To give or not to give? Lessons from the arginine paradox

Arginine is one of the 20 amino acids (AA) found in proteins and synthesized by human cells. However, arginine is also the substrate for a series of reactions leading to the synthesis of other AA and is an obligatory substrate for two enzymes with diverging actions, arginases and nitric oxide synthases (NOS), giving origin to urea and NO, respectively. NO is a very potent vasodilator when produced by endothelial NOS (eNOS). The 'arginine paradox' is the fact that, despite intracellular physiological concentration of arginine being several hundred micromoles per liter, far exceeding the ～5 μM K(M) of eNOS, the acute provision of exogenous arginine still increases NO production. Clinically, an additional paradox is that the largest controlled study on chronic oral arginine supplementation in patients after myocardial infarction had to be interrupted for excess mortality in treated patients. Expression and activity of arginases, which produce urea and divert arginine from NOS, are positively related to exogenous arginine supplementation. Therefore, the more arginine is introduced, the more it is destroyed, eventually leading to impaired NO production. In this review, conditions influencing the low arginine concentrations found in plasma will be reviewed, revising the paradigm that simple replenishment of what is lacking will always produce beneficial consequences.     

Breast cancer in Canada: To screen or not to screen?

Lomas (1988) and Sabatier (1987) have suggested models by which to examine the roles that values, scientific knowledge, institutions, and the learning process play in the formulation of both national and clinical health-care policies. Utilizing their frameworks, this article offers an explanation for the development of high-volume screening mammography policies in Canada, despite the suggested inefficacy of screening technologies for 'unavoidable' illnesses such as carcinoma in the breast. The preliminary results of Canada's National Breast Screening Study further complicate this tissue. Inappropriate framing of the 'problem' in the policy-making process, by actors highly influenced by societal values and scientific evidence, is identified as the reason for present and planned policies and practices contradicting the first principles of health-policy analysis.     

To screen or not to screen for adult malnutrition?

BACKGROUND: There is some controversy about whether all adults receiving healthcare should be routinely screened for nutritional problems. METHODS: (i) A systematic review examined the proposition that malnutrition is under-recognised and under-treated, and that nutritional interventions in malnourished patients, identified through a screening procedure produce clinical benefits (assessed using randomised controlled trials, RCTs). (ii) A systematic review of nutritional screening interventions in populations of malnourished and well-nourished subjects (RCTs and non-RCTs). RESULTS: (i) The prevalence of malnutrition varies according to the criteria used, but is estimated to affect 10-60% of patients in hospital and nursing homes, 10% or more of older free-living subjects, and less than 5% of younger adults. In the absence of formal screening procedures, more than half the patients at risk of malnutrition in various settings do not appear to be recognised and/or are not referred for treatment. RCTs show that nutritional interventions in malnourished patients produce various clinical benefits. (ii) Interventions with nutritional screening in different care settings also generally suggest clinical benefits, but some are limited by small sample sizes and inadequate methodology. Factors that influence outcomes include validity, reliability and ease of using the screening procedure, the 'care gap' that exists between routine and desirable care and the need for other resources, which may increase or decrease following screening. CONCLUSIONS: The frequent failure to recognise and treat malnutrition, especially where it is common, is unacceptable. In such circumstances, the routine use of a simple screening procedure is recommended. Each health care setting should have a transparent policy about nutritional screening, which may vary according to the 'care gap', available resources, and specific populations of patients, in which the prevalence of malnutrition may vary widely.