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Biomedical subjects

M M Paparella

Publications and source records attributed to M M Paparella.

At least 19 recordsLinked to original sources

Pattern changes of mucin gene expression with pneumococcal otitis media.

OBJECTIVE: mucins, known to be important components of the mucociliary transport system in the middle ear and Eustachian tube, are subject to changes under inflammatory conditions. Which mucin genes are up-regulated or activated during an inflammatory reaction of the middle ear and Eustachian tube, however, is poorly understood. The purpose of this study was to characterize mucin gene expression in middle ears and Eustachian tubes with pneumococcal ear infection. METHODS: sixteen rats received intrabullar inoculation of Streptococcus pneumoniae type 6A at 2.5x10(6) colony forming units (CFU). Four animals were sacrificed on days 1, 3, 7, and 14, respectively. The profile of mucin gene expression in the middle ear and Eustachian tube was examined by reverse transcription polymerase chain reaction (RT-PCR) at the above time points. Sixteen rats that received intrabullar inoculation of phosphate-buffered saline (PBS) served as controls. RESULTS: the Muc2 mucin gene was expressed in middle ear mucosa of the control rats. Following pneumococcal inoculation, Muc1-Muc5 mucin genes were expressed in the middle ear mucosa in a time-dependent manner. In the Eustachian tube, the Muc2, Muc4 and Muc5 mucin genes were expressed in both control and pneumococcal inoculation groups. CONCLUSION: Muc1, Muc3, Muc4, and Muc5 mucin genes were activated in the middle ear mucosa by pneumococci, which may contribute to hyper-production of mucin in acute pneumococcal otitis media.

Animals↗

Characterization of mucins in human middle ear and Eustachian tube.

Mucins are important glycoproteins in the mucociliary transport system of the middle ear and Eustachian tube. Little is known about mucin expression within this system under physiological and pathological conditions. This study demonstrated the expression of MUC5B, MUC5AC, MUC4, and MUC1 in the human Eustachian tube, whereas only MUC5B mucin expression was demonstrated in noninflamed middle ears. MUC5B and MUC4 mucin genes were upregulated 4.2- and 6-fold, respectively, in middle ears with chronic otitis media (COM) or mucoid otitis media (MOM). This upregulation of mucin genes was accompanied by an increase of MUC5B- and MUC4-producing cells in the middle ear mucosa. Electron microscopy of the secretions from COM and MOM showed the presence of chainlike polymeric mucin. These data indicate that the epithelium of the middle ear and Eustachian tube expresses distinct mucin profiles and that MUC5B and MUC4 mucins are highly produced and secreted in the diseased middle ear. These mucins may form thick mucous effusion in the middle ear cavity and compromise the function of the middle ear.

Aged↗

Stapes mobilization in otosclerosis.

We performed a retrospective chart study (including surgeon's notes and audiometric results) and an analysis of the archival temporal bones from a patient who had undergone surgery for stapes mobilization in both ears. The stapes footplate was submerged into the vestibule on the right (as a complication of surgery) and absent on the left. One interesting finding was that the patient's hearing had improved on the right despite the presence of the depressed footplate and that the air-bone gap had widened on the left despite the absence of complications on that side.

Aged↗

Histopathologic features of the temporal bone in patients with cystic fibrosis.

OBJECTIVES: To investigate the lower than expected incidence of otitis media in patients with cystic fibrosis (CF) through histopathologic evaluation of temporal bones and to document pathologic findings in the inner ears of patients with CF who received long-term administration of antibacterial and diuretic agents. DESIGN: Clinical records of patients who died of CF were reviewed. Their temporal bones were sectioned, stained with hematoxylin-eosin, and examined histologically. Additional sections were stained with Alcian blue and periodic acid-Schiff for comparison of goblet cell densities from middle ears and auditory tubes of patients with CF with those of control temporal bones. Results were analyzed using the t test. SUBJECTS: Twenty-one temporal bones from 11 patients with CF and 13 bones from 8 age-matched patients without CF were selected. RESULTS: All temporal bones with CF had well-pneumatized mastoids. Temporal bones from 2 patients (3 ears) revealed histological findings of chronic otitis media with effusion. There was a statistically significant reduction in the density of goblet cells in the medial (P = .002) and lateral (P = .05) walls in patients with CF who had no otitis media histologically compared with control temporal bones. Two patients with CF who had otitis media had increased densities of goblet cells. Inner ear damage, due to ototoxic drugs, was seen in most of the temporal bones from patients with CF. CONCLUSION: Low densities of goblet cells in temporal bones with CF may contribute reduced amounts of viscous mucus, which can lead to a low incidence of otitis media.

Adolescent↗

Metastases to temporal bones from primary nonsystemic malignant neoplasms.

OBJECTIVES: To compare histopathological and clinical findings of metastasis to the temporal bone with previous reports and to determine the prevalence of these metastases in patients with nonsystemic cancer. STUDY DESIGN: Retrospective. METHODS: Autopsy records of 864 patients were screened to select those with primary nondisseminated malignant neoplasms. These were evaluated histopathologically for metastasis to and site of involvement within the temporal bone, and histological characteristics of the tumor. Clinical records and autopsy reports were reviewed for demographic data, clinical course, otologic and vestibular manifestations, site of primary and its histological features, extent of metastasis, and mode of spread. RESULTS: Of 212 patients with primary nondisseminated malignant neoplasms, 47 had metastases to the temporal bone (76 temporal bones). Twenty different primary tumors had metastasized, most commonly breast cancer. Hearing loss was the most common otologic symptom (seen in 19 patients [40%]), while 17 (36%) had no otologic or vestibular symptoms. Temporal bone involvement was bilateral in 29 patients (62%). Most metastases to the temporal bone demonstrated hematogenous spread in 58 temporal bones (76.7%), and petrous apex was the most common site of metastases in 63 temporal bones (82.9%). Temporal bone metastases were not observed in cases where the primary tumor was adequately treated. CONCLUSIONS: In the largest series to date, we found temporal bone metastases more frequently than previously reported. Absence of temporal bone involvement in cases in which the primary tumor was adequately treated stresses the need for early management of cancer. Metastatic disease must be considered as a cause of hearing loss in patients with a history of malignant neoplasm.

Adolescent↗

Facial neuroma in the internal auditory canal.

Authors presented two cases of facial neuromas in the internal auditory canal, one without facial palsy and the other with facial palsy. In both cases neuromas were occult and undiagnosed. Although in the first case neuroma was greater than the other, facial palsy was not developed. The mechanism of the facial palsy due to neuromas could not be clearly clarified.

Aged↗

Tympanic membrane and middle ear pathologic correlates in mucoid otitis media.

OBJECTIVE: The goal of this study was to correlate tympanic membrane (TM) and middle ear (ME) pathologies in mucoid otitis media (MOM). METHODS AND MATERIAL: Forty ears with MOM and 56 control ears were retrospectively evaluated for TM and ME pathologies. Comparisons of TM thicknesses in MOM versus control ears were correlated with the Student t test; chi(2) analysis was used to correlate pathologic findings of the TM and ME. RESULTS: Thicknesses in all quadrants except the umbo were increased in MOM because of infiltration of inflammatory cells and fibrosis. The most common ME pathologies were granulation tissue and fibrosis. Significant correlations included (1) TM retraction and ME granulation tissue and fibrosis and (2) pars flaccida, posterosuperior, and anteroinferior thickness and ME granulation tissue and fibrosis. CONCLUSION: TM changes are likely to occur in patients with otitis media with effusion (MOM), and their presence is a strong indication of underlying ME pathology.

Adolescent↗

Identification of MUC5B mucin gene in human middle ear with chronic otitis media.

OBJECTIVES: To identify the mucin gene and its expressing cells in the middle ear mucosa with chronic otitis media (COM), and to study the correlation between infiltration of inflammatory cells in the submucosa and expression of the mucin gene in the mucosal epithelium with COM. STUDY DESIGN: Middle ear mucosal specimens removed from the inferior promontory area of 19 patients undergoing middle ear surgery for COM were studied. METHODS: Sections were stained with H&E, Alcian blue-periodic acid Schiff (AB-PAS), polyclonal MUC5B antibody, and specific MUC5B riboprobe for histological, histochemical, immunohistochemical, and mucin mRNA analyses. RESULTS: H&E staining revealed pseudostratified epithelia in 18 of the middle ear specimens with COM and cuboidal secretory epithelia in one. AB-PAS staining of epithelia revealed abundant secretory cells and their products (glycoconjugates). In situ hybridization and immunohistochemistry studies demonstrated that the secretory cells of the middle ear mucosa with COM expressed MUC5B mucin mRNA and its product MUC5B mucin. CONCLUSIONS: The MUC5B mucin gene and its product were identified in the middle ear secretory cells of patients with COM. Its expression was extensive in pseudostratified mucosal epithelia and related to infiltration of inflammatory cells in the submucosa of the middle ear cleft with COM, suggestive that inflammatory cell products are involved in the production of MUC5B.

Adolescent↗

Otitis media with effusion and early sequelae: flexible approach.

Patients suffering from chronic otitis media often have a variety of associated disease processes and pathologic conditions. The identification and recognition of these factors are critical to the effective treatment of the condition. This article provides an overview of the conditions associated with chronic otitis media, a detailed review of the disease process, and guidelines for surgical therapy.

Acute Disease↗

Tympanoplasty: prudent considerations of silent otitis media and interactions of middle ear and inner ear.

Otitis media is a common problem, often with simple, minimally invasive solutions; however, a small subset of patients progress to chronic disease despite provision of standard therapies. The flexible approach to tympanoplasty is a prudent consideration for patients with chronic otitis media, especially children. This article discusses the findings and implications of silent otitis media, interactions of the middle ear and inner ear, and obstructive sites in the middle ear cleft. Tympanoplasty by the flexible approach is described in the context of these findings.

Acute Disease↗

Improved RNA analysis for immediate autopsy of temporal bone soft tissues.

RNA analysis is essential for understanding biological activities of a cell or tissue. Unfortunately, retrieval of RNA from existing archives of human temporal bones has proven extremely difficult due to degradation of RNA molecules. The major factors that contribute to degradation of RNA in specimens from autopsied temporal bones are tissue autolysis due to time elapsed before autopsy, and technical problems in processing the bones after harvest. We therefore focused on improving the survival of RNA in human temporal bones by shortening the time to autopsy and through modification of the processing technique by removing targeted tissues directly from the temporal bones and by avoiding time-consuming decalcification and celloidin-embedding. Eight temporal bones collected at immediate autopsies were used in this study. Representative mRNAs, ranging from high (MUC5B, physically unstable) to low (beta-actin, physically stable) molecular weights, and from abundant (MUC5B) to non-abundant (MUC1) RNA, were studied by in situ hybridization, Northern blot technique, or both. Using this modified protocol in autopsies performed up to 6 h after death, the existence of mRNAs was demonstrated in all bones studied. This improved method demonstrates the feasibility of the use of autopsied temporal bone tissues for RNA analysis.

Autopsy↗

The theory of the trigger, the bridge and the transmigration in the pathogenesis of acquired cholesteatoma.

The purpose of the study was to evaluate factors in the otitis media process that could play a role in the pathogenesis of acquired cholesteatoma. The study was divided in two parts: firstly the temporal bones of 75 cats and 15 chinchillas with induced otitis media, and 78 human bones with otitis media were evaluated. Special emphasis was placed on epithelial breaks. These breaks were commonly observed, leaving areas of connective tissue of the mucoperiostium in direct contact with the middle ear effusion. As these changes progressed, the effusion became organized, serving as a bridge for granulation tissue. In later stages these areas became totally or partially covered with epithelium. Areas of epithelial breaks became connected to each other through the organized effusion. Cholesteatomas in humans seem to spread using the connective tissue as scaffolding. Secondly, we reviewed 15 chinchillas in which a chemically modified membrane was placed leading from the external auditory canal to the promontory, through a tympanic membrane perforation. Squamous epithelial migration with cholesteatoma formation occurred through the tympanic membrane perforation, collagen membrane, organized effusion and granulation tissue in 53.5% of the experimental animals. The authors propose the theory that for transmigration of squamous epithelium to occur, a trigger (inflammatory process) and a bridge (granulation tissue and organized effusion) are needed in a predisposed subject.

Animals↗

Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats.

Pneumococcal otitis media is associated with the production of potent inflammatory mediators (leukotrienes), but the mechanism by which pneumococcus induces production of leukotrienes in the middle ear is poorly understood. In this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculation of pneumococcus into the middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not detected in control animals. Up-regulation of cPLA2 and 5-LOX in middle ear epithelial cells was accompanied by an increase of high-molecular-weight glycoproteins in middle ear fluid and cells. These findings suggest that pneumococcus activates the lipoxygenase pathway by up-regulating expression of the cPLA2 and 5-LOX genes. This, in turn, may stimulate synthesis and secretion of high-molecular-weight glycoproteins that facilitate production of fluid in the middle ear cleft.

Animals↗

Tympanic membrane/middle ear pathologic correlates in chronic otitis media.

OBJECTIVE: To correlate pathologic findings of the tympanic membrane with pathologic changes in the middle ear cleft in chronic otitis media. STUDY DESIGN: Retrospective. MATERIAL AND METHODS: One hundred-fifty temporal bones from 97 subjects with chronic otitis media (defined as middle ear pathologic changes including granulation tissue, fluid, cholesteatoma, cholesterol granuloma, tympanosclerosis, and ossicular changes) were selected to correlate the presence of these middle ear pathologies with histopathologic changes of the tympanic membrane. The tympanic membrane pathologies included perforation, myringosclerosis, retraction, hemorrhage, fluid-filled cystic spaces, or dilated vessels. Temporal bones were also assessed for atelectasis. Fifty-six normal temporal bones were taken as controls for measurements. RESULTS: Significant correlations between tympanic membrane and middle ear pathology included myringosclerosis and granulation tissue, myringosclerosis and ossicular pathology, retraction and cholesterol granuloma, retraction and cholesteatoma, retraction and ossicular pathology, perforation and ossicular pathology, and hemorrhage and granulation tissue. Additive effects of some pathologies were also observed. Almost half the bones with middle ear pathology had no associated tympanic membrane pathology, whereas multiple pathologic changes in the tympanic membrane generally showed underlying multiple pathologic changes in the middle ear. CONCLUSION: When tympanic membrane pathology is detected otoscopically, its presence, alone or in combination, can be a strong indicator of underlying middle ear pathology. However, a normal-appearing tympanic membrane does not exclude the possibility of middle ear pathology. These findings suggest the need for other diagnostic tools such as multifrequency tympanometry and otoacoustic emissions to complement otoscopy for diagnosis of middle ear pathology, especially in a tympanic membrane that appears "normal."

Adolescent↗

Study of systemic lupus erythematosus in temporal bones.

Despite some reports of sensorineural hearing loss with systemic lupus erythematosus (SLE), its pathologic correlate has remained unidentified due to the scarcity of human temporal bone studies. We here present findings in 14 temporal bones from 7 patients with SLE, examined histologically and immunohistochemically for pathologic conditions in the cochlea that might relate to their otologic histories. Blue-staining concretions were seen in the stria vascularis of 6 ears. Most of the cases showed a loss of spiral ganglion cells, with various degrees of hair cell loss and atrophy of the stria vascularis. One ear demonstrated formation of fibrous tissue and bone throughout the cochlea, with complete loss of the membranous labyrinth. Cochlear hydrops was found in only 1 ear. These findings in temporal bones from patients with SLE are discussed in relation to autoimmune disease of the inner ear.

Adolescent↗

Expression of intercellular adhesion molecule-1 in rat inner ear due to bacterial otitis media.

Expressions of anti-Streptococcus pneumoniae antibody and anti-intercellular adhesion molecule-1 (ICAM-1) antibody in the inner ear were studied immunohistochemically in rats following inoculation of S pneumoniae type 6A into the middle ear cavity. Positive staining with anti-S pneumoniae antibody was detected in the marginal cells of the stria vascularis of rats sacrificed 3 days after S pneumoniae inoculation, but almost no staining was detected in those sacrificed at 14 days. Strong ICAM-1 expression was detected in the basal cell layer of the stria vascularis of rats sacrificed 3 days after inoculation, but the intensity of the staining had decreased by 14 days. These results suggest that the stria vascularis may be a site of the inner ear damage that follows bacterial inoculation into the middle ear cavity. The up-regulated expression of ICAM-1 in the basal cell layer may represent a reaction of the inner ear to the bacterial otitis media.

Animals↗