Sphenomandibular ligament and degenerating Meckel's cartilage revisited: Sequential variations with temporal bone deformity for ligament attachment in near-term human fetuses.

BACKGROUND: The sphenomandibular ligament (SML) is considered to originate from Meckel's cartilage (MC). However, no study has examined how the os goniale contributes to SML development. METHODS: Semiserial histological sections of heads from 18 near-term fetuses at 27-40 weeks of gestation were examined. OBSERVATIONS: The os goniale and the anterior process of the malleus (AP) provided a long, bar-like membranous bone complex that passed through the petrotympanic and tympanosquamosal fissures. Notably, the AP-goniale complex is sometimes elongated inferiorly to join the SML (n = 4 specimens). Along the complex in the bone fissures, a degenerating MC was often present (n = 12). With (n = 6) or without (n = 3) the MC remnant, the tympanic bone (TYB) protruded inferomedially near the tympanosquamosal fissure, and it sometimes continued to a cartilaginous SML (n = 3). The temporal bone squamosa or petrosa provided a similar bony process approaching the SML. The middle meningeal artery often ran between the sphenoid and petrosa. CONCLUSIONS: Most of the specimens (n = 15) exhibited a sequential change from a cartilaginous SML as a continuation of the MC remnant to the ligament after the disappearance of the cartilage. The degenerating MC appeared to cause transformation from the AP-goniale complex and/or TYB to "another ligament" that replaced the usual SML at the upper part. Near the MC remnant, a similar transformation was also suggested on the squamosa or petrosa. The sphenoid spine appeared to originate often from the sphenoid ala major but sometimes from the TYB.

Nasal capsule ossification: A histological study using human foetuses to find an association between the foetus and adult morphologies of the nasal wall.

Recent molecular biology studies have revealed the process of nasal capsule determination. We aimed to create a fate map showing the association between the adult and embryonic components of the nasal wall and nasal capsule derivatives. We examined paraffin-embedded histological sections between 15 mid-term (9-16 weeks) and 12 near-term (27-40 weeks) foetuses. Until 15 weeks, membranous ossification occurred 'along' the capsular cartilage, contributing to the formation of the vomer, maxilla and bony nasal septum as well as the nasal, frontal and lacrimal bones. After 15 weeks, a wide lateral part of the capsule became thin and fragmented, and degenerative cartilage was observed near the lacrimal bone, in the three conchae, and at the inferolateral end of the capsule sandwiched between the maxilla and palatine bone. The disappearing cartilages appeared to be replaced by nearby membranous bones. This type of membranous ossification did not appear to use the capsular cartilage as a 'mould', although the perichondrium may have a role in inducing ossification. Calcified cartilage indicated endochondral ossification in the inferior concha until 15 weeks and, later, at the bases of three conchae and around the future sphenoid sinus (i.e. the concha sphenoidalis). The capsular cartilage extended antero-superiorly over the frontal bone and inserted into the nasal bone. At 40 weeks, the capsular cartilage remained in the cribriform plate and at the inferolateral end along the palatine bone. Consequently, less guidance from the nasal capsule seemed to provide great individual variation in the shape of the wide anterolateral wall of the nasal cavity.

Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Anatomy and pathology of lymphatic vessels under physiological and inflammatory conditions in the mouse diaphragm.

The lymphatic vessels in the parietal pleura drain fluids. Impaired drainage function and excessive fluid entry in the pleural cavity accumulate effusion. The rat diaphragmatic lymphatics drain fluids from the pleura to the muscle layer. Lymphatic subtypes are characterized by the major distribution of discontinuous button-like endothelial junctions (buttons) in initial lymphatics and continuous zipper-like junctions (zippers) in the collecting lymphatics. Inflammation replaced buttons with zippers in tracheal lymphatics. In the mouse diaphragm, the structural relationship between the lymphatics and blood vessels, the presence of lymphatics in the muscle layer, and the distributions of initial and collecting lymphatics are unclear. Moreover, the endothelial junctional alterations and effects of vascular endothelial growth factor receptor (VEGFR) inhibition under pleural inflammation are unclear. We subjected the whole-mount mouse diaphragms to immunohistochemistry. The lymphatics and blood vessels were distributed in different layers of the pleural membrane. Major lymphatic subtypes were initial lymphatics in the pleura and collecting lymphatics in the muscle layer. Chronic pleural inflammation disorganized the stratified layers of the lymphatics and blood vessels and replaced buttons with zippers in the pleural lymphatics, which impaired drainage function. VEGFR inhibition under inflammation maintained the vascular structures and drainage function. In addition, VEGFR inhibition maintained the lymphatic endothelial junctions and reduced the blood vessel permeability under inflammation. These findings may provide new targets for managing pleural effusions caused by inflammation, such as pleuritis and empyema, which are common pneumonia comorbidities.

Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Mitochondrial dysfunction can cause cochlear dysfunction and accelerate noise-induced hearing loss (NIHL). NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and has a role in the assembly and stabilization of complex I. However, the involvement of Ndufs4 in the pathogenesis of NIHL has not been reported. The aim of this study was to evaluate whether Ndufs4 deletion causes vulnerability to noise exposures. The wild-type (WT) and Ndufs4 knockout (KO) mice with C57BL/6J genetic background were used. Cochlear histology and hearing thresholds were assessed after noise exposure at 100 or 86 dB sound pressure level (SPL). Immunostaining showed the widespread expression of Ndufs4 in the cochlea. After noise exposure at 100 dB SPL, auditory brainstem response (ABR) threshold shifts at 4 kHz in Ndufs4 KO mice were significantly higher than that in WT mice. After noise exposure at 86 dB SPL, ABR threshold shifts, wave 1 amplitudes, and the number of synapses in the inner hair cells were not significantly different. RNA sequencing revealed the decreased expression of energy generation-related genes inNdufs4 KO mice. Ndufs4 deficiency accelerates permanent low-frequency threshold shifts after moderate noise exposure.

Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis.

PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Loudness functions for patients with functional hearing loss.

OBJECTIVES: To compare the loudness functions (loudness ratings as a function of sound level) obtained from patients diagnosed as having functional hearing loss (FHL) with those for patients with sensorineural hearing loss (SNHL) and healthy volunteers. DESIGN: Loudness functions for a 1000 Hz tone for patients with FHL and SNHL were assessed based on the categorical loudness scaling method. The data were compared with control data obtained in our facilities. STUDY SAMPLE: 18 patients (33 ears) with FHL and 10 patients (19 ears) with SNHL. RESULTS: For patients with SNHL and healthy volunteers, loudness increased progressively with increasing sound level above the audiometric threshold, with no exceptions. However, for about 70% of the patients with FHL, a different type of loudness function was obtained; the thresholds determined from the loudness function, which were defined as the minimum sound levels at which loudness could be judged, were 10 dB or more lower than the audiometric threshold (>10 dB), and/or the loudness ratings were elevated for a sound at the audiometric threshold. CONCLUSIONS: The results support the hypothesis that patients with FHL often make threshold judgments based on a certain loudness.

Morphology of the Upper Esophageal Sphincter or Cricopharyngeus Muscle Revisited: A Study Using Adult and Fetal Specimens.

Histological examination of specimens from 22 donated elderly cadavers and 15 human fetuses revealed that the cricopharyngeus muscle (CPM) provided (1) posterior circular muscle fibers adjacent to the external aspect of the uppermost esophageal circular muscle and (2) a thin anterior sling connecting to that same muscle. Another thick lateral bundle of longitudinal muscle originated independently from a fascia covering the posterior cricoarytenoideus muscle, extended laterally and posteriorly, and occupied a space after the CPM had disappeared at the anterolateral angle of the esophagus below the cricoid. The thick fascia contained abundant elastic fibers along the internal surface of the pharyngeal constrictors (posteromedial elastic lamina), but was interrupted or discontinued near the cricoid origin of the CPM. As no submucosal smooth muscles or elastic fibers were connected to it, the CPM did not accompany a specific elastic structure at the interface between the pharyngeal and esophageal muscles. In fetuses, the medial half of the CPM was inserted into the cricoid while the lateral half continued to the sternothyroideus muscle or ended at a fascia covering the cricothyroideus. These anterolateral ends provided a mechanical load for longitudinal growth of the pharyngeal constrictors. Consequently, the CPM was unlikely to develop and grow to form the upper esophageal sphincter, and the muscle bundle crossing the lateral aspect of the pharyngo-esophageal junction appeared to have a secondary passive role as a sphincter. This situation contrasts with that of another sphincter in the human body formed from striated muscle. Clin. Anat., 33:782-794, 2020. © 2019 Wiley Periodicals, Inc.

Complications of using Gore-Tex in medialization laryngoplasty: case series and literature review.

PURPOSE: This study was performed to evaluate the incidence and contributing factors of complications associated with medialization laryngoplasty using Gore-Tex in patients with unilateral vocal fold paralysis. METHODS: A retrospective chart review was conducted for all patients who underwent medialization laryngoplasty using Gore-Tex at Tohoku University Hospital between January 2014 and April 2018. A search of series and case reports in PubMed was performed to determine the incidence of complications following medialization laryngoplasty using Gore-Tex. RESULTS: Sixty-eight patient charts were reviewed. Two patients (2.9%) had complications (infection and extrusion into the airway) related to the Gore-Tex implant after surgery. In the 555 medialization laryngoplasty cases reported in both our current data and eight additional articles, there were 11 complications related to the Gore-Tex implant (2.0%). The most common event was extrusion into the lumen, which occurred in six cases (1.1%), followed by persistent inflammation with the granulation formation (0.5%). There were 12 cases of Gore-Tex extrusion (one male, six female, and five of unknown gender). The interval to onset ranged from 1 month to 10 years (median, 49 months). CONCLUSIONS: Our findings serve as a reminder that complications can occur with Gore-Tex implants following medialization laryngoplasty in patients with unilateral vocal fold paralysis, even in the long-term. We suggest that the use of excessively large implants in women and occurrence of postoperative hematoma followed by infection are factors that may cause complications. Nevertheless, Gore-Tex has been proven to be a relatively safe and reliable material for medialization laryngoplasty.

Enteric neurons of the esophagus: an immunohistochemical study using donated elderly cadavers.

PURPOSE: To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals. METHOD: We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker. RESULTS: The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm2 per 1-mm length of the circular esophageal wall. The cervical esophagus usually contained no ganglion cells. The number of parasympathetic ganglion cells was maximal in the upper or middle thoracic esophagus (mean 18-23 cells per section), whereas sympathetic cells were considerably less numerous at any sites (mean 1-3 cells). CONCLUSION: In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features.

Cricoarytenoid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial Tissue.

OBJECTIVE: To clarify composite fibers and cells in the synovial tissues of the cricoarytenoid joint (CA joint). METHODS: Routine histology and immunohistrochemistry using sagittal or nearly sagittal sections obtained from 18 elderly cadaveric specimens. RESULTS: The CA joint capsule was thin and contained few elastic fibers. A limited supportive ligament, namely, a thickened fascia of the posterior cricoarytenoid muscles, was sometimes evident on the lateral aspect of the CA joint. However, even in the weaker medial aspect of the joint, no marked destruction of the synovial tissues was found. The CA joint always contained synovial folds--a short medial fold and long lateral folds--but these contained no or few macrophages, lymphocytes, and blood capillaries. In 2 exceptional specimens showing inflammatory cell infiltration in the submucosal tissue of the larynx, the macrophage-rich area extended toward the capsule and medial synovial fold. CONCLUSIONS: The lateral aspect of the CA joint was likely to be supported mechanically by the muscle-associated tissues. Strong support of the arytenoid by muscles might reduce the degree of CA joint injury with age. However, some patients with hoarseness due to mucosal inflammation of the larynx might have accompanying synovitis and subsequent cartilage injury in the CA joint.

Submucosal Elastic Laminae of the Middle and Lower Pharynx: A Histological Study Using Elderly Cadaveric Specimens.

Although the pharyngeal wall is well known to have high elasticity, the distribution of submucosal elastic fibers has not been described. Observations of histological sections of the mid and lower pharyngeal walls from 15 elderly donated cadavers were made. We found two distinct submucosal tissue layers with a high content of elastic fibers (tentatively termed the "submucosal elastic laminae"). The inferolateral elastic lamina was restricted to the level from the upper part of the arytenoid to the lower end of the inferior cornu of the thyroid cartilage. It originated from the pharyngeal submucosa, extended laterally along the inner aspect of the thyropharyngeal muscle, and inserted into the posterior margin of the thyroid cartilage including the cornu. The posteromedial lamina extended along the supero-inferior axis from a level above the greater horn of the hyoid bone to reach the muscularis mucosae of the cervical esophagus. The inferolateral and posteromedial laminae were connected at levels below the cricoarytenoid joint. Individual variations were evident in their thicknesses (ranging from almost absent to 0.3 mm) as well as the extent of connection between them. In association with striated muscle function, the inferolateral lamina seemed to suspend the lower pharyngeal mucosa, while the posteromedial lamina seemed to provide mucosal fold forcing smoothly peristaltic conveyance of a bolus during swallowing.

Effect of intratympanic application of efinaconazole 10 % solution in the guinea pig.

Efinaconazole 10 % solution is a new triazole antifungal agent developed for the topical treatment of fungal infections of the nails. The current study examined the effect of intratympanic application of efinaconazole 10 % solution in the guinea pig ear. Sixteen male Hartley guinea pigs (weight 501-620 g) were divided into 3 groups to be treated with efinaconazole 10 % solution, gentamicin (50 mg/mL), or saline solution. Topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla once daily for 7 consecutive days. Post-intervention auditory brainstem responses were obtained 7 days after the last treatment. The extent of middle ear damage and hair cell loss was investigated. The efinaconazole- and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the efinaconazole-treated group and medium changes in the gentamicin-treated group. Hair cells were preserved in the efinaconazole- and saline-treated groups, but severe damage was seen in the gentamicin group. In conclusion, efinaconazole 10 % solution applied intratympanically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.

Endoscopic drainage of orbital subperiosteal hematoma secondary to acute rhinosinusitis in a child.

Acute rhinosinusitis is frequently associated with secondary orbital infection, most commonly subperiosteal abscess. Although orbital subperiosteal abscess is a deadly disease that might lead to blind and cavernous sinus thrombosis, recent review of literature showed that immediate surgical intervention might not always be necessary for subperiosteal abscess. Orbital inflammation secondary to sinusitis is common in children, whereas orbital subperiosteal hematoma secondary to sinusitis is extremely rare, with only 11 reported cases, including one case in children. All the cases were treated with surgical intervention. Here we present a 12-year-old girl with rhinosinusitis and proptosis. Emergent endoscopic sinus surgery with partial removal of the lamina papyracea revealed dark brown fluid in the subperiosteal space. The patient was symptom-free 2 weeks after surgery. The present case was treated exclusively via an endonasal approach, whereas all 11 previous cases of subperiosteal hematoma were treated with external incision. The endonasal approach is favorable, especially for young female patients. Our review of literature shows that sudden onset, afebrile, and few signs of inflammation on blood test in patients with subperiosteal lesion may indicate subperiosteal hematoma. Surgery rather than antibiotic administration should be considered for the treatment of suspected subperiosteal hematoma. Treatment through only the endonasal approach is possible even if the hematoma is located in the roof of the orbit.

Central-part laryngectomy is a useful and less invasive surgical procedure for resolution of intractable aspiration.

A novel narrow-field laryngectomy procedure known as central-part laryngectomy (CPL) for less invasive laryngeal diversion in patients with intractable aspiration is introduced. We conducted retrospective case reviews of 15 patients who underwent CPL. In this procedure, an area of the glottis including the mid-part of the thyroid cartilage and cricoid cartilage is removed to separate the digestive tract from the air way. The lateral part of the thyroid cartilage, the entire hypopharyngeal mucosa and epiglottis are preserved. The superior laryngeal vessels and nerve are not invaded. All fifteen patients were relieved of aspiration without major complications. In good accordance with cutting of the cricopharyngeal muscles and removal of the cricoid cartilage, postoperative videofluoroscopy demonstrated smooth passages of barium. Ten of 12 patients who had hoped to resume oral food intake became able to do so after CPL and two others also achieved partial oral deglutition. CPL is a useful procedure for treatment of intractable aspiration and offers considerable advantages over other laryngotracheal diversion procedures from the view point of oral food intake.

HDR syndrome, detected in the neonatal period by newborn hearing screening.

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.

Characteristic findings in the human fetus vestibule: A human temporal bone study.

OBJECTIVE: The "collapse," a highly flexed, dented, or caved membrane between the endo- and peri-lymph of the saccule and utricle in adults, is considered as a morphological aspect of Ménière's syndrome. Likewise, when mesh-like tissues in the perilymphatic space are damaged or lost, the endothelium loses mechanical support and causes nerve irritation. However, these morphologies were not examined in fetuses. METHODS: By using histological sections from 25 human fetuses (crown-rump length[CRL] 82-372 mm; approximately 12-40 weeks), morphologies of the perilymphatic-endolymphatic border membrane and the mesh-like tissue around the endothelium were examined. RESULTS: The highly flexed or caved membrane between the endo- and peri-lymphatic spaces was usually seen in the growing saccule and utricle of fetuses, especially at junctions between the utricle and ampulla at midterm. Likewise, the perilymphatic space around the saccule, utricle and semicircular ducts often lost the mesh-like tissues. The residual mesh-like tissue supported the veins, especially in the semicircular canal. CONCLUSION: Within a cartilaginous or bony room showing a limited growth in size but containing increased perilymph, the growing endothelium appeared to become wavy. Owing to a difference in growth rates between the utricle and semicircular duct, the dentation tended to be more frequently seen at junctions than at free margins of the utricle. The difference in site and gestational age suggested that the deformity was not "pathological" but occurred due to unbalanced growth of the border membrane. Nevertheless, the possibility that the deformed membrane in fetuses was an artifact caused by delayed fixation is not deniable.