0000000000054737
AUTHOR
Jan Gosepath
mRNA Induction and Cytokine Release of Inflammatory Mediators During In Vitro Exposure of Human Nasal Respiratory Epithelia to Acetaldehyde
Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA-protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. C…
Recurrence of pleomorphic adenoma of the parotid gland-predictive value of cadherin-11 and fascin
The predictive value of cadherin-11, tenascin, fascin, and mucin-1 as markers for the likelihood of recurrence in pleomorphic adenoma of the parotid gland was examined. In this retrospective study we analysed 20 tumours from16 patients by immunohistochemistry. Staining intensities were measured using a semiquantitative scoring approach; localisation (tumour centre vs border) as well as clinical data were analysed and correlated with follow-up. Cadherin-11 was increased in recurrent tumours. However, no changes of fascin, tenascin or mucin-1 were observed. Cadherin-11 and fascin were increased in primary tumours of patients with later recurrence, with fascin upregulation restricted to the tu…
An acute exposure to ozone impairs human olfactory functioning
Ozone is a ubiquitous and irritant gas. We questioned whether an acute exposure to 0.2 ppm ozone impaired olfactory functioning.Healthy, normosmic subjects were exposed according to a parallel group design either to 0.2 ppm ozone (n = 15) or to sham (n = 13) in an exposure chamber for two hours. Possible irritating effects were assessed by questionnaire (range 0-5). The detection threshold of n-butanol was measured with the Sniffin' Sticks test before and after exposure. Olfactory thresholds were logarithmized and a two-way analysis of variance (ANOVA) with repeated measurements was carried out to test the effects of exposure (ozone vs. sham) and time (before vs. after exposure). Additional…
Epidural hematoma after cochlear implantation in a 2.5-year-old boy.
OBJECTIVE Report a case of an epidural hematoma after cochlear implantation in a 2.5-year-old boy, the diagnostic and therapeutical emergency management, as well as the postinterventional course and rehabilitation of the child. STUDY DESIGN Retrospective case review. PATIENT Two and a half-year-old boy, suffering from early onset, profound sensorineural hearing loss had been diagnosed at an age of 1.5 years, which had been more severe on the right side initially, but had progressed to bilateral deafness. INTERVENTION AND COMPLICATION: Cochlear implantation on the left side, followed up by an extensive epidural hematoma, causing intracranial compression with a midline shift of 15 mm to the r…
Frequent chromosomal gains in recurrent juvenile nasopharyngeal angiofibroma.
Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor, mostly affecting adolescent males. Some patients develop recurrences after surgery independently of completeness of removal. Only very limited data concerning underlying chromosomal changes are available. We therefore analyzed samples of 22 JNAs, including six recurrences, with comparative genomic hybridization (CGH). Additionally, quantitative image cytometry was used for measurement of DNA aneuploidy in representative samples. Of the 13 primary JNAs without later recurrence, DNA gains were identified on autosomes in only two samples. Four patients with one or two recurrences were included in the study; for one of these, no…
Effects of the Breathe Right Nasal Strips on Nasal Ventilation
The Breathe Right nasal strips are more and more commonly used, mainly by athletes, who hope to enhance their physical performance in competition and training. The effect of the device in such situations is uncertain and perhaps somewhat controversial. To investigate the effects of the nasal strips on nasal ventilation, 20 Caucasian individuals were objectively assessed using anterior rhinomanometry and acoustic rhinometry. The results showed a significant increase in all subjects of transnasal airflow and in the average cross-sectional area of the nasal cavity that quantifies objectively the subjective impression of improved nasal breathing. In such patients where an improvement in nasal …
Acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects.
Abstract The German MAK value of 1-methoxypropanol-2 has been fixed at 100 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects. Twenty subjects were exposed in a crossover design to 100 ppm 1-methoxypropanol-2 and to air in an exposure chamber for 4 h. Subjective symptoms were assessed by questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1β and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1β, 6 and 8, tumor necrosis factor α, granulocyte-m…
mRNA-induction and cytokine release during in vitro exposure of human nasal respiratory epithelia to methyl methacrylate
Abstract Background Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking. Methods In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4 h and after 24 h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-α, IL-1β, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-α, IL-1β, IL-6, IL-8, MCP…
Subacute effects of ozone exposure on cultivated human respiratory mucosa.
This study was designed to investigate subacute effects of long-term exposure of both healthy and chronically inflamed human respiratory mucosa to ozone. Functional and metabolic effects on ciliary beat frequency (CBF), release of interleukin 8 (IL-8), interleukin 4 (IL-4), and γ interferon (g-INF), as well as cellular viability and cytotoxicity, were monitored. Cell cultures of 60 specimens (healthy mucosa: n = 30, inflamed mucosa: n = 30) were exposed to synthetic air and to ozone-enriched synthetic air in different concentrations of WO, 500, and WOO μg/m3. Continuous expositions were performed using an air/liquid interface cell culture technique for a period of 4 weeks. CBF was monitore…
Current Concepts in Therapy of Chronic Rhinosinusitis and Nasal Polyposis
The exact pathophysiological mechanisms leading to chronic rhinosinusitis (CRS) still to a large extent remain obscure. However, recently there has been some progress in elucidating the etiology of nasal polyposis, especially regarding tissue eosinophilia as well as the role of aspirin intolerance and eicosanoid mediators. Endonasal sinus surgery has evolved to be the treatment of choice in CRS and nasal polyposis in all cases where conservative treatment has failed or resulted in only a partial or temporary relief. Today, state of the art in surgical technique includes the ability to combine microscopic and endoscopic procedures. Regardless of technical advances like powered instrumentatio…
Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck
Intraoperative definition of tumor free resection margins in head and neck cancer is challenging. In the current proof-of-principle study we evaluated a novel silica nanoparticle-based agent for its potential use as contrast enhancer. We synthesized silica nanoparticles with an average size of 45 nm and modified these particles with the fluorescence stain fluorescein isocyanate (FITC) for particle detection and with epidermal growth factor receptor (EGFR)-targeting antibodies for enhanced tumor specificity. The nanoparticles exhibited good biocompatibility and could be detected in vitro and in vivo by confocal laser scanning microscopy. Additionally, we show in an ex vivo setting that these…
Aspirin Intolerance in Patients with Chronic Sinusitis
Aspirin intolerance in patients with chronic sinusitis is often a cause of early recurrence of symptoms after surgical treatment. This study assesses 84 patients who were tested for acetylsalicylic acid intolerance after presenting with symptoms like chronic rhinosinusitis, sometimes bronchial asthma, coexisting allergies or a history of aspirin sensitivity. Nasal polyposis was found in a majority of cases, often recurrent after previous surgery. The levels of eicosanoids such as peptido-leukotrienes and prostaglandin E<sub>2</sub> were analyzed in isolated blood cells and compared with a healthy control group. Aspirin-intolerant patients showed elevated basal levels of peptido-…
No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis.
OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular protection against oxidative stress and reactive oxygen species. One major group of antioxidative active enzymes involved in cellular detoxification are the Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1 and variants of them are known, arising from allelic variations of the GST loci. Moreover, functional variants occur in high percentages and have been associated with diseases like bronchial asthma and bronchial hyperresponsiveness. The interplay of oxidative stress, detoxifying genes like GSTs and the genesis of respiratory tract illness is under contradictory debate. In this study, w…
Expression, Localization, and Significance of Vascular Permeability/Vascular Endothelial Growth Factor in Nasal Polyps
Background The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. Objective To study the expression and localization of VPF/VEGF as a putative key factor in nasal polyp development. Methods Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12)…
Evaluation of inflammatory reactions and genotoxic effects after exposure of nasal respiratory epithelia to benzene.
<i>Background:</i> The aim of this study was to identify inflammatory changes as well as genotoxic effects in cultivated human respiratory epithelial cells after in vitro exposure to benzene. <i>Methods:</i> Primary cell cultures of nasal respiratory mucosa were exposed to synthetic air enriched with 5,000 µg/m<sup>3</sup> of benzene at an air/liquid interface over 8 h and then to synthetic air only over the following 24 h. Controls were continuously exposed to synthetic air over 32 h. To detect inflammatory reactions, release of prostaglandin E<sub>2</sub> was quantified using a competitive enzyme immunoassay. The Comet Assay was used to quan…
Fungal DNA is present in tissue specimens of patients with chronic rhinosinusitis.
Background It has been postulated that fungal organisms might represent the immunologic target initiating and maintaining the disease process in patients with chronic rhinosinusitis (CRS). The presence of fungi in nasal mucus has been established by different groups, but so far it has not been shown how the immune system could even recognize such extramucosal—extracorporal—fungal targets. The aim of this study was to determine whether fungal DNA is present in tissue specimens taken from patients with polypoid CRS. Methods Twenty-seven surgical specimens were collected from patients suffering from CRS. Fifteen surgical specimens from healthy ethmoidal mucosa served as controls. A second set …
Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease
Background Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. Methods After sinus surgery, 70 individuals with AERD were randomly allocated to a prospectiv…
The Use of Acoustic Rhinometry in Predicting Outcomes after Sinonasal Surgery
Today's healthcare environment demands objective assessment of surgical outcomes. The recent otolaryngologic literature has established acoustic rhinometry (AR) as a valid instrument to objectively document nasal patency. The purpose of this article is to evaluate the utility of AR in predicting outcomes after sinonasal surgery. All patients scheduled for sinonasal surgery at the Tulane University and University of Mainz Departments of Otolaryngology between 10/1/98 and 12/15/98 were enrolled. All subjects underwent AR and completed a sinonasal outcome survey (SNOT-20) one day before and two months after their surgical procedure. Thirty-one patients were enrolled. The SNOT-20 raw scores im…
Radiofrequency volumetric tissue reduction (RFVTR) of inferior turbinates: a new method in the treatment of chronic nasal obstruction.
Twenty-two Caucasians (16 male and 6 female) with chronic bilateral nasal obstruction due to hypertrophic inferior turbinates were followed up over a three-month period. They were assessed by clinical examination, as active anterior rhinometry, and acoustic rhinometry before and after topical decongestion, preoperatively and three months after surgery. All patients were treated by application of radiofrequency-volumetric-tissue reduction (RFVTR, or somnoplasty) to both inferior turbinates. Initial postoperative edematous response disappeared during the first week after RFVTR. Three months postoperatively 20 of 22 patients (91%) reported subjective improvement of nasal patency. The average …
Analysis of Fifty-Six Cochlear Implant Device Failures
<i>Objective:</i> Our aim was to present a failure analysis after cochlear implant revision surgery in a large series of children and adults and to assess the outcome and audiologic performance. <i>Methods:</i> Fifty-six cochlear implant failures that occurred in 422 devices implanted between 1990 and 2007 at the Department of Otolaryngology, Head and Neck Surgery at the University of Mainz, Germany, were retrospectively analyzed. The causes of failure were reviewed evaluating the individual history, telemetric and intraoperative findings and manufacturer’s investigation reports. <i>Results:</i> We performed 56 surgical revisions in a series of 422 consec…
Yamik Sinus Catheter in the Topical Treatment of Patients with Acute Rhinosinusitis after Previous Sinus Surgery
Background The Yamik sinus catheter was designed as a new device for the topical treatment of rhinosinusitis. It creates intermittent positive and negative intranasal pressure after sealing the ipsilateral nostril and choana with two inflatable cuffs. Affecting the nasal cavity and all paranasal sinuses of one side at a time, it is used to evacuate mucous and secretions as well as and to introduce antiseptic, antibacterial, or antifungal solutions. Methods This study was designed to evaluate the effectiveness of the Yamik catheter in cases of acute purulent rhinosinusitis in patients who previously underwent endonasal sinus surgery for chronic rhinosinusitis. Twenty patients were treated at…
Characteristics of recurrent chronic rhinosinusitis after previous surgical therapy.
Our findings emphasize the role of a thorough diagnostic evaluation preoperatively and a targeted long-term medical therapy following any sinonasal surgery for inflammatory disease. Early onset of long-term aspirin desensitization can address a very predominant inflammatory stimulus in a large number of our patients in an effort to prevent recurrent chronic rhinosinusitis (CRS) after successful surgical therapy.Postoperative recurrence of CRS, regardless of the ongoing evolution of diagnostic and surgical techniques, still poses an unsolved problem.This investigation was designed to further characterize the role of aspirin intolerance (AI) and inhalant allergies as persistent inflammatory s…
New Immunohistologic Findings on the Differential Role of Cyclooxygenase 1 and Cyclooxygenase 2 in Nasal Polyposis
Background Cyclooxygenase 1 (Cox-1) plays a key role in arachidonic acid metabolism and in the pathophysiology and immunology of nasal polyposis in patients suffering from aspirin intolerance. We hypothesize that Cox-2 also might be relevant in the etiology of nasal polyps of aspirin-tolerant patients by their effects on inflammatory mediators as well as on microvascular permeability. Methods Fifty-two surgical specimens were immunohistochemically labeled for Cox-1 and Cox-2. Specimens were taken from chronically inflamed mucosa (n = 19) and from nasal polyps (n = 19) during endonasal sinus surgery. Controls were obtained from healthy nasal respiratory mucosa (n = 14), harvested during turb…
Nasal provocation testing as an international standard for evaluation of allergic and nonallergic rhinitis.
Standardized nasal provocation testing (NPT) has been shown to be a safe and very useful tool in the diagnosis of allergic and nonallergic rhinitis. However, in the United States, its use has been mostly limited to scientific investigations, and it has not yet been widely accepted as a standard diagnostic procedure in clinical practice. NPT aims to identify and quantify the clinical relevance of inhalant allergens or occupational irritants. During NPT, nasal respiratory mucosa is exposed to an airborne substance suspected to cause symptoms in the respective individual. Clinical reactions are monitored in a controlled and standardized fashion. Nasal secretions, symptoms such as itching, snee…
Early stress response of human nasal respiratory epithelia after exposure to 1-methoxypropanol-2
To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, …
Polysomnography and ApneaGraph in patients with sleep-related breathing disorders.
<i>Purpose:</i> To evaluate whether ApneaGraph (AG) and polysomnography (PSG) deliver comparable results in patients with sleep-related breathing disorders. <i>Procedures:</i> A prospective study was performed, which included 14 patients with obstructive sleep apnea syndrome. Apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), obstructive, central and mixed apnea, oxygen saturation (SaO<sub>2</sub>), pulse and body position were simultaneously assessed by PSG and AG in each individual. <i>Results:</i> There was a good correlation between measurements of AG and PSG for AHI, pulse, SaO<sub>2</sub>, body position and ce…
Segmentation and Navigation Support of Clinical Data Sets to Simulate the Bronchoscopy and Rhinoscopy
A training and simulation system for therapy planning is developed based on patient specific imaging data. A real endoscope is used for navigation through the virtual patient. For this purpose sensors were built in the endoscope in order to track the translation, rotation and the angle of the distal end. Pre-processing (segmentation, tissue characterization) speeds-up the volume rendering up to real-time. Collision detection enables a realistic fly through the virtual patient.
Technical Note: Minimal Access Surgery for Cochlear Implantation with MED-EL Devices
<i>Background:</i> Minimally invasive techniques have been described for cochlear implant surgery, but so far this had not been the case for Med-EL devices. <i>Objective:</i> To describe a newly developed minimal access approach for the implantation of Med-EL devices and report our results after up to 1 year of follow-up in 52 patients. <i>Discussion:</i> The use of a minimally invasive approach without raising a flap or extensive drilling of a bony well was feasible in all 52 patients of this series. It shortened the surgical time to an average of 45 min and there were no specific postoperative complications. The average follow-up of 8.4 months was uneve…
Topical Antibiotic, Antifungal, and Antiseptic Solutions Decrease Ciliary Activity in Nasal Respiratory Cells
This study was designed to investigate whether topical solutions, as they are used in the treatment of selected cases of rhinosinusitis, influence nasal mucociliary clearance. The objective of this study was to evaluate the effects of the following topical solutions on the ciliary beat frequency (CBF) of nasal respiratory cells: ofloxacin as an antibiotic; Betadine and hydrogen peroxide (H2O2) as antiseptic; and amphotericin B, itraconazole, and clotrimazole as antifungal solutions. Differences are described between effects of each of these substances and we clarify whether ciliotoxic effects are dose dependent and if they can be reduced or eliminated by diluting the concentration of the a…
Breathe Right Nasal Strips and the Respiratory Disturbance Index in Sleep Related Breathing Disorders
This investigation assesses the effects of Breathe Right nasal strips on the respiratory disturbance index (RDI) measured by polysomnography in patients suffering from obstructive sleep apnea and snoring. The positive effect of these strips on nasal ventilation was shown in earlier studies. Twenty-six patients with an RDI higher than 10 in an initial measurement underwent a second preoperative polysomnography with Breathe Right nasal strips in place. Nineteen of these 26 patients showed reduction of RDI during the second night of polysomnography using the nasal strips, indicating that nasal obstruction seems to be a predominant factor in the etiology of snoring and apnea in these individua…
Low SPINK5 expression in chronic rhinosinusitis
Objectives/Hypothesis: Chronic rhinosinusitis (CRS) is a multifactorial disease that probably arises as a result of genetic diversity and environmental factors. SPINK5 is a serine protease inhibitor, which is supposed to be an important regulator of epithelial barrier maintenance. The role of SPINK5 polymorphisms and expression in CRS, especially in individuals with aspirin intolerance, is unclear. Study Design: SPINK5 single-nucleotide polymorphisms (SNPs) and SPINK5 expression levels were correlated with CRS without (CRSsNP) and with nasal polyps (CRSwNP), aspirin intolerance, asthma, and allergies. Methods: One hundred four nasal tissue samples, 15 from patients with CRSsNP, 59 from pati…
Role of fungus in eosinophilic sinusitis.
Chronic rhinosinusitis is characterized by a broad diagnostic and etiologic spectrum. It has been postulated that fungal organisms might represent the immunologic target initiating and maintaining the disease process in patients with chronic rhinosinusitis as a common denominator. This review analyzes the available data to describe the current understanding of the role of fungus in the pathophysiology of chronic rhinosinusitis.Recent findings have demonstrated that using highly sensitive methods, the detection rate of fungi in nasal mucin can be increased to approximately 100% in patients and in healthy controls. If this ubiquitous fungal contamination were to be related to a causative mech…