Role of cholecystokinin in pancreatic adaptation to massive enterectomy
Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transecti...
Gespeichert in:
| Veröffentlicht in: | Gut 1992-07, Vol.33 (7), p.959-964 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 964 |
|---|---|
| container_issue | 7 |
| container_start_page | 959 |
| container_title | Gut |
| container_volume | 33 |
| creator | Watanapa, P Egan, M Deprez, P H Calam, J Sarraf, C E Alison, M R Williamson, R C |
| description | Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation. |
| doi_str_mv | 10.1136/gut.33.7.959 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1379413</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3970011201</sourcerecordid><originalsourceid>FETCH-LOGICAL-b572t-fbbb5c510a0d51a7fadbbf9749504a23f6658844785bceb45759764844d833863</originalsourceid><addsrcrecordid>eNp9kc9rFDEYhoModa3evAoDil46a7L5fSnoYmu1KCur15BkMm22M5M1yRT3vzdllq16EAIJeR8-no8XgOcIzhHC7O3VmOcYz_lcUvkAzBBhosYLIR6CGYSI15QT-Rg8SWkDIRRCoiNwhBghGIsZOP8WOleFtrLX5WF3KYcbP_ihKmerBxudzt5WutHbXF5hqHKoep2Sv3WVG7KLzubQ756CR63uknu2v4_B97MP6-XH-vLr-cXy3WVtKF_kujXGUEsR1LChSPNWN8a0shhSSPQCt4xRIQjhghrrDKGcSs5I-WlE8WX4GJxOc7ej6V1ji0LUndpG3-u4U0F79Xcy-Gt1FW4VwlwShMuA1_sBMfwcXcqq98m6rtODC2NSHCMIpYQFfPkPuAljHMpyCnEOIVtQjgp1MlE2hpSiaw8qCKq7elSpR2GsuCr1FPzFn_r38NRHyV_tc52s7tpYKvDpgBFc1kB3bvWE-ZTdr0Os441iHHOqvvxYKvLp82r1frVW68K_mXjTb_4v-BtDkLSZ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1770062571</pqid></control><display><type>article</type><title>Role of cholecystokinin in pancreatic adaptation to massive enterectomy</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Watanapa, P ; Egan, M ; Deprez, P H ; Calam, J ; Sarraf, C E ; Alison, M R ; Williamson, R C</creator><creatorcontrib>Watanapa, P ; Egan, M ; Deprez, P H ; Calam, J ; Sarraf, C E ; Alison, M R ; Williamson, R C</creatorcontrib><description>Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>EISSN: 1458-3288</identifier><identifier>DOI: 10.1136/gut.33.7.959</identifier><identifier>PMID: 1644338</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Animals ; Biological and medical sciences ; Cholecystokinin - antagonists & inhibitors ; Cholecystokinin - blood ; Cholecystokinin - physiology ; DNA - metabolism ; Gastroenterology. Liver. Pancreas. Abdomen ; Immunohistochemistry ; Intestine, Small - surgery ; Male ; Medical sciences ; Microscopy, Electron ; Other diseases. Semiology ; Pancreas - drug effects ; Pancreas - pathology ; Pancreas - ultrastructure ; Postoperative Period ; Proglumide - analogs & derivatives ; Proglumide - pharmacology ; Rats ; Rats, Inbred Strains ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><ispartof>Gut, 1992-07, Vol.33 (7), p.959-964</ispartof><rights>1993 INIST-CNRS</rights><rights>Copyright BMJ Publishing Group LTD Jul 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b572t-fbbb5c510a0d51a7fadbbf9749504a23f6658844785bceb45759764844d833863</citedby><cites>FETCH-LOGICAL-b572t-fbbb5c510a0d51a7fadbbf9749504a23f6658844785bceb45759764844d833863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379413/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379413/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4313710$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1644338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watanapa, P</creatorcontrib><creatorcontrib>Egan, M</creatorcontrib><creatorcontrib>Deprez, P H</creatorcontrib><creatorcontrib>Calam, J</creatorcontrib><creatorcontrib>Sarraf, C E</creatorcontrib><creatorcontrib>Alison, M R</creatorcontrib><creatorcontrib>Williamson, R C</creatorcontrib><title>Role of cholecystokinin in pancreatic adaptation to massive enterectomy</title><title>Gut</title><addtitle>Gut</addtitle><description>Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cholecystokinin - antagonists & inhibitors</subject><subject>Cholecystokinin - blood</subject><subject>Cholecystokinin - physiology</subject><subject>DNA - metabolism</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Immunohistochemistry</subject><subject>Intestine, Small - surgery</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Electron</subject><subject>Other diseases. Semiology</subject><subject>Pancreas - drug effects</subject><subject>Pancreas - pathology</subject><subject>Pancreas - ultrastructure</subject><subject>Postoperative Period</subject><subject>Proglumide - analogs & derivatives</subject><subject>Proglumide - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><issn>0017-5749</issn><issn>1468-3288</issn><issn>1458-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc9rFDEYhoModa3evAoDil46a7L5fSnoYmu1KCur15BkMm22M5M1yRT3vzdllq16EAIJeR8-no8XgOcIzhHC7O3VmOcYz_lcUvkAzBBhosYLIR6CGYSI15QT-Rg8SWkDIRRCoiNwhBghGIsZOP8WOleFtrLX5WF3KYcbP_ihKmerBxudzt5WutHbXF5hqHKoep2Sv3WVG7KLzubQ756CR63uknu2v4_B97MP6-XH-vLr-cXy3WVtKF_kujXGUEsR1LChSPNWN8a0shhSSPQCt4xRIQjhghrrDKGcSs5I-WlE8WX4GJxOc7ej6V1ji0LUndpG3-u4U0F79Xcy-Gt1FW4VwlwShMuA1_sBMfwcXcqq98m6rtODC2NSHCMIpYQFfPkPuAljHMpyCnEOIVtQjgp1MlE2hpSiaw8qCKq7elSpR2GsuCr1FPzFn_r38NRHyV_tc52s7tpYKvDpgBFc1kB3bvWE-ZTdr0Os441iHHOqvvxYKvLp82r1frVW68K_mXjTb_4v-BtDkLSZ</recordid><startdate>19920701</startdate><enddate>19920701</enddate><creator>Watanapa, P</creator><creator>Egan, M</creator><creator>Deprez, P H</creator><creator>Calam, J</creator><creator>Sarraf, C E</creator><creator>Alison, M R</creator><creator>Williamson, R C</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19920701</creationdate><title>Role of cholecystokinin in pancreatic adaptation to massive enterectomy</title><author>Watanapa, P ; Egan, M ; Deprez, P H ; Calam, J ; Sarraf, C E ; Alison, M R ; Williamson, R C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b572t-fbbb5c510a0d51a7fadbbf9749504a23f6658844785bceb45759764844d833863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cholecystokinin - antagonists & inhibitors</topic><topic>Cholecystokinin - blood</topic><topic>Cholecystokinin - physiology</topic><topic>DNA - metabolism</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Immunohistochemistry</topic><topic>Intestine, Small - surgery</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Electron</topic><topic>Other diseases. Semiology</topic><topic>Pancreas - drug effects</topic><topic>Pancreas - pathology</topic><topic>Pancreas - ultrastructure</topic><topic>Postoperative Period</topic><topic>Proglumide - analogs & derivatives</topic><topic>Proglumide - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watanapa, P</creatorcontrib><creatorcontrib>Egan, M</creatorcontrib><creatorcontrib>Deprez, P H</creatorcontrib><creatorcontrib>Calam, J</creatorcontrib><creatorcontrib>Sarraf, C E</creatorcontrib><creatorcontrib>Alison, M R</creatorcontrib><creatorcontrib>Williamson, R C</creatorcontrib><collection>Istex</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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanapa, P</au><au>Egan, M</au><au>Deprez, P H</au><au>Calam, J</au><au>Sarraf, C E</au><au>Alison, M R</au><au>Williamson, R C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of cholecystokinin in pancreatic adaptation to massive enterectomy</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>1992-07-01</date><risdate>1992</risdate><volume>33</volume><issue>7</issue><spage>959</spage><epage>964</epage><pages>959-964</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><eissn>1458-3288</eissn><coden>GUTTAK</coden><abstract>Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>1644338</pmid><doi>10.1136/gut.33.7.959</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0017-5749 |
| ispartof | Gut, 1992-07, Vol.33 (7), p.959-964 |
| issn | 0017-5749 1468-3288 1458-3288 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1379413 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Cholecystokinin - antagonists & inhibitors Cholecystokinin - blood Cholecystokinin - physiology DNA - metabolism Gastroenterology. Liver. Pancreas. Abdomen Immunohistochemistry Intestine, Small - surgery Male Medical sciences Microscopy, Electron Other diseases. Semiology Pancreas - drug effects Pancreas - pathology Pancreas - ultrastructure Postoperative Period Proglumide - analogs & derivatives Proglumide - pharmacology Rats Rats, Inbred Strains Stomach. Duodenum. Small intestine. Colon. Rectum. Anus |
| title | Role of cholecystokinin in pancreatic adaptation to massive enterectomy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T23%3A59%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Role%20of%20cholecystokinin%20in%20pancreatic%20adaptation%20to%20massive%20enterectomy&rft.jtitle=Gut&rft.au=Watanapa,%20P&rft.date=1992-07-01&rft.volume=33&rft.issue=7&rft.spage=959&rft.epage=964&rft.pages=959-964&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gut.33.7.959&rft_dat=%3Cproquest_pubme%3E3970011201%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1770062571&rft_id=info:pmid/1644338&rfr_iscdi=true |