Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia
To study the in vivo effect of all- trans-retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. Th...
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description | To study the in vivo effect of all-
trans-retinoic acid (ATRA) and arsenic trioxide (As
2O
3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As
2O
3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α
2-plasminogen inhibitor activity (α
2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As
2O
3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment. |
doi_str_mv | 10.1016/S0049-3848(01)00233-X |
format | Article |
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trans-retinoic acid (ATRA) and arsenic trioxide (As
2O
3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As
2O
3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α
2-plasminogen inhibitor activity (α
2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As
2O
3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/S0049-3848(01)00233-X</identifier><identifier>PMID: 11369412</identifier><identifier>CODEN: THBRAA</identifier><language>eng</language><publisher>New York, NY: Elsevier Ltd</publisher><subject>Acute promyelocytic leukemia ; Adolescent ; Adult ; All- trans-retinoic acid ; Antineoplastic agents ; Arsenic Trioxide ; Arsenicals - pharmacology ; Biological and medical sciences ; Case-Control Studies ; Chemotherapy ; Female ; Hematologic and hematopoietic diseases ; Hemorrhage - drug therapy ; Hemorrhage - etiology ; Hemorrhage - prevention & control ; Hemostasis - drug effects ; Hemostatics - blood ; Humans ; Leukemia, Promyelocytic, Acute - complications ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - physiopathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Oxides - pharmacology ; Pharmacology. Drug treatments ; Thromboplastin - drug effects ; Thromboplastin - metabolism ; Tissue factor ; Tretinoin - pharmacology</subject><ispartof>Thrombosis research, 2001-05, Vol.102 (3), p.197-204</ispartof><rights>2001 Elsevier Science Ltd</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-591e453d54e43fb30a679c3752d4db94ee138b42aa33a9bda8fac51a736e9e943</citedby><cites>FETCH-LOGICAL-c390t-591e453d54e43fb30a679c3752d4db94ee138b42aa33a9bda8fac51a736e9e943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0049-3848(01)00233-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1031364$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11369412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Weili</creatorcontrib><creatorcontrib>Wang, Hongli</creatorcontrib><creatorcontrib>Wang, Xuefeng</creatorcontrib><creatorcontrib>Wu, Fang</creatorcontrib><creatorcontrib>Guo, Weimin</creatorcontrib><creatorcontrib>Qu, Bin</creatorcontrib><creatorcontrib>Shen, Zhixiang</creatorcontrib><creatorcontrib>Wang, Zhenyi</creatorcontrib><title>Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>To study the in vivo effect of all-
trans-retinoic acid (ATRA) and arsenic trioxide (As
2O
3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As
2O
3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α
2-plasminogen inhibitor activity (α
2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As
2O
3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.</description><subject>Acute promyelocytic leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>All- trans-retinoic acid</subject><subject>Antineoplastic agents</subject><subject>Arsenic Trioxide</subject><subject>Arsenicals - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Chemotherapy</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hemorrhage - drug therapy</subject><subject>Hemorrhage - etiology</subject><subject>Hemorrhage - prevention & control</subject><subject>Hemostasis - drug effects</subject><subject>Hemostatics - blood</subject><subject>Humans</subject><subject>Leukemia, Promyelocytic, Acute - complications</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - physiopathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oxides - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Thromboplastin - drug effects</subject><subject>Thromboplastin - metabolism</subject><subject>Tissue factor</subject><subject>Tretinoin - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi1ERZfCI4B8QAgOATt2NvEJRaW0lVYCwSL1Zjn2RDUkcetxgL3y5DjdFfTGaSTPN_-MPhPyjLM3nPH12y-MSVWIRjavGH_NWClEcfWArHhTq6KUdfmQrP4ix-Qx4jfGeM1V9Ygccy7WSvJyRX6f9T3YhDT0tB2GYhvNhMVnSH4K3tLWekfN5GgbEab8sI0-_PIOaJhougZ6AWPAZFJuvfeY5tiZyQJtEYP1JoGjP326zjlzAvophnEHQ7C7hd_A_B1Gb56Qo94MCE8P9YR8_XC2Pb0oNh_PL0_bTWGFYqmoFAdZCVdJkKLvBDPrWllRV6WTrlMSgIumk6UxQhjVOdP0xlbc1GINCpQUJ-TlPvcmhtsZMOnRo4VhMBOEGXXNmpqxZgGrPWhjQIzQ65voRxN3mjO9yNd38vViVjOu7-Trqzz3_LBg7kZw_6YOtjPw4gAYtGbos2vr8V66yOSy_90eg2zjh4eo0XrIWp2P-a-0C_4_l_wBPzuiZw</recordid><startdate>20010501</startdate><enddate>20010501</enddate><creator>Zhao, Weili</creator><creator>Wang, Hongli</creator><creator>Wang, Xuefeng</creator><creator>Wu, Fang</creator><creator>Guo, Weimin</creator><creator>Qu, Bin</creator><creator>Shen, Zhixiang</creator><creator>Wang, Zhenyi</creator><general>Elsevier Ltd</general><general>Elsevier Science</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>20010501</creationdate><title>Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia</title><author>Zhao, Weili ; Wang, Hongli ; Wang, Xuefeng ; Wu, Fang ; Guo, Weimin ; Qu, Bin ; Shen, Zhixiang ; Wang, Zhenyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-591e453d54e43fb30a679c3752d4db94ee138b42aa33a9bda8fac51a736e9e943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acute promyelocytic leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>All- trans-retinoic acid</topic><topic>Antineoplastic agents</topic><topic>Arsenic Trioxide</topic><topic>Arsenicals - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Chemotherapy</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hemorrhage - drug therapy</topic><topic>Hemorrhage - etiology</topic><topic>Hemorrhage - prevention & control</topic><topic>Hemostasis - drug effects</topic><topic>Hemostatics - blood</topic><topic>Humans</topic><topic>Leukemia, Promyelocytic, Acute - complications</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - physiopathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oxides - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Thromboplastin - drug effects</topic><topic>Thromboplastin - metabolism</topic><topic>Tissue factor</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Weili</creatorcontrib><creatorcontrib>Wang, Hongli</creatorcontrib><creatorcontrib>Wang, Xuefeng</creatorcontrib><creatorcontrib>Wu, Fang</creatorcontrib><creatorcontrib>Guo, Weimin</creatorcontrib><creatorcontrib>Qu, Bin</creatorcontrib><creatorcontrib>Shen, Zhixiang</creatorcontrib><creatorcontrib>Wang, Zhenyi</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>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Weili</au><au>Wang, Hongli</au><au>Wang, Xuefeng</au><au>Wu, Fang</au><au>Guo, Weimin</au><au>Qu, Bin</au><au>Shen, Zhixiang</au><au>Wang, Zhenyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>102</volume><issue>3</issue><spage>197</spage><epage>204</epage><pages>197-204</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><abstract>To study the in vivo effect of all-
trans-retinoic acid (ATRA) and arsenic trioxide (As
2O
3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As
2O
3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α
2-plasminogen inhibitor activity (α
2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As
2O
3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>11369412</pmid><doi>10.1016/S0049-3848(01)00233-X</doi><tpages>8</tpages></addata></record> |
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subjects | Acute promyelocytic leukemia Adolescent Adult All- trans-retinoic acid Antineoplastic agents Arsenic Trioxide Arsenicals - pharmacology Biological and medical sciences Case-Control Studies Chemotherapy Female Hematologic and hematopoietic diseases Hemorrhage - drug therapy Hemorrhage - etiology Hemorrhage - prevention & control Hemostasis - drug effects Hemostatics - blood Humans Leukemia, Promyelocytic, Acute - complications Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - physiopathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Oxides - pharmacology Pharmacology. Drug treatments Thromboplastin - drug effects Thromboplastin - metabolism Tissue factor Tretinoin - pharmacology |
title | Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia |
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