One hundred and thirty-two newly diagnosed Asian diabetic patients (39 Malay, 30 Chinese and 63 Indians) have been studied in Kuala Lumpur. The highest proportion of diabetic patients were Indian and the lowest were Chinese. Vascular complications were equally common in Asian diabetic patients as in Europeans; coronary heart disease was relatively more common in Indians and cerebral vascular disease in Chinese. Twenty percent of all Asian diabetic patients requiring admission to hospital also had coronary heart disease, 9% had cerebral vascular disease and 8% had gangrene or ulceration of the feet. In Kuala Lumpur, diabetes is a very important risk factor for coronary heart disease: 17% of all patients admitted to the General Hospital with coronary heart disease were already diabetic.
Kidney stone samples of the types calcium oxalate, uric acid, and xanthine were analyzed for their elemental contents by neutron activation analysis to study both the elemental correlation and influence of element on stone precipitation processes. Elements, such as Al, Au, Br, Ca, Cl, Co, Cr, Fe, Hg, I, K, Mg, Na, Sb, Se, Sr, and Zn, were determined quantitatively. Calcium oxalate stones contained higher concentration of all the elements analyzed compared to uric acid or xanthine stones. The concentrations of Cl, Fe, K, Na, Sr, and Zn were relatively higher than Au, Co, Cr, and Sb. A positive correlation exists between Ca and Zn, whereas a negative correlation exists between Sr and Ca. Zinc may play an important role in the formation of calcium oxalate stone.
Systemic lupus erythematosus (SLE) and gout have been associated infrequently. We describe 3 young adults with SLE who developed tophaceous gout relatively early in the course of their disease. All were underexcretors of uric acid but were studied after the development of renal disease; 2 were treated with diuretics. In 2 cases, gout became obvious while lupus was quiescent.
Uric acid produced by xanthine oxidase (also a source of superoxide radicals) has been known to increase in hypertensive patients. In this study we evaluated the possible involvement of uric acid and xanthine oxidase in the pathogenesis of hypertension by examining their association with mean arterial pressure (MAP) and factors related to blood pressure. These factors include age, quetelet index (weight/height2), cholesterol, creatinine, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K) and urea. Fifty Two (male-19, female-33) normal healthy individuals were studied. Correlation studies of demographic variables showed that age was positively correlated with MAP [r = 0.309, p = 0.026] and cholesterol [r = 0.503, p = 0.000] while quetelet index was positively correlated with age [r = 422, p = 0.000] MAP [r = 0.331, p = 0.016] and xanthine oxidase [r = 0.331, p = 0.016]. MAP was positively correlated with uric acid [r = 0.511, p = 0.000], cholesterol [r = 0.492, p = 0.000] and xanthine oxidase enzyme activity [r = 0.388, p = 0.004] and negatively correlated with plasma calcium [r = 0.603, p = 0.000]. Correlation studies of measured parameters with uric acid and xanthine oxidase showed that uric acid was positively correlated with creatinine [r = 0.627, p = 0.000], plasma magnesium [r 0.442, p = 0.001] and negatively correlated with plasma calcium [r = 0.546, p = 0.000] while xanthine oxidase was negatively correlated with plasma calcium [r = -0.404, p = 0.003] and plasma sodium [r = -0.288, p = 0.038]. Stepwise multiple regression with MAP as dependent variable showed that 65% of total variability of blood pressure can be accounted for by plasma calcium, cholesterol, creatinine, plasma K, plasma Na, uric acid and xanthine oxidase in order of increasing R2 [xanthine oxidase: T-value = 3.26, R2 = 0.653]. It can be concluded that in normotensive subjects, uric acid and xanthine oxidase have significant association with blood pressure and thus are one of the many factors which are involved in the cause or effect of hypertension.
OBJECTIVE: We describe a 10 year observation of the effect of control of hyperuricemia compared with self-medication alone in patients with chronic gout.
METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with chronic gout without tophi or urolithiasis (Group 1) and 71 with those complications (Group 2). Attacks of acute gouty arthritis were treated with nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute arthritis had settled, urate-lowering drugs were instituted in both groups combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years. Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the dropouts were traced and evaluated for comparison with baseline and those who remained in the study. In Group 2 the urate-lowering drugs were continued.
RESULTS: Control of gout and hyperuricemia was achieved in all patients who remained under control: 91.6% of the 299 patients for at least 2 years (short-term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6% (longterm). In Group 1 (chronic gout without complication) only 36.8% had no attacks during 8 years, after they had tapered urate-lowering drug after the first 2 years of the study. In the 61 dropouts the intermittent symptomatic treatment and/or self-medication without longterm control of hyperuricemia resulted after 1 decade in chronic gout with more complications and associated conditions leading to increased morbidity, disability, and comorbidity, and 3 early mortalities.
CONCLUSION: By controlling hyperuricemia, improvement of the prognosis of chronic gout, comorbidity, and early death was achieved compared with self-medication alone. Self-medication in a developing country if continued unchecked may become a public health problem in a population with a high prevalence rate of gout.
The methanol extract from the leaves of Phyllanthus niruri L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats. Fractionation of the extract by resin chromatography led to the isolation of a less polar fraction which exhibited the highest reduction of plasma uric acid. Further antihyperuricemic-guided purification of the fraction afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin (3), of which 1 significantly reversed the plasma uric acid level of hyperuricemic animals to its normal level in a dose-dependent manner, comparable to that of allopurinol, benzbromarone and probenecid which are used clinically for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are potential antihyperuricemic agents worthy of further investigation.
Introduction: Gout is a clinical syndrome resulting from the deposition of monosodium urate monohydrate crystals. Recent studies have shown gout to be a significant metabolic disorder. However, there has been insufficient information on the clinical spectrum in the Malaysian population.
Objective: This study is conducted to review the clinical characteristics of patients with gout.
Study methods: In this cross-sectional study 52 patients with gout were recruited. The records of 13 patients from National University of Malaysia Hospital and 39 patients from Putrajaya Hospital, attending the rheumatology clinic between October and December 2005 were reviewed. Results: Gout was found predominantly among ethnic Malays 83%, and Chinese 17% in these centers. The male to female ratio was 12 :1. The peak age of onset of the disease was less than 40 years in 46% of the subjects. Primary gout in females was seen after menopause. 37% cases had a definitive hereditary incidence. At the first presentation 83% had acute monoarthritis and 17% acute polyarticular arthritis. Podagra was seen in 62%. Peripheral joints involvement was seen in 81% patients. Tophaceous gout was seen in 42%. In 85% cases the disease had a chronic polyarticular course, whereas in 15% the disease remained only at a single joint. In 10% cases, there was associated sero-negative arthritis. Associated disorders included hypertension (65%), diabetes mellitus (33%), dyslipidemia (56%), ischemic heart disease (23%), urate nephropathy (39%), uric acid nephrolithiasis (2%). In 88% of cases, there was associated hyperuricaemia. Most of the patients were overweight with body mass index 25-29 (39%) and obese with body mass index 30-70 (36%). Conclusions: Gout is not an unusual disorder in our centre. The age of onset of gout occurred much earlier with forty-six per cent of patients having their first attack of gout before the age of 40. Primary gout in females was seen after menopause. Majority of patients first presented with acute monoarthritis, of which sixty-two per cent presented with podagra. The incidence of tophi was high. Patients with gout should be screened for other associated disorders like diabetes mellitus, hypertension, dyslipidemia and obesity.
Diabetes prevalence is increasing rapidly in Asian populations but the influence of a family history of diabetes on cardiovascular risk is unknown. To assess this relationship, 120 urban-dwelling Malays were recruited to a cross-sectional case-control study. Sixty were pre-pubertal children, 30 of diabetic parentage (Group 1) and 30 with no diabetes family history (Group 2). Group 1 and 2 subjects were the offspring of adults with (Group 3) or without (Group 4) type 2 diabetes. Subjects were assessed for clinical and biochemical variables defining cardiovascular risk. Principal component analysis assessed clustering of variables in the children. Group 1 subjects had a higher mean waist:hip ratio, diastolic blood pressure and HbA(1c) than those in Group 2, and a lower HDL:total cholesterol ratio (P<0.03). Although there were no correlations between Group 1 and 3 subjects for cardiovascular risk variables, significant associations were found in Groups 2 and 4, especially HbA(1c) and insulin sensitivity (P< or =0.004). Of five separate clusters of variables (factors) identified amongst the children, the strongest comprised diabetic parentage, HbA(1c), insulin sensitivity and blood pressure. Features of the metabolic syndrome are becoming evident in the young non-obese children of diabetic Malays, suggesting that lifestyle factors merit particular attention in this group.
AIM OF THE STUDY: Orthosiphon stamineus (Labiatae) is a traditional folk medicine widely used in Southeast Asia for the treatment of several kidney disorders, gout and as a diuretic. This study was conducted to examine the diuretic and hypouricemic effects of Orthosiphon stamineus leaf extracts.
MATERIALS AND METHODS: The diuretic effect of different methanol extracts was examined by treating different groups of Sprague-Dawley rats with single (2g/kg) oral doses of methanol and methanol:water (1:1) extracts. Hydrochlorothiazide (10mg/kg) was used as positive control in acute study. Methanol and methanol water (1:1) extracts at 0.5 g/kg were administered for a period of 7 consecutive days. Cumulative urine volume and electrolytes (Na+ and K+) concentrations at different time intervals were measured. On the other hand, hypouricemic activity of methanol:water extract (1:1) was experimented using different oral single doses (0.25, 0.5, 1 and 2g/kg). Allopurinol was used as positive control. Uric acid concentration in serum was analyzed by using RP-HPLC at 280 nm.
RESULTS: Sodium and potassium excretion increased significantly (p<0.05 and <0.01) in the first 8h of treatment with a single dose (2g/kg) of the extracts in a pattern comparable to that of the known diuretic hydrochlorothiazide. Meanwhile, repeated administration of 0.5 g/kg methanol:water (1:1) extract showed a significant increase in urine volume (from day 3 to day 7) (p<0.01) and electrolytes excretion (Na+ and K+) from day 2 to day 7 (p<0.05 and <0.01). On the other hand, 0.5, 1 and 2g/kg of methanol:water (1:1) extract and the standard allopurinol reduced the serum urate level in hyperuricemic rats at hour 6.
CONCLUSION: These results provided an evidence of the high tendency of methanol:water (1:1) extract of Orthosiphon stamineus towards diuretic and hypouricemic effects in rats.
Objective: Primary care management of knee osteoarthritis (OA) has received little attention in the scientific literature and the main reason for this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting.
Methods: A cross-sectional survey of 200 randomly selected general practitioners (GPs) in the peninsular states of Malaysia was undertaken using a questionnaire. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment. They were also asked about their usage of conventional and complementary medication.
Results: One hundred and eighty (90%) GPs responded to the questionnaires sent: 77% were in solo practice and 33% in group practice. Most of the GPs surveyed (60%) had been in practice for more than 10 years, 30% for 5-10 years and 10% were in practice for less than 5 years. Of GPs surveyed, 55% saw an average of more than 20 patients per week, 35% about 10-20 patients and 10% less than 10 patients per week. Of GPs surveyed, 65% would arrange an X-ray, 55% would arrange a blood test, mostly serum uric acid, rheumatoid factor and erythrocyte sedimentation rate. Pharmacological management consists of first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (61%), analgesics (35%) or a combination of the two (4%). Non-pharmacological management consisted of advice on exercise (27%), weight reduction (33%) and referral to physiotherapy (10%). Of GPs surveyed, 85% prescribed some form of complementary medications, 60% prescribed glucosamine sulphate, 21% chondroitin sulphate, 11% cod liver oil and 9% evening primrose oil. Only 10% of GPs surveyed perform intra-articular injections.
Conclusion: The data suggest that in the primary care setting, the majority of GPs over-investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesics and NSAIDs. The use of physiotheraphy and non-drug approaches were significantly under-utilized. There is a need to further educate GPs in the management of OA.
Introduction: Primary care management of knee osteoarthritis OA has received little attention in the scientific literature and the main reason of this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting. Materials and Methods: A cross sectional survey of 100 randomly selected general practitioners (GPs) in the northern states of Malaysia (Kedah, Perlis, Pulau Pinang) was undertaken using questionnaires. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment of OA. They were also asked their usage of conventional and complementary medication. Results: 80 (80%) GPs responded to the questionnaires sent. 85% of GPs were in solo practice and 15% in group practice. Most of the GPs surveyed (69%) were in practice for more than 10 years, 21% in 5- 10 years and 10% were in practice for less than 5 years. 65% GPs surveyed see an average of more than 20 patients per week, 25% see about 10- 20 patients and 10% see less than 10 patients per week. 75% of GPs surveyed would arrange an X-ray. 65% of GPs surveyed will arrange a blood test, mostly serum uric acid, rheumatoid factor and ESR. Pharmacological management consists of first line treatment with analgesics (32%), NSAIDs (59%) or a combination of the two (4%). Non-pharmacological management consist of advise an exercise (37%), weight reduction (23%) and referral to physiotherapy (8%). 89% of GPs surveyed prescribed some form of complementary medications. 68% prescribed glucosamine sulphate, 29% chondroitin sulphate, 18% cod liver oil, 12% evening primrose oil. Only 5% of GPs surveyed perform intra- articular injection. Conclusion: The data suggest that in the primary care, majority of GP over investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesic and NSAIDs. The use of physiotherapy and non drug approach were enormously under-utilized. There is a need to further educate GPs in the management of OA.
ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
MATERIAL AND METHODS: The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
RESULTS: Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
CONCLUSIONS: The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
Molybdenum cofactor deficiency is a rare autosomal recessive disorder with devastating neurological manifestations, characterised by neonatal-onset encephalopathy mimicking hypoxic-ischaemic insult, intractable seizure, and feeding and respiratory difficulties. It is often fatal in the early life. We report an affected 8-year-old boy, who presented with severe neurological manifestations since birth, but without clinically-significant seizure. Molybdenum cofactor deficiency must be included in the differential diagnosis of patients presenting with unexplained encephalopathy in the newborn period, and whose neuroimaging findings are consistent with hypoxic ischaemic encephalopathy. The classic laboratory hallmark of this disorder is low serum uric acid, positive urine sulphite dipstick test, and elevated urinary S-sulphocysteine, hypoxanthine and xanthine.
AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia.
METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.
RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.
CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines
To investigate the possible association between serum uric acid levels, serum C-Reactive Protein (CRP), and age-related macular degeneration (ARMD). A total 232 patients of the eye department at Hospital Tuanku Ja'afar, Negeri Sembilan, Malaysia were recruited over 9 weeks. Participants were divided into ARMD (Non-Neovascular ARMD, and Neovascular ARMD) and control groups. 107 participants with non-neovascular ARMD, 6 with neovascular ARMD, and 119 controls participated in the study. The control patients had a similar average Serum Uric Acid level to the average of all patients with ARMD (P = 0.617).