The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study
We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease. Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after ang...
Gespeichert in:
Veröffentlicht in: | Journal of the American College of Cardiology 2003-07, Vol.42 (2), p.211-216 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 216 |
---|---|
container_issue | 2 |
container_start_page | 211 |
container_title | Journal of the American College of Cardiology |
container_volume | 42 |
creator | Fukumoto, Yoshihiro Tsutsui, Hiroyuki Tsuchihashi, Miyuki Masumoto, Akihiro Takeshita, Akira |
description | We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease.
Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis.
We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction.
Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, p = 0.01).
Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures. |
doi_str_mv | 10.1016/S0735-1097(03)00579-5 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73507582</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0735109703005795</els_id><sourcerecordid>3242418711</sourcerecordid><originalsourceid>FETCH-LOGICAL-c588t-26e2ef30dd83f2f2aaebc0950bdb5e68901f445be2a3b9abd9dfcf1a2493576e3</originalsourceid><addsrcrecordid>eNqFkVFrFDEQx4Mo9qx-BCUgFIVunSSX3U1fREptC4U-WJ9DNplwqbubM9ktXF_94s31Dgu--DQP-f0nM_Mj5D2DEwas_vIDGiErBqr5BOIzgGxUJV-QBZOyrYRUzUuy-IsckDc53wFA3TL1mhww3jaykWJB_tyukIbRBoejRWpGR1PIv6g3doop0-ipXcUe84Qp9hSHLvbhwUwhjjRvRpfigMfUUBuHdR_s7mEbMskFY0udVliy-8xpQdcp5jXaKdwjzdPsNm_JK2_6jO_29ZD8_H5-e3ZZXd9cXJ19u66sbNup4jVy9AKca4XnnhuDnQUloXOdxLpVwPxyKTvkRnTKdE45bz0zfKmEbGoUh-Ro17dM8HsuK-khZIt9b0aMc9blWtDIlhfw4z_gXZzTWGbTTELNlozzulByR9myUE7o9TqFwaSNZqC3jvSTI70VoEHoJ0daltyHffe5G9A9p_ZSCvB1B2A5xn3ApLMNWz0upHI37WL4zxePpG2kGw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1506141226</pqid></control><display><type>article</type><title>The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Fukumoto, Yoshihiro ; Tsutsui, Hiroyuki ; Tsuchihashi, Miyuki ; Masumoto, Akihiro ; Takeshita, Akira</creator><creatorcontrib>Fukumoto, Yoshihiro ; Tsutsui, Hiroyuki ; Tsuchihashi, Miyuki ; Masumoto, Akihiro ; Takeshita, Akira ; Cholesterol Embolism Study(CHEST) Investigators</creatorcontrib><description>We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease.
Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis.
We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction.
Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, p = 0.01).
Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/S0735-1097(03)00579-5</identifier><identifier>PMID: 12875753</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute coronary syndromes ; Acute Kidney Injury - etiology ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Arteriosclerosis - complications ; Blood pressure ; Blue Toe Syndrome - etiology ; C-Reactive Protein - metabolism ; Cardiac Catheterization - adverse effects ; Cardiology ; Cardiovascular disease ; Cholesterol ; Confidence intervals ; Coronary vessels ; Creatinine - blood ; Diabetes ; Embolism, Cholesterol - blood ; Embolism, Cholesterol - diagnosis ; Embolism, Cholesterol - epidemiology ; Embolism, Cholesterol - etiology ; Eosinophils ; Heart attacks ; Hemodialysis ; Hospital Mortality ; Humans ; Hypertension ; Hypertension - complications ; Incidence ; Intubation ; Leukocyte Count ; Middle Aged ; Mortality ; Multivariate analysis ; Predictive Value of Tests ; Prospective Studies ; Regression Analysis ; Risk Factors ; Skin Diseases, Vascular - etiology ; Smoking - adverse effects ; Studies ; Syndrome ; Variables</subject><ispartof>Journal of the American College of Cardiology, 2003-07, Vol.42 (2), p.211-216</ispartof><rights>2003 American College of Cardiology Foundation</rights><rights>Copyright Elsevier Limited Jul 16, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-26e2ef30dd83f2f2aaebc0950bdb5e68901f445be2a3b9abd9dfcf1a2493576e3</citedby><cites>FETCH-LOGICAL-c588t-26e2ef30dd83f2f2aaebc0950bdb5e68901f445be2a3b9abd9dfcf1a2493576e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0735-1097(03)00579-5$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12875753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fukumoto, Yoshihiro</creatorcontrib><creatorcontrib>Tsutsui, Hiroyuki</creatorcontrib><creatorcontrib>Tsuchihashi, Miyuki</creatorcontrib><creatorcontrib>Masumoto, Akihiro</creatorcontrib><creatorcontrib>Takeshita, Akira</creatorcontrib><creatorcontrib>Cholesterol Embolism Study(CHEST) Investigators</creatorcontrib><title>The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease.
Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis.
We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction.
Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, p = 0.01).
Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.</description><subject>Acute coronary syndromes</subject><subject>Acute Kidney Injury - etiology</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis of Variance</subject><subject>Arteriosclerosis - complications</subject><subject>Blood pressure</subject><subject>Blue Toe Syndrome - etiology</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cardiac Catheterization - adverse effects</subject><subject>Cardiology</subject><subject>Cardiovascular disease</subject><subject>Cholesterol</subject><subject>Confidence intervals</subject><subject>Coronary vessels</subject><subject>Creatinine - blood</subject><subject>Diabetes</subject><subject>Embolism, Cholesterol - blood</subject><subject>Embolism, Cholesterol - diagnosis</subject><subject>Embolism, Cholesterol - epidemiology</subject><subject>Embolism, Cholesterol - etiology</subject><subject>Eosinophils</subject><subject>Heart attacks</subject><subject>Hemodialysis</subject><subject>Hospital Mortality</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - complications</subject><subject>Incidence</subject><subject>Intubation</subject><subject>Leukocyte Count</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Multivariate analysis</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Regression Analysis</subject><subject>Risk Factors</subject><subject>Skin Diseases, Vascular - etiology</subject><subject>Smoking - adverse effects</subject><subject>Studies</subject><subject>Syndrome</subject><subject>Variables</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFrFDEQx4Mo9qx-BCUgFIVunSSX3U1fREptC4U-WJ9DNplwqbubM9ktXF_94s31Dgu--DQP-f0nM_Mj5D2DEwas_vIDGiErBqr5BOIzgGxUJV-QBZOyrYRUzUuy-IsckDc53wFA3TL1mhww3jaykWJB_tyukIbRBoejRWpGR1PIv6g3doop0-ipXcUe84Qp9hSHLvbhwUwhjjRvRpfigMfUUBuHdR_s7mEbMskFY0udVliy-8xpQdcp5jXaKdwjzdPsNm_JK2_6jO_29ZD8_H5-e3ZZXd9cXJ19u66sbNup4jVy9AKca4XnnhuDnQUloXOdxLpVwPxyKTvkRnTKdE45bz0zfKmEbGoUh-Ro17dM8HsuK-khZIt9b0aMc9blWtDIlhfw4z_gXZzTWGbTTELNlozzulByR9myUE7o9TqFwaSNZqC3jvSTI70VoEHoJ0daltyHffe5G9A9p_ZSCvB1B2A5xn3ApLMNWz0upHI37WL4zxePpG2kGw</recordid><startdate>20030716</startdate><enddate>20030716</enddate><creator>Fukumoto, Yoshihiro</creator><creator>Tsutsui, Hiroyuki</creator><creator>Tsuchihashi, Miyuki</creator><creator>Masumoto, Akihiro</creator><creator>Takeshita, Akira</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20030716</creationdate><title>The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study</title><author>Fukumoto, Yoshihiro ; Tsutsui, Hiroyuki ; Tsuchihashi, Miyuki ; Masumoto, Akihiro ; Takeshita, Akira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-26e2ef30dd83f2f2aaebc0950bdb5e68901f445be2a3b9abd9dfcf1a2493576e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acute coronary syndromes</topic><topic>Acute Kidney Injury - etiology</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis of Variance</topic><topic>Arteriosclerosis - complications</topic><topic>Blood pressure</topic><topic>Blue Toe Syndrome - etiology</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cardiac Catheterization - adverse effects</topic><topic>Cardiology</topic><topic>Cardiovascular disease</topic><topic>Cholesterol</topic><topic>Confidence intervals</topic><topic>Coronary vessels</topic><topic>Creatinine - blood</topic><topic>Diabetes</topic><topic>Embolism, Cholesterol - blood</topic><topic>Embolism, Cholesterol - diagnosis</topic><topic>Embolism, Cholesterol - epidemiology</topic><topic>Embolism, Cholesterol - etiology</topic><topic>Eosinophils</topic><topic>Heart attacks</topic><topic>Hemodialysis</topic><topic>Hospital Mortality</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - complications</topic><topic>Incidence</topic><topic>Intubation</topic><topic>Leukocyte Count</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Multivariate analysis</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Regression Analysis</topic><topic>Risk Factors</topic><topic>Skin Diseases, Vascular - etiology</topic><topic>Smoking - adverse effects</topic><topic>Studies</topic><topic>Syndrome</topic><topic>Variables</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fukumoto, Yoshihiro</creatorcontrib><creatorcontrib>Tsutsui, Hiroyuki</creatorcontrib><creatorcontrib>Tsuchihashi, Miyuki</creatorcontrib><creatorcontrib>Masumoto, Akihiro</creatorcontrib><creatorcontrib>Takeshita, Akira</creatorcontrib><creatorcontrib>Cholesterol Embolism Study(CHEST) Investigators</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fukumoto, Yoshihiro</au><au>Tsutsui, Hiroyuki</au><au>Tsuchihashi, Miyuki</au><au>Masumoto, Akihiro</au><au>Takeshita, Akira</au><aucorp>Cholesterol Embolism Study(CHEST) Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2003-07-16</date><risdate>2003</risdate><volume>42</volume><issue>2</issue><spage>211</spage><epage>216</epage><pages>211-216</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>We sought to determine the incidence of cholesterol embolization syndrome (CES) as a complication of cardiac catheterization and to identify risk factors associated with this disease.
Cholesterol embolization syndrome is a systemic disease caused by distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis.
We prospectively evaluated a total of 1,786 consecutive patients 40 years of age and older, who underwent left-heart catheterization at 11 participating hospitals. The diagnosis of CES was made when patients had peripheral cutaneous involvement (livedo reticularis, blue toe syndrome, and digital gangrene) or renal dysfunction.
Twenty-five patients (1.4%) were diagnosed as having CES. Twelve patients (48%) had cutaneous signs, and 16 patients (64%) had renal insufficiency. Eosinophil counts were significantly higher in CES patients than in non-CES patients before and after cardiac catheterization. The in-hospital mortality rate was 16.0% (4 patients), which was significantly higher than that without CES (0.5%, p < 0.01). All four patients with CES who died after cardiac catheterization had progressive renal dysfunction. The incidence of CES increased in patients with atherosclerotic disease, hypertension, a history of smoking, and the elevation of baseline plasma C-reactive protein (CRP) by univariate analysis. The femoral approach did not increase the incidence, suggesting a possibility that the ascending aorta may be a potential embolic source. As an independent predictor of CES, multivariate regression analysis identified only the elevation of pre-procedural CRP levels (odds ratio 4.6, p = 0.01).
Cholesterol embolization syndrome is a relatively rare but serious complication after cardiac catheterization. Elevated plasma levels of pre-procedural CRP are associated with subsequent CES in patients who undergo vascular procedures.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12875753</pmid><doi>10.1016/S0735-1097(03)00579-5</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0735-1097 |
ispartof | Journal of the American College of Cardiology, 2003-07, Vol.42 (2), p.211-216 |
issn | 0735-1097 1558-3597 |
language | eng |
recordid | cdi_proquest_miscellaneous_73507582 |
source | MEDLINE; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Acute coronary syndromes Acute Kidney Injury - etiology Adult Aged Aged, 80 and over Analysis of Variance Arteriosclerosis - complications Blood pressure Blue Toe Syndrome - etiology C-Reactive Protein - metabolism Cardiac Catheterization - adverse effects Cardiology Cardiovascular disease Cholesterol Confidence intervals Coronary vessels Creatinine - blood Diabetes Embolism, Cholesterol - blood Embolism, Cholesterol - diagnosis Embolism, Cholesterol - epidemiology Embolism, Cholesterol - etiology Eosinophils Heart attacks Hemodialysis Hospital Mortality Humans Hypertension Hypertension - complications Incidence Intubation Leukocyte Count Middle Aged Mortality Multivariate analysis Predictive Value of Tests Prospective Studies Regression Analysis Risk Factors Skin Diseases, Vascular - etiology Smoking - adverse effects Studies Syndrome Variables |
title | The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T03%3A42%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20incidence%20and%20risk%20factors%20of%20cholesterol%20embolization%20syndrome,%20a%20complication%20of%20cardiac%20catheterization:%20a%20prospective%20study&rft.jtitle=Journal%20of%20the%20American%20College%20of%20Cardiology&rft.au=Fukumoto,%20Yoshihiro&rft.aucorp=Cholesterol%20Embolism%20Study(CHEST)%20Investigators&rft.date=2003-07-16&rft.volume=42&rft.issue=2&rft.spage=211&rft.epage=216&rft.pages=211-216&rft.issn=0735-1097&rft.eissn=1558-3597&rft_id=info:doi/10.1016/S0735-1097(03)00579-5&rft_dat=%3Cproquest_cross%3E3242418711%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1506141226&rft_id=info:pmid/12875753&rft_els_id=S0735109703005795&rfr_iscdi=true |