Cohort profile: the Western Australian Sleep Health Study.

BACKGROUND: Epidemiologic and genetic studies of obstructive sleep apnoea (OSA) are limited by a lack of large-scale, well-characterized OSA cohorts. These studies require large sample size to provide adequate power to detect differences between groups. This study describes the development of such a cohort (The Western Australian Sleep Health Study) in OSA patients of Caucasian-European origin attending the only public sleep clinic in Western Australia (WA). AIMS: The main aim of the study is to phenotype 4,000 OSA patients in order to define the genetics of OSA and its co-morbidities. METHODS: Almost all underwent laboratory-based attended polysomnography (PSG). RESULTS: Currently complete data (questionnaire, biochemistry, DNA, and PSG) has been obtained on over 3,000 individuals and will reach the target of 4,000 individuals by the end of 2010. In a separate but related study, we have developed a sleep study database containing data from all patients who have undergone PSG at the sleep laboratory since its inception in 1988 until the present day (over 30,000 PSG studies representing data from approximately 20,000 individuals). In addition, data from both cohorts have been linked prospectively to statutory health data collected by the WA Department of Health. CONCLUSION: This study will be the largest sleep clinic cohort database internationally with access to genetic and epidemiological data. It is unique among sleep clinic cohorts because of its size, the breadth of data collected and the ability to link prospectively to statutory health data. It will be a major tool to comprehensively assess genetic and epidemiologic factors determining OSA and its co-morbidities.

A method to assess 59Fe in residual tissue blood content in mice and its use to correct 59Fe-distribution kinetics accordingly.

BACKGROUND: Dysregulation of body iron-distribution may induce oxidative damage. To investigate the molecular mechanisms of iron homeostasis, corresponding essential genes are manipulated by many working groups. This asks for a simple method to pursue the resulting impact on body iron-distribution in mice. AIM: To develop a method for the assessment of (59)Fe in residual tissue blood content and to correct this influence in (59)Fe body distribution studies. METHODS: Iron status in male adult C57BL6 mice was adjusted by feeding diets with different iron content. Fractional contribution of organs to total body weight was determined after dissection. (59)Fe-labelled blood was injected in recipient mice to estimate total blood volume and residual blood content in all organs and tissues. The main experiment used these data to correct total (59)Fe tissue content at six intervals after (59)Fe injection (12h-28 days). RESULTS AND DISCUSSION: The sum of (59)Fe in all organs was the same as determined in each mouse before dissection. (59)Fe in whole blood remained constant from the 4th day after injection on, and was highest in iron-deficiency. As in other species, residual blood content was highest in spleen and lungs. Nevertheless, (59)Fe in the iron-deficient spleen decreased to zero and intestinal (59)Fe-content also decreased significantly over time after correction for (59)Fe in residual blood. These findings suggest correct assessment of compartment sizes and (59)Fe in residual blood in each organ. CONCLUSIONS: Differences in (59)Fe-distribution between iron status reflected changes in the expression of proteins of iron-transport and its regulation correctly. Thus, the method seems suitable to analyse body iron-distribution in consequence to genetic manipulations of murine iron homeostasis which is a prerequisite to assess possible toxicological consequences of iron supplementation.

On risks and benefits of iron supplementation recommendations for iron intake revisited.

Iron is an essential trace element with a high prevalence of deficiency in infants and in women of reproductive age from developing countries. Iron deficiency is frequently associated with anaemia and, thus, with reduced working capacity and impaired intellectual development. Moreover, the risk for premature delivery, stillbirth and impaired host-defence is increased in iron deficiency. Iron-absorption and -distribution are homeostatically regulated to reduce the risk for deficiency and overload. These mechanisms interact, in part, with the mechanisms of oxidative stress and inflammation and with iron availability to pathogens. In the plasma, fractions of iron may not be bound to transferrin and are hypothesised to participate in atherogenesis. Repleted iron stores and preceding high iron intakes reduce intestinal iron absorption which, however, offers no reliable protection against oral iron overload. Recommendations for dietary iron intake at different life stages are given by the US Food and Nutrition Board (FNB), by FAO/WHO and by the EU Scientific Committee, among others. They are based, on estimates for iron-losses, iron-bioavailability from the diet, and iron-requirements for metabolism and growth. Differences in choice and interpretation of these estimates lead to different recommendations by the different panels which are discussed in detail. Assessment of iron-related risks is based on reports of adverse health effects which were used in the attempts to derive an upper safe level for dietary iron intake. Iron-related harm can be due to direct intestinal damage, to oxidative stress, or to stimulated growth of pathogens. Unfortunately, it is problematic to derive a reproducible cause-effect and dose-response relationship for adverse health effects that suggest a relationship to iron-intake, be they based on mechanistic or epidemiological observations. Corresponding data and interpretations are discussed for the intestinal lumen, the vascular system and for the intracellular and interstitial space, considering interference of the mechanisms of iron homoeostasis as a likely explanation for differences in epidemiological observations.