Birmingham Veteran Affairs Medical Center

Birmingham, AL, United States

Birmingham Veteran Affairs Medical Center

Birmingham, AL, United States
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Zhang J.,University of Alabama at Birmingham | Xie F.,University of Alabama at Birmingham | Delzell E.,University of Alabama at Birmingham | Chen L.,University of Alabama at Birmingham | And 6 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti-tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. Objective: To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. Design, Setting, and Patients: Retrospective cohort study of 463 541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. Main Outcome Measures: Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. Results: Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. Conclusions: Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up. © 2012 American Medical Association. All rights reserved.

Ahmed M.I.,University of Alabama at Birmingham | Desai R.V.,University of Alabama at Birmingham | Gaddam K.K.,University of Alabama at Birmingham | Venkatesh B.A.,Auburn University | And 10 more authors.
JACC: Cardiovascular Imaging | Year: 2012

Objectives: The goal of this study was to define the mechanism of preserved ejection fraction (EF) despite depressed myocardial strains in hypertension (HTN). Background: Concentric left ventricular (LV) remodeling in HTN may have normal or supranormal EF despite depressed myocardial strains. The reason for such discordance is not clear. The aim of this study was to comprehensively evaluate the LV mechanics in a well-defined HTN population to define underlying reasons for such a paradox. Methods: Sixty-seven patients with resistant HTN and 45 healthy control subjects were studied by cardiac magnetic resonance imaging and tissue tagging with 3-dimensional analysis. Amplitude and directional vector of longitudinal (Ell), circumferential (Ecc), and principal strain for maximal shortening (E3) were computed at basal, mid, and distal LV levels, respectively. LV torsion, defined as the rotation angle of apex relative to base, and LV twist, which accounts for the effects of differential LV remodeling on torsion for comparison among the 2 groups, were also calculated. Results: LV mass index and LV mass/LV end-diastolic volume ratio were significantly higher in the HTN group compared with controls, consistent with concentric LV remodeling. Ell and Ecc were significantly decreased in amplitude with altered directional vector in HTN compared with controls. However, the amplitude of E3 was similar in the 2 groups. Torsion and twist were significantly higher in HTN, which was mainly due to increase in apical rotation. The HTN group demonstrated significantly increased LV wall thickening compared with controls that resulted in greater LVEF in the HTN group compared with controls (70% vs. 65%, p < 0.001, respectively). Conclusions: In compensated LV remodeling secondary to HTN, there is increased LV wall thickening with preserved E3 and increased torsion compared with normal controls. This, therefore, contributes to supranormal LVEF in HTN despite depressed longitudinal and circumferential strains. © 2012 American College of Cardiology Foundation.

Schiros C.G.,Auburn University | Dell'Italia L.J.,Birmingham Veteran Affairs Medical Center | Dell'Italia L.J.,University of Alabama at Birmingham | Gladden J.D.,University of Alabama at Birmingham | And 9 more authors.
Circulation | Year: 2012

Background-Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. Methods and Results-Ninety-four patients (age, 54±11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44±14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61±7% to 54±8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. Conclusions-Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR. © 2012 American Heart Association, Inc.

Vaid M.,University of Alabama at Birmingham | Sharma S.D.,University of Alabama at Birmingham | Katiyar S.K.,University of Alabama at Birmingham | Katiyar S.K.,Birmingham Veteran Affairs Medical Center
Cancer Prevention Research | Year: 2010

Dietary grape seed proanthocyanidins (GSP) inhibit photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. As ultraviolet B (UVB)-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) has been implicated in skin cancer risk, we studied whether dietary GSPs enhance repair of UVB-induced DNA damage and, if so, what is the potential mechanism? Supplementation of GSPs (0.5%, w/w) with AIN76A control diet significantly reduced the levels of CPD + cells in UVB-exposed mouse skin; however, GSPs did not significantly reduce UVB-induced CPD + cells in the skin of interleukin-12p40 (IL-12) knockout (KO) mice, suggesting that IL-12 is required for the repair of CPDs by GSPs. Using IL-12 KO mice and their wild-type counterparts and standard photocarcinogenesis protocol, we found that supplementation of control diet with GSPs (0.5%, w/w) significantly reduced UVB-induced skin tumor development in wild-type mice, which was associated with the elevated mRNA levels of nucleotide excision repair genes, such as XPA, XPC, DDB2, and RPA1; however, this effect of GSPs was less pronounced in IL-12 KO mice. Cytostaining analysis revealed that GSPs repaired UV-induced CPD + cells in xeroderma pigmentosum complementation group A (XPA)-proficient fibroblasts from a healthy individual but did not repair in XPA-deficient fibroblasts from XPA patients. Furthermore, GSPs enhance nuclear translocation of XPA and enhanced its interactions with other DNA repair protein ERCC1. Together, our findings reveal that prevention of photocarcinogenesis by GSPs is mediated through enhanced DNA repair in epidermal cells by IL-12- and XPA-dependent mechanisms. ©2010 AACR.

Ahmed M.I.,University of Alabama at Birmingham | Aban I.,University of Alabama at Birmingham | Lloyd S.G.,University of Alabama at Birmingham | Lloyd S.G.,Birmingham Veteran Affairs Medical Center | And 12 more authors.
Journal of the American College of Cardiology | Year: 2012

The purpose of the study was to evaluate the effect of long-term β 1-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR). Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function. Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or β 1-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate. Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the β 1-AR blockade group required mitral valve surgery (p = 0.23). β 1-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428) © 2012 American College of Cardiology Foundation.

Ahmed M.I.,University of Alabama at Birmingham | Gladden J.D.,University of Alabama at Birmingham | Litovsky S.H.,University of Alabama at Birmingham | Lloyd S.G.,University of Alabama at Birmingham | And 7 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: This study assessed myocardial damage in patients with chronic isolated mitral regurgitation (MR) and left ventricular ejection fraction (LVEF) >60%. Background: Typically, MR patients have decreased LVEF after mitral valve (MV) repair despite normal pre-operative LVEF. Methods: Twenty-seven patients with isolated MR had left ventricular (LV) biopsies taken at time of MV repair. Magnetic resonance imaging with tissue tagging was performed in 40 normal subjects and in MR patients before and 6 months after MV repair. Results: LVEF (66 ± 5% to 54 ± 9%, p < 0.0001) and LV end-diastolic volume index (108 ± 28 ml/m2 to 78 ± 24 ml/m2, p < 0.0001) decreased, whereas left ventricular end-systolic (LVES) volume index was 60% above normal pre- and post-MV repair (p < 0.05). The LV circumferential and longitudinal strain rates decreased below normal following MV repair (6.38 ± 1.38 vs. 5.11 ± 1.28, p = 0.0009, and 7.51 ± 2.58 vs. 5.31 ± 1.61, percentage of R to R interval, p < 0.0001), as LVES stress/LVES volume index ratio was depressed at baseline and following MV repair versus normal subjects (0.25 ± 0.10 and 0.28 ± 0.05 vs. 0.33 ± 0.12, p < 0.01). LV biopsies demonstrated cardiomyocyte myofibrillar degeneration versus normal subjects (p = 0.035). Immunostaining and immunoblotting demonstrated increased xanthine oxidase in MR versus normal subjects (p < 0.05). Lipofuscin deposition was increased in cardiomyocytes of MR versus normal subjects (0.62 ± 0.20 vs. 0.33 ± 0.11, percentage of area: p < 0.01). Conclusions: Decreased LV strain rates and LVES wall stress/LVES volume index following MV repair indicate contractile dysfunction, despite pre-surgical LVEF >60%. Increased oxidative stress could cause myofibrillar degeneration and lipofuscin accumulation resulting in LV contractile dysfunction in MR. © 2010 American College of Cardiology Foundation.

Sharma S.D.,Birmingham Veteran Affairs Medical Center | Katiyar S.K.,Birmingham Veteran Affairs Medical Center | Katiyar S.K.,University of Alabama at Birmingham
Pharmaceutical Research | Year: 2010

Purpose: The purpose of this study was to determine the chemopreventive mechanism of dietary grape seed proanthocyanidins (GSPs) against ultraviolet (UV) radiation-induced skin tumor development in mice. Methods: Six-to-seven-week-old SKH-1 hairless mice were subjected to photocarcinogenesis protocol, and exposed to UVB radiation (180 mJ/cm2) three times/week for 24 weeks. Mice were fed a standard AIN76A control diet with or without supplementation with grape seed proanthocyanidins (GSPs; 0.2% or 0.5%, w/w). At the termination of the experiment, mice were sacrificed, and skin and skin tumor samples were harvested and subjected to the analysis of biomarkers related to inflammation using immunostaining, western blot analysis, ELISA and real-time PCR. Results: Dietary GSPs inhibited UVB-induced infiltration of proinflammatory leukocytes and the levels of myeloperoxidase, cyclooxygenase-2 (COX-2), prostaglandin (PG) E2, cyclin D1 and proliferating cell nuclear antigen (PCNA) in the skin and skin tumors compared to non-GSPs-treated UVB irradiated mouse skin and skin tumors. GSPs also significantly inhibited the levels of proinflammatory cytokines, tumor necrosis factor-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001), in UVB-exposed skin and skin tumors. Conclusion: The results from this study clearly suggest that dietary GSPs inhibit photocarcinogenesis in mice through the inhibition of UVB-induced inflammation and mediators of inflammation in mouse skin. © 2010 Springer Science+Business Media, LLC.

Vaid M.,University of Alabama at Birmingham | Sharma S.D.,University of Alabama at Birmingham | Katiyar S.K.,University of Alabama at Birmingham | Katiyar S.K.,Birmingham Veteran Affairs Medical Center
Carcinogenesis | Year: 2010

To develop newer and more effective chemopreventive agents for skin cancer, we assessed the effect of honokiol, a phytochemical from the Magnolia plant, on ultraviolet (UV) radiation-induced skin tumorigenesis using the SKH-1 hairless mouse model. Topical treatment of mice with honokiol in a hydrophilic cream-based topical formulation before or after UVB (180 mJ/cm2) irradiation resulted in a significant protection against photocarcinogenesis in terms of tumor multiplicity (28-60%, P < 0.05 to <0.001) and tumor volume per tumor-bearing mouse (33-80%, P < 0.05 to 0.001, n = 20). Honokiol also inhibited and delayed the malignant progression of papillomas to carcinomas. To investigate the in vivo molecular targets of honokiol efficacy, tumors and tumoruninvolved skin samples from the tumor-bearing mice were analyzed for inflammatory mediators, cell cycle regulators and survival signals using immunostaining, western blotting and enzyme-linked immunosorbent assay. Treatment with honokiol significantly inhibited UVB-induced expression of cyclooxygenase-2, prostaglandin E2 (P < 0.001), proliferating cell nuclear antigen and proinflammatory cytokines, such as tumor necrosis factor-α (P < 0.001), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.001) in the skin as well as in skin tumors. Western blot analysis revealed that honokiol: (i) inhibited the levels of cyclins D1, D2 and E and associated cyclin-dependent kinases (CDKs)2, CDK4 and CDK6, (ii) upregulated Cip/p21 and Kip/p27 and (iii) inhibited the levels of phosphatidylinositol 3-kinase and the phosphorylation of Akt at Ser473 in UVB-induced skin tumors. Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin. © The Author 2010. Published by Oxford University Press. All rights reserved.

Barnes J.,University of Alabama at Birmingham | Dell'Italia L.J.,Birmingham Veteran Affairs Medical Center | Dell'Italia L.J.,University of Alabama at Birmingham
American Journal of the Medical Sciences | Year: 2014

Mitral regurgitation and other conditions marked by a pure isolated volume overload (VO) of the heart result in a progressive form of eccentric left ventricular remodeling and dysfunction. As opposed to the more extensively studied pressure overload, there are no approved medical therapies because an understanding of the underlying pathological mechanisms at work in VO is lacking. Over the past 20 years, our laboratory has identified multiple key biological functions involved in the pathological remodeling in VO. Specifically, we have noted perturbed matrix homeostasis, detrimental adrenergic signaling, increased intracellular reactive oxygen species and an intense inflammatory response that implicates mast cells and their product chymase, which seems to cause extensive remodeling both inside and outside the cardiomyocyte. How these multiple pathways intersect over the course of VO and their response to various single and combined interventions are now the subject of intense investigation. © 2014 Lippincott Williams and Wilkins.

Hage F.G.,University of Alabama at Birmingham | Hage F.G.,Birmingham Veteran Affairs Medical Center | Mansur S.J.,Princeton Baptist Medical Center | Xing D.,University of Alabama at Birmingham | Oparil S.,University of Alabama at Birmingham
Kidney International Supplements | Year: 2013

Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. © 2013 International Society of Nephrology.

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