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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18312156&#x26;dopt=Abstract\">Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18312156&#x22;>Related Articles</a></td></tr></table>        <p><b>Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview.</b></p>        <p>Expert Opin Pharmacother. 2008 Mar;9(4):537-49</p>        <p>Authors:  Smits JP, Blom MT, Wilde AA, Tan HL</p>        <p>Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.</p>        <p>PMID: 18312156 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17970826&#x26;dopt=Abstract\">Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1111/j.1748-1716.2007.01753.x&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17970826&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart.</b></p>        <p>Acta Physiol (Oxf). 2008 Mar;192(3):359-68</p>        <p>Authors:  Lengyel C, Vir&#x26;#xE1;g L, Kov&#x26;#xE1;cs PP, Krist&#x26;#xF3;f A, Pacher P, Kocsis E, Koltay ZM, N&#x26;#xE1;n&#x26;#xE1;si PP, T&#x26;#xF3;th M, Kecskem&#x26;#xE9;ti V, Papp JG, Varr&#x26;#xF3; A, Jost N</p>        <p>AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P &#x26;lt; 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P &#x26;lt; 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.</p>        <p>PMID: 17970826 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18070294&#x26;dopt=Abstract\">Discarding the baby with the bathwater.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0147-8389&#x26;amp;date=2007&#x26;amp;volume=30&#x26;amp;issue=12&#x26;amp;spage=1429&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18070294&#x22;>Related Articles</a></td></tr></table>        <p><b>Discarding the baby with the bathwater.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Dec;30(12):1429-31</p>        <p>Authors:  Kowey PR, Yan GX</p>        <p></p>        <p>PMID: 18070294 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17946595&#x26;dopt=Abstract\">Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1109/IEMBS.2006.260492&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--ieeexplore.ieee.org-images-ieee_pubmedv2_R2.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17946595&#x22;>Related Articles</a></td></tr></table>        <p><b>Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.</b></p>        <p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:4010-5</p>        <p>Authors:  Couderc JP, Vaglio M, Xia X, McNitt S, Hyrien O</p>        <p>Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.</p>        <p>PMID: 17946595 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18294569&#x26;dopt=Abstract\">Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(07)03788-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18294569&#x22;>Related Articles</a></td></tr></table>        <p><b>Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndrome.</b></p>        <p>J Am Coll Cardiol. 2008 Feb 26;51(8):836-42</p>        <p>Authors:  Darbar D, Kimbrough J, Jawaid A, McCray R, Ritchie MD, Roden DM</p>        <p>OBJECTIVES: The goal of this study was to identify markers of torsades de pointes (TdP) in patients with drug-associated long QT syndrome (LQTS). BACKGROUND: Drug-induced LQTS includes individuals developing marked prolongation of ventricular repolarization on exposure to an offending drug. Under these conditions, TdP develops in some but not all patients. METHODS: This was a case-control study of 123 adults with drug-associated LQTS. Patients were divided into LQTS only (LQTS; n = 40, QT &#x26;gt;500 ms on drug) and LQTS + TdP (TdP; n = 83). RESULTS: Baseline QT intervals were similar in the 2 groups (381 +/- 38 ms [LQTS] vs. 388 +/- 43 ms [TdP]). Clinical variables associated with risk of TdP included hypokalemia and female gender; by contrast, persistent atrial fibrillation (AF) at the time of drug discontinuation for QT prolongation was protective despite similar heart rates in AF and sinus rhythm (n = 20, 71 +/- 13 beats/min vs. 69 +/- 13 beats/min). Electrocardiographic variables that significantly increased the risk for TdP included absolute and rate-corrected QT intervals (QTc) on drug therapy, the magnitude of QT and QTc interval prolongation, and the change in T(peak) to T(end) (DeltaT(p)-T(e)), a relatively new index of transmural dispersion of repolarization and potential arrhythmogenicity. Multivariable logistic regression analysis revealed that only gender was predictive for TdP, whereas persistent AF at the time of drug discontinuation for QT prolongation (odds ratio 0.14, 95% confidence interval 0.03 to 0.63, p = 0.01) was negatively associated with the arrhythmia. CONCLUSIONS: This study strongly suggests that despite ongoing rate irregularity, AF reduces the likelihood of developing TdP after the administration of drugs that prolong cardiac repolarization.</p>        <p>PMID: 18294569 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18167038&#x26;dopt=Abstract\">QT Prolongation and delayed atrioventricular conduction caused by acute ingestion of trazodone.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.informaworld.com/openurl?genre=article&#x26;amp;doi=10.1080/15563650701275322&#x26;amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18167038&#x22;>Related Articles</a></td></tr></table>        <p><b>QT Prolongation and delayed atrioventricular conduction caused by acute ingestion of trazodone.</b></p>        <p>Clin Toxicol (Phila). 2008 Jan;46(1):71-3</p>        <p>Authors:  Service JA, Waring WS</p>        <p>Trazodone possesses minimal anticholinergic properties and, therefore, is generally regarded as having less cardiotoxic potential than other antidepressants. This report describes a young woman who developed significant QT prolongation and delayed atrioventricular nodal conduction after acute trazodone overdose. The case adds to the existing literature because it has a number of strengths, namely that confounding drugs and alcohol were lacking, trazodone exposure was confirmed by drug assay, and early presentation to hospital gave a valuable opportunity to study the time-course of the cardiac effects. This case reminds us to consider the possibility of cardiotoxic effects after trazodone overdose, even in young patients with no established cardiovascular disease.</p>        <p>PMID: 18167038 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18309564&#x26;dopt=Abstract\">Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18309564&#x22;>Related Articles</a></td></tr></table>        <p><b>Proceedings of the 6th Annual Safety Pharmacology Society Meeting. San Diego, California, USA. September 26-28, 2006.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):87-275</p>        <p>Authors: </p>        <p></p>        <p>PMID: 18309564 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17689270&#x26;dopt=Abstract\">Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00201-8&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17689270&#x22;>Related Articles</a></td></tr></table>        <p><b>Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):131-44</p>        <p>Authors:  Ollerstam A, Visser SA, Duker G, Forsberg T, Persson AH, Nilsson LB, Bj&#x26;#xF6;rkman JA, Gabrielsson J, Al-Saffar A</p>        <p>INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.</p>        <p>PMID: 17689270 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17643323&#x26;dopt=Abstract\">A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00190-6&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17643323&#x22;>Related Articles</a></td></tr></table>        <p><b>A highly sensitive canine telemetry model for detection of QT interval prolongation: studies with moxifloxacin, haloperidol and MK-499.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):103-14</p>        <p>Authors:  Chaves AA, Zingaro GJ, Yordy MA, Bustard KA, O&#x27;Sullivan S, Galijatovic-Idrizbegovic A, Schuck H, Christian DB, Hoe CM, Briscoe RJ</p>        <p>INTRODUCTION: Preclinical evaluation of delayed ventricular repolarization manifests electrocardiographically as QT interval prolongation and is routinely used as an indicator of potential risk for pro-arrhythmia (potential to cause Torsades de Pointes) of novel human pharmaceuticals. In accordance with ICH S7A and S7B guidelines we evaluated the sensitivity and validity of the beagle dog telemetry (Integrated Telemetry Services (ITS)) model as a preclinical predictor of QT interval prolongation in humans. METHODS: Cardiovascular monitoring was conducted for 2 h pre-dose and 24 h post-dosing with moxifloxacin (MOX), haloperidol (HAL), and MK-499, with a toxicokinetic (TK) evaluation in a separate group of dogs. In both cardiovascular and TK studies, MOX (0, 10, 30 and 100 mg/kg), HAL (0, 0.3, 1, 3 mg/kg) and MK-499 (0, 0.03, 0.3 and 3 mg/kg) were administered orally by gavage in 0.5% methylcellulose. Each dog received all 4 doses using a dose-escalation paradigm. Inherent variability of the model was assessed with administration of vehicle (0.5% methylcellulose) alone for 4 days. RESULTS: Significant increases in QT(c) were evident with 10, 30 and 100 mg/kg of MOX (C(max)&#x26;lt; or =40 microM), 0.3, 1 and 3 mg/kg of HAL (C(max)&#x26;lt; or =0.36 microM) and 0.3 and 3 mg/kg of MK-499 (C(max)&#x26;lt; or =825 nM) with peak increases of 45 (20%), 31 (13%), and 45 (19%) ms, respectively (p&#x26;lt; or =0.05). DISCUSSION: In conclusion, we have demonstrated that the ITS-telemetry beagle dog exhibits low inherent intra-animal variability and high sensitivity to detect small but significant increases in QT/QT(c) interval ( approximately 3-6%) with MOX, HAL and MK-499 in the same range of therapeutic plasma concentrations attained in humans. Therefore, this dog telemetry model should be considered an important preclinical predictor of QT prolongation of novel human pharmaceuticals.</p>        <p>PMID: 17643323 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17588780&#x26;dopt=Abstract\">ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00203-1&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17588780&#x22;>Related Articles</a></td></tr></table>        <p><b>ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):95-102</p>        <p>Authors:  Chiang AY, Bass AS, Cooper MM, Engwall MJ, Menton RG, Thomas K</p>        <p>INTRODUCTION: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset. METHODS: The ILSI/HESI telemetry studies were conducted as a double Latin square design where eight dogs each received a vehicle control and three dose levels of a compound on four separate dosing days. We statistically analyzed the QT/QTc intervals using a repeated measures analysis of covariance and evaluate the powers for QT, QTcF and QTcQ based on simulations. RESULTS: The analyses for QTcF and QTcB intervals show that all six compounds which were known to cause TdP in humans were identified as positive and all six compounds known to be free of TdP events in their clinical use had no statistically significant treatment-related effects, while the analyses for QTcQ identified all positive compounds except pimozide. The power analysis shows that the method can detect a 7% increment of QT, a 5% increment of QTcF, and a 4% increment of QTcQ, with greater than 80% of power when n=8. DISCUSSION: We describe a repeated measures procedure to perform statistical analysis of covariance on Latin square designs and show that it can be used to detect meaningful changes in the analysis of QT/QTc intervals.</p>        <p>PMID: 17588780 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17587603&#x26;dopt=Abstract\">A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00199-2&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17587603&#x22;>Related Articles</a></td></tr></table>        <p><b>A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):265-75</p>        <p>Authors:  Tontodonati M, Fasdelli N, Moscardo E, Giarola A, Dorigatti R</p>        <p>INTRODUCTION: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. METHODS: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. RESULTS: D-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. DISCUSSION: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs.</p>        <p>PMID: 17587603 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17582787&#x26;dopt=Abstract\">Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S1056-8719(07)00204-3&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17582787&#x22;>Related Articles</a></td></tr></table>        <p><b>Evaluation of the guinea pig monophasic action potential (MAP) assay in predicting drug-induced delay of ventricular repolarisation using 12 clinically documented drugs.</b></p>        <p>J Pharmacol Toxicol Methods. 2007 Sep-Oct;56(2):186-93</p>        <p>Authors:  K&#x26;#xE5;gstr&#x26;#xF6;m J, Sj&#x26;#xF6;gren EL, Ericson AC</p>        <p>INTRODUCTION: While the dog in vivo model is commonly employed in the later phase of discovery for assessing drug-induced QT prolongation, an early screening assay is valuable when selecting compounds for further development and when compound availability usually is low. One such screening assay is the anaesthetised guinea pig monophasic action potential (MAP) model. The aim of the present study was to evaluate the ability of this model to detect proarrhythmic properties by testing a set of reference compounds with known clinical profile. Moreover, these results were compared to data previously obtained using in vivo canine QT assays (QT PRODACT study). METHODS: Anaesthetised and ventilated male guinea pigs were vagotomised and pretreated with propranolol. After thoracotomy, a pacing electrode was clipped to the left atrial appendage and a suction MAP electrode positioned on the left ventricular epicardium. The drug or corresponding vehicle was injected intravenously in cumulative doses and MAP duration at 90% repolarisation (MAPD90) was recorded during cardiac pacing. RESULTS: The 8 drugs known to be proarrhythmic in the clinic all displayed dose-dependent prolongation of MAPD90, while the 4 drugs devoid of dysrhythmia in man had no effect. When comparing doses producing a 10% MAPD90 increase with doses reported to increase QTc by 10% in dogs a strong correlation was seen (R(2) 0.94 and 0.58 for anaesthetised and conscious dogs, respectively). DISCUSSION: The guinea pig MAP assay identified all clinically positive drugs while negative drugs were without effect on ventricular repolarisation. Furthermore, a good concurrence is shown between the guinea pig and dog models in identifying compounds with proarrhythmic properties. Overall, the study reinforces the anaesthetised guinea pig MAP model as a reliable assay predicting QT liability of new chemical entities and as a highly sensitive early screening model for cardiovascular risk.</p>        <p>PMID: 17582787 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074575&#x26;dopt=Abstract\">[Drug-induced long QT syndrome]</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074575&#x22;>Related Articles</a></td></tr></table>        <p><b>[Drug-induced long QT syndrome]</b></p>        <p>Nippon Rinsho. 2007 Oct 28;65 Suppl 8:426-9</p>        <p>Authors:  Kishida H</p>        <p></p>        <p>PMID: 18074575 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074530&#x26;dopt=Abstract\">[Adverse effects of cardiovascular agents]</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074530&#x22;>Related Articles</a></td></tr></table>        <p><b>[Adverse effects of cardiovascular agents]</b></p>        <p>Nippon Rinsho. 2007 Oct 28;65 Suppl 8:146-51</p>        <p>Authors:  Tsukada YT, Kishida H</p>        <p></p>        <p>PMID: 18074530 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074575&#x26;dopt=Abstract\">[Drug-induced long QT syndrome]</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074575&#x22;>Related Articles</a></td></tr></table>        <p><b>[Drug-induced long QT syndrome]</b></p>        <p>Nippon Rinsho. 2007 Oct 28;65 Suppl 8:426-9</p>        <p>Authors:  Kishida H</p>        <p></p>        <p>PMID: 18074575 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074530&#x26;dopt=Abstract\">[Adverse effects of cardiovascular agents]</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074530&#x22;>Related Articles</a></td></tr></table>        <p><b>[Adverse effects of cardiovascular agents]</b></p>        <p>Nippon Rinsho. 2007 Oct 28;65 Suppl 8:146-51</p>        <p>Authors:  Tsukada YT, Kishida H</p>        <p></p>        <p>PMID: 18074530 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18182676&#x26;dopt=Abstract\">Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.jco.org/cgi/pmidlookup?view=long&#x26;amp;pmid=18182676&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jco_full.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18182676&#x22;>Related Articles</a></td></tr></table>        <p><b>Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat).</b></p>        <p>J Clin Oncol. 2008 Jan 10;26(2):332-3; discussion 333-4</p>        <p>Authors:  Zhang L, Lebwohl D, Masson E, Laird G, Cooper MR, Prince HM</p>        <p></p>        <p>PMID: 18182676 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18043690&#x26;dopt=Abstract\">Thorough QT study with recommended and supratherapeutic doses of tolterodine.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.clpt.6100328&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18043690&#x22;>Related Articles</a></td></tr></table>        <p><b>Thorough QT study with recommended and supratherapeutic doses of tolterodine.</b></p>        <p>Clin Pharmacol Ther. 2008 Feb;83(2):231-2; author reply 233</p>        <p>Authors:  Olshansky B, Serra DB</p>        <p></p>        <p>PMID: 18043690 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17965747&#x26;dopt=Abstract\">Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1038/sj.bjp.0707513&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17965747&#x22;>Related Articles</a></td></tr></table>        <p><b>Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.</b></p>        <p>Br J Pharmacol. 2007 Dec;152(8):1215-27</p>        <p>Authors:  Michael G, Dempster J, Kane KA, Coker SJ</p>        <p>BACKGROUND AND PURPOSE: Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. EXPERIMENTAL APPROACH: Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. KEY RESULTS: HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. CONCLUSIONS AND IMPLICATIONS: Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.</p>        <p>PMID: 17965747 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18178408&#x26;dopt=Abstract\">Role of implantable cardioverter-defibrillators in patients with methadone-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(07)01891-7&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18178408&#x22;>Related Articles</a></td></tr></table>        <p><b>Role of implantable cardioverter-defibrillators in patients with methadone-induced long QT syndrome.</b></p>        <p>Am J Cardiol. 2008 Jan 15;101(2):209-11</p>        <p>Authors:  Patel AM, Singh JP, Ruskin JN</p>        <p>Patients with methadone-induced long-QT syndrome may experience Torsades de Pointes (TDP) or aborted sudden death requiring the placement of implantable cardioverter-defibrillators (ICDs). Outcomes after ICD implantation in these patients are unknown. Eight patients presenting with methadone-induced long-QT syndrome and episodes of symptomatic TDP were followed after having undergone ICD implantation. The study group included 5 women and 3 men (mean age 48.5 +/- 5 years) receiving methadone doses of 204 +/- 173 mg. All but 1 subject had preserved ventricular function (mean left ventricular ejection fraction 61 +/- 1.1%). All of the patients had prolonged QTc intervals (mean 613 +/- 71 ms) while taking methadone. After ICD implantation, 6 of the 8 patients continued treatment with methadone as a result of intractable dependence. Over a mean follow-up period of 27 months, 1 patient expired from unknown causes. Three of those patients had interrogation-proved ICD shocks for TDP. In conclusion, patients with methadone-induced long-QT syndrome and TDP are at high risk for recurrent arrhythmic events if methadone is continued. This small cohort of patients suggests that ICDs may be lifesaving in those subjects who continue taking methadone after initial episodes of TDP.</p>        <p>PMID: 18178408 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17891537&#x26;dopt=Abstract\">Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1007/s00228-007-0366-5&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17891537&#x22;>Related Articles</a></td></tr></table>        <p><b>Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</b></p>        <p>Eur J Clin Pharmacol. 2007 Nov;63(11):1011-7</p>        <p>Authors:  Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A</p>        <p>OBJECTIVE: To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. METHODS: The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia&#x27;s correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. RESULTS: The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. CONCLUSIONS: Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.</p>        <p>PMID: 17891537 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17891537&#x26;dopt=Abstract\">Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1007/s00228-007-0366-5&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17891537&#x22;>Related Articles</a></td></tr></table>        <p><b>Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</b></p>        <p>Eur J Clin Pharmacol. 2007 Nov;63(11):1011-7</p>        <p>Authors:  Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A</p>        <p>OBJECTIVE: To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. METHODS: The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia&#x27;s correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. RESULTS: The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. CONCLUSIONS: Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.</p>        <p>PMID: 17891537 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17891537&#x26;dopt=Abstract\">Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1007/s00228-007-0366-5&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17891537&#x22;>Related Articles</a></td></tr></table>        <p><b>Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</b></p>        <p>Eur J Clin Pharmacol. 2007 Nov;63(11):1011-7</p>        <p>Authors:  Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A</p>        <p>OBJECTIVE: To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. METHODS: The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia&#x27;s correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. RESULTS: The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. CONCLUSIONS: Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.</p>        <p>PMID: 17891537 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17891537&#x26;dopt=Abstract\">Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1007/s00228-007-0366-5&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17891537&#x22;>Related Articles</a></td></tr></table>        <p><b>Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</b></p>        <p>Eur J Clin Pharmacol. 2007 Nov;63(11):1011-7</p>        <p>Authors:  Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A</p>        <p>OBJECTIVE: To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. METHODS: The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia&#x27;s correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. RESULTS: The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. CONCLUSIONS: Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.</p>        <p>PMID: 17891537 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17891537&#x26;dopt=Abstract\">Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://dx.doi.org/10.1007/s00228-007-0366-5&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17891537&#x22;>Related Articles</a></td></tr></table>        <p><b>Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study.</b></p>        <p>Eur J Clin Pharmacol. 2007 Nov;63(11):1011-7</p>        <p>Authors:  Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A</p>        <p>OBJECTIVE: To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. METHODS: The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia&#x27;s correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. RESULTS: The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. CONCLUSIONS: Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.</p>        <p>PMID: 17891537 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: &#x22;Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=18074444&#x26;dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;/><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=18074444&#x22;>Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&#x26;gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&#x26;gt;moxifloxacin&#x26;gt;telithromycin&#x26;gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&#x26;lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&#x26;gt;erythromycin&#x26;gt;sparfloxacin&#x26;gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&#x26;gt;erythromycin&#x26;gt;moxifloxacin&#x26;gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&#x26;gt;the Purkinje fiber&#x26;gt;HERG&#x26;gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766322&#x26;dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766322&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766322&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17766320&#x26;dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&#x26;amp;pmid=17766320&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17766320&#x22;>Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17956279&#x26;dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17956279&#x22;>Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&#x26;db=PubMed&#x26;cmd=Retrieve&#x26;list_uids=17892500&#x26;dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=&#x22;0&#x22; width=&#x22;100%&#x22;><tr><td align=&#x22;left&#x22;><a href=&#x22;http://www.blackwell-synergy.com/openurl?genre=article&#x26;amp;sid=nlm:pubmed&#x26;amp;issn=0305-1870&#x26;amp;date=2007&#x26;amp;volume=34&#x26;amp;issue=12&#x26;amp;spage=1313&#x22;><img src=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif&#x22; border=&#x22;0&#x22;/></a> </td><td align=&#x22;right&#x22;><a href=&#x22;http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&#x26;amp;cmd=Display&#x26;amp;dopt=PubMed_PubMed&#x26;amp;from_uid=17892500&#x22;>Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18074444&dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18074444\">Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&gt;moxifloxacin&gt;telithromycin&gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&gt;erythromycin&gt;sparfloxacin&gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&gt;erythromycin&gt;moxifloxacin&gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&gt;the Purkinje fiber&gt;HERG&gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766322&dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766322\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766322\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766320&dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766320\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766320\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17956279&dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17956279\">Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17892500&dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0305-1870&amp;date=2007&amp;volume=34&amp;issue=12&amp;spage=1313\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17892500\">Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18074444&dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18074444\">Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&gt;moxifloxacin&gt;telithromycin&gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&gt;erythromycin&gt;sparfloxacin&gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&gt;erythromycin&gt;moxifloxacin&gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&gt;the Purkinje fiber&gt;HERG&gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766322&dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766322\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766322\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766320&dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766320\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766320\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17956279&dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17956279\">Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17892500&dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0305-1870&amp;date=2007&amp;volume=34&amp;issue=12&amp;spage=1313\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17892500\">Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18074444&dopt=Abstract\">In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18074444\">Related Articles</a></td></tr></table>        <p><b>In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.</b></p>        <p>Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32</p>        <p>Authors:  Lu HR, Vlaminckx E, Van de Water A, Rohrbacher J, Hermans A, Gallacher DJ</p>        <p>The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44 microM)&gt;telithromycin=moxifloxacin=erythromycin (+/-100 microM). 2. Assessing their effects on action potential duration (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje fibers, the rank order was: sparfloxacin&gt;moxifloxacin&gt;telithromycin&gt;erythromycin (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline compared to +5% with solvent, P&lt;0.05, respectively). 3. Assessing the drug effects on the APD(60), triangulation, reverse use-dependency, and instability in isolated Langendorff-perfused rabbit hearts, the rank order was: moxifloxacin&gt;erythromycin&gt;sparfloxacin&gt;telithromycin. 4. Assessing their torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in isolated rabbit left ventricular wedge preparations, the rank order for their TdP risk score was: sparfloxacin&gt;erythromycin&gt;moxifloxacin&gt;telithromycin. Additional experiments with grepafloxacin indicate that the rank order to detect grepafloxacin-induced long QT was the wedge preparation&gt;the Purkinje fiber&gt;HERG&gt;the isolated heart, where the isolated heart was unable to detect grepafloxacin-induced APD prolongation. The present study demonstrates that the first three in-vitro models can be used to assess the ability of antibiotic compounds to delay ventricular repolarization. However, with respect to their known clinical effects on QT and TdP incidence, the wedge preparation appears to be more predictive and suitable for detecting torsadogenic action of antibiotics.</p>        <p>PMID: 18074444 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766322&dopt=Abstract\">Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766322\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766322\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv37-44</p>        <p>Authors:  Shantsila E, Watson T, Lip GY</p>        <p>Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.</p>        <p>PMID: 17766322 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17766320&dopt=Abstract\">Drug-induced QT prolongation and proarrhythmia: an inevitable link?</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://europace.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=17766320\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-oxfordjournals_final.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17766320\">Related Articles</a></td></tr></table>        <p><b>Drug-induced QT prolongation and proarrhythmia: an inevitable link?</b></p>        <p>Europace. 2007 Sep;9 Suppl 4:iv16-22</p>        <p>Authors:  Ahmad K, Dorian P</p>        <p>One of the most feared potential adverse effects of many drugs is life threatening or fatal arrhythmia--particularly torsade de pointes (TdP) ventricular tachycardia in conjunction with QT prolongation. To fully understand the implications of QT prolongation, it is essential to have an understanding of the ion currents that comprise repolarization and their relation to electrophysiological abnormalities associated with TdP. Also, the QT interval is subject to patient-specific and sometimes idiosyncratic variability. The following questions are addressed: How close is the relationship between QT prolongation and proarrhythmia? How accurately do QT-interval measurements reflect cardiac repolarization? How representative is a single QT measurement with respect to the QT response to a drug? The presumed relationship between the QT interval and myocardial repolarization will be deconstructed, demonstrating that most of the important aspects of repolarization, and subsequent arrhythmogenesis, cannot be understood only through the simple numerical measurement of the QT interval. Repolarization reserve is also discussed. Suggestions for refining the understanding of drug-induced QT prolongation, TdP, and shortcomings of some current definitions are outlined. We speculate on possible future developments in understanding this relationship.</p>        <p>PMID: 17766320 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17956279&dopt=Abstract\">hERG channel trafficking: novel targets in drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.biochemsoctrans.org/bst/035/1060/bst0351060.htm\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/-PMGifs-Toolbar-button_bst.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17956279\">Related Articles</a></td></tr></table>        <p><b>hERG channel trafficking: novel targets in drug-induced long QT syndrome.</b></p>        <p>Biochem Soc Trans. 2007 Nov;35(Pt 5):1060-3</p>        <p>Authors:  Dennis A, Wang L, Wan X, Ficker E</p>        <p>The cardiac potassium channel hERG (human ether-a-go-go-related gene) encodes the alpha-subunit of the rapid delayed rectifier current I(Kr) in the heart, which contributes to terminal repolarization in human cardiomyocytes. Direct block of hERG/I(Kr) channels by a large number of therapeutic compounds produces acLQTS [acquired LQTS (long QT syndrome)] characterized by drug-induced QT prolongation and torsades de pointes arrhythmias. The cardiotoxicity associated with unintended hERG block has prompted pharmaceutical companies to screen developmental compounds for hERG blockade and made hERG a major target in drug safety programmes. More recently, a novel form of acLQTS has been discovered that may go undetected in most conventional safety assays. Several therapeutic compounds have been identified that reduce hERG/I(Kr) currents not by direct block but by inhibition of hERG/I(Kr) trafficking to the cell surface. Important examples are antineoplastic Hsp90 (heat-shock protein 90) inhibitors such as (i) geldanamycin, (ii) the leukaemia drug arsenic trioxide, (iii) the antiprotozoical pentamidine, (iv) probucol, a cholesterol-lowering drug, and (v) fluoxetine, a widely used antidepressant. Increased awareness of drug-induced hERG trafficking defects will help to further reduce the potentially lethal adverse cardiac events associated with acLQTS.</p>        <p>PMID: 17956279 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17892500&dopt=Abstract\">Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0305-1870&amp;date=2007&amp;volume=34&amp;issue=12&amp;spage=1313\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17892500\">Related Articles</a></td></tr></table>        <p><b>Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.</b></p>        <p>Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1313-6</p>        <p>Authors:  Kang J, Chen XL, Reynolds WP, Rampe D</p>        <p>1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.</p>        <p>PMID: 17892500 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072176&dopt=Abstract\">Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072176\">Related Articles</a></td></tr></table>        <p><b>Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):190-4</p>        <p>Authors:  Wong SC, Roberts JR</p>        <p></p>        <p>PMID: 18072176 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072173&dopt=Abstract\">QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072173\">Related Articles</a></td></tr></table>        <p><b>QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):178-81</p>        <p>Authors:  Manini AF, Raspberry D, Hoffman RS, Nelson LS</p>        <p></p>        <p>PMID: 18072173 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072176&dopt=Abstract\">Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072176\">Related Articles</a></td></tr></table>        <p><b>Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):190-4</p>        <p>Authors:  Wong SC, Roberts JR</p>        <p></p>        <p>PMID: 18072176 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072173&dopt=Abstract\">QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072173\">Related Articles</a></td></tr></table>        <p><b>QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):178-81</p>        <p>Authors:  Manini AF, Raspberry D, Hoffman RS, Nelson LS</p>        <p></p>        <p>PMID: 18072173 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072176&dopt=Abstract\">Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072176\">Related Articles</a></td></tr></table>        <p><b>Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):190-4</p>        <p>Authors:  Wong SC, Roberts JR</p>        <p></p>        <p>PMID: 18072176 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072173&dopt=Abstract\">QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072173\">Related Articles</a></td></tr></table>        <p><b>QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):178-81</p>        <p>Authors:  Manini AF, Raspberry D, Hoffman RS, Nelson LS</p>        <p></p>        <p>PMID: 18072173 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072176&dopt=Abstract\">Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072176\">Related Articles</a></td></tr></table>        <p><b>Case files of the Drexel University Medical Toxicology Fellowship: methadone-induced QTc prolongation.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):190-4</p>        <p>Authors:  Wong SC, Roberts JR</p>        <p></p>        <p>PMID: 18072176 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18072173&dopt=Abstract\">QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18072173\">Related Articles</a></td></tr></table>        <p><b>QT prolongation and Torsades de Pointes following overdose of ziprasidone and amantadine.</b></p>        <p>J Med Toxicol. 2007 Dec;3(4):178-81</p>        <p>Authors:  Manini AF, Raspberry D, Hoffman RS, Nelson LS</p>        <p></p>        <p>PMID: 18072173 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18216002&dopt=Abstract\">Sufficiency of data for resuming use of low-dose droperidol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.ajhp.org/cgi/pmidlookup?view=long&amp;pmid=18216002\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-ajhp_full.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18216002\">Related Articles</a></td></tr></table>        <p><b>Sufficiency of data for resuming use of low-dose droperidol.</b></p>        <p>Am J Health Syst Pharm. 2008 Feb 1;65(3):201</p>        <p>Authors:  Wyllie AR, Carvalhana VV, Burry LD, Teresi JE</p>        <p></p>        <p>PMID: 18216002 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18032235&dopt=Abstract\">Physician awareness of the cardiac effects of methadone: results of a national survey.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18032235\">Related Articles</a></td></tr></table>        <p><b>Physician awareness of the cardiac effects of methadone: results of a national survey.</b></p>        <p>J Addict Dis. 2007;26(4):79-85</p>        <p>Authors:  Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B</p>        <p>BACKGROUND: Levacetylmethadol was withdrawn from the U.S. market as a treatment for opioid-dependent patients in 2003 due to QT prolongation, leaving methadone as the primary therapy for over 200,000 individuals. Methadone was subsequently shown to prolong the QT interval as well. We hypothesized that opioid treatment program physicians are unaware of these safety concerns. METHODS: To assess awareness of methadone\'s QT-prolonging properties, we conducted a national mail survey of physicians licensed as medical directors for accredited U.S. opioid treatment programs in 2006. The primary outcome was knowledge of methadone\'s QT-prolonging effects. Awareness of the cardiac effects of levacetylmethadol and buprenorphine were also assessed. RESULTS: The survey response rate was 66% (692 physicians) of whom 35% were family practitioners, 25% internists, 22% psychiatrists, and 8% self-identified as addiction specialists. While 75% (95% CI, 72-78) correctly identified levacetylmethadol as a QT-prolonging drug, only 41% (95% CI, 37- 45) were aware of methadone\'s QT-prolonging properties. Just 24% (95% CI, 21-27) were aware of methadone\'s association with torsade de pointes. In addition, 52% (95% CI, 48- 56) correctly reported the absence of an association between buprenorphine and QT prolongation. Larger program census and academic setting tended to predict greater awareness of methadone\'s QT-prolonging effects; yet even in these subgroups awareness did not exceed 54%. CONCLUSIONS: Scientific publication alone has been inadequate in raising awareness regarding methadone\'s QT-prolonging properties, even among those who most often prescribe the drug. Universal education initiatives for all accredited opioid treatment programs seem warranted to enhance the safety of this essential therapy.</p>        <p>PMID: 18032235 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18032235&dopt=Abstract\">Physician awareness of the cardiac effects of methadone: results of a national survey.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18032235\">Related Articles</a></td></tr></table>        <p><b>Physician awareness of the cardiac effects of methadone: results of a national survey.</b></p>        <p>J Addict Dis. 2007;26(4):79-85</p>        <p>Authors:  Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B</p>        <p>BACKGROUND: Levacetylmethadol was withdrawn from the U.S. market as a treatment for opioid-dependent patients in 2003 due to QT prolongation, leaving methadone as the primary therapy for over 200,000 individuals. Methadone was subsequently shown to prolong the QT interval as well. We hypothesized that opioid treatment program physicians are unaware of these safety concerns. METHODS: To assess awareness of methadone\'s QT-prolonging properties, we conducted a national mail survey of physicians licensed as medical directors for accredited U.S. opioid treatment programs in 2006. The primary outcome was knowledge of methadone\'s QT-prolonging effects. Awareness of the cardiac effects of levacetylmethadol and buprenorphine were also assessed. RESULTS: The survey response rate was 66% (692 physicians) of whom 35% were family practitioners, 25% internists, 22% psychiatrists, and 8% self-identified as addiction specialists. While 75% (95% CI, 72-78) correctly identified levacetylmethadol as a QT-prolonging drug, only 41% (95% CI, 37- 45) were aware of methadone\'s QT-prolonging properties. Just 24% (95% CI, 21-27) were aware of methadone\'s association with torsade de pointes. In addition, 52% (95% CI, 48- 56) correctly reported the absence of an association between buprenorphine and QT prolongation. Larger program census and academic setting tended to predict greater awareness of methadone\'s QT-prolonging effects; yet even in these subgroups awareness did not exceed 54%. CONCLUSIONS: Scientific publication alone has been inadequate in raising awareness regarding methadone\'s QT-prolonging properties, even among those who most often prescribe the drug. Universal education initiatives for all accredited opioid treatment programs seem warranted to enhance the safety of this essential therapy.</p>        <p>PMID: 18032235 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18035863&dopt=Abstract\">Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18035863\">Related Articles</a></td></tr></table>        <p><b>Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</b></p>        <p>Drug Saf. 2007;30(12):1093-110</p>        <p>Authors:  Shah RR</p>        <p>December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia).In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard of evidence for industry and regulators and almost certainly result in better assessment of benefit/risk, more effective and balanced regulatory actions and better care for patients.</p>        <p>PMID: 18035863 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17970959&dopt=Abstract\">Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1082-720X&amp;date=2007&amp;volume=12&amp;issue=4&amp;spage=338\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17970959\">Related Articles</a></td></tr></table>        <p><b>Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</b></p>        <p>Ann Noninvasive Electrocardiol. 2007 Oct;12(4):338-48</p>        <p>Authors:  Fossa AA, Wisialowski T, Crimin K, Wolfgang E, Couderc JP, Hinterseer M, Kaab S, Zareba W, Badilini F, Sarapa N</p>        <p>BACKGROUND: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. METHODS: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. RESULTS: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio &gt;1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio &gt; 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. CONCLUSIONS: ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.</p>        <p>PMID: 17970959 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17581594&dopt=Abstract\">Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100263\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17581594\">Related Articles</a></td></tr></table>        <p><b>Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</b></p>        <p>Clin Pharmacol Ther. 2008 Jan;83(1):153-9</p>        <p>Authors:  Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA</p>        <p>To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.</p>        <p>PMID: 17581594 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18035863&dopt=Abstract\">Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18035863\">Related Articles</a></td></tr></table>        <p><b>Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</b></p>        <p>Drug Saf. 2007;30(12):1093-110</p>        <p>Authors:  Shah RR</p>        <p>December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia).In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard of evidence for industry and regulators and almost certainly result in better assessment of benefit/risk, more effective and balanced regulatory actions and better care for patients.</p>        <p>PMID: 18035863 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17970959&dopt=Abstract\">Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1082-720X&amp;date=2007&amp;volume=12&amp;issue=4&amp;spage=338\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17970959\">Related Articles</a></td></tr></table>        <p><b>Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</b></p>        <p>Ann Noninvasive Electrocardiol. 2007 Oct;12(4):338-48</p>        <p>Authors:  Fossa AA, Wisialowski T, Crimin K, Wolfgang E, Couderc JP, Hinterseer M, Kaab S, Zareba W, Badilini F, Sarapa N</p>        <p>BACKGROUND: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. METHODS: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. RESULTS: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio &gt;1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio &gt; 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. CONCLUSIONS: ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.</p>        <p>PMID: 17970959 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17581594&dopt=Abstract\">Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100263\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17581594\">Related Articles</a></td></tr></table>        <p><b>Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</b></p>        <p>Clin Pharmacol Ther. 2008 Jan;83(1):153-9</p>        <p>Authors:  Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA</p>        <p>To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.</p>        <p>PMID: 17581594 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18035863&dopt=Abstract\">Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18035863\">Related Articles</a></td></tr></table>        <p><b>Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</b></p>        <p>Drug Saf. 2007;30(12):1093-110</p>        <p>Authors:  Shah RR</p>        <p>December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia).In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard of evidence for industry and regulators and almost certainly result in better assessment of benefit/risk, more effective and balanced regulatory actions and better care for patients.</p>        <p>PMID: 18035863 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17970959&dopt=Abstract\">Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1082-720X&amp;date=2007&amp;volume=12&amp;issue=4&amp;spage=338\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17970959\">Related Articles</a></td></tr></table>        <p><b>Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</b></p>        <p>Ann Noninvasive Electrocardiol. 2007 Oct;12(4):338-48</p>        <p>Authors:  Fossa AA, Wisialowski T, Crimin K, Wolfgang E, Couderc JP, Hinterseer M, Kaab S, Zareba W, Badilini F, Sarapa N</p>        <p>BACKGROUND: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. METHODS: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. RESULTS: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio &gt;1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio &gt; 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. CONCLUSIONS: ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.</p>        <p>PMID: 17970959 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17581594&dopt=Abstract\">Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100263\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17581594\">Related Articles</a></td></tr></table>        <p><b>Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</b></p>        <p>Clin Pharmacol Ther. 2008 Jan;83(1):153-9</p>        <p>Authors:  Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA</p>        <p>To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.</p>        <p>PMID: 17581594 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18035863&dopt=Abstract\">Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18035863\">Related Articles</a></td></tr></table>        <p><b>Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</b></p>        <p>Drug Saf. 2007;30(12):1093-110</p>        <p>Authors:  Shah RR</p>        <p>December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia).In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard of evidence for industry and regulators and almost certainly result in better assessment of benefit/risk, more effective and balanced regulatory actions and better care for patients.</p>        <p>PMID: 18035863 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17970959&dopt=Abstract\">Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1082-720X&amp;date=2007&amp;volume=12&amp;issue=4&amp;spage=338\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17970959\">Related Articles</a></td></tr></table>        <p><b>Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</b></p>        <p>Ann Noninvasive Electrocardiol. 2007 Oct;12(4):338-48</p>        <p>Authors:  Fossa AA, Wisialowski T, Crimin K, Wolfgang E, Couderc JP, Hinterseer M, Kaab S, Zareba W, Badilini F, Sarapa N</p>        <p>BACKGROUND: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. METHODS: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. RESULTS: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio &gt;1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio &gt; 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. CONCLUSIONS: ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.</p>        <p>PMID: 17970959 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17581594&dopt=Abstract\">Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100263\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17581594\">Related Articles</a></td></tr></table>        <p><b>Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</b></p>        <p>Clin Pharmacol Ther. 2008 Jan;83(1):153-9</p>        <p>Authors:  Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA</p>        <p>To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.</p>        <p>PMID: 17581594 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18035863&dopt=Abstract\">Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18035863\">Related Articles</a></td></tr></table>        <p><b>Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.</b></p>        <p>Drug Saf. 2007;30(12):1093-110</p>        <p>Authors:  Shah RR</p>        <p>December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia).In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard of evidence for industry and regulators and almost certainly result in better assessment of benefit/risk, more effective and balanced regulatory actions and better care for patients.</p>        <p>PMID: 18035863 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17970959&dopt=Abstract\">Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1082-720X&amp;date=2007&amp;volume=12&amp;issue=4&amp;spage=338\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17970959\">Related Articles</a></td></tr></table>        <p><b>Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.</b></p>        <p>Ann Noninvasive Electrocardiol. 2007 Oct;12(4):338-48</p>        <p>Authors:  Fossa AA, Wisialowski T, Crimin K, Wolfgang E, Couderc JP, Hinterseer M, Kaab S, Zareba W, Badilini F, Sarapa N</p>        <p>BACKGROUND: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. METHODS: The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. RESULTS: Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio &gt;1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio &gt; 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. CONCLUSIONS: ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.</p>        <p>PMID: 17970959 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17581594&dopt=Abstract\">Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100263\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17581594\">Related Articles</a></td></tr></table>        <p><b>Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies.</b></p>        <p>Clin Pharmacol Ther. 2008 Jan;83(1):153-9</p>        <p>Authors:  Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA</p>        <p>To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.</p>        <p>PMID: 17581594 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17724878&dopt=Abstract\">The influence of carbamazepine plasma level on blood pressure and some ECG parameters in patients with acute intoxication.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17724878\">Related Articles</a></td></tr></table>        <p><b>The influence of carbamazepine plasma level on blood pressure and some ECG parameters in patients with acute intoxication.</b></p>        <p>Przegl Lek. 2007;64(4-5):248-51</p>        <p>Authors:  Ciszowski K, Szpak D, Jenner B</p>        <p>BACKGROUND: Carbamazepine (CBZ) is an antiepileptic drug with tricyclic structure which implies its potential cardinotxic properties, especially in acute poisoning. AIM: To evaluate some cardiovascular effects connected with CBZtoxicity and tofind the relation between them and CBZ plasma level. MATERIAL AND METHODS: 34 patients (18 males, 16 females; median age 24.5) hospitalized in our Department in 1996-1997 and 2005-2006 due to acute CBZ poisoning. Analysis included following parameters: systolic (SBP) and diastolic (DBP) blood pressure, ECG parameters: heart rate (HR), duration of QRS complex, PQ interval and corrected QT interval (QTc) calculated with Bazett\'s (QTc(B)) and Hodges\'s (QTc(H)) formulas. These parameters were compared with reference values for general population available in the literature. Relations between above mentioned parameters and CBZ plasma level were studied by means of Generalized Additive Model (GAM). RESULTS: The reference values were exceeded most often for QRS (62%), DBP and QTc(B) (53%, both) and SBP (50%). The mean number of parameters with exceeded norms was 3.1 per patient (SD = 1.71). We failed to find any significant correlation between CBZ plasma level and any of the studied parameters. Positive correlation between SBP and DBP (r = 0.68; p &lt; 0.001) and negative correlation between QRS and HR (r = -0.50; p = 0.003) were found. CONCLUSION: CBZ could affect different cardiovascular parameters which should be monitored in cases of acute drug poisonings.</p>        <p>PMID: 17724878 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17724878&dopt=Abstract\">The influence of carbamazepine plasma level on blood pressure and some ECG parameters in patients with acute intoxication.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17724878\">Related Articles</a></td></tr></table>        <p><b>The influence of carbamazepine plasma level on blood pressure and some ECG parameters in patients with acute intoxication.</b></p>        <p>Przegl Lek. 2007;64(4-5):248-51</p>        <p>Authors:  Ciszowski K, Szpak D, Jenner B</p>        <p>BACKGROUND: Carbamazepine (CBZ) is an antiepileptic drug with tricyclic structure which implies its potential cardinotxic properties, especially in acute poisoning. AIM: To evaluate some cardiovascular effects connected with CBZtoxicity and tofind the relation between them and CBZ plasma level. MATERIAL AND METHODS: 34 patients (18 males, 16 females; median age 24.5) hospitalized in our Department in 1996-1997 and 2005-2006 due to acute CBZ poisoning. Analysis included following parameters: systolic (SBP) and diastolic (DBP) blood pressure, ECG parameters: heart rate (HR), duration of QRS complex, PQ interval and corrected QT interval (QTc) calculated with Bazett\'s (QTc(B)) and Hodges\'s (QTc(H)) formulas. These parameters were compared with reference values for general population available in the literature. Relations between above mentioned parameters and CBZ plasma level were studied by means of Generalized Additive Model (GAM). RESULTS: The reference values were exceeded most often for QRS (62%), DBP and QTc(B) (53%, both) and SBP (50%). The mean number of parameters with exceeded norms was 3.1 per patient (SD = 1.71). We failed to find any significant correlation between CBZ plasma level and any of the studied parameters. Positive correlation between SBP and DBP (r = 0.68; p &lt; 0.001) and negative correlation between QRS and HR (r = -0.50; p = 0.003) were found. CONCLUSION: CBZ could affect different cardiovascular parameters which should be monitored in cases of acute drug poisonings.</p>        <p>PMID: 17724878 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18030657&dopt=Abstract\">Torsade de pointes during combined treatment with risperidone and citalopram.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-992147\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.thieme.de-images-logo_tc.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=18030657\">Related Articles</a></td></tr></table>        <p><b>Torsade de pointes during combined treatment with risperidone and citalopram.</b></p>        <p>Pharmacopsychiatry. 2007 Nov;40(6):294-5</p>        <p>Authors:  Blaschke D, Parwani AS, Huemer M, Rolf S, Boldt LH, Dietz R, Haverkamp W</p>        <p></p>        <p>PMID: 18030657 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17926152&dopt=Abstract\">Prospective observational multi-poison center study of ziprasidone exposures.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.informaworld.com/openurl?genre=article&amp;doi=10.1080/15563650701639006&amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17926152\">Related Articles</a></td></tr></table>        <p><b>Prospective observational multi-poison center study of ziprasidone exposures.</b></p>        <p>Clin Toxicol (Phila). 2007 Oct-Nov;45(7):782-6</p>        <p>Authors:  Klein-Schwartz W, Lofton AL, Benson BE, Spiller HA, Crouch BI</p>        <p>BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (&gt;0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.</p>        <p>PMID: 17926152 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17926152&dopt=Abstract\">Prospective observational multi-poison center study of ziprasidone exposures.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.informaworld.com/openurl?genre=article&amp;doi=10.1080/15563650701639006&amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17926152\">Related Articles</a></td></tr></table>        <p><b>Prospective observational multi-poison center study of ziprasidone exposures.</b></p>        <p>Clin Toxicol (Phila). 2007 Oct-Nov;45(7):782-6</p>        <p>Authors:  Klein-Schwartz W, Lofton AL, Benson BE, Spiller HA, Crouch BI</p>        <p>BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (&gt;0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.</p>        <p>PMID: 17926152 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17926152&dopt=Abstract\">Prospective observational multi-poison center study of ziprasidone exposures.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.informaworld.com/openurl?genre=article&amp;doi=10.1080/15563650701639006&amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17926152\">Related Articles</a></td></tr></table>        <p><b>Prospective observational multi-poison center study of ziprasidone exposures.</b></p>        <p>Clin Toxicol (Phila). 2007 Oct-Nov;45(7):782-6</p>        <p>Authors:  Klein-Schwartz W, Lofton AL, Benson BE, Spiller HA, Crouch BI</p>        <p>BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (&gt;0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.</p>        <p>PMID: 17926152 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17926152&dopt=Abstract\">Prospective observational multi-poison center study of ziprasidone exposures.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.informaworld.com/openurl?genre=article&amp;doi=10.1080/15563650701639006&amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17926152\">Related Articles</a></td></tr></table>        <p><b>Prospective observational multi-poison center study of ziprasidone exposures.</b></p>        <p>Clin Toxicol (Phila). 2007 Oct-Nov;45(7):782-6</p>        <p>Authors:  Klein-Schwartz W, Lofton AL, Benson BE, Spiller HA, Crouch BI</p>        <p>BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (&gt;0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.</p>        <p>PMID: 17926152 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17926152&dopt=Abstract\">Prospective observational multi-poison center study of ziprasidone exposures.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.informaworld.com/openurl?genre=article&amp;doi=10.1080/15563650701639006&amp;magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.tandf.co.uk-journals-images-informaworld-informaworldbutton.jpg\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17926152\">Related Articles</a></td></tr></table>        <p><b>Prospective observational multi-poison center study of ziprasidone exposures.</b></p>        <p>Clin Toxicol (Phila). 2007 Oct-Nov;45(7):782-6</p>        <p>Authors:  Klein-Schwartz W, Lofton AL, Benson BE, Spiller HA, Crouch BI</p>        <p>BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (&gt;0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.</p>        <p>PMID: 17926152 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17890927&dopt=Abstract\">Screening drugs for QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00045391-200709000-00001\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.lwwonline.com-pt-pt-core-template-journal-lwwgateway-images-pmlogo.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17890927\">Related Articles</a></td></tr></table>        <p><b>Screening drugs for QT prolongation.</b></p>        <p>Am J Ther. 2007 Sep-Oct;14(5):419-20</p>        <p>Authors:  Somberg J</p>        <p></p>        <p>PMID: 17890927 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17890927&dopt=Abstract\">Screening drugs for QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00045391-200709000-00001\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.lwwonline.com-pt-pt-core-template-journal-lwwgateway-images-pmlogo.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17890927\">Related Articles</a></td></tr></table>        <p><b>Screening drugs for QT prolongation.</b></p>        <p>Am J Ther. 2007 Sep-Oct;14(5):419-20</p>        <p>Authors:  Somberg J</p>        <p></p>        <p>PMID: 17890927 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17890927&dopt=Abstract\">Screening drugs for QT prolongation.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00045391-200709000-00001\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.lwwonline.com-pt-pt-core-template-journal-lwwgateway-images-pmlogo.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17890927\">Related Articles</a></td></tr></table>        <p><b>Screening drugs for QT prolongation.</b></p>        <p>Am J Ther. 2007 Sep-Oct;14(5):419-20</p>        <p>Authors:  Somberg J</p>        <p></p>        <p>PMID: 17890927 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17451846&dopt=Abstract\">[An abnormal electrocardiogram in a drug addict patient]</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://linkinghub.elsevier.com/retrieve/pii/S0248-8663(07)00098-7\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17451846\">Related Articles</a></td></tr></table>        <p><b>[An abnormal electrocardiogram in a drug addict patient]</b></p>        <p>Rev Med Interne. 2007 Oct;28(10):709-10</p>        <p>Authors:  Le Page L, Lion-Daolio S, Guillaumont MP, Grignon P, Smail A, Ducroix JP</p>        <p></p>        <p>PMID: 17451846 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17504354&dopt=Abstract\">Is there a relationship between the blood cholinesterase and QTc interval in the patients with acute organophosphate poisoning?</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1368-5031&amp;date=2007&amp;volume=61&amp;issue=6&amp;spage=927\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17504354\">Related Articles</a></td></tr></table>        <p><b>Is there a relationship between the blood cholinesterase and QTc interval in the patients with acute organophosphate poisoning?</b></p>        <p>Int J Clin Pract. 2007 Jun;61(6):927-30</p>        <p>Authors:  Baydin A, Aygun D, Yazici M, Karatas A, Deniz T, Yardan T</p>        <p>Organophosphates cause poisoning as a result of the excessive accumulation of acetylcholine at the cholinergic synapses due to inhibition of acetylcholinesterase (ChE). In the literature, it has been reported that there have been electrocardiographic abnormalities, including QT-interval prolongation in most patients with acute organophosphate poisoning (OPP), and a relation between blood ChE level and clinical severity in acute OPP. The aim of this study is to assess the relationship between blood ChE level and QTc interval in the patients with acute OPP. This retrospective study consists of 20 patients admitted to the emergency intensive care unit. A total of 93 QTc interval and blood ChE measures obtained on the same day from 20 cases were compared for their correlation. There were prolonged QTc intervals in 35.4% of the ECGs. There was a negative correlation between QTc interval and blood ChE measures. In following up the patients with acute OPP, QTc interval may be useful when blood ChE levels are low and may provide complementary information concerning the severity of poisoning. However, further prospective studies, supporting the present results, are needed.</p>        <p>PMID: 17504354 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17938516&dopt=Abstract\">[Pharmacology studies]</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://joi.jlc.jst.go.jp/JST.JSTAGE/fpj/130.299?lang=en&amp;from=PubMed\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkout.jstage.jst.go.jp-logo_nonfree.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17938516\">Related Articles</a></td></tr></table>        <p><b>[Pharmacology studies]</b></p>        <p>Nippon Yakurigaku Zasshi. 2007 Oct;130(4):299-303</p>        <p>Authors:  Yamamoto K</p>        <p></p>        <p>PMID: 17938516 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17938516&dopt=Abstract\">[Pharmacology studies]</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://joi.jlc.jst.go.jp/JST.JSTAGE/fpj/130.299?lang=en&amp;from=PubMed\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkout.jstage.jst.go.jp-logo_nonfree.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17938516\">Related Articles</a></td></tr></table>        <p><b>[Pharmacology studies]</b></p>        <p>Nippon Yakurigaku Zasshi. 2007 Oct;130(4):299-303</p>        <p>Authors:  Yamamoto K</p>        <p></p>        <p>PMID: 17938516 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17938516&dopt=Abstract\">[Pharmacology studies]</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://joi.jlc.jst.go.jp/JST.JSTAGE/fpj/130.299?lang=en&amp;from=PubMed\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--linkout.jstage.jst.go.jp-logo_nonfree.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17938516\">Related Articles</a></td></tr></table>        <p><b>[Pharmacology studies]</b></p>        <p>Nippon Yakurigaku Zasshi. 2007 Oct;130(4):299-303</p>        <p>Authors:  Yamamoto K</p>        <p></p>        <p>PMID: 17938516 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17298480&dopt=Abstract\">Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0306-5251&amp;date=2007&amp;volume=64&amp;issue=2&amp;spage=192\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17298480\">Related Articles</a></td></tr></table>        <p><b>Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases.</b></p>        <p>Br J Clin Pharmacol. 2007 Aug;64(2):192-7</p>        <p>Authors:  Howell C, Wilson AD, Waring WS</p>        <p>AIMS: Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults. METHODS: A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electrocardiographic data were examined in the whole group and a subset that ingested venlafaxine alone. RESULTS: Two hundred and thirty-five patients (65 men) with median (interquartile range) age 34 years (27-43 years) had ingested venlafaxine 1500 mg (919-2800 mg). Tachycardia (40.0%), high blood pressure (28.4%) and mydriasis (36.6%) were common. Corrected QT &gt;450 ms occurred in seven men (11.1%) and 17 women (10.5%) and transient arrhythmia in three patients. There was a positive correlation between stated quantity of venlafaxine ingested and heart rate [rho = 0.195, 95% confidence interval (CI) 0.054, 0.328] and QTc (rho = 0.314, 95% CI 0.089, 0.509). CONCLUSIONS: Venlafaxine overdose is associated with sympathomimetic cardiovascular effects and prolonged QTc, irrespective of coingested drugs. These mechanisms might pose an increased risk of arrhythmia and require further exploration.</p>        <p>PMID: 17298480 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17298480&dopt=Abstract\">Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0306-5251&amp;date=2007&amp;volume=64&amp;issue=2&amp;spage=192\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17298480\">Related Articles</a></td></tr></table>        <p><b>Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases.</b></p>        <p>Br J Clin Pharmacol. 2007 Aug;64(2):192-7</p>        <p>Authors:  Howell C, Wilson AD, Waring WS</p>        <p>AIMS: Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults. METHODS: A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electrocardiographic data were examined in the whole group and a subset that ingested venlafaxine alone. RESULTS: Two hundred and thirty-five patients (65 men) with median (interquartile range) age 34 years (27-43 years) had ingested venlafaxine 1500 mg (919-2800 mg). Tachycardia (40.0%), high blood pressure (28.4%) and mydriasis (36.6%) were common. Corrected QT &gt;450 ms occurred in seven men (11.1%) and 17 women (10.5%) and transient arrhythmia in three patients. There was a positive correlation between stated quantity of venlafaxine ingested and heart rate [rho = 0.195, 95% confidence interval (CI) 0.054, 0.328] and QTc (rho = 0.314, 95% CI 0.089, 0.509). CONCLUSIONS: Venlafaxine overdose is associated with sympathomimetic cardiovascular effects and prolonged QTc, irrespective of coingested drugs. These mechanisms might pose an increased risk of arrhythmia and require further exploration.</p>        <p>PMID: 17298480 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17410120&dopt=Abstract\">Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100194\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17410120\">Related Articles</a></td></tr></table>        <p><b>Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):548-54</p>        <p>Authors:  Salih IS, Thanacoody RH, McKay GA, Thomas SH</p>        <p>We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.</p>        <p>PMID: 17410120 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=16818698&dopt=Abstract\">Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16818698\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_final_free.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=16818698\">Related Articles</a></td></tr></table>        <p><b>Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</b></p>        <p>Clin Cancer Res. 2006 Jul 1;12(13):3997-4003</p>        <p>Authors:  Shah MH, Binkley P, Chan K, Xiao J, Arbogast D, Collamore M, Farra Y, Young D, Grever M</p>        <p>PURPOSE: This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. EXPERIMENTAL DESIGN: A total of 15 patients with metastatic neuroendocrine tumors received a 4-hour i.v. infusion of depsipeptide at 14 mg/m2 on days 1, 8, and 15 every 28 days. Tumor response was assessed at 8-week intervals using Response Evaluation Criteria in Solid Tumors. Most patients were chemo-na&#xEF;ve (n = 12) but receiving long-acting octreotide for carcinoid syndrome (n = 11). All patients had Eastern Cooperative Oncology Group performance status of 0 to 1. RESULTS: The study was terminated prematurely due to an unexpected high number of serious cardiac adverse events so the objective response rate could not be determined. A total of 77 doses of depsipeptide with a median of four doses (range, 2-13) per patient were administered. The most common adverse events included nausea (86%), anorexia (73%), vomiting (66%), and fatigue (73%). A sudden death attributed to possible fatal ventricular arrhythmia occurred within 24 hours after the fifth dose of depsipeptide. Furthermore, asymptomatic grade 2 ventricular tachycardia (n = 2) and prolonged QTc (n = 3) probably related to depsipeptide were observed. Plasma depsipeptide levels measured in a subset of patients failed to reveal differences among patients with or without cardiac adverse events. CONCLUSIONS: Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.</p>        <p>PMID: 16818698 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
document.write('</div>');
document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17410120&dopt=Abstract\">Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100194\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17410120\">Related Articles</a></td></tr></table>        <p><b>Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):548-54</p>        <p>Authors:  Salih IS, Thanacoody RH, McKay GA, Thomas SH</p>        <p>We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.</p>        <p>PMID: 17410120 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=16818698&dopt=Abstract\">Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16818698\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_final_free.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=16818698\">Related Articles</a></td></tr></table>        <p><b>Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</b></p>        <p>Clin Cancer Res. 2006 Jul 1;12(13):3997-4003</p>        <p>Authors:  Shah MH, Binkley P, Chan K, Xiao J, Arbogast D, Collamore M, Farra Y, Young D, Grever M</p>        <p>PURPOSE: This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. EXPERIMENTAL DESIGN: A total of 15 patients with metastatic neuroendocrine tumors received a 4-hour i.v. infusion of depsipeptide at 14 mg/m2 on days 1, 8, and 15 every 28 days. Tumor response was assessed at 8-week intervals using Response Evaluation Criteria in Solid Tumors. Most patients were chemo-na&#xEF;ve (n = 12) but receiving long-acting octreotide for carcinoid syndrome (n = 11). All patients had Eastern Cooperative Oncology Group performance status of 0 to 1. RESULTS: The study was terminated prematurely due to an unexpected high number of serious cardiac adverse events so the objective response rate could not be determined. A total of 77 doses of depsipeptide with a median of four doses (range, 2-13) per patient were administered. The most common adverse events included nausea (86%), anorexia (73%), vomiting (66%), and fatigue (73%). A sudden death attributed to possible fatal ventricular arrhythmia occurred within 24 hours after the fifth dose of depsipeptide. Furthermore, asymptomatic grade 2 ventricular tachycardia (n = 2) and prolonged QTc (n = 3) probably related to depsipeptide were observed. Plasma depsipeptide levels measured in a subset of patients failed to reveal differences among patients with or without cardiac adverse events. CONCLUSIONS: Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.</p>        <p>PMID: 16818698 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17410120&dopt=Abstract\">Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100194\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17410120\">Related Articles</a></td></tr></table>        <p><b>Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):548-54</p>        <p>Authors:  Salih IS, Thanacoody RH, McKay GA, Thomas SH</p>        <p>We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.</p>        <p>PMID: 17410120 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=16818698&dopt=Abstract\">Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16818698\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_final_free.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=16818698\">Related Articles</a></td></tr></table>        <p><b>Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</b></p>        <p>Clin Cancer Res. 2006 Jul 1;12(13):3997-4003</p>        <p>Authors:  Shah MH, Binkley P, Chan K, Xiao J, Arbogast D, Collamore M, Farra Y, Young D, Grever M</p>        <p>PURPOSE: This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. EXPERIMENTAL DESIGN: A total of 15 patients with metastatic neuroendocrine tumors received a 4-hour i.v. infusion of depsipeptide at 14 mg/m2 on days 1, 8, and 15 every 28 days. Tumor response was assessed at 8-week intervals using Response Evaluation Criteria in Solid Tumors. Most patients were chemo-na&#xEF;ve (n = 12) but receiving long-acting octreotide for carcinoid syndrome (n = 11). All patients had Eastern Cooperative Oncology Group performance status of 0 to 1. RESULTS: The study was terminated prematurely due to an unexpected high number of serious cardiac adverse events so the objective response rate could not be determined. A total of 77 doses of depsipeptide with a median of four doses (range, 2-13) per patient were administered. The most common adverse events included nausea (86%), anorexia (73%), vomiting (66%), and fatigue (73%). A sudden death attributed to possible fatal ventricular arrhythmia occurred within 24 hours after the fifth dose of depsipeptide. Furthermore, asymptomatic grade 2 ventricular tachycardia (n = 2) and prolonged QTc (n = 3) probably related to depsipeptide were observed. Plasma depsipeptide levels measured in a subset of patients failed to reveal differences among patients with or without cardiac adverse events. CONCLUSIONS: Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.</p>        <p>PMID: 16818698 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
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document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17410120&dopt=Abstract\">Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100194\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17410120\">Related Articles</a></td></tr></table>        <p><b>Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):548-54</p>        <p>Authors:  Salih IS, Thanacoody RH, McKay GA, Thomas SH</p>        <p>We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.</p>        <p>PMID: 17410120 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=16818698&dopt=Abstract\">Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16818698\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_final_free.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=16818698\">Related Articles</a></td></tr></table>        <p><b>Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</b></p>        <p>Clin Cancer Res. 2006 Jul 1;12(13):3997-4003</p>        <p>Authors:  Shah MH, Binkley P, Chan K, Xiao J, Arbogast D, Collamore M, Farra Y, Young D, Grever M</p>        <p>PURPOSE: This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. EXPERIMENTAL DESIGN: A total of 15 patients with metastatic neuroendocrine tumors received a 4-hour i.v. infusion of depsipeptide at 14 mg/m2 on days 1, 8, and 15 every 28 days. Tumor response was assessed at 8-week intervals using Response Evaluation Criteria in Solid Tumors. Most patients were chemo-na&#xEF;ve (n = 12) but receiving long-acting octreotide for carcinoid syndrome (n = 11). All patients had Eastern Cooperative Oncology Group performance status of 0 to 1. RESULTS: The study was terminated prematurely due to an unexpected high number of serious cardiac adverse events so the objective response rate could not be determined. A total of 77 doses of depsipeptide with a median of four doses (range, 2-13) per patient were administered. The most common adverse events included nausea (86%), anorexia (73%), vomiting (66%), and fatigue (73%). A sudden death attributed to possible fatal ventricular arrhythmia occurred within 24 hours after the fifth dose of depsipeptide. Furthermore, asymptomatic grade 2 ventricular tachycardia (n = 2) and prolonged QTc (n = 3) probably related to depsipeptide were observed. Plasma depsipeptide levels measured in a subset of patients failed to reveal differences among patients with or without cardiac adverse events. CONCLUSIONS: Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.</p>        <p>PMID: 16818698 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('</ul>');
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document.write('<div class=\"rss_feed\">');
document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17410120&dopt=Abstract\">Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100194\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17410120\">Related Articles</a></td></tr></table>        <p><b>Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):548-54</p>        <p>Authors:  Salih IS, Thanacoody RH, McKay GA, Thomas SH</p>        <p>We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.</p>        <p>PMID: 17410120 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=16818698&dopt=Abstract\">Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16818698\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_final_free.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=16818698\">Related Articles</a></td></tr></table>        <p><b>Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors.</b></p>        <p>Clin Cancer Res. 2006 Jul 1;12(13):3997-4003</p>        <p>Authors:  Shah MH, Binkley P, Chan K, Xiao J, Arbogast D, Collamore M, Farra Y, Young D, Grever M</p>        <p>PURPOSE: This phase II study was undertaken to assess objective response and toxicity of histone deacetylase inhibitor depsipeptide in patients with neuroendocrine tumors. EXPERIMENTAL DESIGN: A total of 15 patients with metastatic neuroendocrine tumors received a 4-hour i.v. infusion of depsipeptide at 14 mg/m2 on days 1, 8, and 15 every 28 days. Tumor response was assessed at 8-week intervals using Response Evaluation Criteria in Solid Tumors. Most patients were chemo-na&#xEF;ve (n = 12) but receiving long-acting octreotide for carcinoid syndrome (n = 11). All patients had Eastern Cooperative Oncology Group performance status of 0 to 1. RESULTS: The study was terminated prematurely due to an unexpected high number of serious cardiac adverse events so the objective response rate could not be determined. A total of 77 doses of depsipeptide with a median of four doses (range, 2-13) per patient were administered. The most common adverse events included nausea (86%), anorexia (73%), vomiting (66%), and fatigue (73%). A sudden death attributed to possible fatal ventricular arrhythmia occurred within 24 hours after the fifth dose of depsipeptide. Furthermore, asymptomatic grade 2 ventricular tachycardia (n = 2) and prolonged QTc (n = 3) probably related to depsipeptide were observed. Plasma depsipeptide levels measured in a subset of patients failed to reveal differences among patients with or without cardiac adverse events. CONCLUSIONS: Depsipeptide was associated with a high number of potentially serious cardiac adverse events in patients with metastatic neuroendocrine tumor. As sudden death possibly associated with depsipeptide was observed in this trial, the risks for potentially life-threatening arrhythmia associated with this agent need to be comprehensively evaluated.</p>        <p>PMID: 16818698 [PubMed - indexed for MEDLINE]</p>    </span></li>');
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document.write('<div class=\"rss_feed_title\">PubMed: \"Long QT Syndrome/ch...</div>');
document.write('<ul class=\"rss_item_list\">');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17966685&dopt=Abstract\">Drug-induced long QT syndrome.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"/><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17966685\">Related Articles</a></td></tr></table>        <p><b>Drug-induced long QT syndrome.</b></p>        <p>Hellenic J Cardiol. 2007 Sep-Oct;48(5):296-9</p>        <p>Authors:  Letsas KP, Efremidis M, Filippatos GS, Sideris AM</p>        <p></p>        <p>PMID: 17966685 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17669094&dopt=Abstract\">QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0147-8389&amp;date=2007&amp;volume=30&amp;issue=8&amp;spage=1043\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.blackwell-synergy.com-templates-jsp-_synergy-images-synergy_linkout.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17669094\">Related Articles</a></td></tr></table>        <p><b>QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator.</b></p>        <p>Pacing Clin Electrophysiol. 2007 Aug;30(8):1043-6</p>        <p>Authors:  Ka&#x17A;mierczak J, Peregud-Pogorzelska M, Rzeuski R</p>        <p>The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.</p>        <p>PMID: 17669094 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=17460606&dopt=Abstract\">Factors affecting drug concentrations and QT interval during thioridazine therapy.</a></span> <span class=\"rss_item_desc\">	<table border=\"0\" width=\"100%\"><tr><td align=\"left\"><a href=\"http://dx.doi.org/10.1038/sj.clpt.6100195\"><img src=\"http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--www.nature.com-images-lo_npg.gif\" border=\"0\"/></a> </td><td align=\"right\"><a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&amp;cmd=Display&amp;dopt=PubMed_PubMed&amp;from_uid=17460606\">Related Articles</a></td></tr></table>        <p><b>Factors affecting drug concentrations and QT interval during thioridazine therapy.</b></p>        <p>Clin Pharmacol Ther. 2007 Nov;82(5):555-65</p>        <p>Authors:  Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH</p>        <p>The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with &gt;/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.</p>        <p>PMID: 17460606 [PubMed - indexed for MEDLINE]</p>    </span></li>');
document.write('<li class=\"rss_item\"><span class=\"rss_item_title\"><a class=\"rss_item_link\" href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcg