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Biomedical subjects

B B Larsen

Publications and source records attributed to B B Larsen.

10 recordsLinked to original sources
PubMed2003

Effect of ciclesonide on allergen challenge in subjects with bronchial asthma.

BACKGROUND: The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early-phase (EAR) and late-phase (LAR) reactions after allergen challenge in patients with mild allergic asthma. Also, this study provides further data on safety and tolerance of ciclesonide. METHODS: The study was designed as a double-blind placebo-controlled randomized crossover trial. Following a baseline period, patients were randomized to either of two treatment sequences (ciclesonide/placebo, placebo/ciclesonide) each of which lasted for one week and were separated by 3-5 weeks from the alternate treatment sequence. Patients received 800 micro g ciclesonide twice daily by means of a Cyclohaler. At the end of each treatment patients were subjected to an allergen challenge. RESULTS: Thirteen asthmatic patients (mean FEV1 of 91% predicted) who experienced an EAR and LAR after allergen challenge participated in the study. The time-average FEV1 decreases 0-2 h (2-12 h) after allergen challenge as measure of the EAR (LAR) were significantly reduced (P < 0.05, one-sided) from 0.426 L to 0.233 L (EAR) and from 0.443 L to 0.213 L (LAR), respectively. Thus, the study results suggest that ciclesonide significantly lowered the extent of EAR and LAR compared to placebo. Ciclesonide was well tolerated and no drug-related adverse events were reported. Cortisol excretion in 24-h urine showed no significant difference between ciclesonide and placebo. CONCLUSIONS: The study supports the efficacy and safety of ciclesonide.

Administration, Inhalation↗
PubMed2002

Effect of long-term treatment with inhaled budesonide or theophylline on lung function, airway reactivity and asthma symptoms.

Asthma is characterized by inflammation of the airways and long-term treatment with inhaled glucocorticosteroids improve clinical control in patients previously treated with inhaled rescue beta-2 agonist. We investigated whether the dose of inhaled glucocorticosteroid was related to outcome compared with oral theophylline. Budesonide 800 microg bd, budesonide 200 microg bd, or theophylline (Theo-Dur 300 mg bd was given double-blind, double-dummy and randomized, in a parallel group design for 9 months; when therapy was stopped patients were followed for an additional 3 months. Forced expiratory volume in 1 sec (FEV1), bronchial reactivity and asthma symptom scores were assessed before entering the study and after 1, 2, 3, 5, 7, and 9 months of treatment and monthly after treatment was stopped. Eighty-five patients (38 females and 47 males) were enrolled in the study during 1 1/2 year. Withdrawal from the study due to exacerbations during the treatment period was significantly increased (P <0.01) in the theophylline group. After treatment was stopped more patients withdrew in the budesonide group. In the budesonide 800 microg bd group, FEV1 improved significantly after 1 months treatment (P <0.01) and persisted throughout the study period. In the budesonide 200 microg bd group, FEV1 improved slightly and reached significance (P=0.05) after 5 months of treatment. In the theophylline group, FEV1 was unchanged during the 9 months of treatment. In both budesonide groups, FEV1 deteriorated significantly (P<0.01 and P<0.02, respectively) after termination of study medication and reached pretreatment values during the first month. In the budesonide 800 microg bd group, the concentration of histamine causing a 20% fall in FEV1 (PC20) increased significantly (P<0.01) after 1 months treatment and increased further after 9 months (P<0.0001), equivalent to two doubling dilutions. In the budesonide 200 microg bd, group PC20 histamine significantly increased (P <0.005) after 2 months of treatment and remained constant; theophylline was unchanged. After treatment with budesonide 800 microg bd and 200 microg bd were stopped, PC20 decreased significantly (P<0.002 and P=0.05, respectively) within the first month. PC20 remained unchanged after theophylline was stopped. After budesonide 800 microg bd and 200 microg bd treatment, symptom severity decreased in a dose-related and highly significant manner (P < 0.00001 and P < 0.0001, respectively). With theophylline, asthma symptoms decreased slightly after 1 and 2 months treatment (P < 0.01 and P < 0.02, respectively) and when treatment was stopped no increase in asthma symptoms was evident. Oral theophylline slightly reduced airways symptoms and had no influence on FEV1 and PC20 histamine. Maintenance treatment with inhaled budesonide gave a dose-related reduction in airways obstruction, bronchial reactivity and asthma symptom severity. The efficacy of inhaled corticosteroid was superior to oral theophylline.

Administration, Inhalation↗
PubMed1995

Characterization of human and rat immortalized clones parotid acinar cells with respect to specific proteins and their mRNAs, and receptor-linked adenylate cyclase.

This study reports the isolation and characterization of a rat nontumorigenic parotid acinar cell clone (2RSG), a human nontumorigenic parotid acinar cell clone (2HPC8), and a human tumorigenic acinar clone (2HP1G). The levels of alpha-amylase mRNAs detected when using alpha-amylase cDNA of 1176 and 702 bp for hybridization were higher in 2RSG and 2HPC8 cells than their respective whole parotid glands. The level of these mRNAs decreased in 2HP1G cells. In contrast to alpha-amylase mRNAs levels, the alpha-amylase activity in cultured acinar cells was extremely low in comparison to whole glands, irrespective of species or cell status. The levels of proline-rich protein (PRP) mRNA and parotid secretory protein (PSP) mRNA detected when using PRP cDNA of 600 bp and PSP cDNA of 805 bp for hybridization were higher in 2RSG cells than those in rat parotid glands; the reverse was observed in 2HPC8 cells and human parotid glands. The levels of PRP mRNA and PSP mRNA in 2HPC8 and 2PH1G acinar cells were similar. The level of mRNA was not detectable in murine neuroblastoma cells (NBP2) using the same alpha-amylase cDNA, PRP cDNA and PSP cDNA for hybridization. The PSP level in rat parotid gland was lower than that found in 2RSG cells; the reverse was observed in 2HPC8 cells and human parotid glands. The level of PSP in 2HP1G cells was higher than that found in 2HPC8 cells. Isoproterenol increased the cAMP level in 2RSG, 2HPC8, and 2HP1G clones, being most effective in 2RSG cells, and least effective in 2HPG cells. Prostaglandin E1 (PGE1) also increased cAMP level, being most effective in 2HPC8 cells and ineffective in 2HP1G cells, suggesting that the PGE1 receptor-linked adenylate cyclase becomes inactive upon transformation. These results suggest that the three clonal acinar cells from rat and human parotid glands reported here can be useful in comparative studies on regulation of growth, differentiation, and transformation.

Adenylyl Cyclases↗
PubMed1995

Do inhaled steroids have similar efficacy? A case of bronchial asthma suggesting different efficacy of inhaled glucocorticosteroids.

We report a 35-year-old woman who had had bronchial asthma for 17 years. Her asthma worsened and became unstable on treatment with beclomethasone dipropionate (BDP), budesonide (BUD), and oral glucocorticosteroids (GC). At the age of 31, she had participated in a clinical trial with fluticasone propionate (FP), and after 2 weeks' treatment her asthma was well controlled. Because of pregnancy, her participation was terminated and treatment continued with available inhaled GC; however, the disease deteriorated and treatment with FP was resumed 2 years ago. Lung function normalized after 3 weeks and she has remained clinically stable since.

Administration, Inhalation↗
PubMed1995

Once daily fluticasone propionate aqueous nasal spray controls symptoms of most patients with seasonal allergic rhinitis.

This multicentre, randomized, double-blind, parallel-group study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray 200 micrograms once daily (FPANS 200 micrograms od) with FPANS 200 micrograms twice daily (bd) in patients whose seasonal rhinitis symptoms were not completely controlled with FPANS 200 micrograms od. A total of 549 patients initially received FPANS 200 micrograms od during the open-treatment phase of the study. After 2 weeks, 65% of patients had their symptoms well controlled by FPANS 200 micrograms od and continued with this treatment for a further 2 weeks. The remainder received either FPANS 200 micrograms od or FPANS 200 micrograms bd for a further 2 weeks. Efficacy was evaluated by the analysis of symptom-free days. In the uncontrolled group, there was a significant increase in the percentage of symptom-free days in the FPANS 200 micrograms bd group over the FPANS 200 micrograms od group for nasal blockage on waking (P < 0.05) and nasal blockage during the day (P < 0.05). Similar trends were observed for sneezing, rhinorrhoea, nasal itching, and eye symptoms. There was a significant increase in the percentage of days with a symptom score of less than 2 in FPANS 200 micrograms bd group for nasal blockage during the day (P < 0.05). Adverse events were similar in nature and frequency in each treatment group. It is concluded that in the majority of patients symptoms of seasonal rhinitis are well controlled by FPANS 200 micrograms od. In the minority of patients whose symptoms are not adequately controlled by a once daily dose, FPANS 200 micrograms bd provides additional relief, particularly from nasal blockage.

Administration, Intranasal↗
PubMed1994

Budesonide powder administration for the treatment of grass-pollen-induced allergic rhinitis.

The new dry-powder inhaler system, Turbuhaler, has proved to be equivalent to metered-dose inhalers when used in the nose, and the objective of this study was to investigate the efficacy, dose-response effects, and safety of budesonide powder given in the morning during the grass pollen season to patients with grass-pollen-induced allergic rhinitis. Of 190 randomized patients, 186 were treated and 180 completed this double-blind study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to three parallel treatment groups: budesonide 400 micrograms, budesonide 200 micrograms, or placebo once in the morning. Assessment of efficacy, by comparing changes in mean scores of nasal symptoms from run-in to treatment, showed a statistically significant effect for all symptoms with active treatments, as compared with placebo. The mean reduction of symptom severity was more pronounced in the 400-micrograms group than in the 200-micrograms group, and this difference was statistically significant for runny nose (P < 0.02) and combined nasal symptoms (P < 0.02). Nasal peak-inspiratory flow improved significantly in both budesonide-treated groups, as compared with placebo (P < 0.01 and P < 0.01). During the treatment period, patients on active treatment showed, on average, a reduction of all nasal symptoms, whereas the placebo-treated patients, on average, showed an increase of nasal symptoms. Approximately 40% in the high-dose group felt total control of rhinitis symptoms, as compared with 26% in the low-dose group. There was no difference between budesonide- and placebo-treated groups in side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

The effect of salmeterol on the early- and late-phase reaction to bronchial allergen and postchallenge variation in bronchial reactivity, blood eosinophils, serum eosinophil cationic protein, and serum eosinophil protein X.

The late asthmatic response to bronchial allergen challenge and the associated increase in nonspecific bronchial reactivity provides a model for studying the acute inflammatory mechanisms in asthmatic airways. In 12 asthmatic patients (aged 22-37 years) with known dual reaction to allergen challenge, salmeterol 50 micrograms, 100 micrograms, or placebo was administered as a single dose 10 min before allergen challenge in a double-blind, randomized order on three different study days 2 weeks apart. The bronchial reactivity (BH) to histamine was measured the day before and 24 and 48 h after allergen challenge. Salmeterol significantly inhibited the early (P < 0.02) and the late (P < 0.05) asthmatic reactions. After placebo, mean BH was significantly increased above base line at 24 and 48 h (P < 0.02). After 50 and 100 micrograms salmeterol, BH was less than base line at 24 h and returned to prechallenge values at 48 h. Blood eosinophils increased significantly (P < 0.05) 24 and 48 h after allergen challenge, and no difference was found between treatments. After pretreatment with placebo, serum eosinophil cationic protein (s-ECP) and serum eosinophil protein X (s-EPX) increased significantly (P < 0.05) 24 and 48 h after allergen challenge. After treatment with salmeterol 50 micrograms, s-EPX, but not s-ECP, increased significantly 24 h after challenge, but was normal at 48 h. After salmeterol 100 micrograms, no change in s-EPX or s-ECP was found. The results showed that salmeterol eliminated the allergen-induced dual asthmatic reaction and gave protection against increased BH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

Tissue-specific expression in the salivary glands of transgenic mice.

Using a DNA construct, named Lama, derived from the murine parotid secretory protein (PSP) gene, we have obtained salivary gland specific gene expression in transgenic mice. Lama is a PSP minigene and allows analysis of the PSP gene 5' regulatory region by transgenesis. We show here that the regulatory region included in Lama with 4.6 kb of 5' flanking sequence is sufficient to direct expression specifically to the salivary glands. The expression level in the parotid gland is only about one percent of the PSP mRNA level, while that of the sublingual gland is near the PSP mRNA level. This suggests significant differences in the PSP gene regulation in the two glands. In addition, Lama is a secretory expression vector in which cDNAs or genomic fragments can be inserted. We demonstrate that the Lama construct can direct the expression of a heterologous cDNA encoding the C-terminal peptide of human factor VIII to salivary glands and that the corresponding peptide is secreted into saliva.

Amino Acid Sequence↗
PubMed1991

[The hyperimmunoglobulin E syndrome].

Hyperimmunoglobulin E syndrome is a rare disease. The clinical and immunological features of HIE are discussed on the basis of a case history. A 28 year old woman had a life-long history of infections of the skin and the sinopulmonary tract. Because of elevated serum-IgE and several positive skin- and RAST-tests she had erroneously been classified as having multiple allergies including food allergy. We found a very high serum-IgE and negative challenge test. Additionally we found decreased oxidative metabolism of blood neutrophils and monocytes. This finding could explain the increased susceptibility to infections in HIE-patients.

Adult↗