Loading…
Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic
Background: Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with β-blocker therapy in the obese modern population is unknown. Objective: To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases...
Saved in:
| Published in: | International Journal of Obesity 2011-11, Vol.35 (11), p.1395-1403 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83 |
| container_end_page | 1403 |
| container_issue | 11 |
| container_start_page | 1395 |
| container_title | International Journal of Obesity |
| container_volume | 35 |
| creator | Lee, P Kengne, A.P Greenfield, J.R Day, R.O Chalmers, J Ho, K.K.Y |
| description | Background: Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with β-blocker therapy in the obese modern population is unknown. Objective: To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases body weight. Methods: We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n=11) with uncomplicated hypertension treated with a β-blocker and anthropometrically matched controls (n=19) and (ii) three cross-sectional studies comparing body weight, body mass index (BMI) and waist circumference between β-blocker treated and untreated patients from ambulatory patients attending (a) diabetes outpatient clinic (n=214), (b) hypertension outpatient (n=84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n=11140). Results: Among weight-matched β-blocker users, diet-induced thermogenesis, fat oxidation rate and weekly habitual activity were lower by 50% (P |
| doi_str_mv | 10.1038/ijo.2010.284 |
| format | article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_904225329</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A273528802</galeid><sourcerecordid>A273528802</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83</originalsourceid><addsrcrecordid>eNp90luP1CAUAGBiNO64-uazNjFeHuxIKRTq22bjLdmND7rPhFLoMDIwQhszf8sf4m_y1I6XTdT0gfTwcXp6Dgjdr_C6wrV44bZxTTC8EUFvoFVFeVMy2vKbaIVrzEvMGnaC7uS8xRgzhsltdEKqGlMq-ApdXppRddE7XWTzeTJemSLa4tvXsvNRfzKpGDcmqf3hZfHFuGHjwlC4UMQwx4vYmezGQ2H2rjc7p--iW1b5bO4d11N09frVx_O35cX7N-_Ozy5KzVg1lppgoRraEdY3XdV1tNNC9RWmhPSmbzBEKWWCW9ow2_QKK8YFFhYrbttei_oUPV3y7lOEovMody5r470KJk5ZtnMqVpMW5LP_SmghFRVrBQb6aKGD8ka6YOOYlJ65PCO8ZkQITECt_6Lg-dGAGIx1EL924MkfBzZG-XGTo59GF0O-Dp8vUKeYczJW7pPbqXSAIuc6hYRRy3nUEkYN_MHxz6ZuZ_pf-OdsATw-ApW18japoF3-7SivocsMXLm4DFthMElu45QCzO9fH364eKuiVEOCnFcfYJfB_eJ1g9v6Ozvbxoo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1034815980</pqid></control><display><type>article</type><title>Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic</title><source>Nature</source><creator>Lee, P ; Kengne, A.P ; Greenfield, J.R ; Day, R.O ; Chalmers, J ; Ho, K.K.Y</creator><creatorcontrib>Lee, P ; Kengne, A.P ; Greenfield, J.R ; Day, R.O ; Chalmers, J ; Ho, K.K.Y</creatorcontrib><description>Background: Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with β-blocker therapy in the obese modern population is unknown. Objective: To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases body weight. Methods: We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n=11) with uncomplicated hypertension treated with a β-blocker and anthropometrically matched controls (n=19) and (ii) three cross-sectional studies comparing body weight, body mass index (BMI) and waist circumference between β-blocker treated and untreated patients from ambulatory patients attending (a) diabetes outpatient clinic (n=214), (b) hypertension outpatient (n=84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n=11140). Results: Among weight-matched β-blocker users, diet-induced thermogenesis, fat oxidation rate and weekly habitual activity were lower by 50% (P<0.01), 32% (P=0.04) and 30% (P<0.01), respectively, compared with controls. In β-blocker treated patients, the adjusted mean body weight was 9.2±1.2 kg (P=0.0002) higher among those attending the diabetes clinic, 17.2±3.2 kg (P=0.004) higher among those attending the hypertension clinic and 5.2±0.7 kg (P=0.0003) higher at baseline among participants in the ADVANCE trial compared with patients not treated with β-blockers. BMI displayed a similar difference. Conclusions: EE is reduced and body weight increased in chronic β-blocker users. We hypothesise that chronic β-blockade causes obesity by blunting EE.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/ijo.2010.284</identifier><identifier>PMID: 21304487</identifier><identifier>CODEN: IJOBDP</identifier><language>eng</language><publisher>London: Nature Publishing Group</publisher><subject>631/443/319/333/1465 ; 692/699/2743/393 ; 692/700/565/2194 ; Absorptiometry, Photon ; Adiposity - drug effects ; Adrenergic beta blockers ; Adrenergic beta-Antagonists - administration & dosage ; Adrenergic beta-Antagonists - adverse effects ; Aged ; Antihypertensive Agents - administration & dosage ; Antihypertensive Agents - adverse effects ; Australia - epidemiology ; beta-adrenergic antagonists ; Biological and medical sciences ; Body Mass Index ; Body Weight - drug effects ; Care and treatment ; Case-Control Studies ; complications (disease) ; cross-sectional studies ; Diagnosis ; Energy Metabolism - drug effects ; Epidemiology ; Female ; General aspects ; Health aspects ; Health Promotion and Disease Prevention ; Humans ; hypertension ; Hypertension - drug therapy ; Hypertension - metabolism ; Internal Medicine ; Lipid Peroxidation - drug effects ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Miscellaneous ; noninsulin-dependent diabetes mellitus ; Obesity ; Obesity - chemically induced ; Obesity - epidemiology ; Obesity - metabolism ; original-article ; oxidation ; patients ; Prospective Studies ; Public Health ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; Surveys and Questionnaires ; therapeutics ; thermic effect of food ; Thermogenesis - drug effects ; volunteers ; Waist Circumference ; weight gain</subject><ispartof>International Journal of Obesity, 2011-11, Vol.35 (11), p.1395-1403</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83</citedby><cites>FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24734455$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21304487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, P</creatorcontrib><creatorcontrib>Kengne, A.P</creatorcontrib><creatorcontrib>Greenfield, J.R</creatorcontrib><creatorcontrib>Day, R.O</creatorcontrib><creatorcontrib>Chalmers, J</creatorcontrib><creatorcontrib>Ho, K.K.Y</creatorcontrib><title>Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description>Background: Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with β-blocker therapy in the obese modern population is unknown. Objective: To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases body weight. Methods: We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n=11) with uncomplicated hypertension treated with a β-blocker and anthropometrically matched controls (n=19) and (ii) three cross-sectional studies comparing body weight, body mass index (BMI) and waist circumference between β-blocker treated and untreated patients from ambulatory patients attending (a) diabetes outpatient clinic (n=214), (b) hypertension outpatient (n=84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n=11140). Results: Among weight-matched β-blocker users, diet-induced thermogenesis, fat oxidation rate and weekly habitual activity were lower by 50% (P<0.01), 32% (P=0.04) and 30% (P<0.01), respectively, compared with controls. In β-blocker treated patients, the adjusted mean body weight was 9.2±1.2 kg (P=0.0002) higher among those attending the diabetes clinic, 17.2±3.2 kg (P=0.004) higher among those attending the hypertension clinic and 5.2±0.7 kg (P=0.0003) higher at baseline among participants in the ADVANCE trial compared with patients not treated with β-blockers. BMI displayed a similar difference. Conclusions: EE is reduced and body weight increased in chronic β-blocker users. We hypothesise that chronic β-blockade causes obesity by blunting EE.</description><subject>631/443/319/333/1465</subject><subject>692/699/2743/393</subject><subject>692/700/565/2194</subject><subject>Absorptiometry, Photon</subject><subject>Adiposity - drug effects</subject><subject>Adrenergic beta blockers</subject><subject>Adrenergic beta-Antagonists - administration & dosage</subject><subject>Adrenergic beta-Antagonists - adverse effects</subject><subject>Aged</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Antihypertensive Agents - adverse effects</subject><subject>Australia - epidemiology</subject><subject>beta-adrenergic antagonists</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Body Weight - drug effects</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>complications (disease)</subject><subject>cross-sectional studies</subject><subject>Diagnosis</subject><subject>Energy Metabolism - drug effects</subject><subject>Epidemiology</subject><subject>Female</subject><subject>General aspects</subject><subject>Health aspects</subject><subject>Health Promotion and Disease Prevention</subject><subject>Humans</subject><subject>hypertension</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - metabolism</subject><subject>Internal Medicine</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Miscellaneous</subject><subject>noninsulin-dependent diabetes mellitus</subject><subject>Obesity</subject><subject>Obesity - chemically induced</subject><subject>Obesity - epidemiology</subject><subject>Obesity - metabolism</subject><subject>original-article</subject><subject>oxidation</subject><subject>patients</subject><subject>Prospective Studies</subject><subject>Public Health</subject><subject>Public health. Hygiene</subject><subject>Public health. Hygiene-occupational medicine</subject><subject>Surveys and Questionnaires</subject><subject>therapeutics</subject><subject>thermic effect of food</subject><subject>Thermogenesis - drug effects</subject><subject>volunteers</subject><subject>Waist Circumference</subject><subject>weight gain</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp90luP1CAUAGBiNO64-uazNjFeHuxIKRTq22bjLdmND7rPhFLoMDIwQhszf8sf4m_y1I6XTdT0gfTwcXp6Dgjdr_C6wrV44bZxTTC8EUFvoFVFeVMy2vKbaIVrzEvMGnaC7uS8xRgzhsltdEKqGlMq-ApdXppRddE7XWTzeTJemSLa4tvXsvNRfzKpGDcmqf3hZfHFuGHjwlC4UMQwx4vYmezGQ2H2rjc7p--iW1b5bO4d11N09frVx_O35cX7N-_Ozy5KzVg1lppgoRraEdY3XdV1tNNC9RWmhPSmbzBEKWWCW9ow2_QKK8YFFhYrbttei_oUPV3y7lOEovMody5r470KJk5ZtnMqVpMW5LP_SmghFRVrBQb6aKGD8ka6YOOYlJ65PCO8ZkQITECt_6Lg-dGAGIx1EL924MkfBzZG-XGTo59GF0O-Dp8vUKeYczJW7pPbqXSAIuc6hYRRy3nUEkYN_MHxz6ZuZ_pf-OdsATw-ApW18japoF3-7SivocsMXLm4DFthMElu45QCzO9fH364eKuiVEOCnFcfYJfB_eJ1g9v6Ozvbxoo</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Lee, P</creator><creator>Kengne, A.P</creator><creator>Greenfield, J.R</creator><creator>Day, R.O</creator><creator>Chalmers, J</creator><creator>Ho, K.K.Y</creator><general>Nature Publishing Group</general><general>Nature Publishing Group UK</general><scope>FBQ</scope><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>7TS</scope><scope>7X8</scope></search><sort><creationdate>20111101</creationdate><title>Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic</title><author>Lee, P ; Kengne, A.P ; Greenfield, J.R ; Day, R.O ; Chalmers, J ; Ho, K.K.Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/443/319/333/1465</topic><topic>692/699/2743/393</topic><topic>692/700/565/2194</topic><topic>Absorptiometry, Photon</topic><topic>Adiposity - drug effects</topic><topic>Adrenergic beta blockers</topic><topic>Adrenergic beta-Antagonists - administration & dosage</topic><topic>Adrenergic beta-Antagonists - adverse effects</topic><topic>Aged</topic><topic>Antihypertensive Agents - administration & dosage</topic><topic>Antihypertensive Agents - adverse effects</topic><topic>Australia - epidemiology</topic><topic>beta-adrenergic antagonists</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Body Weight - drug effects</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>complications (disease)</topic><topic>cross-sectional studies</topic><topic>Diagnosis</topic><topic>Energy Metabolism - drug effects</topic><topic>Epidemiology</topic><topic>Female</topic><topic>General aspects</topic><topic>Health aspects</topic><topic>Health Promotion and Disease Prevention</topic><topic>Humans</topic><topic>hypertension</topic><topic>Hypertension - drug therapy</topic><topic>Hypertension - metabolism</topic><topic>Internal Medicine</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Miscellaneous</topic><topic>noninsulin-dependent diabetes mellitus</topic><topic>Obesity</topic><topic>Obesity - chemically induced</topic><topic>Obesity - epidemiology</topic><topic>Obesity - metabolism</topic><topic>original-article</topic><topic>oxidation</topic><topic>patients</topic><topic>Prospective Studies</topic><topic>Public Health</topic><topic>Public health. Hygiene</topic><topic>Public health. Hygiene-occupational medicine</topic><topic>Surveys and Questionnaires</topic><topic>therapeutics</topic><topic>thermic effect of food</topic><topic>Thermogenesis - drug effects</topic><topic>volunteers</topic><topic>Waist Circumference</topic><topic>weight gain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, P</creatorcontrib><creatorcontrib>Kengne, A.P</creatorcontrib><creatorcontrib>Greenfield, J.R</creatorcontrib><creatorcontrib>Day, R.O</creatorcontrib><creatorcontrib>Chalmers, J</creatorcontrib><creatorcontrib>Ho, K.K.Y</creatorcontrib><collection>AGRIS</collection><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>Physical Education Index</collection><collection>MEDLINE - Academic</collection><jtitle>International Journal of Obesity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, P</au><au>Kengne, A.P</au><au>Greenfield, J.R</au><au>Day, R.O</au><au>Chalmers, J</au><au>Ho, K.K.Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic</atitle><jtitle>International Journal of Obesity</jtitle><stitle>Int J Obes</stitle><addtitle>Int J Obes (Lond)</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>35</volume><issue>11</issue><spage>1395</spage><epage>1403</epage><pages>1395-1403</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><coden>IJOBDP</coden><abstract>Background: Sympathetic activation is an important metabolic adaptation limiting weight gain. Propensity of weight gain associated with β-blocker therapy in the obese modern population is unknown. Objective: To determine whether chronic β-blocker therapy reduces energy expenditure (EE) and increases body weight. Methods: We undertook (i) a mechanistic study comparing EE, diet-induced thermogenesis and habitual activity between healthy volunteers (n=11) with uncomplicated hypertension treated with a β-blocker and anthropometrically matched controls (n=19) and (ii) three cross-sectional studies comparing body weight, body mass index (BMI) and waist circumference between β-blocker treated and untreated patients from ambulatory patients attending (a) diabetes outpatient clinic (n=214), (b) hypertension outpatient (n=84) and (c) participants in a multi-centre type 2 diabetes trial (ADVANCE) (n=11140). Results: Among weight-matched β-blocker users, diet-induced thermogenesis, fat oxidation rate and weekly habitual activity were lower by 50% (P<0.01), 32% (P=0.04) and 30% (P<0.01), respectively, compared with controls. In β-blocker treated patients, the adjusted mean body weight was 9.2±1.2 kg (P=0.0002) higher among those attending the diabetes clinic, 17.2±3.2 kg (P=0.004) higher among those attending the hypertension clinic and 5.2±0.7 kg (P=0.0003) higher at baseline among participants in the ADVANCE trial compared with patients not treated with β-blockers. BMI displayed a similar difference. Conclusions: EE is reduced and body weight increased in chronic β-blocker users. We hypothesise that chronic β-blockade causes obesity by blunting EE.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><pmid>21304487</pmid><doi>10.1038/ijo.2010.284</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0307-0565 |
| ispartof | International Journal of Obesity, 2011-11, Vol.35 (11), p.1395-1403 |
| issn | 0307-0565 1476-5497 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_904225329 |
| source | Nature |
| subjects | 631/443/319/333/1465 692/699/2743/393 692/700/565/2194 Absorptiometry, Photon Adiposity - drug effects Adrenergic beta blockers Adrenergic beta-Antagonists - administration & dosage Adrenergic beta-Antagonists - adverse effects Aged Antihypertensive Agents - administration & dosage Antihypertensive Agents - adverse effects Australia - epidemiology beta-adrenergic antagonists Biological and medical sciences Body Mass Index Body Weight - drug effects Care and treatment Case-Control Studies complications (disease) cross-sectional studies Diagnosis Energy Metabolism - drug effects Epidemiology Female General aspects Health aspects Health Promotion and Disease Prevention Humans hypertension Hypertension - drug therapy Hypertension - metabolism Internal Medicine Lipid Peroxidation - drug effects Male Medical sciences Medicine Medicine & Public Health Metabolic Diseases Middle Aged Miscellaneous noninsulin-dependent diabetes mellitus Obesity Obesity - chemically induced Obesity - epidemiology Obesity - metabolism original-article oxidation patients Prospective Studies Public Health Public health. Hygiene Public health. Hygiene-occupational medicine Surveys and Questionnaires therapeutics thermic effect of food Thermogenesis - drug effects volunteers Waist Circumference weight gain |
| title | Metabolic sequelae of β-blocker therapy: weighing in on the obesity epidemic |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T20%3A36%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Metabolic%20sequelae%20of%20%CE%B2-blocker%20therapy:%20weighing%20in%20on%20the%20obesity%20epidemic&rft.jtitle=International%20Journal%20of%20Obesity&rft.au=Lee,%20P&rft.date=2011-11-01&rft.volume=35&rft.issue=11&rft.spage=1395&rft.epage=1403&rft.pages=1395-1403&rft.issn=0307-0565&rft.eissn=1476-5497&rft.coden=IJOBDP&rft_id=info:doi/10.1038/ijo.2010.284&rft_dat=%3Cgale_proqu%3EA273528802%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c551t-c208a64b25d6b1bb4bc8ad10422ded60d6b44587f465f6da0a57808f0a7f9dc83%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1034815980&rft_id=info:pmid/21304487&rft_galeid=A273528802&rfr_iscdi=true |