Stimulation of epithelial healing in chronic postoperative otorrhea using lyophilized cultured keratinocyte lysates.

OBJECTIVE: After tympanoplasty, despite a closed tympanic graft, some patients continue to have persistent otorrhea due to insufficient epithelial healing and granulation tissue formation in the depths of the outer ear canal. When all medical therapies fail, many otologists undertake revision surgery, usually with free skin grafting. To avoid surgery, the authors sought to improve this condition with a lysate of lyophilized cultured allogeneic keratinocytes. STUDY DESIGN AND PATIENTS: In this prospective pilot study, lyophilized cultured allogeneic keratinocyte lysates have been administered in 27 patients. These patients had uncontrollable otorrhea that resisted medical (topical) therapy for at least 6 months. MAIN OUTCOME MEASURE: The criterion of success was a complete epithelialization and cessation of otorrhea. RESULTS: After an average of 2 applications, cessation of otorrhea was achieved in 20 cases (74%). Three patients (11%) relapsed after 3 months. The other ears (63%) still were dry at the 1-year final evaluation. CONCLUSIONS: These results are similar to those obtained after application of sheets of viable cultured keratinocytes of autologous as well as of allogeneic origin. Because the soluble lysate can be incorporated into ototopical drops, the lysate technique is more "user-friendly" and can be applicable in any outpatient clinic. Because keratinocytes contain many growth factors (e.g., epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor), the authors speculate that the release of those intracellular growth factors is responsible for the observed therapeutic effect. This form of therapy by its combination of several growth factors might be considered a more physiologic method than the, also still experimental, growth factor therapy in which high doses of only single growth factor are used.

Tympanic membrane perforations.

The recent literature on the healing of tympanic membrane perforations is reviewed. Research on the migratory phenomena, epithelial migration and keratin dispersion on top of the tympanic membrane, is discussed. The etiology and pathogenesis of tympanic membrane perforations is then briefly described. The literature on the healing process of tympanic membrane on animal experiments as well as observations in humans is amply discussed. Finally different non invasive and or office procedures for tympanic membrane repair are reported.

Myringitis granulosa.

Myringitis granulosa is a rare, localized, chronic inflammation of the lateral surface of the tympanic membrane, characterized by the development and persistence of granulation tissue over the involved area. The clinical and pathologic features of the disease are described, different etiopathogenic possibilities proposed, the literature reviewed and a strategy for treatment presented.

Tympanic grafting materials.

The advantages and disadvantages of different tympanic grafting materials are reviewed and discussed. Temporalis fascia and perichondrium autografts remain the most popular grafting material. For special cases, particular for total ossicular replacement problems, tympanic allografts may be useful. Formaldehyde cross-linked fascia grafts have their advocates. Artificial membranes are still in an experimental phase.

Mastoiditis caused by atypical mycobacteria.

Three case reports of mastoiditis caused by atypical mycobacteria are discussed and a review of the world literature is given. Our aim is to focus the attention of the ENT specialist and the pediatrician on these pathological agents in unilateral recurrent otitis media. The case reports illustrate the importance of histologic and microbiologic examination. Difficulties in the differential diagnosis are mentioned. The therapy is slightly different from lymphadenitis caused by atypical mycobacteria because for mastoiditis we prefer the combination of surgery with medical treatment.

The proliferative capacity of the keratinizing annular epithelium.

Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, the expression of 10 CK polypeptides was investigated. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10 and 14. In addition, basal keratinocytes in the annular region, both tympanic and deep meatal, expressed CK19 (a simple epithelium marker). Suprabasally the hyperproliferative marker CK16 (known to have a limited distribution in healthy epidermis) was expressed in the same area. These data reflect the unusually proliferative nature of this transitional area.

Immunohistochemical analysis of the cytokeratin expression in middle ear cholesteatoma and related epithelial tissues.

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.

A hairy polyp of the middle ear and mastoid cavity.

A case of a 'hairy polyp', a dermoid tumor of the middle ear and the mastoid cavity is described, which is very unusual location. The radiological, surgical and histological features are discussed. Comment is made on the differentiation between dermoid cysts and teratomas and on the scarcity of both tumors in the area of the temporal bone.

The keratinizing tympanic epithelium: an enigma.

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.

A scanning electron-microscopic study of different tympanic grafts.

The surface architecture of dried temporalis fascia autografts and preserved tympanic allografts was investigated by scanning electronmicroscopy. During the storage in formaldehyde-cialit solutions the outer epithelial as well as the inner mucosal layer of tympanic allografts are progressively detached, and finally the lamina propria with outer radial and inner circular fiber arrangement remains. Due to dehydration phenomena irregular "crater-like" defects, surrounded by an amorphous structure, appear in dried fascia autografts. While a real lamina propria graft may induce migration and differentiation of the host's canal wall epithelium into a specific tympanic epithelium, one may imagine epithelial spreading toward the middle ear along the observed defects in dried fascia grafts. This latter observation gives new evidence for the immigration cholesteatoma theory.

A scanning electron microscope study of preserved allograft tympanic membranes: a comparison with autogenous grafts, xenografts and the normal eardrum.

Scanning electron microscopy was used to investigate the surface architecture of the human tympanic membrane. The morphology of the eardrum was compared with the surface structures of preserved tympanic membranes (allografts), fresh air-dried temporalis fascia and preserved calf jugular veins (xenografts). The role of the physical structure and the composition of the extracellular matrix in the regeneration of a tympanic graft is discussed.

An elastic force-length relation for tympanic membrane implants--a preliminary report.

An elastic force-length relation has been recorded for tympanic membrane implants. A model based on the fibre structure of these materials was used to obtain a value for their elastic modulus for tympanic membrane.

A comparative experimental study on nerve repair.

In order to overcome the disadvantages of the classic epi- or perineural nerve suture techniques, attempts have been made to secure nerve endings by a variety of measures, as exemplified by the use of artificial and biological glues. The use of a fibrinogen-thrombin adhesive to seal nerve endings is an easy, time-saving method at surgery and provides excellent coaptation of the severed nerve fascicles with minimal iatrogenic trauma. However, the problem remains of excessive connective tissue proliferation at the junction site or of premature loss of tensile strength before proper nerve healing occurs. The combination of the biological glue with the tubulization technique, associated with a fascicular and/or interfascicular nerve junction, may overcome the disadvantages associated with previous nerve repairs.

[Seromucous otitis and atopic allergy]. / L'otite séro-muqueuse et l'allergie atopique.

The various recent studies conducted are reviewed with the aim of establishing or refuting the hypothesis of a relation between immediate type I allergic reactions and seromucous otitis. Critical analysis of the different publications available is completed by an analysis of a personal series of 58 examinations of serum and secretory IgE levels in children 6 months to 11 years with seromucous otitis. Findings fail to support the hypothesis of type I allergy as a major, primary etiologic factor in seromucous otitis even though this affection can appear as a complication of an allergic diathesis.

Tympanic grafts. An ultrastructural study.

Scanning electron microscopy (SEM) was used to investigate the surface architecture of human tympanic membranes. The morphology of the normal eardrum was compared with the surface structure of preserved tympanic membrane (allograft), fresh air-dried fascia temporalis and preserved calf jugular vein (xenograft). The role of the physical structure and composition of the extra-cellular matrix in the restoration of a tympanic graft is discussed.

Atopic allergy and otitis media with effusion.

To investigate the possible role of type 1 allergy in OME, the immunoglobulin E (IgE) content was determined in 58 middle ear effusions and matched sera, obtained from children with otitis media with effusion (OME). The IgE levels were assayed for IgE by the Phadebas paper radio immunosorbent test (PRIST). Eight cases (14%) showed elevated serum IgE levels, such that an atopic disorder was very likely. However, in nearly all cases the effusion/serum ratio (E/S) was less than one, showing a higher IgE level in the serum than in the effusion. A modified PAP technique for determining surface IgE on mast cells is presented. Positive results were obtained on nasal mucosa specimens in atopic patients with OME but further research on middle ear mucosa in OME is needed. Our results fail to support the concept of type 1 allergy as a major causative factor in OME.

[Nerve anastomoses. Sutures or fibrinogenic glue? Preliminary results]. / Anastomoses nerveuses. Sutures ou colle de fibrinogène? Résultats préliminaires.

A comparative animal experiment was set up between two nerve anastomosis techniques, one by sealing nerve ends with a fibrinogen-thrombine glue and the other by classical perineural suturing. It was concluded that glueing nerve ends, from the surgical-technical point of view is a better method than suturing. It is an easy, time-sparing method which allows excellent coaptation of the severed nerves with minimal iatrogenic trauma. On the long run however some questions remain. There is the problem of induced fibrosis by using high doses of aprotinine and factor XIII at the site of the nerve junctions and on the other hand the influence of fibrinolysis in traumatized tissues, with early decrease of tensile strength at the junctions before nerve healing. So glued nerve ends should be completely free of tension, protected against secondary shearing forces, and also immobilization of the region is required.