Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2) = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male nonsmokers (adjusted beta = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta = -0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta 2-microglobutin (P = 0.02) and N-acetyl-beta-D-glucosaminidase (P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2) = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Exploiting novel cell cycle targets in the development of anticancer agents

In this review we provide a brief background on the cell cycle and then focus on two novel and emerging areas of cell cycle research that may prove to have significant relevance to the development of novel anticancer agents. In particular, we review the emerging evidence to suggest that histone deacetylase inhibitors may possess cancer cell-specific cytotoxicity due to their ability to target a novel G2/M checkpoint. We also review the recent literature supporting the proposition that inhibition of E2F activity in epithelial cancer cells may prove to be a useful differentiation therapy that operates via cell cycle-dependent and cell cycle-independent mechanisms.

Determinants in the development of advanced nursing practice: a case study of primary-care settings in Hong Kong

Different factors have been shown to influence the development of models of advanced nursing practice (ANP) in primary-care settings. Although ANP is being developed in hospitals in Hong Kong, China, it remains undeveloped in primary care and little is known about the factors determining the development of such a model. The aims of the present study were to investigate the contribution of different models of nursing practice to the care provided in primary-care settings in Hong Kong, and to examine the determinants influencing the development of a model of ANP in such settings. A multiple case study design was selected using both qualitative and quantitative methods of data collection. Sampling methods reflected the population groups and stage of the case study. Sampling included a total population of 41 nurses from whom a secondary volunteer sample was drawn for face-to-face interviews. In each case study, a convenience sample of 70 patients were recruited, from whom 10 were selected purposively for a semi-structured telephone interview. An opportunistic sample of healthcare professionals was also selected. The within-case and cross-case analysis demonstrated four major determinants influencing the development of ANP: (1) current models of nursing practice; (2) the use of skills mix; (3) the perceived contribution of ANP to patient care; and (4) patients' expectations of care. The level of autonomy of individual nurses was considered particularly important. These determinants were used to develop a model of ANP for a primary-care setting. In conclusion, although the findings highlight the complexity determining the development and implementation of ANP in primary care, the proposed model suggests that definitions of advanced practice are appropriate to a range of practice models and cultural settings. However, the findings highlight the importance of assessing the effectiveness of such models in terms of cost and long-term patient outcomes.

Does nephron number matter in the development of kidney disease?

The total number of nephrons in normal human kidneys varies over a 10-fold range. This variation in total nephron number leads us to question whether low nephron number increases the risk of renal disease in adulthood. This review considers the available evidence in humans linking low nephron number/reduced nephron endowment and the susceptibility to renal disease. Total nephron number in humans has been directly correlated with birth weight and inversely correlated with age, mean glomerular volume, and hypertension. Low nephron number may be the result of suboptimal nephrogenesis during kidney development and/or loss of nephrons once nephrogenesis has been completed. Low nephron number is frequently, but not always, associated with hypertrophy of remaining glomeruli. This compensatory hypertrophy has also been associated with a greater susceptibility for kidney disease. Three human studies have reported reduced nelphron number in subjects with a history of hypertension. This correlation has been observed in White Europeans, White Americans (but not African Americans) and Australian Aborigines. Studies in additional populations are required, as well as a greater understanding of the fetal environmental and genetic determinants of low nephron number.

The role of the learning community in the development of discipline knowledge and generic graduate outcomes

In this paper we describe a study of learning outcomes at a research-intensive Australian university. Three graduate outcome variables (discipline knowledge and skills, communication and problem solving, and ethical and social sensitivity) are analysed separately using OLS regression and comparisons are made of the patterns of unique contributions from four independent variables (the CEQ Good Teaching and Learning Communities Scales, and two new, independent, scales for measuring Teaching and Program Quality). Further comparisons of these patterns are made across the Schools of the university. Results support the view that teaching and program quality are not the only important determinants of students' learning outcomes. It is concluded that, whilst it continues to be appropriate for universities to be concerned with the quality of their teaching and programs, the interactive, social and collaborative aspects of students' learning experiences, captured in the notion of the Learning Community, are also very important determinants of graduate outcomes, and so should be included in the focus of attempts at enhancing the quality of student learning.