Martin Nue Møller

Angiogenesis in vestibular schwannomas: Expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1†

Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study targets the angiogenic process by investigation of tumor expression of MMP‐2, MMP‐9, and tissue inhibitors of metalloproteinase (TIMP)‐1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored.

Gene expression in the human endolymphatic sac: the solute carrier molecules in endolymphatic fluid homeostasis.

Objectives/Hypothesis The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the solute carrier (SLC) molecules of ion transporters in the human endolymphatic sac. Study Design cDNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic sac tissue samples. Methods Twelve tissue samples of the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample expression of solute carrier family genes, using adjacent dura mater as control. Immunohistochemistry was used for verification of translation of selected genes, as well as localization of the specific protein within the sac. Results An extensive representation of the SLC family genes were upregulated in the human endolymphatic sac, including SLC26a4 Pendrin, SLC4a1 sodium-bicarbonate transporter, SLC9a2 sodium-hydrogen transporter, SLC12a3 thiazide-sensitive Na-Cl transporter, and SLC34a2 sodium-phosphate transporter. Conclusions Several important ion transporters of the SLC family are expressed in the human endolymphatic sac, including Pendrin, the thiazide-sensitive Na-Cl transporter, and the Na-phosphate transporter SLC34a2. The data provide a new knowledge base considering the ion-dependent metabolic mechanisms maintaining inner ear homeostasis. More specifically, the results indicate a strong similarity with the ion transportation occurring in the kidney collecting ducts. In addition, the findings prompt a revision of the theories behind contemporary pharmacological treatment of Ménière’s disease and may broaden the understanding of the pathogenesis of BPPV.

Gene expression demonstrates an immunological capacity of the human endolymphatic sac

The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear.

Oxygenated fixation demonstrates novel and improved ultrastructural features of the human endolymphatic sac.

The purpose of the present study is to describe in detail the ultrastructure of the human endolymphatic sac using a new and improved method of fixation as well as a refined surgical approach in obtaining specimens.

Bacterial invasion of the inner ear in association with pneumococcal meningitis.

Objective To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. Study Design A well-established adult rat model of Streptococcus pneumoniae meningitis was used. Methods Thirty rats were inoculated intrathecally with S. pneumoniae serotype 1, 3 or 9 V and received no additional treatment. The rats were sacrificed when reaching terminal illness or on Day 7 and then prepared for serial sectioning and PAS-Alcian blue staining for light microscopy. Results During the first few days after inoculation, bacteria invade the inner ear through the cochlear aqueduct, into the scala tympani of the cochlea (perilymphatic space). From here, bacteria spreads apically toward the helicotrema and subsequently basally through the scala vestibuli, toward the vestibule and the vestibular system. When the bacteria after 5 to 6 days had reached scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. Conclusion From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral ligament capillary bed occur at later stages. Although internal barriers exist within the inner ear, the spreading of bacteria occurs via the natural pathways of the fluid compartments. Bacterial elimination occurs by local macrophage engulfment.

High variability of facial muscle innervation by facial nerve branches: A prospective electrostimulation study

To examine by intraoperative electric stimulation which peripheral facial nerve (FN) branches are functionally connected to which facial muscle functions.

The human endolymphatic sac expresses natriuretic peptides

The function of the human endolymphatic sac (ES) has been enigmatic for decades. Hypotheses include controlling endolymphatic fluid homeostasis and inner ear immunological defense. Additionally, several studies indicate a possible endocrine capacity and a yet undefined role in intracranial pressure homeostasis. However, no direct evidence of such capacity exists. This study aims to explore and identify the hypothesized endocrine capacity of the human ES.

Clinical Outcome of a Wide-diameter Bone-anchored Hearing Implant and a Surgical Technique With Tissue Preservation.

Objective: To investigate the clinical outcome of a surgical technique with tissue preservation for a wide bone-anchored hearing implant concerning postoperative complications, skin reactions, implant loss, and implant stability. Study Design: Consecutive, prospective case series. Setting: Tertiary referral center. Patients: Twenty-four adult patients with normal skin quality were enrolled. Intervention(s): Implantation of bone-anchored implant was performed using a one-stage linear-incision technique with tissue preservation surgery. Main Outcome Measures(s): Skin and soft tissue reactions according to Holgers grading system. Pain and numbness measured according to visual analogue scale. Implant stability quotient values were recorded using resonance frequency analysis. Follow-up at 10 days, 6 weeks, 6 months, and 1 year after surgery. Results: Primary implant stability was good and a significant increase in implant stability quotient occurred during the first 10 days and continued to be stable throughout the 1-year observation period. No implants were lost. Skin and soft tissue reactions were few, no reaction (Holger grade 0) was observed in 88% of the follow-up examinations and no grade 4 reactions occurred. Pain and numbness were minimal. Conclusion: The wide implant showed good stability initially and throughout the observation period. Skin and soft tissue reactions were rare and minor. No implants were lost.

Endolymphatic sac involvement in bacterial meningitis

Abstract The commonest sequelae of bacterial meningitis are related to the inner ear. Little is known about the inner ear immune defense. Evidence suggests that the endolymphatic sac provides some protection against infection. A potential involvement of the endolymphatic sac in bacterial meningitis is largely unaccounted for, and thus the object of the present study. A well-established adult rat model of Streptococcus pneumoniae meningitis was employed. Thirty adult rats were inoculated intrathecally with Streptococcus pneumoniae and received no additional treatment. Six rats were sham-inoculated. The rats were killed when reaching terminal illness or on day 7, followed by light microscopy preparation and PAS-Alcian blue staining. The endolymphatic sac was examined for bacterial invasion and leukocyte infiltration. Neither bacteria nor leukocytes infiltrated the endolymphatic sac during the first days. Bacteria invaded the inner ear through the cochlear aquaduct. On days 5–6, the bacteria invaded the endolymphatic sac through the endolymphatic duct subsequent to invasion of the vestibular endolymphatic compartment. No evidence of direct bacterial invasion of the sac through the meninges was found. Leukocyte infiltration of the sac occurred prior to bacterial invasion. During meningitis, bacteria do not invade the endolymphatic sac through the dura, but solely through the endolymphatic duct, following the invasion of the vestibular system. Leukocyte infiltration of the sac occurs prior to, as well as concurrent with bacterial invasion. The findings support the endolymphatic sac as part of an innate immune defense system protecting the inner ear from infection.

Innate immune defense in the inner ear – mucines are expressed by the human endolymphatic sac

The human endolymphatic sac has been shown recently to have immunological capacities and has thus been proposed as the main entity protecting the inner ear from pathogen invasion, equivalent to mucosa‐associated lymphoid tissue (MALT). Although the sac expresses molecules of the innate immune system, the potential expression of members of the important mucin family has not been detailed. Thus, this paper explores endolymphatic sac expression of a number of mucins and mucin precursors. Twelve fresh tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery. The expression of Mucin 1, 2, 5B/AC and 16, as well as the core structure elements (mucin precursors) T‐antigen, Tn‐antigen and Sialyl‐Tn‐antigen was investigated by immunohistochemistry. The endolymphatic sac epithelium expressed MUC1 (both apically towards the endolymphatic sac (ES) lumen and basally towards the capillary network), MUC 16 and Tn‐antigen. There was no labeling after incubation with antibodies against T‐antigen, sialyl‐Tn‐antigen, MUC2 and MUC5B/AC. We conclude that the human endolymphatic sac epithelium expresses a number of mucin molecules, which supports the hypothesis of the sac as the primary immunological tissue structure of the inner ear, equivalent to MALT in other organs. The mucins may also play a role in the formation and continuous homeostasis of the inner ear fluids, as well as the pathogenesis of Menieres disease.