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

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity

Robin A Laskey,1 Scott D Richard,2 Ashlee L Smith,1 Jeff F Lin,1 Tiffany L Beck,3 Jamie L Lesnock,1 Joseph L Kelley 3rd,1 Alexander B Olawaiye,1 Paniti Sukumvanich,1 Thomas C Krivak4 1Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, 2Division of Gynecologic Oncology, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, 3Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of UPMC, Pittsburgh, 4Division of Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, PA, USA Purpose: Bevacizumab (Bev) is associated with improved progression-free survival in advanced epithelial ovarian cancer. The use of Bev in patients with gynecologic malignancy is increasing; however, little is known about cumulative toxicity and response in patients retreated with Bev. Our goal was to determine cumulative side effects and response in patients retreated with Bev. Patients and methods: Women with recurrent gynecologic malignancy treated with Bev between January 2007 and March 2012 at a single institution were identified, including a subset who received Bev in a subsequent regimen. The primary outcome was Bev-associated toxicity, and the secondary outcome was response. Results: Of 83 patients that received Bev for recurrent disease, 23 were retreated with Bev and four received Bev maintenance. Three patients (13%) developed grade 3 or 4 hypertension; all had a history of chronic hypertension. One (4.3%) patient developed grade 3 proteinuria, and one (4.3%) developed an enterovaginal fistula. Four patients discontinued Bev secondary to toxicity. Toxicity was not related to the cumulative number of cycles. Twenty-six percent of patients responded to Bev retreatment. On univariate analysis, there was a significant (P=0.003) overall survival advantage when the Bev-free interval was >9 months (95% confidence interval [CI] 4.9–43.7) compared to ≤9 months (95% CI 2.1–11.5), 24.3 months, and 6.8 months. Conclusion: Retreatment of patients with recurrent gynecologic malignancy with Bev did not increase morbidity and was associated with treatment response. Physicians treating women with recurrent disease may consider a Bev-containing regimen even if prior regimen(s) included Bev. Future studies should prospectively evaluate the efficacy of this treatment strategy. Keywords: bevacizumab, gynecologic malignancy, cumulative toxicity, treatment respons

Changes in paraspinal muscles and their association with low back pain and spinal degeneration: CT study

The objectives of the study were to evaluate the association between lumbar paraspinal muscle density, evaluated on computed tomography (CT) and age, sex and BMI; and to evaluate the association of those changes with low back pain (LBP) and spinal degeneration features in a community-based sample. This study was an ancillary project to the Framingham Study. A sample of 3,529 participants aged 40–80 years had a CT scan performed to assess aortic calcification. 187 individuals were randomly enrolled in this study. LBP in the last 12 months was evaluated using self-report questionnaire. Density (in Hounsfield units) of multifidus and erector spinae was evaluated on CT. The prevalence of intervertebral disc narrowing, facet joint osteoarthritis (FJOA), spondylolysis, spondylolisthesis and spinal stenosis were also evaluated. We used linear regression models to examine the association of paraspinal muscles density with age, sex, BMI, LBP, and spinal degeneration features. The results show that in our study, men have higher density of paraspinal muscles than women, younger individuals have higher density than older ones and individuals with lower weight have higher muscle density than overweight. No differences between individuals with and without LBP were found. Significant association was found between L4 multifidus/erector spinae density and FJOA at L4–L5; between multifidus at L4 and spondylolisthesis at L4–5; and between erector spinae at L4 and L5 with disc narrowing at L4–5 and L5–S1, respectively. We conclude that the paraspinal muscle density decreases with age, and increases BMI. It is associated with at some levels FJOA, spondylolisthesis and disc narrowing at the same level, but not associated with occurrence of LBP