Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Goal setting in Dutch paediatric rehabilitation. Are the needs and principal problems of children with cerebral palsy integrated into their rehabilitation goals?

Objective: To evaluate whether the needs and principal problems of children with cerebral palsy (CP) as formulated in their interdisciplinary rehabilitation reports are integrated into the goal descriptions and whether this depends on the nature of the needs and problems. Design: Descriptive multiple-case study. Setting: Five Dutch paediatric rehabilitation facilities. Subjects: The rehabilitation profiles of 41 children with cerebral palsy aged between 4 and 8 years. Methods: The raw text data were extracted and organized, after which two raters independently linked the extracted content to the categories of the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). Matches between needs, problems and goals were identified by ICF-CY code comparisons. Results: The Cohen's kappas for ICF-CY encoding were all in the range of 'fair to good' (0.52-0.78). For five children (12%) no needs had been formulated and the reports of 10 (24%) were excluded from further analyses as they lacked a principal goal. In the 31 reports analysed, 29 (23%) need constructs and 46 (46%) problem constructs were incorporated into the goals. Of the total of 95 goal constructs 49 (52%) were not related to either a need or a problem construct. No clear relationship could be established between the type of needs and problems and their inclusion or exclusion in the principal goals. Conclusion: Overall, the integration of the needs and principal problems of children with their rehabilitation goals was not optimal. However, integration was difficult to objectify because needs, problems and goals were poorly documented