21 results on '"Tom Karagiannis"'
Search Results
2. Diagnosis of Queensland Tick Typhus and African Tick Bite Fever by PCR of Lesion Swabs
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Jin-Mei Wang, Bernard J. Hudson, Matthew R. Watts, Tom Karagiannis, Noel J. Fisher, Catherine Anderson, and Paul Roffey
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Rickettsia ,spotted fever ,PCR ,swabs ,Queensland ,Australia ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report 3 cases of Queensland tick typhus (QTT) and 1 case of African tick bite fever in which the causative rickettsiae were detected by PCR of eschar and skin lesions in all cases. An oral mucosal lesion in 1 QTT case was also positive.
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- 2009
- Full Text
- View/download PDF
3. Exploring Variation in Transformation of Primary Care Practices to Patient-Centered Medical Homes: A Mixed Methods Approach
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Mona Sarfaty, Tom Karagiannis, Evan Bilheimer, Robert D. Lieberthal, Colleen Payton, George Valko, and Manisha Verma
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Medical home ,Cost Control ,Quality Assurance, Health Care ,Leadership and Management ,Sample (statistics) ,Primary care ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Patient-Centered Care ,Humans ,Medicine ,030212 general & internal medicine ,Data collection ,Descriptive statistics ,business.industry ,030503 health policy & services ,Health Policy ,Public Health, Environmental and Occupational Health ,Original Articles ,Pennsylvania ,Workforce ,Thematic analysis ,0305 other medical science ,business ,Delivery of Health Care ,Quality assurance - Abstract
The objective was to quantify the activities required for patient-centered medical home (PCMH) transformation in a sample of small to medium-sized National Committee for Quality Assurance (NCQA) recognized practices, and explore barriers and facilitators to transformation. Eleven small to medium-sized PCMH practices in Southeastern Pennsylvania completed a survey, which was adapted from the 2011 NCQA standards. Semistructured follow-up interviews were conducted, descriptive statistics were computed for the quantitative analysis, and a process of thematic coding was deployed for the qualitative analysis. Practices had considerable quantitative variation in their workforce composition and the PCMH-related activities they implemented. Most practices improved access and continuity through staff training and team-based care as well as expanded data collection for population management. The barriers to PCMH recognition were least burdensome for the largest practices. The heterogeneity of the small PCMH practices within the study sample underscore the need to understand the key transformation issues as efforts to disseminate the PCMH model continue.
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- 2017
4. Systems approach to the pharmacological actions of HDAC inhibitors reveals EP300 activities and convergent mechanisms of regulation in diabetes
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Antony Kaspi, Mark Ziemann, Assam El-Osta, Tom Karagiannis, Haloom Rafehi, and Jun Okabe
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0301 basic medicine ,Cancer Research ,Systems biology ,Gene regulatory network ,Biology ,Bioinformatics ,Epigenesis, Genetic ,03 medical and health sciences ,Diabetes Mellitus ,Histone code ,Humans ,Gene Regulatory Networks ,Molecular Biology ,Cells, Cultured ,Epigenesis ,Epigenomics ,Gene knockdown ,Systems Biology ,Endothelial Cells ,Histone Code ,Histone Deacetylase Inhibitors ,Insulin receptor ,030104 developmental biology ,biology.protein ,Histone deacetylase ,Endothelium, Vascular ,E1A-Associated p300 Protein ,Research Paper - Abstract
Given the skyrocketing costs to develop new drugs, repositioning of approved drugs, such as histone deacetylase (HDAC) inhibitors, may be a promising strategy to develop novel therapies. However, a gap exists in the understanding and advancement of these agents to meaningful translation for which new indications may emerge. To address this, we performed systems-level analyses of 33 independent HDAC inhibitor microarray studies. Based on network analysis, we identified enrichment for pathways implicated in metabolic syndrome and diabetes (insulin receptor signaling, lipid metabolism, immunity and trafficking). Integration with ENCODE ChIP-seq datasets identified suppression of EP300 target genes implicated in diabetes. Experimental validation indicates reversal of diabetes-associated EP300 target genes in primary vascular endothelial cells derived from a diabetic individual following inhibition of HDACs (by SAHA), EP300, or EP300 knockdown. Our computational systems biology approach provides an adaptable framework for the prediction of novel therapeutics for existing disease.
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- 2017
5. Strand breakage by decay of DNA-bound
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Pavel, Lobachevsky, George R, Clark, Patrycja D, Pytel, Brenda, Leung, Colin, Skene, Laura, Andrau, Jonathan M, White, Tom, Karagiannis, Carleen, Cullinane, Boon Q, Lee, Andrew, Stuchbery, Tibor, Kibedi, Rodney J, Hicks, and Roger F, Martin
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Mice, Inbred BALB C ,Radiotherapy ,Mice, Nude ,Electrons ,Radiotherapy Dosage ,DNA ,Neoplasms, Experimental ,Iodine Radioisotopes ,Mice ,Treatment Outcome ,Isotope Labeling ,Animals ,Humans ,Tissue Distribution ,Radiopharmaceuticals ,K562 Cells ,Radiotherapy, Image-Guided - Abstract
Purpose DNA ligands labelled with
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- 2016
6. Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators
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Assam El-Osta, Haloom Rafehi, and Tom Karagiannis
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0301 basic medicine ,Histone Acetyltransferase p300 ,Histone deacetylase 5 ,Histone acetylation and deacetylation ,Binding Sites ,HDAC11 ,General Medicine ,Biology ,HDAC4 ,Molecular biology ,Histone Deacetylases ,Cell biology ,Histone Deacetylase Inhibitors ,Histones ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Histone methyltransferase ,Drug Discovery ,Histone H2A ,Humans ,Histone deacetylase ,Protein Processing, Post-Translational ,Transcription Factors - Abstract
Introduction: Histone deacetylase (HDAC) enzymes control the acetylation status of transcription factors that regulate chromatin structure and gene function. The transcriptional regulatory factors that distinguish histone acetylation and deacetylation patterns by pharmacological HDAC inhibition (HDACi) have not yet been studied. Methods: We analysed sequencing datasets derived from human aortic endothelial cells (HAECs) stimulated with the HDAC inhibitors, Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). We integrated gene expression and histone acetylation profiles with the transcription factor binding site (TFBS) database derived from the Encyclopedia of DNA Elements (ENCODE) project. Results: Overall, TFBS signatures observed in SAHA and TSA stimulated cells were analogous. Histone acetylation was observed at transcription factor binding sites of target genes associated with the silencing factors NRSF, EZH2 and SUZ12. Histone deacetylation was a prominent property of HDACi and correlated with changes in the expression of genes regulated by proteins in transcriptional control such as histone acetyltransferase P300 and lysine demethylase JARID1A, as well as the regulatory factors cMYC, YY1 and STAT family proteins. Conclusion: We identified several transcription factors and coregulators implicated in the regulation of histone modification at target genes mediated by pharmacological HDAC inhibition.
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- 2016
7. Comments on Selected Recent Dysphagia Literature
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Paul Carding, David Hamilton, Joanne Patterson, Pierre-Marie Preux, Karolina Gerreth, Janet Wilson, Tom Karagiannis, and Andrei Holodny
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medicine.medical_specialty ,Lung ,business.industry ,Gastroenterology ,Dysphagia ,Clinical trial ,Speech and Hearing ,Thickened fluids ,medicine.anatomical_structure ,Otorhinolaryngology ,Quality of life ,Internal medicine ,Relative risk ,medicine ,In patient ,medicine.symptom ,business ,Oropharyngeal dysphagia - Abstract
Dysphagia is associated with numerous medical conditions and the major intervention to avoid aspiration in people with dysphagia involves modifying the diet to thickened fluids. This is associated with issues related to patient quality of life and in many cases non-compliance leading to dehydration. Given these concerns and in the absence of conclusive scientific evidence, we designed a study, to further investigate the effects of oral intake of water in people with dysphagia. We monitored lung related complications, hydration levels and assessed quality of life in two groups of people with dysphagia. The control group was allowed only thickened fluids and patients in the intervention group were allowed access to water for a period of five days. Our findings indicate a significantly increased risk in the development lung complications in patients given access to water (6/42; 14.3%) compared to the control group (0/34; no cases). We have further defined patients at highest risk, namely those with degenerative neurologic dysfunction who are immobile or have low mobility. Our results indicate increased total fluid intake in the patients allowed access to water, and the quality of life surveys, albeit from a limited number of patients (24% of patients), suggest the dissatisfaction of patients to diets composed of only thickened fluids. On the basis of these findings we recommend that acute patients, patients with severe neurological dysfunction and immobility should be strongly encouraged to adhere to a thickened fluid or modified solid consistency diet. We recommend that subacute patients with relatively good mobility should have choice after being well-informed of the relative risk. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000107325
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- 2011
8. Genetic and epigenetic events in diabetic wound healing
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Assam El-Osta, Haloom Rafehi, and Tom Karagiannis
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Epigenomics ,medicine.medical_specialty ,Review Article ,Dermatology ,Global Health ,Bioinformatics ,Pathogenesis ,Diabetes mellitus ,Prevalence ,Humans ,Medicine ,Genetic Predisposition to Disease ,Epigenetics ,Chronic metabolic disorder ,Wound Healing ,business.industry ,Limb amputation ,medicine.disease ,Diabetic foot ,Diabetic Foot ,Surgery ,Diabetic wound healing ,Disease Progression ,Wound healing ,business - Abstract
The prevalence of the chronic metabolic disorder, diabetes mellitus, is expected to increase in the coming years and worldwide pandemic levels are predicted. Inevitably, this will be accompanied by an increase in the prevalence of diabetic complications, including diabetic foot ulcers. At present, treatment options for diabetic foot ulcers are in many cases insufficient, and progression of the condition results in the requirement for limb amputation in a proportion of patients. To improve therapy, an increase in our understanding of the pathobiology of diabetic complications such as impaired wound healing is necessary. In this review, recent advances in molecular aspects of normal and impaired diabetic wound healing are discussed. Furthermore, investigations of the role of epigenetic processes in the pathogenesis of impaired diabetic wound healing are now emerging. Indeed, epigenetic changes have already been identified as key factors in diabetes and related complications and these are overviewed in this review.
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- 2010
9. Molecular Mechanisms and Physiology of Disease : Implications for Epigenetics and Health
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Nilanjana Maulik, Tom Karagiannis, Nilanjana Maulik, and Tom Karagiannis
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- Epigenetics, Diseases--Molecular aspects
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In a simplified form, epigenetics refers to heritable changes in phenotype that are not due to changes in the underlying DNA sequence. In this book, epigenetic mechanisms of regulation and dysregulation in health and disease are explored in great depth. Detailed chapters on epigenetic processes including DNA methylation and chromatin post-translational modifications including potential interventions with DNA methyltransferase inhibitors and histone deacetylase inhibitors are explored in initial chapters. These provide a detailed overview and important background to the entire field. The book is then focussed on epigenetic mechanisms involved in various diseases including anti-inflammatory and autoimmune conditions. Important accounts relating to the effects of epigenetics in metabolic syndrome, cardiovascular disease and asthma are the focus of subsequent chapters. The role of epigenetic dysregulation in malignancy is a current topic of interest and represents an intense field of research. A large component of this book is dedicated to the analysis of aberrant epigenetic processes in carcinogenesis and cancer progression. Further, chapters are focused on emerging cancer prevention using nutritional components and anti-cancer therapies particularly with histone deacetylase inhibitors, which have already been approved for the treatment of cutaneous T-cell lymphoma. The emerging role of nanoparticle preparations, especially in the context of delivering potential epigenetic therapies to target cells in various diseases, is also explored in this book. Overall, this book encompasses a wide range of topics related to epigenetic mechanisms in health and disease and would appeal to anyone with an interest in epigenetics, chromatin biology and emerging epigenetic interventions and therapies.
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- 2014
10. Clinical Potential of Histone Deacetylase Inhibitors as Stand Alone Therapeutics and in Combination with other Chemotherapeutics or Radiotherapy for Cancer
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Assam El-Osta and Tom Karagiannis
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Cancer Research ,Cell cycle checkpoint ,Angiogenesis ,Antineoplastic Agents ,Histones ,chemistry.chemical_compound ,Neoplasms ,Radiation, Ionizing ,medicine ,Homeostasis ,Humans ,Enzyme Inhibitors ,Molecular Biology ,Histone Acetyltransferases ,Histone deacetylase 5 ,biology ,Genetic Variation ,Cancer ,Epigenome ,medicine.disease ,Histone Deacetylase Inhibitors ,Histone ,chemistry ,Biochemistry ,biology.protein ,Cancer research ,Histone deacetylase ,Growth inhibition - Abstract
Histone deacetylase inhibitors are emerging as a new class of cancer chemotherapeutics and already are being heralded as the first anti-cancer drugs targeting the epigenome. Through histone hyperacetylation-mediated changes in chromatin conformation and gene expression, histone deacetylase inhibitors induce differentiation, cell cycle arrest, apoptosis, growth inhibition and cell death, which are more pronounced in transformed cell-lines than in normal cells. Additional anti-cancer effects of HDAC inhibitors include inhibition of migration, invasion and angiogenesis in vivo. Indeed, clinical anti-cancer activity has been observed using HDAC inhibitors as single agents or in combination with conventional chemotherapeutics, in phase I and II trials. Furthermore, numerous preclinical studies are suggesting a potential clinical role for HDAC inhibitors in radiotherapy either as radiation sensitizers or protectors. In this article the molecular basis for the clinical potential of HDAC inhibitors, either as stand alone cancer therapeutics or in combination with other chemotherapy agents or ionizing radiation will be overviewed.
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- 2006
11. The Paradox of Histone Deacetylase Inhibitor-Mediated Modulation of Cellular Responses to Radiation
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Assam El-Osta and Tom Karagiannis
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Radiation-Sensitizing Agents ,medicine.drug_class ,Drug Evaluation, Preclinical ,Antineoplastic Agents ,Apoptosis ,Radiation-Protective Agents ,Biology ,Models, Biological ,Neoplasms ,medicine ,Animals ,Humans ,Cancer epigenetics ,Enzyme Inhibitors ,Molecular Biology ,Cell Proliferation ,Clinical Trials as Topic ,Histone deacetylase 5 ,HDAC11 ,Histone deacetylase 2 ,HDAC10 ,Histone deacetylase inhibitor ,Cell Differentiation ,Cell Biology ,Combined Modality Therapy ,HDAC4 ,Histone Deacetylase Inhibitors ,Biochemistry ,Cancer research ,Histone deacetylase ,Developmental Biology - Abstract
Given the widespread use of radiotherapy in cancer, there has been a longstanding interest in the development of chemical compounds that can modify cellular responses to ionizing radiation. Additionally, recent terrorism threats suggesting attacks with 'dirty bombs' containing combinations of radioactive isotopes with conventional explosives, has increased the interest in compounds that can protect from radiation injury. Histone deacetylase inhibitors represent a new class of compounds that can modulate the effects of radiation. Research with histone deacetylase inhibitors has largely focussed on the consequences of their ability to alter gene transcription via histone acetylation and on their properties as anti-cancer agents. They have been shown to cause cell cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. In addition to their intrinsic anti-cancer properties, numerous studies have demonstrated that histone deacetylase inhibitors can modulate cellular responses to other toxicity-inducing modalities including ionizing radiation. The consensus is that histone deacetylase inhibitors markedly enhance the sensitivity of cells to radiation by altering numerous molecular pathways. Intriguingly, a report has also shown that histone deacetylase inhibitors can reduce radiation induced acute and late skin damage using a well-established animal model of cutaneous radiation syndrome. Hence, there is an emerging interest in potential use of histone deacetylase inhibitors as radiation sensitizers or protectors. This review focuses on the different mechanisms by which histone deacetylase inhibitors modify cellular responses to ionizing radiation.
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- 2006
12. The histone deacetylase inhibitor, trichostatin A, enhances radiation sensitivity and accumulation of gammaH2A.X
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Assam El-Osta, Harikrishnan Kaipananickal, and Tom Karagiannis
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Chromatin Immunoprecipitation ,Cancer Research ,medicine.drug_class ,Biology ,Hydroxamic Acids ,Radiation Tolerance ,Histones ,Radiation sensitivity ,medicine ,Humans ,Enzyme Inhibitors ,Phosphorylation ,Tumor Stem Cell Assay ,Caspase 7 ,Pharmacology ,Histone deacetylase 5 ,Caspase 3 ,HDAC11 ,Histone deacetylase 2 ,Histone deacetylase inhibitor ,G1 Phase ,Phosphoproteins ,Histone Deacetylase Inhibitors ,Trichostatin A ,Oncology ,Gamma Rays ,Caspases ,Cancer research ,Molecular Medicine ,Histone deacetylase ,K562 Cells ,Chromatin immunoprecipitation ,medicine.drug - Abstract
Histone deacetylase inhibitors have been shown to induce numerous biologic effects including, altering cell cycle distribution, cytostasis and in certain cases apoptosis. Given their ability to disrupt critical biological processes in cancer cells, these agents are emerging as potential therapeutics for cancer. Recently, it has been identified that histone deacetylase inhibitors can also efficiently enhance the radiation sensitivity of cells, both in vitro and in vivo. In this study, we investigated whether the potent histone deacetylase inhibitor, Trichostatin A, modulates the radiation sensitivity of human erythroleukemic K562 cells. The endpoints we used were clonogenic survival, apoptosis and gammaH2AX immunoprecipitations of soluble chromatin. The findings from clonogenic survival assays indicated that incubation with Trichostatin A 24 hours prior to irradiation enhances the radiation sensitivity of K562 cells. The dose modification factors ranged from 1.1 when cells were incubated with 0.1 microM Trichostatin A to 2.3 at 1 microM Trichostatin A. Similarly, caspase-3 and caspase-7 assays indicated that Trichostatin A potentiates radiation-induced apoptosis in K562 cells, in a concentration dependent manner. Our results suggest the modulation of radiation effects observed at the lower Trichostatin A concentrations was associated with histone hyperacetylation and changes in phosphorylated gammaH2A.X formation on euchromatin. In contrast, at the higher Trichostatin A concentrations mechanisms such as drug-mediated cytotoxicity and G1 cell cycle arrest, contributed to the sensitization effect. More generally, our findings are consistent with those from recent studies and support the development of histone deacetylase inhibitors for use as radiation sensitizers, particularly for targeting radioresistant cancers.
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- 2005
13. Strand breakage by decay of DNA-bound 124I provides a basis for combined PET imaging and Auger endoradiotherapy
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Pavel Lobachevsky, George R. Clark, Patrycja D. Pytel, Brenda Leung, Colin Skene, Laura Andrau, Jonathan M. White, Tom Karagiannis, Carleen Cullinane, Boon Q. Lee, Andrew Stuchbery, Tibor Kibedi, Rodney J. Hicks, Roger F. Martin, Pavel Lobachevsky, George R. Clark, Patrycja D. Pytel, Brenda Leung, Colin Skene, Laura Andrau, Jonathan M. White, Tom Karagiannis, Carleen Cullinane, Boon Q. Lee, Andrew Stuchbery, Tibor Kibedi, Rodney J. Hicks, and Roger F. Martin
- Published
- 2016
- Full Text
- View/download PDF
14. The transformation of primary care: are general practitioners ready?
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Marco Del Canale, Massimo Fabi, Stefano Del Canale, Vittorio Maio, Tom Karagiannis, and Antonio Brambilla
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Nursing ,Primary Health Care ,business.industry ,General Practitioners ,Health Policy ,Health Care Reform ,Medicine ,Primary care ,business ,Physician's Role ,Transformation (music) ,United States - Published
- 2014
15. Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: A retrospective cohort study
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Tom Karagiannis, Vivian Herrera, Renata Kisa, Caitriona O'Neill, Gary Goldenberg, Juzer Lotya, Jacqueline B. Palmer, and Daniel M. Siegel
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Skin Neoplasms ,Adolescent ,Databases, Factual ,Population ,Locally advanced ,Pharmacy ,Dermatology ,Disease ,Insurance Claim Review ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,International Classification of Diseases ,Epidemiology ,medicine ,Humans ,Neoplasm Invasiveness ,Basal cell carcinoma ,Neoplasm Metastasis ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,integumentary system ,business.industry ,Incidence ,Incidence (epidemiology) ,Retrospective cohort study ,Middle Aged ,medicine.disease ,United States ,Surgery ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Background Accurate evaluation of basal cell carcinoma (BCC) in the United States was not possible before the 2011 release of BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Objective We sought to describe BCC (including locally advanced BCC [LABCC]) incidence/prevalence and the characteristics of patients in a commercially insured US population. Methods This retrospective cohort study used Truven Health MarketScan database insurance claims. Patients, aged 18 years or older with 2 or more BCC claims at least 30 days apart from October 1, 2011, to September 30, 2012, were continuously enrolled in medical and pharmacy benefits for 12 months before and after the index claim. A specific algorithm was used to classify patients with LABCC. Results A total of 56,987 patients with BCC were identified (39,035 incident cases; 17,952 prevalent cases). Age-adjusted BCC incidence and prevalence were 226.09 and 342.64 per 100,000 persons, respectively. These values project to 542,782 patients (incidence) and 822,593 patients (prevalence) in the 2012 US population. LABCC was uncommon (471 cases identified; projected US incidence and prevalence: 4399 and 7940 patients, respectively). Limitations Use of medical claims data and retrospective analysis are limitations. Conclusion In a study designed to distinguish patients with LABCC from the general BCC population based on BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes, 0.8% were found to have LABCC, the majority having pre-existing disease.
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- 2016
16. Pulmonary Function and Rescue Medication Use in Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Nonrandomized Studies
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Meryl Mendelson, Jonathan Corren, Bethany Sawchyn, Kimberly Ruiz, Susan Gabriel, Jennifer A. Colby, and Tom Karagiannis
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Omalizumab ,Critical Care and Intensive Care Medicine ,Rescue medication ,Drug usage ,Pulmonary function testing ,Systematic review ,medicine ,In patient ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,medicine.drug - Published
- 2015
17. Exacerbations, Emergency Visits, and Hospitalizations in Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Nonrandomized Studies
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Jonathan Corren, Jennifer A. Colby, Susan Gabriel, Kimberly Ruiz, Bethany Sawchyn, Tom Karagiannis, and Meryl Mendelson
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Systematic review ,business.industry ,Medicine ,In patient ,Omalizumab ,Cardiology and Cardiovascular Medicine ,Critical Care and Intensive Care Medicine ,business ,Intensive care medicine ,medicine.drug - Published
- 2015
18. RNA interference and potential therapeutic applications of short interfering RNAs
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Assam El-Osta and Tom Karagiannis
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Cancer Research ,biology ,Effector ,Mechanism (biology) ,RNA ,Neurodegenerative Diseases ,Computational biology ,Investigational New Drug Application ,Genetic Therapy ,Genomics ,Bioinformatics ,biology.organism_classification ,Macular Degeneration ,RNA interference ,Virus Diseases ,Neoplasms ,Molecular Medicine ,Gene silencing ,Humans ,RNA Interference ,RNA, Small Interfering ,Molecular Biology ,Functional genomics ,Caenorhabditis elegans - Abstract
RNA interference is an endogenous gene-silencing mechanism that involves double-stranded RNA-mediated sequence-specific mRNA degradation. The discovery of this pathway together with the elucidation of the structure and function of short interfering RNAs — the effector molecules of RNA interference — has had an enormous impact on experimental biology. RNA interference technologies are currently the most widely utilized techniques in functional genomic studies. Furthermore, there is an intense research effort aimed at developing short interfering RNAs for therapeutic purposes. A number of proof-of-principle experiments have demonstrated the clinical potential of appropriately designed short interfering RNAs in various diseases including viral infections, cancer and neurodegenerative disorders. Already, in such a short time from their discovery, Acuity Pharmaceuticals (August 2004) and Sirna Therapeutics (September 2004) have filed Investigational New Drug applications with the US FDA to begin clinical trials with modified siRNA molecules in patients with age-related macular degeneration. This review will give a brief overview of the mechanism of RNA interference and applications of the pathway in experimental biology will be discussed. The article will focus on recent developments related to the use of RNA interference technologies in mammalian systems and on potential clinical applications of short interfering RNA-mediated RNA interference.
- Published
- 2005
19. DNA damage repair and transcription
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Assam El-Osta and Tom Karagiannis
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Pharmacology ,Genetics ,DNA repair ,DNA damage ,Cell Biology ,Biology ,Chromatin remodeling ,Cell biology ,Non-homologous end joining ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,chemistry ,Molecular Medicine ,Signal transduction ,Homologous recombination ,Molecular Biology ,Gene ,DNA - Abstract
Double-strand breaks arise frequently in the course of endogenous - normal and pathological - cellular DNA metabolism or can result from exogenous agents such as ionizing radiation. It is generally accepted that these lesions represent one of the most severe types of DNA damage with respect to preservation of genomic integrity. Therefore, cells have evolved complex mechanisms that include cell-cycle arrest, activation of various genes, including those associated with DNA repair, and in certain cases induction of the apoptotic pathway to respond to double-strand breaks. In this review we discuss recent progress in our understanding of cellular responses to DNA double-strand breaks. In addition to an analysis of the current paradigms of detection, signaling and repair, insights into the significance of chromatin remodeling in the double-strand break-response pathways are provided.
- Published
- 2004
20. Epigenetic changes activate widespread signals in response to double-strand breaks
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Assam El-Osta and Tom Karagiannis
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Pharmacology ,Genome instability ,Recombination, Genetic ,Cancer Research ,biology ,DNA Repair ,DNA repair ,DNA damage ,Cell cycle ,Chromatin remodeling ,Chromatin ,Cell biology ,Histone ,Oncology ,biology.protein ,Molecular Medicine ,Animals ,Humans ,Epigenetics ,DNA Damage ,Signal Transduction - Abstract
Double-strand breaks are one the most severe types of DNA damage with respect to cell survival and the preservation of genomic integrity. Therefore, cells have evolved complex mechanisms including cell cycle regulation, activation of repair pathways and in certain cases induction of apoptosis in response to these lesions. The molecular details of many of the cellular responses to double-strand breaks have been well characterized. Our understanding of these responses in the context of chromatin has also progressed recently. In this review, we focus our discussion on the significance of DNA damage-induced chromatin modifications in double-strand break signaling and repair pathways. In particular, findings from recent studies suggest mechanisms by which highly localized double-strand breaks may activate widespread signals throughout the cell by inducing alterations in chromatin structure.
- Published
- 2004
21. Synchrotron-Fourier transform infrared maps of ovalbumin-induced murine chronic allergic airways disease: Correlation with conventional histology
- Author
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Mazarakis, N., Vongsvivut, J., Bambery, K. R., Snibson, K. J., Royce, S. G., and Tom Karagiannis
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