Primary aldosteronism - careful investigation is essential and rewarding

Once considered rare, primary aldosteronism (PAL) is now regarded as the commonest potentially curable and specifically treatable form of hypertension. At Greenslopes Hospital Hypertension Unit (GHHU), the decision in 1991 to screen all (and not just hypokalemic or resistant) hypertensives by aldosterone/renin ratio (ARR) testing led to a 10-fold increase in detection rate of PAL and four-fold increase in removal rate of aldosterone-producing adenomas (APAs). The GHHU/Princess Alexandra Hospital Hypertension Unit PAL series stands at 977 patients and 250 APAs removed with hypertension cured in 50-60% (remainder improved). Reliable detection requires that interfering medications are withdrawn (or their effects considered) before ARR measurement, and reliable methods (such as fludrocortisone suppression testing) to confirm PAL. Adrenal venous sampling is the only dependable way to differentiate APA from bilateral adrenal hyperplasia. Genetic testing has facilitated detection of alucocorticoid-remediable, familial PAL. Identification of mutations causing the more common familial variety described by GHHU in 1991 should further aid in detection of PAL. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Low renin hypertensive states: perspectives, unsolved problems, future research

Some causes of low renin hypertension are familial with known genetic bases. One of them, primary aldosteronism, is specifically treatable by mineralocorticoid receptor blockers or by surgery, and has at least two different familial varieties. These have provided insights into its natural history, with long normotensive and normokalemic phases, and variable expression within the same family. Primary aldosteronism was considered rare, but recent work beginning in 1992 suggests that it might be the most common curable cause of hypertension, worth screening for in every hypertensive. Evidence is now compelling that inappropriate aldosterone for salt status can cause not only hypertension, but vascular inflammation and end-organ damage, preventable by mineralocorticoid receptor blockade.

Antihypertensive treatments obscure familial contributions to blood pressure variation

The linkage and association between inherent blood pressure and underlying genotype is potentially confounded by antihypertensive treatment. We estimated blood pressure variance components (genetic, shared environmental, individual-specific) in 767 adult volunteer families by using a variety of approaches to adjusting blood pressure of the 244 subjects (8.2%) receiving antihypertensive medications. The additive genetic component of variance for systolic pressure was 73.9 mm Hg(2) (SE, 8.8) when measured pressures (adjusted for age by gender within each generation) were used but fell to 61.4 mm Hg(2) (SE, 8.0) when treated subjects were excluded. When the relevant 95th percentile values were substituted for treated systolic pressures, the additive genetic component was 81.9 mm Hg(2) (SE, 9.5), but individual adjustments in systolic pressure ranged from -53.5 mm Hg to +64.5 mm Hg (mean, +17.2 mm Hg). Instead, when 10 mm Hg was added to treated systolic pressure, the additive genetic component rose to 86.6 mm Hg(2) (SE, 10.1). Similar changes were seen in the shared environment component of variance for systolic pressure and for the combined genetic and shared environmental (ie, familial) components of diastolic pressure. There was little change in the individual-specific variance component across any of the methods. Therefore, treated subjects contribute important information to the familial components of blood pressure variance. This information is lost if treated subjects are excluded and obscured by treatment effects if unadjusted measured pressures are used. Adding back an appropriate increment of pressure restores familial components, more closely reflects the pretreatment values, and should increase the power of genomic linkage and linkage disequilibrium analyses.

Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3.

The inheritance of much early-onset Alzheimer disease (AD) has been linked to a dominant-acting locus on chromosome 14. Recently, the gene likely responsible for this genetic linkage has been identified and termed AD3. Five mutations have been found in AD3 that segregate with the disease phenotype in seven AD families and are not present in unaffected individuals. Here we report the existence of a gene encoding a seven transmembrane domain protein very similar to that encoded by AD3 in structure and sequence. This gene is located on chromosome 1, is expressed in a variety of tissues, including brain, and is predicted to harbor mutations causing nonchromosome 14 familial AD. The presence of several S/TPXX DNA binding motifs in both the AD3 protein and the AD3-like protein /AD4 protein suggests a possible role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Ways in which mutations in either gene could lead to AD are discussed.

DNA Mutation of the progranulin (GRN) gene in familial frontotemporal lobar degeneration (FTLD):a study of the pathology of nine cases

Frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP) is a neurodegenerative disease characterized by variable neocortical and allocortical atrophy principally affecting the frontal and temporal lobes. Histologically, there is neuronal loss, microvacuolation in the superficial cortical laminae, and a reactive astrocytosis. A variety of TDP-43 immunoreactive changes are present in FTLD-TDP including neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII), dystrophic neurites (DN) and, oligodendroglial inclusions (GI). Many cases of familial FTLD-TDP are caused by DNA mutations of the progranulin (GRN) gene. Hence, the density, spatial patterns, and laminar distribution of the pathological changes were studied in nine cases of FLTD-TDP with GRN mutation. The densities of NCI and DN were greater in cases caused by GRN mutation compared with sporadic cases. In cortical regions, the commonest spatial pattern exhibited by the TDP-43 immunoreactive lesions was the presence of clusters of inclusions regularly distributed parallel to the pia mater. In approximately 50% of cortical gyri, the NCI exhibited a peak of density in the upper cortical laminae while the GI were commonly distributed across all laminae. The distribution of the NII and DN was variable, the most common pattern being a peak of NII density in the lower cortical laminae and DN in the upper cortical laminae. These results suggest in FTLD-TDP caused by GRN mutation: 1) there are greater densities of NCI and DN than in sporadic cases of the disease, 2) there is degeneration of the cortico-cortical and cortico-hippocampal pathways, and 3) cortical degeneration occurs across the cortical laminae, the various TDP-43 immunoreactive inclusions often being distributed in different cortical laminae.

Selection-adaption-retention dynamics and variety in organisational routines

The notion of routines as mechanisms for achieving stability and change in organisations is well established in the organisational theory literature (Becker, 2004). However the relationship between the dynamics of selection, adaptation and retention and the increase or decrease in the varieties of routines which are the result of these processes, is not as well established theoretically or empirically. This paper investigates the processes associated with the evolution of an inter-organisational routine over time. The paper contributes to theory by advancing a conceptual clarification between the dynamics of organisational routines which produce variation, and the varieties of routines which are generated as a result of such processes; and an explanation for the relationship between selection, adaptation and retention dynamics and the creation of variety. The research is supported by analysis of empirical data pertaining to the procurement of engineering assets in a large asset intensive organisation.

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Abstract Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

Variations on a routine : how selection-adaptation-retention dynamics create variety in organisational routines

The question "what causes variety in organisational routines" is of considerable interest to organisational scholars, and one to which this thesis seeks to answer. To this end an evolutionary theory of change is advanced which holds that the dynamics of selection, adaptation and retention explain the creation of variety in organisational routines. A longitudinal, multi-level, multi-case analysis is undertaken in this thesis, using multiple data collection strategies. In each case, different types of variety were identified, according to a typology, together with how selection, adaptation and retention contribute to variety in a positive or negative sense. Methodologically, the thesis makes a contribution to our understanding of variety, as certain types of variety only become evident when examined by specific types of research design. The research also makes a theoretical contribution by explaining how selection, adaptation and retention individually and collectively contribute to variety in organisational routines. Moreover, showing that routines could be stable, diverse, adaptive and dynamic at the same time; is a significant, and novel, theoretical contribution.

Active ageing among older adults with lifelong intellectual disabilities : the role of familial and nonfamilial social networks

Little research has examined the extent to which active ageing is facilitated by family and nonfamilial support persons of older adults with intellectual disabilities. This study explores the role played by key unpaid carers/support persons of older adults with lifelong intellectual disabilities in facilitating "active ageing." Little research has examined the extent to which active ageing is facilitated by family and nonfamilial support persons of older adults with intellectual disabilities. This study explores the role played by key unpaid carers/support persons of older adults with lifelong intellectual disabilities in facilitating “active ageing.” All key social network members conceived active ageing to mean ongoing activity. Family and extended family members were found to play a crucial role in facilitating independent living and providing opportunities for recreational pursuits for those living in group homes. Members of religious organizations and group home staff provided the same types of opportunities where family support was absent. The findings suggest the need for improvements in resource provision, staff training, and group home policy and building design.

The 'variety effect' is anticipated in meal planning

The 'variety effect' describes the greater consumption that is observed when multiple foods with different sensory characteristics are presented either simultaneously or sequentially. Variety increases the amount of food consumed in test of ad libitum intake. However, outside the laboratory, meals are often planned in advance and then consumed in their entirety. We sought to explore the extent to which the variety effect is anticipated in this pre-meal planning. Participants were shown two food images, each representing a first or a second course of a hypothetical meal. The two courses were either, i) exactly the same food, ii) different foods from the same sensory category (sweet or savoury) or, iii) different foods from a different sensory category. In Study 1 (N = 30) these courses comprised typical ‘main meal’ foods and in Study 2 (N = 30) they comprised snack foods. For each pair of images, participants rated their expected liking of the second course and selected ideal portion sizes, both for the second course and the first and second course, combined. In both studies, as the difference between the courses (from (i) same to (ii) similar to (iii) different) increased, the second course was selected in a larger portion and it was rated as more pleasant. To our knowledge, these are the first studies to show that the variety effect is evident in the energy content of self-selected meals. This work shows that effects of variety are learned and anticipated. This extends our characterisation beyond a passive process that develops towards the end of a meal.

Comparing the availability, price, variety and quality of fruits and vegetables across retail outlets and by area level socioeconomic position

Abstract Objective: To explore whether area-level socioeconomic position or the form of retail stream (conventional versus farmers’ market) are associated with differences in the price, availability, variety and quality of a range of fresh fruit and vegetables. Design: A multi-site cross-sectional pilot study of farmers’ markets, supermarkets and independent fruit and vegetable retailers. Each was surveyed to assess the price, availability, variety and quality of 15 fruit and 18 vegetable items. Setting: Retail outlets were located in South-East Queensland. Subjects: Fifteen retail outlets were surveyed (five of each retail stream). Results: Average basket prices were not significantly different across the socioeconomic spectrum however prices in low socioeconomic areas were cheapest. Availability, variety, and quality did not differ across levels of socioeconomic position however the areas with the most socioeconomic disadvantage scored poorest for quality and variety. Supermarkets had significantly better fruit and vegetable availability than farmers’ markets however price, variety and quality scores were not different across retail streams. Results demonstrate a trend to fruit and vegetable prices being more expensive at farmers’ markets, with the price of the Fruit basket being significantly greater at the organic farmer’s market compared with the non-organic farmers’ markets. Conclusions: Neither area-level socioeconomic position nor the form of retail stream was significantly associated with differences in the availability, price, variety and quality of fruit and vegetables, except for availability which was higher in supermarkets than farmers’ markets. Further research is needed to determine what role farmers’ markets can play in affecting fruit and vegetable intake.

Variety matters

Countercyclical markups are a key transmission mechanism in many endogenous business cycle models. Yet, recent findings suggest that aggregate markups in the US are procyclical. The current model addresses this issue. It extends Galí's (1994) composition of aggregate demand model by endogenous entry and exit of firms and by product variety effects. Endogenous business cycles emerge with procyclical markups that are within empirically plausible ranges.

What are the health needs, familial and social problems of Thai migrants in a local community in Australia? A focus group study

This study explored the health needs, familial and social problems of Thai migrants in a local community in Brisbane, Australia. Five focus groups with Thai migrants were conducted. The qualitative data were examined using thematic content analysis that is specifically designed for focus group analysis. Four themes were identified: (1) positive experiences in Australia, (2) physical health problems, (3) mental health problems, and (4) familial and social health problems. This study revealed key health needs related to chronic disease and mental health, major barriers to health service use, such as language skills, and facilitating factors, such as the Thai Temple. We concluded that because the health needs, familial and social problems of Thai migrants were complex and culture bound, the development of health and community services for Thai migrants needs to take account of the ways in which Thai culture both negatively impacts health and offer positive solutions to problems.