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Biomedical subjects

C Rudack

Publications and source records attributed to C Rudack.

At least 19 recordsLinked to original sources

Primary role of growth-related oncogene-alpha and granulocyte chemotactic protein-2 as neutrophil chemoattractants in chronic rhinosinusitis.

BACKGROUND: The aetiology of chronic rhinosinusitis (CRS) remains unclear. The purpose of this study was to investigate neutrophil-attracting chemokine patterns in CRS without nasal polyposis. METHODS: The biological activity of the chemokines was identified using a two-step high-performance liquid chromatography (HPLC) technique combined with a bioassay in extracts from 55 CRS patients, and in the turbinate mucosa (TM) of patients (N=51) undergoing septumplasty. The biologic activity of each chemokine was assessed using blocking antibodies to chemokines. Immunolocalization of detected neutrophil chemokines was performed by quantitative evaluation of immunohistochemistry. Besides, PCR analysis was performed to quantify neutrophil chemokine mRNA. RESULTS: In CRS, the chemokines primarily detected by two-step HPLC were growth-related oncogene-alpha (GRO-alpha) and the granulocyte chemotactic protein-2 (GCP-2). Blocking of GCP-2 and GRO-alphad each resulted in chemotaxis inhibition rates of 43.3% and 35.9%, respectively, whereas anti-IL-8 and anti-ENA-78 had no effect. Both GCP-2 and GRO-alphad were generally synthesized by the surface epithelium and mucosal glands while GRO-alpha in particular was synthesized by endothelial cells, as shown by immunohistochemistry. The concentrations of the chemokines IL-8 and epithelial cell-derived neutrophil attractant-78 (ENA-78) were low in CRS and TM. CONCLUSION: It appears that both GRO-alpha and GCP-2 contribute to neutrophil chemotaxis in CRS, whereas IL-8 and ENA-78 appear to be of secondary importance for the chemotaxis of neutrophils in this condition. The expression of chemokines in mucosal gland cells is the main phenomenon involved in constitutive neutrophil chemotaxis in the TM.

Adult↗

The effect of endogenous nitric oxide on mechanical ciliostimulation of human nasal mucosa.

BACKGROUND: Endogenous nitric oxide (NO) production by the inducible NO-synthase is enhanced in the nasal respiratory epithelium of patients with allergic rhinitis. Recent experimental data suggest endogenous NO to be strongly involved in the regulation of ciliary activity, the driving force of the mucociliary transport system. OBJECTIVE: In this study, we investigated the effect of endogenous NO on mechanical stimulation of ciliary activity in a nasal mucosa explant model. METHODS: Cultures of nasal mucosa explants were incubated with TNF-alpha and bacterial lipopolysaccharides (LPS) to enhance endogenous NO production. Direct in vitro NO imaging was performed by the fluorescent NO-indicator DAF-2 DA and laser scanning confocal microscopy. Ciliary beat frequency (CBF) was determined using a photoelectric technique. Mechanical stimulation was performed by two consecutive flow increments in a closed perfusion chamber. Endogenous NO-synthesis was blocked by l-NAME before the second flow stimulation. RESULTS: Under control conditions the mean rise of CBF relative to baseline was 30.2% during the first flow increment and 30.7% during the second flow increment. Blocking of the endogenous NO synthesis in TNF-alpha/LPS-stimulated cultures reduced baseline CBF by 10.6+/-2.1% (P<0.05) but the effect of mechanical ciliostimulation on CBF remained unchanged (36.0% vs. 38.2%). CONCLUSION: In conclusion, endogenous NO- and Ca(2+)-dependent mechanical stimulation of ciliary activity probably use independent intracellular signalling pathways. The combination of both effects on ciliary activity is likely to improve the local defence against inhaled allergens in patients with nasal allergies.

Cilia↗

Induction of CXC chemokines in A549 airway epithelial cells by trypsin and staphylococcal proteases - a possible route for neutrophilic inflammation in chronic rhinosinusitis.

While various microorganisms have been recovered from patients with chronic rhinosinusitis, the inflammatory impact of virulence factors, in particular proteases from Staphylococcus aureus and coagulase negative staphylococci on the nasal epithelium, has not yet been investigated. Expression of CXC chemokines was determined in the epithelium of patients with chronic rhinosinusitis by immunohistochemistry. In a cell culture system of A549 respiratory epithelial cells, chemokine levels were quantified by enzyme-linked immunosorbent assay (ELISA) after stimulation with supernatants originating from three different staphylococcal strains or with trypsin, representing a serine protease. Inhibition experiments were performed with prednisolone, with the serine protease inhibitor 4-(2-aminoethyl)-benzenesulphonylfluoride (AEBSF) and with the nuclear transcription factor (NF)-kappaBeta inhibitor (2E)-3-[[4-(1,1-dimethylethyl)phenyl]sulphonyl]-2-propenenitrite (BAY) 11-7085. Electromobility shift assays (EMSA) were used to demonstrate NF-kappaB-dependent protein synthesis. CXC chemokines interleukin (IL)-8, growth-related oncogene alpha (GRO-alpha) and granulocyte chemotactic protein-2 (GCP-2) were expressed in the patients' epithelium whereas epithelial cell-derived neutrophil attractant 78 (ENA-78) was rarely detected. In A549 cells, chemokines IL-8, ENA-78 and GRO-alpha but not GCP-2 were induced by trypsin and almost equal levels were induced by staphylococcal supernatants. IL-8, GRO-alpha and ENA-78 synthesis was suppressed almost completely by AEBSF and BAY 11-7085, whereas prednisolone reduced chemokine levels differentially dependent on the supernatant added. CXC chemokines were detectable in the epithelium of patients with chronic rhinosinusitis. Staphylococcal serine proteases induced CXC chemokines in A549 cells, probably by the activation of proteases activated receptors, and thus might potentially be involved in neutrophilic inflammation in chronic sinusitis.

Adult↗

[Is tracheotomy of angioedema associated with ACE-inhibitor therapy?].

Angioedema of the upper airways associated with angiotensin-converting enzyme inhibitors (ACEI) represent a rare but serious problem. We present two cases from our hospital in order to illustrate the therapeutic consequences resulting from angioedema associated with the intake of ACEIs. Surgical airway management should be considered early if medical treatment fails.

Aged↗

Neutrophil chemokines in epithelial inflammatory processes of human tonsils.

CXC chemokines are thought to play an important role at sites of inflammation. Because ELR(+) CXC chemokines are expressed in different types of tonsillitis we investigated the role of the surface/crypt epithelium of human tonsils in producing ELR(+) CXC chemokines: interleukin (IL)-8 (CXCL8), ENA-78 (CXCL5), GRO-alpha (CXCL1) and GCP-2 (CXCL6). Tonsillar tissue was obtained from patients undergoing tonsillectomy and chemokine expression was investigated by means of immunohistochemistry. A549 cells were used as a model to study kinetics of chemokine expression in epithelial cells. Cells were stimulated with tumour necrosis factor (TNF)-alpha, lipopolysaccharide (LPS) and supernatants derived from aerobic/anaerobic Staphylococcus aureus strains. Chemokine expression was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We observed epithelial expression of IL-8, GRO-alpha and GCP-2 in different types of tonsillitis, whereas ENA-78 was rarely expressed. In A549 cells abundant expression of ENA-78 was detected. IL-8 and GCP-2 are expressed in an acute type of tonsillitis whereas GRO-alpha was frequently detectable both in chronically and acutely inflamed tonsils. ENA-78 does not seem to play a pivotal role in tonsillitis in vivo.

Adolescent↗

Chronic rhinosinusitis--need for further classification?

OBJECTIVE AND DESIGN: The etiology and classification of chronic rhinosinusitis with and without nasal polyps still remain unclear. Based on investigations of inflammation type in biopsies from patients with nasal polyposis and chronic non-polypous rhinosinusitis, we tried to determine whether there is a need for further classification of chronic rhinosinusitis into two disease entities. SUBJECTS: Biopsies of diffuse nasal polyposis (n= 37) and chronic rhinosinusitis without nasal polyps (n= 41) were examined for eosinophil and neutrophil tissue infiltration, degree of inflammation, and involved cytokines in inflammation mechanisms. METHODS: Neutrophil elastase positive neutrophils and CD38-positive lymphocytes were characterized in nasal polyposis and chronic non-polypous rhinosinusitis by immunohistochemistry. Using a monoclonal antibody against eosinophilic cationic protein (ECP) activated eosinophils were identified. In tissue homogenates, albumin was quantified as a marker for inflammation vascular permeability. In addition, interleukin (IL)-8 and IL-5 were determined by means of quantitative ELISA measurements in homogenates. RESULTS: Significantly increased numbers of eosinophils and neutrophils were detected in nasal polyposis. In chronic rhinosinusitis without nasal polyps, tissue infiltration was dominated by lymphocytes and neutrophils. The concentration of albumin and IL-5 was significantly higher in nasal polyps than in chronic rhinosinusitis without nasal polyps. IL-8 protein levels did not differ significantly between the two tissue types. In addition, patients' durations of illness did not differ significantly. CONCLUSIONS: Different types and quantities of inflammatory cells as well as different levels of inflammation support our hypothesis that there is need for further subdivision of chronic rhinosinusitis into two disease entities.

ADP-ribosyl Cyclase↗

[Tubercular spondylitis with retropharyngeal abscess].

In the industrialized countries, the last 15 years have seen an increasing rate of cases of tuberculosis. However, upper cervical spine tuberculosis involving a cold retropharyngeal abscess is extremely rare. We report on a 58 year old female from Sri Lanka presenting with unspecific neck pain and stiffness. She was diagnosed as having extensive tubercular osteodestruction of the second cervical spine body, including epidural and large retropharyngeal abscesses.

Cervical Vertebrae↗

Platelet GPIaC807T polymorphism is associated with negative outcome of sudden hearing loss.

To determine the relevance of inherited prothrombotic risk factors in sudden hearing loss, we investigated 85 patients with sudden hearing loss of >/= 60 dB for the presence of inherited prothrombotic risk factors. The FV G1691A, FII G20210A, GPIa C807T, GPIIIa PIA1/A2, PAI-1 4G/5G, t-PA Alu repeat ID, MTHFR C677T and CBS 844ins68 genotypes were investigated. Allele frequencies found in patients were compared to those of 85 healthy control subjects of the same ethnic background using Chi-squared and odds-ratio analysis. The frequency of the GPIa807T allele was significantly elevated in patients compared to controls. In addition, allele frequency and genotype distribution of GPIa was significantly elevated in the patient group without recovery after 3 months of sudden hearing loss onset. Allele frequencies of all other prothrombotic risk factors investigated here did not differ from those of the control subjects. The single-nucleotide polymorphism of GPIa C807T seems to play a role as a prognostic factor in recovery from sudden hearing loss.

Adolescent↗

Biologically active neutrophil chemokine pattern in tonsillitis.

To gain an insight into the mechanisms of chronic and acute inflammation, the production of neutrophil chemokines in different types of tonsillitis - hyperplastic tonsillitis (HT), recurrent tonsillitis (RT) and peritonsillar abscesses (PA) - was investigated. The chemokines interleukin-8 (IL-8), growth-related oncogene-alpha (GRO-alpha), epithelial cell-derived neutrophil attractant-78 (ENA-78) and granulocyte chemotactic protein-2 (GCP-2) were detected and shown to have different biological activities. With respect to the biological properties of CXC chemokines, the biological activity of the chemokines was identified using a three-step high-performance liquid chromatography (HPLC) technique, a bioassay involving measurement of neutrophil chemotaxis in a single Boyden chamber in tissue of HT, RT and PA. Using reverse transcription-polymerase chain reaction (RT-PCR), the chemokine concentrations were determined in the different tonsillitis entities. The chemokine pattern was dominated in PA by IL-8 and GRO-alpha and in RT by GRO-alpha. Hyperplastic tonsils of patients without a history of infection generated about five times lower IL-8 than PA. A protein concentration of GCP-2 was induced in PA and RT, whereas ENA-78 remained the same in all entities. In conclusion, it would appear that IL-8 was up-regulated in acute inflammation, whereas GRO-alpha dominated in chronic inflammation. ENA-78 seems not to play a pivotal role in inflammatory processes in tonsils. GCP-2 may serve as a substitute chemokine in certain inflammatory conditions as its quantity of mRNA and protein was higher in RT and PA than in HT.

Acute Disease↗

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.

Adolescent↗

[Primary nasal epithelial cells and fibroblasts have inflammation-inducing functions].

BACKGROUND: The appearance of neutrophils in rhinitis and sinusitis led to the working hypothesis that neutrophil-specific attractants commonly called chemokines are generated by stimulation with proinflammatory cytokines and bacteria. The receptor mechanism of chemokine synthesis by bacterial products is under discussion and still has to be elucidated. PATIENTS AND METHODS: The primary nasal cultures of epithelial cells and fibroblasts ( n=4) were incubated with TNF-alpha (tumor necrosis factor) for 24 and 72 h. Bacterial stimulation of the cell cultures was performed by adding supernatants from the mucoid phenotype of Pseudomonas aeruginosa (PA01) in dilution 1:5 for 24 and 72 h. Supernatants were collected and the concentration of the chemokines interleukin-8 (IL-8), GRO-alpha (growth-related oncogene-alpha), and ENA-78 (epithelial neutrophil-activating peptide) were determined by ELISA technique. Our results revealed that the protein concentration of the chemokines GRO-alpha and IL-8 was upregulated by TNF-alpha as well as by bacterial supernatants in epithelial cells. CONCLUSION: We conclude that GRO-alpha and IL-8 were inducible by bacterial supernatants in nasal epithelial cells and fibroblasts.

Chemokine CXCL1↗

[Therapeutic management of necrotizing neck infections].

BACKGROUND: Necrotizing neck infections are uncommon soft-tissue infections, usually caused by virulent, toxin producing bacteria. Necrotizing fasciitis represents a special form of necrotizing soft tissue infection with a mortality rate of up to 76% even though aggressive therapy is recommended. PATIENTS AND METHODS: In the last 2 years we treated four patients with severe necrotizing neck infections and five suffering from necrotizing fasciitis. RESULTS: Microbiological analysis revealed mixed infections with Candida albicans, Streptococcus pyogenes, Fusobacterium, Proprioni bacteria and Staphylococcus. The surgical management was not only restricted to drainage, but also included functional neck dissection in order minimize the spread of the disease. Eight of our patients recovered completely, but one died due to toxic shock as consequence of a delayed in therapy. CONCLUSION: Complete recovery of patients suffering from necrotizing fasciitis depends on early and aggressive surgical therapy including neck dissection and drainage as well as an interdisciplinary strategy of conservative therapy. Hyperbaric oxygen should be considered as a treatment adjunct in patients with necrotizing fasciitis if surgery and antibiotic treatment fail.

Adult↗

[Aeroallergens becoming more significant for allergic rhinitis].

BACKGROUND AND METHODS: Allergic rhinitis is a very common disease with an increasing prevalence to 10-20% over the last 40 years. These studies propose different reasons for this increase. RESULTS: An increasing exposure to outdoor allergens is shown in different geographical and climatic areas, like the rising frequency of reactions to cockroaches in Europe or to mites in tropical areas. New aero-allergens have appeared in the animal and vegetable realms, both in home and professional environments. Respiratory allergy to Ficus benjamina inaugurated a new type of allergy caused by airborne allergens from non-pollinating plants. This is specially important because of the cross-reactions to latex. CONCLUSION: The immunochemical structures of airborne allergens are now better known, and the homologous structures of different allergens largely explain certain cross-reactions. In the future, recombinant allergens will probably lead to better understanding of the role of allergens in inducing and maintaining the allergic reaction and should promote our approach to diagnosis and therapy.

Air Pollutants↗

RANTES, eotaxin and eotaxin-2 expression and production in patients with aspirin triad.

BACKGROUND: Polyposis, asthma, aspirin-intolerance and aspirin-triad are mostly accompanied with eosinophilia of mucosal airways. Chemotactic cytokines, the CC-chemokines regulated on activation, normal T-cell expressed (RANTES), eotaxin, and eotaxin-2 activate and attract eosinophilic leukocytes to the site of inflammation. This points to the implication of CC-chemokines in eosinophilia of nasal tissue of these diseases. METHODS: Therefore, nasal polypous tissue specimens of patients suffering from chronic nasal polypous sinusitis (NP), intrinsic asthma (ATA), aspirin-intolerance (AINA), and aspirin-triad (TRIAD) were investigated. The amount of mRNA and protein of CC-chemokines was analyzed using semi-quantitative reverse transcriptase polymerase chain reaction and chemokine-specific enzyme-immuno-assays. The patterns of CC-chemokines were compared. RESULTS: The mRNA-expression as well as protein synthesis of CC-chemokines was quantified in all tissues investigated. The expression of RANTES-mRNA in NP, ATA, AINA, and TRIAD (averaging 148-324% D-glyceraldehyde-3-phosphate dehydrogenase) and protein synthesis (0.13-0.15 ng/mg tissue weight) did not differ significantly. But the protein synthesis of eotaxin- and eotaxin-2-mRNA was significantly (P < 0.05) higher in TRIAD (3.3 pg/mg and 3.4 ng/mg tissue weight) (4 ng/mg tissue weight), than in NP, ATA, or AINA (1.8 pg/mg and 2.1 ng/mg, 2.1 pg/mg and 1.6 ng/mg, or 1.7 pg/mg and 2.2 ng/mg tissue weight, respectively). CONCLUSION: Patients suffering from TRIAD in association with tissue eosinophilia were characterized by elevated eotaxin and eotaxin-2 mRNA-expression as well as protein-synthesis. This pointed to the implication of eotaxins and RANTES in eosinophilia-associated diseases. Further studies will have to prove, whether the analysis of these chemokines might improve the diagnosis of eosinophilia associated polyposis and initiate the development of new therapeutic strategies.

Adult↗

Neutrophil chemokines in cultured nasal fibroblasts.

BACKGROUND: To gain insight into the mechanisms responsible for tissue neutrophil immigration in sinusitis, primary nasal fibroblasts are analyzed for synthesizing and delivering neutrophil chemokines. METHODS: Primary nasal fibroblast cell culture was treated with tumor necrosis factor (TNF)-alpha concentrations of 20 and 200 ng/ml for 2, 8, 24 and 72 h. Chemokine concentrations in supernatants were determined by enzyme-linked immunoassay (ELISA) and chemokine mRNA expression in fibroblasts was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Biological chemotactic activity was identified by three-step high-performance liquid chromatography (HPLC) and by bioassay measuring neutrophil chemotaxis in a single Boyden chamber system. RESULTS: Interleukin (IL)-8 and growth-related oncogene (GRO)-alpha were induced in nasal fibroblast culture by proinflammatory stimulus. After 24 h of stimulation neutrophil chemotactic activity only was detected for IL-8. Granulocyte chemotactic protein (GCP)-2 mRNA was already significantly up-regulated after 2 h of stimulation. CONCLUSION: Induction of IL-8 protein dominates chemokine synthesis 24 and 72 h after stimulation, whereas induction of GCP-2 mRNA seems to have a role in the early phase after 2 h of exposition with TNF-alpha.

Antimicrobial Cationic Peptides↗