The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review.

There is a lack of knowledge regarding the connection between the ocular and nasal epithelia. This narrative review focuses on conjunctival, corneal, ultrastructural corneal stroma, and nasal epithelia as well as an introduction into their interconnections. We describe in detail the morphology and physiology of the ocular surface, the nasolacrimal ducts, and the nasal cavity. This knowledge provides a basis for functional studies and the development of relevant cell culture models that can be used to investigate the pathogenesis of diseases related to these complex structures. Moreover, we also provide a state-of-the-art overview regarding the development of 3D culture models, which allow for addressing research questions in models resembling the in vivo situation. In particular, we give an overview of the current developments of corneal 3D and organoid models, as well as 3D cell culture models of epithelia with goblet cells (conjunctiva and nasal cavity). The benefits and shortcomings of these cell culture models are discussed. As examples for pathogens related to ocular and nasal epithelia, we discuss infections caused by adenovirus and measles virus. In addition to pathogens, also external triggers such as allergens can cause rhinoconjunctivitis. These diseases exemplify the interconnections between the ocular surface and nasal epithelia in a molecular and clinical context. With a final translational section on optical coherence tomography (OCT), we provide an overview about the applicability of this technique in basic research and clinical ophthalmology. The techniques presented herein will be instrumental in further elucidating the functional interrelations and crosstalk between ocular and nasal epithelia.

The relationship between jugular bulb position and jugular bulb related inner ear dehiscence: a retrospective analysis.

OBJECTIVE: High jugular bulb (HJB) can erode inner ear structures creating a jugular bulb related inner ear dehiscence (JBID). The aim of this study was to analyze the relationship between the position of jugular bulb (JB) and JBID using high-resolution computed tomography (HRCT). MATERIAL AND METHODS: In this retrospective study HRCT images of 552 ears of 276 patients with hearing loss, otogenic vertigo, tinnitus or idiopathic peripheral facial nerve paralysis were analyzed. HJB type-1 was defined when JB dome reached above the inferior part of the round window, but was below the inferior edge of the internal acoustic meatus (IAM). HJB type-2 was defined when the dome of JB was higher than the inferior edge of IAM. The frequencies and types of HJB were evaluated. JBID for each HJB type was determined. Frequencies of JBID eroding the vestibular aqueduct (VA), the cochlear aqueduct and the posterior semicircular canal were examined. RESULTS: HJB type-1 and HJB type-2 were found in 19% (105/552) and in 15.8% (87/552) of studied ears. JBID showed to be in 3.8% (21/552) of all ears. 90.5% (19/21) of JBID revealed eroding of VA. Jugular bulb related cochlear aqueduct dehiscence and jugular bulb related posterior semicircular canal dehiscence were found in one ear each. The frequency of jugular bulb related vestibular aqueduct dehiscence (JBVAD) in patients with HJB reaching above IAM was higher than in patients with HJB lower than IAM. CONCLUSIONS: HJB is common, but JBID is rare. JBID prevalently erodes VA. HJB rising above IAM is most at risk to show JBVAD.

Promontory electrical stimulation to elicit vestibular evoked myogenic potentials (VEMPs).

CONCLUSION: Vestibular evoked myogenic potentials (VEMPs) provoked electrically at the promontory provide a feasible method to record vestibular responses in awake patients. OBJECTIVES: Electrically evoked VEMP testing has been performed by galvanic stimulation at the mastoid so far. The present study examined an electrical stimulation mode close to the otolith organs at the promontory. METHODS: Fourteen cochlear implant candidates who were planned for clinical routine promontory stimulation testing (PST) to assess auditory nerve function underwent promontory VEMP testing. After testing the cochlear nerve function during PST promontory cervical VEMPs (p-c-VEMPs) and promontory ocular VEMPs (p-o-VEMPs) were recorded during subsequent transtympanic electrical stimulation at the promontory. RESULTS: Promontory VEMP testing was well tolerated by the patients. Mean latencies for p-c-VEMPs were 10.30 ± 2.23 ms (p1) and 17.86 ± 3.83 ms (n1). Mean latencies for p-o-VEMPs were 7.64 ± 1.24 ms (n1) and 11.2 ± 1.81 ms (p1). The stimulation threshold level was measured at 0.15 ± 0.07 mA for p-c-VEMPs and at 0.19 ± 0.11 mA for p-o-VEMPs. The discomfort level was found to be at 0.78 ± 0.29 mA for p-c-VEMPs and at 0.69 ± 0.25 mA for p-oVEMPs. Mean p1-n1 amplitude in p-c-VEMPs was 124.78 ± 56.55 µV and p-o-VEMPs showed a mean n1-p1 amplitude of 30.94 ± 18.98 µV.

Jugular bulb abnormalities in patients with Meniere's disease using high-resolution computed tomography.

Temporal bone abnormalities such as hypoplasia of the vestibular aqueduct or hypopneumatization of the mastoid have been described in Meniere's disease (MD). Jugular bulb abnormalities (JBA) are one of the most common temporal bone abnormalities. The aim of this study was to evaluate the frequency of JBA in MD. Radiological data obtained by temporal bone high-resolution computed tomography of 200 ears of 167 MD patients (MD group) and 218 ears of 109 patients with normal inner ear function (control group) were analyzed retrospectively. The frequencies of high jugular bulb (HJB), jugular bulb diverticulum (JBD), inner ear adjacent jugular bulb (IAJB) and jugular bulb related inner ear dehiscence (JBID) were evaluated and compared between MD group and control group. IAJB was differentiated into vestibular aqueduct adjacent jugular bulb (VAAJB), cochlear aqueduct adjacent jugular bulb and posterior semicircular canal adjacent jugular bulb. JBID was further analyzed by differentiating into jugular bulb related vestibular aqueduct dehiscence (JBVAD), jugular bulb related cochlear aqueduct dehiscence and jugular bulb related posterior semicircular canal dehiscence. The frequencies of HJB, JBD and IAJB were higher in MD group compared to control group (21, 13.3 %, p = 0.036; 8.5, 3.7 %, p = 0.037; 13.5, 4.6 %, p = 0.001). No differences between both groups were seen in JBID (4.0, 2.3 %, p = 0.315). Most IAJB and JBID were seen in VAAJB and JBVAD. There is a higher frequency of JBA in patients with MD than in patients without inner ear symptoms. Temporal bones of MD patients might be constituted anatomically different, carrying predisposing factors for the development of clinically apparent MD.

Radiological findings of the cochlear aqueduct in patients with Meniere's disease using high-resolution CT and high-resolution MRI.

The objective of the present study was to evaluate the cochlear aqueduct (CA) in Meniere's disease (MD) and to disclose radiological differences of CA between MD and non-MD patients by means of high-resolution computed tomography (HRCT) and high-resolution magnetic resonance imaging (HRMRI). Radiological data of 86 ears of MD patients which were separated into 52 ears of diseased side group (MD-D group) and 34 ears of contralateral non-affected side group of unilateral MD (MD-ND group), 27 ears of patients with sensorineural hearing loss (SNHL group) and 56 ears of patients with somatoform dizziness and normal hearing (control group) were analyzed retrospectively. The bony type of CA, the bony length of CA, and the bony width of CA medial orifice was measured in HRCT. The visibility of CA in HRMRI was scored. Fluid length in CA and fluid width in medial orifice were measured in HRMRI. Data were compared between MD-D, MD-ND, SNHL, and control group. There were no significant differences in the bony type of CA, bony length of CA, bony width of CA medial orifice, and fluid width of CA medial orifice between MD-D, MD-ND, SNHL and control group (p > 0.05). However, CA fluid length of MD-D (5.13 ± 1.88 mm) and of MD-ND group (5.44 ± 1.81 mm) was significantly shorter than fluid length of SNHL (6.90 ± 1.55 mm) (p < 0.001, p = 0.001) and of control group (7.43 ± 1.24 mm) (p < 0.001, p < 0.001). The ratio between CA fluid length and CA bony length was the smallest in MD-D group (0.403; p = 0.009). CA bony dimensions of affected ears of MD are normal, but CA fluid length is decreased.

Eustachian tube function in patients with inner ear disorders.

The influence of Eustachian tube (ET) dysfunction on the inner ear fluid pressure and thus on the inner ear function in Meniere's disease has been discussed controversially. So far, most of the studies examining ET function in inner ear disorders indirectly analyzed ET function by tympanometric methods. The present study directly studied ET function in inner ear disorders by sonotubometry. Healthy subjects and patients with Meniere's disease, sudden sensorineural hearing loss, cholesteatoma and chronic suppurative otitis media were examined by sonotubometry. Mean increase of sound pressure intensity (dB) and mean duration of sound pressure increase (s) were analyzed. Highest mean increase of sound pressure intensity was seen in healthy subjects when using >5 dB peaks (11.6 ± 0.7 dB) and >0 dB peaks (9.6 ± 0.6 dB). Comparative analysis including bilateral ears showed decreased ET function in patients with cholesteatoma (p = 0.002) and in patients with Meniere's disease (p = 0.003) when using >0 dB peaks. Examination of each specific ET opening maneuver showed impaired ET function in pathological ears of patients with cholesteatoma and with Meniere's disease, during yawning (p = 0.001; p < 0.001), dry swallowing (p = 0.010; p = 0.049), Toynbee maneuver (p = 0.033; p = 0.032) and drinking (p = 0.044; p = 0.027). Mild ET dysfunction is detected in patients with Meniere's disease by direct sonotubometric assessment of ET function.

Hydrostatic fluid pressure in the vestibular organ of the guinea pig.

Since inner ear hair cells are mechano-electric transducers the control of hydrostatic pressure in the inner ear is crucial. Most studies analyzing dynamics and regulation of inner ear hydrostatic pressure performed pressure measurements in the cochlea. The present study is the first one reporting about absolute hydrostatic pressure values in the labyrinth. Hydrostatic pressure of the endolymphatic system was recorded in all three semicircular canals. Mean pressure values were 4.06 cmH(2)O ± 0.61 in the posterior, 3.36 cmH(2)O ± 0.94 in the anterior and 3.85 cmH(2)O ± 1.38 in the lateral semicircular canal. Overall hydrostatic pressure in the vestibular organ was 3.76 cmH(2)O ± 0.36. Endolymphatic hydrostatic pressure in all three semicircular canals is the same (p = 0.310). With regard to known endolymphatic pressure values in the cochlea from past studies vestibular pressure values are comparable to cochlear values. Until now it is not known whether the reuniens duct and the Bast's valve which are the narrowest passages in the endolymphatic system are open or closed. Present data show that most likely the endolymphatic system is a functionally open entity.

Role of neck ultrasound during follow-up care of head and neck squamous cell carcinomas.

CONCLUSION: No impact of neck ultrasound on the detection rate of neck recurrences of head and neck squamous cell carcinomas (HNSCCs) was seen. The outcome of salvage therapy was not influenced by close neck ultrasound monitoring during follow-up. Tendencies of earlier detection of neck recurrences were noticed. OBJECTIVES: Neck ultrasound is more feasible for frequent application than computed tomography, while having comparable sensitivity and specificity in detecting neck metastasis. Before this study the effect of neck ultrasound on salvage therapy of neck recurrences when used in short defined intervals during follow-up was unknown. METHODS: A total of 140 patients with primarily surgically treated HNSCC were enrolled in a follow-up program with defined close time intervals. Neck ultrasound was applied during every follow-up visit. Recurrence rate, survival rate, and outcome of salvage therapy were determined. RESULTS: Overall recurrences occurred in 35.0% of patients. Local, regional, and distant recurrences were found in 11.4%, 7.9%, and 15.7%. Hypopharyngeal carcinoma and advanced staged tumor showed highest recurrence rates. In all, 24.5% of all recurrences were treated successfully by salvage therapy. Resection of local, regional, and distant recurrences resulted in 3-year survival rates of 43.8%, 36.4%, and 4.5%. The outcome of secondary therapy worsened with advancing initial primary tumor stage.

Long-term middle ear pressure measurements in inner ear disorders.

CONCLUSION: Repetitive portable tympanometry is a feasible method to examine long-term middle ear pressure profile. This method might be suitable for detecting patients with Meniere's disease whose middle ear pressure shows intermittently pathological values. OBJECTIVES: Contradictory study results regarding middle ear pressure in patients with Meniere's disease might be due to solitary tympanometric measurements. Pathological pressure conditions in patients with pressure regulation disorders might be missed by a single examination. The aim of the study was to examine the pressure profile of patients with Meniere's disease by long-term measurements. METHODS: Patients with Meniere's disease (n = 33), patients with sudden hearing loss (n = 20), and healthy subjects (n = 30) were examined. Patients carried out long-term middle ear pressure measurements with the portable tympanometer Otoflex 100. Examinations were carried out during daily activities at defined time intervals. RESULTS: Significant negative middle ear pressure were seen in patients with Meniere's disease compared with patients with sudden hearing loss and healthy subjects (p < 0.01). Average middle ear pressure in patients with Meniere's disease was -43 daPa, in patients with sudden hearing loss it was 2 daPa, and in healthy subjects it was 4 daPa. Patients with Meniere's disease showed a large variability of pressure values ranging from strongly pathological to normal values during long-term measurements.

Characterization of cell types during rat liver development.

Hepatic stem cells have been identified in adult liver. Recently, the origin of hepatic progenitors and hepatocytes from bone marrow was demonstrated. Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1. Little is known about liver stem cells during liver development. In this study, we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18 during liver development to identify putative fetal liver stem cell candidates. Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were digested by collagenase-DNAse solution and purified by percoll centrifugation. Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1 and CK-18. Thy1 expression was found at all stages of liver development before and after MACS in immunocytochemistry. Thy1 positive cells were enriched after MACS only in early developmental stages. An enrichment of CK-18 positive cells was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK-18 were identified by double labeling of fetal liver cell isolates. In conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express Thy1. Other progenitors express only CK-18. This indicates the coexistence of different hepatic cell compartments. Isolation and further characterization of such cells is needed to demonstrate their biologic properties.