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Objectives We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years. Methods Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF. Results Neither patient had recurrent microthrombotic disease during a 4-year follow-up. Conclusions As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment.

Molecular effects of various ablative and non-ablative laser treatments on human skin cells—especially primary effects on epidermal keratinocytes and dermal fibroblasts—are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated models exhibited dose-dependent morphological changes resulting in an almost complete recovery of the epidermis 5 days after irradiation. On day 5 after laser injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an upregulation of genes associated with tissue remodeling and wound healing (e.g., COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12 and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On the other hand, we detected a downregulation of matrix metalloproteinases (e.g., MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory cytokine IL1α. Overall, our findings substantiate the understanding of time-dependent molecular changes after CO2 laser treatment. The utilized 3D skin model system proved to be a reliable, accurate, and reproducible tool to explore the effects of various laser settings both on skin morphology and gene expression during wound healing.

Das Verstandnis der biologischen Effekte der Laserbestrahlung auf die menschliche Haut ist ein Schlussel zur Vermeidung von Komplikationen bei der Laserbehandlung. Molekulare Effekte verschiedener ablativer und nicht-ablativer Laserbehandlungen auf menschliche Hautzellen - insbesondere die direkten Effekte auf epidermale Keratinozyten und dermale Fibroblasten - sind bisher nicht vollstandig verstanden. Daher wurde zur Erganzung der bisherigen Erkenntnisse, die meist aus klinischen Beobachtungen und histologischen Untersuchung von Patientenhautbiopsien stammten, ein neuartiges in vitro 3D-Hautmodell fur die Untersuchung von Effekten der Laserbestrahlung auf die menschliche Haut entwickelt, das erstmals eine standardisierte Untersuchung zeitabhangiger molekularer Veranderungen nach Laserbehandlung ermoglicht. Diese Themen sind Gegenstand des vorliegenden Kapitels.

Background and objectives Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin. Materials and methods A microneedling device was used to treat full-thickness 3D skin models. Specimens were harvested at specified time points and qRT-PCR and microarray studies were performed. Frozen sections were examined histologically. Results Microneedling treatment caused morphological changes in the skin model resulting in an almost complete recovery of the epidermis five days after treatment. Microarray analysis identified an upregulation of genes that are associated with tissue remodeling and wound healing (e.g. COL3A1, COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1), immune cell recruitment (CCL11), and a member of the heat shock protein family (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory cytokines (e.g. IL1α, IL1β, IL24, IL36γ, IL36RN), and antimicrobial peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR analyses. Conclusion We present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. This data suggests that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as ablative laser therapies.

Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO

Retinoide haben eine Vielzahl an wichtigen Funktionen wie Regulation von Zellproliferation und -differenzierung und spielen eine wichtige Rolle im Korper, nicht zuletzt fur die Haut. Es erfolgt die Darstellung eines Uberblicks uber Einsatz, Wirk- sowie Nebenwirkungsspektren der pharmakologisch eingesetzten topischen und systemischen Retinoide. Es wurde eine Pubmed/Medline-Literaturrecherche insbesondere unter Berucksichtigung der aktuellen deutschsprachigen und englischsprachigen Literatur vorgenommen. Die Gruppe der pharmakologisch eingesetzten Retinoide umfassen naturliche wie auch synthetisch hergestellte Vitamin-A-Derivate. Wegen ihren Eigenschaften, den Keratinisierungsprozess und die epitheliale Differenzierung der Haut sowie die Proliferation von benignen und malignen Hautzellen zu beeinflussen, fanden Retinoide eine breite Anwendung im Bereich der Dermatopharmakologie. Retinoide sind effektive Medikamente mit weitem therapeutischem Spektrum und breiter klinischer Anwendung in der Dermatologie. Grundliche Kenntnisse uber Nebenwirkungen und eine umfassende Aufklarung des Patienten sind im sicheren Umgang mit Retinoiden essenziell.

A patient with mild oral allergy syndrome presented with a history of anaphylaxis induced by both hazelnuts and peaches. The ensuing work-up showed a double sensitization to proteins in both pathogenesis-related group 10 (e.g. Bet v1, Cor a1, Pru p1) and 14 (e.g. Pru p3, Cor a8). Such double sensitization profiles are increasingly being recognized in Europe.

Background: The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction’s phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation. Objective: The aim of this study was to assess drug-specific cytokine production by means of flow cytometry as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the LTT. Method: Peripheral blood mononuclear cells of 19 patients were incubated with culprit drugs (n = 28) or irrelevant antigens (n = 10). Ten healthy persons served as controls for all different drugs (n = 15). Intracellular interleukin (IL)-5, interferon (IFN)-γ and IL-10 production was investigated using flow cytometry. Accuracy of the flow cytometry test system was confirmed using different statistical tests, i.e. receiver operating characteristic curve and Mann–Whitney rank test. In addition, drug-specific secretion of IL-5, IL-2 and IFN-γ were analysed using enzyme-linked immunosorbent assay (ELISA). Results: Drug-specific cytokine production could be demonstrated in 75% of the patients using flow cytometry and in 79% using ELISA respectively. Combining ELISA and flow cytometry increased the sensitivity to 100%. Analysis of involved T-cell subsets [e.g. CD4+ or CD8+; T helper (TH) 1 or TH 2] allowed characterization of the in vitro lymphocyte reactivity pattern. Conclusions: Analysis of drug-specific cytokine production by means of flow cytometry proved a useful and reliable approach for the in vitro detection and characterization of drug hypersensitivities.

Contact sensitization to azole antimycotics is rare, even though they are widely used. We present the case of a man who developed allergic contact dermatitis due to topical application of a variety of antimycotics. Patch testing revealed positive reactions to clotrimazole, croconazole, oxiconazole and tioconazole. Cross-sensitivity was possible, but multiple sensitizations could not be excluded.

Background: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases.

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

Anaphylaxis represents a severe, systemic and potentially fatal hypersensitivity reaction that severely impairs the life of affected children and their caregivers. With an estimated life time prevalence of 0.05% to 2%, it is not a rare disease. Therefore every physician caring for children at risk for anaphylaxis should be familiar with this disease pattern. Foods are the most frequent triggers in children; less frequent causes include drugs and insect venom. Particularly in case of idiopathic anaphylaxis, systemic mastocytosis should be ruled out as a potential differential diagnosis in this age group as well. First line emergency treatment consists of parenteral epinephrine in a weight-adjusted dosage, and after cardiovascular stabilization systemic antihistamines and corticosteroids as well as inhaled beta-mimetics can be administered. Affected patients, their relatives and other caregivers should receive extensive training in order to guarantee an adequate emergency management of anaphylactic children.

Non-hereditary photodermatoses with well-known trigger factors and idiopathic light eruptions occur quite frequently during childhood and are at least temporarily associated with a marked impairment of quality of life in affected patients and their parents. Thus, it is crucial that the involved specialties are familiar with acquired UV-associated disorders in order to guarantee a quick diagnosis and effective therapy. Additionally, the recurrence of photodermatoses associated with potentially severe long-term complications has to be prevented. This requires a stringent prophylaxis that can only succeed after age-adapted instruction of the patient and parents.

Along with the history, skin tests and provocation tests, in vitro test procedures are essential for the adequate care for patients with allergies. While serological investigations of immediate-type allergic reactions primarily detect allergen-specific IgE antibodies, basophil activation tests with different read-out parameters are available for cellular diagnosis of immediate-type reaction patterns. If clinically necessary, further immunological methods (i. e. immunoblots, lymphocyte transformation tests) can be employed. New options are provided by allergen microarray technology, which makes it possible to determine not only the specific antigenic protein but also to analyze different epitopes.

Secondary food allergies to PR-10 proteins (Bet v1 homologues) are the most common food allergies in Germany. Clinically they present with an oral allergy syndrome (intraoral pruritus and perhaps swelling). When drinks containing PR-10 proteins are rapidly consumed, for example after sporting activities, large concentrations of allergen can be reached without any intraoral symptoms and then lead to anaphylaxis. This phenomenon has often been described for soja milk and occurred in our case with an apple drink with 60% fruit concentration. It seems likely that such cases of anaphylaxis are not adequately represented in the anaphylaxis registry.

Als Morbus Morbihan wird eine Sonderform der Rosazea bezeichnet, bei der durch eine verstarkte Beteiligung der Lymphgefase derbe, kaum eindruckbare Odeme im Gesichtsbereich entstehen. Wangen, Nase und Stirn sind besonders betroffen. Aktuell sind die Therapiemoglichkeiten dieser kosmetisch sehr storenden Erkrankung begrenzt. Allerdings sollten diese aufgrund eines oft sehr starken Leidensdruckes der Patienten nach Moglichkeit in Anspruch genommen werden. Hierin stellen wir neue aktuell verfugbare Therapieoptionen dar. In unserem Fallbeispiel konnten wir durch die systemische Gabe von Isotretinoin 30 mg/Tag uber einen Zeitraum von ca. 12 Monaten eine deutliche Besserung des Hautbefundes erreichen.

Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.

Mikroarrays gewinnen derzeit aufgrund ihrer vielfaltigen Anwendungsmoglichkeiten in unterschiedlichen Gebieten der Forschung und Entwicklung wie auch der Dermatopharmazie und Allergologie an Bedeutung. Mikroarrays sind plane Trager, auf deren Oberflache eine Vielzahl unterschiedlicher, aber in ihrer Position bekannter und adressierbarer DNA-Molekule oder Proteine immobilisiert sind. Seit wenigen Jahren steht zum Nachweis der Transkripte von aktivierten Genen die cDNA- und Oligonukleotidarraytechnologie zur Verfugung, zum Nachweis der Proteine aktivierter Gene die Antikorperarraytechnologie. Die Bestimmung von allergenspezifischem IgE in humanem Serum kann mit Allergenarrays erfolgen. Da die molekularen Mechanismen der Pathogenese von Hautkrebs und Entzundungsdermatosen sowie die Wirkung von Xenobiotika auf die Zellen der Haut in vielen Aspekten ungeklart sind, bieten neue Arraytechnologien die Moglichkeit zur Identifizierung von Markergenen und ermoglichen so die Entwicklung von neuen Therapiestrategien sowie von Prognose- und Diagnosesystemen.

Previous work has identified the optimal two-stage static mixing process for a small-scale pilot rig. Protocols for scale-up to any brewery process line have been specified. A full-size prototype has been installed in a cask ale brewery. In most cases superior product clarity was obtained when the prototype was operated. Unexpected further benefits were demonstrated from mixing downstream of the mixing system and also disturbance and subsequent resettlement in the cask.

In order to optimise the process of fining beer there is a need to model the process in terms of addition, mixing and flocculation. Mixing of beer and finings has been achieved in a small laboratory stirred vessel that enables exact characterisation of the shear conditions and residence time. The performance of the finings was evaluated after settling in Imhoff cones. Results identified an optimum mixing regime comprising two stages; a relatively vigorous and short duration first mix followed by a longer more gentle mix.

A patient with mild oral allergy syndrome presented with a history of anaphylaxis induced by both hazelnuts and peaches. The ensuing work-up showed a double sensitization to proteins in both pathogenesis-related group 10 (e.g. Bet v1, Cor a1, Pru p1) and 14 (e.g. Pru p3, Cor a8). Such double sensitization profiles are increasingly being recognized in Europe.

Retinoids are important in regulating cell proliferation and differentiation and play an important role in the body, including the skin.Our objective is to review the current medical literature regarding use, effects and side-effects of topical and systemic retinoids used for therapy.Pubmed/Medline electronic database was searched for relevant German and English literature.The group of retinoids used for therapeutic purposes includes both naturally occurring and chemically synthesized vitamin A derivates. Because of their influence on keratinization and epithelial differentiation, as well on the proliferation of benign and malignant keratinocytes, retinoids have found a wide application in the field of dermatopharmacology.Retinoids are among the most efficacious drugs used in the treatment of dermatological disorders and have a wide range of biological effects. Thorough knowledge about side-effects and comprehensive information for the patient are essential for safe treatment with retinoids.

Prenatal ultrasonographic (US) detection of congenital adenomatoid malformation (CAM) was made in 18 fetuses at 17–36 weeks' gestation and managed in our institution during a 10-year period (1985–1994). The lesion was left-sided in 13 cases, right-sided in 4, and bilateral in 1. According to Stocker's classification, 12 cases were type I, 4 type II, and 2 type III. The prenatal course was followed with serial US examinations in 13 cases; the size of the lesion was stable in 8 and decreased in 5. Mediastinal shift was usually observed, and amniotic fluid volume was increased in 4 cases. One fetus was aborted. Six infants presented with respiratory distress syndrome and required neonatal surgery; delayed surgery was performed in 9 cases. Spontaneous regression of the lesion was observed on follow-up in 2 cases. Surgery consisted in lobectomy in 8 cases and segmentectomy in 6. The presence of fetal hydrops, type III lesions, and bilateral lung involvement are prenatal factors known to be associated with a poor prognosis. However, this series and a review of the literature suggest that caution should be observed with regard to the initial impression when counseling the parents regarding prognosis.

Secondary food allergies to PR-10 proteins (Bet v1 homologues) are the most common food allergies in Germany. Clinically they present with an oral allergy syndrome (intraoral pruritus and perhaps swelling). When drinks containing PR-10 proteins are rapidly consumed, for example after sporting activities, large concentrations of allergen can be reached without any intraoral symptoms and then lead to anaphylaxis. This phenomenon has often been described for soja milk and occurred in our case with an apple drink with 60% fruit concentration. It seems likely that such cases of anaphylaxis are not adequately represented in the anaphylaxis registry.

Morbihan disease is classified as a special form of rosacea, which presents with persistent facial erythema and solid edema because of marked involvement of the lymphatic vessels. The cheeks, nose and forehead are particularly affected. Currently, the treatment options of this cosmetically very disturbing disease are limited. However, every attempt should be made to provide treatment because of the great emotional suffering of the patients. We review some new currently available therapeutic options for Morbihan disease. In our patient, we were able to achieve a significant improvement with systemic isotretinoin 30 mg/day over a period of 12 months.

Eine Allergie gegenuber menschlicher Spermaflussigkeit ist eine selten diagnostizierte, jedoch potenziell lebensbedrohliche Erkrankung, die sich sowohl als lokale als auch in Form einer systemischen Reaktion manifestieren kann. Wir berichten uber eine 30-jahrige Frau, bei der es nach ungeschutztem Geschlechtsverkehr zu Juckreiz, Rotung und Schwellung vaginal und perivaginal sowie zu Urtikae am Stamm und Angioodemen nuchal und fazial gekommen war. Mittels Scratchtest und Nachweis von spezifischem IgE konnte eine Allergie vom Soforttyp gegenuber Spermaflussigkeit nachgewiesen werden. Risikofaktoren und mogliche Therapieoptionen werden diskutiert.