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Cauley K.A.,Columbia Presbyterian Medical Center | Cataltepe O.,University of Massachusetts Medical School
American Journal of Roentgenology

OBJECTIVE. Hydrocephalus causes changes in the diffusion-tensor properties of periventricular white matter. Understanding the nature of these changes may aid in the diagnosis and treatment planning of this relatively common neurologic condition. Because ventricular size is a common measure of the severity of hydrocephalus, we hypothesized that a quantitative correlation could be made between the ventricular size and diffusion-tensor changes in the periventricular corona radiata. In this article, we investigated this relationship in adult patients with hydrocephalus and in healthy adult subjects. MATERIALS AND METHODS. Diffusion-tensor imaging metrics of the corona radiata were correlated with ventricular size in 14 adult patients with acute hydrocephalus, 16 patients with long-standing hydrocephalus, and 48 consecutive healthy adult subjects. Regression analysis was performed to investigate the relationship between ventricular size and the diffusion-tensor metrics of the corona radiata. Subject age was analyzed as a covariable. RESULTS. There is a linear correlation between fractional anisotropy of the corona radiata and ventricular size in acute hydrocephalus (r = 0.784, p < 0.001), with positive correlation with axial diffusivity (r = 0.636, p = 0.014) and negative correlation with radial diffusivity (r = 0.668, p = 0.009). In healthy subjects, axial diffusion in the periventricular corona radiata is more strongly correlated with ventricular size than with patient age (r = 0.466, p < 0.001, compared with r = 0.058, p = 0.269). CONCLUSION. Axial diffusivity of the corona radiata is linearly correlated with ventricular size in healthy adults and in patients with hydrocephalus. Radial diffusivity of the corona radiata decreases linearly with ventricular size in acute hydrocephalus but is not significantly correlated with ventricular size in healthy subjects or in patients with long-standing hydrocephalus. © American Roentgen Ray Society. Source

Chalmers S.A.,Yeshiva University | Chitu V.,Yeshiva University | Herlitz L.C.,Columbia Presbyterian Medical Center | Sahu R.,Feinstein Institute for Medical Research | And 2 more authors.
Journal of Autoimmunity

Kidney involvement affects 40-60% of patients with lupus, and is responsible for significant morbidity and mortality. Using depletion approaches, several studies have suggested that macrophages may play a key role in the pathogenesis of lupus nephritis. However, "off target" effects of macrophage depletion, such as altered hematopoiesis or enhanced autoantibody production, impeded the determination of a conclusive relationship. In this study, we investigated the role of macrophages in mice receiving rabbit anti-glomerular antibodies, or nephrotoxic serum (NTS), an experimental model which closely mimics the immune complex mediated disease seen in murine and human lupus nephritis. GW2580, a selective inhibitor of the colony stimulating factor-1 (CSF-1) receptor kinase, was used for macrophage depletion. We found that GW2580-treated, NTS challenged mice did not develop the increased levels of proteinuria, serum creatinine, and BUN seen in control-treated, NTS challenged mice. NTS challenged mice exhibited significantly increased kidney expression of inflammatory cytokines including RANTES, IP-10, VCAM-1 and iNOS, whereas GW2580-treated mice were protected from the robust expression of these inflammatory cytokines that are associated with lupus nephritis. Quantification of macrophage related gene expression, flow cytometry analysis of kidney single cell suspensions, and immunofluorescence staining confirmed the depletion of macrophages in GW2580-treated mice, specifically within renal glomeruli. Our results strongly implicate a specific and necessary role for macrophages in the development of immune glomerulonephritis mediated by pathogenic antibodies, and support the development of macrophage targeting approaches for the treatment of lupus nephritis. © 2014 Elsevier Ltd. Source

Gnanaraj J.F.,Internal Medicine Residency Program | Von Haehling S.,Charite - Medical University of Berlin | Anker S.D.,Charite - Medical University of Berlin | Anker S.D.,Center for Clinical and Basic Research | And 2 more authors.
Kidney International

Worsening renal function (WRF) during the treatment of acute decompensated heart failure (ADHF) occurs in up to a third of patients and is associated with worse survival. Venous congestion is increasingly being recognized as a key player associated with WRF in ADHF. Understanding the hemodynamic effects of venous congestion and the interplay between venous congestion and other pathophysiological factors such as raised abdominal pressure, endothelial cell activation, anemia/ iron deficiency, sympathetic overactivity, and stimulation of the renin-angiotensin-aldosterone system will help in devising effective management strategies. Early recognition of venous congestion through novel techniques such as bioimpedance measurements and remote monitoring of volume status combined with customized diuretic regimens may prevent venous congestion and perhaps avoid significant WRF. © 2012 International Society of Nephrology. Source

Armstrong A.J.,Duke University | Eisenberger M.A.,Johns Hopkins University | Halabi S.,Duke University | Oudard S.,University of Paris Descartes | And 4 more authors.
European Urology

Context: We have recently witnessed a rapid increase in the number of effective systemic agents for men with metastatic castration-resistant prostate cancer (CRPC), including novel hormonal therapies (abiraterone acetate and MDV3100), immunotherapies (sipuleucel-T), chemotherapies (cabazitaxel), and bone microenvironment targeting agents (denosumab, radium 223). Given the increasing complexity of treatment decisions for this disease, major research and clinical priorities are (1) finding biomarkers that enable an understanding of the natural history and complex biology of this heterogeneous malignancy, (2) defining predictive biomarkers that identify men most likely to benefit from a given therapy, and (3) identifying biomarkers of early response or progression to optimize outcomes. Objective: In this review, we discuss existing and potential biomarkers in CRPC and how they may currently inform prognosis, aid in treatment selection (predictive value), and relate to survival outcomes (surrogacy). Evidence acquisition: PubMed-based literature searches and abstracts through September 2011 provided the basis for this literature review as well as expert opinion. Evidence synthesis: We address blood and urine-based biomarkers such as prostate-specific antigen, lactate dehydrogenase, total and bone alkaline phosphatase and other bone turnover markers, hemoglobin, and circulating tumor cells in the context of prognosis, prediction, and patient selection for therapy. Given the inherent problems associated with defining progression-free survival in CRPC, the importance of biomarker development and the needed steps are highlighted. We place the discussion of biomarkers within the context of the design/intent of a trial and mechanism of action of a given systemic therapy. We discuss novel biomarker development and the pathway for surrogate or predictive biomarkers to become credentialed as useful tests that inform therapeutic decisions. Conclusions: A greater understanding of biomarkers in CRPC permits a more personalized approach to care that maximizes benefit and minimizes harm and can inform clinical trials tailored to men most likely to derive benefit. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. Source

Nikulina V.,John Jay College of Criminal Justice | Nikulina V.,Columbia Presbyterian Medical Center | Widom C.S.,John Jay College of Criminal Justice | Czaja S.,John Jay College of Criminal Justice
American Journal of Community Psychology

This study examines the roles of childhood neglect and childhood poverty (family and neighborhood) in predicting Posttraumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), academic achievement, and crime in young adulthood. Using existing data from a prospective cohort design study, 1,005 children with documented histories of neglect (N = 507) and matched controls (N = 497) were interviewed in young adulthood (mean age 29). Official criminal histories were also used to assess outcomes. Data were analyzed using logistic and ordinary least squares regressions and hierarchical linear modeling (HLM) to control for neighborhood clustering. Results from HLM revealed that childhood neglect and childhood family poverty uniquely predicted PTSD and adult arrest, MDD was predicted only by childhood family poverty, and a significant interaction between childhood family poverty and childhood neighborhood poverty predicted academic achievement for the control group only. Childhood neglect, childhood family poverty, and childhood neighborhood poverty each contribute to poor outcomes later in life. While interventions should be developed for neglected children to prevent negative outcomes, the current findings suggest that it is also important to consider the ecological context in which these children are growing up. © 2010 Society for Community Research and Action. Source

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