Differential chemokine expression patterns in tonsillar disease.

Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.

[Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) as an example of a rare disease relevant for oto-rhino-laryngology]. / Hereditäre hämorrhagische Teleangiektasie (Morbus Rendu-Osler-Weber) als Beispiel einer seltenen Erkrankung des HNO-Fachgebietes.

Diagnosis and treatment of rare diseases are difficult. Hereditary hemorrhagic telangiectasia (HHT, Rendu-Osler-Weber disorder) is a relatively common rare disease. Because epistaxis is the most frequent manifestation of this disease, affected individuals often approach otorhinolaryngologists first. The latter ones often have a key position for early diagnosis and screening for visceral involvement which can prevent life-threatening complications. Treatment of epistaxis can improve quality of life of affected persons. Diagnosis and treatment of rare diseases can be complex and it can be very helpful to use information resources to ensure a correct management. Various possibilities to access these resources are presented in general and in relation to HHT.

[Brachytherapy for the treatment of head and neck cancer]. / Brachytherapie für die Behandlung von Kopf-Hals-Karzinomen.

Image-Adapted brachytherapy (IABT) is a modern interdisciplinary development of classic radiation therapy, which allows the application of a high radiation dose while avoiding severe adverse events, thereby improving the prognosis of our patients. Indications in head and neck squamous cell carcinoma (HNSCC) include tumours of the floor of mouth, the face, the paranasal sinuses, the naso- and oropharynx, recurrent cancer and incomplete resections due to close vicinity of the tumor to important structures. The application type can be classified as curative, adjuvant, perioperative as a boost with or without external beam radiation (EBRT) or as a palliative treatment. The published results encourage the integration of IABT as part of the therapy of HNSCC, thereby improving the prognosis and quality of life of our patients.

[Brachytherapy in combination with function-preserving surgery of cancer of the paranasal sinus]. / Kombination von Brachytherapie und Chirurgie bei Tumoren mit Orbita-/Schädelbasisinfiltration.

BACKGROUND: Prognosis of patients with advanced/recurrent cancer of paranasal sinuses and orbit with infiltration of the skull base is very bad. Radical surgery does not improve prognosis. A disadvantage of the radical surgery is the functional loss and the residual cosmetic defect. We present the results of a function-preserving surgery in combination with interstitial, image adapted brachytherapy (IABT) for the treatment of these cancers. METHODS AND PATIENTS: Ten patients with paranasal sinus cancer and 16 patients with sarcomas (n=26) were retrospectively analysed. After a maximum tumor resection (mostly R1-R2 resections), 2-12 flexible afterloading plastic tubes were implanted. The postoperative IABT total dose was 10-25 Gy in 2.5 Gy fractions twice daily fractions for 5 days. RESULTS: In all cases the eye was obtained without functional damage. The IABT was well tolerated. The visual and cosmetic results were satisfactory. Postoperative complications occurred in 7 out of 26 cases without a serious long-term adverse event. Significant radiation-induced complications were found in patients with orbital or skull base involvement. The three years overall survival was 60% for rhabdomyosarcoma, and 33% for the paranasal sinus cancers. CONCLUSIONS: These results show that a combined treatment of function-preserving surgery and a IABT is a feasible, successful and well-tolerated option for curative, salvage and palliative therapy for selected patients with advanced or recurrent carcinoma of the paranasal sinuses and orbit.

Psoriasin (S100A7) is a principal antimicrobial peptide of the human tongue.

The human tongue is particularly resistant to bacterial infections although the mouth is continuously exposed to a complex and abundant ensemble of microbes, such as the common intestinal bacterium Escherichia coli. We show that lingual epithelia produce and release, as a primary E. coli-killing compound, the S100 protein psoriasin. No significant reduction in psoriasin release could be achieved through repeated rinsing of the epithelial surface of the tongue. Psoriasin is produced in the upper layers of the lingual epithelia but is lacking in the most superficial and basal cells. It displays a gradient pattern of expression with decreasing expression from the anterior one-third to the posterior portion of the tongue. Thus, psoriasin may be the key to the resistance of the human tongue toward E. coli.

Endothelial and epithelial expression of eotaxin-2 (CCL24) in nasal polyps.

BACKGROUND: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. METHODS: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. RESULTS: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-alpha, INF-gamma, IL-4, or costimulation with TNF-alpha and INF-gamma CCL24 mRNA was significantly enhanced (3.2-19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-alpha, INF-gamma or IL-4 induced CCL24 protein (0.1-0.3 ng/ml) in epithelial cells. Costimulation with TNF-alpha and IL-4 (0.1-30 and 1-30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18-0.31 ng/ml). CONCLUSION: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.

[Strategies of the nasal mucous membranes for defense against infection. Current knowledge of antimicrobial peptides]. / Strategien der Nasenschleimhaut zur Infektabwehr. Aktuelle Erkenntnisse zu antimikrobiellen Peptiden.

Infections of healthy skin or mucous membranes are rare despite constant exposure to microbial colonization. Nonspecific and specific defense mechanisms correspond in the nose: the mucociliary clearance provides very effective mechanical cleaning. If this protection is insufficient, the nasal epithelium comes into close contact with microorganisms. This triggers the recently discovered production of the body's own specific antimicrobial peptides (AP). It seems that it is difficult for microorganisms to form enzyme-induced resistance to AP. This makes AP highly interesting for the development of new antibiotics. The observation that antimicrobial activity can be induced has also led to the hypothesis that natural substances may possibly stimulate endogenous AP production. If this line of defense also fails, the inflammatory cells migrate from the blood into the tissue and, with their capacity for phagocytosis, the enzymatic attack on bacteria can cause a cellular inflammatory reaction in the nasal mucous membrane.

Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement procedure. Recordings were obtained in 96% of these subjects with this standardised procedure. The group results are presented in terms of peak amplitude and latency, slope of the amplitude growth function and ECAP threshold. The effects of aetiological factors and the duration of deafness on the ECAP were also studied. While large intersubject variability and intrasubject variability (across electrodes) were found, results fell within a consistent pattern and a normative range of peak amplitudes and latencies was established. The aetiological factors had little effect on the ECAP characteristics. However, age affected ECAP amplitude and slope of the amplitude growth function significantly; i.e., the amplitude is higher in the lowest age category (15-30 years). Principal component analysis of the ECAP thresholds shows that the thresholds across 5 electrodes can be described by two factors accounting for 92% of the total variance. The two factors represent the overall level of the threshold profiles ('shift') and their slopes across the electrode array ('tilt'). Correlation between these two factors and the same factors describing the T- and C-levels appeared to be moderate, in the range of 0.5-0.6.

[Acute airway obstruction in acquired hemophilia A]. / Akute Atemwegsverlegung durch erworbene Hämophilie A.

We report the case of a 67 year old patient suffering from acute airway obstruction caused by hemorrhage localized to the tongue, mouth cavity and hypopharynx, with no evidence of bleeding in his history. The patient presented initially with a globus feeling of the neck, dysphagia and a sore throat. CT scan revealed a swelling of the lingual and sublingual areas and the pharyngeal wall. Next day, there was an immediate life-threatening event caused by progressive bleeding with airway obstruction and an inability to intubate requiring coniotomy. The etiology of the hemorrhage was confirmed by finding a depletion of factor VIII and the presence of auto-antibody directed against this factor. Based on this case report and a review of the literature, we discuss the diagnosis and treatment of acquired hemophilia.

Sentinel lymph-node biopsy in head and neck cancer.

The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.

[Benign fibro-osseous tumors of the frontal skull base with intracranial extension. Report of 2 cases]. / Gutartige fibroossäre Tumoren der frontalen Schädelbasis mit intrakranieller Ausbreitung. Bericht über 2 Fälle.

We report on two patients with ossifying fibroma of the anterior skull base with intracranial extension. A psammomatoid ossifying fibroma was removed from a 29 year old female patient, and in a 37 year old female patient a cemento ossifying fibroma was removed. The main clinical symptom in both cases was headache. Surgery took place after diagnosis and therapy in an interdisciplinary operation with ENT colleagues. The ossifying fibroma is a benign neoplasm mainly affecting the maxilla and mandible. Complete removal is better than a curettage of the tumor.

Incidence and clinical background of posttonsillectomy bleeding related blood transfusion over 12 years.

Economies in National Health Systems forces ENT surgeons to review their indications for outpatient tonsillectomy. Therefore, it is important to preoperatively identify special risk groups who frequently have extensive posttonsillectomy bleeding with the need of a blood transfusion. Aim of this study was to estimate the incidence for posttonsillectomy bleeding related blood transfusion, to identify risk factors associated with the need for blood transfusion and to release guidelines for posttonsillectomy bleeding of high risk patients. A retrospective study was done on the medical history of 1720 patients who underwent tonsillectomy for chronic tonsillitis between 1982-1993 in the ENT Department at the University of Kiel. The average transfusion rate was 0.52%. End Stage Renal Disease and hypertension combined with a preoperatively decreased Hb and Hct were the risk factors identified leading to a transfusion. These patients should not get a tonsillectomy as an outpatient procedure. The Hb, Hct, PT, PTT, blood type and crossmatch should be drawn and assessed prior to tonsillectomy. We recommend immediate treatment of secondary hemorrhage in those high risk patients under general anesthesia to avoid severe complications.

[Bilateral vestibular loss. Diagnosis and follow-up]. / Der beidseitige Vestibularisausfall. Diagnostik und Krankheitsverlauf.

BACKGROUND: Atypical symptom in patients with bilateral vestibular loss is head movement-induced oscillopsia. The paucity of precise complaints in many patients is surprising. Therefore, bilateral loss of vestibular function is often undiagnosed. PATIENTS: We report on the long-term follow-up in 29 patients. They were monitored for 2-7 years (mean: 4.5 years). RESULTS: Of the 29 patients 16 described oscillopsia. All symptomatic patients had acute bilateral vestibular loss.Patients described that their symptoms improved over a period of 1-2 years. Improvement was not age dependent. CONCLUSIONS: Otoneurologists should be aware of the particular clinical symptoms in bilateral vestibular loss. Regarding clinical features, compensation of bilateral vestibular loss seems to be unlikely only based on central compensatory eye movement reflexes. More likely perceptual adaptations and restriction of head movement are responsible for subjective improvement.

A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel.

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50-99% regression) sustained for > or =28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options.

A newly discovered function of palatine tonsils in immune defence: the expression of defensins.

The palatine tonsils have an undoubted role in the immune defence system. After antigen contact an effective adaptive immune response by B- and T-cell lymphocytes will be released. In addition the palatine tonsils seem to exert influence to the defence by the innate immune system. Therefore, we studied the ability of palatine tonsils to express different alpha and beta defensins and to find out any distinctions in chronic inflamed tonsils. Total RNA of 49 specimens of hyperplastic tonsils and chronic tonsillitis with pathological provided evidence of Actinomyces israelii was isolated using TRIzol protocol, reverse transcribed and the HNP-1, HNP-4, HBD-1 and HBD-2 gene expression densitometric determined, standardised in relation to glycerinaldehyd-3-phosphatdehydrogenase gene expression, after a semiquantitative polymerase chain reaction was performed. mRNA of HNP-1, HNP-4, HBD-1 and HBD-2 was detected in tissue samples, but their amount differed within the two defensin families and tissue of origins. HBD-1 was detected in all 49 tissues of hyperplastic tonsils and chronic tonsillitis. Only in chronic inflamed tonsils the amount of HBD-2 mRNA expression was significant increased. In these specimens also mean relative expression rate of all defensins was observed to be manifestly increased. Palatine tonsils express mRNA for different alpha and beta defensins and this expression suggest a newly supposed function in immune defence: the participation in the innate, non-adaptive immune system. Thus, palatine tonsils have a potentially influence in the growth and control of the physiological mouth bacteria by their bactericidal activity.

[A concept for the assessment of quality of life in patients with carcinomas of the upper aerodigestive tract]. / Konzept zur Erhebung der Lebensqualität bei Patienten mit Karzinomen des oberen Aerodigestivtraktes.

BACKGROUND: The quality of life (QoL) of patients with malignant diseases decreases significantly. OBJECTIVE: The evaluation of QoL is generally not part of the management of patients with head and neck cancer. The aim of this study was to develop an additional disease- and treatment-specific questionnaire to evaluate QoL in surgically treated head and neck cancer patients. PATIENTS AND METHODS: The general QoL was evaluated with the QLQ-C30 questionnaire developed by the European Organisation of Research and Treatment of Cancer (EORTC). RESULTS: The disease-specific QoL was evaluated using the EORTC H&N35 module. The new questionnaire "Kiel Head and Neck 17" (KQL H&N-17) is a disease- and treatment-specific addition especially in regard to side effects caused by surgical treatment. CONCLUSIONS: A wide application of this whole concept is needed to obtain comparable results from studies suitable for evaluating QoL in patients receiving different treatments for their malignant diseases. Moreover, the effectiveness and quality of treatment could be controlled better, which would help to increase the QoL of these patients.

[Collagenase 3 mRNA expression in squamous epithelial carcinomas of the oropharynx]. / Kollagenase-3-mRNA-Expression in Plattenepithelkarzinomen des Oropharynx.

BACKGROUND: Metalloproteinases (MMP) are endopeptidases, which are able to degrade extracellular matrix. It is assumed that MMP play an important role in invasion and metastasis of malignomas. The expression of collagenase-3, also named MMP-13, was already detected in squamous cell carcinoma of the head and neck, but the significance in the process of metastasis is still unclear. PATIENTS AND METHODS: 36 tumor biopsies of oropharyngeal squamous cell carcinoma (10 cases N0, 26 patients N+) and 12 biopsies of normal oropharyngeal mucosa were analysed with reverse transcriptase-PCR and Northern Blot for their mRNA-expression of MMP-13 and TIMP-1, the physiological inhibitor of MMP-13. RESULTS: In 30 of 36 (83.3%) tumor biopsies a MMP-13-mRNA-expression was detected. In 9 of 10 (90%) cases with N0-status and 21 of 26 (80.7%) cases with N(+)-neck the mRNA-expression could be shown. There was no correlation between MMP-13-mRNA-expression and N-status. In 34 tumor biopsies (94.4%) a TIMP-1-expression was detected. MMP-13-mRNA was not detected in normal oropharyngeal mucosa. CONCLUSIONS: It seems that MMP-13-mRNA-expression is not a prognostic factor for metastatic behavior of oropharyngeal cancer and therefore not helpful for further decisions on the therapy.

Overexpression of the human myosin-binding protein-C1 mRNA in laryngeal squamous cell carcinoma cells.

BACKGROUND: To compare gene expression patterns between laryngeal squamous cell carcinoma (SCC) cells and their normal phenotypes to identify genes showing differential expression. MATERIALS AND METHODS: Messenger RNA was isolated from both kinds of cells, reversely transcribed and subjected to differential display reverse transcription (DDRT)-PCR. Gene fragments showing difference in the expression were recovered, reamplified, cloned and sequenced, enabling homology search. Total RNA was isolated from laryngeal SCC cells and adjacent normal mucosa and subjected to Northern hybridization. RESULTS: A 159 bp gene fragment was detected, revealing 96% homology with the human myosin-binding protein-C1 (MYBPC-1) gene. Compared to the benign phenotypes the expression of MYBPC-1 was particularly increased in SCC cells, confirmed by Northern hybridization. CONCLUSION: The results presented in this work may help to extend the diagnostic panoply available for the evaluation of laryngeal tissue conspicuous for malignancy.