Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and nitric oxide synthase inhibitors.

Release of free iron from cellular stores and activation of nitric oxide synthase (NOS) has been implicated in a wide variety of cochlear injuries. In order to evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7-nitroindazole (a relatively selective neuronal NOS (nNOS) inhibitor) or aminoguanidine (a relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic cochlear dysfunction, albino guinea pigs were subjected to 30 min ischemia, and the threshold shifts of the compound action potential (CAP) from pre-ischemic values were compared with those of control animals 4 h after the onset of reperfusion. A statistically significant reduction in the post-ischemic CAP threshold shift was observed in the animals treated with deferoxamine or 3-bromo-7-nitroindazole. However, aminoguanidine did not affect the post-ischemic CAP threshold shift. These results suggest that free iron and nNOS play deleterious roles in the cochlear injury induced by transient ischemia.

Protection of outer hair cells from reperfusion injury by an iron chelator and a nitric oxide synthase inhibitor in the guinea pig cochlea.

To examine whether an active process of the cochlea was injured by ischemia-reperfusion, time courses of distortion-product otoacoustic emissions (DPOAEs) were examined before, during and after 30 min cochlear ischemia using albino guinea pigs. DPOAEs decreased to the minimum level when the animals were subjected to ischemia. When the cochlea was recirculated, DPOAEs initially recovered with time until 20 min after the onset of reperfusion. However, thereafter the amplitude of DPOAEs gradually decreased toward the noise level. Administration of deferoxamine (an iron chelator) or N-nitro-L-arginine (a nitric oxide synthase inhibitor) ameliorated this decrease of DPOAEs during reperfusion and significantly increased the DPOAE amplitudes 60 min after the onset of reperfusion as compared with those in non-treated animals. These results suggest that cochlear reperfusion as well as ischemia injured the active process of the cochlea and that free radicals and nitric oxide play important roles in this injury.

Does xanthine oxidase contribute to the hydroxyl radical generation in ischemia and reperfusion of the cochlea?

We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2-thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and allopurinol, on the threshold shift of the compound action potential (CAP) after transient ischemia of the cochlea. Transient ischemia of 30 min duration was induced in albino guinea pigs via a skull base approach. The animals were treated with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from 10 min before the onset of ischemia to 4 h after the termination of ischemia. Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did not affect the post-ischemic cochlear dysfunction. These results imply that the hydroxyl radical plays an important role in generation of cochlear dysfunction induced by ischemia-reperfusion and that xanthine oxidase may not be the primary source of this radical.

Poly(adenosine diphosphate-ribose) synthetase inhibitor 3-aminobenzamide alleviates cochlear dysfunction induced by transient ischemia.

The present study was undertaken to determine the possible deleterious role played by poly(adenosine diphosphate-ribose) synthetase (PARS) in cochlear ischemia-reperfusion injury. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by pressing the labyrinthine artery at the porus acusticus internus. The animals were given intravenous 3-aminobenzamide (a PARS inhibitor) or physiological saline solution I minute before the onset of reperfusion. The compound action potential thresholds were measured before the onset of ischemia and 4 hours after the onset of reperfusion. A statistically significant reduction in the postischemic compound action potential threshold shift was observed in the animals treated with 3-aminobenzamide after 15 or 30 minutes of ischemia, whereas no statistical difference was found after 60 minutes of ischemia. These results suggest that excessive activation of PARS exerts deleterious effects on the cochlear injury induced by transient ischemia.

Steroid-sensitive nephrotic syndrome associated with Kimura disease.

We report an 11-year-old Japanese boy with Kimura disease and associated nephrotic syndrome. Before the diagnosis of Kimura disease was established, the patient had three episodes of swelling on the left cheek with subsequent nephrotic syndrome. Steroids were effective for both conditions. However, both conditions recurred within months of discontinuation of steroids. For the fourth episode of swelling on the left cheek, cyclosporine (CsA) was used. The subcutaneous tumor responded to CsA and disappeared within a few days. There has been no subsequent relapse of the nephrotic syndrome to date.

Effect of A1 adenosine receptor agonist upon cochlear dysfunction induced by transient ischemia.

The present study was undertaken to determine whether 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective A1 adenosine receptor agonist, attenuated cochlear dysfunction induced by transient ischemia or not. Ischemia of different durations (15, 30 or 60 min) was induced in 46 albino guinea pigs by transiently pressing the labyrinthine artery. CCPA or physiological saline solution was intraperitoneally administered to the animals 15 min prior to ischemia. The post-ischemic CAP threshold shift from the pre-administration value was measured 4 h after the onset of reperfusion to assess post-ischemic cochlear dysfunction. A statistically significant reduction in the CAP threshold shift was seen in CCPA-given animals after 15- and 30-min ischemia, whereas there was no statistical difference after 60-min ischemia. These results suggest that A1 adenosine receptor agonist exerts a protective effect on the cochlear injury induced by transient ischemia of intermediate duration.

Metastatic lymph-node clearance from head and neck epidermoid carcinomas following radiotherapy.

Although tumor clearance is a common criterion in assessing the impact of radiotherapy (RT), it is not always reliable. Patterns of tumor clearance were determined using 91 metastatic lymph nodes (LNs) from 51 patients with head and neck tumors treated by definitive RT (61-80 Gy) or preoperative RT (43-65 Gy). Clearance rate (CR) was estimated as a daily volume decrement expressed as a ratio to the pre-RT LN volume. CR was greater for the so-called radioresponsive nasopharyngeal subgroups and more poorly differentiated than those of oral cavity and well-differentiated, respectively. Histologically, LNs that were removed following RT consisted mainly of fibrous tissues, necrotic tissues, and few cancer cells. There was no difference in CR between the cancer-cell-positive group (n = 21) and the cancer-cell-negative group (n = 31). Although the CR may reflect inherent radiosensitivity of tumor cells, tumor persistence predicts the amount of oncologically inactive materials rather than that of remaining cancer cells.

Dominant hereditary conductive hearing loss due to an ossified stapedius tendon.

Familial conductive deafness is rare. This report confirms the existence of a lineage with congenital conductive hearing loss in 3 generations. The results of otologic evaluations, including pure-tone audiometry, tympanometry, acoustic reflex test, and liquid test, in 14 patients in this family were consistent with the findings of ossicular fixation in 10 patients. Tympanotomies performed in both ears of 4 patients indicated stapes ankylosis caused by ossification of the stapedius tendon. The patients gained normal hearing levels using a simple surgical procedure.

Distortion-product otoacoustic emissions in experimentally induced hydropic ears.

The postoperative changes of distortion-product otoacoustic emissions (DPOAEs) and cochlear potentials were examined using 15 albino guinea pigs in which endolymphatic hydrops was induced by obliterating the endolymphatic sac. DPOAEs (geometric mean: 4,6 and 8 kHz) were measured once before and every week after surgery. At the 2nd (n = 5), 4th (n = 5) and 12th (n = 5) postoperative weeks, endocochlear potential (EP) and compound action potential (CAP) were measured. Although the reduction in DPOAEs at 8 kHz was first detected at the 12th week, the amplitude of DPOAEs at 4 and 6 kHz was already reduced at the first week and decreased gradually thereafter. In contrast to these results, the CAP threshold was not elevated at the 2nd week and a slight increase was first detected at the 4th week. The results obtained in the present study suggest that DPOAEs are more sensitive than CAP in detecting the presence of hydrops.

Free vascularized iliac osteomusculocutaneous flaps based on the lateral circumflex femoral system for repair of large mandibular defects.

A free vascularized iliac osteocutaneous flap based on the ascending and transverse branches of the lateral circumflex femoral system was studied by cadaveric investigation. These composite flaps were successfully used in 2 patients with both large mandibular and soft-tissue defects. The advantages of this flap are that (1) the distal portion of the flap is relatively thin, (2) the pedicle vessels are long and large, (3) the skin territory is extremely wide, (4) repositioning of the patient during the operation is unnecessary, (5) the flap can be elevated while the recipient mandibular region is resected by two teams because the donor site is far from the head and neck regions, (6) the donor scar is in an unexposed area and its location permits easy concealment, and (7) subtotal loss of the mandible can be reconstructed with the use of split crests from either side of the ilium because the external and the internal cortices are fed independently by the lateral circumflex femoral and the deep circumflex iliac systems. This appears to be a new concept for reconstruction of total mandibular loss.

Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors.

We described a 5-month-old girl with Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors. She was admitted to our hospital because she suffered from intractable flexor spasms. Physical examination revealed craniofacial asymmetry, left auricular deformity, scoliosis, and remarkable hypotonia with psychomotor retardation. Abnormal ophthalmological findings included chorioretinopathy with pale and round-shaped peripapillary lacunae, and there was modified hypsarrhythmia in her EEG. MRI revealed multiple brain tumors in the 3rd and the lateral ventricles which are considered to be choroid plexus papilloma with agenesis of the corpus callosum. ACTH therapy was administered because of the intractable seizures. After ACTH therapy, the thresholds of waves I and V were much improved. The interpeak latency of waves I-V of the left ear and the peak latency of wave I of the right ear had been lengthened. Acoustic reflex with contralateral stimulation showed no response in the left ear. These findings indicate that the auditory system is also involved in the Aicardi syndrome and that ACTH is effective for its dysfunction.

The effect of furosemide on the endocochlear potential in ears with experimentally induced endolymphatic hydrops.

The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery.

Effects of nitrogen mustard-N-oxide on ionic activities of inner ear fluid and ionic permeabilities of the cochlear partition in the guinea pig.

The effect of nitrogen mustard-N-oxide (NMO) on the endocochlear potential (EP) was investigated from the aspect of the ion concentrations and permeabilities in the cochlea. Compared with the untreated animals, in NMO-treated animals 20 to 30 hours after administration, the EP was decreased (30.8 +/- 3.5 mV in NMO versus 82.4 +/- 1.6 mV in control), the K+ concentration in perilymph of the scala tympani was increased (8.2 +/- 1.0 mM versus 5.3 +/- 0.7 mM), the K+ concentration in endolymph was decreased (128.5 +/- 10.6 mM versus 157.9 +/- 7.9 mM), and the Na+ concentration in endolymph was increased (9.6 +/- 3.6 mM versus 2.5 +/- 0.4 mM). The permeability coefficient for Na+ of the cochlear partition in the NMO-treated animals significantly decreased, while that for Cl- significantly increased. The negative EP, which presumably exists in the normal state, diminished further (-2.7 mV versus -27.8 mV), and the calculated electrogenic potential of the EP was depressed remarkably (33.5 mV versus 110.2 mV). The results suggest that the effects of NMO involved changes in ion permeabilities of the partition and the inhibition of electrogenic transport processes in the cochlea.

Labyrinthine fistulae caused by cholesteatoma. Improved bone conduction by treatment.

In five cases of labyrinthine fistulae caused by extensive cholesteatoma, more than 30-dB improvement in bone conduction was observed in four postoperative cases and in one case after preoperative administration of antibiotics. In each case, a fistula of more than 2 mm in length was present at the lateral semicircular canal, and membranous labyrinthine wall was exposed when the cholesteatoma membrane was removed. These five cases were considered to be in the stage of serous labyrinthitis. The experience with these cases shows that emergent antibiotic treatment and surgery are appropriate for cases with reduced bone conduction in which labyrinthine fistula caused by cholesteatoma is suspected. In addition, as the reduction of bone conduction does not necessarily preclude the possibility of good postoperative hearing, tympanoplasty may be appropriate even for cases with markedly reduced bone conduction due to labyrinthine fistulae.

[Spontaneous cerebrospinal fluid fistula in association with congenital inner ear anomaly: a case report].

A case of inner ear anomaly (Mondini dysplasia) associated with recurrent meningitis found in a 10 year-old boy is reported. The patient had suffered from bacterial meningitis and CSF rhinorrhea five times in 7 years. The origin of CSF leakage had not been detected by bifrontal craniotomy or trans-sphenoidal operation. In May 1985, the dysplasia of the temporal bone and the inner ear had been pointed out by an otologist. And he underwent operations a few times for closing the CSF fistula at the floor of the internal auditory meatus by translabyrinthine approaches, but in vain. On the 7th of November 1985, under the control of intracranial pressure by continuous ventricular drainage, re-operation was performed. Packing the internal auditory meatus with several pieces of muscle and gelatine sponge stopped the CSF leakage and the recurrence of meningitis.

Efficacy of defibrinogenation and steroid therapies on sudden deafness.

Effects of defibrinogenation therapy and steroid therapy for sudden deafness were compared by paired double-blind testing. The average hearing recovery for five frequencies (250 to 4000 Hz) was more than 30 dB; overall improvement rate was 57.3% (47/82) for the patients assigned to defibrinogenation therapy and 38.7% (31/80) for the patients assigned to steroid therapy. Thus, the former treatment resulted in significantly better hearing recovery.

Extracranial chondroma of the skull base.

We report a case of an extracranial chondroma of the skull base. This tumor occupied mainly the skull base, the nasopharynx and the parapharyngeal space. Magnetic resonance imaging was effective in diagnosis and determining the extent of the lesion. Total extirpation of the lesion was performed via an external cervical approach. A survey of the available literature revealed only three similar cases treated to date.