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class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Ferenc Follath</h3></div><div class="js-work-strip profile--work_container" data-work-id="29619206"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29619206/Spontaneous_Multivessel_Coronary_Artery_Dissection_Spontaneous_Multivessel_Coronary_Artery_Dissection_Surgical_Management_in_a_Postmenopausal_Woman"><img alt="Research paper thumbnail of Spontaneous Multivessel Coronary Artery Dissection Spontaneous Multivessel Coronary Artery Dissection Surgical Management in a Postmenopausal Woman" class="work-thumbnail" src="https://attachments.academia-assets.com/50058928/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29619206/Spontaneous_Multivessel_Coronary_Artery_Dissection_Spontaneous_Multivessel_Coronary_Artery_Dissection_Surgical_Management_in_a_Postmenopausal_Woman">Spontaneous Multivessel Coronary Artery Dissection Spontaneous Multivessel Coronary Artery Dissection Surgical Management in a Postmenopausal Woman</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://curtinedu.academia.edu/JShehatha">J. Shehatha</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FerencFollath">Ferenc Follath</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A 51-year-old postmenopausal woman presented at her local hospital with severe chest pain of sudd...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A 51-year-old postmenopausal woman presented at her local hospital with severe chest pain of sudden onset that radiated to the left arm and neck, shortness of breath, palpitation, and diaphoresis. She had no risk factors for coronary artery disease. Electrocardiographic (ECG) results were consistent with a diagnosis of acute inferior myocardial infarction. Reteplase was administered for thrombolysis. Glyceryl trinitrate and heparin infusion were started, and the patient was transferred to our hospital for further management. Upon arrival, she was free of angina. Approximately 4 hours after admission, severe angina recurred, and she underwent urgent coronary angiography. Extensive dissection involving the left anterior descending and left circumflex coronary arteries was seen (Fig. 1). The right coronary artery was normal. The left ventricular systolic function was normal. Due to ongoing angina and ischemic changes in the inferior and lateral ECG leads, an intra-aortic balloon pump was inserted, and urgent coronary artery bypass surgery was performed. Standard cardiopulmonary bypass and cardioplegia were used. During surgery, an extensive dissection was found, with a " vessel inside the vessel " appearance (Figs. 2A and 2B). There were no atherosclerotic plaques or any signs of atherosclerosis at the sites of the anastomoses or anywhere else in the coronary arteries. The left internal thoracic artery was grafted to the left anterior descending coronary artery, and greater saphe-nous vein grafts were used to bypass the diagonal and obtuse marginal arteries. Two layers of the dissected arteries were approximated and incorporated into a suture line with use of 7-0 Prolene suture (Ethicon Inc., a Johnson & Johnson company; Somer-ville, NJ) (Fig. 2). The patient made an uneventful recovery.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="978987ace15ee7c1ee3791c093605490" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":50058928,"asset_id":29619206,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/50058928/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29619206"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29619206"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29619206; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29619206]").text(description); $(".js-view-count[data-work-id=29619206]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29619206; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29619206']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29619206, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "978987ace15ee7c1ee3791c093605490" } } $('.js-work-strip[data-work-id=29619206]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29619206,"title":"Spontaneous Multivessel Coronary Artery Dissection Spontaneous Multivessel Coronary Artery Dissection Surgical Management in a Postmenopausal Woman","translated_title":"","metadata":{"abstract":"A 51-year-old postmenopausal woman presented at her local hospital with severe chest pain of sudden onset that radiated to the left arm and neck, shortness of breath, palpitation, and diaphoresis. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120142"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120142/Abstract_812_Renal_Function_And_Acute_Heart_Failure_A_Substudy_From_Alarm_hf"><img alt="Research paper thumbnail of Abstract 812: Renal Function And Acute Heart Failure: A Substudy From Alarm-hf" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120142/Abstract_812_Renal_Function_And_Acute_Heart_Failure_A_Substudy_From_Alarm_hf">Abstract 812: Renal Function And Acute Heart Failure: A Substudy From Alarm-hf</a></div><div class="wp-workCard_item"><span>Circulation</span><span>, Oct 28, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120142"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120142"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120142; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120141"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis"><img alt="Research paper thumbnail of Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis">Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis</a></div><div class="wp-workCard_item"><span>Ther Drug Monit</span><span>, 1986</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) f...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120141"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120141"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120141; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120141]").text(description); $(".js-view-count[data-work-id=29120141]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120141; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120141']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120141, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120141]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120141,"title":"Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis","translated_title":"","metadata":{"abstract":"The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.","publication_date":{"day":null,"month":null,"year":1986,"errors":{}},"publication_name":"Ther Drug Monit"},"translated_abstract":"The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.","internal_url":"https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis","translated_internal_url":"","created_at":"2016-10-13T02:38:05.901-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":2425,"name":"Free Radicals","url":"https://www.academia.edu/Documents/in/Free_Radicals"},{"id":9004,"name":"Dialysis","url":"https://www.academia.edu/Documents/in/Dialysis"},{"id":37447,"name":"Ultrafiltration","url":"https://www.academia.edu/Documents/in/Ultrafiltration"},{"id":58380,"name":"Therapeutic drug monitoring","url":"https://www.academia.edu/Documents/in/Therapeutic_drug_monitoring"},{"id":246560,"name":"High Pressure Liquid Chromatography","url":"https://www.academia.edu/Documents/in/High_Pressure_Liquid_Chromatography"},{"id":704276,"name":"Postural Balance","url":"https://www.academia.edu/Documents/in/Postural_Balance"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120140"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788"><img alt="Research paper thumbnail of Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788">Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788</a></div><div class="wp-workCard_item"><span>Deut Med Wochenschr</span><span>, 1984</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Repeated administration of diazepam in two ventilated patients had caused drug cumulation and com...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120140"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120140"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120140; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120140]").text(description); $(".js-view-count[data-work-id=29120140]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120140; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120140']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120140, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120140]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120140,"title":"Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788","translated_title":"","metadata":{"abstract":"Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.","publication_date":{"day":null,"month":null,"year":1984,"errors":{}},"publication_name":"Deut Med Wochenschr"},"translated_abstract":"Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.","internal_url":"https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788","translated_internal_url":"","created_at":"2016-10-13T02:38:05.432-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Verlängertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":10904,"name":"Electroencephalography","url":"https://www.academia.edu/Documents/in/Electroencephalography"},{"id":47139,"name":"Coma","url":"https://www.academia.edu/Documents/in/Coma"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":853012,"name":"Diazepam","url":"https://www.academia.edu/Documents/in/Diazepam"},{"id":2223059,"name":"Flumazenil","url":"https://www.academia.edu/Documents/in/Flumazenil"}],"urls":[{"id":7637257,"url":"http://thieme-connect.de/doi/doi?10.1055/s-2008-1069192"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120139"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics"><img alt="Research paper thumbnail of Metabolism of Antiarrhythmics" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics">Metabolism of Antiarrhythmics</a></div><div class="wp-workCard_item"><span>Curr Drug Metab</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120139"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120139"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120139; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120139]").text(description); $(".js-view-count[data-work-id=29120139]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120139; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120139']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120139, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120139]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120139,"title":"Metabolism of Antiarrhythmics","translated_title":"","metadata":{"abstract":"Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Curr Drug Metab"},"translated_abstract":"Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.","internal_url":"https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics","translated_internal_url":"","created_at":"2016-10-13T02:38:05.056-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Metabolism_of_Antiarrhythmics","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":11558,"name":"Drug interactions","url":"https://www.academia.edu/Documents/in/Drug_interactions"}],"urls":[{"id":7637256,"url":"http://ingentaselect.com/rpsv/cgi-bin/cgi?ini=xref\u0026body=linker\u0026reqdoi=10.2174/1389200043335351"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120138"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition"><img alt="Research paper thumbnail of Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition" class="work-thumbnail" src="https://attachments.academia-assets.com/49566672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition">Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition</a></div><div class="wp-workCard_item"><span>European Heart Journal</span><span>, Feb 1, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5621f18e28665898b25340c203950d49" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566672,"asset_id":29120138,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120138"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120138"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120138; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120138]").text(description); $(".js-view-count[data-work-id=29120138]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120138; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120138']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120138, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5621f18e28665898b25340c203950d49" } } $('.js-work-strip[data-work-id=29120138]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120138,"title":"Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition","translated_title":"","metadata":{"grobid_abstract":"Specific criteria have been established to define the occurrence of myocardial infarction (MI) and stroke in cardiovascular clinical trials, but there is not a consistent definition for heart failure. Heart failure events appear to occur at a rate that is similar to stroke and MI in trials of hypertension, hyperlipidaemia, diabetes, and coronary heart disease, yet a consistent approach to defining heart failure events has not yet been realized. The wide range of definitions used in clinical trials makes it difficult to interpret new data in the context of existing literature. This inconsistency has led to challenges in determining the incidence of heart failure in cardiovascular studies and the effects of interventions on these endpoints. This paper examines issues related to defining heart failure events in cardiovascular clinical trials and presents a definition to formally address this issue.","publication_date":{"day":1,"month":2,"year":2008,"errors":{}},"publication_name":"European Heart Journal","grobid_abstract_attachment_id":49566672},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition","translated_internal_url":"","created_at":"2016-10-13T02:38:04.682-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566672/thumbnails/1.jpg","file_name":"413.full.pdf","download_url":"https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Heart_failure_as_an_endpoint_in_heart_fa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566672/413.full-libre.pdf?1476354530=\u0026response-content-disposition=attachment%3B+filename%3DHeart_failure_as_an_endpoint_in_heart_fa.pdf\u0026Expires=1733175027\u0026Signature=b~xgYY5GvBCAAec-HScPivfuyKJcLLWLk3fMW3S~3ffkrLPSBfezXSzXr7-Ni8bttOzPzkHZxEQEqF-Kkj1Q7Buj9xcTqdlg9GMskk0LAmtyrei6LroQAH7V2xjeclZDtD5hSPFGTFNCBbMeAEG5c~ma6JDdE9502OpWHERKLc~vCCjN9dkoqTYBqupgSsiRdZE~E7LLwkpjQt3re28kgZqvqNkRTYnFFVPox4ZLQmRSyHgFg5RH3pDnZVnhn3NpNr5tZHK3qVXEvBhP2u3X9r2qWQKf~Gi6~H0Gg6aXtPBLKhYdcqs36aYNN1hfVKRkGtE6r7dUbGSxc-GMY50vUA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition","translated_slug":"","page_count":9,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566672/thumbnails/1.jpg","file_name":"413.full.pdf","download_url":"https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Heart_failure_as_an_endpoint_in_heart_fa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566672/413.full-libre.pdf?1476354530=\u0026response-content-disposition=attachment%3B+filename%3DHeart_failure_as_an_endpoint_in_heart_fa.pdf\u0026Expires=1733175027\u0026Signature=b~xgYY5GvBCAAec-HScPivfuyKJcLLWLk3fMW3S~3ffkrLPSBfezXSzXr7-Ni8bttOzPzkHZxEQEqF-Kkj1Q7Buj9xcTqdlg9GMskk0LAmtyrei6LroQAH7V2xjeclZDtD5hSPFGTFNCBbMeAEG5c~ma6JDdE9502OpWHERKLc~vCCjN9dkoqTYBqupgSsiRdZE~E7LLwkpjQt3re28kgZqvqNkRTYnFFVPox4ZLQmRSyHgFg5RH3pDnZVnhn3NpNr5tZHK3qVXEvBhP2u3X9r2qWQKf~Gi6~H0Gg6aXtPBLKhYdcqs36aYNN1hfVKRkGtE6r7dUbGSxc-GMY50vUA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":606,"name":"Cardiology","url":"https://www.academia.edu/Documents/in/Cardiology"},{"id":4531,"name":"Clinical Trial","url":"https://www.academia.edu/Documents/in/Clinical_Trial"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":83306,"name":"Consensus","url":"https://www.academia.edu/Documents/in/Consensus"},{"id":174502,"name":"Incidence","url":"https://www.academia.edu/Documents/in/Incidence"},{"id":179800,"name":"Definition","url":"https://www.academia.edu/Documents/in/Definition"},{"id":896306,"name":"Need","url":"https://www.academia.edu/Documents/in/Need"},{"id":2463778,"name":"Clinical Trials as Topic","url":"https://www.academia.edu/Documents/in/Clinical_Trials_as_Topic"}],"urls":[{"id":7637255,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=20031201"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120137"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship"><img alt="Research paper thumbnail of Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship">Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship</a></div><div class="wp-workCard_item"><span>American Journal of Physiology Lung Cellular and Molecular Physiology</span><span>, Aug 1, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modif...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120137"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120137"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120137; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120137]").text(description); $(".js-view-count[data-work-id=29120137]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120137; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120137']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120137, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120137]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120137,"title":"Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship","translated_title":"","metadata":{"abstract":"Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.","publication_date":{"day":1,"month":8,"year":2004,"errors":{}},"publication_name":"American Journal of Physiology Lung Cellular and Molecular Physiology"},"translated_abstract":"Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.","internal_url":"https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship","translated_internal_url":"","created_at":"2016-10-13T02:38:04.303-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":167,"name":"Physiology","url":"https://www.academia.edu/Documents/in/Physiology"},{"id":2184,"name":"Electron Microscopy","url":"https://www.academia.edu/Documents/in/Electron_Microscopy"},{"id":151448,"name":"American","url":"https://www.academia.edu/Documents/in/American"},{"id":172024,"name":"Analog","url":"https://www.academia.edu/Documents/in/Analog"},{"id":186234,"name":"Medical Physiology","url":"https://www.academia.edu/Documents/in/Medical_Physiology"},{"id":424553,"name":"Trachea","url":"https://www.academia.edu/Documents/in/Trachea"},{"id":788677,"name":"Rabbits","url":"https://www.academia.edu/Documents/in/Rabbits"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1317824,"name":"Amiodarone","url":"https://www.academia.edu/Documents/in/Amiodarone"}],"urls":[{"id":7637254,"url":"http://ajplung.physiology.org/cgi/doi/10.1152/ajplung.00434.2003"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120136"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120136/Presentation_and_outcome_of_critically_ill_medical_and_cardiac_surgery_patients_with_acute_heart_failure"><img alt="Research paper thumbnail of Presentation and outcome of critically ill medical and cardiac-surgery patients with acute heart failure" class="work-thumbnail" src="https://attachments.academia-assets.com/49566668/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120136/Presentation_and_outcome_of_critically_ill_medical_and_cardiac_surgery_patients_with_acute_heart_failure">Presentation and outcome of critically ill medical and cardiac-surgery patients with acute heart failure</a></div><div class="wp-workCard_item"><span>Swiss Medical Weekly Official Journal of the Swiss Society of Infectious Diseases the Swiss Society of Internal Medicine the Swiss Society of Pneumology</span><span>, Mar 1, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="27352d9b7b772c53298cedb00c23c767" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566668,"asset_id":29120136,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566668/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120136"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120136"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120136; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120135"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial"><img alt="Research paper thumbnail of Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial">Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial</a></div><div class="wp-workCard_item"><span>European Journal of Heart Failure</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120135"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120135"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120135; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120135]").text(description); $(".js-view-count[data-work-id=29120135]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120135; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120135']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120135, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120135]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120135,"title":"Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial","translated_title":"","metadata":{"abstract":"Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"European Journal of Heart Failure"},"translated_abstract":"Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.","internal_url":"https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial","translated_internal_url":"","created_at":"2016-10-13T02:38:03.576-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":12426,"name":"Treatment Outcome","url":"https://www.academia.edu/Documents/in/Treatment_Outcome"},{"id":41482,"name":"Multivariate Analysis","url":"https://www.academia.edu/Documents/in/Multivariate_Analysis"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":71284,"name":"Enalapril","url":"https://www.academia.edu/Documents/in/Enalapril"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":413194,"name":"Analysis of Variance","url":"https://www.academia.edu/Documents/in/Analysis_of_Variance"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1380501,"name":"Bisoprolol","url":"https://www.academia.edu/Documents/in/Bisoprolol"},{"id":2366663,"name":"Glomerular Filtration Rate","url":"https://www.academia.edu/Documents/in/Glomerular_Filtration_Rate"},{"id":2463496,"name":"Statistics as Topic","url":"https://www.academia.edu/Documents/in/Statistics_as_Topic"}],"urls":[{"id":7637253,"url":"http://www.lunduniversity.lu.se/lup/publication/2029071"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120134"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine"><img alt="Research paper thumbnail of 2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine">2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine</a></div><div class="wp-workCard_item"><span>Drug Metab Rev</span><span>, 1984</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The generality and flexibility of the computer package NONMEM also confront the user with the dif...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120134"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120134"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120134; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120134]").text(description); $(".js-view-count[data-work-id=29120134]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120134; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120134']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120134, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120134]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120134,"title":"2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine","translated_title":"","metadata":{"abstract":"The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.","publication_date":{"day":null,"month":null,"year":1984,"errors":{}},"publication_name":"Drug Metab Rev"},"translated_abstract":"The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.","internal_url":"https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine","translated_internal_url":"","created_at":"2016-10-13T02:38:03.195-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath","email":"MEVQY3ByazJXOTZDUjNZYXNJQjAzd2ROVmZGTm9GSDBpMVdYNndTckdZMD0tLXBhcEFUWTZhbjVlWVZueHByamY4SUE9PQ==--aec88aef21a33641f82c1a7fe2e6c756b4f86826"},"attachments":[],"research_interests":[{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics"},{"id":53293,"name":"Software","url":"https://www.academia.edu/Documents/in/Software"},{"id":59249,"name":"Computers","url":"https://www.academia.edu/Documents/in/Computers"},{"id":468993,"name":"Lidocaine","url":"https://www.academia.edu/Documents/in/Lidocaine"}],"urls":[{"id":7637252,"url":"http://informapharmascience.com/doi/abs/10.3109/03602538409015068"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120133"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events"><img alt="Research paper thumbnail of Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events" class="work-thumbnail" src="https://attachments.academia-assets.com/49566670/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events">Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events</a></div><div class="wp-workCard_item"><span>Journal of Pharmacology and Experimental Therapeutics</span><span>, Apr 1, 1999</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bf19bc73ce31987474df64194ebe35e4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566670,"asset_id":29120133,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120133"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120133"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120133; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120133]").text(description); $(".js-view-count[data-work-id=29120133]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120133; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120133']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120133, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bf19bc73ce31987474df64194ebe35e4" } } $('.js-work-strip[data-work-id=29120133]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120133,"title":"Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events","translated_title":"","metadata":{"grobid_abstract":"Angiotensin-converting enzyme (ACE) inhibitors are established as first-line therapy in chronic heart failure (CHF). However, little is known about the dosage-plasma-level relationship of ACE inhibitors in CHF and its relation to drug-induced adverse effects. We investigated 45 patients (age 55 Ϯ 10 years) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg b.i.d. (E10, n ϭ 16), 10 mg b.i.d. (E20, n ϭ 18), or 20 mg b.i.d. (E40, n ϭ 11). This dosage was changed three times to treat all patients with lower, higher, and, finally, the initial dosage for 4 weeks each. Patients were examined clinically, by questionnaire, and by spiroergometry. In addition, neurohormones (atrial and brain natriuretic peptide and norepinephrine), enalaprilat trough levels, and serum potassium and creatinine were measured. Enalaprilat trough levels differed significantly between the three groups at study entry but also varied markedly within each group. In addition to the dose of enalapril, serum creatinine, severity of CHF, basal metabolic rate, and body weight significantly influenced enalaprilat trough levels (R 2 ϭ.84, p Ͻ .001). Within-patient comparisons revealed that serum creatinine (107 Ϯ 26 versus 102 Ϯ 20 mol/liter) and potassium (3.8 Ϯ 0.4 versus 3.7 Ϯ 0.3mmol/liter) were higher, cough was more common (scored on a scale of 0 -8: 1.7 Ϯ 2.1 versus 1.4 Ϯ 1.8), and blood pressure was lower (systolic, 112 Ϯ 14 versus 117 Ϯ 13 mm Hg; diastolic, 66 Ϯ 9 versus 69 Ϯ 11 mm Hg) on the highest than on the lowest enalaprilat trough level (all p Ͻ .05). Highly variable enalaprilat trough levels and the fact that adverse effects were more common on high enalaprilat trough levels provide a rationale for individually adjusting ACE-inhibitor dose in case of adverse effects.","publication_date":{"day":1,"month":4,"year":1999,"errors":{}},"publication_name":"Journal of Pharmacology and Experimental Therapeutics","grobid_abstract_attachment_id":49566670},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events","translated_internal_url":"","created_at":"2016-10-13T02:38:02.828-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566670,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566670/thumbnails/1.jpg","file_name":"565.full.pdf","download_url":"https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Plasma_Levels_of_Enalaprilat_in_Chronic.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566670/565.full-libre.pdf?1476354534=\u0026response-content-disposition=attachment%3B+filename%3DPlasma_Levels_of_Enalaprilat_in_Chronic.pdf\u0026Expires=1733175027\u0026Signature=HFf8USZXGDcin8I5bsEfwBjme-wg8m8hP5w8mHWBTlrZQpikBIpXS~VPDCCSw3IvTJ4-UoaA4IT7sjVWGwKNrsXa7V6ByVDpfb8H0zsoQbTJ~UVln3ce-anc61Ot805nPboffgYw3PNXKs~1FDmk4qyQjfMlO0FIyIlYSZps9uUR9Rzna9vZtSXrnmmiofQWb3AoVsoMcHBDWnvQUzE3Y3LOz5PXB7lM4TadOUHzFO-Q6eiPrNYe49k4bO5DMjV3i8I0jqUCkFpF6nmObrJnZXMT-LOweiqDgqoCeOEmReMrfigt3K0M8NJ1dxkP0cXdmlHPEgCQdSqp3oPdH8I8zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566670,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566670/thumbnails/1.jpg","file_name":"565.full.pdf","download_url":"https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Plasma_Levels_of_Enalaprilat_in_Chronic.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566670/565.full-libre.pdf?1476354534=\u0026response-content-disposition=attachment%3B+filename%3DPlasma_Levels_of_Enalaprilat_in_Chronic.pdf\u0026Expires=1733175027\u0026Signature=HFf8USZXGDcin8I5bsEfwBjme-wg8m8hP5w8mHWBTlrZQpikBIpXS~VPDCCSw3IvTJ4-UoaA4IT7sjVWGwKNrsXa7V6ByVDpfb8H0zsoQbTJ~UVln3ce-anc61Ot805nPboffgYw3PNXKs~1FDmk4qyQjfMlO0FIyIlYSZps9uUR9Rzna9vZtSXrnmmiofQWb3AoVsoMcHBDWnvQUzE3Y3LOz5PXB7lM4TadOUHzFO-Q6eiPrNYe49k4bO5DMjV3i8I0jqUCkFpF6nmObrJnZXMT-LOweiqDgqoCeOEmReMrfigt3K0M8NJ1dxkP0cXdmlHPEgCQdSqp3oPdH8I8zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":97269,"name":"Chronic Disease","url":"https://www.academia.edu/Documents/in/Chronic_Disease"},{"id":160656,"name":"Potassium","url":"https://www.academia.edu/Documents/in/Potassium"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":378984,"name":"Spirometry","url":"https://www.academia.edu/Documents/in/Spirometry"},{"id":1146830,"name":"Cross-Over Studies","url":"https://www.academia.edu/Documents/in/Cross-Over_Studies"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1438730,"name":"Creatinine","url":"https://www.academia.edu/Documents/in/Creatinine"}],"urls":[{"id":7637251,"url":"http://jpet.aspetjournals.org/content/289/1/565.abstract"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120132"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120132/Cavernous_destruction_of_an_upper_lung_lobe_in_a_healthy_young_man_An_unusual_roentgenographic_presentation_of_allergic_bronchopulmonary_aspergillosis"><img alt="Research paper thumbnail of Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis" class="work-thumbnail" src="https://attachments.academia-assets.com/49566671/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120132/Cavernous_destruction_of_an_upper_lung_lobe_in_a_healthy_young_man_An_unusual_roentgenographic_presentation_of_allergic_bronchopulmonary_aspergillosis">Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis</a></div><div class="wp-workCard_item"><span>Chest Journal</span><span>, Jun 1, 1994</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6d90d8e75ebba87bb9ac139d2c8fe166" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566671,"asset_id":29120132,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566671/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120132"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120132"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120132; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120132]").text(description); $(".js-view-count[data-work-id=29120132]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120132; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120132']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120132, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6d90d8e75ebba87bb9ac139d2c8fe166" } } $('.js-work-strip[data-work-id=29120132]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120132,"title":"Cavernous destruction of an upper lung lobe in a healthy young man. 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Four healthy subjects received 3-OH-quinidine in increasing oral doses (35,100,300 mg) to achieve serum concentrations in the range of those after quinidine dosing in patients. Blood and urine were collected up to 48 hours and blood pressure, heart rate, and averaged ECG complexes were recorded during 12 hours after dosing. Kinetic analysis revealed differences \u0026om published data for the parent drug. Renal clearance was 1 6 Llhr. The elimination t% was 12.4 hours, substantially longer than that of quinidine. No systematic ECG changes were observed in two subjects with maximum concentrations of 55 and 215 pg/L. In the other two subjects who achieved higher maximum concentrations (447 and 918 \u0026I,), there was a signiscant relationship between the length of the corrected QT interval and the serum concentration of 3-OHquinidine. These first dynamic results indicate that 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine. (CLIN PHARMACOL THER Quinidine is one of the oldest yet still frequently used antiarrhythmic drugs. Quinidine elimination is mainly by metabolism, as only about 25% of a dose is excreted unchanged in urine. The metabolites that have been identified in man after quinidine include 3-OH-q~inidine,~ quinidine-N-oxide,6 quinidine-10-1 1 -dihydrodiol,'' and small amounts of 2'-quinidinone. The major metabolite, 3-OH-quinidine, which is present in blood at relatively high levels even after single doses of the parent drug, has been shown in animals to exert antiarrhythmic activity of the order of that of q~inidine.~ Comparison of the effect of quinidine on QT interval changes after oral and intravenous dosing indicates that some metabolite(s) may be partly responsible for the quinidine effect in man.9 For these reasons, 3-OH-quin-","publication_date":{"day":null,"month":null,"year":1985,"errors":{}},"publication_name":"Clinical Pharmacology and 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WowProfile.WorkStripView({ el: this, workJSON: {"id":29120130,"title":"Practical recommendations for prehospital and early in-hospital management of patients presenting with acute heart failure syndromes","translated_title":"","metadata":{"publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"Critical Care 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src="https://attachments.academia-assets.com/49566674/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120129/Nonpharmacologic_Measures_and_Drug_Compliance_in_Patients_with_Heart_Failure_Data_from_the_EuroHeart_Failure_Survey">Nonpharmacologic Measures and Drug Compliance in Patients with Heart Failure: Data from the EuroHeart Failure Survey</a></div><div class="wp-workCard_item"><span>The American Journal of Cardiology</span><span>, Mar 26, 2007</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7c6f596972d4aae7eee1ab17e3fee9ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120129]").text(description); $(".js-view-count[data-work-id=29120129]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120129; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120129']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120129, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "7c6f596972d4aae7eee1ab17e3fee9ac" } } $('.js-work-strip[data-work-id=29120129]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120129,"title":"Nonpharmacologic Measures and Drug Compliance in Patients with Heart Failure: Data from the EuroHeart Failure Survey","translated_title":"","metadata":{"grobid_abstract":"Advice on lifestyle, diet, vaccination, and therapy are part of the standard management of heart failure (HF). However, there is little information on whether patients with HF recall receiving such recommendations and, if so, whether they report following them. We obtained information on the recall of and adherence to nonpharmacologic advice from patients enrolled in the EuroHeart Failure Survey. This article focuses on 2,331 patients who had a clinical diagnosis of HF during the index admission and attended an interview 12 weeks after discharge. Their mean age was 67 ؎ 12 years and 38% were women. Patients recalled receiving 4.1 ؎ 2.7 items of advice with higher rates in Central Europe and the Mediterranean region. Recall of dietary advice (cholesterol or fat intake, 63%; dietary salt, 60%) was higher than for some other interventions (influenza vaccination, 36%; avoidance of nonsteroidal anti-inflammatory drugs, 17%). Among those who recalled the advice, a substantial proportion indicated that they did not follow advice completely (cholesterol and fat intake, 61%; dietary salt, 63%; influenza vaccination, 75%; avoidance of nonsteroidal anti-inflammatory drugs, 80%), although few patients indicated they ignored the advice completely. Patients who recalled \u003e4 items versus \u003c4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), ␤-blockers (51% vs 38%), and spironolactone (25% vs 21%). In conclusion, after hospitalization for HF, many patients do not recall nonpharmacologic advice. In addition, a substantial proportion of those who recall the advice follow it incompletely. Younger age and prescription of appropriate pharmacologic treatment are associated with higher rates of recall and implementation. © 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;99[suppl]:31D-37D) From the","publication_date":{"day":26,"month":3,"year":2007,"errors":{}},"publication_name":"The American Journal of Cardiology","grobid_abstract_attachment_id":49566674},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120129/Nonpharmacologic_Measures_and_Drug_Compliance_in_Patients_with_Heart_Failure_Data_from_the_EuroHeart_Failure_Survey","translated_internal_url":"","created_at":"2016-10-13T02:38:01.274-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566674/thumbnails/1.jpg","file_name":"j.amjcard.2006.12.01820161013-18679-mlikda.pdf","download_url":"https://www.academia.edu/attachments/49566674/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nonpharmacologic_Measures_and_Drug_Compl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566674/j.amjcard.2006.12.01820161013-18679-mlikda-libre.pdf?1476354529=\u0026response-content-disposition=attachment%3B+filename%3DNonpharmacologic_Measures_and_Drug_Compl.pdf\u0026Expires=1733175027\u0026Signature=TsCl1EvSrJTPnLt8lscny4CxAHPXEFRZMeegEtRd7fg74gVi~59TODaiGmfvXiMcBY3HqcQiZ9qu-AjARG8JYg~YIpa-rQjzQ-MMVJaKRKFA6cPZCOdWxJx0pdju1X7d~joY2Q8Iru-f6dIGxhyIs9gKNUxT62EJ34bPPbe~vWZzZ10Y-cd2Q0k4qBlYhHHVzTG9A2o4z9Zx0Bc3zxZRhVHYiVF1opeytr7wEp0guQDDGz1HJCjFlZjDIODttHT2L60hi0XaG7hyzfeT7Lbl0PtoXWTD2OCamR1g3C3v7fnfe3Snh0CCTAC~V4AodtD1ID2-IdiTjxwL6FoJ6i10Ww__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Nonpharmacologic_Measures_and_Drug_Compliance_in_Patients_with_Heart_Failure_Data_from_the_EuroHeart_Failure_Survey","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566674/thumbnails/1.jpg","file_name":"j.amjcard.2006.12.01820161013-18679-mlikda.pdf","download_url":"https://www.academia.edu/attachments/49566674/download_file?st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nonpharmacologic_Measures_and_Drug_Compl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566674/j.amjcard.2006.12.01820161013-18679-mlikda-libre.pdf?1476354529=\u0026response-content-disposition=attachment%3B+filename%3DNonpharmacologic_Measures_and_Drug_Compl.pdf\u0026Expires=1733175027\u0026Signature=TsCl1EvSrJTPnLt8lscny4CxAHPXEFRZMeegEtRd7fg74gVi~59TODaiGmfvXiMcBY3HqcQiZ9qu-AjARG8JYg~YIpa-rQjzQ-MMVJaKRKFA6cPZCOdWxJx0pdju1X7d~joY2Q8Iru-f6dIGxhyIs9gKNUxT62EJ34bPPbe~vWZzZ10Y-cd2Q0k4qBlYhHHVzTG9A2o4z9Zx0Bc3zxZRhVHYiVF1opeytr7wEp0guQDDGz1HJCjFlZjDIODttHT2L60hi0XaG7hyzfeT7Lbl0PtoXWTD2OCamR1g3C3v7fnfe3Snh0CCTAC~V4AodtD1ID2-IdiTjxwL6FoJ6i10Ww__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":606,"name":"Cardiology","url":"https://www.academia.edu/Documents/in/Cardiology"},{"id":7471,"name":"Life Style","url":"https://www.academia.edu/Documents/in/Life_Style"},{"id":8942,"name":"Treatment","url":"https://www.academia.edu/Documents/in/Treatment"},{"id":9478,"name":"Diet","url":"https://www.academia.edu/Documents/in/Diet"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":108782,"name":"Data","url":"https://www.academia.edu/Documents/in/Data"},{"id":135005,"name":"Patient Compliance","url":"https://www.academia.edu/Documents/in/Patient_Compliance"},{"id":153168,"name":"Data Collection","url":"https://www.academia.edu/Documents/in/Data_Collection"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1863718,"name":"The American","url":"https://www.academia.edu/Documents/in/The_American"}],"urls":[{"id":7637247,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=19118630"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120128"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120128/Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level"><img alt="Research paper thumbnail of Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120128/Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level">Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level</a></div><div class="wp-workCard_item"><span>American Journal of Respiratory Cell and Molecular Biology</span><span>, Dec 20, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120128"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120128"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120128; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120128]").text(description); $(".js-view-count[data-work-id=29120128]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120128; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120128']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120128, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120128]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120128,"title":"Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level","translated_title":"","metadata":{"abstract":"Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.","publication_date":{"day":20,"month":12,"year":2012,"errors":{}},"publication_name":"American Journal of Respiratory Cell and Molecular Biology"},"translated_abstract":"Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. 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href="https://www.academia.edu/29120125/Amiodarone_Inhibits_Arterial_Thrombus_Formation_and_Tissue_Factor_Translation">Amiodarone Inhibits Arterial Thrombus Formation and Tissue Factor Translation</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="3eba49e3c0365222674512f3fc07952a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566576,"asset_id":29120125,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566576/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120125"><a class="js-profile-work-strip-edit-button" 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$('.js-work-strip[data-work-id=29120125]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120125,"title":"Amiodarone Inhibits Arterial Thrombus Formation and Tissue Factor Translation","translated_title":"","metadata":{"ai_title_tag":"Amiodarone's Role in Thrombus and Tissue Factor Inhibition","grobid_abstract":"Background-In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. Methods and Results-Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-␣ and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. 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Death","url":"https://www.academia.edu/Documents/in/Sudden_Death"},{"id":71510,"name":"Endothelial Cells","url":"https://www.academia.edu/Documents/in/Endothelial_Cells"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":213910,"name":"Mitogen Activated Protein Kinase","url":"https://www.academia.edu/Documents/in/Mitogen_Activated_Protein_Kinase"},{"id":244814,"name":"Clinical Sciences","url":"https://www.academia.edu/Documents/in/Clinical_Sciences"},{"id":310960,"name":"mRna expression levels","url":"https://www.academia.edu/Documents/in/mRna_expression_levels"},{"id":474029,"name":"Tumor necrosis factor-alpha","url":"https://www.academia.edu/Documents/in/Tumor_necrosis_factor-alpha"},{"id":500737,"name":"Protein Degradation","url":"https://www.academia.edu/Documents/in/Protein_Degradation"},{"id":501806,"name":"Protein Expression","url":"https://www.academia.edu/Documents/in/Protein_Expression"},{"id":789977,"name":"Coronary Artery Disease","url":"https://www.academia.edu/Documents/in/Coronary_Artery_Disease"},{"id":878419,"name":"Ejection Fraction","url":"https://www.academia.edu/Documents/in/Ejection_Fraction"},{"id":969448,"name":"Carotid Artery","url":"https://www.academia.edu/Documents/in/Carotid_Artery"},{"id":1032923,"name":"Bleeding Time","url":"https://www.academia.edu/Documents/in/Bleeding_Time"},{"id":1156199,"name":"Tissue Factor","url":"https://www.academia.edu/Documents/in/Tissue_Factor"},{"id":1317824,"name":"Amiodarone","url":"https://www.academia.edu/Documents/in/Amiodarone"},{"id":1344345,"name":"Ventricular Arrhythmia","url":"https://www.academia.edu/Documents/in/Ventricular_Arrhythmia"},{"id":1449382,"name":"CAROTID ARTERY INJURIES","url":"https://www.academia.edu/Documents/in/CAROTID_ARTERY_INJURIES"},{"id":1588981,"name":"Protein Biosynthesis","url":"https://www.academia.edu/Documents/in/Protein_Biosynthesis"},{"id":2356404,"name":"Coronary artery","url":"https://www.academia.edu/Documents/in/Coronary_artery"}],"urls":[{"id":7637243,"url":"http://atvb.ahajournals.org/cgi/reprint/28/12/2231.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="5951212" id="papers"><div class="js-work-strip profile--work_container" data-work-id="29619206"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29619206/Spontaneous_Multivessel_Coronary_Artery_Dissection_Spontaneous_Multivessel_Coronary_Artery_Dissection_Surgical_Management_in_a_Postmenopausal_Woman"><img alt="Research paper thumbnail of Spontaneous Multivessel Coronary Artery Dissection Spontaneous Multivessel Coronary Artery Dissection Surgical Management in a Postmenopausal Woman" class="work-thumbnail" src="https://attachments.academia-assets.com/50058928/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29619206/Spontaneous_Multivessel_Coronary_Artery_Dissection_Spontaneous_Multivessel_Coronary_Artery_Dissection_Surgical_Management_in_a_Postmenopausal_Woman">Spontaneous Multivessel Coronary Artery Dissection Spontaneous Multivessel Coronary Artery Dissection Surgical Management in a Postmenopausal Woman</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://curtinedu.academia.edu/JShehatha">J. Shehatha</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/FerencFollath">Ferenc Follath</a></span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A 51-year-old postmenopausal woman presented at her local hospital with severe chest pain of sudd...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A 51-year-old postmenopausal woman presented at her local hospital with severe chest pain of sudden onset that radiated to the left arm and neck, shortness of breath, palpitation, and diaphoresis. She had no risk factors for coronary artery disease. Electrocardiographic (ECG) results were consistent with a diagnosis of acute inferior myocardial infarction. Reteplase was administered for thrombolysis. Glyceryl trinitrate and heparin infusion were started, and the patient was transferred to our hospital for further management. Upon arrival, she was free of angina. Approximately 4 hours after admission, severe angina recurred, and she underwent urgent coronary angiography. Extensive dissection involving the left anterior descending and left circumflex coronary arteries was seen (Fig. 1). The right coronary artery was normal. The left ventricular systolic function was normal. Due to ongoing angina and ischemic changes in the inferior and lateral ECG leads, an intra-aortic balloon pump was inserted, and urgent coronary artery bypass surgery was performed. Standard cardiopulmonary bypass and cardioplegia were used. During surgery, an extensive dissection was found, with a " vessel inside the vessel " appearance (Figs. 2A and 2B). There were no atherosclerotic plaques or any signs of atherosclerosis at the sites of the anastomoses or anywhere else in the coronary arteries. The left internal thoracic artery was grafted to the left anterior descending coronary artery, and greater saphe-nous vein grafts were used to bypass the diagonal and obtuse marginal arteries. Two layers of the dissected arteries were approximated and incorporated into a suture line with use of 7-0 Prolene suture (Ethicon Inc., a Johnson & Johnson company; Somer-ville, NJ) (Fig. 2). 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120141"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis"><img alt="Research paper thumbnail of Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis">Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis</a></div><div class="wp-workCard_item"><span>Ther Drug Monit</span><span>, 1986</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) f...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120141"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120141"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120141; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120141]").text(description); $(".js-view-count[data-work-id=29120141]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120141; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120141']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120141, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120141]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120141,"title":"Evaluation of a Rapid Ultrafiltration Technique for Determination of Quinidine Protein Binding and Comparison with Equilibrium Dialysis","translated_title":"","metadata":{"abstract":"The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.","publication_date":{"day":null,"month":null,"year":1986,"errors":{}},"publication_name":"Ther Drug Monit"},"translated_abstract":"The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.","internal_url":"https://www.academia.edu/29120141/Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis","translated_internal_url":"","created_at":"2016-10-13T02:38:05.901-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Evaluation_of_a_Rapid_Ultrafiltration_Technique_for_Determination_of_Quinidine_Protein_Binding_and_Comparison_with_Equilibrium_Dialysis","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":2425,"name":"Free Radicals","url":"https://www.academia.edu/Documents/in/Free_Radicals"},{"id":9004,"name":"Dialysis","url":"https://www.academia.edu/Documents/in/Dialysis"},{"id":37447,"name":"Ultrafiltration","url":"https://www.academia.edu/Documents/in/Ultrafiltration"},{"id":58380,"name":"Therapeutic drug monitoring","url":"https://www.academia.edu/Documents/in/Therapeutic_drug_monitoring"},{"id":246560,"name":"High Pressure Liquid Chromatography","url":"https://www.academia.edu/Documents/in/High_Pressure_Liquid_Chromatography"},{"id":704276,"name":"Postural Balance","url":"https://www.academia.edu/Documents/in/Postural_Balance"},{"id":1010725,"name":"Protein Binding","url":"https://www.academia.edu/Documents/in/Protein_Binding"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120140"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788"><img alt="Research paper thumbnail of Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788">Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788</a></div><div class="wp-workCard_item"><span>Deut Med Wochenschr</span><span>, 1984</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Repeated administration of diazepam in two ventilated patients had caused drug cumulation and com...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120140"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120140"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120140; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120140]").text(description); $(".js-view-count[data-work-id=29120140]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120140; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120140']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120140, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120140]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120140,"title":"Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten: Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788","translated_title":"","metadata":{"abstract":"Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.","publication_date":{"day":null,"month":null,"year":1984,"errors":{}},"publication_name":"Deut Med Wochenschr"},"translated_abstract":"Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.","internal_url":"https://www.academia.edu/29120140/Verl%C3%A4ngertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788","translated_internal_url":"","created_at":"2016-10-13T02:38:05.432-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Verlängertes_Koma_durch_Sedation_mit_Diazepam_bei_beatmeten_Patienten_Diagnostische_und_therapeutische_Anwendung_des_Benzodiazepin_Antagonisten_Ro_15_1788","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":10904,"name":"Electroencephalography","url":"https://www.academia.edu/Documents/in/Electroencephalography"},{"id":47139,"name":"Coma","url":"https://www.academia.edu/Documents/in/Coma"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":853012,"name":"Diazepam","url":"https://www.academia.edu/Documents/in/Diazepam"},{"id":2223059,"name":"Flumazenil","url":"https://www.academia.edu/Documents/in/Flumazenil"}],"urls":[{"id":7637257,"url":"http://thieme-connect.de/doi/doi?10.1055/s-2008-1069192"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120139"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics"><img alt="Research paper thumbnail of Metabolism of Antiarrhythmics" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics">Metabolism of Antiarrhythmics</a></div><div class="wp-workCard_item"><span>Curr Drug Metab</span><span>, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120139"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120139"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120139; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120139]").text(description); $(".js-view-count[data-work-id=29120139]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120139; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120139']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120139, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120139]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120139,"title":"Metabolism of Antiarrhythmics","translated_title":"","metadata":{"abstract":"Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.","publication_date":{"day":null,"month":null,"year":2004,"errors":{}},"publication_name":"Curr Drug Metab"},"translated_abstract":"Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.","internal_url":"https://www.academia.edu/29120139/Metabolism_of_Antiarrhythmics","translated_internal_url":"","created_at":"2016-10-13T02:38:05.056-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Metabolism_of_Antiarrhythmics","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":11558,"name":"Drug interactions","url":"https://www.academia.edu/Documents/in/Drug_interactions"}],"urls":[{"id":7637256,"url":"http://ingentaselect.com/rpsv/cgi-bin/cgi?ini=xref\u0026body=linker\u0026reqdoi=10.2174/1389200043335351"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120138"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition"><img alt="Research paper thumbnail of Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition" class="work-thumbnail" src="https://attachments.academia-assets.com/49566672/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition">Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition</a></div><div class="wp-workCard_item"><span>European Heart Journal</span><span>, Feb 1, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5621f18e28665898b25340c203950d49" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566672,"asset_id":29120138,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120138"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120138"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120138; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120138]").text(description); $(".js-view-count[data-work-id=29120138]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120138; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120138']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120138, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5621f18e28665898b25340c203950d49" } } $('.js-work-strip[data-work-id=29120138]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120138,"title":"Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition","translated_title":"","metadata":{"grobid_abstract":"Specific criteria have been established to define the occurrence of myocardial infarction (MI) and stroke in cardiovascular clinical trials, but there is not a consistent definition for heart failure. Heart failure events appear to occur at a rate that is similar to stroke and MI in trials of hypertension, hyperlipidaemia, diabetes, and coronary heart disease, yet a consistent approach to defining heart failure events has not yet been realized. The wide range of definitions used in clinical trials makes it difficult to interpret new data in the context of existing literature. This inconsistency has led to challenges in determining the incidence of heart failure in cardiovascular studies and the effects of interventions on these endpoints. This paper examines issues related to defining heart failure events in cardiovascular clinical trials and presents a definition to formally address this issue.","publication_date":{"day":1,"month":2,"year":2008,"errors":{}},"publication_name":"European Heart Journal","grobid_abstract_attachment_id":49566672},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120138/Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition","translated_internal_url":"","created_at":"2016-10-13T02:38:04.682-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566672/thumbnails/1.jpg","file_name":"413.full.pdf","download_url":"https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Heart_failure_as_an_endpoint_in_heart_fa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566672/413.full-libre.pdf?1476354530=\u0026response-content-disposition=attachment%3B+filename%3DHeart_failure_as_an_endpoint_in_heart_fa.pdf\u0026Expires=1733175027\u0026Signature=b~xgYY5GvBCAAec-HScPivfuyKJcLLWLk3fMW3S~3ffkrLPSBfezXSzXr7-Ni8bttOzPzkHZxEQEqF-Kkj1Q7Buj9xcTqdlg9GMskk0LAmtyrei6LroQAH7V2xjeclZDtD5hSPFGTFNCBbMeAEG5c~ma6JDdE9502OpWHERKLc~vCCjN9dkoqTYBqupgSsiRdZE~E7LLwkpjQt3re28kgZqvqNkRTYnFFVPox4ZLQmRSyHgFg5RH3pDnZVnhn3NpNr5tZHK3qVXEvBhP2u3X9r2qWQKf~Gi6~H0Gg6aXtPBLKhYdcqs36aYNN1hfVKRkGtE6r7dUbGSxc-GMY50vUA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Heart_failure_as_an_endpoint_in_heart_failure_and_non_heart_failure_cardiovascular_clinical_trials_the_need_for_a_consensus_definition","translated_slug":"","page_count":9,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566672,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566672/thumbnails/1.jpg","file_name":"413.full.pdf","download_url":"https://www.academia.edu/attachments/49566672/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Heart_failure_as_an_endpoint_in_heart_fa.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566672/413.full-libre.pdf?1476354530=\u0026response-content-disposition=attachment%3B+filename%3DHeart_failure_as_an_endpoint_in_heart_fa.pdf\u0026Expires=1733175027\u0026Signature=b~xgYY5GvBCAAec-HScPivfuyKJcLLWLk3fMW3S~3ffkrLPSBfezXSzXr7-Ni8bttOzPzkHZxEQEqF-Kkj1Q7Buj9xcTqdlg9GMskk0LAmtyrei6LroQAH7V2xjeclZDtD5hSPFGTFNCBbMeAEG5c~ma6JDdE9502OpWHERKLc~vCCjN9dkoqTYBqupgSsiRdZE~E7LLwkpjQt3re28kgZqvqNkRTYnFFVPox4ZLQmRSyHgFg5RH3pDnZVnhn3NpNr5tZHK3qVXEvBhP2u3X9r2qWQKf~Gi6~H0Gg6aXtPBLKhYdcqs36aYNN1hfVKRkGtE6r7dUbGSxc-GMY50vUA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":606,"name":"Cardiology","url":"https://www.academia.edu/Documents/in/Cardiology"},{"id":4531,"name":"Clinical Trial","url":"https://www.academia.edu/Documents/in/Clinical_Trial"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":83306,"name":"Consensus","url":"https://www.academia.edu/Documents/in/Consensus"},{"id":174502,"name":"Incidence","url":"https://www.academia.edu/Documents/in/Incidence"},{"id":179800,"name":"Definition","url":"https://www.academia.edu/Documents/in/Definition"},{"id":896306,"name":"Need","url":"https://www.academia.edu/Documents/in/Need"},{"id":2463778,"name":"Clinical Trials as Topic","url":"https://www.academia.edu/Documents/in/Clinical_Trials_as_Topic"}],"urls":[{"id":7637255,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=20031201"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120137"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship"><img alt="Research paper thumbnail of Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship">Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship</a></div><div class="wp-workCard_item"><span>American Journal of Physiology Lung Cellular and Molecular Physiology</span><span>, Aug 1, 2004</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modif...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120137"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120137"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120137; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120137]").text(description); $(".js-view-count[data-work-id=29120137]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120137; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120137']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120137, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120137]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120137,"title":"Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship","translated_title":"","metadata":{"abstract":"Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.","publication_date":{"day":1,"month":8,"year":2004,"errors":{}},"publication_name":"American Journal of Physiology Lung Cellular and Molecular Physiology"},"translated_abstract":"Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.","internal_url":"https://www.academia.edu/29120137/Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship","translated_internal_url":"","created_at":"2016-10-13T02:38:04.303-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Effects_of_metabolites_and_analogs_of_amiodarone_on_alveolar_macrophages_structure_activity_relationship","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":167,"name":"Physiology","url":"https://www.academia.edu/Documents/in/Physiology"},{"id":2184,"name":"Electron Microscopy","url":"https://www.academia.edu/Documents/in/Electron_Microscopy"},{"id":151448,"name":"American","url":"https://www.academia.edu/Documents/in/American"},{"id":172024,"name":"Analog","url":"https://www.academia.edu/Documents/in/Analog"},{"id":186234,"name":"Medical Physiology","url":"https://www.academia.edu/Documents/in/Medical_Physiology"},{"id":424553,"name":"Trachea","url":"https://www.academia.edu/Documents/in/Trachea"},{"id":788677,"name":"Rabbits","url":"https://www.academia.edu/Documents/in/Rabbits"},{"id":967839,"name":"Structure activity Relationship","url":"https://www.academia.edu/Documents/in/Structure_activity_Relationship"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1317824,"name":"Amiodarone","url":"https://www.academia.edu/Documents/in/Amiodarone"}],"urls":[{"id":7637254,"url":"http://ajplung.physiology.org/cgi/doi/10.1152/ajplung.00434.2003"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120136"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120136/Presentation_and_outcome_of_critically_ill_medical_and_cardiac_surgery_patients_with_acute_heart_failure"><img alt="Research paper thumbnail of Presentation and outcome of critically ill medical and cardiac-surgery patients with acute heart failure" class="work-thumbnail" src="https://attachments.academia-assets.com/49566668/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120136/Presentation_and_outcome_of_critically_ill_medical_and_cardiac_surgery_patients_with_acute_heart_failure">Presentation and outcome of critically ill medical and cardiac-surgery patients with acute heart failure</a></div><div class="wp-workCard_item"><span>Swiss Medical Weekly Official Journal of the Swiss Society of Infectious Diseases the Swiss Society of Internal Medicine the Swiss Society of Pneumology</span><span>, Mar 1, 2009</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="27352d9b7b772c53298cedb00c23c767" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566668,"asset_id":29120136,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566668/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120136"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120136"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120136; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120136]").text(description); $(".js-view-count[data-work-id=29120136]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120136; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120136']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120136, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120135"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial"><img alt="Research paper thumbnail of Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial">Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial</a></div><div class="wp-workCard_item"><span>European Journal of Heart Failure</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120135"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120135"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120135; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120135]").text(description); $(".js-view-count[data-work-id=29120135]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120135; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120135']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120135, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120135]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120135,"title":"Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial","translated_title":"","metadata":{"abstract":"Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"European Journal of Heart Failure"},"translated_abstract":"Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.","internal_url":"https://www.academia.edu/29120135/Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial","translated_internal_url":"","created_at":"2016-10-13T02:38:03.576-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Influence_of_order_and_type_of_drug_bisoprolol_vs_enalapril_on_outcome_and_adverse_events_in_patients_with_chronic_heart_failure_a_post_hoc_analysis_of_the_CIBIS_III_trial","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":12426,"name":"Treatment Outcome","url":"https://www.academia.edu/Documents/in/Treatment_Outcome"},{"id":41482,"name":"Multivariate Analysis","url":"https://www.academia.edu/Documents/in/Multivariate_Analysis"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":71284,"name":"Enalapril","url":"https://www.academia.edu/Documents/in/Enalapril"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":413194,"name":"Analysis of Variance","url":"https://www.academia.edu/Documents/in/Analysis_of_Variance"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1380501,"name":"Bisoprolol","url":"https://www.academia.edu/Documents/in/Bisoprolol"},{"id":2366663,"name":"Glomerular Filtration Rate","url":"https://www.academia.edu/Documents/in/Glomerular_Filtration_Rate"},{"id":2463496,"name":"Statistics as Topic","url":"https://www.academia.edu/Documents/in/Statistics_as_Topic"}],"urls":[{"id":7637253,"url":"http://www.lunduniversity.lu.se/lup/publication/2029071"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120134"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine"><img alt="Research paper thumbnail of 2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine">2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine</a></div><div class="wp-workCard_item"><span>Drug Metab Rev</span><span>, 1984</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The generality and flexibility of the computer package NONMEM also confront the user with the dif...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120134"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120134"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120134; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120134]").text(description); $(".js-view-count[data-work-id=29120134]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120134; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120134']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120134, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120134]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120134,"title":"2. Experience with Nonmem: Analysis of Serum Concentration Data in Patients Treated with Mexiletine and Lidocaine","translated_title":"","metadata":{"abstract":"The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.","publication_date":{"day":null,"month":null,"year":1984,"errors":{}},"publication_name":"Drug Metab Rev"},"translated_abstract":"The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.","internal_url":"https://www.academia.edu/29120134/2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine","translated_internal_url":"","created_at":"2016-10-13T02:38:03.195-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"2_Experience_with_Nonmem_Analysis_of_Serum_Concentration_Data_in_Patients_Treated_with_Mexiletine_and_Lidocaine","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath","email":"MEVQY3ByazJXOTZDUjNZYXNJQjAzd2ROVmZGTm9GSDBpMVdYNndTckdZMD0tLXBhcEFUWTZhbjVlWVZueHByamY4SUE9PQ==--aec88aef21a33641f82c1a7fe2e6c756b4f86826"},"attachments":[],"research_interests":[{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics"},{"id":53293,"name":"Software","url":"https://www.academia.edu/Documents/in/Software"},{"id":59249,"name":"Computers","url":"https://www.academia.edu/Documents/in/Computers"},{"id":468993,"name":"Lidocaine","url":"https://www.academia.edu/Documents/in/Lidocaine"}],"urls":[{"id":7637252,"url":"http://informapharmascience.com/doi/abs/10.3109/03602538409015068"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120133"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events"><img alt="Research paper thumbnail of Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events" class="work-thumbnail" src="https://attachments.academia-assets.com/49566670/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events">Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events</a></div><div class="wp-workCard_item"><span>Journal of Pharmacology and Experimental Therapeutics</span><span>, Apr 1, 1999</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bf19bc73ce31987474df64194ebe35e4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566670,"asset_id":29120133,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120133"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120133"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120133; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120133]").text(description); $(".js-view-count[data-work-id=29120133]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120133; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120133']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120133, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bf19bc73ce31987474df64194ebe35e4" } } $('.js-work-strip[data-work-id=29120133]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120133,"title":"Plasma Levels of Enalaprilat in Chronic Therapy of Heart Failure: Relationship to Adverse Events","translated_title":"","metadata":{"grobid_abstract":"Angiotensin-converting enzyme (ACE) inhibitors are established as first-line therapy in chronic heart failure (CHF). However, little is known about the dosage-plasma-level relationship of ACE inhibitors in CHF and its relation to drug-induced adverse effects. We investigated 45 patients (age 55 Ϯ 10 years) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg b.i.d. (E10, n ϭ 16), 10 mg b.i.d. (E20, n ϭ 18), or 20 mg b.i.d. (E40, n ϭ 11). This dosage was changed three times to treat all patients with lower, higher, and, finally, the initial dosage for 4 weeks each. Patients were examined clinically, by questionnaire, and by spiroergometry. In addition, neurohormones (atrial and brain natriuretic peptide and norepinephrine), enalaprilat trough levels, and serum potassium and creatinine were measured. Enalaprilat trough levels differed significantly between the three groups at study entry but also varied markedly within each group. In addition to the dose of enalapril, serum creatinine, severity of CHF, basal metabolic rate, and body weight significantly influenced enalaprilat trough levels (R 2 ϭ.84, p Ͻ .001). Within-patient comparisons revealed that serum creatinine (107 Ϯ 26 versus 102 Ϯ 20 mol/liter) and potassium (3.8 Ϯ 0.4 versus 3.7 Ϯ 0.3mmol/liter) were higher, cough was more common (scored on a scale of 0 -8: 1.7 Ϯ 2.1 versus 1.4 Ϯ 1.8), and blood pressure was lower (systolic, 112 Ϯ 14 versus 117 Ϯ 13 mm Hg; diastolic, 66 Ϯ 9 versus 69 Ϯ 11 mm Hg) on the highest than on the lowest enalaprilat trough level (all p Ͻ .05). Highly variable enalaprilat trough levels and the fact that adverse effects were more common on high enalaprilat trough levels provide a rationale for individually adjusting ACE-inhibitor dose in case of adverse effects.","publication_date":{"day":1,"month":4,"year":1999,"errors":{}},"publication_name":"Journal of Pharmacology and Experimental Therapeutics","grobid_abstract_attachment_id":49566670},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120133/Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events","translated_internal_url":"","created_at":"2016-10-13T02:38:02.828-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566670,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566670/thumbnails/1.jpg","file_name":"565.full.pdf","download_url":"https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Plasma_Levels_of_Enalaprilat_in_Chronic.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566670/565.full-libre.pdf?1476354534=\u0026response-content-disposition=attachment%3B+filename%3DPlasma_Levels_of_Enalaprilat_in_Chronic.pdf\u0026Expires=1733175027\u0026Signature=HFf8USZXGDcin8I5bsEfwBjme-wg8m8hP5w8mHWBTlrZQpikBIpXS~VPDCCSw3IvTJ4-UoaA4IT7sjVWGwKNrsXa7V6ByVDpfb8H0zsoQbTJ~UVln3ce-anc61Ot805nPboffgYw3PNXKs~1FDmk4qyQjfMlO0FIyIlYSZps9uUR9Rzna9vZtSXrnmmiofQWb3AoVsoMcHBDWnvQUzE3Y3LOz5PXB7lM4TadOUHzFO-Q6eiPrNYe49k4bO5DMjV3i8I0jqUCkFpF6nmObrJnZXMT-LOweiqDgqoCeOEmReMrfigt3K0M8NJ1dxkP0cXdmlHPEgCQdSqp3oPdH8I8zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Plasma_Levels_of_Enalaprilat_in_Chronic_Therapy_of_Heart_Failure_Relationship_to_Adverse_Events","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566670,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566670/thumbnails/1.jpg","file_name":"565.full.pdf","download_url":"https://www.academia.edu/attachments/49566670/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Plasma_Levels_of_Enalaprilat_in_Chronic.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566670/565.full-libre.pdf?1476354534=\u0026response-content-disposition=attachment%3B+filename%3DPlasma_Levels_of_Enalaprilat_in_Chronic.pdf\u0026Expires=1733175027\u0026Signature=HFf8USZXGDcin8I5bsEfwBjme-wg8m8hP5w8mHWBTlrZQpikBIpXS~VPDCCSw3IvTJ4-UoaA4IT7sjVWGwKNrsXa7V6ByVDpfb8H0zsoQbTJ~UVln3ce-anc61Ot805nPboffgYw3PNXKs~1FDmk4qyQjfMlO0FIyIlYSZps9uUR9Rzna9vZtSXrnmmiofQWb3AoVsoMcHBDWnvQUzE3Y3LOz5PXB7lM4TadOUHzFO-Q6eiPrNYe49k4bO5DMjV3i8I0jqUCkFpF6nmObrJnZXMT-LOweiqDgqoCeOEmReMrfigt3K0M8NJ1dxkP0cXdmlHPEgCQdSqp3oPdH8I8zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":97269,"name":"Chronic Disease","url":"https://www.academia.edu/Documents/in/Chronic_Disease"},{"id":160656,"name":"Potassium","url":"https://www.academia.edu/Documents/in/Potassium"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":378984,"name":"Spirometry","url":"https://www.academia.edu/Documents/in/Spirometry"},{"id":1146830,"name":"Cross-Over Studies","url":"https://www.academia.edu/Documents/in/Cross-Over_Studies"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1438730,"name":"Creatinine","url":"https://www.academia.edu/Documents/in/Creatinine"}],"urls":[{"id":7637251,"url":"http://jpet.aspetjournals.org/content/289/1/565.abstract"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120132"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120132/Cavernous_destruction_of_an_upper_lung_lobe_in_a_healthy_young_man_An_unusual_roentgenographic_presentation_of_allergic_bronchopulmonary_aspergillosis"><img alt="Research paper thumbnail of Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis" class="work-thumbnail" src="https://attachments.academia-assets.com/49566671/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120132/Cavernous_destruction_of_an_upper_lung_lobe_in_a_healthy_young_man_An_unusual_roentgenographic_presentation_of_allergic_bronchopulmonary_aspergillosis">Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis</a></div><div class="wp-workCard_item"><span>Chest Journal</span><span>, Jun 1, 1994</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="6d90d8e75ebba87bb9ac139d2c8fe166" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":49566671,"asset_id":29120132,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/49566671/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120132"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120132"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120132; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120132]").text(description); $(".js-view-count[data-work-id=29120132]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120132; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120132']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120132, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "6d90d8e75ebba87bb9ac139d2c8fe166" } } $('.js-work-strip[data-work-id=29120132]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120132,"title":"Cavernous destruction of an upper lung lobe in a healthy young man. 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Four healthy subjects received 3-OH-quinidine in increasing oral doses (35,100,300 mg) to achieve serum concentrations in the range of those after quinidine dosing in patients. Blood and urine were collected up to 48 hours and blood pressure, heart rate, and averaged ECG complexes were recorded during 12 hours after dosing. Kinetic analysis revealed differences \u0026om published data for the parent drug. Renal clearance was 1 6 Llhr. The elimination t% was 12.4 hours, substantially longer than that of quinidine. No systematic ECG changes were observed in two subjects with maximum concentrations of 55 and 215 pg/L. In the other two subjects who achieved higher maximum concentrations (447 and 918 \u0026I,), there was a signiscant relationship between the length of the corrected QT interval and the serum concentration of 3-OHquinidine. These first dynamic results indicate that 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine. (CLIN PHARMACOL THER Quinidine is one of the oldest yet still frequently used antiarrhythmic drugs. Quinidine elimination is mainly by metabolism, as only about 25% of a dose is excreted unchanged in urine. The metabolites that have been identified in man after quinidine include 3-OH-q~inidine,~ quinidine-N-oxide,6 quinidine-10-1 1 -dihydrodiol,'' and small amounts of 2'-quinidinone. The major metabolite, 3-OH-quinidine, which is present in blood at relatively high levels even after single doses of the parent drug, has been shown in animals to exert antiarrhythmic activity of the order of that of q~inidine.~ Comparison of the effect of quinidine on QT interval changes after oral and intravenous dosing indicates that some metabolite(s) may be partly responsible for the quinidine effect in man.9 For these reasons, 3-OH-quin-","publication_date":{"day":null,"month":null,"year":1985,"errors":{}},"publication_name":"Clinical Pharmacology and 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id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "7c6f596972d4aae7eee1ab17e3fee9ac" } } $('.js-work-strip[data-work-id=29120129]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120129,"title":"Nonpharmacologic Measures and Drug Compliance in Patients with Heart Failure: Data from the EuroHeart Failure Survey","translated_title":"","metadata":{"grobid_abstract":"Advice on lifestyle, diet, vaccination, and therapy are part of the standard management of heart failure (HF). However, there is little information on whether patients with HF recall receiving such recommendations and, if so, whether they report following them. We obtained information on the recall of and adherence to nonpharmacologic advice from patients enrolled in the EuroHeart Failure Survey. This article focuses on 2,331 patients who had a clinical diagnosis of HF during the index admission and attended an interview 12 weeks after discharge. Their mean age was 67 ؎ 12 years and 38% were women. Patients recalled receiving 4.1 ؎ 2.7 items of advice with higher rates in Central Europe and the Mediterranean region. Recall of dietary advice (cholesterol or fat intake, 63%; dietary salt, 60%) was higher than for some other interventions (influenza vaccination, 36%; avoidance of nonsteroidal anti-inflammatory drugs, 17%). Among those who recalled the advice, a substantial proportion indicated that they did not follow advice completely (cholesterol and fat intake, 61%; dietary salt, 63%; influenza vaccination, 75%; avoidance of nonsteroidal anti-inflammatory drugs, 80%), although few patients indicated they ignored the advice completely. Patients who recalled \u003e4 items versus \u003c4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), ␤-blockers (51% vs 38%), and spironolactone (25% vs 21%). In conclusion, after hospitalization for HF, many patients do not recall nonpharmacologic advice. In addition, a substantial proportion of those who recall the advice follow it incompletely. Younger age and prescription of appropriate pharmacologic treatment are associated with higher rates of recall and implementation. © 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;99[suppl]:31D-37D) From the","publication_date":{"day":26,"month":3,"year":2007,"errors":{}},"publication_name":"The American Journal of Cardiology","grobid_abstract_attachment_id":49566674},"translated_abstract":null,"internal_url":"https://www.academia.edu/29120129/Nonpharmacologic_Measures_and_Drug_Compliance_in_Patients_with_Heart_Failure_Data_from_the_EuroHeart_Failure_Survey","translated_internal_url":"","created_at":"2016-10-13T02:38:01.274-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":49566674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566674/thumbnails/1.jpg","file_name":"j.amjcard.2006.12.01820161013-18679-mlikda.pdf","download_url":"https://www.academia.edu/attachments/49566674/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nonpharmacologic_Measures_and_Drug_Compl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566674/j.amjcard.2006.12.01820161013-18679-mlikda-libre.pdf?1476354529=\u0026response-content-disposition=attachment%3B+filename%3DNonpharmacologic_Measures_and_Drug_Compl.pdf\u0026Expires=1733175027\u0026Signature=TsCl1EvSrJTPnLt8lscny4CxAHPXEFRZMeegEtRd7fg74gVi~59TODaiGmfvXiMcBY3HqcQiZ9qu-AjARG8JYg~YIpa-rQjzQ-MMVJaKRKFA6cPZCOdWxJx0pdju1X7d~joY2Q8Iru-f6dIGxhyIs9gKNUxT62EJ34bPPbe~vWZzZ10Y-cd2Q0k4qBlYhHHVzTG9A2o4z9Zx0Bc3zxZRhVHYiVF1opeytr7wEp0guQDDGz1HJCjFlZjDIODttHT2L60hi0XaG7hyzfeT7Lbl0PtoXWTD2OCamR1g3C3v7fnfe3Snh0CCTAC~V4AodtD1ID2-IdiTjxwL6FoJ6i10Ww__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Nonpharmacologic_Measures_and_Drug_Compliance_in_Patients_with_Heart_Failure_Data_from_the_EuroHeart_Failure_Survey","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[{"id":49566674,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/49566674/thumbnails/1.jpg","file_name":"j.amjcard.2006.12.01820161013-18679-mlikda.pdf","download_url":"https://www.academia.edu/attachments/49566674/download_file?st=MTczMzE3MTQyOCw4LjIyMi4yMDguMTQ2&st=MTczMzE3MTQyNyw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Nonpharmacologic_Measures_and_Drug_Compl.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/49566674/j.amjcard.2006.12.01820161013-18679-mlikda-libre.pdf?1476354529=\u0026response-content-disposition=attachment%3B+filename%3DNonpharmacologic_Measures_and_Drug_Compl.pdf\u0026Expires=1733175027\u0026Signature=TsCl1EvSrJTPnLt8lscny4CxAHPXEFRZMeegEtRd7fg74gVi~59TODaiGmfvXiMcBY3HqcQiZ9qu-AjARG8JYg~YIpa-rQjzQ-MMVJaKRKFA6cPZCOdWxJx0pdju1X7d~joY2Q8Iru-f6dIGxhyIs9gKNUxT62EJ34bPPbe~vWZzZ10Y-cd2Q0k4qBlYhHHVzTG9A2o4z9Zx0Bc3zxZRhVHYiVF1opeytr7wEp0guQDDGz1HJCjFlZjDIODttHT2L60hi0XaG7hyzfeT7Lbl0PtoXWTD2OCamR1g3C3v7fnfe3Snh0CCTAC~V4AodtD1ID2-IdiTjxwL6FoJ6i10Ww__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":606,"name":"Cardiology","url":"https://www.academia.edu/Documents/in/Cardiology"},{"id":7471,"name":"Life Style","url":"https://www.academia.edu/Documents/in/Life_Style"},{"id":8942,"name":"Treatment","url":"https://www.academia.edu/Documents/in/Treatment"},{"id":9478,"name":"Diet","url":"https://www.academia.edu/Documents/in/Diet"},{"id":49633,"name":"Heart Failure","url":"https://www.academia.edu/Documents/in/Heart_Failure"},{"id":108782,"name":"Data","url":"https://www.academia.edu/Documents/in/Data"},{"id":135005,"name":"Patient Compliance","url":"https://www.academia.edu/Documents/in/Patient_Compliance"},{"id":153168,"name":"Data Collection","url":"https://www.academia.edu/Documents/in/Data_Collection"},{"id":289271,"name":"Aged","url":"https://www.academia.edu/Documents/in/Aged"},{"id":1227768,"name":"Angiotensin Converting Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Angiotensin_Converting_Enzyme_Inhibitors"},{"id":1863718,"name":"The American","url":"https://www.academia.edu/Documents/in/The_American"}],"urls":[{"id":7637247,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=19118630"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="29120128"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/29120128/Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level"><img alt="Research paper thumbnail of Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/29120128/Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level">Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level</a></div><div class="wp-workCard_item"><span>American Journal of Respiratory Cell and Molecular Biology</span><span>, Dec 20, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="29120128"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="29120128"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 29120128; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=29120128]").text(description); $(".js-view-count[data-work-id=29120128]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 29120128; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='29120128']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 29120128, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=29120128]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":29120128,"title":"Amiodarone Alters Late Endosomes and Inhibits SARS Coronavirus Infection at a Post-Endosomal Level","translated_title":"","metadata":{"abstract":"Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.","publication_date":{"day":20,"month":12,"year":2012,"errors":{}},"publication_name":"American Journal of Respiratory Cell and Molecular Biology"},"translated_abstract":"Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.","internal_url":"https://www.academia.edu/29120128/Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level","translated_internal_url":"","created_at":"2016-10-13T02:38:00.891-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":54773906,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Amiodarone_Alters_Late_Endosomes_and_Inhibits_SARS_Coronavirus_Infection_at_a_Post_Endosomal_Level","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":54773906,"first_name":"Ferenc","middle_initials":null,"last_name":"Follath","page_name":"FerencFollath","domain_name":"independent","created_at":"2016-10-10T05:19:59.883-07:00","display_name":"Ferenc Follath","url":"https://independent.academia.edu/FerencFollath"},"attachments":[],"research_interests":[{"id":57570,"name":"Cercopithecus aethiops","url":"https://www.academia.edu/Documents/in/Cercopithecus_aethiops"},{"id":182962,"name":"Life Cycle","url":"https://www.academia.edu/Documents/in/Life_Cycle"},{"id":288383,"name":"Intestinal absorption","url":"https://www.academia.edu/Documents/in/Intestinal_absorption"},{"id":584613,"name":"Cysteine endopeptidases","url":"https://www.academia.edu/Documents/in/Cysteine_endopeptidases"},{"id":871114,"name":"Severe Acute Respiratory Syndrome (SARS)","url":"https://www.academia.edu/Documents/in/Severe_Acute_Respiratory_Syndrome_SARS_"},{"id":902999,"name":"Antiviral Activity","url":"https://www.academia.edu/Documents/in/Antiviral_Activity"},{"id":1166930,"name":"Cytoplasm","url":"https://www.academia.edu/Documents/in/Cytoplasm"},{"id":1242344,"name":"Plasma 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Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. Methods and Results-Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-␣ and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. 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