Monocyte Scintigraphy in Rheumatoid Arthritis: The Dynamics of Monocyte Migration in Immune-Mediated Inflammatory Disease

Background: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. Methods/Principal Findings: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99m-Tc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4x10(-3) (0.95-5.1x10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. Conclusions/Significance: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention

Understanding the unintended consequences of public health policies: the views of policymakers and evaluators

BACKGROUND: Public health policies sometimes have unexpected effects. Understanding how policies and interventions lead to outcomes is essential if policymakers and researchers are to intervene effectively and reduce harmful and other unintended consequences (UCs) of their actions. Yet, evaluating complex mechanisms and outcomes is challenging, even before considering how to predict assess and understand outcomes and UCs when interventions are scaled up. We aimed to explore with UK policymakers why some policies have UCs, and how researchers and policymakers should respond. METHODS: We convened a one-day workshop with 14 people involved in developing, implementing or evaluating social and public health policies, and/or evaluating possible unintended effects. This included senior evaluators, policymakers from government and associated agencies, and researchers, covering policy domains from public health, social policy, poverty, and international development. RESULTS: Policymakers suggested UCs happen for a range of reasons: poor policy design, unclear articulation of policy mechanisms or goals, or unclear or inappropriate evidence use, including evaluation techniques. While not always avoidable, it was felt that UCs could be partially mitigated by better use of theory and evidence, better involvement of stakeholders in concurrent design and evaluation of policies, and appropriate evaluation systems. CONCLUSIONS: UCs can be used to explore the mechanisms underpinning social change caused by public health policies. Articulating these mechanisms is essential for truly evidence-informed decision-making, to enable informed debate about policy options, and to develop evaluation techniques. Future work includes trying to develop a holistic stakeholder-led evaluation process

Prostate carcinoma metastatic to the skin as an extrammamary Paget's disease

Aim: The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified.Discussion and conclusions: We review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin.Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276. © 2012 Petcu et al.; licensee BioMed Central Ltd