Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma
BACKGROUND Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in...
Gespeichert in:
| Veröffentlicht in: | British journal of ophthalmology 1998-07, Vol.82 (7), p.758-762 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 762 |
|---|---|
| container_issue | 7 |
| container_start_page | 758 |
| container_title | British journal of ophthalmology |
| container_volume | 82 |
| creator | Schmidt, Karl-Georg von Rückmann, Andrea Pillunat, Lutz E |
| description | BACKGROUND Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion. METHODS The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamidev placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent. RESULTS Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5)) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p |
| doi_str_mv | 10.1136/bjo.82.7.758 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1722689</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4012601161</sourcerecordid><originalsourceid>FETCH-LOGICAL-b506t-3d1ca6a1ba272cf9569bed02fb1a813e339894e73e2a5240a0e832ffac0baf733</originalsourceid><addsrcrecordid>eNp9kduL1DAYxYMo6-zqm69CQVlf7JjLNJcXQcYrrAqyKvgSvqbpNGOb1KQV9783w5RBffApl_P7Dic5CD0geE0I48_qfVhLuhZrUclbaEU2XJYUC3UbrTDGoiSEk7voPKV9PlJOxBk6U4puGBcrFK_D6Az0hYFYB-9MAb67aSIkWzjfudpNLvi8NdHmu1QEM_cQi3HuMwHD2Ltpbg5s0bldV0zWp8PAGN0A8aYIo_XZctfbYtfDbMIA99CdFvL0_WW9QJ9fv7revi2vPr55t31xVdYV5lPJGmKAA6mBCmpaVXFV2wbTtiYgCbOMKak2VjBLoaIbDNhKRtsWDK6hFYxdoOdH33GuB9sY66cIvV6S6QBO_6141-ld-KmJoJRLlQ0uF4MYfsw2TXpwydi-B2_DnDRXpFKEyww--gfchzn6_LjsJaTiDAuaqadHysSQUrTtKQrB-tCkzk1qSbXQucmMP_wz_gleqsv640WHlAtsI3jj0gmjjFUcH36hPGIuTfbXSYb4XWcTUekPX7YaM_Hp_bevL3WV-SdHvh72_w_4G1fixVw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1778963072</pqid></control><display><type>article</type><title>Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Schmidt, Karl-Georg ; von Rückmann, Andrea ; Pillunat, Lutz E</creator><creatorcontrib>Schmidt, Karl-Georg ; von Rückmann, Andrea ; Pillunat, Lutz E</creatorcontrib><description>BACKGROUND Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion. METHODS The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamidev placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent. RESULTS Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5)) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p <0.001) reduced and was significantly (p<0.03) reduced in vehicle (V) treated eyes (HTPV: 20.3 (0.4)/19.0 (0.4)) and CTLV: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p<0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged. CONCLUSION Dorzolamide increased OPA in HTP and CTL. Drugs stimulating OPA may improve prognosis of POAGs.</description><identifier>ISSN: 0007-1161</identifier><identifier>EISSN: 1468-2079</identifier><identifier>DOI: 10.1136/bjo.82.7.758</identifier><identifier>PMID: 9924367</identifier><identifier>CODEN: BJOPAL</identifier><language>eng</language><publisher>BMA House, Tavistock Square, London, WC1H 9JR: BMJ Publishing Group Ltd</publisher><subject>Aged ; Antihypertensive Agents - therapeutic use ; Biological and medical sciences ; Blood Pressure - drug effects ; Carbonic Anhydrase Inhibitors - therapeutic use ; Cataract - drug therapy ; Cataracts ; dorzolamide ; Drug dosages ; Eye ; Eye surgery ; Female ; Glaucoma ; Glaucoma, Open-Angle - drug therapy ; Heart Rate - drug effects ; Humans ; Intraocular Pressure - drug effects ; Male ; Medical sciences ; Middle Aged ; ocular pulse amplitude ; Optic nerve ; Original articles - Clinical science ; Pharmacology. Drug treatments ; Placebos ; primary open angle glaucoma ; Prospective Studies ; Pulsatile Flow - drug effects ; Sulfonamides - therapeutic use ; Surgery ; Thiophenes - therapeutic use</subject><ispartof>British journal of ophthalmology, 1998-07, Vol.82 (7), p.758-762</ispartof><rights>British Journal of Ophthalmology</rights><rights>1998 INIST-CNRS</rights><rights>Copyright: 1998 British Journal of Ophthalmology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b506t-3d1ca6a1ba272cf9569bed02fb1a813e339894e73e2a5240a0e832ffac0baf733</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1722689/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1722689/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2335603$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9924367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmidt, Karl-Georg</creatorcontrib><creatorcontrib>von Rückmann, Andrea</creatorcontrib><creatorcontrib>Pillunat, Lutz E</creatorcontrib><title>Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma</title><title>British journal of ophthalmology</title><addtitle>Br J Ophthalmol</addtitle><description>BACKGROUND Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion. METHODS The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamidev placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent. RESULTS Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5)) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p <0.001) reduced and was significantly (p<0.03) reduced in vehicle (V) treated eyes (HTPV: 20.3 (0.4)/19.0 (0.4)) and CTLV: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p<0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged. CONCLUSION Dorzolamide increased OPA in HTP and CTL. Drugs stimulating OPA may improve prognosis of POAGs.</description><subject>Aged</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Carbonic Anhydrase Inhibitors - therapeutic use</subject><subject>Cataract - drug therapy</subject><subject>Cataracts</subject><subject>dorzolamide</subject><subject>Drug dosages</subject><subject>Eye</subject><subject>Eye surgery</subject><subject>Female</subject><subject>Glaucoma</subject><subject>Glaucoma, Open-Angle - drug therapy</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>Intraocular Pressure - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>ocular pulse amplitude</subject><subject>Optic nerve</subject><subject>Original articles - Clinical science</subject><subject>Pharmacology. Drug treatments</subject><subject>Placebos</subject><subject>primary open angle glaucoma</subject><subject>Prospective Studies</subject><subject>Pulsatile Flow - drug effects</subject><subject>Sulfonamides - therapeutic use</subject><subject>Surgery</subject><subject>Thiophenes - therapeutic use</subject><issn>0007-1161</issn><issn>1468-2079</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kduL1DAYxYMo6-zqm69CQVlf7JjLNJcXQcYrrAqyKvgSvqbpNGOb1KQV9783w5RBffApl_P7Dic5CD0geE0I48_qfVhLuhZrUclbaEU2XJYUC3UbrTDGoiSEk7voPKV9PlJOxBk6U4puGBcrFK_D6Az0hYFYB-9MAb67aSIkWzjfudpNLvi8NdHmu1QEM_cQi3HuMwHD2Ltpbg5s0bldV0zWp8PAGN0A8aYIo_XZctfbYtfDbMIA99CdFvL0_WW9QJ9fv7revi2vPr55t31xVdYV5lPJGmKAA6mBCmpaVXFV2wbTtiYgCbOMKak2VjBLoaIbDNhKRtsWDK6hFYxdoOdH33GuB9sY66cIvV6S6QBO_6141-ld-KmJoJRLlQ0uF4MYfsw2TXpwydi-B2_DnDRXpFKEyww--gfchzn6_LjsJaTiDAuaqadHysSQUrTtKQrB-tCkzk1qSbXQucmMP_wz_gleqsv640WHlAtsI3jj0gmjjFUcH36hPGIuTfbXSYb4XWcTUekPX7YaM_Hp_bevL3WV-SdHvh72_w_4G1fixVw</recordid><startdate>19980701</startdate><enddate>19980701</enddate><creator>Schmidt, Karl-Georg</creator><creator>von Rückmann, Andrea</creator><creator>Pillunat, Lutz E</creator><general>BMJ Publishing Group Ltd</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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980701</creationdate><title>Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma</title><author>Schmidt, Karl-Georg ; von Rückmann, Andrea ; Pillunat, Lutz E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b506t-3d1ca6a1ba272cf9569bed02fb1a813e339894e73e2a5240a0e832ffac0baf733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Aged</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Carbonic Anhydrase Inhibitors - therapeutic use</topic><topic>Cataract - drug therapy</topic><topic>Cataracts</topic><topic>dorzolamide</topic><topic>Drug dosages</topic><topic>Eye</topic><topic>Eye surgery</topic><topic>Female</topic><topic>Glaucoma</topic><topic>Glaucoma, Open-Angle - drug therapy</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>Intraocular Pressure - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>ocular pulse amplitude</topic><topic>Optic nerve</topic><topic>Original articles - Clinical science</topic><topic>Pharmacology. Drug treatments</topic><topic>Placebos</topic><topic>primary open angle glaucoma</topic><topic>Prospective Studies</topic><topic>Pulsatile Flow - drug effects</topic><topic>Sulfonamides - therapeutic use</topic><topic>Surgery</topic><topic>Thiophenes - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmidt, Karl-Georg</creatorcontrib><creatorcontrib>von Rückmann, Andrea</creatorcontrib><creatorcontrib>Pillunat, Lutz E</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>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</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmidt, Karl-Georg</au><au>von Rückmann, Andrea</au><au>Pillunat, Lutz E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma</atitle><jtitle>British journal of ophthalmology</jtitle><addtitle>Br J Ophthalmol</addtitle><date>1998-07-01</date><risdate>1998</risdate><volume>82</volume><issue>7</issue><spage>758</spage><epage>762</epage><pages>758-762</pages><issn>0007-1161</issn><eissn>1468-2079</eissn><coden>BJOPAL</coden><abstract>BACKGROUND Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion. METHODS The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamidev placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent. RESULTS Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5)) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p <0.001) reduced and was significantly (p<0.03) reduced in vehicle (V) treated eyes (HTPV: 20.3 (0.4)/19.0 (0.4)) and CTLV: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p<0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged. CONCLUSION Dorzolamide increased OPA in HTP and CTL. Drugs stimulating OPA may improve prognosis of POAGs.</abstract><cop>BMA House, Tavistock Square, London, WC1H 9JR</cop><pub>BMJ Publishing Group Ltd</pub><pmid>9924367</pmid><doi>10.1136/bjo.82.7.758</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1161 |
| ispartof | British journal of ophthalmology, 1998-07, Vol.82 (7), p.758-762 |
| issn | 0007-1161 1468-2079 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1722689 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Aged Antihypertensive Agents - therapeutic use Biological and medical sciences Blood Pressure - drug effects Carbonic Anhydrase Inhibitors - therapeutic use Cataract - drug therapy Cataracts dorzolamide Drug dosages Eye Eye surgery Female Glaucoma Glaucoma, Open-Angle - drug therapy Heart Rate - drug effects Humans Intraocular Pressure - drug effects Male Medical sciences Middle Aged ocular pulse amplitude Optic nerve Original articles - Clinical science Pharmacology. Drug treatments Placebos primary open angle glaucoma Prospective Studies Pulsatile Flow - drug effects Sulfonamides - therapeutic use Surgery Thiophenes - therapeutic use |
| title | Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T18%3A37%3A54IST&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=Topical%20carbonic%20anhydrase%20inhibition%20increases%20ocular%20pulse%20amplitude%20in%20high%20tension%20primary%20open%20angle%20glaucoma&rft.jtitle=British%20journal%20of%20ophthalmology&rft.au=Schmidt,%20Karl-Georg&rft.date=1998-07-01&rft.volume=82&rft.issue=7&rft.spage=758&rft.epage=762&rft.pages=758-762&rft.issn=0007-1161&rft.eissn=1468-2079&rft.coden=BJOPAL&rft_id=info:doi/10.1136/bjo.82.7.758&rft_dat=%3Cproquest_pubme%3E4012601161%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=1778963072&rft_id=info:pmid/9924367&rfr_iscdi=true |