Melissa Haswell-Elkins

A global perspective on cadmium pollution and toxicity in non-occupationally exposed population

Cadmium is a non-essential element that has high rates of soil to plant transference compared with other non-essential elements, and certain plant species accumulate large amounts of cadmium from low cadmium content soils. In this paper, levels of cadmium found in major food groups are highlighted together with cadmium levels found in liver and kidney samples from non-occupationally exposed populations. Data on human kidney cadmium levels identified recently, including the study in our own laboratory, are compared with older studies. Human-tissue cadmium contents showed large variations among individuals, but sources of the variation remain unknown. Exposure levels of 30-50 microg per day have been estimated for adults and these levels have been linked to increased risk of bone fracture, cancer, kidney dysfunction and hypertension. Increased mortality was found among individuals showing signs of cadmium renal toxicity compared with those without such signs, suggesting that renal toxicity may be an early warning of complications, sub-clinical or clinical morbidity.

The epidemiology and control of intestinal helminths in the Pulicat Lake region of Southern India. I. Study design and pre- and post-treatment observations on Ascaris lumbricoides infection

The study design of a project to investigate the epidemiology, population dynamics and control of intestinal nematode infections in fishing village communities in Southern India is described. The paper focuses on Ascaris lumbricoides infection and describes changes in prevalence and intensity (worm burdens) with host age, the aggregated frequency distributions of parasite numbers per person, a density-dependent relationship between parasite fecundity and worm burden and rates of reinfection following chemotherapeutic treatment. The age-intensity of infection profile is convex in form, where maximum worm burdens are attained in children in the age range five to nine years. On the basis of juvenile to adult worm ratioos, the life expectancy of Ascaris in man is estimated to be of the order of one year. Rates of reacquisition of worms after chemotherapy are shown to be dependent on host age. Wormy individuals with heavy infections are shown to be predisposed to this state such that they reacquire heavier than average worm burdens following treatment.

Safe levels of cadmium intake to prevent renal toxicity in human subjects.

The present review attempts to provide an update of the scientific knowledge on the renal toxicity which occurs in human subjects as a result of chronic ingestion of low-level dietary Cd. It highlights important features of Cd toxicology and sources of uncertainty in the assessment of health risk due to dietary Cd. It also discusses potential mechanisms for increased susceptibility to Cd toxicity in individuals with diabetes. Exposure assessment on the basis of Cd levels in foodstuffs reveals that vegetables and cereals are the main sources of dietary Cd, although Cd is also found in meat, albeit to a lesser extent. Cd accumulates particularly in the kidney and liver, and hence offal contains relatively high amounts. Fish contains only small quantities of Cd, while crustaceans and molluscs may accumulate larger amounts from the aquatic environment. Data on Cd accumulation in human kidney and liver obtained from autopsy studies are presented, along with results of epidemiological studies showing the relationship between renal tubular dysfunction and kidney Cd burden. These findings suggest that a kidney Cd level of 50 microg/g wet weight is a maximum tolerable level in order to avoid abnormal kidney function. This renal Cd burden corresponds to a urinary Cd excretion of 2 microg/d. Accordingly, safe daily levels of Cd intake should be kept below 30 microg per person. Individual variations in Cd absorption and sensitivity to toxicity predicts that a dietary Cd intake of 30 microg/d may result in a slight renal dysfunction in about 1% of the adult population. The previous guideline for a maximum recommended Cd intake of 1 microg/kg body weight per d is thus shown to be too high to ensure that renal dysfunction does not occur as a result of dietary Cd intake.

Liver fluke infection and cholangiocarcinoma : Model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis

Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, and cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer.

Evidence for predisposition in humans to infection with Ascaris , hookworm, Enterobius and Trichuris in a South Indian fishing community

Studies of patterns of reinfection with four species of intestinal nematodes (Ascaris, hookworm, Trichuris and Enterobius) in 174 individual patients following chemotherapeutic treatment revealed statistical evidence for predisposition to heavy or light infection (relative to the average level in the overall population). Analyses of associations between the abundances of the four species of nematodes within a combined sample of 525 worm burdens showed significant correlations between 5 out of the 6 possible pair-wise comparisons between species. The relevance of these results to the design of control programmes based on chemotherapeutic application is discussed.

A high frequency of hepatobiliary disease and suspected cholangiocarcinoma associated with heavy Opisthorchis viverrini infection in a small community in north-east Thailand

A group of 87 adults from a small village in north-east Thailand was chosen to undergo ultrasound investigation based on their intensity of infection with the liver fluke, Opisthorchis viverrini, or clinical status (history of jaundice, current hepatomegaly). From this group, 8 cases of suspected early cholangiocarcinoma were found, and the diagnostic features of 6 of the 8 were confirmed by computerized tomography scan and endoscopic retrograde cholangiopancreatography. In addition, several cases of mild gall-bladder disease, chronic cholecystitis, cholelithiasis and parenchymal liver disease were detected. A highly significant positive relationship between the intensity of liver fluke worm burden and the severity of biliary tract disease within individuals is reported. These results indicate that Opisthorchis is associated with moderate to severe hepatobiliary disease in a considerable proportion of infected individuals.

Opisthorchis viverrini : relationships between egg counts, worms recovered and antibody levels within an endemic community in Northeast Thailand

Three techniques for estimating the intensity of Opisthorchis viverrini infection in individuals from a Northeast Thai community are compared. Egg counts were determined using a quantitative formalin/ethyl acetate technique, worm burdens were estimated by expulsion chemotherapy and antibody levels were measured by ELISA. Log-transformed worm and egg counts were closely correlated (r = 0.80), suggesting that both measurements provide good assessments of relative intensity of infection. However, no Opisthorchis worms were recovered from 34 people with high egg counts; probably due to problems with the expulsion technique in some individuals. Examination of egg production per fluke indicated that each fluke contributed an average of 180 eggs per gram (epg) of faeces and fecundity was negatively associated with total worm burden. Serum IgG levels correlated significantly with Opisthorchis egg count (r = 0.61) at two independent assessments. Although significant associations were observed between antibody levels and echinostome infection, analysis suggested that these reflected independent associations between these two variables and Opisthorchis infection and age. We conclude that all three measurements are useful for epidemiological studies.

Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography

Twenty‐four locality‐, age‐ and sex‐matched groups of village residents with no light, moderate and heavy Opisthorchis viverrini infection were examined by ultransonography. Highly significant differences were observed between the groups in the relative size of the left lobe of the liver and the fasting and post‐meal size of the gall‐bladder. In addition, indistinct gall‐bladder wall, the presence of gall‐bladder sludge and strongly enhanced portal vein radicle echoes were most frequently observed in the heavily infected group. Two suspected cases of cholangiocarcinoma were identified from the heavy group. The results highlight the importance of intensity of infection on the frequency and severity of fluke‐associated hepatobiliary disease.

Indigenous Australians’ understandings regarding mental health and disorders

The purpose of the present paper was to determine what is currently documented about Indigenous Australians’ understandings of mental health and mental disorders through a meta-synthesis of peer-reviewed qualitative empirical research. The following databases were electronically searched (1995–April 2006): AOA-FT and AIATSIS, Blackwell Synergy, CINAHL and Pre CINHAL, Health source: nursing/academic edition, Medline, Proquest health and medical complete, PsycInfo, Science Direct, Synergy and HealthInfoNet. Eligible studies were those written in English and published in peer-reviewed journals, empirical studies that considered Indigenous peoples understandings of mental health and provided details on methodology. Five articles from four qualitative studies met these criteria. Meta-ethnography was used to identify common themes emerging from the original studies. Reciprocal translation was used to synthesize the findings to provide new interpretations extending beyond those presented in the original studies. An overarching theme emerged from the synthesis: the dynamic interconnectedness between the multi-factorial components of life circumstances. Reciprocal translations and synthesis regarding Indigenous understandings of mental health and illness resulted in five themes: (i) culture and spirituality; (ii) family and community kinships; (iii) historical, social and economic factors; (iv) fear and education; and (v) loss. The application of a meta-synthesis to these qualitative studies provided a deeper insight into Indigenous peoples understandings of mental health and illness. The importance of understanding Indigenous descriptions and perceptions of mental health issues is crucial to enable two-way understandings between Indigenous peoples constructs of wellness and Western biomedical diagnostic labels and treatment pathways for mental disorders and mental health problems.

Immune responsiveness and parasite-specific antibody levels in human hepatobiliary disease associated with Opisthorchis viverrini infection.

Opisthorchis viverrini infection is associated with human hepatobiliary disease and cholangiocarcinoma, but the role of the immune response in the pathogenesis of infection is unclear. Here ultrasonography was used to examine the biliary tracts of residents from an endemic community. Delayed‐type hypersensitivity responses to unrelated antigens, and fluke‐specific IgG and IgA levels in serum of this group were also examined. Relationships between immunological parameters, intensity of infection and radiologically measured variables are reported. Immune responsiveness to unrelated antigens did not vary with intensity of parasite infection or disease status. Of all the variables, IgG levels were most markedly elevated in disease cases compared with normal subjects and were closely associated with gall bladder size and dysfunction. This is consistent with the hypothesis that an immunopathologic mechanism is involved in opisthorchiasis and suggests that antibody levels may be useful in screening populations for fluke‐associated hepatobiliary disease.