Biomedical subjects

Wolf J Mann

Publications and source records attributed to Wolf J Mann.

At least 19 recordsLinked to original sources

PubMed2005

Role of fungus in eosinophilic sinusitis.

PURPOSE OF REVIEW: 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: 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 mechanism in chronic rhinosinusitis, there would have to be an immunologic sensitization in patients in contrast with healthy individuals, which is yet not fully understood. However, studies were able to demonstrate cytokine production in blood-derived lymphocytes in the presence of fungi in patients, but not in healthy controls. Several questions arise. If this is a relevant finding, in what percentage of chronic rhinosinusitis patients could it be causative? Is chronic rhinosinusitis, then, a systemic disease? How is the extramucosal target in the mucin presented to the immune system? Is intranasal, topical antifungal treatment a successful option? SUMMARY: The role of fungal organisms in the etiology of eosinophilic rhinosinusitis is reviewed with respect to novel findings, and arising questions are discussed in the light of recent investigations.

Chronic Disease↗

PubMed2005

VEGF-subtype specific protection of SCC and HUVECs from radiation induced cell death.

The contribution of VEGF (vascular endothelial growth factor) to angiogenesis and tumor aggressiveness has been shown in several tumor types, but no comparative data regarding the impact of the VEGF-subtypes on endothelial and tumor cell protection are available. Therefore, we analysed the cytoprotective effects of the two major soluble VEGF-subtypes, VEGF-121 and -165, on HUVEC cell cultures (human umbilical vein endothelial cells) and squamous cell carcinoma (SCC) cell lines after ionizing radiation. We performed clonogenic analyses and proliferation assays for evaluation of cell survival and proliferative activity. Experiments were performed employing different intensities up to 8 Gy with or without added recombinant VEGF-121 or -165 and compared to non-irradiated cultures. To evaluate a possible contribution of the VEGF-receptors, we performed immunohistochemical stainings of VEGF-R1 (flt), -R2 (KDR,flk), and Neuropilin-1. In the SCC cell lines and HUVEC cultures, cell survival and proliferative activity were reduced in a dosage-dependent manner. The addition of VEGF-121 yielded a significant increase of resistance from 1.2 to 2.7 Gy (+125%) for killing 50% of subjected cells, while VEGF-165 was less effective in this regard (+83%). Conversely, in HUVEC cultures, 50%-survival was increased more strongly by VEGF-165 compared to VEGF-121 (+100% vs. +43%). Accordingly, proliferation was more intensely stimulated in HUVECs by VEGF-165 than by VEGF-121. VEGF-receptors were expressed in all cell cultures analysed at comparable levels. We conclude that the two VEGF-subtypes differentially increase the survival of tumor and endothelial cells after irradiation in vitro. We hypothesise, that the release of VEGF by the tumor protects tumor cells and endothelium resulting in increased radiation resistance.

Carcinoma, Squamous Cell↗

PubMed2004

Vessel density, proliferation, and immunolocalization of vascular endothelial growth factor in juvenile nasopharyngeal angiofibromas.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a rare, highly vascularized neoplasm of the nasopharynx that affects boys and young men. The underlying dysregulated molecular mechanisms remain unclear. The participation of angiogenic growth factors has been suggested, but few studies have been published. OBJECTIVES: To evaluate the expression and localization of vascular endothelial growth factor (VEGF), proliferating cells, and vessel density in JNA. STUDY DESIGN: Immunohistochemical examination of 10 consecutive JNAs (8 primary tumors and 2 recurrent tumors). METHODS: Paraffin-embedded and cryopreserved JNA samples were included. VEGF-, CD31-, and Ki67-specific antibodies were applied and visualized using light microscopy. Vascularization was determined by counting CD31-positive vessels. Proliferating and VEGF-expressing vessels as well as stromal cells were quantified by the same method. Patients' age at the time of surgery and tumor stage were correlated with the immunohistochemical data. RESULTS: All tumors were heavily vascularized, but major differences were noted between the samples. About half of the vessels were proliferating (Ki67 positive) and half of the Ki67-positive cells were also VEGF positive. The tumor stroma was VEGF positive in 8 of 10 samples and proliferating in 5 of these 8. The 5 samples with both VEGF- and Ki67-positive stroma showed high vessel densities. No correlation was observed between age or tumor stage and vessel density, VEGF expression, or Ki67 expression. CONCLUSIONS: In JNA, VEGF is frequently expressed by stromal cells and vessels and is associated with proliferation and increased vessel density. We suggest the promotion of vascularization by VEGF, but the involvement of androgens in JNA angiogenesis still needs to be analyzed.

Adolescent↗

PubMed2004

Juvenile angiofibromas: changing surgical concept over the last 20 years.

OBJECTIVES: Nasopharyngeal angiofibroma is a rare tumor. Several surgical approaches have been established, including transpalatal, lateral rhinotomy, craniofacial, and midface degloving procedures. More recently, less invasive endonasal approaches have been used. In a retrospective study, we analyzed the outcome of surgical treatment for angiofibroma to determine whether an endonasal approach was as effective as other, more invasive techniques for removing the tumors. METHODS: Thirty patients with histologically confirmed angiofibromas were treated by surgical removal at two institutions during a 20-year period. Tumors were staged according to size and extension on the basis of imaging and surgical findings using the Fisch classification. Specific analysis of the operative approaches and recurrence rate by stage were included. Recurrent or residual disease was handled by surgical excision. RESULTS: The number of patients treated increased during the last 10 years in both institutions, but no major changes in distribution of tumor stages were observed. In the most recent years, the endonasal approach has been favored. All 30 patients remain alive and free of disease. CONCLUSIONS: During the last 12 years, we have undergone a marked shift toward endonasal procedures while the tumor stages of the patients treated remained the same. Our results demonstrate that angiofibromas may be managed successfully using less invasive techniques, thereby reducing morbidity, without increasing the chance of recurrence.

Adolescent↗

PubMed2004

Untreated chronic rhinosinusitis: a comparison of symptoms and mediator profiles.

OBJECTIVES/HYPOTHESIS: Since the early 1990s, the knowledge of inflammatory mediators involved in chronic rhinosinusitis has increased extensively. However, until the present no data on trends in mediator levels in the natural course of the exacerbation-free interval of chronic rhinosinusitis have been published. The purpose of the study was to examine how levels of inflammatory mediators and clinical findings in chronic rhinosinusitis relate over time in the absence of acute exacerbation. STUDY DESIGN: Prospective study. METHODS: The authors investigated 12 untreated patients with chronic rhinosinusitis and repeated clinical examinations and measurements of inflammatory mediators in the nasal mucosa (messenger RNA [mRNA]of interleukin-1beta; interleukins 3, 5, 6, and 8 [IL-3, IL-5, IL-6, and IL-8]; interferon gamma; tumor necrosis factor-alpha [TNF-alpha]; monocyte chemotactic proteins 1, 3, and 4 [MCP-1, MCP-3, and MCP-4]; and granulocyte-macrophage colony-stimulating factor [GM-CSF]), as well as measurements of peptido-leukotriene [PLT] and prostaglandin E2 [PGE2]) in nasal secretion over a period of 4 weeks. RESULTS: Clinically speaking, the symptom score significantly improved over the period of 4 weeks, whereas other clinical parameters (computed tomography score, endoscopy score, rhinomanometric values, saccharine transport time, ciliary beat frequency, and olfaction) varied insignificantly. Regarding proinflammatory and inflammatory mediators, only mRNA of IL-1beta, IL-6, IL-8, MCP-1, and TNF-alpha were detected in relevant amounts in nasal mucosa, and their levels decreased only insignificantly over the 4-week period. In nasal secretion, a slight decrease of PGE2 and PLT levels was observed over the same time period. CONCLUSION: Subjective symptoms may show a spontaneous improvement of approximately 25% in patients with so-called "stable" chronic rhinosinusitis over a 4-week period, whereas objective clinical parameters vary insignificantly. Messenger RNA of IL-1beta, IL-6, IL-8, MCP-1, and TNF-alpha, as well as PLT and PGE2 levels, are detectable and appear to play a role in the persistence of inflammation in chronic rhinosinusitis. Their levels decrease only insignificantly over time, even in the absence of acute exacerbation of disease, possibly rendering the mucosa more prone to recurrent acute episodes.

Adult↗

PubMed2004

Clinical and radiologic sequelae of the middle fossa approach to the internal auditory canal.

OBJECTIVE: This retrospective study aimed to characterize the postoperative nonneurotologic complications and radiologic findings after the middle fossa approach to the internal auditory canal (IAC). A grading system for computed tomography (CT) changes was developed. STUDY DESIGN: Sixty-two patients operated between 2000 and 2003 had CT scans of the head on the day after surgery. Their charts and films were reviewed. SETTING: R15 DK 54070-01A1: Tertiary referral center. RESULTS: Nine patients had complications, including seven with cerebrospinal fluid leakage, one with infection, and one with visual disturbances. Only three of these patients had CT changes. Alternatively, 14 patients had CT changes according to our grading system for edema, pneumatocephalus, and hematoma. Three of these patients had complications. The overall complication rate was low (15%), and there were no cases of serious damage to the temporal lobe. CONCLUSION: The middle fossa approach provides safe access to the IAC. With the use of flexible retractors, serious damage to the temporal lobe can be avoided. The CT scan on the first day after surgery is useful for detecting dangerous hematomas but should be correlated to the patient's condition because of non-specific radiologic changes and the potential for complications to be present even in the absence of CT findings.

Adolescent↗

PubMed2004

The cyclooxygenase inhibitor flurbiprofen reduces radiation-induced angiogenic growth factor secretion of squamous cell carcinoma cell lines.

Surgical intervention and radiotherapy still represent the gold standard in the therapy of head and neck squamous cell carcinoma (SCC), although often with unsatisfactory results. Radiation might induce the expression and secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) by unknown mechanisms. These two highly active proangiogenic and cytoprotective factors might contribute to a limited therapeutic success by promoting revascularization and cytoprotection of the radiated tumor. The aim of the present study was to analyze the potential of the cyclooxygenase inhibitor flurbiprofen to reduce radiation-induced increase of VEGF and bFGF secretion of tumor cells. We analyzed the expression of VEGF and bFGF at 72 h after radiation with 30 Gy in four SCC cell lines (De-pt, Hun, Lau, and A549) in cell culture with or without added flurbiprofen. Controls were not exposed to radiation and were analyzed at the same time after culture in the same media. We observed increased VEGF levels in all and increased bFGF levels in three of four lines after radiation. In irradiated cultures with flurbiprofen, VEGF was reduced between 13% and 26% and bFGF was reduced between 84% and 93% compared with radiated cultures without flurbiprofen. We found no reduction of VEGF and bFGF secretion in the unirradiated cultures despite added flurbiprofen. We conclude that flurbiprofen is able to alter the radiation-induced secretion of these two growth factors and might be useful in decreasing the resistance of SCC to radiation.

Carcinoma, Squamous Cell↗

PubMed2003

Expression of angiogenic growth factors in acoustic neurinoma.

OBJECTIVES: Acoustic neurinoma (AN) can grow to a large size, but the growth-promoting molecular pathways remain unknown. As angiogenesis has been described as being activated in many cancers, we undertook this study in order to examine the microvascular network of AN and the expression of angiogenic growth factors and their cognate receptors in AN. The aim was to draw conclusions regarding the underlying mechanisms and potential benefit of a pathway-specific anticancer therapy. MATERIAL AND METHODS: Surgical specimens from 34 patients with AN were analysed immunohistochemically for the expression of vascular endothelial growth factor (VEGF), VEGF-receptor 1 (VEGF-R1), VEGF-receptor 2 (VEGF-R2) and transforming growth factor-beta1 (TGF-beta1). The microvessel density (MVD) was defined using CD31 staining and macrophage infiltration using CD68 staining. MVD was correlated to tumour size, patient age and duration of symptoms. RESULTS: With 1 exception each for VEGF and VEGF-R1, none of the 34 tumours expressed either VEGF, TGF-beta1, VEGF-R1 or -R2. No tumour-infiltrating macrophages were detected. The MVDs determined were low and did not correlate with tumour size, duration of symptoms or patient age. CONCLUSION: These findings indicate that ANs either do not express or express very low levels of the analysed proangiogenic growth factors. We conclude that tumour angiogenesis is not likely to be a relevant mechanism of AN growth and might therefore not be a suitable anticancer therapy target.

Adult↗

PubMed2003

Multilevel temperature-controlled radiofrequency therapy of soft palate, base of tongue, and tonsils in adults with obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: The concept of two-level pharyngeal collapse in patients with obstructive sleep apnea is too simplified. Aggressive multilevel surgeries addressing several airway segments, including skeletal surgery, demonstrate improved success rates. STUDY DESIGN: The study aimed to evaluate the safety and efficacy of multilevel radiofrequency application to soft palate, tonsils, and base of tongue in 16 white patients (mean age, 56.9 +/- 11.1 y; mean body mass index, 27.3 +/- 2.6 kg/m2) with obstructive sleep apnea. There was one dropout. Therapeutic effects after one treatment session were assessed 20.6 +/- 12.6 weeks postoperatively. Treatment outcome measurements were based on Epworth Sleepiness Scale, Likert scales, and polysomnography. METHODS: Every patient received 16 treatment sites with a total dose of 9750 J radiofrequency energy into soft palate, base of tongue, and tonsils. Success was defined as respiratory disturbance index equal to or less than 20 or at least 50% improvement if baseline respiratory disturbance index was less than 20. Statistical analysis was determined with the Spearman rank test. RESULTS: Mean score on Epworth Sleepiness Scale decreased from 11.1 to 8.2 (P =.0001). Of the patients, 53.3% reported improvement of their daytime sleepiness. Snoring was assessed with 10-point Lickert scale, and score decreased from 7.5 to 4.9 (P =.08). Mean respiratory disturbance index decreased from 32.6 +/- 17.4 to 22.0 +/- 15.0 (P =.003). By our definition of success, 5 of 15 patients (33%) have been treated successfully surgically and 4 of 15 (27%) had remarkable improvement after one treatment session; 1 patient (6.6%) demonstrated deterioration. There were two adverse effects, one superficial ulceration of the soft palate and one unilateral tonsillar abscess formation, with an overall complication rate of 13.3% for our patients and 0.41% for all treatment sites (n = 240). CONCLUSION: Moderate to severe obstructive sleep apnea usually requires multilevel pharyngeal surgery. Radiofrequency offers the potential of altering the upper airway on different sites.

Adult↗

PubMed2003

Molecular biologic characteristics of seven new cell lines of squamous cell carcinomas of the head and neck and comparison to fresh tumor tissue.

BACKGROUND: Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the upper aerodigestive tract. Cell lines of these tumors facilitate the investigation of various tumor biological parameters. This study was conducted to compare molecular biologic characteristics between cell lines and fresh tumor tissue. METHODS: In seven SCC-derived cell lines, cytokeratin 5/6 and cytokeratin 19 expression, DNA content, chromosome aberrations and tumorigenicity were assessed in nude rats. Unbalanced numerical and structural chromosomal aberrations were investigated by comparative genomic hybridization (CGH), and results were compared to those obtained in fresh tumor tissues of the same patients. RESULTS: All cell lines expressed cytokeratins 5/6 and 19, indicating their epidermoid origin. Tumor growth after transplantation into nude rats occurred in five of seven cell lines. Routine histology and immunohistochemical examinations confirmed SCC. Aneuploidy was detected in all cell lines, with a 2c deviation index ranging from 1.9 through 9.5 and a 5c exceeding rate ranging from 2.6 through 36.7%. The most frequent chromosomal aberrations in cell lines were overrepresentations of chromosomal material on chromosomes 15q, 7p (5 cases each), 3q, 5p (4 cases each), and 11q and 17q (3 cases each) and losses of chromosomal material on chromosomes 3p, 18q (3 cases each), and 19p and 7q (2 cases each). Comparing these results to CGH analysis of fresh tumor tissue from the same patients, overrepresentations of chromosomal material on 10q, 20q and 21q, along with loss of chromosomal material on 4q was detected more frequently in primary tumors, whereas overrepresentations on 7p and loss of chromosomal material on 7q were more frequently detected in cell lines. Nevertheless, there was a high degree of similarity of chromosomal alterations in cell lines and corresponding fresh tumor tissue. CONCLUSION: The data suggest a high degree of genetic similarity between tumor cells of cell lines and the tumors from which they were derived. Therefore, these cell lines can serve as an accurate model to investigate cell biology of SCC in vitro.

Animals↗

PubMed2003

Association of proliferative activity and size in acoustic neuroma: implications for timing of surgery.

OBJECT: Acoustic neuroma is the most frequent benign tumor of the cerebellopontine angle, and surgery is still the most common form of treatment. To gain better insight into the dysregulated mechanisms causing growth of acoustic neuroma, the authors studied the proliferative activity of 34 consecutive samples by analyzing immunohistochemical staining with Ki-67 and proliferating cell nuclear antigen (PCNA), and apoptosis based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Data from these analyses were correlated with clinical parameters (that is, tumor size, duration of symptoms, and patient age). METHODS: Apoptotic cells were found in none of the tumors. Proliferation measured on staining with Ki-67 and PCNA correlated with tumor size, but not with patient age or duration of symptoms. The authors demonstrated that tumors 18 mm or smaller in diameter have lower proliferation indices and growth rates, compared with tumors larger than 18 mm with high proliferative indices and growth rates. Additionally, they observed that these more aggressive, larger tumors occur mostly in patients younger than 50 years of age. CONCLUSIONS: Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.

Adult↗

PubMed2002

Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization.

Esthesioneuroblastoma (ENB) are rare tumors originating from the olfactory epithelium of the superior nasal cavity. This lesion is morphologically closely related to Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNET). The affiliation of ENB to the pPNET family is still under discussion. Only very limited and contradictory cytogenetic data are available on ENB and only one patient has been analyzed by comparative genomic hybridization (CGH), so far. In the present study, genomic imbalances of three ENB were analyzed by CGH to evaluate (1) a recurrent pattern of imbalances, and (2) its relation to the pPNET family. The CGH analysis of three ENB revealed multiple recurrent aberrations including DNA overrepresentations of chromosomal material of the entire chromosome 19, partial gains of the long arms of chromosomes 8, 15, and 22, and deletions of the entire long arm of chromosome 4. Beside these common aberrations, several single gains and losses occurred, that is, gains on 6p, 10q, 1p, 9q, and 13q. We confirmed the former observation of amplified genetic material on chromosome 8 and found several new, currently not described recurrent genetic aberrations distinct from those described for pPNET. Our findings give evidence that ENB is not part of the pPNET family. We suggest that the combined gain of genetic material on 15q, 22q, and chromosome 8 might be indicative for ENB. To verify our findings and to define prognosis-related aberrations, a larger number of cases needs to be studied.

Aged↗

PubMed2002

[Do blind persons have a better sense of smell than normal sighted people?].

Functional disorders of sense organs may intensify the remaining senses. It is presumed that blind persons do not only hear better and have an intensified tactile sense but also have a stronger sense of smell. Better hearing ability was demonstrated by auditory evoked potentials. We investigated the sense of smell of blind persons by subjective tests (Sniffin' sticks: threshold, discrimination and identification) and for the first time also by objective tests (olfactory evoked potentials and trigeminal evoked potentials) and compared the results with the smelling ability of normal sighted persons by pair matching. Moreover, the investigated persons judged their performance via a questionnaire. The subjective test showed neither differences in the peripheral function nor in the central function between both groups. The amplitudes and latencies of the evoked potentials of vanillin, carbon dioxide and hydrogen sulfide were also not different. Blind persons tried unasked to identify the smell given in the discrimination test and thought themselves to be better in smelling. For the first time the smelling ability of blind people was compared with normal sighted people by objective test methods. Neither with subjective nor with objective methods differences were found.

Adult↗

PubMed2002

Investigations for fine mapping of amplifications in chromosome 3q26.3-28 frequently occurring in squamous cell carcinomas of the head and neck.

OBJECTIVE: Overrepresentations of chromosomal material on the long arm of chromosome 3 frequently occur in squamous cell carcinoma of the head and neck. This experimental study was conducted for further fine mapping of these overrepresentations by interphase fluorescence in situ hybridization (FISH) of tumor cells in cell lines. METHODS: Seven cell lines derived from squamous cell carcinomas of the head and neck were investigated by comparative genomic hybridization to analyze unbalanced chromosomal aberrations. Overrepresentations of chromosomal material on the telomeric part of the long arm of chromosome 3 were further analyzed by interphase FISH using YAC contig clones. RESULTS: Chromosomal aberrations which frequently occurred were overrepresentations on 5p (n = 4), 7p (n = 5), 11q13 (n = 3), 15q (n = 5), 17q (n = 3), 19q (n = 2), 20q (n = 2) and 22q (n = 3). Reoccurring losses of chromosomal material were found in 3p (n = 3), 7q (n = 2), 18q (n = 3) and 19p (n = 2). Gains of chromosomal material on chromosome 3q were found in 4 out of 7 cell lines, with a high copy number of amplifications occurring in the chromosomal region of 3q26.3-28. Further experiments revealed a physical mapping of this amplification to a narrow band of 13.8 Mbp on chromosome 3q, whose amplification borders were represented by the YAC clones 754_f_3 centomeric and 955_b_2 telomeric. CONCLUSIONS: By FISH, the amplification of chromosomal material on 3q could be fine mapped on a narrow band on 3q26.3-27. This aberration can be considered as a breakpoint in tumorigenesis. Putative candidate oncogenes and tumor suppressor genes located in this region might be a target for mutations leading to tumor progression.

Carcinoma, Squamous Cell↗

PubMed2002

Dendritic cell influx differs between the subglottic and glottic mucosae during acute laryngotracheitis induced by a broad spectrum of stimuli.

Clinically, the subglottic and glottic mucosae may react differently, eg, during acute laryngotracheitis. In healthy rats, we showed previously that the composition of the mucosal immune system of the larynx also differs between these areas. Neutrophils, lymphocytes, and dendritic cells (DCs) are part of this mucosal immune system. In particular, DCs occupy a key function. They migrate into inflamed mucosae during the early phase of the immune response, which is normally characterized by an influx of neutrophils. Thus, they help to overcome the time lag between the innate and the adaptive immune responses. In the present study, the influx of DCs, neutrophils, and T lymphocytes into the subglottic and glottic mucosae of rats was examined at different time points after challenge with a broad spectrum of stimuli such as dead Moraxella catarrhalis, viable Bordetella pertussis, viable Sendai virus, and the soluble protein ovalbumin. The number of DCs increased rapidly after the application of the antigens. This increase was as rapid as the increase in neutrophils. Depending on the kind of antigen, their number in the mucosa increased up to 1,000 cells per 0.1 mm2 (Sendai virus). The comparison of different mucosal areas shows that an overwhelming number of immunocompetent cells entered the subglottic mucosa, whereas only a few cells migrated into the adjacent glottic mucosa. In conclusion, after inhalation of different kinds of antigens, the subset of immunocompetent cells investigated in this study entered the laryngeal mucosa in high numbers. The number of DCs entering the laryngeal mucosa was higher than the numbers of the other immune cells investigated. This finding underlines their function as first-line sentinels of the mucosal immune system of the larynx. The observation that the number of cells entering the laryngeal mucosa is location-dependent indicates the ability of adjacent laryngeal regions to react differently. This is similar to the clinical observation of a selective subglottic reaction during acute laryngotracheitis.

Acute Disease↗

PubMed2002

Exposure to 200 ppm of methanol increases the concentrations of interleukin-1beta and interleukin-8 in nasal secretions of healthy volunteers.

This study was designed to investigate subclinical irritating effects of methanol on functional and immunologic parameters in human respiratory epithelia. Twelve healthy, nonsmoking individuals were exposed to concentrations of 20 and 200 ppm of methanol in an exposure chamber. The concentrations of interleukin (IL)-8, IL-1beta, IL-6, and prostaglandin E2 (PGE2) were monitored. The saccharin transport time test was used to evaluate mucociliary transport. Video interference contrast microscopy was used to determine the ciliary beat frequency of nasal epithelial cells. Subjective symptoms were assessed with a questionnaire. The median concentrations of IL-8 and IL-1beta were significantly elevated after exposure to 200 ppm of methanol as compared to exposure to 20 ppm (IL-1beta, 21.4 versus 8.3 pg/mL, p = .001; IL-8, 424 versus 356 pg/mL, p = .02). The release of IL-6 and PGE2 did not change significantly (IL-6, 10.3 versus 6.5 pg/mL, p = .13; PGE2, 13.6 versus 13.4 pg/mL), nor did the ciliary beat frequency or the saccharin transport time. Both IL-8 and IL-1beta proved to be sensitive indicators for subclinical irritating effects of methanol in vivo. The German threshold limit of 200 ppm of methanol does not prevent subclinical inflammatory reactions of the nasal respiratory mucosa.

Adult↗

PubMedDate not supplied

Evaluation of inflammatory reactions and genotoxic effects after exposure of nasal respiratory epithelia to benzene.

BACKGROUND: 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. METHODS: Primary cell cultures of nasal respiratory mucosa were exposed to synthetic air enriched with 5,000 microg/m(3) 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(2) was quantified using a competitive enzyme immunoassay. The Comet Assay was used to quantify the ratio of apoptotic cells with benzene-induced DNA fragmentation. RESULTS: Prostaglandin release as well as DNA fragmentation increased after 8 h of exposure and remained elevated throughout the following 24 h but did not increase in controls. CONCLUSIONS: High concentrations of benzene induce an inflammatory response and possibly fragmentation of DNA in respiratory epithelial cells. These findings have to be discussed with respect to possible mutagenic or carcinogenic effects of benzene in nasal respiratory cells.

Adult↗

PubMedDate not supplied

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 applied solution. In a prospective study, nasal respiratory cells were harvested from healthy individuals and CBF was measured while cells were perfused with cell culture medium and the respective topical solution, using a Dvorak/Stotler exposure chamber. Controls were perfused with cell culture medium only. Video interference contrast microscopy was used to monitor CBF. A decrease of CBF occurred after application of all topical solutions used in this study. Except for clotrimazole, all solutions showed significantly stronger effects at high concentrations compared with diluted solutions. Our results indicate that topical application of antifungal, antibiotic, and antiseptic solutions may cause a marked impairment of mucociliary clearance. The strong dose dependence of these ciliotoxic effects indicates the need for a careful selection of the adequate concentration when using topical treatment in the nose.

Adult↗