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To document polyp formation in the sinus mucosa, the authors of this study subjected New Zealand white rabbits to different modes of manipulation intended to induce inflammation of the maxillary sinus. These manipulations included a combination of bacterial infection and mechanical trauma, the deposition of agarose into the sinus cavity, and the deposition of N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, into the sinus cavity. A majority of animals developed polyps, which were examined by light and electron microscopy. Polyp formation appears to involve epithelial disruption and the migration of immature branching epithelium. While part of the migrating epithelium eventually covers the mucosal defect, other branches spread into the underlying connective tissue, where intraepithelial microcavities with a differentiated, ciliated lining are formed. Fusing cavities separate the developing polyp body from the adjacent mucosa. With the described method, mucosal polyps can be induced with high reproducibility. [ABSTRACT FROM AUTHOR]

Objective: The study evaluated the possible differences in the repair of cricoid cartilage defects treated with recombinant human BMP-2 in young and adult rabbits., Methods: A cricoid defect rabbit model was used. Thirty rabbits were randomly divided into eight groups. Two groups of young rabbits and two groups of adult rabbits were treated with rhBMP-2 delivered on an absorbable collagen sponge, while the other two groups of young rabbits and two groups of adult rabbits were used as controls. The rabbits were killed at 1 week or 4 weeks after surgery. A histomorphometric analysis and an evaluation of the expression of collagen types I, II, and X, and proliferating cell nuclear antigen as well as a study of distribution of calcified matrix, were performed., Results: rhBMP-2 induced a marked chondrogenesis in both experimental age groups. However, in young rabbits the newly formed cartilage appeared more elongate, and the length of perichondrium involved was greater. The host cricoid cartilage of adult rabbits was calcified in large areas and displayed a strong matrix expression of collagen type X as well as collagen type I in the perichondrium, compared to the cricoid of young rabbits. In spite of these differences no immunohistochemical differences were found in the newly formed cartilage of both age groups treated with rhBMP-2. The cricoid cartilage defect was filled with new bone at 4 weeks in both age groups treated with rhBMP-2. New bone tissue had a well-defined trabecular structure., Conclusions: rhBMP-2 triggers appositional cartilage growth from the cricoid perichondrium of young rabbits more easily than from that of adult rabbits. The new bone induced by rhBMP-2 showed a similar immunohistochemical and morphological pattern in both age groups of rabbits.

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.

Objective: Bone morphogenetic protein-2 offers potential benefits for cartilage regeneration. We investigated the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the regeneration of laryngeal cartilage and respiratory epithelium in a rabbit model., Material and Methods: We used a cricoid defect rabbit model. Twenty-four rabbits were randomly divided into four equal groups. Two groups were treated with 5 microg of rhBMP-2 delivered on an absorbable collagen sponge and the other two groups were used as controls. One group of treated rabbits and one group of control rabbits were euthanized 1 week after surgery, while the others were euthanized 4 weeks after surgery. The healing pattern of the laryngeal wound was evaluated by means of histomorphometry., Results: Regeneration of both the epithelial layer and cartilage was significantly better in rabbits treated with rhBMP-2. Four weeks after surgery, the cricoid cartilage defect was completely repaired by new cartilage and new bone in rabbits treated with rhBMP-2. Furthermore, the lining respiratory epithelium healed more rapidly in treated rabbits., Conclusion: rhBMP-2, delivered via an absorbable collagen sponge, induces complete regeneration and repair of rabbit cricoid cartilage defects. It also induces faster relining and regeneration of airway epithelium than in control rabbits.

We examined the structural characteristics of repair tissue induced by recombinant human bone morphogenetic protein-2 in a rabbit model of laryngotracheal reconstruction. Twenty-four New Zealand White rabbits were randomly divided into four groups of six rabbits. Two groups were treated with recombinant human bone morphogenetic protein-2 delivered on an absorbable collagen sponge, while two groups were used as controls. Rabbits were euthanized at 1 and 4 weeks after surgery. The larynx was removed, fixed, and sectioned. The sections were stained with hematoxylin-eosin, safranine O/fast green, and immunostained with an antibody for tissue inhibitor of metalloproteinases-1. In rabbits treated with bone morphogenetic protein-2, the defects were filled with new cartilage and bone at 4 weeks after surgery. There were no discontinuities or gaps at the margins of the cartilage defects. Proteoglycans were synthesized in new cartilage in rabbits treated with bone morphogenetic protein-2, and were present 4 weeks after surgery. The general aspects of the vascular pattern and the pattern of tissue inhibitor of metalloproteinases-1 expression were similar in control and treated rabbits, both 1 week and 4 weeks after surgery. The repair tissue induced by recombinant human bone morphogenetic protein-2 consisted of new cartilage and bone perfectly integrated with host tissue at the site of the cricoid cartilage defects. This new cartilage was able to mature and produce proteoglycans.

In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels - a mechanism distinct from mast cell degranulation.

Lectin expression in both normal and inflamed sinus mucosa in rabbit was investigated histochemically. A different staining pattern was observed in the inflamed mucosa, i.e. the degree of staining reactivity with Canavalia ensiformis (ConA) decreased, whereas staining with Ulex europaeus agglutinin-I (UEA-I), Arachis hypoga (PNA) with neuraminidase pretreatment and Triticum vulgaris (WGA) intensified, indicating an enhanced fucosylation as well as sialylation. Goblet cells were stained with UEA-I, WGA, PNA and PNA with neuraminidase pretreatment, but scarcely with ConA. Positive PNA staining of basal cells and epithelial secretory granules was observed in the inflamed mucosa, especially close to areas where goblet cell development was prolific. It was therefore assumed that basal cells can differentiate into goblet cells-through epithelial secretory cells accompanied by sialylation and/or sulphonation of their mucins. It is concluded that the changes in glycoconjugate expression as well as goblet cell development in the inflamed mucosa are of importance for both local host resistance and defence mechanisms against microorganisms during the early stages of the inflammatory process.

To evaluate the pattern of goblet cell differentiation in sinus mucosa in response to external stimuli, New Zealand White rabbits were subjected to either experimental sinusitis or topical capsalcin application. Sinus mucosa was examined by light microscopy after serial sectioning, whole-mount preparation or immunohistochemistry. The mucosa was also examined by electron microscopy after perfusion fixation or high-pressure freezing. While goblet cells were normally very scarce in the healthy rabbit maxillary sinus mucosa, such cells were frequent after experimental sinusitis or topical capsaicin application. The process of goblet cell differentiation seems to follow a sequential path where serous secretory cells start to produce an increasing amount of mucous granules which appear electron lucent after conventional fixation. Parallel to this shift in secretion production, the cell assumes a bulging appearance after conventional fixation. It is concluded that newly formed goblet cells are recruited from intermediate secretory cell stages rather than from ciliated cells.

The effect of airway infection on neurogenic inflammation is not known. The present study examines the effect of Mycoplasma pulmonis infection on the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the trigeminal ganglion and in the mucosa of the nose and trachea in rats. We compared germ-free (GF), conventionally raised (CV) and specific pathogen-free (SPF) rats. The concentrations of SP and CGRP in the nasal mucosa were assessed with immunohistochemistry, and their prohormonal transcripts in the trigeminal ganglion were assessed with Northern blot. Mucosa was also processed for light microscopy and electron microscopy. SP-like immunoreactivity was greater in the nasal mucosa of infected animals than in uninfected controls. CGRP-like immunoreactivity was greater in the nasal septum, but not in the nasal turbinate, of infected than uninfected animals. In contrast, no change was evident in the expression levels of the prohormonal transcripts in the trigeminal ganglion. Infected nasal and tracheal mucosa was oedematous and locally infiltrated with inflammatory cells. In the nose of uninfected GF rats, subepithelial lymphoid aggregations were scarce and appeared inactive. We conclude that Mycoplasma pulmonis infection results in increased immunoreactivity of substance P, probably within nerves. There was no clear evidence of increased synthesis of the precursors of substance P and calcitonin gene-related peptide.

More than 200 years have passed since the pulsion diverticulum of hypopharynx was first described. This paper reviews different opinions on its etiology over the centuries. The German pathologist F.A. von Zenker, who successfully pursued research on a variety of topics, is often associated with this diverticulum through his classical work from 1867 "Krankheiten des Oesophagus", which deals with the pathogenesis and clinical presentations of this herniation of the posterior mucosal wall. Numerous surgical techniques, which have been practised mainly during this century, are also reviewed. Different options of endoscopic surgery, which is presently the preferred approach at many medical centers, are described and discussed. Our own experience of endoscopic surgery in patients with Zenker's diverticulum is also presented.

To study the possible autocrine growth stimulation of cholesteatoma epithelium, the expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in middle ear cholesteatoma was investigated by immunohistochemical staining techniques. Twenty cholesteatoma samples obtained at operation and six normal skin specimens collected from the external ear canal were used in the study. Immunostaining for TGF-alpha showed a diffuse cytoplasmic staining pattern. It was weakly expressed in the basal layer of the normal epidermal epithelium but was more strongly expressed in all cholesteatoma specimens. EGFR showed a dot-like/diffuse cytoplasmic and cell membrane staining pattern. EGFR-positive cells were seen in the basal layer of normal epidermis. In the cholesteatoma specimens, expression of EGFR was not only confined to the basal layer but persisted into the upper layers of the epithelium. Our findings indicate that an autocrine growth stimulation by TGF-alpha and EGFR may contribute to the unrestrained growth of cholesteatoma epithelium in the middle ear cavity.