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Pumpkin Center, NC, United States

Shelton P.Q.,Carolinas Medical Center | Ivanowicz A.N.,Carolinas Medical Center | Wakeman C.M.,Carolinas Medical Center | Rydberg M.G.,Carolinas Medical Center | And 5 more authors.

Objective: To review the efficacy of treating benign prostatic hyperplasia and very-low-risk prostate cancer (PCa) in patients receiving active surveillance and 5α-reductase inhibitor (5-ARI; finasteride or dutasteride) treatment. Materials and Methods: Eighty-two men with very-low-risk PCa (clinical stage T1c, Gleason score ≤6, <3 biopsy cores positive with ≤50% involvement, and prostate-specific antigen density ≤0.15 ng/mL/g) and benign prostatic hyperplasia (≥30 cm3) received active surveillance and were treated with a 5-ARI. Results: All 82 men completed 1 year of 5-ARI therapy (n = 79) or underwent early biopsy for cause (n = 3). Restaging biopsies were performed for 76 men (22 underwent a second restaging biopsy and 1 a third restaging biopsy), 4 patients were awaiting biopsy, and 2 were lost to follow-up before the first restaging biopsy. At the first restaging biopsy, of the 76 men, 41 (54%) had no PCa, 16 (21%) continued to have very-low-risk PCa, 15 (20%) had progressed to low-risk PCa (>2 cores positive and Gleason score ≤6), and 4 (5%) had progressed to intermediate-risk PCa (Gleason score 7). Of the 76 biopsies, 20 were performed early for cause, with 11 (55%) showing PCa progression. Of the 82 patients, 22 (27%) underwent treatment of PCa. Conclusion: Active surveillance of very-low-risk PCa in the setting of 5-ARI therapy for benign prostatic hyperplasia appears to be a safe therapeutic option, because most (57 of 82; 70%) patients maintained very-low-risk PCa or had negative follow-up biopsies during a 3-year follow-up period. Complementary to the Prostate Cancer Prevention Trial, our results indicate that 5-ARI therapy increases prostate-specific antigen sensitivity and can aid the clinician in appropriately targeting biopsies. © 2013 Elsevier Inc. All Rights Reserved. Source

Sun Y.,Carolinas Medical Center | Mauerhan D.R.,Carolinas Medical Center | Steuerwald N.M.,Cannon Research | Ingram J.,Carolinas Medical Center | And 2 more authors.
BioMed Research International

Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins. © 2014 Yubo Sun et al. Source

Neumann D.R.,Carolinas Rehabilitation | Hammond F.,Carolinas Rehabilitation | Hammond F.,Indiana University | Norton J.,Cannon Research | Blumenthal T.,Wake forest University
Journal of Head Trauma Rehabilitation

Objective: To determine the effectiveness of a modulated acoustic startle reflex paradigm with emotional imagery in studying physiological changes associated with emotional responses in persons with traumatic brain injury (TBI). Setting: Outpatient rehabilitation hospital. Participants: Six individuals with moderate to severe TBI. Mean age was 32 years and mean years postinjury were 9.9. Method: The modulated acoustic startle reflex procedure involved imagery of emotional scripts (joy, anger, fear, and neutral) followed by a startle noise, versus startle noise alone (no script). Measures: Eyeblink and skin conductance response, subjective arousal and valence ratings of the scripts, and general anger questionnaire. Results: Startle blink responses following anger imagery were significantly smaller than those following fear (P = .006) and neutral (P = .023) imagery. Skin conductance response did not change significantly based on the content of the scripts (P = .070). Conclusions: Large startle blink responses indicate avoidance of a stimulus. Our findings suggest that participants with TBI did not have an avoidant reaction to anger-inducing stimuli. Skin conductance response findings may imply arousal impairments. The modulated acoustic startle reflex was effective in measuring emotional responses; however, larger studies comparing persons with TBI with control groups are needed to further explore these findings. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Sun Y.,Cannon Research | Scannell B.P.,Cannon Research | Honeycutt P.R.,Cannon Research | Mauerhan D.R.,Cannon Research | And 2 more authors.
Open Rheumatology Journal

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. © Sun et al.; Licensee Bentham Open. Source

Sun Y.,Cannon Research | Roberts A.,Cannon Research | Mauerhan D.R.,Cannon Research | Sun A.R.,Cannon Research | And 2 more authors.
BioMed Research International

Phosphocitrate (PC) inhibited meniscal calcification and the development of calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the mechanisms remain elusive. This study sought to examine the biological activities of PC in the absence of calcium crystals and test the hypothesis that PC is potentially a meniscal protective agent. We found that PC downregulated the expression of many genes classified in cell proliferation, ossification, prostaglandin metabolic process, and wound healing, including bloom syndrome RecQ helicase-like, cell division cycle 7 homolog, cell division cycle 25 homolog C, ankylosis progressive homolog, prostaglandin-endoperoxide synthases-1/cyclooxygenase-1, and plasminogen activator urokinase receptor. In contrast, PC stimulated the expression of many genes classified in fibroblast growth factor receptor signaling pathway, collagen fibril organization, and extracellular structure organization, including fibroblast growth factor 7, collagen type I, alpha 1, and collagen type XI, alpha 1. Consistent with its effect on the expression of genes classified in cell proliferation, collagen fibril organization, and ossification, PC inhibited the proliferation of OA meniscal cells and meniscal cell-mediated calcification while stimulating the production of collagens. These findings indicate that PC is potentially a meniscal-protective agent and a disease-modifying drug for arthritis associated with severe meniscal degeneration. © 2013 Yubo Sun et al. Source

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