Food-induced anaphylaxis and cofactors - data from the anaphylaxis registry.

Food allergens are frequent causes of anaphylaxis. In particular in children and adolescents they are the most frequent elicitors of severe allergic reactions, and in adults food allergens rank third behind insect venom and drugs. Since July 2006 severe allergic reactions from Germany, Austria, and Switzerland are collected in the anaphylaxis registry. Currently 78 hospitals and private practises are connected. From July 2006 until February 2009 1,156 severe allergic reactions were registered. Among children and adolescents (n = 187, age range from 3 months to 17 years) food allergens were the most frequent triggers, comprising 58% of cases. In the adult group (n = 968, 18 - 85 years) food allergens were in the third position (16.3%) behind insect venom and drugs. In children legumes (31%) and in particular peanuts were frequently responsible food allergens, followed by tree nuts (25%) with hazelnut being the most frequent elicitor. In adults fruits (13.4%) most often induced severe food-dependent anaphylaxis, but also animal products (12.2%); among these most frequently crustaceans and molluscs. Cofactors were often suspected in food-dependent anaphylaxis, namely in 39% of the adult group and in 14% of the pediatric group. In adults drugs (22%) and physical activity (10%) were reported to be the most frequent cofactors, in children physical activity was suspected in 8.7% and drugs in 2.6%. Concomitant diseases like atopic dermatitis, allergic asthma, or allergic rhinoconjunctivitis were reported in 78% of children and adolescents and in 67% of the adults. In conclusion, food-induced anaphylaxis, its cofactors and concomitant diseases are age-dependent. The data offers to identify risk factors of anaphylaxis.

[Intubating laryngeal tube suction disposable: Initial clinical experiences with a novel device for endotracheal intubation]. / Intubationslarynxtubus Suction Disposable: Erste klinische Erfahrungen mit einem neuen Hilfsmittel zur endotrachealen Intubation.

BACKGROUND: According to the recent guidelines supraglottic airways, such as laryngeal tubes are recommended to ensure oxygenation in patients with unexpected difficult airways. The novel Intubating Laryngeal Tube Suction Disposable (iLTS-D) is a modified laryngeal tube designed for secondary tracheal intubation. This pilot study evaluated the use of the iLTS-D in clinical practice with respect to practicality and efficacy. METHODS: In this study the airways of 30 consecutive adult patients with no evidence of a difficult airway undergoing elective ear, nose and throat (ENT) surgery were managed with the iLTS-D. After induction of anesthesia the iLTS-D was placed in position and checked for correct ventilation. Following muscle relaxation, endotracheal intubation through the iLTS-D was performed under continuous visualization using a flexible bronchoscope. Finally, the iLTS-D was removed leaving the endotracheal tube in place. Data were collected anonymously as part of a quality assurance program. Publication of the data was approved by the institutional review board. RESULTS: Initial iLTS-D placement took a median of 17 s (range 12-90 s) and provided sufficient ventilation in all patients; however, the position of the iLTS-D needed to be adjusted in four patients. Endotracheal intubation through the iLTS-D was achieved in 29 out of 30 patients at the first attempt (n = 23) or after 2 attempts (n = 6) and the median time required for intubation was 32 s (range 18-187 s). In five patients no laryngeal structures could initially be identified by bronchoscopy. Blind endotracheal intubation through the iLTS-D was performed in two cases and in two other patients the endotracheal tube was also blindly advanced but into the esophagus. After removal of the endotracheal tube and repositioning of the iLTS-D, successful tracheal intubation was subsequently achieved under bronchoscopic vision. The procedure was aborted and uneventful conventional intubation using direct laryngoscopy was carried out in one patient. The median time for removal of the iLTS-D after successful intubation was 20 s (range 15-80 s). Minor blood stains on the iLTS-D were observed in three patients. With one exception, all problems and adverse events occurred during the first 10 patients. CONCLUSION: This first clinical study demonstrated that in patients with apparently normal airways and in the hands of users without previous experience, the iLTS-D allowed sufficient ventilation in all patients and had a high success rate for subsequent endotracheal intubation. The results are, however, preliminary until confirmed by further studies, particularly in patients with difficult airways.

[Histology after tonsillectomy?]. / Histologie nach Tonsillektomie?

BACKGROUND: The necessity to rule out clinically occult malignancies by routine histological examination of all tonsillectomy specimens is a controversial topic. METHODS: Clinical and histological findings of all patients who underwent tonsillectomy at the University of Bonn, Germany from January 2002 to March 2007 were retrospectively reviewed. A meta-analysis of PubMed literature regarding the histological results of tonsil specimens was performed. The incidence of clinically occult tonsil malignancy was recorded and potential risk factors for malignancy were analyzed. A cost-effectiveness ratio of microscopic analysis of all specimens was also performed. RESULTS: Clinically occult tonsil malignancies were detected in 2 out of the 1,523 patients (0.13%) in this study. In the meta-analysis of 24 studies (61,550 patients) 6 cases of clinically occult tonsil malignancies (0.01%) were identified. Statistically 7,694 tonsils have to be histologically examined to detect 1 case of occult malignancy which corresponds to an average cost per case of 385,000 EUR. DISCUSSION: Considering economical aspects we recommend that histological examination should be performed when the following risk factors are present: a history of cancer, tonsil firmness or lesions, tonsillar asymmetry, swelling of neck lymph nodes, constitutional symptoms, anamnestic unilateral symptoms and prior peritonsillar abscess.

[Tissue engineering of respiratory epithelium. Regenerative medicine for reconstructive surgery of the upper airways]. / Tissue-Engineering von respiratorischem Epithel. Regenerative Medizin für die rekonstruktive Chirurgie der oberen Atemwege.

Reconstruction of long tracheal defects remains an unsolved surgical problem. Tissue engineering of respiratory epithelium is therefore of utmost surgical and scientific interest. Successful cultivation and reproduction of respiratory epithelium in vitro is crucial to seed scaffolds of various biomaterials with functionally active respiratory mucosa. Most frequently, the suspension culture as well as the tissue or explant cultures are used. Collagenous matrices, synthetic and biodegradable polymers, serve as carriers in studies. It is essential for clinical practice that mechanically stable biomaterials be developed that are resorbable in the long term or that cartilaginous constructs produced in vitro be employed which are seeded with respiratory epithelium before implantation. Vascularization of a bioartificial matrix for tracheal substitution is also prerequisite for integration of the constructs produced in vitro into the recipient organism. Here, the state of the art of research, perspectives and limitations of tracheal tissue engineering are reviewed.

[Proliferation and differentiation of human osteoblasts from the nasal septum in a new perfusion culture system]. / Vermehrung und Differenzierung humaner Nasenseptum-Osteoblasten. Ein neuartiges Perfusionskultursystem.

BACKGROUND: Today, perfusion culture systems are mainly used to investigate cellular physiology and to cultivate three-dimensional tissue complexes. As a rule, these systems are relatively expensive and do not enable continuous microscopic monitoring of the growing cells. Simple and inexpensive perfusion culture systems have not been available up to now. METHODS: A novel perfusion culture system was developed in which the modular components consist of a mounting apparatus for inserting various media supply systems, microdispenser pumps, and laminar-flow culture chambers, each with a culture volume of 8 cm(3). The perfusion chambers were inoculated with human osteoblast cells from the tissue culture (5,000/cm(2)) and were perfused for 10 days after adherence of the cells (0.5 ml/min). As a control group, osteoblast-like cells were cultured in identically constructed culture chambers without medium perfusion. After 10 days, the cell counts were determined in accordance with the Coulter principle. Alkaline phosphatase was measured photometrically as a characteristic for differentiation. RESULTS: Compared with the control group, three to four times the quantity of cells were produced within 10 days in the perfusion cultures. The alkaline phosphatase values were equally high or only slightly lower, indicating that osteoblast differentiation of the cells was maintained with a higher proliferation. CONCLUSIONS: As large a number of in vitro proliferated cells as possible is a prerequisite for clinical application of tissue engineering. By continuously supplying medium, the tested perfusion culture system enables a higher rate of proliferation of osteoblast-like cells with maintenance of differentiation. Continuous microscopic monitoring of the cultures is possible using commercially available Petri dishes.

[Cell-based strategies for salivary gland regeneration]. / Zellbasierte Strategien für die Speicheldrüsenregeneration.

Xerostomia as a side effect of radiotherapy or due to Sjögren's disease leads to considerable impairment of the quality of life of the affected patients. Preventive treatment approaches such as intensity-modulated radiotherapy, surgical transfer of a submandibular gland to a site outside the radiation field or administration of amifostin during radiation treatment are not yet completely established in clinical practice and are not applicable for all patients. Symptomatic treatment with pilocarpin or synthetic saliva leads to an improvement of the symptoms only in some patients, and in the case of pilocarpin significant systemic anticholinergic side-effects might occur. Because large numbers of patients are affected and current treatment options are not satisfactory, it is essential to develop new treatment options. In parallel with the in vitro production of functional salivary gland constructs by means of tissue engineering techniques, attempts are currently under way to experimentally restore salivary gland function by genetic treatment approaches such as transfection of the affected salivary glands with aquaporins or pro-angiogenic factors. In addition, the in vivo application of stem cells is under investigation. In the present paper, we discuss the clinical and radiobiological background of xerostomia and highlight possible innovative future treatment options.

[Rare sialadenoma papilliferum in the hard palate: case report and survey of the literature]. / Das seltene Sialadenoma papilliferum am harten Gaumen : Fallbericht und Literaturübersicht.

Sialadenoma papilliferum is a rare tumour of the salivary glands that usually occurs in the oral cavity. Following the course of the salivary glands of the oral mucosa, the hard and soft palate are the most common locations of this tumor. In the international literature, only a few case reports about this entity can be found. We present a 63-year-old patient with a sialadenoma papilliferum accidentally found during diagnostic procedures for progredient dysphagia. Suffering from infrabifurcal cancer of the oesophagus, the patient had undergone partial oesophagectomy 1 year before. Histological verification was performed with a tumor biopsy at the border of hard and soft palate, on the right side. This case is compared with 39 further cases reported in the literature. The therapy of choice is resection of the tumor. Because of the high frequency of recurrence, in sano resection should be planned.

Comparative analysis of nasal and oral mucosa dendritic cells.

BACKGROUND: Mucosal dendritic cells (DC) play a crucial role in tolerance induction as seen in mucosal immunotherapy of atopic diseases. Nevertheless little is known about the phenotypical differences of oral and nasal mucosal DC (nmDC). Recently, we could show that oral mucosal myeloid CD1a(+) DC (omDC) differ from their skin counterparts especially by the expression of high affinity receptor for immunoglobulin E (IgE; FcepsilonRI). However, expression pattern of FcepsilonRI and phenotypical characteristics of CD1a(+) nmDC have not been elucidated in detailed yet. METHODS: We performed detailed phenotypical comparison of nmDC and omDC of atopic and nonatopic individuals. RESULTS: As reported for omDC, FcepsilonRI on nmDC of atopic donors was elevated and mostly occupied by IgE while FcepsilonRI was present only in low amounts on nmDC of nonatopic donors. Nevertheless, the highest FcepsilonRI expression has been observed on omDC. Furthermore, significant amounts of costimulatory molecules CD40, CD80 and CD86 could be detected on nmDC that expressed more CD80 compared with omDC. Moreover, nmDC displayed less major histocompatability complex (MHC) class I and II molecules than omDC. In addition, nmDC expressed more C-type lectins CD205, CD206 as well as myeloid marker CD11b while omDC displayed increased expression of CD207 and lipopolysaccharide (LPS) receptor CD14. CONCLUSION: Together these data imply that nmDC phenotypical differ from omDC which might result in diverse functional properties and might be of relevance for selecting routes for immunotherapy of atopic diseases. Moreover these data provide a basis for further studies investigating immunological mechanisms underlying mucosal immunotherapy.

Eosinophilia in nasal polyposis: its objective quantification and clinical relevance.

BACKGROUND: Eosinophilia within nasal polyps is often taken as a criterion for adjuvant medical treatment postoperatively such as topical steroids. OBJECTIVE: This study was performed in order to validate a new technique for objective quantification of eosinophilia by using laser scanning cytometry (LSC), to compare these results with manual scoring and routine histopathology, and to correlate them with the history of allergy or recurrence. METHODS: LSC was used for semi-automated analysis of single-cell preparations from representative ethmoidal polyps obtained during routine paranasal sinus surgery (n=41). This microscope-based instrument scans the cells after immobilization of cells on a glass slide and after triple staining of cytokeratin, eosinophilic granula, and DNA. The location of each cell is stored with the fluorescence data. Therefore, the morphology of every cell can be documented by re-staining with haemotoxylin and eosin and re-localization on the slide. Subsequently, slides were subjected to manual scoring. The remaining polyps were analysed by routine histopathology. RESULTS: Data from LSC and manual scoring showed good correlation (r=0.81, P<0.001), whereas there were discrepancies with histopathology. Eosinophilia scored by LSC and histopathology was neither correlated with the history of allergy nor with recurrence as determined by Fisher's exact test independent of the definition of eosinophilia (> or =2%, > or =3%, or > or =5% of all cells). CONCLUSION: Scoring eosinophilia by LSC in comparison with histopathology does not contribute to a more reliable basis for adjuvant medical therapy in nasal polyposis. Instead, functional parameters (cytokine production, apoptosis) may serve better.

[Chronic hyperplastic laryngitis following treatment of hypertension with angiotensin converting enzyme-inhibitor]. / Chronisch-hyperplastische Laryngitis. Nach antihypertensiver Therapie mit einem ACE-Inhibitor.

We report the case of a 42 year old patient who developed chronic hyperplastic laryngitis during treatment with the angiotensin converting enzyme-inhibitor Cibacen 10. A severe cough and vocal restrictions with hoarseness were only incompletely cured after changing this anti-hypertensive medication to a adrenergic blocker, combined with a vocal rest and anti-inflammatory inhalation. Therefore we performed a laryngoscopy under general anesthesia and excised the swelling of the vocal cords. Additionally, voice therapy was prescribed and complete restitution achieved. Although hoarseness is documented as a potential side effect of angiotensin converting enzyme-inhibitors, morphological alterations in the vocal cords have not been linked to this type of drug. In our case, prolonged medication with Cibacen 10 led to chronic hyperplastic laryngitis. Initial coughing might have induced the trauma of the epithelium of the vocal cords. Due to the morphological alterations to the vocal cords the patient developed additional functional dysphonia.

Tissue engineering in otorhinolaryngology.

Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network.

[Multimodal treatment strategy for Langerhans cell histiocytosis at head and neck manifestations]. / Interdisziplinäre Therapie der Langerhans-Zell-Histiozytose im Kopf- und Halsbereich.

Langerhans cell histiocytosis (LCH) is a rare disorder with different clinical features. An established standardized treatment does not exist.We present a case report of a patient with localized LCH of the temporal bone and discuss the interdisciplinary treatment strategies. We reviewed the international literature and summarized the current knowledge. Beside a wait and see policy in cases without symptomatic disease, surgery, radiotherapy or chemotherapy, and combinations of these options are used as treatment modalities. While surgery or radiotherapy are preferred in localized (symptomatic) lesions, stage-adapted chemotherapeutic regimens are the treatments of choice in disseminated disease. Treatment selection depends on the individual clinical features.

Tissue engineering of human salivary gland organoids.

Radiation therapy for malignant head and neck tumours is mainly responsible for inadvertent damage of the salivary glands. Xerostomia is the major symptom of this condition, with consequent mucositis, dental caries, dysphagia and nutritional deficits. At present there is no routine treatment for radiation-induced salivary dysfunction. Based on the principles of tissue engineering, this study presents a new experimental concept for reconstituting salivary gland function after radiation therapy for head and neck cancer. Human parotid cells were cultured with two different types of commercially available microcarriers-Cytodex 3 and Cytopore 1-for up to 3 weeks in vitro. Cultures were controlled daily by means of inverted microscopy. Medium samples were tested for alpha-amylase, tissue polypeptide antigen (TPA) and S100 in order to control parotid cell function in vitro. The vitality of the cells was investigated by in vitro staining with erythrosine. Immunocytochemical analysis for amylase and cytokeratin was performed in order to confirm epithelial character and maintain acinar cell type. Parotid gland cells could be cultured in a differentiated and vital state on both types of microcarriers for up to 3 weeks. Almost all of the cultured cells exhibited immunoreactivity for cytokeratin. High concentrations of TPA, a specific marker for salivary duct epithelium, indicated persistent differentiation of this cell type in vitro. Positivity for amylase was detectable in 20-45%, of cells growing on the microcarriers, and especially on Cytodex 3. Decreasing amylase levels in the culture medium indicated functional deficiencies of the remaining acinar cells. Tissue engineering of human salivary gland organoids on microcarriers is a new approach for potential causative treatment of radiation-induced xerostomia. Before clinical application can be considered significant improvements in the in vitro cultivation of salivary gland tissue and scaffold design have to be realized.

[Reconstruction of the frontal bone with individual titanium implants after surgical therapy of osteomyelitis of the frontal bone]. / Rekonstruktion des Os frontale mit individuellen Titanimplantaten nach chirurgischer Therapie der Stirnbeinosteomyelitis.

Individually prefabricated titanium implants enable the reconstruction of the frontal bone after surgical therapy of osteomyelitis without compromising mechanical stability or aesthetic results. Primarily the infected bone tissue is removed. Helical computed tomographic systems are used for the aquisition of patient data. After being transmitted to a computer aided design system (CAD-system) this data is used for construction of the implant geometry using freeform-surfaces. The outer surface contour is derived from the contours of the bone defect. The completed computer-based implant design is finally transformed into control data to run the milling machine which produces the implant from a block of titanium. Modern industrial CAD/CAM-technology allows standardized prefabrication using data from CT-scans. The precision of all implants was predictable and duration of the reconstructive procedure could be reduced. During postoperative follow-up (5-24 months) no loss of implant or recurrence of the osteomyelitis could be observed.

Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice.

alpha(2)-Adrenergic receptors play an essential role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the CNS. However, the role of each of the three highly homologous alpha(2)-adrenergic receptor subtypes (alpha(2A), alpha(2B), alpha(2C)) in this process has not been determined unequivocally. To address this question, the regulation of norepinephrine and dopamine release was studied in mice carrying deletions in the genes encoding the three alpha(2)-adrenergic receptor subtypes. Autoradiography and radioligand binding studies showed that alpha(2)-receptor density in alpha(2A)-deficient brains was decreased to 9 +/- 1% of the respective wild-type value, whereas alpha(2)-receptor levels were reduced to 83 +/- 4% in alpha(2C)-deficient mice. These results indicate that approximately 90% of mouse brain alpha(2)-receptors belong to the alpha(2A) subtype and 10% are alpha(2C)-receptors. In isolated brain cortex slices from wild-type mice a non-subtype-selective alpha(2)-receptor agonist inhibited release of [(3)H]norepinephrine by maximally 96%. Similarly, release of [(3)H]dopamine from isolated basal ganglion slices was inhibited by 76% by an alpha(2)-receptor agonist. In alpha(2A)-receptor-deficient mice, the inhibitory effect of the alpha(2)-receptor agonist on norepinephrine and dopamine release was significantly reduced but not abolished. Only in tissues from mice lacking both alpha(2A)- and alpha(2C)-receptors was no alpha(2)-receptor agonist effect on transmitter release observed. The time course of onset of presynaptic inhibition of norepinephrine release was much faster for the alpha(2A)-receptor than for the alpha(2C)-subtype. After prolonged stimulation with norepinephrine, presynaptic alpha(2C)-adrenergic receptors were desensitized. From these data we suggest that two functionally distinct alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), operate as presynaptic inhibitory receptors regulating neurotransmitter release in the mouse CNS.

Adenosine triphosphatase expression correlates with ciliary activity of respiratory epithelium in vitro.

In vitro culture of respiratory epithelium is of great utility for pharmacological investigations and tissue engineering. Up to now, the degree of differentiation of respiratory cells cultured in vitro has exclusively been estimated by measuring ciliary beat frequency (CBF). Ciliary motility is dependent on the function of the motor protein dynein that is composed of at least two heavy chains, sharing attributes of adenosine triphosphatases (ATPases). CBF is further dependent on medium conditions and does not allow to draw any accurate conclusion on the proportion of fully differentiated ciliated cells in culture. For this reason we introduced the immunohistochemical detection of a 100-kD ATPase subunit as a correlation with dynein activity in human respiratory cell tissue culture. Our results show that the amount of immunohistochemically detectable ATPase-subunit-positive cells strongly correlates with ciliary motility in vitro. Cultures without ciliary activity exhibited no ATPase staining, whereas in cell cultures with excessive ciliary beat, up to 15.1% of the cells were ATPase positive. Immunohistochemical detection of ATPase in respiratory cell cultures seems to be a sensitive and reproducible complement for the characterization of cultured ciliated epithelium.