Characterization and Treatment of the Scarred Vocal Fold

描述(申请人提供)：声带疤痕是声带手术后嗓音不佳的最大原因(平野，1995；Woo，Casper，Colton和Breyer，1994)。这种瘢痕形成导致健康组织被纤维组织取代，纤维组织可以不可挽回地改变声带功能，导致声带粘膜波减少或消失(Benninger，Alessi，Archer等，1996)。当身体(肌肉)和覆盖物(上皮和固有层表层)的分离受到损害时，即使是很小的疤痕也会阻碍声带的功能。由于目前还没有持续有效的治疗疤痕声带的方法，它是最具挑战性的喉部疾病之一(Thibeault和Ford，2003)，也是这次竞争性更新的焦点，即描述喉部疤痕的特征。这个项目的长期目标不再仅仅关注声沟，而是现在包含了声带疤痕这一更为普遍的现象的特征和治疗。这一长期目标将通过1)对照实验室实验和2)计算机模拟实验来表征喉部疤痕及其对发声的影响，包括治疗前后。实验室实验将在动物组织和切除的喉部模型中从细胞水平上研究治疗效果。在过去5年完成的实验的基础上，我们将研究生长因子和维生素A在预防和治疗疤痕中的作用，并尝试更好地描述声带疤痕及其振动后果。我们发现有必要将建模和系统的实验室研究相结合，以解决组织特征、几何形状和手术条件之间的复杂相互作用，以创造合适的临床结果。这一建议是及时的，因为目前还没有一致有效的治疗方法来治疗疤痕，而且它仍然是声音外科尚未解决的问题之一。虽然我们最初5年的研究已经产生了几个指导治疗方案的关键假设，但目前的建议将使我们能够证实和/或进一步澄清这些假设，以便它们将产生更大的影响。

DESCRIPTION (provided by applicant): Vocal fold scarring is the single greatest cause of poor voice after vocal fold surgery (Hirano, 1995; Woo, Casper, Colton and Brewer, 1994). Such scarring results in replacement of healthy tissue by fibrous tissue, which can irrevocably alter vocal fold function, leading to a decreased or absent vocal fold mucosal wave (Benninger, Alessi, Archer et al., 1996). Even small foci of scar can impede vocal fold function when separation of the body (muscle) and cover (epithelium and the superficial layer of the lamina propria) is compromised. Because there is currently no consistently effective treatment for the scarred vocal fold, it is 1 of the most challenging laryngeal disorders to treat (Thibeault and Ford, 2003) and is the focus of this competing renewal on characterizing taryngeal scars. The long-range aim of this project no longer focuses exclusively on sulcus vocalis, but now encompasses the characterization and treatment of the more universal phenomenon of vocal fold scarring. This long-range objective will be accomplished by characterizing laryngeal scarring and its influence on phonation, both pre-and post-treatment, using 1) controlled laboratory experiments, and 2) computer modeling experiments. The laboratory experiments will investigate treatment effects at the cellular level in animal's tissues and excised larynx models. Building on experiments completed over the last 5 years, we will investigate the role of growth factors and vitamin A in preventing and treating scars, and we will attempt to better characterize scars in the vocal fold and their vibratory consequences. We have found it necessary to combine modeling and systematic laboratory investigations to resolve the complex interactions between tissue characteristics, geometry and surgical requisites necessary to create a suitable clinical outcome. This proposal is timely because no consistently effective treatment modality is known for scarring, and it remains 1 of the unsolved problems of phonosurgery. While our initial 5 years of study have yielded several key hypotheses to guide treatment options, the current proposal will enable us to substantiate and/or further clarify these hypotheses so that they will have a greater impact.