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Biomedical subjects

C Bachert

Publications and source records attributed to C Bachert.

At least 19 recordsLinked to original sources

[Steroid sprays in non-infectious rhinitis and sinusitis. Proper and regular spraying does not damage the nasal mucosa].

Glucocorticoids are an effective therapeutic option for most forms of non-infectious rhinitis and sinusitis. In Germany, dexamethasone, beclomethasone diproprionate, flunisolide, fluocortin butyl ester, budesonide, fluticasone proprionate, triamcinolone acetonide and mometasone furoate are available for nasal application. The action of these drugs is mediated by cytoplasmic receptors (glucocorticoid receptors). In addition, receptor-independent immediate effects are also known. To ensure optimal efficacy of corticoid sprays, detailed patient instruction is of importance, with particular emphasis being placed on the correct spraying technique and regular application. Modern preparations are associated with very few side effects. There is no evidence that mucosal atrophy occurs.

Administration, Intranasal↗

Up-regulation of IL-18 in allergic rhinitis.

BACKGROUND: This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1beta in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms. METHODS: We measured IL-18 and IL-1beta concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1beta and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy. RESULTS: In SAR, the increase of IL-18, IL-1beta and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1beta significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1beta, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR. CONCLUSION: This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.

Adult↗

[Statistics on allergology and environmental medicine in the ENT specialty in Germany].

Environmental medicine and allergy were found to be important in the daily ENT practice after statistical analysis and an inquiry among all ENT doctors in Germany. 64% of ENT colleagues do practice allergy, 20% environmental medicine. With reference to all registered ENT doctors 24% are titled allergists, 4% specialists in environmental medicine. Focussing on the teaching there is a big difference between both groups. Whereas training facilities for allergists are reasonable, there are only a few chief instructors for environmental medicine in the ENT society. This fact has to be considered on educational plannings in future.

Allergy and Immunology↗

Elevated levels of myeloperoxidase, pro-inflammatory cytokines and chemokines in naturally acquired upper respiratory tract infections.

Upper respiratory tract infections (URTIs) are characterised by a neutrophilic mucosal infiltration. The purpose of this study was to investigate the time course of release of the cytokines/chemokines interleukins (IL) IL-1beta, IL-1ra, tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8, interferon-gamma (IFN-gamma) and monocyte chemotactic protein (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), myeloperoxidase (MPO) and bradykinin in nasal secretions of patients with a naturally acquired URTI. A total of 117 healthy adult volunteers were recruited for baseline nasal lavages, 39 of whom developed URTI symptoms within 6 months and returned to our centre within 48 h. Lavages were performed daily during the symptomatic period and 3 weeks thereafter, with symptoms no longer present. Compared to baseline, significantly elevated concentrations of total protein, bradykinin, IL-1beta, TNF-alpha, IL-6, IL-8, MCP-1, IFN-gamma, MPO and sICAM-1 were detected in nasal lavage fluids of symptomatic patients, whereas IL-1ra remained unaltered. All studied variables reached baseline 3 weeks after the URTI. Naturally acquired URTI represent a limited, neutrophilic inflammatory reaction, orchestrated by the release of pro-inflammatory cytokines and chemokines.

Adult↗

Decongestant efficacy of desloratadine in patients with seasonal allergic rhinitis.

Recent advances in experimental immunologic approaches to seasonal allergic rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The conventional view of SAR as a local response to inhaled allergens has largely given way to a new view of this disorder as a systemic condition with local tissue manifestations. This concept, together with an increasing recognition of specific mediators' distinct roles in driving the early- and late-phase allergic responses, has opened multiple lines of therapeutic attack within the allergic cascade. Potent inhibition of inflammatory mediator release at distinct points in this cascade is conferred by desloratadine. In addition to the familiar range of SAR symptoms amenable to antihistamine therapy, desloratadine uniquely attenuates patient ratings of nasal congestion. This novel, nonsedating histamine H1-receptor antagonist is the only once-daily antiallergic product with a consistent decongestant effect that begins within hours of the first morning dose and is sustained for the entire treatment period.

Chemotaxis, Leukocyte↗

Mizolastine in the treatment of seasonal allergic rhinoconjunctivitis: a European clinical experience with 5408 patients managed in daily practice (PANEOS SAR Study).

BACKGROUND: Mizolastine, a potent H1 antihistamine with additional antiallergic properties, is marketed for the treatment of allergic rhinoconjunctivitis and urticaria. The objective was to investigate the safety and effectiveness of mizolastine under conditions of daily practice in patients with seasonal allergic rhinoconjunctivitis (SAR). METHODS: In an open multicenter study, mizolastine 10 mg daily was administered for 14 days during the pollen season. Nasal and ocular symptoms, time to onset of symptom relief, and effect of the drug on diurnal alertness were evaluated. Safety was evaluated on the basis of self-reported adverse events (AE). RESULTS: A total of 5408 patients (36+/-14 years of age, females=57%) with a history of SAR for 8+/-9 years were treated for a mean of 17.1+/-5.0 days. SAR symptoms improved in 93% and decreased by at least 50% in 86% of patients; 78% reported improvement after the first drug intake and 51% from the first hour. Sixty-nine percent considered mizolastine more effective than other antihistamines taken previously. The incidence of AE was low (3.8%). CONCLUSION: The high responder rate, the rapid onset of action, and the low incidence of AE observed in this large multicenter study confirm the previously reported beneficial efficacy and safety of mizolastine in the management of SAR.

Adolescent↗

Presence of fluticasone propionate on human nasal mucosal surface and in human nasal tissue over a period of 24 h after intranasal application.

BACKGROUND: Once-daily use of nasally applied glucocorticoids was demonstrated to be effective in the treatment of allergic rhinitis. The aim of the study was to measure concentrations of fluticasone propionate (FP) in nasal secretion and nasal tissue over a period of 1 day after a single application of 100 microg FP. METHODS: Twenty-six patients applied nasal FP spray at different time intervals before surgery. Cotton swabs, used to clean the mucosal surface, and resected nasal tissue were extracted. FP concentrations were determined by RIA. RESULTS: FP was found in nasal secretions in concentrations from 15 to 1 microg/g over a period of 20 h, and in nasal tissue in concentrations from 200 to 13 ng/g up to 24 h after the single application. CONCLUSION: The long-persisting high concentrations of FP provide the pharmacokinetic basis for once-daily treatment.

Administration, Intranasal↗

Total and specific IgE in nasal polyps is related to local eosinophilic inflammation.

BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation and often coexist with asthma. However, the role of atopy and IgE in NP pathogenesis is unclear. OBJECTIVE: We sought to determine whether there is an association between total and specific IgE to a variety of allergens in polyp and nonpolyp tissue and markers of eosinophilic inflammation or skin test results. METHODS: Homogenates were prepared from nasal tissue of 20 patients with NPs and 20 patients without NPs and analyzed for concentrations of IL-5, IL-4, eotaxin, leukotriene (LT) C4/D4/E4, sCD23, and histamine (ELISA). Eosinophil cationic protein (ECP), tryptase, and total and specific IgE for inhalant allergens and Staphylococcus aureus enterotoxins were measured (ImmunoCAP). RESULTS: The concentrations of total IgE, IL-5, eotaxin, ECP, LTC4/D4/E4, and sCD23 were significantly higher in NP tissue compared with nonpolyp tissue. Total IgE was significantly correlated to IL-5, ECP, LTC4/D4/E4, and sCD23 and to the number of eosinophils in NPs. On the basis of the presence of specific IgE antibodies in tissue, 3 NP groups were defined. NP group 1 demonstrated no measurable specific IgE, and NP group 2 selected specific IgE. The third group demonstrated a multiclonal specific IgE, including IgE to S aureus enterotoxins, a high total IgE level, and a high prevalence of asthma. CONCLUSIONS: These studies suggest that there is an association between increased levels of total IgE, specific IgE, and eosinophilic inflammation in NPs, which may be of relevance in the pathophysiology of nasal polyposis. Similarly, the presence of specific IgE to staphylococcal enterotoxins A and B also points to a possible role of bacterial superantigens.

Eosinophils↗

Lumenal endosomal and Golgi-retrieval determinants involved in pH-sensitive targeting of an early Golgi protein.

Despite the potential importance of retrieval-based targeting, few Golgi cisternae-localized proteins have been demonstrated to be targeted by retrieval, and the putative retrieval signals remain unknown. Golgi phosphoprotein of 130 kDa (GPP130) is a cis-Golgi protein that allows assay of retrieval-based targeting because it redistributes to endosomes upon treatment with agents that disrupt lumenal pH, and it undergoes endosome-to-Golgi retrieval upon drug removal. Analysis of chimeric molecules containing domains from GPP130 and the plasma membrane protein dipeptidylpeptidase IV indicated that GPP130 targeting information is contained entirely within its lumenal domain. Dissection of the lumenal domain indicated that a predicted coiled-coil stem domain adjacent to the transmembrane domain was both required and sufficient for pH-sensitive Golgi localization and endosome-to-Golgi retrieval. Further dissection of this stem domain revealed two noncontiguous stretches that each conferred Golgi localization separated by a stretch that conferred endosomal targeting. Importantly, in the absence of the endosomal determinant the Golgi targeting of constructs containing either or both of the Golgi determinants became insensitive to pH disruption by monensin. Because monensin blocks endosome-to-Golgi transport, the finding that the endosomal determinant confers monensin sensitivity suggests that the endosomal determinant causes GPP130 to traffic to endosomes from which it is normally retrieved. Thus, our observations identify Golgi and endosomal targeting determinants within a lumenal predicted coiled-coil domain that appear to act coordinately to mediate retrieval-based targeting of GPP130.

Animals↗

Glucocorticosteroids rapidly inhibit allergen-induced expression of E-selectin in vitro in a mucosal model of allergic rhinitis.

BACKGROUND: Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E-selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30-min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic rhinitis. METHODS: Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml. The expression of E-selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation. RESULTS: In this model, E-selectin expression was significantly upregulated by allergen and rhIL- 1beta within 1 and 2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by > or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l, respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid upregulation of E-selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l. CONCLUSIONS: Allergen-induced E-selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen-induced cytokine release.

Adolescent↗

Value of acoustic rhinometry in environmental medicine.

It is a weak point of environmental medicine that health disturbances, e.g. functional affections of the upper respiratory tract, cannot be objectively judged by physicians resp. researchers. In this study, the validity of acoustic rhinometry, a method giving information on cross-sectional areas of the upper airways by means of ultrasound probing, was tested in 40 volunteers seven times during one year. Furthermore, using a simplified model of the nose the accuracy of this method to measure the minimal cross-sectional area (MCA) in the nose was tested. The measurements were extremely confounded by the mode of connection to the nose (e.g. selected adapter, direction of application) and by the MCA in the nasal cavity. Statistical analyses showed a good reproducibility of measurements repeated within minutes, but suggested an intrapersonal variability over the analyzed examination phases due to apparatus independent factors. However, this variability could not be explained by influencing and confounding factors obtained by questionnaire, medical history, and physical examination. The test model showed little to great errors (1.5 to 568.5%) between the actual and the measured MCA, depending on the diameter. It is concluded that the method of acoustic rhinometry has to be standardized before it's value for environmental medicine can finally be judged. Further studies are necessary that should focus among others on factors influencing the variability of MCA and the effect of MCA on the measurement of the area behind the MCA. So far, the use of acoustic rhinometry for the evaluation of nasal function cannot be recommended.

Acoustics↗

Value of antral puncture in the intensive care patient with fever of unknown origin.

OBJECTIVE: To evaluate the use of maxillary sinus puncture as a routine diagnostic procedure to exclude or confirm purulent sinusitis in intensive care unit (ICU) patients presenting with fever or a septic state of unknown origin. STUDY DESIGN: Retrospective. METHODS: All patients admitted to the ICU at the University Hospital Ghent who required ENT examination to exclude acute sinusitis as possible cause of their otherwise inexplicable fever or septic state underwent maxillary sinus puncture via the inferior meatus. The results of clinical examination and the relation between the presence of foreign bodies (e.g., nasogastric tubes) and culture results from the middle meatus and sinuses were analyzed. RESULTS: One hundred five punctures were performed in 53 patients. Macroscopic purulent effusions were obtained from 25 and nonpurulent effusions from 19 sinuses. The presence of a nasogastric tube did not influence puncture results but significantly increased colonization of the middle meatus. Staphylococcus aureus and Gram-negative agents were frequently cultured from sinus aspirates. Although purulent secretions often reveal no growth, most patients present with a multibacterial (40%) or monobacterial (28%) infection. Simple anterior rhinoscopy reduces the need for antral puncture. Only 8% of punctures in patients with a normal clinical examination were positive. CONCLUSIONS: Antral puncture proves to be a simple, fast, safe, inexpensive, and effective procedure for immediate diagnosis of acute nosocomial sinusitis in ICU patients and is therefore recommended as first procedure in these patients, even when only minor clinical abnormalities are present.

Adolescent↗