Pearlman B.L.,Center for Hepatitis C |
Pearlman B.L.,Georgia Regents University
The Lancet Infectious Diseases | Year: 2012
For the past decade, the standard treatment for chronic hepatitis C infection has been pegylated-interferon plus ribavirin. With US Food and Drug Administration approval of boceprevir and telaprevir-two protease inhibitors-the standard-of-care treatment for genotype-1 infection, the main genotype worldwide, is now peginterferon plus ribavirin and a protease inhibitor. Rates of sustained virological response or cure with triple combination treatment have improved substantially, both in patients who have had previous treatment and in those who have not. Improvements have been most substantial in populations regarded as difficult to treat, such as individuals with cirrhosis. However, despite improved response rates, protease inhibitors have incremental toxic effects, high costs, increased pill burden, and many drug interactions. Moreover, because new antiviral drugs directly inhibit hepatitis C virus, viral resistance has become an important issue, essentially precluding use of protease inhibitor monotherapy, and potentially restricting future treatment options for patients who consequently do not achieve sustained virological response. Protease inhibitors are the first of many antiviral medications that will probably be combined in future interferon-free regimens. © 2012 Elsevier Ltd.
Amin Z.,Georgia Regents University
Catheterization and Cardiovascular Interventions | Year: 2014
The risk of erosion after Amplatzer septal occluder (ASO) device placement in atrial septal defects is well described. Aortic rim deficiency and use of over-sized device increase the risk of erosion. This study attempts to describe device characteristics, anatomical features and echocardiographic predictors that increase the risk of erosion. Methods: From 2005 through 2012, 12 new cases, with nine confirmed and three suspected device erosions where pre-procedural, intra-procedural, and/or post-procedural echocardiograms were available and, were reviewed. Following parameters were evaluated: ASD location (high or low), rims deficiency and consistency, septal mal-alignment, dynamic nature of the defect; device edge relationship toward the transverse sinus (TS), atrial free wall tenting and the size of the defect compared with the size of the device used for closure. Results: We found poor posterior rim consistency, aortic rim absence (in multiple views) and absent aortic rim at O degree in 100% of the patients. Septal mal-alignment and dynamic ASD was present in nearly 50% of the cases. The device was over-sized in three patients only. A 26-mm device was the most common device that resulted in erosion. In cases, where patient had experienced bloody pericardial effusion and the device was in place, device tenting in the TS was observed. Surgical explantation of the device confirmed presence of erosion in all cases. Conclusion: Aortic rim absence in multiple views, poor posterior rim consistency, septal mal-alignment, and dynamic ASD appear to be factors where erosion risk increases significantly. A thorough assessment of the device edge by echocardiography in short-axis may show device tenting of the atrial free wall into the TS. This finding should be a strong indictor to recommend surgical removal of device after occurrence of pericardial effusion. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.
Neunert C.E.,Georgia Regents University
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013
Immune thrombocytopenia (ITP) is an autoimmune-mediated condition that results from antibody-mediated destruction of platelets and impaired megakaryocyte platelet production. ITP patients exhibit severe thrombocytopenia and are at risk for significant hemorrhage. Few randomized trials exist to guide management of patients with ITP. Ultimately, each patient requires an individualized treatment plan that takes into consideration the platelet count, bleeding symptoms, health-related quality of life, and medication side effects. This article provides an up-to-date review of management strategies drawing on links between the expanding amounts of clinical trial data and associated biology studies to enhance understanding of the disease heterogeneity with regard to the complex pathogenesis and response to treatment.
Bharucha A.E.,Clinical Enteric Neuroscience Translational and Epidemiological Research Program |
Rao S.S.C.,Georgia Regents University
Gastroenterology | Year: 2014
Gastroenterologists frequently encounter pelvic floor disorders, which affect 10% to 15% of the population. The anorectum is a complex organ that collaborates with the pelvic floor muscles to preserve fecal continence and enable defecation. A careful clinical assessment is critical for the diagnosis and management of defecatory disorders and fecal incontinence. Newer diagnostic tools (eg, high-resolution manometry and magnetic resonance defecography) provide a refined understanding of anorectal dysfunctions and identify phenotypes in defecatory disorders and fecal incontinence. Conservative approaches, including biofeedback therapy, are the mainstay for managing these disorders; new minimally invasive approaches may benefit a subset of patients with fecal incontinence, but more controlled studies are needed. This mini-review highlights advances, current concepts, and controversies in the area. © 2014 by the AGA Institute.
Neunert C.E.,Georgia Regents University
Blood | Year: 2013
Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that the majority undergo remission and severe thrombocytopenia is infrequent. Details regarding bleeding manifestations, however, remain poorly categorized. We report here long-term data from the Intercontinental Cooperative ITP Study Group Registry II focusing on natural history, bleeding manifestations, and management. Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24 months thereafter. Median platelet counts were 214 × 10(9)/L (interquartile range [IQR] 227, range 1-748), 211 × 10(9)/L (IQR 192, range 1-594), and 215 × 10(9)/L (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet count <20 × 10(9)/L was uncommon (7%, 7%, and 4%, respectively). Remission occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12 months, and 24% between 12 and 24 months. There were no reports of intracranial hemorrhage, and the most common site of bleeding was skin. In patients with severe thrombocytopenia we observed a trend toward more drug treatment with increasing number of bleeding sites. Our data support that ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare.
Lambert N.A.,Georgia Regents University
Science Signaling | Year: 2010
G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), transduce various sensory and nonsensory signals. It is now widely accepted that these receptors associate with each other as homomeric or heteromeric dimers or as higher-order oligomers. This realization raises a number of questions regarding the quaternary structure of GPCRs and the function of GPCR oligomers: How does ligand binding in one protomer affect an associated protomer? What is the functional unit that activates downstream signaling molecules? What parts of the receptor form the interfaces between protomers? Where along the pathway from synthesis to degradation do oligomers form? Do they ever dissociate? Until recently, this last question has attracted little attention, and GPCR dimers and oligomers have generally been considered to be stable structures. However, biophysical studies have now begun to address this question, and the answer that is emerging will require a reassessment of the stable dimer model. Copyright 2008 the American Association for the Advancement of Science; all rights reserved.
Harris R.B.S.,Georgia Regents University
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2014
Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. © 2013 Elsevier B.V.
Georgia Regents University | Date: 2015-10-26
An orthotic and assistive device for persons with disabilities is provided. The device is configured to allow the user to safely and more fully participate in conventional activities, such as riding a horse and a bicycle. Components of the device support the user and maintain the user in a desired form. Components of the device are inexpensively and quickly produced by 3D printing. As such, components can be custom fit for each user to enhance the effectiveness of the device.
Georgia Regents University | Date: 2015-08-21
It has been discovered that PIK3 (PIK3delta) selectively modulates the activation and proliferation of natural Tregs. Methods of modulating immune responses by modulating PIK3 bioavailability or biological activity are provided.
Georgia Regents University, H. Lee Moffitt Cancer Center and Research Institute | Date: 2016-01-11
Methods of treating a disease or disorder characterized by cells with increased or aberrant expression of cytokeratin-8 (CK8) are disclosed. The methods typically include administering to a subject in need thereof a pharmaceutical composition including an effective amount of a CK8 inhibitor. Exemplary diseases include thyroid cancers, particularly thyroid cancers characterized by poorly differentiated or undifferentiated cells. In the most preferred embodiments the cancer is an anaplastic thyroid cancer or a poorly differentiated papillary thyroid cancer. Disclosed inhibitors include, functional nucleic acids, inhibitory anti-CK8 antibodies, inhibitory peptides, and small molecules.