisolone 50 mg daily with subsequent reduction in the size of cervical lymphadenopathy and parotid swelling.

    KEYWORDS: Lymphadenopathy; Granuloma; Sjogren; Sarcoidosis.
  3. Fulltext IgA rheumatoid factor as a serological predictor of poor response to tumour necrosis factor α inhibitors in rheumatoid arthritis
    Sakthiswary R, Shaharir SS, Mohd Said MS, Asrul AW, Shahril NS
    Int J Rheum Dis, 2014 Nov;17(8):872-7.
    PMID: 25292482 DOI: 10.1111/1756-185X.12443
    AIM: The main objective of this study is to elucidate the role of immunoglobulin A (IgA) rheumatoid factor (RF) in predicting the clinical response to tumour necrosis factor α inhibitors (TNFi) among patients with rheumatoid arthritis (RA).
    METHOD: We recruited all patients with RA who were ever on TNFi for a minimum duration of 3 months at our centre. Based on the European League Against Rheumatism response criteria, subjects were further divided into responders and non-responders. Age-matched RA patients who were on conventional disease-modifying anti-rheumatic drugs and in remission were enrolled as controls. Subjects were tested for quantitative values of IgA, IgM, IgG RF and anti-citrulinated cyclic peptides (CCP). Further, all subjects were assessed for the disease activity score that includes 28 joints (DAS28) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI).
    RESULTS: A total of 31 subjects with RA who had received TNFi and 15 controls were enrolled in this study. There was a trend for the non-responders (n = 10) to have higher levels of all isotypes of RF and anti-CCP. However, only the IgA RF and anti-CCP levels were significantly higher in the non-responder group compared to the responders and controls (P = 0.001, P = 0.034, respectively). On multivariate analysis, only the IgA RF remained significant (OR 0.989; 95% CI 0.980-0.999; P = 0.026).
    CONCLUSION: IgA RF is potentially a novel predictor of response to TNFi in RA patients. Testing for pretreatment IgA RF levels could be a reasonable consideration before commencement of TNFi.
    Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  4. Fulltext Osteoporosis awareness among primary care physicians in Malaysia
    Das Gupta E, Goh EM, Gun SC, Hussein H, Shahril NS, Yeap SS, et al.
    EXCLI J, 2013;12:521-2.
    PMID: 27034635
  5. Knowledge of osteoporosis among primary care doctors in Malaysia. [Abstract]
    Das Gupta E, Goh EML, Gun SC, Hussein H, Shahril NS, Yeap SS
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A53.
    Background: In the ageing population, osteoporosis (OP) is becoming an increasingly common medical condition. Effective interventions are available that should enable clinicians to limit the magnitude of the burden but this will require the proper knowledge of OP and its management. Objective: To explore family physicians' perceptions of OP and to identify their educational needs in this area.
    Method: Self administered questionnaires about OP knowledge and management were distributed to attendees of Rheumatology Workshops for primary care physicians between March and November 2005, in Malaysia.
    Results: A total of 134 primary care physicians participated in this survey comprising 53% private practitioners, 44% government doctors, 2.2% from academic institutions and 0.7% not stated. The majority 73 (54.4%) had practiced for more than 10 years, 29 (21.6%) under 5 years and 32 (23.9%) between 5 and 10 years. 127 (94.4%) of them saw patients with osteoporosis. Those who had qualified for over 10 years were more likely to treat OP (p = 0.012). 82% felt that osteoporosis was under-diagnosed whereas 14.9% thought it was over diagnosed. This was not related to specialty or years qualified. Regarding the reasons for under-diagnosis of osteoporosis, 71% stated that they had no access to DXA screening, 74% had no access to heel ultrasound, 66% felt the disease was asymptomatic, 37% felt that investigations were costly and only 11% perceived the problem as a lack of referral for specialist opinion. Majority of respondents recognized the risk factors for OP such as increasing age (93%), post menopausal state (90%), positive family history (70%) and a previous low trauma fracture (65%). 7% were not sure how to further investigate a case of OP. For all categories of bone density, under 50% would advise changes in life-style measures. For osteopenia, 65.7% recommended calcium, 54.5% activated vitamin D products. For OP, 79.1% would use bisphosphonates, 50% calcium. In established OP, 80.6% would use bisphosphonates, 44% calcium. Usage of HRT and SERMs ranged between 20% and 30% in all categories. 63% were aware of the Malaysian Clinical Practice Guidelines on Osteoporosis. 22% would not refer to a specialist, whereas 50.4% would refer severe cases only. Almost all (98%) requested for further continuing medical education on OP.
    Conclusions: In this study, the majority of primary care physicians had a reasonable working knowledge of the management of OP. However, 71% had no access to DXA. Therefore, awareness needs to be supplemented by adequate facilities to further improve the management of OP in the community.
  6. Adverse pregnancy outcomes among multi-ethnic systemic lupus erythematosus patients in Malaysia
    Shaharir SS, Maulana SA, Shahril NS, Mohd R, Mustafar R, Said MSM, et al.
    Lupus, 2020 Sep;29(10):1305-1313.
    PMID: 32660312 DOI: 10.1177/0961203320938871
    BACKGROUND: Despite the improvement in the live birth rate among patients with systemic lupus erythematosus (SLE), they are still at an increased risk of adverse pregnancy outcomes (APOs).

    OBJECTIVE: To determine the prevalence and factors associated with APOs in the multi-ethnic SLE populations in Malaysia.Methodology: This was a retrospective review of the consecutive SLE patients who attended the outpatient clinic in two major rheumatology centres from January 2016 until December 2019 with complete pre-pregnancy, antenatal and intra-partum records. APOs include pregnancy loss, prematurity, pre-eclampsia, intra-uterine growth restriction (IUGR) and maternal death. Univariate and multivariable logistic regression with generalised estimating equation (GEE) analyses were performed to determine the factors associated with APOs.

    RESULTS: A total of 153 patients with 240 pregnancies were included and the majority of the patients were Malay (69.9%), followed by Chinese (24.2%) and Indian (5.9%). The prevalence of APOs was 61.7% with the commonest complication being prematurity (28.3%), followed by pregnancy loss (24.6%) and pre-eclampsia (21.8%). Logistic regression model-based GEE analysis revealed that the independent predictors of APOs were active haematological system during pregnancy, pre-pregnancy active disease, Indian patients and positive lupus anticoagulant. Hydroxychloroquine use was associated with lower APOs including pre-eclampsia, prematurity and IUGR in the univariate analyses but it was no longer significant in the GEE analysis.

    CONCLUSION: The prevalence of APOs was high particularly among the Indian patients. Positive lupus anticoagulant and pre-pregnancy active disease were the factors strongly associated with APOs in our multi-ethnic cohort. Hydroxychloroquine may protect against APOs but further larger studies are needed to confirm this.

  7. Celastrol attenuates high-fructose diet-induced inflammation and insulin resistance via inhibition of 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues
    Abu Bakar MH, Mohamad Khalid MSF, Nor Shahril NS, Shariff KA, Karunakaran T
    Biofactors, 2022 Jan;48(1):111-134.
    PMID: 34676604 DOI: 10.1002/biof.1793
    High fructose consumption has been linked to low-grade inflammation and insulin resistance that results in increased intracellular 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)-induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co-administrations upon HFrD in rats and evaluate its potential to modulate 11β-HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor-kappa B (NF-κB)-driven inflammation, reduced c-Jun N-terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β-HSD1 towards oxidoreductase activity (IC50 value = 4.3 nM) in comparison to other HSD-related enzymes. Inhibition of 11β-HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD-induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β-HSD1 activity in adipose tissues.
  8. Fulltext Successful febuxostat desensitization in a patient with febuxostat hypersensitivity: A Malaysian experience
    Sulaiman N, Othman AZ, Shahril NS, Abdul Rashid AM, Md Noh MSF
    SAGE Open Med Case Rep, 2017;5:2050313X17749080.
    PMID: 29318019 DOI: 10.1177/2050313X17749080
    Over the years, allopurinol has been widely used as the preferred choice of urate lowering therapy in patients with gout. However, its role in patients with renal impairment is limited; and adverse reactions are well documented. Febuxostat, a newer oral non-purine xanthine oxidase inhibitor has been proven in several trials to be more effective and tolerable compared to allopurinol and may be used in patients with renal impairment. Here, we describe a case of successful febuxostat desensitization in a patient with a history of allopurinol- and febuxostat-induced adverse cutaneous reaction, as well as the protocol utilized.
  9. Fulltext Risk factors for symptomatic Avascular Necrosis (AVN) in a multi-ethnic Systemic Lupus Erythematosus (SLE) cohort
    Shaharir SS, Chua SH, Mohd R, Mustafar R, Noh MM, Shahril NS, et al.
    PLoS One, 2021;16(3):e0248845.
    PMID: 33739994 DOI: 10.1371/journal.pone.0248845
    Avascular necrosis of bone (AVN) is increasingly being recognized as a complication of SLE and causes significant disability due to pain and mobility limitations. We studied the prevalence and factors associated with avascular necrosis (AVN) in a multiethnic SLE cohort. SLE patients who visited the outpatient clinic from October 2017 to April 2019 were considered eligible. Their medical records were reviewed to identify patients who developed symptomatic AVN, as confirmed by either magnetic resonance imaging or plain radiography. Subsequently, their SLE disease characteristics and treatment were compared with the characteristics of patients who did not have AVN. Multivariable logistic regression analyses were performed to determine the independent factors associated with AVN among the multiethnic SLE cohort. A total of 390 patients were recruited, and the majority of them were females (92.6%); the patients were predominantly of Malay ethnicity (59.5%), followed by Chinese (35.9%) and Indian (4.6%). The prevalence of symptomatic AVN was 14.1%, and the mean age of AVN diagnosis was 37.6 ± 14.4 years. Both univariate and multivariable logistic regression analyses revealed that a longer disease duration, high LDL-C (low density lipoprotein cholesterol), positive anti-cardiolipin (aCL) IgG and anti-dsDNA results, a history of an oral prednisolone dose of more than 30 mg daily for at least 4 weeks and osteoporotic fractures were significantly associated with AVN. On the other hand, hydroxychloroquin (HCQ), mycophenolate mofetil (MMF) and bisphosphonate use were associated with a lower risk of AVN. No associations with ethnicity were found. In conclusion, several modifiable risk factors were found to be associated with AVN, and these factors may be used to identify patients who are at high risk of developing such complications. The potential protective effects of HCQ, MMF and bisphosphonates warrant additional studies.
  10. Fulltext Anti-MDA5 dermatomyositis after COVID-19 vaccination: a case-based review
    Gonzalez D, Gupta L, Murthy V, Gonzalez EB, Williamson KA, Makol A, et al.
    Rheumatol Int, 2022 Sep;42(9):1629-1641.
    PMID: 35661906 DOI: 10.1007/s00296-022-05149-6
    Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21 ); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75-85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195-197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646 ). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine.
  11. Fulltext Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors
    Mohd Radzuan SN, Phongphane L, Abu Bakar MH, Che Omar MT, Nor Shahril NS, Supratman U, et al.
    RSC Adv, 2024 Feb 29;14(11):7684-7698.
    PMID: 38444963 DOI: 10.1039/d3ra08642a
    New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
  12. Fulltext Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report
    Ibrahim A, Ghazali WSW, Misyail A, Najwa L, Khan AH, Amir WM, et al.
    BMC Neurol, 2023 Mar 22;23(1):117.
    PMID: 36949469 DOI: 10.1186/s12883-023-03170-1
    BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies.

    CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline.

    CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links