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INTRODUCTION: Ocular imaging strategies have evolved to facilitate the diagnosis of optic neuropathy. This study aimed to evaluate the pathogenesis of visual disturbance associated with paranasal mucocele via magnetic resonance imaging (MRI). METHODS: A total of 19 patients with mucocele and visual disturbance who underwent endoscopic sinus surgery, orbital MRI, and sinus computed tomography were included. The age, sex, days from onset to surgery, eye pain, and imaging findings were analyzed. The results were compared between two groups: 7 patients with preoperative visual acuity worse than 20/200 (the poor group) and 12 patients with equal or better than 20/200 (the fair group). RESULTS: Imaging showed a high compression rate of the orbit in 17 (89.5%) and enlargement of the subarachnoid space around the optic nerve in 15 (78.9%) of 19 patients. Preoperative vision was significantly poor in cases with hyperintense regions in the optic nerve on T2-weighted imaging, indicating the presence of optic neuritis. No cases showed severe inflammation of the cyst or the presence of intraorbital fat tissue. CONCLUSION: MRI-based diagnosis proved useful in evaluating pathological factors, such as orbital compression, ischemia, and optic neuritis, in individual cases. It can help in gaining insight into the pathogenesis and developing appropriate treatment strategies for visual disturbances associated with paranasal mucocele.
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In the treatment of head and neck cancer (HNC), any delay in omit initiation worsens the overall prognosis. Thus, the early start of HNC treatment is crucial. Unfortunately, treatment delays persist in clinical practice. There are several possible reasons for this. One reason is that patients with HNC do not visit an ear, nose, and throat (ENT) doctor. This is because non-ENT doctors (e.g., general practitioners {GPs}) lack expertise in HNC and therefore may unrecognize it. Therefore, guiding patients with suspected HNC symptoms to an otorhinolaryngologist, an HNC specialist, is necessary. To determine the departments that patients with potential HNC symptoms tend to select, we administered a questionnaire survey to 140 participants. Fewer than 60% of respondents indicated they would consult an otorhinolaryngologist even when recognizing symptoms suggestive of HNC. Notably, a significantly low percentage of respondents mentioned they would consult an otorhinolaryngologist for neck masses. Public awareness of HNC symptoms, especially the association between a neck mass and HNC, is limited. The lack of understanding by the general public regarding the relationship between neck masses and HNC is a challenge to prompt initiation of treatment.
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We speculated that increased blood-plasma levels of Substance P may serve as an indicator of glottal incompetence, which is usually indicated by reduced maximum phonation time. We performed an initial study to test the plausibility of this hypothesis. Patients with dysphonia caused by glottal incompetence were asked to perform vocal exercises for six months to reduce glottal incompetence and we compared the plasma concentration of Substance P before and after the vocal exercise to detect correlation between maximum phonation time and plasma concentration of Substance P. Based on the results, we further hypothesized that patients exhibiting dysphonia with maximum phonation time less than 14 s, in particular less than 10 sec, caused by glottal incompetence may have increased plasma concentration of Substance P with the results of elevated thresholds of cough reflex associated with subclinical aspiration in airways. Further study is needed on patients with decreased Substance P levels, with low scores on Activities of Daily Living and who are hospitalized with aspiration pneumonia.
ABSTRACT
We present a case of internal carotid artery (ICA) stenosis caused by mechanical stimulation by the hyoid bone (HB) and thyroid cartilage (TC). A 78-year-old man with a history of right ICA stenting four years previously was admitted for abrupt onset of dysarthria and left hemiparesis and diagnosed with ischemic stroke by magnetic resonance imaging. Three-dimensional computed tomographic angiography revealed internal carotid in-stent restenosis. Furthermore, the HB and TC contacted with the right ICA. Treatment involved antiplatelet therapy, partial HB and TC resection, and carotid artery restenting. Posttreatmently, the ICA was restored and stenosis improved. Since restenosis may occur posttreatmently in patients with carotid artery stenosis caused by mechanical stimulation of the HB and TC, it is necessary to consider treatments including not only carotid artery stenting but also partial bone structures resection and carotid endarterectomy.
Subject(s)
Carotid Stenosis , Fractures, Bone , Ischemic Stroke , Stroke , Male , Humans , Aged , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/etiology , Carotid Stenosis/surgery , Ischemic Stroke/complications , Hyoid Bone/diagnostic imaging , Hyoid Bone/pathology , Constriction, Pathologic/complications , Constriction, Pathologic/pathology , Thyroid Cartilage , Stents/adverse effects , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Fractures, Bone/complications , Stroke/diagnostic imaging , Stroke/etiology , Stroke/therapyABSTRACT
BACKGROUND: Pharyngoesophageal dysphagia sometimes develops after esophagectomy. However, severe dysphagia after esophagectomy due to cricopharyngeus muscle dysfunction is a rare complication. There are no recommended clinical treatments for cricopharyngeus muscle dysfunction after esophagectomy. We report a case of myotomy for cricopharyngeus muscle dysfunction after esophagectomy. CASE PRESENTATION: A 75-year-old man with mild dysphagia diagnosed with advanced esophageal cancer by esophagogastroduodenoscopy at a clinic was admitted to our hospital. He had occasional mild dysphagia when he swallowed solid foods. After chemotherapy, the patient underwent minimally invasive esophagectomy with regional lymph node dissection and was reconstructed with a gastric conduit and cervical anastomosis by the retrosternal route. Aspiration pneumonia developed after esophagectomy without paralysis of the vocal cords. In esophagoscopy, there was no stricture around the anastomosis. However, severe pharyngoesophageal dysphagia with cricopharyngeus muscle dysfunction was revealed by videofluoroscopic examination. Bilateral cricopharyngeal myotomy was performed because balloon dilations had failed. The histological findings revealed atrophy and fibrosis of the cricopharyngeus muscle fibers. Pharyngoesophageal dysphagia improved immediately after myotomy. The patient swallowed solid food easily without dysphagia 12 months after myotomy. CONCLUSION: Dysphagia after esophagectomy was worsened by cricopharyngeus muscle dysfunction. Cricopharyngeus myotomy may lead to long improvement of pharyngo-oesophageal dysphagia after esophagetomy.
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OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.
Subject(s)
Conservative Treatment/methods , Hygiene/education , Laryngeal Diseases/therapy , Patient Education as Topic/methods , Polyps/therapy , Program Evaluation , Female , Humans , Laryngeal Diseases/pathology , Laryngoscopy/statistics & numerical data , Male , Middle Aged , Polyps/pathology , Treatment Outcome , Vocal Cords/pathologyABSTRACT
OBJECTIVE: The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. STUDY DESIGN: Prospective multicenter cohort study. METHODS: All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan). RESULTS: In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears. CONCLUSION: The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:E371-E377, 2017.
Subject(s)
Ear, Middle/microbiology , Microbiota , Otitis Media/microbiology , Actinobacteria/isolation & purification , Adolescent , Adult , Aged , Bacteroidetes/isolation & purification , Child , Child, Preschool , Chronic Disease , Female , Firmicutes/isolation & purification , Humans , Infant , Male , Middle Aged , Otitis Media/surgery , Prospective Studies , Proteobacteria/isolation & purification , RNA, Ribosomal, 16S/analysis , Tympanoplasty , Young AdultABSTRACT
OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.
Subject(s)
Deglutition Disorders/rehabilitation , Exercise/physiology , Glottis/physiopathology , Pneumonia, Aspiration/prevention & control , Age Factors , Aged , Aged, 80 and over , Aging/physiology , Deglutition Disorders/complications , Deglutition Disorders/diagnosis , Humans , Japan , Laryngoscopy/methods , Middle Aged , Patient Compliance/statistics & numerical data , Pneumonia, Aspiration/etiology , Prognosis , Recovery of Function , Reference Values , Risk Assessment , Severity of Illness Index , Sex Factors , Treatment OutcomeABSTRACT
The hearing loss caused by GJB2 mutations is usually congenital in onset, moderate to profound in degree, and non-progressive. The objective of this study was to study genotype/phenotype correlations and to document 14 children with biallelic GJB2 mutations who passed newborn hearing screening (NHS). Genetic testing for GJB2 mutations by direct sequencing was performed on 924 individuals (810 families) with hearing loss, and 204 patients (175 families) were found to carry biallelic GJB2 mutations. NHS results were obtained through medical records. A total of 18 pathological mutations were identified, which were subclassified as eight inactivating and 10 non-inactivating mutations. p.I128M and p.H73Y were identified as novel missense GJB2 mutations. Of the 14 children with biallelic GJB2 mutations who passed NHS, eight were compound heterozygotes and 3 were homozygous for the c.235delC mutation in GJB2, and the other three combinations of non-c.235delC mutations identified were p.Y136X-p.G45E/p.V37I heterozygous, c.512ins4/p.R143W heterozygous, and p.V37I/p.R143W heterozygous. These 14 cases demonstrate that the current NHS does not identify all infants with biallelic GJB2 mutations. They suggest that the frequency of non-penetrance at birth is approximately 6.9% or higher in DFNB1 patients and provide further evidence that GJB2 hearing loss may not always be congenital in onset.
Subject(s)
Connexins/genetics , Hearing Loss/diagnosis , Hearing Loss/genetics , Mutation , Neonatal Screening/methods , Amino Acid Sequence , Child, Preschool , Connexin 26 , Genetic Association Studies , Heterozygote , Humans , Infant , Infant, Newborn , Molecular Sequence DataABSTRACT
OBJECTIVE: This study aimed to investigate the effects of a tongue-holding maneuver (THM) during swallowing using a novel high-resolution manometry (HRM) system. STUDY DESIGN: Case series with planned data collection. MATERIALS AND METHODS: Thirty-three asymptomatic Japanese adults were studied. A solid-state HRM assembly with 36 circumferential sensors spaced 1-cm apart was positioned to record pressures from the velopharynx to the upper esophagus at rest and during swallowing. The maximum values of the dry swallowing pressures at the velopharynx, mesohypopharynx, upper esophageal sphincter (UES), and distance from the nostril to each point of maximum values with and without the THM were measured. RESULTS: The distance from the nostril to the UES was statistically shorter when swallowing with the THM than without the THM (paired t test, P=0.009). The maximum pressure at UES was greater when swallowing with the THM than without the THM, although there was no statistically significant difference (paired t test, P=0.051). There was no difference in the pressures and the distance between swallowing with or without the THM at any other site. CONCLUSIONS: These findings suggest that the THM may not have a potential to facilitate compensatory swallowing power when swallowing.
Subject(s)
Deglutition Disorders/physiopathology , Tongue/physiopathology , Adult , Analysis of Variance , Deglutition Disorders/rehabilitation , Female , Humans , Male , Manometry/methods , Middle AgedABSTRACT
CONCLUSIONS: Our results suggest that summating potential/action potential (SP/AP) area ratio may not necessarily have higher sensitivity in the diagnosis of endolymphatic hydrops of Meniere's disease (MD) than SP/AP amplitude ratio in transtympanic electrocochleography (ECochG). OBJECTIVE: Recent studies suggested that SP/AP area curve ratio was more sensitive to endolymphatic hydrops in comparison with SP/AP amplitude ratio in extratympanic ECochG. The purpose of the present study was to evaluate the utility of the SP/AP area curve ratio in transtympanic ECochG for the diagnosis of MD. PATIENTS AND METHODS: A retrospective chart review of 198 patients (209 ears) was conducted in cases of MD. RESULTS: With regard to SP/AP amplitude ratio, 57.1% in definite cases of MD (group 1), 39.6% in probable cases of MD (group 2), and 50.0% in the cases who had transformed from probable MD to definite MD (group 3) showed abnormally high values, respectively. Abnormally high values were observed in 43.9%, 27.7%, and 30.0% in SP/AP area ratio in groups 1, 2, and 3, respectively, indicating that abnormal values were observed more frequently in the amplitude ratio than in the area ratio in all three groups.
Subject(s)
Action Potentials/physiology , Audiometry, Evoked Response , Endolymphatic Hydrops/physiopathology , Meniere Disease/physiopathology , Signal Processing, Computer-Assisted , Endolymphatic Hydrops/diagnosis , Female , Humans , Male , Meniere Disease/diagnosis , Reference Values , Retrospective StudiesABSTRACT
OBJECTIVES/HYPOTHESIS: This study aimed to demonstrate the feasibility of a novel high-resolution manometry system, and to establish normal values of swallowing pressures along the velopharynx and upper esophagus. STUDY DESIGN: Prospective study. METHODS: Thirty-three asymptomatic adult Japanese controls were studied. A solid-state high-resolution manometry assembly with 36 circumferential sensors spaced 1 cm apart was positioned to record pressures during swallowing from the velopharynx to the upper esophagus. The maximum values of the swallowing (dry and 5 mL of water) pressures at velopharynx, meso-hypopharynx, and at the upper esophageal sphincter (UES) were measured. The resting UES pressure, the length of the part in the cervical esophagus showing the resting UES pressure, and the distances from the nostril to the above-mentioned points of pressure measurement were also measured. RESULTS: The maximum value of dry and water swallowing pressures at the velopharynx, meso-hypopharynx and UES, and the distances from the nasal vestibulum to each point in men were 141.1 +/- 73.5 (mm Hg, mean +/- standard deviation) and 162.7 +/- 94.9, 175.3 +/- 59.7 and 182.9 +/- 83.6, 172.7 +/- 73.8 and 236.1 +/- 78.9, and 10.0 +/- 1.3 (cm) and 10.1 +/- 1.4, 14.1 +/- 1.5 and 14.4 +/- 1.3, 17.9 +/- 1.7 and 18.0 +/- 1.4, respectively. Those in women were 118.9 +/- 38.0 (mm Hg) and 124.7 +/- 43.4, 165.9 +/- 41.5 and 167.3 +/- 65.0, 149.2 +/- 68.7 and 243.7 +/- 87.4, and 9.5 +/- 1.2 (cm) and 9.4 +/- 1.2, 13.0 +/- 1.5 and 12.8 +/- 1.4, 15.8 +/- 1.5 and 16.0 +/- 1.3, respectively. The maximum value of resting UES pressure, the length of the part in the cervical esophagus showing the resting UES pressure and the distance from the nostril to the mid-point of the width of the resting UES pressure in men and in women were 70.2 +/- 30.0 mm Hg, 4.0 +/- 0.7 cm, 19.1 +/- 1.3 cm, and 61.8 +/- 26.7 mm Hg, 3.6 +/- 0.6 cm, 17.0 +/- 1.2 cm, respectively. CONCLUSION: The present study provides anatomical and physiological information about normal swallowing along the velopharynx and upper esophagus, which will be an aid to the future clinical and investigative studies.
Subject(s)
Deglutition/physiology , Manometry , Pharynx/physiology , Adult , Esophageal Sphincter, Upper/physiology , Female , Humans , Male , Manometry/methodsABSTRACT
BACKGROUND: Basic fibroblast growth factor (b-FGF) has recently been shown to have a positive effect on the treatment of postoperative mastoid cavity problem, but its ototoxicity has not been investigated. OBJECTIVE: To investigate the effect of b-FGF on the inner ear of guinea pigs. STUDY DESIGN AND SETTING: In groups A (n = 10) and B (n =11), b-FGF was applied into the left external auditory canal and the middle ear, respectively. The right ear served as a control. At 1 week after b-FGF administration, the endocochlear DC potential (EP) was measured, and morphology of the cochleae was examined by scanning electron microscopy. RESULTS: In group A, the EP values of experimental ears and controls were 90.0 +/- 8.4 (mV, mean +/- SD) and 89.4 +/- 4.3 (P > 0.05). In group B, the values were 86.5 +/- 11.4 and 87.5 +/- 6.1, respectively, (P > 0.05). Morphological findings showed no damage on the cochlear. CONCLUSION: Application of b-FGF to the external and middle ears does not seem to have an apparent risk of ototoxicity.
Subject(s)
Ear, Inner/drug effects , Fibroblast Growth Factor 2/administration & dosage , Administration, Topical , Animals , Cell Count , Cochlea/drug effects , Cochlea/physiology , Electrophysiology , Guinea Pigs , Hair Cells, Auditory, Inner/drug effects , Hair Cells, Auditory, Outer/drug effects , Male , Microscopy, Electron, ScanningABSTRACT
OBJECTIVE: Erbium (Er.) YAG laser may be usable for middle ear surgery because of its ability to ablate bony tissue. We investigated the inner ear damage caused by the fenestration to the inner ear with Er. YAG laser. DESIGN: We investigated the influence of Er. YAG laser on the inner ear using electrophysiological technique. RESULTS: Several cases had a decrease in endocochlear potential (EP) and cochlear microphonics (CM) after the fenestration to the inner ear. CONCLUSIONS: Er. YAG laser is safe if it is used for the small and superficial fenestration to the stapes footplate. However, a few extra pulses after fenestration are dangerous.
Subject(s)
Fenestration, Labyrinth/methods , Laser Therapy , Acoustic Stimulation , Animals , Cochlear Microphonic Potentials/physiology , Guinea PigsABSTRACT
OBJECTIVE: To investigate the effect of 5-fluorouracil (5-FU) ointment on the inner ear of guinea pigs. STUDY DESIGN AND SETTING: In group A (n = 7), 5-FU ointment was applied into the left external auditory canal. In group B (n = 10), 5-FU ointment was applied to the left middle ear through myringotomy. In both groups, the right ear served as a control. One week later the endocochlear DC potential (EP) was measured and morphology of the cochleae was examined using scanning electron microscopy (SEM) and light microscopy. RESULTS: In group A, there was no significant difference between the EP values of the experimental side and the control side. In group B, there was a statistically significant difference between them (P < 0.05). Morphologic findings showed no damage. CONCLUSION: 5-FU ointment application to the external ear seems to be safe but its application to the middle ear may pose some risk of ototoxicity.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/toxicity , Ear, Inner/drug effects , Fluorouracil/administration & dosage , Fluorouracil/toxicity , Administration, Topical , Animals , Ear, Inner/physiology , Electrophysiology , Evoked Potentials, Auditory , Guinea Pigs , Hair Cells, Auditory/drug effects , Male , Microscopy, Electron, Scanning , Ointments , Stria Vascularis/drug effectsABSTRACT
Toxic shock-like syndrome (TSLS) is known to progress rapidly into septic shock and multiple organ failure with necrotizing soft tissue infection and high mortality. We report a rare case of TSLS of the head and neck. A 55-year-old man reporting redness and swelling of the neck and suspected of a deep neck abscess was found in computed tomography and magnetic resonance imaging to have no abscess. Infection spread rapidly and CRP rose while platelets and blood pressure decreased leading us to suspect TSLS. Pus culture yielded Streptcoccus pyogenes, Group A. We administered high-dose penicillin, clindamycin, and gabexate mesilate with intensive supporting care, leading to a successful outcome. TSLS is a life-threatening infection, but early diagnosis and appropriate therapy may reverse this threat.
Subject(s)
Cellulitis/etiology , Shock, Septic/diagnosis , Streptococcal Infections/diagnosis , Streptococcus pyogenes , Humans , Male , Middle AgedABSTRACT
In this study, we measured human endolymphatic sac potential (ESP) in 8 patients with vestibular schwannoma and in five patients with Ménière's disease during surgery. ESP was measured with a glass electrode filled with 154 mM NaCl and with an outside tip diameter ranging from 2 to 3 microm. The mean value of human ESP in patients with vestibular schwannoma was +13.3+/-1.9 mV. Since electron microscopy showed that the endolymphatic sacs of the eight patients with vestibular schwannoma were normal in the ultrastructures the value can be close to normal human ESP. While in Ménière's disease, three cases showed low potentials and two cases showed almost the same values observed as in the eight patients with vestibular schwannoma. In the two cases with Ménière's disease, the epithelial cells of the endolymphatic sac were preserved. Our study can be considered as the first successful measurement of human ESP and revealed the existence of Ménière's disease having normal endolymphatic sac in function as well as morphology.
Subject(s)
Endolymphatic Sac/physiopathology , Meniere Disease/physiopathology , Neuroma, Acoustic/physiopathology , Adult , Aged , Electrophysiology , Endolymphatic Sac/pathology , Epithelial Cells/pathology , Female , Humans , Male , Meniere Disease/pathology , Microscopy, Electron , Microscopy, Electron, Scanning , Middle Aged , Neuroma, Acoustic/pathologyABSTRACT
The effect of manipulation of pH on the ototoxicity of systemic cisplatin was studied in Wistar rats. After control auditory brainstem responses (ABR) were performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.4) or basic (pH 9.0) phosphate-buffered saline (PBS) was applied to fill the round window niche (RWN). After 30 min, 13 mg/kg cisplatin solution or saline was administered intraperitoneally. After 3 days, follow-up ABRs were performed and cochleae were processed for morphological analysis. Animals that received basic PBS on the RWN and cisplatin intraperitoneally had significantly smaller ABR threshold shifts compared to rats pretreated with neutral pH buffer (P<0.05). Animals that received acidic PBS on the RWN and systemic cisplatin showed significantly greater ABR threshold shifts compared to those pretreated with neutral pH buffer (P<0.05). No significant threshold changes were observed in animals that received buffer of any pH on the RWN, followed by saline intraperitoneally. Semiquantitative analysis of hair cell survival confirmed a protective effect by basic PBS against cisplatin and a synergistic effect by acidic PBS on cisplatin ototoxicity (P<0.05). It appears that changes in cochlear pH can modulate the ototoxic effects of systemically applied cisplatin.
Subject(s)
Antineoplastic Agents/poisoning , Cisplatin/poisoning , Ear/pathology , Ear/physiology , Protons , Round Window, Ear/metabolism , Animals , Antineoplastic Agents/administration & dosage , Auditory Threshold/drug effects , Body Weight/drug effects , Cell Count , Cell Survival/drug effects , Cisplatin/administration & dosage , Evoked Potentials, Auditory, Brain Stem/drug effects , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/pathology , Hydrogen-Ion Concentration , Injections, Intraperitoneal , Male , Rats , Rats, WistarABSTRACT
Cisplatin is an antineoplastic agent that produces a number of dose-limiting side effects, including ototoxicity. We investigated the effect of pH on cisplatin ototoxicity. Auditory brainstem responses (ABR) were recorded in chinchillas. Then the auditory bullae were opened and acidic (pH=6.5), neutral (pH=7.4) or alkaline (pH=10.2) phosphate-buffered saline (PBS) was applied to the round window membrane. After 30 min, any remaining solution was removed and cisplatin solution was applied to the round window membrane. After 3 days, follow-up ABRs were performed and the cochleae were processed for morphological analysis. Neutral PBS+cisplatin administration resulted in profound threshold changes at all frequencies. Acidic PBS+cisplatin administration showed had a trend of increased threshold changes, but the change did not reach statistical significance. However, the degree of hair cell loss was significantly higher than that of the neutral PBS-cisplatin group. Alkaline PBS significantly reduced cisplatin-induced threshold changes (P<0.05) compared to the neutral PBS group. Because the pH of cisplatin solution was 6.0, pH 6.0 PBS was applied to round window membrane. This acidic PBS solution did not cause any hearing impairment. These results demonstrate that pH can modulate the ototoxic effects of cisplatin.