Neurotoxicity of mercury sulfide in the vestibular ocular reflex system of guinea pigs.

A traditional Chinese mineral medicine, cinnabar, naturally occurring mercuric sulfide (HgS), is still occasionally prescribed, but the neurotoxic effects of HgS have not been elucidated. In this paper, an animal model of the purified HgS intoxication was established in guinea pigs in order to study neurotoxicity and pathophysiology of the vestibular ocular reflex system (VOR). Guinea pigs were dosed with HgS by gastric gavage (0.01, 0.1 and 1.0 g/kg per day) for 7 consecutive days. By means of caloric testing coupled with the electronystagmographic (ENG) recording in guinea pigs, we have found that HgS at a dose of 0.1 g/kg induced reversible caloric hypofunction pattern and at a higher dose of 1.0 g/kg induced irreversible hypofunction of caloric test. Monitoring the mercury contents of various tissues (blood, kidney, liver and cerebellum) by continuous flow and cold vapor atomic absorption spectrometry (AAS) revealed that a certain amount of HgS could be absorbed from the gastrointestinal tract and was detectable in these tissues. In addition to the induced dysfunction of VOR system, HgS also caused disturbance of motor performance in guinea pigs. In enzyme assay, Na+/K+-ATPase activity of cerebellum was also significantly inhibited by HgS. Morphological studies showed partial cell loss only in the cerebellar Purkinje cell layer, but not in the granule cell layer, nor in the vestibular labyrinth. All of these findings suggest that cerebellar Purkinje cells are the sensitive target site responsible for HgS-inducing dysfunctions of both VOR system and the motor performance in guinea pigs. Thus, it is concluded that caloric test coupled with ENG recording in VOR system is certainly a sensitive biomarker for monitoring the neurotoxicity of HgS.

Penicillin-G enhanced production of thuringiensin by Bacillus thuringiensis sp. darmstadiensis.

The effect of penicillin-G on the production of the potential microbial insecticide thuringiensin by Bacillus thuringiensis sp. darmstadiensis was studied. Shake flask and 3-L jar fermentor studies showed that the addition of 360 units/mL penicillin-G at 9 h, when the fermentable sugar in the medium was about to be mostly consumed, improved thuringiensin production by more than 1-fold relative to the control. The dosage of 360 units/mL penicillin-G had only a modest effect on the growth of the microorganism. However, cell growth was inhibited at higher dosages of the antibiotic. Since penicillin-G could interfere with cell wall synthesis, which facilitated the release of thuringiensin, a high thuringiensin productivity of 2600 mg/L was attained in this study, which is about 2-10-fold higher than those values reported in the literature.

Clinical significance of rebound nystagmus.

OBJECTIVE/HYPOTHESIS: Magnetic resonance imaging (MRI) examination is performed in cases of rebound nystagmus to elucidate the responsible site for rebound nystagmus. METHODS: Patients with vertigo or tinnitus received a battery of audiological and neuro-otological tests. Those who had rebound nystagmus were rechecked by electronystagmography and examined by MRI. RESULTS: Ten patients had a second-degree nystagmus evoked by changing direction of fixation, from the lateral to the forward gaze. All patients displayed positive MRI findings in cerebellum or brainstem, including tumor in seven cases and stroke in three cases. Moreover, in seven of eight cases with unilateral lesions, rebound nystagmus was ipsilateral with respect to the side of the lesion. CONCLUSION: Rebound nystagmus implies a lesion in cerebellum or brainstem for which MRI examination is 100% sensitive. It has a certain lateralizing value, with its direction away from the lesioned side.

Role of clonazepam in the treatment of idiopathic downbeat nystagmus.

OBJECTIVE/HYPOTHESIS: Downbeat nystagmus is defined as spontaneous nystagmus present with fixation in the primary position or lateral gaze. Those who have downbeat nystagmus but negative magnetic resonance imaging results are termed as idiopathic. Patients with idiopathic downbeat nystagmus, although unconcerned with their etiology, have visual symptoms such as oscillopsia, diplopia, or blurred vision. The purpose of this study is to evaluate the efficacy of clonazepam in treating idiopathic downbeat nystagmus. METHODS: Patients with downbeat nystagmus were rechecked by electronystagmography (ENG); then 0.5 mg clonazepam was administered orally. One hour later, follow-up ENG was performed again to evaluate the evolution of the downbeat nystagmus. If the test was effective, then 1.0 mg clonazepam twice daily was administered to the patients. RESULTS: Seven cases had downbeat nystagmus, including idiopathic in five, cerebellar degeneration in one, and cerebellopontine angle tumor in one. The efficacy rate for the clonazepam test was 100% in five cases of idiopathic downbeat nystagmus, whereas it was ineffective in the case of cerebellar degeneration. After long-term therapy with clonazepam, all patients with idiopathic downbeat nystagmus experienced elimination of oscillopsia, relief of diplopia, and improvement of visual acuity. Although temporary relief of downbeat nystagmus was observed 1 hour after the clonazepam test, downbeat nystagmus was not eliminated permanently. CONCLUSION: We recommend long-term therapy by clonazepam with a dosage of 1.0 mg twice daily in cases of idiopathic downbeat nystagmus. Reducing the downbeat nystagmus as well as eliminating the oscillopsia can be anticipated.

Otitis media with effusion in patients with nasopharyngeal carcinoma, postirradiation.

Eighteen patients with nasopharyngeal carcinoma were subjected to eustachian tube function testing before and 6 months and 5 years after irradiation at the university hospital to investigate the chronological changes of tubal function induced by irradiation and to study the development of otitis media with effusion after irradiation. Improvement of tubal function was found 5 years after irradiation in those ears without otitis media. However, in patients who had otitis media with effusion after irradiation, deterioration of tubal function was persistent, and inflammatory reaction was detected in the upper respiratory tract, including the maxillary sinus and nasopharynx. Thus, the development of otitis media with effusion after irradiation in patients with nasopharyngeal carcinoma is attributable to both tubal and inflammatory factors. Insertion of a ventilatory tube in ears can relieve tubal obstruction but can possibly aggravate the inflammatory process. Therefore, it is our opinion that myringotomy plus local treatment may be preferable to insertion of a ventilatory tube in patients with nasopharyngeal carcinoma who have otitis media with effusion.

A 10-year longitudinal study of tubal function in patients with nasopharyngeal carcinoma after irradiation.

OBJECTIVE: To follow up the chronological change of tubal function in patients with nasopharyngeal carcinoma for 10 years after irradiation. DESIGN: Patients with nasopharyngeal carcinoma were subjected to eustachian tube function tests before irradiation and 6 months, 5 years, and 10 years after irradiation. SETTING: University hospital. PATIENTS: Ten patients (20 ears), 7 men and 3 women. RESULTS: Twelve (60%) of the ears had patulous tubes 10 years after irradiation, which might result from atrophy of peritubal tissues. The occurrence of a patulous tube was independent of the radiation dosage, but it was related to the interval since irradiation. CONCLUSIONS: Development of a patulous tube is associated with correction of organic obstruction of the eustachian tube. Resolution of the inflammatory reaction plays the most important role in recovery of function of the tube. Therefore, the prevalence of middle ear complications is low 10 years after irradiation.

Extension of nasopharyngeal carcinoma and otitis media with effusion.

In 35 patients with nasopharyngeal carcinoma that occupied the fossa of Rosenmüller, the relationship of the tumor, assessed by computed tomographic scans, to otitis media with effusion and ventilatory function of the eustachian tube was examined. Incidence of otitis media with effusion was low when the tumor was limited to the fossa of Rosenmüller (stage I), and high when the tumor extended from the fossa to the parapharyngeal space (stage II). Passive opening of the eustachian tube remained normal until the tumor occupied the parapharyngeal space (stage III). However, active tubal opening was impaired in stage I and the impairment increased with the tumor stage. These results indicate that tumor extension from the fossa of Rosenmüller to the parapharyngeal space and resultant poor active tubal opening cause the development of otitis media with effusion in patients with nasopharyngeal carcinoma.

Effect of smoking on the treatment of vertigo.

OBJECTIVE: To study the effect of smoking on patients with vertigo. SETTING: University hospital. PATIENTS: Thirty patients with vertigo who smoke and 30 patients with vertigo who don't smoke were age-, sex-, and diagnosis-matched and given the same medication consecutively for 3 months. Then treatment efficacy was compared between two groups to investigate the relationship between smoking and vertigo. RESULTS: The efficacy of treatment of vertigo in the smoking group (30%) was lower than the nonsmoking group (74%). Intractable vertigo is related to smoking behavior but unrelated to either smoking year or tobacco year (exposure to smoking). CONCLUSIONS: For patients with vertigo who smoke during the course of treatment, the treatment may be ineffective. Therefore, neurotologists should inquire about the smoking history in vertigo patients and advise them to abstain from smoking.

Argon laser irradiation of the otolithic organ.

An argon laser was used to irradiate the otolithic organs of guinea pigs and cynomolgus monkeys. After stapedectomy, the argon laser (1.5 W x 0.5 sec/shot) irradiated the utricle or saccule without touching the sensory organs. The stapes was replaced over the oval window after irradiation. The animals used for acute observation were killed immediately for morphologic studies; those used for long-term observation were kept alive for 2, 4, or 10 weeks. Acute observation revealed that sensory and supporting cells were elevated from the basement membrane only in the irradiated area. No rupture of the membranous labyrinth was observed. Long-term observation revealed that the otolith of the macula utriculi had disappeared in 2-week specimens. The entire macula utricili had disappeared in 10-week specimens. No morphologic changes were observed in cochlea, semicircular canals, or membranous labyrinth. The saccule showed similar changes.

Intracranial relapse of nasopharyngeal carcinoma manifested as sudden deafness.

OBJECTIVE: To differentiate tumor relapse from postirradiation sudden deafness (PISD) in patients with nasopharyngeal carcinoma (NPC). STUDY DESIGN: A retrospective study from December 1991 to November 1999. SETTING: University hospital. PATIENTS: Twenty-five irradiated NPC patients with sudden deafness were investigated. All patients received local examination of ears, nose, nasopharynx, and throat fields, as well as a battery of audiologic and neurotologic tests. RESULTS: Three patients with sudden deafness within 3 years after irradiation received a diagnosis of tumor relapse. Magnetic resonance imaging revealed cerebellopontine angle metastasis in one and intracranial invasion in two. Comparison of the remaining 22 NPC patients who had PISD showed that the mean interval between the completion of irradiation to the onset of sudden deafness was 10+/-5 years. CONCLUSION: Magnetic resonance imaging should be performed to exclude intracranial relapse if sudden deafness develops in a patient with NPC within 5 years after irradiation.

Recovery of caloric function in experimental perilymph fistula.

Twenty of 46 guinea pigs with experimental perilymph fistula that showed canal paresis on an ice water caloric test during the first week after operation were studied on the following days to observe the progression and final outcome of the caloric test. Two weeks after operation, 12 animals showed persistent canal paresis, whereas 8 animals developed a normal caloric response. Resolution of the caloric response progressed from canal paresis, via caloric irregularity, to a final return of normal caloric response. Morphological study of animals with recovery of caloric function shows healing of the previously ruptured membrane, with preservation of the contour of the membranous labyrinth in the lateral semicircular duct, and intact sensorineural elements. Recovery of caloric function may serve not only as an important diagnostic sign in patients with healed perilymph fistula, even without surgical proof, but also as an expectation for the recovery of hearing loss.

Mechanism of hearing loss in irradiated ears: a long-term longitudinal study.

A 10-year longitudinal follow-up study of hearing was conducted in patients with nasopharyngeal carcinoma (NPC) in order to elucidate the mechanism of hearing loss in irradiated ears. Ten NPC patients were subjected to a battery of audiological tests before irradiation and 6 months, 5 years, and 10 years after irradiation. The tests included pure tone audiometry, tympanometry, eustachian tube function testing, and myringotomy to confirm middle ear effusion. The prevalences of otitis media with effusion (OME) were 25%, 25%, 40%, and 25% at the 4 testing periods described above, respectively. The prevalences of chronic otitis media were 0%, 0%, 15%, and 25%, respectively. In myringotomized ears (n = 17), the mean hearing levels for both air conduction and bone conduction were preserved from the preirradiation period to 10 years after irradiation. In contrast, in grommeted ears (n = 3), the mean hearing levels for both air conduction and bone conduction deteriorated progressively from the preirradiation period to 10 years after irradiation. We conclude that hearing can be preserved in NPC patients 10 years after irradiation if middle ear inflammation is well controlled. We do not recommend grommet insertion in irradiated NPC patients with OME, as it may result in persistent otorrhea and hearing deterioration.

Vestibular pathophysiologic changes in experimental perilymphatic fistula.

An animal model of experimental perilymphatic fistula (EPLF) was developed in the guinea pig in order to study vestibular pathophysiology. In experimental animals, 4 microL of perilymph was suctioned from one cochlea via the round window membrane. Changes in vestibular function were as follows. 1) During the acute stage (5 hours postoperatively), spontaneous nystagmus directed toward the normal side was noted in 57.4% of the EPLF animals. This lasted less than 24 hours. 2) One week postoperatively, direction-fixed positional nystagmus toward the lesioned ear was present in 22.7% of the EPLF animals, especially when the lesioned ear was positioned inferiorly. 3) With the ice water caloric test, no response was present in 58.1% of the EPLF animals and an irregular response was found in 22.6% of them, 1 week postoperatively. These results tend to indicate that tests of vestibular function may differentiate between patients with Meniere's disease and those with perilymphatic fistula. Histologic findings indicate that a floating labyrinth is the cause of positional nystagmus and caloric irregularity. The absence of caloric responses was associated with collapse of the vestibular labyrinth.

Eustachian tube function of patients with nasopharyngeal carcinoma.

Prolonged observations of the eustachian tube (ET) function were made on 40 ears of 20 patients with nasopharyngeal carcinoma (NPC) who survived more than 5 years after radiotherapy in a state of remission. The ET function tests included passive opening, inflation-deflation, and clearance, and were performed before, at 6 months, and at 5 years after radiotherapy. The test results were found to be worst at 6 months after radiotherapy and improved at 5 years after radiotherapy. Tubal obstruction and inflammation are the main causes of the ET malfunction that results in otitis media with effusion (OME) in NPC patients after radiotherapy. Insertion of a ventilation tube into the ear with OME can relieve tubal obstruction but can aggravate inflammation. Thus, myringotomy and aspiration of effusion and local treatment may be preferable to insertion of a ventilation tube in NPC patients with OME. When hearing improvement in prolonged survival of NPC patients with OME is needed, the use of amplification is recommended.

Patulous eustachian tube in long-term survivors of nasopharyngeal carcinoma.

This article reports on 21 long-term (10 years) survivors of nasopharyngeal carcinoma, divided into 2 groups: those subjected to an inflation-deflation test and a clearance function test in a longitudinal study, and those receiving sonotubometry in a cross-sectional study. On the inflation-deflation test, 12 (55%) out of 22 ears had a patulous eustachian tube, and on sonotubometry, 10 (50%) out of 20 ears also revealed a patulous eustachian tube. Except for 4 ears with chronic otitis media, the ears had resolved to a normal eardrum appearance at 10 years postirradiation. The phenomenon might be attributed to both restoration of the impaired tubal function and the development of a patulous tube.