ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

HypothesisThere are at least three possible molecular models of cholesteatoma pathogenesis. Cholesteatoma may arise as a result of 1) the induction of a preneoplastic or neoplastic transformation event; 2) a defective wound-healing process; and/or 3) a pathologic collision of the host inflammatory response, normal middle ear epithelium, and a bacterial infection.BackgroundThere have been a number of speculations concerning the factors that foster the development of cholesteatoma. Before resolving the molecular basis for the pathogenesis of cholesteatomas, it is important to present and test plausible models that could explain how a cholesteatoma becomes invasive, migratory, hyperproliferative, aggressive, and recidivistic.MethodsThe authors evaluated by various techniques (e.g., immunohistochemistry, flow cytometry, and image analysis) a large number of cholesteatomas of all types (e.g., primary and secondary acquired, recurrent, and congenital) and a range of normal tissues (tympanic membrane, canal wall skin, and postauricular skin) for the expression of various proteins (e.g., p53, ectopeptidases, tryptase) and for the presence of DNA aneuploidy.Results and ConclusionsThe authors' published and unpublished studies to date support several suppositions concerning the pathology of cholesteatomas. First, cholesteatoma epithelium behaves more like a wound-healing process than a neoplasm. The available evidence to date does not indicate that cholesteatomas have inherent genetic instability, a critical feature of all malignant lesions. Second, the induction of hyperproliferative cells in all layers of the cholesteatoma epidermis implicates a potential idiopathic response to both internal events as well as external stimuli in the form of cytokines released by infiltrating inflammatory cells. Third, the presence of bacteria may provide a critical link between the cholesteatoma and the host, which prevents the cholesteatoma epithelium from terminating specific differentiation programs and returning to a quiescent state in which it becomes minimally proliferative, nonmigratory, and noninvasive. Fourth, none of our data suggest that there are any obvious molecular or cellular differences among the various types of cholesteatomas (e.g., primary and secondary acquired, recidivistic, and congenital). Continued research should delineate the precise molecular and cellular dysfunction involved in the pathogenesis of cholesteatomas and how this knowledge can be useful in the clinical management of cholesteatomas.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThis study aimed to determine whether chronic otitis media (COM) with cholesteatoma over time is associated with a decrease in neurosensory function.Study DesignThis study was a review of a database of all patients with cholesteatoma treated surgically.SettingThe study was conducted at a tertiary care medical center and specialty hospital.PatientsThere were children and adults with unilateral COM with acquired, nontraumatic cholesteatoma in this study.InterventionsAll patients received preoperative pure-tone bone conduction and speech audiometry.Main Outcome MeasuresInteraural difference between the cholesteatomatous and normal ears comparing bone conduction pure-tone average (BC-PTA), pure-tone threshold at 4,000 Hz (BC4000), and/or speech discrimination score (SDS) as measured by a repeated measures analysis of covariance, with age as a covariate was examined.ResultsA significant difference between ears for SDS and BC4000 that does not vary with age was identified. A significant interaural difference for the BC-PTA that varies with patient age was identified.ConclusionsChronic otitis media with cholesteatoma is associated with a decrease in neurosensory function, even in the absence of frank inner ear invasion.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

HypothesisMonoclonal antibodies directed against cytokeratin subtypes in cholesteatoma produce growth inhibition of keratinocytes.BackgroundDespite 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.MethodsKeratinocytes and skin fibroblasts were trypsinized, counted, and seeded in mutliwell 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 311-thymidine were harvested. Cellular DNA was processed for quantification of 3H-thymidinc incorporation with a beta scintillation counter. Cells exposed to antibody are reported as percent inhibition relative to controls.ResultsInhibition 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.ConclusionsThese 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.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundCholesteatoma is a destructive lesion of the middle ear or mastoid process or both. The molecular and cellular defects that result in the clinical hallmarks of acquired and congenital cholesteatomas, namely invasion, migration, uncoordinated proliferation, altered differentiation, aggressiveness, and recidivism, are unknown. Determining the existence of defects in the normal biology, biochemistry, and genetic complement of the major cellular constituents comprising a cholesteatoma (i.e., fibroblasts and keratinocytes) is critical to the understanding of the pathogenesis of cholesteatomas. It has been speculated that the development of human cholesteatomas is due, in part, to the altered control of cellular proliferation, which tilts the balance toward the aggressive, invasive growth of squamous epithelium within the middle ear. However, whether this altered control is due to defects in the mechanisms and underlying genes that control proliferation, or to cytokines released from infiltrating inflammatory cells, or to some other mechanism is unknown. The nuclear phosphoprotein p53 tumor suppressor gene plays a critical regulatory role in cell cycle control and apoptosis. In the current article, the authors have analyzed congenital, primary and secondary acquired, and recurrent cholesteatomas for the altered expression of p53 and Ki-67, a marker of active proliferation.Methodsp53 and Ki-67 expression was determined by immunohistochemical assays using specific monoclonal antibodies. Results: The authors' results indicate that p53 is elevated 9- to 20-fold in all cholesteatomas when compared to the expression of p53 in normal postauricular skin or tympanic membrane. However, there is no concomitant increase in Ki- 67 expression in cholesteatomas.ConclusionsThese data indicate a defect in cholesteatomas in the mechanisms that p53 engages (i.e., cell cycle control or apoptosis or both). In addition, these data further suggest that there is no intrinsic difference between any clinicopathologic group of cholesteatomas, at least with respect to p53-expression and, presumably, p53 function.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThis study aimed to investigate the occurrence of an “open” form of congenital cholesteatoma to facilitate better understanding of the different histopathologic forms and their differing clinical presentations.Study DesignRetrospective case review.SettingTertiary referral center.PatientsTen patients diagnosed with congenital cholesteatoma, that is, a white “pearl” behind an intact tympanic membrane with no history of trauma, ear surgery, perforation, or otorrhea.Main Outcome MeasuresAudiometry, high-resolution computed tomography scan of the temporal bones and intraoperative findings.ResultsTwo of 10 patients had lesions located in the anterosuperior quadrant of the mesotympanum. Four patients had lesions involving the entire middle ear cleft. Four patients had lesions in the posterosuperior quadrant. Seven of the patients were found to have a typical “closed” cyst, whereas the remaining three patients showed an open cholesteatoma matrix.ConclusionsApparently, there are two types of congenital middle ear cholesteatoma: a closed keratotic cyst and an open matrix. Patients with open cholesteatomas may have a clinical presentation that is uniquely different from the classical description of congenital cholesteatoma.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Hypothesis/BackgroundThe mucoperiosteal lining of the middle ear cavity is subject to radical changes during and after acute infection. Among these is the formation of mucosal polyps. Previous studies on experimental acute otitis media have shown a marked impact of penicillin on mucosal histomorphology. This study reports on the effect of penicillin administration on polyp formation.MethodsThe mucosa of 75 rat middle ears in a model of acute otitis media was examined. Whole-mount and section preparations from 25 normal ears, 25 ears inoculated withStreptococcus pnewnoniae, and 25 inoculated, penicillintreated ears were inspected for number, size, anatomic localization, and histopathologic morphology of occurring polyps.ResultsThe total number of polyps was unaffected by penicillin administration, although polyps occurred in fewer ears. The polyps from treated ears tended to be smaller and stalky, appeared later in the timespan covered, and often were located around the tubal orifice. Histopathologic morphology of polyp base, core, and epithelial covering was otherwise unaffected by penicillin.ConclusionsAdministration of penicillin has inconspicuous effect on the formation of polyps in experimental otitis media caused byS. pneumoniaein contrast to a marked impact on mucosal goblet cell density and other histopathologic features reported in previous studies.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThis study aimed to evaluate the histologic examination of bone tissue surrounding three titanium implants, which were removed since the patients presented with longstanding pain in the implant area. The histologic examination was both qualitatively and quantitatively performed. Furthermore, could an explanation be obtained for the pain in the implant area, which, after removal of the percutaneous implant, disappeared immediately?Study DesignRetrospective case review; clinical histomorphometric.SettingUniversity Hospital Nijmegen, Goteborg University, Sweden.PatientsThree patients of a consecutive series of 189; 1 man and 2 women who had received a bone-anchored, percutaneous, skin-penetrating, commercially pure titanium implant in the temporal bone, on which a transducer was mounted. The implants were removed because of pain in the implant area from the three patients after 31 months, 18 months, and 8 months, respectively.Main Outcome MeasuresThe percentage of direct bone-tometal contact was 81%, 59%, and 42%, respectively. The percentage of bone volume between the threads of the screw was 90, 78, and 75, respectively.ResultsThe qualitatively histologic findings showed no major differences among the three investigated samples. Quantitatively, the amount of osseointegration depended on the duration of implantation.ConclusionsDirect bone-to-metal contact and the bone volume between the threads increased as the implantation time increased. No explanation was found for the longstanding pain in the implant area and the relief of pain after removal of the percutaneous implant.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThis study reports the results of 14,449 stapedectomy operations performed during the past 40 years.Study DesignThe study design was a retrospective case review. Approximately 100 operations were selected from each of the past 40 years, for a total of 5,444 operations, from which the results with the whole group were extrapolated.SettingAll operations were performed in a hospital during the first 30 years and in an ambulatory surgery center in the past 10 years.PatientsAll patients in the study were the private patients of the author and were operated on by him personally. These patients had otosclerosis only.InterventionsStapedectomy was performed on all patients.Main Outcome MeasuresThe change in hearing after the operation was reported. Using the hearing of the average for 500, 1,000, and 2,000 Hz, the criteria for success were defined as closure of the air-bone gap to 10 dB or less and no decline in speech discrimination of > 10 %.ResultsIn the primary stapedectomy group, success was achieved in 95.1% of ears after 1 year, 94.7% of ears after 2-5 years, and 62.5% after > 0 years. In the revision stapedectomy group, success was achieved in 71.1% after 1 year, 62.4% after 2-5 years, and 59.4% after 6-36 years.ConclusionsThe immediate success rate after primary and revision stapedectomy declines slowly over time, because of delayed conductive hearing loss and further sensorineural hearing loss, more than one would expect in matched control subjects without otosclerosis. Stapedectomy has stood the test of time as the first successful microsurgical operation.

ISSN:0192-9763    

出版商:OVID    

年代:1998

数据来源: OVID