Competition in health research: the experience of the John Curtin School of Medical Research

BACKGROUND: In 2002 the Australian National Competitive Grants System was opened to the Institute of Advanced Studies at the Australian National University as part of a commitment to transparency, competitiveness, and collaboration in national research funding. RESULTS: The block grant to the John Curtin School of Medical Research had progressively eroded over many years. Access to the National Competitive Grants Schemes and associated infrastructure (through an agreed 'buy-in' price of 20% of block funding) has succeeded in its aims and in reversing this progressive effective decrease in funding. CONCLUSION: Access to the National Competitive Grant Scheme has allowed the John Curtin School of Medical Research to contribute more broadly to Australia's health and medical research effort through increased collaboration, in a transparent and competitive funding environment

Best practices in use of research evidence to inform health decisions

The WHO Advisory Committee on Health Research (ACHR) is committed to the notion that WHO should exemplify best practice in use of research evidence to inform decisions about health. A major ongoing initiative of the ACHR is the Sub-committee on the Use of Research Evidence (SURE). This group is examining WHOs roles and responsibilities in the use of health research to inform decisions about health. WHOs leadership has expressed strong support for this initiative. The series of articles being published in Health Research Policy and Systems, which examine the methods used by WHO and other organisations to formulate recommendations about health, is part of the background documentation SURE has produced to inform ACHRs advice to WHO. It is critical that health policy makers look to research, not ignorance, as the basis for action in health, and that health professionals look to evidence, not opinion, as the basis for delivery of care

Blood Pressure and Control of Cardiovascular Risk

Two key early 20th century notions, the first the primacy of diastolic pressure in determining risk, and the second that hypertension is a discrete disorder, have proved to be incorrect. We now recognize the primacy of systolic pressure as a risk factor for cardiovascular disease and that hypertension is an arbitrary definition. In the early 21st century, we are moving away from a dichotomous approach to risk classification, and away from notions of hypertension and normotension towards an appreciation that blood pressure-related risk is continuous. In parallel, there has been a paradigm shift from a single risk factor approach to comprehensive cardiovascular disease risk prevention. Accordingly, prevention of cardiovascular disease requires a focus on lowering of blood pressure and modification of associated risk factors rather than simply treatment of hypertension. This emphasis is reflected in the World Health Organization (WHO) – International Society of Hypertension (ISH) 2003 statement on management of hypertension

Assessing outcomes of health and medical research: do we measure what counts or count what we can measure?

Governments world wide are increasingly demanding outcome measures to evaluate research investment. Health and medical research outputs can be considered as gains in knowledge, wealth and health. Measurement of the impacts of research on health are difficult, particularly within the time frames of granting bodies. Thus evaluations often measure what can be measured, rather than what should be measured. Traditional academic metrics are insufficient to demonstrate societal benefit from public investment in health research. New approaches that consider all the benefits of research are needed

Cardiovascular consequences of cortisol excess

Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia. This review analyses the relationship of cortisol excess, both locally and at tissue level, to these cardiovascular risk factors, and to putative mechanisms for hypertension. Previous studies have examined correlations between cortisol, blood pressure, and other parameters in the general population and in Cushing's syndrome. This review also details changes induced by short-term cortisol administration in normotensive healthy men

Glucocorticoid-induced hypertension and the nitric oxide system

Glucocorticoid hormones, both naturally occurring and synthetic, have long been recognized as a major cause of hypertension. There are well-described experimental models of glucocorticoid-induced hypertension, such as adrenocorticotropic hormone-and dexamethasone-induced hypertension in rats, although the exact mechanism of glucocorticoid-induced hypertension remains unclear. It was initially considered to be due to mineralocorticoid receptor activation but more recent studies have not supported this notion. Current evidence demonstrates the importance of the nitric oxide (NO) system and interactions between NO and reactive oxygen species in the development of glucocorticoid-induced hypertension. This review highlights the pathways contributing to NO deficiency, which encompass the availability of l-arginine, endothelial NO synthase function and the extent of NO inactivation during oxidative stress

Nitric oxide donation lowers blood pressure in adrenocorticotrophic hormone-induced hypertensive rats.

Adrenocorticotrophic hormone (ACTH) elevates systolic blood pressure (SBP) and lowers plasma reactive nitrogen intermediates in rats. We assessed the ability of NO donation from isosorbide dinitrate (ISDN) to prevent or reverse the hypertension caused by ACTH. In the prevention study, male Sprague Dawley rats were treated with ACTH (0.2 mg/kg/day) or saline control for 8 days, with either concurrent ISDN (100 mg/kg/day) via the drinking water or water alone. Animals receiving ISDN via the drinking water were provided with nitrate-free water for 8 hours every day. In the reversal study ISDN (100 mg/kg) or vehicle was given as a single oral dose on day 8. SBP was measured daily by the indirect tail-cuff method in conscious, restrained rats. ACTH caused a significant increase in SBP compared with saline (P < 0.0015). In the prevention study, chronic administration of ISDN (100 mg/kg/day) did not affect the SBP in either group. In the reversal study, ISDN significantly lowered SBP in ACTH-treated rats at 1 and 2.5 hours (132 +/- 3 mmHg (1 h) and 131 +/- 2 mmHg (2.5 h) versus 143 +/- 3 mmHg (0 h), P < 0.002), but not to control levels. It had no effect in control (saline treated) rats. In conclusion, the lowering of SBP by NO donation is consistent with the notion that ACTH-induced hypertension involves an impaired bioavailability or action of NO in vivo

Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection

Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection. The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated Heat-killed vaccines were prepared from “immunogenic” organisms which had produced upper urinary tract infection associated with high titers of hemag-glutinating antibody to O antigen and “nonimmunogenic” organisms which had produced upper urinary tract infection without a rise in antibody titer. “Immunogenic” 06 vaccine produced high titers of antibody in patients regarded as possibly “poor producers” of antibody, but “nonimmunogenic” 011 vaccine was not associated with a rise in titer in patients previously regarded as “good producers”. These vaccines were significantly different in immunogenicity (P < 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P < 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper urinary tract infection.Immunogénicité de l'antigène O d'Escherichia coli dans les infections du haut appareil urinaire. Le rôle de l'immunogénicité de l'organisme infectant (Escherichia coli) dans la réponse immune à l'antigène O au cours des infections du haut appareil urinaire a été étudié. Des vaccins tués par la chaleur ont été préparés à partir d'organismes “immunogéniques” qui ont été responsables d'infection du haut appareil urinaire associées à des titres élevés d'anticorps hémagglutinants contre l'antigène O et d'organismes “non immunogéniques” qui ont produit une infection du haut appareil sans augmentation du titre d'anticorps. Le vaccin “immunogénique” 06 produit des titres élevés d'anticorps chez des malades considérés comme de faibles producteurs d'anticorps et le vaccin “non immunogénique” 011 ne détermine pas d'augmentation du titre chez des malades antérieurement considérés comme de “bons producteurs”. Ces vaccins diffèrent significativement en “immunogénicité” (P < 0, 05). Cinq vaccins ont été essayés chez 50 rats. La différence dans les titres d'hémmaglutination vis à vis de l'antigène O est très significative entre 06 et 011 (P < 0, 001). L'immunogénicité de l'organisme infectant parait être un facteur important dans la détermination de la réponse immune à l'antigène O au cours des infections du haut appareil urinaire

N-Acetylcysteine prevents but does not reverse dexamethasone-induced hypertension

1. We have shown previously that N-acetylcysteine (NAC) prevents the increase in blood pressure induced by adrenocorticotropin treatment. The present study investigated the effect of NAC on dexamethasone (Dex)-induced hypertension. 2. Male Sprague-Dawle