Claudia Rudack

IL-5 synthesis is upregulated in human nasal polyp tissue

BACKGROUNDnIn most nasal polyps, tissue eosinophilia is a striking finding, the pathologic mechanism of which is not understood.nnnOBJECTIVEnThis study was performed to investigate a possibly distinct cytokine and chemokine pattern that could explain the characteristic tissue eosinophilia in nasal polyps.nnnMETHODSnPolyps from 23 patients and turbinate tissue from 18 control subjects were investigated. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, IL-1RA, RANTES, GRO-alpha) of tissue homogenates was measured by ELISA. Immunohistochemistry was performed in selected samples to detect IL-5+, major basic protein-positive, and EG2+ cells.nnnRESULTSnIL-5 was detectable in only one sample of tissue from 18 control subjects but was found in 18 of 23 nasal polyps. Immunohistochemistry revealed an abundant number of IL-5+ cells, of which 69.5% could be identified as eosinophils by morphology. IL-6, IL-8, IL-10, tumor necrosis factor-alpha, GRO-alpha, and RANTES were detected in all specimens, without significant differences between groups (p > or = 0.05), whereas significnatly higher concentrations of IL-1 beta and IL-1RA were found in turbinate mucosa (p < or = 0.05). IL-3 was not detectable: granulocyte-macrophage colony-stimulating factor could only occasionally be found.nnnCONCLUSIONnThis study indicates that IL-5 plays a key role in the pathophysiology of eosinophilic nasal polyps and may be produced by eosinophils.

Cytokines in nasal polyposis, acute and chronic sinusitis.

Cytokines are potent biologic factors involved in the regulation of inflammation, immune defense, and wound healing. Recently, growing interest has developed in the role of cytokines in chronic sinusitis and nasal polyposis. In the present study, we investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a specific form of rhinosinusitis is associated with the expression of a certain cytokine profile. Sinus mucosa from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8) and controls of turbinate mucosa (n = 7) were sampled. The cytokine protein content (IL-1β, JL-3, IL-4, IL-5, IL-6, JL-8, IL-13, GM-CSF, interferon-γ) of tissue homogenates was measured using ELISA technique. In acute sinusitis, the synthesis of proinflammatory cytokines and of the neutrophil chemokine IL-8 and IL-3 appeared to be upregulated. Chronic sinusitis mucosa demonstrated no significantly increased concentrations of the measured cytokines. In bilateral nasal polyposis, but not in antrochoanal polyps, the eosinophil related cytokine IL-5 was strongly upregulated. From these findings, it appears that specific cytokine patterns are found in different forms of sinusitis, and that IL-5 may represent the most important cytokine responsible for tissue eosinophilia in nasal polyposis.

Vascular risk factors in sudden hearing loss

Low density lipoprotein (LDL) and fibrinogen apheresis was recently reported to be an effective therapy in sudden hearing loss (SHL). In this study, we investigated whether lipoprotein and/or fibrinogen plasma concentrations, related gene polymorphisms and other cardiovascular risk factors are also risk factors for SHL. Total cholesterol, HDL and LDL cholesterol plasma concentrations, fibrinogen levels, and two functionally relevant fibrinogen polymorphisms were determined in 142 consecutive patients and in 84 age- and sex-matched control subjects of the same ethnic background, using routine laboratory methods and PCR analysis. In addition, we determined the platelet glycoprotein Ia (GPIa) C807T polymorphism, which was recently proposed to be a genetic risk factor for SHL, and we compared the patients and controls clinical characteristics. Total and LDL cholesterol concentrations were not different between patients and controls. Fibrinogen plasma levels were significantly increased in SHL patients (260+/-57 vs. 239+/-110 mg/dl, p=0.002). However, fibrinogen was not related to SHL in multivariate analysis, and none of the investigated fibrinogen polymorphisms was associated with SHL. By contrast, T allele carriers of the GPIa 807 polymorphic site had an increased risk to develop SHL (OR 1.81) and were more likely not to recover from SHL, compared to C allele carriers (OR 3.0). Moreover, significantly more SHL patients were current smokers (56.3% vs. 19.3% in the control group, p<0.0001). In conclusion, there is a partial overlap between classical coronary risk factors and risk factors for SHL. Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) are apparently no major risk factors for SHL, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking are associated with an increased risk for SHL. Altogether these findings suggest a vascular involvement in the pathogenesis of SHL and may have important implications for the development of therapeutic and preventive strategies.

Proinflammatory cytokines in allergic rhinitis

Allergic diseases such as allergen-induced rhinitis represent an inflammatory reaction that is characterized by the chemotaxis and activation of various cell populations. A high degree of cell-to-cell communication is needed to orchestrate this inflammatory immune response. A variety of cytokines and adhesion receptors seem to play an important role in the allergic late phase reaction. Here we demonstrate that proinflammatory cytokines such as interleukin(IL)-1, IL-8 and TNF-α (tumor necrosis factor-alpha) can be detected in nasal secretions and mucosa by enzyme-linked immunosorbent assay and immunohistochemistry. The increased expression of adhesion receptors in mucosa specimens of patients with seasonal allergic rhinitis points to their role in regulating the cellular migration and probably represents a key event in allergic inflammation. We established an in vitro model using freshly taken nasal mucosa to study the induction of adhesion receptors by proinflammatory cytokines. E-selectin, an endothelial receptor, was strongly upregulated by IL-1β, TNF-α and allergen. The induction due to allergen exposure of the mucosa was markedly inhibited by soluble cytokine receptors (sIL-1R, TNF-BP) or by a receptor antagonist (IL-Ira) and prednisolone, These findings indicate that proinflammatory cytokines may be key factors for the upregulation of adhesion processes in human nasal mucosa and the activation of various cell populations involved in the allergic inflammation. They therefore represent a main target for new therapeutic strategies.

Effect of prednisolone on cytokine synthesis in nasal polyps.

To investigate steroid effects on eosinophils and their associated cytokines in nasal polyps, we sampled nasal polyp tissue from 20 subjects during routine surgery. Freshley removed polyps were cut into small pieces and incubated in culture medium for 24 h in different concentrations of prednisolone (10(-2)-10(-6) mol/L). Cell viability was assessed by means of trypan dye exclusion of the supernatants. The number of eosinophils was quantified by means of cytocentrifuge smears stained by May-Giemsa-Grunwald stain. The cytokine protein content of interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by ELISA technique in supernatants and in homogenates of nasal polyp tissue. Our results revealed a significant reduction in the number of eosinophils and total number of vital cells at concentrations of 10(-3) and 10(-2) mol/L. GM-CSF and IL-5 protein levels were significantly reduced in supernatants and in homogenates after treatment with prednisolone, whereas IL-3 synthesis was not diminished. Corticosteroid effects known to inhibit synthesis of eosinophil-associated cytokines could be measured in terms of a significant decrease in IL-5 and GM-CSF protein level as well as in a decrease in the number of vital cells.

Neither MRI, CT nor US is superior to diagnose tumors in the salivary glands – an extended case study

ObjectivesUltrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) are the most common radiological procedures for the diagnosis of tumor-like lesions of the salivary glands. The aim of the present study was to determine whether MRI or CT provide additional information besides that delivered by US.Study design/Methods109 patients with a tumor-like lesion of the salivary glands underwent surgery. MRI and CT were arranged in 73 and in 40 patients respectively, whereas all 109 patients were prospectively diagnosed by US. The results of CT, MRI and US were compared with the histological outcome. Furthermore, the recent rise in the number of CT and MRI studies was investigated.ResultsOn CT and MRI, there was no rise in the percentage of malignant tumors or advanced surgical procedures. In respect of the radiological assessment of the lesion (benign/malignant) and the correct diagnosis, CT, MRI and US were comparable in terms of sensitivity, specificity and accuracy. No significant difference was found in the Chi-square test (p > 0.05).ConclusionThe evaluation of the preoperative results of CT, MRI and US revealed no advantage for CT or MRI; these procedures are only required in specific cases. An update or revision of the current preoperative diagnostic management is deemed necessary.

Efficacy and safety of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis

IntroductionThis study evaluated the efficacy and safety of mometasone furoate nasal spray (MFNS) in patients with chronic sinusitis.MethodsIn this double-blind, placebocontrolled, multicenter, parallel-group study, 60 patients with persistent sinusitis symptoms were randomized to receive either MFNS 200 μg twice daily or placebo, for 16 weeks (112 days). Eventually, 53 patients terminated the study in regular course.ResultsTotal Symptom Scores (TSS) in patients receiving MFNS changed by a mean of −7.27 (95% CI −9.71, −4.84), versus −5.35 (95% CI −6.73, −3.96) in the placebo group (P=0.51). MFNS reduced nasal congestion and discharge scores, and improved patients’ olfactory function. There were few side effects. Considerably more patients in the MFNS group were satisfied with the treatment than those who had received placebo (P<0.05). Also, more patients would take the medication again in the event of symptoms, compared with those who had taken placebo (P<0.05). Furthermore, the MFNS patients would recommend it to others.ConclusionThe positive patient assessment and few side effects are reflected in the efficacy evaluation performed by the physicians. The endoscopic results under MFNS were always numerically more favorable than those under placebo, and the overall difference reached statistical significance (P<0.01). MFNS offers an effective and safe treatment for chronic rhinosinusitis.

Tinnitusbehandlung mit Lidocain? Ein klinischer Erfahrungsbericht

ZusammenfassungUm die Wirksamkeit von Lidocain und Tocainid auf Tinnitus aurium zu überprüfen, untersuchten wir retrospektiv von 1993 bis Mai 1995 77 Patienten. Während des stationären Aufenthalts erhielten die Patienten eine Testdosis Lidocain i.v. und bei positivem Ansprechen auf die Testdosis eine sich anschließende medikamentöse Therapie mit Tocainid, einem oral verabreichbaren Strukturanalogon des Lidocains. Die tinnitussupprimierende Wirkung wurde entsprechend den subjektiven Angaben und anhand einer visuellen Analogskala klassifiziert. Unsere Ergebnisse zeigen, daß von 77 Patienten nur 19 Patienten eine Tinnitussuppression unterschiedlicher Ausprägung angaben. Von ihnen wählten 14 Patienten eine weiterführende Therapie mit Tocainid (3×400xa0mg/Tag); 5 Patienten lehnten die Therapie wegen möglicher Nebenwirkungen ab; 3 Monate nach der Verordnung von Tocainid hatten 10 Patienten das Medikament wegen Nebenwirkungen und 3 Patienten wegen mangelnder Wirkung abgesetzt. Wir schätzen die therapeutische Erfolgsquote für die Behandlung des Tinnitus aurium mit Lidocain bedeutend geringer ein als dies im Schrifttum der Fall ist. Das oral anwendbare Stukturanalogon Tocainid kommt wegen der hohen Rate an Nebenwirkungen und nicht ausreichender Tinnitussuppression allenfalls in besonderen Einzelfällen als Behandlungsmöglichkeit in Frage.SummaryThe efficacy of intravenous lidocaine therapy in patients suffering form severe tinnitus aurium has been reported for many years although pharmacological mechanisms for its use are not fully understood. In order to evaluate the effectiveness of lidocaine therapy in the treatment of tinnitus we performed a retrospective study on 77 patients suffering from tinnitus who were treated between 1993 and 1995. All patients were given a test dose of lidocaine after a saline placebo infusion. Suppression of tinnitus was classified according to a visual analogue scale. Our results showed that 19 of the 77 patients investigated experienced different degrees of reduced tinnitus. Fourteen of these latter patients also were treated with oral tocainide 3×400xa0mg/day. Treatment was stopped in 13 of the patients because of side-effects or an insufficient effect on tinnitus. Our findings suggest that lidocaine and tocainide do not have a significant role in pharmacological treatment of tinnitus except in certain cases of long-standing severe tinnitus.

Rhinosinusitis – Langfassung: S2-Leitlinie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

1Universitäts-HNO-Klinik, Mannheim; 2Kliniek voor Neus-, Keel& Oorheelkunde, UZ Gent, Belgien; 3Homburg/Saar; 4Klinik und Poliklinik für Hals-, Nasen-, Ohrenkrankheiten, Kopfund Halschirurgie, Greifswald; 5Zentrum für Rhinologie und Allergologie, Wiesbaden; 6Institut für Medizinische Statistik, Informatik und Epidemiologie, Universität zu Köln; 7Klinik und Poliklinik für Hals-, Nasenund Ohrenheilkunde, Münster; 8Institut für Chirurgische Forschung, Marburg; 9HNO-Klinik, Universitätsklinikum Düsseldorf, 10Hals-Nasen-Ohrenklinik, Städtisches Klinikum Karlsruhe

Extracellular Matrix Components in Nasal Polyposis

Objective --Macroscopically, tissue hydration in nasal polyps seems to be a phenomenon of unknown etiology. As the macromolecular composition of extracellular matrix (ECM) determines to a large extent tissue hydration, which in turn determines tissue volume, we investigated ECM components in nasal polyps (NP) in comparison to nasal mucosa of the inferior turbinate (TM) and sinus mucosa from patients with chronic sinusitis without polyps (CS). Material and Methods --The following parameters were determined: (i) the dry weight of freeze-dried NP, TM and CS; (ii) the total protein content (Bio-Rad Protein Assay) of the tissue; (iii) the quality of proteins, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); (iv) the amount of albumin, using nephelometry; and (v) the amount of hyaluronic acid, using a chemical method: deaminative hydrolysis with carbazole. Results --In 20 NP we found a significantly elevated total protein content compared to TM (n = 20) and CS (n = 15), referred to 0.1 g dry of tissue. In SDS-PAGE of NP (n = 20) a protein band at ≈ 70 kDa, representing albumin, dominated, in comparison to TM. The amount of albumin was significantly increased in NP compared to CS and TM. In contrast, the amount of the glycosaminoglycan, hyaluronic acid, was not elevated in NP or CS. Conclusion --Albumin was significantly increased in NP and CS, possibly as a result of inflammatory plasma exudation mechanisms. Hyaluronic acid seems to play no role in the tissue hydration of NP.