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

The Role of Antibiotics in Nasal Fractures after Closed Reduction

Background:. Nasal fractures represent the most common fracture in facial trauma. The role of prophylactic antibiotics in these injuries is debated, given low infection rates and demonstrated risks of antibiotics. We studied the isolated effect of prophylactic antibiotics on infection rate in patients with nasal fracture after closed reduction. Methods:. Retrospective cohort study of a prospectively maintained facial trauma database was conducted. Demographics, comorbidities, fracture classifications, and management of patients who received antibiotics at the time of closed nasal reduction were compared against those who did not receive antibiotics. Infection rates between groups were analyzed. Multivariate analysis was conducted to control for confounding variables. Qualitative analysis was performed for patients who experienced infection following nasal fracture. Results:. A total of 282 patients met inclusion criteria (n = 144, antibiotic; n = 138, nonantibiotic). Six patients experienced infection. There was no difference in infection rate between antibiotic and nonantibiotic groups (2.0% versus 2.2%; P = 0.90). On multivariate regression, antibiotics did not significantly decrease odds of infection (OR 1.7 [0.17–13.6]; P = 0.64). Moreover, patients with open nasal fractures did not have significantly higher odds of infection (OR 1.9 [0.08–20.8]; P = 0.64). Similarly, increasing severity of injury based on Rohrich classification did not significantly impact odds of infection (OR 0.68 [0.23–1.9]; P = 0.46). All six infections were managed at the bedside, with zero infections following operating room management (P = 0.32). Conclusions:. Prophylactic antibiotics do not decrease infection rates following nasal fractures managed by closed reduction. Bedside management may be a risk factor for the development of infection; however, this finding requires further evaluation

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture

Vitamin D and cancer: the promise not yet fulfilled

The negative association of the latitude where people live and the incidence of non cutaneous cancer in that population in North America has been demonstrated in many studies for many types of cancer. Since the intensity of UVB exposure decreases with increasing latitude, and UVB exposure provides the mechanism for vitamin D production in the skin, the hypothesis that increased vitamin D provides protection against the development of cancer has been proposed. This hypothesis has been tested in a substantial number of prospective and case control studies and in a few randomized clinical trials (RTC) assessing whether either vitamin D intake or serum levels of 25 hydroxyvitamin D (25OHD) correlate (inversely) with cancer development. Most of the studies have focused on colorectal, breast, and prostate cancer. The results have been mixed. The most compelling data for a beneficial relationship between vitamin D intake or serum 25OHD levels and cancer have been obtained for colorectal cancer. The bulk of the evidence also favors a beneficial relationship for breast cancer, but the benefit of vitamin D for prostate and skin cancer in clinical populations has been difficult to demonstrate. RTCs in general have been flawed in execution or too small to provide compelling evidence one way or the other. In contrast, animal studies have been quite consistent in their demonstration that vitamin D and/or its active metabolite 1,25 dihydroxyvitamin D (1,25(OH)(2)D) can prevent the development and/or treat a variety of cancers in a variety of animal models. Furthermore, 1,25(OH)(2)D has been shown to impact a number of cellular mechanisms that would be expected to underlie its anticancer effects. Thus there is a dilemma animal and cellular studies strongly support a role for vitamin D in the prevention and treatment of cancer, but the clinical studies for most cancers have not yet delivered compelling evidence that the promise from preclinical studies has been fulfilled in the clinic