Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol

Background: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as...

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Veröffentlicht in:Journal of allergy and clinical immunology 2001-12, Vol.108 (6), p.938-945
Hauptverfasser: Milgrom, Henry, Skoner, David P., Bensch, George, Kim, Kenneth T., Claus, Raymond, Baumgartner, Rudolf A.
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container_end_page 945
container_issue 6
container_start_page 938
container_title Journal of allergy and clinical immunology
container_volume 108
creator Milgrom, Henry
Skoner, David P.
Bensch, George
Kim, Kenneth T.
Claus, Raymond
Baumgartner, Rudolf A.
description Background: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. Objective: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. Methods: Asthmatic children aged 4 to 11 years (n = 338; FEV1, 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV1 (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. Results: All active treatments significantly improved the primary endpoint in comparison with placebo (P < .001). Significant differences in FEV1 were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P < .05 vs placebo; P < .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QTc interval, and glucose (P > .05). All active treatments decreased serum potassium (range, –0.3 to –0.6; P < .002 vs placebo), and RAC 2.5 mg caused the greatest change (P < .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. Conclusion: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses. (J Allergy Clin Immunol 2001;108:938-45.)
doi_str_mv 10.1067/mai.2001.120134
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Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. Objective: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. Methods: Asthmatic children aged 4 to 11 years (n = 338; FEV1, 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV1 (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. Results: All active treatments significantly improved the primary endpoint in comparison with placebo (P &lt; .001). Significant differences in FEV1 were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P &lt; .05 vs placebo; P &lt; .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QTc interval, and glucose (P &gt; .05). All active treatments decreased serum potassium (range, –0.3 to –0.6; P &lt; .002 vs placebo), and RAC 2.5 mg caused the greatest change (P &lt; .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. Conclusion: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses. (J Allergy Clin Immunol 2001;108:938-45.)</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1067/mai.2001.120134</identifier><identifier>PMID: 11742271</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>(R)-albuterol ; (S)-albuterol ; Adrenergic beta-Agonists - therapeutic use ; albuterol ; Albuterol - adverse effects ; Albuterol - pharmacokinetics ; Albuterol - therapeutic use ; asthma ; Asthma - drug therapy ; Asthma - physiopathology ; Biological and medical sciences ; bronchodilator ; Bronchodilator Agents - therapeutic use ; Child ; Child, Preschool ; Double-Blind Method ; Female ; FEV1 ; Forced Expiratory Volume - drug effects ; Histamine and antagonists. Allergy ; Humans ; Levalbuterol ; Male ; Medical sciences ; pediatric ; Pharmacology. Drug treatments ; racemic albuterol ; Stereoisomerism ; β-agonist</subject><ispartof>Journal of allergy and clinical immunology, 2001-12, Vol.108 (6), p.938-945</ispartof><rights>2001 Mosby, Inc.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-5271b49f29b1612540f2b47c2cd0cd26648b02c8ad24aa6cc369b0552e4449f43</citedby><cites>FETCH-LOGICAL-c445t-5271b49f29b1612540f2b47c2cd0cd26648b02c8ad24aa6cc369b0552e4449f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1067/mai.2001.120134$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=13410037$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11742271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Milgrom, Henry</creatorcontrib><creatorcontrib>Skoner, David P.</creatorcontrib><creatorcontrib>Bensch, George</creatorcontrib><creatorcontrib>Kim, Kenneth T.</creatorcontrib><creatorcontrib>Claus, Raymond</creatorcontrib><creatorcontrib>Baumgartner, Rudolf A.</creatorcontrib><creatorcontrib>for the Levalbuterol Pediatric Study Group</creatorcontrib><creatorcontrib>Levalbuterol Pediatric Study Group</creatorcontrib><title>Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. Objective: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. Methods: Asthmatic children aged 4 to 11 years (n = 338; FEV1, 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV1 (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. Results: All active treatments significantly improved the primary endpoint in comparison with placebo (P &lt; .001). Significant differences in FEV1 were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P &lt; .05 vs placebo; P &lt; .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QTc interval, and glucose (P &gt; .05). All active treatments decreased serum potassium (range, –0.3 to –0.6; P &lt; .002 vs placebo), and RAC 2.5 mg caused the greatest change (P &lt; .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. Conclusion: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses. (J Allergy Clin Immunol 2001;108:938-45.)</description><subject>(R)-albuterol</subject><subject>(S)-albuterol</subject><subject>Adrenergic beta-Agonists - therapeutic use</subject><subject>albuterol</subject><subject>Albuterol - adverse effects</subject><subject>Albuterol - pharmacokinetics</subject><subject>Albuterol - therapeutic use</subject><subject>asthma</subject><subject>Asthma - drug therapy</subject><subject>Asthma - physiopathology</subject><subject>Biological and medical sciences</subject><subject>bronchodilator</subject><subject>Bronchodilator Agents - therapeutic use</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>FEV1</subject><subject>Forced Expiratory Volume - drug effects</subject><subject>Histamine and antagonists. Allergy</subject><subject>Humans</subject><subject>Levalbuterol</subject><subject>Male</subject><subject>Medical sciences</subject><subject>pediatric</subject><subject>Pharmacology. Drug treatments</subject><subject>racemic albuterol</subject><subject>Stereoisomerism</subject><subject>β-agonist</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10DFv1DAUwHELUdGjMLMhL7DlajtOcmZDVaFIJzG0zNbL84vOyIkPO9fqvn3dXkSnTral33uy_ox9kmItRdtdjuDXSgi5lkrIWr9hKylMV7Ub1bxlKyGMrNpOm3P2Pue_orzrjXnHzqXstFKdXLG8jQ-Vi5l4oHsI_WGmFAP3E8edDy7RxB_8vOOQ590I3_gtDDQfOUyO0zB4BDw-4zjuIfkcF74PgNTHZ5fKdfTI_2__wM4GCJk-LucF-_Pj-u7qptr-_vnr6vu2Qq2buWrKB3ttBmV62UrVaDGoXneo0Al0qm31phcKN-CUBmgR69b0omkUaV3GdH3Bvp727lP8d6A829FnpBBgonjIVpZKphNNgZcniCnmnGiw--RHSEcrhX3qbEtn-9TZnjqXic_L6kM_knvxS9gCviwAMkIYEkzo84urtRSi7oozJ0clxL2nZDN6mpCcT4SzddG_-olHjYWZcA</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Milgrom, Henry</creator><creator>Skoner, David P.</creator><creator>Bensch, George</creator><creator>Kim, Kenneth T.</creator><creator>Claus, Raymond</creator><creator>Baumgartner, Rudolf A.</creator><general>Mosby, Inc</general><general>Elsevier</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>7T2</scope><scope>7T5</scope><scope>7U2</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20011201</creationdate><title>Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol</title><author>Milgrom, Henry ; Skoner, David P. ; Bensch, George ; Kim, Kenneth T. ; Claus, Raymond ; Baumgartner, Rudolf A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-5271b49f29b1612540f2b47c2cd0cd26648b02c8ad24aa6cc369b0552e4449f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>(R)-albuterol</topic><topic>(S)-albuterol</topic><topic>Adrenergic beta-Agonists - therapeutic use</topic><topic>albuterol</topic><topic>Albuterol - adverse effects</topic><topic>Albuterol - pharmacokinetics</topic><topic>Albuterol - therapeutic use</topic><topic>asthma</topic><topic>Asthma - drug therapy</topic><topic>Asthma - physiopathology</topic><topic>Biological and medical sciences</topic><topic>bronchodilator</topic><topic>Bronchodilator Agents - therapeutic use</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>FEV1</topic><topic>Forced Expiratory Volume - drug effects</topic><topic>Histamine and antagonists. Allergy</topic><topic>Humans</topic><topic>Levalbuterol</topic><topic>Male</topic><topic>Medical sciences</topic><topic>pediatric</topic><topic>Pharmacology. Drug treatments</topic><topic>racemic albuterol</topic><topic>Stereoisomerism</topic><topic>β-agonist</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Milgrom, Henry</creatorcontrib><creatorcontrib>Skoner, David P.</creatorcontrib><creatorcontrib>Bensch, George</creatorcontrib><creatorcontrib>Kim, Kenneth T.</creatorcontrib><creatorcontrib>Claus, Raymond</creatorcontrib><creatorcontrib>Baumgartner, Rudolf A.</creatorcontrib><creatorcontrib>for the Levalbuterol Pediatric Study Group</creatorcontrib><creatorcontrib>Levalbuterol Pediatric Study Group</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>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Milgrom, Henry</au><au>Skoner, David P.</au><au>Bensch, George</au><au>Kim, Kenneth T.</au><au>Claus, Raymond</au><au>Baumgartner, Rudolf A.</au><aucorp>for the Levalbuterol Pediatric Study Group</aucorp><aucorp>Levalbuterol Pediatric Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>108</volume><issue>6</issue><spage>938</spage><epage>945</epage><pages>938-945</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. Objective: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. Methods: Asthmatic children aged 4 to 11 years (n = 338; FEV1, 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV1 (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. Results: All active treatments significantly improved the primary endpoint in comparison with placebo (P &lt; .001). Significant differences in FEV1 were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P &lt; .05 vs placebo; P &lt; .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QTc interval, and glucose (P &gt; .05). All active treatments decreased serum potassium (range, –0.3 to –0.6; P &lt; .002 vs placebo), and RAC 2.5 mg caused the greatest change (P &lt; .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. Conclusion: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses. (J Allergy Clin Immunol 2001;108:938-45.)</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>11742271</pmid><doi>10.1067/mai.2001.120134</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects (R)-albuterol
(S)-albuterol
Adrenergic beta-Agonists - therapeutic use
albuterol
Albuterol - adverse effects
Albuterol - pharmacokinetics
Albuterol - therapeutic use
asthma
Asthma - drug therapy
Asthma - physiopathology
Biological and medical sciences
bronchodilator
Bronchodilator Agents - therapeutic use
Child
Child, Preschool
Double-Blind Method
Female
FEV1
Forced Expiratory Volume - drug effects
Histamine and antagonists. Allergy
Humans
Levalbuterol
Male
Medical sciences
pediatric
Pharmacology. Drug treatments
racemic albuterol
Stereoisomerism
β-agonist
title Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol
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