Contribution of intracranial vertebral artery asymmetry to vestibular neuropathy.

OBJECTIVES: To test the hypothesis that vertebral artery hypoplasia (VAH) may affect the lateralisation of vestibular neuropathy (VN), probably through haemodynamic effect on the vestibular labyrinth. METHODS: 69 patients with unilateral VN were examined with a magnetic resonance angiographic (MRA) and caloric test. 50 healthy subjects served as controls. The diagnosis of intracranial VAH was based on MRA if <0.22 cm in VA diameter and a diameter asymmetry index >40%. The authors then correlated the canal paretic side with the VAH side. RESULTS: MRA study revealed 29 VAH (right/left: 23/6) in VN subjects and six VAH in controls (right/left: 5/1). The RR of VAH in VN subjects compared with controls was elevated (RR=2.2; 95% CI 1.8 to 2.8). There was a high accordance rate between the side of VAH and VN. Among 29 patients with unilateral VAH, 65.5% (N=19) had an ipsilateral VN, in which left VAH showed a higher accordance rate (83.3%) than the right side (60.9%). VN subjects with vascular risk factors also had a higher VAH accordance rate (81%) than those without (25%). CONCLUSIONS: VAH may serve as a regional haemodynamic negative contributor and impede blood supply to the ipsilateral vestibular labyrinth, contributing to the development of VN, which could be enhanced by atherosclerotic risk factors and the left-sided location.

cAMP mediates transepithelial K+ and Na+ transport in a strial marginal cell line.

Because cytoplasmic cAMP has been reported to be the secondary messenger mediating K+ transport in marginal cells of freshly isolated stria vascularis, the possible role of cAMP in ion transport processes of an immortalized marginal cell line (MCPV-8) showing evidence of K+ and Na+ reabsorption was evaluated in this study. Confluent MCPV-8 monolayers were mounted into Ussing chambers and perfused on both sides with perilymph-like Ringer's solution. Transepithelial short-circuit current (I(SC)), resistance (R(T)) and open-circuit voltage (V(T)) were measured using voltage clamp technique. The following results were obtained. (1) Addition of forskolin (10(-4) M) to the basolateral perfusate increased I(SC) to 311 +/- 42%; no significant change in RT was observed. Addition of BaCl2 (2 mM) to the apical perfusate at the maximal response of forskolin blocked 50-60% of I(SC) and subsequent addition of amiloride (10(-5) M) to the apical perfusate further blocked I(SC) to a value close to 0. (2) To evaluate the effect of cellular cAMP on Ba2+-sensitive K+ current, amiloride-sensitive Na+ current was blocked first by addition of amiloride (10(-5) M) to the apical perfusate; subsequent addition of 3-isobutyl-1-methylxanthine (IBMX, 1 mM) or N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP, 1 mM) to the basolateral perfusate increased I(SC) to 175 +/- 13 and 411 +/- 32%, respectively. The stimulated I(SC) was blocked to close to 0 by addition of BaCl2 (2 mM) to the apical perfusate. N2,2'-O-Dibutyrylguanosine 3',5'-cyclic monophosphate (dbcGMP, 1 mM) had no effect on I(SC). (3) To assess the effect of cellular cAMP on amiloride-sensitive Na+ current, Ba2+-sensitive K+ current was blocked in advance by addition of BaCl2 to the apical perfusate; subsequent addition of IBMX or dbcAMP to the basolateral perfusate increased I(SC) to 219 +/- 21% and 388 +/- 39%, respectively. The stimulated I(SC) was blocked to close to 0 by addition of amiloride to the apical perfusate. dbcGMP had no effect on I(SC). Hence, these results suggest that cellular cAMP is the secondary messenger that mediates the transepithelial transport of both K+ and Na+ in MCPV-8 monolayers.

Establishment and characterization of a strial marginal cell line maintaining vectorial electrolyte transport.

E6/E7 genes of human papilloma virus type 16 were used to immortalize a primary culture of marginal cells (MC) from gerbils. One of the cloned lines was selected which demonstrated preservation of the main characteristics of the MC, both morphologically and physiologically. Electron microscopic examination showed well-developed junctional complexes and apical microvilli which suggested its epithelial origin. Polymerase chain reaction (PCR) demonstrated the incorporation of E6/E7 genes with the genome. Reverse transcription PCR revealed the existence of mRNA of the IsK channel, a unique marker of MC among the inner ear cells, in this clone. Flow cytometric analysis of this cell line's DNA content was diploid. Numerous large domes formed after confluence of the cell monolayer. Electrophysiologic studies displayed evidence of apical K+ and Na+ channels which were blocked by Ba2+ (2 mM) and amiloride (10(-5) M), respectively. Existence of basolateral Na,K-ATPase and Na+/Cl-/K+ cotransporter was shown by blockage by ouabain (10(-3) M) and bumetanide (50 microM), individually. Injection of the cell line to nude mice failed to induce growth of tumors. This cell line was serum-, density- and anchorage-dependent when cultured in plastic dishes. In conclusion, this cell line shows characteristics of well-differentiated MC maintaining the major ionic transport processes, and provides us a good model to study the possible mechanisms and regulating factors of endolymph production.

Expression of IsK protein mRNA in cultured rat strial marginal cells.

A cell culture system of marginal cells (MC) of the rat stria vascularis was established by the explant method. When grown on plastic dishes, cultured MC showed a polygonal "cobblestone-like" appearance. Dome formation, composed of several hundreds to thousands of cells, occurring after confluence suggested that vectorial transport of ion(s) with accompanying fluid developed in the cultured MC. Transmission electron microscopy demonstrated junctional complexes formed of tight junctions and desmosomes at the upper lateral membranes. The polymerase chain reaction (PCR) product, amplified with primers made from the cDNA reverse transcribed from cultured MC, yielded a distinct band compatible with the expected size of the PCR products amplified from cDNA of positive control groups containing IsK protein, indicating that cultured MC expressed the IsK protein mRNA. The results show that cultured MC can form large domes and express the most characteristic IsK protein, indicating that they maintain their vectorial electrolyte transport function and, possibly, the ability to secrete K+ in this condition.

Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium.

OBJECTIVE: To investigate the immunolocalisation of beta-dystroglycan (beta-DG) and specific matrix metalloproteinases (MMPs)-3, -9, -13 and a disintegrin like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) within the joint tissues of patients with osteoarthritis (OA) and unaffected controls. DESIGN: Cartilage, synovium and synovial fluid were obtained from the hip joints of five osteoarthritic (patients undergoing total hip replacement) and five control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for beta-DG protein using Western blot technique and by immunohistochemistry for tissue distribution of beta-DG, MMP-3, -9, -13, and ADAMTS-4. RESULTS: beta-DG was detected in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Importantly, beta-DG was detected in endothelium of blood vessels of OA synovium, but not in the control endothelium. In the endothelium of osteoarthritic synovial blood vessels, beta-DG co-localised with MMP-3 and -9. MMP-13 and ADAMTS-4 showed no endothelial staining, and only weak staining of the vascular smooth muscle was found. In contrast, we did not detect beta-DG protein in cartilage or synovial fluid. CONCLUSIONS: beta-DG has been shown to have a role in angiogenesis, and our results demonstrate for the first time that there are clear differences in beta-DG staining between OA and control synovial blood vessels. The specific immunolocalisation of beta-DG within endothelium of inflamed OA blood vessels and its co-localisation with MMP-3 and -9, reported to have pro-angiogenic roles and believed to be involved in beta-DG cleavage, may also suggest that beta-DG plays a role in angiogenesis accompanying OA.

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Tympanoplasty for pars flaccida.

BACKGROUND: The formation of a retraction pocket of the pars flaccida remains a difficult problem for otologists to treat. It may lead to ossicular erosion and the development of a cholesteatoma, especially when the pocket is adherent to the malleus neck. We designed a new method of surgery for the treatment of small attic cholesteatomas. METHODS: From 1986 to 1996, 20 patients with a retraction pocket of the pars flaccida or a small attic cholesteatoma underwent surgery as described below. The complete lesion was removed after widening the posterior-superior bony external ear canal wall and placing pieces of conchal cartilage (usually less than 10 pieces, according to their scutum defect) lateral to the malleus neck or incus. The temporalis fascia was then laid. RESULTS: The average follow-up period was 32 months. The paired t-test was used to compare the results of preoperative and postoperative air conduction and air-bone gap. The preoperative average air conduction was 31.17 dB and the air-bone gap was 15.09 dB. The postoperative average air conduction was 20.66 dB and the air-bone gap was 3.09 dB. The difference between preoperative and postoperative measurements was considered significant (p < 0.05). No recurrent retraction pockets or cholesteatomas were noted during follow-up. CONCLUSIONS: Tympanoplasty for correction of a retraction pocket of the pars flaccida can prevent further attic retraction and the development of cholesteatomas. Postoperative hearing results were also encouraging.

[Tympanoplasty on only-hearing ears].

It presents a dilemma whether an only-hearing ear with chronic otitis media should be managed surgically. From August 1981 to December 1988, 26 only-hearing ears were operated on by the authors. All of them had chronic otitis media and, furthermore, 7 ears had cholesteatomas. Prior to the operation, the patients must be informed in detail and really understand the risk of the operation. Tympanoplasty type I (16 ears), tympanoplasty type III (4 ears), classic modified radical mastoidectomy (1 ear), tympanoplasty type III with cartilage obliteration (3 ears), and tympanoplasty for pars flaccida (2 ears) were performed. After an average of 4 years and 2 months of follow-up, 16 ears showed hearing improvement but 10 ears remained the same. The average hearing gain was 12.7 dB. The operation on only-hearing ears should be performed by the most experienced otosurgeon. In these cases, special precautions were taken during surgery to minimize the potential for intraoperative or postoperative hearing loss.

Type III tympanoplasty with cartilage obliteration for cholesteatoma surgery.

BACKGROUND: The main objective of cholesteatoma surgery is complete eradication of the disease. Another goal is to preserve hearing acuity. We reviewed type III tympanoplasty with cartilage obliteration for cholesteatomatous ears. To evaluate the role of ossiculoplasty, the functional results of classic and modified type III tympanoplasties were compared. METHODS: Thirty-six cholesteatomatous ears undergoing type III tympanoplasty with cartilage obliteration were reviewed. The same operator performed these operations from 1984 until 1995. According to the CAO staging system, there were five early, 16 moderate and 15 advanced-stage cases of cholesteatoma. Using the anterior approach, all operations were canal-wall-down type III tympanoplasties with "tailored" open cavity and cartilage obliteration. There were 24 classic and 12 modified type III tympanoplasties. RESULTS: The average follow-up duration was 7.2 years. Neither recidivistic cholesteatoma nor retraction pocket was observed postoperatively. There was an improvement in atelectatic score after surgery. The mean postoperative air-bone gap (ABG) was 15.8 +/- 10.7 dB and the mean closure of the ABG was 4.0 +/- 14.3 dB. After the disease stage and preoperative hearing status were adjusted using regression analysis, there was no significant difference in hearing results between ears that underwent classic or modified type III tympanoplasties. CONCLUSIONS: We performed the canal-wall-down tympanoplasty with cartilage obliteration using the anterior approach for treatment of cholesteatoma. Such surgical techniques eradicate the cholesteatoma, prevent its recurrence and create a clean ear. Hearing reconstruction can also be accomplished in a single-stage procedure offering a serviceable hearing acuity.

[Neonatal hearing screening].

Auditory deprivation in early life significantly effects speech, language, cognition and learning development. The importance of neonatal hearing screening in order to detect and manage children with hearing impairment during the critical period before three years of age can't be neglected. The neonatal hearing screening program at Veterans General Hospital, Taipei, under a cooperation of audiologists, otologists and pediatricians, identified 1885 neonates for hearing loss from September 1990 to August 1991. There were two study groups, a high risk group of hearing impairment and a non-high risk group. We performed hearing screening and followed-up for the failure at initial test using methods including behavioral observation audiometry, auditory brainstem response, tympanogram, pneumatic otoscopy and questionnaire. Approximately 2.7% of neonates were classified as high risk for hearing loss, the incidence of hearing loss was 8% to 14% in this group. The incidence of hearing loss in non-high risk group was 0.11%. If both groups were contained that the incidence of hearing loss was 0.32% to 0.48%, 0.11% with a sensorineural hearing loss, 0.21% to 0.37% with a conductive hearing loss. Both behavioral audiometry (89% false negative rate) and questionnaire (50% return rate) were not effective for screening purposes in this study. Our results also indicated that the most advantage of using a high risk register lay in the fact that only 2.7% of a total population needed to be screened to identify approximately 67% to 78% of hearing-impaired babies. This saved both time and money.

[Ventilation tube insertion for treating adult otitis media with effusion].

The etiologic factors and treatment of otitis media with effusion (OME) in children are well described and established. On the contrary, little has been published with regard to OME in adults and its treatment. To further investigate this problem, we reviewed the records of all adult patients who had received ventilation tube (VT) insertion for OME in VGH-Taipei from 1983 to 1986. There were 335 VT insertions performed on 140 adult patients whose follow-up periods were longer than 6 months. Among them, fifty patients received more than one VT insertion due to recurrence of OME in one or both ears. The average follow-up period was more than 4 years. The coexistence of nasal diseases was found in 46% of the adult OME patients. The mean extrusion time of the VT was 10.2 months. After VT insertions, the improvements of mean air conduction and mean air-bone conduction gap were 10.1 and 11.8 dB respectively. After the extrusion or removal of VT, there was no recurrence of OME in 50 ears (14.9%). Recurrence of OME occurred in 199 ears (59.4%). Dry persistent perforations of the eardrums were found in 27 ears (8.1%). Discharging persistent perforations were noted in 24 ears (7.2%). No recurrence of OME was observed in 24.2% of the ears with serous effusion fluids, whereas only 4.8% of the ears with mucoid fluids were free from recurrence during the follow-up period. Post-intubation otorrhea, which was the most common complication, developed in 92 ears (27.5%). Our results suggest that the recurrence rate of OME after extrusion of VT is high in the adult patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Infant hearing screening with an automated auditory brainstem response screener and the auditory brainstem response.

From 1653 babies hospitalized in the Veterans General Hospital-Taipei from 1993 to 1995, 260 infants at risk of hearing impairment were selected. The risk criteria of hearing impairment for neonates were based on the recommendation of the US Joint Committee on Infant Hearing, 1990 Position Statement. All these infants were screened with the Algo-1 Plus, an automated auditory brainstem response (ABR) screener at a mean postconceptional age of 40.7 +/- 4.5 weeks. Thirty-nine cases (39/260, 15%) involving 57 ears (57/520, 11%), failed the screening. Except for one infant who died, the babies had an ABR test for both air- and bone-conducted stimuli and an otological examination. The case-specific incidence of conductive hearing deficit at the initial ABR test was 5.4%. The prevalence of sensorineural hearing deficits was between 2.3% confirmed and 3.1% including infants who did not have follow-up tests. The kappa-value that indicated agreement between the Algo-1 and ABR results was 0.64, and the overall efficiency of using Algo-1 to correctly identify pass or failure of the ABR was 83%.

Effects of acute brainstem compression on auditory brainstem response in the guinea pig.

BACKGROUND: The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. METHODS: Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. RESULTS: Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. CONCLUSIONS: This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.

Malignant otitis externa.

BACKGROUND: Malignant otitis externa is an infrequent but severe infection of the external auditory canal, most often affecting elderly diabetic patients. Early diagnosis is necessary due to its high morbidity and mortality. METHODS: From 1990 to 1997, all patients with malignant otitis externa at the Veterans General Hospital-Taipei were reviewed retrospectively. The clinical features and the strategy of diagnosis and treatment are discussed. RESULTS: Twelve patients with an average age of 65.3 years were included. Eleven of these patients were diabetic. All had the presenting symptoms of otalgia and otorrhea at diagnosis. Bacterial cultures grew Pseudomonas aeruginosa in eight patients and methicillin-resistant Staphylococcus aureus in four patients. The mean duration of admission was 82 days. Appropriate antibiotics were given according to the results of bacterial culture and sensitivity test. 99Technetium scans and 67gallium scans were performed to evaluate the extent of involvement and monitor the effects of treatment. Eventually, four patients died due to renal failure, meningitis, pneumonia and upper gastrointestinal bleeding, respectively. CONCLUSIONS: Malignant otitis externa is a life-threatening infection arising from the external auditory canal. A high degree of suspicion for malignant otitis externa is mandatory. Vigorous local and systemic antimicrobial treatment should be initiated early in the course of the disease to achieve a satisfactory outcome. 99Technetium and 67gallium scans are important for the diagnosis and evaluation of the treatment results.