bromochloroacetic-acid and Cholesteatoma

We report a late recurrence of a cholesteatoma of the left kidney after 15 years. Both the initial case and the recurrence were treated by endourologic and percutaneous approaches.

Topics: Cholesteatoma; Female; Flank Pain; Hematuria; Humans; Keratins; Kidney Calculi; Kidney Diseases; Kidney Pelvis; Magnetic Resonance Imaging; Middle Aged; Nephrostomy, Percutaneous; Recurrence; Time Factors; Tomography, X-Ray Computed; Ultrasonography

After an epoch in which was pretended to explain the etiopathogenetic phenomena observed in Cholesteatoma through enzymatic studies, nowadays other investigations focus the topic in the possible presence of immunobiologic alterations at cellular level, so the research work is directed to the occurrence, distribution and activity of several growth factors and leukins. In this paper the AA. made a perusal of the new acquisitions and devote themselves to two important aspects of the cholesteatoma: the biologic behaviour of the squamous cell epithelia with an uncontrolled growth and to the immunobiologic mechanisms responsible for the bone resorption.

Topics: Bone Resorption; Cholesteatoma; Ear, Middle; Epithelial Cells; HLA-DR Antigens; Humans; Keratinocytes; Keratins; Osteolysis; Transforming Growth Factor alpha

Presentation of 6 cases of renal cholesteatoma in 4 male and 2 female patients ranging between 30 and 67 years of age. The most consistent clinical data was a history of relapsing nephritic colic of long-evolution. The average time to diagnose was 19 years. In 50% cases an association to malignant neoplastic pathology was found. The clinical diagnosis was based on the urography and the histopathological examination of the material passed with the urine. Renal exeresis was performed in 5 cases. One was treated in a conservative fashion. Also the etiology causes, diagnostic procedure and other therapeutic possibilities were reviewed.

Topics: Adult; Cholesteatoma; Female; Follow-Up Studies; Humans; Keratins; Kidney Diseases; Male; Middle Aged

Cholesteatoma is the growth of keratinizing squamous epithelium in the middle ear. It is associated with severe complications and has a poorly understood etiopathogenesis. Here, we present the results from extensive bioinformatics analyses of the first large-scale proteomic investigation of cholesteatoma. The purpose of this study was to take an unbiased approach to identifying alterations in protein expression and in biological processes, in order to explain the characteristic phenotype of this skin-derived tumor. Five different human tissue types (cholesteatoma, neck of cholesteatoma, tympanic membrane, external auditory canal skin, and middle ear mucosa) were analyzed. More than 2,400 unique proteins were identified using nanoLC-MS/MS based proteomics (data deposited to the ProteomeXchange), and 295 proteins were found to be differentially regulated in cholesteatoma. Validation analyses were performed by SRM mass spectrometry. Proteins found to be up- or down-regulated in cholesteatoma were analyzed using Ingenuity Pathway Analysis and clustered into functional groups, for which activation state and associations to disease processes were predicted. Cholesteatoma contained high levels of pro-inflammatory S100 proteins, such as S100A7A and S100A7. Several proteases, such as ELANE, were up-regulated, whereas extracellular matrix proteins, such as COL18A1 and NID2, were under-represented. This may lead to alterations in integrity and differentiation of the tissue (as suggested by the up-regulation of KRT4 in the cholesteatoma). The presented data on the differential protein composition in cholesteatoma corroborate previous studies, highlight novel protein functionalities involved in the pathogenesis, and identify new areas for targeted research that hold therapeutic potential for the disease.

Topics: Adolescent; Adult; Aged; Child; Cholesteatoma; Computational Biology; Connective Tissue; Down-Regulation; Female; Humans; Keratins; Male; Middle Aged; Proteome; Proteomics; Reproducibility of Results; Up-Regulation; Young Adult

Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

Topics: Animals; Cholesteatoma; Ear, Middle; Epidermis; Epithelial Cells; Epithelium; Gene Expression Regulation; Humans; Immunohistochemistry; Keratins; Mice; Tissue Distribution

S100 proteins were reported to be involved in different biological activities such as transduction of intracellular calcium signalling. It has been reported that each member of the S100 protein family exhibits a distinct tissue-specific pattern of expression. Furthermore, altered S100 protein expression and function correlate with many diseases. The expression of S100A1 was reported to be increased in different tissue with hyperplasia. The external auditory canal cholesteatoma (EACC) is a benign hyperplasia of the auditory meatal skin. However, without treatment, EACC destroys adjacent tissue. Seventeen EACC specimens were collected and investigated immunohistochemically against S100A1. Normal auditory meatal skin served as control. In the EACC, S100A1 showed a more homogeneous staining pattern, positively expressed throughout the epithelial layers. The keratin debris showed no detectable expression of S100A1. In the auditory meatal skin (control), S100A1 was only expressed in the basal layer of the epithelium. We showed that there are different staining patterns in normal auditory meatal skin, middle ear cholesteatoma and external auditory canal cholesteatomas. The immunoreactivity increased with the stage of the disease. Contrary to that reported previously in the middle ear cholesteatomas, the reactivity was strongest in the upper epithelial layers. In our collective, the epithelial matrix of the EACC showed strong reactivity throughout all the layers. Surprisingly, there is no study regarding the connection between growth factors and S100A1. In previous experiments we showed significant increase of growth factors in EACC. This correlates with our new data concerning S100A1. This is the first study to show the different reactivity pattern of S100A1 in the external auditory canal cholesteatoma.

Topics: Adult; Aged; Cholesteatoma; Ear Canal; Ear Diseases; Female; Gene Expression Regulation; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Signal Transduction

Topics: Aged; Aged, 80 and over; Cholesteatoma; Diagnosis, Differential; Ear Canal; Ear Diseases; Epithelium; Female; Humans; Keratins

We implanted keratin and poly(methyl methacrylate) (PMMA) particles to the surface of mouse calvariae to produce a quantitative, localized, inflammatory bone remodeling similar to that seen in cholesteatoma. Both types of particles resulted in increased osteoclast density compared with controls. Osteoclasts infiltrated from marrow and vascular spaces and were active at the periphery of these spaces leading to significant bone remodeling, as demonstrated by the incorporation of bone-labelling fluorophores. Osteoclasts were rarely found on the surface of the calvariae, and mineral apposition rate at the ventral surface was not altered in keratin-implanted animals compared with nonoperated controls. While not useful for the study of the root cause of cholesteatoma, this model will allow the study ofpathologic bone remodeling related to cholesteatoma in a genetically defined animal.

Topics: Animals; Bone and Bones; Bone Diseases; Bone Remodeling; Calcification, Physiologic; Cholesteatoma; Disease Models, Animal; Inflammation; Keratins; Mice; Mice, Inbred C57BL; Osteoclasts; Osteolysis; Peptide Fragments; Skull

Monoclonal antibodies directed against cytokeratin subtypes in cholesteatoma produce growth inhibition of keratinocytes.. Despite elegant surgical procedures for cholesteatoma, residual disease is an important clinical problem. Although gross cholesteatoma removal usually is feasible, microscopic foci of residual keratinocytes may develop into clinically significant disease. This study was designed to evaluate the keratinocyte cytotoxicity of monoclonal antibodies directed against a cytokeratin subtype relatively unique to cholesteatoma.. Keratinocytes and skin fibroblasts were trypsinized, counted, and seeded in multiwell plates. The cells were exposed to mouse monoclonal antibody to cytokeratin 10 at dilutions of 1:10, 1:25, 1:50, 1:100, and 1:200 with six replicates. After 24-, 48-, and 96-hour incubations, cells that had been pulsed with 3H-thymidine were harvested. Cellular DNA was processed for quantification of 3H-thymidine incorporation with a beta scintillation counter. Cells exposed to antibody are reported as percent inhibition relative to controls.. Inhibition ranged from 88.9% for the 1:10 concentration to 26.9% for the 1:200 concentration after 24 hours of incubation. Similar effects were noted at the 48- and 96-hour intervals. Overall, the effect was significantly more pronounced on the keratinocytes than inhibition on skin fibroblasts.. These results suggest that monoclonal antibodies have in vitro activity against keratinocytes. Additional investigation of a possible role for cytokeratin monoclonal antibodies should be pursued with a goal of developing a clinically useful biologic adjunct for cholesteatoma management.

Topics: Animals; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Cell Culture Techniques; Cell Division; Cholesteatoma; Growth Inhibitors; Humans; Keratinocytes; Keratins; Mice; Thymidine; Time Factors

The formation of Cholesteatoma is often accompanied by infection, and is very likely to be influenced by inflammatory mediators. Endotoxin, a strong inflammatory mediator, may play an important role in cholesteatoma pathogenesis. It has been demonstrated in middle ear effusions, and it causes marked reactions in middle ear epithelium and epidermis, both in vivo and in vitro. The effect of endotoxin on a simulation of the advancing front of cholesteatoma was investigated in this study. We developed a co-culture model composed of a simultaneous culture of rat middle ear mucosa and rat meatal epidermis in one culture dish, to which endotoxin was added. During the culture period the addition of endotoxin to the co-culture delayed take-over of the meatal epidermis by the middle ear mucosa, in comparison with control cultures. Morphological changes included the clustering of microvilli in co-cultures exposed to endotoxin. Although these results are preliminary, they suggest that endotoxin disturbs the normal healing process of the middle ear cavity.

Topics: Animals; Antibodies, Monoclonal; Cells, Cultured; Cholesteatoma; Communicable Diseases; Culture Techniques; Desmosomes; Ear, Middle; Endotoxins; Epidermis; Keratins; Microscopy, Electron; Microvilli; Rats

Expression patterns of cytokeratins (CKs) in normal skin, in pars flaccida type cholesteatoma (PFTC), and in pars tensa type cholesteatoma (PTTC) were examined by means of one- and two-dimensional electrophoretic techniques. Both CKs 14 and 5 pair (CKs 14/5) and CKs 10/1 were found in all materials. Neither CKs 16/6 nor 19 was found in the skin. CKs 16/6 and 19 were both found in 3 out of 5 PFTCs, only CKs 16/6 in 1 out of 5 and neither CKs 16/6 nor 19 in 1 out of 5. CKs 16/6 and 19 were both found in 1 out of 3 PTTCs, only CKs 16/6 in 1 out of 3 and neither CKs 16/6 nor 19 in 1 out of 3. There was no significant difference in the CKs expression patterns between PFTC and PTTC. The expression of CKs 16/6 and 19 suggested that their matrix epithelia were hyperproliferative. However, not all of the cholesteatomas were always hyperproliferative. Patterns of the terminal differentiation of CKs 1, 5, 10 and 14 in the PFTC or the PTTC were basically the same as those in the skin. In the cholesteatoma, eack CK gradually diminished in molecular weight in the cornified layer and debris. Desmosomal proteins were abundant in skin but not in cholesteatomas.

Topics: Adult; Child; Cholesteatoma; Culture Techniques; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Immunoblotting; Keratins; Male; Middle Aged; Tympanic Membrane

The accumulation of keratinizing epithelium in the middle ear cavity is a crucial factor in the pathogenesis of cholesteatoma. We hypothesize that keratinocytes from the skin of the ear canal migrate and hyperproliferate in response to inflammation in the middle ear cavity to cause accumulation of keratin debris. In the present study, we investigated the expression of specific cytokeratins (CKs) in the cholesteatoma matrix to determine whether cholesteatoma is a hyperproliferative disease. Cytokeratin expression was examined in cholesteatoma, meatal skin, and tympanic membrane with two monoclonal antibodies, one for both cytokeratins 13 and 16 (antibody K8.12), and another for cytokeratin 13 only (antibody KS-1A3). CK 13 (MW 51 KD) is a marker of differentiation and CK 16 (MW 48 KD) is a marker of hyperproliferation of keratinocytes. The use of immunoblot probes showed that CKs 13 and 16 were present in cholesteatoma. Immunofluorescent staining showed the presence of CK 16 in the suprabasal layer of cholesteatoma, which was located near the external ear canal. CK 13 was localized in the suprabasal layer of meatal skin and tympanic membrane. CK 13 was localized in the basal layer of the cholesteatoma, distal to the external ear canal, but not in the meatal skin and tympanic membrane. Taken together, the present data suggest that cholesteatoma is a hyperproliferative disease and that cholesteatoma expresses CK 16 near the external ear canal and transforms to express CK 13 during growth distally.

Topics: Cholesteatoma; Ear Canal; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Gene Expression; Head and Neck Neoplasms; Humans; Immunoblotting; Keratins; Skin; Sodium Dodecyl Sulfate; Tympanic Membrane

A variety of solutions were tested in vitro to find a suitable solvent which could be used in clinical practice for cholesteatoma debris. Though a little weak as a solvent, a liquid soap composed mainly of plant oil did not cause irritation of the middle ear mucosa, and was thought to be a promising solvent with which to rinse away tenacious debris, especially when used in combination with hydrogen peroxide.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Humans; Hydrogen Peroxide; Keratins; Soaps; Solubility; Solvents; Therapeutic Irrigation

The expression of epithelial markers (cytokeratins, Filaggrin, BerEp4 and EMA), collagen IV and Ki67 was studied immunohistochemically in cholesteatoma and compared with that in epidermis of meatal skin, squamous epithelium of eardrum and simple epithelium of middle ear mucosa. MNF116 (cytokeratin 10, 17, 18) stained the full layer of normal epithelium and all cholesteatoma specimens. CK10 and Filaggrin were expressed in the upper layer of epidermis but more diffusely in cholesteatoma. BerEp4 was found in the basal layer of normal epithelium but was detected in most epithelial cells in cholesteatoma matrix. Variability was observed in EMA and CK14 immunostaining. Collagen IV was localized in the basement membrane of normal epithelium with a continuously staining pattern, an observation also made in the cholesteatomas studied. However, in one of these small areas the basement membrane was not stained with collagen IV. Ki67 was expressed in nuclei of the cells in the basal layer of normal epithelium but extended to epithelial cells in the upper layers of cholesteatoma matrix. The results of the present study indicate that the expression pattern of epithelial markers in cholesteatoma corresponds to that in normal epidermis. The increasing expression of BerEp4 and Ki67 confirms the hyperproliferative nature of cholesteatoma. Whether or not the lack of expression of collagen IV in one of the cholesteatomas reflects a true degradation of the basement membrane needs further investigation in extended materials.

Topics: Cholesteatoma; Collagen; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins

Several factors seem to contribute to the series of events in the pathogenesis of otitis media and cholesteatoma. Endotoxin is likely to be one of these factors, since it has been found in human middle ear effusions and since injection of this substance into the middle ear, in animal experiments, gave rise to prominent reactions. Provoking of epithelial cells in vitro with endotoxin led to distinct cell responses that might be associated with cholesteatoma formation. In this study the effect of endotoxin on serially cultured rat middle ear epithelium, rat meatal epidermis, and human keratinocytes was investigated. Endotoxin strongly stimulated the proliferation of middle ear epithelium and human keratinocytes and inhibited that of meatal epidermis. Furthermore, endotoxin affected the morphology of the three types of tissue. Rat middle ear epithelium revealed epithelial cell tracks with interconnecting bridge-like structures protruding above the culture plane, whereas rat meatal epidermis showed increased terminal differentiation expressing large areas of blister-like structures detaching from the culture dish. Cross-linked envelope analysis of human keratinocytes showed an increased terminal differentiation that was morphologically confirmed but was not confirmed by cytokeratin analysis. The results of this study support the hypothesis that endotoxin may play an important role in the pathogenesis of otitis media and cholesteatoma.

Topics: Animals; Antibodies, Monoclonal; Cell Movement; Cholesteatoma; Culture Techniques; Ear Ossicles; Ear, Middle; Endotoxins; Epidermis; Epithelium; Humans; Keratinocytes; Keratins; Otitis Media; Rats

Immunohistochemical investigations were carried out to further reveal the pattern of cytokeratin (CK) expression in middle ear cholesteatoma. Using chain-specific monoclonal antibodies and the indirect immunoperoxidase technique, 10 out of 19 CK polypeptides were screened in cryoslices of fresh postmortem eardrums and external ear canal specimens. Our data, combined with those published before, indicate an intimate relationship between middle ear cholesteatoma lesions and epidermal tissues in the immediate vicinity. Our CK data do not favor the metaplastic origin of cholesteatoma, because the CK complement of cholesteatoma lesions does not include major and typical CK constituents of the middle ear mucosa.

Topics: Antibodies, Monoclonal; Biomarkers; Cholesteatoma; Ear Canal; Ear Diseases; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Tympanic Membrane

Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear altering its growth properties. This epithelium is believed to have hyperproliferative properties. Keratin 16 is accepted as a molecular marker for hyperproliferative epithelia. Two monoclonal antibodies K8.12 (directed against keratin 13) and KS.1A3 (directed against keratin 13 and 16) were used in an alkaline phosphatase anti-alkaline-phosphatase (APAAP)-technique to compare the expression of both keratin 13 and keratin 16 in normal human skin and aural cholesteatoma. Furthermore, the cytokeratin expression was compared to that of normal skin and palatine tonsil using one-dimensional gel electrophoresis. For both monoclonal antibodies, normal ear skin was stained only in the basal layer. In contrast, in the cholesteatoma samples the immunostaining of the antibody KS-1A3 was done not only in the basal cell layer but also in the suprabasal cells of the stratum spinosum and stratum granulosum. Using gel-electrophoresis, the presence of cytokeratin 16 was demonstrated in the cholesteatoma samples only. These results support the hyperproliferative character of cholesteatoma epithelium.

Topics: Cell Division; Cholesteatoma; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Gene Expression; Humans; Immunoenzyme Techniques; Keratins; Palatine Tonsil; Skin

Immunohistochemical investigations were carried out to determine the pattern of cytokeratin (CK) expression in middle ear cholesteatoma and related epithelia. Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, we examined 10 CK polypeptides for expression. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10, and 14. In addition, basal keratinocytes in the annular region of the pars tensa expressed CK 19 (a simple epithelium marker), while suprabasally the hyperproliferative marker CK 16 was expressed. These data reflect the unusual proliferative nature of this region. The unexpected appearance of CK 16 (known to have a limited distribution in healthy epidermis) clearly relates to its expression in the neighboring deep meatus. The medial simple epithelium of the eardrum revealed mucosal CKs 7, 8, 14, 18, and 19. Acquired cholesteatoma lesions, besides CKs 5, 10, and 14, consistently expressed CK 16 in suprabasal layers. These results constitute the first direct molecular evidence for the hyperproliferative nature of the cholesteatoma matrix. Overall, our CK data suggest that aural cholesteatoma lesions and epidermal tissue in this area are related. However, they do not explain the mechanism(s) by which the eardrum or meatal epithelia might invade the middle ear cavity. Congenital cholesteatomas expressed CKs 5, 10, 14, and 16 equally. These CK data do not support the idea of a metaplastic origin from middle ear mucosa; instead, they suggest activation of an ectodermal rest in the middle ear cavity.

Topics: Adult; Cholesteatoma; Ear Diseases; Ear, External; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Keratins; Tympanic Membrane

The position of a cell in a stratified squamous epithelium correlates with its state of differentiation as well as with the expression of certain cytokeratins. By means of both immunohistochemistry using the APAAP method and high resolution one-dimensional gel electrophoresis, specimens of cholesteatoma epithelium and normal ear skin were investigated whether they contain keratin 16 (K 16) which is known to be a marker of hyperproliferation. It could be shown that K 16 is expressed in all layers of cholesteatoma epithelium. Further to prove this fact gel electrophoresis was used showing a protein band at the localization of keratin 16. Hence, cholesteatoma can be seen as a locally hyperproliferative disease.

Topics: Cell Division; Cholesteatoma; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Epithelium; Humans; Immunoenzyme Techniques; Keratins

Although cholesteatomas are more commonly found in the middle ear and the mastoid, the disease can occur in the external ear canal. All cases of ear canal cholesteatoma treated by the author were reviewed. There were nine ears in seven patients, who had an average age of 62 years. The lesions ranged in size from a few millimeters to extensive mastoid destruction. Smaller lesions can be managed by frequent cleaning as an office procedure. Larger lesions require surgery, either canaloplasty or mastoidectomy. The otolaryngologist should suspect this disease in the elderly. Microscopic examination of the ear with meticulous cleaning of all wax, especially in elderly patients, is most useful in detecting early disease. Frequent applications of mineral oil to the canal should be used in the management of the disease and to prevent recurrence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Audiometry; Bone Diseases; Cerumen; Cholesteatoma; Ear Canal; Ear Diseases; Female; Follow-Up Studies; Granulation Tissue; Humans; Keratins; Male; Mastoid; Middle Aged; Mineral Oil

Cholesteatoma of the middle ear is characterized by the presence of hyperproliferative keratinizing squamous epithelium in the middle ear cavity and destruction of adjacent bone. Interleukin 1 (IL-1) is an autocrine growth factor for normal keratinocytes and is capable of inducing bone degradation. The distribution of two molecular species of IL-1, IL-1 alpha and IL-1 beta, was investigated immunohistochemically in the hyperproliferative epithelium of cholesteatoma, in normal epidermis of the auditory canal and of the retroauricular region, and in nonkeratinizing tonsillar epithelium. In all squamous epithelia examined, IL-1 alpha and IL-1 beta were present in comparable amounts. The IL-1 content of cholesteatoma epithelium was clearly increased in relation to normal skin keratinocytes. All cellular layers of cholesteatoma epithelium stained strongly and uniformly for Il-1 alpha and IL-1 beta, whereas the keratin layer was negative for IL-1. No particularly strong reaction with basal cells was detected. In the connective tissue under the squamous epithelium of cholesteatoma, intensely positive cells were scattered between negative stromal cells. Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-macrophage lineage, stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, and contribute to the enhancement of bone destruction in the presence of cholesteatoma.

Topics: Cholesteatoma; Ear Canal; Ear Diseases; Ear, External; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Interleukin-1; Keratins; Palatine Tonsil

The surgical management of labyrinthine fistulas caused by cholesteatoma remains controversial. Forty cases (41 ears) of labyrinthine fistulas were reviewed. This represented 10% of our total series of cholesteatomas in adults and children (426 ears). Clinical presentation, extent of disease, results of fistula testing and audiometric studies, and radiographic findings were analyzed. A canal wall-down procedure was performed in all but one patient. Generally an attempt was made to completely remove the cholesteatoma, to graft the fistulous area, and to reconstruct the middle ear mechanism in one stage. The matrix was preserved in patients with large fistulas where the involved ear was the only hearing one, when the matrix was adherent to the underlying optic duct, and in selected elderly persons. Long-term followup did not reveal a significant difference in hearing, degree of vertigo, or incidence of recidivism when those patients in whom the matrix was removed were compared with those in whom the matrix was preserved. The importance of recognizing the presence of a labyrinthine fistula preoperatively is stressed, along with the need to be prepared for an unexpected fistula. Operative management is described.

Topics: Adolescent; Adult; Aged; Child; Cholesteatoma; Fistula; Hearing Loss, Conductive; Hearing Loss, Sensorineural; Humans; Keratins; Labyrinth Diseases; Mastoid; Middle Aged; Postoperative Complications; Recurrence; Retrospective Studies; Vertigo

Both the centrifugal keratin dispersion on the pars tensa as well as the centripetal proliferative properties at the inferior annular tympanic region are discussed. There is evidence, histological and clinical, that these features are two distinct and different phenomena which both have clinical implications. While the centrifugal keratin dispersion is a physiological cleaning mechanism, the cytokeratin expression demonstrates the unusual but for years clinically noticed proliferative nature of the lower annular epithelium and provides biochemical evidence for a relationship between this epithelium and cholesteatoma formation.

Topics: Cell Movement; Cholesteatoma; Culture Techniques; Ear Diseases; Epithelial Cells; Humans; Keratins; Rupture; Tympanic Membrane

Monoclonal antibodies with defined specifications for individual cytokeratins were used to stain the epithelia of the external auditory meatus, the middle ear and cholesteatoma. The observed staining indicated that the epithelium of the external auditory meatus has a pattern of keratin expression typical of epidermis in general and the epithelium of the middle ear resembles simple columnar epithelia. The pattern of staining of cholesteatoma closely resembled that of the skin of the external auditory meatus.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Diseases; Ear, External; Ear, Middle; Epithelium; Humans; Keratins; Staining and Labeling; Tympanic Membrane

The immunohistological characteristics of retraction pockets, cholesteatoma matrix and granulomatous tissue were compared in 14 samples from pediatric cholesteatoma. The junction between epidermis and the middle ear mucosa appeared as the most inflammatory area, displaying the characteristics of delayed type hypersensitivity. CD1 + Langerhans cells were observed in all epidermic areas, but expressed class II molecules only in the vicinity of polymorphonuclear infiltrates. Numerous mast cells and IgA producing cells were also observed, suggesting that defenses from the mucosal immune system are summoned and contribute to the pathogenesis of cholesteatoma.

Topics: Adolescent; Antigen-Presenting Cells; Child; Child, Preschool; Cholesteatoma; Ear, Middle; Female; Fluorescent Antibody Technique; Granuloma; Humans; Immunoglobulins; Keratins; Langerhans Cells; Male; Otitis Media; T-Lymphocyte Subsets

The expression of cytokeratins varies with the type of epithelium, the state of differentiation, and pathological conditions. In this study, the differential expression of cytokeratins in external meatal skin and middle ear epithelium was used for a pathogenetic study of cholesteatoma lesions and infection-induced epidermoid formations in the middle ear of the rat. Immunocytochemistry generally revealed an epidermal-type cytokeratin profile in the cholesteatoma matrix, except for the focal expression of nonepidermal cytokeratins at the invasion front. Comparable observations were made in the middle ear of the rat after an infection-induced invasion of epidermal cells from the meatal skin. An infection-induced-cornifying metaplastic lesion of the middle ear epithelium revealed nonepidermal cytokeratin expression. The results of this combined study suggested that the cholesteatoma specimens studied had an epidermal origin. The expression of nonepidermal cytokeratins was considered to result from a state of hyperproliferation rather than from metaplasia.

Topics: Animals; Cholesteatoma; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Eustachian Tube; Humans; Immunoenzyme Techniques; Keratins; Rats; Rats, Inbred Strains

A histochemical study was performed to determine the involvement of epidermal transglutaminase (ETgase) in the keratinization of middle ear cholesteatomatous lesions, and to compare it with its role in the middle ear mucosa and epidermis. In a first assay, we localized the (E)Tgase activity in situ. A second immunohistochemical assay revealed the distribution of the particulate form of ETgase, which is involved in cross-linked envelope formation. A remarkable difference between strongly keratinized epidermal tissues and the cholesteatoma matrix is the frequent observation in the latter of the remnants of (E)Tgase activity in cytosol, even in advanced stages of differentiation. As a consequence, the cell-membrane-associated ETgase activity, and thus the extent of cross-linking within the envelope, is at a lower level than expected. This aspect is reminiscent of the keratinization phenomenon manifested by thin epidermal tissues. In addition, our findings are the first to show that ETgase is a substantial marker of middle ear mucosa.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Transglutaminases

A histochemical study was performed to clarify further the role played by epidermal transglutaminase (ETgase) in the keratinization of aural cholesteatoma. Weakly and strongly keratinized epidermal tissues and healthy middle ear mucosa were included as references. A first assay revealed the distribution of non-specified acyl donor substrates. In a second assay, the topography of involucrin was assessed immunohistochemically. In both epidermal and cholesteatoma matrix tissues, the presence of acyl donors was not restricted to the sites of (E)Tgase activity, but was almost uniformly extended throughout living layers. In reference tissues, residual acyl donors were poorly detected in horny layers, while they were more abundant in the stratum corneum of the cholesteatomas studied. The presence of involucrin along the cell membrane was observed at varying distances throughout the spinous and granular layers, depending upon the epidermal and matrix configurations. In thick epithelia, involucrin rapidly became concentrated at the cell periphery (in spinous keratinocytes), while in thin epithelia it was usually associated with cell flattening. This latter staining profile was observed more frequently in cholesteatomatous tissues. In addition, we regularly noticed an immediately suprabasal accumulation of involucrin, suggesting a locally hyperproliferative state of the matrix. An insufficient availability of acyl donors, especially involucrin, could not be used to explain the defective ETgase-mediated cross-linking of cholesteatoma cell membranes during terminal stages of differentiation. The present investigation may be the first to demonstrate the presence of involucrin in middle ear mucosa.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Protein Precursors; Transglutaminases

An indirect immunofluorescent method with monoclonal anti-cytokeratin antibodies was used to localize various cytokeratins in human middle ear cholesteatoma. The 50 K/58 K and 56.5 K/65-67 K paired cytokeratins are markers of skin type and were found in the specimens of human middle ear cholesteatomas studied. In contrast, the 40 K and 45 K cytokeratins (markers of simple epithelia), the 48 K cytokeratin (marker of hyperproliferative epidermal disease) and the 51 K cytokeratin (marker of internal organ epithelia) were absent in human middle ear cholesteatoma. These findings indicate that the pattern of cytokeratins in human middle ear cholesteatoma is similar to that of skin but is different from those of simple epithelium, internal organ epithelia, and hyperproliferative epidermal disease. These findings also support the skin type epithelial origin of cholesteatoma and strongly favor the migration theory in the genesis of cholesteatomas.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Diseases; Ear, Middle; Epithelium; Fluorescent Antibody Technique; Humans; Keratins

Specimens of cholesteatoma matrix, meatal epidermis, and middle ear epithelium were removed during surgery, and immunohistochemical techniques were used to investigate cytokeratin expression. The use of five chain-specific anticytokeratin monoclonal antibodies and one broad specific anticytokeratin monoclonal antibody showed the divergent behavior of middle ear epithelium compared with the cytokeratin expression of the other two types of epithelium. Middle ear epithelium was characterized by the presence of cytokeratins 4, 8, 18, and 19, whereas in both cholesteatoma and meatal epidermis cytokeratin 10 predominated. Furthermore, cholesteatoma showed an infrequent focal presence of cytokeratins 4, 18, and 19. The similarity between cholesteatoma and meatal epidermis with respect to morphology, and the presence of cytokeratin 10 support an epidermal origin of cholesteatoma. However, a metaplastic origin cannot be excluded, because of the infrequent occurrence of a small amount of cytokeratins 4, 18, and 19 in cholesteatoma matrix that was not found in meatal epidermis but was a component of the cytokeratin pattern of middle ear epithelium.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Canal; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Keratins

The purpose of this study was to determine whether anatomic differences in the tympanic membranes of various species could explain differences in the propensity to form aural cholesteatomas and retraction pockets. Tympanic membranes from humans, dogs, cats, rabbits, guinea pigs, rats, gerbils, and mice were examined histologically. The pars flaccida and pars tensa varied greatly among the species studied. The guinea pig's pars flaccida was very small and had a thin lamina propria. In contrast, the lamina propria of the rabbit and cat pars flaccida were thick. The amount of collagen, elastin, mast cells, and macrophages varied widely. The human and gerbilline tympanic membranes were anatomically dissimilar; for example, the human pars flaccida and pars tensa contained more and denser collagen than did those of the gerbil. The presence of macrophages or mast cells did not correlate with the propensity to develop cholesteatomas. Therefore, anatomic differences among these species do not explain why some develop aural cholesteatomas and others do not.

Topics: Animals; Cats; Cholesteatoma; Collagen; Cricetinae; Dogs; Elastin; Gerbillinae; Humans; Keratins; Mast Cells; Mice; Rabbits; Rats; Species Specificity; Tympanic Membrane

Cytokeratin expression was studied in human middle ear cholesteatoma lesions, using a variety of immunohistological techniques and a wide range of polyclonal antisera and monoclonal antibodies against cytokeratin (CK) subgroups or individual CK polypeptides. The expression of the other cytoskeletal proteins, vimentin and desmin, was also investigated. Middle ear mucosa and epidermal tissues were used as reference tissues. Our investigations also included epithelial structures present in the cholesteatoma perimatrix and in dermal tissues. The results indicate that, compared with epidermal tissues, the expression profile of CKs in cholesteatoma matrix is representative of a hyperproliferative disease. Evaluating the presence of a marker of terminal keratinization - the 56.5 kD acidic CK n degrees 10 - we found supportive evidence of a pronounced retardation of its expression, which did not parallel histological differentiation. In epidermal tissues, the first prickle cell layers are CK10 positive whereas in many cholesteatomas this finding was observed near the stratum granulosum only. Probing the early stages of keratinization - the 58 kD basic CK n degrees 5 and the 50 kD acidic CK n degrees 14 - we regularly observed an extended staining area in the cholesteatoma matrix. In epidermal reference tissues, only the basal and nearest suprabasal layers were convincingly labeled. As a rule, non-epidermal CKs did not belong to the cholesteatoma CK set. However, exceptions to that rule were noticed as a focal or more extended expression of one or more non-epidermal CKs in about half of the cases. Together with the extended CK5 topography, this is further evidence that CK expression is seriously affected by the diseased state. CK expression in the perimatrix is limited to mucous glands, either normal, atrophic or hyperplastic. CKs n degrees 4, 5, 7, 14, 18 and 19, also displayed by middle ear mucosa, were consistently observed. Where ductal arrangements were present, CK10 was also detected, in analogy with the CK10 registration in ductal portions of mucous glands in the external ear canal skin. The absence of CK8 in mucous glands of the perimatrix, however, strongly differentiates these structures from the mucous gland acini and ducti in the external ear canal, where CK8 is systematically expressed. Vimentin staining was restricted to dendritic cells of the matrix (Langerhans cells) and to perimatrix fibroblasts, blood cells and vascular endothelium. Coexpression

Topics: Animals; Antibodies, Monoclonal; Cattle; Cholesteatoma; Ear Neoplasms; Ear, Middle; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Mucous Membrane; Rabbits; Skin; Vimentin

The accumulation of desquamated keratinizing squamous epithelial cells appears to be a crucial factor in the pathogenesis of middle ear cholesteatomas. The accumulation of keratin debris is due to the proliferation and the terminal differentiation of basal keratinocytes. Since cholesteatomas are usually associated with inflammatory reactions in the middle ear cavity, we examined the effects of a granulation tissue conditioned medium on the terminal differentiation of basal keratinocytes in vitro. This conditioned medium stimulated the terminal differentiation of basal keratinocytes by showing: (a) increased incorporation of 3H-leucine into cell envelopes; (b) an increased number of SDS-insoluble cell envelopes; and (c) increased transglutaminase activity (as a marker for terminal cellular differentiation). Our present studies further suggest that inflammatory granulation tissue plays an important role in the clinical growth and development of the cholesteatoma.

Topics: Animals; Cell Differentiation; Cholesteatoma; Culture Media; Ear Diseases; Epidermis; Granulation Tissue; Keratins; Rats; Rats, Inbred Lew

Amniotic fluid cellular content (AFCC), especially keratinized, non-nucleated squamous epithelial cells and lanugo hair, have been detected in the fetal and neonatal ear. We wished to evaluate the incidence, amount and histological findings of AFCC in the neonatal and early infant period. Temporal bones (n = 63) from children aged 10 min to 70 days were examined. AFCC was discovered in 39 of 43 bones in neonates. In children of 31-70 days of age, AFCC was present in 11 of 20 bones. A measurement of the amount of AFCC was performed; the maximum was 11.47 mm3 with a mean of 2.40 mm3. Histological findings varied from the mere presence of AFCC to the formation of epithelialized granulation tissue. This granulation tissue was found in 19 of the bones. Theoretical clinical implications are considered for middle ear adhesions, otitis media and cholesteatoma.

Topics: Amniotic Fluid; Child, Preschool; Cholesteatoma; Ear Diseases; Ear, Middle; Epidermal Cells; Epithelium; Foreign-Body Reaction; Granulation Tissue; Hair; Humans; Infant; Infant, Newborn; Keratins; Otitis Media; Skin; Temporal Bone; Tissue Adhesions

Since the rate of epidermal basal cell proliferation appears to be a crucial factor in the development of acquired cholesteatoma, we studied the effect of prostaglandin E2 (PGE2) and endotoxin on the growth of keratinocytes. PGE2 and endotoxins are inflammatory mediators in chronic otitis media. Various concentrations of endotoxin and PGE2 were added to keratinocytes derived from newborn rats. The synthesis of DNA was then studied by incorporation of 3H-thymidine into the keratinocytes. We found that either endotoxin or PGE2 alone inhibited DNA synthesis by keratinocytes, while endotoxin (10 micrograms/ml) and PGE2 (10 ng/ml) together stimulated DNA synthesis by keratinocytes. These findings suggest that inflammatory mediators, such as endotoxin plus PGE2, in chronic otitis media stimulate the growth of epidermal basal cells of cholesteatoma.

Topics: Animals; Bone Resorption; Cell Differentiation; Cell Division; Cholesteatoma; Dinoprostone; Drug Synergism; Endotoxins; Epidermal Cells; Keratins; Prostaglandins E; Rats; Rats, Inbred Lew

Keratin debris is a constant feature in middle-ear cholesteatoma. Keratin prepared from rat skin induced a foreign-body granuloma in the subcutaneous space in the rat. In vitro this granuloma produced high levels of bone-resorbing factors: prostaglandin E2, osteoclast-activating factor, and leucine aminopeptidase. In the in vivo study, keratin-induced granuloma in the rat middle ear caused partial resorption of the cochlear wall. Macrophages, fibroblasts, and osteoclastlike cells were found at bone-resorption areas. These cells appeared to be responsible for bone resorption through production of prostaglandin E2, osteoclast-activating factor, and proteases.

Topics: Animals; Bone Resorption; Carrageenan; Cholesteatoma; Dinoprostone; In Vitro Techniques; Keratins; Leucyl Aminopeptidase; Lymphokines; Male; Otitis Media; Prostaglandins E; Rats

The aim of this study was to culture keratinocytes from migratory skin and from cholesteatomatous matrix. At operation, cholesteatomatous matrix, normal drumhead and non-migratory stratifying skin from the extrameatal incision were obtained. Successful cultures of keratinocytes were produced in 4 out of 5 attempts. The cholesteatomatous keratinocytes produced slower growing colonies with an abnormal pattern of keratinization, whereas the drumhead produced rapidly growing colonies with a more regular pattern of keratinization, similar to those obtained from a vertically stratifying epidermis. This method may offer new fields of study in the investigation of cholesteatoma.

Topics: Adolescent; Adult; Child; Cholesteatoma; Culture Techniques; Ear Neoplasms; Ear, Middle; Humans; Keratins

Cholesteatoma of the urinary tract is a rare condition which can be diagnosed radiographically. The radiographic findings of stringy intraluminal defects or nodules that may lightly calcify or coalesce to form a discrete mass in association with calculi and/or obstruction are characteristic. A history of chronic urinary tract infection, renal colic, and desquamated epithelial cells in the urine further support the diagnosis.

Topics: Adult; Aged; Cholesteatoma; Colic; Female; Humans; Keratins; Kidney Diseases; Kidney Pelvis; Male; Middle Aged; Nephrectomy; Ureter; Urinary Tract Infections; Urography; Urologic Diseases

Topics: Animals; Chickens; Cholesteatoma; Ear Diseases; Ear, Middle; Germ Cells; Humans; Keratins; Mucous Membrane; Phenotype; Skin; Skin Physiological Phenomena; Vitamin A

Topics: Acetylcysteine; Acid Phosphatase; Alkaline Phosphatase; Cholesteatoma; Ear Diseases; Humans; Keratins; Microbial Collagenase

For the extraction of soft keratins from bovine snout or human epidermis the best results were obtained with a detergent (sodium dodecyl sulphate, SDS) or hydrogen bond breaking agent (urea) in a reducing medium (2-mercaptoethanol, 2-ME). N-acetylcysteine was a little less effective. Keratins from both sources gave typical sets of protein bands with molecular weights between 40.000 and 70.000 daltons. Upon electrofocusing special precautions had to be taken to avoid reoxidation and reaggregation of protein subunits. Keratins from aural cholesteatomas were obtained by extraction with SDA and 2-ME, with N-acetylcysteine alone and to a lesser extent with urea and 2-ME. The pattern of these keratins on SDS-gel is less complicated than that obtained from human skin or bovine snout. Histophotometric results argue for a clear analogy between the nuclear DNA metabolism in normal skin epidermis and cholesteatoma matrix. The only differences of potential relevance are the much wider range of the nuclear DNA amount in cholesteatoma stratum basale cells compared with basal cells in normal epidermis, and the higher persistence of nuclear DNA in cholesteatoma stratum granulosum, indicating postponement of keratinocyte terminal differentiation.

Topics: Animals; Cattle; Cholesteatoma; DNA; Ear Diseases; Epithelium; Humans; Keratins; Nose; Proteins

An attic cholesteatoma is defined as an epidermoid cyst found in the attic. This is differentiated from an infected retraction pocket of the pars tensa or a retraction pocket cholesteatoma. Stratified squamous epithelium may also be present in the middle ear as other clinical or pathological entities, such as metaplastic islands of the mucosa in chronic ears with central perforations. Histological examination of 22 temporal bones with attic cholesteatomas has shown them to reside mainly medial to the ossicular chain. This explains the difficulty they have in self-cleansing, as well as the ensuing secondary infection. When a similar process occurs lateral to the ossicles, a self-cleansing nature's atticotomy may be formed. The aetiology of an attic epidermoid cyst, i.e., an attic cholesteatoma, is usually considered to be an invasive retraction from the external ear. However, it is difficult to accept invasion of external canal skin into the upper medial attic. This is especially so in the face of such biological phenomena as epithelial contact inhibition, or the invariable outward migration of stratified squamous epithelium from the edges of retraction pockets as well as from cholesteatoma perforations. Also, large cholesteatomas usually present themselves from the "beginning" simultaneously with their perforations; no documentation of an evolving process from a pre-existing perforation exists at present. Marginal perforations, which have later evolved into attic cholesteatomas have so far not been documented. On the other hand, retraction pockets of the pars tensa or pars flaccida associated with some middle ear negative pressure do occur, however, it is yet to be shown that such retractions can reach the medial part of the ossicular chain and form epidermoid-like cysts there. Therefore, the possibility that an attic cholesteatoma often arises primarily in the attic and presents itself secondarily in the external canal as a "perforated" epidermoid cyst, is to be considered. The possibility that a congenital rest is responsible for such an epidermoid cyst has often been put forward, but evidence that such rests actually exist has not yet been presented. The frequency with which cholesteatoma sacs found in the attic show mucosal cells as part of their lining, suggests a metaplastic phenomenon. This means that the epithelial cells of the middle ear lining may have changed from mucosal into keratinizing cells (or even vice versa). Metaplastic changes of muco

Topics: Cholesteatoma; Ear Diseases; Epidermal Cyst; Epithelium; Eustachian Tube; Humans; Keratins; Metaplasia; Mucus; Temporal Bone; Tympanic Membrane

In a collection of 1,100 operated ears, 426 of which had cholesteatoma and 674 had not, the various defects of the ossicular chain are described and related to the nature of the disease and the site of perforation. The analysis showed marked differences between the various diseases and in the frequency of the individual ossicular defects or combinations of defects. Defects of the head of the malleus and of the body of the incus were found exclusively in chiolesteatomas, most often those affecting the attic. Isolated defects of the malleus handle were most common in cholesteatoma of the parts tensa and in total perforations. Defects of the long process of the incus occurred in 74--88 per cent of cholesteatomatous diseases, defects of the stapedial arch in 47 per cent of ears with sinus cholesteatoma. In granulating otitis without cholesteatoma and in sequelae to otitis there was less ossicular pathology, and 57 per cent of these ears had an intact ossicular chain. Total or posterior perforations were associated with pathology of the ossicles more often than inferior or anterior perforations. All cases with destruction of the body of the incus and the head of the malleus showed squamous epithelium in close relation to the ossicular defect, indicating a marked--presumably enzymatic--influence by the squamous epithelium upon the bone resorption.

Topics: Bone Resorption; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Ear, Middle; Epithelium; Humans; Keratins

Two patients who had undergone radical mastoid surgery developed an isolated focus of cholesteatoma embedded in the sternomastoid muscle just below the mastoid tip. In one instance the etiology was felt to be iatrogenic implantation of squamous epithelium. In the second, unrecognized extension from the mastoid tip probably occurred. The purpose of this paper is to describe and discuss in detail the clinical and pathological features of these two cases.

Topics: Adolescent; Aged; Cholesteatoma; Connective Tissue; Ear Diseases; Epithelium; Female; Humans; Keratins; Male; Mastoid

The structure of middle ear cholesteatoma obtained at surgical interventions in 12 patients was investigated by light and electron microscopy. Keratinizing squamous epithelium with underlying granulomatous, partly necrotic tissue showing signs of an acute or chronic inflammatory reaction was observed. Cholesterol clefts were only observed in two specimens in which a chronic hemorrhage was present. It is proposed that a cholesteatoma starts by immigration of epidermal tissue from the tympanic membrane. Destruction of the middle ear components and of the neighboring osseous walls results from invasion of squamous epithelium, underlying necrotizing connective tissue, and keratin.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Epithelial Cells; Epithelium; Humans; Keratins

Topics: Angiography; Cholesteatoma; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Kidney Diseases; Kidney Pelvis; Microscopy, Electron; Middle Aged

Topics: Acid Phosphatase; Biopsy; Cholesteatoma; Ear, Middle; Epithelial Cells; Epithelium; Histocytochemistry; Humans; Keratins; Nucleotidases; Phospholipids; Staining and Labeling

Topics: Adult; Aged; Autopsy; Child; Cholesteatoma; Chronic Disease; Connective Tissue; Ear, Middle; Epithelial Cells; Epithelium; Granulation Tissue; Humans; Hyperplasia; Hypertrophy; Keratins; Male; Metaplasia; Microtomy; Middle Aged; Mucous Membrane; Otitis Media; Staining and Labeling; Temporal Bone; Tympanic Membrane

Topics: Alkaline Phosphatase; Cholesteatoma; Cysteine; Ear Diseases; Epithelium; Glycerophosphates; Histocytochemistry; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iodoacetates; Keratins; Phosphatidylcholines; Skin Diseases; Sulfhydryl Compounds

Topics: Bone and Bones; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Epithelium; Granulation Tissue; Humans; Keratins; Mucus; Otitis Media

Topics: Adult; Aged; Child; Cholesteatoma; Diagnosis, Differential; Female; Humans; Keratins; Kidney Diseases; Kidney Pelvis; Male; Metaplasia; Middle Aged; Nephrectomy; Radiography; Tuberculosis, Renal; Urinary Tract Infections

Topics: Cholesteatoma; Cholinesterases; Ear Canal; Electrophoresis; Epithelial Cells; Epithelium; Esterases; Globulins; Granulation Tissue; Histocytochemistry; Humans; Keratins; Methods; Oxidoreductases

Topics: Cholesteatoma; Humans; Keratins; Otitis Media; Surgical Procedures, Operative