Biomedical subjects

Jan Gosepath

Publications and source records attributed to Jan Gosepath.

8 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

Inverted malignant pilomatricoma of the neck.

Malignant pilomatricoma is an uncommon malignant follicular adnexal tumor with a predilection for the head and neck among older males. We report the case of a male with an inverted malignant pilomatricoma of the left neck. The initial diagnostics and the treatment pointed to carcinoma of unknown primary (CUP syndrome). The preoperative diagnostic tests included ultrasound examination, CT scan and fine-needle aspiration cytology. However, the preoperative diagnostics did not provide any further information, leading to doubts concerning the initially proposed diagnosis. Histology of the resected tumor revealed a malignant pilomatricoma. We report the clinical presentation and the management of this case and discuss the clinical and histological findings.

Hair Diseases↗

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↗

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↗

PubMedDate not supplied

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 repeated visits to the outpatient clinic of our institution. At each visit, their clinical symptoms as well as findings on anterior rhinoscopy, nasal endoscopy, and A-mode ultrasound were evaluated. RESULTS: Acute disease resolved completely within 10 days of treatment in 17 of the 20 patients. Two patients discontinued treatment after repeated visits, showing only mild improvement. One patient felt uncomfortable during the application of the Yamik catheter and did not continue after the initial treatment. CONCLUSION: Our results suggest that the Yamik catheter may be a helpful device in the topical treatment of acute rhinosinusitis and it appears possibly helpful in patients who suffer from episodes of acute purulent infection after previous sinus surgery.

Administration, Intranasal↗

PubMedDate not supplied

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 of controls consisted of five surgical specimens of acoustic neuroma, which were included to rule out contamination within the protocol. All paranasal tissue samples were treated and rinsed carefully with a solution of Dithiothreitol to digest any nasal mucus and ensure that only tissue was examined. A highly sensitive two-step polymerase chain reaction (PCR) was applied to detect fungal DNA, using one universal primer for unspecific detection of fungal DNA and a second primer pair specific for Alternaria. RESULTS: Fungal DNA was detected in all 27 CRS specimens equally with both PCR primers. Controls from healthy paranasal mucosa were positive using the panfungal primers in 10 of 15 cases but were all negative for Alternaria DNA. PCR was negative for fungal DNA in all five neuroma specimens. CONCLUSIONS: Fungal DNA can be detected within sinonasal tissue specimens of patients suffering from CRS. These findings need to be discussed with respect to the proposed hypothesis of the immune system recognizing extramucosal organisms and initiating an immune response in sensitized patients.

Adolescent↗