Tamás Karosi

Measles virus prevalence in otosclerotic stapes footplate samples

Hypothesis: The cause of otosclerosis is still unknown. Persistent measles virus infection of the otic capsule is supposed to be one of the etiologic factors in otosclerosis. Chronic viral antigen expression on the surface of infected cells can induce a secondary autoimmune reaction against the otic capsule. Background: In the past 15 years, some reports proposed the possible etiologic role of measles virus in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse-transcriptase polymerase chain reaction amplification of the viral RNA, detecting the viral proteins by immunohistochemistry and detecting antimeasles immunoglobulin G in the perilymph samples. Many concerns were elicited by these results. Methods: Nucleic acid was extracted from pulverized, frozen stapes footplate samples of otosclerotic patients. Measles virus RNA was amplified by reverse-transcriptase polymerase chain reaction: reverse transcription and the first round polymerase chain reaction amplification was performed by heat stable recombinant Thermus thermophilus polymerase, whereas in the nested round, polymerase chain reaction Taq-polymerase was used. Measles virus nucleoprotein RNA-specific oligonucleotide primers were used in these reactions. An Edmonston-type measles virus served as a positive control and cortical bone fragments or stapes superstructures served as negative controls. Results: Among 34 otosclerotic patients, 20 stapes footplate samples contained measles virus RNA. Measles virus RNA was not detected in other bone specimens of the patients. Conclusion: The etiologic role of measles virus in the pathogenesis of otosclerosis should be considered. The 14 negative samples may be genetically determined otosclerotic cases.

Detection of Osteoprotegerin and TNF‐alpha mRNA in Ankylotic Stapes Footplates in Connection With Measles Virus Positivity

Hypothesis: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)‐alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis.

Codetection of Measles Virus and Tumor Necrosis Factor-Alpha mRNA in Otosclerotic Stapes Footplates†

Hypothesis: Otosclerosis is a disease of unknown etiology causing conductive or sensorineural hearing loss. Persistent measles virus infection of the otic capsule is considered to be one of the etiologic factors in otosclerosis.

Biofilm detection in chronic rhinosinusitis by combined application of hematoxylin-eosin and gram staining.

The pathomechanism of chronic rhinosinusitis with nasal polyposis (CRS/NP) seems to be unclear. Bacterial-, fungal- and combined biofilms might play a potential role in the pathogenesis of various inflammatory diseases and recently in CRS/NP. A prospective, blinded observational study was performed to confirm that the combination of conventional hematoxylin–eosin (HE) and Gram staining protocols could be used to detect bacterial and fungal biofilms in patients with CRS/NP. A total of 50 patients with CRS/NP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of 12 patients undergoing septoplasty for nasal obstruction without CRS/NP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to HE and Gram staining. Biofilm was detected in 44 of 50 patients with CRS/NP and in none of 12 negative controls. In our series, HE method showed an obvious correlation with the results of Gram staining and was allocated to be a good predictor of biofilm existence. It was found that the microscopic structure and thickness of biofilms were strongly associated with the integrity of nasal mucosa and with the characteristics of subepithelial cellular infiltration. This study confirmed the presence of bacterial and fungal biofilms on the surface of NPs obtained from patients with CRS. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected histologically. In conclusion, HE staining combined with Gram protocol is a robust and reliable method for the detection of bacterial and fungal biofilms in CRS/NP.

Disease-Associated Novel CD46 Splicing Variants and Pathologic Bone Remodeling in Otosclerosis†

Objective/Hypothesis: Otosclerotic bone is supposed to show unique CD46 expression pattern because otosclerosis is an organ‐specific disease with viral etiology.

Etiopathogenesis of otosclerosis

The objectives of our study was to review our current knowledge of the etiopathogenesis of otosclerotic bone remodeling including genetics, viral infection, autoimmunity and inflammation and to discuss disease pathogenesis with relevance to pharmacotherapy. Relevant publications on the etiopathogenesis, molecular biology, genetics and histopathology of otosclerosis from 1984 to 2009 were analyzed. Otosclerosis is a bone remodeling disorder of the human otic capsule; however, the etiopathogenesis remains unclear. Genetic predisposition, disturbed bone metabolism, persistent measles virus infection, autoimmunity, and hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. Since diagnosis of otosclerosis is still based on histopathological examination of the removed stapes footplate, systemic prospective studies based on comprehensive histopathological and molecular biological analysis are necessary to obtain further information on the background of the disease.

Antimeasles immunoglobulin g for serologic diagnosis of otosclerotic hearing loss.

Hypothesis: Persistent measles virus infection of the otic capsule is suggested to be an etiologic factor in otosclerosis. Otosclerosis is a disease of complex unknown etiology causing progressive conductive and/or sensorineural hearing loss (HL).

Low-frequency ultrasound for biofilm disruption in chronic rhinosinusitis with nasal polyposis: In vitro pilot study†

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Although biofilms are characterized by an extremely high resistance against chemical and physical agents, low‐frequency ultrasound (LFU) treatment has been suspected to be an efficient and safe method for biofilm disruption.

Otosclerosis: an autoimmune disease?

OBJECTIVES To review our current knowledge of the etiopathogenesis of otosclerotic bone remodeling including genetics, viral infection, autoimmunity and inflammation and to discuss disease pathogenesis with relevance for pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications on the etiopathogenesis, molecular biology, genetics and histopathology of otosclerosis from 1984 to 2009 were analyzed. RESULTS AND CONCLUSIONS Otosclerosis is a bone remodeling disorder of the human otic capsule, however, the etiopathogenesis remains unclear. Genetic predisposition, disturbed bone metabolism, persistent measles virus infection, autoimmunity, hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. Since, diagnosis of otosclerosis is still based on histopathological examination of the removed stapes footplate, systemic prospective studies based on comprehensive histopathological and molecular biological analysis are necessary to get further information about the background of disease.

Two Subgroups of Stapes Fixation: Otosclerosis and Pseudo-Otosclerosis†

Hypothesis: Stapes ankylosis is a disease with variable histopathology and can be caused by otosclerosis or pseudo‐otosclerosis. Viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplate and reverse‐transcriptase polymerase chain reaction (RT‐PCR) amplification of the viral RNA.