{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:25:49Z","timestamp":1778736349200,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T00:00:00Z","timestamp":1402358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>High negative pressure in the middle ear was thought to be closely related to the etiology of retraction\u2010type cholesteatoma. Recently, it has been detected that mechanical forces are important factors in epithelial turnover and affect cytoskeletal remodeling. Continuous negative pressure in the middle ear may possibly accelerate the proliferation and differentiation of epithelial cells of the tympanic membrane.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Animal experimental study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eleven adult male Sprague\u2010Dawley rats were used, and continuous negative pressure was loaded by connecting a catheter from the rat's middle ear to the supply route of an implantable microinfusion pump, iPRECIO. At 7 days after implantation of the device, an otoendoscopic examination and micro\u2010computed tomography (CT) analysis of the temporal bone were performed; the temporal bones were then collected for histological and immunohistochemical analysis. The degree of proliferation and differentiation of epithelial cells of the tympanic membrane was investigated immunohistochemically using the anti\u2013cytokeratin\u20105 and anti\u2013cytokeratin\u201010 antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Otoendoscopic examination revealed retraction of the pars flaccida in all of the ears under negative pressure. In the micro\u2010CT analysis, soft tissue density area in the hypotympanum was observed in all ears under negative pressure. Histological analysis revealed thickened epithelium of the pars flaccida. In this region, the thickness of layers with cytokeratin\u20105\u2013positive cells and cytokeratin\u201010\u2013positive cells were increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Continuous negative pressure in the middle ear can lead to thickening of the epithelium of the pars flaccida, and may accelerate the proliferation and differentiation of epithelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic> 124:2404\u20132410, 2014<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.24767","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T14:29:31Z","timestamp":1402410571000},"page":"2404-2410","source":"Crossref","is-referenced-by-count":14,"title":["Influence of continuous negative pressure in the rat middle ear"],"prefix":"10.1002","volume":"124","author":[{"given":"Naotaro","family":"Akiyama","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Yamamoto\u2010Fukuda","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00168024"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0709(81)80037-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016489609137716"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348948609500619"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20604"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000276181"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3175"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-08-0703"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200106000-00018"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200211000-00005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480500475633"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052718"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016488309132882"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/014107687907200221"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215100054402"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091182"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00361.2009"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-011-0179-6"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1004171517639"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S47279"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199805000-00011"},{"key":"e_1_2_6_23_1","first-page":"197","volume-title":"Chronic Otitis Media. 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