Effects of endolymphatic and perilymphatic application of salicylate in the pigeon. I: Single fiber activity and cochlear potentials.

The effects of salicylate on the mammalian cochlea function are well documented. However, there is a lack of reports on salicylate effects on the avian auditory periphery and it might well be that salicylate is not ototoxic at all in submammalian vertebrates. We therefore recorded single fiber activities, compound action potential (CAP) and endocochlear potential (EP) during application of salicylate (calculated final concentration of about 2-18 mmol/l) into the scala media of pigeons. We furthermore recorded CAP and EP during perilymphatic perfusion of salicylate (2-20 mmol/l). Salicylate applied into the scala media led to an elevation of tip threshold in single fibers ranging from 5 to 35 dB. The characteristic frequencies of the fibers were not changed. This effect on auditory nerve fibers was reflected in an elevation of CAP thresholds. The mean spontaneous discharge rate was either slightly increased or remained unchanged in the majority of fibers. Perilymphatic salicylate perfusion also led to an elevation of CAP thresholds that was reversible following subsequent perfusion with artificial perilymph. The EP remained unchanged in both application modes. The effects of salicylate were dose dependent and more pronounced in the mid- to high-frequency range. These results are consistent with an action of salicylate on the process (electrical or mechanical, or both) responsible for the sensitivity and frequency selectivity in the avian peripheral hearing organ.

Effects of endolymphatic and perilymphatic application of salicylate in the pigeon. II: Fine structure of auditory hair cells.

Large doses of salicylate are known to cause reversible ototoxic effects including fine structural alterations of the auditory hair cells in mammals. To investigate possible fine structural correlates of salicylate effects on pigeon auditory hair cells, the basilar papillae following perilymphatic or endolymphatic application of salicylate were fixed and processed for transmission electron microscopy. The pigeon auditory hair cells possessed organelles typically described in avians. A single or multi-layered array of cisternae along the cytoplasmic side of the lateral plasma membrane, i.e. subsurface cisternae that are characteristic for mammalian outer hair cells, was not seen. The most prominent fine structural alterations of hair cells after salicylate application were an increase in the luminal width of smooth and rough endoplasmic reticulum as well as the frequent occurrence of prominent single-membrane-bound vesicles filled with electron-dense bodies. Based on the assumption that subsurface cisternae represent a specialized form of endoplasmic reticulum, the present findings indicate that the structural correlates of salicylate toxicity are similar in mammalian and avian auditory hair cells.

Lacunar dilatations of intrafusal and extrafusal terminal cisternae, annulate lamellae, confronting cisternae and tubulofilamentous inclusions within the spectrum of muscle and nerve fiber changes in myotonic dystrophy.

In 3 out of 5 muscle spindles available in skeletal muscle biopsy specimens from 30 patients with myotonic dystrophy (MD) unusually large lacunar dilatations of terminal cisternae were observed that had thus far only been reported in extrafusal muscle fibers. Cytoplasmic annulate lamellae, confronting cisternae and regularly proliferated terminal cisternae, as well as intranuclear tubulovesicular inclusions were found in extrafusal muscle fibers that in combination with concentric membranous bodies seen in perineurial cells and Schwann cells generally emphasize an involvement of the endoplasmic reticulum in the pathogenesis of MD. In addition, a nuclear inclusion body was observed composed of tubulofilamentous structures with close similarity to those thought to be rather specific for inclusion body myositis. Vesicles filled with amorphous material originating from outer spindle capsule cells were suggested to indicate matrical lipidic debris leading to "ghost bodies" and calcifying globules. Light microscopical evaluation of 8 sural nerve specimens revealed a neuropathy in only 2 patients that was predominantly axonal in type and of slight to moderate severity with a secondary demyelinating component in 1 patient. These findings add to the large spectrum of muscle and nerve fiber changes in MD underlining the phenotypic multiplicity of a well defined genetic defect.

Effects of salicylate on shape, electromotility and membrane characteristics of isolated outer hair cells from guinea pig cochlea.

A reversible tinnitus and hearing loss have long been known to result from large doses of salicylate. Cochlear electrophysiology and otoacoustic emission studies suggest that the drug may interfere with outer hair cell electromotility. Exposure of isolated outer hair cells to sodium salicylate concentrations ranging from 0.05 to 10 mM reveals a dose dependent, reversible loss of turgidity and dimunition of electromotility. There was also a change in membrane conductance with salicylate superfusion that occurred later in time from the onset of shape and electromotility changes. There was no evidence of dose dependence for the change in membrane conductance, nor was the change reversible. The changes in shape and electromotility that we observe in vitro may impair cochlear partition movements in vivo and could account, at least in part, for the salicylate-induced hearing loss and effects on otoacoustic emissions.

[Injuries of the head and neck in suicidal intention]. / Verletzungen des Kopfes und des Halses in suizidaler Absicht.

BACKGROUND: Injuries of the head and neck with suicidal intention might create serious situations that require rapid and interdisciplinary treatment. METHODS AND PATIENTS: Twenty-seven patients with suicidal head and neck injuries were treated at the Department of oto-rhino-laryngology, head and neck surgery, University of Wurzburg/Germany, between 1991 and 2002. The medical histories were analyzed retrospectively. RESULTS: Twenty-three of them were male, 4 female. Mean age at time of attempted suicidal was 48 years (18 - 90). One patient was already treated for a psychiatric disorder. None of the patients had a suicidal attempt in the history. Nine patients suffered from a pharynx or larynx trauma after strangulation. Four out of seven patients with cutting or stabbing injuries showed a perforation of the upper airways. Nine patients had gunshot traumas, one of them with perforation of the pharynx. Thirteen patients underwent immediate endoscopy under general anaesthesia followed by a neck exploration in 3 patients. Six patients received a temporary tracheotomy. All patients were considered suicidal for the duration of stay in the ENT-department resulting in a permanent supervision. All patients were transferred to a psychiatric unit as soon as possible for further treatment. A statistically significant accumulation was observed during the last third of a year. Over the period of 11 years, suicidal injuries of the head and neck tend to occur more frequently. CONCLUSIONS: The presented study emphasizes the need of immediate surgical and intensive care treatment of patients with head and neck injuries due to suicide attempts as well as an adequate psychiatric supervision during as well as after the surgical treatment.

[Deep neck infections and mediastinitis]. / Tiefe Halsinfektionen und Mediastinitis. Eine schwerwiegende Komplikation nach schwieriger endotrachealer Intubation.

Deep neck infections and subsequent mediastinitis can occur as lethal complications after endotracheal intubation. A 53 year old female patient developed a neck abscess and mediastinitis due to esophageal perforation after endotracheal intubation. Neck and mediastinal exploration were performed as primary surgical treatment in cooperation with thoracic surgeons. Drainage tubes for neck and mediastinum were inserted and irrigated frequently. The abscess cavity was re-examined twice after primary surgery. Microbiological tests were performed at regular intervals to guarantee appropriate antibiotic therapy. This case demonstrates the importance of early and extensive surgical intervention and the necessity of interdisciplinary cooperation in treating such infections.

Immunohistochemical and fine structural characterization of primary carcinoid tumors of the larynx.

Carcinoid tumors belong to the group of neuroendocrine tumors of epithelial origin, i.e., neuroendocrine carcinomas. These neoplasms usually occur in the gastrointestinal tract or bronchial system but are very rare neoplasms in the larynx. Since carcinoid tumors in this latter site may appear to be undifferentiated by light microscopy, they may possibly be misinterpreted and their neuroendocrine characteristics may remain unrecognized. Using immunohistochemical methods, three carcinoid tumors were studied and showed positive immunostaining for markers of epithelial origin (cytokeratins, epithelial membrane antigen, carcino-embryonic antigen) and, in particular, for markers of neuroendocrine differentiation (chromogranin, synaptophysin, neuron-specific enolase). All tumors expressed calcitonin-, serotonin- and adrenocorticotropic-hormone-like immunoreactivity. In contrast, three poorly differentiated squamous cell carcinomas showed positive immunostaining for epithelial markers but did not show any immunoreactivity with markers of endocrine characteristics. Fine structurally, carcinoid tumor cells contained neurosecretory-type granules scattered throughout the cytoplasm. The present study demonstrated that (1) carcinoid tumors of the larynx possess distinct immunohistochemical characteristics that allow a clear classification, (2) it is advisable to use a battery of primary antibodies rather than rely on specificity and sensitivity of a single marker to establish diagnosis and (3) the fine structural demonstration of neurosecretory-type granules serves as a reliable adjunct to diagnosis.

[Medical aspects of diving in otorhinolaryngology. I. Barotrauma and decompression sickness]. / Tauchmedizinische Aspekte in der Hals-Nasen-Ohrenheilkunde. I. Barotrauma und Dekompressionskrankheit.

Recreational scuba diving has become immensely popular in recent years and is no longer restricted to individualists or adventurers. During a dive, the human body with its gas-filled cavities is exposed to an increased ambient pressure. In the present review article, aspects of diving and hyperbaric medicine related to the otolaryngology field are presented. The basics of physics, physiology and pathophysiology that are essential to understand the effects of an increased and varying ambient pressure are reviewed. Barotrauma of the outer, middle and inner ear, the paranasal sinuses, face, teeth and larynx are explained and classified in those during the compression and decompression phase. This is followed by a discussion of inner ear decompression sickness. The present article will provide a background and foundation for both, an adequate treatment of these diseases and a critical and responsible health education of the diver.

Increase of elastic fibres in muscle spindles of rats following single or repeated denervation with or without reinnervation.

Muscle spindles in the lower lumbrical muscles of rats were studied by transmission electron microscopy following denervation with or without reinnervation. The number and total area of elastic fibres per muscle spindle increased at 3-12 months following various experimental procedures: (1) denervation and reinnervation after a single crush lesion to the sciatic nerve; (2) reinnervation after four-fold repeated crush injuries; and (3) transection and suture of the nerve. The increased number of oxytalan and elaunin fibres, the precursors of mature elastic fibres, within these muscle spindles provided further evidence for their numerical and dimensional increase. An attachment site of elastic fibres at the spindle pole was identified at the inner cells of the outer spindle capsule. The processes of these cells embraced terminating elastic fibres tightly. Attachment of elastic fibres to intrafusal muscle fibres was less conspicuous since they were not similarly embraced but were rather indistinctly, though closely, associated with the basal lamina along longitudinal surface indentations of intrafusal muscle fibres. It is concluded from this series of experiments that muscle spindles, as dynamic mechanoreceptors, maintain their elastic properties even under pathological conditions. The increase of elastic fibres following denervation and reinnervation represents an obviously meaningful reaction that may compensate for loss of tonic properties of muscle spindles without causing stiffness.

Stapes surgery in osteogenesis imperfecta patients.

Osteogenesis imperfecta (OI), or the Van der Hoeve-de Kleyn syndrome, is a heterogeneous group of connective tissue disorders. The key features in this disease are bone fragility with a tendency to spontaneous fractures and deformations. The classical traid of symptoms involves a conductive and/or sensorineural hearing impairment together with a tendency to spontaneous bone fractures and blue sclerae. Between January 1988 and December 1994, ear surgery was performed on eight ears of six OI patients who presented with mixed hearing loss preoperatively. Pathological changes observed in the middle ear were atrophy and/or fractures of the stapedial crura in combination with thickening and fixation of the stapes footplate. Partial stapedectomy was performed in seven cases and a neo-window was created in the promontory of one patient when an overhanging facial canal obscured visualization of the oval window niche. Pre- and postoperative bone conduction thresholds did not differ in any of the patients. Postoperatively, mean values of the air-bone gap in the main speech frequency range were below 10 dB. Functional results following stapes surgery in patients with otosclerosis during the same time interval (n = 857) did not differ significantly. These data indicate that stapes surgery in OI patients can be performed with the same functional predictability as in otosclerosis patients, even though the underlying etiology is considerably different.

Abnormal sensory and motor reinnervation of rat muscle spindles following nerve transection and suture.

Muscle spindles from the lower lumbrical muscles of rats were studied by transmission and scanning electron microscopy following reinnervation (i) after a single sciatic nerve crush lesion and (ii) after transection and immediate epineurial suture of the sciatic nerve. In all muscle spindles, regenerated sensory or motor nerve endings were encountered 3 months after making the lesions although in the nerve-transection group, regenerated nerve endings were seen less frequently before 6 months of recovery. Abnormalities in reinnervated spindles following neurotomy comprised: (1) multiplicity of axonal sprouts (hyperinnervation), sometimes irregularly related to, although never in direct contact with, regenerated sensory nerve endings; (2) altered contact relationships between sensory nerve endings and intrafusal muscle fibers; (3) abnormal structure of nerve endings; and (4) irregular association of Schwann cell processes to regenerated sensory nerve endings. These findings indicate that reinnervation of muscle spindles following transection and suture of a peripheral nerve, i.e., after complete interruption of its continuity, in fact, occurs although the fine structural abnormalities observed are supposed to interfere with adequate functional restoration.

[Diving medicine aspects in otorhinolaryngology. II. Diving-specific illnesses and dysfunctions as well as assessment for diving fitness]. / Tauchmedizinische Aspekte in der Hals-Nasen-Ohrenheilkunde. II. Tauchspezifische Erkrankungen und Funktionsstörungen sowie Tauchtauglichkeitsuntersuchung.

Scuba diving with compressed air has become a recreational sport that can be performed at all stages of adulthood. The human body including all gas-filled cavities are exposed to an increased ambient pressure during a dive. In the present review article, specific aspects of diving related disorders are that are of importance in the otolaryngology field are presented and discussed: the multitude of causes for divers' vertigo and the so called divers ear. Furthermore, useful recommendations in the assessment of physical fitness for diving are presented. This review will provide a background and foundation for both, an adequate treatment of these diseases and a critical and responsible health education of the diver.

[Paranasal sinus surgery in chronic sinus disease and benign tumors indications, concepts and complications at a teaching institution]. / Chirurgische Eingriffe an den Nasennebenhöhlen bei Sinusitiden und benignen Tumoren. Indikationen, Konzepte und Komplikationen einer Weiterbildungseinrichtung.

BACKGROUND AND METHODS: The medical records of 635 patients that underwent paranasal sinus surgery for chronic sinus disease or benign tumors during a 6.5 year span were assessed retrospectively to evaluate the status of sinus surgery at a teaching institution. The parameters analyzed were indication for surgery, surgical approach, extent of the procedures and complications. RESULTS: The ratio between male and female patients was 2 : 1, with an average age of 44 (+/- 16) years. In 137 cases (21.5 %), revision surgery in patients previously treated at the University of Wuerzburg was necessary. In 80 cases (12.6 %), prior surgery had been performed elsewhere. The majority of the procedures (91.3 %) were carried out using endonasal techniques. External, transethmoid (6.5 %) or transmaxillar (2.2 %) approaches were chosen in 8.7 % of all cases, mainly when the preoperative diagnoses were mucoceles (65.2 %), benign tumors (40.9 %) or orbital complications (33.3 %). Surgery was assisted exclusively by the microscope in 78.7 %, solely by the endoscope in 15.9 % and with a combination of both optical tools in 5.4 % of all cases. The total rate of complications was 8.2 %. Minor complications were seen in 8.1 % of the endonasal and 4.9 % of the external transethmoid procedures. While no major complications occurred during endonasal or extranasal transmaxillar surgery, liquorrhoe was documented in three extranasal transethmoid procedures (7.3 %). Neither permanent impairment of vision, nor post-operative meningitis nor surgery-related mortality was observed in any case. CONCLUSION: The study gives an overview over the paranasal sinus surgeries performed at a teaching institution, independent of the experience of the surgeon. It confirms the results of previous investigations and indicates that endonasal sinus surgery is a reproducible and reliable procedure that can be safely applied at a teaching institution. The results also show that the indication for extranasal approaches is further reduced to the less invasive endonasal techniques.

[Non-Hodgkin's lymphoma simulating chorioretinitis]. / Non-Hodgkin-Lymphom mit dem Erscheinungsbild einer Chorioretinitis.

Lymphoma affecting the eye is a special form of Non-Hodgkin's Lymphoma, which was formerly described as reticulum cell sarcoma and is now mostly identified as highly malignant lymphoma. The clinical findings include posterior uveitis with dense opacities of the vitreous body. We present two female patients with minor opacities of the vitreous body, thus permitting funduscopic inspection and leading to the diagnosis of chorioretinitis. Fundus examination of the first patient revealed confluent infiltrates in both eyes. She developed progressive neurological symptoms within 10 weeks and died of respiratory insufficiency. All parenchymatous organs and the central and peripheral nervous system showed multifocal infiltration with cells deriving from a malignant T-cell lymphoma. The second patient presented with subretinal infiltration surrounding the right optic nerve head. Over the following weeks the infiltrations first spread towards the temporal fundus and then disappeared spontaneously, forming scars with atrophy of the pigment epithelium.

Myenteric plexus neuropathy in infantile hypertrophic pyloric stenosis.

The myenteric plexus and intramuscular nerve bundles in the circular muscle layer of the pylorus from 37 children with infantile hypertrophic pyloric stenosis (IHPS) obtained at pyloromyotomy were studied by light and electron microscopy and compared to six control cases without clinical evidence of IHPS. In certain IHPS cases degenerative alterations of the axons predominated. The axonal changes consisted of (1) severely increased variability of diameters with evidence of degeneration and regeneration of some axons, (2) accumulation of electron-dense bodies, lysosomes and pleomorphic membranous cytoplasmic bodies, (3) increase in the number of maloriented neurofilaments, and (4) aggregation of glycogen granules. Degenerative changes or immaturity of perikarya of neurons and glial cells in the myenteric plexus were not a significant feature. While axonal changes predominated in some IHPS cases there were severe changes of smooth muscle cells in others suggesting that a primarily neurogenic type of IHPS can be distinguished from a predominantly myogenic type. Although the etiology of the axonal changes in IHPS is not clear, it is suggested that they play an important role in the pathogenesis of pyloric stenosis and hypertrophy.

Infantile hypertrophic pyloric stenosis: myopathic type.

Smooth muscle cell biopsies obtained at pyloromyotomy from 37 children with infantile hypertrophic pyloric stenosis (IHPS) were studied by light and electron microscopy and compared with 6 autopsy control cases without any clinical evidence of this disorder. In cases with IHPS an apparently irregular increase in the number of smooth muscle cells by mitosis was accompanied by an increase of the endoplasmic reticulum, proliferation of mitochondria and regressive changes, such as shrinkage, swelling, necrosis and apoptosis of smooth muscle cells. Other alterations, seen in some but not all cases consisted of large numbers of unusual dense granules some of which were clearly associated with actin filaments and, therefore, regarded as derivatives of the normally occurring dense bodies. Furthermore, intermyofibrillar and subsarcolemmal glycogen accumulations, various nuclear abnormalities and pleomorphic membranous cytoplasmic or nuclear bodies occurred. While smooth muscle cell abnormalities predominated in some cases of IHPS, in others there were more severe axonal changes in the myenteric plexus. It is suggested, therefore, that a primarily myogenic type of IHPS can be distinguished from a predominantly neurogenic type.

Immunohistochemical reactivity of neuropeptides in plastic-embedded semithin sections of the myenteric plexus in infantile hypertrophic pylorus stenosis.

Pyloric biopsies obtained at pyloromyotomy from 46 infants were studied by light and electron microscopy and compared to 8 autopsy control cases without any evidence of infantile hypertrophic pyloric stenosis (IHPS). A positive family history of this disorder was recorded in 8 cases (2 girls and 6 boys). The most frequent changes in the myenteric plexus comprised axonal alterations. In glial cells, cytoplasmic vacuolisation or an increase of intermediate filaments occurred. In ganglion cells, vacuolisation of perikaryal cytoplasm or dense bodies were observed. No obvious differences were seen between sporadic and hereditary cases. In addition to these fine structural alterations, immunohistochemistry in 6 IHPS cases and 4 controls revealed differences in the distribution of substance P, bombesin, calcitonin gene related peptide and enkephalin-like immunoreactivity within the myenteric plexus between IHPS and control cases. The immunoreactivity, however, was unevenly distributed from case to case and even within individual cases. The reduction of immunoreactivity corresponded, at least in part, to an increase of neurofilaments or abnormal organelles within axons. Increased immunoreactivity was apparently related to focal accumulation of dense cored vesicles noted in the preceding study. It is suggested that these and other changes reported interfere with the normal gastrointestinal reflex mechanisms leading to intestinal obstruction.

Scanning electron microscopic study of denervated and reinnervated intrafusal muscle fibers in rats.

Isolated muscle spindles from lower lumbrical muscles of rats were used to study the 3-dimensional organization of intrafusal structures by scanning electron microscopy following (a) complete denervation, (b) reinnervation after a single crush lesion of the sciatic nerve, or (c) reinnervation after transection and immediate suture of this nerve. One week after complete denervation, previous sites of intrafusal motor endplates were transformed into sarcolemmal ovoid bulges. These bulges persisted in denervated muscle spindles up to 12 weeks. Regenerated motor nerve endings were detected on intrafusal muscle fibers 1 month, and thereafter following sciatic nerve crush injuries, and 3 months and later following transection and suture of the nerve. Furthermore, 3 different types of subsynaptic areas of motor nerve terminals were observed. The scanning electron microscopic technique also allowed visualization of splitting and fusion of intrafusal muscle fibers. The findings are discussed in view of their possible functional implications.

Electron-dense lipidic capillary deposits in Rett syndrome.

Conjunctival, muscle, and peripheral artery biopsies were examined by light and electron microscopy in a patient with clinically diagnosed Rett syndrome. In capillaries, amorphous and membranous electron-dense deposits were observed (a) endoluminally attached to endothelial cell membranes, (b) within junctional clefts of adjacent endothelial cells, and (c) at abluminal sites of endothelial cells. In addition, electron-dense deposits lay isolated or inside multivesicular bodies in endothelial cells and pericytes. These findings have not been reported before in Rett syndrome. They were not seen in age-matched normal or pathological control cases and are suggested to indicate deposition of an as yet unknown lipidic plasma component possibly in association with impairment of the blood-tissue barrier.