Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats

OBJECTIVESIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Critical care medicine 2000-07, Vol.28 (7), p.2522-2527
Hauptverfasser: Tamion, Fabienne, Richard, Vincent, Bonmarchand, Guy, Leroy, Jacky, Hiron, Martine, Daveau, Maryvonne, Thuillez, Christian, Lebreton, Jean-Pierre
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2527
container_issue 7
container_start_page 2522
container_title Critical care medicine
container_volume 28
creator Tamion, Fabienne
Richard, Vincent
Bonmarchand, Guy
Leroy, Jacky
Hiron, Martine
Daveau, Maryvonne
Thuillez, Christian
Lebreton, Jean-Pierre
description OBJECTIVESIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. DESIGNA prospective, controlled animal study. SETTINGA university research laboratory. SUBJECTSMale Wistar rats. INTERVENTIONSHemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MEASUREMENTS AND MAIN RESULTSMPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85 ± 6; MPG 35 ± 5 mL/kg;p < .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-α (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-α and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-α and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. CONCLUSIONReactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.
doi_str_mv 10.1097/00003246-200007000-00055
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71275326</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71275326</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3855-b9f133b45c7622948d6f77188d92ccb228d457276c30520ca815d4df5ea4a0b13</originalsourceid><addsrcrecordid>eNp1kVuL1DAYhoMo7jjrX5BciHfVHJv0UhZPsCAs7nVIky_TOmmzJq1L_71ZZzzcbODLAZ7vDXmCEKbkLSWdekfq4Ey0DXvYqVpNLSmfoB2VvB5Yx5-iHSEdabjo-AV6Ucp3QqiQij9HFzWEUan1Dh1uwK8OPC7bvAxQxoJTwOMcop0mu6S8Ybct6TjOUHC_YYtDBsDZ-tHZiIuzP2E-QMY2LHUeYEo5D_YwOlyG5I41qsJLuUTPgo0FXp7XPbr9-OHb1efm-uunL1fvrxvHtZRN3wXKeS-kUy1jndC-DUpRrX3HnOsZ074-ganWcSIZcVZT6YUPEqywpKd8j96ccu9y-rFCWcw0Fgcx2hnSWoyiTEnO2grqE-hyKiVDMHd5nGzeDCXmQbL5I9n8lWx-S66tr853rP0E_r_Gk9UKvD4DtgqKIdvZjeUfJ1pCa_YeiRN2n2KVV45xvYdsBrBxGcxjf8x_AaW6k9M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71275326</pqid></control><display><type>article</type><title>Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Tamion, Fabienne ; Richard, Vincent ; Bonmarchand, Guy ; Leroy, Jacky ; Hiron, Martine ; Daveau, Maryvonne ; Thuillez, Christian ; Lebreton, Jean-Pierre</creator><creatorcontrib>Tamion, Fabienne ; Richard, Vincent ; Bonmarchand, Guy ; Leroy, Jacky ; Hiron, Martine ; Daveau, Maryvonne ; Thuillez, Christian ; Lebreton, Jean-Pierre</creatorcontrib><description>OBJECTIVESIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. DESIGNA prospective, controlled animal study. SETTINGA university research laboratory. SUBJECTSMale Wistar rats. INTERVENTIONSHemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MEASUREMENTS AND MAIN RESULTSMPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85 ± 6; MPG 35 ± 5 mL/kg;p &lt; .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-α (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-α and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-α and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. CONCLUSIONReactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.</description><identifier>ISSN: 0090-3493</identifier><identifier>EISSN: 1530-0293</identifier><identifier>DOI: 10.1097/00003246-200007000-00055</identifier><identifier>PMID: 10921588</identifier><identifier>CODEN: CCMDC7</identifier><language>eng</language><publisher>Hagerstown, MD: Copyright by by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antioxidants - pharmacology ; Biological and medical sciences ; Blood Transfusion, Autologous ; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care ; Enzyme-Linked Immunosorbent Assay ; Free Radical Scavengers - pharmacology ; Glycine - analogs &amp; derivatives ; Glycine - pharmacology ; Intensive care medicine ; Interleukin-6 - biosynthesis ; Macrophages, Peritoneal - drug effects ; Macrophages, Peritoneal - metabolism ; Male ; Medical sciences ; Rats ; Rats, Wistar ; Resuscitation - methods ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Complementary - isolation &amp; purification ; Shock, Hemorrhagic - metabolism ; Shock, Hemorrhagic - therapy ; Sulfhydryl Compounds - pharmacology ; Tumor Necrosis Factor-alpha - biosynthesis</subject><ispartof>Critical care medicine, 2000-07, Vol.28 (7), p.2522-2527</ispartof><rights>Copyright © by 2000 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3855-b9f133b45c7622948d6f77188d92ccb228d457276c30520ca815d4df5ea4a0b13</citedby><cites>FETCH-LOGICAL-c3855-b9f133b45c7622948d6f77188d92ccb228d457276c30520ca815d4df5ea4a0b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=1460100$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10921588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tamion, Fabienne</creatorcontrib><creatorcontrib>Richard, Vincent</creatorcontrib><creatorcontrib>Bonmarchand, Guy</creatorcontrib><creatorcontrib>Leroy, Jacky</creatorcontrib><creatorcontrib>Hiron, Martine</creatorcontrib><creatorcontrib>Daveau, Maryvonne</creatorcontrib><creatorcontrib>Thuillez, Christian</creatorcontrib><creatorcontrib>Lebreton, Jean-Pierre</creatorcontrib><title>Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats</title><title>Critical care medicine</title><addtitle>Crit Care Med</addtitle><description>OBJECTIVESIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. DESIGNA prospective, controlled animal study. SETTINGA university research laboratory. SUBJECTSMale Wistar rats. INTERVENTIONSHemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MEASUREMENTS AND MAIN RESULTSMPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85 ± 6; MPG 35 ± 5 mL/kg;p &lt; .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-α (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-α and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-α and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. CONCLUSIONReactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Transfusion, Autologous</subject><subject>Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Glycine - analogs &amp; derivatives</subject><subject>Glycine - pharmacology</subject><subject>Intensive care medicine</subject><subject>Interleukin-6 - biosynthesis</subject><subject>Macrophages, Peritoneal - drug effects</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Resuscitation - methods</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Complementary - isolation &amp; purification</subject><subject>Shock, Hemorrhagic - metabolism</subject><subject>Shock, Hemorrhagic - therapy</subject><subject>Sulfhydryl Compounds - pharmacology</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><issn>0090-3493</issn><issn>1530-0293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kVuL1DAYhoMo7jjrX5BciHfVHJv0UhZPsCAs7nVIky_TOmmzJq1L_71ZZzzcbODLAZ7vDXmCEKbkLSWdekfq4Ey0DXvYqVpNLSmfoB2VvB5Yx5-iHSEdabjo-AV6Ucp3QqiQij9HFzWEUan1Dh1uwK8OPC7bvAxQxoJTwOMcop0mu6S8Ybct6TjOUHC_YYtDBsDZ-tHZiIuzP2E-QMY2LHUeYEo5D_YwOlyG5I41qsJLuUTPgo0FXp7XPbr9-OHb1efm-uunL1fvrxvHtZRN3wXKeS-kUy1jndC-DUpRrX3HnOsZ074-ganWcSIZcVZT6YUPEqywpKd8j96ccu9y-rFCWcw0Fgcx2hnSWoyiTEnO2grqE-hyKiVDMHd5nGzeDCXmQbL5I9n8lWx-S66tr853rP0E_r_Gk9UKvD4DtgqKIdvZjeUfJ1pCa_YeiRN2n2KVV45xvYdsBrBxGcxjf8x_AaW6k9M</recordid><startdate>200007</startdate><enddate>200007</enddate><creator>Tamion, Fabienne</creator><creator>Richard, Vincent</creator><creator>Bonmarchand, Guy</creator><creator>Leroy, Jacky</creator><creator>Hiron, Martine</creator><creator>Daveau, Maryvonne</creator><creator>Thuillez, Christian</creator><creator>Lebreton, Jean-Pierre</creator><general>Copyright by by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc</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>200007</creationdate><title>Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats</title><author>Tamion, Fabienne ; Richard, Vincent ; Bonmarchand, Guy ; Leroy, Jacky ; Hiron, Martine ; Daveau, Maryvonne ; Thuillez, Christian ; Lebreton, Jean-Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3855-b9f133b45c7622948d6f77188d92ccb228d457276c30520ca815d4df5ea4a0b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Transfusion, Autologous</topic><topic>Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Glycine - analogs &amp; derivatives</topic><topic>Glycine - pharmacology</topic><topic>Intensive care medicine</topic><topic>Interleukin-6 - biosynthesis</topic><topic>Macrophages, Peritoneal - drug effects</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Resuscitation - methods</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Complementary - isolation &amp; purification</topic><topic>Shock, Hemorrhagic - metabolism</topic><topic>Shock, Hemorrhagic - therapy</topic><topic>Sulfhydryl Compounds - pharmacology</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tamion, Fabienne</creatorcontrib><creatorcontrib>Richard, Vincent</creatorcontrib><creatorcontrib>Bonmarchand, Guy</creatorcontrib><creatorcontrib>Leroy, Jacky</creatorcontrib><creatorcontrib>Hiron, Martine</creatorcontrib><creatorcontrib>Daveau, Maryvonne</creatorcontrib><creatorcontrib>Thuillez, Christian</creatorcontrib><creatorcontrib>Lebreton, Jean-Pierre</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>Tamion, Fabienne</au><au>Richard, Vincent</au><au>Bonmarchand, Guy</au><au>Leroy, Jacky</au><au>Hiron, Martine</au><au>Daveau, Maryvonne</au><au>Thuillez, Christian</au><au>Lebreton, Jean-Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats</atitle><jtitle>Critical care medicine</jtitle><addtitle>Crit Care Med</addtitle><date>2000-07</date><risdate>2000</risdate><volume>28</volume><issue>7</issue><spage>2522</spage><epage>2527</epage><pages>2522-2527</pages><issn>0090-3493</issn><eissn>1530-0293</eissn><coden>CCMDC7</coden><abstract>OBJECTIVESIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. DESIGNA prospective, controlled animal study. SETTINGA university research laboratory. SUBJECTSMale Wistar rats. INTERVENTIONSHemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MEASUREMENTS AND MAIN RESULTSMPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85 ± 6; MPG 35 ± 5 mL/kg;p &lt; .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-α (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-α and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-α and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. CONCLUSIONReactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.</abstract><cop>Hagerstown, MD</cop><pub>Copyright by by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc</pub><pmid>10921588</pmid><doi>10.1097/00003246-200007000-00055</doi><tpages>6</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0090-3493
ispartof Critical care medicine, 2000-07, Vol.28 (7), p.2522-2527
issn 0090-3493
1530-0293
language eng
recordid cdi_proquest_miscellaneous_71275326
source MEDLINE; Journals@Ovid Complete
subjects Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Antioxidants - pharmacology
Biological and medical sciences
Blood Transfusion, Autologous
Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care
Enzyme-Linked Immunosorbent Assay
Free Radical Scavengers - pharmacology
Glycine - analogs & derivatives
Glycine - pharmacology
Intensive care medicine
Interleukin-6 - biosynthesis
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - metabolism
Male
Medical sciences
Rats
Rats, Wistar
Resuscitation - methods
Reverse Transcriptase Polymerase Chain Reaction
RNA, Complementary - isolation & purification
Shock, Hemorrhagic - metabolism
Shock, Hemorrhagic - therapy
Sulfhydryl Compounds - pharmacology
Tumor Necrosis Factor-alpha - biosynthesis
title Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T20%3A17%3A57IST&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=Reduced%20synthesis%20of%20inflammatory%20cytokines%20by%20a%20free%20radical%20scavenger%20after%20hemorrhagic%20shock%20in%20rats&rft.jtitle=Critical%20care%20medicine&rft.au=Tamion,%20Fabienne&rft.date=2000-07&rft.volume=28&rft.issue=7&rft.spage=2522&rft.epage=2527&rft.pages=2522-2527&rft.issn=0090-3493&rft.eissn=1530-0293&rft.coden=CCMDC7&rft_id=info:doi/10.1097/00003246-200007000-00055&rft_dat=%3Cproquest_cross%3E71275326%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=71275326&rft_id=info:pmid/10921588&rfr_iscdi=true