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Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Anaphylaxis is an acute, potentially fatal, systemic hypersensitivity reaction that warrants prompt diagnosis and management. It continues to be challenging to anticipate who may be at risk of a severe, life-threatening allergic reaction. Anaphylaxis can be caused by a range of allergens, such as certain foods, medications, latex, insect stings, etc. Cofactors that augment the severity of clinical symptoms and increase the risk of poor outcomes include exercise, stress, infectious diseases, underlying mast cell disease, active allergic disease such as asthma, advanced age, intake of certain medications, history of previous anaphylaxis, and delayed or missed administration of adrenaline. According to the European Anaphylaxis Registry, food is the major elicitor of anaphylaxis, especially eggs, cow milk, and nuts, in children and adolescents. Reaction to insect venom has also been noted in young adulthood. Early recognition of signs and symptoms and prompt treatment are crucial in anaphylaxis management to avoid serious and even fatal outcomes. It is crucial for both individuals and clinicians to identify the cause of anaphylaxis. Biomarkers of anaphylaxis, such as histamine, tryptase, platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, CCL-2, hsa-miR-451a, may be useful in diagnosis and management. The purpose of this review article is to present a comprehensive overview of current evidence and expert opinions regarding the risk factors that predispose individuals to anaphylaxis. Additionally, it provides insights into potential biomarkers and genetic markers for accurate diagnosis and management. This review underscores the significance of expert guidance in enhancing patient outcomes and enabling self-management of anaphylactic episodes.

Abstract Background Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first‐line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self‐administrable devices, especially in community settings. Different commercial AAIs have been authorized to be marketed in Europe. For an AAI to be efficacious, a rapid adrenaline delivery in patients, including those who are overweight or obese, resulting in an optimal cardiovascular (CV) response, is a key feature. AAIs are designed to achieve this requirement, which is reflected in their differing functional properties such as primary container selection, drug delivery mechanism (cartridge‐or syringe‐based), needle length, needle gauge, and adrenaline dose (150 μg, 300 μg, or 500 μg). However, the differences in functional properties across these devices may play a critical role in achieving these requirements as well as the differences in ergonomics in the handling of these devices. The purpose of this review Considering the dynamic pharmacokinetic/pharmacodynamic (PK/PD) profiles of different AAIs marketed in Europe and their effect on adrenaline delivery, the expert panel, also serving as author for this paper have carried out a detailed analysis of the PK/PD profiles of four AAIs, namely, Anapen, Emerade, EpiPen, and Jext, to delineate the adrenaline delivery and their subsequent physiological effects on the backdrop of device characteristics, dose strength, and the skin‐to‐muscle distances of the participants.

Background: Immunoglobulin E (IgE) blood tests are used to detect sensitizations and potential allergies. Recent studies suggest that specific IgE sensitization patterns due to molecular interactions affect an individual's risk of developing allergic symptoms. Objective: The aim of this study was to reveal specific IgE sensitization patterns and investigate their clinical implications in Hymenoptera venom allergy. Methods: In this cross-sectional study, 257 hunters or fishers with self-filled surveys on previous Hymenoptera stings were analyzed. Blood samples were taken to determine Hymenoptera IgE sensitization levels. Using dimensionality reduction and clustering, specific IgE for 10 Hymenoptera venom allergens were evaluated for clinical relevance. Results: Three clusters were unmasked using novel dimensionality reduction and clustering methods solely based on specific IgE levels to Hymenoptera venom allergens. These clusters show different characteristics regarding previous systemic reactions to Hymenoptera stings. Conclusion: Our study was able to unmask non-linear sensitization patterns for specific IgE tests in Hymenoptera venom allergy. We were able to derive risk clusters for anaphylactic reactions following hymenoptera stings and pinpoint relevant allergens (rApi m 10, rVes v 1, whole bee, and wasp venom) for clustering.

Introduction: Patients with atopic dermatitis (AD) have several potential stressors including the symptoms of the disease itself, the stigmatization due to their appearance, and emotional and psychological strain. Psychological factors and stress can trigger and exacerbate the symptoms of skin diseases and there is evidence that stress has a relevant clinical effect on the function of skin cells in vivo. Our objective was to evaluate in a pilot study the feasibility, acceptance, and effectiveness of a Mindfulness-Based Stress Reduction (MBSR) programme in AD patients in a clinical setting. Methods: 10 patients took part in an 8-week MBSR programme, which included, e.g., mindful and conscious awareness of the body and bodywork, and seated meditation. We assessed sociodemographics and disease related variables with standardized measures at predefined time points including Score of Atopic Dermatitis, Patient Oriented Eczema Measure, Dermatology Life Quality Index, Perceived Stress Questionnaire, Freiburg Mindfulness Inventory (FMI), and others. Participants also gave qualitative feedback regarding the effects of the intervention. Results: The mean age was 53.10 years (SD = 15.04), seven patients were female, and disease duration was 36.6 years (SD = 25.5). Calculating pre-post effect sizes (Cohen’s d), the FMI indicated significant improvement in the “presence” and “acceptance” subscales. There was also tendency for less stress. This was confirmed by the qualitative statements of the participants. Conclusions: The MBSR programme is feasible and acceptable for AD patients. Considering the long disease history and the severity of disease burden, the effects of this intervention seem promising as an adjunct to conventional treatments for patients with AD.

Abstract The pathophysiology of atopic dermatitis (AD) is highly complex and understanding of disease endotypes may improve disease management. Immunoglobulins E (IgE) against human skin epitopes (IgE autoantibodies) are thought to play a role in disease progression and prolongation. These antibodies have been described in patients with severe and chronic AD, suggesting a progression from allergic inflammation to severe autoimmune processes against the skin. This review provides a summary of the current knowledge and gaps on IgE autoreactivity and self-reactive T cells in children and adults with AD based on a systematic search. Currently, the clinical relevance and the pathomechanism of IgE autoantibodies in AD needs to be further investigated. Additionally, it is unknown whether the presence of IgE autoantibodies in patients with AD is an epiphenomenon or a disease endotype. However, increased knowledge on the clinical relevance and the pathophysiologic role of IgE autoantibodies and self-reactive T cells in AD can have consequences for diagnosis and treatment. Responses to the current available treatments can be used for better understanding of the pathways and may shed new lights on the treatment options for patients with AD and autoreactivity against skin epitopes. To conclude, IgE autoantibodies and self-reactive T cells can contribute to the pathophysiology of AD based on the body of evidence in literature. However, many questions remain open. Future studies on autoreactivity in AD should especially focus on the clinical relevance, the contribution to the disease progression and chronicity on cellular level, the onset and therapeutic strategies.

Background: Allergies have an enormous individual and economic impact worldwide and affect more than one quarter of the population in Germany. Various factors influence the development of allergies: besides genetic predisposition the environment in which a person is raised and living also plays a role. The aim of the study was to evaluate differences in allergy prevalence in relation to age, sex, occupation, and living area (settlement structures). Methods: A cross-sectional study using a paper-based questionnaire about allergies was performed at the Munich Oktoberfest 2016. Participants were divided into 4 occupational groups and compared using descriptive statistics and multiple regression. Results: Overall, 2701 individuals (mean age 51.9 ± 15.3 years; 53.5% women) participated in the study. The overall rate of any self-reported allergy was 27.3% in the study population, in which women were more likely to be affected than men (OR = 1.82; 95% CI [1.50; 2.22]). Compared to farmers, all other occupational groups had a higher risk of reporting pollen allergies. Participants from rural areas (OR = 0.38; 95% CI [0.26; 0.58]) and suburban areas (OR = 0.44; 95% CI [0.30; 0.64]) were significantly less affected by allergies than participants from urban areas. Around 45.2% of the participants affected by allergies reported not receiving any treatment at all. Conclusion: Differences in the self-reported prevalence of allergies were shown for age groups, sex, living area, and occupation. Especially the reported pollen allergy prevalence ranged widely between different occupations, indicating that those individuals with an occupational exposure to pollen may have a lower risk than indoor workers. Overall, there remains a high need for sufficient treatment of allergies.

Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are limited. To estimate the annual extra out-of-pocket spending due to AE among patients in Europe, a cross-sectional study using computer-assisted phone interviewing of patients with AE was performed in 9 European countries. A total of 1,189 patients (56% women) with AE, who were either eligible for, or on, systemic treatment, participated in the study between October 2017 and March 2018. Mean extra spending on everyday necessities was €927 per patient per year for healthcare expenses, and this figure was slightly, but not statistically significantly, influenced by the severity of AE. Emollients and moisturizers accounted for the highest monthly costs, followed by medication that was not reimbursed, doctors’ and hospital costs. AE-related out-of-pocket costs pose a substantial burden for affected individuals, are higher than in other chronic diseases, and should always be included in economic assessments of the impact of this disease.

Purpose: This study aimed to assess the safety, efficacy, and patient satisfaction of superficial radiation therapy in the treatment of Peyronie's disease (PD) in a retrospective analysis. Methods and materials: We performed a retrospective analysis of 83 patients who underwent radiation therapy between 1999 and 2008 with 8 fractions of 4 Gy over a period of 6 months. With a mean follow-up time of 52 months, patients responded to a comprehensive questionnaire that covered patient characteristics, disease duration before radiation therapy, course of disease, treatment response, side effects, and patient satisfaction. Results: After a mean follow-up time of 52 months, 78% of the treated patients reported that PD progression had stopped. Furthermore 47% of patients had a symptom regression. Only 7% of patients reported PD progression. The penile curvature was improved in 49% of patients, and plaque induration could be reduced in 42% of patients. Moreover, 71% of patients reported substantial pain relief, as measured by a visual analogue scale (1 = not satisfied; 10 = very satisfied). Treatment satisfaction was rated with a median of 8 in a visual analogue scale out of 10. Side effects included transient erythema in 38.6% of patients and 9.6% reported of transient or chronic dryness. No severe side effects were observed. Conclusions: Radiation therapy for PD in the disease's early stages proved to be a safe and well-tolerated method with good results in pain relief, especially in patients aged

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Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.

ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

Summary Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by segmental accelerated aging and early death from coronary artery disease or stroke. Nearly 90% of HGPS sufferers carry a G608G mutation within exon 11 of LMNA, producing a truncated form of prelamin A, referred to as “progerin”. Here, we report the isolation of naïve multipotent skin-derived precursor (SKP) cells from dermal fibroblast cultures from HGPS donors. These cells form spheres and express the neural crest marker, nestin, in addition to the multipotent markers, OCT4, Sox2, Nanog and TG30; these cells can self-renew and differentiate into smooth muscle cells (SMCs) and fibroblasts. The SMCs derived from the HGPS-SKPs accumulate nuclear progerin with increasing passages. A subset of the HGPS-naïve SKPs express progerin in vitro and in situ in HGPS skin sections. This is the first in vivo evidence that progerin is produced in adult stem cells, and implies that this protein could induce stem cells exhaustion as a mechanism contributing to aging. Our study provides a basis on which to explore therapeutic applications for HGPS stem cells and opens avenues for investigating the pathogenesis of other genetic diseases.

Chloracne is the most sensitive and specific marker for a possible dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) intoxication. It is clinically characterized by multiple acneiform comedone-like cystic eruptions mainly involving face in the malar, temporal, mandibular, auricular/retroauricular regions, and the genitalia, often occurring in age groups not typical for acne vulgaris. Histopathology is essential for a definite diagnosis, which exhibits atrophy or absence of sebaceous glands as well as infundibular dilatation or cystic formation of hair follicles, hyperplasia of epidermis, and hyperpigmentation of stratum corneum. The appearance of chloracne and its clinical severity does not correlate with the blood levels of dioxins. Pathogenesis of chloracne remains largely unclear. An “aryl hydrocarbon receptor”-mediated signaling pathway affecting the multipotent stem cells in the pilosebaceous units is probably the major molecular mechanism inducing chloracne. Chloracne is resistant to all the available treatment modalities used to treat acne. The aim of treatment is to lower or to eliminate the accumulated dioxins in the body at the very beginning of intoxication, e.g., by using dioxin-chelating substances such as synthetic dietary fat substitutes. The problem of dioxin contamination and its potential health hazards should be taken seriously in the wave of industrial globalization in the twenty-first century. Clinicians, especially dermatologists, are in the forefront of early diagnosis of dioxin intoxication.

Abstract is missing (Short communication)

History of the World Allergy Organization: In 1951, the leaders in allergy from all over the world came together to form the International Association of Allergology and Clinical Immunology (IAACI). For the next 60 years, the allergy world converged at the IAACI triennial meetings, which became biennial in 2003. The international meetings, originally named the International Congress of Allergology and Clinical Immunology (ICACI), are now the World Allergy Congress (WAC) hosted by the World Allergy Organization (WAO). Everyone who has aspired to have worldwide recognition has played a part in IAACI-WAO. The History of the World Allergy Organization traces the global arc of the allergy field over the past 60 years. The current officers of WAO elected to focus on this rich history, inviting prominent leaders who are interested in being part of this history project to write about their time with IAACI-WAO. This series will be presented in Cancún, México, as part of the XXII World Allergy Congress (December 4-8, 2011). Leading up to the Congress in Cancún, the World Allergy Organization Journal is presenting segments of the History as part of the ''Notes of Allergy Watchers Series.'' Please enjoy.--Michael A. Kaliner, MDHistorian and Past President (2006-2007)World Allergy Organization Key-words: World Allergy Organization, World Allergy Organization Journal, World Allergy Congress 2005, Allergy and Clinical Immunology News

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010.The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously).The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed. Keywords: anaphylaxis, risk factors, clinical diagnosis, epinephrine (adrenaline), antihistamines, glucocorticoids

Background: Allergic diseases represent an increasing problem in public health in most modern societies as their prevalence has risen markedly during recent decades. Nevertheless, the causes of this increase are not yet fully explained.Objective: We investigated the correlation of Western lifestyle pattern in varying intensity to the prevalence of atopic diseases in 5 small villages on Karkar Island, in northeast Papua New Guinea.Methods: Two hundred forty-eight native people from 5 villages on tropical Karkar Island have been included in this study. The degree of Western lifestyle was assessed (questionnaire and observation) for each village. The prevalence of atopic diseases was evaluated by personal and family history, physical and dermatological examination, skin prick test (10 allergens), and measurement of total and specific immunoglobulin E levels (20 common allergens).Results: The more easily accessible and thus more ''modern'' and westernized coastal villages showed a significantly higher prevalence of habitants suffering from atopic diseases than a traditional mountain village (6.8% vs 0.0%, P = 0.034, Fisher exact test). A total of 4.4% (11/248) of the examined islanders suffered from an atopic disease. Atopic eczema seems to be absent on Karkar Island.Conclusions: The results of this study suggest that so-called Western lifestyle may contribute to the development of atopic diseases. Keywords: allergy prevalence, atopic disease, modern versus traditional lifestyle, Westernization, infections, parasites, public health, tropics, Papua New Guinea, Karkar Island

Although the pathophysiology of immunoglobulin E (IgE)-mediated allergic rhinoconjunctivitis and bronchial asthma is rather well established, the role of allergy in atopic eczema (AE) is still controversial. By a technique called atopy patch test, aeroallergens like house dust mite, animal dander, or pollen were proven as relevant trigger factors in a subgroup of patients with AE. The atopy patch test is an epicutaneous patch test with such allergens known to elicit IgE-mediated reactions, and used for the evaluation of eczematous skin reactions. In a series of single-center and multicenter studies, a method was developed, standardized, and compared with other diagnostic techniques (radioallergosorbent test, skin prick test) in AE patients. With regard to clinical history, the most specific results were obtained with the atopy patch test (allergen-dependent, 69%-92%), whereas sensitivity was higher for skin prick test (range, 69%-82%) and specific IgE (range, 65%-94%). The characterization of a patient subgroup with relevant IgE-mediated allergy may lead to more efficient avoidance and eventually even specific immunotherapy strategies in the management of AE. Keywords: IgE, diagnostic techniques, atopy patch test, atopic eczema

Itch is the major symptom of many allergic or inflammatory skin diseases, yet it is still difficult to measure objectively. This article shows and updates the development and approaches of central nervous system investigation of itch.Human neuroimaging studies on the physiology and pathophysiology of itch sensation have been hampered by the lack of a reproducible ''on-off'' stimulus. Short-term alternating temperature modulation of histamine-induced itch has recently been shown to provide on-off characteristics.Recent studies with functional magnetic resonance imaging demonstrate that itch sensation in healthy volunteers is processed by a network of brain regions contributing to the encoding of sensory, emotional, attentional, evaluative, and motivational aspects of itch. Keywords: itch, cerebral processing, neuroimaging, histamine

Specific immunotherapy (SIT) protocols for nutritional allergens have only recently been established with a focus on oral allergy syndrome because of pollen cross-reacting antibodies. For these patients, a substantial number of studies have been published suggesting benefits from SIT. The situation in true anaphylaxis to food allergens such as peanut allergy is more complex, and therapeutic strategies are based on individual protocols rather than controlled studies. However, in defined cases, SIT represents a promising approach for a durable protection from life-threatening risks after accidental ingestion. Keywords: allergen-specific immunotherapy, food allergy, long-term effect

1575 veröffentlichte Rocco Rodio in Neapel in seinem Libro di ricercate eine Fantasia über den Kirchenhymnus “Ave maris stella”. Im Kontext der progressiven Beiträge zur Tastenmusik seiner italienischen Zeitgenossen Antonio Valente (1575), Claudio Merulo und Andrea Gabrieli erscheint Rodios Cantus firmus-Satz geradezu anachronistisch. Doch Rodios Intention ist die des Kontrapunktikers. Für ihn war die kontrapunktische Kunst die entscheidende Basis des kompositorischen Handwerkes. Rodios Intention wird beleuchtet durch das Umfeld seines Wirkens –den diskussionsfreudigen Akademien in Neapel– und durch Ereignisse in Rom und Palermo, die im Auftritt des Spaniers Sebastián Raval gipfeln. Ihren eigentlichen musikhistorischen Kontext findet Rodios „Ave maris stella“ in der (liturgischen) Orgelmusik von Antonio de Cabezón, Manuel Rodriguez Coelho und Jean Titelouze und vielleicht sogar von António Carreira.

[de] Ein großer Teil des Musikrepertoires für Tasteninstrumente im 16. Jahrhundert bestand aus intavolierter Vokalmusik - Bearbeitungen von Motetten, Messsätzen und Chansons. Markante und teilweise wenig bekannte Beispiele zeigen verschiedene Funktionen der Intavolierungen. Zu nennen sind das Organistenrepertoire (liturgisches Umfeld), die Musik zur Erbauung und Unterhaltung und die pädagogische Funktion. Als Bestandteil der Ars Organistum waren Intavolierungen wichtig um professionell das Improvisieren von Musik und das Komponieren zu erlernen. Exemplarisch dokumentieren besonders H. Scheidemann, die beiden Gabrielis, J. de Lublin, P. Philips, die beiden Cabezóns und einige anonyme Komponisten aus England und Frankreich, dass ihre Kunst des Intavolierens weit über den Übertragungsmodus hinausgeht, bis hin zum virtuosen Arrangement und zur kunstvollen Paraphrase. Die Intentionen der Komponisten in Verbindung mit den Möglichkeiten der Tasteninstrumente prägen den Charakter und den Umformungsgrad einer Intavolierung.

Background Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromilieu. As T helper cell differentiation not only depends on dendritic cell-derived cytokines but also on cell-cell-contact mediated mechanisms, we studied the expression of notch ligands and myeloid differentiation primary response protein 88 (MyD88) in dendritic cells matured in the presence of aqueous birch pollen extracts and pollen-associated E1-phytoprostanes.Methods Human monocyte-derived dendritic cells were stimulated with aqueous birch pollen extracts in the absence or presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta-1 and −4, jagged-1 and −2 and of myd88 were determined. Regulation of Delta-4 and MyD88 by aqueous pollen extracts was assessed on protein level. The contribution of notch signaling to T helper cell differentiation was analyzed in allogeneic T cell stimulation assays.Results In immature dendritic cells, stimulation with pollen extracts resulted in an induction of both delta and jagged notch ligands. The lipopolysaccharide-induced up-regulation of delta-1 and −4 and of myd88 was decreased by aqueous pollen extracts, whereas jagged expression was induced. Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on protein level. The Th2-skewing activity was contained in a fraction of aqueous pollen extracts enriched for molecules

A 21-year-old patient experienced asthmatic attacks when cleaning the cage of his budgerigar. Skin tests and radioallergosorbent test were positive to grass pollen and negative for budgerigar feathers and feces. When the food of the bird, a mixture of grain, was tested, a positive reaction to millet was found. Nasal provocation test with millet was positive. Specific immunoglobulin E antibodies against millet were detected in the radioallergosorbent test and in immunoblot analysis. The immunoblot showed specific immunoglobulin E antibodies against a 60-kd protein in millet of birdseed and against a 60-and 36-kd protein in common millet. Immediate-type allergy to millet is rare and occurs mostly as anaphylactic reaction after ingestion of millet but may also occur as asthmatic attack after inhalation of millet. Keywords: bronchial asthma, type I allergy, millet, bird food

There are two meanings for the terminology cyclic lamentations {Lamemtationes Jeremiae Prophetae): the liturgical cyclus combinâtes lections - number and the textportions of the lections differ by changing time and regions. But the focus of this essay lies on the musical cyclus. Returning musical sets or particels of sets will serve to structure and to attach the lamentation. Examples from the late 15th century show lamentations in a simple strophic form with strong orientation on cantus planus (tonus lamentationum). During the 16th century more elaborated cyclic forms had been composed - returning musical sets became paraphrased. They structure the musical cyclus while returning Jerusalem-sets have the function of a refrain. Cyclic elements are specific to the form of the lamentations. Many composers used them in a individual manner.

Psoriasis is characterized by an apoptosis-resistant and metabolic active epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell-induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis patients sensitized to nickel (n = 14) to investigate underlying mechanisms of psoriasis and ACD simultaneously. All patients developed a clinically and histologically typical dermatitis upon nickel challenge even in close proximity to pre-existing psoriasis plaques. However, the ACD reaction was delayed as compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole genome expression analysis revealed alterations in numerous pathways related to metabolism and proliferation in non-involved skin of psoriasis patients as compared to non-psoriatic individuals, indicating that even in clinically non-involved skin of psoriasis patients molecular events opposing contact dermatitis may occur. Immunohistochemical comparison of ACD reactions as well as in vitro secretion analysis of lesional T cells showed a higher Th17 and neutrophilic migration as well as epidermal proliferation in psoriasis, while ACD reactions were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these findings, we hypothesized an ACD reaction directly on top of a pre-existing psoriasis plaque might influence the clinical course of psoriasis. We observed a strong clinical inflammation with a mixed psoriasis and eczema phenotype in histology. Surprisingly, the initial psoriasis plaque was unaltered after self-limitation of the ACD reaction. We conclude that sensitized psoriasis patients develop a typical, but delayed ACD reaction which might be relevant for patch test evaluation in clinical practice. Psoriasis and ACD are driven by distinct and independent immune mechanisms.

BACKGROUND: Skin testing can expose allergic subjects to potential systemic reactions, sensitization against unrelated proteins, and increased risk of future sting reactions. Therefore the continuous improvement of in vitro diagnostic methods is desirable. Recombinant allergens have been shown to improve the sensitivity of specific IgE (sIgE) detection in vitro whilst no data is available regarding their application and reliability in basophil activation test (BAT). Here we aimed to compare the specificity and sensitivity of recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 in both specific IgE (sIgE) detection in vitro and basophil activation test. METHODS: sIgE detection by ELISA or ImmunoCAP and BAT towards the panel of recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 were performed in 43 wasp venom allergic patients with a history of anaphylactic reaction and sIgE seropositivity, as well as 17 controls defined as subjects with a history of repetitive wasp stings but absence of any allergic symptom. RESULTS: The BAT performed with the recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 markedly improved the specificity of diagnosis in wasp venom allergic subjects when compared to the respective sIgE detection in serum. CONCLUSIONS: BAT performed with the recombinant allergens Ves v 5, Ves v 3 and Ves v 1 provides an emerging highly specific in vitro method for the detection of wasp venom allergy, compared to the sIgE detection. Recombinant allergens applied to BAT represent a step forward in developing reliable in vitro tests for specific diagnosis of allergy.

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial / antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. “Eczema school” educational programs have been proven to be helpful. Keywords: Atopic dermatitis, Eczema, Therapy, Guideline

BackgroundEvidence is compelling for a positive correlation between climate change, urbanisation and prevalence of allergic sensitisation and diseases. The reason for this association is not clear to date. Some data point to a pro-allergenic effect of anthropogenic factors on susceptible individuals.ObjectivesTo evaluate the impact of urbanisation and climate change on pollen allergenicity.MethodsCatkins were sampled from birch trees from different sites across the greater area of Munich, pollen were isolated and an urbanisation index, NO2 and ozone exposure were determined. To estimate pollen allergenicity, allergen content and pollen-associated lipid mediators were measured in aqueous pollen extracts. Immune stimulatory and modulatory capacity of pollen was assessed by neutrophil migration assays and the potential of pollen to inhibit dendritic cell interleukin-12 response. In vivo allergenicity was assessed by skin prick tests.ResultsThe study revealed ozone as a prominent environmental factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond that, ozone induced changes in lipid composition and chemotactic and immune modulatory potential of the pollen. Higher ozone-exposed pollen was characterised by less immune modulatory but higher immune stimulatory potential.ConclusionIt is likely that future climate change along with increasing urbanisation will lead to rising ozone concentrations in the next decades. Our study indicates that ozone is a crucial factor leading to clinically relevant enhanced allergenicity of birch pollen. Thus, with increasing temperatures and increasing ozone levels, also symptoms of pollen allergic patients may increase further.

Background and Study Aims. The association between Helicobacter pylori (H. pylori) and chronic spontaneous urticaria (CSU) remains controversial. This study explored the role of H. pylori in CSU among different virulent genotypes patients. Patients and Methods. Patients infected by H. pylori were sorted into two groups as group A (with CSU) and group B (without CSU). The tissue materials were taken via endoscopy for polymerase chain reaction study to determine virulence factors. After H. pylori eradication therapy, the eradication rate and response of urticaria were evaluated by using C13-UBT and a three-point scale (complete remission, partial remission, or no improvement). Results. The results were comparable between patients of groups A and B in terms of H. pylori infection rates and eradication rate. Longitudinal follow-up of 23.5 months showed complete remission of urticaria in 63.6% but no improvement in 36.4% of the patients after H. pylori eradication. H. pylori infected patients with different virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin gene A signal region and middle region have similar remission rates for CSU. Conclusions. Current study suggests that H. pylori may play a role in the development and disease course of CSU but may be irrelevant to different virulent genotypes.

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 x 10(-20) and 7.08 x 10(-19) in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 x 10(-4) and P = 1.95 x 10(-3)). The "top" SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 x 10(-7)-4.46 x 10(-8)) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.

Background: A type-IV-allergic reaction to German camomile (Matricaria chamomilla) in a form of allergic contact dermatitis is not unusual. However, only a few cases of anaphylactic reaction to camomile have been described in the literature. Case Summary: We present the case of a 38-year-old Caucasian man who developed an episode of severe anaphylaxis with generalized urticaria, angioedema and severe dyspnoea one hour after consuming camomile tea. Laboratory examination demonstrated a total serum IgE of 123 kU/l with specific IgE against camomile (4.94 kU/l, class 3). Skin prick test and labial provocation test with camomile showed a strong positive reaction. Discussion: Our case confirms the presence of a type-I allergy to orally ingested camomile and indicates that the incidence and risk may be underestimated. Additonal response to mugwort and pollen-derived food allergens should be evaluated in patients sensitised to camomile due to a higher incidence of allergic cross-reactivity.

ZusammenfassungHintergrund: Zur Wirksamkeit der Homöopathie bei atopischem Ekzem (atopische Dermatitis, Neurodermitis constitutionalis atopica) liegen zwar eine Reihe von Kasuistiken, aber keine kontrollierten Therapiestudien vor. Methoden: Monozentrische, randomisierte Doppelblindstudie, in der individuell verordnete homöopathische Arzneien mit Placebo verglichen wurden. Eingeschlossen wurden junge Erwachsene im Alter von 18–35 Jahren mit atopischem Ekzem. Nach einer unbehandelten Eingangsperiode von 4 Wochen wurden alle Patienten 32 Wochen lang behandelt und beobachtet. Als Begleitmedikation waren nur indifferente Salben zugelassen. Hauptzielkriterium war der Multiparameter-Score (MP-Score) von Costa und Saurat. Ergebnisse: Von 744 gescreenten Patienten wurden 24 randomisiert und analysiert (10 Verum, 14 Placebo). Beide Gruppen waren zu Therapiebeginn vergleichbar, die Verumgruppe war allerdings signifikant schwerer erkrankt (p = 0,034, t-Test). 10 Patienten (5 je Gruppe) brachen die Studie vorzeitig ab, vor allem wegen Nicht-Wirksamkeit der Therapie und notwendiger Begleitbehandlungen. In beiden Gruppen fiel der MP-Score deutlich: in der Verumgruppe von 54,5 ±11,0 auf 40,7 ±12,5, in der Placebogruppe von 45,9 ±7,6 auf 32,7 ±21,8, was in einem leichten, nicht signifikanten Gruppenunterschied von 5,6 Punkten zugunsten der Placebogruppe mündete (CI: –9,0 bis 20,2; p = 0,46; ANCOVA). In den sekundären Zielparametern (Lebensqualität, Krankheitsverarbeitung, allgemeine Einschätzung des Therapieerfolgs) ergaben sich ebenfalls keine signifikanten Gruppenunterschiede (jeweils p > 0,15). Schlussfolgerungen: Individualisierte homöopathische Arzneien hatten in dieser Studie zum atopischen Ekzem keinen über Placebo hinausgehenden Effekt. Die Generalisierbarkeit der Ergebnisse ist aufgrund der geringen Fallzahlen und des hohen Prozentsatzes nicht eingeschlossener Patienten eingeschränkt.Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: The reaction of tissues to ionizing radiation involves alterations in cell-cell and cell-matrix interactions mediated by cellular adhesion molecules. The aim of this study was to develop and evaluate an artificial skin organ model for the analysis of radiation effects. Material and Methods: A human co-culture system consisting of the spontaneously immortalized keratinocyte cell line HaCaT and primary HDFa fibroblasts embedded into a collagen sponge was established. This skin organ model has been characterized and evaluated for its suitability for radiobiological investigations. For that purpose, expression of ß 1-integrin following irradiation was compared in the skin organ model and in HaCaT monolayer cells (FACScan and immunohistochemistry). Furthermore, the influence of ionizing radiation on DNA fragmentation was investigated in the skin organ model (TUNEL assay). Results: The novel skin organ model showed characteristics of human skin as demonstrated by cytokeratin and Ki-67 immunoreactivity and by electron microscopy. A single dose of 5 Gy X-irradiation induced an upregulation of ß 1-integrin expression both in the skin organ model and in HaCaT cells. Following irradiation, ß 1-integrin immunoreactivity was intensified in the upper layers of the epidermis equivalent whereas it was almost absent in the deeper layers. Additionally, irradiation of the skin organ model also caused a marked increase of DNA fragmentation. Conclusion: These results demonstrate that the novel skin organ model is suitable to investigate cellular radiation effects under three-dimensional conditions. This allows to investigate radiation effects which cannot be demonstrated in monolayer cell cultures. [ABSTRACT FROM AUTHOR]