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Hill S.,Oklahoma Medical Research Foundation | Hill S.,Oklahoma City Medical Center | Hill S.,University of Texas Health Science Center at San Antonio | Van Remmen H.,Oklahoma Medical Research Foundation | Van Remmen H.,Oklahoma City Medical Center
Redox Biology | Year: 2014

Mitochondria are principal regulators of cellular function and metabolism through production of ATP for energy homeostasis, maintenance of calcium homeostasis, regulation of apoptosis and fatty acid oxidation to provide acetyl CoA for fueling the electron transport chain. In addition, mitochondria play a key role in cell signaling through production of reactive oxygen species that modulate redox signaling. Recent findings support an additional mechanism for control of cellular and tissue function by mitochondria through complex mitochondrial-nuclear communication mechanisms and potentially through extracellular release of mitochondrial components that can act as signaling molecules. The activation of stress responses including mitophagy, mitochondrial number, fission and fusion events, and the mitochondrial unfolded protein response (UPRMT) requires mitochondrial-nuclear communication for the transcriptional activation of nuclear genes involved in mitochondrial quality control and metabolism. The induction of these signaling pathways is a shared feature in long-lived organisms spanning from yeast to mice. As a result, the role of mitochondrial stress signaling in longevity has been expansively studied. Current and exciting studies provide evidence that mitochondria can also signal among tissues to up-regulate cytoprotective activities to promote healthy aging. Alternatively, mitochondria release signals to modulate innate immunity and systemic inflammatory responses and could consequently promote inflammation during aging. In this review, established and emerging models of mitochondrial stress response pathways and their potential role in modulating longevity are discussed. © 2014.


Scofield R.H.,The University of Oklahoma Health Sciences Center | Scofield R.H.,Oklahoma Medical Research Foundation | Scofield R.H.,Oklahoma City Medical Center
Arthritis Research and Therapy | Year: 2011

Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary glands. The known functions of IL-21 in facilitating differentiation, proliferation, and survival of both B and T cells mesh well with the findings in Sjögren's syndrome. Demonstration of IL-21 as a fundamental aspect of the pathophysiology of Sjögren's syndrome could lead to the development of anti-IL-21 therapy for this disease. © 2011 BioMed Central Ltd.


Marlar R.A.,Oklahoma City Medical Center | Marlar R.A.,The University of Oklahoma Health Sciences Center | Gausman J.N.,Oklahoma City Medical Center
American Journal of Hematology | Year: 2011

Heterozygous deficiency of Protein S (PS) increases the risk for developing thrombosis. Many acquired conditions alter plasma PS levels. These complex interactions of PS in plasma make it imperative that clinical PS assay limitations are understood so that the assays are reliable, reproducible and specific to diagnose true genetic abnormalities based on plasma phenotype alone. Unfortunately, the diagnosis of PS deficiency is difficult and complicated. Three basic assays can be utilized for assessing PS in plasma: PS activity assay, Free PS antigen assay, and Total PS antigen assay. This article will review these clinical assays and their associated problems. We also discuss the confounding and interfering factors that make it difficult to obtain an accurate diagnosis of PS deficiency. © 2011 Wiley-Liss, Inc.


Bensadon B.A.,The University of Oklahoma Health Sciences Center | Teasdale T.A.,The University of Oklahoma Health Sciences Center | Odenheimer G.L.,The University of Oklahoma Health Sciences Center | Odenheimer G.L.,Oklahoma City Medical Center
Academic Medicine | Year: 2013

For more than half a century, scientific research has documented widespread avoidance and even denial of aging. Though nothing new, aversive reactions to the elderly are not only unfortunate but dangerous today, as increasing life expectancy and consequent demand for specialized geriatric medical care vastly outpace the supply of qualified clinicians equipped to provide it. This discrepancy has led to a crisis that is not easily resolved. At the same time, geriatrics reports the highest level of physician satisfaction among medical specialties. How can this apparent disconnect be explained, and what can be done about it? Citing evidence from medicine and other health care disciplines, the authors address these questions by emphasizing the role of aging-related attitudes, a complex but theoretically modifiable construct. Successful educational interventions are described, including the authors' experience at the helm of a monthlong geriatrics clerkship for fourth-year medical students. Novel suggestions are provided to combat the daunting challenges to achieving a workforce that is sufficient both in number and training to effectively meet the needs of the fastest-growing segment of the U.S. population. As patients continue to age across most medical specialties, the importance of geriatric curricula, particularly those sensitizing learners to the need for a systems-based, biopsychosocial (i.e., interdisciplinary) model of care, cannot be overemphasized. Such training, it is argued, should be a standard component of medical education, and future research should focus on identifying specific curricular content and teaching methods that most effectively achieve this end.


Rabadi M.H.,Oklahoma City Medical Center | Rabadi M.H.,University of Oklahoma | Vincent A.S.,University of Oklahoma
Disability and Rehabilitation | Year: 2013

Background: Multiple sclerosis (MS) is a disease which has a variable clinical presentation followed by a variable clinical course. Therefore, accuracy of clinical rating scales to measure disability at initial clinical presentation and during follow-up visits is essential to accurately capture the variability inherent in this disease. This is particularly vital when attempting to identify the efficacy of interventions. Objective: This observational study in veterans with MS compared the Kurtkze Expanded Disability Status Scale (EDSS) and the Total Functional Independence Measure (TFIM) scale as measures of MS-related disability. Methods: We retrospectively reviewed the electronic charts of 76 veterans with MS who are regularly followed in our VA MS clinic. Local Institutional Review Board approval was obtained for the protocol. Data were analyzed using SAS (SAS System for Windows, version 9.2, SAS Institute Inc., Cary, NC, USA). Chi-square and Fisher exact tests were used to assess categorical variables. Kruskal-Wallis tests evaluated the relationships between MS types [relapsing-remitting MS (RR), secondary progressive MS (SP), primary progressive MS (PP) and clinical isolated syndrome (CIS)] and the initial TFIM, EDSS and Impairment Index (II) scores. Results: The EDSS score accurately measured MS-related impairment at initial evaluation and follow-up relative to an II. However, the EDSS score did not change over time, compared to the TFIM suggesting reduced sensitivity of the EDSS for detecting change in MS-related disability over time. Conclusions: This suggests TFIM scale is a more sensitive measure of MS-related disability than EDSS for use in future MS clinical trials.Implications for RehabilitationThis study highlights that given the paucity of scales to which EDSS has been compared, TFIM is a valuable adjunct to EDSS in measuring MS-related disability.TFIM is able to accurately measure the severity of MS-related disability and help provide for services patients with MS-related disability would need.TFIM is an easy to administer and a sensitive scale to measure the change in MS-related disability following interventions. © 2013 Informa UK Ltd. All rights reserved.


Marlar R.A.,Oklahoma City Medical Center | Marlar R.A.,The University of Oklahoma Health Sciences Center | Gausman J.N.,Oklahoma City Medical Center | Engel J.W.,Oklahoma City Medical Center
Seminars in Thrombosis and Hemostasis | Year: 2014

The clinical hemostasis laboratory is a complex testing arena which employs numerous coagulation assays and spans several different test methodologies. Adding further complexity, these test results are expressed in a wide variety of unique units (concentration, activity, time, percentage, and ratio). Unfortunately, many of these reference values are derived from a local plasma pool or manufacturer's standards, as there are few established international standards. These three main issues complicate the validation and performance of the coagulation testing. Before an assay can be introduced into clinical use, both analytical and clinical performance parameters must be validated or verified using the standard validation procedures of the laboratory. This article summarizes the initial evaluation and validation processes of the coagulation laboratory, which sometimes can be difficult concepts to implement. A standardized validation protocol is described in this article and, if used, will help to objectively evaluate the assay performance and determine if it meets acceptable laboratory criteria. © 2014 by Thieme Medical Publishers, Inc.


Rabadi M.H.,Oklahoma City Medical Center | Vincent A.S.,Oklahoma City Medical Center
Journal of Spinal Cord Medicine | Year: 2011

Objective: The overall goal of this observational study was to determine whether modifiable vascular risk factors contribute to the prevalence of pressure ulcers (PrU) in veterans with traumatic spinal cord injury (SCI). Background: Given the increasingly limited financial resources in hospitals and clinics, identifying risk factors associated with the development of PrU in persons with SCI will be a major step in reducing the cost of care for these individuals, and may improve their quality of life. Method: We retrospectively reviewed the electronic charts of 87 veterans with SCI who are being followed regularly in our SCI clinic and are enrolled in the SCI registry. The data collected included the basic demographics, presence of modifiable vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and current smoking; presence of incontinence and depression; and results from blood drawn for hemoglobin level, blood urea nitrogen, creatinine, and albumin levels and lipid profile on veteran's initial enrollment. Local Institution Review Board approval was obtained for the protocol. Results: Of the 87 veterans with SCI, 27 had PrU. Comparisons between those with and without PrU found no significant differences for the demographic variables of age, gender, age of SCI onset, or SCI duration, but there was a trend for the groups to differ in ethnicity (P=0.05). Similarly, the presence of modifiable vascular risk factors including hypertension, diabetes mellitus, hyperlipidemia, and current smoking did not differ between those with and without PrU. There were 36 pressure ulcer sites observed in 27 people. The proportion of pressure ulcer sites (of the 36) significantly differed by SCI severity based on the American Spinal Injury Association (ASIA) score (P<0.0001). Conclusion: This study suggests that the presence of PrU was influenced by the severity of the SCI without any contribution from modifiable vascular risk factors. © The Academy for Spinal Cord Injury Professionals, Inc. 2011.


Gentry C.A.,Oklahoma City Medical Center | Williams R.J.,Oklahoma City Medical Center
Diagnostic Microbiology and Infectious Disease | Year: 2015

This study sought to characterize the trends in antimicrobial susceptibility rates for Pseudomonas aeruginosa causing bacteremias across the US Veterans Healthcare Administration from 2007 through 2013 utilizing a national clinical database. Data were gathered from 107 Veterans Affairs medical centers involving 4418 patients with 4826 blood cultures with positive growth of P. aeruginosa. Susceptibility rates of β-lactam antimicrobials, carbapenems, fluoroquinolones, and aminoglycosides all significantly increased throughout the 7-year period, closely corresponding to a significant decline in the incidence of P. aeruginosa blood cultures of nosocomial origin. Several statistically significant increases in susceptibility rates were found for antimicrobial agents across different geographic regions of the United States. There were no statistically significant decreases in susceptibility rates for any antimicrobial agents for any region. Levels of multidrug resistance significantly declined throughout the study period in 2 regions and increased in 1. Additional efforts should evaluate variables associated with these improvements. © 2015.


Gausman J.N.,Oklahoma City Medical Center | Marlar R.A.,Oklahoma City Medical Center | Marlar R.A.,The University of Oklahoma Health Sciences Center
American Journal of Clinical Pathology | Year: 2011

Our purpose was to determine whether the in vitro (or "spiked curve") method for the therapeutic heparin range is an accurate and valid method for heparin monitoring. Many laboratories use the in vitro method for determining the activated partial thromboplastin time (APTT)-based unfractionated heparin (UFH) therapeutic range as a more practical method to determine the therapeutic heparin range. Is this a valid method compared with the recommended ex vivo method? Plasma samples from patients receiving UFH and a normal plasma pool spiked with UFH were compared for 8 APTT reagents (18 lots). The in vitro curve has significantly increased lower limit and upper limit values and has a significantly widened range compared with the ex vivo method. When APTT values are compared with both methods, more samples are underheparinized with the in vitro curve method. The in vitro method is not a valid method to determine an accurate therapeutic heparin range. © American Society for Clinical Pathology.


Marlar R.A.,Oklahoma City Medical Center | Marlar R.A.,The University of Oklahoma Health Sciences Center | Gausman J.N.,Oklahoma City Medical Center
International Journal of Laboratory Hematology | Year: 2014

Thrombophilia is a complex disease process, which clinically expresses as venous thrombosis. The presence of a genetic defect in one of the major contributing components (protein C [PC], protein S [PS], and antithrombin [AT]) to thrombophilia can be determined by clinical laboratory assays. However, understanding the limitations and problems associated with assays is paramount to an accurate analysis of the genetic status. This review will discuss the major analytical issues and provide recommendations for assaying PC, PS, and AT in plasma. Recommendations are also made about pre-analytical and postanalytical issues clinically affecting these assays. © 2014 John Wiley & Sons Ltd.

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