Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

A Study on Vocal Attack During Voice Therapy Exercises Using Photoglottography.

OBJECTIVE: There are various exercises for voice therapy, but current evidence is insufficient to decide the most effective training technique for each type of dysphonia. This study focused on vocal attack as one of the causes of dysphonia. Hence, vocal attack during voice therapy exercises was investigated using photoglottogram (PGG). METHODS: Eighteen healthy adult subjects (10 males and 8 females) were included in this study. The first to fifth vocal waves during natural voice, hard and soft voice onset, and semi-occluded vocal tract exercises (SOVTE: humming, tubing, and lip trill) were assessed. We also calculated the 25% vocal fold open quotient (OQ) using a PGG and compared these parameters. RESULTS: The 25% OQ did not show any sex-related differences. In the first wave, the 25% OQ for hard attack was significantly lower than that for soft attack, tongue-out humming, and lip trill. In contrast, the 25% OQ value for soft attack was significantly higher than that for humming, 6 mm tube phonation, and lip trill. The 25% OQ values differed between SOVTE procedures; it was higher for the 13 mm tube phonation than for the 6 mm tube phonation. The 25% OQ at voice onset in the first to fifth waves differed depending on the SOVTE technique, indicating different voice onset patterns. CONCLUSIONS: These results suggest that appropriate selection of SOVTE tailored for each patient may have benefit in further voice improvement. Future research should focus on conducting a similar study on patients with dysphonia.

Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

The dynamics of deglutition during head rotation using dynamic 320-row area detector computed tomography.

Objective: We aimed to elucidate the dynamics of deglutition during head rotation by acquiring 320-row area detector computed tomography (320-ADCT) images and analyzing deglutition during head rotation. Methods: This study included 11 patients experiencing globus pharyngeus. A 320-ADCT was used to acquire images in two types of viscosity (thin and thick), with the head rotated to the left. We measured the movement time of deglutition-related organs (soft palate, epiglottis, upper esophageal sphincter [UES], and true vocal cords) and pharyngeal volume (bolus ratio at the start of UES opening [Bolus ratio], pharyngeal volume contraction ratio [PVCR], and pharyngeal volume before swallowing [PVBS]). A two-way analysis of variance was performed for statistical analysis, and all items were compared for significant differences in terms of head rotation and viscosity. EZR was used for all statistical analyses (p-value <.05). Results: Head rotation significantly accelerated the onset of epiglottis inversion and UES opening compared with no head rotation. The duration of epiglottis inversion with the thin viscosity fluid was significantly longer. The bolus ratio increased significantly with thick viscosity. There was no significant difference in viscosity and head rotation in terms of PVCR. PVBS increased significantly with head rotation. Conclusion: The significantly earlier start of epiglottis inversion and UES opening due to head rotation could be caused by: (1) swallowing center; (2) pharyngeal volume; and (3) pharyngeal contraction force. Thus, we plan to further analyze swallowing with head rotation by combining swallowing CT with manometry and examine its relationship with pharyngeal contraction force. Level of Evidence: 3b.

A complex muscle fiber network in the cricothyroid muscle: a scanning electron microscopic study.

OBJECTIVES: To examine the three-dimensional ultrastructure of cricothyroid (CT) muscle fibers to elucidate their morphologic characteristics with regard to the specific functions of the muscle. STUDY DESIGN: An anatomic animal study. METHODS: The CT muscles of five adult rats were processed using the HCl-hydrolysis method to remove the peri- and intramuscular connective tissue components. The fine muscle fiber arrangements were observed by scanning electron microscopy. RESULTS: Complex muscle fiber interconnections (myomyous junctions) were identified in the muscles. Myomyous junctions were characterized by the connection of many villous processes that were 1 to 2 mum in diameter and 2 to 4 mum in length with a serrated appearance at the ends of a lateral branch or a bifurcating trunk of the muscle fibers. CONCLUSIONS: Myomyous junctions form a complex muscle fiber network, which is thought to synchronize the activity of the CT muscle fibers. This is the first three-dimensional demonstration of the muscle fiber network in the CT muscle; this network may play a major role in the functional specificity of the CT muscle.

Scanning electron microscopic study of the muscle fiber arrangement in the rat cricopharyngeal muscle.

CONCLUSIONS: Myomyous junctions comprise a complex muscle fiber network, which is thought to synchronize the activity of the cricopharyngeal (CP) muscle fibers. Myomyous and myotendinous junctions explain the heterogeneity in muscle fiber length which contributes to the efficient behavior of the muscle. This scanning electron microscopy (SEM) study demonstrated the complex muscle fiber arrangement of the CP muscle and improved on the previous description of its morphological specificity. OBJECTIVE: To examine the 3D ultrastructure of the inferior pharyngeal constrictor muscle fibers to obtain further knowledge of their morphological characteristics with regard to the specific functions of the muscle in deglutition. MATERIAL AND METHODS: Six adult rats were used. Their CP and thyropharyngeal (TP) muscles were obtained and processed using the HCl hydrolysis method to remove i.m. connective tissue. The fine muscle fiber structure was observed by means of SEM. RESULTS: Multifaceted muscle fiber interconnections (myomyous junctions) were identified in the CP muscle. The myomyous junctions were characterized by the tight connection of many finger-like processes at the ends of a lateral branch or bifurcating trunk of the muscle fibers. In addition, muscle fibers occasionally tapered and ended within the muscle belly, forming myotendinous junctions. The TP muscle lacked these structures.

Preventive effects of bortezomib on denervation-induced atrophy of the intrinsic laryngeal muscles: an experimental study in the rat.

CONCLUSION: Bortezomib was effective in attenuating atrophy of the posterior cricoarytenoid (PCA) muscle, but not the thyroarytenoid (TA) muscle. This was probably due to differences in the fiber composition of the two muscles. The PCA muscle is composed of a combination of fast- and slow-twitch fibers, and therefore is more resistant to atrophy than the TA muscle, which is composed solely of fast-twitch fibers. OBJECTIVES: To investigate the preventive effects of bortezomib on denervation-induced atrophy of the TA and PCA muscles in the rat. METHODS: Following transection of the left recurrent laryngeal nerve, bortezomib (100 µg/kg) was administered subcutaneously on post-denervation days 1 and 4, followed by a 10-day rest period every 14 days; each 2-week period constituted a single treatment cycle. In controls, saline was administered instead. Animals were killed for histological examination at 4 (n = 6), 8 (n = 7), and 12 (n = 7) weeks post-denervation. Muscle atrophy was assessed using three indices: wet muscle weight, muscle fiber cross-sectional area, and the number of muscle fibers/mm(2). The effects of bortezomib were evaluated by comparing the left (L) and right (R) muscles, with sequential changes in the L/R ratio assessed. RESULTS: In saline-administered animals, atrophy of the left-sided TA and PCA muscles progressed rapidly during the first 4 weeks post-denervation, following which progression slowed. Atrophy was greater in the TA compared with the PCA muscle, although this difference was not statistically significant. In bortezomib-administered animals, atrophy of the PCA muscle was attenuated significantly at post-denervation weeks 8 and 12; no such reduction in atrophy was observed for the TA muscle.

Japanese version of voice handicap index for subjective evaluation of voice disorder.

Recently, the Voice Handicap Index (VHI), developed in the United States, has been highlighted as a means to assess a patient's perceptions of the severity of his or her voice disorder. The VHI is based on a self-administered questionnaire that quantifies the degree of a patient's disability related to his/her voice disorder. The questionnaire was translated into Japanese and applied to Japanese patients with various kinds of disordered voice or dysphonia. The results were analyzed and the usefulness discussed. In this study, 546 patients (281 males and 265 females) were included. Mean VHI scores were 36.2/120 in males and 44.1/120 in females. In the male patients, VHI scores were the highest among teens. However, VHI scores did not vary with age in the female patients. Patients with vocal fold paralysis, functional dysphonia, psychological dysphonia, and spasmodic dysphonia showed relatively high VHI scores, whereas those with laryngeal granuloma and laryngopharyngeal reflux disease showed low scores. In most diseases, functional and physiological scores were higher than emotional scores. In any treated patients, those with vocal nodule, vocal polyp, polypoid vocal fold, and recurrent laryngeal nerve paralysis, VHI scores decreased after therapeutic intervention. These findings suggest that the Japanese VHI is a useful tool for monitoring a patient's psychological status, choosing appropriate treatment, and assessing the therapeutic outcome.

Endoscopic laryngeal findings in Japanese patients with laryngopharyngeal reflux symptoms.

Objective. To know the characteristics of endoscopic laryngeal and pharyngeal abnormalities in Japanese patients with laryngopharyngeal reflux symptoms (LPRS). Methods. A total of 146 endoscopic images of the larynx and pharynx (60 pairs for the rabeprazole group and 13 pairs for the control group) were presented to 15 otolaryngologists blinded to patient information and were scored according to several variables potentially associated with laryngopharyngeal reflux. The median value of the 15 scores for each item from each image was obtained. The mean pretreatment scores of each item and total score were assessed in both rabeprazole and control groups. In the rabeprazole group, the endoscopic findings before and after the 4-week treatment with rabeprazole were compared. Changes between corresponding duration in the control group were also evaluated. Results. The median and mean pretreatment total score was 3 and 3.02, respectively, from the 73 patients with LPRS. No significant differences were observed before and after treatment in either the rabeprazole or control groups for any item or total score. In 24 patients with a high pretreatment score (total score ≥ 4) from the rabeprazole group, significant decreases in scores for "thick endolaryngeal mucous" (0.54 to 0.17, P = 0.017) and total (4.77 to 3.58, P = 0.0003) were observed after the 4-week treatment.

Age-related remodeling of the hypopharyngeal constrictor muscle and its subneural apparatuses: a scanning electron microscopical study in rats.

Age-related remodeling of the hypopharyngeal constrictor muscle was studied by comparing the morphological features of the subneural apparatus (SNA) of the thyropharyngeal (TP) and cricopha ryngeal (CP) muscles in young and old rats. Scanning electron microscopy revealed that the TP and CP muscles had both gutter- and depression-type SNAs, although different proportions of the two types of apparatus were found in each muscle. In young-adult rats, the gutter-type SNA was predominant in the TP muscle, whereas in the CP muscle the depression type was predominant. By contrast, in old rats, the depression-type SNA was predominant in the TP muscle, while no such transformation of the dominant SNA was noted in the CP muscle. In addition, the number of type IIb and type I muscle fibers was lower and greater, respectively, in older animals compared with those of younger animals. Furthermore, there were more type IIc fibers in the TP muscle of old rats, but no difference in the CP muscle between young and old animals. These findings suggest that the transformation of SNAs and the muscle fibers of the hypopharyngeal constrictor muscle takes place during aging and that their remodeling processes differ in the TP and CP muscles.