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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 217 records · Page 12Linked to original sources
PubMed1988

A double-blind dose-response study of budesonide by inhalation in patients with bronchial asthma.

Budesonide by inhalation and placebo were tested in 18 patients with moderate chronic bronchial asthma. Three dose levels of budesonide were used (25, 100 and 400 micrograms q.i.d.) and the patients were to take two puffs q.i.d. in all periods. The active treatment was investigated using double-blind cross-over technique, and placebo at the end of the trial. The duration of each treatment period was 2 weeks. The study showed a high drop-out frequency while on placebo and that the PEF values were influenced in a dose-dependent way by budesonide. In spite of the double-blindness the patients had a tendency towards overuse of the trial aerosol on the lowest dose, but they used significantly less than prescribed during the period with the highest dose. No side effects were reported.

Administration, Inhalation↗
PubMed1988

Extracellular deposit of the cationic proteins ECP and EPX in tissue infiltrations of eosinophils related to tissue damage.

In a series of eosinophil inflammatory states affecting various organs (heart, gut, bladder and skin) we performed an immunohistochemical study of the eosinophil cationic proteins ECP and EPX. A strong correlation was noted between the liberation of ECP and EPX and tissue necrosis in all organs. In most cases ECP and EPX were found on the same location. However, one case indicated a possible differential release. Extracellular ECP and EPX were revealed concurrently with the two polyclonal antibodies and the monoclonal EG2 antibody. The latter binds to both ECP and EPX, but only during secretion. Since EG2 does not differentiate between ECP and EPX, but only during secretion. Since EG2 does not differentiate between EXP and EPX, it is for the first time demonstrated that both cationic proteins are correlated to tissue damage. The chymotrypsin-like cationic protein (CCP), related to neutrophils, showed a low correlation with the eosinophil cationic proteins in cases of tissue damage. The hypothesis is put forward that the release of eosinophil granule proteins and especially ECP results in a non-specific tissue damage.

Adult↗
PubMed1988

Respiratory symptoms in Danish farmers: an epidemiological study of risk factors.

An epidemiological study was performed with a self administered questionnaire in a representative sample of 1685 Danish farmers. The purpose of the study was to assess the prevalence of self reported asthma, wheezing during work, and symptoms of chronic bronchitis and to evaluate possible risk factors for the development of these symptoms. A response rate of 73.3% was obtained. The prevalence of asthma was 7.7% and of chronic bronchitis 23.6% in responders. The prevalence of asthma and chronic bronchitis increased from 3.6% and 17.9% in 31-50 year old farmers to 11.8% and 33.0% in 51-70 year old farmers, and from 5.5% and 17.5% in dairy farmers to 10.9% and 32.0% in pig farmers. A logistic regression analysis with correction for age and smoking habits confirmed that pig farming was a risk factor for asthma (odds ratio 2.03), chronic bronchitis (odds ratio 1.53), and wheezing during work (odds ratio 3.33).

Adult↗
PubMed1988

Eosinophil granule proteins in serum after allergen challenge of asthmatic patients and the effects of anti-asthmatic medication.

Thirteen allergic asthmatic patients were challenged six times each and serum levels of ECP (eosinophil cationic protein), EPX (eosinophil protein-x) and blood counts of eosinophil granulocytes were measured in blood obtained before and at regular intervals after challenge. Three challenges were performed in a blinded and randomized fashion and included a one-dose pretreatment with the inhalant anti-asthmatic drugs disodium cromoglycate, terbutaline and budesonide. One challenge was performed after 4 weeks' pretreatment with the inhalant budesonide and one was a histamine challenge. Pre-challenge levels of ECP were significantly reduced both after 4 weeks and after a one-dose treatment with budesonide whereas the EPX levels were reduced only after the former. Blood eosinophil counts were unaffected by the challenge whereas the ECP levels were significantly reduced after the placebo challenge and when premedicated with disodium cromoglycate and terbutaline. The EPX levels stayed unaltered at the placebo challenge but were significantly reduced when the patients were premedicated with terbutaline. ECP and EPX levels as well as blood eosinophil counts before challenge were significantly related to the development of the late asthmatic reaction. The results again focus on a relation between the eosinophil granulocyte and asthma and suggest that an increased activity of the blood eosinophil, as suggested by the raised serum levels of the granule proteins ECP and EPX, is one prerequisite for the development of chronic asthma.

Adult↗
PubMed1988

Epithelial injury by human eosinophils.

The human eosinophil is armed with a number of very potent cytotoxic granule proteins that upon extracellular release may produce considerable damage. The toxic effect of the proteins seems to be quite unselective, involving most mammalian and nonmammalian cells including the epithelial cells. The demonstration of a close relation between the deposition of eosinophil granule proteins and areas of epithelial cell destruction in a variety of diseases including asthma and the fact that cytotoxic concentrations of the proteins have been measured in the fluid phase suggest that the eosinophil participates actively in the pathogenesis of airway diseases. The protection towards the adverse actions of the eosinophil, particularly towards their proteins, therefore seems vital. The discovery of alpha-2-macroglobulin as a specific binder of eosinophil cationic protein may be relevant in this regard.

Asthma↗
PubMed1988

Exocytosis in normal anterior pituitary cells. Quantitative correlation between growth hormone release and the morphological features of exocytosis.

We have used high-pressure freezing techniques to study exocytosis in rat anterior pituitary cells. The cells were either unstimulated or exposed to 1 nM growth hormone releasing factor (GRF) for 10 min before ultrarapid freezing. The magnitude of growth hormone (GH) release was then correlated with the number of exocytotic events observed with freeze-fracture electron microscopy. High-pressure freezing of unfixed and uncryoprotected specimens permits cryofixation of samples up to 1 mm diam (0.5 mm thick) without ice crystal damage, and arrests exocytotic events within 10 ms. Our studies comparing conventionally fixed specimens with those prepared by high-pressure freezing confirm that areas of intramembrane particle clearing at potential exocytotic sites are an artifact of conventional fixation and/or cryoprotection techniques. The cells exposed to 1 nM GRF released approximately fivefold more GH than did unstimulated cells. Morphologically, we have observed a 3.3-fold increase in the number of exocytotic events in GRF-stimulated cells, 33.7 events/100 micron2 compared with 10.4 events/100 micron2 for unstimulated cells. In additional experiments, we studied the effects of two inhibitors of GRF-induced exocytosis, somatostatin and sodium isethionate. Both compounds elicit the same response, a parallel decrease in exocytotic events and in secreted product. We conclude that high-pressure freezing, combined with freeze-fracture and freeze-substitution processing techniques, is an excellent tool for studying the morphological aspects of exocytosis. In the present investigation, it has allowed us to quantitatively relate the biochemistry and morphology of exocytosis in anterior pituitary cells.

Animals↗
PubMed1988

Serum concentrations and accumulation of silver in skin during three months treatment with an anti-smoking chewing gum containing silver acetate.

Silver acetate chewing gum was used for 12 weeks as a smoking deterrent in 21 adults. The effect of silver on serum concentrations, its accumulation in the skin and the risk of developing clinically evident argyria were investigated. Serum concentrations of silver clearly rose after chewing gum use had started, and concentrations quickly returned to normal after use had ceased. In most cases the number of silver granules in skin biopsies, observed by autometallography, increased after the gum had been used for 12 weeks. No one developed clinical signs of argyria. Silver acetate containing remedies can be used as an aid to stop smoking, but the consumption must be monitored to avoid accumulation of larger amounts of silver in the body.

Acetates↗
PubMed1987

Evaluation of the addition of cromolyn sodium to bronchodilator maintenance therapy in the long-term management of asthma.

Three hundred ninety-seven patients, aged 5 to 63 years, took part in a year-long international multicenter, double-blind, placebo-controlled trial. The patients, whose asthma was considered not adequately controlled, were divided into two groups according to their principal medication at entry (group A, oral and/or inhaled beta 2-bronchodilators; group B, methylxanthines, with or without beta 2-agonists) and randomly allocated to additional treatment with cromolyn sodium (metered-dose inhaler, 2 mg, four times a day, or capsules, 20 mg, four times a day) or matching placebo. A 2-month baseline preceded 10 to 12 months of treatment. After 4 to 8 weeks of treatment, patients were encouraged to reduce bronchodilator usage. Patients used diary cards to record asthma severity, sleep difficulty, morning and evening peak expiratory flow rates, days of disruption of normal activity, use of test treatments, and concomitant medication. Significant differences favoring cromolyn sodium (p less than 0.05 and better) were observed for most of the treatment period in respect to (1) asthma severity, (2) morning and evening peak expiratory flow rates, and (3) days of disruption of normal activity. Patients receiving cromolyn sodium experienced fewer exacerbations and tended to use less concomitant medication than patients receiving placebo. Patients' opinions of treatment significantly favored cromolyn sodium. These results demonstrate the value of the addition of cromolyn sodium to existing therapy in the long-term management of asthma and endorse its use as a first-line treatment.

Adolescent↗
PubMed1987

Heat-labile neutrophil chemotactic activity in subjects with asthma after allergen inhalation: relation to the late asthmatic reaction and effects of asthma medication.

Neutrophil chemotactic activity (NCA) in serum is raised in subjects with asthma after inhalation of an allergen. Two kinds of NCA have been demonstrated, heat-stable and heat-labile. In addition, inhibitory activity is generated after inhalation challenge. In the present study we have investigated the relationship of heat-labile NCA to the development of the late asthmatic reaction (LAR) in 13 subjects with asthma after allergen challenge and the effects of asthma medication on the formation of this activity. Heat-labile NCA peaked 120 to 240 minutes after challenge and demonstrated at this time significant (p less than 0.001) quantitative relationships to the ensuing LAR. The inhalant corticosteroid, budesonide, significantly inhibited (p less than 0.001) the generation of heat-labile NCA and the development of LAR both after a single dose and after 4 weeks of pretreatment. Single-dose disodium cromoglycate pretreatment, initially, slightly enhanced (p less than 0.05) heat-labile NCA but, after 120 minutes, slightly inhibited (p less than 0.05) the activity. Disodium cromoglycate also slightly abrogated the development of LAR. Single-dose pretreatment with the beta 2-agonist, terbutaline, inhibited generation of heat-labile NCA (p less than 0.001) but was without effect on LAR. It is concluded that the generation of heat-labile NCA is related to the development of the LAR and may be of importance for the attraction of inflammatory cells to the lung in the development of the inflammatory reaction probably responsible for LAR. However, the pharmacologic control of heat-labile NCA indicates that the process is multifactorial and not solely dependent on the generation of NCAs detected in serum.

Adult↗
PubMed1987

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗
PubMed1986

An immunofluorescent method for a specific demonstration of granulocytes and some of their proteins (ECP and CCP).

Using p-benzoquinone as a fixative the non-specific fluorescence of granulocytes and especially the eosinophils is removed for both FITC and TRITC. In this way we have been able to detect the eosinophil cationic protein (ECP) and the chymotrypsin-like cationic protein (CCP) in human lung tissue and by double immunofluorescent labelling shown that these two proteins very likely are related to eosinophils respectively the neutrophils.

Adult↗
PubMed1986

Red wine asthma: a controlled challenge study.

Drinking red wine may provoke bronchospasm in subjects with asthma. In order to reveal some of the possible agents involved in this reaction, 18 patients with a history of red wine-induced asthma were studied. They received, in a double-blind fashion, red wine with low sulfur dioxide (SO2) and high amine, high SO2 and high amine and low SO2 and low amine content. In each challenge, the wine was administered in stepwise increasing quantities until a total of 385 ml or a fall in peak expiratory flow of greater than 15% was reached. Nine subjects demonstrated a significant fall in peak flow in one or more challenges. In all cases the most severe reaction was observed after the wine with high SO2 content. The study suggests that SO2 is the most important factor in red wine-induced asthma. It is recommended that wine labels provide information on the SO2 content.

Adult↗
PubMed1986

Chemotactic activity of LTB4 in man.

An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 microM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilia instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTB4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Adult↗