{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:14:16Z","timestamp":1787012056523,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,12,8]],"date-time":"2017-12-08T00:00:00Z","timestamp":1512691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA006973"],"award-info":[{"award-number":["P30 CA006973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 TR 001079"],"award-info":[{"award-number":["UL1 TR 001079"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>In animal studies, intramuscular vincristine injections have been shown to block reinnervation of the denervated target muscle. This application could be used selectively to influence recovery patterns following injury of recurrent laryngeal nerves (RLNs). However, vincristine is currently Food and Drug Administration approved only for intravenous use. A formal toxicity trial of intramuscular injections was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Animal study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen female canines underwent direct laryngoscopy with injection of moderate\u2010 (0.4 mg, n = 8) or high\u2010dose (0.6 mg, n = 8) vincristine into the posterior cricoarytenoid (PCA) muscles. Plasma samples were collected at various time points postinjection and vincristine levels determined. At 24 hours (n = 7) or 14 days (n = 9) postinjection, animals were anesthetized and videolaryngoscopy documented vocal fold mobility and mucosal appearance. Adductor function was measured during stimulation of the RLN. Larynges were processed for histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen minutes after injection, plasma vincristine levels averaged 10.2% \u00b1 6.7% of the intravenous maximum, suggesting about 90% of the vincristine remained within the PCA muscle. Plasma levels were usually below detectable limits within 24 hours. At the end points, all animals had grossly normal\u2010appearing mucosa and full range of motion. Laryngeal adductor strength was normal in all cases. Histology showed moderate to severe acute inflammation in the submucosa only in the high\u2010dose group at 24 hours. There was no necrosis of muscle or mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intramuscular vincristine injections into the canine PCA muscles resulted in no significant local toxicity, even at the maximum dose. It would be reasonable to evaluate this treatment strategy in a phase I human trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 128:E247\u2013E250, 2018<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.26998","type":"journal-article","created":{"date-parts":[[2017,12,8]],"date-time":"2017-12-08T11:42:52Z","timestamp":1512733372000},"source":"Crossref","is-referenced-by-count":6,"title":["Toxicity trial of canine posterior cricoarytenoid intramuscular vincristine injections"],"prefix":"10.1002","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-0144","authenticated-orcid":false,"given":"Randal C.","family":"Paniello","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University, St. Louis St. Louis Missouri U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8933-5477","authenticated-orcid":false,"given":"Neel K.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University, St. Louis St. Louis Missouri U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Chernock","sequence":"additional","affiliation":[{"name":"Department of Pathology Washington University, St. Louis St. Louis Missouri U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200105000-00016"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200105000-00006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24951"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489414566182"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911801210"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23519"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1979.03290330015011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199704)28:4<314::AID-MPO13>3.0.CO;2-C"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/08880010390203936"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2011.604676"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-509X.197731"},{"key":"e_1_2_7_13_1","unstructured":"Guidance for industry: M3(R2) nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. 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