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Biomedical subjects

D Brors

Publications and source records attributed to D Brors.

At least 19 recordsLinked to original sources

Posterior canal wall reconstruction with a composite cartilage titanium mesh graft in canal wall down tympanoplasty and revision surgery for radical cavities.

OBJECTIVES: To investigate posterior external ear canal wall reconstruction with a composite cartilage titanium mesh graft in canal wall down tympanoplasty and revision surgery for open mastoids. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral centre. METHODS: As a preliminary study, 15 selected patients underwent reconstruction of a posterior ear canal wall defect with titanium mesh. Large defects of the posterior external auditory canal wall, resulting from canal wall down tympanoplasty or present in revision surgery, were eliminated by reconstruction using a titanium mesh. The mesh was covered with conchal cartilage and attached to the cortical mastoid bone using 3-mm titanium screws. RESULTS: All patients maintained a normal contour of the external ear canal, without depression, extrusion or infection. There were no failures, based on short-term post-operative controls. However, two procedures had to be revised due to incomplete coverage of the titanium mesh. CONCLUSIONS: This study shows that reconstruction of the posterior ear canal wall with a composite cartilage titanium mesh is a valuable method for preserving the morphology of the external auditory canal in selected cases. Problems occurring in canal wall down tympanomastoidectomy and radical cavities may therefore be avoided. However, long-term results have yet to be evaluated.

Adult↗

[Sentinel node mapping in head and neck squamous cell carcinoma].

BACKGROUND: Commonly used staging procedures often cannot predict the absence of lymphatic micro- metastases in squamous cell carcinoma (SCC) of the head and neck. Therefore in many cases an elective neck dissection (ND) is necessary. In the surgical therapy of melanoma or breast cancer the presence of metastases can be evaluated securely by identification and examination of the sentinel lymph node (SLN). The type of surgical procedure is usually chosen in regard to the histopathological result. The present study evaluates the applicability of this concept for SCC of the head and neck. METHODS: Radioactive labeled micro-albumin particles were injected preoperatively around the tumor in 38 patients without proven metastases. Following the excision of the primary tumor the sentinel lymph node/s were detected and dissected and ND was completed. Histological examination of the tissue was performed to evaluate whether the SLN reflected the lymphatic status. RESULTS: In two cases (5.1 %) no SLN were detected. ND was completed in 32 cases. In nine cases (28.1 %) the SLN were infiltrated by the primary tumor. In 22 cases (68.8 %) SLN and ND revealed a N(0) stage. In one case (3.1 %) we could not identify a metastasis because of the anatomical closeness of the SLN to the primary. The negative predictive value was 96 %. CONCLUSION: Predictive value regarding metastases to the neck was higher with the detection of SLN than with conventional staging procedures. Whether the detection of a tumor-free SLN is an indication not to perform an elective neck dissection is a matter of discussion, especially under the aspect of the effective reduction of postoperative morbidity.

Adult↗

[Infection transfer between the maxillary sinus and endocranium].

BACKGROUND: Rhinogenous brain abscesses usually originate from a frontal sinusitis, rarely from the ethmoidal system or the maxillary sinus. However, there are different pathways that can lead to the transfer of a maxillary infection to the endocranial compartment. PATIENT: A patient with frontal brain abscesses originating from a maxillary sinus infection is presented and diagnostic steps, therapy as well as pathophysiology are discussed. PATHOPHYSIOLOGY: The venous plexus of the maxillary sinus drains through the posterior wall of the antrum of Highmore into the deep facial vein that leads into the pterygoid plexus and then through the rete foraminis ovalis into the cavernous sinus. In addition, numerous small veins perforate the osseous roof of the maxillary sinus and enter the orbit joining the superior or inferior ophthalmic vein. They are also connected to the cavernous sinus or the pterygoid plexus. A number of veins perforate the anterior wall of the maxillary sinus communicating with the angular vein that drains into the superior ophthalmic vein and into the cavernous sinus. From the cavernous sinus, the blood arrives at the deep middle cerebral vein that usually communicates through the white substance towards the brain's superficial venous system. CONCLUSION: The presence of these maxillo-cerebral venous anastomoses explains the spread of infection from the maxillary sinus to the white substance of the brain without any direct association with the base of the skull.

Adult↗

[Experimental investigations of CO2 laser application in middle ear ossicles].

BACKGROUND: During the last few years, several laser systems have been applied for procedures in middle ear surgery. In this study, we determined the technical parameters for the dissection of the middle ear ossicles with the CO(2) laser and analyzed the histological findings. METHODS: The malleus necks of 16 human temporal bones were dissected under standardized conditions using a CO(2) laser with a power output between 35 and 55 kW/cm(2). The specimens were fixed and histological probes of 50- micro m thickness were prepared. RESULTS: The laser outputs led to crater diameters from 0.14 to 0.55 mm. As an analogy between laser energy and thermal tissue destruction, three zones of thermal damage were differentiated: a cinder zone, a carbonization zone, and a zone of dehydration. The metrical dimensions of these zones did not show any correlation to the applied laser energy. CONCLUSIONS: The data of this study show that commercially available CO(2) lasers are sufficient for a safe and effective partial resection of middle ear ossicles using a power output of 35 kW/cm(2).

Ear Ossicles↗

Involvement of ras activation in toxic hair cell damage of the mammalian cochlea.

To identify possible intracellular mediators of hair cell (HC) death due to ototoxins, we treated basal-turn, neonatal, rat HCs in vitro with several intracellular signaling inhibitors, prior to and during gentamicin exposure. The general guanine nucleotide-binding protein (G-protein) inhibitor, GDP-betaS (1 mM), provided potent HC protection, suggesting involvement of G-proteins in the intracellular pathway linking gentamicin exposure to HC death. ADP-betaS had minimal effect, indicating that the protection is specific to guanosine diphosphate (GDP)-binding, rather than a general reaction to nucleotides. Azido-GTP(32) photolabeling and gel electrophoresis indicated activation of an approximately 21 kDa G-protein in HCs after exposure to gentamicin. Spectroscopic analysis of peptide fragments from this band matched its sequence with H-Ras. The Ras inhibitors B581 (50 microM) and FTI-277 (10 microM) provided potent protection against damage and reduced c-Jun activation in HC nuclei, suggesting that activation of Ras is functionally involved in damage to these cells due to gentamicin.

Animals↗

Regeneration of inner ear cells from stem cell precursors--a future concept of hearing rehabilitation?

The use of stem cells offers new and powerful strategies for future tissue development and engineering. Common features of stem cells are both their capacity for self-renewal and the ability to differentiate into mature effector cells. Since the establishment of embryonic stem cells from early human embryos, research on and clinical application of human ES cells belong to the most controversial topics in our society. Great hopes are based upon the remarkable observation that human ES cells can be greatly expanded in vitro, and that they can differentiate into various clinically important cell types. Recent advances in the cloning of mammals by nuclear transplantation provide new concepts for autologous replacement of damaged and degenerated tissues. In contrast, somatic stem cells of the adult organism were considered to be more restricted in their developmental potential. However, recent investigations suggest that somatic stem cells may have a wider differentiation potential than previously thought. In otology, initial experiments have revealed neural stem cell survival in cochlear cell cultures and under neurotrophin influence, neural stem cells seemed to develop into a neuronal phenotype. Further studies have to be carried out to investigate the full potential of stem cells as well as the molecular mechanisms that are involved in regulating cellular identity and plasticity. Clinically, advances in stem cell biology may provide a permanent source of replacement cells for treating human diseases and could open the development of new concepts for cell and tissue regeneration for a causal treatment of chronic degenerative diseases.

Animals↗

[Histomorphometric assessment of spiral ganglion neurite outgrowth in vitro].

BACKGROUND: During the last years, various groups of growth factors have been identified to influence spiral ganglion cell survival and neurite extension in the mammalian cochlea. To evaluate and compare the effects of different growth factors, a precise histomorphometrical analysis of neurite outgrowth patterns has to be applied. The here presented technique is compared to already published methods, that only approximately estimate the neurite length. METHOD: A software has been developed to analyse digitalised scans of spiral ganglion cells and to measure the length of the neurites. Therefore, the neurites are being separated in any given number of straight lines. The totals of these lines can then be added like a polygon. This polygon method was compared to a semi-quantitative procedure in which the neurite length was determined by concentric circles that were crossed by the neurites in a certain distance. The accuracy of both methods was analysed. Both methods were performed in 20 specimen of neonatal rat spiral ganglion cells after in vitro stimulation with neurotrophic factors. RESULTS: The semi-quantitative method has shown to involve a systematic error between +/- 10 to 15 %. The polygon method, on the contrary, has a systematic error of around +/- 1 %, which admits much more accurate measurement of spiral ganglion neurite outgrowth. CONCLUSION: With the described polygon method, spiral ganglion neurite growth patterns in cell culture studies can be characterised more precisely and, thus, helps to better differentiate the action domain of neurotrophic factors.

Animals↗

[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↗

[Rescue of auditory hair cells from ototoxicity by CEP-11 004, an inhibitor of the JNK signaling pathway].

The hair cells (HCs) are the most vulnerable elements in the cochlea and damage to them is the most common cause of sensorineural hearing loss (SNHL). Understanding the intracellular events that lead to the death of HCs is a key to developing protective strategies. Recently, it has been shown that the c-Jun-N-terminal kinase (JNK) pathway is activated in HCs in response to aminoglycosides and CEP-1347, an inhibitor of the JNK signaling pathway protected HCs from ototoxicity. We have studied another inhibitor (CEP-11 004) of this signaling pathway in its ability to protect HCs from aminoglycoside ototoxicity in vitro. Organ of Corti explants from p5 rat basal turns were maintained in tissue culture and treated with CEP-11 004 for 12 hours. They were then treated with CEP-11 004 plus gentamicin for 72 hours. Significantly less HC death was observed compared to gentamicin alone. CEP-11 004 alone had no effect on HCs. We conclude that the JNK signaling pathway plays a role in aminoglycoside ototoxicity signaling.

Animals↗

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↗

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↗

[Metastases to the paranasal sinuses: case report and review of the literature].

The case of an 87-year old man with widespread prostatic cancer is reported. During the autopsy macroscopically visible metastases were found within the frontal sinuses. These tumor masses destroyed the posterior osseous wall of the frontal sinus and formed polypoid bulging masses. In contrast to the macroscopically unaffected mucous membrane of the sphenoid sinus the maceration specimen of the skull base demonstrated a spongious-mossy, osteoplastic metastasis, lining the sphenoid sinus like a tapestry. This affection started from an exhaustive osteoplastic metastasis within the clivus. No metastases could be found in both antrums or the ethmoids. Retrospectively no symptoms from the paranasal sinuses could be eruated, only occasional pain of the frontal bone. The review of the world literature with 123 reports revealed 169 cases. Renal cell carcinomas most frequently metastasize into the paranasal sinuses (67 cases), followed by bronchogenic carcinomas (15 cases). Thyroid cancers and cancers of the mammary gland are responsible for 13 respectively 14 cases. The prostate also adds 12 cases. The paranasal sinuses are affected in diminishing frequency: maxillary sinus (55 cases), sphenoid sinus (37 cases), ethmoidal cells (23 cases) and frontal sinus (15 cases). In 38 cases exhaustive metastases affecting two or more paranasal sinuses are reported. The statement of literature, that metastases affecting the paranasal sinuses are much more frequent than reported, cannot be supported by our study, because the intensive autoptic investigation of 50 skulls of patients suffering from widespread cancers revealed no further cases of metastatic processes of the paranasal sinuses.

Aged↗

Magnetic resonance imaging in patients with sudden hearing loss, tinnitus and vertigo.

OBJECTIVE: The etiopathogenesis in audiovestibular symptoms can be elusive, despite extensive differential diagnosis. This article addresses the value of magnetic resonance imaging (MRI) in analysis of the complete audiovestibular pathway. STUDY DESIGN: Retrospective evaluation. SETTING: Tertiary referral center. PATIENTS: Consecutive sample of 354 patients (mean age 49 years, range 8 to 86 years) with audiovestibular disorders. INTERVENTION: Contrast-enhanced MRI of the head with thin-slice investigation of the inner ear, internal auditory meatus, and cerebellopontine angle. MAIN OUTCOME MEASURE: All MRIs were evaluated by experienced independent investigators. Statistical analysis was performed using the Statistical Package of Social Sciences data analysis 9.0. RESULTS: MRI abnormalities were seen in 122 of 354 patients (34.5%). The MRIs revealed the following: 4 pathologic conditions (1.1%) of the cochlea/labyrinth, 23 abnormalities (6.5%) at the internal auditory meatus/cerebellopontine angle, 12 pathologic lesions (3.4%) that involved the central audiovestibular tract at the brainstem, 78 microangiopathic changes of the brain (22%), 3 focal hyperintensities of the brain that turned out to be the first evidence of multiple sclerosis in 2 patients and sarcoidosis in 1 patient, and 1 temporal metastasis. Other pathologic conditions, such as parotid gland or petrous bone apex tumors, were unrelated to the audiovestibular symptoms. CONCLUSIONS: This study indicates that contrast-enhanced MRI can be used to assess a significant number of different pathologic conditions in patients with audiovestibular disorders.

Adolescent↗

Long-term study of endonasal duraplasty and review of the literature.

Many different techniques have been proposed to repair frontobasal dura mater lesions. Because of its low morbidity and high success rate, the endonasal approach has become a preferred route for treating cerebrospinal fluid fistulas of the anterior skull base. This article presents a retrospective evaluation of 136 endonasal duraplasties (126 patients) performed between July 1980 and May 1998 at a tertiary care facility. Follow-up consisted of clinical examinations including nasal endoscopy, objective measures, and telephone interviews. The following measures were used to evaluate the results of these duraplasties: postoperative nasal fluorescein endoscopy in 71 cases, computed tomographic cisternography in 2, nasal fluorescein endoscopy with computed tomographic cistemography in 19, magnetic resonance imaging in 6, and nasal fluorescein endoscopy with magnetic resonance imaging in 1. Tight closure was accomplished in 129 dural lesions (94.9%) on the first attempt. In 3 cases, recurrence of cerebrospinal fluid leakage was treated successfully by 1 endonasal revision, and in 1 case, a tight duraplasty was achieved after 2 endonasal revisions. Its high success rate, low rate of morbidity, and good long-term results recommend endonasal duraplasty as a primary treatment modality for frontobasal dural lesions. For extended frontobasal dural lesions, for which intracranial dural repair is the preferred approach, the endonasal approach should be used to close additional dural leaks of the sphenoid sinus.

Cerebrospinal Fluid↗

[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↗

Sternberg's canal--cause of congenital sphenoidal meningocele.

We present a case of a 29-year-old female complaining of right-sided watery nasal discharge. Radiological investigations identified an intrasphenoidal meningocele. The origin of the meningocele was pinpointed to the right parasellar region and was confirmed surgically. The parasellar bony defect appeared to be due to persistence of the lateral craniopharyngeal canal (Sternberg's canal). Therefore, we assume a congenital origin for the intrasphenoidal meningocele found in the patient. Acquired bony defects of the sphenoid sinus are unlikely at the fusion planes of the different sphenoid bone components. Knowledge of the complex ontogeny of the sphenoid bone is an important key to differentiating between congenital and acquired sphenoid sinus meningoceles.

Adult↗

Conductive hearing loss in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome is a rare genetic overgrowth syndrome presenting with organomegaly, abdominal wall defects, macroglossia, and postnatal hypoglycemia. Head and neck manifestations of this abnormality include flame nevus of the forehead and characteristic sulci of the ear lobe. We present a 7-year-old child with Beckwith-Wiedemann syndrome and a rare finding of conductive hearing loss on both sides due to congenital malleus and stapedial fixation. Small fenestra stapedotomy and mobilization of malleus fixation in the epitympanum improved the child's hearing. The bony fixation of the malleus and stapes is explained as atavism of the processus anterior mallei and peripheral lamina stapedialis in embryological development.

Beckwith-Wiedemann Syndrome↗