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Biomedical subjects

P Franz

Publications and source records attributed to P Franz.

At least 19 recordsLinked to original sources
PubMed1999

Intracochlear position of cochlear implant electrodes.

There are many different types of cochlear implants available on the market today and they are constantly being re-evaluated and changed. Knowledge of the exact position of the electrode within the cochlea is important in order to improve the electrical stimulation of the hearing nerve by the implants. The stimulating electrodes are usually located peripherally within the scala tympani, although several attempts have been made to develop peri-modiolar located electrode arrays. In this study, our goal was to evaluate the intracochlear positions of Nucleus, Combi 40/Combi 40 +, and newly developed peri-modiolar positioned electrodes by inserting them into fresh human temporal bones. After insertion, the bones were then histologically processed with the electrodes in situ, following perilymphatic formalin perfusion and methylmethacrylate embedding. Sections of the bones 80-100 microm thick were prepared using a sawing, grinding and polishing technique. This technique resulted in excellent preservation of the inner ear structures and clear identification of each electrode. The different types of electrodes were then evaluated as to their insertion depth, trauma to cochlear structures and location in relation to the scala tympani walls.

Cadaver↗
PubMed1999

Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating factor-1.

Osteopetrosis describes a group of skeletal metabolic diseases of heterogeneous etiology and varied severity that produces a generalized accumulation of skeletal mass, the result of reduced bone resorption. Inherited in a variety of species including humans, the most severe forms are lethal. Among common features are progressive blindness and deafness of controversial etiologies for which there are no universally effective treatments. We have studied the auditory responsiveness and auditory ossicle quantitative histomorphology and temporal bone vasculature in the toothless (tl) rat, a lethal osteopetrotic mutation with few osteoclasts, very low bone turnover, and limited angiogenesis in the axial skeleton. Compared with normal littermates, 3-week-old mutants showed significantly reduced auditory responsiveness, a hearing loss due to abnormalities in both form and tissue composition of the stapes, and little capillary sprouting in the vascular bed of the temporal bone. Treatment of mutants with colony-stimulating factor 1 (CSF-1), known to greatly reduce sclerosis in the axial skeleton, significantly improved hearing, stapedial form and tissue composition, and angiogenesis in the temporal bone. In normal rats, the stapes consisted of 89.3% bone, 9.1% mineralized cartilage, and 0.8% porosity. In osteopetrotic rats, the stapes consisted of 48.3% bone, 35.9% mineralized cartilage, and 15.9% porosity, while after CSF-1 treatment, the bone content increased to 55.2%, cartilage was decreased to 21.7%, and porosity increased to 23.0%, respectively. This is the first demonstration of an auditory abnormality in an osteopetrotic animal mutation and shows that the hearing loss in tl rats can be significantly improved following treatment with CSF-1.

Animals↗
PubMed1998

Effects of TGF-beta on eosinophil chemotaxis.

Transforming growth factor-beta (TGF-beta), which can decrease the effects of interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on eosinophil viability, has been shown to be chemotactic for neutrophils. However, there is little information on its effects on eosinophil chemotaxis. Because TGF-beta has recently been found in increased concentrations in asthmatic sputum, we investigated whether TGF-beta could influence eosinophil migration and eosinophil viability. Purified eosinophils from normal donors were incubated with increasing concentrations of TGF-beta. Chemotaxis was measured with a modified Boyden chamber technique. In addition, eosinophils were incubated for 96 h with either IL-3, IL-5 or GM-CSF (1 ng/ml) together with increasing concentrations of TGF-beta. Eosinophil viability was then determined with propidium jodide and flow cytometry. Eosinophil chemotaxis was significantly increased in the presence of TGF-beta in concentrations between 10(-9) and 10(-4) microg/ml. The optimal concentration of TGF-beta in this assay was between 10(-9) and 10(-8) microg/ml. The chemotactic effect of TGF-beta diminished when higher as well as lower concentrations (between 10[-12] and 10[-3] microg/ml) were employed. In contrast, inhibition of eosinophil survival induced by IL-3, IL-5 and GM-CSF reached its maximum at concentrations of TGF-beta between 10(-4) and 10(-3) microg/ml. From these data we conclude that TGF-beta in low concentrations can induce eosinophil chemotaxis whereas higher concentrations reduce eosinophil survival mediated by IL-3, IL-5 and GM-CSF.

Cell Survival↗
PubMed1998

Inhibition of HLA-DR expression on activated human blood eosinophils by transforming growth factor-beta1.

Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)-DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), can up-regulate HLA-DR expression. However, little is known about antagonistic factors that might down-regulate HLA-DR expression on eosinophils. In this study we investigated whether transforming growth factor-beta (TGF-beta), which has been shown to reduce survival of activated eosinophils, can also modulate HLA-DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL-3 and GM-CSF for 24 h and HLA-DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA-DR, incubation with GM-CSF and IL-3 increased HLA-DR expression on eosinophils. TGF-beta alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-beta and either GM-CSF or IL-3 significantly decreased HLA-DR expression compared to eosinophils incubated with either GM-CSF or IL-3 alone and this was not reversed by addition of IL-5. This effect of TGF-beta on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-beta antibodies. Our results suggest that TGF-beta can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.

Cells, Cultured↗
PubMed1998

Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family.

A four-generation family suffering from an autosomal-dominant, congenital, nonprogressive, nonsyndromic hearing loss was found in a rural region of Austria. The hearing loss was moderate to severe, a pure tone audiogram showing a U-shaped form with maximum loss at 2, 000 Hz. An initial genome search led to a lod score of 3.01 with markers on chromosome 15. This locus was registered as DFNA8 in the HUGO data base. Further sampling of the family, however, yielded data that reduced the maximal lod score with chromosome 15 markers to 1.81. The genome search was restarted using an ABITM genotyper, which eventually detected several positive two-point lod scores with markers from the long arm of chromosome 11. The highest value was 3. 6, which was seen with the marker D11S934. Haplotype analysis excluded the gene from the chromosomal region proximal from D11S898 and distal to D11S1309. These results place the gene in the region of the hearing loss gene DFNA12. Recent evidence suggests that the somewhat different phenotypes found in these two families are due to two different mutations in the human alpha-tectorine gene (Verhoeven et al., 1998).

Austria↗
PubMed1997

CGRP and substance P in intraepithelial neuronal structures of the human upper respiratory system.

The distribution of intraepithelial nerve fibres and neuroendocrine cells within the surface and glandular epithelium of human nasal mucosa and larynx was examined using immunohistochemical techniques. Neuronal structures were immunostained for the general neuroendocrine marker protein gene-product (PGP) 9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings contained PGP 9.5 and were found within the respiratory surface epithelium of the nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these nerve fibres showed positive immunoreactivties with antibodies against SP and CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts passing the basal membrane and reaching the luminal part were detected. These nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of nerve fibres within the squamous surface epithelium was detected in the subglottic and epiglottic region containing CGRP and SP in a small subpopulation of nerve fibres. Single intraepithelial taste buds in the epiglottic region and neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.

Calcitonin Gene-Related Peptide↗
PubMed1997

Expression of glial and neuronal marker proteins (S-100, glial fibrillary acidic protein, and neuron-specific enolase) by myxoid cells in the human larynx.

Areas of myxoid connective tissue were regularly found in the aryepiglottic and vestibular folds of operative resections (n = 10) or fresh postmortem specimens (n = 5) of the human larynx. Myxoid tissue was often attached to elastic cartilage (epiglottic, arytenoid, and corniculate cartilage) or spatially related to mucosal glands. This was characterized by ramified cells (myxoid cells) in an ample acidic matrix with few strands of collagen fibers. Extracellular matrix showed alcianophilia at pH 2.5 and metachromasia while tissue digestion with hyaluronidase abolished these staining reactions. Immunohistochemistry revealed reactivity of myxoid cells for S-100 alpha and S-100 beta protein, glial fibrillary acidic protein, and neuron-specific enolase. Elastic cartilage chondrocytes also stained for these markers while fibroblasts remained unstained. Reactivity for identical-neuroectodermal marker proteins of myxoid cells and chondrocytes indicated their close relationship. The presence of myxoid tissue in the larynx, as evidenced by stellate cells immunoreactive for neuroectodermal marker proteins, should be considered when using these markers in diagnostic pathology.

Chondrocytes↗
PubMed1997

[Initial experiences with the Combi-40 cochlear implant. Surgical aspects].

The rehabilitation of profoundly deaf patients by means of cochlear implants has become a well established form of therapy. Recently, large scale studies have pointed out a variety of surgical complications. A multiplicity of new implant types are each placing more specific demands on the surgeons. Based on the experience with about 160 cochlear implantations in total, the most suitable surgical technique for the implantation of the Combi 40 cochlear implant which has been used in 41 cases is presented. An extended retroauricular incision is made and a caudally based flap is fashioned. The implant bed is drilled 0.5-1 cm behind and above the mastoid cavity. Between the implant bed and the mastoid cavity a groove for the electrodes is drilled cranial of the implant site in the right ear and caudal in the left ear. Access to the scala tympani is gained by a promontory cochleostomy via a posterior tympanotomy of 2x3 mm. Videocontrolled microendoscopes are used to inspect the scala tympani prior to electrode insertion. Electrode insertions depths of up to 30 mm are usually achieved. The electrode and the implant are secured with ionomer-based cement. The described technique has up to now been successfully performed in 30 adults and 11 children.

Adult↗
PubMed1997

Endothelin-1 causes luminal constrictions in rat cochlear veins.

Serum levels of the vasoconstrictor endothelin-1 (ET-1) increase in ischemia and systemic hypertension. We examined the effects of ET-1 on the cochlear microvasculature. Blood vessels were cast with methacrylate in adult male Wistar Kyoto rats, 10 min after intravenous injection of ET-1 (1.0 microg/kg); control animals received saline. Systemic blood pressure was recorded continuously. ET-1 increased the average systolic pressure by 18% and average diastolic pressure by 22% (P < 0.01). Scanning electron microscopy of cast vessels showed multiple circumscribed luminal constrictions on: (1) postcapillary venules; (2) collecting veins; (3) where collecting veins merged with the spiral modiolar vein; (4) on the spiral modiolar vein itself. Circumscribed constrictions in arteries were not observed. In ET-1 injected animals focal contractions of collecting veins reduced luminal width by 13.4% +/- 2.9 (P < 0.01). In control rats, constrictions on venous casts were minimal and constrictions on arteries were not observed. The present study shows that ET-1 is involved in local control of cochlear blood flow in that it focally contracts cochlear veins. It is suggested that this might be due to the high affinity of ET-1 receptors and/or the large number of ET-1 receptors on contractile cells in venous walls.

Animals↗
PubMed1997

Association of midoesophageal diverticula with oesophageal motor disorders. Videofluoroscopy and manometry.

PURPOSE: To evaluate the prevalence and clinical significance of associated oesophageal motor disorders in patients with midoesophageal diverticula. MATERIAL AND METHODS: We retrospectively reviewed videofluoroscopic and, if available, manometric studies of 30 patients with midoesophageal diverticula. The type of diverticulum and the presence and nature of oesophageal motor disorders were assessed. RESULTS: Videofluoroscopy showed that 24 patients had 26 pulsion-type diverticula and 6 patients had 7 traction-type diverticula. Oesophageal motor disorders were demonstrated in 21 of the 24 patients with pulsion-type diverticula and in 3 of the 6 with traction-type diverticula. Nineteen patients had nonspecific motor disorders, 5 had achalasia, and 5 had gastrooesophageal reflux or oesophagitis. CONCLUSION: Midoesophageal diverticula are most often of the pulsion-type and tend to be associated with an oesophageal motor disorder. Motor disorders are predominantly nonspecific, but achalasia may be encountered as well.

Adult↗
PubMed1997

Localization of endothelin-1 and endothelin-3 in the cochlea.

The distribution of endothelin-1 (ET-1) and endothelin-3 (ET-3) was studied by indirect immunostaining of decalcified guinea pig and rat cochleae. No species differences were observed. Perikarya and processes of spiral ganglion cells were highly reactive for both ET-1 and ET-3. The epithelial lining of the cochlear duct stained for ET-1 and ET-3, but reactivity for ET-1 was higher in the lining cells of the inner sulcus, Claudius', and Hensen's cells, while the tympanic covering layer of the basilar membrane stained stronger for ET-3 compared to ET-1. In the stria vascularis, all cell types stained for ET-3, while marginal cells were more reactive for ET-1. Spiral ligament fibroblasts were reactive for ET-1, but not for ET-3. Connective tissue cells of the spiral limbus stained for both endothelins. The region of synapses on outer hair cells reacted for ET-1 and ET-3 but sensory cells remained unstained. Endothelins are discussed to act as modulatory peptides, possibly interfering with nitric oxide, prostaglandins, and atrial natriuretic peptide in the lateral cochlear wall (lateral cochlear wall, i.e. stria vascularis and spiral ligament). The occurrence of endothelins in cochlear neurons suggest their potential role as neurotransmitters.

Animals↗
PubMed1997

Caroverine in tinnitus treatment. A placebo-controlled blind study.

This study was performed to examine whether a single infusion of caroverine, a quinoxaline-derivative, can be used successfully in the treatment of inner ear tinnitus. Microiontophoretical experiments in guinea-pigs have shown that caroverine acted as a potent competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazone-proprionic acid (AMPA) receptor antagonist and, in higher dosages, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. According to our working hypothesis of the pathophysiology of inner ear tinnitus (cochlear-synaptic tinnitus), these forms of tinnitus occur when the physiological activity of the NMDA and AMPA receptors at the subsynaptic membranes of inner hair cell afferents is disturbed. In total, 60 patients with inner ear tinnitus of assumed cochlear-synaptic pathophysiology were included in the study: after computerized randomization, 30 were treated with caroverine and 30 with placebo. For a response to have occurred, tinnitus had to show a reduction in both subjective rating and psychoacoustic measurement (tinnitus matching). In the caroverine group, 63.3% responded to therapy immediately after the infusion. In the placebo group, none of the patients treated showed a significant response according to the defined success criteria. The results confirm our working hypothesis on the genesis of cochlear-synaptic tinnitus.

Adult↗
PubMed1997

Cochlear implant deep electrode insertion: extent of insertional trauma.

We have recently undertaken deep insertions of the Combi-40 cochlear implant electrode (Med-E1 Corp., Innsbruck, Austria) into apical regions of the scala tympani using a cochleostomy approach. In order to examine the extent of the insertional trauma, 12 fresh human temporal bones were implanted with original Combi-40 electrodes. The specimens were histologically processed with the implants in place by employing a sawing and grinding technique. In most cases, only very discrete distortions of the epithelium of the spiral ligament occurred within the middle cochlear turns. Furthermore, a slight displacement of the basilar membrane caused by the electrode was occasionally seen. However, in 2 cases more severe damage such as basilar membrane rupture and electrode displacement was found. Attempts to insert the electrode beyond the point of first resistance resulted in electrode kinking within the basal cochlear turn with subsequent fracture of the osseous spiral lamina. According to our results, deep electrode insertions do not aggravate the insertional trauma provided no force is applied when resistance is felt.

Cochlea↗
PubMed1996

Flexible fiberoptic endoscopy and laser surgery in obliterated cochleas: human temporal bone studies.

BACKGROUND AND OBJECTIVE: The use of conventional drilling procedures in cochlear implant surgery of ossified cochleae poses special risks to the facial nerve and the carotid artery. This study evaluated the alternate use of flexible fiberoptic endoscopy and mid-infrared laser surgery for recanalization of partially and artificially obliterated cochleae in freshly dissected human cadavers. STUDY DESIGN/MATERIALS AND METHODS: A pulsed Holmium:YAG-laser (lambda = 2120 nm) was used in the free-running mode (1180 mJ, 250 microseconds pulse, 5 Hz). A 660 microns optic quartz fiber was positioned in the center of the round window niche and slowly--endoscopically guided--advanced in contact shooting over 1.5 cm, creating by vaporization and photoablation a passage through the artificial bony occlusion in the basal segment of the cochlea. RESULTS: In all experiments, laser application (110-130 pulses) resulted in complete recanalization of the bony occlusions without damaging surrounding structures. The microendoscopy proved capable of guiding the laser fiber through the curved segment of the basal turn allowing identification of normal bone, bone cement, and laser-treated bone cement. CONCLUSION: If partial ossification of the basal turn is present, this technique could give access to place analog as well as digital implants deep within the cochlea.

Cochlea↗