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S Dazert

Publications and source records attributed to S Dazert.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase influences neurotrophin-induced spiral ganglion neurite growth].

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) is considered to be an important enzyme in cell signaling, mediating certain aspects of neurotrophin signals from the cell surface receptor to the nucleus. METHODS: The participation of PI3K in the mediation of neurotrophin-induced effects in the spiralganglion (SG) of neonatal rats was investigated in vitro. SG explants were stimulated with neurotrophin (NT)-3 and treated with Wortmannin, a specific inhibitor of PI3K. After fixation and immunhistochemical staining, the growth of the SG neurites was evaluated. RESULTS: Stimulation with NT-3 lead to significant increases in number and length of neurites, when compared to non-stimulated controls. Treatment of NT-3 stimulated SG explants resulted in a dose-dependent reduction of both parameters, whereas the neurite growth of non-stimulated control explants was not significantly influenced by the incubation with Wortmannin. CONCLUSIONS: The results demonstrate that neurotrophin-induced neurite growth from SG explants can be modulated with the PI3K inhibitor Wortmannin and indicate that PI3K is a key enzyme in the mediation of NT-3 effects in cochlear neurons. These observations together with results of previous studies suggest that the activation of PI3K as well as Ras and MEK are essential for neurite growth in cochlear neurons. Further knowledge of cell signaling mechanisms influencing SG neurite growth could lead to new therapeutical strategies for the treatment of inner ear diseases.

Androstadienes↗
PubMed2001

Sigmoid and transverse sinus thrombosis after closed head injury presenting with unilateral hearing loss.

Sinus thrombosis has rarely been associated with closed head injury; more often, thrombosis of the sigmoid or transverse sinus is caused by otogenic inflammations or tumours, or occurs during pregnancy. Symptoms are frequently vague, while untreated thrombus progression may be fatal due to venous congestion and infarction. We report a 32-year-old man presenting with right hearing loss, tinnitus and headache 2 days after a closed head injury. Neurological examination showed no additional abnormality. The EEG showed focal bifrontal slowing. CT revealed a fracture of the occipital bone. MRI and MRA demonstrated complete thrombosis of the right sigmoid and transverse sinuses. After 2 weeks of intravenous heparin therapy followed by warfarin, the patient's hearing improved and MRI and MRA showed complete recanalisation of the sigmoid and transverse sinuses. Venous sinus thrombosis can be an undetected sequel to head injury. Appropriate imaging studies should be carried out to enable therapy to be started as soon as possible.

Adult↗
PubMed2001

Ras/MEK but not p38 signaling mediates NT-3-induced neurite extension from spiral ganglion neurons.

Neurotrophin (NT)-3 is expressed in the neuronal target tissue of the developing rat cochlea and has been shown to promote the survival and neurite outgrowth of spiral ganglion (SG) neurons, suggesting a role for this protein during the innervation of the organ of Corti. In other neurons, NT-3 can mediate neuritogenesis and survival via a number of intracellular signal pathways. To date, the intracellular transduction pathways involved in the mediation of NT-3 effects have not been investigated in SG neurons. To determine whether the activities of NT-3 on SG neurons are dependent on the activation of mitogen-activated protein kinase kinases (MEK)/extracellular-signal-regulated kinases (ERK), Ras, and/or p38, SG explants from postnatal-day 4 rats were cultured with NT-3 and increasing concentrations of the MEK inhibitor U0126, the Ras farnesyl-transferase inhibitor (FTI)-277, and the p38 inhibitor SB203580. After fixation and immunocytochemical labeling, neurite growth was evaluated. A dose-dependent decrease of the effects of NT-3 on length and number of processes was observed in the U0126- and FTI-277-treated SG neurons. In contrast, SB203580 had no significant effect on NT-3-mediated stimulation of neurite growth, in terms of either number or length. The results suggest that NT-3 effects on SG neurons are mediated primarily by the Ras/MEK/ERK signaling pathway.

Animals↗
PubMed2001

In vivo adenoviral transduction of the neonatal rat cochlea and middle ear.

Virally mediated gene transfer to the adult mammalian ear appears to be a powerful strategy to investigate gene function in the auditory system and to develop new therapeutic treatment for hearing impaired patients. However, there has been little work done in the neonatal middle and inner ear. In this study, a recombinant adenoviral (AdV) vector was used for gene transfer of a beta-galactosidase (beta-gal) reporter gene to the neonatal middle ear and cochlea of 5 day old rats. For transduction of middle ear, AdV was injected through the tympanic membrane into the tympanic cavity. Three and 7 days later, strong expression of beta-gal was observed in epithelial cells of the mucosa, but not in the underlying stroma or mesenchyme. There was little or no infiltration of leukocytes. No expression of beta-gal was detected inside the cochlea or vestibular system. When AdV was injected into the basal turn of the cochlea, high levels of beta-gal expression were observed in cells lining the perilymphatic space and in parts of the spiral ligament 3, 7 and 21 days later. Spiral ganglion cells did not express beta-gal. However, virally mediated gene transfer was observed in some cells of the organ of Corti. A moderate infiltration of leukocytes into the labyrinth was observed, but no vestibular or auditory dysfunction. These results demonstrate that neonatal middle ear and cochlear cells can be successfully transduced with an AdV vector in vivo, without obvious morphological signs of inflammation or cellular damage. AdV vectors provide a tool for investigation of the role of genes in influencing the development of middle and inner ear structures. Virally mediated expression of protective genes could also be used to rescue hair cells or spiral ganglion cells from congenital degeneration or damage.

Adenoviridae↗
PubMed2000

[Effect of fibroblast growth factor-1 (FGF-1) on spiral ganglion cells of the mammalian cochlea].

Transient expression by hair cells, increasing levels of FGF-1 mRNA in neonatal rat spiral ganglion neurons and strong expression in adulthood, make FGF-1 a candidate to be associated with development and maintenance of the mammalian spiral ganglion. To test this hypothesis, dissociated spiral ganglion cells from 5 day old rats were cultured in the presence of FGF-1 at 100 ng/ml plus heparan sulfate proteoglycans (HSPG) at 500 ng/ml for 72 hours. Spiral ganglion cells incubated with FGF-1/HSPG achieved an average neurite length of 323 microns while control cells gained an average neurite length of 203 microns. The results of this study are consistent with our previous findings in whole spiral ganglion explants (3) where FGF-1 incubation significantly stimulated neurite outgrowth at about the same range. However, stimulation of neurite outgrowth in dissociated spiral ganglion cells suggests that FGF-1 directly binds to FGF receptors on the surface of spiral ganglion neurons and/or neurites instead of acting via intermediate cells such as glia. Since FGF receptor mRNA was found to be expressed only at very low levels in neonatal spiral ganglion neurons (7) it is possible that the receptors are highly localized, perhaps to neurite growth cones. Alternatively, an unknown FGF receptor or splice variant may be expressed in these cells. Adequate FGF-1 application to the human inner ear may stimulate spiral ganglion cell survival and neurite extension after hair cell loss in patients suitable for cochlear implant treatment. By creating a closer contact between spiral ganglion cells and the electrode, FGF-1 might also improve the efficacy of cochlear implants.

Animals↗
PubMed2000

["Vibrant Soundbridge" middle ear implant for auditory rehabilitation in sensory hearing loss. I. Clinical aspects, indications and initial results].

BACKGROUND: The adequate therapy for patients suffering from a sensory hearing loss consists of fitting electronic hearing devices. Conventional hearing aids, however, present with significant inherent drawbacks such as insufficient amplification in the high frequency range, problems with the ear mold (feed back, occlusion, external otitis), or distortion of sound with an "unnatural" hearing impression. METHODS: The partially implantable middle ear device Vibrant Soundbridge provides a sound wave conversion into mechanical vibrations at the middle ear ossicles using the Floating Mass Transducer (FMT). The audiological advantages are due to a direct moving force to the perilymph via incus and stapes. The Vibrant Soundbridge system is indicated in patients with a medium to severe symmetrical sensory hearing loss and a normal middle ear. Candidates need previous experience with conventional hearing aids without satisfactory results. RESULTS: The eight operated patients report a "natural" quality of sound and speech, a better hearing perception at high frequencies and the absence of feed back phenomena. Audiological evaluation and questionnair results support the patients subjective hearing impression. CONCLUSIONS: The Vibrant Soundbridge improves hearing quality in patients with sensory hearing loss. The hearing implant is indicated in particular in patients that are unable to wear conventional hearing aids.

Adult↗
PubMed2000

[An anesthesia technique for experimental studies and microsurgical ear interventions in newborn rodents].

BACKGROUND: Experimental investigations on laboratory animals usually require sufficient anesthesia with adequate analgesia and sedation. The technique used should be reliable and easily controllable by the investigator. Here, we present a technique for anesthesia to facilitate invasive and noninvasive investigations in newborn rats and mice. METHODS: Using a custom made breathing mask, anesthesia was induced in these animals with inhalation of gaseous nitrous oxide-oxygen (equal volume at 1 l/min) and halothane (3% by volume). To maintain anesthesia, halothane insufflation was reduced to 1-1.5% by volume. After completion of the experimental procedure, the application of the inhalative gases was determined and substituted by oxygen at 2 l/min. Anesthesia was performed in spontaneously breathing animals. Heart frequency and oxygenation were monitored using a commercially available pulse oximeter. RESULTS: Using the above described technique in neonatal rodents, microsurgery of the ear was performed without signs of pain or major bleeding. Auditory brain stem responses were recorded clearly and reproducible. CONCLUSIONS: This method represents a noninvasive, well tolerated and easy controllable anesthetic procedure which has proven to provide a sufficient and reliable sedation in neonatal rodents for surgical and nonsurgical investigations.

Anesthesia, Inhalation↗
PubMed2000

Angiogenesis and angiogenic growth factors in middle ear cholesteatoma.

HYPOTHESIS: This study aimed to analyze the localization and distribution of vessels and of these angiogenic growth factors: basic fibroblast growth factor (FGF-2), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) in middle ear cholesteatoma in comparison with normal middle ear mucosa and auditory meatal skin. BACKGROUND: Angiogenesis is particularly important in many normal and pathologic processes, including wound healing and inflammation. Because proliferating tissues require an enhanced blood supply, angiogenesis appears to be a prerequisite for the expansion of cholesteatoma. METHODS: The expression of FGF-2, TGF-alpha, TGF-beta1, and VEGF was studied by immunohistochemistry. The amount of vessels (collagen type IV staining) was determined by an automatic imaging analyzing system. RESULTS: The results showed an altered expression and distribution of VEGF, FGF-2, TGF-alpha, and TGF-beta1 in cholesteatoma in relation to middle ear mucosa and auditory meatal skin. The results were consistent with rapidly growing, activated keratinocytes and stromal cells. Vascularization within the perimatrix of cholesteatoma showed a 4.3-fold increase compared with middle ear mucosa and a twofold increase compared with ear canal skin. An increase of 3.2- to 4-fold in the number of vessels was observed. A close relationship was seen between the density of capillaries, degree of inflammation, and expression of the angiogenic factors investigated, and an increased number of microvessels in cholesteatoma tissue. CONCLUSIONS: Angiogenesis enables and supports the sustained migration of keratinocytes into the middle ear cavity. Therefore, it is a pivotal factor in the destructive behavior of middle ear cholesteatoma.

Angiogenesis Inducing Agents↗
PubMed1999

[Epidermoid formation in the pathogenesis of congenital cholesteatoma--a current review].

BACKGROUND: Many theories have been suggested regarding the origin, pathogenesis, diagnosis, and incidence of congenital cholesteatoma. REVIEW OF LITERATURE: An overview on the current literature on congenital cholesteatoma of the middle ear is presented. It comprises the possible etiology and pathogenesis of congenital cholesteatoma. Among other theories, germ scattering, metaplasia, ingrowth of meatal epidermis, and reflux of amniotic fluid have been proposed. Special emphasis is put on the epidermoid formation theory, which has been described by Michaels and others. CONCLUSIONS: It is widely accepted that congenital cholesteatomas may originate from the postpartum persistence of epidermoid formations. Nevertheless, a clear transition from epidermoid formation to congenital cholesteatoma has yet to be confirmed.

Cholesteatoma, Middle Ear↗
PubMed1998

Focal delivery of fibroblast growth factor-1 by transfected cells induces spiral ganglion neurite targeting in vitro.

Sensory cells in the cochlea of the rat transiently express acidic fibroblast growth factor (FGF-1) during the developmental period of terminal innervation in the sensory epithelium. To explore the potential role of FGF-1 in terminal innervation events, the response of cochlear ganglion neurons to FGF-1 was evaluated in culture. Explants from the spiral ganglion of postnatal day 5 rats were cultured in the presence of exogenous FGF-1, with or without heparin. FGF-1 in the culture medium produced a dose-dependent increase in the number and length of neurites produced by spiral ganglion neurons, a response that was enhanced by heparin. To assess the effects of FGF-1 produced by a focal, cellular source, additional explants were cocultured with 3T3 cell transfectants that secrete FGF-1. Neurites that came into contact with FGF-1 secreting cells branched, formed bouton-like terminal swellings on the surface of the transfectants, and stopped extending. The results suggest that FGF-1 may stimulate neurite extension into the sensory epithelium of the cochlea and that focal production of FGF-1 may contribute to the formation of contacts on sensory cells by developing neurites.

3T3 Cells↗
PubMed1998

Receptor-targeted delivery of an intracellular toxin to outer hair cells by fibroblast growth factor.

The presence and distribution of functional, high-affinity receptors for fibroblast growth factors (FGFs) in the neonatal organ of Corti were probed using the intracellular toxin saporin conjugated to basic FGF (FGF-2). FGFs that bind to high-affinity FGF receptors are internalized as part of the normal process of receptor inactivation. The receptor can thus be used for the targeted delivery of molecules conjugated to FGF into the cytoplasm. Incubation of postnatal day 5 (P5) rat organ of Corti cultures with FGF-saporin caused a dose dependent destruction of outer hair cells, Deiters cells and outer pillar cells. Inner hair cells and other cells were unaffected. Organ of Corti cultures at P0 and P10 showed much less damage than at P5. The results suggest that outer hair cells and adjacent supporting cells in the organ of Corti transiently express high-affinity FGF receptors, and that these receptors can mediate the intracellular delivery of bioactive molecules.

Animals↗
PubMed1997

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro.

To determine if transforming growth factor alpha (TGF alpha) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10(-3) M) exposure either with or without growth factor pretreatment. After TGF alpha (500 ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGF alpha in organ of Corti explants.

Animals↗
PubMed1997

Transfection of neonatal rat cochlear cells in vitro with an adenovirus vector.

A recombinant adenovirus vector containing a beta-galactosidase reporter gene was used to transfect neonatal rat organ of Corti or spiral ganglion explants in vitro. Infection at appropriate titers (10(6)-10(7) pfu/ml) transduced virtually all cells in the cultures after 72 hr. However, spiral ganglion neurons and cells in the inner hair cell regions of the organ of Corti showed the highest levels of expression. Viral titers that produced high levels of beta-galactosidase expression did not appear to damage the cultures, and did not inhibit neurite outgrowth from spiral ganglion cells. However, higher titers (10(8)-10(9) pfu/ml) clearly diminished explant viability and inhibited neurite extension. The results demonstrate that cochlear cells can be transfected successfully with an adenovirus vector, at viral titers which do not induce obvious signs of cellular damage or dysfunction.

Adenoviridae↗
PubMed1997

Performance of ionomeric cement (Ionocem) in the reconstruction of the posterior meatal wall after curative middle-ear surgery.

The hybrid bone-substitute ionomeric cement is suitable for restoring the original anatomy of the posterior canal wall. During a four-year period the posterior meatal wall was rebuilt with ionomeric cement in 74 patients. The canal wall was totally rebuilt in 38 patients, two-thirds rebuilt in 22 cases, and one-third rebuilt in 14 cases. On the meatal side, the canal wall was covered by a musculo-periosteal (Palva) flap. In the majority of cases, the drum was closed with (cartilage)-perichondrium. Revisions were performed in 27 patients (due partially to cholesteatoma, and/or poor visualization of radical mastoidectomy cavities). The ears were non-infected at the time of operation. Permanent epithelialization of the bone replacement material was achieved in 57 cases, with secondary closure of a cutaneous defect of the meatal wall being required in six cases. The auditory canal wall had to be removed in 17 patients owing to deficient soft-tissue coverage, persistent inflammation, and/or partial adhesive processes with development of cholesteatoma. In terms of surgical technique, utilization of the material over a follow-up period of maximally seven years proved it to be a sophisticated procedure for reconstructing the meatal wall. Despite the finesse of the surgical technique employed, the overall failure rate of 31 per cent was inadmissibly high. Implantation of the material should therefore be restricted to middle ears with permanent ventilation and no trace of infection.

Adult↗
PubMed1997

[Oropharyngeal fat hernia in Madelung's neck as a rare cause of acute dysphagia].

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disorder clinically characterized by the presence of nonencapsulated lipomatous tissue around the neck, shoulders, and upper part of the thorax. The entity is frequently associated with peripheral neuropathy, chronic hepatopathy, and alcoholism. Despite of the cosmetically aspect of the patient with a reduced range of motion of the head and neck, MSL is asymptomatic in most cases. CASE REPORT: A 61-year-old man with Madelung's disease complaining of acute dysphagia is presented. Magnetic resonance imaging revealed an oropharyngeal fat prolapse originating from the lipomatous tissue at the neck site. A symmetric resection of the neck fat with removal of the fat prolapse resulted in a satisfying functional and cosmetically outcome. CONCLUSION: To prevent complications and cosmetically disfigurement, early surgical intervention is recommended.

Acute Disease↗
PubMed1997

[Long-term outcome after frontal sinus obliteration with an ionomer bone substitute in the cat. I: Histological results].

BACKGROUND: Osteoplastic frontal sinus surgery in combination with sinus obliteration may occasionally be performed for indications such as severe sinus inflammations, extensive wall fractures involving the nasofrontal duct, or osteomas. The material most frequently used for this obliteration is autogenous adipose tissue. Autografts such as muscle, cartilage, and bone chips have been also recommended for this purpose. In order to avoid the surgical procedure required for harvesting an autograft from other body sites, alloplastic materials have been suggested for frontal sinus obliteration. METHODS: In an animal study using cats, the mucous lining of the frontal sinus was removed, the nasofrontal duct sealed with semifluid ionomer cement, and the cavity filled up with a solid and porous ionomer-based microimplant. RESULTS: Histological investigations were performed up to two years after surgery. Increasing obliteration of the sinus cavity by bone regeneration, starting from the sinus wall, as well as formation of connective tissue between the cement grains was detected as early as one month after implantation. Osteoblasts lining the osteoid layer were considered to be an indication of active bone regeneration. Osteogenesis inside the sinus cavity continuously progressed during the following months. Two years after implantation, osteoid and newly mineralized bone encircled the microimplants leading to an almost complete obliteration. There was no evidence for mucosal regeneration or foreign body reaction. CONCLUSIONS: Because of its osteoconductive effect, biocompatibility, and biostability the ionomer-based microimplant is a suitable alloplastic material for frontal sinus obliteration.

Animals↗
PubMed1997

[Long-term outcome after obliteration of the cat frontal sinus with ionomer bone substitute. II: Histomorphometric measurements].

BACKGROUND: Stenosis or occlusion of the nasofrontal duct with subsequent recurrent frontal sinusitis or mucocele formation may require osteoplastic surgery in combination with frontal sinus obliteration. METHODS: To study its suitability as an implant material in sinuses, granular ionomeric cement was applied for frontal sinus obliteration in 15 cats. The frontal sinus specimens were processed for histological studies after 1, 3, 6, 12, and 24 months, respectively. To obtain quantitative data from the histological sections, areas of osteoid, connective tissue, and implanted ionomeric cement were measured with a computerized digitizing pad and compared to the total area of each frontal sinus. To our knowledge, histomorphometrical analysis of mesenchymal tissue reactions in close contact to an alloplastic material inside the frontal sinus cavity has not been described to date. RESULTS: Bone regeneration, starting from the sinus wall, was detected as early as one month after implantation. The quantitative data for osteoid indicated increasing osteoneogenesis and decreasing connective tissue growth inside the sinus cavity over the period of investigation. Two years after surgery, the osteoid represented 43.5%, the connective tissue 10.7%, and the ionomeric cement 45% of the whole cavity. The implanted cement did not show a significant degradation after two years. CONCLUSION: The results of the present study demonstrated the biocompatibility and biostability of the ionomer-base microimplant.

Animals↗