Effect of Nitrous Oxide Anesthesia on Plasma Homocysteine and Endothelial Function

Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. The authors studie...

Full description

Saved in:
Bibliographic Details
Published inAnesthesiology (Philadelphia) Vol. 109; no. 4; pp. 657 - 663
Main Authors MYLES, Paul S, CHAN, Matthew T. V, KAYE, David M, MCLLROY, David R, LAU, Chung-Wai, SYMONS, Joel A, SHAOHUI CHEN
Format Journal Article
LanguageEnglish
Published Hagerstown, MD Lippincott 01.10.2008
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations. The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates. Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.
AbstractList Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations. The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates. Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.
Background Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. Methods The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations. Results The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates. Conclusions Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.
Author LAU, Chung-Wai
CHAN, Matthew T. V
MYLES, Paul S
KAYE, David M
SYMONS, Joel A
SHAOHUI CHEN
MCLLROY, David R
Author_xml – sequence: 1
  givenname: Paul S
  surname: MYLES
  fullname: MYLES, Paul S
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 2
  givenname: Matthew T. V
  surname: CHAN
  fullname: CHAN, Matthew T. V
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 3
  givenname: David M
  surname: KAYE
  fullname: KAYE, David M
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 4
  givenname: David R
  surname: MCLLROY
  fullname: MCLLROY, David R
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 5
  givenname: Chung-Wai
  surname: LAU
  fullname: LAU, Chung-Wai
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 6
  givenname: Joel A
  surname: SYMONS
  fullname: SYMONS, Joel A
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
– sequence: 7
  surname: SHAOHUI CHEN
  fullname: SHAOHUI CHEN
  organization: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Australia
BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20697361$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/18813045$$D View this record in MEDLINE/PubMed
BookMark eNpdkF1LwzAUQINM3If-A5G8-NiZmzRp-jjGpsLYRPS5pOkNVtpkNB24f29lQ8Gny4VzLpczJSMfPBJyC2wOLM8eFpvtnJUMBArQoBXPq_KCTEBynQBkckQmjDGRCMb5mExj_BzWTAp9RcagNQiWygl5XTmHtqfB0W3dd-EQ6e6rrpAuPMb-A2NtaPD0pTGxNfQptMEeY4-1R2p8RVe-CgPV1Kah64O3fR38Nbl0pol4c54z8r5evS2fks3u8Xm52CRWaOgToYSUCocvFDcyV7ZE7iRYIVlqwGrkaQ6pcUJnIsNKmtSl6FgFudKaMxQzkp7u2i7E2KEr9l3dmu5YACt-EhVDouJ_okG7O2n7Q9li9SedmwzA_Rkw0ZrGdcbbOv5ynKk8EwrEN8GOcQ0
CODEN ANESAV
CitedBy_id crossref_primary_10_1177_0333102410365105
crossref_primary_10_1155_2019_4618798
crossref_primary_10_1016_j_ahj_2008_11_015
crossref_primary_10_1080_14779072_2020_1767594
crossref_primary_10_1016_j_brainres_2020_146645
crossref_primary_10_1016_S0246_0289_10_45303_7
crossref_primary_10_1097_ALN_0000000000000908
crossref_primary_10_3389_fcvm_2016_00023
crossref_primary_10_1213_ANE_0b013e3181f7e2c4
crossref_primary_10_1097_ALN_0000000000004823
crossref_primary_10_1016_S1283_0771_20_44497_4
crossref_primary_10_1213_ANE_0b013e31826e7632
crossref_primary_10_2174_0115672050288199240408035201
crossref_primary_10_1007_s40140_016_0167_4
crossref_primary_10_1016_j_transproceed_2014_10_014
crossref_primary_10_1016_S1280_4703_10_70430_8
crossref_primary_10_1097_ACO_0b013e32834f6c4c
crossref_primary_10_4103_0019_5049_193711
crossref_primary_10_1093_bja_aex328
crossref_primary_10_2478_aiht_2020_71_3437
crossref_primary_10_1007_s12630_021_02094_z
crossref_primary_10_1016_j_fct_2022_112894
crossref_primary_10_1213_ANE_0000000000001053
crossref_primary_10_1111_aas_13724
crossref_primary_10_1016_S0034_9356_10_70167_5
crossref_primary_10_1002_14651858_CD008984_pub2
crossref_primary_10_1007_s00540_011_1283_4
crossref_primary_10_1097_ACO_0b013e32833e1520
crossref_primary_10_1213_ANE_0b013e31822402f5
crossref_primary_10_1093_bja_aet416
crossref_primary_10_1111_bcp_12813
crossref_primary_10_1093_bja_aet215
crossref_primary_10_1093_bja_aes164
crossref_primary_10_1213_ANE_0b013e3182032521
crossref_primary_10_1002_acn3_50838
crossref_primary_10_1038_s41598_021_91014_8
crossref_primary_10_1016_S0140_6736_14_60893_X
crossref_primary_10_1213_ANE_0b013e31824590a5
crossref_primary_10_4103_0019_5049_153041
crossref_primary_10_1097_ALN_0000000000000122
crossref_primary_10_1038_s41598_018_34187_z
crossref_primary_10_1186_s12871_021_01388_5
crossref_primary_10_1007_s10877_017_0055_6
crossref_primary_10_1007_s00540_013_1729_y
crossref_primary_10_1016_j_pain_2011_07_015
crossref_primary_10_1517_14740330903003778
crossref_primary_10_1016_j_jtha_2022_10_002
crossref_primary_10_1016_S1280_4703_20_44230_6
crossref_primary_10_1080_14779072_2019_1598262
crossref_primary_10_1097_FPC_0b013e328328d54c
crossref_primary_10_1111_j_1365_2044_2010_06375_x
crossref_primary_10_1016_j_hlc_2017_01_019
crossref_primary_10_1093_bmb_ldx050
crossref_primary_10_1097_ALN_0000000000001603
crossref_primary_10_1097_EJA_0000000000000935
crossref_primary_10_1080_22201173_2010_10872663
crossref_primary_10_1093_bja_aew410
crossref_primary_10_21673_anadoluklin_358521
crossref_primary_10_1016_j_anrea_2020_04_005
crossref_primary_10_1080_22201173_2010_10872662
crossref_primary_10_1378_chest_12_1752
crossref_primary_10_1097_ACO_0b013e32835f8151
crossref_primary_10_1213_ANE_0000000000001749
crossref_primary_10_1016_S1283_0771_10_70256_5
ContentType Journal Article
Copyright 2008 INIST-CNRS
Copyright_xml – notice: 2008 INIST-CNRS
DBID IQODW
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
DOI 10.1097/ALN.0b013e31818629db
DatabaseName Pascal-Francis
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
DatabaseTitleList MEDLINE
CrossRef
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
EISSN 1528-1175
EndPage 663
ExternalDocumentID 10_1097_ALN_0b013e31818629db
18813045
20697361
Genre Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
-~X
.-D
.3C
.55
.GJ
.XZ
.Z2
01R
026
08R
0R~
1CY
1J1
23M
2WC
354
40H
4Q1
4Q2
4Q3
53G
5GY
5RE
5VS
6J9
71W
77Y
7O~
AAAXR
AAEJM
AAGIX
AAHPQ
AAJCS
AAMOA
AAMTA
AAPBV
AAQKA
AAQQT
AARTV
AASOK
AASXQ
AAUGY
AAWTL
AAXQO
ABASU
ABBUW
ABDIG
ABOCM
ABPTK
ABXVJ
ABZAD
ACCJW
ACDDN
ACEWG
ACGFO
ACGFS
ACILI
ACLED
ACOAL
ACRZS
ACWDW
ACWRI
ACXNZ
ADBBV
ADFPA
ADGGA
ADNKB
AE3
AE6
AEBDS
AEETU
AENEX
AFDTB
AFFNX
AFUWQ
AGINI
AHOMT
AHRYX
AHVBC
AHXIK
AIJEX
AJIOK
AJJEV
AJNWD
AJNYG
AJRGT
AKALU
AKULP
ALMA_UNASSIGNED_HOLDINGS
ALMTX
AMJPA
AMKUR
AMNEI
AOHHW
AWKKM
BAWUL
BCGUY
BOYCO
BQLVK
BS7
BYPQX
C45
CS3
DIK
DIWNM
DUNZO
E.X
EBS
EEVPB
EJD
EX3
F2K
F2L
F2M
F2N
F5P
FCALG
FL-
FW0
GNXGY
GQDEL
GX1
H0~
HZ~
IKREB
IKYAY
IN~
IPNFZ
IQODW
J5H
JF7
JF9
JG8
JK3
JK8
K-A
K-F
K8S
KD2
KMI
L-C
L7B
M18
N4W
N9A
N~7
N~B
N~M
O9-
OAG
OAH
OB3
OBH
OCUKA
ODA
ODMTH
ODZKP
OGROG
OHH
OHYEH
OJAPA
OK1
OL1
OLB
OLG
OLH
OLL
OLU
OLV
OLW
OLY
OLZ
OPUJH
ORVUJ
OUVQU
OVD
OVDNE
OVIDH
OVLEI
OVOZU
OWU
OWV
OWW
OWX
OWY
OWZ
OXXIT
P-K
P2P
R58
RIG
RLZ
S4R
S4S
T8P
TEORI
TR2
TSPGW
TWZ
V2I
W2D
W3M
WH7
WOQ
WOW
X3V
X3W
X7M
XXN
XYM
YFH
YOC
YQI
YQJ
ZA5
ZFV
ZGI
ZXP
ZY1
ZZMQN
AAAAV
AAIQE
AASCR
AAUEB
ABJNI
ABVCZ
ACXJB
ADHPY
AFEXH
AFSOK
AHQNM
AINUH
AJZMW
CGR
CUY
CVF
ECM
EIF
ERAAH
HLJTE
NPM
AAYXX
CITATION
ID FETCH-LOGICAL-c381t-363556e04562a596cbe2f51c3504a1c8e24914af38737ed5a4f4ef0d1968820e3
ISSN 0003-3022
IngestDate Fri Aug 23 01:44:55 EDT 2024
Sat Sep 28 07:46:14 EDT 2024
Sun Oct 22 16:04:51 EDT 2023
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 4
Keywords Anesthesia
Language English
License CC BY 4.0
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c381t-363556e04562a596cbe2f51c3504a1c8e24914af38737ed5a4f4ef0d1968820e3
OpenAccessLink https://pubs.asahq.org/anesthesiology/article-pdf/109/4/657/245660/0000542-200810000-00014.pdf
PMID 18813045
PageCount 7
ParticipantIDs crossref_primary_10_1097_ALN_0b013e31818629db
pubmed_primary_18813045
pascalfrancis_primary_20697361
PublicationCentury 2000
PublicationDate 2008-10-01
PublicationDateYYYYMMDD 2008-10-01
PublicationDate_xml – month: 10
  year: 2008
  text: 2008-10-01
  day: 01
PublicationDecade 2000
PublicationPlace Hagerstown, MD
PublicationPlace_xml – name: Hagerstown, MD
– name: United States
PublicationTitle Anesthesiology (Philadelphia)
PublicationTitleAlternate Anesthesiology
PublicationYear 2008
Publisher Lippincott
Publisher_xml – name: Lippincott
References 2021031819552949900_R31-14
2021031819552949900_R10-14
2021031819552949900_R25-14
International Brachial Artery Reactivity Task Force (2021031819552949900_R13-14)
American College of Cardiology (2021031819552949900_R3-14)
2021031819552949900_R23-14
2021031819552949900_R29-14
2021031819552949900_R27-14
2021031819552949900_R19-14
2021031819552949900_R20-14
2021031819552949900_R2-14
2021031819552949900_R4-14
2021031819552949900_R11-14
2021031819552949900_R15-14
2021031819552949900_R8-14
2021031819552949900_R17-14
2021031819552949900_R30-14
2021031819552949900_R1-14
ENIGMA Trial Group (2021031819552949900_R6-14)
2021031819552949900_R28-14
2021031819552949900_R22-14
2021031819552949900_R24-14
2021031819552949900_R26-14
2021031819552949900_R9-14
2021031819552949900_R21-14
2021031819552949900_R14-14
2021031819552949900_R5-14
2021031819552949900_R12-14
2021031819552949900_R16-14
2021031819552949900_R7-14
2021031819552949900_R18-14
References_xml – ident: 2021031819552949900_R24-14
– ident: 2021031819552949900_R16-14
– ident: 2021031819552949900_R4-14
– ident: 2021031819552949900_R1-14
– ident: 2021031819552949900_R9-14
– ident: 2021031819552949900_R12-14
– ident: 2021031819552949900_R22-14
– ident: 2021031819552949900_R26-14
– ident: 2021031819552949900_R21-14
– ident: 2021031819552949900_R27-14
– ident: 2021031819552949900_R11-14
– ident: 2021031819552949900_R31-14
– ident: 2021031819552949900_R3-14
  contributor:
    fullname: American College of Cardiology
– ident: 2021031819552949900_R17-14
– ident: 2021031819552949900_R8-14
– ident: 2021031819552949900_R13-14
  contributor:
    fullname: International Brachial Artery Reactivity Task Force
– ident: 2021031819552949900_R19-14
– ident: 2021031819552949900_R29-14
– ident: 2021031819552949900_R14-14
– ident: 2021031819552949900_R5-14
– ident: 2021031819552949900_R23-14
– ident: 2021031819552949900_R15-14
– ident: 2021031819552949900_R25-14
– ident: 2021031819552949900_R6-14
  contributor:
    fullname: ENIGMA Trial Group
– ident: 2021031819552949900_R2-14
– ident: 2021031819552949900_R30-14
– ident: 2021031819552949900_R10-14
– ident: 2021031819552949900_R20-14
– ident: 2021031819552949900_R18-14
– ident: 2021031819552949900_R28-14
– ident: 2021031819552949900_R7-14
SSID ssj0007538
Score 2.275853
Snippet Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to...
Background Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was...
SourceID crossref
pubmed
pascalfrancis
SourceType Aggregation Database
Index Database
StartPage 657
SubjectTerms Aged
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anesthetics, Inhalation - adverse effects
Arginine - analogs & derivatives
Arginine - blood
Biological and medical sciences
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Female
Homocysteine - blood
Humans
Male
Medical sciences
Middle Aged
Nitrous Oxide - adverse effects
Oxidative Stress
Prospective Studies
Time Factors
Title Effect of Nitrous Oxide Anesthesia on Plasma Homocysteine and Endothelial Function
URI https://www.ncbi.nlm.nih.gov/pubmed/18813045
Volume 109
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagXJAQAvFaHpUP3FaBOLbzOFYIKI_2UG2lva0cP7Qr7SZRm0qUX89MnMTZUiTgEq3sjSP5-zyeGc-MCXmbaC6Zc1mkMmEjwbWGJZWryLpYWw77U1KioXhymh6fi69LuQwhQV12SVu-0z9vzSv5H1ShDXDFLNl_QHYcFBrgN-ALT0AYnn-FcV96GGMxNu0FBrPWPzYGDwRA1q_t5UbhWUADCvJOzdf1rtZYtxn1SnSX28pg-tUWfea4vY0QjbWV-1F8mSZQRdH7gmUlmzWG2I4uhJPr7VDv_2obfKmYuODTgborxeeLEFD7TV3bMaJ-Pgkk-DI4B33P2Z5TIh_D22BP6QVpAo3M34oyStq4mFBKTORm6qtU_ybPfZ3go--nwWHLwAYrzJ74B1SaXYcxy3OGZ79hdxtjDoeuu-RekhUSDfXPyxAOBGZbPqRWFtn72z6JBWb7Qfa0mAeNuoQF5fxNKDfsk05PWTwiD3sDgx55tjwmd2z1hJx5ptDa0Z4ptGMKDUyhdUU9U-iUKfAPQydMoQNTnpLzTx8XH46j_jaNSINW1kYcVcvUdiavkkWqS5s4yWCtxkIxnVswxJlQjucZz6yRSjgBK9aAiAYrLLb8GTmo6sq-IFRlupBGChDeKbzElZEFFyItBUtM4eSMRMPsrBpfNGU1BDvAxK5uTuyMHO5N4fhSEqdFxlM2I8_9nIbheiBe_rHnFbkfmPmaHLQXV_YNKJBtedgh_wurx25L
link.rule.ids 315,786,790,27957,27958
linkProvider Geneva Foundation for Medical Education and Research
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effect+of+nitrous+oxide+anesthesia+on+plasma+homocysteine+and+endothelial+function&rft.jtitle=Anesthesiology+%28Philadelphia%29&rft.au=Myles%2C+Paul+S&rft.au=Chan%2C+Matthew+T+V&rft.au=Kaye%2C+David+M&rft.au=McIlroy%2C+David+R&rft.date=2008-10-01&rft.eissn=1528-1175&rft.volume=109&rft.issue=4&rft.spage=657&rft_id=info:doi/10.1097%2FALN.0b013e31818629db&rft_id=info%3Apmid%2F18813045&rft.externalDocID=18813045
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0003-3022&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0003-3022&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0003-3022&client=summon