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Quantitated determination of proteins in perilymph in patients with acoustic neuromas.

Perilymph, cerebrospinal fluid (CSF) and plasma from 19 patients with acoustic neuromas were examined for albumin, alpha 2-macroglobulin and IgG. Patients with otosclerosis were used as controls. A highly significant increase of the tested proteins was found in perilymph from patients with acoustic neuromas. Determination of the tau-transferrin, which is a specific CNS protein, could neither be demonstrated in plasma nor in perilymph. This is in favour of the assumption that perilymph is plasma-derived and not concentrated CSF. Various causes for the high protein concentrations are discussed, and it is suggested that the increase is caused by a blockage of the neuroaxonal transport mechanisms.

Adult↗

Ototoxicity of neomycin and its penetration through the round window membrane into the perilymph.

The ototoxicity of neomycin and its concentration in the perilymph after direct application on the round window membrane were studied. After placing 5 mg of neomycin on the round window membrane of guinea pigs for various time intervals, concentration of the drug in the perilymph was determined by high performance liquid chromatography, and the cochlea was examined by light microscopy. Neomycin penetrated the round window membrane quite easily, and its concentration in the perilymph became extremely high in a short time and then decreased gradually. This indicates that high concentration of neomycin in the perilymph can be attained by application of a small amount of the drug on the round window membrane. Ototoxicity of neomycin was observed after application for 4 hours. Cochlear damage increased as neomycin application time became longer, but no consistent relationship was noted between the concentration of neomycin and the amount of damage. This result is discussed from the point of concentration and persistence of the drug in the inner ear fluids.

Animals↗

Comparative perilymph permeability of cephalosporins and its significance in the treatment and prevention of suppurative labyrinthitis.

Cephalosporins are nonototoxic antibiotics that provide excellent coverage for almost all bacteria that can cause suppurative labyrinthitis. In this study we performed comparative perilymph permeability determinations of the three cephalosporins that we deemed to have the most clinical potential in these varied situations. Perilymph pharmacokinetic profiles were established for ceftazidime, cefuroxime, and cefotaxime and its metabolite desacetylcefotaxime in 36 guinea pigs by using the technique of high-performance liquid chromatography. At 1, 2, 3, 4, and 6 hours after intravenous administration of the three cephalosporins at a dose of 100 mg/kg of body weight, ceftazidime consistently exhibited the highest perilymph concentration. Desacetylcefotaxime showed the next highest capacity for penetration into perilymph. Keeping in mind that the choice of drug for the treatment of suppurative labyrinthitis should be based foremost on culture and sensitivity studies, we consider ceftazidime to be the first-line agent for treatment and prevention of both meningogenic labyrinthitis and labyrinthitis complicating acute or chronic otitis media.

Animals↗

The Tullio phenomenon and perilymph fistula.

Establishing the diagnosis of perilymph fistula remains a dilemma. At this time, identification of an active perilymph fistula can be confirmed only by surgery. On the basis of clinical history and audiovestibular testing, 54 patients underwent middle ear exploration for possible perilymph fistula at the Colorado Ear Clinic between July 1980 and June 1986. This group represents approximately 1% of all surgical procedures performed during that period. Seven patients (12%) were found to have the Tullio phenomenon preoperatively. Six of these were found to have active, free-flowing fistulas at the time of exploration. The presence of a Tullio phenomenon may be helpful in preoperative assessment of a patient with suspected perilymph fistula.

Acoustic Stimulation↗

Traumatic perilymph fistula in infants: a case report.

Traumatic perilymph fistula is reported to be rare in infants because of the small size of the infant external meatus. We treated an infant with a traumatic perilymph fistula in the right ear. A metallic wire had penetrated the tympanic membrane. Horizontal-rotatory nystagmus was also observed. Computed tomographic images revealed dislocation of the ossicles. The perilymph fistula was closed under general anesthesia. The incus-stapes joint was separated and the footplate of the stapes was dislocated. Leakage of the perilymph fluid was apparent from the oval window and this fistula was closed with connective tissue. The perforation of the tympanic membrane was closed with temporal fascia. After surgery, the spontaneous nystagmus disappeared. The patient is under observation as an outpatient and is growing normally.

Child, Preschool↗

Perilymph fistulas.

A perilymph fistula is an abnormal communication between the fluids surrounding the membranous labyrinth and the middle ear space. Because of the potential hazards of meningitis, permanent hearing loss, and occasionally incapacitating vestibular symptoms, early recognition and prompt repair of the perilymph leak is important. One hundred thirty three cases of perilymph fistulas are presented, stressing the clinical characteristics, evaluation, and management of patients with this otologic entity. The historical and contemporary literature on this subject is reviewed. A pathophysiological basis for perilymph fistula formation is presented, based upon certain anatomic, physiologic and mechanical principles involving the temporal bone and surrounding structures. For the purpose of publication, the Materials and Methods and Evaluation sections of the paper have been omitted. These are available from the author upon request in mimeographed form. The interested reader may wish to refer to items 80 and 133 in the Bibliography, previous publications by the author in which the bulk of the data used in the omitted sections can be found.

Cerebrospinal Fluid↗

Effects of persistent perilymph fistula on the inner ear.

To study the effects of a persistent perilymph fistula on the cochlea, a small cannula was inserted into the scala tympani of the basal turn of cochlea in guinea pigs. A month later, cochlear morphology and blood flow were studied using either histological evaluation or the microsphere surface preparation technique. Some animals showed no cochlear morphologic changes or no cochlear blood-flow reduction, even if tubal patency was maintained and perilymph leakage lasted for 1 month. This suggests that a prolonged perilymph fistula, per se, causes no permanent cochlear damage. However, in some animals, hair cell damage and cochlear blood-flow disorders were observed. These observations and the causes of hearing loss in clinical cases of perilymph fistula were studied.

Animals↗

Measurement of oxygen tension in human perilymph.

The oxygen tension of the human perilymph has been determined without complications by using a technique based upon the polarographic principle. Carbon dioxide produced the most marked increase in oxygen tension in the human perilymph. No change in the perilymphatic PO2 was observed after administration of eupaverine and low molecular weight dextran. 5% CO2-95%O2 has been found to be the gas mixture producing the largest increase in oxygen tension in the human perilymph, without side effects. In order to achieve maximal oxygenation of the perilymph, the therapeutic administration of 5% CO2-95% O2 should continue for at least 30 minutes. At this preliminary stage it is not possible to assess the accuracy of the presented technique in determining the presence of a vascular disorder of the inner ear in patients.

Blood Pressure↗

Electrophoretic separation and identification of perilymph proteins in cases of acoustic neuroma.

Previous studies of perilymph proteins have emphasised the difficulty of obtaining samples free of blood or serum proteins. The present investigation has established a method of polyacrylamide gel electrophoresis, which enables contaminated specimens to be readily identified and therefore discarded. Analysis of uncontaminated samples has confirmed the presence of an elevated perilymph protein in cases of acoustic neurinomata. Perilymph proteins have been separated and identified and although no characteristic pattern of proteins associated with acoustic neurinomata has emerged, further work should be undertaken to establish the site of origin of perilymph proteins and the pattern of abnormalities to be expected in pathological processes.

Electrophoresis, Polyacrylamide Gel↗

Cathepsin D activity in otosclerotic bone and perilymph.

Otosclerotic bone and perilymph samples obtained during stapedectomy operations from patients suffering from pure conductive hearing loss of at least 40 dBs air-bone gap at 500 Hz. Control perilymph samples derived from patients suffering from round window membrane rupture or Meniere's disease. Enzyme activities were determined using a synthetic fluorogenic substrate by fluorescence spectrophotometry. No significant differences have been found between the protein content of otosclerotic and normal or non-otosclerotic perilymph samples. Cathepsin D activity was significantly higher (p less than 0.001) in the otosclerotic perilymph samples. Otosclerotic stapes footplate contained more activity than normal meatal cortical bone as well, though the difference was not significant. Biological significance of the elevated Cathepsin D activity must be considered.

Cathepsin D↗

Pressure relationship between perilymph and endolymph in guinea pigs.

The pressure difference between the perilymph and the endolymph was studied in guinea pigs, using two sets of a servo-nulling system. Asphyxia caused characteristic pressure changes both in the perilymph and in the endolymph, but no pressure difference was seen between them. When the perilymphatic space was opened to the atmosphere, asphyxia did not cause such dynamic pressure changes either on the perilymph or the endolymph. An increase in the perilymphatic pressure induced by the infusion of artificial cerebrospinal fluid into the subarachnoid space resulted in an increase in the endolymphatic pressure, but no pressure difference between the endolymph and the perilymph was evident, regardless of the patency of the vestibular aqueduct. The authors conclude that the endolymphatic pressure is dependent on the perilymphatic pressure and there is no pressure difference between them.

Animals↗

[Protein concentration of perilymph in guinea pigs after noise exposure].

The protein concentration in the perilymph of noise-exposed guinea pigs was investigated using a micromethod described previously. The animals were exposed to wide band noise at 140 dB for one hour unilaterally in a closed acoustic system. Perilymph was obtained after exposure at different intervals: immediately, 6 or 24 hours later. From animals exposed to noise, it is particularly more difficult to obtain perilymph without blood contamination than from normal ones. Even post mortem, it is difficult to obtain samples without blood contamination and without hemolysis, particularly from the scala tympani. Therefore, some animals were perfused intra-arterially with Ringer solution or with Infukoll M 40 before decapitation. After exposure to noise only a small increase in protein concentration of the perilymph can be detected in the noise-exposed ears of animals perfused intra-arterially. The difference in concentration is most distinct in samples extracted 6 hours after noise exposure had ceased. No reliable clue to the source of this protein could be obtained from these investigations.

Animals↗

[Protein study on perilymph susbstitution during cerebrospinal fluid flow through cochlear aqueduct].

Total protein contents in the perilymphy of Scala vestibuli and Scala tympani as well as in the cerobrospinal fluid (CSF) of guinea-pigs were determined, by which specimens were taken under the following various conditions: With or without subarachnoidal puncture before perilymph collection, by varying the amount of perilymph taken from Scala tympani, by fractionating collection and under post mortem condition. The results suggest that under physiological conditions the CSF also flows through the cochleae aqueduct and the protein concentration in the Scala tympani decreases especially in the basal winding. Because the protein content in CSF is inaverage four times lower than in fluids of the inner ear it is of preference to consider the question of connection between the CSF and the fluids of the inner ear. In the specimens taken the blood contamination was estimated on the basisof erythrocytes in the connection capillaries under microscope. The protein content in the perilymph of Scala vestibuli was found significantly higher in relation to perilymph of Scala tympani.

Animals↗

Pressure transfer between the perilymph and the cerebrospinal fluid compartments in cats.

This is a review of our studies of the labyrinthine fluid pressure in cats subjected to pressure changes in the middle ear (implosive routes) and the cerebrospinal fluid compartment (explosive routes) as well as to changes in vascular and ambient pressures. The perilymph, cerebrospinal fluid (CSF), middle ear, venous and arterial pressures were measured with the cochlear aqueduct (CA) patent as well as surgically blocked. Experiments on explosive pressure changes revealed that the perilymph pressure was regulated by the CSF in case of CA patency. The CSF influence was dominant enough to obscure any direct effect on the labyrinth from other sources. With the CA obstructed the CSF influence on the labyrinth was apparently mainly via the endolymphatic sac and duct although limited and much delayed. Systemic arterial pressure changes had a pronounced influence on the perilymph pressure, but this effect was revealed only when the CSF influence was reduced by CA obstruction. Experiments on implosive and ambient pressure changes suggested that there was no fundamental difference in the perilymph response to equivalent levels of implosive versus hypobaric pressure. Three factors determined the effect of implosive and hypobaric pressure: the patency of the CA, the rate of the pressure change, and the eustachian tube function.

Air Pressure↗

[Dexamethasone pharmacokinetics in perilymph of guinea pig after different topical administrations].

OBJECTIVE: To determine pharmacokinetics profiles of dexamethasone (DEX) in perilymph of guinea pig with different intratympanic administrations, and to provide experimental evidence for clinical choice about administration. METHOD: Two different topical administrations placing a granule gelfoam soaked with DEX (10 g/L) in the niche of round window of guinea pig and infusing tympanic bulb with DEX solution (10 g/L) were conducted. Perilymph of the scala tympani was sampled 1-6 h after administration. DEX in the samples was assayed with high-performance liquid chromatography. RESULT: The concentrations of DEX in perilymph after placing a granule gel-foam soaked with DEX in the niche of round window were significantly higher than that after intratympanic infusing. The half-life time of DEX after placing a granule gelfoam was longer. CONCLUSION: DEX could effectively penetrate round window membrane into perilymph after different intratympanic administrations, and the method of placing a granule gelfoam soaked with DEX in the niche of round window is more effective than that of intratympanic infusing.

Administration, Topical↗

Perilymph fistula.

Perilymph fistula, an abnormal communication between the inner ear and the middle ear, is an enigmatic otologic disorder which may present with auditory or vestibular symptoms. It is typically located at the oval or round windows, but several other locations have been suggested. It may be congenital or spontaneous, or due to trauma or surgery. It often poses a diagnostic dilemma because of the lack of a definitive test. Among the differential diagnoses of the perilymph fistula are Ménière's disease, infection, tumor and central nervous system disorders. Clinically, the definitive diagnosis of a perilymph fistula can only be made by exploratory tympanotomy. A current review of the etiology, diagnosis and management of perilymph fistula is presented.

Diagnosis, Differential↗

Large perilymph fistulas.

Perilymph fistulas may manifest themselves either by otologic symptoms, as in cases of small fistulas, or primarily through neurologic symptoms, as with large fistulas. A case history is presented of a 3-year-old girl with recurrent bouts of meningitis who was found to have a large perilymph fistula. She had a right undeveloped cochlea and labyrinth, as well as multiple defects of the medial wall of her middle ear. The only way of preventing the recurrent bouts of bacterial meningitis in cases of large perilymph fistulas is surgical repair. Our conclusion is that, considering the problems involved in cases of large congenital perilymph fistulas, a simple closure of the fistula is not sufficient and the method of choice is obliteration of a deeper structure--such as the vestibule itself.

Child, Preschool↗

[Gentamycin in distributive balance between serum, perilymph and liquor in guinea-pig after dosage in therapeutical range (author's transl)].

Dosage of gentamycin in therapeutical range just as in higher doses results in a distributive balance between serum, perilymph and liquor under the condition of steady serum levels. After high doses the perilymph levels compared to the serum levels are relatively lower than after less doses. The distributive balance is reached after about 7 h in doses, which lead to concentrations of the serum levels of the supposed ototoxic critical range. Afterwards the concentration in the inner ear doesn't increase. In steady state, the concentration in serum is always higher than in perilymph, whereas the perilymph concentration is always higher than the one in liquor.

Animals↗