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Biomedical subjects

M Wagenmann

Publications and source records attributed to M Wagenmann.

At least 19 recordsLinked to original sources

[MALT lymphoma of the orbit].

MALT lymphomas of the orbit are rare orbital tumors; the differential diagnosis needs to exclude inflammatory pseudotumors of the orbit, but also benign lymphoproliferations, pseudolymphomas, and other orbital neoplasms. After histological confirmation of the diagnosis staging is necessary, and - as long as the disease is localized exclusively in the orbit - radiation therapy should be started. The clinical picture of MALT lymphoma and its differential diagnosis and treatment are discussed with reference to an actual case.

Aged↗

The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge.

BACKGROUND: Late phase reactions after allergen challenge can be understood as a correlate of the inflammatory reaction in allergic rhinitis. METHODS: To investigate which cytokines are involved in it and to dissect direct and indirect effects of nasal allergen challenge, we performed unilateral nasal allergen provocation with the disc method in 12 seasonal allergic volunteers. Symptom scores, nasal secretions and nasal airflow were quantified. In the secretions that were collected in the early phase and for 8 h after provocation, we measured histamine, and the cytokines interleukin (IL)-1beta, IL-8, IL-4, and the natural antagonist of IL-1beta, IL-1 receptor type 1 (IL-1Ra) using enzyme-linked immunosorbent (ELISA)-assays. Control challenges with diluent instead of allergen were performed in all subjects. RESULTS: We demonstrated a bilateral increase in nasal secretion weights in the early and late phase. Histamine was significantly increased in the early and late phase in nasal secretions from both nostrils. IL-1beta increased in the late phase only, where it was also found on the unchallenged, contralateral side. Its antagonist IL-1Ra was found in very high quantities (1000-fold higher than IL-1beta) but demonstrated only marginal changes after provocation. IL-8 was increased in both nostrils early and late after challenge, whereas IL-4 was significantly elevated in the late phase. CONCLUSIONS: We described the time course of mediator and cytokine release into nasal secretions after allergen challenge. We hypothesize that the observed indirect effects on the unchallenged, contralateral side can be at least partially attributed to neuronal reflexes.

Adult↗

[Symptoms and therapy for pregnancy rhinitis].

Pregnancy rhinitis is a common condition with long-lasting nasal congestion without signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing completely within 2 weeks of delivery. Risk factors are smoking, sensitisation to house dust mites and chronic sinusitis. Hormonal influences are most likely; however, a definitive pathophysiological concept does not exist. Various treatment options are presented and a stepwise therapeutic strategy for pregnancy rhinitis is developed.

Administration, Intranasal↗

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↗

Serum level and tissue expression of c-erbB-1 and c-erbB-2 proto-oncogene products in patients with squamous cell carcinoma of the head and neck.

The proto-oncogene products erbB-l (EGF-Receptor) and erbB-2 (HER-2/neu), distinct members of the epidermal growth factor receptor family, are frequently overexpressed in squamous cell carcinoma of the head and neck (SCCHN). The accumulation of these transmembrane proteins may lead to significant amounts of the respective extracellular receptor domains (ECD) that are shed from the tumour cell surface and enter blood circulation, thus representing potential serum tumour markers. For erbB-l and erbB-2, we determined the ECD serum levels with enzyme-linked immunosorbent assays and evaluated the protein expression in tumour tissue by immunohistochemistry. The present study included 49 patients (37 untreated, 12 recurrences) and the same number of age- and sex-matched healthy controls. In 24 patients ECD serum levels were determined before and 6 weeks after surgery. Mean ECD serum levels for erbB-1 and erbB-2 were 54.8+/-1.6 and 153.7+/-6.1 fmol/ml in cancer patients, and 54+/-1.5 and 147.9+/-4.5 fmol/ml in healthy controls, respectively. There was no significant difference between untreated and recurrent disease. Serum ECD follow-ups 6 weeks after surgery revealed a significant 12.3% decline of erbB-1 but no change of erbB-2 values. Immunohistochemistry showed strong staining for erbB-1 in 78% and erbB-2 in 47% of the SCCHN specimens. No correlation was detectable between receptor ECD serum levels and receptor tissue expression, tumour stage, and tumour differentiation. Hence, ECD serum levels of erbB-1 and erbB-2 are not considered to be valuable tumour markers in SCCHN.

Adult↗

[Cytokine pattern in various forms of sinusitis].

BACKGROUND: Inflammatory sinus diseases include acute sinusitis, chronic purulent sinusitis, and chronic polypoid rhinosinusitis. We investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a distinct form of rhinosinusitis is associated with the expression of a specific cytokine profile. METHODS AND PATIENTS: Fresh sinus mucosa obtained during routine surgery 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 homogenized. The cytokine protein content (IL-1 beta,IL-3,IL-5,IL-6,IL-8,GM-CSF) of tissue homogenates was measured using ELISA technique. RESULTS: In the group of proinflammatory cytokines, the protein levels measured for interleukin IL-8, a proinflammatory cytokine, IL-1 beta, and IL-6 were elevated in acute sinusitis. In the group of eosinophil-activating cytokines interleukin-3, -5 and granulocyte an makrophage-colony stimulating factor, we measured a significantly elevated protein level of IL-5 in nasal polyp tissue in contrast to significantly elevated IL-3 protein level in chronic sinusitis. CONCLUSIONS: These findings suggest that IL-8 plays a pivotal role in neutrophil-dominated and IL-5 in eosinophil-dominated sinusitis. IL-3 seems to sustain chronic inflammation.

Biopsy↗

[Treatment of tinnitus with lidocaine? A report of clinical experiences].

The efficacy of intravenous lidocaine therapy in patients suffering from 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. 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 x 400 mg/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.

Administration, Oral↗

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↗

Bilateral increases in histamine after unilateral nasal allergen challenge.

Studying the inflammatory response that follows the early response to nasal challenge with antigen provides a better understanding of allergic rhinitis than just studying the immediate (early) response. Nine allergic volunteers were challenged unilaterally with antigen-containing discs, and bilateral changes in physiologic responses as well as in the concentration of histamine in nasal secretions were measured for 11 h. We found significant immediate increases in symptoms, sneezes, ipsilateral nasal airway resistance, and ipsilateral histamine in the early phase response. Two-thirds of the allergen-challenged volunteers showed increases in physiologic parameters or histamine in the hours after allergen challenge. The pooled data of all subjects exhibited significant increases in bilateral nasal airway resistance and in ipsilateral and contralateral histamine, hours after unilateral provocation. These responses differed significantly from control subjects. In another group of 11 volunteers challenged ipsilaterally with antigen, the number of basophils increased both on the side of challenge and on the contralateral side. The magnitude of the increase on the ipsilateral side correlated with the increase on the contralateral side (r(s) = 0.72). The basophils are the most likely source of the contralateral increase in histamine as they are on the ipsilateral side. Although the mechanisms underlying this contralateral increase in basophils and histamine are not known, we speculate that delayed, neurogenic responses play a contributory role.

Adult↗

Unilateral nasal allergen challenge leads to bilateral release of prostaglandin D2.

BACKGROUND: Multiple mediators including prostaglandin D2 and leukotriene B4 have been shown to increase in nasal secretions during the early response to nasal challenge with antigen. OBJECTIVE: Our objective was to investigate the time course of prostanoid and leukotriene B4 release into nasal secretions on both the ipsilateral and contralateral side after a unilateral nasal allergen challenge. METHODS: We performed a controlled, randomized trial. Six volunteers were challenged unilaterally with antigen or diluent in a randomized order and discs were used to collect nasal secretions from both nostrils at 2 min intervals for 20 min after the challenge. Prostanoids and leukotriene B4 (LTB4) in recovered nasal secretions were measured by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS). RESULTS: Nasal allergen challenge resulted in a significant and immediate increase in symptoms and sneezing. PGD2 was significantly elevated above diluent values (0.6 +/- 0.6 pg) 30 s after removal of the allergen disc (P < 0.05), reached its peak (423.2 +/- 182.4 pg) at 2 min and then slowly decreased. PGD2 also increased on the contralateral side after unilateral allergen challenge, reaching peak values about six times lower than on the ipsilateral side (70.8 +/- 21.7 pg at 6 min). Levels of 9a, 11b-PGF2 after antigen provocation became significantly higher than after diluent (0 +/- 0 pg) on the ipsilateral side at 2 min (17.2 +/- 5.9 pg), and reached peak levels at 4 min (25.1 +/- 8.0 pg). LTB4 also increased significantly on the side of challenge. For the other prostanoids measured (PGF2, PGF2 alpha, TxB2, 6kPGF1 alpha), no significant changes in either ipsilateral or contralateral secretions were observed after allergen challenge. CONCLUSIONS: Our study described the kinetics of PGD2 and LTB4 release as well as the contralateral release of PGD2.

Adult↗

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↗

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↗

The effect of terfenadine on unilateral nasal challenge with allergen.

To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.

Adult↗

Onset and duration of inhibition of ipratropium bromide nasal spray on methacholine-induced nasal secretions.

We performed a randomized, double-blind, placebo-controlled cross-over study with two different concentrations of ipratropium bromide (Atrovent) nasal spray to evaluate its onset and duration of inhibition. Twenty-four subjects with perennial rhinitis participated in the trial. Fifteen minutes to 12 hours after administration of ipratropium bromide (42 or 168 micrograms/nostril) or placebo nasal spray, methacholine challenges were performed and nasal secretion weights measured. After placebo administration the effect of methacholine remained unchanged over the 12-h-period. Both the 42 and 168 micrograms/nostril doses significantly inhibited the nasal hypersecretions induced by methacholine challenge within 15 min of treatment (P < 0.05). The 168 micrograms dose of ipratropium bromide continued to significantly reduce secretion weights through 6 hours, but the effectiveness of the 42 micrograms dose disappeared within 3 h. In addition to having a longer duration, the 168 micrograms/nostril dose produced approximately twice the inhibitory effect of the 42 micrograms dose.

Adult↗

Comparison of the secretory response of the nasal mucosa to methacholine and histamine.

To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine-induced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation.

Adult↗