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1.
Clin Otolaryngol ; 48(6): 895-901, 2023 11.
Article in English | MEDLINE | ID: mdl-37555629

ABSTRACT

OBJECTIVES: To investigate if prophylactic antibiotics (PA) in conjunction with myringoplasty of clean and uninfected ears entails a reduction of postoperative infections within 6 weeks after surgery, and whether it affects the healing rate of the tympanic membrane (TM) at follow-up, 6-24 months after surgery. DESIGN: A retrospective cohort study of prospectively collected data. SETTING: Data extracted from The Swedish Quality Register for Ear Surgery (SwedEar), the years 2013-2019. PARTICIPANTS: All patients in SwedEar with a registered clean conventional myringoplasty (tympanoplasty type I) including a follow-up visit. MAIN OUTCOME MEASURES: The effect of PA use on TM healing rate at follow-up and postoperative infection within 6 weeks of surgery. RESULTS: In the study group (n = 1665) 86.2% had a healed TM at follow-up. There was no significant difference between the groups that had PA administered (87.2%) or not (86.1%). A total of 8.0% had a postoperative infection within 6 weeks. Postoperative infection occurred in 10.2% of the group that received PA (n = 187) compared with 7.7% of the group that did not receive PA. However, this difference was not statistically significant. Postoperative infection within 6 weeks significantly lowered the frequency of healed TMs. CONCLUSION: PA administered during clean conventional myringoplasty does not improve the chance of having a healed TM at follow up, nor decrease the risk of having a postoperative infection within 6 weeks after surgery.


Subject(s)
Anti-Bacterial Agents , Myringoplasty , Surgical Wound Infection , Tympanic Membrane Perforation , Tympanic Membrane , Wound Healing , Humans , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/statistics & numerical data , Cohort Studies , Myringoplasty/adverse effects , Myringoplasty/statistics & numerical data , Registries/statistics & numerical data , Retrospective Studies , Sweden/epidemiology , Treatment Outcome , Tympanic Membrane Perforation/drug therapy , Tympanic Membrane Perforation/epidemiology , Tympanic Membrane Perforation/surgery , Tympanic Membrane/drug effects , Tympanic Membrane/injuries , Tympanic Membrane/surgery , Follow-Up Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Wound Healing/drug effects
2.
Drug Deliv ; 28(1): 1256-1271, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34142922

ABSTRACT

ABSTRACTSOur previous study first investigated feasibility of applying ultrasound (US) and microbubbles (MBs) via external auditory canal to facilitate drug delivery into inner ear. However, most drugs are in aqueous formulae and eliminated via Eustachian tubes after drug application. In this study, feasibility of sustained release of thermosensitive poloxamer 407 (P407)-based MB gel for US mediation-enhanced inner ear drug (dexamethasone, DEX) delivery was investigated. The sol-to-gel transition temperature showed that mixture of DEX and only 10% and 12.5% P407 in MBs can be used for in vitro and in vivo drug delivery experiments. In in vitro Franz diffusion experiments, the release rates of 12.5% P407-MBs + US groups in the model using DEX as the delivered reagent at 3 h resulted in values 1.52 times greater than those of 12.5% P407-MBs groups. In guinea pigs, by filling tympanic bulla with DEX in 12.5% P407-MBs (DEX-P407-MBs), USMB applied at post-treatment days 1 and 7 induced 109.13% and 66.67% increases in DEX delivery efficiencies, respectively, compared to the group without US. On the 28th day after US-mediated P407-MB treatment, the safety assessment showed no significant changes in the hearing thresholds and no damage to the integrity of cochlea or middle ear. These are the first results to demonstrate feasibility of US-modified liquid form DEX-P407-MB cavitation for enhancing permeability of round window membrane. Then, a gel form of DEX-P407-MBs was generated and thus prolonged the release of DEX in middle ear to maintain the therapeutic DEX level in inner ear for at least 7 days.


Subject(s)
Adrenal Cortex Hormones/pharmacokinetics , Dexamethasone/pharmacokinetics , Ear, Inner/metabolism , Microbubbles , Poloxamer/chemistry , Adrenal Cortex Hormones/administration & dosage , Animals , Chemistry, Pharmaceutical , Delayed-Action Preparations , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Drug Carriers/chemistry , Drug Liberation , Ear, Inner/drug effects , Guinea Pigs , Rheology , Tympanic Membrane/drug effects , Tympanic Membrane/metabolism , Ultrasonics
3.
Sci Rep ; 11(1): 5176, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33664323

ABSTRACT

Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.


Subject(s)
Biofilms/drug effects , Ear, Middle/diagnostic imaging , Otitis Media with Effusion/drug therapy , Otitis Media/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Ceftriaxone/pharmacology , Chinchilla/microbiology , Disease Models, Animal , Ear, Middle/drug effects , Ear, Middle/microbiology , Ear, Middle/pathology , Humans , Otitis Media/diagnostic imaging , Otitis Media/microbiology , Otitis Media/pathology , Otitis Media with Effusion/diagnostic imaging , Otitis Media with Effusion/microbiology , Otitis Media with Effusion/pathology , Tomography, Optical Coherence , Tympanic Membrane/drug effects , Tympanic Membrane/microbiology , Tympanic Membrane/pathology
4.
Mol Ther ; 28(12): 2662-2676, 2020 12 02.
Article in English | MEDLINE | ID: mdl-32818431

ABSTRACT

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane injection, and topical tympanic membrane application. We demonstrate, for the first time, that ASOs delivered directly to the ear correct Ush1c expression in inner ear tissue, improve cochlear hair cell transduction currents, restore vestibular afferent irregularity, spontaneous firing rate, and sensitivity to head rotation, and successfully recover hearing thresholds and balance behaviors in USH1C mice. We conclude that local delivery of ASOs to the middle and inner ear reach hair cells and can rescue both hearing and balance. These results also demonstrate the therapeutic potential of ASOs to treat hearing and balance deficits associated with Usher syndrome and other ear diseases.


Subject(s)
Cell Cycle Proteins/genetics , Cytoskeletal Proteins/genetics , Ear, Middle/drug effects , Genetic Therapy/methods , Hair Cells, Auditory/drug effects , Mutation , Oligonucleotides, Antisense/administration & dosage , Usher Syndromes/genetics , Usher Syndromes/therapy , Vestibule, Labyrinth/drug effects , Administration, Topical , Animals , Animals, Newborn , Disease Models, Animal , Female , Gene Knock-In Techniques , Hair Cells, Auditory/metabolism , Hearing/drug effects , Injections , Male , Mice , Mice, Inbred C57BL , Tympanic Membrane/drug effects , Vestibule, Labyrinth/metabolism
5.
Audiol Neurootol ; 25(6): 291-296, 2020.
Article in English | MEDLINE | ID: mdl-32403103

ABSTRACT

INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.


Subject(s)
Dexamethasone/administration & dosage , Evoked Potentials, Auditory, Brain Stem/drug effects , Glucocorticoids/administration & dosage , Hearing Loss, Noise-Induced/drug therapy , Hearing/drug effects , Tympanic Membrane/drug effects , Animals , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Injection, Intratympanic , Male , Rats , Rats, Sprague-Dawley , Treatment Outcome
6.
Laryngoscope ; 130(10): 2455-2460, 2020 10.
Article in English | MEDLINE | ID: mdl-31808957

ABSTRACT

OBJECTIVE: To report audiovestibular outcomes following endolymphatic shunt surgery (ELS) and intratympanic gentamicin injections (ITG) in patients with Meniere's disease (MD). STUDY DESIGN: Retrospective matched cohort study METHODS: Patients with MD refractory to medical management between 2004 and 2017 were reviewed: 44 patients underwent ELS and had outcomes available, while 27 patients underwent ITG and had outcomes available. Mean follow-up durations for the ELS and ITG groups were 39.1 and 43.3 months, respectively. Twenty-six patients from the ELS group and 24 patients from the ITG group were then included in a pretreatment hearing- and age-matched analysis. Main outcome measures were successful control of vertigo, pure-tone average (PTA; 0.5, 1, 2 and 4 kHz), word recognition score (WRS), and treatment complications. RESULTS: A matched analysis showed vertigo control rates of 73.1% in the ELS group and 66.8% in the ITG group, which were not significantly different (P = .760). The change in PTA following treatment was statistically similar between the ELS group (6.2 dB) and ITG group (4.6 dB) (P = .521), while the change in WRS for the ELS group (+3.9 %) was significantly more favorable than the ITG group (-13.6 %) (P = .046). Chronic post-treatment unsteadiness was reported in 25.0% of the ITG group and was not encountered in the ELS group (P = .009). CONCLUSION: ELS provided successful vertigo control at least as well as ITG with a lower incidence of audiovestibular complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2455-2460, 2020.


Subject(s)
Endolymphatic Shunt , Gentamicins/therapeutic use , Meniere Disease/therapy , Protein Synthesis Inhibitors/therapeutic use , Audiometry, Pure-Tone , Female , Gentamicins/administration & dosage , Humans , Male , Middle Aged , Protein Synthesis Inhibitors/administration & dosage , Retrospective Studies , Tympanic Membrane/drug effects
7.
Otolaryngol Head Neck Surg ; 162(2): 204-210, 2020 02.
Article in English | MEDLINE | ID: mdl-31791190

ABSTRACT

OBJECTIVE: Commercial ear drops contain ingredients reported to be inactive. We sought to evaluate such excipients for possible cytotoxicity on human and mouse tympanic membrane (TM) fibroblasts. STUDY DESIGN: Prospective, in vitro. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Mouse and human TM fibroblasts were treated with 1:10 dilutions of benzalkonium chloride (BKC) 0.0025%, 0.006%, or 0.01%; benzyl alcohol 0.9%; polysorbate 80 (PSB) 2.5%; glycerin 2.4%; povidone 0.2%; or water (control), twice within 24 hours or 4 times within 48 hours, for 2 hours each time. Cells were placed back in growth media after the treatments. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed. RESULTS: Mouse fibroblasts had lower survival in only the PSB-treated cells compared to the control (P < .0001) after 24 hours. After 48 hours, PSB killed nearly all mouse fibroblasts (P < .0001). BKC decreased fibroblast survival in a dose-dependent manner (P < .001). In human TM fibroblasts, all excipients except povidone and benzyl alcohol after 24 hours and povidone after 48 hours reduced cell survival compared to control (P = .012 to P < .0001). The cytotoxicity of BKC in human TM fibroblasts was also dose dependent (<.0001). PSB was less cytotoxic to human fibroblasts. Phase-contrast images mirrored the cytotoxicity findings. CONCLUSION: Polysorbate 80 and benzalkonium chloride, at concentrations found in commercial ear drops, may be cytotoxic to human and mouse TM fibroblasts. "Inactive" ingredients may need to be considered when evaluating clinical outcomes with commercial ear drops.


Subject(s)
Excipients/administration & dosage , Quinolones/administration & dosage , Tympanic Membrane/pathology , Animals , Cells, Cultured , Child , Fibroblasts/drug effects , Fibroblasts/pathology , Follow-Up Studies , Humans , Male , Mice , Prospective Studies , Tympanic Membrane/drug effects
8.
Otol Neurotol ; 40(10): 1386-1391, 2019 12.
Article in English | MEDLINE | ID: mdl-31592822

ABSTRACT

HYPOTHESIS: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). BACKGROUND: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. METHODS: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone-all commercial formulations and at standard clinical concentrations-and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. RESULTS: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (p = 0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (p = 0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (p = 0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (p = 0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (p = 0.42). All TMPS were healed at day 42. CONCLUSIONS: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids.


Subject(s)
Ciprofloxacin/adverse effects , Dexamethasone/adverse effects , Neomycin/adverse effects , Ofloxacin/adverse effects , Quinolones/adverse effects , Tympanic Membrane Perforation/chemically induced , Tympanic Membrane/drug effects , Animals , Ciprofloxacin/administration & dosage , Dexamethasone/administration & dosage , Female , Hydrocortisone/administration & dosage , Male , Methylprednisolone Hemisuccinate/analogs & derivatives , Middle Ear Ventilation , Neomycin/administration & dosage , Ofloxacin/administration & dosage , Prostheses and Implants , Quinolones/administration & dosage , Random Allocation , Rats , Rats, Sprague-Dawley
9.
Otol Neurotol ; 40(7): e739-e746, 2019 08.
Article in English | MEDLINE | ID: mdl-31295207

ABSTRACT

HYPOTHESIS AND BACKGROUND: The clinical treatment of sudden sensorineural hearing loss currently relies on the administration of steroids, either systemically or via intratympanic injections. Intratympanic injections bypass the hemato-cochlear barrier, reducing its systemic side effects. The efficacy of the injections is limited through rapid drug clearance via the Eustachian tube, and through nonoptimal properties of slow-release drug carriers. A new slow-release drug delivery vehicle based on hexyl-substituted-poly-lactic-acid (HexPLA), with the highest possible safety profile and complete bio-degradability, has been evaluated for safety and efficacy in a standardized guinea pig model of intratympanic injection. METHODS: A total of 83 animals received through retrobullar injection either empty Nile-red-colored HexPLA vehicle, 5%-dexamethasone-HexPLA, 5%-dexamethasone suspension, or a sham operation. Long-term residence time of vehicle, biocompatibility, click- and pure-tone hearing thresholds, and dexamethasone levels in the perilymph were prospectively assessed. RESULTS: At 1 week after injection, HexPLA vehicle was morphologically present in the middle ear and perilymph levels in the 5%-dexamethasone-HexPLA were on average 2 to 3 µg/ml and one order of magnitude higher compared with those of the 5%-dexamethasone suspension group. No significant postoperative morphological or functional changes were observed up to 3 months postdelivery. CONCLUSIONS: HexPLA is safe, fully biocompatible, and efficient for sustained high-dose, intratympanic delivery of dexamethasone at least for 1 week and therefore of high interest for the treatment of sudden sensorineural hearing loss and other acute inner ear diseases. Due to the favorable chemical properties, a wide range of other drugs can be loaded into the vehicle further increasing its potential value for otological applications.


Subject(s)
Biopolymers/administration & dosage , Dexamethasone/administration & dosage , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/drug therapy , Injection, Intratympanic , Polyesters/administration & dosage , Tympanic Membrane/drug effects , Animals , Delayed-Action Preparations/administration & dosage , Female , Guinea Pigs , Hearing/drug effects , Treatment Outcome
10.
Int J Pediatr Otorhinolaryngol ; 126: 109597, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31351349

ABSTRACT

OBJECTIVES: Myringosclerosis commonly occurs as a long-term complication of ventilation during the treatment of otitis media. We aimed to determine the effects of rosmarinic acid as an antioxidant on experimentally induced myringosclerosis. METHODS: Twenty-four male Sprague-Dawley rats, weighing 250-300 g, were unilaterally myringotomized and randomly separated into three groups. Group 1 received no treatment (control group) (n = 8); Group 2 received topical rosmarinic acid (n = 8); Group 3 received oral rosmarinic acid (n = 8). On the twenty-first day, the right ears were examined by otomicroscope and findings of myringosclerosis were recorded. Finally, all of the rats were euthanized and the tympanic membrane (TM) thickness and the severity of middle ear mucosal inflammation were evaluated histopathologically. RESULTS: The myringosclerosis severity, TM thickness, and inflammation scores were found to be significantly higher in the control group than in the topical and systemic treatment groups (p < 0.05). There were no statistically significant differences in terms of TM thickness and inflammation scores between the topical and systemic treatment groups (p > 0.05). While moderate and severe myringosclerosis were higher in the control group, mild myringosclerosis was found to be higher in both treatment groups. CONCLUSION: The local and oral administration of rosmarinic acid suppressed inflammation, reduced TM thickness, and prevented the development of myringosclerosis in myringotomized rats.


Subject(s)
Antioxidants/therapeutic use , Cinnamates/therapeutic use , Depsides/therapeutic use , Myringosclerosis/prevention & control , Postoperative Complications/prevention & control , Tympanic Membrane/drug effects , Administration, Oral , Administration, Topical , Animals , Antioxidants/pharmacology , Cinnamates/pharmacology , Depsides/pharmacology , Male , Middle Ear Ventilation/adverse effects , Myringosclerosis/etiology , Random Allocation , Rats , Rats, Sprague-Dawley , Treatment Outcome , Tympanic Membrane/pathology , Rosmarinic Acid
11.
Acta Otolaryngol ; 139(7): 598-603, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31050574

ABSTRACT

Background: Inner ear hemorrhage is increasingly recognized as a cochlear lesion that can cause profound sudden sensorineural hearing loss (SSNHL). Objectives: To investigate changes of cochlear and vestibular function and to compare therapeutic recovery from profound SSNHL induced by different etiologies. Material and methods: Eighty patients with profound SSNHL (≥90 dB) were divided into an inner ear hemorrhage group and a non-inner ear hemorrhage group by MRI. Statistical analysis was performed to compare the therapeutic effects from vertigo and hearing loss and the outcomes of follow-up in the two groups. Results: There were significant differences between the two groups in terms of the overall 14-day therapeutic response rate (20 vs. 48%), the incidence of imbalance (26.7 vs. 6%), the incidence of semicircular canal dysfunction on the affected side (60 vs. 20%), the incidence of abnormal C-VEMP and O-VEMP on the affected side (63.3 vs. 38%; and 60 vs. 30%, respectively), the average hearing threshold (74.2 ± 10.7 vs. 53.6 ± 11.4 dB), and the word recognition score (65.5 ± 21.7 vs. 83.5 ± 24.5%) at a 12-month follow-up. Conclusions and significance: A higher percentage of patients with profound SSNHL induced by inner ear hemorrhage were associated with vertigo and had a poor prognosis.


Subject(s)
Glucocorticoids/administration & dosage , Hearing Loss, Sensorineural/diagnostic imaging , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sudden/diagnostic imaging , Hemorrhage/complications , Hyperbaric Oxygenation/methods , Adult , Audiometry , Cohort Studies , Ear, Inner/physiopathology , Female , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sensorineural/therapy , Hearing Loss, Sudden/etiology , Hearing Loss, Sudden/physiopathology , Hearing Loss, Sudden/therapy , Hemorrhage/diagnostic imaging , Hospitals, University , Humans , Injection, Intratympanic , Magnetic Resonance Imaging/methods , Male , Middle Aged , Recovery of Function , Retrospective Studies , Risk Assessment , Severity of Illness Index , Treatment Outcome , Tympanic Membrane/drug effects
12.
J Laryngol Otol ; 133(6): 466-476, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31099325

ABSTRACT

OBJECTIVE: To investigate whether oxytocin can prevent ototoxicity related to acoustic trauma. METHODS: Twenty-eight rats were divided into four groups: noise (group 1), control (group 2), noise plus oxytocin (group 3), and oxytocin (group 4). Intratympanic oxytocin was administered on days 1, 2, 4, 6, 8 and 10 in groups 3 and 4. Groups 1 and 3 were exposed to acoustic trauma. Distortion product otoacoustic emission and auditory brainstem response testing were performed in all groups. RESULTS: In group 1, auditory brainstem response thresholds increased significantly after acoustic trauma. In group 3, auditory brainstem response thresholds increased significantly on day 1 after acoustic trauma, but there were no significant differences between thresholds at baseline and on the 7th and 21st days. In group 1, significant differences were observed between distortion product otoacoustic emission signal-to-noise ratios measured before and on days 1, 7 and 21 after acoustic trauma. In group 3, no significant differences were observed between the distortion product otoacoustic emission signal-to-noise ratios measured before and on days 7 and 21 after acoustic trauma. CONCLUSION: Oxytocin had a therapeutic effect on rats exposed to acoustic trauma in this experiment.


Subject(s)
Hearing Loss, Noise-Induced/drug therapy , Hearing Loss, Noise-Induced/pathology , Oxytocin/pharmacology , Tympanic Membrane/drug effects , Animals , Biopsy, Needle , Disease Models, Animal , Evoked Potentials, Auditory, Brain Stem/drug effects , Hearing Loss, Noise-Induced/diagnosis , Immunohistochemistry , Injections, Intralesional , Male , Otoacoustic Emissions, Spontaneous/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Reference Values , Signal-To-Noise Ratio , Statistics, Nonparametric , Treatment Outcome
13.
Am J Vet Res ; 80(4): 325-334, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30919672

ABSTRACT

OBJECTIVE: To determine whether an enrofloxacin-silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy. ANIMALS: 6 healthy adult New Zealand White rabbits. PROCEDURES: Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears/treatment) and scanning electron microscopic (1 ear/treatment) examination. RESULTS: Most hearing thresholds (11/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to > 95 dB (the upper test limit) in saline solution-treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine.


Subject(s)
Enrofloxacin/toxicity , Silver Sulfadiazine/toxicity , Tympanic Membrane Perforation/drug therapy , Tympanic Membrane/drug effects , Tympanic Membrane/injuries , Animals , Ear, Middle/pathology , Female , Hearing , Humans , Male , Middle Ear Ventilation , Rabbits , Tympanic Membrane/pathology
14.
Acta Otolaryngol ; 139(2): 111-116, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30794063

ABSTRACT

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is commonly encountered in clinical practice. AIM/OBJECTIVE: Determine if local administration of corticosteroids to the inner ear can improve hearing and speech intelligibility after the failure of conventional treatment for SSNHL loss when administered for 10 days after the onset of the hearing loss in a large cohort of 77 patients. MATERIALS AND METHODS: A Silverstein MicroWick™ was placed under local anesthesia and endoscopic control in the round window niche, allowing self-administration of methylprednisolone twice daily for four weeks. RESULTS: An improvement of the pure tone average was shown in 31% of patients. Speech intelligibility improved significantly in 55% of the total cohort and in 34% of the population with a stable pure tone average. Among the 77 patients, 22% used a hearing aid. Only 14% of the patients were hearing-aid users in the group with an improvement in speech intelligibility as opposed to 31% in the failure group. CONCLUSION AND SIGNIFICANCE: Local administration of steroids to the inner ear through the round window route improves hearing and speech intelligibility in patients after failure of conventional therapy. The use of a hearing aid was reduced by 50% when speech intelligibility was improved.


Subject(s)
Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/diagnosis , Hearing Loss, Sudden/drug therapy , Methylprednisolone/therapeutic use , Tympanic Membrane/drug effects , Adult , Audiometry, Pure-Tone , Databases, Factual , Dexamethasone/therapeutic use , Female , Hearing Tests , Humans , Injections, Intralesional , Male , Middle Aged , Prognosis , Reference Values , Retrospective Studies , Risk Assessment , Speech Intelligibility/drug effects , Statistics, Nonparametric , Treatment Outcome
15.
Int J Pharm ; 559: 201-209, 2019 Mar 25.
Article in English | MEDLINE | ID: mdl-30684597

ABSTRACT

Acute otitis media (AOM), an infection in the middle ear, is usually treated through systemic administration of antibiotics because the stratum corneum of the intact tympanic-membrane (TM) possesses low permeability that holds against the ototopical antibiotics use. Therefore, the objective of this work was to encapsulate levofloxacin (LFX) into polyethylene glycol 400 (PEG 400) decorated nanoliposomes (PNLs) as an approach for drug delivery through the intact tympanic-membrane. LFX loaded-PNLs were primed by ethanol injection technique. A 23 full factorial design, using Design-Expert® software, was developed to optimize formulation variables. Particle size, polydispersity index, zeta potential and entrapment efficiency percent of the formulae were determined. The optimal formulation (F7, prepared using 30:1 phospholipid to drug weight ratio, 30 mg cholesterol and 125 mg PEG 400) exhibited improved ex vivo trans-tympanic permeation compared to nanoliposomes lacking PEG 400 and drug solution. In addition, F7 showed greater extent of in vivo deposition of LFX in the intact TM compared to drug solution. Furthermore, in vivo histopathological examination proved the tolerability of the PNLs after ototopical application. Overall, the obtained results revealed that PNLs could be promising for LFX delivery through intact TM providing means for the ototopical drug application for treatment of acute middle ear infections.


Subject(s)
Levofloxacin/administration & dosage , Levofloxacin/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , Otitis Media/drug therapy , Polyethylene Glycols/chemistry , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Drug Delivery Systems/methods , Ear, Middle/drug effects , Male , Nanoparticles/administration & dosage , Particle Size , Permeability/drug effects , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/chemistry , Rabbits , Tympanic Membrane/drug effects
16.
Auris Nasus Larynx ; 46(2): 172-177, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30072162

ABSTRACT

OBJECTIVES: In this experimental study, the effect of hesperidin on the treatment of acute otitis media (AOM) was investigated in an AOM-induced rat model. METHODS: In total, 35 rats were randomly divided into the following five groups (n=7): group 1 (control), group 2 (AOM with no treatment), group 3 (AOM+antibiotic), group 4 (AOM+hesperidin), and group 5 (AOM+hesperidin+antibiotic). On day 14, group 3,4 and 5 rats were given antibiotic and hesperidin via gavages, respectively. Histopathological and immunological analyses were performed and the results analyzed. RESULTS: Serum levels of TNF-α, IL-4, IL-6 and IL-1ß were significantly decreased in the hesperidin- and antibiotic-treated groups compared to the AOM group. The AOM+antibiotic and AOM+hesperidin groups demonstrated reduced histological damage compared to the AOM group. Between the AOM+antibiotic and AOM+hesperidin groups, significant differences in tympanic membrane thickness(ThicTM), inflammation(Inf), and sclerosis(Sc) values were observed. However, no difference in epithelial damage(DamEpith), was seen between the two groups. There was a significant difference in the AOM+antibiotic and AOM+antibiotic+hesperidin groups compared to AOM group (P<0.001). CONCLUSIONS: In this study, we observed that both antibiotic and hesperidin treatment reduced AOM symptoms in an AOM-induced rat model. The values in AOM+antibiotic+hesperidin group were markedly lower than those of the other groups. From our results, we propose that hesperidin, in combination with antibiotics, may provide a successful alternative treatment for AOM compared with antibiotics used alone.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cytokines/drug effects , Hesperidin/pharmacology , Otitis Media/immunology , Tympanic Membrane/drug effects , Acute Disease , Animals , Anti-Bacterial Agents/therapeutic use , Cytokines/immunology , Disease Models, Animal , Drug Therapy, Combination , Epithelium/drug effects , Epithelium/pathology , Hesperidin/therapeutic use , Inflammation , Interleukin-1beta/drug effects , Interleukin-1beta/immunology , Interleukin-4/immunology , Interleukin-6/immunology , Organ Size , Otitis Media/drug therapy , Otitis Media/pathology , Rats , Sclerosis , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/immunology , Tympanic Membrane/pathology
17.
J Int Adv Otol ; 15(1): 22-27, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30541727

ABSTRACT

OBJECTIVES: Topical treatment is first choice in the treatment of uncomplicated chronic otitis media. It was intended to assess auditory and histopathological safety of ototopical use of mercurochrome solution in rats with induced tympanic membrane perforation. MATERIALS AND METHODS: The study was conducted on 21 female Wistar-Albino rats which were randomly assigned into 3 groups. In all rats, perforation was performed at right tympanic membrane. Distortion product otoacoustic emissions (DPOAEs) measurements were performed at frequencies of 2000, 3000 and 4000 Hz (with L1/L2: 70 /70 dB at 2f1-f2 frequency; f2/f1 ratio: 1:22) before recovery from anesthesia and signal-to-noise ratio (SNR) were recorded. Normal saline, 2% mercurochrome and gentamicin were given to group 1, 2 and 3 twice daily over a week, respectively. Rats were sacrificed after DPOAE measurements on day 14. Right temporal bone specimens were examined under light microscope after processing. RESULTS: Based on DPOAE results, there was no significant difference among groups before treatment. On day 14, significant differences were found in DPOAE measurements at 3000 and 4000 Hz, and in mean SNR values in 2% mercurochrome and gentamicin groups when compared to normal saline group while no significant difference was detected at 2000 Hz among groups. In addition, significant degeneration was detected in Corti organs, spiral ganglions and stria vascularis in groups 2 and 3. CONCLUSION: In this study, it was observed that mercurochrome use in external otitis and otitis media with tympanic membrane perforation could cause ototoxicity and concluded that the solution should be used cautiously.


Subject(s)
Hearing/drug effects , Merbromin/adverse effects , Ototoxicity/complications , Tympanic Membrane Perforation/drug therapy , Tympanic Membrane/drug effects , Administration, Topical , Animals , Anti-Bacterial Agents/administration & dosage , Cochlea/drug effects , Cochlea/ultrastructure , Female , Gentamicins/administration & dosage , Merbromin/administration & dosage , Merbromin/therapeutic use , Merbromin/toxicity , Organomercury Compounds/therapeutic use , Otitis Externa/drug therapy , Otitis Media/drug therapy , Perceptual Distortion/drug effects , Rats , Rats, Wistar , Signal-To-Noise Ratio
18.
Otolaryngol Head Neck Surg ; 160(2): 361-363, 2019 02.
Article in English | MEDLINE | ID: mdl-30511891

ABSTRACT

The duration of contact time of intratympanic steroids at the round window is a variable that can potentially affect the ultimate concentration within the cochlea. By placing Gelfoam saturated with dexamethasone directly over the round window, contact time is prolonged and potentially increases the dexamethasone concentration within the cochlea. This technique is simple, readily available with standard instruments and ingredients, and easily done in the office.


Subject(s)
Dexamethasone/administration & dosage , Gelatin Sponge, Absorbable/administration & dosage , Hearing Loss, Sudden/diagnosis , Round Window, Ear/drug effects , Tympanic Membrane/drug effects , Administration, Topical , Aged, 80 and over , Audiometry, Pure-Tone , Female , Follow-Up Studies , Hearing Loss, Sudden/drug therapy , Humans , Instillation, Drug , Male , Middle Aged , Sampling Studies , Treatment Outcome
19.
Int J Pediatr Otorhinolaryngol ; 115: 71-76, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30368398

ABSTRACT

OBJECTIVE: To research the ototoxicity of xylitol after intratympanic injection in mice ear model. METHODS: 24 female mice Balb/c mice (48 ears) included in the study. The mice were divided into 4 groups as 6 mice were found (12 ears) in each group. Solutions of 0.9% NaCl solution (Group A), 155 mg/ml (Group B), 310 mg/ml (Group C) and 620 mg/ml (Group D) xylitol, were applied into the middle ear cavity. Microscopic ear examination and auditory brainstem response test were done for each mouse before application of xylitol and on the 1st, 3rd and 10th day of injection. RESULTS: There are some statistically significant alterations found in the threshold values at 8000, 12000, 16000, 24000 Hz frequencies when each group were compared in itself on day 0, 1,3 and 10, which were independent from the increasing dosage. CONCLUSION: According to our findings intratympanic xylitol injection does not have any ototoxic effect in the inner ear. To evaluate the effects of xylitol more clinical studies are need to carried out.


Subject(s)
Ear Diseases/chemically induced , Tympanic Membrane/drug effects , Xylitol/pharmacology , Animals , Disease Models, Animal , Ear, Inner/drug effects , Ear, Middle/drug effects , Evoked Potentials, Auditory, Brain Stem/drug effects , Female , Injection, Intratympanic , Mice , Mice, Inbred BALB C
20.
J Laryngol Otol ; 132(9): 790-795, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30232949

ABSTRACT

OBJECTIVE: The application of moisture to the ear is anecdotally claimed to relieve the pain from otic barotrauma that can arise during aircraft descent. This claim was tested in a randomised double-blind study on an aircraft with eight participants heavily predisposed to barotrauma. METHODS: On the outward flight, half the participants wore 'active' devices that applied moisture to the external ear; the remainder wore placebo devices that contained no moisture, but were otherwise identical. On the return flight, the groups were reversed. Participants wore the devices from just before descent until landing, unless they experienced symptoms of barotrauma, in which case they switched to what they knew was an active device. RESULTS: There were no significant differences between conditions regarding the appearance of the tympanic membrane on landing or the discomfort levels immediately before and after any switch. CONCLUSION: Applying moisture is ineffective for passengers heavily predisposed to otic barotrauma.


Subject(s)
Barotrauma/epidemiology , Ear, Middle/injuries , Earache/prevention & control , Tympanic Membrane/injuries , Acoustic Impedance Tests/methods , Adult , Aerospace Medicine/methods , Air Travel/statistics & numerical data , Barotrauma/drug therapy , Barotrauma/prevention & control , Double-Blind Method , Ear, Middle/drug effects , Ear, Middle/pathology , Earache/etiology , Female , Health Knowledge, Attitudes, Practice , Humans , Incidence , Male , Middle Aged , Placebos/adverse effects , Severity of Illness Index , Treatment Outcome , Tympanic Membrane/drug effects , Tympanic Membrane/pathology
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