Non-invasive objective evaluation of radiotherapy-induced dry mouth.

BACKGROUND: Dry mouth is a common complaint in patients undergoing radiotherapy. Here, we employed the oral moisture meter Mucus III to evaluate dry mouth in head and neck tumor patients before and after they underwent radiotherapy. METHODS: We recruited 17 newly diagnosed patients with pharyngeal squamous cell carcinoma or unknown primary squamous cell carcinoma, who received head and neck radiation therapy at Tokyo University Hospital in 2008-2010. The primary sites were the epipharynx (n = 1), oropharynx (n = 6), or hypopharynx (n = 5); it was unknown in five cases. Salivary function was assessed by a dry mouth questionnaire, resting saliva test, chewing gum test, and Mucus III, before (n = 17), immediately after radiotherapy (n = 10), and at 3 (n = 9) and 12 months after radiotherapy (n = 11). RESULTS: The questionnaire, resting saliva test, and chewing gum test at 3 and 12 months after radiotherapy indicated a significantly decreased resting and stimulated whole saliva flow rate than prior radiotherapy (P < 0.05 and P < 0.001). In contrast, Mucus III results showed significant worsening of xerostomia at 12 months after radiotherapy (P < 0.05). CONCLUSION: Mucus III has been proven to be an objective diagnostic tool for patients with serious dry mouth, such as in patients with Sjogren's syndrome. However, we did not find a perfect correlation between Mucus III and other objective (resting saliva and chewing gum) and subjective (questionnaire) measures of dry mouth. To precisely diagnose radiotherapy-induced dry mouth, further improvement to the method is needed.

Trial of Chinese medicine Wu-Ling-San for acute low-tone hearing loss.

PURPOSE: We used new criteria to elucidate the demographics of acute low-tone sensorineural hearing loss (ALHL) and tested the Chinese medicine Wu-Ling-San as a treatment for ALHL. PROCEDURES: We reviewed the medical records of patients with ALHL seen at the outpatient clinic of the Social Insurance Central General Hospital in Tokyo from April 2006 through August 2011. Patients were treated with an oral steroid, a diuretic, or Wu-Ling-San; alone or in combination. RESULTS: We identified 130 definite and 48 probable ALHL cases. The mean age and male-to-female ratio in probable cases were significantly higher than those in definite cases (p < 0.05). The steroid-Wu-Ling-San combination was significantly more effective (100% recovery) than the diuretic alone (59%), Wu-Ling-San alone (62%), or the steroid-diuretic combination (60%, p < 0.05). CONCLUSIONS: ALHL can develop in older patients more frequently than we expected. The steroid-Wu-Ling-San combination is a possible new treatment for ALHL.

Recurrent hoarseness due to inflammatory vocal fold lesions in a patient with Crohn's disease.

Crohn's disease is a chronic inflammatory bowel disease characterized by discontinuous chronic inflammation that may affect virtually all organs, including the head and neck. Laryngeal involvement in Crohn's disease is very rare, and only 9 cases have been reported. All 9 patients complained of difficulty in breathing due to edema and ulceration from the larynx to the hypopharynx. The present patient was a 31-year-old woman who had experienced the intestinal symptoms of Crohn's disease starting 20 months earlier and complained of hoarseness, sore throat, and odynophagia. The hoarseness worsened gradually because of limited ulceration of the vocal fold without edema. We describe the first case in which limited ulceration occurred on the vocal fold without airway involvement.

Objective and non-invasive evaluation of dry mouth.

OBJECTIVE: This study was designed to evaluate the moisture checker (MucusIII), a new device for measuring moisture of the oral submucosa. METHODS: Defective salivary secretion was induced by sialoadenectomy (n=8), while the remaining five guinea pigs underwent sham surgery (control group). We measured the unstimulated salivary flow rate, wetness of the oral mucosa using the oral tester (L-SALIVO) and moisture of the submucosa of the tongue using MucusIII. All tests were performed before (baseline) and 1 month after surgery. RESULTS: Sialoadenectomy significantly reduced both the salivary flow rate and the tester reading at 10 and at 30s (p<0.01). The vale due to the MucusIII as significantly reduced in animals with sialoadenectomy (p<0.01). CONCLUSION: The MucusIII is a device for objective evaluation of the moisture of the oral cavity.

Hearing levels in patients with microtia: correlation with temporal bone malformation.

OBJECTIVE: To evaluate the relationship between hearing level and temporal bone abnormalities in patients with microtia. STUDY DESIGN: Retrospective case series study between 1992 and 2004. SETTING: Academic, tertiary care referral medical center. PATIENTS: We evaluated 115 ears of 89 patients (68 males, 21 females; mean age, 11 yr; range, 5-44 yr) with microtia. MAIN OUTCOME MEASURES: Hearing level was examined in patients with microtia. Developmental abnormalities of the temporal bone were evaluated by Jahrsdoerfer's computed tomography (CT) scoring system using high-resolution CT (HRCT) scans of the temporal bone. Temporal bone malformation scores were divided into four subgroups: ossicular development, windows connected to the cochlea, aeration of the middle ear cavity, and facial nerve aberration. Patients were divided into the stenosis and atresia groups on the basis of the appearance of the external auditory canal (EAC). We also evaluated the relationships between hearing level and four subtotal scores of the HRCT findings in the stenosis and atresia groups. RESULTS: There was no relationship between hearing level and total points of HRCT scoring system or between hearing level and severity of microtia scored by Marx classification. With regard to subtotal points related to ossicles (4 points), the hearing level in ears with low scores (<2) (64.7 +/- 1.6 dB) was significantly different (P = .03) from that in ears with high scores (> or =2) (54.0 +/- 2.8 dB) in the stenosis group. In the atresia group, the hearing level was 64.3 +/- 2.2 dB in ears with low scores and 62.3 +/- 1.1 in ears with high scores (P > .5). As for subtotal points related to the windows connected to cochlea (2 points), the hearing level was 64.8 +/- 2.6 dB in ears with low scores (0) and 55.9 +/- 2.4 dB in ears with high scores (> = 1) in the stenosis group. In the atresia group, the hearing level was 67.7 +/- 2.3 dB in ears with low scores and 61.5 +/- 1.0 in ears with high scores. There was significant difference between ears with low and high scores in the stenosis group (P = .03) and atresia group (P = .009). There was no significant difference between ears with low and high scores with respect to the subtotal points related to aeration of the middle ear cavity and aberration of the facial nerve. CONCLUSION: The hearing level in microtic ears correlated with the formation of oval/round windows and ossicular development but not with the degree of middle ear aeration, facial nerve aberration, or severity of microtia. The hearing level can also serve as an indictor, such as the HRCT findings, to determine whether a subject's hearing will likely improve after reconstructive surgery.

Large jugular bulb diverticulum invading the internal auditory canal.

OBJECTIVES: We report, with neuro-otologic findings, a very rare case of a large jugular bulb diverticulum eroding the internal auditory canal (IAC). METHODS: We present the imaging and functional studies of a 29-year-old woman in whom a large jugular bulb diverticulum on the left side was found incidentally. RESULTS: Imaging studies revealed a normal external auditory canal, middle ear, and inner ear, but a large jugular bulb diverticulum extending superiorly on the left side had eroded the IAC from below and behind with destruction of the petrous bone. Caloric responses and facial movements were normal. Vestibular evoked myogenic potentials with bone conduction stimuli were absent on the left, indicating dysfunction of the left inferior vestibular system. CONCLUSIONS: This is the first report in the English-language literature of detailed imaging and functional findings in a very large diverticulum invading the IAC. Vestibular evoked myogenic potentials were useful in uncovering subclinical inferior vestibular system dysfunction in the jugular bulb diverticulum invading the IAC.

Results of hearing tests after total middle ear reconstruction.

CONCLUSIONS: Patients treated by mastoidectomy in the past often present with hearing loss and cavity problems such as pus discharge. Total middle ear reconstruction (TMER) improves the hearing of these patients by correcting cavity problems and resolution of ear discharge, which facilitates ossicular chain reconstruction such as type III or type IV tympanoplasty. OBJECTIVE: To evaluate the effectiveness of TMER in improving hearing. PATIENTS AND METHODS: We reviewed the audiograms of 56 ears of 48 patients who underwent TMER in combination with either type III or type IV tympanoplasty. Audiometric pure tone thresholds averaged over three frequencies (500, 1000, and 2000, pure tone average) were measured and compared before and after surgery. Successful outcome was defined as improvement of 15 dB or more. The mean follow-up was 5.7 years (range 1.1-12.6). We also analyzed the relations between hearing improvement and factors such as type of tympanoplasty (types III and IV), choice between one-stage and two-stage operation, and the interval between original mastoidectomy and final operation. RESULTS: The mean hearing gain was 13.6 (+/-11.9) dB. Twenty-seven procedures (48.2%) were considered successful, with improvement of 15 dB or more. The results of type III tympanoplasty group were significantly superior to those of type IV (p<0.05, Student's t test). One- and two-stage surgery did not significantly influence outcome. The interval between the initial operation correlated weakly and negatively (r = - 0.266, p<0.05) with hearing gain.

An effective management regimen for laryngeal granuloma caused by gastro-esophageal reflux: combination therapy with suggestions for lifestyle modifications.

According to our previous study, lifestyle modification in combination with drug therapy is much more effective than drug therapy alone in cases of laryngopharyngeal reflux (LPR). Most patients with LPR will have chronic gastro-esophageal reflux diseases (GERD) and require long-term medical therapy for control, resulting in high total expenditure on pharmacologic agents. We combined pharmacologic management with lifestyle modifications for the management of GERD with successful outcomes in patients with GERD-related laryngeal granulomas. Although further studies are needed, guidance concerning lifestyle modifications in combination with PPI therapy may be not only a clinically effective but also a cost-effective method for the management of laryngeal granulomas caused by gastro-esophageal reflux.

Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo.

Hair cell loss in the mammalian cochlea is irreversible and results in permanent hearing loss. Math1, the basic helix-loop-helix transcription factor homolog of the Drosophila atonal gene, is a positive regulator of hair cell differentiation during cochlear development. Developing hair cells express Math1, and nonsensory cells do not. We set out to determine the outcome of overexpression of Math1 in nonsensory cells of the cochlea on the phenotype of these cells. We demonstrate that in vivo inoculation of adenovirus with the Math1 gene insert into the endolymph of the mature guinea pig cochlea results in Math1 overexpression in nonsensory cochlear cells, as evident from the presence of Math1 protein in supporting cells of the organ of Corti and in adjacent nonsensory epithelial cells. Math1 overexpression leads to the appearance of immature hair cells in the organ of Corti and new hair cells adjacent to the organ of Corti in the interdental cell, inner sulcus, and Hensen cell regions. Axons are extended from the bundle of auditory nerve toward some of the new hair cells, suggesting that the new cells attract auditory neurons. We conclude that nonsensory cells in the mature cochlea retain the competence to generate new hair cells after overexpression of Math1 in vivo and that Math1 is necessary and sufficient to direct hair cell differentiation in these mature nonsensory cells.

Correlation between microtia and temporal bone malformation evaluated using grading systems.

OBJECTIVE: To evaluate the relationships between temporal bone abnormalities and the severity of microtia in Japanese patients using objective grading systems. DESIGN: Retrospective case series study conducted between 1992 and 2003. SETTING: Academic, tertiary care, referral medical center. PATIENTS: One hundred forty-two ears of 109 Japanese patients (85 male and 24 female patients; mean age, 12.8 years [range, 2-36 years]) with microtia. MAIN OUTCOME MEASURES: The severity of microtia was classified according to Marx classification. Developmental abnormalities of the temporal bone were evaluated by a computed tomographic (CT) scoring system modified after the system used by Jahrsdoerfer and colleagues, using high-resolution CT scans of the temporal bone. Correlations between the scores obtained from these 2 grading systems were evaluated using a nonparametric statistical method. RESULTS: Male preponderance and incidence of bilateral cases of approximately 30% were observed in our Japanese patients with microtia. There was no significant difference in the severity of microtia between unilateral and bilateral cases. The mean +/- SEM total points in the CT scoring system (full marks, 10) was 7.9 +/- 0.4 for grade I microtia, 6.6 +/- 0.6 for grade II, and 6.4 +/- 0.3 for grade III; the total points correlated inversely with the microtia grade. Development of the auricle correlated significantly with aeration in the middle ear spaces but not with ossicular development or formation of the oval/round windows. Proportion of acceptable surgical candidates according to the CT scoring system (>5 points) was 79% for grade I microtia, 52% for grade II microtia, and 65% for grade III microtia. CONCLUSION: The principle "the better developed the auricle, the better developed middle ear" was confirmed in Japanese patients with microtia; however, even with grade II/III microtia, more than half of the patients were considered suitable for atresia surgery.

Neuro-otologic findings in unilateral isolated narrow internal auditory meatus.

OBJECTIVE: To report neuro-otologic findings concerning the four nerves in the internal auditory meatus (IAM) in patients with isolated congenitally narrow IAM and explore the implications regarding ontogeny of the nerves in the IAM. DESIGN: Retrospective case series study. SETTING: University hospital. SUBJECTS: Five consecutive patients between 1997 and 2002 with unilateral isolated narrow IAM demonstrated by high-resolution computed tomography whose chief complaint was hearing loss (1 male and 4 females, 4 right sides and 1 left; age range 5-37 years, mean 20 years; IAM diameter at the porus: 26-33% of that on the normal side). MAIN OUTCOME MEASURES: Functional studies concerning the VIIth cranial nerve and the three branches of the VIIIth cranial nerve. RESULTS: In all ears, auditory brain stem responses were absent, the speech discrimination score was 0%, and otoacoustic emissions were absent or markedly reduced compared with those on the normal side. Caloric responses were absent in two ears, reduced in two ears, and normal in one ear. Galvanic body sway tests showed no responses in the two ears in which caloric responses were absent. Inferior vestibular nerve function was estimated as normal in all ears on the basis of vestibular evoked myogenic potential recordings. Facial nerve functions were normal in all patients. CONCLUSIONS: In isolated congenital stenosis of IAM, dysfunction of each nerve in the IAM can occur independently. In the ontogeny of the VIIIth cranial nerve, the cochlear and superior vestibular nerves tended to be involved together, whereas the cochlear and inferior vestibular nerves appeared independent of each other.

Vocal cord paralysis after surgery for thoracic aortic aneurysm.

OBJECTIVE: To determine the incidence, etiology, prognosis, and treatment of vocal cord paralysis (VCP) after surgery for thoracic aortic aneurysm (TAA). STUDY DESIGN: Retrospective study performed between 1989 and 1995. SETTING: Academic, tertiary care, referral medical center. PATIENTS: Seventy-one TAA patients underwent surgery at the Kameda Medical Center between 1989 and 1995. RESULTS: Sixty-two of 71 patients were examined postoperatively for voice quality. Twenty patients (32%) had hoarseness develop caused by VCP, as confirmed by laryngoscopy. The left recurrent laryngeal nerve had been sacrificed in 1 patient during surgery, but it was preserved in the remaining 19 patients. Unilateral left VCP was noted in 19 patients, and bilateral VCP occurred in 1 patient. The incidence of VCP was higher in those patients who underwent surgery for type I aneurysms (9 of 14 patients, 64%). In 16 of the 19 patients (84%) who received follow-up for > 6 months, vocal cord movement did not return to normal. Surgery to improve voice quality, arytenoid adduction in five patients and intracordal injection in two patients, was performed with success. CONCLUSIONS: Our results indicate that surgery for TAA is associated with a relatively high incidence of VCP. VCP occurred despite preservation of the recurrent laryngeal nerve, and the paralysis did not show a spontaneous recovery even 6 months after surgery.

Gene transfer into supporting cells of the organ of Corti.

To utilize the rapidly accumulating genetic information for developing new therapeutic technologies for inner ear disease, it is necessary to design technologies for expressing transgenes in the inner ear, especially in the organ of Corti. We examined the outcome of an adenovirus gene transfer into the organ of Corti via the scala media in guinea pigs. The transgene insert is the bacterial lacZ gene driven by a cytomegalovirus promoter. We demonstrate that the inoculation is detrimental to the hair cells that surround the site of inoculation, but the supporting cells in the organ of Corti survive and retain the ability to express the reporter transgene beta-gal. The ability to deliver transgenes that are expressed in the supporting cells is an important step in the development of clinically applicable treatments that involve hair cell regeneration.

The role of the external auditory canal in the development of the malleal manubrium in humans.

OBJECTIVE: To determine if the external auditory canal (EAC) plays a role in the induction and proper positioning of the malleal manubrium in humans. STUDY DESIGN: Retrospective study between 1994 and 2002. SETTING: Academic, tertiary care referral medical center. Patients Fifty-five ears of 50 patients with congenital atresia (n = 47) or stenosis (n = 8) of the EAC, for which meatoplasty was performed at the University hospital between 1994 and 2002. MAIN OUTCOME MEASURES: The presence of the manubrium was examined during surgery, and the corre-lation between the presence of the manubrium and the grade of the microtia was evaluated. RESULTS: The manubrium was identified in all ears with EAC stenosis, whereas it was absent in all ears with EAC atresia. No correlation was observed between manubrium formation and auricular deformity. CONCLUSIONS: Our results demonstrated a close relationship between the formation of the EAC and that of the malleal manubrium in humans. This is consistent with the recent findings in knockout mice. This information is useful for surgical intervention in cases of congenital EAC anomalies.

Total middle ear reconstructive surgery for the radicalized ear.

OBJECTIVE: To evaluate the efficacy of total middle ear reconstructive surgery (TMRS) for patients with open cavity problems. STUDY DESIGN: Retrospective study of patients treated between 1994 and 1997. SETTING: Tertiary care, referral medical center. PATIENTS: Fifty-nine consecutive patients (62 ears) with open cavity problems (draining ears) who underwent TMRS. MAIN OUTCOME MEASURES: Postoperative states of the ears and complications were evaluated in two groups, with and without persistent purulent otorrhea at the time of surgery. RESULTS: In the noninfected group, ears without otorrhea were maintained in 12 (100%) of 12 ears in the short term and 10 (83%) of 12 ears in the long term. In the infected group, the proportions were 40 (80%) of 50 ears and 35 (73%) of 48 ears, for the short and long terms, respectively. Hollowing and/or retraction of the reconstructed canal wall was observed in 1 (8%) of 12 ears of the noninfected group and in 15 (31%) of 48 ears of the infected group after long-term follow-up. Postoperative complications were encountered in 9 ears (14.5%) in the infected group only. CONCLUSIONS: Total middle ear reconstructive surgery is considered useful for the management of persistent discharge from radicalized cavities. It was found important to minimize infection at the time of surgery to achieve satisfactory results.

Use of cartilage plate as tympanic membrane in total middle ear reconstructive surgery for infected radicalized ear.

OBJECTIVE: To evaluate the usefulness of cartilage plates as tympanic membranes combined with total middle ear reconstructive surgery for radicalized ears. STUDY DESIGN: Retrospective study between 1994 and 1999. SETTING: Tertiary care referral medical center. PATIENTS: Seven patients had seven ears with severe chronic otorrhea after radical mastoidectomy. All patients had severe to profound sensorineural hearing loss and expected a trouble-free ear rather than improved hearing after surgery. Patients were followed up for 4 years postoperatively. METHODS: After the middle ear space was cleaned, the tympanic membrane was reconstructed using a plate prepared from the tragal cartilage. The major part of the posterior wall was reconstructed using a conchal cartilage plate. Cortical bone segments were inserted to support the cartilage plate. RESULTS: Preoperatively, cultures of ear discharge were positive for various bacteria. Recovery with dry eardrums was noted in six patients, and one patient showed minimal erosion. No postoperative complications were encountered, but the hearing threshold did not improve postoperatively. CONCLUSIONS: Total middle ear reconstructive surgery is suitable for patients with chronic otorrhea complicating radical mastoidectomy. The use of cartilage plates seems to be clinically appropriate, particularly for patients with severe infection who expect a trouble-free ear rather than hearing gain after surgery.

Induction of growth factor expression is reduced during healing of tympanic membrane perforations in glucocorticoid-treated rats.

The participation of growth factors in wound healing of tympanic membranes (TMs) is established. To determine the possible role of these growth factors in normal healing, we examined the regulation of keratinocyte growth factor (KGF), transforming growth factor-alpha (TGF-alpha), and basic fibroblast growth factor (bFGF) messenger RNA (mRNA) expression in wounded TMs of glucocorticoid-treated rats; these rats have severe wound healing abnormalities. Induction of KGF, TGF-alpha, and bFGF mRNA expression after TM injury was significantly reduced in these rats. Moreover, we found that the average number of bromodeoxyuridine-positive cells in a glucocorticoid-treated group was significantly lower than that in controls. The data suggest that reduced expression of these genes might be partially responsible for the wound healing defects seen in these animals. These results provide a possible explanation for the beneficial effect of exogenous KGF, TGF-alpha, or bFGF in treatment of wound healing disorders of the TM.

Direct application of keratinocyte growth factor, basic fibroblast growth factor and transforming growth factor-alpha during healing of tympanic membrane perforation in glucocorticoid-treated rats.

Peptide growth factors and cytokines modulate both normal and impaired wound healing. Topical application of growth factors in the form of ear drops may counteract impairment of wound healing in the tympanic membrane (TM). We applied keratinocyte growth factor (KGF), transforming growth factor (TGF)-alpha or basic fibroblast growth factor (bFGF) to the perforated TMs of rats in which healing impairment had been caused by systemic administration of a glucocorticoid. Histologic studies of the injured TM, including anti-5-bromo-2'-deoxyuridine immunohistochemistry, were performed on the third day after wounding. In the control ear, epidermal migration was markedly inhibited by glucocorticoid treatment and no hyperplasia was observed in any layer at the perforation edge. TMs treated with KGF showed marked hyperplasia in the epithelial layer at the perforation edge. In the bFGF- and TGF-alpha-treated groups, hyperplasia was observed in the epithelial and intermediate layers of the TM near the malleus handle and annulus, while no hyperplasia was seen in any layer at the perforation edge. Only KGF, therefore, improved epidermal migration in the TM, while all the growth factors tested induced hyperplasia in the TM.

Assessment of total middle ear reconstruction by patient survey correlated with clinical findings.

OBJECTIVE: Our objective was to assess, by patient survey and clinical examination, the results of correctional total middle ear reconstruction of problematic mastoid cavities following radical or modified radical mastoidectomy. SETTING: This study was performed in an academic tertiary referral center. PATIENTS: The study consisted of a retrospective survey, using the modified hearing satisfaction scale, of 50 patients, who had undergone total middle ear reconstruction of their problematic mastoid cavities. The survey results were correlated with their postoperative clinical findings. RESULTS: Postoperatively, 98% of these patients expressed satisfaction in terms of improvement of their preexisting otorrhea (median of 4.32 satisfied), 65% were satisfied with their hearing and 85% were satisfied with the overall of this operation. The survey results had a good correlation with the audiometric findings and the clinical findings, i.e. the surgery resulted in a dry ear in all 50 patients and 51% of these patients showed hearing improvement of more than 5 dBHL. CONCLUSIONS: This study indicates that most patients were satisfied with the outcomes of this operation. The patients' point of view and the postoperative clinical data both indicate that total middle ear reconstruction is an excellent procedure for correcting problematic mastoid cavities following a radical or modified radical mastoidectomy. The hearing satisfaction scale is a useful instrument for assessing patient satisfaction following this surgical procedure.