OUHSC

Oklahoma, OK, United States
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Gardner A.W.,The University of Oklahoma Health Sciences Center | Montgomery P.S.,The University of Oklahoma Health Sciences Center | Zhao Y.D.,OUHSC | Silva-Palacios F.,Cardiovascular Section | And 3 more authors.
Journal of Vascular Surgery | Year: 2017

Objective: The primary aim of the study was to assess whether both the amount and pace of daily walking were associated with circulating antioxidant capacity in symptomatic patients with peripheral artery disease (PAD). Methods: Community-based walking was measured in 244 men and women who were limited by symptomatic PAD during a 1-week period in which they wore an ankle-mounted step activity monitor. Patients were further characterized by circulating antioxidant capacity with the OxiSelect (Cell Biolabs Inc, San Diego, Calif) hydroxyl radical antioxidant capacity (HORAC) activity assay. Results: To assess the amount of walking, patients were grouped into low (≤2440 strides/d), middle (2441-3835 strides/d), and high (>3835 strides/d) stride tertiles. HORAC was higher in the middle (P = .03) and high (P = .01) stride tertiles than in the low tertile, but there was no difference between middle and high tertiles (P = .44). To assess the pace of walking, patients were grouped into slow (<25.0 strides/min), middle (25.0-31.6 strides/min), and fast (>31.6 strides/min) cadence tertiles. HORAC was higher in the high cadence tertile than in the low (P < .01) and middle (P < .01) tertiles, but there was no difference between low and middle tertiles (P = .48). Similar findings were obtained on group differences in HORAC after adjusting for age, sex, race, and ankle-brachial index for both the amount and pace of daily walking. Conclusions: Walking >2440 strides each day and walking at a cadence faster than 31.6 strides/min for 30 minutes each day are both associated with greater circulating antioxidant capacity in symptomatic patients with PAD. The clinical significance is that a home-based walking program may be one approach to increase endogenous antioxidant capacity. © 2017 Society for Vascular Surgery.


Gardner A.W.,University of Oklahoma | Parker D.E.,OUHSC | Montgomery P.S.,University of Oklahoma | Khurana A.,Cardiovascular Section | And 2 more authors.
Journal of Vascular Surgery | Year: 2010

Objectives: To compare the pattern of daily ambulatory activity in men and women with intermittent claudication, and to determine whether calf muscle hemoglobin oxygen saturation (StO 2) is associated with daily ambulatory activity. Methods: Forty men and 41 women with peripheral arterial disease limited by intermittent claudication were assessed on their community-based ambulatory activity patterns for 1 week with an ankle-mounted step activity monitor and on calf muscle StO 2 during a treadmill test. Results: Women had lower adjusted daily maximal cadence (mean ± SE) for 5 continuous minutes of ambulation (26.2 ± 1.2 strides/min vs 31.0 ± 1.2 strides/min; P = .009), for 1 minute of ambulation (43.1 ± 0.9 strides/min vs 47.2 ± 0.9 strides/min; P = .004), and for intermittent ambulation determined by the peak activity index (26.3 ± 1.2 strides/min vs 31.0 ± 1.2 strides/min; P = .009). Women also had lower adjusted time to minimum calf muscle StO 2 during exercise (P = .048), which was positively associated with maximal cadence for 5 continuous minutes (r = 0.51; P < .01), maximal cadence for 1 minute (r = 0.42; P < .05), and peak activity index (r = 0.44; P < .05). These associations were not significant in men. Conclusion: Women with intermittent claudication ambulate slower in the community setting than men, particularly for short continuous durations of up to 5 minutes and during intermittent ambulation at peak cadences. Furthermore, the daily ambulatory cadences of women are correlated with their calf muscle StO 2 during exercise, as women who walk slower in the community setting reach their minimum calf muscle StO 2 sooner than those who walk at faster paces. Women with intermittent claudication should be encouraged to not only walk more on a daily basis, but to do so at a pace that is faster than their preferred speed. Copyright © 2010 by the Society for Vascular Surgery.


Gardner A.W.,The University of Oklahoma Health Sciences Center | Gardner A.W.,Veterans Affairs Medical Center | Parker D.E.,OUHSC | Montgomery P.S.,The University of Oklahoma Health Sciences Center | Blevins S.M.,General Internal Medicine Section
Journal of Vascular Surgery | Year: 2014

Background It is not clear whether subgroups of patients with peripheral artery disease (PAD) and claudication respond more favorably to exercise rehabilitation than others. We determined whether sex and diabetes were factors associated with the response to exercise rehabilitation in patients with claudication. Methods Eighty patients were randomized to home-based and supervised exercise programs, and 60 finished with complete exercise intervention data. Exercise consisted of intermittent walking to near maximal claudication pain for 3 months. Primary outcome measures included claudication onset time (COT) and peak walking time. Patients were partitioned into diabetic and nondiabetic groups and then further partitioned by sex to form four groups. Results Overall, exercise adherence was high (84%), and there was no significant difference (P >.05) in the amount of exercise completed among the four groups. All groups had significant improvements (P <.05) in COT and peak walking time after exercise rehabilitation, except for diabetic women (P >.05). Only 37% of women with diabetes had an increase in COT compared with 100% of men with diabetes (P <.01), and their risk ratio for nonresponse was 9.2 (P <.0001). Conclusions Women with PAD and claudication, particularly those with diabetes, represent a vulnerable subgroup of patients who respond poorly to a program of exercise rehabilitation. Diabetic women with PAD and claudication may need a greater dose of exercise or another intervention separate from or in combination with exercise to elicit improvements in claudication measures that are similar to nondiabetic women and to diabetic and nondiabetic men. © 2014 by the Society for Vascular Surgery.


Gardner A.W.,The University of Oklahoma Health Sciences Center | Gardner A.W.,Veterans Affairs Medical Center | Alaupovic P.,Oklahoma Medical Research Foundation | Parker D.E.,OUHSC | And 3 more authors.
International Journal of Vascular Medicine | Year: 2013

Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n=17) or untreated (n=12) with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P<0.05) and lower values of Lp-A-I:A-II (P<0.05) than controls. The PAD group taking statins had lower age-adjusted values for apoB (P<0.05), Lp-A-II:B:C:D:E (P<0.05), Lp-B:E + Lp-B:C:E (P<0.05), Lp-B:C (P<0.05), and Lp-A-I (P<0.05) than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670. © 2013 Andrew W. Gardner et al.


PubMed | Oklahoma Medical Research Foundation and OUHSC
Type: Journal Article | Journal: PloS one | Year: 2015

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardts disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic.


Gardner A.W.,The University of Oklahoma Health Sciences Center | Gardner A.W.,Veterans Affairs Medical Center | Parker D.E.,OUHSC | Montgomery P.S.,The University of Oklahoma Health Sciences Center | And 5 more authors.
International Journal of Vascular Medicine | Year: 2014

We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 156 subjects with peripheral artery disease (PAD) and 16 healthy control subjects. Furthermore, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the two groups. The PAD group had a 164% higher value for endothelial cell apoptosis (P < 0.001) and a 62% higher value for endothelial cellular reactive oxygen species production (P < 0.001) than the control group. Furthermore, the PAD group had lower systemic antioxidant capacity measured by hydroxyl radical antioxidant capacity activity (P < 0.001), higher inflammatory and vascular measures of high-sensitivity C-reactive protein (P < 0.001), interleukin-8 (P < 0.001), serum amyloid A (P < 0.001), vascular cell adhesion molecule-1 (P < 0.001), adiponectin (P < 0.001), apolipoprotein B (P = 0.013), apolipoprotein CIII (P = 0.035), lower vascular endothelial growth factor-A (P < 0.001), and hepatocyte growth factor (P < 0.001) than the control group. Subjects with PAD have greater endothelial apoptosis and oxidative stress than control subjects with low burden of comorbid conditions and cardiovascular risk factors. Furthermore, subjects with PAD have lower systemic antioxidant capacity and angiogenic measures and higher circulating inflammatory parameters. © 2014 Andrew W. Gardner et al.


PubMed | The University of Oklahoma Health Sciences Center, State University of New York at Buffalo, Cardiovascular Section and OUHSC
Type: Journal Article | Journal: Journal of clinical & translational endocrinology | Year: 2016

To determine whether diabetes and sex were factors associated with ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication.Ambulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, 6-minute walk test, and 4-meter walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers.Men and women with diabetes had greater prevalence (p = 0.007 and p = 0.015, respectively) of coronary artery disease (CAD) than patients without diabetes. To assure that this difference did not influence planned comparisons, the data set was stratified on CAD. Diabetic men with CAD had a lower peak walking time (PWT) during the treadmill test and a slower 4-meter gait speed compared to non-diabetic men with CAD (p < 0.05). Diabetic women with CAD had a lower PWT compared to their non-diabetic counterparts (p < 0.01). Additionally, diabetic men with CAD had higher pigment epithelium-derived factor (p < 0.05) than their non-diabetic counterparts, and diabetic women with CAD had higher leptin (p < 0.01) and interleukin-8 levels (p < 0.05).In patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF.


Mellis A.M.,OUHSC
The Journal of the Oklahoma State Medical Association | Year: 2011

Ewing sarcoma, also referred to as primitive neuroectodermal tumor (PNET), is a malignancy, histologically characterized by Homer-Wright rosettes and small round cells, that presents most commonly in bone or soft tissue in the pediatric and adolescent populations. We report the case of a patient that presents with intermittent gross hematuria, abdominal mass and elevated blood pressure. After surgical excision of the renal mass, the rare finding of a primary renal Ewing's sarcoma was discovered. After surgery the patient was additionally treated with chemotherapy. After presenting this case, we briefly discuss the unique case of isolated renal Ewing's sarcoma, including incidence and treatment.


Conley S.M.,OUHSC | Al-Ubaidi M.R.,OUHSC | Han Z.,OUHSC | Naash M.I.,OUHSC
FASEB Journal | Year: 2014

Retinal degeneration slow (RDS/PRPH2) is critical for the formation of the disc/lamella rim in photoreceptor outer segments (OSs), but plays a different role in rods vs. cones. Without RDS, rods fail to form OSs, however, cones lacking RDS (in the rds-/- / Nrl-/-) exhibit balloon-like OSs devoid of lamellae. We show that distribution of most proteins in the lamella and PM domains is preserved even in the absence of RDS, rim, and lamella structures. However, the rim protein prominin-1 exhibits altered trafficking and OS localization, suggesting that proper targeting and distribution of rim proteins may require RDS. Our ultrastructural studies show that in cones, OS formation is initiated by the growth of opsin-containing membrane with RDS-mediated rim formation as a secondary step. This is directly opposite to rods and significantly advances our understanding of the role of the rim in cone OS morphogenesis. Furthermore, our results suggest that the unique folded lamella architecture of the cone OS may maximize density or proximity of phototransduction proteins, but is not required for OS function or for protein distribution and retention in different membrane domains. © FASEB.


PubMed | The University of Oklahoma Health Sciences Center and OUHSC
Type: | Journal: International journal of vascular medicine | Year: 2017

We compared the changes in ambulatory outcomes between men and women with symptomatic peripheral arterial disease (PAD) following completion of a supervised, on-site, treadmill exercise program, and we determined whether exercise training variables and baseline clinical characteristics were predictive of changes in ambulatory outcomes in men and women. Twenty-three men and 25 women completed the supervised exercise program, consisting of intermittent walking to mild-to-moderate claudication pain for three months. Men and women significantly increased claudication onset time (COT) (

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