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Biomedical subjects

C Bachert

Publications and source records attributed to C Bachert.

At least 91 records · Page 5Linked to original sources
PubMed1998

Mizolastine therapy also has an effect on nasal blockade in perennial allergic rhinoconjunctivitis. RIPERAN Study Group.

BACKGROUND: Mizolastine is a new, nonsedating antihistamine with additional anti-inflammatory properties, providing relief in allergic rhinitis and urticaria. The aim of this study was to determine the efficacy and safety of 10 mg o.d. mizolastine given to patients with perennial allergic rhinoconjunctivitis. METHODS: This double-blind, placebo-controlled study involved 257 patients suffering from the disease for more than 10 years. They were allocated, after a 1-week placebo run-in, to receive mizolastine (n = 133) or placebo (n = 124) for 4 weeks. RESULTS: Mizolastine-treated patients showed significantly greater alleviation of nasal symptoms, with a mean decrease of 36% compared with pretreatment score, compared to a mean decrease of 10% in placebo patients (P < 0.001). Nasal blockade responded favorably to mizolastine compared to placebo and was associated with a significant reduction in rhinoscopy findings (P = 0.030). Likewise, the mean ocular symptom score decreased 40% in mizolastine-treated patients compared to 7% in the placebo group (P < 0.003). The safety profile of mizolastine was satisfactory and similar to that of placebo. CONCLUSIONS: In patients suffering from perennial allergic rhinoconjunctivitis, mizolastine is a safe and potent treatment. Mizolastine's pronounced effect on nasal blockade could possibly be linked to its anti-inflammatory properties.

Adult↗
PubMed1997

Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia.

Nasal polyps, which often occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of eosinophils. Using a method for detecting eosinophils with DNA strand breaks, we found direct evidence for inhibition of eosinophil apoptosis in this model of tissue eosinophilia. By using Southern blot analysis linked to reverse transcription-PCR, we detected a mRNA signal specific for IL-5 in all nasal polyps. The identification of IL-5 as a major eosinophil survival factor was confirmed by ELISA measurements using tissue homogenates. Moreover, immunohistochemical analysis of the nasal polyp tissues demonstrated that IL-5 was localized in lymphocytes, mast cells, and eosinophils. Treatment of the eosinophil-infiltrated tissue with neutralizing anti-IL-5 mAb induced eosinophil apoptosis and decreased tissue eosinophilia. Therefore, IL-5 may represent an important cytokine responsible for the delay of the death process in eosinophils in nasal polyps. In addition, a previously suggested IL-4-dependent specific recruitment of eosinophils into the inflamed tissue could be excluded by our studies. Taken together, these findings suggest a novel mechanism by which eosinophils specifically accumulate in pathologic human tissues.

Apoptosis↗
PubMed1997

IL-5 synthesis is upregulated in human nasal polyp tissue.

BACKGROUND: In most nasal polyps, tissue eosinophilia is a striking finding, the pathologic mechanism of which is not understood. OBJECTIVE: This study was performed to investigate a possibly distinct cytokine and chemokine pattern that could explain the characteristic tissue eosinophilia in nasal polyps. METHODS: Polyps 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. RESULTS: IL-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. CONCLUSION: This study indicates that IL-5 plays a key role in the pathophysiology of eosinophilic nasal polyps and may be produced by eosinophils.

Adult↗
PubMed1997

[Allergic rhinitis. Pathophysiology, diagnosis, differential diagnosis and therapy].

Allergic diseases caused by inhalant allergens are considered to be a major health problem. Allergic rhinitis, now affecting about 15% of the population, represents an inflammatory reaction, that may lead to asthma and chronic sinusitis as subsequent problems. Diagnosis should be based on a step-by-step concept, that also takes the clinical relevance of sensibilisations and other forms of nasal hyperreactivity into account. The aims of therapy are to limit the inflammatory reaction and to restore patient's quality of life. To achieve this goal, avoidance measures, immunotherapy and antiallergic drugs are currently used. The indication for and the performance of an immunotherapy demands special knowledge, and also the different drug activities and possible side effects should be thoroughly considered.

Allergens↗
PubMed1997

Inflammatory mechanisms in chronic sinusitis.

Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.

Acute Disease↗
PubMed1997

Microbiology of chronic sinusitis.

Much controversy still exists about the role of viruses, bacteria and fungi in sinusitis. Until recently, it was not really known that the sinuses take part in the infectious process of a common cold (viral rhinitis). Indeed, CT scans show that in the vast majority of otherwise healthy volunteers with a common cold, and without a previous history of recurrent or chronic sinusitis, the sinuses are involved too. A viral rhinitis alone, however, does not seem to be able to elicit a "clinical" acute sinusitis. Bacteria determine the clinical picture and outcome of sinusitis. There is not much controversy about the role of bacteria in acute sinusitis, S. pneumoniae, H. influenzae and M. catarrhalis being the most frequently involved bacteria. Much more conflicting reports are published about the normal flora of the sinuses, the role of anaerobes and the microbiology of chronic sinusitis. In this chapter the defense and pathophysiologic mechanisms of viral, bacterial and fungal infection of the nasal and sinusal mucosa are described. It is postulated that, although bacteria are very important in acute sinusitis, their role in chronic sinusitis is minimal, the bacteria being opportunistic colonisers.

Acute Disease↗
PubMed1996

Risk factors for latex hypersensitivity in childhood.

As hypersensitivity to natural rubber latex (NRL) has become an increasingly recognized problem in children, identification of all groups at risk seems important. In this study hypersensitivity to NRL was evaluated in 337 children with potential risk factors. We identified by questionnaire children's underlying diseases, history of surgical procedures, evidence of atopy and patient's history of NRL-specific reactions. Hypersensitivity to NRL and other allergens relevant in the Düsseldorf area was evaluated by skin prick test and specific IgE. In 9.2% of all children hypersensitivity to NRL was observed. Significant risk factors for hypersensitivity to NRL were, among the underlying diseases, spina bifida (odds ratio 29.2), hydrocephalus internus (10.1), gastrointestinal malformation (5.2) and atopy (2.2). Surgical procedures with significant risk were the implantation of a ventriculo-peritoneal shunt (15.7) and surgery of the gastrointestinal tract (3.1). Frequency of surgical procedures correlated (p < 0.001) with risk of hypersensitivity. Frequent surgery and atopy were found to have an additional effect on the risk of hypersensitivity. Information about previous NRL-specific reactions obtained by questionnaire was of little predictive value when performing multivariate analysis. For children at high risk for hypersensitivity to NRL preoperative evaluation and, in case of hypersensitivity, preventive measures seem to be advised.

Adolescent↗
PubMed1996

Intranasal levocabastine provides fast and effective protection from nasal allergen challenge.

A total of 22 asymptomatic patients with a documented history of allergic rhinitis participated in this single-centre, double-blind, randomized, placebo-controlled, cross-over trial undertaken to assess the efficacy and tolerability of levocabastine nasal spray (0.5 mg/ml) in the prevention of allergen-induced nasal symptoms. Objective assessment of nasal symptoms revealed that the severity of sneezing was significantly lower following treatment with levocabastine (p < 0.001), with rhinorrhoea also tending to be less severe in the levocabastine-treated group (0.05 < p < 0.1). Rhinomanometry and acoustic rhinometry failed to reveal any significant intergroup differences, and there were no differences in nasal albumin concentrations between the two treatment groups. Patients' VAS ratings revealed significant differences in favour of levocabastine for sneezing (p < 0.001) and itching (p < 0.05), with the severity of rhinorrhoea also tending to be lower during treatment with this topical antihistamine (0.05 < p < 0.1). The mean total symptom score was also significantly lower in levocabastine-treated patients (p < 0.05). Levocabastine was well tolerated. Only two adverse events were reported: fatigue in one patient, and vesicular rash with facial oedema and urticaria in another. In conclusion, intranasal levocabastine provided effective protection from nasal allergen challenge and would appear to be a valuable therapeutic approach in patients with allergic rhinitis.

Administration, Intranasal↗
PubMed1995

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-alpha (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-1 beta, TNF-alpha 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-1ra) 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.

Cell Adhesion Molecules↗
PubMed1995

Elevated levels of interleukins IL-1 beta, IL-6 and IL-8 in naturally acquired viral rhinitis.

We studied the cytokines IL(interleukin)-1 beta, IL-4, IL-6 and IL-8 in nasal lavage samples from 20 patients with naturally acquired viral rhinitis and 5 healthy controls without nasal complaints. IL-1 beta, IL-6 and IL-8 levels in lavage fluid from the viral rhinitis patients were significantly elevated when compared to control subjects. IL-4 was not measurable in any of the samples. The cytokine levels in secretions from the healthy controls remained stable intraindividually on 5 consecutive sampling days. We suggest that cytokines such as IL-1 beta, IL-6 and IL-8, but not IL-4, are involved in the pathophysiology of the common cold.

Adult↗
PubMed1995

Oral antihistamine/decongestant treatment compared with intranasal corticosteroids in seasonal allergic rhinitis.

This international, multicentre, randomized, double-blind, double-dummy, parallel-group trial was undertaken to compare the efficacy and tolerability of once-daily astemizole-D (10 mg astemizole plus 240 mg pseudoephedrine) with beclomethasone nasal spray (0.05 mg/ml) two puffs/nostril administered twice daily in a total of 204 patients with seasonal allergic rhinitis. Treatment duration was 4 weeks. Although investigator assessments of symptom severity were generally comparable in the two treatment groups throughout the trial, statistically significant differences in favour of astemizole-D for sneezing and ocular symptoms were apparent at the end of the 4-week treatment period (P < 0.05). Patient diary data support these findings, with significant differences in favour of the antihistamine/decongestant combination reported for ocular symptoms after 2 weeks of treatment (P < 0.05) and non-significant trends for sneezing after 2 weeks and ocular symptoms over the entire treatment period (P = 0.07). Use of rescue medication for ocular symptoms was also significantly lower in the astemizole-D treatment group (P < 0.05). A wide range of adverse experiences were reported, however, there were no statistically significant differences in the type or incidence of those between the two treatment groups. In conclusion, astemizole-D appears to be at least as effective and well tolerated as intranasal beclomethasone in the treatment of seasonal allergic rhinitis, providing at least comparable relief from all nasal symptoms including congestion and significantly greater relief from ocular symptoms than the topical steroid.

Administration, Intranasal↗
PubMed1995

Obstetric complications and autoantibodies in schizophrenia.

Our hypothesis stated that patients with schizophrenia who had obstetric complications (OC) were more likely to have autoimmune abnormalities than those without OC. OC were rated using a checklist. Anti-brain autoantibodies were measured in serum using an enzyme immunoassay. Autoantibodies to non-CNS tissues were detected using serological procedures. There were no significant differences between the groups with respect to anti-brain antibodies, but patients with OC (n = 24) had a significantly higher prevalence of autoantibodies to non-CNS tissues than patients without OC (n = 25). Both groups were receiving neuroleptic drugs. OC may contribute to autoimmune abnormalities among patients with schizophrenia.

Adult↗
PubMed1994

Metachromatic, IgE-bearing and tryptase-containing cells on the nasal mucosal surface in provoked allergic rhinitis.

We studied the relationship between mast cells or basophils and symptoms in provoked allergic rhinitis. Nasal brush and lavage samples were obtained before nasal allergen challenge and every 2 h for 12 h after the challenge in 10 allergics and 3 controls. The cells were identified by their metachromatic staining properties (brush and lavage samples) or with immunohistochemical methods using specific antibodies to IgE and tryptase, a selective mast-cell marker (brush samples). Histamine was determined in the brush samples using liquid chromatography. After an initial decrease, the numbers of metachromatic, IgE-bearing and tryptase-containing cells, as well as the histamine content of the cells in the brush samples, increased during the subsequent observation hours. The prechallenge cell and histamine values correlated with the symptom score 15 min after the challenge. The prechallenge lavage samples lacked metachromatic cells, but these cells were found in increasing numbers after the provocation. Three of the patients differed from the remaining seven in that their prechallenge brush samples contained many positively stained cells. All patients showed a positive cellular response to the allergen challenge, but these three individuals showed the most vivid response. The morphology of the metachromatic cells in the prechallenge brush samples agreed with that of mast cells, but the morphology of metachromatic cells which outnumbered tryptase-containing cells in samples at 8 to 12 h rather agreed with their being basophils.

Adult↗