Localization of chat-like immunoreactivity in the vestibular endorgans of the rat.

In vertebrates acetylcholine (ACh) has been generally considered as a neurotransmitter of the vestibular efferent system. The precise localization and innervation of the cholinergic nerve endings in the vestibular sensory periphery is still unknown. We examined choline acetyltransferase (ChAT)-like immunoreactivity in all five endorgans of the rat vestibule with light and electron microscopy using a modified pre-embedding immunostaining technique. The results were: (1) ChAT-like immunoreactivity was widespread in all five endorgans of the vestibule and confined to the vesiculated efferent nerve endings. (2) Two types of ChAT-like immunostained nerve endings can be identified according to their size and innervation pattern: a large nerve ending and a small--middle size one. (3) Vestibular endorgans differ in their ChAT-like immunoreactivity: staining is dense in the macula of the utricule and the three ampullary cristae, but less so in the macula of the saccule. (4) We found also a regional difference of the ChAT-like immunostaining in ampullary crista. ChAT-like immunostained nerve endings were predominant in the periphery close to the semilunar plane, and less in density in the central area. These findings demonstrate that ACh is a major neurotransmitter in the vestibular efferent system.

A quantitative study of nerve fibers in the human facial nerve.

The facial and intermediate nerves were quantitatively evaluated in seven patients who died from systemic malignancies not involving the facial nerve. In addition, five of the specimens were also qualitatively evaluated by measuring the total and axon diameters of the facial and intermediate nerve fibers. In two cases the facial nerve fibers were counted at five different levels. The total number of myelinated nerve fibers in the facial nerve varied from 7500 to 9370. The total number of myelinated nerve fibers in the intermediate nerve varied between 3120 and 5360. The peak diameter of the facial nerve axon was between 4 and 6 microns, and was between 2 and 3 microns in the intermediate nerve. When comparing nerve segments at different anatomical levels, the largest amount of nerve fibers was found at the level of the middle mastoid portion. However, this number did not reach the amount of nerve fibers counted in the internal acoustic meatus.

[Trans-septo-sphenoidal operation for pituitary adenoma in 92 patients: results and follow-up endocrine studies]. / Transseptosphenoidale Operation von Hypophysenadenomen bei 92 Patienten: Ergebnisse und endokrine Verlaufskontrolle.

The short- and long-term therapeutic results of transseptosphenoidal adenomectomy were studied retrospectively in 92 patients with pituitary tumors (42 nonsecreting adenomas, 21 GH-, 15 PRL-, 10 ACTH-, 2 TSH-, and 2 FSH-secreting adenomas). Severe surgically related complications were not observed. The early remission rate was 53.7% in nonsecreting, 57.1% in GH-secreting, 60% in PRL-secreting, 88.9% in ACTH-secreting, and 75% in TSH- or FSH-secreting adenomas. The recurrence rate in patients with nonsecreting adenomas was 47.1%, with GH-secreting adenomas 10%, with ACTH-secreting adenomas 25%, and with TSH- or FSH-secreting adenomas 66.7%, respectively. A long-term cure rate of 69.2% was observed in prolactinomas in combination with a facultative dopamine agonist therapy. More patients had normal pituitary function concerning TSH, ACTH, and LH/FSH post-operatively (48.9% versus 46.6% preoperatively). These data confirm that transseptosphenoidal surgery is a safe and selective treatment for pituitary adenomas with efficient preservation of the normal pituitary gland.

Multicentre evaluation of the temporal bones obtained from a patient with suspected Menière's disease.

A multicentre study of the inner ears of an 88-year-old patient with vertiginous spells and severe hearing loss in the left ear was performed, employing regular and block surface preparations, light and electron microscopy with qualitative and quantitative evaluation of the cochlear and vestibular nerves. There was severe hydrops of the left cochlea and saccule. Reissner's membrane extended into the vestibule and herniated into the perilymphatic space of the non-ampullated end of the horizontal canal. Furthermore, the short canal connecting the posterior ampulla with the utricle had a small, exceedingly thin balloon-like expansion. Only slight hydrops limited to the cochlea was found in the right ear. Sensorineural degeneration was much more pronounced in the left cochlea than in the right. The number of cochlear and vestibular nerve fibres was greatly reduced in the left ear where more fibres with degenerative changes were present. In both specimens the number of myelinated nerve fibres in osseous spiral lamina was smaller than that in the cochlear nerve in the internal auditory canal. Changes occurred in the endolymphatic sacs but were considered non-specific. In this case severe, apparently progressive hydrops and sensorineural degeneration, characteristic of Menière's disease, were associated with atypical onset of clinical symptoms at a late age.

Quantitative evaluation of the human cochlear nerve.

In 18 human temporal bones of patients with normal hearing or sensory neural deafness, the cochlear neurons were evaluated at the level of the peripheral axons in the osseous spiral lamina, the ganglion cells in the spiral ganglion and the central axons in the cochlear nerve in the inner acoustic meatus. The total number and the segmental distribution were both determined.

Auditory brainstem response thresholds in a mouse mutant with selective outer hair cell loss.

Mutant animals with a particular type of cochlear pathology are an excellent model for studying the functional role of various cells of the cochlea. In homozygous WV/WV mutant mice we found a selective loss of outer hair cells as a constant defect with no progressive degeneration of the organ of Corti. The mice were followed throughout their lives and exhibited auditory brainstem responses that were elevated to about 50 dB SPL as compared to normal control animals. Sequential temporal bone studies showed that there was a selective loss of outer hair cells throughout the entire cochlea as seen in surface preparations. The inner hair cells were present in normal numbers and appeared to be essentially normal.

Analysis of the human auditory nerve.

In human temporal bones of patients with normal hearing or sensory neural deafness, the cochlear neurons were quantitatively and qualitatively evaluated at the level of the osseous spiral lamina, the spiral ganglion and the cochlear nerve. We found from 32,000 to 31,000 myelinated nerve fibres in the cochlear nerve of normal hearing individuals and any lower number in cases of sensory neural deafness. There was in general a good correspondence between the counted numbers of the myelinated nerve fibres in the osseous spiral lamina, the spiral ganglion cells and the myelinated nerve fibres in the cochlear nerve in the inner acoustic meatus. The diameter of the peripheral axons of the type I neurons are about half the diameter of the central axons. The average diameter of the central axons is 2.5 millimicrons with a narrow distribution in children, but an increasingly larger range of fiber calibers with increasing age (0.5 to 7 microns in the 40 to 50 year age group adults).

Hearing with selective inner hair cell loss.

In a comparative model study, the effect of selective inner hair cell loss on hearing threshold was investigated. Functional testing was related to a detailed morphological evaluation. Inner ears of homozygous Bronx waltzer mice (bv/bv) were investigated using light microscopy with Nomarski interference contrast optics and transmission electron microscopy. Hearing thresholds were determined using click evoked auditory brainstem responses at different ages. The histological evaluation was performed immediately after determination of the hearing threshold. The functional and histological findings were compared to the normal controls of the same age. Scattered loss of up to 70% of inner hair cells was found to cause only moderate elevation of hearing threshold.

The spiral ganglion and the innervation of the human organ of Corti.

Five human cochleas were evaluated using the block surface method. The numbers of hair cells, nerve fibres in the osseous spiral lamina, and spiral ganglion cells were determined and correlated. The ultrastructural organization corresponds essentially to that of the mammalian ear, with the exception of multiple synaptic contacts of afferent nerve fibres with inner hair cells and surprisingly large numbers of outer spiral fibres.

Intermediate filaments in the cochleas of normal and mutant (w/wv, sl/sld) mice.

Using monoclonal and polyclonal antibodies to intermediate filaments in the cochleas of normal and mutant mice, we were able to distinguish between different cell types of the stria vascularis. Immunostaining for vimentin was found in the intermediate and basal cells of the stria vascularis of the normal mice. In contrast, vimentin was seen to stain only the basal cells in the mutant mice, confirming our previous findings of the absence of intermediate cells in these cases of hereditary deafness. Immunostaining for cytokeratin was identical in both the mutant and control mice.

Macroprolactinomas and functionless pituitary tumours. Immunostaining and effect of dopamine agonist therapy.

In 32 patients with macroprolactinomas or functionless pituitary macroadenomas biochemical and clinical data were correlated with PRL immunocytochemistry. Serum PRL levels revealed a positive correlation with tumour PRL content. Hyperprolactinaemia of 3000 mU/l or more was found only in patients with PRL-positive tumours. In 15 patients with borderline hyperprolactinaemia (below 3000 mU/l), 7 PRL-positive and 8 PRL-negative macroadenomas were found, and in 9 normoprolactinaemic patients 4 PRL-positive and 5 PRL-negative macroadenomas. Patients with PRL-immunostainable tumours had significantly higher median basal serum PRL (P less than or equal to 0.05) than patients with PRL-negative tumours. PRL stimulation after TRH, basal and GnRH-stimulated FSH and LH did not show significant differences between the two groups. A discriminant analysis using 6 biochemical variables was attempted to differentiate between PRL-negative and -positive tumours, which would be helpful in patients with borderline hyperprolactinaemia. Dopamine agonist therapy led to suppression of serum PRL with few exceptions in patients with PRL-positive and -negative tumours, whereas shrinkage was only observed in PRL-immunostainable tumours with high serum PRL levels (over 18,000 mU/l). All patients with PRL-negative tumours showed no change or even growth of the tumour despite dopamine agonist therapy. Our observations indicate that a pituitary macroadenoma associated with serum PRL of more than 3000 mU/l is most probably a prolactinoma (tumour immunostainable for PRL). Dopamine agonist therapy is effective in PRL suppression and tumour shrinkage in most of these patients. Macroadenomas without hormone hypersecretion or with borderline hyperprolactinaemia below 3000 mU/l may or may not contain PRL-immunostainable cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Pigment anomaly-associated inner ear deafness.

In order to investigate the pathogenesis of pigment anomaly-associated hereditary deafness, we studied black-eyed white mutant mice, which become severely deaf in early life and lacked neural crest-derived melanocytes. In the inner ear, the primary alteration appears to be located in the stria, which remains much thinner than normal and lacks intermediate cells. Melanocytes are identified with the histochemical Dopa reaction. This reaction is positive in intermediate stria cells in many animals of different ages, proving that they are derived from melanocytes. No tyrosinase-positive reactions were found in the mutant mice. This clearly indicates that the lack of intermediate stria cells is the crucial factor in the pathogenesis of pigment anomaly-associated inner ear deafness.

The block surface method for evaluation of human inner ears.

Experience with the application of the block surface technique to human inner ears, its advantages and problems are discussed. The usefulness of this technique depends essentially on the fixation quality, which is directly related to the postmortem time delay of efficient fixation by perilymphatic perfusion. Some typical structural features of the human inner ear are shown.

The prognostic influence of induction chemotherapy on advanced head and neck carcinoma.

We examined the influence of induction chemotherapy integrated with surgery and postoperative radiotherapy on 5-year treatment results of 107 patients suffering from advanced head and neck carcinomas. The chemotherapy regimen consisted of one to three cycles of a combination of cisplatin, methotrexate and bleomycin. The overall response rate to induction chemotherapy was 58% with a 26% complete response rate. Using actuarial life tables, survival was 44% for all patients. The initial tumor stages were found to be predictive for patients' responses to chemotherapy as well as for their survivals. The overall response rate was 65% for T-3 tumors vs 29% for T-4 tumors. Five-year survival was 54% for T-3 vs 24% for T-4 tumors. The other predictive factor for survival was response to chemotherapy. Five-year survival was 73% for those patients achieving a complete response vs 17%-37% for patients with any residual disease after drug treatment. Since a favorable response to chemotherapy was strongly associated with a lesser T-stage as well as with significantly better survival of patients in our study, we conclude that induction chemotherapy may best benefit those patients with smaller tumors. Our findings show that a complete response to chemotherapy can also serve as a good prognostic sign, although an a priori better prognosis is still associated with patients who have smaller tumors.

Receptoneural and innervation aspects of the inner ear anatomy with respect to cochlear mechanics.

The important features of the innervation pattern of the organ of Corti are reviewed and the possible functional implications discussed. The numerical characteristics, the pattern, the structural features and the central connections of the afferent and efferent innervation of the inner and outer hair cells indicate that the information-transfer from the organ of Corti to the central nervous system occurs essentially in the inner hair cell system with its numerous associated neurons and that the functional emphasis of the outer hair cell system is in the periphery at the receptor cell level, probably by monitoring the receptor organ.

Anatomy of cochlear innervation.

In this review of cochlear innervation, the differences in the innervation of outer and inner hair cells are emphasized. Of the afferent neurons, 90 to 95 per cent are large, myelinated type I neurons, exclusively connected in an essentially radial unbranched manner to the inner hair cells; 5 to 10 per cent are small, mostly unmyelinated type II neurons connected to the outer hair cells with considerable spiral extension and branching. The few small type II neurons, with their thin unmyelinated axons, probably have a minor functional importance for centripetal information transfer. The functional emphasis of the outer hair cell system is likely at the level of the receptor cells where the outer hair cells monitor receptor function. The efferent innervation also consists of at least two types of neurons. Small neurons from the lateral superior olivary nucleus project to the inner hair cell area in a predominantly homolateral fashion, making almost exclusively synaptic contacts with the afferent dendrites associated with the inner hair cells. Larger neurons from the medial nucleus of the trapezoid body and periolivary nucleus provide the abundant efferent nerve supply of the outer hair cells, predominantly contralateral. They have mostly large synaptic contacts, and, in some species exclusively, with the receptor cells, indicating again the functional emphasis of the outer hair cell system at the receptor cell level.

Histopathology of noise deafness.

The psychophysical effects of sound stimulation at increasing intensity include adaptation, temporary threshold shift, and permanent hearing loss. The mechanisms involved in permanent loss are direct mechanical destruction, following high intensity noise exposure, and metabolic decompensation with subsequent degeneration of sensory elements, following moderate intensity noise exposure. Both these cause their own pattern of cochlear histological abnormality, while the only morphological correlate to temporary threshold shift is an increase in the number and size of liposomes, mainly in the outer hair cells after longer periods of repeated temporary threshold shift. There are critical intensity levels which determine the type and extent of damage, and for any given exposure intensity a saturation of damage is reached over time. There is great variability in acoustic cochlear damage, especially that of the delayed metabolic type, the type which results from conditions which predominate in our actual noise environment.

Three-year results of combined modality therapy in locally advanced, resectable squamous cell carcinoma of the head and neck.

Results of a combined therapy, consisting of preoperative chemotherapy, radical resection and postoperative irradiation, of 51 locally advanced, previously untreated, resectable squamous cancers of the head and neck are reported. The overall response rate to chemotherapy was 58.5% (with 33% complete remissions) and higher in carcinomas of the oral cavity and hypopharynx than of the supraglottis and oropharynx. Three year survival was 53% for the entire group, 75% for hypopharyngeal, 58% for oral, 50% for supraglottic and 32% for oropharyngeal lesions, in responders to chemotherapy statistically significant higher than in non responders and only 18% in the fifteen patients who developed recurrences.

Factors inducing retrograde degeneration of the cochlear nerve.

The process of retrograde secondary degeneration is described and its mechanism, discussed. The extent of degeneration following transection of the central or peripheral axon and following various types of damage to the organ of Corti, including the time course of degeneration, is presented in animal experimentation and human temporal bones. Of greatest practical importance is secondary neuronal degeneration induced by alteration in the organ of Corti. The effect of damage to the outer hair cells, inner hair cells, supporting structures in the Corti, and nerve endings or peripheral dendrites is analyzed and related to different types of inner ear disease.

Degeneration of cochlear neurons after amikacin intoxication in the rat.

Intoxication with high doses of the aminoglycoside antibiotic amikacin in a supranormal sensitive period in the rat induces complete destruction of the inner and outer hair cells in the organ of Corti in all turns, whereas the supporting cells remain partially preserved in the upper turns. With increasing survival time, the number of ganglion cells in the spiral ganglion decreases progressively, reaching a minimum of about 10% surviving cells after 12 months. Both type I and type II neurons are subject to retrograde degeneration, although type-II cells degenerate more slowly than type-I cells. The presence or absence of supporting cells in the organ of Corti does not seem to influence neuronal degeneration. This retrograde degeneration is similar in all animals so far studied but its time course is different from different species. Retrograde degeneration after destruction of Corti's organ is a long-lasting process and is never completed at once. This must be taken into consideration in the treatment of total deafness with electric stimulation of surviving neurons.