Suppression of the vestibular short-latency evoked potential by electrical stimulation of the central vestibular system.

In an attempt to view the effects of the efferent vestibular system (EVS) on peripheral dynamic vestibular function, we have monitored the Vestibular short-latency Evoked Potential (VsEP) evoked by pulses of bone conducted vibration during electrical stimulation of the EVS neurons near the floor of the fourth ventricle in the brainstem of anesthetized guinea pigs. Given the reported effects of EVS on primary afferent activity, we hypothesized that EVS stimulation would cause a slight reduction in the VsEP amplitude. Our results show a substantial (>50%) suppression of the VsEP, occurring immediately after a single EVS current pulse. The effect could not be blocked by cholinergic drugs which have been shown to block efferent-mediated vestibular effects. Shocks produced a short-latency P1-N1 response immediately after the electrical artifact which correlated closely to the VsEP suppression. Ultimately, we have identified that this suppression results from antidromic blockade of the afferent response (the VsEP). It would appear that this effect is unavoidable for EVS stimulation, as we found no other effects.

Development of a SiYAlON glaze for improved osteoconductivity of implantable medical devices.

The application of bioactive coatings onto orthopaedic appliances is commonly performed to compensate for the otherwise bioinert nature of medical devices and to improve their osseointegration. Calcium phosphates, hydroxyapatite (HAp), and bioglasses are commercially available for this purpose. Until recently, few other inorganic compounds have been identified with similar biofunctionality. However, silicon nitride (Si3 N4 ) has emerged as a new orthopaedic material whose unique surface chemistry also enhances osteoconductivity. Recent research has confirmed that its minority intergranular phase, consisting of silicon yttrium aluminum oxynitride (SiYAlON), is principally responsible for this improvement. As a result, it was hypothesized that SiYAlON itself might serve as an effective osteoconductive coating or glaze for medical devices. To test this hypothesis, a process inspired by traditional ceramic whiteware glazing was developed. A slurry containing ingredients similar to the intergranular SiYAlON composition was applied to a Si3 N4 surface, which was then subjected to a heat treatment to form a glaze. Various analytical tools were employed to assess its chemistry and morphology. It was found that the glaze was comprised predominately of Y5 Si3 O12 N, a compound commonly referred to as N-apatite, which is isostructural to native HAp. Subsequent exposure of the glazed surface to acellular simulated body fluid led to increased deposition of biomimetic HAp-like crystals, while exposure to Saos-2 osteosarcoma cells in vitro resulted in greater HAp deposition relative to control samples. The observation that SiYAlON exhibits enhanced osteoconductivity portends its potential as a therapeutic aid in bone and tissue repair. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1084-1096, 2018.

Hearing Assessment after Treatment of Nasopharyngeal Carcinoma with CRT and IMRT Techniques.

OBJECTIVES: This study analyzed the long-term hearing loss after treatment of primary nasopharyngeal carcinoma to elucidate its causal factors. METHODS: Ninety-two nasopharyngeal carcinoma patients were treated with radiotherapy or chemoradiotherapy. Pure tone audiometry was performed before the therapy and annually up to 9 years after completing treatment. The hearing thresholds were corrected for age-related deterioration and compared to the results without adjusting for age. RESULTS: The mean air and bone conduction threshold with and without correction for age-related deterioration differed significantly 2-9 years after completing radiotherapy (p < 0.05). The audiometry results with age correction showed a flattened configuration compared to the results without age correction. The total radiation dose and radiation modality showed a causal relationship with a greater incidence of hearing loss after therapy (p < 0.05). There was more deterioration in the air and bone hearing thresholds with conformal radiotherapy than intensity-modulated radiotherapy (p < 0.001). A radiation dose >72 cGy resulted in more severe hearing loss than <72 cGy (p < 0.05). CONCLUSION: Hearing loss after completing therapy should be corrected for age-related hearing deterioration to reveal the true extent to which the loss is a therapeutic complication. Both the radiation modality used and the dose were significantly associated with hearing loss.

Cochlear effects of intraoperative use of Mesna in cholesteatoma surgery.

BACKGROUND AND AIM OF THE WORK: Mesna is thiol compound proposed as chemical dissector in otolaryngologic surgery. The aim of this study was to address the issue of possible ototoxicity from topical administration of MESNA into the middle ear during otologic surgery. METHODS: Audiological findings of patients (n=55) who underwent canal wall up tympanomastoidectomy with the ancillary use of Mesna in 1-year period were retrospectively reviewed. We identified another set of 51 patients who had undergone otologic surgery without the use of Mesna to serve as a control group. Preoperative and postoperative mean bone conduction thresholds were calculated and compared between the two groups for the frequencies of 500,1000,2000, and 3000; 4000 and 8000 Hz were further analyzed to search for high-frequency sensorineural hearing loss. RESULTS: Fifty-five patients were operated on with the ancillary use of Mesna and 51 underwent surgery with traditional mechanical dissection alone. When mean preoperative bone conduction values were compared with postoperative values, no significant differences were found for any of the frequencies tested in both groups. Analyzing changes in bone conduction at 4000 and 8000 Hz a slight worsening was observed in both groups. CONCLUSIONS: We found no difference in hearing thresholds between the treatment and control groups. Thus, the results of this study confirmed data obtained in laboratory animal models demonstrating that intraoperative use of Mesna in middle ear surgery is safe and does not lead to ototoxic effects.

Ototoxicity of polymyxin B, neomycin, and hydrocortisone suspension in tympanoplasty surgery.

OBJECTIVES: (1) To determine the safety of using a commercially available suspension of polymyxin B, neomycin, and hydrocortisone (PNH) in tympanoplasty surgery. (2) To apply evidence-based medicine to tympanoplasty surgery when considering potential ototoxicity. STUDY DESIGN: Case series with chart review. SETTING: Tertiary otology practice, single surgeon. METHODS: Approval for this study was obtained from the St. Dominic-Jackson Memorial Hospital Institutional Review Board. Data were gathered on 272 consecutive type 1, underlay tympanoplasties for which both pre- and postoperative audiometric data were available over a 10-year period. In each surgery, gelatin sponge saturated in a commercially available PNH suspension was placed in the middle ear to support the graft. Patients ranged in age from 3 years to 79 years. Preoperative and postoperative bone conduction thresholds were measured at 500, 1000, 2000, 3000, and 4000 Hz. RESULTS: The average change in sensorineural hearing as measured by bone conduction thresholds was negligible, with a slight improvement in all frequencies tested except 4000 Hz. The changes by frequencies were as follows: 500 Hz (-1.624 dB), 1000 Hz (-1.399 dB), 2000 Hz (-0.975 dB), 3000 Hz (-0.596 dB), and 4000 Hz (+0.560 dB). The 5-frequency average change was -0.545 dB. CONCLUSIONS: The commonly used otic solution containing polymyxin B, neomycin, and hydrocortisone demonstrates no ototoxicity in tympanoplasty surgery and is safe to use in this setting.

Roles of an anti-tuberculosis medication and surgery in patients with tuberculous otitis media.

CONCLUSION: The standard treatment for tuberculous otitis media (TOM) without complications consists of anti-tuberculosis (anti-TB) medication, with which we experienced good treatment outcomes. However, surgery is required for recovery of anatomy and hearing function. OBJECTIVE: To determine the clinical characteristics of TOM that might optimize diagnosis and to evaluate the differences in clinical courses between patients treated with and without surgery. METHODS: We analyzed 14 patients (16 ears) who had been diagnosed and treated for TOM. Radiologic findings, laboratory data, and audiometry results were also evaluated. Patients were divided into a chemotherapy group and a surgery group according to treatment modality. RESULTS: Temporal bone CT (TBCT) showed total occupation of the tympanic cavity by soft tissue and little evidence of ossicular erosion. In the chemotherapy group, dry ears were obtained in all but one patient (14 ears) after treatment. Normalized tympanic membrane (TM) was found in 50% in the chemotherapy group and in 75% in the surgery group. The air-bone gap (ABG) changed from 40.3 +/- 2.5 dB to 47.0 +/- 19.2 dB in the chemotherapy group and from 35.2 +/- 7.6 dB to 30.2 +/- 11.4 dB in the surgery group. After treatment, ABG improved by > 10 dB in one ear in the chemotherapy group and in four ears in the surgery group.

Tissue response around silicon nitride implants in rabbits.

The chemical and dimensional stability associated with suitable fracture toughness and propitious tribological characteristics make silicon nitride-based ceramics potential candidates for biomedical applications, mainly as orthopedic implants. Considering this combination of properties, silicon nitride components were investigated in relation to their biocompatibility. For this study, two cylindrical implants were installed in each tibia of five rabbits and were kept in the animals for 8 weeks. During the healing time, tissue tracers were administrated in the animals so as to evaluate the bone growth around the implants. Eight weeks after the surgery, the animals were euthanized and histological analyses were performed. No adverse reactions were observed close to the implant. The osteogenesis process occurred during the entire period defined by the tracers. However, this process occurred more intensely 4 weeks after the surgery. In addition, the histological analyses showed that bone growth occurred preferentially in the cortical areas. Different kinds of tissue were identified on the implant surface, characterized by lamellar bone tissue containing osteocytes and osteons, by a noncalcified matrix containing osteoblasts, or by the presence of collagen III, which may change to collagen I or remain as a fibrous tissue. The results demonstrated that silicon nitride obtained according to the procedure proposed in this research is a biocompatible material.

Preliminary experience with beta-tricalcium phosphate for use in mastoid cavity obliteration after mastoidectomy.

OBJECTIVE: To examine the efficacy and safety of mastoid cavity obliteration using highly purified beta-tricalcium phosphate (beta-TCP) after mastoidectomy in middle ear surgery. PATIENTS: Thirteen patients with cholesteatoma invading the mastoid cavity or showing severe pathologic changes in the mastoid cavity. INTERVENTION: Twelve patients underwent mastoid obliteration with highly purified beta-TCP during the first- and/or second-stage operation of a 2-stage canal-up operation: 5 patients during the first and second stages, and 7 patients during the second stage only. One patient with cholesteatoma underwent mastoid obliteration with highly purified beta-TCP during a 1-stage canal-up operation. In total, beta-TCP was applied in 18 ear operations. MAIN OUTCOME MEASURES: All patients underwent multislice computed tomography (CT) before and after surgery to assess the condition of the middle ear. The amount of residual beta-TCP granules in the mastoid cavity was assessed using the following granular shadow grading scale: Grade 0, no granular shadow in the mastoid cavity; Grade 1, residual granular shadows in part of the mastoid cavity; and Grade 2, granular shadows in most of the mastoid cavity. To assess any harmful effect of beta-TCP implanted in the mastoid cavity, continuous postoperative discharge and delayed wound healing were recorded. In addition, the bone conduction threshold was assessed using pure-tone audiometry, and the patients were asked whether they experienced vertigo or dizziness during the postoperative follow-up. RESULTS: All the patients who underwent multislice CT less than 11.4 months after mastoid cavity obliteration with beta-TCP were Grade 2 on the granular shadow grading scale, whereas all those who underwent multislice CT more than 53.8 months after mastoid obliteration were Grade 0. No patient had continuous postoperative discharge, delayed wound healing, or extrusion of beta-TCP granules. No patient showed deterioration of the bone conduction threshold more than 10 dB after mastoid cavity obliteration with highly purified beta-TCP or complained of postoperative vertigo or dizziness. CONCLUSION: Highly purified beta-TCP may be safe and reliable for mastoid obliteration. Highly purified beta-TCP may also be useful in other surgical procedures, including posterior wall reconstruction of the external auditory canal and scutum plasty.

Treatment of idiopathic hyperphosphatasia with intensive bisphosphonate therapy.

UNLABELLED: In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability. INTRODUCTION: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy. MATERIALS AND METHODS: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored. RESULTS: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1-3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p < 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from -2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis. CONCLUSIONS: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization.

[Recovery of hearing: results of delayed medical treatment in patients with idiopathic sudden hearing loss]. / Erholung der Hörschwelle bei verzögert einsetzender Therapie des Hörsturzes.

For the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL), a variety of studies about intravenous drug administration with the beginning of treatment in the early period of less then one week after the onset of hearing loss have been performed. In contrast, very little information is available about the efficacy of intravenous drug therapy for ISSNHL with the beginning of treatment later than four weeks after the onset of hearing loss. In a retrospective chart review we studied the treatment results of 57 patients with ISSNHL with beginning of treatment later than four weeks after the onset of hearing loss with no spontaneous recovery of hearing. Patients received a treatment with intravenous administration of Dextran (concentration 40 g/l with NaCl 0.9%) and Procain-HCl (a derivative of the local anaesthetic lidocaine,400-800 mg in a 500 ml rheologic infusion of Dextran 40). 25% of the patients showed a significant improvement of 10 dB or more in hearing threshold at 1000 Hz measured in bone-conducted pure tone audiometry. In a subjective evaluation 53% of the patients noticed a subjective improvement of their individual hearing thresholds.

Fluoride therapy for cochlear otosclerosis? an audiometric and computerized tomography evaluation.

The progress of sensorineural hearing loss (SNHL) in patients with cochlear otosclerosis was compared for 19 patients treated with fluoride for 1-5 years and 22 untreated controls. CT scans of eight patients before and after fluoride treatment were evaluated visually. Fluoride therapy arrested the progression of SNHL in the low (250, 500 and 1,000 Hz) (p < 0.001) and high (2 and 4 kHz) (p = 0.008) frequencies. It seemed to be more effective for the higher frequencies in cases with an initial SNHL of < 50 dB. Fluoride administration for 4 years did not seem to be superior to a shorter treatment period (1-2 years). For six patients followed up after discontinuing fluoride therapy there was minimal deterioration in SNHL. There was no clear relationship between the size and site of otospongiotic lesions on CT and the severity of SNHL. Follow-up with CT evaluation did not provide reliable information as to the efficacy of fluoride therapy.

[Local antibiotic administration decreases risk of inner ear damage in effodation]. / Lokale Antibiotika-Applikation verringert das Risiko einer Innenohrschädigung bei Effodation.

BACKGROUND: Mobilising the stapes via the removal of the tympanosclerotic plaques from the oval window niche (effodation) and stapedectomy or malleovestibulopexy are the different procedures generally available for the surgical therapy of stapes fixation due to tympanosclerosis. These techniques bear a significant risk of sensory hearing loss. Here we analyse our results using the mobilisation technique together with locally applied antibiotics. PATIENTS: Nineteen ears in seventeen patients with tympanosclerosis involving the stapes and its footplate which underwent stapes mobilisation between 1991 and 1999 have been investigated retrospectively. According to the literature this operation has a high risk of cochlear hearing loss. To reduce this risk, azlocillin was instilled locally during removal of tympanosclerotic plaques. RESULTS: Different operation techniques have been used: classic type III with placement of a cartilage disc on the head of the stapes (4), interposition of the incus (3), interposition of the head of malleus (1), interposition of a ceramic-PORP (6) and cartilage columella in cases of significant stapes footplate erosion (3). In two operations the chain was intact and no reconstruction was necessary. Pure-tone-audiometry showed no significant decrease of bone-conduction thresholds. Preoperatively 4 (21.1%) ears had an average air-bone-gap < or = 30 dB, while postoperatively 15 (78.9%) ears had this level of hearing. CONCLUSIONS: Until the exact causes of the loss of hearing after mobilisation or stapedectomy in cases of tympanosclerosis are known, the local administration of antibiotics is certainly recommended, bearing in mind the initial hypothesis that infection may be jointly responsible for cochlear hearing loss on mobilisation or stapedectomy in cases of tympanosclerosis.

[Combined use of rhBMP2/BCB and free periosteum in repairing segmental defects in radii of rabbits].

OBJECTIVE: To study the efficacy of combined use of rhBMP2/BCBand free periosteal graft in repairing segmental bony defects. METHODS: A new grafting material (rhBMP2/BCB) was made by combining recombinant human BMP2 (rhBMP2) and an antigen-free bovine cancellous bone (BCB) as a carrier. rhBMP2/BCB was used alone in conjunction with free periosteal graft to repair a 1.5 cm defect in the radius of the rabbit. The defect-repairing capability for each of the treatment modalities was assessed radiographically, biomechanically, and by densitometry and histological studies. RESULTS: rhBMP2/BCB used alone was capable of healing the defect in large by 16 weeks, with a similar repair process and mechanism seen with RBX. Combined use of rhBMP2/BCB and free periosteal graft was superior in terms of increased amount and quality of the new bone formed at the early stage of the repair process (within 12 weeks) to rhBMP2/BCB used in isolation, with the defect basically healed by 12 weeks. CONCLUSIONS: Both methods are effective in repairing segmental bony defects, with rhBMP2/BCB used in conjunction with free periosteal graft being most preferred, considering the satisfactory osteogenesis, osteoconduction and osteoinduction.

Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy.

Little is known about cisplatin ototoxicity in pediatric patients. Measurement of otoacoustic emissions is a rapid, reproducible, objective method of evaluating hearing. We examined whether transient-evoked otoacoustic emissions in pediatric patients exposed to cisplatin in the past correlated with audiographic findings. Twelve patients were entered into the study (mean age at treatment 7.8 years, mean cumulative dose 442.5 mg/mm2, mean 7.1 doses). Hearing at 3000 Hz was preserved in 82.6% of patients. In the higher frequencies significant sensorineural hearing loss was noted: 43.5% at 4 kHz; 81.0% at 6 kHz; and 90.5% at 8 kHz. Transient-evoked otoacoustic emissions were measurable in 11 of 12 patients. Middle ear disease accounted for abnormal otoacoustic emission seen in three patients (1 with effusion, 2 with significant negative middle ear pressure). When the middle ear was normal, a statistically significant correlation was seen between the transient-evoked otoacoustic emissions reproducibility and pure-tone threshold (correlation coefficient = -0.69, p = 0.008). Increased hearing loss was also associated with young age at first dose of cisplatin (p = 0.044), high number of chemotherapy cycles (p = 0.042), and high cumulative dose (p = 0.042).

Intratympanic gentamicin treatment for Meniere's disease.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of a modified intratympanic gentamicin technique in patients with intractable unilateral or bilateral Meniere's disease. METHODS: A retrospective review of 25 consecutive patients who underwent gentamicin treatment for Meniere's disease was conducted between 1992 and 1996. Two separate delivery systems were used during this study, with the last 13 subjects undergoing placement of the new system (flanged polyethylene tubing). RESULTS: Follow-up averaged 23 months. Absence of vertigo spells was reported in 88%, and substantial control was achieved in 12%. Four of five patients with bilateral disease achieved complete control. Results for the two delivery systems were not significantly different. Absence of ice-water caloric response was seen in 75% (15 of 20) patients. Clinically significant sensorineural hearing loss occurred in 5 (20%) of 25 ears. Nonserviceable hearing developed in only two (8%) patients. CONCLUSIONS: Our results support the previously reported efficacy and relative safety of gentamicin infusion therapy for intractable Meniere's disease. Polyethylene tubing may be more advantageous than T-tube delivery because of anatomic concerns in certain patients.

[Hearing loss caused by high dose carboplatin therapy]. / Hörverlust durch Hochdosis-Carboplatintherapie.

BACKGROUND: Carboplatin is regarded as a non-ototoxic or low-grade ototoxic chemotherapeutic agent. METHOD: We report on three patients with a recurrence of testicular cancer after cisplatin chemotherapy who suffered hearing loss after subsequent high-dose carboplatin therapy. RESULTS: Audiometry demonstrated carboplatin-induced hearing loss primarily in the mid-range and high frequencies up to 45 dB at 3 kHz and up to 55 dB at 8 kHz. In two of three patients, transitory-evoked otoacoustic emissions were absent after carboplatin therapy. CONCLUSION: Following first-line cisplatin chemotherapy, salvage treatment with high-dose carboplatin can generate hearing loss in the middle and high frequencies.

The influence of fluoridation of drinking water on the long-term hearing results of stapedectomy.

The long-term hearing results of stapedectomy were assessed in 294 patients with otosclerosis living in an area where the natural waters have a very low fluoride content. Only patients with an initially successful outcome were included. Patients having an additional known cause of hearing loss were excluded. The mean follow-up period was 9 yr. From the best hearing levels achieved 6 to 12 months after surgery, the mean air conduction thresholds showed an annual impairment of 0.4 to 1.1 dB/year and bone conduction thresholds an annual impairment of 0.5 to 1.0 dB/year. There was no significant difference between patients drinking fluoridated tap water and those drinking low-fluoride water. It is concluded that a daily sodium fluoride intake of 1 to 3 mg in a low-fluoride area is too small to have a significant effect on hearing impairment after stapedectomy.

[Possibilities for preserving hearing in labyrinth fistulas of different degrees of severity]. / Möglichkeiten des Hörerhalts bei Labyrinth-Fisteln von unterschiedlichem Schweregrad.

The labyrinthine fistula continues to be one of the most common complications in ears with cholesteatoma. Fifty-one patients with labyrinthine fistula were identified in a series of 1243 cases with cholesteatoma operated upon between 1989 and 1993 at the University ENT Clinic Wuerzburg. The surgical management concept comprised of removing the cholesteatoma matrix, categorizing the fistula type, and immediate covering of the labyrinthine capsule defect with bone dust, perichondrium and fibrin glue. The classification system of the fistulae used in the study used the depth of labyrinthine involvement as a criterion and also took into account the possibility of intentional or accidental damage to the labyrinth during surgical manipulation (Fig. 1). From 1991 on, patients were treated with 500 mg of Presnisolon 21 hydrogen succinate in a single intravenous dose, at the time the fistula was corrected. The postoperative hearing results were graded based on the extend of preservation of inner ear function at or near the preoperative level. None of the patients who had corticosteroid therapy suffered a profound sensory neural hearing loss (Fig. 2, 3), whereas five ears without steroids and a deep fistula lost function completely. The study concluded that corticosteroids have a beneficial impact on postoperative outcome in cases with severe injury to the membranous labyrinth.

Osteoconductive properties of methylpyrrolidinone chitosan in an animal model.

Bone defects were surgically produced in the tibiae of rabbits and medicated with freeze-dried methylpyrrolidinone chitosan. Histological observations 60 d after surgery showed a considerable presence of neoformed bone tissue, as opposed to controls, originating from the pre-existing bone as well as from the periosteum. The cationic nature and the chelating ability of the methylpyrrolidinone chitosan apparently favoured mineralization. Endosteal-periosteal and bone marrow osteoblast-like precursors, stimulated by growth factors entrapped in the coagulum-polysaccharide mixture, gave rise to intramembranous bone formation. The ultrastructural examination evidenced that bone osteoid was followed by mineralization of the tissue.