Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats
OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodyna...
Gespeichert in:
Veröffentlicht in: | Critical care medicine 2003-01, Vol.31 (1), p.215-220 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 220 |
---|---|
container_issue | 1 |
container_start_page | 215 |
container_title | Critical care medicine |
container_volume | 31 |
creator | Asfar, Pierre Pierrot, Marc Veal, Nary Moal, Frédéric Oberti, Frédéric Croquet, Vincent Douay, Olivier Gallois, Yves Saumet, Jean-Louis Alquier, Philippe Calès, Paul |
description | OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).
DESIGNProspective, randomized, controlled experimental study with repeated measures.
SETTINGInvestigational animal laboratory.
SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats).
INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values.
MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p < .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p < .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p < .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET).
CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation. |
doi_str_mv | 10.1097/00003246-200301000-00033 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72975215</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72975215</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</originalsourceid><addsrcrecordid>eNp1kcGOFCEQholx446jr2D6ordWoKCBo9mou8kkXvZOGKDtVroZqW7HeftlndE9yaXyw1dQ-SCkYfQ9o0Z9oHUBF13La6WspvZxB56RDZNQAzfwnGwoNbQFYeCavET8TikTUsELcs24FJIyvSH9Lh_bkDE2SyxpPJSIOM7NOB1K_hWxwRMucRp94-bQ4CG52Q9zjUOccjjNrh5hUxv6tI6h9YNLKc7fYmjiHPKSf1e0uAVfkaveJYyvL3VL7j9_ur-5bXdfv9zdfNy1HnQHbaeAdV4rbTjsqZd-Hxk3lPJeGKr0XnZaSQCgIFnouRFgQuCOGiaFUQa25N352jr9zzXiYqcRfUx17JhXtIobJXlVtCX6DPqSEUvs7aGMkysny6h9VGz_Krb_FNs_imvrm8sb636K4anx4rQCby-AQ-9SX6qzEZ84ITRopSonztwxpyoff6T1GIsdokvLYP_3xfAAv_WS1g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72975215</pqid></control><display><type>article</type><title>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Asfar, Pierre ; Pierrot, Marc ; Veal, Nary ; Moal, Frédéric ; Oberti, Frédéric ; Croquet, Vincent ; Douay, Olivier ; Gallois, Yves ; Saumet, Jean-Louis ; Alquier, Philippe ; Calès, Paul</creator><creatorcontrib>Asfar, Pierre ; Pierrot, Marc ; Veal, Nary ; Moal, Frédéric ; Oberti, Frédéric ; Croquet, Vincent ; Douay, Olivier ; Gallois, Yves ; Saumet, Jean-Louis ; Alquier, Philippe ; Calès, Paul</creatorcontrib><description>OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).
DESIGNProspective, randomized, controlled experimental study with repeated measures.
SETTINGInvestigational animal laboratory.
SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats).
INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values.
MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p < .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p < .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p < .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET).
CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</description><identifier>ISSN: 0090-3493</identifier><identifier>EISSN: 1530-0293</identifier><identifier>DOI: 10.1097/00003246-200301000-00033</identifier><identifier>PMID: 12545018</identifier><identifier>CODEN: CCMDC7</identifier><language>eng</language><publisher>Hagerstown, MD: by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Cardiovascular system ; Emergency and intensive care: infection, septic shock ; Hemodynamics - drug effects ; Intensive care medicine ; Lypressin - analogs & derivatives ; Lypressin - pharmacology ; Lypressin - therapeutic use ; Male ; Medical sciences ; Microcirculation ; Pharmacology. Drug treatments ; Random Allocation ; Rats ; Rats, Wistar ; Shock, Septic - drug therapy ; Splanchnic Circulation - drug effects ; Statistics, Nonparametric ; Survival Analysis ; Terlipressin ; Vascular wall ; Vasoconstrictor Agents - pharmacology ; Vasoconstrictor Agents - therapeutic use</subject><ispartof>Critical care medicine, 2003-01, Vol.31 (1), p.215-220</ispartof><rights>2003 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</citedby><cites>FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14483877$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12545018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asfar, Pierre</creatorcontrib><creatorcontrib>Pierrot, Marc</creatorcontrib><creatorcontrib>Veal, Nary</creatorcontrib><creatorcontrib>Moal, Frédéric</creatorcontrib><creatorcontrib>Oberti, Frédéric</creatorcontrib><creatorcontrib>Croquet, Vincent</creatorcontrib><creatorcontrib>Douay, Olivier</creatorcontrib><creatorcontrib>Gallois, Yves</creatorcontrib><creatorcontrib>Saumet, Jean-Louis</creatorcontrib><creatorcontrib>Alquier, Philippe</creatorcontrib><creatorcontrib>Calès, Paul</creatorcontrib><title>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</title><title>Critical care medicine</title><addtitle>Crit Care Med</addtitle><description>OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).
DESIGNProspective, randomized, controlled experimental study with repeated measures.
SETTINGInvestigational animal laboratory.
SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats).
INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values.
MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p < .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p < .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p < .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET).
CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Emergency and intensive care: infection, septic shock</subject><subject>Hemodynamics - drug effects</subject><subject>Intensive care medicine</subject><subject>Lypressin - analogs & derivatives</subject><subject>Lypressin - pharmacology</subject><subject>Lypressin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcirculation</subject><subject>Pharmacology. Drug treatments</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Shock, Septic - drug therapy</subject><subject>Splanchnic Circulation - drug effects</subject><subject>Statistics, Nonparametric</subject><subject>Survival Analysis</subject><subject>Terlipressin</subject><subject>Vascular wall</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasoconstrictor Agents - therapeutic use</subject><issn>0090-3493</issn><issn>1530-0293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcGOFCEQholx446jr2D6ordWoKCBo9mou8kkXvZOGKDtVroZqW7HeftlndE9yaXyw1dQ-SCkYfQ9o0Z9oHUBF13La6WspvZxB56RDZNQAzfwnGwoNbQFYeCavET8TikTUsELcs24FJIyvSH9Lh_bkDE2SyxpPJSIOM7NOB1K_hWxwRMucRp94-bQ4CG52Q9zjUOccjjNrh5hUxv6tI6h9YNLKc7fYmjiHPKSf1e0uAVfkaveJYyvL3VL7j9_ur-5bXdfv9zdfNy1HnQHbaeAdV4rbTjsqZd-Hxk3lPJeGKr0XnZaSQCgIFnouRFgQuCOGiaFUQa25N352jr9zzXiYqcRfUx17JhXtIobJXlVtCX6DPqSEUvs7aGMkysny6h9VGz_Krb_FNs_imvrm8sb636K4anx4rQCby-AQ-9SX6qzEZ84ITRopSonztwxpyoff6T1GIsdokvLYP_3xfAAv_WS1g</recordid><startdate>200301</startdate><enddate>200301</enddate><creator>Asfar, Pierre</creator><creator>Pierrot, Marc</creator><creator>Veal, Nary</creator><creator>Moal, Frédéric</creator><creator>Oberti, Frédéric</creator><creator>Croquet, Vincent</creator><creator>Douay, Olivier</creator><creator>Gallois, Yves</creator><creator>Saumet, Jean-Louis</creator><creator>Alquier, Philippe</creator><creator>Calès, Paul</creator><general>by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</general><general>Lippincott</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>200301</creationdate><title>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</title><author>Asfar, Pierre ; Pierrot, Marc ; Veal, Nary ; Moal, Frédéric ; Oberti, Frédéric ; Croquet, Vincent ; Douay, Olivier ; Gallois, Yves ; Saumet, Jean-Louis ; Alquier, Philippe ; Calès, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Emergency and intensive care: infection, septic shock</topic><topic>Hemodynamics - drug effects</topic><topic>Intensive care medicine</topic><topic>Lypressin - analogs & derivatives</topic><topic>Lypressin - pharmacology</topic><topic>Lypressin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcirculation</topic><topic>Pharmacology. Drug treatments</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Shock, Septic - drug therapy</topic><topic>Splanchnic Circulation - drug effects</topic><topic>Statistics, Nonparametric</topic><topic>Survival Analysis</topic><topic>Terlipressin</topic><topic>Vascular wall</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasoconstrictor Agents - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asfar, Pierre</creatorcontrib><creatorcontrib>Pierrot, Marc</creatorcontrib><creatorcontrib>Veal, Nary</creatorcontrib><creatorcontrib>Moal, Frédéric</creatorcontrib><creatorcontrib>Oberti, Frédéric</creatorcontrib><creatorcontrib>Croquet, Vincent</creatorcontrib><creatorcontrib>Douay, Olivier</creatorcontrib><creatorcontrib>Gallois, Yves</creatorcontrib><creatorcontrib>Saumet, Jean-Louis</creatorcontrib><creatorcontrib>Alquier, Philippe</creatorcontrib><creatorcontrib>Calès, Paul</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asfar, Pierre</au><au>Pierrot, Marc</au><au>Veal, Nary</au><au>Moal, Frédéric</au><au>Oberti, Frédéric</au><au>Croquet, Vincent</au><au>Douay, Olivier</au><au>Gallois, Yves</au><au>Saumet, Jean-Louis</au><au>Alquier, Philippe</au><au>Calès, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</atitle><jtitle>Critical care medicine</jtitle><addtitle>Crit Care Med</addtitle><date>2003-01</date><risdate>2003</risdate><volume>31</volume><issue>1</issue><spage>215</spage><epage>220</epage><pages>215-220</pages><issn>0090-3493</issn><eissn>1530-0293</eissn><coden>CCMDC7</coden><abstract>OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).
DESIGNProspective, randomized, controlled experimental study with repeated measures.
SETTINGInvestigational animal laboratory.
SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats).
INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values.
MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p < .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p < .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p < .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET).
CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</abstract><cop>Hagerstown, MD</cop><pub>by the Society of Critical Care Medicine and Lippincott Williams & Wilkins</pub><pmid>12545018</pmid><doi>10.1097/00003246-200301000-00033</doi><tpages>6</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0090-3493 |
ispartof | Critical care medicine, 2003-01, Vol.31 (1), p.215-220 |
issn | 0090-3493 1530-0293 |
language | eng |
recordid | cdi_proquest_miscellaneous_72975215 |
source | MEDLINE; Journals@Ovid Complete |
subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Cardiovascular system Emergency and intensive care: infection, septic shock Hemodynamics - drug effects Intensive care medicine Lypressin - analogs & derivatives Lypressin - pharmacology Lypressin - therapeutic use Male Medical sciences Microcirculation Pharmacology. Drug treatments Random Allocation Rats Rats, Wistar Shock, Septic - drug therapy Splanchnic Circulation - drug effects Statistics, Nonparametric Survival Analysis Terlipressin Vascular wall Vasoconstrictor Agents - pharmacology Vasoconstrictor Agents - therapeutic use |
title | Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T13%3A00%3A27IST&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=Low-dose%20terlipressin%20improves%20systemic%20and%20splanchnic%20hemodynamics%20in%20fluid-challenged%20endotoxic%20rats&rft.jtitle=Critical%20care%20medicine&rft.au=Asfar,%20Pierre&rft.date=2003-01&rft.volume=31&rft.issue=1&rft.spage=215&rft.epage=220&rft.pages=215-220&rft.issn=0090-3493&rft.eissn=1530-0293&rft.coden=CCMDC7&rft_id=info:doi/10.1097/00003246-200301000-00033&rft_dat=%3Cproquest_cross%3E72975215%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=72975215&rft_id=info:pmid/12545018&rfr_iscdi=true |