69 results on '"V. Paddock"'
Search Results
52. Contribution of hydrolyzed nucleic acids and their constituents to the apparent amino acid composition of biological compounds
- Author
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Gregory B. Wilson, An-Chuan Wang, and Gary V. Paddock
- Subjects
chemistry.chemical_classification ,Hydrolyzed protein ,Chemistry ,Nucleotides ,Hydrolysis ,Biophysics ,Nucleosides ,Cell Biology ,DNA ,Biochemistry ,Xanthoproteic reaction ,Photo-reactive amino acid analog ,Amino acid ,Pyrimidines ,RNA, Transfer ,Purines ,Glycine ,Nucleic acid ,Organic chemistry ,Nucleotide ,Chromatography, Thin Layer ,Amino Acids ,Molecular Biology - Abstract
Acid hydrolysis of protein-free mixtures of nucleotides, nucleosides, and nucleic acids yields amino acids, free bases, and possibly other unidentified fragments when analyzed by thin-layer chromatography and by standard amino acid analysis. Glycine is the predominant amino acid detected, which may constitute 47–97% of the apparent amino acid composition, depending on the type of material subjected to hydrolysis. Obviously, hydrolyzed nucleic acids or their constituents can therefore contribute to the apparent amino acid composition of a supposedly pure peptide or of other more complex mixtures of compounds mistakenly believed to contain only protein. To circumvent this problem, we suggest that nucleotides or nucleic acid moieties should be removed from any product for which the amino acid composition is desired, and that whenever a large glycine peak is noted in a hydrolyzed sample, the presence of nucleic acids or their constituents should be suspected.
- Published
- 1979
53. Detection of 'dialyzable transfer factor' in vitro: structural and chemical characterization of the activity specific for tuberculin
- Author
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H. Hugh Fudenberg, Gary V. Paddock, and Gregory B. Wilson
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Chemical Phenomena ,Chemistry ,General Neuroscience ,Transfer factor ,Ribose ,Oligonucleotides ,Tuberculin ,Transfer Factor ,General Biochemistry, Genetics and Molecular Biology ,In vitro ,History and Philosophy of Science ,Biochemistry ,Immunology ,Cell Migration Inhibition ,Chromatography, Gel ,Leukocytes ,Humans ,Amino Acids ,Dialysis ,Oligopeptides - Published
- 1979
54. HUMAN TRANSFER FACTOR: EXOGENOUS LABELLING, PURIFICATION, AND ROLE OF RIBONUCLEIC ACID SEGMENT11Publication no. 547 from the Department of Basic and Clinical Immunology and Microbiology. Research supported in part by USPHS Grant CA-25946
- Author
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Amanda M. Williams, H. Hugh Fudenberg, Gary V. Paddock, and Gregory B. Wilson
- Subjects
chemistry.chemical_compound ,Chromatography ,Biochemistry ,chemistry ,Sephadex ,Phenol extraction ,Reversed-phase chromatography ,Cellulose ,Polyacrylamide gel electrophoresis ,Pyrophosphate ,High-performance liquid chromatography ,Ethanol precipitation - Abstract
Publisher Summary This chapter presents data on the structures of both human transfer factor (TF) moieties derived from dialysates of leukocyte extracts (DLE) and on the radioactive labeling and subsequent further purification of human TF–H7. It describes experiments in which human TF–H5 and TF–H7 are purified from crude DLE by Sephadex G-25 chromatography, phenol extraction, ethanol precipitation, HPLC, cellulose TLC, and boronate affinity chromatography. In some cases, cellulose TLC was substituted for high-pressure reverse phase liquid chromatography and phenol extraction followed by ethanol precipitation was substituted for Sephadex G-25 chromatography. Bovine TF–C5 was similarly purified from material released by immune lymph node cells. Poiyethyleneimine cellulose (PEI) TLC was performed using ascending homochromatography at room temperature without prior wetting of the surface with water. The chapter presents degradation experiments with tobacco acid pyrophosphatase. This enzyme degrades pyrophosphate linkages such as those found in ATP or eucaryotic mRNA. As it is known that TAP has difficulty cleaving some pyrophoshate linkages, enough TAP is used to cleave the 5' cap linkage from 3μg of mRNA even though the physical amounts of each TP were below microgram levels. TF–H7 can be radiolabelled with 125 I using the method of Prensky. This finding and the ability to study TF–H7 using PEI–TLC and acrylamide gel electrophoresis open up new frontiers for research on the structure of TF.
- Published
- 1983
- Full Text
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55. CONTRIBUTORS
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K. Acott, Katsuhiko Akashi, Michel Allaray, Philippe Allard, Ralph G.I. Ashorn, Peter Baram, J. Berger, Jean Saint Blancard, J.F. Bonissent, William Borkowsky, Patrice Brunet-Lecomte, Denis Burger, Merrill W. Chase, Jean François Constant, Hervé de Muizon, Alain Blanchard de Vaucouleurs, J. Denis, K. Dogbe, Minter H. Dopson, Dominique Dormont, S. Doumerc, C.R. Drogemuller, John M. Dwyer, A. Ederlenis, A. Faggioni, Eugenia Floyd, Xavier Foullon, H. Hugh Fudenberg, Eva Gajdošová, Allan L. Goldstein, Lynn E. Greenberg, Gérald Haguenauer, Jean Hainaut, Troels Herlin, Jean-Denis Heyraud, Mary Jane Hicks, Robert S. Holzman, Jiro Inui, Jorgen Jensen, Wayburn S. Jeter, James F. Jones, Louise Just, Eliisa Karhumäki, Robert H. Keller, Jean Kermarec, Amanullah Khan, Charles H. Kirkpatrick, Phillip Klesius, Kai J.E. Krohn, H. Sherwood Lawrence, B. Lesourd, Thianda Manzara, M.R. Marescot, Vlastimil Mayer, John E. McClure, Eva Mitrová, Martin L. Morin, R. Moulias, Rebecca T. Newell, Tohru Nishihara, Tomohiko Ohno, Yasuto Okubo, Ctirad Oravec, Gary V. Paddock, Emily E. Paulling, Jean Pellegrin, J.F. Person, Eskild A. Petersen, J. Phillips, Ch. Pilet, Robert Pilson, G. Pizza, Guy Rocquet, F. Rosenfeld, Stephen J. Rozzo, Koji Saito, Thomas E. Schindler, Michael J. Schumacher, Erkki Seppälä, E. Jane Stuart, Leonard D. Stuart, Masayoshi Tanaka, Shigenori Tanaka, Kristian Thestrup-Pedersen, Marc Thinot, M. Thiollet, Kwong Y. Tsang, Mária Valášková, Jean Pierre Valleix, A.A. Vandenbark, Heikki Vapaatalo, D.L. Venton, R. Mark Vetto, J.M. Vich, Dimitri Viza, Amanda M. Williams, Gregory B. Wilson, Hideo Yamaguchi, and Hugh Zachariae
- Published
- 1983
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56. Structure and Regulation of Duck Globin Genes
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Fu-Kuen Lin, Gary V. Paddock, Jim Gaubatz, Robert Frankis, and William McNeill
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Genetics ,Globin genes ,Biology - Published
- 1984
- Full Text
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57. Nucleotide sequences for the duck globin mRNAs
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R C, Frankis and G V, Paddock
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Ducks ,Base Sequence ,Animals ,DNA ,RNA, Messenger ,Chickens ,Globins - Abstract
Normal adult ducks possess two main types of hemoglobin: a major species (80%), HbI (alpha I2 beta I2), and a minor species (20%), HbII (alpha II2 beta II2). We have cloned recombinant cDNAs for the duck globin mRNAs using the ribosubstitution floppy loop technique. We present here the sequence for a duck alpha globin mRNA closely related to the chicken alpha D globin mRNA. Our new sequence data also include the 5' noncoding regions of the duck alpha A, alpha D, and beta globin mRNAs. Analysis of the untranslated regions of these mRNAs reveals several conserved sequences which may be important in the regulation of gene expression.
- Published
- 1984
58. Globin proteins of the normal and anemic duck
- Author
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R.M.G. Nair, Robert Frankis, Michael J. Weise, and Gary V. Paddock
- Subjects
Hemolytic anemia ,Anemia, Hemolytic ,Chemical Phenomena ,Hemoglobins, Abnormal ,Biophysics ,Alpha (ethology) ,Biochemistry ,Hemoglobins ,medicine ,Animals ,Globin ,Amino Acids ,Alpha globulin ,Molecular Biology ,Chromatography, High Pressure Liquid ,Gel electrophoresis ,Isoelectric focusing ,Chemistry ,Hemoglobin A ,medicine.disease ,Peptide Fragments ,Globins ,Disease Models, Animal ,Ducks ,Hemoglobin ,Alpha chain - Abstract
The red blood cells of normal adult ducks contain two main hemoglobins. The most abundant type, HbA, comprises approximately 80% of the total, with the remaining 20% being made up of HbD. An attempt was made to determine whether during hemolytic anemia a special alpha globin chain (alpha s) replaces the alpha chain of HbA found in normal animals. This special stress alpha globin, whose existence has been seriously questioned, was originally postulated to explain the sequence discrepancies obtained between alpha chains of normal and anemic chickens and ducks. Using gel electrophoresis, isoelectric focusing, and HPLC peptide mapping techniques no qualitative differences between the alpha A globins of normal and anemic animals were found. The nature of the beta globin chains present in adult ducks has also never been rigorously established. In this work, a variety of techniques, including HPLC, gel electrophoresis, and microcolumn amino acid analysis, were used to examine the beta chains from each hemoglobin. Using these methods, no differences were found between the beta globin chains of the two hemoglobins.
- Published
- 1985
59. Construction of recombinant cDNA via a ribosubstituted hairpin
- Author
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Jim Gaubatz and Gary V. Paddock
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S1 nuclease ,Messenger RNA ,Base Sequence ,Biophysics ,DNA, Recombinant ,RNA-Directed DNA Polymerase ,Cell Biology ,Alkaline hydrolysis (body disposal) ,Biology ,Ribonucleotides ,Biochemistry ,Molecular biology ,law.invention ,Globins ,chemistry.chemical_compound ,chemistry ,law ,Complementary DNA ,Recombinant DNA ,Potential source ,RNA, Messenger ,Cloning, Molecular ,Molecular Biology ,DNA - Abstract
A new technique for recombinant cDNA construction is presented in which ribonucleotides are added to the 3′ end of cDNA via ribosubstitution prior to synthesis of the second DNA strand. The hairpin floppy loop is then opened by alkaline hydrolysis. This method eliminates the requirement for S1 nuclease and thus shows promise as a means for preservation of mRNA 5′-end sequences in recombinant cDNAs and for eliminating a potential source of error in those sequences.
- Published
- 1980
60. Determination of Globin mRNA Sequences and Their Insertion into Bacterial Plasmids
- Author
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Winston Salser, Russ Higuchi, Zakar P, Roberts J, Clarke P, Gary M. Studnicka, Browne F, Howard C. Heindell, and Gary V. Paddock
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Genetics ,chemistry.chemical_compound ,Plasmid ,chemistry ,Biochemistry ,Sequence analysis ,Complementary DNA ,Nucleic acid ,RNA ,Biology ,Molecular cloning ,Gene ,DNA - Abstract
Publisher Summary This chapter reviews that cDNA serves as the template for synthesis of a variety of products used in various phases. The synthesis products include 32 P-labeled RNA for sequence analysis of fragments resulting from a cleavage at G residues, 32 P-labeled dC- or dT-substituted RNAs for specific cleavage at U or at C residues, and duplex gene copies for insertion into bacterial plasmids. It reviews that molecular cloning approach is applied to a wide variety of eukaryotic mRNAs. One of the advantages of the technique that is developed for the insertion of eukaryotic mRNA copies into bacterial plasmids is that a rigorous purification is not necessary; the act of cloning such material definitively eliminates all contaminating eukaryotic nucleic acid sequences. This should be especially useful to the researcher who, for instance, has a mixture of 10 different mRNA species that are difficult to separate. To obtain the corresponding sequences in pure form, it suffices to make cDNA copies of the mixture of mRNAs, convert this mixture of cDNAs to duplex gene copies, insert the DNA into bacterial plasmids and introduce the mixture of plasmids thus obtained into bacteria. Since each bacterial transformant can receive only one of the eukaryotic gene inserts, analysis of a few dozen bacterial clones should suffice to provide one with a clone for each of the interesting sequences. With such clones, it is possible to produce milligram quantities of these sequences in duplex form, sufficient for the most rapid sequencing techniques.
- Published
- 1977
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61. PURIFICATION AND STRUCTURAL ANALYSIS OF THE TRANSFER FACTOR-LIKE ACTIVITY DETECTED IN VITRO BY LEUKOCYTE MIGRATION INHIBITION
- Author
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A. C. Wang, H. Hugh Fudenberg, Gregory B. Wilson, Gary V. Paddock, and Robert E. Lovins
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Leukocyte migration ,Chemistry ,Transfer factor ,In vitro ,Cell biology - Published
- 1979
- Full Text
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62. Dialyzable leukocyte extracts contain thymosin
- Author
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G B, Wilson, G V, Paddock, E, Floyd, R T, Newell, and M H, Dopson
- Subjects
Molecular Weight ,Thymosin ,Hot Temperature ,Rosette Formation ,Leukocytes ,Humans ,Isoelectric Point ,Cross Reactions - Abstract
Trypsinization of human T-lymphocytes removes surface receptors which bind to sheep erythrocytes (E). Human dialyzable leukocytes extracts (DLE) and thymosin (Fraction V) have been shown to significantly increase the rate of regeneration of T-lymphocyte E-receptors. Both physical-chemical and immunochemical results reported herein indicate that the enhancing effect of human DLE preparations on the rate of regeneration of T-lymphocyte E-receptors is due at least in part to the presence of thymosin alpha 1-peptide in these preparations. Thymosin alpha 1-peptide purified from thymosin Fraction V and putative thymosin alpha 1 preparations purified from human DLEs were each active not only in increasing the rate of regeneration of T-lymphocyte E-receptors removed by trypsinization but also were active in vitro in markedly increasing the number of E-rosetting cells in two patients with immunodeficiency disease manifested in part as a reduction in the normal percentage of mature T-lymphocytes capable of forming E-rosettes.
- Published
- 1984
63. Basic laboratory procedures in diagnostic virology
- Author
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H. Hugh Fudenberg and Gary V. Paddock
- Subjects
Philosophy ,Immunology ,Immunology and Allergy ,Library science ,Environmental ethics ,Diagnostic virology ,Pathology and Forensic Medicine - Published
- 1978
- Full Text
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64. Acute kidney injury after radial or femoral artery access in ST-segment elevation myocardial infarction: AKI-SAFARI.
- Author
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Marbach JA, Wells G, Santo PD, So D, Chong AY, Russo J, Labinaz M, Dick A, Froeschl M, Glover C, Hibbert B, Marquis JF, MacDougall A, Kass M, Paddock V, Quraishi AUR, Chandrasekhar J, Ghosh N, Bernick J, and Le May M
- Subjects
- Acute Kidney Injury blood, Acute Kidney Injury epidemiology, Aged, Creatinine blood, Female, Humans, Logistic Models, Male, Middle Aged, Percutaneous Coronary Intervention methods, Percutaneous Coronary Intervention statistics & numerical data, Acute Kidney Injury etiology, Femoral Artery, Percutaneous Coronary Intervention adverse effects, Radial Artery, ST Elevation Myocardial Infarction surgery
- Abstract
Background: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI., Methods: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline., Results: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38)., Conclusions: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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65. Transfemoral Aortic Valve Replacement (TAVR): Is Incorporation of Interventional Radiologists into the Team Beneficial?
- Author
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Légaré JF, Hassan A, O'Brien A, Archer B, Ferguson D, Forgie R, Teskey R, McGrath B, and Paddock V
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- 2019
- Full Text
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66. A reproductive justice approach to understanding women's experiences with HPV and cervical cancer prevention.
- Author
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Sundstrom B, Smith E, Delay C, Luque JS, Davila C, Feder B, Paddock V, Poudrier J, Pierce JY, and Brandt HM
- Subjects
- Adult, Aged, Early Detection of Cancer methods, Early Detection of Cancer psychology, Early Detection of Cancer standards, Female, Focus Groups methods, Health Knowledge, Attitudes, Practice, Humans, Mass Screening methods, Mass Screening psychology, Mass Screening standards, Middle Aged, Papillomavirus Infections psychology, Qualitative Research, Reproductive Health Services trends, South Carolina, Uterine Cervical Neoplasms diagnosis, Papillomavirus Infections complications, Reproductive Health Services standards, Social Justice, Uterine Cervical Neoplasms prevention & control
- Abstract
Cervical cancer is a preventable disease. HPV infection has been linked to more than 90% of cervical cancers. A vaccine to prevent the acquisition of HPV has been available since 2006. The purpose of this study was to investigate women's perceptions of cervical cancer prevention, including HPV vaccination. A reproductive justice framework guided data collection and analysis. In 2016, researchers conducted 70 in-depth, semi-structured qualitative interviews with women aged 19-78 years in South Carolina. A purposive sampling approach was employed to maximize requisite variety based on social, economic, and environmental axes of inequality. Participants self-identified as white (53%), African American (33%), and Hispanic (9%). Data analysis included an inductive constant comparative method to identify patterns and themes across the interviews. Misinformation about the prevalence and risk of HPV and cervical cancer led to "othering" of women with HPV-related diagnoses based on the flawed assumption of not being at risk. Participants described a lack of knowledge about the effectiveness and safety of the HPV vaccine. Social norms influenced participants' perceptions of HPV vaccination and cervical cancer, including concerns about sexual activity and intergenerational communication. Participants' social construction of identity, including race/ethnicity, socioeconomic position, ability, age, gender, sexual orientation, and immigration status, impacted their perceptions of cervical cancer screening and the HPV vaccine. In particular, participants believed that the HPV vaccine was "only for girls" and identified gender norms that limited uptake. Participants described barriers to accessing health care and cervical cancer screening, including cost, health insurance, and life changes (e.g., pregnancy, relocating). Many participants experienced an abnormal Papanicolaou test and described follow-up care, including biopsies and treatment for cervical dysplasia. Findings from this study offer insight into women's identity and perceptions of cervical cancer prevention. Results provide practical recommendations to increase women's agency in the development of successful public health interventions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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67. Regional differences in aortic valve replacements: Atlantic Canadian experience.
- Author
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McGuire C, Yip AM, MacLeod JB, Paddock V, Lutchmedial S, Nadeem N, Hirsch G, Adams C, Melvin K, Connors S, Hassan A, and Légaré JF
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, New Brunswick, Newfoundland and Labrador, Nova Scotia, Transcatheter Aortic Valve Replacement statistics & numerical data, Aortic Valve surgery, Bioprosthesis statistics & numerical data, Heart Valve Diseases surgery, Heart Valve Prosthesis statistics & numerical data, Heart Valve Prosthesis Implantation statistics & numerical data
- Abstract
Background: Transcatheter aortic valve implantation (TAVI) is evolving rapidly and is increasingly being adopted in the treatment of aortic valve disease. The goal of this study was to examine regional differences in surgical aortic valve replacement (SAVR) and TAVI across Atlantic Canada., Methods: We identified all patients who underwent SAVR or TAVI between Jan. 1, 2010, and Dec. 31, 2014, in New Brunswick, Nova Scotia and Newfoundland and Labrador. Data obtained included patient demographic characteristics and surgical procedure details. We performed univariate descriptive analyses and calculated crude and age- and sex-adjusted incidence rates., Results: A total of 3042 patients underwent SAVR or TAVI during the study period, 1491 in Nova Scotia, 1042 in New Brunswick and 509 in Newfoundland and Labrador. Patient demographic characteristics were similar across regions. A much higher proportion of patients in Newfoundland and Labrador (43.6%) than in Nova Scotia (4.2%) or New Brunswick (13.6%) received a mechanical versus a bioprosthetic valve. Rates of TAVI increased over the study period, with New Brunswick adopting their program before Nova Scotia (144 v. 74 procedures). Adjusted rates of all AVR procedures remained stable in Nova Scotia (40-50 per 100 000 people). Adjusted rates were lower in New Brunswick and Newfoundland and Labrador than in Nova Scotia; they increased slowly in New Brunswick over the study period., Conclusion: Despite geographical proximity and similar patient demographic characteristics, there existed regional differences in the management of aortic valve disease within Atlantic Canada. Further study is required to determine whether the observed differences in age- and sex-adjusted rates of AVR may be explained by geographical disease-related differences, varying practice patterns or barriers in access to care.
- Published
- 2018
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68. Structural Heart Disease Intervention: The Canadian Landscape.
- Author
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Asgar AW, Horlick E, McKenzie K, Brass N, Cantor WJ, Chan A, Della Siega A, Gobeil JF, Kassam S, Love MP, Mansour S, Martucci G, Nadeem N, Natarajan MK, Paddock V, Rodés-Cabau J, Traboulsi M, Velianou JL, Welsh RC, Wood D, and Webb JG
- Subjects
- Blood Vessel Prosthesis Implantation methods, Canada epidemiology, Cardiac Catheterization methods, Cross-Sectional Studies, Heart Valve Diseases epidemiology, Humans, Prevalence, Retrospective Studies, Blood Vessel Prosthesis Implantation statistics & numerical data, Cardiac Catheterization statistics & numerical data, Heart Valve Diseases surgery, Surveys and Questionnaires
- Abstract
Cardiovascular disease encompasses coronary artery disease and valvular heart disease, and the prevalence of both increases with age. Over the past decade, the landscape of interventional cardiology has evolved to encompass a new set of percutaneous procedures outside the coronary tree, including transcatheter aortic valve implantation, transcatheter mitral valve repair, and left atrial appendage occlusion. These interventions have sparked a new discipline within interventional cardiology referred to as structural heart disease (SHD) intervention. The access to and numbers of such procedures performed in Canada is currently unknown. This "first of its kind" survey of structural interventions provides insight into the landscape of SHD intervention in Canada and the challenges faced by cardiologists to deliver this important care., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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69. Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: quaternary amines.
- Author
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Hunt T, Atherton-Watson HC, Axford J, Collingwood SP, Coote KJ, Cox B, Czarnecki S, Danahay H, Devereux N, Howsham C, Hunt P, Paddock V, Paisley D, and Young A
- Subjects
- Amines pharmacology, Bronchi cytology, Dose-Response Relationship, Drug, Epithelial Cells metabolism, Epithelial Sodium Channels metabolism, Humans, Sodium Channel Blockers chemistry, Structure-Activity Relationship, Amines chemistry, Drug Design, Epithelial Cells drug effects, Epithelial Sodium Channel Blockers, Sodium Channel Blockers chemical synthesis, Sodium Channel Blockers pharmacology
- Abstract
We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC(50) of 200nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED(50) of 44μgkg(-1) at 1h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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