James illen Va Medical Center

Johnson City, TN, United States

James illen Va Medical Center

Johnson City, TN, United States

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Bossaer J.B.,East Tennessee State University | Thomas C.M.,James illen Va Medical Center
Journal of Oncology Practice | Year: 2017

Purpose Drug interactions are a concern in oncology with the shift toward oral antineoplastics (OAs). Using electronic databases to screen for drug interactions with OAs is a common practice. There is little literature to guide clinicians on the reliability of these systems with OAs. The primary objective of this study was to explore the sensitivity of commonly available drug interaction databases in detecting drug interactions with OAs. Methods A list of 20 drug interactions with OAs was developed by two Board-certified oncology pharmacists. The list included multiple types of drug interactions. The sensitivity in detecting these interactions by MicroMedex, Facts & Comparisons, Lexi-Interact, and Epocrates were evaluated. These databases were chosen based on their local availability and widespread use in practice. Drugs.com was evaluated as a surrogate for a patientaccessible drug interaction database. The CochranQtest was used to assess the sensitivity distribution across the five groups. Results Lexi-Interact and Drugs.com had a sensitivity of 95% for the 20 tested drug interaction pairs. Epocrates had a sensitivity of 90%, and both Micromedex and Facts & Comparisons had a sensitivity of 70%. There was a statistically significant difference (P = .016) in the distribution across the databases in detecting clinically significant drug interactions. Conclusion Commonly used databases for identifying drug interactions with oral antineoplastics vary significantly in their sensitivity. Clinicians should not rely on a single database and should consider using multiple resources as well as sound clinical judgment. Further work is needed in this area. © 2017 American Society of Clinical Oncology. All rights reserved.

Krishnaswamy G.,East Tennessee State University | Krishnaswamy G.,James illen Va Medical Center
Inflammation and Allergy - Drug Targets | Year: 2012

Urticaria can be a chronic and debilitating affliction and is a relatively common disorder affecting between 10- 20% of the population. Common causes include reactions to medication, food allergen, physical stimuli and venoms. Urticaria can be acute or chronic. Chronic urticaria lasts for more than 6 weeks and is commonly difficult to treat. The use of immunosuppressive agents for this disorder when antihistamines fail can result in significant morbidity. Recent advances in the pathogenesis, etiology, diagnosis and management of chronic urticaria have led to new paradigms in treatment of this disorder. Cyclosporine is often the most effective but has some unique adverse effects that may prevent it from being used in some patients. The use of intravenous immunoglobulin (IVIG) has proven effective in a variety of reports and we will review the mechanisms likely involved in the successful control of urticarial symptoms by immunomodulating therapy using IVIG. In this review, we will discuss mechanisms and pathogenesis of urticaria and the specific role of intravenous immunoglobulin (IVIG) in this disorder, especially in refractory or steroid-dependent cases. © 2012 Bentham Science Publishers.

Yao Z.Q.,James illen Va Medical Center | Yao Z.Q.,East Tennessee State University | Moorman J.P.,James illen Va Medical Center | Moorman J.P.,East Tennessee State University
Archivum Immunologiae et Therapiae Experimentalis | Year: 2013

Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared with the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection. © 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.

Pate M.B.,East Tennessee State University | Smith J.K.,East Tennessee State University | Chi D.S.,East Tennessee State University | Krishnaswamy G.,East Tennessee State University | Krishnaswamy G.,James illen Va Medical Center
Clinical and Molecular Allergy | Year: 2010

Background: Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production.Methods: Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis.Results: Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency.Conclusion: Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments. © 2010 Pate et al; licensee BioMed Central Ltd.

Song E.,East Tennessee State University | Jaishankar G.B.,East Tennessee State University | Saleh H.,East Tennessee State University | Jithpratuck W.,East Tennessee State University | And 3 more authors.
Clinical and Molecular Allergy | Year: 2011

Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon. © 2011 Song et al; licensee BioMed Central Ltd.

Youssef D.,East Tennessee State University | Shams W.,East Tennessee State University | Shams W.,James illen Veterans Affairs Medical Center | Bailey B.,East Tennessee State University | And 2 more authors.
Journal of Hospital Infection | Year: 2012

Contaminated blood cultures constitute diagnostic challenges and place a burden on healthcare services. An observational retrospective study was undertaken to evaluate the effect of routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, on blood culture contamination rates. The contamination rate of the entire facility was 2.6% before the procedural change, and this decreased significantly to 1.5% after the procedural change (P < 0.001) over the first 12 months of the intervention. Routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, was effective in reducing blood culture contamination rates. © 2012 The Healthcare Infection Society.

Wilson R.H.,James illen Va Medical Center | Wilson R.H.,East Tennessee State University | Farmer N.M.,East Tennessee State University | Gandhi A.,East Tennessee State University | And 2 more authors.
Journal of Speech, Language, and Hearing Research | Year: 2010

Purpose: To establish normative data for children on the Words-in-Noise Test (WIN; R. H. Wilson, 2003; R. H. Wilson & R. McArdle, 2007). Method: Forty-two children ineachof 7 age groups, rangingin age from6to12years (n = 294), and 24 young adults (age range: 18-27 years) with normal hearing for pure tones participated. All listeners were screened at 15 dB HL (American National Standards Institute, 2004) with the octave interval between 500 and 4000 Hz. Randomizations of WIN Lists 1, 2, and 1 or WIN Lists 2, 1, and 2 were presented with the noise fixed at 70 dB SPL, followed by presentation at 90 dB SPL of the 70 Northwestern University Auditory Test No. 6 (T. W. Tillman & R. Carhart, 1966) words used in the WIN. Finally, the Peabody Picture Vocabulary Test-Revised (L. M. Dunn & L. M. Dunn, 1981) was administered. Testing was conducted in a quiet room. Results: There were 3 main findings: (a) The biggest change inrecognition performance occurred between the ages of 6 and 7 years; (b) from 9 to 12 years, recognition performance was stable; and (c) performance by young adults (18-27 years) was slightly better (1-2 dB) than performance by the older children. Conclusion: The WIN can be used with children as young as 6 years of age; however, age-specific ranges of normal recognition performance must be used. © American Speech-Language-Hearing Association.

Dai J.,East Tennessee State University | El Gazzar M.,East Tennessee State University | Li G.Y.,East Tennessee State University | Moorman J.P.,East Tennessee State University | And 3 more authors.
Journal of Innate Immunity | Year: 2015

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature suppressor cells that are generated due to aberrant myelopoiesis under pathological conditions. Although MDSCs have been recognized for more than 20 years under the guise of different monikers, these particular populations of myeloid cells gained more attention recently due to their immunosuppressive properties, which halt host immune responses to growing cancers or overwhelming infections. While MDSCs may contribute to immune homeostasis after infection or tissue injury by limiting excessive inflammatory processes, their expansion may be at the expense of pathogen elimination and thus may lead to disease persistence. Therefore, MDSCs may be either damaging or obliging to the host by attenuating, for example, antitumor or anti-infectious immune responses. In this review, we recapitulate the biological and immunological aspects of MDSCs, including their generation, distribution, trafficking and the factors involved in their activation, expansion, suppressive functions, and interplay between MDSCs and regulatory T cells, with a focus on the perspectives of infection and inflammation. © 2014 S. Karger AG, Basel.

Zhang Y.,East Tennessee State University | Zhang Y.,PLA Fourth Military Medical University | Ma C.J.,East Tennessee State University | Wang J.M.,East Tennessee State University | And 8 more authors.
PLoS ONE | Year: 2011

T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection.

Youssef D.,James illen Va Medical Center | Ilyas S.,James illen Medical Center | Chaudhary H.,James illen Medical Center | Al-Abbadi M.A.,James illen Medical Center
Head and Neck Pathology | Year: 2011

In this case report, we describe an unusual case of mycobacterial associated inflammatory pseudotumor that occurred in a patient with a previous history of cocaine abuse. We discuss inflammatory pseudotumor (IPT) in general and emphasize the rare entity where an associated mycobacterial infection is seen. The histogenesis is not yet completely understood. The lesion can pose challenges for practicing pathologists and a misdiagnosis of malignancy can occur at multiple facets. A discussion about the differential diagnosis and clues to make the distinction is presented. In addition to spindle cell proliferation, the presence of a background of mixed inflammatory cell infiltrate and foamy macrophages are clues to make the diagnosis. In the case of mycobacteria associated IPT, Acid Fast Bacilli (AFB) stains will easily highlight the organisms confirming the diagnosis. © 2011 Springer Science+Business Media, LLC.

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