10 results on '"Rachel Huddart"'
Search Results
2. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 , OPRM1 , and COMT Genotypes and Select Opioid Therapy
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Caroline Flora Samer, Larisa H. Cavallari, Andrew A. Monte, Andrew A. Somogyi, Rachel Huddart, Evan D. Kharasch, Kelly E. Caudle, Gualberto Ruaño, J. Steven Leeder, Andrea Gaedigk, Sara L. Van Driest, Cynthia A. Prows, Kristine R. Crews, Teri E. Klein, Todd C. Skaar, Henry M. Dunnenberger, Cyrine E. Haidar, Daniel J. Müller, John T. Callaghan, Mohamed Nagy, and Katrin Sangkuhl
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medicine.medical_specialty ,Genotype ,Pharmacogenomic Variants ,Receptors, Opioid, mu ,Pain ,Catechol O-Methyltransferase ,digestive system ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,Pharmacology ,ddc:617 ,business.industry ,Codeine ,Guideline ,Pharmacogenomic Testing ,Analgesics, Opioid ,Cytochrome P-450 CYP2D6 ,Hydrocodone ,Opioid ,030220 oncology & carcinogenesis ,Tramadol ,business ,Oxycodone ,Pharmacogenetics ,medicine.drug ,Methadone - Abstract
Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.
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- 2021
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3. Pharmacogenomics in dermatology: tools for understanding gene-drug associations
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Russ B. Altman, Teri E. Klein, Roxana Daneshjou, and Rachel Huddart
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Drug ,medicine.medical_specialty ,Databases, Factual ,Drug-Related Side Effects and Adverse Reactions ,business.industry ,media_common.quotation_subject ,Genetic data ,Dermatology ,Skin Diseases ,Article ,Clinical Practice ,Drug treatment ,Knowledge base ,Pharmacogenetics ,Pharmacogenomics ,Health care ,medicine ,Humans ,Surgery ,Dermatologic Agents ,Precision Medicine ,business ,media_common - Abstract
Pharmacogenomics aims to associate human genetic variability with differences in drug phenotypes in order to tailor drug treatment to individual patients. The massive amount of genetic data generated from large cohorts of patients with variable drug phenotypes have led to advances in this field. Understanding the application of pharmacogenomics in dermatology could inform clinical practice and provide insight for future research. The Pharmacogenomics Knowledge Base and the Clinical Pharmacogenetics Implementation Consortium are among the resources to help clinicians and researchers navigate the many gene-drug associations that have already been discovered. The implementation of clinical pharmacogenomics within health care systems remains an area of ongoing development. This review provides an introduction to the field of pharmacogenomics and to current pharmacogenomics resources using examples of gene-drug associations relevant to the field of dermatology.
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- 2019
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4. Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype
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Cristina Rodríguez-Antona, Rachel Huddart, Keito Hoshitsuki, Teri E. Klein, Richard J.H. Smith, Joshua Wolf, Michelle Whirl-Carrillo, William G. Newman, Kelly E. Caudle, John H McDermott, Peter S. Steyger, and Neal Cody
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Genotype ,Pharmacogenomic Variants ,medicine.drug_class ,Hearing loss ,Hearing Loss, Sensorineural ,Antibiotics ,Clinical Decision-Making ,MT-RNR1 ,Bioinformatics ,030226 pharmacology & pharmacy ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Pharmacology (medical) ,Gene ,Pharmacology ,business.industry ,Guideline ,medicine.disease ,Anti-Bacterial Agents/adverse effects ,Ototoxicity ,Aminoglycosides/adverse effects ,RNA, Ribosomal/genetics ,Anti-Bacterial Agents ,Pharmacogenomic Testing ,Hearing Loss, Sensorineural/chemically induced ,Aminoglycosides ,Pharmacogenetics ,RNA, Ribosomal ,030220 oncology & carcinogenesis ,Sensorineural hearing loss ,Patient Safety ,medicine.symptom ,business - Abstract
Aminoglycosides are widely used antibiotics with notable side effects such as nephrotoxicity, vestibulotoxicity and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
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- 2021
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5. PharmGKB summary
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Rachel Huddart, Melissa Clarke, Russ B. Altman, and Teri E. Klein
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PharmGKB ,MEDLINE ,Bioinformatics ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Genetics ,medicine ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Molecular Biology ,Genetics (clinical) ,Extramural ,business.industry ,Analgesics, Opioid ,Pharmacogenetics ,Molecular Medicine ,business ,Oxycodone ,Metabolic Networks and Pathways ,030217 neurology & neurosurgery ,medicine.drug - Published
- 2018
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6. Are Randomized Controlled Trials Necessary to Establish the Value of Implementing Pharmacogenomics in the Clinic?
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Rachel Huddart, Michelle Whirl-Carrillo, Katrin Sangkuhl, and Teri E. Klein
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Pharmacology ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Pharmacogenomic Variants ,business.industry ,Drug Resistance ,Article ,law.invention ,Randomized controlled trial ,Pharmacogenetics ,law ,Pharmacogenomics ,Humans ,Medicine ,Pharmacology (medical) ,Medical physics ,Precision Medicine ,business ,Value (mathematics) ,Randomized Controlled Trials as Topic - Published
- 2019
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7. PharmGKB summary: sertraline pathway, pharmacokinetics
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Rachel Huddart, J. Kevin Hicks, Russ B. Altman, D. Max Smith, Margarita Bobonis Babilonia, Jeffrey R. Strawn, Teri E. Klein, and Laura B. Ramsey
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Pharmacogenomic Variants ,Serotonin reuptake inhibitor ,Pharmacology ,Article ,Sertraline ,Genetics ,medicine ,Humans ,Drug Interactions ,General Pharmacology, Toxicology and Pharmaceutics ,Molecular Biology ,Genetics (clinical) ,chemistry.chemical_classification ,business.industry ,Mental Disorders ,Social anxiety ,Panic ,medicine.disease ,Toxic epidermal necrolysis ,chemistry ,Molecular Medicine ,Antidepressant ,Major depressive disorder ,medicine.symptom ,business ,Selective Serotonin Reuptake Inhibitors ,medicine.drug ,Tricyclic ,Signal Transduction - Abstract
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly prescribed to treat several psychiatric disorders including major depressive disorder, panic, generalized and social anxiety disorders as well as obsessive-compulsive disorder (OCD) [1]. It has similar efficacy to other SSRIs and is considered to cause fewer side effects than some antidepressants, such as tricyclic antidepressants [2, 3]. However, sertraline-induced adverse events such as reversible hepatic injury and Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported [4, 5]. Sertraline is a secondary amine with two chiral centers [6–9]. The potent cis-(1S,4S) enantiomer is used as an antidepressant in either a tablet or an oral solution [1, 7, 10], although the (1R,4R) enantiomer also inhibits serotonin reuptake [10].
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- 2019
8. PharmGKB summary: ondansetron and tropisetron pathways, pharmacokinetics and pharmacodynamics
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Rachel Huddart, Russ B. Altman, and Teri E. Klein
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Serotonin ,PharmGKB ,Tropisetron ,Pharmacology ,Article ,Ondansetron ,Pharmacokinetics ,Cytochrome P-450 CYP1A2 ,Genetics ,medicine ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Molecular Biology ,Genetics (clinical) ,Extramural ,business.industry ,Serotonin metabolism ,Cytochrome P-450 CYP2D6 ,Inactivation, Metabolic ,Molecular Medicine ,Serotonin Antagonists ,Receptors, Serotonin, 5-HT3 ,business ,Metabolic Networks and Pathways ,medicine.drug - Published
- 2019
9. Standardized biogeographic grouping system for annotating populations in pharmacogenetic research
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Carlos Bustamante, Michelle Whirl-Carrillo, Alison E. Fohner, Rachel Huddart, Christopher R. Gignoux, Genevieve L. Wojcik, Alice B. Popejoy, Russ B. Altman, and Teri E. Klein
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PharmGKB ,media_common.quotation_subject ,Population ,Geographic Mapping ,Context (language use) ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Population Groups ,Genetic variation ,Humans ,Pharmacology (medical) ,Genetic variability ,1000 Genomes Project ,Allele ,10. No inequality ,education ,Allele frequency ,030304 developmental biology ,media_common ,Pharmacology ,0303 health sciences ,education.field_of_study ,Genetic Variation ,Classification ,Pharmacogenomic Testing ,Geography ,Genetics, Population ,Evolutionary biology ,Pharmacogenetics ,030220 oncology & carcinogenesis ,Pharmacogenomics ,Genetic structure ,Topography, Medical ,Diversity (politics) - Abstract
The frequencies of pharmacogenetic alleles vary considerably between populations which has important implications for the impact of these alleles in different populations. However, current population grouping methods to communicate these patterns are insufficient as they are inconsistent and fail to reflect the distribution of genetic variability around the world. To facilitate and standardize the reporting of global variability in pharmacogenetic allele frequencies, we present nine broad biogeographical groups, defined by global autosomal genetic structure. These groups are based on data from large-scale initiatives, including the 1000 Genomes Project and the Human Genome Diversity Project, and reflect population genetic history, genetic distances between populations, and geographical proximity, with borders falling predominantly along national boundaries to simplify application of the grouping system. The geographically-defined groups are American, Central/South Asian, East Asian, European, Near Eastern, Oceanian, and Sub-Saharan African. Because of their distinct genetic patterns and frequent inclusion in published data, we also present two admixed groups: African American/Afro-Caribbean and Latino. Here, we characterize this population grouping system in the context of broad genomic data and present its utility for annotating pharmacogenetic studies and alleles. We recognize that broadly grouping global populations is an oversimplification of human diversity, does not capture complex social and cultural identity, and uses arbitrary geographic borders. However, this grouping method is consistent with robust population genetic patterns and meets a need of the pharmacogenetics field by enabling consistent communication of the scale of variability in global allele frequencies.
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- 2019
10. Novel Adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man
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Leo Swadling, Richard D Antrobus, Ayako Kurioka, Eleanor Barnes, C Willberg, M. Naddeo, Stefano Colloca, Maria Luisa Esposito, Virginia Ammendola, Antonella Folgori, Kira Smith, Stephen Aston, Joel Meyer, Geraldine O'Hara, Loredana Siani, Fabiana Grazioli, Adrian V. S. Hill, Cinzia Traboni, Paul Klenerman, Stefania Capone, Anthony Brown, Alfredo Nicosia, Riccardo Cortese, Ye Oo, Abby Harrison, Rachel Townsend, Rachel Huddart, David H. Adams, E., Barne, A., Folgori, S., Capone, L., Swadling, S., Aston, A., Kurioka, J., Meyer, R., Huddart, K., Smith, R., Townsend, A., Brown, R., Antrobu, V., Ammendola, M., Naddeo, G., O’Hara, C., Willberg, A., Harrison, F., Grazioli, M. L., Esposito, L., Siani, C., Traboni, Y., Oo, D., Adam, A., Hill, S., Colloca, Nicosia, Alfredo, R., Cortese, and P., Klenerman
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Interleukin 2 ,CD4-Positive T-Lymphocytes ,Viral Hepatitis Vaccines ,EXPRESSION ,Time Factors ,Genotype ,adenoviru ,T cell ,T-Lymphocytes ,design ,Heterologous ,Hepacivirus ,Biology ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,medicine.disease_cause ,HEPATITIS-C VIRUS ,Article ,Viral vector ,Adenoviridae ,Interferon-gamma ,vaccine ,INFECTION ,medicine ,Humans ,PROTECTION ,SPONTANEOUS CLEARANCE ,Cell Proliferation ,Tumor Necrosis Factor-alpha ,HEK 293 cells ,MEMORY ,PERSISTENCE ,General Medicine ,Virology ,Hepatitis C ,gene therapy ,medicine.anatomical_structure ,HEK293 Cells ,Immunology ,HCV ,biology.protein ,Leukocytes, Mononuclear ,immune-response ,Interleukin-2 ,CD8(+) ,CD8 ,medicine.drug - Abstract
Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge. We aimed to elicit HCV-specific T cells with the potential for protection using a recombinant adenoviral vector strategy in a phase 1 study of healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes [human adenovirus 6 (Ad6) and chimpanzee adenovirus 3 (ChAd3)]. Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells consisted of both CD4(+) and CD8(+) T cell subsets; secreted interleukin-2, interferon-gamma, and tumor necrosis factor-alpha; and could be sustained for at least a year after boosting with the heterologous adenoviral vector. Studies using major histocompatibility complex peptide tetramers revealed long-lived central and effector memory pools that retained polyfunctionality and proliferative capacity. These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV.
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- 2012
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