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H Magnussen

Publications and source records attributed to H Magnussen.

At least 19 recordsLinked to original sources
PubMed1995

[Duration of the effect of inhaled corticosteroids on lung function and sensitivity of the respiratory tract in patients with bronchial asthma].

AIM: The effects of cessation of therapy with inhaled steroids on symptoms, lung function, and airway responsiveness in stable bronchial asthma should be examined. PATIENTS AND METHODS: During a 4-week run-in period 24 patients inhaled beclomethasone dipropionate (BDP) 2000 micrograms/d and salbutamol 800 micrograms/d. This was followed by a 6-week treatment period during which the patients obtained either placebo plus 800 micrograms salbutamol or 2000 micrograms BDP plus 800 micrograms salbutamol in a randomized double-blind design. Symptoms, lung function, and airway responsiveness to histamine were measured before and after the run-in period and at the end of each week during the treatment period. RESULTS: Airway responsiveness was assessed as the concentration of inhaled histamine which caused a 20% fall in FEV1 compared to baseline (PC20). During the run-in period, 21 of the 24 patients showed an increase of PC20 (p = 0.0005). In the placebo group, 5 patients had to cease the protocol after 1 to 4 weeks of the treatment period because of intolerable symptoms and severe worsening of lung function; PC20 on entry was significantly smaller in these patients compared to those who completed the protocol (p = 0.01). After 6 weeks, FEV1 had decreased by 8.5% (p = 0.005) and PC20 by 1.71 doubling concentrations (p = 0.0003). In the BDP group, all patients completed the study and PC20 after the treatment period was significantly higher (p = 0.04) in the BDP than in the placebo group. CONCLUSION: Our data suggest that patients on long-term inhaled steroid therapy with a high degree of bronchial hyperresponsiveness are more likely to show early deterioration of their clinical state after cessation of inhaled steroids.

Administration, Inhalation↗
PubMed1995

Antagonism of beta-adrenoceptor-mediated relaxations of human bronchial smooth muscle by carbachol.

Activation of muscarinic M2 receptors has been suggested to account, in part, for the reduced relaxant potency of beta-adrenoceptor agonists in canine and guinea-pig tracheal smooth muscle pre-contracted with muscarinic agonists as compared to histamine. The aim of the present study was to determine whether the potency of isoprenaline is reduced in human bronchial ring preparations pre-contracted with carbachol as compared to histamine and whether activation of muscarinic M2 receptors contributes to this effect. Cumulative concentration-effect curves to isoprenaline were obtained in the absence and presence of muscarinic M2 receptor antagonism by methoctramine (0.3 microM) in bronchial ring preparations pre-contracted to equivalent isometric tensions with either histamine (10 microM) or carbachol (1 microM). The relaxant potency of isoprenaline was reduced in preparations pre-contracted with carbachol compared to histamine, but there was no significant effect of muscarinic M2 receptor antagonism on either the potency or maximal relaxation by isoprenaline. In conclusion, increased functional antagonism of beta-adrenoceptor-mediated relaxation by muscarinic agonists can be demonstrated in human bronchial smooth muscle, but muscarinic M2 receptors do not appear to contribute to this effect.

Adult↗
PubMed1995

Relationship between bronchoalveolar lavage neutrophil numbers and lavage fluid elastase and antielastase activities.

Elastase and antielastase activities were measured in bronchoalveolar lavage fluid (BALF) and their relationship to bronchoalveolar lavage (BAL) neutrophil numbers was assessed in order to determine whether the elevated BAL neutrophil count can predict a shift in the elastase/antielastase balance. BAL samples were obtained from 133 randomly selected patients undergoing diagnostic bronchoscopy with BAL. Elastase and antielastase activities were determined using the synthetic substrate MeO-Suc-Ala-Ala-Pro-Val-pNA. In a random subset of 24 samples, the antioxidant capacity was measured as the inhibition of peroxyl radical-mediated oxidation of B-phycoerythrin. Only 7 of the BAL samples exhibited measurable elastase activity and all but one of these had a BAL neutrophil count greater than 100 x 10(3)/ml. Antielastase activity was measurable in 124 samples exhibiting no free elastase activity. There was a tendency for lower antielastase activity to be associated with higher neutrophil numbers, but this did not translate into a statistically significant correlation over all samples. There was no significant correlation between antioxidant capacity and either the neutrophil number or antielastase activity. It is concluded that BAL neutrophil numbers do not, in general, predict the status of elastase/antielastase balance in the epithelial lining fluid and that the antioxidant mechanisms in the epithelial lining fluid do not appear to be related to the antielastase capacity.

Adult↗
PubMed1995

Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes.

In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized. The BAL fluid of nine patients with histologically proven isolated pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.

Adult↗
PubMed1995

Short term effect of methotrexate in severe steroid-dependent asthma.

The steroid-sparing capacity of methotrexate in asthmatics is still being debated. The present study was undertaken to evaluate the effect of low-dose methotrexate on steroid consumption in patients with severe asthma, who require very high doses of systemic corticosteroids. We conducted a randomized, double-blind, parallel clinical trial in 24 patients with long-standing asthma. After a 3-week run-in period, patients received a 16-week course of either 15 mg of oral methotrexate weekly or matched placebo in addition to their previous asthma therapy. The daily steroid dose (at run-in 30 +/- 14 mg/day in the methotrexate group; 25 +/- 9 mg/day in the placebo group (NS)) decreased by 24% in the methotrexate group (p < 0.01) and by 5% in the placebo group (NS) during weeks 9-16 of the treatment period when compared with run-in values. However, there was no difference in steroid consumption between the two groups at any time. We conclude that in patients with severe asthma who require very high doses of systemic corticosteroids, short-term treatment with methotrexate allows only a marginal steroid reduction. Our study does not support the use of methotrexate as a steroid-sparing agent in asthmatics.

Administration, Oral↗
PubMed1995

Differences in basal and induced DNA single-strand breaks between human peripheral monocytes and lymphocytes.

The aim of this study was to compare the susceptibility of peripheral monocytes and lymphocytes to oxidant-induced DNA single-strand breaks (SSB). DNA damage was assessed by the alkaline single-cell gel electrophoresis (SCGE) assay. Total peripheral mononuclear leukocytes (PML), PML enriched in lymphocytes and PML enriched in monocytes were used. The basal rate of SSB was measured after in vitro incubation of cells for 1 h in phosphate-buffered saline, and the induced rate after incubation in 10 microM or 50 microM H2O2. Incubation was performed at 4 degrees C to limit the possible influence of DNA repair. Lymphocyte-enriched PML were obtained after adhesion of the monocytes to tissue-culture treated plastic, and monocyte-enriched PML by removal of monocytes from the plastic through trypsin. In all samples, cell differentiation was performed using an immunofluorescence technique with antibodies against T- and B-lymphocytes and cytospin preparations. The rate of SSB was determined by visual scoring according to 6 predefined categories of DNA damage and was expressed as mean score (range 0-500) per 100 cells. There was a linear relationship between the percentage of lymphocytes in the samples and the basal rate of SSB (p < 0.001, slope 0.67 score units per %). The same was true for induced DNA damage after incubation in 10 microM H2O2 (p < 0.001, slope 3.80 score units per %) or 50 microM H2O2 (p < 0.001, slope 3.22 score units per %). These regression analyses revealed a 2.9-fold greater rate of basal DNA damage in lymphocytes compared to monocytes and an 11.3-fold greater rate for the damage induced by 10 microM H2O2. We conclude that there are marked differences in the rate of basal and induced SSB between lymphocytes and monocytes, suggesting differences in antioxidant capacity between the two cell populations. These findings indicate that the assessment of SSB for biomonitoring and genotoxicity testing using PML has to take into account possible changes in cellular composition.

Adult↗
PubMed1995

Migration and proliferation of guinea pig and human airway epithelial cells in response to tachykinins.

Restoration of the epithelial lining of a damaged airway is a necessary component of airway repair. Tachykinins, including substance P (SP) and neurokinin A (NKA), are localized to sensory nerves within the airway mucosa. These tachykinins regulate several airway functions, but their role in the repair of the epithelium has not been explored. To determine whether tachykinins stimulate migration and proliferation of airway epithelial cells, guinea pig tracheal epithelial (GPTE) and human bronchial epithelial (HBE) cells were grown in primary culture for 4-5 days. Epithelial cell migration was assessed in a blindwell chemotaxis chamber, and proliferation was determined by immunohistochemistry after incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). Both GPTE and HBE cells migrated after stimulation with 10(-11) M NKA [23.0 +/- 3.6 vs. 5.4 +/- 1.2 cells per 10 high-power fields (hpf), P < 0.001, n = 8 for GPTE cells; 18.4 +/- 2.3 vs. 3.8 +/- 0.5 cells per 10 hpf for control, P < 0.001, n = 4 for HBE cells]. Migration was stimulated within 2 h, was maximal after 6 h, and was attenuated substantially by the neurokinin 2 (NKA)-receptor antagonist SR-48968. NKA-stimulated migration was both chemokinetic and chemotactic, and it could be blocked by inhibition of protein synthesis with cyclohexamide, inhibition of microtubular function with colchicine, or inhibition of actin microfilament elongation with cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hydrogen peroxide contracts human airways in vitro: role of epithelium.

The effects of hydrogen peroxide (H2O2) on human airway smooth muscle tone were determined in vitro. Treatment with H2O2 led to transient concentration-related contractions in the organ bath, amounting to 118 +/- 14 mg (mean +/- SE; n = 12) at 1 mM H2O2, and to greater and more prolonged contractions under superfusion conditions, amounting to 451 +/- 71 mg (n = 17) at 1 mM H2O2. Epithelial removal augmented the response to H2O2 in both systems. Addition of catalase (500 U/ml) abolished the effects of H2O2. Pretreatment of superfused tissues with indomethacin (3 microM) shifted the concentration-effect curve to H2O2 rightward and almost abolished the response to 1 mM H2O2 in epithelium-intact preparations (n = 16; P < 0.05); the response in epithelium-denuded tissues was also significantly inhibited (n = 16; P < 0.05). Pretreatment of the tissues with the TP prostanoid-receptor antagonist GR-32191B (1 microM) also inhibited the contractile effect of H2O2 in epithelium-intact and -denuded tissues. In separate experiments, H2O2 resulted in concentration-related generation of prostaglandin (PG) D2 from isolated airway preparations. The amount of PGD2 released was not different in tissues with intact epithelium compared with those without (n = 9; NS). We conclude that H2O2 exerts on isolated human airways a contractile effect that is augmented by epithelium removal and is largely mediated by prostanoids. The source of PGD2 does not appear to be the epithelium, which we suggest serves mainly as a barrier against H2O2-mediated bronchoconstriction.

Aged↗
PubMed1995

Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals.

Idiopathic pulmonary fibrosis (IPF) is characterized by a huge alveolar oxidant burden and a deficiency of glutathione, a major antioxidant, in the pulmonary epithelial lining fluid (ELF). Therefore, a rational therapeutic strategy is to increase lung glutathione to augment the pulmonary antioxidant protective screen. To evaluate this concept, different doses of N-acetylcysteine (NAC), a glutathione precursor, were administered intravenously to eight patients with pulmonary fibrosis and six control subjects. In patients, bronchoalveolar lavage fluid (BALF) total glutathione increased significantly from 0.99 +/- 0.25 microM to 1.79 +/- 0.37 microM within 3 h following 1.8 g NAC, whereas 4.8 g NAC had no additional effect (1.47 +/- 0.34 microM). In the control subjects, NAC did not significantly alter BALF total glutathione (baseline: 0.79 +/- 0.17 microM, 600 mg NAC: 0.92 +/- 0.33 microM, 1.8 g NAC: 1.39 +/- 0.41 microM, 4.8 g NAC: 1.33 +/- 0.46 microM). The same was true in ELF, 1.8 g NAC significantly raised ELF total glutathione in patients from 186 +/- 47 microM to near normal levels (373 +/- 103 microM), with no further increase following 4.8 g NAC (293 +/- 62 microM). In the control subjects, ELF total glutathione remained unchanged independent of the NAC dose (baseline: 342 +/- 91 microM, 600 mg NAC: 385 +/- 135 microM, 1.8 g NAC: 633 +/- 220 microM, 4.8 g NAC: 646 +/- 263 microM). The increases in total glutathione were almost entirely due to increased levels of reduced glutathione, the form functional as an antioxidant. No adverse effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1995

The effect of 1 ppm nitrogen dioxide on bronchoalveolar lavage cells and inflammatory mediators in normal and asthmatic subjects.

Several studies have suggested that patients with bronchial asthma are more susceptible to the potential effects of nitrogen dioxide (NO2) than healthy subjects, with respect to airway responsiveness and lung function. We investigated whether these differences are paralleled by differences in the cellular and biochemical response within the airway lumen. Twelve subjects with mild extrinsic asthma and eight normal subjects breathed either filtered air or 1 ppm NO2 in a single-blind manner during intermittent exercise for 3 h. Bronchoscopy with bronchoalveolar lavage (BAL) was performed one hour after each exposure, and on a third day without exposure (baseline day). Prostanoids, leukotrienes and histamine were analysed in BAL fluid, and the cellular composition of BAL fluid was assessed. In the asthmatic subjects, NO2 induced a small mean drop in forced expiratory volume in one second (FEV1). Differential cell counts in BAL fluid did not reveal significant effects of NO2. Levels of 6-keto-prostaglandin1 alpha (6-keto-PGF1 alpha) were decreased, and levels of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2) in BAL fluid were increased after NO2 compared to filtered air exposure; whereas, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), histamine and leukotriene levels did not change significantly. The normal subjects showed no change in lung function parameters and a small increase in TxB2 after breathing NO2. We conclude that in subjects with mild asthma NO2 is capable of inducing an activation of cells, which is compatible with enhancement of airway inflammation, even if lung function parameters and cellular composition of BAL fluid are not markedly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Drug-resistant tuberculosis in northern Germany: a retrospective hospital-based study of 1,055 patients from 1984 until 1993.

For the past decade, there have been no data on the time course of drug resistant tuberculosis and on risk factors for drug resistance in former West Germany. We reviewed the medical records of all patients with positive cultures for Mycobacterium tuberculosis from 1984 until 1993 in a hospital near Hamburg. Drug-susceptibility testing was performed for isoniazid, rifampicin, ethambutol, and streptomycin, using the modified proportion method. Of 1,055 patients, 9.6% had isolates resistant to one or more drugs. Of the isolates, 5.8% showed resistance to isoniazid or rifampicin and 1.8% to both isoniazid and rifampicin. There was no significant change of the resistance rate during the study period. Twenty six percent of 89 patients from South America, Africa or Asia had isolates resistant to one or more drugs, compared with 7.6% of 799 patients born in Germany (odds ratio (OR) 4.2; 95% confidence interval (95% CI) 2.5-7.3). Among patients born in Germany, 32% of 101 patients with a history of prior anti-tuberculosis drug therapy had resistant organisms, versus 4.2% of 698 patients without prior therapy (OR 10.7; 95% CI 6.1-18.7). Resistance rates for 35 patients, who had been treated within the last 5 yrs, and for 65 patients, who had been treated more than 5 yrs ago, were 57 and 17%, respectively (OR 6.6; 95% CI 2.9-16.6). Our results suggest that there is no increase in the proportion of drug-resistant tuberculosis in our hospital, and that patients with a recent history of antituberculosis drug therapy and patients from South America, Africa, or Asia are at high risk for drug resistance.

Adult↗
PubMed1995

Modulation of fibroblast activity in histiocytosis X by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibrosis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidence of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B-chain of PDGF) expression was measured by gene hybridization revealing an upregulated c-sis transcript in the group of histiocytosis X and patients, whereas no c-sis expression was detectable in the control group. The alveolar macrophage supernatants from histiocytosis X patients and from the control group were incubated with a human lung fibroblast cell line (WI-38). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen III peptide concentration in fibroblast supernatants. Tritiated thymidine uptake was increased 1.6 times in histiocytosis X compared with the control group (p < 0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants from histiocytosis X were elevated 2.5 times compared with the control group (p < 0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (AA- and BB-chain) resulting in an 80% decrease of tritiated thymidine uptake and procollagen-III-peptide production in the group of histiocytosis X patients compared with native supernatants. No significant change in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T-lymphocyte marker did not show significant differences in both groups excluding unspecific antibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen production.

Adult↗
PubMed1995

Intractable cough associated with the supine body position. Effective therapy with nasal CPAP.

We describe five patients with severe nocturnal cough and daytime somnolence in whom the coughing attacks are triggered by assuming the supine body position. Quantity and quality of the nocturnal cough were evaluated in the sleep laboratory with and without nasal continuous positive airway pressure (N-CPAP). Air flow characteristics were assessed using flow volume and airway resistance loops. Airway anatomy was evaluated bronchoscopically. In all five patients, the cough had a barking quality. Flow-volume loops showed an expiratory collapse phenomenon in two of the patients. Endoscopically, all five patients had signs of airway collapse. All patients had difficulty falling asleep because of coughing and were awakened by it frequently. Sleep times ranged from 2.5 to 4.5 h per night. With N-CPAP pressures ranging from 5 to 13 cm H2O, all five patients had clinically significant improvement in their symptoms. Their sleep times increased to a range of 5 to 7.5 h per night and the daytime somnolence markedly improved or resolved. All five patients requested a N-CPAP unit for home use. We conclude that a cough that is predominantly associated with or exacerbated by the supine body position may be treated effectively with N-CPAP.

Adult↗
PubMed1995

Pharmacological characterization of the muscarinic receptor subtype mediating contraction of human peripheral airways.

The postjunctional muscarinic receptors mediating contraction of human bronchial smooth muscle have been characterized using four nonselective muscarinic receptor agonists and eight subtype selective and nonselective muscarinic antagonists. Carbachol, methacholine, oxotremorine M and (+)-cis-dioxolane all caused concentration-related contractions of human bronchial smooth muscle with a rank order of potency (pD2) of (+)-cis-dioxolane (7.3 +/- 0.2) > oxotremorine M (6.7 +/- 0.2) > carbachol (6.4 +/- 0.1) > methacholine (5.8 +/- 0.2, n = 5 for all). Maximum contractions were not significantly different between agonists, whether expressed as absolute my tension changes or as a percentage of the maximum response to 0.3 mM histamine. Antagonist apparent affinities (pKB) were determined against carbachol-induced contractions and the following rank order was obtained; 4-DAMP (9.4 +/- 0.3) > or = atropine (9.1 +/- 0.1) > zamifenacin (7.6 +/- 0.1) > hexahydrosiladifenidol (HHSiD; 7.1 +/- 0.1) > or = himbacine (7.0 +/- 0.3) > or = pirenzepine (6.8 +/- 0.2) > para-fluoro-hexahydrosiladifenidol (p-F-HHSiD; 6.7 +/- 0.1) > methoctramine (5.3 +/- 0.2). This rank order of antagonist affinities is consistent with activation of M3 receptors. The affinities of HHSiD, p-F-HHSiD and zamifenacin were, however, lower than those reported in guinea pig trachea.

Adult↗