Makoto Hara

Experimental perilymphatic fistula.

Perilymphatic fistula was produced in guinea pigs by injecting artificial perilymph into the subarachnoid space of the posterior fossa. Rupture of the round window was confirmed by direct observation of the round window membrane under a surgical microscope during the injection. The animals were either vitally fixed or kept alive for one to three months before fixation. Conventional celloidin embedding method was used for serial sectioning. In immediate observation, nine cochleas showed hydrops, seven showed collapse, and 20 of 36 cochleas showed no change. Changes in the vestibular apparatus varied, with collapse of the membranous vestibular labyrinth as the main change. Delayed observation revealed 16 normal cochleas and four collapses and no hydrops out of 20 ears. Of these 20, nine ears showed normal vestibular apparatus, nine collapse, and two saccule hydrops. Loss of the outer hair cells was observed in five of 20 cochleas. Marked compression of the organ of Corti was seen in both immediate and delayed observations.

Experimental herpes simplex virus and cytomegalovirus labyrinthitis.

Herpes simplex virus (HSV) and guinea pig cytomegalovirus (GPCMV) were inoculated into the middle ear of guinea pigs. The routes of passage of middle ear infection to the inner ear are hematogenous and/or via the cochlear windows. The presence of GPCMV inclusion body-bearing cells within the cochlea strongly suggests the hematogenous route, as in some animals the inner ear does not show cell infiltration and precipitate. When viral infection approaches the cochlear windows, the first morphological changes observed are the presence of precipitate in the inner ear fluids and the appearance of macrophages. These changes are particularly marked near the windows. Direct invasion of the infection into the inner ear after rupture of the round window membrane results in hemorrhage and marked cell infiltration. Inclusion body-bearing cells are found scattered within the exudate. Possible emperipolesis is frequently observed. No cells or tissues can escape involvement in viral labyrinthitis. Fibrosis and ossification eventually occur. Anomaly of the cochlea, the mirror image of the organ of Corti, was observed in the offspring of a guinea pig in whom cytomegalovirus was inoculated into the inner ear.

Histopathologic study of the perilymph-suctioned labyrinth.

A small amount of perilymph was suctioned from the scala tympani through the round window membrane of guinea pigs. The animals either were killed immediately after the suctioning or were kept alive for 1 to 3 months. For morphologic study, the conventional celloidin embedding method was employed, and the temporal bones were serially sectioned. Various kinds and degrees of changes in the membranous labyrinth were observed: Hydrops, collapse, and rupture. Loss of outer hair cells in the upper turns of the cochlea was noted in the 1- to 3-month recovery specimens. These findings are identical to those found in animals in which artificial perilymph was injected into the subarachnoid space in order to produce experimental perilymphatic fistula. After comparing morphologic changes of the membranous labyrinth following use of each method, we concluded that perilymph suctioning from the round window can be used as an animal model of perilymphatic fistula.

Morphology of the membrana limitans.

The morphology of the membrana limitans (ML) was studied by light and electron microscopy to further understand its functional significance. The ML is a porous shield composed of a few to several layers of tightly packed fibrocytes that separate the perilymphatic space of the cochlea and saccule from that of the utricle and canal system. These fibrocytes are thinner on the side of the vestibule. They show many desmosomes and gap junctions and are interspersed with fibrils. The 3-dimensional reconstruction from celloidin sections shows that the ML, as it is viewed from the anterior side, is rectangular in shape, with various surface curvatures and an invagination toward the internal aperture of the vestibular aqueduct. Horseradish peroxidase, a tracer substance, placed on either side of the ML fails to pass to the opposite side. The ML and trabecular meshwork may be a factor contributing to differential sensitivity of cochlear and vestibular sensory cells in the presence of noxious substances.

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 μL 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 Menieres 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.

Clip electrode method for recording eye movements in experimental animals

SummaryBoth the guinea pig and squirrel monkey were used in this study. An animal model for inner ear disease was established, and each animal was subjected to vestibular function tests consisting of spontaneous nystagmus recording, positional testing, caloric testing, and optokinetic stimulation testing. Recordings of nystagmus in the guinea pig and squirrel monkey were successfully obtained by using newly devised clip electrodes. A variety of nystagmic patterns in animal models following experimentally created perilymphatic fistula and labyrinthectomy are presented in this study.

An effective management regimen for laryngeal granuloma caused by gastro-esophageal reflux: combination therapy with suggestions for lifestyle modifications

According to our previous study, lifestyle modification in combination with drug therapy is much more effective than drug therapy alone in cases of laryngopharyngeal reflux (LPR). Most patients with LPR will have chronic gastro-esophageal reflux diseases (GERD) and require long-term medical therapy for control, resulting in high total expenditure on pharmacologic agents. We combined pharmacologic management with lifestyle modifications for the management of GERD with successful outcomes in patients with GERD-related laryngeal granulomas. Although further studies are needed, guidance concerning lifestyle modifications in combination with PPI therapy may be not only a clinically effective but also a cost-effective method for the management of laryngeal granulomas caused by gastro-esophageal reflux.

Walking through a human ear.

A computer animation system was developed to show the inside of a human ear as if the viewer were walking through it. A surface model of the human temporal bone was graphically reconstructed from serially sectioned celloidin specimens. In order to input the outline curves of ear structures, several reference marks were drilled into a celloidin block prior to sectioning. A sliding microtome was put on a worktable with a specially designed motor-driven drill. The machine made it possible to drill holes perpendicular to the plane to be used for serial sectioning. Superimposed outline curves and the reference marks were fed into a computer, and their shapes were altered by scaling, rotation, and translation before triangulation for surface coating. Parts of the structures of the ear were painted in different colours.

An electrophysiologic study of experimental perilymphatic fistula

This study was undertaken to elucidate the mechanism that causes sensorineural hearing loss in clinical cases with perilymphatic fistula. Perilymph was experimentally aspirated through the round window membrane in 17 guinea pigs. The extent of cochlear damage was examined electrophysiologically as well as histopathologically. Immediately after aspiration, several types of changes in summating potential (SP) were observed. Two animals without a polarity change of the SP showed only slight threshold changes in both cochlear microphonic and action potentials, and no specific histopathologic changes in the cochlea. Reversed polarity of the SP was observed in three animals, of which one showed a high-amplitude negative SP followed by rapidly progressive hearing loss. Bulging of Reissners membrane was confirmed histopathologically in this case. The SP disappeared in the remaining 12 animals. In animals with profound electrophysiologic changes, bulging or rupture of Reissners membrane and damaged hair cells were observed. These findings suggest that an abrupt change in perilymphatic pressure produces morphologic changes in the membranous labyrinth, causing changes in the vibration function of the cochlear partition and in the function of the organ of Corti. Abrupt pressure imbalance may be a causative factor of sensorineural hearing loss in the case of perilymphatic fistula.

Childbirth in true hermaphrodite

14-year-old Japanese girl with a 46,XX karyotype underwent an exploratory laparotomy for signs of virilization. The left ovary and other pelvic organs were of female type. The right gonad was found to be an ovotestis which was removed. At age of 25, the patient gave birth to a normal male infant by full-term, vaginal delivery. In the literature, this is the third case of normal delivery in 7 true hermaphrodites with pregnancy and childbirth.