Treatment Of Middle Ear Disease Research Articles

Inhibition of TGF-β signaling enables long-term proliferation of mouse primary epithelial stem/progenitor cells of the tympanic membrane and the middle ear mucosa

The surface of the middle ear is composed of the tympanic membrane (TM) and the middle ear mucosa (MEM). A number of diseases and conditions such as otitis media, middle ear cholesteatoma, and perforation of the TM have been reported to cause dysfunction of the middle ear, ultimately leading to high-frequency hearing loss. Despite its importance in repairing the damaged tissues, the stem/progenitor cells of the TM and the MEM epithelia remains largely uncharacterized due, in part, to the lack of an optimal methodology to expand and maintain stem/progenitor cells long-term. Here, we show that suppression of TGF-β signaling in a low Ca2+ condition enables long-term proliferation of p63-positive epithelial stem/progenitor cells of the TM and the MEM while avoiding their malignant transformation. Indeed, our data show that the expanded TM and MEM stem/progenitor cells respond to Ca2+ stimulation and differentiate into the mature epithelial cell lineages marked by cytokeratin (CK) 1/8/18 or Bpifa1, respectively. These results will allow us to expand epithelial stem/progenitor cells of the TM and MEM in quantity for large-scale analyses and will enhance the use of mouse models in developing stem cell-mediated therapeutic strategies for the treatment of middle ear diseases and conditions.

Clinical retrospective study on the efficacy and safety of endoscopic ear surgery for adhesive otitis media

Currently, the optimum surgical approach for treating adherent otitis media is debatable. The traditional treatment is usually performed by microscopic tympanoplasty combined with temporal myofascial tympanic tube placement. In recent years, the application of whole ear endoscopic surgery in the treatment of middle ear diseases has gradually increased, otoendoscopy has been used in the operation of adhesive otitis media, but its safety and effectiveness are still controversial. This study retrospectively analyzed 17 patients with adhesive otitis media treated by endoscopic ear surgery (EES) in our hospital from January 2018 to July 2021 over a 6-month period post-surgery. Of the 17 patients, 8 were males and 9 were females (mean age, 53 years; age range, 24-70 years). There were 12 and 5 cases of adhesive otitis media involving the left and right ear, respectively. The patients had follow-up evaluations 1 week, 2 weeks, 1 month, 3 months, and 6 months after surgery. A total of 17 patients with adhesive otitis were enrolled, including 1 patient with Dornhoffer stage II; 6 patients with stage III; and 10 patients with stage IV. Adhesive otitis media was combined with middle ear cholesteatoma in 4 patients (24%). Fourteen patients (82%) had disruption or interruption of the ossicular chain (8 malleus, 14 incus, and 4 stapes lesions), 11 of whom had artificial ossicular chain reconstruction [8 with partial ossicular reconstruction prosthesis (PORP) and 3 with total ossicular reconstruction prosthesis (TORP) implantation]. All patients had good tympanic membrane and graft morphology, no invaginations, and no perforations. The mean postoperative air-conduction hearing threshold [49.06±22.15 dB hearing level (dB HL)] and mean air-bone gap (19.94±10.00 dB HL) were significantly improved compared with the preoperative values (65.29±21.53 and 32.53±8.21 dB HL, respectively; P<0.05). No recurrences, secondary cholesteatomas, or secondary surgeries were reported. EES seems to be a safe and effective surgical method for the management of adhesive otitis media. The study has limitations due to its small sample size and lack of controlled studies. It still needs to be proven in clinical randomized controlled trials.

Evaluation of age-related changes in middle-ear structures by wideband tympanometry

Background Presbycusis is bilateral sensorineural hearing loss associated with the progressive degeneration of cochlear and central auditory pathways with aging. Aims/Objectives We aimed to reveal age-related changes in middle ear function by using wideband tympanometry (WBT). Materials and Methods Fifty-eight patients diagnosed with presbycusis were compared to 52 audiologically healthy participants. WBT measurement was performed on both ears via wideband click stimulus with a tympanometer device using probe tone frequencies of 226–8000 Hz. Results There were no statistically significant differences detected among the resonance frequencies or maximum absorbance ratios measured in both ears between groups (p > .05). The mean absorbance of the right and left ears at 4000 and 8000 Hz was statistically higher in the patient group than in the healthy controls (r = 0.038, 0.030; l = 0.015, 0.012). Moreover, mean compliance values were found to be significantly lower in the patient group than in the control group (r = 0.030 and l = 0.040). Conclusion The significant differences detected in compliance and absorbance values for high frequencies in presbycusis patients were remarkable. Thus, it has been shown that WBT yields an advantage compared to traditional tympanometry in the diagnosis and treatment of middle ear diseases.

Non-Typeable Haemophilus influenzae Infection of the Junbo Mouse.

Acute otitis media, inflammation of the middle ear bulla, is the most common bacterial infection in children. For one of the principal otopathogens, non-typeable Haemophilus influenzae (NTHi), animal models allow us to investigate host-microbial interactions relevant to the onset and progression of infection and to study treatment of middle ear disease. We have established a robust model of NTHi middle ear infection in the Junbo mouse. Intranasal inoculation with NTHi produces high rates of bulla infection and high bacterial titers in bulla fluids; bacteria can also spread down the respiratory tract to the mouse lung. An innate immune response is detected in the bulla of Junbo mice following NTHi infection, and bacteria are maintained in some ears at least up to day 56 post-inoculation. The Junbo/NTHi infection model facilitates studies on bacterial pathogenesis and antimicrobial intervention regimens and vaccines for better treatment and prevention of NTHi middle ear infection. © 2017 by John Wiley & Sons, Inc.

The clinical and radiological status of contralateral ears in unilateral cholesteatoma patients

To evaluate the clinical and radiological features and the risk of middle ear disease in the contralateral ears of unilateral cholesteatoma with clinical and radiological assessment. Fifty-two patients with unilateral cholesteatoma and 30 control subjects underwent otoscopic and audiologic examination. Temporal bone computed tomography was performed to evaluate the pneumatization of the temporal bones, the status of anterior epitympanic space and eustachian tube. Then, the parameters of the temporal bone pneumatization were calculated. 28% of the contralateral ears in the cholesteatoma patients showed abnormal tympanic membrane findings. In the audiologic examination, 10% of the contralateral ears showed moderate hearing loss and 3% showed severe hearing loss. Aeration areas were 1.81 ± 1.01, 2.50 ± 1.31 and 4.49 ± 1.45 cm(2), aeration ratios were 24, 28 and 42%, in cholesteatoma, contralateral and control ears, respectively. Development of the anterior epitympanic space and eustachian tube patency was reduced in contralateral ears relative to control ears. The degree of temporal bone pneumatization, eustachian tube function, and development of the anterior epitympanic space are significantly decreased in the contralateral ears of unilateral cholesteatoma patients, and there is an increased risk of middle ear diseases. Continuous monitoring of the contralateral ear is crucial for early detection and optimal treatment of middle ear disease.

Pneumocephalus Due to Middle Ear Inflation

Middle ear inflation procedures are widely used for diagnosis and treatment of middle ear disease. Although its values are controversial, it is used in testing eustachian tube function or treating middle ear diseases, such as effusions or atelectasis. Physicians rarely experience complications with this procedure; thus, complications following middle ear inflation are rare. Known adverse effects of middle ear inflation procedures include pneumocele, brain hematoma, and air embolization. Pneumocephalus is one of the rare complications of middle ear inflation. It is a potentially fatal condition, and although middle ear inflation is used around the world, it is rarely encountered by general physicians and even otolaryngologists. We report a case of pneumocephalus that occurred immediately following a middle ear inflation procedure using a pneumatic otoscope with myringotomy (paracentesis).

Aural Cholesteatoma in Twenty Dogs

To determine the clinical course in dogs with aural cholesteatoma. Case series. Dogs (n=20) with aural cholesteatoma. Case review (1998-2007). Twenty dogs were identified. Clinical signs other than those of chronic otitis externa included head tilt (6 dogs), unilateral facial palsy (4), pain on opening or inability to open the mouth (4), and ataxia (3). Computed tomography (CT) was performed in 19 dogs, abnormalities included osteoproliferation (13 dogs), lysis of the bulla (12), expansion of the bulla (11), bone lysis in the squamous or petrosal portion of the temporal bone (4) and enlargement of associated lymph nodes (7). Nineteen dogs had total ear canal ablation-lateral bulla osteotomy or ventral bulla osteotomy with the intent to cure; 9 dogs had no further signs of middle ear disease whereas 10 had persistent or recurrent clinical signs. Risk factors for recurrence after surgery were inability to open the mouth or neurologic signs on admission and lysis of any portion of the temporal bone on CT imaging. Dogs admitted with neurologic signs or inability to open the mouth had a median survival of 16 months. Early surgical treatment of aural cholesteatoma may be curative. Recurrence after surgery is associated with advanced disease, typically indicated by inability to open the jaw, neurologic disease, or bone lysis on CT imaging. Presence of aural cholesteatoma may affect the prognosis for successful surgical treatment of middle ear disease.

Perioperative Management of Intracranial Aneurysms and Otologic Disease

Diagnosis and treatment of asymptomatic, unruptured intracranial aneurysms (UIA) are areas of longstanding controversy in the neurologic and neurosurgical literature. Treatment decisions require careful consideration of both the potential for aneurysm rupture as well as the risks associated with repair. Studies examining the natural history of UIA, the morbidity and mortality associated with subarachnoid hemorrhage (SAH), and the various treatment options have led to general guidelines for UIA management. In the literature, the simultaneous presence of otologic disease and UIA has not been introduced or addressed. It is unknown whether surgical treatment of middle ear disease has an effect on the natural history of UIA. Two illustrative patients with UIA discovered incidentally on radiographic evaluation of middle ear disease are presented. Patients were managed according to diagnostic and treatment strategies developed and validated in the neurosurgical literature. Both patients underwent uneventful endovascular embolization of their intracranial aneurysms before middle ear surgery. The intra- and postoperative courses were uncomplicated without symptoms related to either their history of intracranial aneurysms or the prior embolization. Application of neurosurgical diagnostic and treatment algorithms to otology patients in the perioperative setting is appropriate. Established risk factors such as the size and location of the intracranial aneurysm, prior SAH, and patient age should guide treatment planning in all cases of UIA. Additional research is needed to evaluate the influence of otologic procedures on the natural history of UIA. In addition, studies are needed to evaluate the role of preoperative screening for UIA in otologic surgery candidates.

Ketotifen induced inhibition of histamine release in a non-IgE model of middle ear effusion

The inhibitory effects of ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, were examined on a non-IgE experimental model of middle ear effusion. Thirty rats were divided into three groups. Group A (n = 9) was subjected to mechanical stimulation of the external auditory canal (EAC); group B (n = 11) was pre-treated with intraperitoneal administration of 0.2 mg ketotifen, 90 min before mechanical stimulation of the EAC; and group C (n = 10), the control group, was neither exposed to mechanical stimulation nor given ketotifen. Thirty minutes after completion of the experiment, the eardrums were inspected, histamine levels were determined by a fluorometric assay, and the pars flaccida underwent histological assessment. An attic effusion was observed in group A; a similar phenomenon but to a lesser extent was also seen in group B. Statistical analysis confirmed that the mean histamine concentration of the rinsing fluid obtained from group A was significantly higher than that of group C (p = 0.004) or group B (p = 0.008). No significant difference was found between the mean histamine concentration of groups C and group B (p = 0.311). Histological assessment revealed that the thickness of the pars flaccida of group A was considerably greater than that of groups C and B and was characterized by marked edema. Furthermore, the pars flaccida mast cell population was significantly depleted compared with groups C and B. The data indicate that mechanical stimulation of the EAC triggered the pars flaccida mast cells to degranulate in a non-mediated IgE fashion and that histamine is implicated in most of these histological changes. It is concluded that administration of ketotifen before mechanical stimulation of the EAC had a stabilizing effect and abolished mast cell degranulation, therefore, may be considered as a potential therapeutic agent for the treatment of middle ear disease in the pediatric population.

Audiologic and tympanometric findings in children with cleft lip and palate.

To evaluate the otologic and audiologic status of 50 children with repaired cleft lip, cleft palate, or both in Hacettepe University, Ankara, Turkey. Audiometric and tympanometric evaluation of 100 ears in 50 children were performed. Hearing levels < or = 15 dB and middle ear pressures between -50 to +50 decaPascals were considered to be normal. Results were examined according to cleft type and laterality. The least and most affected frequencies were calculated. A simple evaluation of speech characteristics including nasal resonance, nasal air escape, and errors of articulation was also performed. Sixty-three of the 100 ears had normal hearing status, whereas 40 had normal middle ear pressures. No evidence was found to suggest that individual cleft type and laterality of the ear had any effect on hearing loss or middle ear disease. Two-thirds of the patients had normal or acceptable degree of language skills. The final hearing status of patients with cleft palate is a result of a combination of surgical correction, developmental factors, and treatment of middle ear disease. Early and aggressive ventilation tube placement is the standard of cleft care in many countries. Our long-term hearing outcome is relatively good in a population not treated with routine insertion of ventilation tubes. The majority of patients also have satisfactory speech. Patients with cleft palate should have close follow-up for middle ear disease, but further research is warranted to determine the aggressive usage of ventilation tubes.

Adenovirus-mediated in vivo gene transfer in guinea pig middle ear mucosa.

This article describes a study designed to assess the feasibility of using recombinant adenovirus for delivering therapeutic peptides in vivo in the guinea pig middle ear cleft. A recombinant adenoviral vector AdCMVsp1 LacZ containing the Escherichia coli beta-galactosidase was injected into the middle ear space. Qualitative assessment of cell middle ear transfection was performed on day 2 by light microscopy study, after injecting a multiplicity of infection (MOI) ranging from 0 to 1000. At an MOI of 30, 30% of the promontory area epithelial cells were stained. An MOI of 50 stained 60% of the cells and an MOI of 100 or more stained more than 90% of the cells. The duration of cell transfection was studied after injecting an MOI of 50. The percentage of stained cells was 60% on day 2, 10% on day 7, and 0% on day 14. Middle ear mucosal inflammation, consisting of a granulocytic infiltrate, was observed when an MOI above 50 was used. Even at a high MOI (500), no staining could be found in the cochlea, in the facial nerve, in the brain, or in visceral organs. These data suggest that recombinant adenovirus vectors can be used to transfer genes in the middle ear. This method appears to be safe, and may be envisaged as a short-duration treatment to transfer genes in vivo in the treatment of middle ear diseases.

Toynbee Memorial Lecture 1992: facts and fantasies in modern otology: the ear doctor's dilemma.

Until it is accepted that many of the recommendations for surgical treatment of middle ear disease, based on impressions formed twenty years ago, are misleading, attempts to rationalize the use of hospital resources will be little more than cosmesis. Responsibility for the initiation of cost-effective reform is primarily that of surgeons and requires urgent self-audit and the provision of realistic advice to patients (and administrators) as to what benefits microsurgery of the ear can offer.

Treatment of Middle ear Disease for O-R-L Specialists

Treatment of Middle ear Disease for O-R-L Specialists

Importance of early diagnosis and treatment of middle ear diseases in children. M. P. Boebinoer, New Orleans Med.‐ and Surg. Jour., July, 1918

Importance of early diagnosis and treatment of middle ear diseases in children. M. P. Boebinoer, New Orleans Med.‐ and Surg. Jour., July, 1918

Treatment of middle ear disease

Treatment of middle ear disease