Rajitha Wickremasinghe

Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?

BackgroundThe rising prevalence of chronic kidney disease (CKD) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care resources. This community based study was conducted to identify potential predictors of microalbuminuria in a randomly selected sample of adults from the North Central Province (NCP) of Sri Lanka, where the burden of CKD is pronounced and the underlying cause still unknown.MethodsExposures to possible risk factors were determined in randomly recruited subjects (425 females and 461 males) from selected areas of the NCP of Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test.ResultsMicroalbumnuria was detected in 6.1% of the females and 8.5% of the males. Smoking (p < 0.001), alcohol use (p = 0.003), hypertension (p < 0.001), diabetes (p < 0.001), urinary tract infection (UTI) (p = 0.034) and consumption of water from wells in the fields (p = 0.025) were associated with microalbuminuria. In the binary logistic regression analysis, hypertension, diabetes mellitus, UTI, drinking well water in the fields, smoking and pesticide spraying were found to be significant predictors of microalbuminuria.ConclusionsHypertension, diabetes mellitus, UTI, and smoking are known risk factors for microalbuminuria. The association between microalbuminuria and consumption of well water suggests an environmental aetiology to CKD in NCP. The causative agent is yet to be identified. Investigations for cadmium as a potential causative agent needs to be initiated.

Patterns of multisite pain and associations with risk factors

Summary In a large cross‐sectional survey, pain affecting 6–10 anatomical sites showed substantially different associations with risk factors from pain limited to 1–3 sites. ABSTRACT To explore definitions for multisite pain, and compare associations with risk factors for different patterns of musculoskeletal pain, we analysed cross‐sectional data from the Cultural and Psychosocial Influences on Disability (CUPID) study. The study sample comprised 12,410 adults aged 20–59 years from 47 occupational groups in 18 countries. A standardised questionnaire was used to collect information about pain in the past month at each of 10 anatomical sites, and about potential risk factors. Associations with pain outcomes were assessed by Poisson regression, and characterised by prevalence rate ratios (PRRs). Extensive pain, affecting 6–10 anatomical sites, was reported much more frequently than would be expected if the occurrence of pain at each site were independent (674 participants vs 41.9 expected). In comparison with pain involving only 1–3 sites, it showed much stronger associations (relative to no pain) with risk factors such as female sex (PRR 1.6 vs 1.1), older age (PRR 2.6 vs 1.1), somatising tendency (PRR 4.6 vs 1.3), and exposure to multiple physically stressing occupational activities (PRR 5.0 vs 1.4). After adjustment for number of sites with pain, these risk factors showed no additional association with a distribution of pain that was widespread according to the frequently used American College of Rheumatology criteria. Our analysis supports the classification of pain at multiple anatomical sites simply by the number of sites affected, and suggests that extensive pain differs importantly in its associations with risk factors from pain that is limited to only a small number of anatomical sites.

Impact of low-level exposure to organophosphates on human reproduction and survival

Despite their widespread and longstanding use for the public good, organophosphate (OP) pesticides have led to many adverse effects on human health. Environmental exposure to OPs and adverse reproductive outcomes in men and women working on or living near farms are increasingly reported worldwide. The aim of the current review is to determine whether exposure to OPs, at levels lower than that which results in clinical manifestations of acute OP poisoning, leads to an adverse impact on fertility, growth and development, and to highlight possible effects for further investigation. There is evidence of impaired fertility due to a reduction in semen quality and possibly lower testosterone levels in exposed males. There is also evidence of impairment of fetal growth and development brought about by prenatal exposure to OPs. Paraoxonase gene (PON1) activity in the fetus and during early childhood makes the fetus and child more vulnerable to OP poisoning, suggesting that OP exposure has a greater impact on fetal and infant growth and development than on adults when exposed to the same concentrations of pesticides. This review raises concerns that exposure to OP pesticides at levels currently regarded as safe adversely affect human reproductive function and survival.

The CUPID (Cultural and Psychosocial Influences on Disability) Study: Methods of Data Collection and Characteristics of Study Sample

Background The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample. Methods/Principal Findings A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI). Conclusions/Significance The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively.

Cadmium a metalloestrogen: are we convinced?

Metalloestrogens are inorganic metal ions that bind to and activate oestrogen receptors. They are implicated in the aetiology of oestrogen‐dependent diseases such as cancers of the breast and endometrium as well as endometriosis. Cadmium is one of the most studied metalloestrogens. In this review, scientific evidence for the oestrogenic effects of cadmium is critically evaluated to determine if there is sufficient evidence to support cadmium as an aetiological factor of oestrogen‐dependent disease in humans. Results of the review indicated that, although the in vitro and in vivo evidence of the oestrogenic properties of cadmium was persuasive, evidence from population‐based human studies remains conflicting. Considerable knowledge gaps exist on the potential oestrogenic effect of cadmium in humans. Research that focuses on bridging these knowledge gaps would be useful in preventing and managing oestrogen‐dependent disease in humans. Copyright

Could ochratoxin A in food commodities be the cause of chronic kidney disease in Sri Lanka

Ochratoxin A (OA) is a naturally occurring mycotoxin with nephrotoxic properties that can contaminate plant food products. OA concentrations were assessed in commonly consumed food items in the North Central Province of Sri Lanka, where chronic kidney disease is diagnosed at epidemic proportions. Ninety-eight randomly selected food samples were analysed. Mycotoxin was detected in the extract by using a MycoMonitor Ochratoxin A ELISA assay kit (Helica Biosystems Inc., USA). The levels of OA found in these food commodities were below the recommended statutory maximum limit and are unlikely to be a potential risk factor for nephropathy in the North Central Province of Sri Lanka.

The efficacy of micronutrient supplementation in reducing the prevalence of anaemia and deficiencies of zinc and iron among adolescents in Sri Lanka.

Objective:To determine the effectiveness of combined iron and zinc over the iron or zinc-only supplementation in correcting deficiency and possible interactive effects in a group of adolescent school children.Subjects and methods:Schoolchildren (n=821) of 12–16 years of age were randomized into four groups and supplemented with iron (50 mg/day), zinc (14 mg/day), iron+zinc or placebo capsules 5 days per week for 24 weeks. Anthropometry, and haemoglobin (Hb), serum zinc (SZn) and serum ferritin (SF) concentrations were determined before and after the intervention.Results:There were no significant effects between-groups in their weight, height and Hb concentrations with the intervention when compared with the placebo group. Iron-only and combination-supplemented groups had reached mean SF concentrations of 55.1 μg/l with no difference between them (P=0.99). The zinc-only group had a mean change of 4.3 μmol//l whereas the combine-supplemented group had a mean change of 4.0 μmol/l (P=0.82). The prevalence of anaemia was found to be 70.3% in the iron group at baseline; this was reduced to 14.5% after the supplementation. In the combine-supplemented group anaemia, prevalence was reduced from 64.8 to 19.3%.Conclusions:Zinc alone or in combination with iron has not shown a significant improvement in growth in adolescence. Severe and moderate forms of anaemia were successfully treated in children who received iron supplementation. Initial high prevalence of low SZn and iron stores was significantly improved with micronutrient supplementation.

Low folic acid status and its association with anaemia in urban adolescent girls and women of childbearing age in Sri Lanka

Folic acid deficiency is implicated in the aetiology of nutritional anaemia and adverse pregnancy outcomes for the fetus. Data on folic acid status among adolescent girls and non-pregnant, non-lactating young women are limited. We assessed folic acid status in a random sample of 552 subjects (277 adolescent girls aged 15-18.9 years and 275 women aged 19-30 years) living in Colombo, Sri Lanka. The association of low folic acid status with anaemia was evaluated. Socio-economic, food intake and anthropometric data were obtained. Hb, serum folic acid, vitamin B12 and ferritin and plasma homocysteine concentrations were measured. Forty-three per cent of subjects studied had low serum folic acid concentrations (<3 ng/ml) and 47 % had low Fe stores (serum ferritin <20 microg/l). Overall prevalence of anaemia was 12.9 %, and 43.9 % of anaemic subjects had both low folic acid status and depleted Fe stores (serum ferritin <12 microg/l). Both low folate status and depleted Fe stores were significantly associated with anaemia (odds ratio = 2.32; 95 % CI 1.34, 4.01 and odds ratio = 5.98; 95 % CI 3.36, 10.63, respectively). Serum folic acid concentration was associated (r = 0.108, P = 0.015) with folate intake as indicated by a computed folate index. Folate index was associated inversely with household size and positively with economic status and education level. In this study population low folic acid status, besides depleted Fe stores, was associated with anaemia. The high prevalence of low folic acid status observed highlights the need for nutrition education to improve intakes of folate, Fe and other micronutrients among adolescent girls and young women.

Fetal effects of environmental exposure of pregnant women to organophosphorus compounds in a rural farming community in Sri Lanka

Background. The possible deleterious effects of low-grade, chronic environmental and occupational exposure to organophosphorus compounds (OPCs) are not well documented. Objective. To investigate the possible effects of low-level, chronic exposure of pregnant mothers to OPCs on the fetus by measuring OPC levels, and using markers of OPC exposure, oxidative stress and oxidative tissue damage. Methods. Toxicity was assessed by measuring (i) OPC levels in breast milk and plasma from maternal and cord blood using gas chromatography, (ii) maternal and fetal butyrylcholinesterase (BChE) activity using inhibition assays, (iii) antioxidant status of the fetus using superoxide dismutase activity assays, (iv) oxidative stress in the fetus by determining malondialdehyde (MDA) concentrations, and (v) examining for fetal DNA fragmentation using electrophoresis. Samples were obtained from consenting mothers living in a farming community in southern Sri Lanka at the end of the pesticide spray season (study group) and just before the commencement of the spray season (in-between spray season; control group). Results. Organophosphate residues were detected in only two subjects (chlorpyrifos in maternal and cord blood of one during the spray season and dimethoate in breast milk of another during the in between spray season), but the test employed was capable of only detecting concentrations above 0.05mg/l. However, cord blood obtained during the spray season showed significant inhibition of BChE activity, increased oxidative stress and more DNA fragmentation when compared with cord blood obtained during the in-between spray season. Conclusions. Inhibition of cord blood BChE activity indicates fetal exposure to organophosphorus compounds during times when there is a high probability of environmental drift. This provides a plausible explanation for the increased oxidative stress and high DNA fragmentation in the fetus. Long-term outcomes of such exposures are unknown.

Sedentary Behaviour and Physical Activity in South Asian Women: Time to Review Current Recommendations?

Objective Our aims were to describe activity and sedentary behaviours in urban Asian women, with dysglycaemia (diagnosed at recruitment), and without dysglycaemia and examine the relative contribution of these parameters to their glycaemic status. Methods 2800 urban women (30–45 years) were selected by random cluster sampling and screened for dysglycaemia for a final sample of 272 newly diagnosed, drug naive dysglycaemic and 345 normoglycaemic women. Physical activity and sedentary behaviours were assessed by the International Physical Activity Questionnaire (IPAQ). Demographic data, diet and anthropometry were recorded. Logistic regression analysis assessed contribution of all parameters to dysglycaemia and exposure attributable fractions were calculated. Results The mean energy expenditure on walking (2648.5±1023.7 MET-min/week) and on moderate and vigorous physical activity (4342.3±1768.1 MET-min/week) for normoglycemic women and dysglycaemic women (walking;1046.4±728.4 MET-min/week, moderate and vigorous physical activity; 1086.7±1184.4 MET-min/week) was above the recommended amount of physical activity per week. 94.3% of women spent >1000 MET-minutes/week on activity. Mean sitting and TV time for normoglycaemic and dysglycaemic women were 154.3±62.8, 38.4±31.9, 312.6±116.7 and 140.2±56.5 minutes per day respectively. Physical activity and sedentary behaviour contributed to dysglycaemia after adjustment for family history, diet, systolic blood pressure and Body Mass Index. Exposure attributable fractions for dysglycaemia were; lower physical activity: 78%, higher waist circumference: 94%, and TV viewing time: 85%. Conclusions Urban South Asian women are at risk of dysglycaemia at lower levels of sedentary behaviour and greater physical activity than western populations, indicating the need for re-visiting current physical activity guidelines for South Asians.