Displaying publications 1 - 20 of 36 in total

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  1. Fulltext Novel therapeutic targets in rheumatoid arthritis
    Sakthiswary R
    Medicine & Health, 2018;13(1):12-19.
    MyJurnal
    Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune disease worldwide. Although incurable, there are available therapies to effectively control the disease activity and minimize the joint damage. Numerous cytokines, enzymes and other forms of proteins have been implicated in the disease process of RA. In general, pharmacological therapies in RA target cytokine pathways. Despite a wide variety of disease modifying antirheumatic drugs (DMARD), a significant proportion of patients remain refractory to the available therapies. Hence, the search for newer drugs with different modes of actions is an ongoing process. The present review aimed to explore novel therapeutic targets in RA based on data from the literature. Inhibitors of spleen tyrosine kinase, choline kinase, galectin 3 and hypoxia-inducible factor may have a promising role in the

  2. Methotrexate in systemic lupus erythematosus: a systematic review of its efficacy
    Sakthiswary R, Suresh E
    Lupus, 2014 Mar;23(3):225-35.
    PMID: 24399812 DOI: 10.1177/0961203313519159
    OBJECTIVE: The objective of this review is to evaluate the evidence for efficacy of methotrexate (MTX) in systemic lupus erythematosus (SLE).
    METHODS: A comprehensive, computerized search was performed in MEDLINE (PubMed), EMBASE and the Cochrane Controlled Trials registry to screen for studies that examined the efficacy of MTX in adult SLE patients. The Jadad scoring system was used to assess study quality, and data were pooled using the random effects model.
    RESULTS: Of the 53 articles that were identified, 44 were excluded. Nine studies (including three randomized controlled and six observational) were eligible for inclusion. All of the included studies predominantly involved patients with arthritis or mucocutaneous features. There was significant reduction of the SLE Disease Activity Index (SLEDAI) among MTX-treated patients when compared with controls (p = 0.001, odds ratio (OR) 0.444, 95% confidence interval (CI) 0.279 to 0.707). There was also significant reduction in the average dose of corticosteroids among MTX-treated patients when compared with controls (p = 0.001, OR 0.335, 95% CI 0.202 to 0.558). The effect of MTX on laboratory and serological markers, including erythrocyte sedimentation rate, anti-dsDNA and complement levels (C3 and C4), could not be determined because of the limited numbers of controlled trials.
    CONCLUSION: The use of MTX is associated with significant reductions in SLEDAI and the average dose of corticosteroids in adult patients with SLE.
    KEYWORDS: SLE; Systemic lupus erythematosus; efficacy; lupus; methotrexate
  3. Fulltext Correlation of rheumatoid factor serotypes and computed tomography findings in rheumatoid arthritis related interstitial lung disease
    Sakthiswary R., Radhika S., Syahrul Sazliyana, S., Abdul Wahab, A.
    Medicine & Health, 2019;14(2):203-211.
    MyJurnal
    The most common extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). RA related ILD (RA-ILD) is associated with significant morbidity and mortality. The main objective of this study was to determine the correlation between the rheumatoid factor (RF) serotypes and the severity of RA-ILD based on computed tomography (CT) findings. We recruited a total of 100 RA patients who were tested for IgA RF, IgG RF and IgM RF and had high resolution CT chest performed. Seventy-two patients had ILD changes on HRCT of the chest and were included in this study. We found that the the CT scores for ground glass showed significant positive correlation with disease duration and IgA RF levels whereas the fibrosis scores had significant relationship with multiple clinical covariates i.e age, disease duration, IgA RF levels, IgG RF levels and anti-CCP levels. On multivariate analysis, only IgA levels remained significantly (p
  4. Fulltext Eosinophilic Gastroenteritis as the initial manifestation of Hypereosinophilic Syndrome
    Narisa, S.S., Shanti, P., Jeevinesh, N.A., Sakthiswary, R.
    Medicine & Health, 2013;8(2):0-0.
    MyJurnal
    Eosinophilic gastroenteritis, an inflammatory disease of unknown etiology, commonly involves the stomach and small intestine with eosinophilic infiltration. Here, we report an unusual case of eosinophilic gastroenteritis involving the entire digestive tract as a manifestation of hypereosinophilic syndrome (HES). A 22-year-old woman presented to us with diarrhoea, pleural effusion, ascites and marked peripheral oeosinophilia. Stool specimens were negative for parasites, ova, bacteria, and fungi. Endoscopic studies showed pangastritis and duodenitis. Biopsy specimens of the oesophagus, stomach, duodenum, ileum, and colon demonstrated oeosinophilic infiltration. A diagnosis of hypereosinophilic syndrome with eosinophilic gastroenteritis involving the entire digestive tract was made. Hence, she was treated with prednisolone. Symptoms and peripheral oeosinophilia rapidly resolved with treatment, and radiological investigations revealed resolution of effusion. This case illustrates the wide spectrum of clinical manifestation of the disease, whereby it involves the entire digestive tract and it also emphasizes the diagnostic yields of endoscopic biopsies.
  5. Myocardial infarction false alarm: initial electrocardiogram and cardiac enzymes
    Gupta ED, Sakthiswary R
    Asian Cardiovasc Thorac Ann, 2014 May;22(4):397-401.
    PMID: 24771726 DOI: 10.1177/0218492313484917
    The objectives of this study were to determine the incidence of a myocardial infarction "false alarm" and evaluate the efficacy of the initial electrocardiogram and cardiac enzymes in diagnosing myocardial infarction in Malaysia.
  6. Bone metabolism and histomorphometric changes in murine models treated with sclerostin antibody: a systematic review
    Das S, Sakthiswary R
    Curr Drug Targets, 2013 Dec;14(14):1667-74.
    PMID: 24354585
    Preventing osteoporotic fractures in millions of individuals may significantly reduce the associated morbidity and health-care expenditures incurred. As such, the search for newer anti-osteoporotic agents has been ongoing for years. Genetic studies have proven that the secreted protein sclerostin is one of the main culprits, which negatively regulates the bone formation. Recently, sclerostin-neutralizing monoclonal antibodies (Scl-Ab) in rodent studies have shown positive effects on bone homeostasis. An extensive search of the literature was performed in the BIOSIS, Cinahl, EMBASE, Pub- Med, Web of Science and Cochrane Library databases to evaluate the published murine studies on the effects of Scl-Ab on the bone metabolism and histomorphometric parameters. Our systematic review depicts a significant association between Scl-Ab administration and improvement in bone formation, bone density, bone volume and trabecular thickness.
  7. The effects of TNF α antagonist therapy on bone metabolism in rheumatoid arthritis: a systematic review
    Sakthiswary R, Das S
    Curr Drug Targets, 2013 Dec;14(13):1552-7.
    PMID: 23848441
    Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.
  8. Fulltext Stem cell therapy in neurodegenerative diseases: From principles to practice
    Sakthiswary R, Raymond AA
    Neural Regen Res, 2012 Aug 15;7(23):1822-31.
    PMID: 25624807 DOI: 10.3969/j.issn.1673-5374.2012.23.009
    The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society. The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years. Beyond substitution of the lost neurons, stem cells act as immunomodulators and neuroprotectors. A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context. In this review, we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field, particularly between 2010 and 2012. Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.
  9. Fulltext Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis
    Sakthiswary R, D'Cruz D
    Medicine (Baltimore), 2014 Oct;93(16):e86.
    PMID: 25310743 DOI: 10.1097/MD.0000000000000086
    Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.
  10. Fulltext Has the median nerve involvement in rheumatoid arthritis been overemphasized?
    Sakthiswary R, Singh R
    Rev Bras Reumatol Engl Ed, 2016 09 30;57(2):122-128.
    PMID: 28343616 DOI: 10.1016/j.rbre.2016.09.001
    Rheumatoid arthritis (RA) is a well and widely recognized cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasized throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA.
  11. Fulltext Predictors of diastolic dysfunction in rheumatoid arthritis
    Sakthiswary R, Das S
    Saudi Med J, 2015 May;36(5):525-9.
    PMID: 25935171 DOI: 10.15537/smj.2015.5.10751
    The main objective was to determine the predictors of diastolic dysfunction in rheumatoid arthritis (RA). Articles pertaining to diastolic dysfunction in RA were retrieved from Scopus, EBSCO, PubMed, Web of Science, and Cochrane Library databases. Keywords such as: diastolic, cardiac, left ventricular function, heart failure, rheumatoid arthritis, and cardiac failure were used. Studies, which examined factors, or predictors of diastolic dysfunction in RA, and those with echocardiographic evaluation of diastolic dysfunction, were included. A total of 8 studies met the eligibility criteria. Most studies (6 out of 7 studies) demonstrated a significant inverse relationship between the E (early)/A (late) ratio and disease duration. The pooled analysis using the random effects model revealed a significant but weak inverse relationship between the ratio of the E to A ventricular filling velocities (E/A) ratio and the disease duration (p less than 0.05, r=-0.385). There was a significant relationship between E/A ratio and disease duration in RA.

    Study site: Hospital Kuala Lumpur (HKL)
  12. Fulltext The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review
    Sakthiswary R, Raymond AA
    PLoS One, 2013;8(1):e55275.
    PMID: 23383135 DOI: 10.1371/journal.pone.0055275
    BACKGROUND: Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.

    METHODS: THE FOLLOWING DATABASES WERE SEARCHED: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms "lupus", "systemic lupus erythematosus", "SLE and "vitamin D". We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.

    RESULTS: A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.

    CONCLUSION: There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.

  13. Successful treatment of acute kidney injury secondary to haeme nephropathy in paroxysmal nocturnal haemoglobinuria with alkaline diuresis
    Sakthiswary R, Das S, Fadilah SA
    EXCLI J, 2012;11:198-203.
    PMID: 27298607
    Paroxysmal nocturnal haemoglobinuria (PNH) also known as 'Marchiafava Micheli syndrome' is a rare condition which can lead to both acute and chronic forms of renal failure through renal tubular haemosiderin deposition. A 45-year-old lady with underlying PNH, presented with complaints of fever, productive cough followed by dark coloured urine. Investigations revealed pancytopenia with a markedly raised creatinine from her baseline (from 65 mmol/L to 385 mmol/L) consistent with acute kidney injury (AKI). Renal biopsy confirmed the diagnosis of haeme nephropathy. The renal impairment improved rapidly and normalised over a period of 5 days with alkaline diuresis (AD). The patient did not require haemodialysis unlike most other reported cases of AKI secondary to haeme nephropathy in PNH. This is the second reported case of AKI in PNH which was successfully treated with AD alone emphasizing the role of AD as a promising therapeutic strategy in this condition.
  14. Fulltext Predictors of frequent oral analgesic use in rheumatoid arthritis
    Das Gupta E, Tee HS, Sakthiswary R
    Pak J Med Sci, 2014 Sep;30(5):976-81.
    PMID: 25225510 DOI: 10.12669/pjms.305.5112
    Objective: The main objective of this study was to determine the predictors of frequent oral analgesic use among Rheumatoid Arthritis (RA) patients who were prescribed with the above medication on an ‘as needed’ basis.
    Methods: Patients with RA were recruited consecutively from the Rheumatology outpatient clinics in this cross-sectional study. The sociodemographic data, frequency of oral analgesic intake, Patient Global Assessment (PGA) scores and HAQ (Health Assessment Questionnaire) scores were determined by interviewing the subjects. Subjects were divided into 2 groups; frequent users (3 days and above in a week) and less frequent users (less than 3 days in a week).
    Results: In a total of 112 subjects, 39 (34.8%) were frequent analgesic users. Both the HAQ and PGA scores were significantly higher among the frequent users (p < 0.05). Using multivariate analysis, the HAQ scores (p=0.015, odds ratio 3.161 [95% confidence interval of 1.246-8.015]) and PGA scores (p=0.039 odds ratio 1.291 [95% confidence interval of 1.012-1.646]) were found to be independent predictors of frequent analgesic use.
    Conclusions: Our study confirms that the frequency of analgesic intake in Rheumatoid Arthritis has a significant relationship with patient-reported functional capacity and well being.
    KEY WORDS: Analgesic, Rheumatoid arthritis.

    Study site: Rheumatology clinic, Hospital Tunku Jaafar, Seremban, Negeri Sembilan, Malaysia
  15. Spot urine potassium as a potential screening test for aldosterone breakthrough
    Sakthiswary R, Wong M, Isa ZM, Nor Azmi K
    Clin Ter, 2012;163(3):195-8.
    PMID: 22964690
    Treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may suppress aldosterone production only in the initial phase of treatment and subsequently lead to a rising level of aldosterone to baseline or higher. This phenomenon is described as aldosterone breakthrough. Apart from serial plasma aldosterone levels, there are no other test to identify this condition. The purpose of this study was to evaluate the role of spot urine potassium as a potential screening test for aldosterone breakthrough.
  16. Fulltext Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis
    Burska AN, Sakthiswary R, Sattar N
    PLoS One, 2015;10(6):e0128889.
    PMID: 26110878 DOI: 10.1371/journal.pone.0128889
    OBJECTIVE: Beyond the joints, TNFi (tumour necrosis factor inhibitor) therapy may confer systemic benefits in rheumatoid arthritis (RA). Several studies have investigated the role of TNFi on insulin resistance/sensitivity (IR/IS). This question is of general interest given the emerging evidence linking inflammation and insulin resistance. The main aim of this review was to summarise the published data and to determine the effects of TNFi on IR/IS.
    METHODS: We searched the PubMed and ISI Web of Knowledge databases for studies which examined the effects of TNFi on IR/IS. The studies were assessed independently by two reviewers according to a pre-specified protocol. The data on Homeostatic Model Assessment for Insulin resistance (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were pooled and reported as standard difference in means (SDM) with 95% confidence interval (CI) using a random-effects model.
    RESULTS: A total of eight studies with 260 subjects met the selection criteria. The duration of the studies was from 8 weeks to 12 months. There was statistically significant reduction in HOMA index in six out of eight studies and four reported significant increment in QUICKI. The pooled analysis revealed significant reduction in HOMA [SDM-0.148, 95%CI[-0.278 to -0.017], p=0.026] and increment in QUICKI [SDM 0.312, 95%CI[0.019 to 0.606], p=0.037] with TNFi.
    CONCLUSION: There is emerging evidence to support that TNFi therapy improves IS and reduces IR in RA. Further, well conducted trials are needed to determine if such effects translate to lower incidence of diabetes in RA or other autoimmune conditions on biologic therapy.
  17. Antinuclear antibodies predict a higher number of pregnancy loss in unexplained recurrent pregnancy loss
    Sakthiswary R, Rajalingam S, Norazman MR, Hussein H
    Clin Ter, 2015;166(2):e98-101.
    PMID: 25945451 DOI: 10.7417/CT.2015.1827
    OBJECTIVE: The etiology of recurrent pregnancy loss (RPL) is unknown in a significant proportion of patients. Autoimmune processes have been implicated in the pathogenesis. The role of antinuclear antibody (ANA) in this context is largely undetermined. In an attempt to address the lack of evidence in this area, we explored the clinical significance of antinuclear antibody (ANA) in unexplained RPL.
    MATERIALS AND METHODS: We studied 68 patients with RPL and 60 healthy controls from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1: 80 and above was considered positive. We compared the pregnancy outcome between the ANA positive and ANA negative RPL cases.
    RESULTS: The incidence of ANA positivity among the cases (35.3%) was significantly higher than the controls (13.3%) (p=0.005). ANA positive cases showed significantly higher number of RPL (p=0.006) and lower number of successful pregnancies (p=0.013) compared to the ANA negative cases . The ANA titre had a significant association with the number of RPL (p<0.05, r=0.724) but not with the number of successful pregnancies (p=0.054).
    CONCLUSIONS: ANA positivity predicts a less favorable pregnancy outcome in RPL. Our findings suggest that the ANA titre is a useful positive predictor of the number of RPL. Hence, ANA test is a potential prognostic tool for this condition which merits further research.
  18. Fulltext Anti-citrullinated cyclic peptide antibody and functional disability are associated with poor sleep quality in rheumatoid arthritis
    Rajalingam S, Sakthiswary R, Hussein H
    Arch Rheumatol, 2017 Mar;32(1):15-20.
    PMID: 30375543 DOI: 10.5606/ArchRheumatol.2017.5960
    Objectives: This study aims to determine the predictors of poor sleep quality in rheumatoid arthritis (RA).

    Patients and methods: This was a monocentric, cross sectional, case-control study which was conducted at the Putrajaya Hospital, Malaysia. We recruited 46 patients with RA (3 males; 43 females; mean age 48.15±14.96) and 46 age and sex-matched healthy controls (3 males; 43 females; mean age 47.11±12.22). RA patients were assessed for their disease activity based on disease activity score in 28 joints, disease damage based on radiographic erosions, and functional status based on Health Assessment Questionnaire Disability Index. The Pittsburgh Sleep Quality Index (PSQI) scores were determined by interviewing all the subjects. Subjects with RA were further subdivided based on their PSQI scores as "good sleepers" with PSQI scores of <5 and "poor sleepers" with PSQI scores of ≥5.

    Results: The percentage of poor sleepers was significantly higher among RA patients (47.83% versus 9.57%). Median scores of 5 out of 7 components of the PSQI were higher among RA patients compared to controls. Among poor sleepers with RA, a significantly higher proportion tested positive for anti-citrullinated cyclic peptide autoantibodies (p=0.037). Besides, poor sleepers had significantly higher median Health Assessment Questionnaire Disability Index (p=0.017) than good sleepers. However, both Health Assessment Questionnaire Disability Index (p=0.968) and anti-citrullinated cyclic peptide (p=0.431) were insignificant when entered in the equation of a logistic regression model.

    Conclusion: The findings of this study demonstrate a link between functional disability, anti-citrullinated cyclic peptide antibodies, and sleep quality in RA.
  19. Left atrial volume index is an independent predictor of major adverse cardiovascular events in acute coronary syndrome
    Gunasekaran R, Maskon O, Hassan HH, Safian N, Sakthiswary R
    Can J Cardiol, 2012 Sep-Oct;28(5):561-6.
    PMID: 22560463 DOI: 10.1016/j.cjca.2012.02.015
    Left atrial volume index (LAVI) is well proven to be a reliable method of determining left atrial size, which has prognostic implications in cardiovascular diseases. Studies demonstrate that increased LAVI is a predictor of mortality in myocardial infarction, but its association with other major adverse cardiovascular events (MACEs) among patients post acute coronary syndrome (ACS) has not been adequately evaluated.
  20. Fulltext Severe psoriatic acroosteolysis in the absence of psoriatic arthropathy
    Sakthiswary R, Naicker AS, Htwe O, Shahrir MS, Sazliyana SS
    BMJ Case Rep, 2011;2011.
    PMID: 22669957 DOI: 10.1136/bcr.09.2011.4794
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