Harukazu Hiraumi

Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid- resistant sudden sensorineural hearing loss: a prospective clinical trial

BackgroundSudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL.MethodsPatients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy.ResultsIn total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015) at 24 weeks. No serious adverse events were observed.ConclusionsTopical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.

Relief of Post-Tonsillectomy Pain by Release of Lidocaine From Fibrin Glue

Objectives Pain inevitably develops after resection of the palatine tonsil (tonsillectomy). Therefore, we applied a mixture of lidocaine and fibrin glue to the tonsillar fossae immediately after tonsillectomy and evaluated its analgesic effects.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment

BackgroundTo date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.MethodsWe randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events.ResultsIn the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001).ConclusionsThe positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness.Trial registrationUMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

Ectopic Pituitary Adenoma With Malignant Transformation

We report here a case of ectopic pituitary adenoma with malignant transformation after repeated relapses. First, an ectopic pituitary adenoma producing follicle-stimulating hormone was found in the nasal cavity extending to the frontal cranial fossa. Despite repeated surgical resections of the tumor, it recurred three times in 2 years. The tumor gradually showed cellular atypia, mitosis, and necrosis. Immunohistochemical analyses revealed that the expressions of proliferating cell nuclear antigen and MIB-1 increased progressively. Moreover, the expression of p53 was detected at the second recurrence. Finally, at the third recurrence the tumor showed dissemination to the subarachnoid space and multiple metastases in the brain. The patient died of the tumor 10 months after the last resection. These findings indicate that the ectopic pituitary adenoma became malignant. To our knowledge, this is the first report on malignant transformation of ectopic pituitary adenoma. It is important to know that ectopic pituitary adenomas show malignant transformation and that the above parameters (proliferating cell nuclear antigen, MIB-1, and p53) may be useful indicators of the malignant potential of both ectopic and sellar pituitary tumors.

Efficacy of omalizumab in eosinophilic chronic rhinosinusitis patients with asthma

Disclosures: Authors have nothing to disclose. [3] Yesudian PD, Penny M, Azurdia RM, King CM. Ibuprofen-induced acute generalized exanthematous pustulosis. Int J Dermatol. 2004;43:208e210. [4] Rastogi S, Modi M, Dhawan V. Acute localized exanthematous pustulosis (ALEP) caused by Ibuprofen: a case report. Br J Oral Maxillofac Surg. 2009;47: 132e134. [5] Romano A, Torres MJ, Castells M, Sanz ML, Blanca M. Diagnosis and management of drug hypersensitivity reactions. J Allergy Clin Immunol. 2011;127 (3 Suppl):S67eS73. [6] Drew AC, Eusebius NP, Kenins L, de Silva HD, Suphioglu C, Rolland JM, et al. Hypoallergenic variants of the mayor latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol. 2004;173:5872e5879. [7] Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts. Eur J Dermatol. 2010;20:425e433. [8] Torres MJ, Mayorga C, Blanca M. Nonimmediate allergic reactions induced by drugs: pathogenesis and diagnostic tests. J Invest Allergol Clin Immunol. 2009; 19:80e90.

Increased expression of integrin β-4 in papillary thyroid carcinoma with gross lymph node metastasis

Although the prognosis is generally good for patients with papillary thyroid carcinoma, gross nodal metastasis of carcinoma has a poor prognosis. It is necessary to clarify how carcinoma progresses to gross nodal metastasis in order to establish a cure. The adhesion molecule integrin β‐4 is considered to be related to cell migration and metastasis in many carcinomas. In the present study, we examined integrin β‐4 expression in 65 cases of human papillary thyroid carcinoma using immunohistochemical methods. Expression of integrin β‐4 was found in all papillary carcinomas, but in few normal thyrocytes. Interestingly, integrin β‐4 expression in the carcinomas with gross (˘3 cm) lymph node metastasis was significantly higher than that in carcinomas with small (<3 cm) or no lymph node metastasis. These results suggest that integrin β‐4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas.

Transnasal bamboo foreign body lodged in the sphenoid sinus

Transnasal sphenoid sinus foreign body is a rare condition. We report a very rare case of transnasal bamboo foreign body lodged in the sphenoid sinus without damages to the orbital wall or skull base. A 69-year-old man fell down onto a bamboo stick, which snapped after penetrating his face through the right nostril. CT demonstrated that the bamboo stick stuck into the middle meatus, penetrated the ethmoid sinus just medial to the lamina papyracea and reached to the sphenoid sinus. No abnormal findings were detected in the orbit or skull base. The foreign body was removed from the nasal cavity without any complication. The endoscope was useful for evaluating possible injuries in the orbit and skull base and confirming the absence of residual foreign bodies.

A recovery from enhancement of activation in auditory cortex of patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE We previously reported enhanced activation of auditory cortex in patients with bilateral chronic inner-ear hearing loss. To determine whether this enhancement can exhibit a short-term alteration, we measured auditory evoked magnetic fields (AEFs) in patients with idiopathic sudden sensorineural hearing loss (ISSHL) in the acute phase (AP) and recovery phases (RPs). METHODS We recorded AEFs in two unilateral ISSHL patients at three time points (AP, RP1, and RP2) using a whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally to the affected and healthy ear at four different intensities (40-70 dB HL). RESULTS Both patients showed the enhancement of N100 m moment at AP and not at RPs in response to the affected ear stimulation, and stronger N100 m moment in ipsilateral than contralateral hemisphere in response to the healthy ear stimulation at AP. CONCLUSIONS Enhancement of N100 m amplitude occurs in ISSHL patients and disappears on the scale of days. Enhancement of activity in the auditory cortex derived from inner-ear hearing loss can thus exhibit short-term change. SIGNIFICANCE The results of this study provide first evidence for a recovery from enhancement of activation in the auditory cortex following injury of peripheral hearing organ.

Effects of continuous masking noise on tone-evoked magnetic fields in humans

Two different types of steep loudness growth have been reported in detail in psychoacoustical studies but have rarely been evaluated by objective methods in humans. One occurs in inner-ear hearing-impaired patients and is known as loudness recruitment. Another similar phenomenon is observed in healthy subjects with concurrent presence of background noise. Concerning the first type, our previous study using magnetoencephalography (MEG) showed that enhancement of the dipole moment of N100m with increase in stimulus intensity was greater in patients than in normal individuals. However, it is unclear whether the enhancement of activity in auditory cortex will also be detected with background noise in healthy subjects. To elucidate the effects of continuous background noise on tone-evoked cortical activity, we measured auditory-evoked magnetic fields (AEFs) from 7 normal-hearing subjects in two different conditions, with and without 55 dB SPL continuous masking white noise (noise/quiet conditions). The stimuli were 200 ms 1-kHz tones delivered monaurally and randomly at 4 different intensities (40-70 dB SPL) with constant 1-s interstimulus intervals. The N100m increased in amplitude and decreased in latency as a function of stimulus intensity in both noise and quiet conditions. The dipole moment of N100m was significantly smaller in the noise than in the quiet condition, showing that continuous background noise suppresses the strength of tone-evoked cortical responses. The mechanisms underlying these two psychoacoustically similar phenomena of rapid loudness growth thus differ.

Inner ear drug delivery system from the clinical point of view

Abstract Conclusion: Three types of inner ear drug delivery systems (DDS) that were ready to be applied in clinics were developed. Objectives: To develop clinically applicable inner ear DDS for the treatment of inner ear disorders. Methods: Inner ear DDS using clinically applicable materials were developed and evaluated. Results: The systemic application of stealth-type nanoparticles encapsulating betamethasone provided superior therapeutic results for the treatment of noise-induced hearing loss compared with the systemic application of betamethasone in mice. Microparticles made of biodegradable polymer (poly (lactic/glycolic) acid, PLGA) encapsulating lidocaine were placed on the round window membrane of guinea pigs, and resulted in reasonable concentrations of lidocaine in the cochlea without serious adverse effects. The phase I/IIa clinical trial of the application of insulin-like growth factor-1 (IGF-1) in combination with gelatin hydrogel on the round window membrane was conducted, recruiting patients with acute sensorineural hearing loss after the failure of systemic application of steroids.