Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen
Summary We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non‐myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All...
Gespeichert in:
| Veröffentlicht in: | British journal of haematology 2006-06, Vol.133 (6), p.649-654 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 654 |
|---|---|
| container_issue | 6 |
| container_start_page | 649 |
| container_title | British journal of haematology |
| container_volume | 133 |
| creator | Resnick, Igor B. Aker, Memet Shapira, Michael Y. Tsirigotis, Panagiotis D. Bitan, Menachem Abdul‐Hai, Ali Samuel, Simcha Ackerstein, Aliza Gesundheit, Benjamin Zilberman, Irina Miron, Svetlana Yoffe, Luba Lvovich, Alex Slavin, Shimon Or, Reuven |
| description | Summary
We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non‐myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild‐to‐moderate severity was the only observed regimen‐related toxicity. The cumulative incidence of acute graft‐versus‐host disease (GvHD) grade II–IV and III–IV was 8·3% and 0%, respectively. With a median follow‐up period of 45 months, the 5‐year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols. |
| doi_str_mv | 10.1111/j.1365-2141.2006.06084.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_198497782</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1062336811</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4744-bbad8994269cef2c0594fc9dea102a10f8c77b40329aa51b8060ab5663e453193</originalsourceid><addsrcrecordid>eNqNkMFu1DAQhi1ERZeFV0AWEscEO3Hi-MChVECpKvUCZ2viTFZeOU5qJ233xiPwjDwJDrui11qybHm-fzz6CKGc5Tytj_ucl3WVFVzwvGCszlnNGpE_viCb_4WXZMMYkxlnojknr2PcM8ZLVvFX5JzXkgkhig05XDg37tCjNTTOOFCDztE5gI-TAz_DbEdP-zHQiPcYkIK5W2zAjkKqxznFwAMOFugSrd9RoL1bOgjQWo9_fv1uISZ4Cjilt9neIw24swP6N-SsBxfx7enckp9fv_y4vMpubr99v7y4yYyQQmRtC12jlChqZbAvDKuU6I3qEDgr0u4bI2UrWFkogIq3TVIBbVXXJYqq5KrckvfHvlMY7xaMs96PS_DpS81VI5SUTZGg5giZMMYYsNdTsAOEg-ZMr8r1Xq9m9WpWr8r1P-X6MUXfnfov7YDdU_DkOAEfTgBEA65Pbo2NT5yUUvE075Z8OnIP1uHh2QPoz9dX6638C5o6nus</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>198497782</pqid></control><display><type>article</type><title>Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Resnick, Igor B. ; Aker, Memet ; Shapira, Michael Y. ; Tsirigotis, Panagiotis D. ; Bitan, Menachem ; Abdul‐Hai, Ali ; Samuel, Simcha ; Ackerstein, Aliza ; Gesundheit, Benjamin ; Zilberman, Irina ; Miron, Svetlana ; Yoffe, Luba ; Lvovich, Alex ; Slavin, Shimon ; Or, Reuven</creator><creatorcontrib>Resnick, Igor B. ; Aker, Memet ; Shapira, Michael Y. ; Tsirigotis, Panagiotis D. ; Bitan, Menachem ; Abdul‐Hai, Ali ; Samuel, Simcha ; Ackerstein, Aliza ; Gesundheit, Benjamin ; Zilberman, Irina ; Miron, Svetlana ; Yoffe, Luba ; Lvovich, Alex ; Slavin, Shimon ; Or, Reuven</creatorcontrib><description>Summary
We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non‐myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild‐to‐moderate severity was the only observed regimen‐related toxicity. The cumulative incidence of acute graft‐versus‐host disease (GvHD) grade II–IV and III–IV was 8·3% and 0%, respectively. With a median follow‐up period of 45 months, the 5‐year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2006.06084.x</identifier><identifier>PMID: 16704442</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Anemia, Aplastic - therapy ; Antilymphocyte Serum - therapeutic use ; Biological and medical sciences ; Child ; Cyclophosphamide - therapeutic use ; Female ; fludarabine ; Graft vs Host Disease - prevention & control ; Hematologic and hematopoietic diseases ; Hematology ; Hematopoietic Stem Cell Transplantation - methods ; Humans ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - therapeutic use ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Mucositis - chemically induced ; non‐myeloablative HSCT ; Opportunistic Infections - etiology ; Pilot Projects ; Quality of Life ; severe aplastic anaemia ; Transplantation Chimera ; Transplantation Conditioning - methods ; Treatment Outcome ; Vidarabine - analogs & derivatives ; Vidarabine - therapeutic use</subject><ispartof>British journal of haematology, 2006-06, Vol.133 (6), p.649-654</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright Blackwell Publishing Jun 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4744-bbad8994269cef2c0594fc9dea102a10f8c77b40329aa51b8060ab5663e453193</citedby><cites>FETCH-LOGICAL-c4744-bbad8994269cef2c0594fc9dea102a10f8c77b40329aa51b8060ab5663e453193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2141.2006.06084.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2141.2006.06084.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17779166$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16704442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Resnick, Igor B.</creatorcontrib><creatorcontrib>Aker, Memet</creatorcontrib><creatorcontrib>Shapira, Michael Y.</creatorcontrib><creatorcontrib>Tsirigotis, Panagiotis D.</creatorcontrib><creatorcontrib>Bitan, Menachem</creatorcontrib><creatorcontrib>Abdul‐Hai, Ali</creatorcontrib><creatorcontrib>Samuel, Simcha</creatorcontrib><creatorcontrib>Ackerstein, Aliza</creatorcontrib><creatorcontrib>Gesundheit, Benjamin</creatorcontrib><creatorcontrib>Zilberman, Irina</creatorcontrib><creatorcontrib>Miron, Svetlana</creatorcontrib><creatorcontrib>Yoffe, Luba</creatorcontrib><creatorcontrib>Lvovich, Alex</creatorcontrib><creatorcontrib>Slavin, Shimon</creatorcontrib><creatorcontrib>Or, Reuven</creatorcontrib><title>Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non‐myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild‐to‐moderate severity was the only observed regimen‐related toxicity. The cumulative incidence of acute graft‐versus‐host disease (GvHD) grade II–IV and III–IV was 8·3% and 0%, respectively. With a median follow‐up period of 45 months, the 5‐year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Anemia, Aplastic - therapy</subject><subject>Antilymphocyte Serum - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Female</subject><subject>fludarabine</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Humans</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mucositis - chemically induced</subject><subject>non‐myeloablative HSCT</subject><subject>Opportunistic Infections - etiology</subject><subject>Pilot Projects</subject><subject>Quality of Life</subject><subject>severe aplastic anaemia</subject><subject>Transplantation Chimera</subject><subject>Transplantation Conditioning - methods</subject><subject>Treatment Outcome</subject><subject>Vidarabine - analogs & derivatives</subject><subject>Vidarabine - therapeutic use</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMFu1DAQhi1ERZeFV0AWEscEO3Hi-MChVECpKvUCZ2viTFZeOU5qJ233xiPwjDwJDrui11qybHm-fzz6CKGc5Tytj_ucl3WVFVzwvGCszlnNGpE_viCb_4WXZMMYkxlnojknr2PcM8ZLVvFX5JzXkgkhig05XDg37tCjNTTOOFCDztE5gI-TAz_DbEdP-zHQiPcYkIK5W2zAjkKqxznFwAMOFugSrd9RoL1bOgjQWo9_fv1uISZ4Cjilt9neIw24swP6N-SsBxfx7enckp9fv_y4vMpubr99v7y4yYyQQmRtC12jlChqZbAvDKuU6I3qEDgr0u4bI2UrWFkogIq3TVIBbVXXJYqq5KrckvfHvlMY7xaMs96PS_DpS81VI5SUTZGg5giZMMYYsNdTsAOEg-ZMr8r1Xq9m9WpWr8r1P-X6MUXfnfov7YDdU_DkOAEfTgBEA65Pbo2NT5yUUvE075Z8OnIP1uHh2QPoz9dX6638C5o6nus</recordid><startdate>200606</startdate><enddate>200606</enddate><creator>Resnick, Igor B.</creator><creator>Aker, Memet</creator><creator>Shapira, Michael Y.</creator><creator>Tsirigotis, Panagiotis D.</creator><creator>Bitan, Menachem</creator><creator>Abdul‐Hai, Ali</creator><creator>Samuel, Simcha</creator><creator>Ackerstein, Aliza</creator><creator>Gesundheit, Benjamin</creator><creator>Zilberman, Irina</creator><creator>Miron, Svetlana</creator><creator>Yoffe, Luba</creator><creator>Lvovich, Alex</creator><creator>Slavin, Shimon</creator><creator>Or, Reuven</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</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>7T5</scope><scope>H94</scope></search><sort><creationdate>200606</creationdate><title>Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen</title><author>Resnick, Igor B. ; Aker, Memet ; Shapira, Michael Y. ; Tsirigotis, Panagiotis D. ; Bitan, Menachem ; Abdul‐Hai, Ali ; Samuel, Simcha ; Ackerstein, Aliza ; Gesundheit, Benjamin ; Zilberman, Irina ; Miron, Svetlana ; Yoffe, Luba ; Lvovich, Alex ; Slavin, Shimon ; Or, Reuven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4744-bbad8994269cef2c0594fc9dea102a10f8c77b40329aa51b8060ab5663e453193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Anemia, Aplastic - therapy</topic><topic>Antilymphocyte Serum - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Female</topic><topic>fludarabine</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Humans</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mucositis - chemically induced</topic><topic>non‐myeloablative HSCT</topic><topic>Opportunistic Infections - etiology</topic><topic>Pilot Projects</topic><topic>Quality of Life</topic><topic>severe aplastic anaemia</topic><topic>Transplantation Chimera</topic><topic>Transplantation Conditioning - methods</topic><topic>Treatment Outcome</topic><topic>Vidarabine - analogs & derivatives</topic><topic>Vidarabine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Resnick, Igor B.</creatorcontrib><creatorcontrib>Aker, Memet</creatorcontrib><creatorcontrib>Shapira, Michael Y.</creatorcontrib><creatorcontrib>Tsirigotis, Panagiotis D.</creatorcontrib><creatorcontrib>Bitan, Menachem</creatorcontrib><creatorcontrib>Abdul‐Hai, Ali</creatorcontrib><creatorcontrib>Samuel, Simcha</creatorcontrib><creatorcontrib>Ackerstein, Aliza</creatorcontrib><creatorcontrib>Gesundheit, Benjamin</creatorcontrib><creatorcontrib>Zilberman, Irina</creatorcontrib><creatorcontrib>Miron, Svetlana</creatorcontrib><creatorcontrib>Yoffe, Luba</creatorcontrib><creatorcontrib>Lvovich, Alex</creatorcontrib><creatorcontrib>Slavin, Shimon</creatorcontrib><creatorcontrib>Or, Reuven</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Resnick, Igor B.</au><au>Aker, Memet</au><au>Shapira, Michael Y.</au><au>Tsirigotis, Panagiotis D.</au><au>Bitan, Menachem</au><au>Abdul‐Hai, Ali</au><au>Samuel, Simcha</au><au>Ackerstein, Aliza</au><au>Gesundheit, Benjamin</au><au>Zilberman, Irina</au><au>Miron, Svetlana</au><au>Yoffe, Luba</au><au>Lvovich, Alex</au><au>Slavin, Shimon</au><au>Or, Reuven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2006-06</date><risdate>2006</risdate><volume>133</volume><issue>6</issue><spage>649</spage><epage>654</epage><pages>649-654</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non‐myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild‐to‐moderate severity was the only observed regimen‐related toxicity. The cumulative incidence of acute graft‐versus‐host disease (GvHD) grade II–IV and III–IV was 8·3% and 0%, respectively. With a median follow‐up period of 45 months, the 5‐year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>16704442</pmid><doi>10.1111/j.1365-2141.2006.06084.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1048 |
| ispartof | British journal of haematology, 2006-06, Vol.133 (6), p.649-654 |
| issn | 0007-1048 1365-2141 |
| language | eng |
| recordid | cdi_proquest_journals_198497782 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adolescent Adult Anemia, Aplastic - therapy Antilymphocyte Serum - therapeutic use Biological and medical sciences Child Cyclophosphamide - therapeutic use Female fludarabine Graft vs Host Disease - prevention & control Hematologic and hematopoietic diseases Hematology Hematopoietic Stem Cell Transplantation - methods Humans Immunosuppressive Agents - adverse effects Immunosuppressive Agents - therapeutic use Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Mucositis - chemically induced non‐myeloablative HSCT Opportunistic Infections - etiology Pilot Projects Quality of Life severe aplastic anaemia Transplantation Chimera Transplantation Conditioning - methods Treatment Outcome Vidarabine - analogs & derivatives Vidarabine - therapeutic use |
| title | Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T18%3A26%3A24IST&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=Allogeneic%20stem%20cell%20transplantation%20for%20severe%20acquired%20aplastic%20anaemia%20using%20a%20fludarabine%E2%80%90based%20preparative%20regimen&rft.jtitle=British%20journal%20of%20haematology&rft.au=Resnick,%20Igor%20B.&rft.date=2006-06&rft.volume=133&rft.issue=6&rft.spage=649&rft.epage=654&rft.pages=649-654&rft.issn=0007-1048&rft.eissn=1365-2141&rft.coden=BJHEAL&rft_id=info:doi/10.1111/j.1365-2141.2006.06084.x&rft_dat=%3Cproquest_cross%3E1062336811%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=198497782&rft_id=info:pmid/16704442&rfr_iscdi=true |