Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.
Osteoarthritis and falls are common conditions affecting older individuals which are associated with disability and escalating health expenditure. It has been widely assumed that osteoarthritis is an established risk factor for falls in older people. The relationship between osteoarthritis and falls has, quite surprisingly, not been adequately elucidated, and published reports have been conflicting. Our review of the existing literature has found limited evidence supporting the current assumption that the presence of osteoarthritis is associated with increased risk of falls with suggestions that osteoarthritis may actually be protective against falls related fractures. In addition, joint arthroplasty appears to increase the risk of falls in individuals with osteoarthritis.
Lupus associated protein loosing enteropathy (LUPLE) is a rare gastrointestinal manifestation of SLE. We presented a case of painless ascites from serve hypoalbuminaemia secondary to LUPLE. The patient responded to a course of intravenous cyclophosphamide. The remission was maintained by azathioprine and low dose prednisolone.
We report a 13-year-old girl diagnosed with systemic lupus erythematosus (SLE) who presented with left-sided chest pain, with ECG changes and elevation troponins that were suggestive of an acute inferior wall myocardial infarction (MI). Her multi-slice computed tomography coronary angiogram and standard angiogram were normal. The cardiac magnetic resonance imaging revealed an area of infarcted myocardium that was in the right coronary artery territory. We believe her MI was most likely secondary to coronary vasospasm. MI is rare and coronary vasospasm is an uncommon cause of MI in children and adolescents with SLE.
Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE.
INTRODUCTION: osteoarthritis (OA) of knee has been reported as a risk factor for falls and reduced balance in the elderly. This systematic review evaluated the effectiveness of physical therapies in improving balance and reducing falls risk among patients with knee OA.
METHODS: a computerised search was performed to identify relevant studies up to November 2013. Two investigators identified eligible studies and extracted data independently. The quality of the included studies was assessed by the PeDro score.
RESULTS: a total of 15 randomised controlled trials involving 1482 patients were identified. The mean PeDro score was 7. The pooled standardised mean difference in balance outcome for strength training = 0.3346 (95% CI: 0.3207-0.60, P = 0.01 < 0.00001, P for heterogeneity = 0.85, I(2) = 0%). Tai Chi = 0.7597 (95% CI: 0.5130-1.2043, P<=0.0014, P for heterogeneity = 0.26, I(2) = 0%) and aerobic exercises = 0.6880 (95% CI: 0.5704-1.302, P < 0.00001, P for heterogeneity = 0.71, I(2) = 0%). While pooled results for falls risk outcomes in, strength training, Tai chi and aerobics also showed a significant reduction in reduced risk of falls significantly with pooled result 0.55 (95% CI: 0.41-0.68, P < 0.00001, P for heterogeneity = 0.39, I(2) = 6%).
CONCLUSION: strength training, Tai Chi and aerobics exercises improved balance and falls risk in older individuals with knee OA, while water-based exercises and light treatment did not significantly improve balance outcomes. Strength training, Tai Chi and aerobics exercises can therefore be recommended as falls prevention strategies for individuals with OA. However, a large randomised controlled study using actual falls outcomes is recommended to determine the appropriate dosage and to measure the potential benefits in falls reduction.
KEYWORDS: Tai Chi; elderly; exercises; falls; older people; osteoarthritis
AIM: To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort.
METHODS: Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated.
RESULTS: There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012).
CONCLUSION: In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc.
KEYWORDS: Malaysia; autoantibodies; clinical profile; systemic sclerosis
Interferon-gamma (IFN-γ) is known to potentiate the progression of inflammatory diseases, such as inflammatory bowel disease and atherosclerosis. IFN-γ has been found to disrupt the barrier integrity of epithelial and endothelial cell both in vivo and in vitro. However, the mechanisms of IFN-γ underlying increased endothelial cell permeability have not been extensively elucidated. We reported that IFN-γ exhibits a biphasic nature in increasing endothelial permeability. The changes observed in the first phase (4-8 h) involve cell retraction and rounding in addition to condensed peripheral F-actin without a significant change in the F-/G-actin ratio. However, cell elongation, stress fiber formation, and an increased F-/G-actin ratio were noticed in the second phase (16-24 h). Consistent with our finding from the permeability assay, IFN-γ induced the formation of intercellular gaps in both phases. A delayed phase of increased permeability was observed at 12 h, which paralleled the onset of cell elongation, stress fiber formation, and increased F-/G-actin ratio. In addition, IFN-γ stimulated p38 mitogen-activated protein (MAP) kinase phosphorylation over a 24 h period. Inhibition of p38 MAP kinase by SB203580 prevented increases in paracellular permeability, actin rearrangement, and increases in the F-/G-actin ratio caused by IFN-γ. Our results suggest that p38 MAP kinase is activated in response to IFN-γ and causes actin rearrangement and altered cell morphology, which in turn mediates endothelial cell hyperpermeability. The F-/G-actin ratio might be involved in the regulation of actin distribution and cell morphology rather than the increased permeability induced by IFN-γ.
Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue.
The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.
Immortalized human endothelial cells are widely used as in vitro models for debilitating conditions such as cancer, cardiovascular and ocular diseases. Human microvascular endothelial cell (HMEC-1) is immortalized via stable transfection with a gene encoding SV40 large antigen whilst telomerase-immortalized human microvascular endothelial (TIME) cells is immortalized by engineering the human telomerase catalytic protein (hTERT) into primary microvascular endothelial cells. Here, we established a three-dimensional (3D) spheroid invasion assay with HMEC-1 and TIME and compared the difference in their ability to invade through the collagen matrix in response to exogenous growth factors, namely vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and 'mild' overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172-0.940), p = 0.042]. Individuals with clinical OA and 'severe' overall symptoms had increased risk of falls compared to those with 'mild' OA [OR: 4.487(1.883-10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation.
Study site: teaching hospital’s geriatrics, primary care and specialty clinics, and the emergency department in Kuala Lumpur, Malaysia
Endothelial cell activation is characterized by increased endothelial permeability and increased expression of cell adhesion molecules (CAMs). This allows monocyte adherence and migration across the endothelium to occur and thereby initiates atherogenesis process. Asiatic acid is a major triterpene isolated from Centella asiatica (L.) Urban and has been shown to possess anti-oxidant, anti-hyperlipidemia and anti-inflammatory activities.
Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.
The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
OBJECTIVES: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients.
METHODS: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated.
RESULTS: Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030).
CONCLUSIONS: The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24-hour pH study should be considered more frequently in the assessment of SSc patients.
OBJECTIVE: To compare the relationship between postural control and knee and hip osteoarthritis in older adults with and without a history of falls.
METHODS: Fallers were those with ≥ 2 falls or 1 injurious fall over 12 months. Non-fallers were volunteers with no falls in the past year. Radiological evidence of osteoarthritis with no reported symptoms was considered "asymptomatic osteoarthritis", while "symptomatic osteoarthritis" was defined as radiographic osteoarthritis with pain or stiffness. Dynamic postural control was quantified with the limits of stability test measured on a balance platform (Neurocom® Balancemaster, California, USA). Parameters assessed were end-point excursion, maximal excursion, and directional control.
RESULTS: A total of 102 older individuals, mean age 73 years (standard deviation 5.7) years were included. The association between falls and poor performance in maximal excursion and directional control was confounded by age and comorbidities. In the same linear equation model with falls, symptomatic osteoarthritis remained independently associated with poor end-point excursion (β-coefficient (95% confidence interval) -6.80 (-12.14 to -1.42)).
CONCLUSION: Poor performance in dynamic postural control (maximal excursion and directional control) among fallers was not accounted for by hip/knee osteoarthritis, but was confounded by old age and comorbidities. Loss of postural control due to hip/knee osteoarthritis is not a risk factor for falls among community-dwelling older adults.
Study site: Departments of Emergency Medicine, Primary Care and Geriatric Medicine, in a teaching hospital in Kuala Lumpur, Malaysia
The purpose of this study was to investigate the role of fear of falling (FoF) and psychological symptoms in explaining the relationship between osteoarthritis (OA) symptom severity and falls. Individuals aged ≥65 years with ≥2 falls or ≥1 injurious fall over the past 12 months were included in the falls group, while volunteers aged ≥65 years with no history of falls over 12 months were recruited as controls. The presence of lower extremity OA was determined radiologically and clinically. Severity of symptoms was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. FoF and psychological status were measured with the shortened version of the Falls Efficacy Scale-International and the 21-item Depression, Anxiety and Stress Scale (DASS-21), respectively. Of 389 (229 fallers, 160 non-fallers) potential participants, mean (SD) age: 73.74 (6.60) years, 141 had clinical OA and 171 had radiological OA. Fallers with both radiological OA and clinical OA had significantly higher FoF and DASS-21 scores than non-fallers. FoF was significantly positively correlated with symptom severity in fallers and non-fallers with radiological and clinical OA. Depression, anxiety, and stress scores were only significantly correlated with symptom severity among fallers but not non-fallers in both clinical and radiological OA. The relationship between mild symptoms and reduced risk of falls compared to no symptoms in those with radiological OA was attenuated by increased anxiety. The increased falls risk associated with severe symptoms compared to mild symptoms in clinical OA was attenuated by FoF. FoF may, therefore, be a potentially modifiable risk factor for OA-associated falls which could be considered in future intervention studies.
BACKGROUND: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.
OBJECTIVE: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems.
DESIGN: Randomized controlled trial.
SETTING: University of Malaya Medical Centre.
PARTICIPANTS: Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds.
MAIN OUTCOME MEASURE: Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated.
METHODS: Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months.
RESULTS: Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found.
CONCLUSION: Home-based balance and strength exercises benefited older fallers with OA and gait and balance disorders by improving postural control, with no observable trend in reduction of fall recurrence. Our findings will now inform a future, adequately powered, randomized controlled study using fall events as definitive outcomes.
AIM: To determine the incidence and direct costs of NSAID-induced upper GI adverse events in Malaysian rheumatology patients.
METHODS: A retrospective, multi-centre, cohort study of rheumatology patients on long-term NSAIDs was conducted. Clinical data of patients treated between 2010 and 2013 were collected for a 24-month follow-up period. The costs of managing upper GI adverse events were based on patient level resource use data.
RESULTS: Six hundred and thirty-four patients met the inclusion criteria: mean age 53.4 years, 89.9% female, diagnosis of rheumatoid arthritis (RA; 59.3%), osteoarthritis (OA; 10.3%) and both RA and OA (30.3%). Three hundred and seventy-one (58.5%) patients were prescribed non-selective NSAIDs and 263 (41.5%) had cyclo-oxygenase-2 inhibitors. Eighty-four upper GI adverse events occurred, translating into a risk of 13.2% and an incidence rate of 66.2 per 1000 person-years. GI adverse events comprised: dyspepsia n = 78 (12.3%), peptic ulcer disease (PUD) n = 5 (0.79%) and upper GI bleeding (UGIB) n = 1 (0.16%). The total direct healthcare cost of managing adverse events was Malaysian Ringgit (MR) 37 352 (US dollars [USD] 11 419) with a mean cost of MR 446.81 ± 534.56 (USD 136.60 ± 163.42) per patient, consisting mainly of GI pharmacotherapy (33.8%), oesophagoduodenoscopies (23.1%) and outpatient clinic visits (18.2%). Mean cost per patient by GI events were: dyspepsia, MR 408.98 ± 513.29 (USD125.03 ± 156.92); PUD, MR 805.93 ± 578.80 (USD 246.39 ± 176.95); UGIB, MR 1601.94 (USD 489.74, n = 1).
CONCLUSION: The economic burden of GI adverse events due to long-term NSAIDs use in Malaysian patients with chronic rheumatic diseases is modest.
Study site: Rheumatology clinics, Hospital Putrajaya, Hospital Selayang, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia