The incidence and mortality of acute epiglottitis were retrospectively analysed covering a 12-year period, 1975-1987. The diagnosis was made by the laryngoscopic findings in 95% of patients. Based on 902 hospitalized patients, a mean annual incidence of 4.9 cases per 100,000 children and adults was found. Although adult patients predominated (60%), the incidence was far higher in children, 13.8 per 100,000 compared with 3.9 per 100,000 in adults. Two peaks in incidence were identified, one for the youngest children, and the second for young adults (15-29 years). Over the years the incidence varied little in adults, but decreased significantly in children over the last 6 years studied. The data presented indicate acute epiglottitis to be a more frequent disorder than previously believed but with less risk of a fatal outcome. The mortality rate was below 1% in children and adults and the annual incidence of death from acute epiglottitis was estimated at 0.5 cases per million. The primary admission of these patients to ENT units seems to be the single factor having the most powerful impact on mortality.

In order to study the etiology of the intramural maxillary cyst, which is the origin of the choanal polyp, an antrotomy was performed on 27 patients with such cysts. The cyst-fluid was analysed with respect to protein distribution and bacterial growth. The findings indicate an inflammatory process characterized by high concentrations of immunoglobulins and by consumption of complement and antiproteases. The growth of bacteria, primarily an oral flora found in the cyst-fluids studied, and the sites of cyst attachment, may indicate an epithelial residue of the dental list as the origin of the intramural cyst. It is further suggested that bacterial substances will provoke an inflammatory response, giving rise to an expansion of the cyst. In all cases studied, the cyst-fluid was capable of gelling after a couple of minutes at room temperature. This observation seems to be a reliable diagnostic procedure at antral aspiration, distinguishing the cyst-fluid from the serous transudate of the serous sinusitis, which according to our results, does not have this capacity to form a gel.

To study the origin of the choanal polyp, the maxillary sinus was surgically explored using a preservative technique. An antral cyst or a cystic rudiment, usually attached to the inferolateral aspect of the sinus wall, was disclosed in 15 patients with this condition. As a part of the choanal polyp, the antral cyst exhibited a macroarchitecture and microarchitecture identical to the structure of the common intramural cyst of the maxillary sinus as studied in nine patients. It is concluded that the choanal polyp develops from the expanding intramural cyst protruding through the maxillary ostium and into the nasal cavity.

The ototoxic potential of ethacrynic acid, defined as causing morphologic damage to hair cells or adjacent supporting structures, was analyzed in an organ culture model exposing inner ear structures to concentrations attainable during clinical conditions (0.1 to 10 micrograms/ml). In low doses more) ethacrynic acid caused generalized toxic effects on the tissue morphology of many types of inner ear tissues and an arrest of tissue differentiation. Although by definition ethacrynic acid is an ototoxic agent, there is, at least in the in vitro system, a very narrow dose range between the selective hair cell damaging concentration and that causing generalized toxic effects.

In the Shaker-2 mouse mutant, a cochleo-saccular type of genetically induced inner ear degeneration occurs. Morphological signs of degeneration are evident in the 3rd postnatal week and a severe and almost total degeneration has occurred by the age of 6-9 weeks. There are no qualitative differences between the brain of the normal CBA/J mouse and that of the Shaker-2 mouse. The growth of the auditory brainstem nuclei (dorsal cochlear nucleus and ventral cochlear nucleus) in the mutant Sh-2 mouse has stopped by 14 days of age--but not in the normal CBA/J mouse. The brainstem as a whole continues to grow between 14 and 140 days of age in both strains. The early cochlear degeneration coincides with the critical period when a normal input from the peripheral receptor organ is necessary for the maturation of the central auditory pathway.

The ototoxic potential of cisplatin was analyzed in an organ culture model exposing the hair cells and other inner ear structures to cisplatin doses from 0.1 to 10 micrograms/ml. Selective hair cell degeneration was obvious at concentrations of 0.1 microgram/ml. Incubation with 1 microgram/ml caused morphologic damage in the supporting cells in both the cochlear and vestibular parts of the labyrinth. Exposure to 10 micrograms/ml during five days caused a total collapse of the membranous labyrinth. The morphologic degeneration pattern at the ultrastructural level is nonspecific, except that nuclear chromatin was either swollen and disintegrated or considerably condensed. Based on inner ear concentrations equivalent to aminoglycoside antibiotics in the range of 0.1 to 10 micrograms/ml, cisplatin is, in the in vitro model used in this study, the most ototoxic drug known. However, because of its single dose administration and long intervals between administration, clinical ototoxicity is less pronounced than that from aminoglycoside antibiotics.

The waltzing guinea pig is born with a clinically apparent vestibular dysfunction. In the present study otoconia in the maculae utriculi were studied with scanning electron microscopy in animals aged from newborn to six months old. Malformed otoconia, dumbbell-shaped and asymmetrically shaped otoconia occurred together with otoconia showing various degrees of morphologic degeneration. It is suggested that the otoconial pathologic condition starts prenatally and that an abnormal composition of endolymph may further contribute to the vestibular dysfunction.

Surface pathology of inner ear structures so far described in detail concern cochlear and vestibular hair cells and the stria vascularis. In man, surgical intervention into the inner ear is very uncommon and when performed is in general with the primary objective of destroying the diseased peripheral end organs. The vast majority of inner ear tissue available for use with scanning electron microscopy (SEM) is therefore obtained from animals. The present paper reviews the progression of surface pathology caused by aminoglycoside antibiotics, acoustic overstimulation and in a guinea pig strain with genetic inner ear disease. The primary site of onset of surface pathology differs, depending on the underlying cause. Advanced surface pathology shows a similar type of morphological degeneration independent of cause. The combination of SEM and energy dispersive X-ray microanalysis (XRMA) of inner ear pathology has as yet been reported in only three studies, all concerning inner ear fluids or otoconia.

The early development and maturation of vestibular hair cells in the CBA/CBA mouse were analyzed at the ultrastructural level with conventional transmission electron microscopy and freeze fracturing. Cells differentiating into future hair cells pass their terminal mitosis close to the otocyst lumen. The earliest morphologic sign of differentiation into future hair cells was the arrangement of microvilli in a regular fashion. Hair cell cytodifferentiation occurred with a gradient from the hair cell surface to the base. In parallel with the maturation of sensory hairs a structural intracellular rebuilding occurred: the number of polyribosomes and amount of rough endoplasmic reticulum decreased, the nucleus moved basally, and mitochondria accumulated in the supranuclear region. Both tight junctions and gap junctions occurred initially on developing hair cells. From the sixteenth gestational day on, gap junctions disappeared, indicating an uncoupling phenomenon. Afferent nerve terminals developed before efferent nerve endings. Maturation of innervation occurred, for the most part, postnatally, and after that hair cells reached mature morphology.

The cytodifferentiation and maturation of vestibular hair cells, and the pathological development of vestibular type I hair cells, were followed in a strain of the waltzing guinea pig. The hair cells are first identified on the 30th gestational day. During the next 7-10 days the number of hair cells increases considerably in parallel with cytodifferentiation: the development of stereocilia, the cuticular plate, the afferent nerve terminals and the formation of synaptic contacts. On the 48th gestational day efferent nerve terminals are identified as are also a large number of fully developed nerve calyces. Differentiation into hair cells type I and type II was clearly evident at this stage. The first pathological finding appeared on the 38th gestational day as fusion of stereocilia. Actin filament rods in type I hair cells are identified with certainty on the 60th gestational day. In parallel with the in vivo development, inner ear explants (30-50th gestational days) were cultured in vitro. In this material actin filament rods were found already in 30th gestational day explants cultured 8 days in vitro. At this stage also hair cell protrusion and sensory hair fusion occurred.

The crista ampullaris, the macula utriculi and the macula sacculi in the waltzing guinea pig were investigated with light microscopy, transmission and scanning electron microscopy. The degenerative changes consist of increasing degrees of apical protrusion of the type I hair cell into the endolymphatic space and of sensory hair fusion. The development of an intracellular actin filament rod in the type I hair cell is coupled to the degenerative changes of the apical part of the cell. Progressive hair cell degeneration with actin rod formation and sensory hair fusion as two important findings in the degenerative pattern is observed in type I hair cells of all sensory areas in the vestibular part of the labyrinth in the waltzing guinea pig. Scanning electron microscopy, shows a concentration of the more advanced stages of degenerative changes to the central part of the crista ampullaris and to the striolar area in the macula utriculi and in the macula sacculi. The fact that there is a concentration of sensory cell damage in the central areas of the vestibular end organs in genetically induced inner ear disease as well as in other inner ear damage supports the concept that the central areas have a different function. This paper further supports earlier suggestions that the type I and type II hair cells are genetically different cell types having different functions.

Using immunohistochemical methods, actin and fimbrin were identified and localized in vestibular epithelia iin the normal guinea pig and in the waltzing guinea pig. In the normal guinea pig, actin was found in the stereocilia and in the cuticular plate. Fimbrin was detected in the stereocilia but surprisingly not in the cuticular plate. As fimbrin was found in the cuticular plates in cochlear hair cells it is suggested that the hair cells in the two organs have different mechanoreceptor properties which can demand different cuticular plate stability. In the waltzing guinea pig, actin was found in the stereocilia, in the rod and n the cuticular plate. Fimbrin was seen in the stereocilia and in the rod, but could not be detected in the cuticular plate. These results emphasize the resemblance between the rod and the stereocilia. It is suggested that the rod is a genetically induced pathological intracellular type of stereocilium which grows in an uncontrolled manner.

Sixty‐three patients with squamous cell carcinoma of the anterior two‐thirds of the tongue were treated with preoperative external radiotherapy (mean target dose 42.60 Gray or 4260 rad) and surgery. The expected 5‐year survival, expressed as life table estimate of percent of survivors, was 77% for patients with Stage I tumors, 69% with Stage II, and 13% for patients with tumors in Stages III‐IV (p < 0.001). Fourteen patients experienced local recurrences, 7 had homolateral neck metastases, 4 had contralateral neck metastases and 3 had distant metastases. In 15 cases no cancer could be detected at review of the surgical specimens, but 2 of these died of their cancers. In 43 cases cancer was present in the specimens, and 26 of these died of their cancer (p < 0.01).

The embryonic inner ear of the guinea pig was cultured one to ten days in vitro. The explantation occurred on the 30th and 40th gestational days, respectively. Hair cells were found in various stages of cytodifferentiation. Both hair cells and supporting cells were ultrastructurally preserved at the end of the period in vitro. The gross morphologic features of the crista ampullaris were still immature. The embryonic inner ear of the guinea pig can be maintained in organ culture until at least as late as the 46th gestational day.

The waltzing guinea pig exhibits genetically induced inner ear disease which develops into deafness and vestibular disorder. The type I hair cell in vestibular end organs shows specific pathology, featuring protrusion of the hair cell apex, sensory hair fusion and an intracellular actin filament rod. With the freeze-fracturing technique, consecutive stages of degeneration of the apical part of the type I hair cell are shown. Different possible mechanisms underlying these changes are discussed. It is probable that the genetically induced prenatally developed hair cell pathology is related to a pathological development of actin filaments and their connections in the apical cytosk-eleton.

A system for histological grading of malignancy was applied to ninety-five squamous cell carcinomas from the anterior 2/3 of the tongue. Three parameters relating to the tumour cell population and three parameters relating to the tumour-host relationship were evaluated. The expected 5-year survival expressed as % survivors was 88% for patients with tumours having total malignancy scores of less than 13 points. 65% for 13-16 and 44% for patients with tumours having scores of more than 16. The prognostic significance for 5-year survival was statistically valid for the three different groups of malignancy scoring. The conventional classification according to mode of differentiation did not give equally good correlations for survival or occurrence of metastases. For the evaluation of the biological behaviour of lingual carcinomas, histological grading of malignancy is a better method.

The waltzing guinea pig suffers from hereditary deafness and vestibular disorder. In vestibular organs, hair cells of Type I develop pathologically and will eventually degenerate. They show fusion of sensory hairs, protrusion of the cuticular plate and contain a rod-shaped inclusion body. With fixation techniques designed to preserve proteins it is shown that this rod has a filamentous substructure reminding one of stereocilia. The packing density of the filaments is similar and circular packing patterns are seen within both structures. However, the rod has an irregular cross-section, as opposed to the circular circumference of stereocilia. The filaments in the rod were identified as containing the protein actin (as those in the stereocilia) by decoration with sub-fragment S-1 of myosin. All filaments in the rod have an identical functional polarity, pointing up from the nucleus towards the cuticular plate. This is contrary to that seen in stereocilia, which have filaments pointing down towards the cuticular plate. It is concluded that the rod is not developed by random polymerization of actin but is the result of co-ordinated assembly reminiscent of that which gives rise to stereocilia. The genetic defect appears to be related to mechanisms which determine the site of nucleation and the functional orientation of actin filaments during development.