Doris Lang-Loidolt

Plasmapheresis reverses all side-effects of a cisplatin overdose – a case report and treatment recommendation

BackgroundCisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death.Case presentationWe report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m2 of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae.ConclusionTo date, no general accepted guidelines for the treatment of cisplatin overdoses are available. Along with the experience from other published cases, our report shows that plasmapheresis is capable of lowering cisplatin plasma and serum levels efficiently. Therefore, plasma exchange performed as soon as possible can ameliorate all side effects of a cisplatin overdose and be a potential tool for clinicians for treatment. However, additional intensive supportive treatment-modalities are necessary to control all occurring side effects.

Development of Molecular Methods for Identification of Schizophyllum commune from Clinical Samples

ABSTRACT In the last 50 years, to our knowledge, only 16 cases of diseases caused by Schizophyllum commune in humans have been reported. Within only 6 months, we found four isolates of this basidiomycetous fungus, obtained from patients suffering from chronic sinusitis. The cultures of the isolated fungi showed neither clamp connections nor fruiting bodies (basidiocarps), which are distinctive features for S. commune, but fast-growing cottony white mycelium only. This was harvested, and DNA was extracted. The internal transcribed spacer region of the ribosomal DNA (rDNA) was amplified with fungus-specific primers, and the PCR products were sequenced. Two strains of S. commune, collected from branches of a European hornbeam (Carpinus betulus) and a tree of heaven (Ailanthus altissima), respectively; four specimens from the herbarium of the Institute of Botany, Karl-Franzens-University Graz; and two strains from internationally known culture collections (CBS 340.81 [ATCC 44201] and CBS 405.96) were investigated in the same way. The sequence data of all strains were compared and showed homology of over 99% in this 660-bp-long fragment of rDNA. With these results, a map of restriction enzyme cutting sites and a primer set specific for S. communewere created for reliable identification of this human pathogenic fungus.

EP4 receptor stimulation down-regulates human eosinophil function

Accumulation of eosinophils in tissue is a hallmark of allergic inflammation. Here we observed that a selective agonist of the PGE2 receptor EP4, ONO AE1-329, potently attenuated the chemotaxis of human peripheral blood eosinophils, upregulation of the adhesion molecule CD11b and the production of reactive oxygen species. These effects were accompanied by the inhibition of cytoskeletal rearrangement and Ca2+ mobilization. The involvement of the EP4 receptor was substantiated by a selective EP4 antagonist, which reversed the inhibitory effects of PGE2 and the EP4 agonist. Selective kinase inhibitors revealed that the inhibitory effect of EP4 stimulation on eosinophil migration depended upon activation of PI 3-kinase and PKC, but not cAMP. Finally, we found that EP4 receptors are expressed by human eosinophils, and are also present on infiltrating leukocytes in inflamed human nasal mucosa. These data indicate that EP4 agonists might be a novel therapeutic option in eosinophilic diseases.

Seasonal proteome changes of nasal mucus reflect perennial inflammatory response and reduced defence mechanisms and plasticity in allergic rhinitis.

INTRODUCTION Nasal mucus and its proteins are a defence against allergens. We sought to investigate dynamic proteome changes in allergic rhinitis upon environmental allergen provocation. METHODS Nasal mucus was collected in and out of pollen season from allergic rhinitis patients (N=10) and healthy controls (N=12). Liquid chromatography-tandem mass spectrometry was performed. Proteins were identified by SwissProt database search and quantified from normalized areas under curve of precursor ion chromatograms. Gene enrichment analysis was performed with Cytoscape/BINGO software. RESULTS In total 430 different proteins were detected in both groups, 203 (47.2%) were newly identified. In allergics CLU and IGKC were significantly more abundant in season (2.2 and 2.1-fold respectively). GSTP1 (0.5-fold), ELANE (0.4-fold), HIST1H2BK (0.3-fold), S100A8 (0.2-fold), S100A12 (0.2-fold) and ARHGDIB (0.1-fold) were significantly less abundant in season. In healthy controls UBC, TUBA1B, HBB and FABP5 were only present in season. Ig kappa chain V-I region DEE (5.3-fold), CLU (5.0-fold), TXN (4.3-fold), MSMB (3.2-fold) and Ig heavy chain V-III region BRO (2.7-fold) were significantly more abundant in season. MUC5B (0.5-fold), SLPI (0.2-fold) and S100P (0.2-fold) were significantly less abundant in season. CONCLUSION Contrary to their symptoms allergic rhinitis patients show perennial inflammatory response lacking adequate reaction to allergens in season. BIOLOGICAL SIGNIFICANCE Many studies dealing with allergic rhinitis are focused on the nasal epithelium. This is the first study to analyse the nasal mucus as primary defence barrier on a proteomic level in and out of pollen season and contrary to the leading opinion shows that allergic patients show a perennial inflammatory response with reduced reaction to allergens whereas healthy controls react on proteome basis towards enhanced defence in season despite lacking allergic sensitization.

Potential correlations of dentogenic factors to the development of clinically verified fungus balls: A retrospective computed tomography–based analysis

Fungus balls are a common disease of the paranasal sinuses, usually involving the maxillary sinus. To clarify the pathology, we analyzed patients treated for maxillary sinus fungus balls to see whether the latter correlated with dentogenic factors.

Apolipoproteins have a potential role in nasal mucus of allergic rhinitis patients: A proteomic study

Nasal mucus is a defense barrier against aeroallergens. We recently found apolipoproteins to be elevated in the nasal mucus of allergic rhinitis patients. Apolipoproteins are involved in lipid metabolism, have immunomodulatory properties, and may represent interesting novel biomarkers. This study aims to validate our findings and analyze whether the increased abundance of apolipoproteins in nasal mucus is a local or systemic phenomenon in allergic rhinitis.

Are stents beneficial in endoscopic choanal atresia repair of newborns and children? Case series of 11 patients.

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Altered Inhibitory Function of the E-Type Prostanoid Receptor 4 in Eosinophils and Monocytes from Aspirin-Intolerant Patients

Prostaglandin (PG) E2 has been implicated in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). E-type prostanoid (EP) receptor 4 is known to confer inhibitory signals to eosinophils and monocytes, amongst others. In this study, we investigated whether the responsiveness of eosinophils and monocytes to PGE2 and EP4 receptor activation is altered in AERD patients. While the expression of the EP4 receptor in eosinophils was unaltered in AERD patients, inhibition of eosinophil chemotaxis by PGE2 or the EP4 agonist CAY10598 was less pronounced in AERD patients as compared to healthy control subjects. In monocytes, we found no changes in basal or lipopolysaccharide (LPS)-stimulated PGE2 synthesis, but the response to EP4 receptor activation with respect to inhibition of LPS-induced tumor necrosis factor-α release was reduced in AERD patients, especially in the presence of aspirin (acetylsalicylic acid). Our data point towards a decreased sensitivity of inhibitory EP4 receptor that may play a role in AERD.

Extracts of different pollen species and their effect on human tear fluid and an epithelial cell line

Abstract Purpose: Hazelnut and birch pollen are known to destroy tear film components and attack ocular surface cells. We investigated further pollen species from different plant families, whether they show similar effects on human tear fluid and an epithelial cell line in vitro, to provide a broad basis for further research on pollen reactions affecting the tear film and ocular surface. Materials and methods: Regional pollen species from different plant families (Adoxaceae, Betulaceae, Fagaceae, Juglandaceae, Malvaceae, Oleaceae, Pinaceae, Plantaginaceae, Poaceae, Salicaceae, Sapindaceae) were collected. Their proteolytic activity was evaluated by Zymography. Human tear fluid and cells of an epithelial cell line were incubated with pollen extracts. Tear fluid was analyzed by Polyacrylamide gel electrophoresis (PAGE). Cytomorphology was assessed microscopically and cell viability by proliferation (MTS), water-soluble tetrazolium (WST-1) assay and the impedance-based xCELLigence real-time analysis (RTCA). Results: Zymography revealed significant protease activity and PAGE showed the degradation of tear proteins by different pollen species. Cells incubated with pollen extracts presented dose- and time-dependent cytomorphological changes. MTS, WST-1, and RTCA revealed cytostatic as well as cytotoxic effects of pollen extracts. Conclusions: Pollen species from different plant families exert proteolytic activity and degrade human tear fluid as well as epithelial cells, which may play a crucial role in the pathogenesis of allergic and non-allergic reactions affecting the ocular surface.

Comparison of tear proteome in allergic rhinoconjunctivitis patients and controls with respect to pollen season.

Tear fluid comprises electrolytes, lipids, mucins and proteins among other components [1]. Tear composition reflects the physiological condition of underlying tissue but can be altered in disease related to the eye or other organs and systemic diseases like diabetes [2]. Several tear proteomic studies for diseases other than allergic rhinoconjunctivitis exist proofing the feasibility of proteomic approaches to tear fluid [3-6]. This article is protected by copyright. All rights reserved.