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  • van Hage-Hamsten, M, et al. (författare)
  • Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis
  • 2002
  • Ingår i: Clinical and Experimental Allergy. - Wiley. - 1365-2222. ; 32:10, s. 1448-1453
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. Results All 10 patients tolerated the highest accumulated dose, 8.124 mug, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
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  • Östensson, Ellinor, et al. (författare)
  • The economic burden of human papillomavirus-related precancers and cancers in Sweden
  • 2017
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • High-risk (HR) human papillomavirus (HPV) infection is an established cause of malignant disease. We used a societal perspective to estimate the cost of HR HPV-related cervical, vulvar, vaginal, anal, and penile precancer and cancer, and oropharyngeal cancer in Sweden in 2006, 1 year before HPV vaccination became available in the country. Materials and methods This prevalence-based cost-of-illness study used diagnosis-specific data from national registries to determine the number of HR HPV-related precancers and cancers. The HR HPV-attributable fractions of these diseases were derived from a literature review and applied to the total burden to estimate HR HPV-attributable costs. Direct costs were based on health care utilization and indirect costs on loss of productivity due to morbidity (i.e., sick leave and early retirement) and premature mortality. Results The total annual cost of all HR HPV-attributable precancers and cancers was €94 million (€10.3/inhabitant). Direct costs accounted for €31.3 million (€3.4/inhabitant) of the total annual cost, and inpatient care amounted to €20.7 million of direct costs. Indirect costs made up €62.6 million (€6.9/inhabitant) of the total annual cost, and premature mortality amounted to €36 million of indirect costs. Cervical precancer and cancer was most costly (total annual cost €58.4 million). Among cancers affecting both genders, anal precancer and cancer, and oropharyngeal cancer were the most costly (€11.2 million and €11.9 million, respectively). For oropharyngeal cancer, males had the highest health care utilization and represented 71% of the total annual cost. Penile precancer and cancer was least costly (€2.6 million). Conclusion The economic burden of HR HPV-related precancers and cancers is substantial. The disease-related management and treatment costs we report are relevant as a point of reference for future economic evaluations investigating the overall benefits of HPV vaccination in females and males in Sweden.
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  • Abolhalaj, Milad, et al. (författare)
  • Profiling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils.
  • 2018
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 8:8030
  • Tidskriftsartikel (refereegranskat)abstract
    • Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop effective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, flow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset-selective biomarkers associated with tonsillar cancer. We describe, for the first time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c-CD141- myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specific for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of effector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by different DC subsets in malignant tonsils and confirm expression of CD206/MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer.
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  • Ahlström-Emanuelsson, Cecilia, et al. (författare)
  • Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.
  • 2007
  • Ingår i: Respiratory Medicine. - Elsevier. - 1532-3064. ; 101:6, s. 1106-1112
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. White available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. Objective: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. Methods: Patients were examined in a pollen season model. Budesonide 64 mu g, alone and in combination with formoterot 9 mu g, as well as formoterot 9 mu g alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobutin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. Results: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobutin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. Conclusion: The present dose of formoterot does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.
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  • Ahlström-Emanuelsson, Cecilia, et al. (författare)
  • Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
  • 2002
  • Ingår i: Annals of Allergy, Asthma & Immunology. - American College of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
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  • Alenmyr, Lisa, et al. (författare)
  • Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.
  • 2012
  • Ingår i: Basic & Clinical Pharmacology & Toxicology. - Wiley-Blackwell. - 1742-7843. ; 110, s. 264-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.
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