Urticaria

Urticaria is a very common skin disease which was already described in the ancient world. Questions still remain about its pathogenesis and management remain open. Compared to other common skin diseases, the published evidence is rather low. The clinical symptoms with pruritic transient wheals and/or angioedema are caused by mediators (particularly histamine) released by activated mast cells and basophils. The mechanism of target cell activation has not been clarified in detail for most urticaria subtypes. Different urticaria subtypes should be distinguished. Spontaneous forms are more common than inducible forms. Chronic urticaria and urticaria in certain age groups (children, pregnancy) can be difficult to manage. Therefore, international consensus resulting in the regular update of urticaria guidelines can be very helpful. Currently, these updated guidelines include a three‐step treatment algorithm for chronic spontaneous urticaria. Only the first step of this algorithm, second generation H1‐antihistamine in standard dose, utilized approved drugs. However after omalizumab was established as a third line choice in the guideline algorithm, it has approved in many countries for chronic spontaneous urticaria without response to H1‐antihistamines. The exact mechanism of action of omalizumab in urticaria has not been fully elucidated. Unrevealing this mechanism might result in a deeper understanding of urticaria pathogenesis and the development of further therapeutic strategies.     

Kontaktallergie auf Dentalmaterialien

The oral mucosa is constantly exposed to a large number of potentially irritating and sensitizing dental materials. Dental materials used for fillings and fixed or removable replacements must have a good biocompatibility. Metals including palladium are used in alloys for the production of the core of crowns, onto which porcelain is bonded for the generation of an artificial tooth to which the patient can develop an allergic contact dermatitis. The clinical manifestations of contact allergy to dental materials are not uniform. Objective symptoms of a contact allergy include a stomatitis and lichenoid reactions. However, patients may present with more subjective affections of the oral mucosa including burning, pain and dryness which need to be differentiated from a real contact allergic reaction. In this article we focus on the management of contact allergy to dental materials.     

Classification and management of tracheoesophageal and tracheopharyngeal fistulas after laryngectomy

OBJECTIVES: Tracheoesophageal fistulas (TEF) and tracheopharyngeal fistulas (TPF) are intentionally created for prosthetic or surgical voice restoration after laryngectomy or can develop after radiotherapy or surgical interventions. If the fistula does not shrink or close spontaneously or does not respond to conservative measures, surgical closure of the fistula is indicated. STUDY DESIGN: Retrospective study of 177 patients. METHODS: Data of 168 laryngectomy patients who needed a voice prosthesis (VP) replacement were obtained. Our experiences with nine severe TEF/TPF were analyzed, and a classification of these fistulas depending on the anatomic and clinical appearance was developed. RESULTS: TEF/TPF can be divided into five types: high TEF with leakage through the VP (type Ia), high TEF with leakage around the VP (type Ib), enlarged high TEF (type II), deep TEF (type III), TPF (type IV), and TPF associated with pharynx stenosis (type V). Persisting TEF/TPF after unsuccessful attempts at surgical closure in four patients and the surgical solutions and procedures in these rare cases are discussed in detail. CONCLUSIONS: Leakage of TEF in prosthetic voice restoration usually responds well to conservative measures. If these measures fail, and in all cases of TPF, surgical intervention is necessary for transtracheostomal or transcervical closure with multilayer sutures of the esophagus and trachea. Persisting TEF/TPF after unsuccessful surgical attempts at revision surgery remain challenging. Our experiences show that tracheostoma transposition for dissociation of the cranial end of the trachea and the hypopharynx and esophagus is essential for effective closure. In rare cases of TPF combined with pharyngoesophageal stricture formation, a resection and immediate reconstruction of the stenotic pharyngoesophageal segment with a tube-shaped fasciocutaneous radial forearm flap must be considered.     

Role of extracellular adenosine triphosphate in the cytotoxic T- lymphocyte-mediated lysis of antigen presenting cells

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma- activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.     

The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Background  

It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis.